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Sample records for chronic macrophage-mediated demyelinating

  1. Interleukin-10 overexpression promotes Fas-ligand-dependent chronic macrophage-mediated demyelinating polyneuropathy.

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    Dru S Dace

    Full Text Available BACKGROUND: Demyelinating polyneuropathy is a debilitating, poorly understood disease that can exist in acute (Guillain-Barré syndrome or chronic forms. Interleukin-10 (IL-10, although traditionally considered an anti-inflammatory cytokine, has also been implicated in promoting abnormal angiogenesis in the eye and in the pathobiology of autoimmune diseases such as lupus and encephalomyelitis. PRINCIPAL FINDINGS: Overexpression of IL-10 in a transgenic mouse model leads to macrophage-mediated demyelinating polyneuropathy. IL-10 upregulates ICAM-1 within neural tissues, promoting massive macrophage influx, inflammation-induced demyelination, and subsequent loss of neural tissue resulting in muscle weakness and paralysis. The primary insult is to perineural myelin followed by secondary axonal loss. Infiltrating macrophages within the peripheral nerves demonstrate a highly pro-inflammatory signature. Macrophages are central players in the pathophysiology, as in vivo depletion of macrophages using clodronate liposomes reverses the phenotype, including progressive nerve loss and paralysis. Macrophage-mediate demyelination is dependent on Fas-ligand (FasL-mediated Schwann cell death. SIGNIFICANCE: These findings mimic the human disease chronic idiopathic demyelinating polyneuropathy (CIDP and may also promote further understanding of the pathobiology of related conditions such as acute idiopathic demyelinating polyneuropathy (AIDP or Guillain-Barré syndrome.

  2. Chronic inflammatory demyelinative polyneuropathy

    DEFF Research Database (Denmark)

    Said, Gérard; Krarup, Christian

    2013-01-01

    Chronic inflammatory demyelinative polyneuropathy (CIDP) is an acquired polyneuropathy presumably of immunological origin. It is characterized by a progressive or a relapsing course with predominant motor deficit. The diagnosis rests on the association of non-length-dependent predominantly motor ...

  3. [Chronic inflammatory demyelinating polyradiculoneuropathy].

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    Franques, J; Azulay, J-P; Pouget, J; Attarian, S

    2010-06-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a demyelinating chronic neuropathy of immune origin whose diagnosis is based upon clinical, biological and electrophysiological data; previously critical to the diagnosis the nerve biopsy is now restricted to the rare situations where accurate diagnosis cannot be reached using these data alone. CIDP are mainly idiopathic, but a few associated diseases must be sought for as they require specific attention. Such associated diseases must particularly be discussed when the manifestations are severe or resistant to immunomodulating or immunosuppressive agents. Indeed, idiopathic CIDP are usually responsive to these treatments. The effectiveness of these treatments is limited by the importance of the secondary axonal loss. The dependence or the resistance may sometimes justify the association of several immunomodulating treatments. A single randomized controlled trial support the use of cytotoxic drugs and none with rituximab.

  4. Chronic inflammatory demyelinating polyradiculoneuropathy.

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    Van den Bergh, Peter Y K; Rajabally, Yusuf A

    2013-06-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is the most common autoimmune neuropathy. The diagnosis depends on the clinical presentation with a progressive or relapsing course over at least 2 months and electrophysiological evidence of primary demyelination. Whereas typical CIDP is quite easily recognizable because virtually no other neuropathies present with both distal and proximal motor and sensory deficit, atypical CIDP, focal and multifocal variants in particular, may represent a difficult diagnostic challenge. CIDP very likely is an underdiagnosed condition as suggested also by a positive correlation between prevalence rates and sensitivity of electrophysiological criteria. Since no 'gold standard' diagnostic marker exists, electrophysiological criteria have been optimized to be at the same time as sensitive and as specific as possible. Additional supportive laboratory features, such as increased spinal fluid protein, MRI abnormalities of nerve segments, and in selected cases nerve biopsy lead to the correct diagnosis in the large majority of the cases. Objective clinical improvement following immune therapy is also a useful parameter to confirm the diagnosis. The pathogenesis and pathophysiology of CIDP remain poorly understood, but the available evidence for an inflammatory origin is quite convincing. Steroids, intravenous immunoglobulin (IVIG), and plasma exchange (PE) have been proven to be effective treatments. IVIG usually leads to rapid improvement, which is useful in severely disabled patients. Repeat treatment over regular time intervals for many years is often necessary. The effect of steroids is slower and the side-effect profile may be problematic, but they may induce disease remission more frequently than IVIG. An important and as of yet uncompletely resolved issue is the evaluation of long-term outcome to determine whether the disease is still active and responsive to treatment.

  5. Chronic inflammatory demyelinating polyneuropathy

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    Polyneuropathy - chronic inflammatory; CIDP; Chronic inflammatory polyneuropathy; Guillain-Barré - CIDP ... Health care providers also consider CIDP as the chronic form of Guillain-Barré syndrome. The specific triggers ...

  6. Chronic inflammatory demyelinating polyneuropathy in two siblings.

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    Gabreëls-Festen, A A; Hageman, A T; Gabreëls, F J; Joosten, E M; Renier, W.O.; Weemaes, C M; ter Laak, H J

    1986-01-01

    A familial occurrence of chronic inflammatory demyelinating polyneuropathy is reported. The diagnostic problems in distinguishing the progressive form of this disease in childhood from hereditary motor and sensory neuropathy types I and III are discussed. Criteria for a definite diagnosis of chronic inflammatory demyelinating polyneuropathy are proposed.

  7. Chronic Acquired Demyelinating Polyneuropathy following Renal Transplantation

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    Younger, D. S.; Stuart Orsher

    2013-01-01

    The clinical, laboratory, and treatment findings of a patient with chronic acquired demyelinating polyneuropathy (CADP) in association with renal transplantation are described. Like the present case, many such patients have been described under the rubric of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

  8. Chronic dysimmune neuropathies: Beyond chronic demyelinating polyradiculoneuropathy

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    Khadilkar Satish

    2011-01-01

    Full Text Available The spectrum of chronic dysimmune neuropathies has widened well beyond chronic demyelinating polyradiculoneuropathy (CIDP. Pure motor (multifocal motor neuropathy, sensorimotor with asymmetrical involvement (multifocal acquired demylinating sensory and motor neuropathy, exclusively distal sensory (distal acquired demyelinating sensory neuropathy and very proximal sensory (chronic immune sensory polyradiculopathy constitute the variants of CIDP. Correct diagnosis of these entities is of importance in terms of initiation of appropriate therapy as well as prognostication of these patients. The rates of detection of immune-mediated neuropathies with monoclonal cell proliferation (monoclonal gammopathy of unknown significance, multiple myeloma, etc. have been facilitated as better diagnostic tools such as serum immunofixation electrophoresis are being used more often. Immune neuropathies associated with malignancies and systemic vasculitic disorders are being defined further and treated early with better understanding of the disease processes. As this field of dysimmune neuropathies will evolve in the future, some of the curious aspects of the clinical presentations and response patterns to different immunosuppressants or immunomodulators will be further elucidated. This review also discusses representative case studies.

  9. Management strategies in chronic inflammatory demyelinating polyradiculoneuropathy

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    Patel Kamakshi

    2010-01-01

    Full Text Available Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP is a chronic, proximal and distal, asymmetrical or symmetrical, motor and sensory demyelinating polyneuropathy with a progressive course for at least 2 months. The accurate diagnosis is crucial as CIDP is amenable to treatment. Recent advances have provided new strategies and options for management of this syndrome. In this article, we review the clinical and diagnostic features as well as discuss recent insights and treatment strategies along with our experience in the management of patients with CIDP.

  10. Aggregation of MBP in chronic demyelination

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    Frid, Kati; Einstein, Ofira; Friedman-Levi, Yael; Binyamin, Orli; Ben-Hur, Tamir; Gabizon, Ruth

    2015-01-01

    Objectives Misfolding of key disease proteins to an insoluble state is associated with most neurodegenerative conditions, such as prion, Parkinson, and Alzheimer’s diseases. In this work, and by studying animal models of multiple sclerosis, we asked whether this is also the case for myelin basic protein (MBP) in the late and neurodegenerative phases of demyelinating diseases. Methods To this effect, we tested whether MBP, an essential myelin component, present prion-like properties in animal models of MS, as is the case for Cuprizone-induced chronic demyelination or chronic phases of Experimental Autoimmune Encephalomyelitis (EAE). Results We show here that while total levels of MBP were not reduced following extensive demyelination, part of these molecules accumulated thereafter as aggregates inside oligodendrocytes or around neuronal cells. In chronic EAE, MBP precipitated concomitantly with Tau, a marker of diverse neurodegenerative conditions, including MS. Most important, analysis of fractions from Triton X-100 floatation gradients suggest that the lipid composition of brain membranes in chronic EAE differs significantly from that of naïve mice, an effect which may relate to oxidative insults and subsequently prevent the appropriate insertion and compaction of new MBP in the myelin sheath, thereby causing its misfolding and aggregation. Interpretation Prion-like aggregation of MBP following chronic demyelination may result from an aberrant lipid composition accompanying this pathological status. Such aggregation of MBP may contribute to neuronal damage that occurs in the progressive phase of MS. PMID:26273684

  11. [Chronic inflammatory demyelinating neuropathies and their variants

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    Vallat, J.-M.; Tabaraud, F.; Magy, L.; Macian, F.

    2002-12-01

    The Chronic Inflammatory Demyelinating Polyradiculoneuropathies (CIDP) constitute a syndrome whose incidence is difficult to evaluate, and is probably underestimated. In the course of this presentation, we deliberately restricted discussion to issues raised in recent years concerning the extent of this syndrome. We discuss diagnostic criteria, especially electrophysiological ones. As the criteria proposed by the ad hoc committee of the American Academy of Neurology in 1991 have been questioned due to lack of sensitivity, new ones have been proposed recently. We briefly discuss the different types of chronic dysimmune demyelinating neuropathy: not only the CIDP, but also the Lewis and Sumner syndrome or multifocal inflammatory demyelinating neuropathy and the multiple conduction block neuropathies. At last, we point out the consistent finding of axonal involvement in the course of a chronic demyelinating neuropathy; over time, it can become predominant, which may make diagnosis difficult by suggesting a chronic axonal neuropathy that may be assumed to be primary. Consideration of these points may help clinicians recognize more chronic dysimmune neuropathies, for which immunosuppressive therapy has been found to be effective.

  12. Steroids for Chronic Inflammatory Demyelinating Polyneuropathy

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    J Gordon Millichap

    2005-03-01

    Full Text Available The efficacy and safety of high-dose, intermittent IV methylprednisolone (IVMP as initial and long-term maintenance therapy for chronic inflammatory demyelinating polyneuropathy (CIDP were analyzed by a retrospective review of outcome data derived from patients’ medical records between 1992 and 2003 at Washington University School of Medicine, St Louis, MO.

  13. Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

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    ... and abnormal sensations. CIDP is closely related to Guillain-Barre syndrome and it is considered the chronic counterpart ... and abnormal sensations. CIDP is closely related to Guillain-Barre syndrome and it is considered the chronic counterpart ...

  14. Challenges in pediatric chronic inflammatory demyelinating polyneuropathy.

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    Haliloğlu, Göknur; Yüksel, Deniz; Temoçin, Cağri Mesut; Topaloğlu, Haluk

    2016-12-01

    Chronic inflammatory demyelinating neuropathy, a treatable immune-mediated disease of the peripheral nervous system is less common in childhood compared to adults. Despite different sets of diagnostic criteria, lack of a reliable biologic marker leads to challenges in diagnosis, follow-up and treatment. Our first aim was to review clinical presentation, course, response to treatment, and prognosis in our childhood patients. We also aimed to document diagnostic and therapeutic pitfalls and challenges at the bedside. Our original cohort consisted of 23 pediatric patients who were referred to us with a clinical diagnosis of chronic inflammatory demyelinating neuropathy. Seven patients reaching to an alternative diagnosis were excluded. In the remaining patients, diagnostic, treatment and follow-up data were compared in typical patients who satisfied both clinical and electrodiagnostic criteria and atypical patients who failed to meet minimal research chronic inflammatory demyelinating neuropathy electrodiagnostic requirements. Eight of 16 patients (50%) met the minimal chronic inflammatory demyelinating neuropathy research diagnostic requirements. There was only a statistically significant difference (p = 0.010) in terms of European Neuromuscular Centre childhood chronic inflammatory diagnostic mandatory clinical criteria between the two groups. Misdiagnosis due to errors in electrophysiological interpretation (100%, n = 8), cerebrospinal fluid cytoalbuminologic dissociation (100%, n = 4 and/or subjective improvement on any immunotherapy modality (80 ± 19.27%)) was frequent. Pediatric CIDP is challenging in terms of diagnostic and therapeutic pitfalls at the bedside. Diagnostic errors due to electrophysiological interpretation, cerebrospinal fluid cytoalbuminologic dissociation, and/or subjective improvement on immunotherapy should be considered.

  15. Chronic inflammatory demyelinating polyradiculoneuropathy associated intracranial hypertension.

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    Altinkaya, Ayca; Topcular, Baris; Sakalli, Nazan Karagoz; Kuscu, Demet Yandim; Kirbas, Dursun

    2013-06-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired immune-mediated demyelinating neuropathy. In this report, we detail the course of a 58-year-old male patient who had headache and double vision followed by progressive paresthesia and difficulty in walking. The patient had bilateral papilledema and mild leg weakness, absent ankle jerks and loss of sensation in distal parts of his lower and upper extremities. His electromyography (EMG) was concordant with CIDP and lumbar puncture revealed high opening pressure. The polyradiculoneuropathy as well as the papilledema and elevated cerebrospinal fluid (CSF) pressure improved under steroids. The improvement in intracranial hypertension (IHT) and papilledema under steroid treatment suggests that the IHT in this patient might be associated with CIDP.

  16. [Pathogenesis of chronic inflammatory demyelinating polyneuropathy].

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    Aranami, Toshimasa; Yamamura, Takashi

    2013-05-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is considered to be a demyelinating autoimmune disorder in the peripheral nervous system. Concerning cellular immune response, activity of IFN-gamma producing Th1 and IL-17 producing Th17 cells might be accelerated in patients with CIDP, while regulatory function of CD4+ CD25(high) Foxp3+ regulatory T cells might be diminished. Humoral immune responses against several myelin components such as myelin protein zero and gangliosides such as GM1 might be also induced in a part of patients with CIDP. Besides, growing body of evidences suggest that immune response against several molecules expressed in the noncompact myelin might be involved in the pathogenesis of CIDP.

  17. Acute clinical onset chronic inflammatory demyelinating polyneuropathy in a dog.

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    Molín, Jéssica; Márquez, Mercedes; Raurell, Xavier; Matiasek, Kaspar; Ferrer, Isidre; Pumarola, Martí

    2011-09-01

    We report a case of acute-onset ambulatory paraparesis with electrophysiological abnormalities compatible with axonal and demyelinating lesions in a Rottweiler dog. Although the clinical findings were compatible with acute canine idiopathic polyneuropathy, postmortem investigations revealed a chronic demyelinating polyneuropathy affecting the nerve roots. Due to the combination of acute clinical presentation and chronic pathologic features, this case is consistent with the acute-onset form of chronic inflammatory demyelinating polyneuropathy (A-CIDP).

  18. Treatment of chronic inflammatory demyelinating polyradiculoneuropathy.

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    Lehmann, Helmar C; Hughes, Richard A C; Hartung, Hans-Peter

    2013-01-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a sporadically occurring, acquired neuropathic condition of autoimmune origin with chronic progressive or relapsing-remitting disease course. CIDP is a treatable disorder; a variety of immunosuppressive and immunomodulatory agents are available to modify, impede, and even reverse the neurological deficits and sequelae that manifest in the course of the disease. However, in many cases CIDP is not curable. Challenges that remain in the treatment of CIDP patients are well recognized and include a remarkably individual heterogeneity in terms of disease course and treatment response as well as a lack of objective and feasible measures to predict and monitor the responsiveness to the available therapies. In this chapter an overview of the currently used drugs in the treatment of CIDP patients is given and some important and controversial issues that arise in the context of care for CIDP patients are discussed.

  19. The electrodiagnostic distinctions between chronic familial and acquired demyelinative neuropathies.

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    Lewis, R A; Sumner, A J

    1982-06-01

    We compared the electrodiagnostic studies of 40 patients with chronic acquired demyelinative neuropathy and 18 patients with familial demyelinative neuropathy. Patients with acquired neuropathy had differential slowing of conduction velocity when distal latencies were compared with more proximal conduction velocities in the same nerve, when equivalent segments of different nerves were compared, and when dispersion of compound motor action potentials was examined. Conduction block was noted in some patients. Patients with familial disease had uniform conduction slowly of all nerve segments, and conduction block was not seen. Chronic acquired demyelinative neuropathy is characterized by multifocal slowing of nerve conduction, whereas familial demyelinative neuropathy is characterized by uniform conduction slowing.

  20. [Acute-Onset Chronic Inflammatory Demyelinating Polyradiculoneuropathy].

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    Kanbayashi, Takamichi; Sonoo, Masahiro

    2015-11-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is characterized by an insidious onset showing progression over two months. However, up to 16% of CIDP patients may show acute presentation similar to Guillain-Barré syndrome (GBS). Such cases are termed acute-onset CIDP (A-CIDP). Distinguishing A-CIDP from GBS, especially the acute inflammatory demyelinating polyneuropathy (AIDP) subtype, is critical because therapeutic strategies and outcomes may differ between the two syndromes. Regarding clinical features, A-CIDP is less likely to have autonomic nervous system involvement, facial weakness, a preceding infectious illness, or the need for mechanical ventilation, in comparison with AIDP. Electrophysiological features are usually quite similar between the two, although follow-up studies may elucidate key differences. Around 8%-16% of GBS patients may show clinical deterioration shortly after improvement or stabilization following initial immunological therapy. Such a situation is termed treatment-related fluctuation (TRF; GBS-TRF). The distinction between GBS-TRF and A-CIDP is an important clinical issue because maintenance treatment is often required in CIDP. The diagnosis of A-CIDP should be considered when the condition of a patient with GBS deteriorates after nine weeks from onset, or when deterioration occurs three times or more.

  1. Treatment of chronic inflammatory demyelinating polyneuropathy.

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    Kleyman, Inna; Brannagan, Thomas H

    2015-07-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is one of the acquired demyelinating neuropathies and is considered to be immune mediated. Diagnosis is typically based on clinical history, neurologic examination, electrophysiologic studies, CSF studies, and pathologic examination. Early diagnosis and treatment is important to prevent irreversible axonal loss and optimize improvement in function. The first-line agents for treatment are intravenous immunoglobulin (IVIg), corticosteroids, and plasmapheresis, which have all been demonstrated to be effective in controlled studies. Studies have not shown a significant difference between these three treatments, and the initial choice of therapy is often based on availability, cost, ease of administration, and side effect profile. If patients do not respond to one of these agents, they may respond to one of the others and sometimes in combination. If the first-line agents are not effective, chemotherapeutic or immunosuppressive agents may be considered. There are limited controlled studies of these modalities, and they are often used in conjunction with a first-line treatment. The majority of patients require long-term therapy to maintain a response and to prevent relapse.

  2. Early identification of 'acute-onset' chronic inflammatory demyelinating polyneuropathy.

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    Sung, Jia-Ying; Tani, Jowy; Park, Susanna B; Kiernan, Matthew C; Lin, Cindy Shin-Yi

    2014-08-01

    Distinguishing patients with acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy prior to relapse is often challenging at the onset of their clinical presentation. In the present study, nerve excitability tests were used in conjunction with the clinical phenotype and disease staging, to differentiate between patients with acute-onset chronic inflammatory demyelinating polyneuropathy and patients with acute inflammatory demyelinating polyneuropathy at an early stage, with the aim to better guide treatment. Clinical assessment, staging and nerve excitability tests were undertaken on patients initially fulfilling the diagnostic criteria of acute inflammatory demyelinating polyneuropathy soon after symptom onset and their initial presentation. Patients were subsequently followed up for minimum of 12 months to determine if their clinical presentations were more consistent with acute-onset chronic inflammatory demyelinating polyneuropathy. Clinical severity as evaluated by Medical Research Council sum score and Hughes functional grading scale were not significantly different between the two cohorts. There was no difference between the time of onset of initial symptoms and nerve excitability test assessment between the two cohorts nor were there significant differences in conventional nerve conduction study parameters. However, nerve excitability test profiles obtained from patients with acute inflammatory demyelinating polyneuropathy demonstrated abnormalities in the recovery cycle of excitability, including significantly reduced superexcitability (P chronic inflammatory demyelinating polyneuropathy, a different pattern occurred with the recovery cycle shifted downward (increased superexcitability, P inflammatory demyelinating polyneuropathy and acute-onset chronic inflammatory demyelinating polyneuropathy could be clearly separated into two non-overlapping groups. Studies of nerve excitability may be able to

  3. Chronic inflammatory demyelinating polyradiculoneuropathy: from bench to bedside.

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    Peltier, Amanda C; Donofrio, Peter D

    2012-07-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is the most common treatable chronic autoimmune neuropathy. Multiple diagnostic criteria have been established, with the primary goal of identifying neurophysiologic hallmarks of acquired demyelination. Treatment modalities have expanded to include numerous immunomodulatory therapies, although the best evidence continues to be for corticosteroids, plasma exchange, and intravenous immunoglobulin (IVIg). This review describes the pathology, epidemiology, pathogenesis, diagnosis, and treatment of CIDP.

  4. Cranial magnetic resonance imaging in chronic demyelinating polyneuropathy.

    OpenAIRE

    Hawke, S H; Hallinan, J M; McLeod, J G

    1990-01-01

    Twenty one patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and five patients with chronic demyelinating polyneuropathy associated with benign monoclonal paraproteinaemia none of whom had signs or symptoms of central nervous system disease, had cranial magnetic resonance imaging (MRI) on a 1.5 Tesla unit. Areas of increased white matter signal intensity were seen in one of 10 patients aged less than 50 years and in five of 16 patients aged more than 50 years. In ...

  5. Ocular Neuromyotonia Associated with Chronic Inflammatory Demyelinating Polyneuropathy.

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    Kung, Nathan H; Bucelli, Robert C; McClelland, Collin M; Van Stavern, Gregory P

    2015-10-01

    Ocular neuromyotonia (ONM) is a neuro-ophthalmic disorder characterized by episodic diplopia caused by contraction of one or more ocular muscles due to spontaneous excitation of the respective ocular motor nerve. We report a patient whose ocular neuromyotonia arose in the setting of a subacute demyelinating polyneuropathy consistent with chronic inflammatory demyelinating polyneuropathy (CIDP) and subsequently resolved following the initiation of intravenous immunoglobulin (IVIg) for her neuropathy. Our patient provides additional evidence towards the role of demyelination and ephaptic neurotransmission in ocular neuromyotonia and also represents the first reported case of ocular neuromyotonia associated with a systemic neurological condition.

  6. Evaluation of a patient with suspected chronic demyelinating polyneuropathy.

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    Jani-Acsadi, Agnes; Lewis, Richard A

    2013-01-01

    Demyelinating neuropathies are typically characterized by physiological slowing of conduction velocity and pathologically by segmental loss of myelin and in some instances, evidence of remyelination. Clinically, patients with demyelinating neuropathy can be seen with inherited disorders (Charcot-Marie-Tooth disease) or acquired disorders, typically immune-mediated or inflammatory. The acquired disorders can be either acute or subacute as seen in the acute inflammatory demyelinating polyneuropathy (AIDP) form of Guillain-Barré syndrome or chronic progressive or relapsing disorders such as chronic inflammatory demyelinating polyneuropathy. It is important to develop a logical approach to diagnosing these disorders. This requires an understanding of the clinical, genetic, physiological, and pathological features of these neuropathies. Clinically, important features to consider are the temporal progression, degree of symmetry, and involvement of proximal as well as distal muscles. Genetically, recognizing the different inheritance patterns and age of onset allow for a coordinated approach to determining a specific genotype. Physiologically, besides nerve conduction slowing, other physiological hallmarks of demyelination include temporal dispersion of compound motor action potentials (CMAP) on proximal stimulation, conduction block, and distal CMAP duration prolongation with certain patterns of involvement pointing to specific disorders. This chapter focuses on these various aspects of the evaluation of patients with chronic acquired demyelinating neuropathies to develop a comprehensive and thoughtful diagnostic concept.

  7. Motor variant of chronic inflammatory demyelinating polyneuropathy in a child.

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    Sinno, Durriyah D; Darras, Basil T; Yamout, Bassem I; Rebeiz, Jean G; Mikati, Mohamad A

    2008-06-01

    Only 2 cases of pure motor chronic demyelinating inflammatory polyneuropathy in the pediatric age group have been reported in the literature. We report on a motor variant of chronic demyelinating inflammatory polyneuropathy with anti-ganglioside antibodies, diagnosed in a 5-year-old girl who presented with progressive motor weakness over a period of 12 months with no sensory involvement. She initially responded partially to intravenous immunoglobulin therapy (1 gm/kg/month for 6 months), and then demonstrated sustained but incomplete improvement on chronic prednisone therapy (1-2 mg/kg/day), on which she has continued since 1 year and 4 months after her initial presentation 3 years ago.

  8. Diagnosis and treatment of chronic acquired demyelinating polyneuropathies.

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    Latov, Norman

    2014-08-01

    Chronic neuropathies are operationally classified as primarily demyelinating or axonal, on the basis of electrodiagnostic or pathological criteria. Demyelinating neuropathies are further classified as hereditary or acquired-this distinction is important, because the acquired neuropathies are immune-mediated and, thus, amenable to treatment. The acquired chronic demyelinating neuropathies include chronic inflammatory demyelinating polyneuropathy (CIDP), neuropathy associated with monoclonal IgM antibodies to myelin-associated glycoprotein (MAG; anti-MAG neuropathy), multifocal motor neuropathy (MMN), and POEMS syndrome. They have characteristic--though overlapping--clinical presentations, are mediated by distinct immune mechanisms, and respond to different therapies. CIDP is the default diagnosis if the neuropathy is demyelinating and no other cause is found. Anti-MAG neuropathy is diagnosed on the basis of the presence of anti-MAG antibodies, MMN is characterized by multifocal weakness and motor conduction blocks, and POEMS syndrome is associated with IgG or IgA λ-type monoclonal gammopathy and osteosclerotic myeloma. The correct diagnosis, however, can be difficult to make in patients with atypical or overlapping presentations, or nondefinitive laboratory studies. First-line treatments include intravenous immunoglobulin (IVIg), corticosteroids or plasmapheresis for CIDP; IVIg for MMN; rituximab for anti-MAG neuropathy; and irradiation or chemotherapy for POEMS syndrome. A correct diagnosis is required for choosing the appropriate treatment, with the aim of preventing progressive neuropathy.

  9. Chronic inflammatory demyelinating polyneuropathy associated with primary biliary cirrhosis.

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    Murata, Ken-ya; Ishiguchi, Hiroshi; Ando, Ryuki; Miwa, Hideto; Kondo, Tomoyoshi

    2013-12-01

    We report a patient with chronic inflammatory demyelinating polyneuropathy associated with primary biliary cirrhosis (PBC). Except for minimal biochemical abnormalities, clinical symptoms of PBC were not observed, and we diagnosed our patient with asymptomatic PBC from the results of a liver biopsy. Although the patient noticed little muscle weakness, an electrophysiological study demonstrated slow conduction velocities and prolonged distal latencies, with definite conduction blocks in the median, ulnar, and tibial nerves. The disturbed sensory pattern was asymmetrical, and sensory nerve action potentials were not evoked. From these observations, we diagnosed this patient with chronic inflammatory demyelinating polyneuropathy. Neuropathy associated with PBC is very rare. We must differentiate demyelinating neuropathy with PBC in patients with asymmetrical sensory dominant neuropathy with high immunoglobulin M titers, and investigate for the presence of anti-mitochondrial antibodies to rule out a complication of asymptomatic PBC.

  10. Intravenous immunoglobulin treatment in chronic inflammatory demyelinating polyneuropathy

    NARCIS (Netherlands)

    P.A. van Doorn (Pieter)

    1990-01-01

    textabstractPatients with a chronic inflammatory demyelinating polyneuropathy (CIDP) may respond to treatment with corticosteroids and to plasmapheresis, which was demonstrated in controlled clinical studies. In an uncontrolled study it was found that 13/17 CIDP patients had a rapid and clinical imp

  11. Child neurology: chronic inflammatory demyelinating polyradiculoneuropathy in children.

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    Markowitz, Jennifer A; Jeste, Shafali S; Kang, Peter B

    2008-12-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disorder characterized by patchy demyelination of nerve roots and distal nerves. The course may be monophasic progressive or relapsing-remitting. CIDP is less common in children than in adults. As in adults, children with CIDP present with proximal and distal weakness and loss of deep tendon reflexes. Children are most often brought to medical attention due to gait disturbance and falling. As in adults, immunomodulatory treatment is the mainstay of therapy. Based on the small number of case series available, children with CIDP seem have a more favorable long-term course than adults.

  12. Characteristic MRI features of chronic inflammatory demyelinating polyradiculoneuropathy.

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    Abe, Yuichi; Terashima, Hiroshi; Hoshino, Hideki; Sassa, Kaori; Sakai, Tetsuro; Ohtake, Akira; Kubota, Masaya; Yamanouchi, Hideo

    2015-10-01

    We present characteristic magnetic resonance imaging (MRI) features in a pediatric female patient with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Muscle weakness developed at 8 years old and fluctuated during the clinical course over 7 years. Electrophysiological studies showed a demyelination pattern with moderately delayed nerve conduction velocity, as well as dispersion phenomenon. MRI showed marked changes in thickening of the spinal nerve roots and their peripheral nerves in the lumber and brachial plexuses, as well as in the bilateral trigeminal nerves. It is suggested that these MRI features are characteristic and strongly supportive of the diagnosis of CIDP with a prolonged clinical course.

  13. Chronic inflammatory demyelinating polyneuropathy in common variable immunodeficiency.

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    Özdemir, Özlem; Okan, Mehmet S; Kilic, Sara S

    2012-04-01

    Common variable immunodeficiency comprises a heterogeneous group of primary antibody deficiencies with complex clinical and immunologic phenotypes. Immune dysregulation leads to the generation of multiple autoantibodies against various antigenic targets in patients with common variable immunodeficiency. Chronic inflammatory demyelinating polyneuropathy is a heterogeneous disorder that indicates an autoimmune response against peripheral nerve myelin. We describe a 7-year-old girl with common variable immunodeficiency who developed chronic inflammatory polyneuropathy. A 5-day course of intravenous immunoglobulin (500 mg/kg/day) improved her neurologic disorder. Chronic inflammatory demyelinating polyneuropathy should be added to the broadening spectrum of neurologic complications in common variable immunodeficiency. Early detection and consequent treatment may reverse the neurologic sequelae.

  14. Peripheral nerve proteins as potential autoantigens in acute and chronic inflammatory demyelinating polyneuropathies.

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    Lim, Jia Pei; Devaux, Jérôme; Yuki, Nobuhiro

    2014-10-01

    Guillain-Barré syndrome is classified into acute inflammatory demyelinating polyneuropathy and acute motor axonal neuropathy. Whereas autoantibodies to GM1 or GD1a induce the development of acute motor axonal neuropathy, pathogenic autoantibodies have yet to be identified in acute inflammatory demyelinating polyneuropathy and chronic inflammatory demyelinating polyneuropathy. This review highlights the importance of autoantibodies to peripheral nerve proteins in the physiopathology of acute and chronic inflammatory demyelinating polyneuropathies. Moreover, we listed up other potential antigens, which may become helpful biomarkers for acquired, dysimmune demyelinating neuropathies based on their critical functions during myelination and their implications in hereditary demyelinating neuropathies.

  15. Childhood chronic inflammatory demyelinating polyneuropathy with nonuniform pathologic features.

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    Luan, Xinghua; Zheng, Riliang; Chen, Bin; Yuan, Yun

    2010-08-01

    Nonuniform pathologic changes in chronic inflammatory demyelinating polyneuropathy were previously reported only in adult humans. We analyzed the pathologic features of 12 children, aged 2-17 years, with chronic inflammatory demyelinating polyneuropathy. Six patients manifested a preceding illness. Five patients presented a chronic, monophasic course, and seven presented a relapsing-remitting course. Three patients exhibited multiple cranial-nerve involvement. Five of 12 (41.7%) patients presented nonuniform features. Two subtypes of nonuniform lesions were revealed. One exhibited varying myelinated fiber content between nerve fascicles, and one exhibited onion bulbs involving a variable number of fascicles. Macrophages were evident in 11 patients, and the number of CD3-positive T cells in the nonuniform group was greater compared with the uniform group (P = 0.045). Our results demonstrate that childhood chronic inflammatory demyelinating polyneuropathy exhibits pathologically nonuniform features, thus providing more evidence to assist in differential diagnoses of pediatric patients. However, clinical and electrophysiologic features, as well as responses to treatment, were similar in the nonuniform and uniform groups.

  16. Chronic inflammatory demyelinating polyneuropathy after treatment with interferon-alpha.

    Science.gov (United States)

    Hirotani, Makoto; Nakano, Hitoshi; Ura, Shigehisa; Yoshida, Kazuto; Niino, Masaaki; Yabe, Ichiro; Sasaki, Hidenao

    2009-01-01

    Interferon-alpha (IFN-alpha), though widely used for the treatment of chronic viral hepatitis, may be associated with the occurrence of autoimmune disorders. In this case report, a patient with chronic hepatitis C virus infection had chronic inflammatory demyelinating polyneuropathy (CIDP) after the initiation of IFN-alpha therapy. The neurological symptoms of this patient continued to progress even though the treatment with IFN-alpha had been withdrawn; the symptoms improved dramatically following treatment with intravenous immunoglobulin. This case may therefore provide an important clue to understand the immune mechanism of CIDP and IFN-alpha.

  17. [Anesthetic Management of Three Patients with Chronic Inflammatory Demyelinating Polyradiculoneuropathy].

    Science.gov (United States)

    Maruyama, Naoko; Wakimoto, Mayuko; Inamori, Noriko; Nishimura, Shinya; Mori, Takahiko

    2015-08-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronically progressing or relapsing disease caused by immune-mediated peripheral neuropathy. We report the anesthetic management of three CIDP patients who underwent elective orthopedic surgeries. Owing to the risk of neuraxial anesthetics triggering demyelination, general anesthesia was selected to avoid epidural or spinal anesthesia or other neuraxial blockade. It was also judged prudent to avoid prolonged perioperative immobilization, which might compress vulnerable peripheral nerves. For Patient 1, general anesthesia was induced with propofol, remifentanil, and sevoflurane, and was maintained with sevoflurane and remifentanil. For Patients 2 and 3, general anesthesia was induced and maintained with propofol and remifentanil. For tracheal intubation, under careful monitoring with peripheral nerve stimulators, minimal doses of rocuronium (0.6-0.7 mg x kg(-1)) were administered. When sugammadex was administered to reverse the effect of rocuronium, all patients rapidly regained muscular strength. Postoperative courses were satisfactory without sequelae.

  18. Epidemiology of chronic inflammatory demyelinating polyneuropathy abroad and in Russia

    Directory of Open Access Journals (Sweden)

    T. E. Popova

    2015-01-01

    Full Text Available Current article provides an overview of the results of epidemiological studies of chronic inflammatory demyelinating polyneuropathy (CIDP in Russia and abroad. It is shown that the prevalence of CIDP is different in countries, due to the use of different diagnostic criteria. It should be noted that the reliability of epidemiological prevalence and incidence is affected by difficulties of diagnosis of atypical forms of the disease.

  19. CLINICAL CHARACTERISTICS OF PATIENTS WITH CHRONIC ACQUIRED DEMYELINATING POLYNEUROPATHY

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    M. Ghabace

    2005-09-01

    Full Text Available Chronic acquired demyelinating neuropathy (CADP is heterogeneous ill both clinical and laboratory features. This study was performed to define the clinical. clccuodiagnostic and histological findings. course and response 10 therapy in patients with CADI'. Thirty patients (20 men and 10 women with CADI' were studied. Diagnostic criteria were based on clinical presentation. clcctrophysiolcgical studies. cerebrospinal fluid (CSF protein level and sural nerve biopsy findings. Response 10 treatment was assessed by changes in average muscle score (A:vlS. Twenty-one patients conformed to the diagnostic criteria of chronic inflammatory demyelinating polyneuropathy (Cf Dl" and 9 to distal acquired demyelinating symmetric neuropathy (DADS. The course was monophasic in Cl (23~/~-, relapsing in I0 (40(~/;1 and chronic progressive in 8 (30':••;,: 4( 13°•'( had ucutc presentation with subsequent progression or relapsing course. Motor nerve conduction velocity (i"--INCV of less than 70°,-( and greater than 70'~;(, of normal were seen in 18 (60'~'; and 12 (40{~-;1 patients. respectively. Conduction block was observed in 14 (47(~/o and CSF protein levels WCl"C elevaled in 19 patients (66':--;. Demyelination was reported in 61(;--( and 58% of the biopsies performed in patients with MNCV <: 70'~";l and> 70'}'( of normal. respectively. The association between "•lNCV and histologic findings was no! significant. Twenty-one patients were treated with intravenous immunoglobulin (lVlg. Fifteen patients  83(;-{1 with ClDP had significant improvement in AfvlS following the iuitial fVlg treatment (P n.ol. This study highlights the heterogeneity of clinical and laboratory findings in C:"IP and the importance of early treatment.

  20. Chronic inflammatory demyelinating polyradiculoneuropathy in a patient with Crohn's disease.

    Science.gov (United States)

    Ohyagi, Masaki; Ohkubo, Takuya; Yagi, Yousuke; Ishibashi, Satoru; Akiyama, Junko; Nagahori, Masakazu; Watanabe, Mamoru; Yokota, Takanori; Mizusawa, Hidehiro

    2013-01-01

    Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract that is frequently accompanied by systemic complications. Neuropathologies have not been well investigated as extraintestinal manifestations of CD. We herein report the case of a 36-year-old man with CD who presented with progressive weakness and numbness. A neurological examination and the results of a nerve conduction study and a sural nerve biopsy led to a diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Plasma exchanges were initially effective; however, the effects gradually declined starting 10 days after the plasma exchange (PE). These results suggest that humoral factors may play an important role in CIDP associated with CD.

  1. Fibrillary glomerulonephritis combined with chronic inflammatory demyelinating polyneuropathy

    Directory of Open Access Journals (Sweden)

    Woo Kyung Sung

    2015-06-01

    Full Text Available A 58-yr-old man presented with leg edema and subacute weakness of his bilateral lower extremities. Urinary and serum immunoelectrophoresis revealed the presence of lambda-type Bence Jones proteins. He was ultimately diagnosed with monoclonal gammopathy of undetermined significance (MGUS. A renal biopsy specimen showed fibrillary glomerulonephritis (FGN, which was randomly arranged as 12–20 m nonbranching fibrils in the basement membranes. Immunofluorescence studies were negative for immunoglobulin (IgG, IgM, IgA, C3, and kappa light chains in the capillary walls and mesangial areas. A Congo red stain for amyloid was negative. Electromyography and nerve conduction velocity examinations results were compatible with the presence of demyelinating polyneuropathy. This case showed a rare combination of FGN, without Ig deposition, and MGUS combined with chronic inflammatory demyelinating polyneuropathy (CIDP.

  2. Reconstruction magnetic resonance neurography in chronic inflammatory demyelinating polyneuropathy.

    Science.gov (United States)

    Shibuya, Kazumoto; Sugiyama, Atsuhiko; Ito, Sho-ichi; Misawa, Sonoko; Sekiguchi, Yukari; Mitsuma, Satsuki; Iwai, Yuta; Watanabe, Keisuke; Shimada, Hitoshi; Kawaguchi, Hiroshi; Suhara, Tetsuya; Yokota, Hajime; Matsumoto, Hiroshi; Kuwabara, Satoshi

    2015-02-01

    To study distribution and patterns of nerve hypertrophy in chronic inflammatory demyelinating polyneuropathy (CIDP), magnetic resonance neurography with 3-dimensional reconstruction of short tau inversion recovery images was performed in 33 patients. This technique clearly showed longitudinal morphological changes from the cervical roots to the nerve trunks in the proximal arm. Nerve enlargement was detected in 88% of the patients. According to the clinical subtype of CIDP, typical CIDP patients showed symmetric and root-dominant hypertrophy, whereas Lewis-Sumner syndrome patients had multifocal fusiform hypertrophy in the nerve trunks. The patterns of nerve hypertrophy presumably reflect the different pathophysiology of each CIDP subtype.

  3. Autoantibodies against vinculin in patients with chronic inflammatory demyelinating polyneuropathy.

    Science.gov (United States)

    Beppu, Minako; Sawai, Setsu; Satoh, Mamoru; Mori, Masahiro; Kazami, Takahiro; Misawa, Sonoko; Shibuya, Kazumoto; Ishibashi, Masumi; Sogawa, Kazuyuki; Kado, Sayaka; Kodera, Yoshio; Nomura, Fumio; Kuwabara, Satoshi

    2015-10-15

    To identify the target molecules of chronic inflammatory demyelinating polyneuropathy (CIDP), we used proteomic-based approach in the extracted proteins from porcine cauda equina. Two of 31 CIDP patients had markedly elevated serum autoantibodies against vinculin, a cell adhesion protein. Both of the patients with anti-vinculin antibodies had similar clinical manifestation, which are compatible with those of "typical" CIDP. Immunocytochemistry showed that vinculin was stained at the myelin sheath of the sciatic nerves by serum samples. Our results suggest that vinculin is a possible immunological target molecule in a subpopulation of typical CIDP patients.

  4. Gene expression changes in chronic inflammatory demyelinating polyneuropathy skin biopsies.

    Science.gov (United States)

    Puttini, Stefania; Panaite, Petrica-Adrian; Mermod, Nicolas; Renaud, Susanne; Steck, Andreas J; Kuntzer, Thierry

    2014-05-15

    Chronic-inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated disease with no known biomarkers for diagnosing the disease or assessing its prognosis. We performed transcriptional profiling microarray analysis on skin punch biopsies from 20 CIDP patients and 17 healthy controls to identify disease-associated gene expression changes. We demonstrate changes in expression of genes involved in immune and chemokine regulation, growth and repair. We also found a combination of two upregulated genes that can be proposed as a novel biomarker of the disorder.

  5. Novel immunotherapeutic strategies in chronic inflammatory demyelinating polyneuropathy.

    Science.gov (United States)

    Mathis, Stéphane; Vallat, Jean-Michel; Magy, Laurent

    2016-02-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic immune-mediated neuropathy: it is clinically heterogeneous (relapsing-remitting form, chronic progressive form, monophasic form or CIDP having a Guillain-Barré syndrome-like onset), but potentially treatable. Although its pathophysiology remains largely unknown, CIDP is considered an immune-mediated neuropathy. Therefore, many immunotherapies have been proposed in this peripheral nervous system disorder, the most known efficient treatments being intravenous immunoglobulin, corticosteroids and plasma exchange. However, these therapies remain unsatisfactory for many patients, so numerous other immunotherapeutic strategies have been evaluated, based on their immunosuppressant or immunomodulatory potency. We have performed a large review of the literature about treatment in CIDP, with a special emphasis on novel and alternative immunotherapeutic strategies.

  6. Clinical trials in CIDP and chronic autoimmune demyelinating polyneuropathies.

    Science.gov (United States)

    Dalakas, Marinos C

    2012-05-01

    The main chronic autoimmune neuropathies include chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN), and anti-myelin-associated glycoprotein (MAG) demyelinating neuropathy. On the basis of randomized controlled studies, corticosteroids, intravenous immunoglobulin (IVIg), and plasmapheresis provide short-term benefits in CIDP. MMN responds only to IVIg. Because in MMN and CIDP, IVIg infusions are required every 3-6 weeks to sustain benefits or long-term remissions, there is a need for "IVIg-sparing" agents. In CIDP, immunosuppressive drugs, such as azathioprine, cyclosporine, methotrexate, mycophenolate, and cyclophosphamide, are used, but controlled trials have not shown that they are effective. Controlled trials have also not shown benefit to any agents in anti-MAG neuropathy. However, clinicians use many immunosuppressive drugs in both settings, but all have potentially serious side effects and are only effective in some patients. Thus, there is a need for new therapies in the inflammatory and paraproteinemic neuropathies. New agents targeting T cells, B cells, and transmigration and transduction molecules are discussed as potential treatment options for new trials. The need for biomarkers that predict therapeutic responses or identify patients with active disease is emphasized, and the search for better scoring tools that capture meaningful changes after response to therapies is highlighted.

  7. Intrathecal Dexmedetomidine for Anaesthetic Management of a Patient with Chronic Inflammatory Demyelinating Polyneuropathy

    Science.gov (United States)

    Srinivasalu, D

    2016-01-01

    Chronic demyelinating disorders have multifactorial origin but common important physiologic and anaesthetic considerations. Choice of anaesthesia technique and the drugs used, undertanding the pros and cons of using central neuraxial blocks will help in successful management of such patients. We describe the anaesthetic management of a 34-year-old male with chronic inflammatory demyelinating polyneuropathy posted for cystolithotripsy. PMID:27790558

  8. [Chronic inflammatory demyelinating polyradiculoneuropathy: clinical heterogeneity and therapeutic perspectives].

    Science.gov (United States)

    Leger, Jean-Marc; Bombelli, Francesco; Tran-Thanh, Hung; Chassande, Bénédicte; Maisonobe, Thierry; Viala, Karine

    2010-01-01

    Since the first description of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) by PJ Dyck's group at the Mayo Clinic 35 years ago, a wide range of publications have underlined the clinical, electrophysiologic and histopathologic heterogeneity of this disease. Expert consensus opinion is that CIDP should be considered in any patient with progressive symmetrical or asymmetrical polyradiculoneuropathy whose clinical course is relapsing and remitting or progresses for more than two months, especially if there are positive sensory symptoms, proximal weakness, are flexia without wasting, or preferential loss of vibration or joint-position sense. Electrophysiologic features of demyelinating polyneuropathy (especially conduction blocks) and elevated protein levels in cerebrospinal fluid may assist with the diagnosis. However, various clinical pictures have been described in patients with CIDP including pure motor or sensory impairment, and distal, multifocal or focal distribution. Two specific points have recently been emphasized:--while most CIDP patients have chronic onset, acute onset resembling Guillain-Barré syndrome may sometimes occur;--pure sensory forms may require different diagnostic strategies, including the use of somatosensory evoked potentials showing abnormal proximal sensory conduction, and nerve biopsy showing macrophage-associated demyelination, onion bulb formation, demyelinated and partially remyelinated nerve fibres, endoneurial edema, endoneurial mononuclear cell infiltration, and variation between fascicles. Several sets of diagnostic criteria for CIDP have been proposed, with different sensitivities and specificities. The European Federation of Neurological Societies/Peripheral Nerve Society criteria strike a balance between specificity, which needs to be higher for research purposes than for clinical diagnosis, and sensitivity, which, if too low, might lead to some cases being missed. CIDP patients may have a variety of

  9. A case of chronic inflammatory demyelinating polyneuropathy presented with unilateral ptosis.

    Science.gov (United States)

    Izadi, Sadegh; Karamimagham, Sina; Poursadeghfard, Maryam

    2014-01-01

    Chronic Inflammatory Demyelinating Polyneuropathy is an autoimmune disease with progressive and relapsing courses. The main clinical presentations are diffuse deep tendon hyporeflexia or areflexia and symmetric proximal-distal muscles weakness. Myasthenia gravis is also an immune mediated disease with fluctuating ocular and bulbar symptoms and sometimes weakness. Although both myasthenia gravis and chronic inflammatory demyelinating polyneuropathy are immune mediated disorders, clinical presentations are obviously different in the two diseases. Herein, we will report a case of chronic inflammatory demyelinating polyneuropathy who presented with isolated unilateral ptosis. Initially, the patient was managed as ocular type of myasthenia gravis, but after progression to general limb weakness and areflexia, the diagnosis of chronic inflammatory demyelinating polyneuropathy was made. Although unilateral ptosis is a typical feature of myasthenia gravis, it may be seen as the first presentation of chronic inflammatory demyelinating polyneuropathy as well which mimics myasthenia gravis disease.

  10. Childhood chronic inflammatory demyelinating polyneuropathy: an overview of 10 cases in the modern era.

    Science.gov (United States)

    Ware, Tyson L; Kornberg, Andrew J; Rodriguez-Casero, M Victoria; Ryan, Monique M

    2014-01-01

    Chronic inflammatory demyelinating polyneuropathy is a rare condition in children. In this article, we report our experience in the management of 10 cases of childhood chronic inflammatory demyelinating polyneuropathy in a single center, in the era of contrast-enhanced magnetic resonance imaging (MRI), genetic microarray, and chronic inflammatory demyelinating polyneuropathy disease activity status. Robust neurophysiologic abnormalities were present in all cases and both MRI and lumbar puncture were useful adjuncts in diagnosis. Genetic microarray is a simple technique useful in excluding the most common hereditary demyelinating neuropathy. Intravenous immunoglobulin was an effective first-line therapy in most cases, with refractory cases responding to corticosteroids and rituximab. We found the chronic inflammatory demyelinating polyneuropathy disease activity status useful for assessing outcome at final follow-up, whereas the modified Rankin score was better for assessing peak motor disability.

  11. Clinical and electrophysiological parameters distinguishing acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy.

    Science.gov (United States)

    Dionne, Annie; Nicolle, Michael W; Hahn, Angelika F

    2010-02-01

    Up to 16% of chronic inflammatory demyelinating polyneuropathy (CIDP) patients may present acutely. We performed a retrospective chart review on 30 acute inflammatory demyelinating polyneuropathy (AIDP) and 15 acute-onset CIDP (A-CIDP) patients looking for any clinical or electrophysiological parameters that might differentiate AIDP from acutely presenting CIDP. A-CIDP patients were significantly more likely to have prominent sensory signs. They were significantly less likely to have autonomic nervous system involvement, facial weakness, a preceding infectious illness, or need for mechanical ventilation. With regard to electrophysiological features, neither sural-sparing pattern, sensory ratio >1, nor the presence of A-waves was different between the two groups. This study suggests that patients presenting acutely with a demyelinating polyneuropathy and the aforementioned clinical features should be closely monitored as they may be more likely to have CIDP at follow-up.

  12. Subcutaneous immunoglobulin preserves muscle strength in chronic inflammatory demyelinating polyneuropathy

    DEFF Research Database (Denmark)

    Markvardsen, L H; Harbo, T; Sindrup, S H;

    2014-01-01

    BACKGROUND AND PURPOSE: Subcutaneous immunoglobulin (SCIG) is superior to placebo treatment for maintenance of muscle strength during 12 weeks in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). The present study evaluated whether SCIG preserves muscle strength for 1 year...... in an open-label follow-up study. METHODS: Seventeen responders to intravenous immunoglobulin (IVIG) who had participated in the previous study of SCIG versus placebo in CIDP were included. After one IVIG infusion 2 weeks prior to baseline, all continued on SCIG treatment at weekly equal dosage and were...... remained unchanged. CONCLUSION: SCIG preserves muscle strength and functional ability in patients with CIDP who previously responded to IVIG. SCIG should be considered as an alternative in long-term treatment of CIDP patients....

  13. Chronic inflammatory demyelinating polyradiculoneuropathy: from pathology to phenotype.

    Science.gov (United States)

    Mathey, Emily K; Park, Susanna B; Hughes, Richard A C; Pollard, John D; Armati, Patricia J; Barnett, Michael H; Taylor, Bruce V; Dyck, P James B; Kiernan, Matthew C; Lin, Cindy S-Y

    2015-09-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an inflammatory neuropathy, classically characterised by a slowly progressive onset and symmetrical, sensorimotor involvement. However, there are many phenotypic variants, suggesting that CIDP may not be a discrete disease entity but rather a spectrum of related conditions. While the abiding theory of CIDP pathogenesis is that cell-mediated and humoral mechanisms act together in an aberrant immune response to cause damage to peripheral nerves, the relative contributions of T cell and autoantibody responses remain largely undefined. In animal models of spontaneous inflammatory neuropathy, T cell responses to defined myelin antigens are responsible. In other human inflammatory neuropathies, there is evidence of antibody responses to Schwann cell, compact myelin or nodal antigens. In this review, the roles of the cellular and humoral immune systems in the pathogenesis of CIDP will be discussed. In time, it is anticipated that delineation of clinical phenotypes and the underlying disease mechanisms might help guide diagnostic and individualised treatment strategies for CIDP.

  14. Improving the management of chronic inflammatory demyelinating polyradiculoneuropathy.

    Science.gov (United States)

    Allen, Jeffrey A; Bril, Vera

    2016-06-01

    This article considers several issues of current interest relating to the management of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), including diagnostic pitfalls, differences between CIDP patients with and without concurrent diabetes mellitus and how to best measure treatment response in daily practice. Despite the availability of diagnostic criteria, many patients diagnosed with CIDP do not meet these criteria; reasons for misdiagnosis are discussed. There are no definitive predictors of treatment response in CIDP; however, certain clinical and electrophysiological characteristics may be helpful. Patients with CIDP and concurrent diabetes present an additional diagnostic challenge; the differences between these groups, including possible differences in response predictors are discussed. Finally, the most appropriate outcome measures for use in daily practice are considered.

  15. Long-term immunoglobulin therapy for chronic inflammatory demyelinating polyradiculoneuropathy.

    Science.gov (United States)

    Rajabally, Yusuf A

    2015-05-01

    Immunoglobulins are an effective but expensive treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Although the goal is to improve function, use of functional scales to monitor therapy is not widespread. Limited recent evidence suggests that doses lower than those used traditionally may be as effective. There are no proven correlations of effective dose with weight, disease severity, or duration. The clinical course of CIDP is heterogeneous and includes monophasic forms and complete remissions. Careful monitoring of immunoglobulin use is necessary to avoid overtreatment. Definitive evidence for immunoglobulin superiority over steroids is lacking. Although latest trial evidence favors immunoglobulins over steroids, the latter may result in higher remission rates and longer remission periods. This article addresses the appropriateness of first-line, high-dose immunoglobulin treatment for CIDP and reviews important clinical questions regarding the need for long-term therapy protocols, adequate monitoring, treatment withdrawal, and consideration of corticosteroids as an alternative to immunoglobulin therapy.

  16. New insights into the management of chronic inflammatory demyelinating polyradiculoneuropathy.

    Science.gov (United States)

    Rajabally, Yusuf A; Blomkwist-Markens, Patricia H; Katzberg, Hans D

    2015-01-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and its variants can be challenging to diagnose and treat. A combination of clinical, electrophysiological and laboratory features is often required to reach a diagnosis. New data are emerging about potential biomarkers and factors that may indicate treatment needs in individual patients. High-quality evidence exists for the efficacy of intravenous immunoglobulin (IVIG) in the treatment of CIDP, including quality of life (QoL) benefits. Besides pharmacological treatment, psychological factors must also be addressed to improve patients' QoL. Home-based IVIG infusion therapy is currently a well-established approach in some countries. A 6-month pilot study conducted in Ontario, Canada, provided proof of safety and patient acceptance of home-based IVIG therapy, although some logistical issues emerged.

  17. Chronic inflammatory demyelinating polyneuropathy associated with diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Farzad Fatehi

    2013-01-01

    Full Text Available Various forms of neuropathy are seen diabetic patients; chronic inflammatory demyelinating polyneuropathy (CIDP seems not to be infrequent neuropathy in patients suffering from diabetes and it seems to be more common than in the general population; on the contrary, some authorities do not support pathogenetic association between diabetes mellitus (DM and CIDP. Also, there are some controversies on the subject of CIDP treatment in diabetic patients. Some studies showed that patients with CIDP-DM considerably had recovered following treatment with immunotherapeutic modalities like (Intravenous immunoglobulin IVIG and conversely, some else have argued against the prescription of IVIG in this group and recommend treatment with corticosteroids and provided that resistant, rituximab may be beneficial. The main limitation in most studies is the inadequate number of cases and as a result, problematic decision making in treatment. This article represents an inclusive review of diabetic CIDP presentation and treatment.

  18. [Treatment's initiation in chronic inflammatory demyelinating polyradiculopathy (CIDP)].

    Science.gov (United States)

    Uzenot, D; Azulay, J-P; Pouget, J

    2007-09-01

    Treatment's initiation in chronic inflammatory demyelinating polyradiculopathy (CIDP) remains a difficult medical decision. Only plasma exchanges, intravenous immunoglobulins (IVIg) and corticosteroids are proven effective treatments. Immunosuppressors are actually not first-line treatments in CIDP. Particular CIDP forms are associated with different response to treatments: pure motor CIDP should be treated by IVIg, and corticosteroids should only carefully be used in Lewis-Sumner syndrome. Otherwise, IVIg are first-line treatment in diabetic patients. Patients must be informed of side's effects and expected clinical effects. Early treatment was actually not proved to prevent axonal damages in CIDP patients, and waiting seems to be the best therapeutic option in poorly symptomatic patients. Recently, clinical guidelines were proposed to help clinician in this treatment choice, but there is no consensus about the best dose, duration or administration way to CIDP treatments. Further studies should be performed to clarify these points and to determine immunosuppressor agents place in treatment strategy.

  19. [Subcutaneous immunoglobulin. Treatment in chronic inflammatory demyelinating polyradiculo-neuropathy].

    Science.gov (United States)

    Nogués, Martín A; Varela, Francisco J; Seminario, Gisela; Insúa, María C; Bezrodnik, Liliana

    2016-01-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired disease that may affect nerve roots and peripheral nerves. Despite its low incidence, diagnosis is particularly important because there are different effective treatments. Human immunoglobulin is one of the mainstays of the treatment. Although there are few studies up to date, subcutaneous immunoglobulin (IgSC) has been proposed as an alternative to intravenous administration with similar efficacy. We present three cases with definite CIDP, classified according to the European Federation of Neurological Societies / Peripheral Nerve, Society (EFNS /PNS) criteria in which was used SCIgG as a treatment after success with the intravenous route. The Overall Neuropathy Limitations Scale (ONLS) was used to estimate the changes in the muscular strength before and after treatment.

  20. Specific features of chronic inflammatory demyelinating polyneuropathy in children

    Directory of Open Access Journals (Sweden)

    A. L. Kurenkov

    2012-01-01

    Full Text Available Chronic inflammatory demyelinating polyneuropathy (CIDP is an autoimmune peripheral neuropathy that affects both adults and children. The basis for the paper is the analysis of 5 cases of CIDP in children (3 girls and 2 boys aged 5 to 17 years, followed up for 3 to 6 years. The types of its clinical picture and electromyographic changes at different disease stages are considered in detail. The course of the disease is traced during therapy with corticosteroids and intravenous human immunoglobulin and plasmapheresis. The results of the authors’ observations are compared with those of investigations conducted by other authors. The consideration of the diagnosis of CIDP and its treatment options focuses on that the international standards must be necessarily met to minimize errors in its differential diagnosis and management of these patients, and to make the prognosis for the disease.

  1. Astrogliosis during acute and chronic cuprizone demyelination and implications for remyelination

    Directory of Open Access Journals (Sweden)

    Tuan Q. Le

    2012-10-01

    Full Text Available In multiple sclerosis, microglia/macrophage activation and astrocyte reactivity are important components of the lesion environment that can impact remyelination. The current study characterizes these glial populations relative to expression of candidate regulatory molecules in cuprizone demyelinated corpus callosum. Importantly, periods of recovery after acute or chronic cuprizone demyelination are examined to compare conditions of efficient versus limited remyelination, respectively. Microglial activation attenuates after early demyelination. In contrast, astrocyte reactivity persists throughout demyelination and a 6-week recovery period following either acute or chronic demyelination. This astrocyte reaction is characterized by (a early proliferation, (b increased expression of GFAP (glial fibrillary acidic protein, Vim (vimentin, Fn1 (fibronectin and CSPGs (chondroitin sulphate proteoglycans and (c elaboration of a dense network of processes. Glial processes elongated in the axonal plane persist throughout lesion areas during both the robust remyelination that follows acute demyelination and the partial remyelination that follows chronic demyelination. However, prolonged astrocyte reactivity with chronic cuprizone treatment does not progress to barrier formation, i.e. dense compaction of astrocyte processes to wall off the lesion area. Multiple candidate growth factors and inflammatory signals in the lesion environment show strong correlations with GFAP across the acute cuprizone demyelination and recovery time course, yet there is more divergence across the progression of chronic cuprizone demyelination and recovery. However, differential glial scar formation does not appear to be responsible for differential remyelination during recovery in the cuprizone model. The astrocyte phenotype and lesion characteristics in this demyelination model inform studies to identify triggers of non-remyelinating sclerosis in chronic multiple sclerosis

  2. Astrogliosis During Acute and Chronic Cuprizone Demyelination and Implications for Remyelination

    Directory of Open Access Journals (Sweden)

    Norah Hibbits

    2012-10-01

    Full Text Available In multiple sclerosis, microglia/macrophage activation and astrocyte reactivity are important components of the lesion environment that can impact remyelination. The current study characterizes these glial populations relative to expression of candidate regulatory molecules in cuprizone demyelinated corpus callosum. Importantly, periods of recovery after acute or chronic cuprizone demyelination are examined to compare conditions of efficient versus limited remyelination, respectively. Microglial activation attenuates after early demyelination. In contrast, astrocyte reactivity persists throughout demyelination and a 6-week recovery period following either acute or chronic demyelination. This astrocyte reaction is characterized by (a early proliferation, (b increased expression of GFAP (glial fibrillary acidic protein, Vim (vimentin, Fn1 (fibronectin and CSPGs (chondroitin sulphate proteoglycans and (c elaboration of a dense network of processes. Glial processes elongated in the axonal plane persist throughout lesion areas during both the robust remyelination that follows acute demyelination and the partial remyelination that follows chronic demyelination. However, prolonged astrocyte reactivity with chronic cuprizone treatment does not progress to barrier formation, i.e. dense compaction of astrocyte processes to wall off the lesion area. Multiple candidate growth factors and inflammatory signals in the lesion environment show strong correlations with GFAP across the acute cuprizone demyelination and recovery time course, yet there is more divergence across the progression of chronic cuprizone demyelination and recovery. However, differential glial scar formation does not appear to be responsible for differential remyelination during recovery in the cuprizone model. The astrocyte phenotype and lesion characteristics in this demyelination model inform studies to identify triggers of non-remyelinating sclerosis in chronic multiple sclerosis

  3. Newer therapeutic options for chronic inflammatory demyelinating polyradiculoneuropathy.

    Science.gov (United States)

    Kuitwaard, Krista; van Doorn, Pieter A

    2009-05-29

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated disorder with variable symptoms and severity that can be difficult to diagnose. Intravenous immunoglobulin, plasma exchange and corticosteroids have all been proven to be beneficial in randomized controlled trials, although the proof for corticosteroids is less clear. Although these treatments are likely to be similar in efficacy, they differ in terms of their cost, availability and adverse effects. These characteristics should be taken into account when deciding which treatment to offer a patient. If there is no response to the first treatment option, one of the other treatments should be tried. Patients with a pure motor CIDP may deteriorate after corticosteroid treatment. Some patients do not respond or become refractory or intolerant to these conventional treatments. Those who become unresponsive to therapy should be checked again for the appearance of a monoclonal protein or other signs of malignancy. Over the years, small non-randomized studies have reported possible beneficial effects of various immunosuppressive agents. A Cochrane review concluded that currently there is insufficient evidence to decide whether these immunosuppressive drugs are beneficial in CIDP. When giving immunosuppressive drugs, one should be aware that some might even cause demyelinating disease. It is difficult to prove beneficial effects of these newer treatments since they have only been used in small groups of patients, who are refractory to other treatments, and often in combination with other treatments. CIDP patients can deteriorate during or after infections or improve spontaneously, making it more difficult to judge treatment efficacy. Various treatments for CIDP are described such as azathioprine, ciclosporin, cyclophosphamide, interferons, methotrexate, mycophenolate mofetil, rituximab and etanercept. An overview of these newer treatments, their mode of action, adverse effects and

  4. Challenges in the treatment of chronic inflammatory demyelinating polyradiculoneuropathy.

    Science.gov (United States)

    Guimarães-Costa, R; Iancu Ferfoglia, R; Viala, K; Léger, J-M

    2014-10-01

    Chronic idiopathic demyelinating polyradiculoneuropathy (CIDP) is a rare disease, the most frequent one within the spectrum of the so-called "chronic immune-mediated neuropathies". Challenges in the treatment of CIDP firstly concern its diagnosis, which may be difficult, mainly for the atypical forms. Secondly, challenges encompass the choice of the first-line treatment, such as corticosteroids, intravenous immunoglobulins (IVIg), and plasma exchanges (PE) that have been proven as efficacious by several randomized controlled trials (RCT). Recent reports have focused on both different regimens of corticosteroids, and the occurrence of relapses following treatment with either corticosteroids or IVIg. These data may be helpful for the choice of the first-line treatment and may result in changing the guidelines for treatment of CIDP in clinical practice. The third and more difficult challenge is to manage long-term treatment for CIDP, since no immunomodulatory treatment has to date been proven as efficacious in this situation. Lastly, challenges in the treatment concern the choice of the best outcome measure for CIDP in RCT and clinical practice. The aim of this article is to overview the results of the more recently reported published trials for CIDP, and to give some insights for the current and future management of CIDP.

  5. Randomised controlled trial comparing two different intravenous immunoglobulins in chronic inflammatory demyelinating polyradiculoneuropathy

    NARCIS (Netherlands)

    K. Kuitwaard; L.H. van den Berg; M. Vermeulen; E. Brusse; E.A. Cats; A.J. van der Kooi; N.C. Notermans; W.L. van der Pol; I.N. van Schaik; S.I. van Nes; W.C.J. Hop; P.A. van Doorn

    2010-01-01

    Background Different preparations of intravenous immunoglobulin (IVIg) are considered to have comparable clinical efficacy but this has never been formally investigated. Some patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) report that some IVIg brands are more effectiv

  6. Clinical and electrophysiological study of chronic inflammatory demyelinating polyneuropathy

    Institute of Scientific and Technical Information of China (English)

    秦绍森; 玛依努尔; 王湘

    2001-01-01

    Objective To investigate the clinical and electrophysiological features of chronic inflammatory demyelinating polyneuropathy (CIDP) . Methods The clinical symptoms and signs of 11 patients with CIDP were studied, motor conduction velocity( MCV), sensory con-duction velocity (SCV) and Electromyography (EMG) were also respectively carried out on 54 motor nerves, 28 sensory nerves and 21 musclesof these 11 cases. The amplitudes of compound muscle action potential(CAMP) obtained from distal and proximal ends were compared to as-certain the presence of conduction block (CB) by stimulating the segments starting from the distal ends. Results More than 3 nerves werefound involved in 10 out of 11 cases, slow MCV were found in 52%, prolongation of the distal latency in 64%, reduction of the amplitudes ofCAMP in 68%, CB in 26%, slow SCV in 85. 7%. EMG revealed neurogenic damage in 81%. Conclusion CIDP is a peripheral de- myelinating neuropathy involving not only the prox imal and distal segments but also the sensory and motor nerves. If there were no conditionsto perform nerve biopsy, testing of protein in CSF and electrophysiology mightbe of important diagnostic value for CIDP.

  7. Electrophysiological features of POEMS syndrome and chronic inflammatory demyelinating polyneuropathy.

    Science.gov (United States)

    Guo, Xiuming; Qin, Xinyue; Zhang, Yuping; Huang, Cheng; Yu, Gang

    2014-04-01

    Polyneuropathy is often an initial manifestation of polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes (POEMS) syndrome and therefore this disorder is frequently misdiagnosed as chronic inflammatory demyelinating polyneuropathy (CIDP). We reviewed electrophysiological data in 20 patients with POEMS syndrome and 36 matched patients with CIDP to compare the electrophysiological features of POEMS syndrome and CIDP. Compared with CIDP controls, POEMS patients demonstrated (1) less prolonged distal motor latency and less reduced motor nerve and sensory nerve conduction velocities, (2) greater reduction of amplitudes of compound motor action potentials (CMAP) in distal stimulation, and similar reduction of amplitudes of CMAP in proximal stimulation, (3) similar reduction of amplitudes of sensory nerve action potentials (SNAP) in median and ulnar nerves, and a greater reduction of amplitudes of SNAP in tibial and peroneal nerves, (4) less temporal dispersion, (5) less frequent conduction block, (6) more frequent neurogenic injury in the muscles of the upper and lower limbs, and more frequent neurogenic injury in the muscles of the lower than upper limbs, (7) similar F wave and H reflex abnormalities, and (8) less frequent skin sympathetic response abnormalities. We concluded that before development of typical clinical manifestations, POEMS neuropathy can be distinguished from CIDP by neural electrophysiological examination. These electrophysiological features can be used for early diagnosis and initiating correct treatment of POEMS syndrome.

  8. Stance Postural Strategies in Patients with Chronic Inflammatory Demyelinating Polyradiculoneuropathy.

    Directory of Open Access Journals (Sweden)

    Steno Rinalduzzi

    Full Text Available Polyneuropathy leads to postural instability and an increased risk of falling. We investigated how impaired motor impairment and proprioceptive input due to neuropathy influences postural strategies.Platformless bisegmental posturography data were recorded in healthy subjects and patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP. Each subject stood on the floor, wore a head and a hip electromagnetic tracker. Sway amplitude and velocity were recorded and the mean direction difference (MDD in the velocity vector between trackers was calculated as a flexibility index.Head and hip postural sway increased more in patients with CIDP than in healthy controls. MDD values reflecting hip strategies also increased more in patients than in controls. In the eyes closed condition MDD values in healthy subjects decreased but in patients remained unchanged.Sensori-motor impairment changes the balance between postural strategies that patients adopt to maintain upright quiet stance. Motor impairment leads to hip postural strategy overweight (eyes open, and prevents strategy re-balancing when the sensory context predominantly relies on proprioceptive input (eyes closed.

  9. Interferon-gamma in progression to chronic demyelination and neurological deficit following acute EAE

    DEFF Research Database (Denmark)

    Renno, T; Taupin, V; Bourbonnière, L;

    1998-01-01

    The cytokine interferon-gamma (IFNgamma) is implicated in the induction of acute CNS inflammation, but it is less clear what role if any IFNgamma plays in progression to chronic demyelination and neurological deficit. To address this issue, we have expressed IFNgamma in myelinating oligodendrocytes....... In contrast to control mice, which remit from EAE with resolution of glial reactivity and leukocytic infiltration, transgenics showed chronic neurological deficits. While activated microglia/macrophages persisted in demyelinating lesions for over 100 days, CD4(+) T lymphocytes were no longer present in CNS....... IFNgamma therefore may play a role in chronic demyelination and long-term disability following the induction of demyelinating disease. Because IFNgamma may have neural as well as immune-infiltrating origins, these findings generate a new perspective on its role in the CNS....

  10. [Demyelinating polyneuropathies in patients with diabetes mellitus and chronic alcoholic intoxication].

    Science.gov (United States)

    Kovrazhkina, E A

    2012-01-01

    Frequency and nosological attribution of demyelinating polyneuropathies in patients with diabetes mellitus and alcoholism were determined. Eighty-six inpatients with alcoholic (n=46) and diabetic (n=40) polyneuropathy were examined clinically and using electroneuromyography (ENMG). A demyelinating pathogenetic variant was identified by clinical and ENMG data in 27 (31%) patients. Nine patients (33%) had dysimmune polyneuropathies (acute and chronic inflammatory demyelinating polyneuropathy). Polyneuropathies were specified as toxic/metabolic with the prevalence of a demyelinating component within the main disease in 18 (67%) patients. Clinical and ENMG-signs of the demyelinating variant of alcoholic and diabetic neuropathy are presented. The efficacy of the antioxidant berlition was shown for toxic/metabolic polyneuropathies while the addition of immune modulators was needed for treatment of dysimmune polyneuropathy.

  11. Chronic inflammatory demyelinating polyradiculoneuropathy complicating anti TNF α therapy for chronic plaque psoriasis.

    Science.gov (United States)

    Ahmed, Zahra; Powell, Robert; Llewelyn, Gareth; Anstey, Alex

    2011-12-01

    A 53-year-old woman with chronic plaque psoriasis treated with adalimumab (antitumour necrosis factor (anti TNF) α therapy) for 10 months presented with an 8 week history of hyperesthesia in a 'glove and stocking' distribution and clumsiness on walking. Nerve conduction studies confirmed the clinical diagnosis of a chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). She was admitted and treated with intravenous immunoglobulin and oral steroids and made an excellent recovery. To our knowledge, this is the first published report of CIDP associated with anti TNF α therapy given to treat psoriasis.

  12. [Treatment options for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)].

    Science.gov (United States)

    Kuntzer, T

    2006-04-01

    Limits of treatment in chronic inflammatory demyelinating poly(radiculo)neuropathies (CIDP) patients are better known thanks to recent Cochrane reviews. (1) Randomized controlled trials have only focused on short-term effects, but most patients need long-term therapy, (2) There are three proven effective treatments available (prednisone; intravenous immunoglobulin or IVIg and plasma exchange or PE) which are useful in more than 60 p. 100 of patients, (3) New open studies indicated possible efficacy for mycophenolate, rituximab, etanercept, ciclosporine and interferons, and (4) Whether CIDP variants need specific treatment is still unknown. Many CIDP patients need treatment for years. The fear of side effects during long-term steroid treatment, the high costs of IVIg, the necessity for specialized equipment and the invasive nature of PE, are important factors determining the choice for one of these treatments. In most up-to-date treatment options, patients are initially treated with IVIg at a dosage of 2 g/kg administered for 25 days, clinical improvement can be judged within 10 days. The percentage of patients responding seems to be approximately 70 percent, with a very high chance (approximately 85 percent) that repeated administration of IVIg will be necessary, explaining why most neurologists add an immunosuppressive drug at this stage, but there is no consensus concerning the best drug to be used. Combinations of drugs are most likely to be useful in the next future, using IVIg, prednisone, and a immunosuppressor agent, such as mycophenolate, rituximab, etanercept, or ciclosporine. General measures to rehabilitate patients and to manage symptoms like fatigue and other residual findings are important.

  13. Hereditary And Acquired Chronic Demyelination Neuropathies : A Clinical, electrophysiological And Histopathological Study

    Directory of Open Access Journals (Sweden)

    Menon A

    1999-01-01

    Full Text Available Differentiating hereditary motor sensory neuropathy (HMSN from chronic inflammatory demyelinating polyneuropathy (CIDP is often difficult especially when the disease starts at an early age and has protracted course. This study compares the clinical, electro, physiological and histopathological features of hereditary and acquired chronic demyelinating neuropathies. Records of 26 patients of chronic demyelinating neuropathy who underwent sural nerve biopsy were reviewed; HMSN 9, CIDP 13, chronic relapsing demyelinating polyneuropathy (CRDP-4, Salient features of the HMSN group were: Consanguineous parentage-4, onset in first decade-9, skeletal markers-7, absence of positive sensory symptoms- 7 and clinically thickened nerves-6. None of the patients with acquired neuropathy had skeletal markers, 11 had positive sensory symptoms and only 4 had nerve thickening. Electrophysiological evaluation in 22 motor nerves in the HMSN group revealed: inexcitable nerves -13, prolonged distal latency - 6, slow conduction velocity-8 and prolonged f wave latency-3. The 44 motor nerves in patients with acquired neuropathy showed: inexcitable nerves- 7, prolonged distal latency-35, slow conduction velocity-34, f wave prolongation-30 and conduction block 9. Elevated CSF protein was noticed only in acquired group (77%. Pathologically in HMSN the fibre loss was always diffuse and onion bulb formation was frequent while endoneural edema and inflammatory infiltration were absent in this group. Selection of patients with chronic demyelinating neuropathies for therapeutic modulation needs comprehensive clinical and laboratory evaluation.

  14. Contactin 1 IgG4 associates to chronic inflammatory demyelinating polyneuropathy with sensory ataxia.

    Science.gov (United States)

    Miura, Yumako; Devaux, Jérôme J; Fukami, Yuki; Manso, Constance; Belghazi, Maya; Wong, Anna Hiu Yi; Yuki, Nobuhiro

    2015-06-01

    A Spanish group recently reported that four patients with chronic inflammatory demyelinating polyneuropathy carrying IgG4 autoantibodies against contactin 1 showed aggressive symptom onset and poor response to intravenous immunoglobulin. We aimed to describe the clinical and serological features of Japanese chronic inflammatory demyelinating polyneuropathy patients displaying the anti-contactin 1 antibodies. Thirteen of 533 (2.4%) patients with chronic inflammatory demyelinating polyneuropathy had anti-contactin 1 IgG4 whereas neither patients from disease or normal control subjects did (P = 0.02). Three of 13 (23%) patients showed subacute symptom onset, but all of the patients presented with sensory ataxia. Six of 10 (60%) anti-contactin 1 antibody-positive patients had poor response to intravenous immunoglobulin, whereas 8 of 11 (73%) antibody-positive patients had good response to corticosteroids. Anti-contactin 1 IgG4 antibodies are a possible biomarker to guide treatment option.

  15. Cerebellar white matter inflammation and demyelination in chronic relapsing experimental allergic encephalomyelitis

    DEFF Research Database (Denmark)

    Wanscher, B.; Sørensen, P. S.; Juhler, M.;

    1993-01-01

    Experimental allergic encephalomyelitis, demyelination, inflammation, immunology, neuropathology......Experimental allergic encephalomyelitis, demyelination, inflammation, immunology, neuropathology...

  16. Supramaximal Stimulus Intensity as a Diagnostic Tool in Chronic Demyelinating Neuropathy

    Science.gov (United States)

    Parker, Vivien; Warman Chardon, Jodi; Mills, Julie; Goldsmith, Claire; Bourque, Pierre R.

    2016-01-01

    Objective. The ability to correctly identify chronic demyelinating neuropathy can have important therapeutic and prognostic significance. The stimulus intensity value required to obtain a supramaximal compound muscle action potential amplitude is a commonly acquired data point that has not been formally assessed as a diagnostic tool in routine nerve conduction studies to identify chronic neuropathies. We postulated that this value was significantly elevated in chronic demyelinating neuropathy. Methods. We retrospectively reviewed electrophysiology laboratory records to compare the stimulus intensity values recorded during median and ulnar motor nerve conduction studies. The groups studied included normal controls (n = 42) and the following diagnostic categories: chronic inflammatory demyelinating neuropathy (CIDP) (n = 20), acquired inflammatory demyelinating neuropathy (AIDP) (n = 13), Charcot Marie Tooth (CMT) type 1 or 4C (n = 15), carpal tunnel syndrome (CTS) (n = 11), and amyotrophic lateral sclerosis (ALS) (n = 18). Results. Supramaximal intensities were significantly higher in patients with CMT (median nerve: 43.4 mA) and CIDP (median nerve: 38.9 mA), whereas values similar to normal controls (median nerve: 25.3 mA) were obtained in ALS, CTS, and AIDP. Conclusions. Supramaximal stimulus intensity may be used as an additional criterion to identify the pathophysiology of neuropathy. We postulate that endoneurial hypertrophic changes may increase electrical impedance and thus the threshold of excitation at nodes of Ranvier. PMID:27413732

  17. Supramaximal Stimulus Intensity as a Diagnostic Tool in Chronic Demyelinating Neuropathy

    Directory of Open Access Journals (Sweden)

    Vivien Parker

    2016-01-01

    Full Text Available Objective. The ability to correctly identify chronic demyelinating neuropathy can have important therapeutic and prognostic significance. The stimulus intensity value required to obtain a supramaximal compound muscle action potential amplitude is a commonly acquired data point that has not been formally assessed as a diagnostic tool in routine nerve conduction studies to identify chronic neuropathies. We postulated that this value was significantly elevated in chronic demyelinating neuropathy. Methods. We retrospectively reviewed electrophysiology laboratory records to compare the stimulus intensity values recorded during median and ulnar motor nerve conduction studies. The groups studied included normal controls (n=42 and the following diagnostic categories: chronic inflammatory demyelinating neuropathy (CIDP (n=20, acquired inflammatory demyelinating neuropathy (AIDP (n=13, Charcot Marie Tooth (CMT type 1 or 4C (n=15, carpal tunnel syndrome (CTS (n=11, and amyotrophic lateral sclerosis (ALS (n=18. Results. Supramaximal intensities were significantly higher in patients with CMT (median nerve: 43.4 mA and CIDP (median nerve: 38.9 mA, whereas values similar to normal controls (median nerve: 25.3 mA were obtained in ALS, CTS, and AIDP. Conclusions. Supramaximal stimulus intensity may be used as an additional criterion to identify the pathophysiology of neuropathy. We postulate that endoneurial hypertrophic changes may increase electrical impedance and thus the threshold of excitation at nodes of Ranvier.

  18. Anaesthetic management and implications of a case of chronic inflammatory demyelinating polyneuropathy

    Directory of Open Access Journals (Sweden)

    Babita Gupta

    2011-01-01

    Full Text Available A 60-year-old man with chronic inflammatory demyelinating polyneuropathy (CIDP was posted for surgery of the neck femur fracture and was successfully managed. We discuss the anaesthetic considerations during regional and general anaesthesia of this patient with CIDP. A brief review of the available literature reveals no consensus on the choice of anaesthetic management.

  19. Chronic Inflammatory Demyelinating Polyneuropathy Following Anti-TNF-α Therapy With Infliximab for Crohn's Disease

    Science.gov (United States)

    Concepcion, Orestes; Schlachterman, Alexander; Glover, Sarah; Forsmark, Christopher Y.

    2016-01-01

    We present a 29-year-old male with Crohn's disease who developed chronic inflammatory demyelinating polyneuropathy (CIDP) related to infliximab therapy. He developed lower extremity weakness and dysesthesia 3 weeks after a fourth infliximab dose. Laboratory examination revealed an elevated cerebrospinal fluid protein without pleocytosis. The patient initially responded to plasmapheresis therapy with marked symptomatic improvement, but relapsed and was refractory to subsequent treatments with plasmaphereisis, intravenous immunoglobulin, and glucocorticoids. While a causal relationship between infliximab and CIDP cannot be proven, clinicians should monitor Crohn's disease patients who are receiving TNF-α antagonists for neurologic symptoms suggestive of demyelinating disease. PMID:27144200

  20. Diffuse spinal and intercostal nerve involvement in chronic inflammatory demyelinating polyradiculoneuropathy: MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Oguz, B.; Oguz, K.K.; Cila, A. [Dept. of Radiology, Hacettepe Univ. Faculty of Medicine, Ankara (Turkey); Tan, E. [Dept. of Neurology, Hacettepe Univ. Faculty of Medicine, Ankara (Turkey)

    2003-12-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an uncommon demyelinating disorder with a relapsing and remitting or continuously progressive course. Hypertrophic nerve roots, sometimes associated with gadolinium enhancement, has been reported more commonly in lumbar spine and less commonly in the brachial plexus and cervical roots; however, diffuse involvement of intercostal nerves bilaterally has never been reported previously. We present MRI findings which include diffuse enlargement and mild enhancement of roots and extraforaminal segments of nerves in all segments except a short segment between T12-L2 as well as all the intercostal nerves in a case of CIPD with a 10-year history. (orig.)

  1. Serum cytokine and chemokine profiles in patients with chronic inflammatory demyelinating polyneuropathy.

    Science.gov (United States)

    Beppu, Minako; Sawai, Setsu; Misawa, Sonoko; Sogawa, Kazuyuki; Mori, Masahiro; Ishige, Takayuki; Satoh, Mamoru; Nomura, Fumio; Kuwabara, Satoshi

    2015-02-15

    To identify serum cytokine networks specific to chronic inflammatory demyelinating polyneuropathy (CIDP), serum samples of two subgroups (18 patients with typical CIDP and 12 patients with multifocal acquired demyelinating sensory and motor neuropathy [MADSAM]) were analyzed with multiplex magnetic bead-based cytokine assay. TNF-α, HGF, MIP-1β and IL-1β levels were significantly higher in total CIDP patients than in normal controls. Of these, HGF levels were elevated in typical CIDP patients, but not in MADSAM patients. Patients with high HGF levels showed good responses to steroid treatment. Different cytokine profiles among the CIDP subtypes presumably reflect differences in pathophysiology.

  2. Chronic inflammatory demyelinating polyneuropathy in adults: diagnostic approaches and first line therapy

    Directory of Open Access Journals (Sweden)

    N. А. Suponevа

    2016-01-01

    Full Text Available Chronic inflammatory demyelinating polyneuropathy (CIDP is among the key reasons of chronic polyneuropathies in adults. Diagnostic algorithm of CIDP in adults is presented. Diagnosis of CIDP is based on clinical and electrodiagnostic criteria of European Federation of Neurological Societies/Peripheral Nervous System in 2010. Principles of CIDP treatment are discussed, including modern trends of standard and 10 % IVIG solutions. 

  3. Treatment of chronic immune-mediated neuropathies: chronic inflammatory demyelinating polyradiculoneuropathy, multifocal motor neuropathy, and the Lewis-Sumner syndrome.

    Science.gov (United States)

    Sederholm, Benson H

    2010-09-01

    Current treatment approaches for the management of chronic immune-mediated peripheral neuropathies are reviewed, including chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN), and the Lewis-Sumner syndrome (LSS). A summary of existing evidence for commonly used treatment modalities, such as corticosteroids, intravenous immune globulin (IVIG), and plasma exchange is provided. Evidence for the use of additional immunosuppressant and immunomodulatory agents is also reviewed.

  4. Characterization of a new rat model for chronic inflammatory demyelinating polyneuropathies.

    Science.gov (United States)

    Brun, Susana; Beaino, Wissam; Kremer, Laurent; Taleb, Omar; Mensah-Nyagan, Ayikoe Guy; Lam, Chanh D; Greer, Judith M; de Seze, Jérôme; Trifilieff, Elisabeth

    2015-01-15

    Our objective was to develop a chronic model of EAN which could be used as a tool to test treatment strategies for CIDP. Lewis rats injected with S-palmitoylated P0(180-199) peptide developed a chronic, sometimes relapsing-remitting type of disease. Our model fulfills electrophysiological criteria of demyelination with axonal degeneration, confirmed by immunohistopathology. The late phase of the chronic disease was characterized by accumulation of IL-17(+) cells and macrophages in sciatic nerves and by high serum IL-17 levels. In conclusion, we have developed a reliable and reproducible animal model resembling CIDP that can now be used for translational drug studies.

  5. Overview of the pathogenesis and treatment of chronic inflammatory demyelinating polyneuropathy with intravenous immunoglobulins

    Directory of Open Access Journals (Sweden)

    Mohamed Mahdi-Rogers

    2010-03-01

    Full Text Available Mohamed Mahdi-Rogers, Yusuf A RajaballyNeuromuscular Clinic, Department of Neurology, University Hospitals of Leicester, Leicester, UKAbstract: Chronic inflammatory demyelinating polyneuropathy (CIDP is an acquired heterogeneous disorder of immune origin affecting the peripheral nerves, causing motor weakness and sensory symptoms and signs. The precise pathophysiology of CIDP remains uncertain although B and T cell mechanisms are believed to be implicated. Intravenous immunoglobulins (IVIg have been shown in a number of trials to be an effective treatment for CIDP. IVIg is thought to exert its immunomodulatory effects by affecting several components of the immune system including B-cells, T-cells, macrophages and complement. This article provides an overview of the pathogenesis of CIDP and of its treatment with IVIg.Keywords: chronic inflammatory demyelinating polyneuropathy, intravenous immunoglobulin, pathogenesis, treatment

  6. Functional Roles of Syk in Macrophage-Mediated Inflammatory Responses

    Directory of Open Access Journals (Sweden)

    Young-Su Yi

    2014-01-01

    Full Text Available Inflammation is a series of complex biological responses to protect the host from pathogen invasion. Chronic inflammation is considered a major cause of diseases, such as various types of inflammatory/autoimmune diseases and cancers. Spleen tyrosine kinase (Syk was initially found to be highly expressed in hematopoietic cells and has been known to play crucial roles in adaptive immune responses. However, recent studies have reported that Syk is also involved in other biological functions, especially in innate immune responses. Although Syk has been extensively studied in adaptive immune responses, numerous studies have recently presented evidence that Syk has critical functions in macrophage-mediated inflammatory responses and is closely related to innate immune response. This review describes the characteristics of Syk-mediated signaling pathways, summarizes the recent findings supporting the crucial roles of Syk in macrophage-mediated inflammatory responses and diseases, and discusses Syk-targeted drug development for the therapy of inflammatory diseases.

  7. Chronic inflammatory demyelinating polyradiculoneuropathy and variants: where we are and where we should go.

    Science.gov (United States)

    Nobile-Orazio, Eduardo

    2014-03-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic and often disabling sensory motor neuropathy postulated as caused by an immune attack against peripheral nerve myelin. In addition to a classic sensory–motor polyneuropathy, other phenotypes of CIDP have been described including the Lewis- Sumner syndrome, distal acquired demyelinating symmetric (DADS) neuropathy, pure motor CIDP, pure sensory CIDP including chronic immune sensory polyradiculopathy (CISP), and focal CIDP. These phenotypes are currently considered to be variants of CIDP, even if the possibility that they represent different demyelinating neuropathies cannot be fully excluded considering differences in their response to therapy. Several data support the role of the immune system in the pathogenesis of CIDP even if the precise targets and actors (antibodies and lymphocytes) of this immune response remain uncertain. Recent studies have shown that the therapeutic response may differ in patients with peculiar clinical presentations supporting the hypothesis that different pathogenetic mechanisms may underlie the heterogeneity of CIDP. The majority of patients with CIDP show improvement after immune therapies including corticosteroids, plasma exchange, and high-dose intravenous immunoglobulin (IVIg). It remains unclear why none of the other immune therapies that were reported to be variably effective in other immune disorders proved to be effective also in CIDP.

  8. Sural nerve biopsy in chronic inflammatory demyelinating polyneuropathy: Are supportive pathologic criteria useful in diagnosis?

    Directory of Open Access Journals (Sweden)

    Kulkarni Girish

    2010-01-01

    Full Text Available Background : According to American Academy of Neurology (AAN criteria, demonstration of demyelination in the sural nerve by teased fiber or ultrastructure is considered mandatory for diagnosis of chronic inflammatory demyelinating polyneuropathies (CIDP. In resource-restricted settings where these techniques are not freely available, it is useful to determine the utility of ′supportive′ pathologic criteria (subperineurial edema, inflammation, onion bulb formation, and demyelination proposed by AAN for diagnosis of CIDP. Settings and Design : Tertiary care hospital, retrospective study. Patients and Methods : Forty-six patients with idiopathic CIDP (32 with progressive course and 14 with relapsing-remitting course satisfying AAN clinical and electrophysiologic criteria evaluated between January 1991 and August 2004 were reviewed. Frequency of specific pathological alterations such as demyelination, inflammation, onion bulb formation, and axonal changes in sural nerve biopsies was evaluated. Statistical Analysis : SPSS statistical package was used to calculate mean, range, and standard deviation. Student′s t test, chi-square test, and ANOVA were used for determining statistical significance. Results and Conclusion : Reduction in myelinated fiber density was most frequent (93.5%, followed by demyelination (82.8%, inflammation (58.7%, and onion bulb formation (28.3%. Endoneurial inflammation was frequent in the relapsing-remitting form and epineurial inflammation and axonal changes in those with progressive course. Greater disability at presentation, poor response to immunomodulation, and lower CSF protein levels was seen in those with axonal pathology. Pathological abnormalities were demonstrable in all (100%, whereas electrophysiological abnormalities were detected in 90.8%, suggesting that supportive histologic AAN criteria are helpful in diagnosis of CIDP.

  9. Unmyelinated nerve fiber degeneration in chronic inflammatory demyelinating polyneuropathy

    NARCIS (Netherlands)

    Bosboom, WMJ; Van den Berg, LH; Dieks, HJG; Plante, E; Veldman, H; Franssen, H; Wokke, JHJ

    2000-01-01

    To determine whether unmyelinated nerve fibers escape degeneration as one might expect in an immune response exclusively directed at myelin, we performed a morphometric examination of unmyelinated axons and myelinated nerve fibers in sural nerve biopsy specimens of 14 patients with a chronic inflamm

  10. Dysautonomic polyneuropathy as a variant of chronic inflammatory "demyelinating" polyneuropathy?

    Science.gov (United States)

    Wolf, Hans-Heinrich; Kornhuber, Malte Erich; Weis, Joachim; Posa, Andreas

    2016-08-01

    This report describes the clinical course over almost one decade of a male patient presenting with immune-mediated pure autonomic neuropathy resembling a distinct variant of chronic dysimmune polyneuropathies. We suppose autoantibodies directed against epitopes on autonomic axons or neurons causative for the symptoms.

  11. Progesterone and nestorone promote myelin regeneration in chronic demyelinating lesions of corpus callosum and cerebral cortex.

    Science.gov (United States)

    El-Etr, Martine; Rame, Marion; Boucher, Celine; Ghoumari, Abdel M; Kumar, Narender; Liere, Philippe; Pianos, Antoine; Schumacher, Michael; Sitruk-Ware, Regine

    2015-01-01

    Multiple Sclerosis affects mainly women and consists in intermittent or chronic damages to the myelin sheaths, focal inflammation, and axonal degeneration. Current therapies are limited to immunomodulators and antiinflammatory drugs, but there is no efficient treatment for stimulating the endogenous capacity of myelin repair. Progesterone and synthetic progestins have been shown in animal models of demyelination to attenuate myelin loss, reduce clinical symptoms severity, modulate inflammatory responses and partially reverse the age-dependent decline in remyelination. Moreover, progesterone has been demonstrated to promote myelin formation in organotypic cultures of cerebellar slices. In the present study, we show that progesterone and the synthetic 19-nor-progesterone derivative Nestorone® promote the repair of severe chronic demyelinating lesions induced by feeding cuprizone to female mice for up to 12 weeks. Progesterone and Nestorone increase the density of NG2(+) oligodendrocyte progenitor cells and CA II(+) mature oligodendrocytes and enhance the formation of myelin basic protein (MBP)- and proteolipid protein (PLP)-immunoreactive myelin. However, while demyelination in response to cuprizone was less marked in corpus callosum than in cerebral cortex, remyelination appeared earlier in the former. The remyelinating effect of progesterone was progesterone receptor (PR)-dependent, as it was absent in PR-knockout mice. Progesterone and Nestorone also decreased (but did not suppress) neuroinflammatory responses, specifically astrocyte and microglial cell activation. Therefore, some progestogens are promising therapeutic candidates for promoting the regeneration of myelin.

  12. [A case of asymmetric demyelinating neuropathy in a patient with chronic graft-versus-host disease].

    Science.gov (United States)

    Matsumoto, Hideyuki; Seki, Naoko; Yamamoto, Tomotaka; Oshima, Kumi; Asai, Takashi; Motokura, Toru; Ugawa, Yoshikazu; Goto, Jun; Tsuji, Shoji

    2005-10-01

    A 47-year-old man, who suffered from acute lymphocytic leukemia at 45 years old and was treated with hematopoietic stem cell transplantation at 46 years old after the induction of complete remission by the standard chemotherapy, developed the symptoms of chronic graft-versus-host disease (cGVHD) such as dry eyes, dry mouth, skin thickening, skin scaling, skin pigmentation and impaired liver function. He was admitted to our hospital because of the acute development of diplopia and weakness of his left upper extremity accompanying with the exacerbation of other symptoms of cGVHD. Neurological examinations revealed the right abducens nerve palsy and asymmetric muscular weakness of the extremities; the proximal part of the left upper extremity and the distal part of the right upper extremity were markedly involved. Neurophysiological studies including magnetic motor root stimulation revealed demyelinating neuropathy specifically involving the motor nerves. On the basis of these findings, a diagnosis of peripheral neuropathy associated with cGVHD was made. Nighteen reports are available on peripheral neuropathy in cGVHD patients, but to date little is known about the pathophysiology of this condition. Most of those patients have been diagnosed as having symmetric demyelinating polyneuropathy, such as Guillain-Barré syndrome or chronic inflammatory demyelinating polyneuropathy. In this study, contrary to previous reports, the asymmetric involvement of motor nerves is noteworthy. Accumulation and further analyses of the cases like the present case are necessary to elucidate the pathogenesis of peripheral neuropathy in cGVHD.

  13. A review of the use of biological agents for chronic inflammatory demyelinating polyradiculoneuropathy.

    Science.gov (United States)

    Stübgen, Joerg-Patrick

    2013-03-15

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is a group of idiopathic, acquired, immune-mediated inflammatory demyelinating diseases of the peripheral nervous system. A majority of patients with CIDP respond to "first-line" treatment with IVIG, plasmapheresis and/or corticosteroids. There exists insufficient evidence to ascertain the benefit of treatment with "conventional" immunosuppressive drugs. The inconsistent efficacy, long-term financial burden and health risks of non-specific immune altering therapy have drawn recurrent attention to the possible usefulness of a variety of biological agents that target key aspects in the CIDP immunopathogenic pathways. This review aims to give an updated account of the scientific rationale and potential use of biological therapeutics in patients with CIDP. No specific treatment recommendations are given. The discovery, development and application of biological markers by modern molecular diagnostic techniques may help identify drug-naïve or treatment-resistant CIDP patients most likely to respond to targeted immunotherapy.

  14. Erythromelalgia-like presentation of chronic acquired demyelinating polyneuropathy in a setting of past alcohol abuse.

    Science.gov (United States)

    Chuquilin, Miguel; Dhand, Upinder K

    2016-02-01

    Erythromelalgia may be primary or secondary to an underlying medical condition. Association with small fiber neuropathy and axonal large fiber peripheral neuropathy has been described. Erythromelalgia in the setting of acquired demyelinating neuropathy has not been reported. We report a 52-year-old woman with severe erythromelalgia, pain and burning, progressive weakness, hyporeflexia and distal pan-sensory deficits. Cerebrospinal fluid protein was 219 mg/dL. Nerve conduction study revealed extreme (ten-fold) prolongation of distal motor latencies, markedly slow motor nerve conduction, reduced terminal latency index, reduced distal compound muscle action potential (CMAP) amplitude, possible conduction blocks, and distal denervation. Treatment with intravenous immunoglobulin, prednisone and azathioprine resulted in marked clinical and electrophysiological improvement. Our patient fulfills the diagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP); however, the unique electrodiagnostic features and presentation with erythromelalgia may represent a CIDP variant or a novel dysimmune neuropathy, or may partly be related to neurotoxic effects of prior alcohol abuse.

  15. Acquired inflammatory demyelinating neuropathies.

    Science.gov (United States)

    Ensrud, E R; Krivickas, L S

    2001-05-01

    The acquired demyelinating neuropathies can be divided into those with an acute onset and course and those with a more chronic course. The acute neuropathies present as Guillain-Barré syndrome and include acute inflammatory demyelinating polyradiculoneuropathy (AIDP), Miller Fisher syndrome, acute motor axonal neuropathy (AMAN), acute motor and sensory axonal neuropathy (AMSAN), and acute pandysautonomia. The chronic neuropathies are collectively known as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and include MADSAM (multifocal acquired demyelinating sensory and motor neuropathy, also know as Lewis-Sumner syndrome) and DADS (distal acquired demyelinating symmetric neuropathy) as variants. The clinical features, pathology, pathogenesis, diagnosis, treatment, rehabilitation, and prognosis of these neuropathies are discussed.

  16. Involvement of the central nervous system in chronic inflammatory demyelinating polyneuropathy: a clinical, electrophysiological and magnetic resonance imaging study.

    OpenAIRE

    Ormerod, I E; Waddy, H M; Kermode, A G; Murray, N M; Thomas, P. K.

    1990-01-01

    In a consecutive series of 30 patients with chronic inflammatory demyelinating polyneuropathy (CIDP) minor clinical evidence of CNS involvement was found in five. Cranial magnetic resonance imaging (MRI) was performed in 28 and revealed abnormalities consistent with demyelination in nine patients aged less than 50 years and abnormalities in five aged 50 years or over. Measurements of central motor conduction time (CMCT) were obtained in 18 and showed unilateral or bilateral abnormalities in s...

  17. Dispersion of compound muscle action potential in hereditary neuropathies and chronic inflammatory demyelinating polyneuropathy.

    Science.gov (United States)

    Stanton, Michael; Pannoni, Valerie; Lewis, Richard A; Logigian, Eric L; Naguib, Demian; Shy, Michael E; Cleland, James; Herrmann, David N

    2006-10-01

    Distal compound muscle action potential (DCMAP) dispersion, defined as a DCMAP duration > or = 9 ms, and proximal-distal (P-D) CMAP dispersion are considered useful in the electrodiagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP). Distal and P-D CMAP dispersion have not been fully studied in hereditary neuropathies, and it is not known whether these measures distinguish hereditary from acquired demyelination. We compared DCMAP duration and P-D CMAP dispersion in 91 genetically characterized hereditary neuropathies and 33 subjects with CIDP. DCMAP dispersion was more frequent in nerves affected by CIDP (41.5%) than in Charcot-Marie-Tooth disease (CMT)1A (24.4%), CMT1B (7.4%), hereditary neuropathy with liability to pressure palsies (HNPP) (10.5%), or CMTX (9.8%). P-D CMAP dispersion was more frequent in CIDP (27.7% of nerves) than in hereditary neuropathies (16.3%) when applying American Academy of Neurology (AAN) criteria; however, its frequency was similar in CIDP and the hereditary neuropathies using the more restrictive criteria of the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM). Although dispersion is more common in CIDP than in the hereditary neuropathies, DCMAP and P-D dispersion occur in at least one motor nerve in a significant proportion of hereditary neuropathies, and cannot be used in isolation to distinguish acquired from hereditary demyelination.

  18. Relapse with Dysphagia in a Case of Chronic Inflammatory Demyelinating Polyradiculoneuropathy.

    Science.gov (United States)

    Teramoto, Hiroko; Morita, Akihiko; Hara, Makoto; Ninomiya, Satoko; Shigihara, Shuntaro; Kusunoki, Susumu; Kamei, Satoshi

    2015-01-01

    Glossopharyngeal and/or vagus nerve involvement is infrequent in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We herein report the case of a 69-year-old Japanese woman who presented with muscle weakness and numbness of the extremities with dysphagia. The serum anti-ganglioside GM1 immunoglobulin IgM antibody levels were elevated, and treatment with intravenous immunoglobulin (IVIg) resulted in a dramatic improvement; the weakness, numbness and dysphagia all resolved. However, relapse comprising dysphagia alone occurred on hospital day 26, and treatment with IVIg again proved extremely effective. IVIg therapy can be effective against cranial nerve involvement in cases of CIDP.

  19. Subcutaneous immunoglobulin in responders to intravenous therapy with chronic inflammatory demyelinating polyradiculoneuropathy

    DEFF Research Database (Denmark)

    Markvardsen, Lars Høj; Debost, J-C; Harbo, Thomas;

    2013-01-01

    BACKGROUND AND PURPOSE: We hypothesized that subcutaneous administration of immunoglobulins (SCIG) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is feasible, safe and superior to treatment with saline for the performance of muscle strength. METHODS: Thirty patients with motor...... involvement in maintenance therapy with intravenous immunoglobulin (IVIG) fulfilling the EFNS/PNS criteria for CIDP, aged 18-80 years, were randomized either to SCIG at a dose corresponding to their pre-study IVIG dose or to subcutaneous saline given twice or thrice weekly for 12 weeks at home. At the start...

  20. [Diagnostic strategy for chronic inflammatory demyelinating polyradiculoneuropathy. Recommendations of the French working group].

    Science.gov (United States)

    Magy, L

    2008-12-01

    The diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) requires a careful clinical and neurophysiological evaluation, often completed by CSF analysis. In numerous cases, this diagnosis is straightforward and leads to rapid initiation of an immunomodulatory treatment. However, some patients are not diagnosed because of atypical clinical and/or neurophysiological features, and do not benefit from a potentially effective treatment. In this context, a working group was composed with the task of establishing recommendations on diagnostic strategies for CIDP in the main clinical situations where this diagnosis may be suspected. We have summarized these recommendations and tried to present them in the form of a decision-making algorithm.

  1. Acute-onset chronic inflammatory demyelinating polyneuropathy with focal segmental glomerulosclerosis.

    Science.gov (United States)

    Quek, Amy May Lin; Soon, Derek; Chan, Yee Cheun; Thamboo, Thomas Paulraj; Yuki, Nobuhiro

    2014-06-15

    Inflammatory neuropathies have been reported to occur in association with nephrotic syndrome. Their underlying immuno-pathogenic mechanisms remain unknown. A 50-year-old woman concurrently presented with acute-onset chronic inflammatory demyelinating polyneuropathy and nephrotic syndrome secondary to focal segmental glomerulosclerosis. Both neuropathy and proteinuria improved after plasma exchange and steroids. Literature review of cases of concurrent inflammatory neuropathies and nephrotic syndrome revealed similar neuro-renal presentations. This neuro-renal condition may be mediated by autoantibodies targeting myelin and podocytes.

  2. Unusual features in chronic inflammatory demyelinating polyneuropathy: Good outcome after prolonged ventilatory support

    Directory of Open Access Journals (Sweden)

    Sanjeev Jha

    2011-01-01

    Full Text Available Severe respiratory muscle paralysis and ventilatory failure is rare in chronic inflammatory demyelinating polyneuropathy (CIDP. We report a 14 year child who presented with respiratory failure, bulbar and multiple cranial nerves involvement along with bilateral phrenic nerve paralysis. He was diagnosed with CIDP after electrophysiological evaluation. He required AMBU ventilation for about 4 months (including domiciliary use, after which he recovered significantly. Along with several unusual features of CIDP, this report highlights good example of steady basic intensive care to save lives and rewarding outcome of prolonged respiratory support, provided by AMBU ventilation which is a rather primitive, but inexpensive device.

  3. Successful treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) in systemic lupus erythematosus (SLE) with oral cyclophosphamide.

    Science.gov (United States)

    Jasmin, R; Sockalingam, S; Shahrizaila, N; Cheah, T-E; Zain, A A; Goh, K-J

    2012-09-01

    Peripheral neuropathy is a known manifestation of systemic lupus erythematosus. However, the association of primary autoimmune inflammatory neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP) with SLE is uncommon. We report a 26-year-old man who simultaneously presented with severe CIDP and photosensitive rash, but was unresponsive to intravenous immunoglobulin infusion and continued to progress. He was found to have underlying SLE and improved with combined corticosteroid and immunosuppressive therapy with oral cyclophosphamide. CIDP with underlying SLE may be more resistant to conventional therapy with IVIG, requiring the addition of other immunosuppressive agents.

  4. A recurrence of Guillain-Barr and eacute; syndrome or a case of acute-onset chronic inflammatory demyelinating polyneuropathy in the course of chronic hepatitis B?

    Directory of Open Access Journals (Sweden)

    Guner Celik Koyuncu

    2016-12-01

    Full Text Available Chronic inflammatory demyelinating polyneuropathy is a demyelinating polyneuropathy characterized by distal/proximal weakness, which shows gradual progression over a period of 8 weeks or longer. Guillan-Barre Syndrome is a condition characterized by acute monophasic paralysis typically following an infectious assault, and it usually peaks in severity over 3-4 weeks at most. Although rare, there are acute-onset chronic inflammatory demyelinating polyneuropathy cases that show progression over a period shorter than 4 weeks, as is the case in Guillan-Barre Syndrome .This report discusses a case of chronic inflammatory demyelinating polyneuropathy in a HBsAg-positive patient, which started as Guillan-Barre Syndrome but showed 3 recurrences within 6 months, each with rapidly progressing quadriplegia, respiratory arrest, and elevated liver enzymes and HBV DNA. [Cukurova Med J 2016; 41(4.000: 782-786

  5. Chronic inflammatory demyelinating polyradiculoneuropathy: diagnostic and therapeutic challenges for a treatable condition.

    Science.gov (United States)

    Vallat, Jean-Michel; Sommer, Claudia; Magy, Laurent

    2010-04-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic neuropathy of supposed immune origin. Understanding of its pathophysiology has recently improved, although its causes remain unclear. The classic presentation of CIDP includes sensory and motor symptoms in the distal and proximal segments of the four limbs with areflexia, evolving over more than 8 weeks. Raised protein concentrations in CSF and heterogeneous slowing of nerve conduction are typical of the condition. In addition to this usual phenotype, distribution of symptoms, disease course, and disability can be heterogeneous, leading to underdiagnosis of the disorder. Diagnosis is sometimes challenging and can require use of imaging and nerve biopsy. Steroids and intravenous immunoglobulin are effective, and plasma exchange can be helpful as rescue therapy. The usefulness of immunosuppressants needs to be established. The identification of specific diagnostic markers and new therapeutic strategies with conventional or targeted immunotherapy are needed to improve the outlook for patients with CIDP.

  6. Chronic Inflammatory Demyelinating Polyneuropathy in Children: A Review of Clinical Characteristics and Recommendations for Treatment

    Directory of Open Access Journals (Sweden)

    Narges Karimi

    2015-07-01

    Full Text Available Context: Chronic inflammatory demyelinating polyradiculopathy (CIDP is an acquired and autoimmune neuropathy, characterized by a chronic, rapidly progressive, symmetric weakness. In children, abnormal gait is as a first symptom of muscle weakness. Evidence Acquisition: The diagnosis of CIDP is on the basis of clinical characteristics, electrodiagnostic that shows the severity of the disease, lumbar puncture and spine magnetic resonance imaging (MRI. Results: The first-line treatments in childhood CIDP are intravenous immunoglobulin (IVIG, corticosteroids, and plasmapheresis. Response to first-line therapies is usually satisfactory; nevertheless, recommendations regarding the choice of second-line therapy can only be prepared on the basis of the existing practice described in some of the case reports. Conclusions: This review demonstrated the clinical presentation, diagnosis, and treatment of childhood CIDP.

  7. Does the chronic inflammatory demyelinating polyradiculoneuropathy due to secondary cause differ from primary?

    Directory of Open Access Journals (Sweden)

    Vaibhav Wadwekar

    2011-01-01

    Full Text Available Background: The clinical presentation, neurophysiological findings, and outcome may vary between primary and secondary chronic inflammatory demyelinating polyradiculopathy (CIDP. Objective: To compare clinical and electrodiagnostic features of primary and secondary CIDP. Setting: Tertiary care teaching referral hospital. Materials and Methods: The CIDP patients who were diagnosed as per European Federation of Neurological Societies/Peripheral Nerve Society criteria were included and subjected to detailed history and examinations. The clinical disability was graded on a 0-10 scale. Neurophysiology included motor and sensory nerve conductions and F wave studies of all four limbs. Based on investigations for underlying diseases, the patients were categorized into primary or secondary CIDP. Prednisolone was prescribed in all and azathioprine added in resistant cases. The secondary CIDP group received specific treatment in addition. The outcome was assessed at 3 months, 6 months, and last follow-up. Results: A total of 65 patients aged 17 to 72 years were included and 20 were females. Twenty-five patients had secondary CIDP and include diabetes mellitus (16, POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (4, monoclonal gammopathy of undetermined significance (2, myeloma (1, lymphoma (1, and malignancy (1. The secondary CIDP patients were older (48.35 vs 41.0 years, had less relapsing remitting (0 vs 6 and more frequent dysautonomia (7 vs 1. The demyelinating features were more marked in primary CIDP group and had better outcome compared with secondary CIDP. Conclusions: Of the total patients with CIDP, 38.5% of patients had secondary CIDP which was associated with progressive course, less demyelinating features, and worse prognosis.

  8. Ultrasonographic nerve enlargement of the median and ulnar nerves and the cervical nerve roots in patients with demyelinating Charcot-Marie-Tooth disease: distinction from patients with chronic inflammatory demyelinating polyneuropathy.

    Science.gov (United States)

    Sugimoto, Takamichi; Ochi, Kazuhide; Hosomi, Naohisa; Takahashi, Tetsuya; Ueno, Hiroki; Nakamura, Takeshi; Nagano, Yoshito; Maruyama, Hirofumi; Kohriyama, Tatsuo; Matsumoto, Masayasu

    2013-10-01

    Demyelinating Charcot-Marie-Tooth disease (CMT) and chronic inflammatory demyelinating polyneuropathy (CIDP) are both demyelinating polyneuropathies. The differences in nerve enlargement degree and pattern at multiple evaluation sites/levels are not well known. We investigated the differences in nerve enlargement degree and the distribution pattern of nerve enlargement in patients with demyelinating CMT and CIDP, and verified the appropriate combination of sites/levels to differentiate between these diseases. Ten patients (aged 23-84 years, three females) with demyelinating CMT and 16 patients (aged 30-85 years, five females) with CIDP were evaluated in this study. The nerve sizes were measured at 24 predetermined sites/levels from the median and ulnar nerves and the cervical nerve roots (CNR) using ultrasonography. The evaluation sites/levels were classified into three regions: distal, intermediate and cervical. The number of sites/levels that exhibited nerve enlargement (enlargement site number, ESN) in each region was determined from the 24 sites/levels and from the selected eight screening sites/levels, respectively. The cross-sectional areas of the peripheral nerves were markedly larger at all evaluation sites in patients with demyelinating CMT than in patients with CIDP (p demyelinating CMT and CIDP were 0.90 and 0.94, respectively, with the cut-off value set at four. Nerve ultrasonography is useful to detect nerve enlargement and can clarify morphological differences in nerves between patients with demyelinating CMT and CIDP.

  9. Chronic inflammatory demyelinating polyneuropathy disease activity status: recommendations for clinical research standards and use in clinical practice

    NARCIS (Netherlands)

    K.C. Gorson; I.N. van Schaik; I.S.J. Merkies; R.A. Lewis; R.J. Barohn; C.L. Koski; D.R. Cornblath; R.A.C. Hughes; A.F. Hahn; M. Baumgarten; J. Goldstein; J. Katz; M. Graves; G. Parry; P.A. van Doorn

    2010-01-01

    Defining long-term outcomes in chronic inflammatory demyelinating polyneuropathy (CIDP) has been complicated by varying definitions of treatment response and differing scales measuring impairment or disability. An expert panel was convened to devise a CIDP Disease Activity Status (CDAS) and to class

  10. Chronic inflammatory demyelinating polyradiculoneuropathy in a boy with systemic lupus erythematosus.

    Science.gov (United States)

    Zoilo, Morel Ayala; Eduardo, Benadón; Enrique, Faugier; del Rocio, Maldonado V M

    2010-05-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired, autoimmune peripheral neuropathy. Systemic lupus erythematosus (SLE) is a multisystemic, autoimmune disease that can affect the central nervous system in about 40% of patients, with prevalence and incidence unknown in the pediatric population due to lack of multicenter studies. We report the case of a 13-year-old Mexican boy, diagnosed with CIDP at the onset of SLE, beginning with progressive muscle weakness of lower and upper limbs, without affection of the central nervous system. The patient had positive ANA, antiDNAdc, antiBeta2glycoprotein, anti-cardiolipin, ANCA-C and X. He received intravenous immunoglobulin, cyclophosphamide, steroids, and azathioprine and showed clinical improvement. It is important to take into account the presence of peripheral neurological disorders in patients with pediatric SLE, considering CIDP as an uncommon presentation, making the diagnosis important for better treatment and evolution.

  11. Recurrent hypogeusia in a patient with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

    Science.gov (United States)

    Kawaguchi, Norihiko; Sugeno, Naoto; Endo, Kaoru; Miura, Emiko; Misu, Tatsuro; Nakashima, Ichiro; Itoyama, Yasuto

    2012-04-01

    Hypogeusia, a condition with diminished sense of taste, is caused by several conditions, including zinc deficiency and as a side-effect of drugs, but is not common in neurological disorders. A 55-year-old Japanese man with a 30-year history of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) presented with hypogeusia during hospitalization for a recurrence of CIDP. The hypogeusia improved after treatment with high-dose intravenous methylprednisolone (HIMP). Two years later, hypogeusia developed again. A complete taste deficit was revealed by a filter paper test. Brain MRI showed enhancement of the bilateral facial nerve ganglia. Hypogeusia was partially ameliorated after extensive immunosuppressive therapy with repeated HIMP and plasma exchange. Improvement was more prominent in the area innervated by the chorda tympani nerve than that innervated by the glossopharyngeal nerve. To our knowledge, this is the first report of recurrent hypogeusia, which might be caused by cranial nerve injury associated with CIDP.

  12. Nerve sonography in multifocal motor neuropathy and chronic inflammatory demyelinating polyneuropathy

    Directory of Open Access Journals (Sweden)

    D. S. Druzhinin

    2016-01-01

    Full Text Available The quantitative ultrasound characteristics (USC of the median, ulnar nerve at different levels and the spinal nerves in patients with multifocal motor neuropathy (MMN; n=13; 40,4 ± 12,6 years old and chronic inflammatory demyelinating polyneuropathy (CIDP; n = 7; 47,3 ± 11,2 year old did not reveal statistical difference in cross sectional area (CSA between analyzed groups. Patients with MMN have more pronounced asymmetry of CSA in comparison with CIDP patients which have a symmetrical pattern of diffuse nerve involvement. Quantitative USC has shown to be not informative enough in differentiation of MMN and CIDP. The qualitative analysis (QA according to 3 described types of nerve changes has shown that CIDP is characterized by the prevalence of type 3 pattern (85.8 % while MMN – by type 2 (69.2 %. The sensitivity and specificity of proposed QA patterns in nerve USC need to be analyzed in additional investigations. 

  13. IFN-beta gene deletion leads to augmented and chronic demyelinating experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Teige, Ingrid; Treschow, Alexandra; Teige, Anna;

    2003-01-01

    Since the basic mechanisms behind the beneficial effects of IFN-beta in multiple sclerosis (MS) patients are still obscure, here we have investigated the effects of IFN-beta gene disruption on the commonly used animal model for MS, experimental autoimmune encephalomyelitis (EAE). We show that IFN......-beta knockout (KO) mice are more susceptible to EAE than their wild-type (wt) littermates; they develop more severe and chronic neurological symptoms with more extensive CNS inflammation and demyelination. However, there was no discrepancy observed between wt and KO mice regarding the capacity of T cells...... to proliferate or produce IFN-gamma in response to recall Ag. Consequently, we addressed the effect of IFN-beta on encephalitogenic T cell development and the disease initiation phase by passive transfer of autoreactive T cells from KO or wt littermates to both groups of mice. Interestingly, IFN-beta KO mice...

  14. Office immunotherapy in chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy.

    Science.gov (United States)

    Dyck, Peter J; Taylor, Bruce V; Davies, Jenny L; Mauermann, Michelle L; Litchy, William J; Klein, Christopher J; Dyck, P James B

    2015-10-01

    Intravenous immunoglobulin [IVIg], plasma exchange [PE], and corticosteroids are efficacious treatment in chronic inflammatory demyelinating polyneuropathy [CIDP]. IVIg is effective in multifocal motor neuropathy [MMN]. NIS, NIS-weakness, sum scores of raw amplitudes of motor fiber (CMAPs) amplitudes, and Dyck/Rankin score provided reliable measures to detect and scale abnormality and reflect change; they are therefore ideal for office management of response-based immunotherapy (R-IRx) of CIDP. Using efficacious R-IRx, a large early and late therapeutic response (≥ one-fourth were in remission or had recovered) was demonstrated in CIDP. In MMN only an early improvement with late non-significant worsening was observed. The difference in immunotherapy response supports a fundamental difference between CIDP (immune attack on Schwann cells and myelin) and MMN (attack on nodes of Ranvier and axons).

  15. Treatment of Chronic Inflammatory Demyelinating Polyneuropathy: From Molecular Bases to Practical Considerations

    Directory of Open Access Journals (Sweden)

    Paolo Ripellino

    2014-01-01

    Full Text Available Chronic inflammatory demyelinating polyneuropathy (CIDP is an autoimmune disease of the peripheral nervous system, in which both cellular and humoral immune responses are involved. The disease is clinically heterogeneous with some patients displaying pure motor form and others also showing a variable degree of sensory dysfunction; disease evolution may also differ from patient to patient, since monophasic, progressive, and relapsing forms are reported. Underlying such clinical variability there is probably a broad spectrum of molecular dysfunctions that are and will be the target of therapeutic strategies. In this review we first explore the biological bases of current treatments and subsequently we focus on the practical management that must also take into account pharmacoeconomic issues.

  16. IVIG regulates BAFF expression in patients with chronic inflammatory demyelinating polyneuropathy (CIDP).

    Science.gov (United States)

    Ritter, Christian; Förster, Dominik; Albrecht, Philipp; Hartung, Hans-Peter; Kieseier, Bernd C; Lehmann, Helmar C

    2014-09-15

    Recent studies indicate that the cytokine B-cell activating factor (BAFF) is involved in the pathogenesis of chronic inflammatory demyelinating polyneuropathy (CIDP). Intravenous immunoglobulin (IVIg) is standard treatment for CIDP and is known to rapidly modulate increased serum levels of pro-inflammatory cytokines. We evaluated the expression profile of BAFF and its corresponding BAFF-receptor in samples from CIDP patients, focusing on rapid changes before and after IVIg treatment. In CIDP patients BAFF serum concentrations were elevated compared to controls. Treatment with high-dose IVIg restored those elevated BAFF serum levels. Whereas treatment with IVIg did not affect BAFF production in monocytes, antibodies against BAFF could be detected in IVIg preparations, which may explain the short-term decrease of BAFF levels after IVIg treatment. Our data suggest that BAFF plays an important role in the pathogenesis of CIDP and may serve as marker for IVIg treatment response.

  17. POEMS Syndrome in a Juvenile Initially Diagnosed as Treatment Resistant Chronic Inflammatory Demyelinating Polyneuropathy.

    Science.gov (United States)

    Krish, Sonia N; Nguyen, Thy; Biliciler, Suur; Kumaravel, Manickam; Wahed, Amer; Risin, Semyon; Sheikh, Kazim A

    2015-12-01

    POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) is a disorder that mainly affects adults. We report a pediatric patient, initially considered to have Guillain-Barré syndrome, who continued to have progression of neuropathic disease leading to the diagnosis of chronic inflammatory demyelinating polyneuropathy. Diagnosis of POEMS was established by an abnormal bone marrow biopsy, prompted by laboratory and imaging findings, which became abnormal later in the course of the disease. POEMS syndrome is extremely rare in children, and neuropathic features in this age group have not been previously described. This case illustrates that "Guillain-Barré syndrome-like" initial presentation for POEMS, which has not been previously reported. It also emphasizes that in children with progressive acquired neuropathies that are treatment unresponsive, POEMS syndrome should be considered.

  18. Treatment of pediatric chronic inflammatory demyelinating polyneuropathy: Challenges, controversies and questions.

    Science.gov (United States)

    Desai, Jay; Ramos-Platt, Leigh; Mitchell, Wendy G

    2015-01-01

    Pediatric chronic inflammatory demyelinating polyneuropathy (CIDP) is an uncommon acquired disorder of unknown cause, presumed to have an immunological basis. We report 20 patients seen at Children's Hospital Los Angeles over a period of 10 years. The outcome of our patients was favorable in a vast majority with good response to various treatments instituted. However, residual neurologic deficit was common. The choice of treatment modality was empirical and selected by the treating neurologist. Intravenous immunoglobulin (IVIG) and corticosteroids were most commonly utilized for treatment. Plasmapheresis, mycophenolate mofetil, rituximab, cyclophosphamide, azathioprine, and abatacept were added if the patients were refractory to IVIG or became corticosteroid dependent. The spectrum of disease severity ranged from a single monophasic episode, to multiphasic with infrequent relapses with good response to IVIG, to progressive disease refractory to multiple therapies.

  19. Treatment of pediatric chronic inflammatory demyelinating polyneuropathy: Challenges, controversies, and questions

    Directory of Open Access Journals (Sweden)

    Jay Desai

    2015-01-01

    Full Text Available Pediatric chronic inflammatory demyelinating polyneuropathy (CIDP is an uncommon acquired disorder of unknown cause, presumed to have an immunological basis. We report 20 patients seen at Children′s Hospital Los Angeles over a period of 10 years. The outcome of our patients was favorable in a vast majority with good response to various treatments instituted. However, residual neurologic deficit was common. The choice of treatment modality was empirical and selected by the treating neurologist. Intravenous immunoglobulin (IVIG and corticosteroids were most commonly utilized for treatment. Plasmapheresis, mycophenolate mofetil, rituximab, cyclophosphamide, azathioprine, and abatacept were added if the patients were refractory to IVIG or became corticosteroid dependent. The spectrum of disease severity ranged from a single monophasic episode, to multiphasic with infrequent relapses with good response to IVIG, to progressive disease refractory to multiple therapies.

  20. [Anesthetic management of a Dialysis Patient with Chronic Inflammatory Demyelinating Polyneuropathy].

    Science.gov (United States)

    Takahashi, Yoshihiro; Hara, Koji; Sata, Takeyoshi

    2015-11-01

    We report the successful management of anesthesia in a 46-year-old male dialysis patient with chronic inflammatory demyelinating polyneuropathy (CIDP). He underwent an osteosynthesis of the ankle joint using general anesthesia combined with epidural anesthesia. The anesthetic concerns in patients with CIDP are the possibility of postoperative respiratory dysfunction due to anesthetics or muscle relaxants and that of postoperative neurological deterioration due to spinal or epidural anesthesia. In this case, sevoflurane (1.5-2%) did not cause respiratory dysfunction postoperatively and muscle relaxant effect of rocuronium was effectively reversed by sugammadex. Epidural anesthesia using ropivacaine (0.2-0.375%) and fentanyl did not worsen the neurological symptoms of CIDP post-operatively.

  1. Intravenous immunoglobulin inhibits BAFF production in chronic inflammatory demyelinating polyneuropathy - a new mechanism of action?

    Science.gov (United States)

    Bick, Sandra; Tschernatsch, Marlene; Karg, Anne; Fuehlhuber, Verena; Trenczek, Tina E; Faltermeier, Kathrin; Hackstein, Holger; Kaps, Manfred; Blaes, Franz

    2013-03-15

    Chronic-inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated disease treated with intravenous immunoglobulin (IVIg). The underlying mechanism of action remains incompletely understood. The B-cell activating factor BAFF contributes to B-cell homeostasis and (auto-)antibody production. BAFF was recently identified as one key molecule in the development of autoimmune diseases. Herein, we demonstrate that BAFF serum levels are elevated in CIDP patients. IVIg treatment resulted in a significant decrease of BAFF serum level. In vitro, IVIg inhibited BAFF in monocytes. Consequently, we identified BAFF as a new target for IVIg in CIDP treatment and provide a new, Fcγ-receptor independent, mechanism of action for IVIg.

  2. Increased severity of experimental autoimmune encephalomyelitis, chronic macrophage/microglial reactivity, and demyelination in transgenic mice producing tumor necrosis factor-alpha in the central nervous system

    DEFF Research Database (Denmark)

    Taupin, V; Renno, T; Bourbonnière, L

    1997-01-01

    /microglial reactivity was evident in demyelinating lesions in spinal cord, but T cells were not detected during chronic disease. The participation of TNF-alpha in the demyelinating process is thus more probably due to the perpetuation of macrophage/microglial activation than to direct cytotoxicity of myelin...

  3. [Chronic inflammatory demyelinating polyneuropathy after treatment with pegylated interferon alpha 2b in a patient with HIV/HCV coinfection: case report].

    Science.gov (United States)

    Bassetti, Bil Randerson; Trés, Eduardo Sturzeneker; Ciríaco, Jovana Gobbi Marchesi; Pinto Neto, Lauro Ferreira Silva

    2010-01-01

    Chronic inflammatory demyelinating polyneuropathy has a strong association with HIV and HCV infection. A rare association between chronic inflammatory demyelinating polyneuropathy and hepatitis C treatment with pegylated interferon alpha was described recently. We described the first case of chronic inflammatory demyelinating polyneuropathy associated with pegylated interferon alpha 2b in a white man infected with HIV and HCV. The patient recovered completely with the use of intravenous hyperimmune immunoglobulin. Infectologists and hepatologists should be alert regarding this rare and serious association, which requires immediately drug discontinuation and early treatment.

  4. Chronic Inflammatory Demyelinating Polyneuropathy with Reversible Dementia: A New Clinical Entity?

    Science.gov (United States)

    Samaniego, Jorge

    2013-01-01

    Introduction Classic chronic inflammatory demyelinating polyneuropathy (CIDP), an acquired demyelination of peripheral nerves and nerve roots presents with symmetric motor and sensory involvement, weakness in proximal and distal muscles, globally diminished or absent reflexes, painful dysesthesias, and back pain with no brain involvement. In this case, a highly functional lawyer presents with reversible dementia and motor and sensory symptoms consistent with CIDP. This case may represent a new clinical entity of CIDP with reversible dementia. Case Report A 60-year-old man presented with progressive weakness, and cognitive dysfunction in the form of dementia over the last 8 weeks. Sensory and motor weakness continued to progress affecting upper and lower extremities with both proximal and distal muscle groups to the point where the patient was unable to move without assistance. The patient had word finding difficulty, short-term memory impairment, and was disoriented, despite his comprehension being intact. Initial Montreal Cognitive Assessment (MoCA) was 12/30. Initial neurologic exam was notable for muscle strength 3/5, globally depressed deep tendon reflexes. Lumbar puncture revealed elevated protein with no pleocytosis and no serum paraprotein. EMG/NCS demonstrated mixed sensorimotor axonal and demyelination peripheral polyneuropathy. CIDP was diagnosed based on clinical history according to Koski criteria. He was started on a 5-day treatment of IVIG, after which he had marked cognitive improvement after just one dose and improvement in weakness after the second dose of IVIG. Three weeks after IVIG treatment, the patient's cognitive function was back at baseline with MoCA score 29/30; no further word finding difficulty, and no short term memory impairment. At discharge, the patient's weakness had significantly improved to the point where he was able to walk with only the aid of a walker. His neurologic exam had improved as well as his muscle strength 4/5 and 2

  5. Alemtuzumab in the treatment of IVIG-dependent chronic inflammatory demyelinating polyneuropathy.

    LENUS (Irish Health Repository)

    Marsh, E A

    2010-06-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is an idiopathic immune mediated neuropathy causing demyelination and conduction block thought to occur as the result of an aberrant autoimmune response resulting in peripheral nerve inflammation mediated by T cells and humoral factors. Diagnosis commonly prompts initial treatment with steroids or intravenous immunoglobulin (IVIG) on which 5-35% subsequently become dependent to maintain function. Despite a number of small scale trials, the role for alternative long-term immunosuppression remains unclear. Alemtuzumab is a humanised monoclonal antibody targeting the CD52 antigen present on the surface of lymphocytes and monocytes. A single intravenous infusion results in rapid and profound lymphopoenia lasting >12 months. We report its use and clinical outcome in a small series of patients with severe IVIG-dependent CIDP. Seven patients (4 Males; 3 Females) who had failed to respond to conventional immunosuppression were treated in 5 centres receiving 9 courses of alemtuzumab (dose range 60-150 mg). Following treatment, mean monthly IVIG use fell 26% from 202 to 149 g and IVIG administration frequency from 22 to 136 days. Two patients had prolonged remission, two patients had a partial response and no clear benefit was observed in the remaining three patients (2 Males, 1 Females). Responding patients had a younger age at onset (19.5 years) and shorter disease duration than non-responders. Three patients developed autoimmune disease following treatment. Alemtuzumab may offer an alternative treatment for a subset of early onset IVIG dependent CIDP patients failing conventional immunosuppressive agents, but concerns about toxicity may limit its use.

  6. [A case of chronic inflammatory demyelinating polyradiculoneuropathy concomitant with acquired von Willebrand syndrome].

    Science.gov (United States)

    Ueda, Maki; Kawamura, Nobutoshi; Tateishi, Takahisa; Shigeto, Hiroshi; Ohyagi, Yasumasa; Kira, Jun-ichi

    2011-05-01

    We report a case of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) concomitant with acquired von Willebrand syndrome. A 33-year-old man developed motor and sensory polyneuropathy with electrophysiological conduction slowing. At this time, M-protein was absent He was diagnosed with CIDP and received intravenous immunoglobulin and subsequent oral corticosteroids, which resulted in almost complete remission for over 10 years. At the age of 44, he presented with chronic anemia. Laboratory tests and colonoscopy revealed that he had acquired von Willebrand syndrome with monoclonal gammopathy of undetermined significance (IgG lambda type) and colon cancer. Bleeding symptoms were.resolved with intravenous immunoglobulin, but not with supplementation of factor VIII. Shortly after successful excision of the cancer, CIDP and acquired von Willebrand syndrome simultaneously recurred. Intravenous immunoglobulin produced rapid improvement of both neurological and hematological abnormalities. Concurring CIDP and acquired von Willebrand syndrome in the present case may indicate that the conditions have a partly common immunological background including monoclonal gammopathy and a potential common autoantibody-mediated mechanism. Alternatively, dysfunction of von Willebrand factor may increase blood-nerve barrier permeability, inducing the recurrence of CIDP.

  7. Childhood chronic inflammatory demyelinating polyradiculoneuropathy: combined analysis of a large cohort and eleven published series.

    Science.gov (United States)

    McMillan, Hugh J; Kang, Peter B; Jones, H Royden; Darras, Basil T

    2013-02-01

    The clinical presentation, disease course, response to treatment, and long-term outcome of thirty childhood chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients are presented representing the largest cohort reported to date. Most children (60%) presented with chronic (>8-weeks) symptom-onset while a smaller proportion showed sub-acute (4-8 weeks) or acute (''GBS-like''; CIDP series providing a comprehensive review of 143 childhood CIDP cases. The combined initial or first-line treatment response across all studies was favourable for IVIG (79% patients) and corticosteroids (84% patients). Response to first-line plasma exchange was poor (only 14% patients improved) although it may offer some transient or partial benefit as an adjuvant or temporary therapy for selected patients. The combined long-term outcome of our cohort and the literature reveals a favourable prognosis for most patients. The combined modified Rankin scale decreased from 3.7 (at presentation) to 0.7 (at last follow-up). This review provides important data pertaining to clinical course, treatment response and long-term outcome of this relatively uncommon paediatric autoimmune disease.

  8. What's new in chronic inflammatory demyelinating polyradiculoneuropathy in 2007-2008?

    Science.gov (United States)

    van Schaik, Ivo N

    2008-12-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)-related research has made progress in the field of pathogenesis, genetics, and treatment. The number of circulating CD4(+) CD25(+) T-regulatory cells was shown to be reduced in CIDP patients. Increased frequency of genotype GA13-16 of the SH2D2A gene encoding for a T-cell-specific adapter protein in CIDP patients may result in a defective control and elimination of autoreactive T cells. IVIg treatment has been shown to increase numbers and function of peripheral CD4(+) CD25(+) T-regulatory cell in a mouse model. These findings shed new light on the understanding of why peripheral tolerance is breached in CIDP patients and why the disease becomes chronic and adds another possible mechanism of action of intravenous immunoglobulin to the already long list. Long-term effectiveness of IVIg has now been proven. Subcutaneous immunoglobulin could be an alternative for IVIg, but this has to be explored further in well-designed trials. Autologous stem cell transplantation has been tried in refractory patients, but larger trials are necessary to assess safety and effect of this treatment.

  9. Acute-onset chronic inflammatory demyelinating polyneuropathy in hantavirus and hepatitis B virus coinfection

    Science.gov (United States)

    Lim, Jong Youb; Lim, Young-Ho; Choi, Eun-Hi

    2016-01-01

    Abstract Introduction: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired autoimmune disorder with progressive weakness. Acute-onset CIDP resembles Guillain-Barre syndrome (GBS), a rapidly progressive disorder, and follows a chronic course. To our knowledge, no case of acute-onset CIDP in hantavirus and hepatitis B virus (HBV) coinfection has been reported previously. Clinical findings: We report a case of acute-onset CIDP that was initially diagnosed as GBS. Diagnoses: A 44-year-old male logger complained of acute quadriplegia and dyspnea. Mechanical ventilation was initiated. He was an HBV carrier with mild elevation of hepatic enzyme, and positive for hantavirus antibody. He was diagnosed with GBS and immunoglobulin therapy was administered. Interventions: After 8 months, quadriplegia and hypesthesia recurred. Immunoglobulin therapy at this time had no effect, but steroid therapy had some effect. Outcomes: A diagnosis of CIDP was made. After 2 months, severe extremity pain and dyspnea developed again, and steroid pulse therapy was initiated. Conclusion: Besides GBS, acute-onset CIDP can occur with hantavirus and HBV coinfection. Patients with this coinfection in whom GBS has been initially diagnosed should be followed up for a long time, because of the possibility of relapse or deterioration, and acute-onset CIDP should always be considered. PMID:27930572

  10. Spinal primitive neuroectodermal tumor mimicking as chronic inflammatory demyelination polyneuropathy: a case report and review of literature.

    Science.gov (United States)

    Chan, Sophelia H S; Tsang, Dickson S F; Wong, Virginia C N; Chan, Godfrey C F

    2015-02-01

    We report a young boy who presented with progressive weakness of lower extremities associated with areflexia and abnormal electrophysiological findings initially suggestive of chronic inflammatory demyelinating polyneuropathy. Initial lumbosacral spinal magnetic resonance imaging (MRI) showed thickened descending spinal nerve roots only. Immunomodulating therapy was given but with limited clinical response. Repeated spine magnetic resonance imaging showed cauda equina and also new spinal cord extramedullary contrast enhancement. The initial extensive investigations including open biopsy did not point to any specific diagnosis. Only through pursuing a repeated biopsy, the diagnosis of the spinal peripheral primitive neuroectodermal tumor was confirmed. This case highlights the diagnostic challenges of the spinal peripheral primitive neuroectodermal tumor that could have an initial chronic inflammatory demyelinating polyneuropathy-like presentation. The literature review confirms that this is a rare condition and cauda equina origin has only been reported in adults and teenagers, and this is the first reported case in a young child.

  11. Severity and patterns of blood-nerve barrier breakdown in patients with chronic inflammatory demyelinating polyradiculoneuropathy: correlations with clinical subtypes.

    Directory of Open Access Journals (Sweden)

    Fumitaka Shimizu

    Full Text Available OBJECTIVE: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP is currently classified into clinical subtypes, including typical and atypical forms (multifocal acquired demyelinating sensory and motor neuropathy (MADSAM and distal acquired demyelinating symmetric neuropathy (DADS. The aim of this study was to elucidate the patterns and severity of breakdown of the blood-nerve barrier (BNB in each CIDP subtype. METHODS: We evaluated the effects of sera obtained from patients with typical CIDP, MADSAM and DADS and control subjects on the expression levels of tight junction proteins and transendothelial electrical resistance (TEER value in human peripheral nerve microvascular endothelial cells (PnMECs. RESULTS: The sera obtained from the patients with the three clinical phenotypes of CIDP decreased the amount of claudin-5 protein levels and TEER values in the PnMECs. In addition, the sera obtained from typical CIDP patients more prominently reduced claudin-5 protein levels and TEER values in the PnMECs than did that obtained from the MADSAM and DADS patients. Furthermore, the severity of BNB disruption after exposure to the sera was associated with higher Hughes grade, lower MRC score, more pronounced slowing of motor nerve conduction in the median nerve and higher frequency of abnormal temporal dispersion. CONCLUSIONS: Sera derived from typical CIDP patients destroy the BNB more severely than those from MADSAM or DADS patients. The extent of BNB disruption in the setting of CIDP is associated with clinical disability and demyelination in the nerve trunk. These observations may explain the phenotypical differences between CIDP subtypes.

  12. Peripheral Nerve Ultrasonography in Chronic Inflammatory Demyelinating Polyradiculoneuropathy and Multifocal Motor Neuropathy: Correlations with Clinical and Neurophysiological Data

    Directory of Open Access Journals (Sweden)

    Aristide Merola

    2016-01-01

    Full Text Available Objective. This cross-sectional study analyzes the pattern of ultrasound peripheral nerve alterations in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP and multifocal motor neuropathy (MMN at different stages of functional disability. Material and Methods. 22 CIDP and 10 MMN patients and a group of 70 healthy controls were evaluated with an ultrasound scan of the median, ulnar, peroneal, tibial, and sural nerves. Results were correlated with clinical disability scales and nerve conduction studies. Results. Patients with intermediate functional impairment showed relatively larger cross-sectional areas than subjects with either a milder (p<0.05 or more severe impairment (p<0.05, both in CIDP and in MMN. In addition, MMN was associated with greater side-to-side intranerve variability (p<0.05, while higher cross-sectional areas were observed in CIDP (p<0.05 and in nerve segments with predominantly demyelinating features (p<0.05. Higher CSA values were observed in nerves with demyelinating features versus axonal damage (p<0.05 for CIDP; p<0.05 for MMN. Discussion and Conclusions. Greater extent of quantitative and qualitative US alterations was observed in patients at intermediate versus higher functional disability and in nerves with demyelinating versus axonal damage. CIDP and MMN showed differential US aspects, with greater side-to-side intranerve variability in MMN and higher cross-sectional areas in CIDP.

  13. Diffusion tensor imaging of peripheral nerve in patients with chronic inflammatory demyelinating polyradiculoneuropathy: a feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Kakuda, Takako; Fukuda, Hiroshi; Tanitame, Keizo; Takasu, Miyuki; Date, Shuji; Awai, Kazuo [Hiroshima University, Department of Diagnostic Radiology, Graduate School of Biomedical Sciences, Hiroshima (Japan); Ochi, Kazuhide; Ohshita, Tomohiko; Matsumoto, Masayasu [Hiroshima University, Department of Clinical Neuroscience and Therapeutics, Graduate School of Biomedical Science, Hiroshima (Japan); Kohriyama, Tatsuo [Department of Neurology, Hiroshima City Hospital, Hiroshima (Japan); Ito, Katsuhide [Department of Radiology, Onomichi General Hospital, Onomichi, Hiroshima-ken (Japan)

    2011-12-15

    The purpose of this study was to assess the clinical feasibility of diffusion tensor imaging (DTI) for the evaluation of peripheral nerves in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Using a 3-T magnetic resonance imaging scanner, we obtained DTI scans of the tibial nerves of 10 CIDP patients and 10 sex- and age-matched healthy volunteers. We prepared fractional anisotropy (FA) maps, measured the FA values of tibial nerves, and compared these values in the two study groups. In nine patients, we also performed tibial nerve conduction studies and analyzed the correlation between the FA values and parameters of the nerve conduction study. The tibial nerve FA values in CIDP patients (median 0.401, range 0.312-0.510) were significantly lower than those in healthy volunteers (median 0.530, range 0.469-0.647) (Mann-Whitney test, p < 0.01). They were significantly correlated with the amplitude of action potential (Spearman correlation coefficient, p = 0.04, r = 0.86) but not with nerve conduction velocity (p = 0.79, r = 0.11). Our preliminary data suggest that the noninvasive DTI assessment of peripheral nerves may provide useful information in patients with CIDP. (orig.)

  14. Variations of the perforin gene in patients with chronic inflammatory demyelinating polyradiculoneuropathy.

    Science.gov (United States)

    Buttini, S; Cappellano, G; Ripellino, P; Briani, C; Cocito, D; Osio, M; Cantello, R; Dianzani, U; Comi, C

    2015-01-01

    Perforin (PRF) has a key role in the function of cytotoxic T and natural killer cells. Rare variations of PRF1 predispose to autoimmunity. Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disease of the peripheral nervous system, involving defective lymphocyte apoptosis. The aim of this study was to investigate the role of PRF1 in CIDP. The entire coding region of PRF1 was sequenced in 94 patients and 158 controls. We found three missense variations leading to amino acid substitutions and one nonsense variation resulting in a premature stop codon. All variations would decrease PRF activity. Their overall frequency was significantly higher in patients than in controls (odds ratio (OR)=4.47). The most frequent variation was p.Ala91Val (OR=3.92) previously associated with other autoimmune diseases. Clinical analysis showed that PRF1 variations were more frequent in relapsing patients and in patients displaying axonal damage. These data suggest that PRF1 variations may influence CIDP development and course.

  15. Spinal cord involvement in chronic inflammatory demyelinating polyradiculoneuropathy: a clinical and MRI study.

    Science.gov (United States)

    Ioannidis, Panagiotis; Parissis, Dimitris; Karapanayiotides, Theodoros; Maiovis, Pantelis; Karacostas, Dimitris; Grigoriadis, Nikolaos

    2015-06-01

    Concomitant central nervous system (CNS) involvement in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is rare. Although the spinal nerve roots may present MRI abnormalities in CIDP, hitherto, the spinal cord has been investigated in a single study. We retrospectively investigated clinically and with MRI a cohort of patients with definite CIDP diagnosis (EFNS/PNS criteria) for evidence of brain and spinal cord involvement, who were initially admitted in our department during the last 4 years. Among 12 patients with CIDP (men: 8, mean age: 59.3 years, mean disease duration: 3.8 years), nine patients had their MRI scan during a clinical relapse and three during remission. Brain MRI did not document typical multiple sclerosis lesions in any patient. We did not identify any MRI abnormalities in ten patients without clinical evidence of spinal cord involvement. Conversely, MRI disclosed extensive lesions of the thoracic cord in two patients with an overt spinal cord syndrome, whom we describe. This represents the biggest MRI study of CIDP patients who have been investigated for spinal cord involvement. Our data support earlier observations that a minority of CIDP patients may additionally develop CNS involvement of variable degree.

  16. Long-Lasting Cranial Nerve III Palsy as a Presenting Feature of Chronic Inflammatory Demyelinating Polyneuropathy

    Directory of Open Access Journals (Sweden)

    Rossella Spataro

    2015-01-01

    Full Text Available We describe a patient with chronic inflammatory demyelinating polyneuropathy (CIDP in which an adduction deficit and ptosis in the left eye presented several years before the polyneuropathy. A 52-year-old man presented with a 14-year history of unremitting diplopia, adduction deficit, and ptosis in the left eye. At the age of 45 a mild bilateral foot drop and impaired sensation in the four limbs appeared, with these symptoms showing a progressive course. The diagnostic workup included EMG/ENG which demonstrated reduced conduction velocity with bilateral and symmetrical sensory and motor involvement. Cerebrospinal fluid studies revealed a cytoalbuminologic dissociation. A prolonged treatment with corticosteroids allowed a significant improvement of the limb weakness. Diplopia and ptosis remained unchanged. This unusual form of CIDP presented as a long-lasting isolated cranial nerve palsy. A diagnostic workup for CIDP should therefore be performed in those patients in which an isolated and unremitting cranial nerve palsy cannot be explained by common causes.

  17. Chronic inflammatory demyelinating polyneuropathy: quality of life, sociodemographic profile and physical complaints

    Directory of Open Access Journals (Sweden)

    Patricia Leila dos Santos

    2014-03-01

    Full Text Available Whereas an evaluation of quality of life and possible impacts on the mental state of a patient may help to evaluate the evolution of chronic inflammatory demyelinating polyneuropathy (CIDP, the aim of this study was to study the psychological profile of patients, and evaluate quality of life associated with the disease. Method 41 patients were evaluated using a Mini-Mental State Examination (MMSE and a Short-Form Health Survey (SF-36. Results The mean age of the patients was 50.6 years, 63.4% men. Of the participants, 65.9% had other health problems, 39% reported needing help with activities of daily living, 49% slept less than 8 hours per night, and 34.1% complained of some memory deficit. The average MMSE score was 26. Impairment of functional capacity and pain were the more important altered health states. Conclusion CIDP has important social and economic impacts, owing to functional impairments that can lead to professional and personal limitations.

  18. Brachial and lumbar plexuses in chronic inflammatory demyelinating polyradiculoneuropathy: MRI assessment including apparent diffusion coefficient

    Energy Technology Data Exchange (ETDEWEB)

    Adachi, Yuko; Sato, Noriko; Yamashita, Fumio; Kida, Jiro; Takahashi, Tomoyuki [National Center Hospital of Neurology and Psychiatry, Department of Radiology, Kodaira, Tokyo (Japan); Okamoto, Tomoko [National Center Hospital of Neurology and Psychiatry, Department of Neurology, Kodaira, Tokyo (Japan); Sasaki, Masayuki; Komaki, Hirofumi [National Center Hospital of Neurology and Psychiatry, Department of Child Neurology, Kodaira, Tokyo (Japan); Matsuda, Hiroshi [Saitama Medial University Hospital, Department of Nuclear Medicine, Iruma-gun, Saitama (Japan)

    2011-01-15

    Our purpose was to clarify the magnetic resonance (MR) imaging characteristics of the brachial and lumbar plexuses in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) using various kinds of sequences, including diffusion-weighted images (DWI). We evaluated the MR imaging findings for lumbar and/or brachial nerve plexuses in 13 CIDP patients and 11 normal volunteers. The nerve swelling was evaluated in comparison with normal controls by coronal short tau inversion recovery (STIR), and signal abnormalities were evaluated by coronal STIR, T1-weighted images, and DWIs. The degrees of contrast enhancement and apparent diffusion coefficient (ADC) values of the plexus were also assessed. In the patient group, diffuse enlargement and abnormally high signals were detected in 16 out of 24 plexuses (66.7%) on STIR, a slightly high signal was detected in 12 of 24 plexuses (50%) on T1-weighted images, and a high-intensity signal was detected in 10 of 18 plexuses (55.6%) on DWIs with high ADC values. Contrast enhancement of the plexuses was revealed in 6 of 19 plexuses (31.6%) and was mild in all cases. There were statistically significant differences between the ADC values of patients with either swelling or abnormal signals and those of both normal volunteers and patients without neither swelling nor abnormal signals. There were no relationships between MR imaging and any clinical findings. STIR is sufficient to assist clinicians in diagnosing CIDP. T1-weighted images and DWIs seemed useful for speculating about the pathological changes in swollen plexuses in CIDP patients. (orig.)

  19. Circulating subsets and CD4(+)CD25(+) regulatory T cell function in chronic inflammatory demyelinating polyradiculoneuropathy.

    Science.gov (United States)

    Sanvito, Lara; Makowska, Anna; Gregson, Norman; Nemni, Raffaello; Hughes, Richard A C

    2009-01-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an inflammatory disease of the peripheral nervous system that is probably autoimmune in origin. Different components of the adaptive and innate immunity may be responsible for the aberrant response towards nerve antigens. To investigate this, we examined lymphocyte subsets and regulatory T cell (Treg) function in the blood of CIDP patients, healthy controls (HC) and subjects with non-immune mediated neuropathies (other neuropathies, ON). We used flow cytometry to determine the frequency of monocytes, B cells, natural killer (NK) and NK-T cells, total and activated CD4(+) and CD8(+) T cells, effector memory and central memory CD4(+) and CD8(+) T cells, and CD4(+)CD25(high)Foxp3(+) Tregs. Treg function was studied after polyclonal stimulation and antigen specific stimulation with myelin protein peptides in CIDP and HC. There was an increased frequency of monocytes (p = 0.02) and decreased frequency of NK cells (p = 0.02) in CIDP compared with HC but not ON. There were no significant differences in other populations. Treg function was impaired in CIDP compared to HC (p = 0.02), whilst T cell proliferation to myelin protein peptides before and after depletion of Tregs was not different between patients and controls. This study shows increased circulating monocytes and reduced NK cells in CIDP. Although Treg frequency was not altered, we confirm that Tregs display a defect of suppressive function. Myelin protein peptides were not the target of the altered peripheral regulation of the immune response. The mechanisms of peripheral immune tolerance in CIDP and their relevance to the pathogenesis deserve further exploration.

  20. Steroids for chronic inflammatory demyelinating polyradiculoneuropathy: evidence base and clinical practice.

    Science.gov (United States)

    Press, R; Hiew, F L; Rajabally, Y A

    2016-04-01

    Evidence-based therapies for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) consist of corticosteroids, intravenous immunglobulins (IVIg), and plasma exchange. Steroids represent the oldest treatment used historically. In countries where readily available and affordable, IVIg tends to be favored as first-line treatment. The reason for this preference, despite substantially higher costs, is the perception that IVIg is more efficacious and safer than corticosteroids. However, the unselected use of IVIg as a first-line treatment option in all cases of CIDP raises issues of cost-effectiveness in the long-term. Furthermore, serious although rare, particularly thromboembolic side effects may result from their use. Recent data from randomized trials suggest pulsed corticosteroids to have a higher potential in achieving therapy-free remission or longer remission-free periods compared with IVIg, as well as relatively low rates of serious side effects when given as pulsed intravenous infusions during short periods of time. These specific advantages suggest that pulsed steroids could in many cases be used, as the first, rather than second choice of treatment when initiating immunomodulation in CIDP, primarily in hopes of achieving a remission after the short-term use. This article reviews the evidence base for the use of corticosteroids in its various forms in CIDP and factors that may influence clinicians' choice between IVIg and pulsed steroid treatment. The issue of efficacy, relapse rate and time, and side effect profile are analyzed, and some aspects from the authors' experience are discussed in relation to the possibility of using the steroid option as first-line therapy in a large proportion of patients with CIDP.

  1. Epidemiologic variability of chronic inflammatory demyelinating polyneuropathy with different diagnostic criteria: study of a UK population.

    Science.gov (United States)

    Rajabally, Yusuf A; Simpson, Benjamin S; Beri, Sushil; Bankart, John; Gosalakkal, Jayaprakash A

    2009-04-01

    Epidemiologic data on chronic inflammatory demyelinating polyneuropathy (CIDP) is limited, and previous studies have shown variable results. The frequencies of CIDP subtypes remain unknown. Variations due to use of different diagnostic criteria have not been studied. We examined the prevalence and incidence of CIDP in Leicestershire and Rutland, UK (population 963,600). Prevalence day was 1 May 2008. The prevalence of CIDP fulfilling the 2006 clinical and electrophysiologic European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) criteria was 4.77 per 100,000 (95% confidence interval [CI] 3.49-6.37). Using the 1991 American Academy of Neurology (AAN) criteria, the prevalence was 1.97 per 100,000 in this population (95% CI 1.19-3.08). Lewis-Sumner syndrome was diagnosed in 15.2% of patients, and 23.9% had pure sensory onset. Over 40% required no immunotherapy, and 84.6% of those treated responded. More than 80% of the AAN criteria-negative but EFNS/PNS criteria-positive patients were responsive to treatment. Both sets of criteria were equally likely to identify patients who required therapy. The mean annual incidence rate over the 3 years preceding the prevalence day was 0.70 per 100,000/year using EFNS/PNS criteria (95% CI 0.43-1.08), and 0.35 per 100,000/year using AAN criteria (95% CI 0.17-0.64). We conclude that the AAN criteria may underestimate prevalence and incidence of the disease. The EFNS/PNS criteria provide higher diagnostic sensitivity and are of greater clinical relevance, and they also offer a useful breakdown of the epidemiologic data for CIDP subtypes.

  2. [Successful treatment of HIV-associated chronic inflammatory demyelinating polyneuropathy by early initiation of highly active anti-retroviral therapy].

    Science.gov (United States)

    Kume, Kodai; Ikeda, Kazuyo; Kamada, Masaki; Touge, Tetsuo; Deguchi, Kazushi; Masaki, Tsutomu

    2013-01-01

    A 47-year-old man with HIV infection presented with lower leg dominant dysesthesia, muscle weakness and sensory ataxia of 3 month's duration. Nerve conduction studies (NCS) showed demyelination change in the median and tibial nerves and sensory nerve action potential (SNAP) in the sural nerve was not evoked. Somatosensory evoked potential (SEP) showed the delayed N9 latency. Diagnose of HIV-associated chronic inflammatory demyelinating polyneuropathy (CIDP) was made. Although the CD4 lymphocyte counts were relatively preserved (466/μl), highly active anti-retroviral therapy (HAART) was started according to a new guideline for the use of antiretroviral agents in HIV-1-infected adults and adolescents recommending early initiation of treatment. After six months, HIV1-RNA was not detected and the CD4 lymphocyte counts showed a recovering trend (585/μl). His symptoms had disappeared, except for dysesthesia in the tip of a toe. Repeated NCS demonstrated full recovery from the demyelination and appearance of SNAP in the sural nerve. The improvement of his symptoms and NCS findings has been maintained for two years. Although effectiveness of immunotherapies such as oral prednisone, high-dose immunoglobulins and plasmapheresis have been reported in HIV-associated CIDP, early initiation of HAART may be also important for favorable prognosis in HIV-associated CIDP.

  3. Autoimmune Demyelinating Polyneuropathy as a Manifestation of Chronic Graft-versus-Host Disease after Adult Cord Blood Transplantation in a Patient with Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Fredrick Hogan

    2014-01-01

    Full Text Available Immune mediated demyelinating disease after allogeneic stem cell transplantation is a rare entity with unclear etiology. Acute inflammatory demyelinating polyneuropathy (AIDP has been reported after related and adult unrelated allogeneic stem cell transplantation but no such case has been reported after unrelated cord blood transplantation. We hereby present the first case of AIDP after double umbilical cord blood transplantation (DUCBT. A 55-year-old man with chronic lymphocytic leukemia (CLL received a cord blood transplant for relapsed refractory disease with high risk cytogenetics. On day 221, patient presented with skin rash, tingling in both lower extremites, and ascending paralysis that progressed rapidly over the course of 2 days. The workup resulted in a diagnosis of AIDP and administration of intravenous immunoglobulins plus steroids was initiated. Motor and sensory powers were fully recovered and his chronic GVHD was managed for several months with single agent sirolimus.

  4. Subcutaneous immunoglobulin for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (The PATH Study): study protocol for a randomized controlled trial

    OpenAIRE

    van Schaik, Ivo N; van Geloven, Nan; Bril, Vera; Hartung, Hans-Peter; Lewis, Richard A.; Sobue, Gen; Lawo, John-Philip; Mielke, Orell; Cornblath, David R.; Merkies, Ingemar S. J.; ,

    2016-01-01

    Background Subcutaneous administration of Ig (SCIg) has gained popularity as an alternative route of administration but has never been rigorously examined in chronic inflammatory demyelinating polyneuropathy (CIDP). Methods/design The primary objective of the PATH study (Polyneuropathy and Treatment with Hizentra) is to determine the efficacy of two different doses of SCIg IgPro20 (0.2 g/kg bw or 0.4 g/kg bw) in a 24-week maintenance treatment of CIDP in comparison to placebo. The primary eff...

  5. [Correlation between dental pulp demyelination degree and pain visual analogue scale scores data under acute and chronic pulpitis].

    Science.gov (United States)

    Korsantiia, N B; Davarashvili, X T; Gogiashvili, L E; Mamaladze, M T; Tsagareli, Z G; Melikadze, E B

    2013-05-01

    The aim of study is the analysis of pulp nerve fibers demyelination degree and its relationship with Visual Analogue Scale (VAS) score that may be measured as objective criteria. Material and methods of study. Step I: electron micrografs of dental pulp simples with special interest of myelin structural changes detected in 3 scores system, obtained from 80 patients, displays in 4 groups: 1) acute and 2) chronic pulpitis without and with accompined systemic deseases, 20 patients in each group. Dental care was realized in Kutaisi N1 Dental clinic. Step II - self-reported VAS used for describing dental pain. All data were performed by SPSS 10,0 version statistics including Spearmen-rank and Mann-Whitny coefficients for examine the validity between pulp demyelination degree and pain intensity in verbal, numbered and box scales. Researched Data were shown that damaged myelin as focal decomposition of membranes and Schwann cells hyperthrophia correspond with acute dental pain intensity as Spearman index reported in VAS numbered Scales, myelin and axoplasm degeneration as part of chronic gangrenous pulpitis disorders are in direct correlation with VAS in verbal, numbered and behavioral Rating Scales. In fact, all morphological and subjective data, including psychomotoric assessment of dental painin pulpitis may be used in dental practice for evaluation of pain syndrome considered personal story.

  6. Acute inflammatory demyelinating polyneuropathy associated with pegylated interferon 2a therapy for chronic hepatitis C virus infection

    Institute of Scientific and Technical Information of China (English)

    Vijay Khiani; Thomas Kelly; Adeel Shibli; Donald Jensen; Smruti R Mohanty

    2008-01-01

    The combination of pogylated interferon (Peg-IFN) and ribavirin is the standard of care for chronic hepatitis C virus (HCV) infection treatment. In general, common side effects related to this combination therapy are mild and are very well tolerated. However, peripheral neuropathy including demyelinating polyneuropathy related to Peg-IFN is extremely rare. We present the first case of an acute inflammatory demyelinating polyneuropathy (AIDP)associated with Peg-IFN-α 2a (Pegasys) after 16 wk of a combination therapy with Pegasys and ribavirin in a 65-year-old woman with chronic HCV infection.She developed tingling, numbness, and weakness of her upper and lower extremities and was hospitalized for acute neurological deficits. Her clinical course,neurological findings, an electromyogram (EHG), nerve conductions studies (NCS), muscle biopsy, and a sural nerve biopsy were all consistent with AIDP likely related to Pegasys use. The patient recovered completely with the use of intravenous immunoglobulin (IVIG) including physical therapy and neurological rehabilitation. It is very important that gastroenterologists and/or hepatologists recognize this rare neurological complication related to Peg-IFN treatment very early, since it requires a prompt discontinuation of therapy including an immediate referral to a neurologist for the confirmation of diagnosis, management, and the prevention of long-term neurological deficits.

  7. Intraventricular injections of mesenchymal stem cells activate endogenous functional remyelination in a chronic demyelinating murine model

    Science.gov (United States)

    Cruz-Martinez, P; González-Granero, S; Molina-Navarro, M M; Pacheco-Torres, J; García-Verdugo, J M; Geijo-Barrientos, E; Jones, J; Martinez, S

    2016-01-01

    Current treatments for demyelinating diseases are generally only capable of ameliorating the symptoms, with little to no effect in decreasing myelin loss nor promoting functional recovery. Mesenchymal stem cells (MSCs) have been shown by many researchers to be a potential therapeutic tool in treating various neurodegenerative diseases, including demyelinating disorders. However, in the majority of the cases, the effect was only observed locally, in the area surrounding the graft. Thus, in order to achieve general remyelination in various brain structures simultaneously, bone marrow-derived MSCs were transplanted into the lateral ventricles (LVs) of the cuprizone murine model. In this manner, the cells may secrete soluble factors into the cerebrospinal fluid (CSF) and boost the endogenous oligodendrogenic potential of the subventricular zone (SVZ). As a result, oligodendrocyte progenitor cells (OPCs) were recruited within the corpus callosum (CC) over time, correlating with an increased myelin content. Electrophysiological studies, together with electron microscopy (EM) analysis, indicated that the newly formed myelin correctly enveloped the demyelinated axons and increased signal transduction through the CC. Moreover, increased neural stem progenitor cell (NSPC) proliferation was observed in the SVZ, possibly due to the tropic factors released by the MSCs. In conclusion, the findings of this study revealed that intraventricular injections of MSCs is a feasible method to elicit a paracrine effect in the oligodendrogenic niche of the SVZ, which is prone to respond to the factors secreted into the CSF and therefore promoting oligodendrogenesis and functional remyelination. PMID:27171265

  8. Distribution of Th17 cells and Th1 cells in peripheral blood and cerebrospinal fluid in chronic inflammatory demyelinating polyradiculoneuropathy.

    Science.gov (United States)

    Chi, Li Jun; Xu, Wan Hai; Zhang, Zong Wen; Huang, Hui Tao; Zhang, Li Ming; Zhou, Jin

    2010-12-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated demyelinating disease of the peripheral nervous system. Th17 and Th1 cells contribute to the pathogenesis of most autoimmune diseases, but little is known about their distribution and reciprocal relationship in CIDP. In this study, we analyzed the distribution of Th17, Th1, and Th17/Th1 cells in the peripheral blood and cerebrospinal fluid (CSF). The results showed that the frequency of Th17 cells was significantly higher in the peripheral blood mononuclear cell (PBMCs) and CSF of active CIDP in comparison with remitting CIDP or to other non-inflammatory neurological diseases (ONDs), accompanied by similar findings for Th17/Th1 cells. Both active and remitting CIDP have higher percentage of Th1 cells in the CSF than OND. CSF protein levels positively correlated with the frequencies of Th17 cells either in the PBMCs or CSF of active CIDP, while there was no significant correlation with Th1 cells. In line with these observations, the levels of interleukin-17 (IL-17) in plasma and transcript factors retinoic acid receptor-related orphan receptor (ROR)γt expressed by PBMCs were significantly higher in the active CIDP than remitting CIDP or OND. In summary, our preliminary findings suggest that elevated numbers of inflammatory T cells, especially for Th17 cells, might be an important determinant in the evolution of CIDP.

  9. Pulsed high-dose dexamethasone versus standard prednisolone treatment for chronic inflammatory demyelinating polyradiculoneuropathy (PREDICT study): a double-blind, randomised, controlled trial.

    NARCIS (Netherlands)

    Schaik, I.N. van; Eftimov, F.; Doorn, P.A. van; Brusse, E.; Berg, L.H. van den; Pol, W.L. van der; Faber, C.G.; Oostrom, J.C. van; Vogels, O.J.M.; Hadden, R.D.; Kleine, B.U.; Norden, A.G.W. van; Verschuuren, J.J.; Dijkgraaf, M.G.; Vermeulen, M.

    2010-01-01

    BACKGROUND: Pulsed high-dose dexamethasone induced long-lasting remission in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in a pilot study. The PREDICT study aimed to compare remission rates in patients with CIDP treated with high-dose dexamethasone with rates in pa

  10. Pulsed high-dose dexamethasone versus standard prednisolone treatment for chronic inflammatory demyelinating polyradiculoneuropathy (PREDICT study) : a double-blind, randomised, controlled trial

    NARCIS (Netherlands)

    van Schaik, Ivo N.; Eftimov, Filip; van Doorn, Pieter A.; Brusse, Esther; van den Berg, Leonard H.; van der Pol, W. Ludo; Faber, Catharina G.; van Oostrom, Joost C. H.; Vogels, Oscar J. M.; Hadden, Rob D. M.; Kleine, Bert U.; van Norden, Anouk G. W.; Verschuuren, Jan J. G. M.; Dijkgraaf, Marcel G. W.; Vermeulen, Marinus

    2010-01-01

    Background Pulsed high-dose dexamethasone induced long-lasting remission in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in a pilot study. The PREDICT study aimed to compare remission rates in patients with CIDP treated with high-dose dexamethasone with rates in pat

  11. Pulsed high-dose dexamethasone versus standard prednisolone treatment for chronic inflammatory demyelinating polyradiculoneuropathy (PREDICT study): a double-blind, randomised, controlled trial

    NARCIS (Netherlands)

    I.N. van Schaik; F. Eftimov; P.A. van Doorn; E. Brusse; L.H. van den Berg; W.L. van der Pol; C.G. Faber; J.C. van Oostrom; O.J. Vogels; R.D. Hadden; B.U. Kleine; A.G. van Norden; J.J. Verschuuren; M.G. Dijkgraaf; M. Vermeulen

    2010-01-01

    Background Pulsed high-dose dexamethasone induced long-lasting remission in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in a pilot study. The PREDICT study aimed to compare remission rates in patients with CIDP treated with high-dose dexamethasone with rates in pat

  12. A randomised, double-blinded, placebo controlled trial of the effect of subcutaneous immunoglobulin on muscular performance in chronic inflammatory demyelinating polyneuropathy

    DEFF Research Database (Denmark)

    Jakobsen, Johannes Klitgaard; Markvardsen, Lars Høj; Harbo, Thomas;

    Objective: We hypothesised that the effect of subcutaneous infusion of immunoglobulins(SCIG) on muscular performance in chronic inflammatory demyelinating polyneuropathy(CIDP) is superior to that of placebo and equals the therapeutic effect of intravenous infusion(IVIG). Background Subcutaneous...

  13. Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial

    NARCIS (Netherlands)

    R.A.C. Hughes (Richard); P. Donofrio (Peter); V. Bril (Vera); M.C. Dalakas (Marinos); C. Deng (Chunqin); K. Hanna (Kim); H.P. Hartung; N. Latov (Norman); I.S.J. Merkies (Ingemar); P.A. van Doorn (Pieter)

    2008-01-01

    textabstractBackground: Short-term studies suggest that intravenous immunoglobulin might reduce disability caused by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) but long-term effects have not been shown. We aimed to establish whether 10% caprylate-chromatography purified immune

  14. Intravenous immunoglobulin treatment in chronic inflammatory demyelinating polyradiculoneuropathy, a time to start and a time to stop.

    Science.gov (United States)

    Adrichem, Max E; Eftimov, Filip; van Schaik, Ivo N

    2016-09-01

    Intravenous immunoglobulin (IVIg) is often used as preferred treatment in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Several studies highlighted the short-term efficacy of IVIg for CIDP yet many patients need maintenance therapy. Notwithstanding the fact IVIg has been used for over 30 years in CIDP, there is only limited evidence to guide dosage and interval during maintenance treatment. The variation in disease course, lack of biomarkers, and fear of deterioration after stopping IVIg makes long-term treatment challenging. Recent studies suggest a proportion of patients receive unnecessary IVIg maintenance treatment. This review provides an overview of the use of IVIg for CIDP treatment, focusing on evidence for long-term IVIg use.

  15. Peripheral Nerve Ultrasonography in Chronic Inflammatory Demyelinating Polyradiculoneuropathy and Multifocal Motor Neuropathy: Correlations with Clinical and Neurophysiological Data.

    Science.gov (United States)

    Merola, Aristide; Rosso, Michela; Romagnolo, Alberto; Peci, Erdita; Cocito, Dario

    2016-01-01

    Objective. This cross-sectional study analyzes the pattern of ultrasound peripheral nerve alterations in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) at different stages of functional disability. Material and Methods. 22 CIDP and 10 MMN patients and a group of 70 healthy controls were evaluated with an ultrasound scan of the median, ulnar, peroneal, tibial, and sural nerves. Results were correlated with clinical disability scales and nerve conduction studies. Results. Patients with intermediate functional impairment showed relatively larger cross-sectional areas than subjects with either a milder (p CIDP and in MMN. In addition, MMN was associated with greater side-to-side intranerve variability (p CIDP (p CIDP; p CIDP and MMN showed differential US aspects, with greater side-to-side intranerve variability in MMN and higher cross-sectional areas in CIDP.

  16. Genetics of Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): current knowledge and future directions.

    Science.gov (United States)

    Blum, Stefan; McCombe, Pamela A

    2014-06-01

    Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are thought to be autoimmune diseases. There have been many attempts to find a human leukocyte antigen (HLA) association with GBS and CIDP with little success. There have been studies of other plausible genes in GBS and CIDP and the role of these genes in GBS and CIDP and the data from these genetic studies is reviewed. Some of the genes that have been studied are immune related and some others have nervous system effects. The studies are limited by small numbers. Some of the genes show association with disease severity rather than disease susceptibility. The need for more detailed molecular studies of the role of HLA molecules and the need for modern genetic approaches to GBS and CIDP are explained.

  17. Subcutaneous versus intravenous immunoglobulin in drug-naïve patients with chronic inflammatory demyelinating polyneuropathy (CIDP)

    DEFF Research Database (Denmark)

    Markvardsen, L H; Sindrup, S H; Christiansen, I;

    2016-01-01

    BACKGROUND AND PURPOSE: Subcutaneous immunoglobulin (SCIG) is superior to placebo treatment for maintenance of muscle strength during 12 weeks in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). The present study evaluated whether SCIG preserves muscle strength for 1 year...... in an open-label follow-up study. METHODS: Seventeen responders to intravenous immunoglobulin (IVIG) who had participated in the previous study of SCIG versus placebo in CIDP were included. After one IVIG infusion 2 weeks prior to baseline, all continued on SCIG treatment at weekly equal dosage and were...... remained unchanged. CONCLUSION: SCIG preserves muscle strength and functional ability in patients with CIDP who previously responded to IVIG. SCIG should be considered as an alternative in long-term treatment of CIDP patients....

  18. Disease-modifying therapy in multiple sclerosis and chronic inflammatory demyelinating polyradiculoneuropathy: common and divergent current and future strategies.

    Science.gov (United States)

    Melzer, N; Meuth, S G

    2014-03-01

    Multiple sclerosis (MS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) represent chronic, autoimmune demyelinating disorders of the central and peripheral nervous system. Although both disorders share some fundamental pathogenic elements, treatments do not provide uniform effects across both disorders. We aim at providing an overview of current and future disease-modifying strategies in these disorders to demonstrate communalities and distinctions. Intravenous immunoglobulins (IVIG) have demonstrated short- and long-term beneficial effects in CIDP but are not effective in MS. Dimethyl fumarate (BG-12), teriflunomide and laquinimod are orally administered immunomodulatory drugs that are already approved or likely to be approved in the near future for the basic therapy of patients with relapsing-remitting MS (RRMS) due to positive results in Phase III clinical trials. However, clinical trials with these drugs in CIDP have not (yet) been initiated. Natalizumab and fingolimod are approved for the treatment of RRMS, and trials to evaluate their safety and efficacy in CIDP are now planned. Alemtuzumab, ocrelizumab and daclizumab respresent monoclonal antibodies in advanced stages of clinical development for their use in RRMS patients. Attempts to study the safety and efficacy of alemtuzumab and B cell-depleting anti-CD20 antibodies, i.e. rituximab, ocrelizumab or ofatumumab, in CIDP patients are currently under way. We provide an overview of the mechanism of action and clinical data available on disease-modifying immunotherapy options for MS and CIDP. Enhanced understanding of the relative effects of therapies in these two disorders may aid rational treatment selection and the development of innovative treatment approaches in the future.

  19. Liposomal glucocorticosteroids in treatment of chronic autoimmune demyelination: long-term protective effects and enhanced efficacy of methylprednisolone formulations.

    Science.gov (United States)

    Linker, Ralf A; Weller, Charlotte; Lühder, Fred; Mohr, Alexander; Schmidt, Jens; Knauth, Michael; Metselaar, Josbert M; Gold, Ralf

    2008-06-01

    Liposomal encapsulation leads to enhanced efficacy of glucocorticosteroids (GS) in treatment of autoimmune diseases. Here we compare liposomal prednisolone (PL) to liposomal methylprednisolone (MPL) in chronic-relapsing myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE), a model closely reflecting aspects of multiple sclerosis (MS). At the maximum of the first relapse, a single dose of PL or MPL was applied at 10 mg/kg or at 4 mg/kg and compared to classical methylprednisolone (MP) pulse therapy. PL at 10 mg/kg was superior to free MP with long-term efficacy and a sustained protection even during the second and third relapse. At the same time, in vivo magnetic resonance imaging of rat brains revealed a significant reduction of T2-lesions after PL application. Comparison of PL and MPL at 10 mg/kg disclosed superior effects for MPL with an enhanced reduction of inflammatory infiltration as well as preservation of myelin and axons. Dose titration experiments underscored a dose-dependent efficacy of liposomal GS with a sustained efficacy especially of the higher dosage. In histological analyses, PL10 was superior in reducing macrophage and T cell infiltration as well as demyelination and axonal loss while the lower dosages were still at least as effective as free MP. FACS analyses revealed an effect of liposome formulations on T cell numbers, the CD4/CD8 ratio, frequencies of regulatory T cells and adhesion molecule expression. In summary, liposomal GS and especially methylprednisolone formulations display an enhanced efficacy not only in acute inflammatory, but also in chronic demyelinating models of MS and confer long-term protection from relapses. These findings lay the groundwork for applying liposomal GS in clinical MS trials in the near future.

  20. Osmotic demyelination syndrome in a normonatremic patient of chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Atul Abhishek Jha

    2014-01-01

    Full Text Available Osmotic Demyelination Syndrome (ODS is associated with rapid correction of hyponatremia or fluid shifts, and is characterized by neurological involvement related to pons, brainstem or other areas of the brain. All possible measures should be taken to prevent this serious disorder. Diagnosing this condition early is very important and requires a high index of suspicion. The treatment is purely supportive and most patients may show dramatic recovery. ODS occurring in normonatremic and hypernatremic patients is very rare. We report a case of an 18-year-old boy of end-stage renal disease who presented with an episode of acute gastroenteritis. He was managed with aggressive intravenous fluids, hemodialysis and other supportive therapy. But, he developed altered sensorium and seizures that progressed to features of spastic quadriparesis and lower cranial nerve palsy. Neuroimaging showed hyperintensities in pons and midbrain suggestive of ODS. The patient had normal sodium levels at all times and had no evidence of hyponatremia. The patient was managed with hemodialysis, physiotherapy and other conservative measures and had a gradual clinical and radiological recovery.

  1. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society - First Revision

    NARCIS (Netherlands)

    P.Y.K. van den Bergh; R.D.M. Hadden; P. Bouche; D.R. Cornblath; A. Hahn; I. Illa; C.L. Koski; J.M. Leger; E. Nobile-Orazio; J. Pollard; C. Sommer; P.A. van Doorn; I.N. van Schaik

    2010-01-01

    Background: Consensus guidelines on the definition, investigation, and treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) have been previously published in European Journal of Neurology and Journal of the Peripheral Nervous System. Objectives: To revise these guidelines. M

  2. Acute inflammatory demyelinating polyneuropathy after treatment with pegylated interferon alfa-2a in a patient with chronic hepatitis C virus infection: a case report

    Directory of Open Access Journals (Sweden)

    Lahbabi Mounia

    2012-09-01

    Full Text Available Abstract Introduction The combination of polyethylene glycol (PEGylated interferon (pegylated interferon and ribavirin has been shown to be an effective treatment for chronic hepatitis C virus. In general, common side effects related to this combination therapy are mild and are well tolerated. However, peripheral neuropathy including demyelinating polyneuropathy related to PEG-interferon α2a (pegylated interferon alfa-2a is extremely rare. In the literature, only one case of acute inflammatory demyelinating polyneuropathy related to PEG-interferon α2a has been published previously. Case presentation To the best of our knowledge we present only the second case of acute inflammatory demyelinating polyneuropathy related to PEG-interferon α2a, occurring in a 63-year-old Caucasian man. He developed tingling, numbness, and weakness of his upper and lower extremities with acute neurological deficits after five weeks of a combination therapy with PEG-interferon α2a and ribavirin for chronic hepatitis C virus infection. His clinical course, neurological findings, and his electromyogram results were all consistent with acute inflammatory demyelinating polyneuropathy. Our patient recovered completely after interferon was stopped and symptomatic treatment and a further electromyogram showed a disappearance of neuropathy. Four weeks later, PEG-interferon α2a was reintroduced with a gradually increasing dose without any reappearance of neurological symptoms allowing hepatitis C seroconversion. Conclusions Recognition of this rare yet possible presentation is important for early and accurate diagnosis and treatment. This case report also suggests that the reintroduction of PEGylated interferon in patients who had presented with acute inflammatory demyelinating polyneuropathy related to interferon α may be safe, but this must be confirmed by further studies.

  3. Demyelination as a Target for Cell-Based Therapy of Chronic Blast-Induced Traumatic Brain Injury

    Science.gov (United States)

    2015-10-01

    associated demyelination, with the goal of testing a therapeutic strategy to enhance remyelination using human glial restricted progenitors (hGRPs; Q...associated demyelination are explored, with the goal of testing a therapeutic strategy to enhance remyelination that uses glial restricted progenitors

  4. A randomised, double-blinded, placebo-controlled trial of the effect of subcuta-neous immunoglobulin on muscular performance in chronic inflammatory de-myelinating polyneuropathy

    DEFF Research Database (Denmark)

    Harbo, Thomas; Markvardsen, Lars Høj; Sindrup, Søren Hein;

    Objectives: Subcutaneous treatment with large amounts of immunoglobulins is feasible and effective in multifocal motor neuropathy and has been reported in a few cases in chronic inflammatory demyelinating polyneuropathy (CIDP). We hypothesized that the effect of subcutaneous treatment with immuno......Objectives: Subcutaneous treatment with large amounts of immunoglobulins is feasible and effective in multifocal motor neuropathy and has been reported in a few cases in chronic inflammatory demyelinating polyneuropathy (CIDP). We hypothesized that the effect of subcutaneous treatment...... with immunoglobulins (SCIG) on muscular performance is superior to placebo and equals the effect of intravenous infusion (IVIG). Methods: Subjects with motor involvement in maintenance therapy with IVIG fulfilling the EFNS/PNS criteria for CIDP, aged 18 - 80 years were considered for participation. Exclusion criteria...

  5. A randomized, double-blind, placebo-controlled trial of the effect of subcutaneous immunoglobulin on muscular performance in chronic inflammatory demyelinating polyneuropathy

    DEFF Research Database (Denmark)

    Markvardsen, Lars Høj; Harbo, Thomas; Sindrup, Søren Hein;

    We hypothesized that subcutaneous administration of immunoglobulins (SCIG) in chronic inflammatory demyelinating polyneuropathy (CIDP) is feasible and safe and superior to treatment with saline for the performance of muscle strength. Patients with motor involvement in maintenance therapy with int......We hypothesized that subcutaneous administration of immunoglobulins (SCIG) in chronic inflammatory demyelinating polyneuropathy (CIDP) is feasible and safe and superior to treatment with saline for the performance of muscle strength. Patients with motor involvement in maintenance therapy...... with intravenous immunoglobulin (IVIg) fulfilling the EFNS/PNS criteria for CIDP, aged 18-80 years, were randomised either to SCIG at a dose determined from their pre-study IVIg dose or to subcutaneous saline given twice or thrice weekly for 12 weeks at home. At the start and end of the trial, as well as two weeks...... of immunoglobulins in CIDP is feasible, safe and effective and seems an attractive alternative to IVIg....

  6. Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial

    OpenAIRE

    Hughes, Richard; Donofrio, Peter; Bril, Vera; Dalakas, Marinos; Deng, Chunqin; Hanna, Kim; Hartung, H P; Latov, Norman; Merkies, Ingemar; van Doorn, Pieter

    2008-01-01

    textabstractBackground: Short-term studies suggest that intravenous immunoglobulin might reduce disability caused by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) but long-term effects have not been shown. We aimed to establish whether 10% caprylate-chromatography purified immune globulin intravenous (IGIV-C) has short-term and long-term benefit in patients with CIDP. Methods: 117 patients with CIDP who met specific neurophysiological inflammatory neuropathy cause and treat...

  7. 慢性炎性脱髓鞘性多发性神经病的治疗进展%Therapeutic advance of chronic inflammatory demyelinating polyneuropathy

    Institute of Scientific and Technical Information of China (English)

    张兴文; 崔丽英

    2005-01-01

    慢性炎性脱髓鞘性多发性神经病(chronic inflammatory demyelinating polyradiculopathy,CIDP)是一种获得性的免疫介导的周围神经病.临床特征包括进展性或复发性的肢体无力、感觉缺失和腱反射消失等.

  8. A diagnosis challenge-L4 nerve root compression as the initial presentation of chronic inflammatory demyelinating polyneuropathy.

    Science.gov (United States)

    Cojocaru, Inimioara Mihaela; Alexianu, Marilena; Bastian, Alexandra; Sapira, Violeta; Herţea, Cristina; Cojocaru, M

    2012-01-01

    The authors present the case of a 65-year-old woman who was admitted for paraparesis and paresthesias in the inferior limbs. The neurological examination revealed the difficulty in extension of the right foot and of the right toe, accompanied by paresthesias located in the anterolateral area of the right leg, dorsum and plantar area of the foot, the reduction of the right knee jerk, and of the ankle tendon jerk both sides. The vertebro-spinal MRI showed lumbar canal stenosis with L4 intraforaminal compression on the right, and L2-L3 on the left. CSF examination revealed mild increase in protein concentration. The morphological picture of the sural nerve biopsy was compatible with a chronic inflammatory neuropathy and severe muscular lesions of neurogenic origin were observed on right gastrocnemius muscle biopsy. The diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) was established. Solu-medrol (0.5 g/d)-5 days, then medrol (prednisolone) was done, followed by improving of the symptomatology. For the relapse of the disease intravenous immunoglobulins (IVIG)-0.4 g/kg/d-5 days was the elective treatment. Six months later she presented a new relapse. IVIG were administered with the remission of the sensitive symptoms. A chronic treatment with medrol was recommended. The diagnosis of L4 disc herniation was obvious in the studied case, but the electroneurographic examination brought extra data for the associated diagnosis of CIDP whose onset was asymmetrical and initially paucisymptomatic. Neither the electroneurographic examination nor the CSF examination were total relevant for CIDP, imposing the sural nerve biopsy. The diagnosis of CIDP involves a team-work composed of neurologist, electroneurophysiologist and neuropathologist.

  9. A current view of the diagnosis, clinical variants, response to treatment and prognosis of chronic inflammatory demyelinating polyradiculoneuropathy.

    Science.gov (United States)

    Viala, Karine; Maisonobe, Thierry; Stojkovic, Tanya; Koutlidis, Régine; Ayrignac, Xavier; Musset, Lucile; Fournier, Emmanuel; Léger, Jean-Marc; Bouche, Pierre

    2010-03-01

    We retrospectively analyzed 146 patients fulfilling the European Federation of Neurological Societies and the Peripheral Nerve Society (EFNS/PNS) criteria for definite chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) to (1) evaluate the relevance of these criteria, (2) assess the frequency of CIDP variants, and (3) determine the response to treatment and the prognosis. We found that 75% of these patients fulfilled the main EFNS/PNS clinical and electrophysiological criteria (type I). The remaining patients were diagnosed using laboratory tools as supportive criteria. The common form of CIDP represented 51% of patients. We observed a high frequency of the sensory variant (35% of patients) and the rapid onset form (18%). A positive response to treatment was observed in 87% of patients, with a similar efficacy of prednisone and IVIg. However, in the long term, 40% of treated patients remained dependent on treatment. The IVIg dependency rate was higher than the prednisone or plasma exchange dependency rate (55%, 18%, and 23%, respectively; p = 0.0054). Severe handicap was observed in 24% of patients.

  10. Impairment of circulating CD4+CD25+ regulatory T cells in patients with chronic inflammatory demyelinating polyradiculoneuropathy.

    Science.gov (United States)

    Chi, Li-Jun; Wang, Hua-Bing; Wang, Wei-Zhi

    2008-03-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated peripheral nervous system disease. CD4+CD25+ T regulatory cells (Tregs) have been unequivocally shown to be critical in maintaining immune tolerance and preventing auto-immune diseases by suppressing self-reactive T cells. Thus, we hypothesized that the numbers and/or the function of Tregs would be deranged during the progressive or relapse phases of CIDP. The number of Tregs was determined by flow cytometry according to their characteristic CD4+CD25(high) membrane phenotype. Functional characterization of Tregs was analyzed by suppression of proliferation and secretion of cytokines by co-cultured effector CD4+CD25- T cells. FOXP3 message expression level was assessed by quantitative real-time polymerase chain reaction. The results showed significant reduction in both the number and the suppressive function of Tregs in the patients with CIDP compared with healthy controls. Also, Tregs isolated from CIDP patients expressed lower levels of FoxP3 mRNA. During the progressive or the relapsing phases of CIDP, the number of Tregs was reduced, and the suppressive function of them decreased. These findings may be helpful to our understanding of the possible role of Tregs in the pathogenesis of CIDP.

  11. Subcutaneous vs intravenous administration of immunoglobulin in chronic inflammatory demyelinating polyneuropathy: an Italian cost-minimization analysis.

    Science.gov (United States)

    Lazzaro, Carlo; Lopiano, Leonardo; Cocito, Dario

    2014-07-01

    Prior researches have suggested that home-based subcutaneous immunoglobulin (SCIG) is equally effective and can be less expensive than hospital-based intravenous immunoglobulin (IVIG) in treating chronic inflammatory demyelinating polyneuropathy (CIDP) patients. This economic evaluation aims at comparing costs of SCIG vs IVIG for CIDP patients in Italy. A 1-year model-based cost-minimization analysis basically populated via neurologists' opinion was undertaken from a societal perspective. Health care resources included immunoglobulin; drugs for premedication and complications (rash, headache, and hypertension) management; time of various health care professionals; pump for SCIG self-administration; infusion disposables. Non-health care resources encompassed transport and parking; losses of working and leisure time for patients and caregivers. Unit or yearly costs for resources valuation were mainly obtained from published sources. Costs were expressed in Euro () 2013. An extensive one-way sensitivity analysis (OWSA) and a scenario SA tested the robustness of the base case findings. Overall costs per patient amount to 49,534.75 (SCIG) and 50,895.73 (IVIG); saving in favour of SCIG reaches 1360.98. For both SCIG and IVIG, the cost driver was immunoglobulin (94.06 vs 86.06 % of the overall costs, respectively). Sensitivity analyses confirmed the consistency of the baseline results. SCIG may be a cost-saving therapy for Italian CIDP patients.

  12. Acquired versus familial demyelinative neuropathies in children.

    Science.gov (United States)

    Miller, R G; Gutmann, L; Lewis, R A; Sumner, A J

    1985-01-01

    The electrophysiologic differences between chronic acquired demyelinative neuropathy and the demyelinative form of Charcot-Marie-Tooth disease have recently been reported. The present report extends these observations to include the genetically determined demyelinating neuropathies seen in metachromatic leukodystrophy, Krabbe's leukodystrophy, and Cockayne's syndrome. The electrophysiologic features of metachromatic leukodystrophy (five patients), Krabbe's (four patients), and Cockayne's syndrome (three patients) were all similar. There was uniform slowing of conduction (both in different nerves and in different nerve segments), and conduction block was not seen. These findings are consistent with a uniform degree of demyelination in multiple nerves and throughout the entire length of individual axons. Thus, uniform slowing of nerve conduction constitutes strong evidence for a familial demyelinative neuropathy, as opposed to the multifocal slowing seen in acute and chronic acquired demyelinative neuropathy.

  13. [Topics of chronic inflammatory demyelinating polyradiculoneuropathy--diagnosis and treatment situation in Japan].

    Science.gov (United States)

    Iijima, Masahiro

    2013-05-01

    CIDP is a motor and sensory neuropathy characterized by chronic, step-wised, or relapsing progression. Both cellular and humoral autoimmunity targeting the myelin sheath is assumed as the main mechanism of CIDP pathogenesis. While the AAN diagnostic criteria have been the main method in Japan, the EFNS/PNS criteria recently replaced them because of their good diagnostic sensitivity and clinical superiority. The first-line therapy for CIDP patients in Japan is intravenous immunoglobulin (IVIg), corticosteroids, and phasmapheresis, the same as in other countries. Regarding therapeutics, two major differences between Japan and other countries exist. Firstly, while half-dose IVIg (1 g/kg body weight) every three weeks was established as maintenance therapy as a result of the ICE study in 2008, full-dose IVIg (2 g/kg body weight over five days) once a month is still accepted in Japan for highly recurrent patients. Secondly, Japanese clinicians prefer immune adsorption plasmapheresis (IAPP) instead of plasma exchange (PE) among three types of plasmapheresis (IAPP, PE, and double-filtered plasmapheresis [DFPP]). These differences could be due to the characteristic and independent health insurance system in Japan. Using recent knowledge and diagnostic criteria, clinical trials have been based on these global platforms. Recently, efforts have been made to share these platforms with a worldwide vision.

  14. Chronic inflammatory demyelinating polyneuropathy due to the administration of pegylated interferon α-2b: a neuropathology case report.

    Science.gov (United States)

    Shiga, Kensuke; Tanaka, Eijiroh; Isayama, Reina; Mizuno, Toshiki; Itoh, Kyoko; Nakagawa, Masanori

    2012-01-01

    We report a 35-year-old man who developed weakness in his extremities five months after pegylated interferon α (IFNα)-2b was administered. The serum tumor necrosis factor-α (TNFα) was elevated and nerve conduction studies revealed demyelination both in the distal and intermediate segments. The sural nerve pathology showed mild demyelinating process. The cessation of IFNα and administration of intravenous immunoglobulin improved both his clinical symptoms and the temporal dispersion in motor nerve conduction study. IFNα-induced CIDP is presumably a transient immunological condition that requires immunomodulatory therapy. The elevated serum TNFα may implicate the degree of downstream autoimmunity induced by IFNα.

  15. The characteristics of chronic inflammatory demyelinating polyneuropathy in patients with and without diabetes--an observational study.

    Directory of Open Access Journals (Sweden)

    Samantha K Dunnigan

    Full Text Available INTRODUCTION: We aimed to determine whether the clinical characteristics and electrodiagnostic classification of nerve injury, and response to treatment differed in patients diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP with and without diabetes. METHODS: CIDP patients with diabetes (CIDP+DM (n = 67 and without diabetes (CIDP-DM (n = 67 underwent clinical examination and nerve conduction studies (NCS. CIDP-DM patients were selected using age and gender matching with the existing CIDP+DM cohort. Patients treated with immunotherapies were classified as responders (R (n = 46 or non-responders (NR (n = 54 based on clinical response to treatment. The groups were compared using analysis of variance, contingency tables and Kruskal-Wallis analyses. RESULTS: CIDP+DM subjects had more severe neuropathy based on higher lower limb vibration potential thresholds (VPT(p = 0.004, higher Toronto Clinical Neuropathy Score (TCNS (p = 0.0009, more proximal weakness (p = 0.03, more gait abnormality (p = 0.03 and more abnormal NCS. CIDP+DM subjects had more abnormal sural NCS with lower sural sensory nerve action potential amplitudes (2.4±3.0 µV, 6.6±6.0 µV, p<0.0001 and slower sural nerve conduction velocities (38.6±5.4 m/s, 41.0±5.3 m/s, p = 0.04. CIDP-DM subjects were more likely to receive immune therapies (93% vs 57%, p = <0.0001, despite no significant differences in treatment responder rates (p = 0.71. Patients who responded to therapy had shorter duration of CIDP than non-responders (8.0±6.0 y vs 11.9±7.6 y, p = 0.004. DISCUSSION: The clinical phenotype and electrophysiological profile of CIDP patients differs according to the presence or absence of diabetes. Despite CIDP+DM patients having more severe clinical and electrophysiological neuropathy, they are less likely to receive disease-modifying/specific therapy, yet have similar response rates to treatment as those without

  16. Electrotonic potentials in simulated chronic inflammatory demyelinating polyneuropathy at 20°C-42°C.

    Science.gov (United States)

    Stephanova, D I; Daskalova, M

    2015-06-01

    Threshold electrotonus changes have been studied following warming to 37°C and cooling to 25°C in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). To extend the tracking of these changes also during hypothermia (≤ 25°C) and hyperthermia (≥ 40°C), and to explain their mechanisms, we investigate the effects of temperature (from 20°C to 42°C) on polarizing nodal and internodal electrotonic potentials and their current kinetics in previously simulated case of 70% CIDP. The computations use our temperature-dependent multi-layered model of the myelinated human motor nerve fiber. While the changes of electrotonic potentials and their current kinetics are largely similar for the physiological range of 28-37°C, they are altered during hypothermia and hyperthermia in the normal and CIDP cases. The normal (at 37°C) resting membrane potential is further depolarized or hyperpolarized during hypothermia or hyperthermia, respectively, and the internodal current types defining these changes are the same for both cases. Unexpectedly, our results show that in the CIDP case, the lowest and highest critical temperatures for blocking of electrotonic potentials are 20°C and 39°C, while in the normal case the highest critical temperature for blocking of these potentials is 42°C. In the temperature range of 20-39°C, the relevant potentials in the CIDP case, except for the lesser value (at 39°C) in hyperpolarized resting membrane potential, are modified: (i) polarizing nodal and depolarizing internodal electrotonic potentials and their defining currents are increased in magnitude; (ii) inward rectifier (I IR ) and leakage (I Lk ) currents, defining the hyperpolarizing internodal electrotonic potential, are gradually increased with the rise of temperature from 20°C to 39°C, and (iii) the accommodation to long-lasting hyperpolarization is greater than to depolarization. The present results suggest that the electrotonic potentials in patients with

  17. Demyelination as a Target for Cell-Based Therapy of Chronic Blast-Induced Traumatic Brain Injury

    Science.gov (United States)

    2015-10-01

    disabling behavioral and cognitive abnormalities noted in significant number of combat veterans. These clinical phenotypes suggest impairment in...associated demyelination, with the goal of testing a therapeutic strategy to enhance remyelination using human glial restricted progenitors (hGRPs; Q... abnormalities noted in significant number of combat veterans. These clinical phenotypes suggest impairment in distributed cerebral functions dependent on the

  18. The Oligodendrocyte Progenitor Response to Demyelination

    Science.gov (United States)

    2006-01-01

    most prevalent demyelinating disease, remyelination becomes limited with repeated or chronic episodes of demyelination (Ozawa et al., 1994). Factors...mice exhibit deformity of the spinal cord ( scoliosis ) and die within the first few postnatal weeks. Therefore, this study used heterozygous hPDGF-A tg

  19. Tumefactive Brain Demyelination Accompanying MADSAM Neuropathy

    Directory of Open Access Journals (Sweden)

    Şefik Evren Erdener

    2015-09-01

    Full Text Available Multifocal acquired demyelinating sensory and motor (MADSAM neuropathy is characterized by asymmetric multifocal motor and sensory loss and conduction blocks in peripheral nerves. Peripheral demyelinating diseases may be accompanied by demyelination in central nervous system (CNS. In this report, a MADSAM patient with a solitary tumefactive demyelinating lesion in brain is presented. Neuroimaging due to a visual field defect revealed a right parietooccipital lesion, which was initially misdiagnosed as a tumor. Pathological examination showed that it was demyelinating in nature. Peripheral nervous symptoms of the patient developed two years later and she was then diagnosed with MADSAM. There was prominent clinical and electrophysiological response to steroid treatment. Tumefactive brain involvement was not previously reported for MADSAM neuropathy, although it was documented in a single case with typical chronic inflammatory demyelinating polyneuropathy (CIDP. CNS involvement should therefore be considered in MADSAM patients.

  20. Delayed functional expression of neuronal chemokine receptors following focal nerve demyelination in the rat: a mechanism for the development of chronic sensitization of peripheral nociceptors

    Directory of Open Access Journals (Sweden)

    Monahan Patrick E

    2007-12-01

    Full Text Available Abstract Background Animal and clinical studies have revealed that focal peripheral nerve axon demyelination is accompanied by nociceptive pain behavior. C-C and C-X-C chemokines and their receptors have been strongly implicated in demyelinating polyneuropathies and persistent pain syndromes. Herein, we studied the degree to which chronic nociceptive pain behavior is correlated with the neuronal expression of chemokines and their receptors following unilateral lysophosphatidylcholine (LPC-induced focal demyelination of the sciatic nerve in rats. Results Focal nerve demyelination increased behavioral reflex responsiveness to mechanical stimuli between postoperative day (POD 3 and POD28 in both the hindpaw ipsilateral and contralateral to the nerve injury. This behavior was accompanied by a bilateral increase in the numbers of primary sensory neurons expressing the chemokine receptors CCR2, CCR5, and CXCR4 by POD14, with no change in the pattern of CXCR3 expression. Significant increases in the numbers of neurons expressing the chemokines monocyte chemoattractant protein-1 (MCP-1/CCL2, Regulated on Activation, Normal T Expressed and Secreted (RANTES/CCL5 and interferon γ-inducing protein-10 (IP-10/CXCL10 were also evident following nerve injury, although neuronal expression pattern of stromal cell derived factor-1α (SDF1/CXCL12 did not change. Functional studies demonstrated that acutely dissociated sensory neurons derived from LPC-injured animals responded with increased [Ca2+]i following exposure to MCP-1, IP-10, SDF1 and RANTES on POD 14 and 28, but these responses were largely absent by POD35. On days 14 and 28, rats received either saline or a CCR2 receptor antagonist isomer (CCR2 RA-[R] or its inactive enantiomer (CCR2 RA-[S] by intraperitoneal (i.p. injection. CCR2 RA-[R] treatment of nerve-injured rats produced stereospecific bilateral reversal of tactile hyperalgesia. Conclusion These results suggest that the presence of chemokine

  1. A case of a 17-year-old male with neurofascin-155 antibody-positive chronic inflammatory demyelinating polyradiculoneuropathy presenting with tremor and ataxia.

    Science.gov (United States)

    Itaya, Kazuhiro; Inoue, Manabu; Iizuka, Natsuko; Shimizu, Yuki; Yuki, Nobuhiro; Ichikawa, Hiroo

    2016-09-29

    A 17-year-old male with no medical history noticed weakness of his limbs with imbalance and subsequent finger tremors. Physical examination revealed features of polyneuropathy, including diffuse weakness, distal symmetrical numbness with impaired deep sensation and areflexia in all limbs. Postural tremor was present in fingers. Ataxia was apparent in both lower limbs, causing a wide-based gait with a positive Romberg sign. Cerebrospinal fluid contained elevated total protein without pleocytosis. A nerve conduction study disclosed demyelinating features with prolonged terminal latencies, slow velocities with delayed F-wave latencies, and prominent temporal dispersion. These findings led to diagnosis of typical chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with notable feature of postural finger tremor and ataxia of unknown cause. These atypical features prompted us to examine neurofascin-155 (NF155) antibodies, which were positive. No significant improvement occurred after initial administration of intravenous immunoglobulin and subsequent plasma exchange. However, corticosteroids with intravenous pulse therapy followed by oral prednisolone significantly improved the symptoms. Patients with CIDP with anti-NF155 antibodies may have similar clinical features and constitute a CIDP subgroup. In such patients, corticosteroids may be more effective than intravenous immunoglobulin. Further studies are needed to define the features of this subgroup and determine effective therapy for CIDP.

  2. [Autopsy case of a patient with Charcot-Marie-Tooth disease type 1A and suspected chronic inflammatory demyelinating polyradiculoneuropathy, which was later diagnosed as amyotrophic lateral sclerosis].

    Science.gov (United States)

    Higuchi, Yujiro; Sakiyama, Yusuke; Nishihira, Yasushi; Endo, Kazuhiro; Suwazono, Shugo; Suehara, Masahito

    2012-01-01

    We report an autopsy case of a 74-year-old man with late onset Charcot-Marie-Tooth disease type 1A (CMT1A) diagnosed by genetic screening, later associated with amyotrophic lateral sclerosis (ALS). At the age of 70 years, the patient was admitted to our hospital because of progressive weakness and dysesthesia in the right upper limb. In the early stages of the illness, he was diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and transient improvement was achieved with intravenous immunoglobulin. However, the symptoms progressively worsened and became refractory. Gene analysis revealed PMP22 gene duplication, which confirmed CMT1A. On sural nerve biopsy, severe demyelinating neuropathy and abundant onion-bulb formations with endoneurial infiltration of inflammatory cells were observed. Thereafter, pseudo-bulbar palsy and respiratory muscle weakness developed insidiously and progressed rapidly along with muscle weakness in the limbs and trunk. The patient died about four years after the onset of this disease. Postmortem examination showed moderate neuronal cell loss, Bunina bodies, and TDP-43-positive inclusions in the anterior horn cells. The spinal cord revealed axonal loss and extensive macrophage permeation in the corticospinal tracts. On the basis of these findings, the final neuropathological diagnosis was ALS. This is the first report of an autopsy case of CMT1A complicated with ALS. We here discuss the significant clinical and neuropathological findings of this case.

  3. 慢性炎性脱髓鞘性多发性神经病的药物治疗现状%Current Medical Treatment of Chronic Inflammatory Demyelinating Polyradiculopathy

    Institute of Scientific and Technical Information of China (English)

    陈远春

    2010-01-01

    @@ 慢性炎性脱髓鞘性多发性神经病(Chronic inflammatory demyelinating polyradiculopathy,CIDP)是一种获得性的周围神经脱髓鞘性疾病,以反复发作的肌无力为特征,可伴感觉缺失和腱反射消失等.

  4. Transcriptome Analysis of Peripheral Blood in Chronic Inflammatory Demyelinating Polyradiculoneuropathy Patients Identifies TNFR1 and TLR Pathways in the IVIg Response.

    Science.gov (United States)

    Richard, Alexandra; Corvol, Jean-Christophe; Debs, Rabab; Reach, Pauline; Tahiri, Khadija; Carpentier, Wassila; Gueguen, Justine; Guillemot, Vincent; Labeyrie, Céline; Adams, David; Viala, Karine; Cohen Aubart, Fleur

    2016-05-01

    We have studied the response to intravenous immunoglobulins (IVIg) by a transcriptomic approach in 11 chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients (CIDP duration = 6 [0.83-6.5] years). RNA was extracted from cells in whole blood collected before and 3 weeks after IVIg treatment, and hybridized on Illumina chips. After RNA quality controls, gene expression was analyzed using statistical tests fitted for microarrays (R software, limma package), and a pathway analysis was performed using DAVID software. We identified 52 genes with expression that varied significantly after IVIg (fold change [FC] > 1.2, P CIDP pathophysiology and the response to IVIg. We conclude that responder patients have stronger inflammatory activity that is lessened by IVIg.

  5. Studies of HLA associations in male and female patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

    Science.gov (United States)

    McCombe, Pamela A; Csurhes, Peter A; Greer, Judith M

    2006-11-01

    HLA associations are found to differ with the gender of the patient in some autoimmune diseases. Here we have investigated whether there are gender-related HLA associations in Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), both of which occur more frequently in male patients than in females. In GBS, no particular HLA associations were noted, except for a slight negative association in both males and females for carriage of HLA-DR5. In CIDP, the gene frequency and the frequency of individuals positive for HLA-DR2 were greater in female patients than female controls, although this was statistically significant only for the gene frequency. Furthermore more female CIDP patients were homozygous for DR2, than male CIDP patients, or male or female controls and patients with GBS. This suggests that sex-related factors may interact with the risk associated with carriage of HLA-DR2 for development of CIDP.

  6. Epstein-Barr virus antibodies in serum and cerebrospinal fluid from multiple sclerosis, chronic inflammatory demyelinating polyradiculoneuropathy and amyotrophic lateral sclerosis.

    Science.gov (United States)

    Nociti, V; Frisullo, G; Marti, A; Luigetti, M; Iorio, R; Patanella, A K; Bianco, A; Tonali, P A; Grillo, R L; Sabatelli, M; Batocchi, A P

    2010-08-25

    Elevated anti-Epstein-Barr virus (EBV) antibody levels are present in serum of Multiple sclerosis (MS) patients but literature lacks of studies comparing anti-EBV antibody levels between MS and other neurological diseases. We evaluate anti-VCA IgG and IgM, anti-EBNA1 IgG, anti-Cytomegalovirus IgG and IgM titres in serum and cerebrospinal fluid (CSF) of 267 MS, 50 Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) and 88 Amyotrophic Lateral Sclerosis (ALS) patients. We found increased titres of anti-EBV-IgG in serum and CSF of MS subjects as compared to CIDP and ALS patients thus providing additional evidence for a possible involvement of EBV in MS.

  7. Mechanisms of action of IVIg and therapeutic considerations in the treatment of acute and chronic demyelinating neuropathies.

    Science.gov (United States)

    Dalakas, Marinos C

    2002-12-24

    Intravenous immunoglobulin (IVIg) is an immunomodulating agent that has multiple activities, including modulation of complement activation products, suppressing idiotypic antibody, saturating Fc receptors on macrophages, and suppressing various inflammatory mediators including cytokines, chemokines, and metalloproteinases. Because all these factors are implicated to various degrees in the pathogenesis of immune-mediated demyelination of the PNS, administration of IVIg could be beneficial in treating neuropathies by suppressing the immune-mediated processes that are directed against myelin or axonal antigenic targets. This article outlines the actions of IVIg in CIDP and other autoimmune neuropathies based on data derived from in vivo and in vitro studies. The predominant mechanisms by which IVIg exerts its action on these neuropathies appear to be a combined effect on complement inactivation, neutralization of idiotypic antibodies, cytokine inhibition, and saturation of Fc receptors on endoneurial macrophages.

  8. The Role of Tissue Macrophage-Mediated Inflammation on NAFLD Pathogenesis and Its Clinical Implications

    Science.gov (United States)

    Carpino, Guido; Oliveira, Felipe L.; Panera, Nadia

    2017-01-01

    The obese phenotype is characterized by a state of chronic low-grade systemic inflammation that contributes to the development of comorbidities, including nonalcoholic fatty liver disease (NAFLD). In fact, NAFLD is often associated with adipocyte enlargement and consequent macrophage recruitment and inflammation. Macrophage polarization is often associated with the proinflammatory state in adipose tissue. In particular, an increase of M1 macrophages number or of M1/M2 ratio triggers the production and secretion of various proinflammatory signals (i.e., adipocytokines). Next, these inflammatory factors may reach the liver leading to local M1/M2 macrophage polarization and consequent onset of the histological damage characteristic of NAFLD. Thus, the role of macrophage polarization and inflammatory signals appears to be central for pathogenesis and progression of NAFLD, even if the heterogeneity of macrophages and molecular mechanisms that govern their phenotype switch remain incompletely understood. In this review, we discuss the role of adipose and liver tissue macrophage-mediated inflammation in experimental and human NAFLD. This focus is relevant because it may help researchers that approach clinical and experimental studies on this disease advancing the knowledge of mechanisms that could be targeted in order to revert NAFLD-related fibrosis.

  9. European Federation of Neurological Societies Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society (Reprinted from Journal of the Peripheral Nervous System, vol 10, pg 220-228, 2005)

    NARCIS (Netherlands)

    R.A.C. Hughes; P. Bouche; D.R. Cornblath; E. Evers; R.D.M. Hadden; A. Hahn; I. Illa; C.L. Koski; J.M. Leger; E. Nobile-Orazio; J. Pollard; C. Sommer; P. van den Bergh; P.A. van Doorn; I.N. van Schaik; M.M. Mehndiratta; R. Hughes; J.B. Winer; R. de Haan; M. Vermeulen; P. Agarwal

    2006-01-01

    Numerous sets of diagnostic criteria have sought to define chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and randomized trials and systematic reviews of treatment have been published. The objective is to prepare consensus guidelines on the definition, investigation and treatment o

  10. pSTAT1, pSTAT3, and T-bet as markers of disease activity in chronic inflammatory demyelinating polyradiculoneuropathy.

    Science.gov (United States)

    Madia, Francesca; Frisullo, Giovanni; Nociti, Viviana; Conte, Amelia; Luigetti, Marco; Del Grande, Alessandra; Patanella, Agata Katia; Iorio, Raffaele; Tonali, Pietro Attilio; Batocchi, Anna Paola; Sabatelli, Mario

    2009-06-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is considered an auto-immune disorder. We evaluated expression of pSTAT1, T-bet, and pSTAT3 in circulating T-cells, B-cells, and monocytes and spontaneous production of interleukin-17 (IL17), interferon-gamma (IFN gamma), and interleukin-10 (IL10) by peripheral blood mononuclear cells (PBMCs) from 14 active CIDP patients compared with 6 patients with long-lasting remission and 20 controls. Active disease patients showed higher pSTAT1, T-bet, and pSTAT3 in CD4(+) T-cells than controls (p CIDP patients than controls (p = 0.0011, p = 0.0041, p = 0.0413, respectively) and remission patients (p = 0.0073, p = 0.0274, p = 0.0251, respectively). Moreover in CD8(+) T-cells, pSTAT3 expression was higher in active CIDP patients than in remission patients (p = 0.0345) and in controls (p = 0.0023). IL17 and IFN gamma production were significantly higher in active CIDP patients than in controls (p CIDP patients (p = 0.0073). IL10 levels were higher in active phase patients than in controls (p = 0.0334). Our data suggest that pSTAT1, T-bet, and pSTAT3 can be considered putative markers of disease activity and potential targets for specific therapies.

  11. Understanding the consequences of chronic inflammatory demyelinating polyradiculoneuropathy from impairments to activity and participation restrictions and reduced quality of life: the ICE study.

    Science.gov (United States)

    Merkies, Ingemar S J; Hughes, Richard A C; Donofrio, Peter; Bril, Vera; Dalakas, Marinos C; Hanna, Kim; Hartung, Hans-Peter; Latov, Norman; van Doorn, Pieter A; Deng, Chunqin

    2010-09-01

    A randomized trial (ICE trial) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) demonstrated significantly more improvement with intravenous immunoglobulin (Gamunex(®), Talecris Biotherapeutics, Inc., Research Triangle Park, NC) than placebo. To understand the relationship between CIDP impairments, activity and participation restrictions, and quality of life (QoL) in this trial, we investigated the association between scales representing these outcome levels. Gamunex or placebo was given every 3 weeks for up to 24 weeks to 117 patients in an initial treatment period after which treatment failures were crossed over (alternative treatment). We assessed impairments, activity and participation, and SF-36 component mental (MCS) and physical summaries (PCS). Regression analyses of baseline data were performed (all subjects) and change from baseline to endpoint (Gamunex-treated group only) to determine correlations between outcomes. Grip strength, medical research council (MRC) sum score, and inflammatory neuropathy cause and treatment (INCAT) sensory sum score were the strongest explanatory variables of disability (at baseline: r(2) = 0.46; change from baseline: r(2) = 0.66). Only up to half of the variance in QoL scores (PCS at baseline: r(2) = 0.30; change from baseline: r(2) = 0.41; MCS: at baseline: r(2) = 0.10; change from baseline: r(2) = 0.24) was explained by impairment and activity and participation measures. Future studies are required to elucidate the impact of CIDP on disability and QoL changes, because the obtained correlations provide only partial explanation.

  12. Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) associated to hereditary neuropathy with liability to pressure palsies (HNPP) and revealed after influenza AH1N1 vaccination.

    Science.gov (United States)

    Remiche, Gauthier; Abramowicz, Marc; Mavroudakis, Nicolas

    2013-12-01

    Neurological complications of AH1N1 vaccination such as Guillain-Barré syndrome were described in the previous years. Several reports suggest that hereditary neuropathies may be a predisposing factor for immune-mediated neuropathies. We report the case of a 54-year-old female who developed chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) 5 weeks after AH1N1 vaccination. She had no previous neurological history, but neurophysiological features led us to suspect an underlying hereditary neuropathy. PMP22 gene analysis showed a typical deletion, confirming the diagnosis of hereditary neuropathy with liability to pressure palsies (HNPP). We observed a significant clinical and neurophysiological improvement of the neuropathy after intravenous immunoglobulin treatment. This is, to our knowledge, the first reported case of CIDP potentially triggered by AH1N1 vaccination. This and previous observations suggest that genetic-determined neuropathies could predispose to the occurrence of immune-mediated neuropathies. One must recall the possibility of a superimposed hereditary neuropathy like HNPP in patients with a clinical presentation of CIDP, especially when positive family history or unexpected neurophysiological features are present.

  13. Paraneoplastic brainstem encephalomyelitis and atypical form of chronic inflammatory demyelinating polyneuropathy in patient with testicular germinal tumor-is this an overlap syndrome? a case report.

    Science.gov (United States)

    Gogol, Paweł; Gogol, Anna; Opuchlik, Andrzej; Dziewulska, Dorota

    2015-01-01

    Paraneoplastic neurologic syndromes are diagnosed when neurologic symptoms are associated with neoplasm and other causative factors are excluded. They may precede or be simultaneous to various types of neoplasms, mainly malignant. In men up to 45-50 years old the most common cancer causing the paraneoplastic syndrome is testicle tumor, manifesting usually as limbic/brain stem encephalitis and myelitis. Usually effective treatment of underlying neoplasm brings resolution of neurologic symptoms. But corticosteroids and intravenuous immunoglobulins are also used. In the presented case a 37-year-old man was primarily diagnosed and treated for progressive tetraparesis with signs of both upper and lower motor neuron dysfunction, associated with bulbar symptoms. Having various diagnostic procedures performed an atypical form of chronic inflammatory demyelinating polyradiculoneuronopathy was primarily suspected, but eventually a discovery of endodermal sinus tumor in the testicle enabled to state the diagnosis of possible paraneoplastic syndrome. In spite of chemotherapy the patient died shortly after the diagnosis because of infectious complications. Histopathology displayed intense inflammatory changes in the brain stem as well as in cranial nerves and cervical spinal cord. The same immunological process evoked by various pathogenetic factors (infection vs. neoplasm) may cause similar clinical picture and hinder the diagnosis. Most importantly it may delay the proper way of treatment.

  14. Cost-utility of Intravenous Immunoglobulin (IVIG compared with corticosteroids for the treatment of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP in Canada

    Directory of Open Access Journals (Sweden)

    Campbell Kaitryn

    2010-06-01

    Full Text Available Abstract Objectives Intravenous immunoglobulin (IVIG has demonstrated improvement in chronic inflammatory demyelinating polyneuropathy (CIDP patients in placebo controlled trials. However, IVIG is also much more expensive than alternative treatments such as corticosteroids. The objective of the paper is to evaluate, from a Canadian perspective, the cost-effectiveness of IVIG compared to corticosteroid treatment of CIDP. Methods A markov model was used to evaluate the costs and QALYs for IVIG and corticosteroids over 5 years of treatment for CIDP. Patients initially responding to IVIG could remain a responder or relapse every 12 week model cycle. Non-responding IVIG patients were assumed to be switched to corticosteroids. Patients on corticosteroids were at risk of a number of adverse events (fracture, diabetes, glaucoma, cataract, serious infection in each cycle. Results Over the 5 year time horizon, the model estimated the incremental costs and QALYs of IVIG treatment compared to corticosteroid treatment to be $124,065 and 0.177 respectively. The incremental cost per QALY gained of IVIG was estimated to be $687,287. The cost per QALY of IVIG was sensitive to the assumptions regarding frequency and dosing of maintenance IVIG. Conclusions Based on common willingness to pay thresholds, IVIG would not be perceived as a cost effective treatment for CIDP.

  15. Polirradiculoneuropatia desmielinizante inflamatória crônica: estudo de 18 pacientes Chronic inflammatory demyelinating polyradiculoneuropathy: study of 18 patients

    Directory of Open Access Journals (Sweden)

    Leandro C. Calia

    1997-01-01

    Full Text Available Neste estudo prospectivo, analisamos as características clínicas, evolução e resposta terapêutica de 18 pacientes com a forma idiopática de polirradiculoneuropatia desmielinizante inflamatória crônica, que foram acompanhados por período que variou de 4 a 127 meses. O sexo masculino predominou sobre o feminino (1,25:1 e a idade de início dos sintomas variou de 6 a 85 anos. Observamos a preponderância da forma de evolução progressiva (61,1% sobre a forma recidivante (38,9%, bem como a baixa ocorrência de fatores predisponentes (16,7%. Todos os pacientes apresentavam comprometimento sensitivo e motor, associado a hipo ou arreflexia, enquanto apenas três (16,7% apresentavam comprometimento de nervos cranianos. No exame do liquor, as taxas de proteínas estavam elevadas em 88,9% dos pacientes, com média de 203,4 mg/dl. A eletroneuromiografia mostrou alterações desmielinizantes em todos os pacientes, associadas a alterações axonais em 94,4% deles. Em todos os sete pacientes submetidos a biopsia de nervo sural encontramos alterações compatíveis com desmielinização/remielinização. A análise com imunofluorescência, realizada em três pacientes foi normal em um e evidenciou depósito de anticorpos anti-CD3 em dois e anti-HLA-Dr em um. Optamos pela prednisona como tratamento inicial em todos os pacientes, sendo mantida posteriormente em doses reduzidas e em dias alternados em 72,2% deles. Dois pacientes (11,1% estão assintomáticos mesmo após retirada total da medicação e introduzimos azatioprína, associada ou não ao corticóide, nos quatro pacientes com má resposta à prednisona. Até a última avaliação, 16 pacientes (88,9% evoluíram com melhora funcional.This is a prospective study that describes 18 patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP, idiopathic type. The patients have been followed for a period of 4 to 127 months. We evaluated the clinical characteristics, the evolution

  16. Diffusion tensor imaging can be used to detect lesions in peripheral nerves in patients with chronic inflammatory demyelinating polyneuropathy treated with subcutaneous immunoglobulin

    Energy Technology Data Exchange (ETDEWEB)

    Markvardsen, Lars H.; Andersen, Henning [Aarhus University Hospital, Department of Neurology, Aarhus C (Denmark); Vaeggemose, Michael [Aarhus University Hospital, Department of Neurology, Aarhus C (Denmark); Aarhus University Hospital, Department of Diagnostic Imaging: MR Research Centre, Aarhus (Denmark); Ringgaard, Steffen [Aarhus University Hospital, Department of Diagnostic Imaging: MR Research Centre, Aarhus (Denmark)

    2016-08-15

    Magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) has shown that fractional anisotropy (FA) is lower in peripheral nerves in chronic inflammatory demyelinating polyneuropathy (CIDP). We examined whether DTI correlates to muscle strength or impairment. MRI of sciatic and tibial nerves was performed on 3-T MR scanner by obtaining T2- and DTI-weighted sequences with fat saturation. On each slice of T2-weighted (T2w) and DTI, the tibial and sciatic nerves were segmented and served for calculation of signal intensity. On DTI images, pixel-by-pixel calculation of FA and apparent diffusion coefficient (ADC) was done. Muscle strength at knee and ankle was determined by isokinetic dynamometry and severity of CIDP by neuropathy impairment score (NIS). Fourteen CIDP patients treated with subcutaneous immunoglobulin were compared to gender- and age-matched controls. T2w values expressed as a nerve/muscle ratio (nT2w) were unchanged in CIDP versus controls 0.93 ± 0.21 versus 1.02 ± 0.21 (P = 0.10). FA values were lower in CIDP compared to controls 0.38 ± 0.07 versus 0.45 ± 0.05 (P < 0.0001), and ADC values were higher in CIDP versus controls 1735 ± 232 versus 1593 ± 116 x 10{sup -6} mm{sup 2}/s (P = 0.005). In CIDP, FA values correlated to clinical impairment (NIS) (r = -0.57, P = 0.03), but not to muscle strength. FA value in the sciatic nerve distinguishes CIDP from controls with a sensitivity and a specificity of 92.9 %. CIDP patients have unchanged nT2w values, lower FA values, and higher ADC values of sciatic and tibial nerves compared to controls. FA values correlated to NIS but were unrelated to muscle strength. DTI of sciatic nerves seems promising to differentiate CIDP from controls. (orig.)

  17. Central neuroinvasion and demyelination by inflammatory macrophages after peripheral virus infection is controlled by SHP-1.

    Science.gov (United States)

    Christophi, George P; Massa, Paul T

    2009-12-01

    SHP-1 is a protein tyrosine phosphatase that negatively regulates cytokine signaling and inflammatory gene expression. Mice genetically lacking SHP-1 (me/me) display severe inflammatory demyelinating disease following intracranial inoculation with the BeAn strain of Theiler's murine encephalomyelitis virus (TMEV) compared to infected wild-type mice. Furthermore, SHP-1-deficient mice show a profound and predominant infiltration of blood-derived macrophages into the CNS following intracerebral injection of TMEV, and these macrophages are concentrated in areas of demyelination in brain and spinal cord. In the present study we investigated the role of SHP-1 in controlling CNS inflammatory demyelination following a peripheral instead of an intracerebral inoculation of TMEV. Surprisingly, we found that while wild-type mice were entirely refractory to intraperitoneal (IP) infection by TMEV, in agreement with previous studies, all SHP-1-deficient mice displayed profound macrophage neuroinvasion and macrophage-mediated inflammatory demyelination. Moreover, SHP-1 deficiency led to increased expression of inflammatory molecules in macrophages, serum, and CNS following IP infection with TMEV. Importantly, pharmacological depletion of peripheral macrophages significantly decreased both paralysis and CNS viral loads in SHP-1-deficient mice. In addition, peripheral MCP-1 neutralization attenuated disease severity, decreased macrophage infiltration into the CNS, and decreased monocyte numbers in the blood of SHP-1-deficient mice, implicating MCP-1 as an important mediator of monocyte migration between multiple tissues. These results demonstrate that peripheral TMEV infection results in a unique evolution of macrophage-mediated demyelination in SHP-1-deficient mice, implicating SHP-1 in the control of neuroinvasion of inflammatory macrophages and neurotropic viruses into the CNS.

  18. 慢性炎症性脱髓鞘性多发性神经病的神经电图与肌电图研究%Study the Neural Electrical Diagram and Electromyography in Chronic Inflammatory Demyelinating Multiple Psycho

    Institute of Scientific and Technical Information of China (English)

    杨颖颖

    2016-01-01

    目的:分析在患有慢性炎症脱髓鞘多发神经病患者的临床诊断和治疗中,神经电图与肌电图的相关情况。方法选择我院2015年4月~2016年4月收治的21例慢性炎症脱髓鞘多发神经病患者作为实验的研究组,再选择同期到我院接受体检的正常人作为对照组,对两组对象分别进行神经电图与肌电图检测,分析两组对象的相关指标。结果研究组的各项指标与对照组相比差异具有统计学意义(P<0.05)。结论在慢性炎症脱髓鞘多发神经病患者诊治中,神经电图与肌电图值得应用。%ObjectiveTo analyze the clinical diagnosis and treatment of chronic inflammatory demyelinating polyneuropathy patients,related electroneurography and electromyography.MethodsIn our hospital from April 2015 to April 2016,21 cases of chronic inflammatory demyelinating polyneuropathy patients were treated as experimental study group,normal people over to our hospital for physical examination selected as the control group,the subjects of two groups were electroneurography and electromyography detection,analysis of the relevant indicators of the two groups.Results The indexes compared with the control group,the difference was statisticaly significant(P<0.05). Conclusion In the treatment of chronic inflammatory demyelinating polyneuropathy patients.

  19. Therapeutical Advances in Chronic Inflammatory Demyelinating Polyneuropathy (review)%慢性炎症性脱髓鞘性多发性神经病的治疗进展

    Institute of Scientific and Technical Information of China (English)

    矫毓娟; 张伟赫

    2011-01-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is one of the acquired autoimmune peripheral neuropathy with various therapeutical methods. This article reviewed the therapeutical advances in CIDP.%慢性炎症性脱髓鞘性多发性神经病是一种获得性周围神经自身免疫性疾病,是可治疗的慢性多发性神经病之一.本文就其各种治疗方法作一综述.

  20. Viral induced demyelination.

    Science.gov (United States)

    Stohlman, S A; Hinton, D R

    2001-01-01

    Viral induced demyelination, in both humans and rodent models, has provided unique insights into the cell biology of oligodendroglia, their complex cell-cell interactions and mechanisms of myelin destruction. They illustrate mechanisms of viral persistence, including latent infections in which no infectious virus is readily evident, virus reactivation and viral-induced tissue damage. These studies have also provided excellent paradigms to study the interactions between the immune system and the central nervous system (CNS). Although of interest in their own right, an understanding of the diverse mechanisms used by viruses to induce demyelination may shed light into the etiology and pathogenesis of the common demyelinating disorder multiple sclerosis (MS). This notion is supported by the persistent view that a viral infection acquired during adolescence might initiate MS after a long period of quiescence. Demyelination in both humans and rodents can be initiated by infection with a diverse group of enveloped and non-enveloped RNA and DNA viruses (Table 1). The mechanisms that ultimately result in the loss of CNS myelin appear to be equally diverse as the etiological agents capable of causing diseases which result in demyelination. Although demyelination can be a secondary result of axonal loss, in many examples of viral induced demyelination, myelin loss is primary and associated with axonal sparing. This suggests that demyelination induced by viral infections can result from: 1) a direct viral infection of oligodendroglia resulting in cell death with degeneration of myelin and its subsequent removal; 2) a persistent viral infection, in the presence or absence of infectious virus, resulting in the loss of normal cellular homeostasis and subsequent oligodendroglial death; 3) a vigorous virus-specific inflammatory response wherein the virus replicates in a cell type other than oligodendroglia, but cytokines and other immune mediators directly damage the

  1. Macrophages mediate cardioprotective cellular postconditioning in acute myocardial infarction.

    Science.gov (United States)

    de Couto, Geoffrey; Liu, Weixin; Tseliou, Eleni; Sun, Baiming; Makkar, Nupur; Kanazawa, Hideaki; Arditi, Moshe; Marbán, Eduardo

    2015-08-03

    Ischemic injury in the heart induces an inflammatory cascade that both repairs damage and exacerbates scar tissue formation. Cardiosphere-derived cells (CDCs) are a stem-like population that is derived ex vivo from cardiac biopsies; they confer both cardioprotection and regeneration in acute myocardial infarction (MI). While the regenerative effects of CDCs in chronic settings have been studied extensively, little is known about how CDCs confer the cardioprotective process known as cellular postconditioning. Here, we used an in vivo rat model of ischemia/reperfusion (IR) injury-induced MI and in vitro coculture assays to investigate how CDCs protect stressed cardiomyocytes. Compared with control animals, animals that received CDCs 20 minutes after IR had reduced infarct size when measured at 48 hours. CDCs modified the myocardial leukocyte population after ischemic injury. Specifically, introduction of CDCs reduced the number of CD68+ macrophages, and these CDCs secreted factors that polarized macrophages toward a distinctive cardioprotective phenotype that was not M1 or M2. Systemic depletion of macrophages with clodronate abolished CDC-mediated cardioprotection. Using both in vitro coculture assays and a rat model of adoptive transfer after IR, we determined that CDC-conditioned macrophages attenuated cardiomyocyte apoptosis and reduced infarct size, thereby recapitulating the beneficial effects of CDC therapy. Together, our data indicate that CDCs limit acute injury by polarizing an effector macrophage population within the heart.

  2. Atypical idiopathic inflammatory demyelinating lesions

    DEFF Research Database (Denmark)

    Wallner-Blazek, Mirja; Rovira, Alex; Fillipp, Massimo;

    2013-01-01

    Atypical lesions of a presumably idiopathic inflammatory demyelinating origin present quite variably and may pose diagnostic problems. The subsequent clinical course is also uncertain. We, therefore, wanted to clarify if atypical idiopathic inflammatory demyelinating lesions (AIIDLs) can be class...

  3. HCV-related central and peripheral nervous system demyelinating disorders.

    Science.gov (United States)

    Mariotto, Sara; Ferrari, Sergio; Monaco, Salvatore

    2014-01-01

    Chronic infection with hepatitis C virus (HCV) is associated with a large spectrum of extrahepatic manifestations (EHMs), mostly immunologic/rheumatologic in nature owing to B-cell proliferation and clonal expansion. Neurological complications are thought to be immune-mediated or secondary to invasion of neural tissues by HCV, as postulated in transverse myelitis and encephalopathic forms. Primarily axonal neuropathies, including sensorimotor polyneuropathy, large or small fiber sensory neuropathy, motor polyneuropathy, mononeuritis, mononeuritis multiplex, or overlapping syndrome, represent the most common neurological complications of chronic HCV infection. In addition, a number of peripheral demyelinating disorders are encountered, such as chronic inflammatory demyelinating polyneuropathy, the Lewis-Sumner syndrome, and cryoglobulin-associated polyneuropathy with demyelinating features. The spectrum of demyelinating forms also includes rare cases of iatrogenic central and peripheral nervous system disorders, occurring during treatment with pegylated interferon. Herein, we review HCV-related demyelinating conditions, and disclose the novel observation on the significantly increased frequency of chronic demyelinating neuropathy with anti-myelin-associated glycoprotein antibodies in a cohort of 59 consecutive patients recruited at our institution. We also report a second case of neuromyelitis optica with serum IgG autoantibody against the water channel aquaporin-4. The prompt recognition of these atypical and underestimated complications of HCV infection is of crucial importance in deciding which treatment option a patient should be offered.

  4. Combined concurrent nanoshell loaded macrophage-mediated photothermal and photodynamic therapies

    Science.gov (United States)

    Hirschberg, Henry; Trinidad, Anthony; Christie, Catherine E.; Peng, Qian; Kwon, Young J.; Madsen, Steen

    2015-02-01

    Macrophages loaded with gold nanoshells (AuNS), that convert near infrared light to heat, can be used as transport vectors for photothermal hyperthermia of tumors. The purpose of this study was to investigate the effects of combined macrophage mediated photothermal therapy (PTT) and PDT on head and neck squamous cell carcinoma (HNSCC). The results provide proof of concept for the use of macrophages as a delivery vector of AuNS for photothermal enhancement of the effects of PDT on squamous cell carcinoma. A significant synergy was demonstrated with combined PDT and PTT compared to each modality applied separately.

  5. Transcriptional changes in canine distemper virus-induced demyelinating leukoencephalitis favor a biphasic mode of demyelination.

    Science.gov (United States)

    Ulrich, Reiner; Puff, Christina; Wewetzer, Konstantin; Kalkuhl, Arno; Deschl, Ulrich; Baumgärtner, Wolfgang

    2014-01-01

    Canine distemper virus (CDV)-induced demyelinating leukoencephalitis in dogs (Canis familiaris) is suggested to represent a naturally occurring translational model for subacute sclerosing panencephalitis and multiple sclerosis in humans. The aim of this study was a hypothesis-free microarray analysis of the transcriptional changes within cerebellar specimens of five cases of acute, six cases of subacute demyelinating, and three cases of chronic demyelinating and inflammatory CDV leukoencephalitis as compared to twelve non-infected control dogs. Frozen cerebellar specimens were used for analysis of histopathological changes including demyelination, transcriptional changes employing microarrays, and presence of CDV nucleoprotein RNA and protein using microarrays, RT-qPCR and immunohistochemistry. Microarray analysis revealed 780 differentially expressed probe sets. The dominating change was an up-regulation of genes related to the innate and the humoral immune response, and less distinct the cytotoxic T-cell-mediated immune response in all subtypes of CDV leukoencephalitis as compared to controls. Multiple myelin genes including myelin basic protein and proteolipid protein displayed a selective down-regulation in subacute CDV leukoencephalitis, suggestive of an oligodendrocyte dystrophy. In contrast, a marked up-regulation of multiple immunoglobulin-like expressed sequence tags and the delta polypeptide of the CD3 antigen was observed in chronic CDV leukoencephalitis, in agreement with the hypothesis of an immune-mediated demyelination in the late inflammatory phase of the disease. Analysis of pathways intimately linked to demyelination as determined by morphometry employing correlation-based Gene Set Enrichment Analysis highlighted the pathomechanistic importance of up-regulated genes comprised by the gene ontology terms "viral replication" and "humoral immune response" as well as down-regulated genes functionally related to "metabolite and energy generation".

  6. Transcriptional changes in canine distemper virus-induced demyelinating leukoencephalitis favor a biphasic mode of demyelination.

    Directory of Open Access Journals (Sweden)

    Reiner Ulrich

    Full Text Available Canine distemper virus (CDV-induced demyelinating leukoencephalitis in dogs (Canis familiaris is suggested to represent a naturally occurring translational model for subacute sclerosing panencephalitis and multiple sclerosis in humans. The aim of this study was a hypothesis-free microarray analysis of the transcriptional changes within cerebellar specimens of five cases of acute, six cases of subacute demyelinating, and three cases of chronic demyelinating and inflammatory CDV leukoencephalitis as compared to twelve non-infected control dogs. Frozen cerebellar specimens were used for analysis of histopathological changes including demyelination, transcriptional changes employing microarrays, and presence of CDV nucleoprotein RNA and protein using microarrays, RT-qPCR and immunohistochemistry. Microarray analysis revealed 780 differentially expressed probe sets. The dominating change was an up-regulation of genes related to the innate and the humoral immune response, and less distinct the cytotoxic T-cell-mediated immune response in all subtypes of CDV leukoencephalitis as compared to controls. Multiple myelin genes including myelin basic protein and proteolipid protein displayed a selective down-regulation in subacute CDV leukoencephalitis, suggestive of an oligodendrocyte dystrophy. In contrast, a marked up-regulation of multiple immunoglobulin-like expressed sequence tags and the delta polypeptide of the CD3 antigen was observed in chronic CDV leukoencephalitis, in agreement with the hypothesis of an immune-mediated demyelination in the late inflammatory phase of the disease. Analysis of pathways intimately linked to demyelination as determined by morphometry employing correlation-based Gene Set Enrichment Analysis highlighted the pathomechanistic importance of up-regulated genes comprised by the gene ontology terms "viral replication" and "humoral immune response" as well as down-regulated genes functionally related to "metabolite and energy

  7. The frequencies of Killer immunoglobulin-like receptors and their HLA ligands in chronic inflammatory demyelinating polyradiculoneuropathy are similar to those in Guillian Barre syndrome but differ from those of controls, suggesting a role for NK cells in pathogenesis.

    Science.gov (United States)

    Blum, Stefan; Csurhes, Peter; McCombe, Pamela

    2015-08-15

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired inflammatory neuropathy, which has similar clinical and pathological features to Guillain-Barré Syndrome (GBS), but differs in time course. We investigated the frequency of genes encoding Killer immunoglobulin-like receptors and their HLA ligands in subjects with CIDP, in subjects with GBS and in healthy controls. There were no differences in KIR gene frequency among the 3 groups. The gene frequencies for HLA-B Bw4-I were significantly greater in CIDP than HC, but did not differ from GBS. The frequency of the combination of 3DL1/HLA-B Bw4I was greater in CIDP than HC, but did not differ from that of GBS. These data raise the possibility of NK cell function being an important factor in the pathogenesis of CIDP.

  8. Macrophage-mediated tumor cytotoxicity: role of macrophage surface sialic acid.

    Science.gov (United States)

    Cameron, D J

    1983-02-01

    Cell surface sialic acid levels were compared for monocytes and macrophages obtained from normal volunteers and breast cancer patients. Equal quantities of sialic acid were found on the monocytes obtained from normal volunteers and breast cancer patients. Approximately 60% more cell surface sialic acid was found on the macrophages from breast cancer patients than was found on the macrophages from normal volunteers. In order to determine whether cell surface sialic acid had any effect on macrophage-mediated cytotoxicity, macrophages were pretreated with neuraminidase (NANAse) prior to co-cultivation with tumor cells. The normal macrophages, after neuraminidase treatment, no longer retained their ability to kill tumor cells. However, when macrophages from breast cancer patients were treated with NANAse, no difference was observed in the ability of untreated and NANAse treated macrophages to kill tumor cells.

  9. Functional Roles of p38 Mitogen-Activated Protein Kinase in Macrophage-Mediated Inflammatory Responses

    Directory of Open Access Journals (Sweden)

    Yanyan Yang

    2014-01-01

    Full Text Available Inflammation is a natural host defensive process that is largely regulated by macrophages during the innate immune response. Mitogen-activated protein kinases (MAPKs are proline-directed serine and threonine protein kinases that regulate many physiological and pathophysiological cell responses. p38 MAPKs are key MAPKs involved in the production of inflammatory mediators, including tumor necrosis factor-α (TNF-α and cyclooxygenase-2 (COX-2. p38 MAPK signaling plays an essential role in regulating cellular processes, especially inflammation. In this paper, we summarize the characteristics of p38 signaling in macrophage-mediated inflammation. In addition, we discuss the potential of using inhibitors targeting p38 expression in macrophages to treat inflammatory diseases.

  10. Chronic inflammatory demyelinating polyradiculoneuropathy: two cases with cervical spinal cord compression Polirradiculoneuropatia desmielinizante inflamatória crônica: dois casos com síndrome de compressão medular

    Directory of Open Access Journals (Sweden)

    Marcos R.G. de Freitas

    2005-09-01

    Full Text Available Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP is a peripheral nerve disorder probably due to an immunological disturb. It evolves either in a steadily progressive or in a relapsing and fluctuating course. Weakness is mainly in the lower limbs proximally and distally. The electromyography is demyelinating. The cerebral spinal fluid protein is most of times elevated. Sometimes enlarged nerves are found. There are few cases described with spinal cord compression due to hypertrophic spinal nerve roots. Two patients (females, 66 and 67 years old with diagnosis of a long standing CIDP are described. In the first one, the evolution was characterized by remission and relapsing course. The second patient had a chronic and progressive course. These patients presented after a long evolution a cervical spinal cord compression syndrome due to hypertrophic cervical roots. Neurologists must be aware of the possibility of development of spinal cord compression by enlarged spinal roots in patients with a long standing CIDP.A polirradiculoneuropatia desmielinizante inflamatória crônica (PDIC é uma afecção dos nervos periféricos de natureza autoimune, com evolução por surtos de exacerbação e remissão ou de evolver progressivo. O acometimento motor é predominante, com fraqueza proximal e distal nos membros inferiores. A eletroneuromiografia é do tipo desmielinizante com bloqueio de condução nervosa em dois ou mais nervos. Há aumento de proteínas do líquor. Com a evolução da doença pode haver espessamento dos nervos distal e/ou proximalmente. Excepcionalmente ocorre compressão da medula espinhal em qualquer segmento por raízes próximas hipertrofiadas. Foram estudadas duas mulheres de 66 e 67 anos respectivamente com quadro de PDIC de longa evolução. A primeira tinha evolução por surtos e na segunda o evolver era progressivo. Nos dois casos o espessamento proximal dos nervos provocou síndrome de compressão medular alta

  11. Polineuropatia desmielinizante inflamatória crônica pós-tratamento com interferon peguilado alfa 2b em um paciente co-infectado HIV/HCV: relato de caso Chronic inflammatory demyelinating polyneuropathy after treatment with pegylated interferon alpha 2b in a patient with HIV/HCV coinfection: case report

    Directory of Open Access Journals (Sweden)

    Bil Randerson Bassetti

    2010-02-01

    Full Text Available A polineuropatia desmielinizante inflamatória cônica possui forte associação com a infecção pelo HIV e HCV. Uma rara associação entre PDIC e o tratamento da hepatite C com interferon peguilado alfa foi descrita recentemente. Nós descrevemos o primeiro caso de polineuropatia desmielinizante inflamatória crônica em um paciente branco, sexo masculino infectado por HIV e HCV associado a interferon peguilado alfa 2b. O paciente recuperou-se completamente após o uso de imunoglobulina hiperimune endovenosa. Infectologistas e hapatologistas devem estar atentos à esta rara e grave associação, que exige imediata descontinuação da droga e tratamento precoce.Chronic inflammatory demyelinating polyneuropathy has a strong association with HIV and HCV infection. A rare association between chronic inflammatory demyelinating polyneuropathy and hepatitis C treatment with pegylated interferon alpha was described recently. We described the first case of chronic inflammatory demyelinating polyneuropathy associated with pegylated interferon alpha 2b in a white man infected with HIV and HCV. The patient recovered completely with the use of intravenous hyperimmune immunoglobulin. Infectologists and hepatologists should be alert regarding this rare and serious association, which requires immediately drug discontinuation and early treatment.

  12. Chronic Inflammatory Polyneuropathy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2007-02-01

    Full Text Available Thirteen children with chronic inflammatory demyelinating polyneuropathy monitored between 1975 and 2005 are reported from Centre hospitalier universitaire Sainte-Justine, Montreal, Canada.

  13. 慢性炎性脱鞘性多发性神经病临床及电生理特点%Clinical and electrophysiological characteristics of chronic inflammatory demyelinating polyneuropathy

    Institute of Scientific and Technical Information of China (English)

    郭晓玲; 李卫来; 李琳; 李岩; 黄旭升; 陈朝晖

    2014-01-01

    目的 探讨慢性炎性脱髓鞘性神经病(chronic inflammatory demyelinating polyneuropathy,CIDP)的临床及电生理特点.方法 对2001-2011年确诊的56例CIDP患者的临床特点进行分析,并对所有患者进行神经传导速度、波幅、潜伏期及肌电图测定,与32例正常组肌电图进行对照.结果 患病组脑脊液检查47例(83.9%)表现为蛋白-细胞分离现象,所有患者肌电图均表现神经源性损害,两组间运动传导除近端潜伏期比较无统计学差异,其他各项差异均有统计学意义.结论 CIDP存在广泛的周围神经损害,存在以脱髓鞘为主伴轴索变性的电生理改变.

  14. Neuroradiological evaluation of demyelinating disease

    OpenAIRE

    Tillema, Jan-Mendelt; Pirko, Istvan

    2013-01-01

    Central nervous system inflammatory demyelinating disease can affect patients across the life span. Consensus definitions and criteria of all of the different acquired demyelinating diseases that fall on this spectrum have magnetic resonance imaging criteria. The advances of both neuroimaging techniques and important discoveries in immunology have produced an improved understanding of these conditions and classification. Neuroimaging plays a central role in the accurate diagnosis, prognosis, ...

  15. DEMYELINATING OPTIC NEURITIS IN CHILDREN

    OpenAIRE

    Alper, Gulay; Wang, Li

    2008-01-01

    Acute demyelinating optic neuritis in children can occur in isolation or be associated with acute disseminated encephalomyelitis, multiple sclerosis or neuromyelitis optica. Clinical features, neuroimaging, cerebrospinal fluid findings and long term prognosis were reviewed in 26 children diagnosed with optic neuritis at the first presentation of demyelinating disease. The risk factors for the subsequent diagnosis of multiple sclerosis were analyzed. The mean duration of follow-up was 6.2 year...

  16. Olfactory system and demyelination.

    Science.gov (United States)

    Garcia-Gonzalez, D; Murcia-Belmonte, V; Clemente, D; De Castro, F

    2013-09-01

    Within the central nervous system, the olfactory system represents one of the most exciting scenarios since it presents relevant examples of long-life sustained neurogenesis and continuous axonal outgrowth from the olfactory epithelium with the subsequent plasticity phenomena in the olfactory bulb. The olfactory nerve is composed of nonmyelinated axons with interesting ontogenetic interpretations. However, the centripetal projections from the olfactory bulb are myelinated axons which project to more caudal areas along the lateral olfactory tract. In consequence, demyelination has not been considered as a possible cause of the olfactory symptoms in those diseases in which this sense is impaired. One prototypical example of an olfactory disease is Kallmann syndrome, in which different mutations give rise to combined anosmia and hypogonadotropic hypogonadism, together with different satellite symptoms. Anosmin-1 is the extracellular matrix glycoprotein altered in the X-linked form of this disease, which participates in cell adhesion and migration, and axonal outgrowth in the olfactory system and in other regions of the central nervous system. Recently, we have described a new patho-physiological role of this protein in the absence of spontaneous remyelination in multiple sclerosis. In the present review, we hypothesize about how both main and satellite neurological symptoms of Kallmann syndrome may be explained by alterations in the myelination. We revisit the relationship between the olfactory system and myelin highlighting that minor histological changes should not be forgotten as putative causes of olfactory malfunction.

  17. Chronic inflammatory demyelinating polyradiculoneuropathy in chronic graft-versus-host disease following allogeneic hematopoietic stem cell transplantation: case report Polirradiculoneuropatia desmielinizante inflamatória crônica na doença do enxerto contra o hospedeiro após transplante de células hematopoiéticas alogênicas: relato de caso

    Directory of Open Access Journals (Sweden)

    Paulo José Lorenzoni

    2007-09-01

    Full Text Available The chronic inflammatory demyelinating polyradiculoneuropathy (CIDP is an unusual but important complication of hematopoietic stem cell transplantation (HSCT rarely reported to date. We describe a 17-year-old woman with a diagnosis of acute myeloid leukemia due to Fanconi's anemia who was submitted to allogeneic HSCT and developed CIDP as part of graft-versus-host disease. Investigation showed high cerebrospinal fluid protein; electrophysiological studies revealed sensory-motor demyelinating polyradiculoneuropathy; muscle and nerve biopsy were compatible with CIDP.A polirradiculoneuropatia desmielinizante inflamatória crônica (CIDP é uma incomum, porém, importante complicação do transplante de células hematopoiéticas (HSCT raramente relatada até a data. Nós descrevemos uma mulher de 17 anos com diagnóstico de leucemia mielóide aguda por anemia de Fanconi que foi submetida à HSCT e desenvolveu CIDP como parte da doença do enxerto contra o hospedeiro. A investigação mostrou elevação na proteína no líquor; estudo eletrofisiológico revelando polirradiculoneuropatia desmielinizante sensitivo-motora; e biópsia de músculo e nervo compatível com CIDP.

  18. Quantifying Demyelination in NK venom treated nerve using its electric circuit model

    Science.gov (United States)

    Das, H. K.; Das, D.; Doley, R.; Sahu, P. P.

    2016-03-01

    Reduction of myelin in peripheral nerve causes critical demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, etc. Clinical monitoring of these diseases requires rapid and non-invasive quantification of demyelination. Here we have developed formulation of nerve conduction velocity (NCV) in terms of demyelination considering electric circuit model of a nerve having bundle of axons for its quantification from NCV measurements. This approach has been validated and demonstrated with toad nerve model treated with crude Naja kaouthia (NK) venom and also shows the effect of Phospholipase A2 and three finger neurotoxin from NK-venom on peripheral nerve. This opens future scope for non-invasive clinical measurement of demyelination.

  19. 慢性炎症性脱髓鞘性多发性神经病治疗的研究进展%Research Progress of Treatment of Chronic Inflammatory Demyelinating Polyneuropathy

    Institute of Scientific and Technical Information of China (English)

    王书玉

    2012-01-01

    Chronic inflammatory demyelinating polyneuropathy is an immune-mediated disease of the peripheral nervous system, which can be difficult to diagnose and treat due to the diversity of the clinical manifestations and disease process. Intravenous immunoglobulin, corticosteroids and plasma exchange have all been proven to be beneficial in randomized controlled trials. Treatment solution should be made taking the cost,effect and adverse effects into account. When patients do not respond or become refractory or intolerant to these conventional treatments,other treatments such as azathioprine, ciclosporin A, cyclophosphamide, in-terferons,methotrexate,mycophenolate mofetil,rituximab and etanercept should be considered.%慢性炎症性脱髓鞘性多发性神经病是由免疫介导的周围神经病,其临床表现及病程多样,诊断及治疗困难.静脉注射免疫球蛋白、糖皮质激素及血浆置换在随机对照试验中被证明有效,在制订治疗方案时应结合医疗成本、药物疗效、不良反应等因素.如果对常规治疗无效或变得难治不能耐受时应该考虑其他治疗,如硫唑嘌呤、环孢素、环磷酰胺、干扰素、甲氨蝶呤、霉酚酸酯、利妥昔单抗、依那西普等药物.

  20. Interferon beta-1a in chronic inflammatory demyelinating polyneuropathy: case report Interferon beta en polineuropatía crónica inflamatoria desmienlinizante: caso clínico

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    Andrés Maria Villa

    2004-09-01

    Full Text Available Chronic inflammatory demyelinating polyneuropathy (CIDP is an acquired immune-mediated neuropathy. It presents with a course of progression which may be slow and steady or step-wise or relapsing. Sensory ataxic polyneuropathy may be the only clinical manifestation of this disease. Treatment with interferon beta1a (INF beta1a has been tried with different results in patients who were refractory to other, more conventional, immunomodulatory therapies. Here we report on a patient who had a relapsing form of pure sensory ataxic CIDP and who failed to respond to intravenous human immunoglobulin. He was put on INF beta1a for 3 years. During this period he suffered no relapses while his condition stabilized.La polineuropatía crónica inflamatoria desmielinizante (PCID es una neuropatía inmuno-mediada, que presenta un curso clínico primariamente progresivo o en forma de recaídas. Las manifestaciones sensoriales pueden ser su unica forma de expresión clínica. El tratamiento con interferon beta 1a (IFN beta1a ha sido ensayado en varias oportunidades, con diferentes respuestas terapéuticas, en pacientes refractarios a las terapias inmunomoduladoras convencionales. Nosotros comunicamos un paciente con una forma ataxica recurrente de PCID, que no respondió al tratamiento con inmunoglobulina endovenosa. Posteriormente fue tratado con IFN beta 1 a por tres años. Durante el período de seguimiento no mostró nuevas recaídas y su cuadro neurológico se estabilizó.

  1. 儿童慢性炎症性脱鞘性多神经病的临床和病理改变特点%Clinical and pathological features in the childhood chronic inflammatory demyelinating polyneuropathy

    Institute of Scientific and Technical Information of China (English)

    栾兴华; 郑日亮; 陈彬; 常杏芝; 熊辉; 吕俊兰; 袁云

    2008-01-01

    目的 探讨儿童慢性炎症性脱鞘性多神经病(chronic inflammatory demyelinating polyneuropathy,CI-DP)的临床及病理改变特点.方法 根据欧洲神经肌肉病中心修订的儿童CIDP诊断标准诊断的10例17岁以下患者,收集其临床资料,进行周围神经电生理以及腓肠神经的病理检查.结果 所有患者主要表现为肢体无力,分别有4例和3例出现四肢感觉减退和颅神经损害.9例有脑脊液蛋白细胞分离现象.10例均出现运动或感觉神经传导速度减慢及远端潜伏期延长,9例患者的动作电位波幅降低.所有患者的有髓神经纤维出现轻-重度减少,其中3例患者的纤维脱失程度在不同束间存在差异,6例患者以脱髓鞘为主;3例以轴索损害为主.1例患者仅出现轻微改变.9例患者存在炎细胞浸润.结论 儿童CIDP以肢体无力为主.部分患者以轴索损害为主,神经纤维脱失程度可以存在束间差异.

  2. Microglial cystatin F expression is a sensitive indicator for ongoing demyelination with concurrent remyelination.

    Science.gov (United States)

    Ma, Jianmei; Tanaka, Kenji F; Shimizu, Takahiro; Bernard, Claude C A; Kakita, Akiyoshi; Takahashi, Hitoshi; Pfeiffer, Steven E; Ikenaka, Kazuhiro

    2011-05-01

    Demyelination coincides with numerous changes of gene expression in the central nervous system (CNS). Cystatin F, which is a papain-like lysosomal cysteine proteinase inhibitor that is normally expressed by immune cells and not in the brain, is massively induced in the CNS during acute demyelination. We found that microglia, which are monocyte/macrophage-lineage cells in the CNS, express cystatin F only during demyelination. By using several demyelinating animal models and the spinal cord tissues from multiple sclerosis (MS) patients, we examined spatiotemporal expression pattern of cystatin F by in situ hybridization and immunohistochemistry. We found that the timing of cystatin F induction matches with ongoing demyelination, and the places with cystatin F expression overlapped with the remyelinating area. Most interestingly, cystatin F induction ceased in chronic demyelination, in which remyelinating ability was lost. These findings demonstrate that the expression of cystatin F indicates the occurrence of ongoing demyelination/remyelination and the absence of cystatin F expression indicates the cessation of remyelination in the demyelinating area.

  3. Effect of intravenous immunoglobulin in Guilain-Barre syndrome, myasthenia gravis and chronic idiopathic demyelinative polyneuropathy, A survey in Imam Khomeini Hospital

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    Qaffarpoor M

    1999-09-01

    Full Text Available With retrospective evaluation of 44 patients suffering from Guilan-Barre Syndrome (GBS, Chronic Idiopathic Demtyelinative Polyradiculoneuropathy (CIDP and Myasthenia Gravis (MG treated with intravenous immunoglobulin, we found following results: 1 Initial symptoms of improvement on forth or fifth days. 2 Maximum recovery for CIDP and MG were after 16-24 and 3-11 days, respectively. 3 No major complication, but mild side effects in 32% of patients. 4 In patients with GBS one grade improvement achieved after 8-30 days. 5 Intravenous immunoglobulin (IVIG plus plasmapheresis had no advantages over IVIG alone. 6 No reasonable conclusion about relapsing rate and duration of response due to follow up restrictions.

  4. Alcoholism with central pontine demyelination: a case report

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    Rohit Arora

    2014-02-01

    Full Text Available Central pontine myelinolysis is a non-inflammatory demyelinating disease characterized by loss of myelin with relative neuron sparing, associated with rapid correction of hyponatremia and sometimes hypernatremia or chronic alcoholism. We are reporting a case of 52 year old male patient who was chronic alcoholic from past 20 years, presented to us with complaints of altered sensorium and dysarthria of 5 days duration .He was investigated and diagnosed as case of central pontine myelinosis associated with chronic alcoholism. [Int J Basic Clin Pharmacol 2014; 3(1.000: 230-232

  5. Machine learning approach identifies new pathways associated with demyelination in a viral model of multiple sclerosis

    Science.gov (United States)

    Ulrich, Reiner; Kalkuhl, Arno; Deschl, Ulrich; Baumgärtner, Wolfgang

    2010-01-01

    Abstract Theiler’s murine encephalomyelitis is an experimentally virus-induced inflammatory demyelinating disease of the spinal cord, displaying clinical and pathological similarities to chronic progressive multiple sclerosis. The aim of this study was to identify pathways associated with chronic demyelination using an assumption-free combined microarray and immunohistology approach. Movement control as determined by rotarod assay significantly worsened in Theiler’s murine encephalomyelitis -virus-infected SJL/J mice from 42 to 196 days after infection (dpi). In the spinal cords, inflammatory changes were detected 14 to 196 dpi, and demyelination progressively increased from 42 to 196 dpi. Microarray analysis revealed 1001 differentially expressed genes over the study period. The dominating changes as revealed by k-means and functional annotation clustering included up-regulations related to intrathecal antibody production and antigen processing and presentation via major histocompatibility class II molecules. A random forest machine learning algorithm revealed that down-regulated lipid and cholesterol biosynthesis, differentially expressed neurite morphogenesis and up-regulated toll-like receptor-4-induced pathways were intimately associated with demyelination as measured by immunohistology. Conclusively, although transcriptional changes were dominated by the adaptive immune response, the main pathways associated with demyelination included up-regulation of toll-like receptor 4 and down-regulation of cholesterol biosynthesis. Cholesterol biosynthesis is a rate limiting step of myelination and its down-regulation is suggested to be involved in chronic demyelination by an inhibition of remyelination. PMID:19183246

  6. Inflammation, demyelination, and degeneration - recent insights from MS pathology.

    Science.gov (United States)

    Stadelmann, Christine; Wegner, Christiane; Brück, Wolfgang

    2011-02-01

    Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system which responds to anti-inflammatory treatments in the early disease phase. However, the pathogenesis of the progressive disease phase is less well understood, and inflammatory as well as neurodegenerative mechanisms of tissue damage are currently being discussed. This review summarizes current knowledge on the interrelation between inflammation, demyelination, and neurodegeneration derived from the study of human autopsy and biopsy brain tissue and experimental models of MS.

  7. [Therapeutic responsiveness in chronic inflammatory demyelinating polyradiculoneuropathy].

    Science.gov (United States)

    Iijima, Masahiro

    2011-11-01

    CIDP is autoimmune-associated peripheral neuropathy characterized by motor and sensory disturbances in each limb. While various phenotypes have been reported in CIDP, the essential pathogenesis is not elucidated yet. Clinicopathological study indicated axonal dysfunction (muscle atrophy and decreased compound muscular action potentials) is one of the most important factors in IVIg Non-responders. Furthermore, single nucleotide polymorphism (SNP) haplotype/diplotype analysis within a linkage disequilibrium block indicates transient axonal glycoprotein 1 (TAG-1), which controls proper distribution of potassium channels in juxtaparanode, is an important factor for IVIg responsiveness. Gene expression analysis of biopsied nerves supported the hypothesis that CIDP pathogenesis is involved in humoral and cellular immune system. With respect to IVIg responsiveness, expression profiles indicate whole CIDP patients need conventional immune-modulating therapies in somewhat, while we should re-consider how to use them. From aspects of gene expression results, Non-responders need not only conventional immune-modulating therapies but also other original modalities which could intervene the pathogenesis except Schwann/inflammatory cells while Responders with IVIg dependence should need stronger and longer immune-suppression.

  8. Disinhibition of Cathepsin C Caused by Cystatin F Deficiency Aggravates the Demyelination in a Cuprizone Model

    Science.gov (United States)

    Liang, Junjie; Li, Ning; Zhang, Yanli; Hou, Changyi; Yang, Xiaohan; Shimizu, Takahiro; Wang, Xiaoyu; Ikenaka, Kazuhiro; Fan, Kai; Ma, Jianmei

    2016-01-01

    Although the precise mechanism underlying initial lesion development in multiple sclerosis (MS) remains unclear, CNS inflammation has long been associated with demyelination, and axonal degeneration. The activation of microglia/macrophages, which serve as innate immune cells in the CNS, is the first reaction to even minor pathologic changes in the CNS and is considered an initial pathogenic event in MS. Microglial activation accompanies a variety of gene expressions, including cystatin F (Cys F), which belongs to the cystatin superfamily and is one of the cathepsin inhibitors. In our previous study we showed that Cys F has a unique expression pattern in microglia/macrophages in the demyelination process. Specifically, the timing of Cys F induction correlated with ongoing demyelination, and the sites of Cys F expression overlapped with areas of remyelination. Cys F induction ceased in chronic demyelination when remyelination capacity was lost, suggesting that Cys F expressed by microglia/macrophages may play an important role in demyelination and/or remyelination. The functional role of Cys F in demyelinating disease of the CNS, however, is unclear. Cys F gene knockout mice were used in the current study to clarify the functional role of Cys F in the demyelination process in a cuprizone-induced demyelination animal model. We demonstrated that absence of the Cys F gene and the resulting disinhibition of cathepsin C (Cat C) aggravates the demyelination, and this finding may be related to the increased expression of the glia-derived chemokine, CXCL2, which may attract inflammatory cells to sites of myelin sheath damage. This effect was reversed by knock down of the Cat C gene. The findings gain further insight to function of Cat C in pathophysiology of MS, which may have implications for therapeutics for the prevention of neuroinflammation-involved neurological disorders in the future. PMID:28066178

  9. Demyelination versus remyelination in progressive multiple sclerosis.

    Science.gov (United States)

    Bramow, Stephan; Frischer, Josa M; Lassmann, Hans; Koch-Henriksen, Nils; Lucchinetti, Claudia F; Sørensen, Per S; Laursen, Henning

    2010-10-01

    The causes of incomplete remyelination in progressive multiple sclerosis are unknown, as are the pathological correlates of the different clinical characteristics of patients with primary and secondary progressive disease. We analysed brains and spinal cords from 51 patients with progressive multiple sclerosis by planimetry. Thirteen patients with primary progressive disease were compared with 34 with secondary progressive disease. In patients with secondary progressive multiple sclerosis, we found larger brain plaques, more demyelination in total and higher brain loads of active demyelination compared with patients with primary progressive disease. In addition, the brain density of plaques with high-grade inflammation and active demyelination was highest in secondary progressive multiple sclerosis and remained ~18% higher than in primary progressive multiple sclerosis after adjustments for other plaque types and plaque number (Pprogressive multiple sclerosis. By contrast, there were no group differences in the brain load or frequency of low-grade inflammatory plaques with slowly expanding demyelination. Spinal cord lesion loads and remyelination capacity were also comparable in the two patient groups. Remyelinated areas were more vulnerable than the normal-appearing white matter to new demyelination, including active demyelination in secondary progressive multiple sclerosis. 'Recurrent' slowly expanding demyelination, affecting remyelinated areas, and the load of slowly expanding demyelination correlated with incomplete remyelination in both groups. In turn, incomplete remyelination in the spinal cord correlated with higher disease-related disability (determined retrospectively; r = -0.53; Pprogressive multiple sclerosis. These patients may, thereby, be spared symptoms until the spinal cord is affected. By contrast, recurrent active demyelination of repaired myelin could explain why similar symptoms often develop in consecutive relapses in relapsing

  10. The topograpy of demyelination and neurodegeneration in the multiple sclerosis brain.

    Science.gov (United States)

    Haider, Lukas; Zrzavy, Tobias; Hametner, Simon; Höftberger, Romana; Bagnato, Francesca; Grabner, Günther; Trattnig, Siegfried; Pfeifenbring, Sabine; Brück, Wolfgang; Lassmann, Hans

    2016-03-01

    Multiple sclerosis is a chronic inflammatory disease with primary demyelination and neurodegeneration in the central nervous system. In our study we analysed demyelination and neurodegeneration in a large series of multiple sclerosis brains and provide a map that displays the frequency of different brain areas to be affected by these processes. Demyelination in the cerebral cortex was related to inflammatory infiltrates in the meninges, which was pronounced in invaginations of the brain surface (sulci) and possibly promoted by low flow of the cerebrospinal fluid in these areas. Focal demyelinated lesions in the white matter occurred at sites with high venous density and additionally accumulated in watershed areas of low arterial blood supply. Two different patterns of neurodegeneration in the cortex were identified: oxidative injury of cortical neurons and retrograde neurodegeneration due to axonal injury in the white matter. While oxidative injury was related to the inflammatory process in the meninges and pronounced in actively demyelinating cortical lesions, retrograde degeneration was mainly related to demyelinated lesions and axonal loss in the white matter. Our data show that accumulation of lesions and neurodegeneration in the multiple sclerosis brain does not affect all brain regions equally and provides the pathological basis for the selection of brain areas for monitoring regional injury and atrophy development in future magnetic resonance imaging studies.

  11. 糖尿病合并慢性炎性脱髓鞘性多发性神经病一例报告与文献复习%Diabetes mellitus combined with chronic inflammatory demyelinating polyneuropathy:A case report and ;literature review

    Institute of Scientific and Technical Information of China (English)

    杨茜; 赵志刚; 马跃华; 杨俊朋; 马媛媛

    2015-01-01

    Diabetes mellitus (DM ) combined with chronic inflammatory demyelinating polyneuropathy (CIDP) is rarely occurred and is difficult to distinguish from diabetic peripheral neuropathy (DPN). Here we reported a case of DM‐CIDP who was misdiagnosed as DPN in the initial treatment. Lumbar puncture , electrophysiological and other relevant examinations were helpful to timely and accurately dignose DM‐C ID P.%糖尿病合并慢性炎性脱髓鞘性多发性神经病(DM‐CIDP)临床少见。就诊时,本例误诊为糖尿病周围神经病变(DPN),在治疗过程中完善腰椎穿刺术、神经电生理等相关检查后最终确诊为DM‐CIDP。

  12. An Occult Malignancy Behind a Demyelinating Disease

    Directory of Open Access Journals (Sweden)

    Saberio Lo Presti MD

    2016-10-01

    Full Text Available We report a case of a 38-year-old man presenting with bilateral lower extremity weakness and paresthesias that progressed during a 4-month period to severe polyneuropathy forcing the patient to be bed bound. Throughout his multiple hospitalizations, he was treated erroneously for chronic inflammatory demyelinating polyneuropathy, without significant improvement in his symptoms. In addition, he developed hepatosplenomegaly (organomegaly; endocrinopathies such as diabetes mellitus, central hypogonadism, and hypothyroidism; monoclonal spike evidenced in the serum electrophoresis; and hyperpigmentation of skin, altogether consistent with POEMS syndrome. During his last hospitalization he developed excruciating pain on his left hip, and imaging revealed the presence of a 9 × 6 cm osteolytic mass with sclerotic rim in the left acetabulum. Biopsy of the mass confirmed an isolated IgG lambda plasmacytoma. The patient received radiation to his left acetabular lesion followed by left hip replacement. Subsequently, the patient underwent autologous bone marrow transplant. Eighteen months after his initial presentation, he had satisfactory clinical response and is functional without significant limitations. POEMS syndrome is a rare paraneoplastic syndrome secondary to an underlying plasma cell disorder, which can oftentimes be overlooked and misdiagnosed. The median age of presentation is 51 years, and only 31% of the cases occur in fairly young patients under the age of 45 as evidenced in this case. As clinicians, we should be aware of the constellation of features associated with POEMS syndrome and be able to recognize them promptly.

  13. An Occult Malignancy Behind a Demyelinating Disease

    Science.gov (United States)

    Lo Presti, Saberio; Kanagarajah, Prashanth; Pirela, Daniela; Morlote, Diana; Cusnir, Mike

    2016-01-01

    We report a case of a 38-year-old man presenting with bilateral lower extremity weakness and paresthesias that progressed during a 4-month period to severe polyneuropathy forcing the patient to be bed bound. Throughout his multiple hospitalizations, he was treated erroneously for chronic inflammatory demyelinating polyneuropathy, without significant improvement in his symptoms. In addition, he developed hepatosplenomegaly (organomegaly); endocrinopathies such as diabetes mellitus, central hypogonadism, and hypothyroidism; monoclonal spike evidenced in the serum electrophoresis; and hyperpigmentation of skin, altogether consistent with POEMS syndrome. During his last hospitalization he developed excruciating pain on his left hip, and imaging revealed the presence of a 9 × 6 cm osteolytic mass with sclerotic rim in the left acetabulum. Biopsy of the mass confirmed an isolated IgG lambda plasmacytoma. The patient received radiation to his left acetabular lesion followed by left hip replacement. Subsequently, the patient underwent autologous bone marrow transplant. Eighteen months after his initial presentation, he had satisfactory clinical response and is functional without significant limitations. POEMS syndrome is a rare paraneoplastic syndrome secondary to an underlying plasma cell disorder, which can oftentimes be overlooked and misdiagnosed. The median age of presentation is 51 years, and only 31% of the cases occur in fairly young patients under the age of 45 as evidenced in this case. As clinicians, we should be aware of the constellation of features associated with POEMS syndrome and be able to recognize them promptly. PMID:27790622

  14. Demyelinating Peripheral Neuropathy Due to Renal Cell Carcinoma

    Science.gov (United States)

    Nishioka, Kenya; Fujimaki, Motoki; Kanai, Kazuaki; Ishiguro, Yuta; Nakazato, Tomoko; Tanaka, Ryota; Yokoyama, Kazumasa; Hattori, Nobutaka

    2017-01-01

    Renal cell carcinoma (RCC) patients who develop a paraneoplastic syndrome may present with neuromuscular disorders. We herein report the case of a 50-year-old man who suffered from progressive gait disturbance and muscle weakness. The results of a nerve conduction study fulfilled the criteria of chronic inflammatory demyelinating polyneuropathy. An abdominal CT scan detected RCC, the pathological diagnosis of which was clear cell type. After tumor resection and a single course of intravenous immunoglobulin therapy, the patient's symptoms drastically improved over the course of one year. The patient's neurological symptoms preceded the detection of cancer. A proper diagnosis and the initiation of suitable therapies resulted in a favorable outcome. PMID:28049985

  15. 老年人慢性炎症性脱髓鞘性多发性神经病临床病理分析%Clinicopathological analysis of chronic inflammatory demyelinating polyneuropathy in the elderly

    Institute of Scientific and Technical Information of China (English)

    张宁; 李刚; 肖波; 刘运海; 蔡艳; 梁静慧

    2008-01-01

    目的 研究老年人慢性炎症性脱髓鞘性多发性神经病(CIDP)的临床和病理特征.方法对11例老年CIDP患者的临床表现、脑脊液检查、肌电图检查及腓肠神经活检病理结果进行总结分析. 结果 本组患者发病前有上呼吸道感染2例;首发症状为四肢远端麻木无力3例,双下肢远端麻木无力5例.双上肢远端麻木无力2例,抬头困难1例;患者均有运动障碍,伴感觉障碍8例.肢体肌肉萎缩3例,伴有肌肉压痛1例.腱反射减弱或消失8例,颅神经损害5例,自主神经受累3例,累及呼吸肌1例,复发3例;发病高峰期改良Rankin评分平均3.02分;脑脊液检查有明显蛋白细胞分离5例;肌电图示神经原性损害10例,肌原性伴神经原性损害1例;病理检查结果示髓鞘脱失6例,炎性细胞浸润6例,明显髓鞘再生2例,轴索肿胀变性2例;激素治疗8例有效. 结论 老年CIDP患者首发症状多为肢体远端麻木无力;大部分有感觉障碍;可有颅神经和自主神经损害;腓肠神经活检有助于老年CIDP诊断;激素治疗大部分有效.%Objective To study the clinical and pathological features in the elderly patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Methods The features of the clinical manifestation, cerebrospinal fluid, electromyogram(EMG) and the biopsy results of sural nerve were presented and analyzed in 11 elderly patients with CIDP. Results Two cases had history of upper respiratory tract infection before the onset. As the initial symptoms , there were three cases with distal limb numbness, five cases with both distal lower extremities numbness, two cases with both distal upper extremities numbness and one case with difficulties to raise his head. Motor disorder was common to all the patients. There were eight patients with sensory dysfunction, three with limb muscle atrophy, one with muscle tenderness, eight with tendon reflexes weakened or disappeared, five with cranial nerve

  16. A Mechanism of Virus-Induced Demyelination

    Directory of Open Access Journals (Sweden)

    Jayasri Das Sarma

    2010-01-01

    Full Text Available Myelin forms an insulating sheath surrounding axons in the central and peripheral nervous systems and is essential for rapid propagation of neuronal action potentials. Demyelination is an acquired disorder in which normally formed myelin degenerates, exposing axons to the extracellular environment. The result is dysfunction of normal neuron-to-neuron communication and in many cases, varying degrees of axonal degeneration. Numerous central nervous system demyelinating disorders exist, including multiple sclerosis. Although demyelination is the major manifestation of most of the demyelinating diseases, recent studies have clearly documented concomitant axonal loss to varying degrees resulting in long-term disability. Axonal injury may occur secondary to myelin damage (outside-in model or myelin damage may occur secondary to axonal injury (inside-out model. Viral induced demyelination models, has provided unique imminent into the cellular mechanisms of myelin destruction. They illustrate mechanisms of viral persistence, including latent infections, virus reactivation and viral-induced tissue damage. These studies have also provided excellent paradigms to study the interactions between the immune system and the central nervous system (CNS. In this review we will discuss potential cellular and molecular mechanism of central nervous system axonal loss and demyelination in a viral induced mouse model of multiple sclerosis.

  17. [Multifocal demyelinating polyneuropathy with persistent conduction block (Lewis-Sumner syndrome)].

    Science.gov (United States)

    Mezaki, T; Kaji, R; Hamano, T; Kimura, J; Kameyama, M

    1990-11-01

    Multifocal demyelinating neuropathy with persistent conduction block (Lewis-Sumner syndrome) is a variant of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), which often clinically simulates a motor neuron disease (MND). We report here three patients initially suspected to have MND, who later were diagnosed as a Lewis-Sumner syndrome. One of them showed a remarkable clinical improvement after immunoglobulin therapy. The definitive diagnosis of this syndrome rests upon nerve conduction studies, uncovering multiple sites of persistent conduction block. Technically, it is important to exclude insufficient stimulus which may lead to an erroneous impression of conduction block. Magnetic stimulation, as compared to electric current, elicited larger responses possibly because of deeper current penetration. We found this mode of stimulation useful especially in testing focal demyelination requiring full activation of a diseased nerve at a most proximal segment.

  18. N-linked glycans within the A2 domain of von Willebrand factor modulate macrophage-mediated clearance.

    Science.gov (United States)

    Chion, Alain; O'Sullivan, Jamie M; Drakeford, Clive; Bergsson, Gudmundur; Dalton, Niall; Aguila, Sonia; Ward, Soracha; Fallon, Padraic G; Brophy, Teresa M; Preston, Roger J S; Brady, Lauren; Sheils, Orla; Laffan, Michael; McKinnon, Thomas A J; O'Donnell, James S

    2016-10-13

    Enhanced von Willebrand factor (VWF) clearance is important in the etiology of von Willebrand disease. However, the molecular mechanisms underlying VWF clearance remain poorly understood. In this study, we investigated the role of VWF domains and specific glycan moieties in regulating in vivo clearance. Our findings demonstrate that the A1 domain of VWF contains a receptor-recognition site that plays a key role in regulating the interaction of VWF with macrophages. In A1-A2-A3 and full-length VWF, this macrophage-binding site is cryptic but becomes exposed following exposure to shear or ristocetin. Previous studies have demonstrated that the N-linked glycans within the A2 domain play an important role in modulating susceptibility to ADAMTS13 proteolysis. We further demonstrate that these glycans presented at N1515 and N1574 also play a critical role in protecting VWF against macrophage binding and clearance. Indeed, loss of the N-glycan at N1515 resulted in markedly enhanced VWF clearance that was significantly faster than that observed with any previously described VWF mutations. In addition, A1-A2-A3 fragments containing the N1515Q or N1574Q substitutions also demonstrated significantly enhanced clearance. Importantly, clodronate-induced macrophage depletion significantly attenuated the increased clearance observed with N1515Q and N1574Q in both full-length VWF and A1-A2-A3. Finally, we further demonstrate that loss of these N-linked glycans does not enhance clearance in VWF in the presence of a structurally constrained A2 domain. Collectively, these novel findings support the hypothesis that conformation of the VWF A domains plays a critical role in modulating macrophage-mediated clearance of VWF in vivo.

  19. Inhibition of System Xc(-) Transporter Attenuates Autoimmune Inflammatory Demyelination.

    Science.gov (United States)

    Evonuk, Kirsten S; Baker, Brandi J; Doyle, Ryan E; Moseley, Carson E; Sestero, Christine M; Johnston, Bryce P; De Sarno, Patrizia; Tang, Andrew; Gembitsky, Igor; Hewett, Sandra J; Weaver, Casey T; Raman, Chander; DeSilva, Tara M

    2015-07-15

    T cell infiltration into the CNS is a significant underlying pathogenesis in autoimmune inflammatory demyelinating diseases. Several lines of evidence suggest that glutamate dysregulation in the CNS is an important consequence of immune cell infiltration in neuroinflammatory demyelinating diseases; yet, the causal link between inflammation and glutamate dysregulation is not well understood. A major source of glutamate release during oxidative stress is the system Xc(-) transporter; however, this mechanism has not been tested in animal models of autoimmune inflammatory demyelination. We find that pharmacological and genetic inhibition of system Xc(-) attenuates chronic and relapsing-remitting experimental autoimmune encephalomyelitis (EAE). Remarkably, pharmacological blockade of system Xc(-) 7 d after induction of EAE attenuated T cell infiltration into the CNS, but not T cell activation in the periphery. Mice harboring a Slc7a11 (xCT) mutation that inactivated system Xc(-) were resistant to EAE, corroborating a central role for system Xc(-) in mediating immune cell infiltration. We next examined the role of the system Xc(-) transporter in the CNS after immune cell infiltration. Pharmacological inhibitors of the system Xc(-) transporter administered during the first relapse in a SJL animal model of relapsing-remitting EAE abrogated clinical disease, inflammation, and myelin loss. Primary coculture studies demonstrate that myelin-specific CD4(+) Th1 cells provoke microglia to release glutamate via the system Xc(-) transporter, causing excitotoxic death to mature myelin-producing oligodendrocytes. Taken together, these studies support a novel role for the system Xc(-) transporter in mediating T cell infiltration into the CNS as well as promoting myelin destruction after immune cell infiltration in EAE.

  20. Treatment Responsiveness in CIDP Patients with Diabetes Is Associated with Higher Degrees of Demyelination.

    Directory of Open Access Journals (Sweden)

    Alon Abraham

    Full Text Available Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP is one of several chronic treatable acquired demyelinating neuropathies.To explore the association between the degree of demyelination in CIDP, and treatment responsiveness.A retrospective chart review of CIDP subjects assessed between 1997 and 2013 was performed to compare treatment responsiveness using different sets of criteria.99 CIDP patients were included, 34 with diabetes mellitus (DM. Treatment responsiveness was higher in CIDP-DM fulfilling 1 or more EFNS/PNS criteria, (63% vs. 31%, p = 0.03, and in CIDP+DM fulfilling 2 or more criteria (89% vs. 36%, p = 0.01. Nonetheless, treatment responsiveness in CIDP+DM had the highest odds ratio (3.73, p = 0.01. Similar results were also shown in simplified uniform study criteria, with 10% cut off values for CIDP-DM, compared to 30% for CIDP+DM.In CIDP+DM, higher degrees of demyelination are associated with treatment responsiveness, implying the need to adjust current criteria in these patients.

  1. Autoimmune antigenic targets at the node of Ranvier in demyelinating disorders.

    Science.gov (United States)

    Stathopoulos, Panos; Alexopoulos, Harry; Dalakas, Marinos C

    2015-03-01

    Mounting evidence suggests that autoantibodies contribute to the pathogenesis of demyelination in the PNS and CNS. Rapid reversal of electrophysiological blockade after plasmapheresis or intravenous immunoglobulin treatment for acute or chronic inflammatory demyelinating polyneuropathy is more likely to result from removal or neutralization of an antibody that impairs saltatory conduction than from remyelination. Although up to 30% of patients with acute or chronic inflammatory demyelinating polyneuropathy harbour autoantibodies, specific antigens have been identified in no more than 13% of cases. To date, autoantigens identified at the node of Ranvier include neurofascin 186, gliomedin and possibly moesin in the nodal domain, and contactin-1, Caspr1 and neurofascin 155 in the paranodal domain. In some patients with multiple sclerosis, paranodal CNPase and juxtaparanodal contactin-2 trigger a humoral response. This Review explores the molecular anatomy of the node of Ranvier, focusing on proteins with extracellular domains that could serve as antigens. The clinical implications of node-specific antibody responses are addressed, and the best approaches to identify antibodies that target nodal proteins are highlighted. Also discussed are the roles of these antibodies as either secondary, disease-exacerbating responses, or as a primary effector mechanism that defines demyelination or axonal degeneration at the node, identifies disease subtypes or determines response to treatments.

  2. Demyelination versus remyelination in progressive multiple sclerosis

    DEFF Research Database (Denmark)

    Bramow, Stephan; Frischer, Josa M; Lassmann, Hans

    2010-01-01

    The causes of incomplete remyelination in progressive multiple sclerosis are unknown, as are the pathological correlates of the different clinical characteristics of patients with primary and secondary progressive disease. We analysed brains and spinal cords from 51 patients with progressive...... multiple sclerosis by planimetry. Thirteen patients with primary progressive disease were compared with 34 with secondary progressive disease. In patients with secondary progressive multiple sclerosis, we found larger brain plaques, more demyelination in total and higher brain loads of active demyelination...... compared with patients with primary progressive disease. In addition, the brain density of plaques with high-grade inflammation and active demyelination was highest in secondary progressive multiple sclerosis and remained ~18% higher than in primary progressive multiple sclerosis after adjustments...

  3. Treatment of chronic inflammatory neuropathies

    NARCIS (Netherlands)

    F. Eftimov

    2015-01-01

    This thesis focuses on the efficacy of existing and alternative treatments in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) and explores predictors of treatment response in patients with CIDP treated with corticosteroids. The efficacy of intra

  4. CXCL10 and trafficking of virus-specific T cells during coronavirus-induced demyelination.

    Science.gov (United States)

    Stiles, Linda N; Liu, Michael T; Kane, Joy A C; Lane, Thomas E

    2009-09-01

    Chronic expression of CXC chemokine ligand 10 (CXCL10) in the central nervous system (CNS) following infection with the neurotropic JHM strain of mouse hepatitis virus (JHMV) is associated with an immune-mediated demyelinating disease. Treatment of mice with anti-CXCL10 neutralizing antibody results in limited CD4+ T cell infiltration into the CNS accompanied by a reduction in white matter damage. The current study determines the antigen-specificity of the T lymphocytes present during chronic disease and evaluates how blocking CXCL10 signaling affects retention of virus-specific T cells within the CNS. CXCL10 neutralization selectively reduced accumulation and/or retention of virus-specific CD4+ T cells, yet exhibited limited effect on virus-specific CD8+ T cells. The response of CXCL10 neutralization on virus-specific T cell subsets is not due to differential expression of the CXCL10 receptor CXCR3 on T cells as there was no appreciable difference in receptor expression on virus-specific T cells during either acute or chronic disease. These findings emphasize the importance of virus-specific CD4+ T cells in amplifying demyelination in JHMV-infected mice. In addition, differential signals are required for trafficking and retention of virus-specific CD4+ and CD8+ T cells during chronic demyelination in JHMV-infected mice.

  5. 大剂量静脉人免疫球蛋白联合激素治疗慢性格林-巴利综合症效果分析%Curative Effects of High-dose Intravenous Immunoglobulins Combining with Steroids for Chronic Inflammatory Demyelinating Polyneruropathoes

    Institute of Scientific and Technical Information of China (English)

    郭蓉

    2007-01-01

    目的 研究大剂量静脉用人血免疫球蛋白(IVIg)联合类固醇激素与单独应用类固醇激素对慢性炎症性脱髓鞘性多发性神经病(chronic inflammatory demyelinating polyneruropathoes,CIDP)的治疗效果对比.方法 CIDP患者共32例,应用IVIg联合糖皮质激素治疗15例设为实验组,年龄17~67岁;仅用糖皮质激素治疗17例,年龄21~69岁,设为对照组.治疗前和治疗后分别测定患者的肌力(Fugl-Meyer运动积分)、日常生活能力(Barthel指数).结果 治疗前后Fugl-Meyer运动积分和Barthel指数的对比发现实验组与对照组比较差异有统计学意义(P<0.01),肌力恢复和日常生活能力恢复程度明显增加.结论 IVIg联合激素治疗CIDP的效果比单独用激素治疗效果要好,且越早越好.

  6. Demyelinating polyneuropathy in Leber hereditary optic neuropathy.

    NARCIS (Netherlands)

    Gilhuis, H.J.; Schelhaas, H.J.; Cruysberg, J.R.M.; Zwarts, M.J.

    2006-01-01

    We report a patient with Leber hereditary optic neuropathy (G11778A mtDNA) and a severe demyelinating neuropathy, for which no other cause except his mitochondrial disorder could be found. The involvement of the peripheral nervous system of patients with LHON, in particular with a 11778 mtDNA, is di

  7. Acquired Demyelinating Syndromes and Pediatric Multiple Sclerosis

    NARCIS (Netherlands)

    I.A. Ketelslegers (Immy)

    2014-01-01

    markdownabstract__Abstract__ Acquired inflammatory demyelinating diseases of the central nervous system (CNS) cause damage to myelin sheaths and typically result in white matter lesions due to inflammation, myelin loss and axonal pathology. Clinically, this may result in transient, relapsing or pro

  8. Paediatric UK demyelinating disease longitudinal study (PUDDLS

    Directory of Open Access Journals (Sweden)

    Likeman Marcus

    2011-07-01

    Full Text Available Abstract Background There is evidence that at least 5% of Multiple sclerosis (MS cases manifest in childhood. Children with MS present with a demyelinating episode involving single or multiple symptoms prior to developing a second event (usually within two years to then meet criteria for diagnosis. There is evidence from adult cohorts that the incidence and sex ratios of MS are changing and that children of immigrants have a higher risk for developing MS. A paediatric population should reflect the vanguard of such changes and may reflect trends yet to be observed in adult cohorts. Studying a paediatric population from the first demyelinating event will allow us to test these hypotheses, and may offer further valuable insights into the genetic and environmental interactions in the pathogenesis of MS. Methods/Design The Paediatric UK Demyelinating Disease Longitudinal Study (PUDDLS is a prospective longitudinal observational study which aims to determine the natural history, predictors and outcomes of childhood CNS inflammatory demyelinating diseases. PUDDLS will involve centres in the UK, and will establish a cohort of children affected with a first CNS inflammatory demyelinating event for long-term follow up by recruiting for approximately 5 years. PUDDLS will also establish a biological sample archive (CSF, serum, and DNA, allowing future hypothesis driven research. For example, the future discovery of a biomarker will allow validation within this dataset for the evaluation of novel biomarkers. Patients will also be requested to consent to be contacted in the future. A secondary aim is to collaborate internationally with the International Paediatric Multiple Sclerosis Study Group when future collaborative studies are proposed, whilst sharing a minimal anonymised dataset. PUDDLS is the second of two jointly funded studies. The first (UCID-SS is an epidemiological surveillance study that already received ethical approvals, and started on the 1st

  9. Tumefactive Demyelinating Lesions in Multiple Sclerosis and Associated Disorders.

    Science.gov (United States)

    Frederick, Meredith C; Cameron, Michelle H

    2016-03-01

    Tumefactive demyelinating lesions are rare consequences of central nervous system (CNS) idiopathic inflammatory demyelinating diseases. Tumefactive demyelinating lesions pose a diagnostic challenge because they can mimic tumors and abscesses and because they can be caused by a heterogeneous range of disorders. This article reviews the recent literature on the clinical presentation; radiographic features; prognosis; and management of tumefactive demyelinating lesions in multiple sclerosis, acute demyelinating encephalomyelitis, neuromyelitis optica, and the rare variants of multiple sclerosis including Schilder's disease, Marburg acute multiple sclerosis, and Balo's concentric sclerosis.

  10. Solitary osteosclerotic plasmacytoma: association with demyelinating polyneuropathy and amyloid deposition

    Energy Technology Data Exchange (ETDEWEB)

    Voss, S.D.; Hall, F.M. [Dept. of Radiology, Beth Israel Deaconess Medical Center, Boston, MA (United States); Harvard Medical School, Boston, MA (United States); Murphey, M.D. [Dept. of Radiologic Pathology, Armed Forces Institute of Pathology, Washington, DC (United States); Dept. of Radiology and Nuclear Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD (United States); Department of Radiology, University of Maryland School of Medicine, Baltimore, Maryland (United States)

    2001-09-01

    A 51-year-old man presented with a 1-year history of polyneuropathy necessitating the use of a wheelchair. Initial diagnosis was idiopathic chronic inflammatory demyelinating polyneuropathy (CIDP) and associated monoclonal gammopathy. Investigations for multiple myeloma, including bone marrow aspiration and biopsy, were negative. What was initially felt to be an incidental osteosclerotic focus noted on the radiographic bone survey was eventually shown to be a solitary osteosclereotic plasmacytoma with associated amyloid. This dramatically altered treatment. This case emphasizes the importance of including osteosclerotic plasmacytoma in the differential diagnosis of a focal sclerotic bone lesion in the clinical setting of polyneuropathy. These lesions are less likely to progress to multiple myeloma than lytic plasma cell neoplasms, and the presence of polyneuropathy often results in earlier diagnosis and treatment with enhanced prospect of cure. The finding of amyloid deposition within the osteosclerotic lesion may be of prognostic importance. (orig.)

  11. Multifocal acquired demyelinating sensory and motor neuropathy: the Lewis-Sumner syndrome.

    Science.gov (United States)

    Saperstein, D S; Amato, A A; Wolfe, G I; Katz, J S; Nations, S P; Jackson, C E; Bryan, W W; Burns, D K; Barohn, R J

    1999-05-01

    We report 11 patients with multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy, defined clinically by a multifocal pattern of motor and sensory loss, with nerve conduction studies showing conduction block and other features of demyelination. The clinical, laboratory, and histological features of these patients were contrasted with those of 16 patients with multifocal motor neuropathy (MMN). Eighty-two percent of MADSAM neuropathy patients had elevated protein concentrations in the cerebrospinal fluid, compared with 9% of the MMN patients (P < 0.001). No MADSAM neuropathy patient had elevated anti-GM1 antibody titers, compared with 56% of MMN patients (P < 0.01). In contrast to the subtle abnormalities described for MMN, MADSAM neuropathy patients had prominent demyelination on sensory nerve biopsies. Response to intravenous immunoglobulin treatment was similar in both groups (P = 1.0). Multifocal motor neuropathy patients typically do not respond to prednisone, but 3 of 6 MADSAM neuropathy patients improved with prednisone. MADSAM neuropathy more closely resembles chronic inflammatory demyelinating polyneuropathy and probably represents an asymmetrical variant. Given their different clinical patterns and responses to treatment, it is important to distinguish between MADSAM neuropathy and MMN.

  12. Microglia Play a Major Role in Direct Viral-Induced Demyelination

    Directory of Open Access Journals (Sweden)

    Dhriti Chatterjee

    2013-01-01

    Full Text Available Microglia are the resident macrophage-like populations in the central nervous system (CNS. Microglia remain quiescent, unable to perform effector and antigen presentation (APC functions until activated by injury or infection, and have been suggested to represent the first line of defence for the CNS. Previous studies demonstrated that microglia can be persistently infected by neurotropic mouse hepatitis virus (MHV which causes meningoencephalitis, myelitis with subsequent axonal loss, and demyelination and serve as a virus-induced model of human neurological disease multiple sclerosis (MS. Current studies revealed that MHV infection is associated with the pronounced activation of microglia during acute inflammation, as evidenced by characteristic changes in cellular morphology and increased expression of microglia-specific proteins, Iba1 (ionized calcium-binding adaptor molecule 1, which is a macrophage/microglia-specific novel calcium-binding protein and involved in membrane ruffling and phagocytosis. During chronic inflammation (day 30 postinfection, microglia were still present within areas of demyelination. Experiments performed in ex vivo spinal cord slice culture and in vitro neonatal microglial culture confirmed direct microglial infection. Our results suggest that MHV can directly infect and activate microglia during acute inflammation, which in turn during chronic inflammation stage causes phagocytosis of myelin sheath leading to chronic inflammatory demyelination.

  13. Guillain-Barré syndrome (demyelinating) six weeks after bariatric surgery: A case report and literature review.

    Science.gov (United States)

    Ishaque, Noman; Khealani, Bhojo A; Shariff, Amir H; Wasay, Muhammad

    2015-01-01

    Obesity is a major health problem worldwide. Bariatric surgery has been increasingly used to manage obesity. Many acute as well as chronic neurological complications have been reported after bariatric surgery including Guillain-Barré syndrome (GBS). An autoimmune process has been postulated as the underlying pathophysiology. Most of the reported cases of GBS after bariatric surgery are of the axonal variety. Here, we report a case of a demyelinating variety of GBS in a young woman who presented with acute onset of progressive weakness and paresthesia of all limbs within six weeks after bariatric surgery. She was treated with intravenous immunoglobulin (IVIG) and rehabilitation. She had complete recovery on follow-up. We believe that onset of acute inflammatory demyelinating polyradiculoneuropathy (AIDP), which is demyelinating variety of GBS, is associated with changes in immune system after bariatric surgery.

  14. Electrophysiologic study of chronic inflammatory demyelinating polyneuropathy by using segmental stimulation in the median nerve and ulnar nerve%正中神经和尺神经分段刺激在慢性炎性脱髓鞘性多发性神经病中的电生理研究

    Institute of Scientific and Technical Information of China (English)

    王晋荣; 王进华; 叶憬; 杨伟丽

    2013-01-01

    目的 探讨运动神经传导速度(MCV)、复合肌肉动作电位(CMAP)与肌力减退的关系和传导阻滞(CB)在慢性炎性脱髓鞘性多发性神经病(chronic inflammatory demyelinating polyradiculoneuritis,CIDP)中的表现特点.方法 30例CIDP患者在进行常规MCV、远端潜伏期(DML)、F波、感觉神经传导速度(SCV)、肌电图(EMG)测定的基础上,在正中神经采用由远到近的“腕-肘-腋-Erb's点”4点3段刺激,尺神经采用由远到近的“腕-肘下-肘上-腋-Erb's点”5点4段刺激,记录各段刺激后CMAP各参数及MCV的变化.结果 CMAP波幅衰减、面积衰减、时程增加以及MCV减慢与临床肌力减退无相关性,dCMAP波幅与上肢远端肌力呈正相关;患者中80.00%在正中神经、73.33%在尺神经发现了1个或多个节段的CB,且出现节段无明显选择性.结论 dCMAP波幅降低与CIDP患者肌力减退有相关性.在CIDP中CB出现率高,且较为弥散地在各节段中出现.%Objective To investigate the relationship between motor conduction velocity (MCV) and compound muscle action potential (CMAP) and muscle strength impairment; and to study the characteristics of conduction block (CB) in chronic inflammatory demyelinating polyneuropathy (CIDP). Methods 30 patients with CIDP formed the study population. All patients were examined by MCV, distal motor latency (DML), F wave, sensory nerve conduction velocity (SCV) and electromyography (EMG). Stimulations were perfomed at 4 sites of the median nerve from distal to proximal (wrist, elbow, axilla, Erb' s point) and 5 sites of the ulnar nerve (wrist, below elbow, above elbow, axilla, Erb' s point), while all the parameters of CMAP and MCV were recorded. Results There were no correlations between the CAMP amplitude attenuation, area, duration increase, MCV reduction and the clinical muscle strength. However, there was positive correlation between the amplitude of the dCMAP and the distal muscle strength in the upper

  15. 糖尿病合并慢性炎症性脱髓鞘性多发性神经病-4例临床分析并文献回顾%Diabetic chronic inflammatory demyelinating neuropathy-4 cases of clinical analysis and literature review

    Institute of Scientific and Technical Information of China (English)

    阳柏凤; 文延斌; 李静; 周文斌; 谢仁明

    2014-01-01

    目的 探讨糖尿病(diabetic mellitus,DM)合并慢性炎性脱髓鞘性多发性神经病(chronic inflammatory demyelinating polyneuropathy,CIDP)的临床、电生理特点,并与糖尿病周围神经病(diabetic peripheral neuropathy,DPN)进行早期鉴别诊断.方法 回顾性分析4例DM合并CIDP患者的临床表现、电生理检查及诊疗特征.结果 4例DM合并CIDP患者中,1例仅表现为对称性肢体乏力,其余3例均伴有对称性的麻木或疼痛,仅1例患者伴有颅神经损害;4例患者均存在腱反射均减弱或消失,病程均超过2个月,且均有脑脊液蛋白-细胞分离现象;4例患者肌电图检查均提示脱髓鞘病变为主,使用激素冲击治疗后症状均好转,其中2例复发患者分别采用丙种球蛋白和血浆置换术治疗后症状好转,4例患者目前均恢复良好.结论 当糖尿病患者出现周围神经病变时,早期根据其临床特征及辅助检查,诊断其是否合并CIDP,并对DM合并CIDP患者合理使用免疫抑制治疗效果良好.

  16. Directional diffusivity as a magnetic resonance (MR) biomarker in demyelinating disease

    Science.gov (United States)

    Benzinger, Tammie L. S.; Cross, Anne H.; Xu, Junqian; Naismith, Robert; Sun, Shu-Wei; Song, Sheng-Kwei

    2007-09-01

    Directional diffusivities derived from diffusion tensor magnetic resonance imaging (DTI) measurements describe water movement parallel to (λ ||, axial diffusivity) and perpendicular to (λ⊥radial diffusivity) axonal tracts. λ || and λ⊥ have been shown to differentially detect axon and myelin abnormalities in several mouse models of central nervous system white matter pathology in our laboratory. These models include experimental autoimmune encephalomyelitis (EAE), (1) myelin basic protein mutant mice with dysmyelination and intact axons, (2) cuprizone-induced demyelination, and remyelination, with reversible axon injury (2, 3) and a model of retinal ischemia in which retinal ganglion cell death is followed by Wallerian degeneration of optic nerve, with axonal injury preceding demyelination. (4) Decreased λ|| correlates with acute axonal injury and increased λ⊥ indicates myelin damage. (4) More recently, we have translated this approach to human MR, investigating acute and chronic optic neuritis in adults with multiple sclerosis, brain lesions in adults with multiple sclerosis, and acute disseminated encephalomyelitis (ADEM) in children. We are also investigating the use of this technique to probe the underlying structural change of the cervical spinal cord in acute and chronic T2- hyperintense lesions in spinal stenosis, trauma, and transverse myelitis. In each of these demyelinating diseases, the discrimination between axonal and myelin injury which we can achieve has important prognostic and therapeutic implications. For those patients with myelin injury but intact axons, early, directed drug therapy has the potential to prevent progression to axonal loss and permanent disability.

  17. NF-κB/AP-1-Targeted Inhibition of Macrophage-Mediated Inflammatory Responses by Depigmenting Compound AP736 Derived from Natural 1,3-Diphenylpropane Skeleton

    Directory of Open Access Journals (Sweden)

    Van Thai Ha

    2014-01-01

    Full Text Available AP736 was identified as an antimelanogenic drug that can be used for the prevention of melasma, freckles, and dark spots in skin by acting as a suppressor of melanin synthesis and tyrosinase expression. Since macrophage-mediated inflammatory responses are critical for skin health, here we investigated the potential anti-inflammatory activity of AP736. The effects of AP736 on various inflammatory events such as nitric oxide (NO/prostaglandin (PG E2 production, inflammatory gene expression, phagocytic uptake, and morphological changes were examined in RAW264.7 cells. AP736 was found to strongly inhibit the production of both NO and PGE2 in lipopolysaccharide- (LPS- treated RAW264.7 cells. In addition, AP736 strongly inhibited both LPS-induced morphological changes and FITC-dextran-induced phagocytic uptake. Furthermore, AP736 also downregulated the expression of multiple inflammatory genes, such as inducible NO synthase (iNOS, cyclooxygenase- (COX- 2, and interleukin- (IL- 1β in LPS-treated RAW264.7 cells. Transcription factor analysis, including upstream signalling events, revealed that both NF-κB and AP-1 were targeted by AP736 via inhibition of the IKK/IκBα and IRAK1/TAK1 pathways. Therefore, our results strongly suggest that AP736 is a potential anti-inflammatory drug due to its suppression of NF-κB-IKK/IκBα and AP-1-IRAK1/TAK1 signalling, which may make AP736 useful for the treatment of macrophage-mediated skin inflammation.

  18. Oligodendrocyte ablation as a tool to study demyelinating diseases

    Institute of Scientific and Technical Information of China (English)

    Ahdeah Pajoohesh-Ganji; Robert H. Miller

    2016-01-01

    Multiple sclerosis (MS) is an autoimmune mediated neurodegenerative disease characterized by demyelin-ation and oligodendrocyte (OL) loss in the central nervous system and accompanied by local inlfammation and inifltration of peripheral immune cells. Although many risk factors and symptoms have been iden-tified in MS, the pathology is complicated and the cause remains unknown. It is also unclear whether OL apoptosis precedes the inlfammation or whether the local inlfammation is the cause of OL death and demyelination. This review brielfy discusses several models that have been developed to speciifcally ablate oligodendrocytes in an effort to separate the effects of demyelination from inlfammation.

  19. Acute Demyelination in a Person with Amphetamine Abuse

    Directory of Open Access Journals (Sweden)

    Serge Weis

    2011-01-01

    Full Text Available We report the case of a 31-year-old woman, admitted to the hospital for chest pain, dying a few days later from septic multiorgan failure, and showing at autopsy foci of acute demyelination in the occipital lobe. Gas chromatography/mass spectrometry analysis revealed the presence of amphetamine in the demyelinated area, which might be considered as the pathogenic agent, since other causes for demyelination could be excluded. This case represents the first report showing a demyelinating process due to a street drug.

  20. An unusual case of osmotic demyelination syndrome without electrolyte changes in a patient with diabetes

    Directory of Open Access Journals (Sweden)

    Shrikant S Kote

    2016-01-01

    Full Text Available Central pontine myelinolysis (CPM is a demyelinating disease of the pons which is also associated with the demyelination of extrapontine areas of the central nervous system. Although the aetiology and pathogenesis are unclear, CPM is usually associated with hyponatremia or its rapid correction. Malnutrition and chronic alcoholism are also the common underlying conditions. Herein, we report a rare presentation of ODS, secondary to hyperosmolar hyperglycaemic state. We observed a 37-year-old female with diabetes type 1 and hypertension who presented with ataxia, dysarthria and pseudobulbar effect which evolved over a duration of few weeks at home with no evidence of hyponatremia or its rapid correction and no history of alcohol abuse or malnutrition.

  1. Osmotic demyelination syndrome with recent chemotherapy in normonatremic patient: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sungjae; Baek, Hye Jin; Jung, Hyun Kyung; Kim, Seon Jeong; Lee, Yedaun; Lee, Kwaghwi; Ryu, Ji Hwa; Kim, Hong Dae [Dept. of Radiology, Haeundae Paik Hospital, Inje University College of Medicine, Busan (Korea, Republic of)

    2014-11-15

    Osmotic demyelination syndrome (ODS), an acquired demyelinating condition of the central pons and/or other regions of the brain, is frequently associated with rapid correction of hyponatremia. There are several reports of ODS in other clinical setting such as malnutrition, alcoholism, transplantation, malignancy, and chronic debilitating illness. However, cases of ODS associated with chemotherapy have not been frequently reported. Here, we describe a case of ODS in a normonatremic patient recently underwent chemotherapy for colon cancer. The diagnosis was confirmed by MRI showing a typical T2 hyperintensity in the central pons. This case suggests that ODS is not always associated with hyponatremia and that ODS can have a favorable clinical and radiologic prognosis.

  2. 远端潜伏期指数在POEMS综合征和慢性炎症性脱髓鞘性多发性神经根神经病鉴别诊断中的价值研究%Role of Terminal Latency Index in Differentiation between POEMS Syndrome and Chronic Inflammatory Demyelinating Polyradiculoneuropathy

    Institute of Scientific and Technical Information of China (English)

    乔凯; 黄俊; 陈向军; 王毅

    2014-01-01

    Aim To determine the role of terminal latency index (TLI) in differentiation between POEMS syndrome and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Methods Median and ulnar nerve conduction studies including motor conduction velocity (MCV), distal motor latency (DML) and terminal latency index (TLI) of 18 POEMS patients were compared between 58 matched CIDP patients and 30 normal controls. Results In 18 POEMS patients, the average age at evaluation was 51.56±8.77 years old and that of 58 CIDP patients was (46.34±16.38) years old. Except the ulnar terminal latency index in CIDP, POEMS and CIDP patients demonstrated prolonged distal latencies, low conduction velocities and increased terminal latency indexes compared with the normal group. POEMS had reduced conduction velocities and higher terminal latency indexes than CIDP. Increased TLI was found in 55.6%(median nerve) and 52.9%(ulnar nerve) POEMS and that in CIDP patients was 25.9%(median nerve) and 22.4%(ulnar nerve). Decreased TLI was found in 24.1%(median) and 20.7%(ulnar) CIDP patients and none in POEMS. Temporal dispersion (TD) and conduction block (CB) were more often seen in CIDP patients with increased TLI than that in POEMS. Conclusion Compared with CIDP, POEMS showed greater slowing of the intermediate nerve segments and relatively more uniform demyelination. About 1/4 CIDP demonstrated more distal conduction slowing and more TD and CB especially in those with increased TLI. Terminal latency index combined with TD and CB may be helpful in differentiating POEMS from CIDP.%目的:探讨远端潜伏期指数(TLI)在鉴别POEMS综合征和慢性炎症性脱髓鞘性多发性神经根神经病(CIDP)中的应用价值。方法分析18例POEMS综合征(POEMS组)、58例CIDP患者(CIDP组)和30名正常者(对照组)的正中神经和尺神经运动传导参数,包括远端潜伏期、传导速度和TLI。结果 POEMS组与CIDP组正中神经和尺神经传导速度以及TLI存在差

  3. Comparison of clinical manifestations and electrophysiological features in patients with chronic inflamma-tory demyelinating polyneuropathy and Type-I Charcot Marie Tooth Disease%慢性炎性脱髓鞘性多发性神经病与腓骨肌萎缩症-I型的临床及神经电生理比较

    Institute of Scientific and Technical Information of China (English)

    刘璟洁; 韩萍; 高震; 巩付华; 马晓灵; 向莉

    2016-01-01

    Objectives To compare clinical manifestations and electrophysiological features in patients with chron⁃ic inflammatory demyelinating polyneuropathy (CIDP) and Type-I Charcot Marie Tooth Disease (CMT-I) for guiding dif⁃ferential diagnosis. Methods Data including clinical manifestations and electrophysiological indexes was collected from thirty-one CIDP cases and 28 CMT-I cases. Correlation analysis was used to assess the association of the severity of electrophysiology with the severity of clinical symptoms. Results There were statistically significant differences in onset site, sensory dysfunction, foot deformity and cerebrospinal fluid protein between these two groups (P0.05). Conclusions Differential diagnoses of CIDP and CMT-I can be made based on clinical manifestations and electro⁃physiological features.%目的:比较慢性炎性脱髓鞘性多发性神经病(chronic inflammatory demyelinating polyneuropathy, CI⁃DP)与腓骨肌萎缩症-I型(type-I Charcot Marie Tooth disease,CMT-I)的临床及神经电生理特点,以指导两者的鉴别诊断。方法纳入CIDP患者31例、CMT-I患者28例,收集其一般临床资料并对两组患者进行神经电生理检测,比较两组患者的临床特点及电生理指标,并对电生理严重程度与临床症状严重程度进行相关性分析。结果CIDP与CMT-I两组患者起病部位、主观感觉障碍、足部畸形、脑脊液蛋白比较有统计学差异(P<0.05)。运动末梢潜伏期(distal motor latency, DML)、运动传导速度(motor conduction velocity, MCV)、感觉传导速度(sensory conduction velocity, SCV)、传导阻滞/波形离散、下肢神经继发性轴索变性具有统计学差异(P<0.05)。失神经电位、MUAP形态异常、募集减少具有统计学差异(P<0.05)。CIDP临床症状严重程度与电生理严重程度有相关性(r=0.84, P<0.05);而CMT-I临床症状严重程度与电生理严重程度分离,不具有相关性(r=0.27, P

  4. Microglial recruitment, activation, and proliferation in response to primary demyelination

    DEFF Research Database (Denmark)

    Remington, Leah T; Babcock, Alicia A; Zehntner, Simone P;

    2007-01-01

    We have characterized the cellular response to demyelination/remyelination in the central nervous system using the toxin cuprizone, which causes reproducible demyelination in the corpus callosum. Microglia were distinguished from macrophages by relative CD45 expression (CD45(dim)) using flow cyto...

  5. A peritoneal dialysis patient with osmotic demyelination syndrome

    Directory of Open Access Journals (Sweden)

    Hing Ming Cheng

    2016-04-01

    Full Text Available A peritoneal dialysis patient with cirrhosis presented with drowsiness, vomiting, and mild hyponatremia. Despite no active correction of hyponatremia, she developed convulsion and quadriplegia. Magnetic resonance imaging of the brain showed changes of osmotic demyelination syndrome. This case illustrates that osmotic demyelination syndrome may occur in peritoneal dialysis without rapid correction of hyponatremia.

  6. Time-Dependent Progression of Demyelination and Axonal Pathology in MP4-Induced Experimental Autoimmune Encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    Johanna Prinz

    Full Text Available Multiple sclerosis (MS is an autoimmune disease of the central nervous system (CNS characterized by inflammation, demyelination and axonal pathology. Myelin basic protein/proteolipid protein (MBP-PLP fusion protein MP4 is capable of inducing chronic experimental autoimmune encephalomyelitis (EAE in susceptible mouse strains mirroring diverse histopathological and immunological hallmarks of MS. Lack of human tissue underscores the importance of animal models to study the pathology of MS.Twenty-two female C57BL/6 (B6 mice were immunized with MP4 and the clinical development of experimental autoimmune encephalomyelitis (EAE was observed. Methylene blue-stained semi-thin and ultra-thin sections of the lumbar spinal cord were assessed at the peak of acute EAE, three months (chronic EAE and six months after onset of EAE (long-term EAE. The extent of lesional area and inflammation were analyzed in semi-thin sections on a light microscopic level. The magnitude of demyelination and axonal damage were determined using electron microscopy. Emphasis was put on the ventrolateral tract (VLT of the spinal cord.B6 mice demonstrated increasing demyelination and severe axonal pathology in the course of MP4-induced EAE. Additionally, mitochondrial swelling and a decrease in the nearest neighbor neurofilament distance (NNND as early signs of axonal damage were evident with the onset of EAE. In semi-thin sections we observed the maximum of lesional area in the chronic state of EAE while inflammation was found to a similar extent in acute and chronic EAE. In contrast to the well-established myelin oligodendrocyte glycoprotein (MOG model, disease stages of MP4-induced EAE could not be distinguished by assessing the extent of parenchymal edema or the grade of inflammation.Our results complement our previous ultrastructural studies of B6 EAE models and suggest that B6 mice immunized with different antigens constitute useful instruments to study the diverse

  7. 异基因造血干细胞移植后慢性炎症性脱髓鞘性多发神经病变一例并文献复习%Chronic inflammatory demyelinating polyneuropathy after allogeneic hematopoietic stem cell transplantation: a case report and review of the literature

    Institute of Scientific and Technical Information of China (English)

    胡凯; 王继军; 万伟; 克晓燕

    2011-01-01

    目的 提高对异基因造血干细胞移植( allo-HSCT)后并发慢性炎症性脱髓鞘性多发神经病变( CIDP)的认识,探讨其临床特点、诊断及治疗.方法 报道1例慢性粒细胞白血病患者allo-HSCT 后发生CIDP的临床和实验室检查特征及治疗经过.结果 患者在移植后发生急性及慢性移植物抗宿主病(GVHD),在第+105天起出现慢性迁延反复的多发部位神经系统症状,以面瘫、四肢肌力减退、排尿困难为主,经多次腰椎穿刺脑脊液检查以及神经电生理检查,除外其他神经系统疾病后诊断为CIDP.经静脉丙种球蛋白、糖皮质激素、免疫抑制剂治疗及功能锻炼,GVHD及CIDP有所改善,但终因长期免疫抑制继发感染而死亡.结论 allo-HSCT后CIDP是一种罕见的、诊治困难的神经系统并发症,为移植相关的多种因素所致,GVHD及免疫系统紊乱是主要原因,应及时诊断,合理治疗.%Objective To study chronic inflammatory demyelinating polyneuropathy (CIDP) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and the clinical manifestation,diagnosis and treatment.Methods The clinical manifestation,laboratory examination,treatment and outcome of a patient with chronic myeloid leukemia after allo-HSCT were studied.Results Acute and chronic graft-versus-host disease(GVHD) were occurred in the patient followed by chronic multiple nervous system symptoms from +105 day including facioplegia,decreased muscle strength and dysuria.According to clinical manifestation,results of cerebrospinal fluid exam and electroneurophysiology exam,CIDP was diagnosed.The clinical condition was improved after treatment with intravenous immunoglobulin,glucocorticoid, immunosuppressive agents and functional exercises,but the patient died of secondary infection finally.Conclusion CIDP after allo-HSCT is a rare complication of nervous system and difficult to diagnose and treat.Numerous transplant-related causes are probably

  8. Clinical Implication of Antibody Against Sulfatide in Guillain-Barré Syndrome Associated Chronic Inflammatory Demyelinating Polyradiculoneuropathy%炎性周围神经病患者血清和脑脊液中抗硫脂抗体的临床意义

    Institute of Scientific and Technical Information of China (English)

    吴德云; 李晓光; 郭玉璞; 陈琳

    2003-01-01

    目的通过测定炎性周围神经病患者血清和脑脊液(CSF)中抗硫脂抗体水平,探讨其临床意义和可能的致病机制. 方法应用ELISA法检测30例急性吉兰-巴雷(Guillain-Barré syndrome,GBS)患者、24例慢性吉兰-巴雷(chronic inflammatory demyelinating polyradiculoneuropathy,CIDP)患者血清和CSF中抗硫脂抗体水平. 结果 (1)GBS患者血清中高滴度抗硫脂抗体与疾病组和正常对照组比较差异无显著性 (P>0.05);CSF中IgM-抗硫脂抗体阳性率与各对照组比较差异有极显著性 (P<0.01);(2)CIDP患者血清中高滴度抗硫脂抗体与正常对照组比较差异有显著性 (P<0.05),CSF中IgM-抗硫脂抗体阳性率与各对照组比较差异有显著性(P<0.05);(3)抗硫脂抗体阳性的GBS患者多有主观感觉障碍,差异有显著性(P<0.05);抗硫脂抗体阳性的CIDP患者多为感觉轴索性损害,差异有显著性(P<0.05);(4)轻、重型组GBS患者血清和CSF中抗硫脂抗体水平之间差异无显著性(P>0.05);(5)GBS组、CIDP组血清中抗体水平与配对的CSF中抗体水平无相关性. 结论 (1)GBS患者CSF中IgM-抗硫脂抗体有可能作为感觉神经受累的一项临床辅助参考指标,抗硫脂抗体的水平与疾病的临床严重程度及预后无明显关系;(2)CIDP患者CSF中IgM-抗硫脂抗体可作为感觉轴索型CIDP的临床辅助参考指标.

  9. Intravenous transplantation of mouse embryonic stem cells attenuates demyelination in an ICR outbred mouse model of demyelinating diseases

    Institute of Scientific and Technical Information of China (English)

    Kidsadagon Pringproa; Anucha Sathanawongs; Chananthida Khamphilai; Sarocha Sukkarinprom; Apichart Oranratnachai

    2016-01-01

    Induction of demyelination in the central nervous system (CNS) of experimental mice using cuprizone is widely used as an animal model for studying the pathogenesis and treatment of demyelination. How-ever, different mouse strains used result in different pathological outcomes. Moreover, because current medicinal treatments are not always effective in multiple sclerosis patients, so the study of exogenous cell transplantation in an animal model is of great importance. hTe aims of the present study were to establish an alternative ICR outbred mouse model for studying demyelination and to evaluate the effects of intrave-nous cell transplantation in the present developed mouse model. Two sets of experiments were conducted. Firstly, ICR outbred and BALB/c inbred mice were fed with 0.2% cuprizone for 6 consecutive weeks; then demyelinating scores determined by luxol fast blue stain or immunolabeling with CNPase were evaluated. Secondly, attenuation of demyelination in ICR mice by intravenous injection of mES cells was studied. Scores for demyelination in the brains of ICR mice receiving cell injection (mES cells-injected group) and vehicle (sham-inoculated group) were assessed and compared. hTe results showed that cuprizone signiif-cantly induced demyelination in the cerebral cortex and corpus callosum of both ICR and BALB/c mice. Additionally, intravenous transplantation of mES cells potentially attenuated demyelination in ICR mice compared with sham-inoculated groups. hTe present study is among the earliest reports to describe the cuprizone-induced demyelination in ICR outbred mice. Although it remains unclear whether mES cells or trophic effects from mES cells are the cause of enhanced remyelination, the results of the present study may shed some light on exogenous cell therapy in central nervous system demyelinating diseases.

  10. Optic neuritis: Experience from a south Indian demyelinating disease registry

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    Lekha Pandit

    2012-01-01

    Full Text Available Background: Natural history of optic neuritis (OPN has not been studied in India. Aim: To study consecutive patients with optic neuritis as the initial manifestation of the neurologic disease and with disease duration of 3 or more years registered in the Mangalore Demyelinating Disease Registry. Materials and Methods: The study included 59 patients with a primary diagnosis of optic neuritis (confirmed by either an ophthalmologist or a neurologist or both. All the patients were investigated and followed-up in the clinic. Results: During the follow-up of the 59 patients, 29 (49% patients developed multiple sclerosis (MS; 3 (5% patients neuromyelitis optica (NMO; and 13 (22% patients chronic relapsing inflammatory optic neuritis (CRION, while the remaining 14 (24% did not either progress or relapse, monophasic OPN. An initial abnormal magnetic resonance imaging predicted conversion to MS in all 7 patients who had imaging at onset. Patients with NMO were left with significant residual visual loss distinguishing NMO from MS. In this large series of patients with CRION, nearly 50% of patients had deterioration in vision while steroids were being tapered. Long-term immunosuppression was essential for maintaining good visual outcome in both NMO and CRION. Conclusions: Optic neuritis in India appears similar to that in the West with nearly 50% developing MS in the long term.

  11. 节段性运动神经传导测定在慢性炎性脱髓鞘性多发性神经根神经病和腓骨肌萎缩症1型之间的差异%Difference of segmental motor nerve conduction study between chronic inflammatory demyelinating polyradiculoneuropathy and Clarcot-Marie-Tooth type 1

    Institute of Scientific and Technical Information of China (English)

    刘明生; 崔丽英; 冯新红; 管宇宙; 李本红; 杜华

    2010-01-01

    目的 探讨节段性运动神经传导测定在慢性炎性脱髓鞘性多发性神经根神经病(chronic inflammatory demyelinating polyradiculoneuropathy,CIDP)和腓骨肌萎缩症1型(Charcot-MarieTooth type1,CMT1)鉴别诊断中的价值.方法 收集16例CIDP和13例CMT1患者,进行节段性运动神经传导测定,比较两组远端运动潜伏期、运动神经传导速度,以及近端和远端比较复合肌肉动作电位波幅、面积和时限变化的差异.结果 CIDP和CMT1患者远端运动潜伏期分别为(5.6±3.4)、(9.3±2.1)ms(t=5.347,P=0.000),运动传导速度分别为(31.1±14.3)、(22.2±5.8)m/s(t=6.369,P=0.000),近端和远端比较波幅下降百分比M5o分别为29.7%和4.9%(Z=7.141,P=0.000).在CIDP患者,所有测定神经中40.3%(25/62)远端潜伏期正常,18.1%(26/144)的神经节段传导速度正常,而在CMT1中所有测定神经的远端潜伏期均延长,所有测定节段的传导速度均减慢.在CIDP患者29.2%的神经节段可见传导阻滞或异常波形离散,而在CMT1仅有3.0%的节段可见传导阻滞(x2=20.829,P=0.000).结论 当针对CIDP和CMT1进行鉴别时,如果节段性运动神经传导测定发现传导阻滞和异常波形离散、不同神经节段传导速度下降程度差别较大,可以支持 CIDP的诊断.%Objective to assess the utility of segmental motor nerve conduction study in differential diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy(CIDP)and Charcot-Marie-Tooth type 1(CMT1).Methods A segmental motor nerve conduction study was performed on 16 patients with CIDP and 13 patients with CMT1.Distal motor latency,motor nerve conduction velocity,the changes of amplitude,area and duration of compound motor action potential over conventional segment were compared between the groups.Results Distal motor latency was (5.6±3.4) ms in CIDP and (9.3±2.1) ms in CMT1(t=5.347 P=0.000),motor nerve conduction velocity was (31.1±14.3) m/s in CIDP and(22.2±5.8)m/s(t=6.369,P=0

  12. Alternating sudden sensorineural hearing loss in demyelinating disorders

    Directory of Open Access Journals (Sweden)

    Rajeev Gupta

    2016-01-01

    Full Text Available Multiple sclerosis (MS is the most common demyelinating disease of the central nervous system. MS is a neuromotor disorder which progresses with remissions and relapsing periods. Symptoms of MS plaques may regress completely or heal by leaving sequelae. Symptomatology of MS may be very variable. These symptoms usually show variations depending on the localization of demyelinated plaques in the central nervous system. In this case, we are presenting a case of sudden sensorineural hearing loss in alternate ears with magnetic resonance images suggestive of demyelinating disorders. These hearing losses are improved completely as disease has remission and relapsing periods.

  13. Bispecific-armed, interferon gamma-primed macrophage-mediated phagocytosis of malignant non-Hodgkin's lymphoma.

    Science.gov (United States)

    Ely, P; Wallace, P K; Givan, A L; Graziano, R F; Guyre, P M; Fanger, M W

    1996-05-01

    To show that macrophages can be effectively targeted against malignant B cells, bispecific antibodies (BsAb) were constructed from two antibodies having specificity for the high-affinity Fc receptor for IgG (Fc gamma RI/CD64) and the B-cell differentiation antigens CD19 and CD37. Using a flow cytometry-based assay and confocal imaging, we show that these constructs mediated significant phagocytosis of B lymphocytes by macrophages that could be enhanced with interferon gamma (IFN gamma) and IFN gamma in combination with macrophage colony-stimulating factor. BsAb-dependent phagocytosis was triggered through Fc gamma RI and could be blocked only by using F(ab')2 fragments from the parent molecule or by cross-linking Fc gamma RI. BsAb-dependent phagocytosis was not blocked by antibodies to the other Fc receptors, Fc gamma RII and Fc gamma RIII. Because these antibody constructs bind to an epitope outside the Fc gamma RI ligand binding site, we show that autologous serum, polyclonal IgG, and monomeric IgG1 did not block BsAb-dependent phagocytosis, whereas autologous serum and the IgG fractions blocked parent molecule monoclonal antibody-dependent phagocytosis due to the avid binding of monomeric IgG to Fc gamma RI. Finally, BsAb-mediated phagocytosis was effective against the malignant B cells of patients with mantle cell lymphoma, prolymphocytic leukemia, and chronic lymphocytic leukemia. Based on these studies, we propose that BsAbs may provide an effective means of immunomodulation for patients with B-cell malignancies.

  14. Acute Demyelinating Disease after Oral Therapy with Herbal Extracts

    Directory of Open Access Journals (Sweden)

    Alex Kostianovsky

    2011-06-01

    Full Text Available Central nervous system demyelinating processes such as multiple sclerosis and acute disseminated encephalomyelitis constitute a group of diseases not completely understood in their physiopathology. Environmental and toxic insults are thought to play a role in priming autoimmunity. The aim of the present report is to describe a case of acute demyelinating disease with fatal outcome occurring 15 days after oral exposure to herbal extracts.

  15. 慢性炎性脱髓鞘性多发性神经根神经病周围神经细胞免疫与临床研究%An immunopathological study on biopsied sural nerves of chronic inflammatory demyelinating polyradiculoneuropathy(CIDP)

    Institute of Scientific and Technical Information of China (English)

    李放; 贾建平

    2007-01-01

    目的 研究慢性炎性脱髓鞘性多发性神经根神经病(chronic inflammatory demyelinating polyradic-uloneuropathy,CIDP)细胞免疫染色结果与临床、电生理和病理的关系.方法 经周围神经活检确诊的12例CIDP神经活检标本和10例其它神经系统疾病患者的周围神经标本,用免疫组织化学染色的方法标记神经内膜的淋巴细胞、巨噬细胞和表达鼠抗人白细胞DR抗原(HLA-DR)的细胞,并分别计数,比较2组患者阳性细胞数量;分析CIDP患者3种阳性细胞数与临床、电生理和病理的关系.结果 CIDP组与对照组比较,鼠抗人白细胞共同抗原(LCA)单克隆抗体、鼠抗人巨细胞(CD68)单克隆抗体、HDL-DR单克隆抗体的计数均有明显差异,P值分别为0.001、0.006和0.002;CIDP组HLA-DR阳性计数与CD68阳性计数之间有明显差异,P值为0.04,神经内膜水肿的LCA计数和无水肿的LCA计数比较有明显差异,P值为0.03,CD68阳性细胞在感觉神经传导速度减慢、神经纤维中重度减少的患者较相应的亚组有明显增高,且有显著差异,P值均为0.01,HLA-DR阳性计数在神经纤维中重度减少的患者也较相应的亚组有明显增高,有统计学差异,P值为0.01.结论 CIDP患者神经内膜的炎性细胞浸润是较多见的病理特点,并与神经内膜水肿有关,巨噬细胞的浸润与感觉神经传导速度减慢以及神经纤维数量减少有关,病程较长时巨噬细胞和雪旺氏细胞都可能为HLA-Ⅱ类抗原的抗原提呈细胞,雪旺氏细胞可能不仅为抗原提呈细胞,还可能同时参与对髓鞘的吞噬与破坏.

  16. Application of Contact Heat Evoked Potentials in chronic inflammatory demyelinating polyradiculoneuritis%接触性热痛诱发电位在慢性炎性脱髓鞘性多发性周围神经病中的应用

    Institute of Scientific and Technical Information of China (English)

    易敏; 姚源蓉; 谢炳玓

    2011-01-01

    Objective To study the characteristics of nociceptive conduction system in chronic inflammatory demyelinating polyradiculoneuritis (CIDP) hy Contact Heat Evoked Potentials (CHEPs) , to evaluate its application value in the diagnosis of CIDP. Methods Twenty-one patients diagnosed as CIDP and thirty-two heathy controls were included in this study , stimulated by CHEP stimulator. The latency of Cz/N was recorded.The A8fibers of peripheral nerves and N-wave latencies were analyzed and compared, while nervous conduction velocities were tested and the positive rates were compared. Results (1) CHEPs wave eduction rates in control were significantly higher than CIDP group. (2) The VAS scores in CIDP were significantly lower than control group (P < 0.05). (3) The Aδfihers conduction velocities in CIDP were significantly lower than control group (P <0.05). (4) The reduced rates of Aδfiher conduction velocity in upper limbs were lower than lower limbs (P < 0.05 ).(5) N-wave latencies of upper proximal and lower proximal limbs in CIDP group were not signiricantly different from control group (P > 0.05) , while N-wave latencies of upper distal and lower distal limbs in CIDP group were significantly longer than control group (P < 0.05). (6) The abnormality rates of Aδfibers in CHEPs were higher than MCV and SCV (P < 0.05). Conclusions CHEPs can present the ahnormal regions and damaged degree of nociceptive conduction system in CIDP patients and is more sensitive than traditional nervous conduction velocities. CHEPs may be used as an electrophysiology reference index for the clinical diagnosis of CIDP.%目的:应用接触性热痛诱发电位(CHEPs)技术研究慢性炎性脱髓鞘性多发性周围神经病(CIDP)患者的痛觉传导通路病变特点,探讨CHEPs在CIDP诊断中的应用价值.方法:选取确诊为CIDP的患者21例及对照组32例,应用CHEP刺激器进行刺激,记录Cz/N的潜伏期,分析比较外周神经Aδ纤维及N波峰潜伏期,同时

  17. Movement disorders and the osmotic demyelination syndrome.

    Science.gov (United States)

    de Souza, Aaron

    2013-08-01

    With the advent of MRI, osmotic demyelination syndromes (ODS) are increasingly recognised to affect varied sites in the brain in addition to the classical central pontine lesion. Striatal involvement is seen in a large proportion of cases and results in a wide variety of movement disorders. Movement disorders and cognitive problems resulting from ODS affecting the basal ganglia may occur early in the course of the illness, or may present as delayed manifestations after the patient survives the acute phase. Such delayed symptoms may evolve over time, and may even progress despite treatment. Improved survival of patients in the last few decades due to better intensive care has led to an increase in the incidence of such delayed manifestations of ODS. While the outcome of ODS is not as dismal as hitherto believed - with the acute akinetic-rigid syndrome associated with striatal myelinolysis often responding to dopaminergic therapy - the delayed symptoms often prove refractory to medical therapy. This article presents a review of the epidemiology, pathophysiology, clinical features, imaging, and therapy of movement disorders associated with involvement of the basal ganglia in ODS. A comprehensive review of 54 previously published cases of movement disorders due to ODS, and a video recording depicting the spectrum of delayed movement disorders seen after recovery from ODS are also presented.

  18. Demyelinating disease masquerading as a surgical problem: a case series

    Directory of Open Access Journals (Sweden)

    Awang Saufi M

    2009-08-01

    Full Text Available Abstract Introduction We report three cases of demyelinating disease with tumor-like presentation. This information is particularly important to both neurosurgeons and neurologists who should be aware that inflammatory demyelinating diseases can present as a mass lesion, which is indistinguishable from a tumor, both clinically and radiologically, especially when there is no evidence of temporal dissemination of this disease. Case presentation The first patient was a 42-year-old Malay woman who developed subacute onset of progressive quadriparesis with urinary incontinence. Magnetic resonance imaging of her spine showed an intramedullary lesion at the C5-C7 level. She was operated on and biopsy was suggestive of a demyelinating disease. Retrospective history discovered two episodes of acute onset of neurological deficits with partial recovery and magnetic resonance imaging of her brain revealed demyelinating plaques in the centrum semiovale. The second patient was a 16-year-old Malay boy who presented with symptoms of raised intracranial pressure. A computed tomography brain scan revealed obstructive hydrocephalus with a lesion adjacent to the fourth ventricle. An external ventricular drainage was inserted. Subsequently, a stereotactic biopsy was taken and histopathology was reported as demyelination. Retrospective history revealed similar episodes with full recovery in between episodes. The third case was a 28-year-old Malay man who presented with acute bilateral visual loss and confusion. Magnetic resonance imaging of his brain showed a large mass lesion in the right temporoparietal region. Biopsy was consistent with demyelinating disease. Reexamination of the patient revealed bilateral papillitis and not papilledema. Visual evoked potential was prolonged bilaterally. In all three cases, lumbar puncture for cerebrospinal fluid study was not carried out due to lack of patient consent. Conclusions These cases illustrate the importance of

  19. Demyelinizing neurological disease after treatment with tumor necrosis factor alpha-inhibiting agents in a rheumatological outpatient clinic

    DEFF Research Database (Denmark)

    Theibich, Ali; Dreyer, Lene; Magyari, Melinda;

    2014-01-01

    Biological treatment with inhibitors of the pro-inflammatory cytokine TNF-alpha has dramatically improved the disease course of several chronic rheumatologic conditions. Adverse events (AEs) are primarily infections and hypersensitivity reactions. Demyelinizing neurological symptoms resembling...... multiple sclerosis (MS) have been described as a rare AE. During about 10-year use of anti TNF-alpha, the Danish Medicines Agency has recorded eight cases of MS like AEs. The objective of this study was to estimate the incidence of demyelinizing AEs both in the central and peripheral nervous system after...... treatment with anti TNF-alpha in a cohort of patients from a large rheumatologic outpatient clinic in Copenhagen. In a 4-year period from January 2008 to December 2011, approximately 550 patients annually were undergoing treatment with anti TNF-alpha inhibitors in our department. We collected data on all...

  20. [Chronic polyradiculoneuritis and its frontiers].

    Science.gov (United States)

    Vallat, J M; Tabaraud, F; Magy, L; Macian, F

    2002-12-01

    The Chronic Inflammatory Demyelinating Polyradiculoneuropathies (CIDP) constitute a syndrome whose incidence is difficult to evaluate, and is probably underestimated. In the course of this presentation, we deliberately restricted discussion to issues raised in recent years concerning the extent of this syndrome. We discuss diagnostic criteria, especially electrophysiological ones. As the criteria proposed by the ad hoc committee of the American Academy of Neurology in 1991 have been questioned due to lack of sensitivity, new ones have been proposed recently. We briefly discuss the different types of chronic dysimmune demyelinating neuropathy: not only the CIDP, but also the Lewis and Sumner syndrome or multifocal inflammatory demyelinating neuropathy and the multiple conduction block neuropathies. At last, we point out the consistent finding of axonal involvement in the course of a chronic demyelinating neuropathy; over time, it can become pre-dominant, which may make diagnosis difficult by suggesting a chronic axonal neuropathy that may be assumed to be primary. Consideration of these points may help clinicians recognize more chronic dysimmune neuropathies, for which immunosuppressive therapy has been found to be effective.

  1. Combined central and peripheral demyelination: Clinical features, diagnostic findings, and treatment.

    Science.gov (United States)

    Cortese, A; Franciotta, D; Alfonsi, E; Visigalli, N; Zardini, E; Diamanti, L; Prunetti, P; Osera, C; Gastaldi, M; Berzero, G; Pichiecchio, A; Piccolo, G; Lozza, A; Piscosquito, G; Salsano, E; Ceroni, M; Moglia, A; Bono, G; Pareyson, D; Marchioni, E

    2016-04-15

    Combined central and peripheral demyelination (CCPD) is rare, and current knowledge is based on case reports and small case series. The aim of our study was to describe the clinical features, diagnostic results, treatment and outcomes in a large cohort of patients with CCPD. Thirty-one patients entered this retrospective, observational, two-center study. In 20 patients (65%) CCPD presented, after an infection, as myeloradiculoneuropathy, encephalopathy, cranial neuropathy, length-dependent peripheral neuropathy, or pseudo-Guillain-Barré syndrome. Demyelinating features of peripheral nerve damage fulfilling European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) electrodiagnostic criteria for CIDP were found in 23 patients (74%), and spatial dissemination of demyelinating lesions on brain MRI fulfilling the 2010 McDonald criteria for multiple sclerosis (MS) in 11 (46%). Two thirds of the patients had a relapsing or progressive disease course, usually related to the appearance of new spinal cord lesions or worsening of the peripheral neuropathy, and showed unsatisfactory responses to high-dose corticosteroids and intravenous immunoglobulins. The clinical presentation of CCPD was severe in 22 patients (71%), who were left significantly disabled. Our data suggest that CCPD has heterogeneous features and shows frequent post-infectious onset, primary peripheral nervous system or central nervous system involvement, a monophasic or chronic disease course, inadequate response to treatments, and a generally poor outcome. We therefore conclude that the current diagnostic criteria for MS and CIDP may not fully encompass the spectrum of possible manifestations of CCPD, whose pathogenesis remains largely unknown.

  2. Diffusion-weighted imaging in acute demyelinating myelopathy

    Energy Technology Data Exchange (ETDEWEB)

    Zecca, Chiara; Cereda, Carlo; Tschuor, Silvia; Staedler, Claudio; Nadarajah, Navarajah; Bassetti, Claudio L.; Gobbi, Claudio [Ospedale Regionale di Lugano, Servizio di Neurologia e Neuroradiologia, Neurocenter of Southern Switzerland, Lugano (Switzerland); Wetzel, Stephan [Swiss Neuro Institute (SNI), Abteilung fuer Neuroradiologie, Hirslanden Klinik Zuerich, Zuerich (Switzerland); Santini, Francesco [University of Basel Hospital, Division of Radiological Physics, Basel (Switzerland)

    2012-06-15

    Diffusion-weighted imaging (DWI) has become a reference MRI technique for the evaluation of neurological disorders. Few publications have investigated the application of DWI for inflammatory demyelinating lesions. The purpose of the study was to describe diffusion-weighted imaging characteristics of acute, spinal demyelinating lesions. Six consecutive patients (two males, four females; aged 28-64 years) with acute spinal cord demyelinating lesions were studied in a prospective case series design from June 2009 to October 2010. We performed magnetic resonance imaging studies from 2 to 14 days from symptom onset on the patients with relapsing remitting multiple sclerosis (n = 3) or clinically isolated syndrome (n = 3). Main outcome measures were diffusion-weighted imaging and apparent diffusion coefficient pattern (ADC) of acute spinal cord demyelinating lesions. All spinal lesions showed a restricted diffusion pattern (DWI+/ADC-) with a 24% median ADC signal decrease. A good correlation between clinical presentation and lesion site was observed. Acute demyelinating spinal cord lesions show a uniform restricted diffusion pattern. Clinicians and neuro-radiologists should be aware that this pattern is not necessarily confirmatory for an ischaemic aetiology. (orig.)

  3. Control of demyelination for recovery of spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    WU Bo; REN Xian-jun

    2008-01-01

    Since loss of of oligodendrocytes and consequent demyelination of spared axons severely impair the functional recovery of injured spinal cord,it is reasonably expected that the reduction of oligodendroglial death and enhanced remyelination of demyelinated axons will have a therapeutic potential to treat spinal cord injury.Amelioration of axonal myelination in the injured spinal cord is valuable for recovery of the neural function of incompletely injured patients.Here,this article presents an overview about the pathophysiology and mechanism of axonal demyelination in spinal cord injury and discusses its therapeutic significance in the treatment of spinal cord injury.Moreover,it further introduces the recent strategies to improve the axonal myeliantion to facilitate functional recovery of spinal cord injury.

  4. Diffusion Magnetic Resonance Imaging May Provide Prognostic Information in Osmotic Demyelination Syndrome: Report of a Case

    Energy Technology Data Exchange (ETDEWEB)

    Dervisoglu, E.; Yegenaga, I.; Anik, Y.; Sengul, E.; Turgut, T. [Kocaeli Univ. (Turkey). Internal Medicine

    2006-03-15

    Hyponatremia and its rapid correction may cause osmotic demyelination syndrome (ODS) with damage to the pontine and extrapontine areas of the brain. The damage may become persistent or may regress and disappear during follow-up. We describe the case of a 35-year-old woman with chronic renal failure who was admitted to the emergency department with profound hyponatremia which was corrected rapidly after hemodialysis treatment. During follow-up, she developed quadriparesis and dysartria. Magnetic resonance imaging (MRI) demonstrated abnormalities characteristic of ODS in the pons as well as the basal ganglia with increased signal intensity on T2 and diffusion-weighted (DW) MRI and low apparent diffusion coefficient (ADC) values. After the sixth day, her clinical status improved progressively. Control MRI revealed rapid normalization of the ADC values during the first week and month parallel to the clinical improvement. However, the hyperintensities on T2-weighted images persisted. Four months later the MRI findings were completely normal. The close relationship between the ADC abnormality and the clinical status suggests that DW-MRI may be useful in predicting the prognosis of ODS. Keywords: Apparent diffusion coefficient; correction of hyponatremia; magnetic resonance imaging; osmotic demyelination.

  5. Electrophysiologic features of inherited demyelinating neuropathies: a reappraisal.

    Science.gov (United States)

    Lewis, R A; Sumner, A J

    1999-09-14

    The observation that inherited demyelinating neuropathies tend to have uniform conduction slowing and acquired disorders (CIDP and variants) have nonuniform or multifocal slowing was made before the identification of genetic defects of specific myelin constituents that cause the different forms of Charcot-Marie-Tooth and other inherited disorders involving peripheral nerve myelin. It is becoming clear that the electrophysiologic aspects of these disorders are more complex than previously realized. We review the current information available on the electrophysiologic features of the inherited demyelinating neuropathies in hopes of clarifying the clinical electrodiagnostic features of these disorders as well as to shed light on the physiologic consequences of the different genetic mutations.

  6. Demyelination determinants map to the spike glycoprotein gene of coronavirus mouse hepatitis virus.

    Science.gov (United States)

    Das Sarma, J; Fu, L; Tsai, J C; Weiss, S R; Lavi, E

    2000-10-01

    Demyelination is the pathologic hallmark of the human immune-mediated neurologic disease multiple sclerosis, which may be triggered or exacerbated by viral infections. Several experimental animal models have been developed to study the mechanism of virus-induced demyelination, including coronavirus mouse hepatitis virus (MHV) infection in mice. The envelope spike (S) glycoprotein of MHV contains determinants of properties essential for virus-host interactions. However, the molecular determinants of MHV-induced demyelination are still unknown. To investigate the mechanism of MHV-induced demyelination, we examined whether the S gene of MHV contains determinants of demyelination and whether demyelination is linked to viral persistence. Using targeted RNA recombination, we replaced the S gene of a demyelinating virus (MHV-A59) with the S gene of a closely related, nondemyelinating virus (MHV-2). Recombinant viruses containing an S gene derived from MHV-2 in an MHV-A59 background (Penn98-1 and Penn98-2) exhibited a persistence-positive, demyelination-negative phenotype. Thus, determinants of demyelination map to the S gene of MHV. Furthermore, viral persistence is insufficient to induce demyelination, although it may be a prerequisite for the development of demyelination.

  7. Spinal cord demyelination combined with hyperhomocysteinemia: a case report

    Directory of Open Access Journals (Sweden)

    Hao MM

    2014-11-01

    Full Text Available Meimei Hao, Yan Zhang, Shuangxing Hou, Yanling Chen, Ming Shi, Gang Zhao, Yanchun Deng Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of China Abstract: Hyperhomocysteinemia (HHcy has been recognized as an independent risk factor for atherosclerotic vascular disease. Here we report a patient who suffered from spinal cord demyelination combined with HHcy. The patient was admitted to our hospital with a diagnosis of acute myelitis. However, hormone therapy was ineffective. Further investigations revealed that he had HHcy and a homozygous mutation of the gene encoding methylenetetrahydrofolate reductase (MTHFR c.677C>T, which is a key enzyme involved in homocysteine metabolism. In view of these findings, we treated the patient with B vitamins and his symptoms gradually improved. Spinal magnetic resonance imaging performed 3 months after onset showed near recovery of the lesion. To our knowledge, similar reports are rare. Keywords: demyelination, hyperhomocysteinemia, homocysteine, methylenetetrahydrofolate reductase, methylation

  8. Isolated paroxysmal dysarthria caused by a single demyelinating midbrain lesion.

    Science.gov (United States)

    Codeluppi, Luca; Bigliardi, Guido; Chiari, Annalisa; Meletti, Stefano

    2013-10-16

    Paroxysmal dysarthria is an unusual condition characterised by brief episodes of dysarthria with the sudden onset and frequent recurrence. It has been mainly reported in multiple sclerosis and an association with midbrain lesions has been claimed; however, most of the reported patients had multiple brain alterations so it was difficult to associate this symptom with a specific lesion site. We illustrate the cases of two patients with an isolated demyelinating midbrain lesion presenting paroxysmal dysarthria as the only symptom; both participants had oligoclonal bands in the cerebrospinal fluid and an unremarkable follow-up. Both patients had benefit from carbamazepine treatment, similarly to previously reported cases. Our report confirms that a demyelinating midbrain lesion is sufficient to provoke paroxysmal dysarthria. It is noteworthy that an erroneous diagnosis of psychogenic disorders was initially made in both cases, highlighting the importance not to underestimate isolated paroxysmal symptoms in clinical practice.

  9. Polarization of macrophages and microglia in inflammatory demyelination

    Institute of Scientific and Technical Information of China (English)

    Li Cao; Cheng He

    2013-01-01

    Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system,and microglia and macrophages play important roles in its pathogenesis.The activation of microglia and macrophages accompanies disease development,whereas depletion of these cells significantly decreases disease severity.Microglia and macrophages usually have diverse and plastic phenotypes.Both pro-inflammatory and antiinflammatory microglia and macrophages exist in MS and its animal model,experimental autoimmune encephalomyelitis.The polarization of microglia and macrophages may underlie the differing functional properties that have been reported.In this review,we discuss the responses and polarization of microglia and macrophages in MS,and their effects on its pathogenesis and repair.Harnessing their beneficial effects by modulating their polarization states holds great promise for the treatment of inflammatory demyelinating diseases.

  10. Osmotic demyelination syndrome with a dysequilibrium syndrome: reversible MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Agildere, A.M.; Coskun, M.; Boyvat, F. [Baskent University Medical School Hospital, Radiology Department, Ankara (Turkey); Benli, S. [Baskent University Medical School Hospital, Neurology Department, Ankara (Turkey); Erten, Y.; Oezdemir, N. [Baskent University Medical School Hospital, Nephrology Department, Ankara (Turkey)

    1998-04-01

    Neurological disorders may be seen in end-stage renal disease patients due to uraemia or to complications of dialysis. A dysequilibrium syndrome may be seen, usually soon after or towards the end of haemodialysis. This group of patients has no particular findings on MRI. On the other hand, the osmotic demyelination syndrome has definitive MRI findings, not to date reported with the dysequilibrium syndrome. We report a patient with end-stage renal disease and the dysequilibrium syndrome who showed findings of osmotic demyelination on MRI. The patient had a convulsion after a first haemodialysis, with quadriparesis and hyperactive deep tendon reflexes and bilateral Babinski signs. The upper motor neurone signs lasted for a week. Meanwhile, he was also dysarthric and had dysphagia. He recovered neurologically without any residuum following appropriate treatment and there was improvement on MRI. (orig.) With 3 figs., 11 refs.

  11. Cerebrospinal fluid analysis in the context of CNS demyelinating diseases

    Directory of Open Access Journals (Sweden)

    Sandro Luiz de Andrade Matas

    2013-09-01

    Full Text Available The central nervous system demyelinating diseases are a group of disorders with different etiologies, characterized by inflammatory lesions that are associated with loss of myelin and eventually axonal damage. In this group the most studied ones are multiple sclerosis (MS, neuromyelitis optic (NMO and acute disseminated encephalomyelitis (ADEM. The cerebrospinal fluid is essential to differentiate between these different syndromes and to define multiple sclerosis, helping to assess the probability of Clinical Isolated Syndrome turn into multiple sclerosis.

  12. Orthostatic intolerance in multifocal acquired demyelinating sensory and motor neuropathy.

    Science.gov (United States)

    Tramontozzi, Louis A; Russell, James A

    2012-09-01

    We report a patient with orthostatic intolerance and syncope as a major clinical manifestation of an acquired multifocal neuropathy with the clinical, electrodiagnostic, and cerebrospinal fluid features of multifocal acquired demyelinating sensory and motor neuropathy or the Lewis-Sumner syndrome. Immunomodulatory therapy led to clinical remission of both somatic and autonomic signs and symptoms. We are unaware of a previous description of symptomatic dysautonomia in this disorder.

  13. Case report: acute demyelinating encephalomyelitis following viper bite

    OpenAIRE

    Xu, Anyi; Shan, Renfei; Huang, Daochao; Zhou, Jiajia; Keenoo, Anaswasseem; Qin, Jie

    2016-01-01

    Abstract The most serious complications of the central nervous system that occur after venomous snake bite are intracranial hemorrhage and ischemic stroke. We present a rarely seen central nervous system complication, acute demyelinating encephalomyelitis, after a treated Deinagkistrodon's viper bite. On April 5, 2015, a 50-year-old male farmer was bitten on his right leg by a Deinagkistrodon's viper. The bite rendered the victim unconscious for 14 days, during which he was treated with tetan...

  14. Central nervous system inflammatory demyelinating disorders of childhood

    OpenAIRE

    Kamate Mahesh; Chetal Vivek; Tonape Venkatesh; Mahantshetti Niranjana; Hattiholi Virupaxi

    2010-01-01

    Background and Objectives: Childhood Central Nervous System (CNS) inflammatory demyelinating disorders (CIDD) are being diagnosed more commonly now. There is ambiguity in the use of different terms in relation to CIDD. Recently, consensus definitions have been proposed so that there is uniformity in studies across the world. The prevalence of these disorders and the spectrum varies from place to place. This study was undertaken to study the clinico-radiological profile and outcome of children...

  15. Improvement of advanced postvaccinal demyelinating encephalitis due to plasmapheresis

    Directory of Open Access Journals (Sweden)

    Andreas Rogalewski

    2007-01-01

    Full Text Available Andreas Rogalewski1, Jörg Kraus3, Martin Hasselblatt2, Christoffer Kraemer1, Wolf-Rüdiger Schäbitz11Department of Neurology; 2Institute of Neuropathology, University of Muenster, Germany, 3Paracelsus Private Medical University and Salzburger Landesklinken, Christian-Doppler-Klinik, Department of Neurology, Salzburg, AustriaAbstract: We report a case of acute demyelinating encephalitis that occurred after viral vaccination against hepatitis A-, hepatitis B-, and poliovirus and vaccination against bacterial toxins of diphtheria and tetanus. After different diagnosis had been excluded, we diagnosed postvaccinal demyelinating encephalitis and started treatment with high dose intravenous methylprednisolone, followed by peroral application in decreasing dosages for three weeks. A few days after the treatment with methylprednisolone had been finished, the patient’s medical condition deteriorated again. Thus, we initiated plasma exchange at an advanced state of illness, which led to significant continuous improvement. The role of plasma exchange is discussed controversially, in particular the issue of timing. We report a case that shows improvement due to plasmapheresis several weeks after symptom onset.Keywords: ADEM, vaccination, encephalitis, plasmapheresis, demyelination, plasma exchange

  16. Gastroparesis secondary to a demyelinating disease: a case series

    Directory of Open Access Journals (Sweden)

    Bonino John

    2007-01-01

    Full Text Available Abstract Background Gastroparesis has a number of etiologies. The main ones are secondary to a complication from diabetes mellitus, related to post vagotomy or post gastric surgical resections, or idiopathic when the etiology is unclear. Gastroparesis secondary to a demyelinating disease of the brain is unusual. Case presentation A 22-year-old woman was referred for acute onset of intractable nausea and vomiting. She also had cerebellar deficits, dysphagia and paresthesias. Magnetic resonance imaging (MRI of the brain revealed an isolated area of demyelination in the medullary region. Another 24-year-old woman had a similar presentation with right hemiplegia and MRI of the brain revealed a distal medullary region. Both these patients had an abnormal gastric emptying test. Gastroparesis and neurological deficits improved with intravenous corticosteroids. While the former patient has had no further recurrences, the latter patient developed multiple sclerosis within three months of presentation. Conclusion A demyelinating disease is a rare cause gastropareis, but should be suspected when symptoms of gastroparesis are associated with neurological deficits. MRI might help in the diagnosis and intravenous coriticosteroids can address the underlying disease process and improve gastric emptying, especially when used early during the course of the disease.

  17. Gastroparesis secondary to a demyelinating disease: a case series

    Science.gov (United States)

    Reddymasu, Savio C; Bonino, John; McCallum, Richard W

    2007-01-01

    Background Gastroparesis has a number of etiologies. The main ones are secondary to a complication from diabetes mellitus, related to post vagotomy or post gastric surgical resections, or idiopathic when the etiology is unclear. Gastroparesis secondary to a demyelinating disease of the brain is unusual. Case presentation A 22-year-old woman was referred for acute onset of intractable nausea and vomiting. She also had cerebellar deficits, dysphagia and paresthesias. Magnetic resonance imaging (MRI) of the brain revealed an isolated area of demyelination in the medullary region. Another 24-year-old woman had a similar presentation with right hemiplegia and MRI of the brain revealed a distal medullary region. Both these patients had an abnormal gastric emptying test. Gastroparesis and neurological deficits improved with intravenous corticosteroids. While the former patient has had no further recurrences, the latter patient developed multiple sclerosis within three months of presentation. Conclusion A demyelinating disease is a rare cause gastropareis, but should be suspected when symptoms of gastroparesis are associated with neurological deficits. MRI might help in the diagnosis and intravenous coriticosteroids can address the underlying disease process and improve gastric emptying, especially when used early during the course of the disease. PMID:17266755

  18. 神经超声在Chacot-Marie-Tooth1型和慢性炎性脱髓鞘性多发性神经根神经病鉴别诊断中的价值%The utility of peripheral nerve ultrasound in differentiating Charcot-Marie-Tooth type 1 from chronic inflammatory demyelinating polyradiculoneuropathy

    Institute of Scientific and Technical Information of China (English)

    刘明生; 牛婧雯; 李亦; 吴双; 管宇宙; 崔丽英

    2016-01-01

    CharcotMarie-Tooth type 1 (CMT1) from chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).Methods Eighteen patients with CIDP,13 patients with CMT1 and 16 healthy controls were recruited prospectively from Peking Union Medical College Hospital between January 2014 and July 2015 for this study.Ultrasonographic tests were performed via nerve tracing from wrist to axilla on median and ulnar nerve with a 10 MHz linear array probe.The cross sectional areas (CSAs) were measured at 10 defined sites of the nerves,respectively.Results CSAs (mm2) at all sites of median nerve were significantly increased in CMT1 than in CIDP (10.5 ±5.3 vs7.8 ±2.4,10.9 ±3.6 vs 6.8 ±1.9,11.5 ±5.0 vs7.3 ±1.8,13.5 ± 4.4vs7.2±2.5,16.0±4.5vs7.2±2.1,17.1±5.1vs7.0±2.8,21.0±4.5vs9.5±4.8,24.3±6.9 vs 9.5 ±4.3,23.9 ±6.0 vs 10.2 ±4.3,22.4 ±6.7 vs 9.8 ±2.1;t=2.141,4.766,2.935,4.858,6.715,6.602,7.148,7.100,8.078,6.498,respectively,all P < 0.05).CSAs (mm2) at all sites of ulnar nerve were significantly increased in CMT1 than in CIDP (7.9 ± 1.8 vs 4.0 ± 1.3,8.9 ± 2.0 vs 4.9 ± 1.3,13.5±1.9 vs6.5±2.4,15.0±4.3 vs 6.5 ±1.5,15.8 ±4.4 vs 6.8 ±3.3,11.6±2.3 vs6.9± 3.1,10.2±3.2vs7.6±2.8,14.0±3.0vs6.6±2.1,19.2±3.7vs7.6±4.4,18.1±3.6vs6.3± 2.5;t =7.652,7.414,9.194,6.893,6.443,4.766,2.561,7.897,8.113,11.554,respectively,all P < 0.05).CSAs at 8 sites of median nerve and 8 sites of ulnar nerve were significantly increased in CIDP than in healthy controls.Receiver operation characteristic curve analysis revealed that CSA was suited for differentiating CMT1 from CIDP,and the area under curve in 8 sites of median nerve and 9 sites in ulnar nerve was more than 0.9.Conclusions CSAs measured at different sites by peripheral nerve ultrasound in CMT1 were significantly increased than in CIDP.Measurement of CSAs by peripheral nerve ultrasound can be used for differentiating CMTI from CIDP.

  19. IFNγ Influences Type I Interferon Response and Susceptibility to Theiler's Virus-Induced Demyelinating Disease

    OpenAIRE

    Bowen, Jenna L.; Olson, Julie K.

    2013-01-01

    Theiler's murine encephalomyelitis virus (TMEV) induces a demyelinating disease in susceptible SJL mice that has similarities to multiple sclerosis in humans. TMEV infection of susceptible mice leads to a persistent virus infection of the central nervous system (CNS), which promotes the development of demyelinating disease associated with an inflammatory immune response in the CNS. TMEV infection of resistant C57BL6 mice results in viral clearance without development of demyelinating disease....

  20. The Effect of Stereotactic Injections on Demyelination and Remyelination: a Study in the Cuprizone Model.

    Science.gov (United States)

    Tejedor, Laura Salinas; Wostradowski, Tanja; Gingele, Stefan; Skripuletz, Thomas; Gudi, Viktoria; Stangel, Martin

    2017-01-26

    Remyelination is the natural repair mechanism in demyelinating disorders of the central nervous system (CNS) such as multiple sclerosis. Several animal models have been used to study demyelination and remyelination. Among toxic animal models, oral administration of the toxin cuprizone leads to white and gray matter demyelination. In contrast, focal demyelination models include the stereotactic application of a toxin such as lysolecithin or ethidium bromide. The injection procedure generates a local disruption of the blood-brain barrier (BBB) and might thus trigger a local inflammatory reaction and consequently may influence demyelination and remyelination. In order to study such consequences, we applied stereotactic injections in the cuprizone model where demyelination and remyelination are mediated independent of this procedure. Immunohistochemistry was performed to detect the presence of lymphocytes and activated glial cells in the injection area. Blood protein stainings were used to assess the integrity of the BBB and myelin staining to evaluate demyelination and remyelination processes. Stereotactic injection led to a local disruption of the BBB as shown by local extravasation of blood proteins. Along the injection canal, T and B lymphocytes could be detected and there was a tendency of a higher microgliosis and astrocytosis. However, these changes did not influence demyelination and remyelination processes at the site of injection, in the corpus callosum, or in the cerebral cortex. Our results suggest that a local stereotactic injection has no major impact on CNS demyelination and remyelination.

  1. Chronic hepatitis B infection presenting with chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): a case report

    OpenAIRE

    Weng, Ching-Fu; Chan, Ding-Cheng; Chen, Ya-Fang; Liu, Fei-Chih; Liou, Horng-Huei

    2015-01-01

    Introduction Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids is a brainstem disorder characterized by perivascular pathologic reaction with lymphocyte infiltration and leading to diplopia, facial palsy, dysarthria, and gait ataxia. It was thought to be an autoimmune disorder without distinct pathogenesis. Chronic hepatitis B virus infection has been proposed in correlation with autoimmune diseases, including central nervous system demyelinating di...

  2. Histological correlation of diffusional kurtosis and white matter modeling metrics in cuprizone-induced corpus callosum demyelination.

    Science.gov (United States)

    Falangola, Maria F; Guilfoyle, David N; Tabesh, Ali; Hui, Edward S; Nie, Xingju; Jensen, Jens H; Gerum, Scott V; Hu, Caixia; LaFrancois, John; Collins, Heather R; Helpern, Joseph A

    2014-08-01

    The cuprizone mouse model is well established for studying the processes of both demyelination and remyelination in the corpus callosum, and it has been utilized together with diffusion tensor imaging (DTI) to investigate myelin and axonal pathology. Although some underlying morphological mechanisms contributing to the changes in diffusion tensor (DT) metrics have been identified, the understanding of specific associations between histology and diffusion measures remains limited. Diffusional kurtosis imaging (DKI) is an extension of DTI that provides metrics of diffusional non-Gaussianity, for which an associated white matter modeling (WMM) method has been developed. The main goal of the present study was to quantitatively assess the relationships between diffusion measures and histological measures in the mouse model of cuprizone-induced corpus callosum demyelination. The diffusional kurtosis (DK) and WMM metrics were found to provide additional information that enhances the sensitivity to detect the morphological heterogeneity in the chronic phase of the disease process in the rostral segment of the corpus callosum. Specifically, in the rostral segment, axonal water fraction (d = 2.6; p < 0.0001), radial kurtosis (d = 2.0; p = 0.001) and mean kurtosis (d = 1.5; p = 0.005) showed the most sensitivity between groups with respect to yielding statistically significant p values and high Cohen's d values. These results demonstrate the ability of DK and WMM metrics to detect white mater changes and inflammatory processes associated with cuprizone-induced demyelination. They also validate, in part, the application of these new WMM metrics for studying neurological diseases, as well as helping to elucidate their biophysical meaning.

  3. Functional Role of Milk Fat Globule-Epidermal Growth Factor VIII in Macrophage-Mediated Inflammatory Responses and Inflammatory/Autoimmune Diseases

    OpenAIRE

    Young-Su Yi

    2016-01-01

    Inflammation involves a series of complex biological processes mediated by innate immunity for host defense against pathogen infection. Chronic inflammation is considered to be one of the major causes of serious diseases, including a number of autoimmune/inflammatory diseases, cancers, cardiovascular diseases, and neurological diseases. Milk fat globule-epidermal growth factor 8 (MFG-E8) is a secreted protein found in vertebrates and was initially discovered as a critical component of the mil...

  4. Immunological Demyelination Triggers Macrophage/Microglial Cells Activation without Inducing Astrogliosis

    Directory of Open Access Journals (Sweden)

    Frank Cloutier

    2013-01-01

    Full Text Available The glial scar formed by reactive astrocytes and axon growth inhibitors associated with myelin play important roles in the failure of axonal regeneration following central nervous system (CNS injury. Our laboratory has previously demonstrated that immunological demyelination of the CNS facilitates regeneration of severed axons following spinal cord injury. In the present study, we evaluate whether immunological demyelination is accompanied with astrogliosis. We compared the astrogliosis and macrophage/microglial cell responses 7 days after either immunological demyelination or a stab injury to the dorsal funiculus. Both lesions induced a strong activated macrophage/microglial cells response which was significantly higher within regions of immunological demyelination. However, immunological demyelination regions were not accompanied by astrogliosis compared to stab injury that induced astrogliosis which extended several millimeters above and below the lesions, evidenced by astroglial hypertrophy, formation of a glial scar, and upregulation of intermediate filaments glial fibrillary acidic protein (GFAP. Moreover, a stab or a hemisection lesion directly within immunological demyelination regions did not induced astrogliosis within the immunological demyelination region. These results suggest that immunological demyelination creates a unique environment in which astrocytes do not form a glial scar and provides a unique model to understand the putative interaction between astrocytes and activated macrophage/microglial cells.

  5. The value of electromyography in differentiating intramedullary tumor from inflammatory demyelinating disease of cervical region

    Institute of Scientific and Technical Information of China (English)

    王红芬

    2014-01-01

    Objective To investigate the value of needle electromyography(EMG)in differentiating intramedullary tumor from inflammatory demyelinating disease of cervical region.Methods Patients hospitalized in the Chinese PLA General Hospital from March 2008 to June 2013 with abnormalities on MRI of cervical vertabra and preliminary diagnosed as intramedullary tumor or inflammatory demyelinating disease of cervical region were enrolled in the

  6. Acquired Demyelinating Syndromes: Focus on Neuromyelitis Optica and childhood-onset Multiple Sclerosis

    NARCIS (Netherlands)

    E.D. van Pelt - Gravesteijn (Daniëlle)

    2016-01-01

    markdownabstractAcquired demyelinating syndromes (ADS) cover a broad spectrum of central nervous system (CNS) inflammatory demyelinating syndromes, of which multiple sclerosis (MS) is the most common subtype. This thesis focuses on two relatively rare clinical subtypes of ADS: neuromyelitis optica s

  7. C5b-9 complement complex in autoimmune demyelination and multiple sclerosis: dual role in neuroinflammation and neuroprotection.

    Science.gov (United States)

    Rus, Horea; Cudrici, Cornelia; Niculescu, Florin

    2005-01-01

    Complement system activation plays an important role in innate and acquired immunity. Activation of complement leads to the formation of C5b-9 terminal complex. While C5b-9 can promote cell lysis, sublytic assembly of C5b-9 on plasma membranes induces cell cycle activation and survival. Multiple sclerosis (MS) and its animal model experimental allergic encephalomyelitis (EAE) are inflammatory demyelinating diseases of the central nervous system (CNS) mediated by activated lymphocytes, macrophages/microglia and the complement system. Complement activation may contribute to the pathogenesis of these diseases through its dual role: the ability of activated terminal complex C5b-9 to promote demyelination and the capacity of sublytic C5b-9 to protect oligodendrocytes (OLG) from apoptosis. By inducing EAE in C5-deficient mice, we showed that complement C5 promotes remyelination and protects oligodendrocytes from apoptotic cell death. These findings indicate that activation of complement C5b-9 plays a pro-inflammatory role in the acute phase of the disease, but may also be neuroprotective during the chronic phase of the disease.

  8. Primary demyelinating disease simulating infiltrating glioma on CT

    Energy Technology Data Exchange (ETDEWEB)

    Nakasu, Yoko; Suda, Kinya; Handa, Jyoji; Hazama, Fumitada (Shiga Univ. of Medical Science, Otsu (Japan))

    1982-12-01

    Demyelinating diseases of the brain may show mass effects and/or contrast enhancement on CT scans, simulating the appearance of infiltrating glioma. A 36-year-old male, had suffered from gait disturbance and convulsive attacks involving the right lower limb since the age of 30. He had gradually developed character changes and urine incontinence. Six months prior to admission he experienced several attacks of generalized convulsions. On admission, he showed a mild hemiparesis, bilateral Babinski signs, and ataxic gait. He was disoriented and had memory disturbance and moria. CT scan showed low density areas in the bilateral frontal lobes Fand corpus callosum associated with a mild mass effect. Contrast study revealed irregular enhancement along the edge of the low density area and another small enhancing lesion in the left temporal lobe. This CT finding was interpreted as that of ''butterfly'' glioma. Craniotomy and right frontal lobectomy were performed. Histological study, however, demonstrated demyelination in the white matter associated with perivascular proliferation of lymphocytes. The final diagnosis was the 'transitional sclerosis' of Poser.

  9. Remarkable Role of Indoleamine 2,3-Dioxygenase and Tryptophan Metabolites in Infectious Diseases: Potential Role in Macrophage-Mediated Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Yuki Murakami

    2013-01-01

    Full Text Available Indoleamine 2,3-dioxygenase 1 (IDO1, the L-tryptophan-degrading enzyme, plays a key role in the immunomodulatory effects on several types of immune cells. Originally known for its regulatory function during pregnancy and chronic inflammation in tumorigenesis, the activity of IDO1 seems to modify the inflammatory state of infectious diseases. The pathophysiologic activity of L-tryptophan metabolites, kynurenines, is well recognized. Therefore, an understanding of the regulation of IDO1 and the subsequent biochemical reactions is essential for the design of therapeutic strategies in certain immune diseases. In this paper, current knowledge about the role of IDO1 and its metabolites during various infectious diseases is presented. Particularly, the regulation of type I interferons (IFNs production via IDO1 in virus infection is discussed. This paper offers insights into new therapeutic strategies in the modulation of viral infection and several immune-related disorders.

  10. A 17 year-old girl with a demyelinating disease requiring mechanical ventilation: a case report

    Directory of Open Access Journals (Sweden)

    Katsenos Chrysostomos

    2013-01-01

    Full Text Available Abstract Background Demyelinating diseases cause destruction of the myelin sheath, while axons are relatively spared. Pathologically, demyelination can be the result of an inflammatory process, viral infection, acquired metabolic derangement and ischemic insult. Three diseases that can cause inflammatory demyelination of the CNS are: Multiple sclerosis (MS, Acute disseminated encephalomyelitis (ADEM and Acute hemorrhagic leucoencephalitis. Differentiation is not always easy and there is considerable overlaping. Data about adults with acute demyelination requiring ICU admission is limited. Case presentation A 17 year old Greek female was hospitalised in the ICU because of acute respiratory failure requiring mechanical ventilation. She had a history of febrile disease one month before, acute onset of paraplegia, diplopia, progressive arm weakness and dyspnea. Her consciousness was not impaired. A demyelinating central nervous system (CNS disease, possibly post infectious encephalomyelitis (ADEM was the underlying condition. The MRI of the brain disclosed diffused expanded cerebral lesions involving the optic nerve, basal ganglia cerebellum, pons and medulla oblongata. There was also extended involvement of the cervical and thoracic part of the spinal cord. CSF leukocyte count was elevated with lymphocyte predominance. The patient required mechanical ventilation for two months. Then she was transferred to a rehabilitation centre. Three years later she remains paraplegic. Since then she has not suffered any other demyelination attack. Conclusions Demyelinating diseases can cause acute respiratory failure when the spinal cord is affected. Severe forms of these diseases, making necessary ICU admission, is less frequently reported. Intensivists should be aware of the features of these rare diseases.

  11. Microglial Hv1 proton channel promotes cuprizone-induced demyelination through oxidative damage.

    Science.gov (United States)

    Liu, Junli; Tian, Daishi; Murugan, Madhuvika; Eyo, Ukpong B; Dreyfus, Cheryl F; Wang, Wei; Wu, Long-Jun

    2015-10-01

    NADPH oxidase (NOX)-dependent reactive oxygen species (ROS) production in inflammatory cells including microglia plays an important role in demyelination and free radical-mediated tissue injury in multiple sclerosis (MS). However, the mechanism underlying microglial ROS production and demyelination remains largely unknown. The voltage-gated proton channel, Hv1, is selectively expressed in microglia and is required for NOX-dependent ROS generation in the brain. In the present study, we sought to determine the role of microglial Hv1 proton channels in a mouse model of cuprizone-induced demyelination, a model for MS. Following cuprizone exposure, wild-type mice presented obvious demyelination, decreased myelin basic protein expression, loss of mature oligodendrocytes, and impaired motor coordination in comparison to mice on a normal chow diet. However, mice lacking Hv1 (Hv1(-/-) ) are partially protected from demyelination and motor deficits compared with those in wild-type mice. These rescued phenotypes in Hv1(-/-) mice in cuprizone-induced demyelination is accompanied by reduced ROS production, ameliorated microglial activation, increased oligodendrocyte progenitor cell (NG2) proliferation, and increased number of mature oligodendrocytes. These results demonstrate that the Hv1 proton channel is required for cuprizone-induced microglial oxidative damage and subsequent demyelination. Our study suggests that the microglial Hv1 proton channel is a unique target for controlling NOX-dependent ROS production in the pathogenesis of MS.

  12. Functional Role of Milk Fat Globule-Epidermal Growth Factor VIII in Macrophage-Mediated Inflammatory Responses and Inflammatory/Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Young-Su Yi

    2016-01-01

    Full Text Available Inflammation involves a series of complex biological processes mediated by innate immunity for host defense against pathogen infection. Chronic inflammation is considered to be one of the major causes of serious diseases, including a number of autoimmune/inflammatory diseases, cancers, cardiovascular diseases, and neurological diseases. Milk fat globule-epidermal growth factor 8 (MFG-E8 is a secreted protein found in vertebrates and was initially discovered as a critical component of the milk fat globule. Previously, a number of studies have reported that MFG-E8 contributes to various biological functions including the phagocytic removal of damaged and apoptotic cells from tissues, the induction of VEGF-mediated neovascularization, the maintenance of intestinal epithelial homeostasis, and the promotion of mucosal healing. Recently, emerging studies have reported that MFG-E8 plays a role in inflammatory responses and inflammatory/autoimmune diseases. This review describes the characteristics of MFG-E8-mediated signaling pathways, summarizes recent findings supporting the roles of MFG-E8 in inflammatory responses and inflammatory/autoimmune diseases, and discusses MFG-E8 targeting as a potential therapeutic strategy for the development of anti-inflammatory/autoimmune disease drugs.

  13. Functional Role of Milk Fat Globule-Epidermal Growth Factor VIII in Macrophage-Mediated Inflammatory Responses and Inflammatory/Autoimmune Diseases.

    Science.gov (United States)

    Yi, Young-Su

    2016-01-01

    Inflammation involves a series of complex biological processes mediated by innate immunity for host defense against pathogen infection. Chronic inflammation is considered to be one of the major causes of serious diseases, including a number of autoimmune/inflammatory diseases, cancers, cardiovascular diseases, and neurological diseases. Milk fat globule-epidermal growth factor 8 (MFG-E8) is a secreted protein found in vertebrates and was initially discovered as a critical component of the milk fat globule. Previously, a number of studies have reported that MFG-E8 contributes to various biological functions including the phagocytic removal of damaged and apoptotic cells from tissues, the induction of VEGF-mediated neovascularization, the maintenance of intestinal epithelial homeostasis, and the promotion of mucosal healing. Recently, emerging studies have reported that MFG-E8 plays a role in inflammatory responses and inflammatory/autoimmune diseases. This review describes the characteristics of MFG-E8-mediated signaling pathways, summarizes recent findings supporting the roles of MFG-E8 in inflammatory responses and inflammatory/autoimmune diseases, and discusses MFG-E8 targeting as a potential therapeutic strategy for the development of anti-inflammatory/autoimmune disease drugs.

  14. Imaging and clinical properties of inflammatory demyelinating pseudotumor in the spinal cord

    Institute of Scientific and Technical Information of China (English)

    Ying Wang; Min Wang; Hui Liang; Quntao Yu; Zhihui Yan; Min Kong

    2013-01-01

    Inflammatory demyelinating pseudotumor usual y occurs in the brain and rarely occurs in the spinal cord. On imaging, inflammatory demyelinating pseudotumor appears very similar to intramedul ary tumors such as gliomas. It is often misdiagnosed as intramedul ary tumor and surgical y resected. In view of this, the clinical and magnetic resonance imaging manifestations and the pathological fea-tures of 36 cases of inflammatory demyelinating pseudotumor in the spinal cord were retrospec-tively analyzed and summarized. Most of these cases suffered from acute or subacute onset and exhibited a sensorimotor disorder. Among them, six cases were misdiagnosed as having intrame-dul ary gliomas, and inflammatory demyelinating pseudotumor was only identified and pathologi-cal y confirmed after surgical resection. Lesions in the cervical and thoracic spinal cord were com-mon. Magnetic resonance imaging revealed edema and space-occupying lesions to varying de-grees at the cervical-thoracic junction, with a predominant feature of non-closed rosette-like rein-forcement (open-loop sign). Pathological examination showed perivascular cuffing of predominantly dense lymphocytes, and demyelination was observed in six of the misdiagnosed cases. These re-sults suggest that tumor-like inflammatory demyelinating disease in the spinal cord is a kind of special demyelinating disease that can be categorized as inflammatory pseudotumor. These solitary lesions are easily confused with intramedul ary neoplasms. Patchy or non-closed reinforcement (open-ring sign) on magnetic resonance imaging is the predominant property of inflammatory de-myelinating pseudotumor, and inflammatory cel infiltration and demyelination are additional patho-logical properties.

  15. Gasperini syndrome as clinical manifestation of pontine demyelination

    Directory of Open Access Journals (Sweden)

    Krasnianski M

    2009-09-01

    Full Text Available Abstract The Gasperini syndrome is a very rare brainstem disease characterized by the typical combination of ipsilateral lesions of the cranial nerves V-VII and dissociated contralateral hemihypesthesia, whereas both contralateral and ipsilateral hypacusis was described. Since the first description in 1912, only a few cases of this crossed brainstem syndrome were published so far. Pontine infarction and bleedings were the reported causes of the syndrome. Here we report a 44-year-old man with the classical Gasperini syndrome due to pontine demyelination in multiple sclerosis. The clinical findings were correlated with changes on MRI. The present case shows that classical crossed brainstem syndromes are topological terms not invariably associated with brainstem ischemia in particular vascular areas and may contribute to the differential diagnosis of peripheral facial nerve palsy.

  16. CT and MRI 'ring sign' may be due to demyelination: diagnostic pitfall.

    LENUS (Irish Health Repository)

    Kamel, M H

    2012-02-03

    We report a case of acute demyelinating encephalomyelitis (ADEM) in which both CT and MRI showed multiple ring-enhancing lesions suggestive of abscesses or brain tumour. This is a relatively rare phenomenon.

  17. A review of MRI evaluation of demyelination in cuprizone murine model

    Science.gov (United States)

    Krutenkova, E.; Pan, E.; Khodanovich, M.

    2015-11-01

    The cuprizone mouse model of non-autoimmune demyelination reproduces some phenomena of multiple sclerosis and is appropriate for validation and specification of a new method of non-invasive diagnostics. In the review new data which are collected using the new MRI method are compared with one or more conventional MRI tools. Also the paper reviewed the validation of MRI approaches using histological or immunohistochemical methods. Luxol fast blue histological staining and myelin basic protein immunostaining is widespread. To improve the accuracy of non-invasive conventional MRI, multimodal scanning could be applied. The new quantitative MRI method of fast mapping of the macromolecular proton fraction is a reliable biomarker of myelin in the brain and can be used for research of demyelination in animals. To date, a validation of MPF method on the CPZ mouse model of demyelination is not performed, although this method is probably the best way to evaluate demyelination using MRI.

  18. Clinical features and magnetic resonance image analysis of 15 cases of demyelinating leukoencephalopathy induced by levamisole

    Science.gov (United States)

    YAN, RUIFANG; WU, QINGWU; REN, JIPENG; CUI, HONGKAI; ZHAI, KAIHUA; ZHAI, ZHANSHENG; DUAN, QINGHONG

    2013-01-01

    The aim of this study was to explore the diagnostic value of magnetic resonance imaging (MRI) for levamisole-induced demyelinating leukoencephalopathy. The clinical features and MRI findings of 15 patients with levamisole-induced demyelinating leukoencephalopathy were retrospectively analyzed. The abnormality rate of the patients was demonstrated to be 100% by MRI, and scattered multiple cerebral foci were observed in all of the patients. The majority of the foci were located at the centrum ovale, peri-lateral cerebral ventricles and basal ganglia, while the remainder were located in the brain stem and cerebellum, as well as in the white matter regions of the temporal, frontal, apical and occipital lobes. In addition, mottling and ring-shaped enhancements were observed. The study demonstrated that MRI effectively displays demyelinating leukoencephalopathy, and that the combination of MRI with the medical history of the patient is of significance for the early diagnosis, differentiation and treatment of demyelinating leukoencephalopathy. PMID:23935721

  19. A review of MRI evaluation of demyelination in cuprizone murine model

    Energy Technology Data Exchange (ETDEWEB)

    Krutenkova, E., E-mail: len--k@yandex.ru; Pan, E.; Khodanovich, M., E-mail: khodanovich@mail.tsu.ru [National Research Tomsk State University, Lenina pr., 36, Tomsk (Russian Federation)

    2015-11-17

    The cuprizone mouse model of non-autoimmune demyelination reproduces some phenomena of multiple sclerosis and is appropriate for validation and specification of a new method of non-invasive diagnostics. In the review new data which are collected using the new MRI method are compared with one or more conventional MRI tools. Also the paper reviewed the validation of MRI approaches using histological or immunohistochemical methods. Luxol fast blue histological staining and myelin basic protein immunostaining is widespread. To improve the accuracy of non-invasive conventional MRI, multimodal scanning could be applied. The new quantitative MRI method of fast mapping of the macromolecular proton fraction is a reliable biomarker of myelin in the brain and can be used for research of demyelination in animals. To date, a validation of MPF method on the CPZ mouse model of demyelination is not performed, although this method is probably the best way to evaluate demyelination using MRI.

  20. miR-181a Induces Macrophage Polarized to M2 Phenotype and Promotes M2 Macrophage-mediated Tumor Cell Metastasis by Targeting KLF6 and C/EBPα

    Science.gov (United States)

    Bi, Jia; Zeng, Xianxin; Zhao, Lin; Wei, Qian; Yu, Lifeng; Wang, Xinnan; Yu, Zhaojin; Cao, Yaming; Shan, Fengping; Wei, Minjie

    2016-01-01

    Macrophages can acquire a variety of polarization status and functions: classically activated macrophages (M1 macrophages); alternatively activated macrophages (M2 macrophages). However, the molecular basis of the process is still unclear. Here, this study addresses that microRNA-181a (miR-181a) is a key molecule controlling macrophage polarization. We found that miR-181a is overexpressed in M2 macrophages than in M1 macrophages. miR-181a expression was decreased when M2 phenotype converted to M1, whereas it increased when M1 phenotype converted to M2. Overexpression of miR-181a in M1 macrophages diminished M1 phenotype expression while promoting polarization to the M2 phenotype. In contrast, knockdown of miR-181a in M2 macrophages promoted M1 polarization and diminished M2 phenotype expression. Mechanistically, Bioinformatic analysis revealed that Kruppel-like factor 6 (KLF6) and CCAAT/enhancer binding protein-α (C/EBPα) is a potential target of miR-181a and luciferase assay confirmed that KLF6 and C/EBPα translation is suppressed by miR-181a through interaction with the 3′UTR of KLF6 and C/EBPα mRNA. Further analysis showed that induction of miR-181a suppressed KLF6 and C/EBPα protein expression. Importantly, miR-181a also diminishes M2 macrophages-mediated migration and invasion capacity of tumor cells. Collectively, our results suggest that miR-181a plays a significant role in regulating macrophage polarization through directly target KLF6 and C/EBPα. PMID:27673564

  1. Nogo receptor inhibition enhances functional recovery following lysolecithin-induced demyelination in mouse optic chiasm.

    Directory of Open Access Journals (Sweden)

    Fereshteh Pourabdolhossein

    Full Text Available BACKGROUND: Inhibitory factors have been implicated in the failure of remyelination in demyelinating diseases. Myelin associated inhibitors act through a common receptor called Nogo receptor (NgR that plays critical inhibitory roles in CNS plasticity. Here we investigated the effects of abrogating NgR inhibition in a non-immune model of focal demyelination in adult mouse optic chiasm. METHODOLOGY/PRINCIPAL FINDINGS: A focal area of demyelination was induced in adult mouse optic chiasm by microinjection of lysolecithin. To knock down NgR levels, siRNAs against NgR were intracerebroventricularly administered via a permanent cannula over 14 days, Functional changes were monitored by electrophysiological recording of latency of visual evoked potentials (VEPs. Histological analysis was carried out 3, 7 and 14 days post demyelination lesion. To assess the effect of NgR inhibition on precursor cell repopulation, BrdU was administered to the animals prior to the demyelination induction. Inhibition of NgR significantly restored VEPs responses following optic chiasm demyelination. These findings were confirmed histologically by myelin specific staining. siNgR application resulted in a smaller lesion size compared to control. NgR inhibition significantly increased the numbers of BrdU+/Olig2+ progenitor cells in the lesioned area and in the neurogenic zone of the third ventricle. These progenitor cells (Olig2+ or GFAP+ migrated away from this area as a function of time. CONCLUSIONS/SIGNIFICANCE: Our results show that inhibition of NgR facilitate myelin repair in the demyelinated chiasm, with enhanced recruitment of proliferating cells to the lesion site. Thus, antagonizing NgR function could have therapeutic potential for demyelinating disorders such as Multiple Sclerosis.

  2. Effects of deep heating provided by therapeutic ultrasound on demyelinating nerves.

    Science.gov (United States)

    Aydin, Elif; Tastaban, Engin; Omurlu, Imran Kurt; Turan, Yasemin; Şendur, Ömer Faruk

    2016-04-01

    [Purpose] Physiotherapeutic heating agents are classified into two groups: superficial-heating agents and deep-heating agents. Therapeutic ultrasound is a deep-heating agent used to treat various musculosketal disorders. Numerous studies have attempted to determine the impact of ultrasound on healthy nerve conduction parameters. However, the instantaneous effects of deep heating via ultrasound on demyelinating nerves do not appear to have been described previously. The present study aimed to assess and compare the impact of ultrasound on demyelinating nerve and healthy nerve conduction parameters. [Subjects and Methods] Carpal tunnel syndrome was used as a focal demyelination model. Thirty-two hands of 25 participants with carpal tunnel syndrome were enrolled in the study. Ultrasound parameters were 3.3 MHz, 1.0 W/cm(2), 8 minutes, and continuous wave. Electrodiagnostic studies were performed initially, at the midpoint (4th min), and immediately after (8th min) ultrasound application. [Results] Reduced motor conduction velocity was found in demyelinating nerves at the 4th and 8th minutes. Ulnar nerve onset latency was significantly prolonged in the 8th minute recording, compared to the initial value. There were no significant differences in relative velocity and latency changes between demyelinating and normal nerves. [Conclusion] Deep heating via ultrasound may inversely affect conduction velocity in demyelinating nerves.

  3. Effects of deep heating provided by therapeutic ultrasound on demyelinating nerves

    Science.gov (United States)

    Aydin, Elif; Tastaban, Engin; Omurlu, Imran Kurt; Turan, Yasemin; Şendur, Ömer Faruk

    2016-01-01

    [Purpose] Physiotherapeutic heating agents are classified into two groups: superficial-heating agents and deep-heating agents. Therapeutic ultrasound is a deep-heating agent used to treat various musculosketal disorders. Numerous studies have attempted to determine the impact of ultrasound on healthy nerve conduction parameters. However, the instantaneous effects of deep heating via ultrasound on demyelinating nerves do not appear to have been described previously. The present study aimed to assess and compare the impact of ultrasound on demyelinating nerve and healthy nerve conduction parameters. [Subjects and Methods] Carpal tunnel syndrome was used as a focal demyelination model. Thirty-two hands of 25 participants with carpal tunnel syndrome were enrolled in the study. Ultrasound parameters were 3.3 MHz, 1.0 W/cm2, 8 minutes, and continuous wave. Electrodiagnostic studies were performed initially, at the midpoint (4th min), and immediately after (8th min) ultrasound application. [Results] Reduced motor conduction velocity was found in demyelinating nerves at the 4th and 8th minutes. Ulnar nerve onset latency was significantly prolonged in the 8th minute recording, compared to the initial value. There were no significant differences in relative velocity and latency changes between demyelinating and normal nerves. [Conclusion] Deep heating via ultrasound may inversely affect conduction velocity in demyelinating nerves. PMID:27190467

  4. Demyelinating evidences in CMS rat model of depression: a DTI study at 7 T.

    Science.gov (United States)

    Hemanth Kumar, B S; Mishra, S K; Trivedi, R; Singh, S; Rana, P; Khushu, S

    2014-09-05

    Depression is among the most debilitating diseases worldwide. Long-term exposure to stressors plays a major role in development of human depression. Chronic mild stress (CMS) seems to be a valid animal model for depression. Diffusion tensor imaging (DTI) is capable of inferring microstructural abnormalities of the white matter and has shown to serve as non-invasive marker of specific pathology. We developed a CMS rat model of depression and validated with behavioral experiments. We measured the diffusion indices (mean diffusivity (MD), fractional anisotropy (FA), axial (λ∥) and radial (λ⊥) diffusivity) to investigate the changes in CMS rat brain during depression onset. Diffusion indices have shown to be useful to discriminate myelin damage from axon loss. DTI was performed in both control and CMS rats (n=10, in each group) and maps of FA, MD, λ∥ and λ⊥ diffusivity values were generated using in-house built software. The diffusion indices were calculated by region of interest (ROI) analysis in different brain regions like the frontal cortex, hippocampus, hypothalamus, cingulum, thalamus, caudate putamen, corpus callosum, cerebral peduncle and sensory motor cortex. The results showed signs of demyelination, reflected by increased MD, decreased FA and increased λ⊥. The results also suggest a possible role of edema or inflammation concerning the brain morphology in CMS rats. The overall finding using DTI suggests there might be a major role of loss of myelin sheath, which leads to disrupted connectivity between the limbic area and the prefrontal cortex during the onset of depression. Our findings indicate that interpretation of these indices may provide crucial information about the type and severity of mood disorders.

  5. Inflammation and primary demyelination induced by the intraspinal injection of lipopolysaccharide.

    Science.gov (United States)

    Felts, Paul A; Woolston, Anne-Marie; Fernando, Himali B; Asquith, Stephen; Gregson, Norman A; Mizzi, Oliver J; Smith, Kenneth J

    2005-07-01

    Inflammation is a prominent feature of several disorders characterized by primary demyelination, but it is not clear whether a relationship exists between inflammation and myelin damage. We have found that substantial demyelination results from the focal inflammatory lesion caused by the injection of lipopolysaccharide (LPS; 200 ng) directly into the rat dorsal funiculus. Within 24 h, such injections caused a focal inflammatory response consisting of a substantial number of polymorphonuclear cells and ED1-positive and inducible nitric oxide synthase (iNOS)-positive macrophages/microglia. The number of inflammatory cells was substantially reduced by day 7. OX-52-positive T-cells were less frequently observed but were present in the meninges at 8 h, reached a maximum in the dorsal funiculus at 7 days, and were rare at 14 days. The inflammation was followed by the appearance of a large lesion of primary demyelination that encompassed up to approximately 75% of the cross-sectional area of the dorsal funiculus. Treatment with dexamethasone significantly reduced the number of cells expressing iNOS, but did not prevent the demyelination. By 28 days the lesions were largely remyelinated, usually by Schwann cells. These changes were not observed in control, saline-injected animals. We conclude that the intraspinal injection of LPS results in inflammation and subsequently in prominent demyelination. The mechanisms underlying the demyelination are not clear, but it is notable that it typically begins with disruption of the adaxonal myelin. Indeed, there is an early loss of myelin-associated glycoprotein within the lesion, despite the persistence of proteolipid protein. This combination is a feature of the pattern III lesion recently described in multiple sclerosis (Lucchinetti et al., 2000), and we therefore suggest that LPS-induced demyelination may serve as the first experimental model available for the study of this type of multiple sclerosis lesion.

  6. IFNγ influences type I interferon response and susceptibility to Theiler's virus-induced demyelinating disease.

    Science.gov (United States)

    Bowen, Jenna L; Olson, Julie K

    2013-08-01

    Theiler's murine encephalomyelitis virus (TMEV) induces a demyelinating disease in susceptible SJL mice that has similarities to multiple sclerosis in humans. TMEV infection of susceptible mice leads to a persistent virus infection of the central nervous system (CNS), which promotes the development of demyelinating disease associated with an inflammatory immune response in the CNS. TMEV infection of resistant C57BL6 mice results in viral clearance without development of demyelinating disease. Interestingly, TMEV infection of resistant mice deficient in IFNγ leads to a persistent virus infection in the CNS and development of demyelinating disease. We have previously shown that the innate immune response affects development of TMEV- induced demyelinating disease, thus we wanted to determine the role of IFNγ during the innate immune response. TMEV-infected IFNγ-deficient mice had an altered innate immune response, including reduced expression of innate immune cytokines, especially type I interferons. Administration of type I interferons, IFNα and IFNß, to TMEV-infected IFNγ-deficient mice during the innate immune response restored the expression of innate immune cytokines. Most importantly, administration of type I interferons to IFNγ-deficient mice during the innate immune response decreased the virus load in the CNS and decreased development of demyelinating disease. Microglia are the CNS resident immune cells that express innate immune receptors. In TMEV-infected IFNγ-deficient mice, microglia had reduced expression of innate immune cytokines, and administration of type I interferons to these mice restored the innate immune response by microglia. In the absence of IFNγ, microglia from TMEV-infected mice had reduced expression of some innate immune receptors and signaling molecules, especially IRF1. These results suggest that IFNγ plays an important role in the innate immune response to TMEV by enhancing the expression of innate immune cytokines

  7. Cuprizone-induced demyelination in mice: age-related vulnerability and exploratory behavior deficit

    Institute of Scientific and Technical Information of China (English)

    Hongkai Wang; Chengren Li; Hanzhi Wang; Feng Mei; Zhi Liu; Hai-Ying Shen; Lan Xiao

    2013-01-01

    Schizophrenia is a mental disease that mainly affects young individuals (15 to 35 years old) but its etiology remains largely undefined.Recently,accumulating evidence indicated that demyelination and/or dysfunction of oligodendrocytes is an important feature of its pathogenesis.We hypothesized that the vulnerability of young individuals to demyelination may contribute to the onset of schizophrenia.In the present study,three different age cohorts of mice,i.e.juvenile (3 weeks),young-adult (6 weeks) and middle-aged (8months),were subjected to a 6-week diet containing 0.2% cuprizone (CPZ) to create an animal model of acute demyelination.Then,age-related vulnerability to CPZ-induced demyelination,behavioral outcomes,and myelination-related molecular biological changes were assessed.We demonstrated:(1) CPZ treatment led to more severe demyelination in juvenile and young-adult mice than in middle-aged mice in the corpus callosum,a region closely associated with the pathophysiology of schizophrenia; (2)the higher levels of demyelination in juvenile and young-adult mice were correlated with a greater reduction of myelin basic protein,more loss of CC-1-positive mature oligodendrocytes,and higher levels of astrocyte activation; and (3) CPZ treatment resulted in a more prominent exploratory behavior deficit in juvenile and young-adult mice than in middle-aged mice.Together,our data demonstrate an age-related vulnerability to demyelination with a concurrent behavioral deficit,providing supporting evidence for better understanding the susceptibility of the young to the onset of schizophrenia.

  8. Analysis of the host transcriptome from demyelinating spinal cord of murine coronavirus-infected mice.

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    Ruth Elliott

    Full Text Available Persistent infection of the mouse central nervous system (CNS with mouse hepatitis virus (MHV induces a demyelinating disease pathologically similar to multiple sclerosis and is therefore used as a model system. There is little information regarding the host factors that correlate with and contribute to MHV-induced demyelination. Here, we detail the genes and pathways associated with MHV-induced demyelinating disease in the spinal cord. High-throughput sequencing of the host transcriptome revealed that demyelination is accompanied by numerous transcriptional changes indicative of immune infiltration as well as changes in the cytokine milieu and lipid metabolism. We found evidence that a Th1-biased cytokine/chemokine response and eicosanoid-derived inflammation accompany persistent MHV infection and that antigen presentation is ongoing. Interestingly, increased expression of genes involved in lipid transport, processing, and catabolism, including some with known roles in neurodegenerative diseases, coincided with demyelination. Lastly, expression of several genes involved in osteoclast or bone-resident macrophage function, most notably TREM2 and DAP12, was upregulated in persistently infected mouse spinal cord. This study highlights the complexity of the host antiviral response, which accompany MHV-induced demyelination, and further supports previous findings that MHV-induced demyelination is immune-mediated. Interestingly, these data suggest a parallel between bone reabsorption by osteoclasts and myelin debris clearance by microglia in the bone and the CNS, respectively. To our knowledge, this is the first report of using an RNA-seq approach to study the host CNS response to persistent viral infection.

  9. Complete blood count and acetylcholinesterase activity of lymphocytes of demyelinated and ovariectomized rats treated with resveratrol.

    Science.gov (United States)

    Martins, Danieli B; Mazzanti, Cinthia M; Costa, Márcio M; França, Raqueli; Pagnoncelli, Marcielen; Maciel, Roberto M; Schmatz, Roberta; Oliveira, Lizielle; Morsch, Vera; Facco, Grasiela; Visentini, Diandra; Mann, Thais; Mazzanti, Alexandre; Lopes, Sonia T A

    2012-12-01

    Resveratrol is a phytoestrogen that has many beneficial actions. This study aimed to evaluate the effect of resveratrol on the complete blood count (CBC) and the acetylcholinesterase (AChE) activity of lymphocytes of ovariectomized rats experimentally demyelinated by ethidium bromide (EB). Forty adult female Wistar rats (60 days, 200-220 g) were divided randomly into five groups (n = 4) to evaluate the demyelination phase and five groups (n = 4) to evaluate the remyelination phase. In each phase, the groups consisted of sham rats-G1; ovariectomized rats, not demyelinated, treated only with vehicle (ethanol 25%)-G2; demyelinated ovariectomized rats treated only with vehicle-G3; ovariectomized rats, not demyelinated, treated with resveratrol-G4; and demyelinated ovariectomized rats treated with resveratrol-G5. Only during the remyelination phase, CBC showed a significant difference (p < 0.05) in the number of monocytes between G2 and G5 groups. In the demyelination phase, there was a significant decrease (p < 0.05) in the AChE activity in the G4 group, while the G5 group was statistically similar to the G1, G2 and G4 groups. In the remyelination phase, there were no significant differences in the AChE activity among the groups. The treatment for 7 days with resveratrol with or without the experimental demyelization with EB appears to influence the AChE activity of lymphocytes, without changing the number of these cells in the circulation. However, in the remyelination phase, there seems to be stabilization in its effect on the lymphocyte AChE activity.

  10. Extensive cortical remyelination in patients with chronic multiple sclerosis.

    Science.gov (United States)

    Albert, Monika; Antel, Jack; Brück, Wolfgang; Stadelmann, Christine

    2007-04-01

    Recent studies revealed prominent cortical demyelination in patients with chronic multiple sclerosis (MS). Demyelination in white matter lesions is frequently accompanied by remyelination. This repair process, however, often remains incomplete and restricted to the lesion border. In the present study, we examined the frequency and extent of remyelination in cortical and white matter lesions in autopsy brain tissue of 33 patients with chronic MS. The majority of patients (29 of 33) harbored cortical demyelination. Remyelination of cortical lesions was identified light microscopically by the presence of thin and irregularly arranged myelin sheaths, and confirmed by electron microscopy. Extensive remyelination was found in 18%, remyelination restricted to the lesion border in 54%, and no remyelination in 28% of cortical lesions. A direct comparison of the extent of remyelination in white matter and cortical lesions of the same patients revealed that remyelination of cortical lesions was consistently more extensive. In addition, g-ratios of fibers in areas of "normal appearing cortex" yielded values consistent with remyelination. Our data confirm the high prevalence of cortical demyelination in chronic MS and imply that the propensity to remyelinate is high in cortical MS lesions.

  11. Idiopathic inflammatory-demyelinating diseases of the central nervous system

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    Rovira Canellas, A. [Vall d' Hebron University Hospital, Magnetic Resonance Unit (I.D.I.), Department of Radiology, Barcelona (Spain); Rovira Gols, A. [Parc Tauli University Institute - UAB, UDIAT, Diagnostic Centre, Sabadell (Spain); Rio Izquierdo, J.; Tintore Subirana, M.; Montalban Gairin, X. [Vall d' Hebron University Hospital, Neuroimmunology Unit, Department of Neurology, Barcelona (Spain)

    2007-05-15

    Idiopathic inflammatory-demyelinating diseases (IIDDs) include a broad spectrum of central nervous system disorders that can usually be differentiated on the basis of clinical, imaging, laboratory and pathological findings. However, there can be a considerable overlap between at least some of these disorders, leading to misdiagnoses or diagnostic uncertainty. The relapsing-remitting and secondary progressive forms of multiple sclerosis (MS) are the most common IIDDs. Other MS phenotypes include those with a progressive course from onset (primary progressive and progressive relapsing) or with a benign course continuing for years after onset (benign MS). Uncommon forms of IIDDs can be classified clinically into: (1) fulminant or acute IIDDs, such as the Marburg variant of MS, Balo's concentric sclerosis, Schilder's disease, and acute disseminated encephalomyelitis; (2) monosymptomatic IIDDs, such as those involving the spinal cord (transverse myelitis), optic nerve (optic neuritis) or brainstem and cerebellum; and (3) IIDDs with a restricted topographical distribution, including Devic's neuromyelitis optica, recurrent optic neuritis and relapsing transverse myelitis. Other forms of IIDD, which are classified clinically and radiologically as pseudotumoral, can have different forms of presentation and clinical courses. Although some of these uncommon IIDDs are variants of MS, others probably correspond to different entities. MR imaging of the brain and spine is the imaging technique of choice for diagnosing these disorders, and together with the clinical and laboratory findings can accurately classify them. Precise classification of these disorders may have relevant prognostic and treatment implications, and might be helpful in distinguishing them from tumoral or infectious lesions, avoiding unnecessary aggressive diagnostic or therapeutic procedures. (orig.)

  12. Multiple sclerosis deep grey matter: the relation between demyelination, neurodegeneration, inflammation and iron.

    Science.gov (United States)

    Haider, Lukas; Simeonidou, Constantina; Steinberger, Günther; Hametner, Simon; Grigoriadis, Nikolaos; Deretzi, Georgia; Kovacs, Gabor G; Kutzelnigg, Alexandra; Lassmann, Hans; Frischer, Josa M

    2014-12-01

    In multiple sclerosis (MS), diffuse degenerative processes in the deep grey matter have been associated with clinical disabilities. We performed a systematic study in MS deep grey matter with a focus on the incidence and topographical distribution of lesions in relation to white matter and cortex in a total sample of 75 MS autopsy patients and 12 controls. In addition, detailed analyses of inflammation, acute axonal injury, iron deposition and oxidative stress were performed. MS deep grey matter was affected by two different processes: the formation of focal demyelinating lesions and diffuse neurodegeneration. Deep grey matter demyelination was most prominent in the caudate nucleus and hypothalamus and could already be seen in early MS stages. Lesions developed on the background of inflammation. Deep grey matter inflammation was intermediate between low inflammatory cortical lesions and active white matter lesions. Demyelination and neurodegeneration were associated with oxidative injury. Iron was stored primarily within oligodendrocytes and myelin fibres and released upon demyelination. In addition to focal demyelinated plaques, the MS deep grey matter also showed diffuse and global neurodegeneration. This was reflected by a global reduction of neuronal density, the presence of acutely injured axons, and the accumulation of oxidised phospholipids and DNA in neurons, oligodendrocytes and axons. Neurodegeneration was associated with T cell infiltration, expression of inducible nitric oxide synthase in microglia and profound accumulation of iron. Thus, both focal lesions as well as diffuse neurodegeneration in the deep grey matter appeared to contribute to the neurological disabilities of MS patients.

  13. Gadolinium enhancement patterns of tumefactive demyelinating lesions: correlations with brain biopsy findings and pathophysiology.

    Science.gov (United States)

    Kobayashi, Masaki; Shimizu, Yuko; Shibata, Noriyuki; Uchiyama, Shinichiro

    2014-10-01

    Tumefactive demyelinating lesions (TDLs) can mimic brain tumors on radiological images. TDLs are often referred to as tumefactive multiple sclerosis (TMS), but the heterogeneous nature and monophasic course of TDLs do not fulfill clinical and magnetic resonance imaging (MRI) criteria for multiple sclerosis. Redefining TDLs, TMS and other inflammatory brain lesions is essential for the accurate clinical diagnosis of extensive demyelinating brain lesions. We retrospectively analyzed MRI from nine TDL cases that underwent brain biopsy. Patterns of gadolinium enhancement on MRI were categorized as homogenous, inhomogeneous, patchy and diffuse, open ring or irregular rim, and were compared with pathological hallmarks including demyelination, central necrosis, macrophage infiltration, angiogenesis and perivascular lymphocytic cuffing. All cases had coexistence of demyelinating features and axonal loss. Open-ring and irregular rim patterns of gadolinium enhancement were associated with macrophage infiltrations and angiogenesis at the inflammatory border. An inhomogeneous pattern of gadolinium enhancement was associated with perivascular lymphocytic cuffing. Central necrosis was seen in cases of severe multiple sclerosis and hemorrhagic leukoencephalopathy. These results suggest that the radiological features of TDLs may be related to different pathological processes, and indicate that MRI may be useful in understanding their pathophysiology. Further investigation is needed to determine the precise disease entity of these inflammatory demyelinating brain lesions.

  14. Pain and spinal cord imaging measures in children with demyelinating disease

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    Nadia Barakat

    2015-01-01

    Full Text Available Pain is a significant problem in diseases affecting the spinal cord, including demyelinating disease. To date, studies have examined the reliability of clinical measures for assessing and classifying the severity of spinal cord injury (SCI and also to evaluate SCI-related pain. Most of this research has focused on adult populations and patients with traumatic injuries. Little research exists regarding pediatric spinal cord demyelinating disease. One reason for this is the lack of reliable and useful approaches to measuring spinal cord changes since currently used diagnostic imaging has limited specificity for quantitative measures of demyelination. No single imaging technique demonstrates sufficiently high sensitivity or specificity to myelin, and strong correlation with clinical measures. However, recent advances in diffusion tensor imaging (DTI and magnetization transfer imaging (MTI measures are considered promising in providing increasingly useful and specific information on spinal cord damage. Findings from these quantitative imaging modalities correlate with the extent of demyelination and remyelination. These techniques may be of potential use for defining the evolution of the disease state, how it may affect specific spinal cord pathways, and contribute to the management of pediatric demyelination syndromes. Since pain is a major presenting symptom in patients with transverse myelitis, the disease is an ideal model to evaluate imaging methods to define these regional changes within the spinal cord. In this review we summarize (1 pediatric demyelinating conditions affecting the spinal cord; (2 their distinguishing features; and (3 current diagnostic and classification methods with particular focus on pain pathways. We also focus on concepts that are essential in developing strategies for the detection, monitoring, treatment and repair of pediatric myelitis.

  15. Complement activation in autoimmune demyelination: dual role in neuroinflammation and neuroprotection.

    Science.gov (United States)

    Rus, Horea; Cudrici, Cornelia; Niculescu, Florin; Shin, Moon L

    2006-11-01

    Multiple sclerosis and its animal model experimental allergic encephalomyelitis are inflammatory demyelinating diseases of the central nervous system mediated by activated lymphocytes, macrophages/microglia and the complement system. Complement activation and the C5b-9 terminal complex contribute to the pathogenesis of these diseases through its role to promote demyelination. C5b-9 was also shown to protect oligodendrocytes from apoptosis both in vitro and in vivo. Our findings indicate that activation of complement and C5b-9 assembly plays a pro-inflammatory role in the acute phase, but may also be neuroprotective.

  16. Spatio-Temporal Patterns of Demyelination and Remyelination in the Cuprizone Mouse Model.

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    Ian Tagge

    Full Text Available Cuprizone administration in mice provides a reproducible model of demyelination and spontaneous remyelination, and has been useful in understanding important aspects of human disease, including multiple sclerosis. In this study, we apply high spatial resolution quantitative MRI techniques to establish the spatio-temporal patterns of acute demyelination in C57BL/6 mice after 6 weeks of cuprizone administration, and subsequent remyelination after 6 weeks of post-cuprizone recovery. MRI measurements were complemented with Black Gold II stain for myelin and immunohistochemical stains for associated tissue changes. Gene expression was evaluated using the Allen Gene Expression Atlas. Twenty-five C57BL/6 male mice were split into control and cuprizone groups; MRI data were obtained at baseline, after 6 weeks of cuprizone, and 6 weeks post-cuprizone. High-resolution (100 μm isotropic whole-brain coverage magnetization transfer ratio (MTR parametric maps demonstrated concurrent caudal-to-rostral and medial-to-lateral gradients of MTR decrease within corpus callosum (CC that correlated well with demyelination assessed histologically. Our results show that demyelination was not limited to the midsagittal line of the corpus callosum, and also that opposing gradients of demyelination occur in the lateral and medial CC. T2-weighted MRI gray/white matter contrast was strong at baseline, weak after 6 weeks of cuprizone treatment, and returned to a limited extent after recovery. MTR decreases during demyelination were observed throughout the brain, most clearly in callosal white matter. Myelin damage and repair appear to be influenced by proximity to oligodendrocyte progenitor cell populations and exhibit an inverse correlation with myelin basic protein gene expression. These findings suggest that susceptibility to injury and ability to repair vary across the brain, and whole-brain analysis is necessary to accurately characterize this model. Whole

  17. Cockayne syndrome-xeroderma pigmentosum complex with demyelination: A rare association

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    Usha Rani Singh

    2012-01-01

    Full Text Available Xeroderma pigmentosum-Cockayne syndrome (XP-CS includes facial freckling and early skin cancers typical of XP and some features typical of CS, such as mental retardation, spasticity, short stature, and hypogonadism. XP-CS does not include skeletal involvement, the facial phenotype of CS, or CNS demyelination and calcifications. We present a rare patient whose genome probably harbored a specific combination of mutations producing a rare double syndrome of XP-CS, with facial phenotype of CS, and CNS demyelination.

  18. The therapeutic potential of mesenchymal stem cells & FGF8 in chronic demyelinating diseases

    OpenAIRE

    Cruz Martinez, Pablo

    2015-01-01

    Diferentes investigadores han demostrado el potencial terapéutico de las células madre mesenquimales (MSCs) en diversos trastornos neurodegenerativos, incluyendo las enfermedades desmielinizantes. Sin embargo, este efecto se observó por lo general únicamente a nivel local, en el área donde se inyectaban las células madre. Junto a ello, los tratamientos actuales que modifican los mecanismos patológicos son capaces de mejorar los síntomas de la enfermedad, pero con frecuencia son insuficientes ...

  19. [On the mechanisms and diagnosis of conduction disturbances due to demyelination with special reference to multifocal demyelinating neuropathy (Lewis-Sumner)].

    Science.gov (United States)

    Kaji, R; Kimura, J

    1991-12-01

    Multifocal demyelinating neuropathy with persistent conduction block can mimic motor neuron disease, but is potentially reversible. Its diagnosis rests upon electrophysiological demonstration of focal conduction block at multiple sites. Conduction block is the most important mechanism causing clinical symptoms in peripheral nerve demyelination. On the other hand, conduction slowing is not always associated with clinical symptoms. In 2 out of 9 patients with multifocal demyelinating motor neuropathy, MRI showed focal swelling of the nerve at the site of conduction block. Both of them had elevated titers of anti-GM1 antibodies. In one, we biopsied a portion of the medial pectoral nerve, which was adjacent to the focal swelling, at surgical exploration. Pathological findings included very thin myelin associated with large diameter fibers and small onion bulb formation, suggesting that remyelinative process is abortive in this disease leading to persistent conduction block. Anti-GM1 antibodies bound to the denuded axoplasmic membrane may interfere with the process by masking the cell surface markers. The reason why the sensory fibers are spared is unclear, but it may be possible that GM1 in sensory axons have less affinity to the antibody than that in motor fibers.

  20. A novel model of demyelination and remyelination in a GFP-transgenic zebrafish

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    Yangwu Fang

    2014-12-01

    Full Text Available Demyelinating diseases consist of a variety of autoimmune conditions in which the myelin sheath is damaged due to genetic and/or environmental factors. During clinical treatment, some patients undergo partial remyelination, especially during the early disease stages. However, the mechanisms that regulate demyelination remain unclear. The myelin structure, myelin formation and myelin-related gene expression are highly conserved between mammals and zebrafish. Therefore, the zebrafish is an ideal model organism to study myelination. In this study, we generated a transgenic zebrafish Tg(mbp:nfsB-egfp expressing a fusion protein composed of enhanced green fluorescent protein (EGFP and NTR from the myelin basic protein (mbp promoter. Tg(mbp:nfsB-egfp expressed NTR-EGFP reproducibly and hereditarily in oligodendrocytes along the spinal cord. Treatment of zebrafish larvae Tg(mbp:nfsB-egfp with metronidazole (Mtz resulted in the selective ablation of oligodendrocytes and led to demyelination, accompanied by behavioral changes, including decreased total movement distance, velocity, total movement time and fast movement time. After withdrawal of Mtz for a seven day recovery period, the expression of EGFP and MBP protein was observed again which indicates remyelination. Additionally, locomotor capacity was restored. Collectively, Tg(mbp:nfsB-egfp, a heritable and stable transgenic line, provides a novel, powerful tool to study the mechanisms of demyelination and remyelination.

  1. Loss of Saltation and Presynaptic Action Potential Failure in Demyelinated Axons

    Science.gov (United States)

    Hamada, Mustafa S.; Popovic, Marko A.; Kole, Maarten H. P.

    2017-01-01

    In cortical pyramidal neurons the presynaptic terminals controlling transmitter release are located along unmyelinated axon collaterals, far from the original action potential (AP) initiation site, the axon initial segment (AIS). Once initiated, APs will need to reliably propagate over long distances and regions of geometrical inhomogeneity like branch points (BPs) to rapidly depolarize the presynaptic terminals and confer temporally precise synaptic transmission. While axon pathologies such as demyelinating diseases are well established to impede the fidelity of AP propagation along internodes, to which extent myelin loss affects propagation along BPs and axon collaterals is not well understood. Here, using the cuprizone demyelination model, we performed optical voltage-sensitive dye (VSD) imaging from control and demyelinated layer 5 pyramidal neuron axons. In the main axon, we find that myelin loss switches the modality of AP propagation from rapid saltation towards a slow continuous wave. The duration of single AP waveforms at BPs or nodes was, however, only slightly briefer. In contrast, by using two-photon microscopy-guided loose-seal patch recordings from axon collaterals we revealed a presynaptic AP broadening in combination with a reduced velocity and frequency-dependent failure. Finally, internodal myelin loss was also associated with de novo sprouting of axon collaterals starting from the primary (demyelinated) axon. Thus, the loss of oligodendrocytes and myelin sheaths bears functional consequences beyond the main axon, impeding the temporal fidelity of presynaptic APs and affecting the functional and structural organization of synaptic connectivity within the neocortex.

  2. Remyelination After Cuprizone-Induced Demyelination Is Accelerated in Juvenile Mice.

    Science.gov (United States)

    Pfeifenbring, Sabine; Nessler, Stefan; Wegner, Christiane; Stadelmann, Christine; Brück, Wolfgang

    2015-08-01

    Remyelination capacity decreases with age in adult mice, but data comparing remyelination capacity after toxic demyelination in developing mice versus adult mice are not available. We treated 3-week-old and adult C57BL/6 mice with cuprizone for 1 to 5 weeks and studied demyelination/remyelination and cellular reactions in the corpus callosum and motor cortex by histology, immunohistochemistry, and electron microscopy. We compared results between the 2 treated groups and age-matched controls. In juvenile mice, significant demyelination was detectable in the corpus callosum on Week 2 and in the motor cortex on Week 5. Oligodendrocyte loss, microglial activation, and acute axonal damage peaked on Week 2. Increased numbers of oligodendrocyte precursor cells were evident on Week 1, and remyelination was detectable on Week 3. Juvenile mice showed more rapid demyelination than adult mice, which may be related to greater vulnerability of oligodendrocytes, lower myelin content, or dose-dependent cuprizone effects. Earlier activation of microglia and proliferation of oligodendrocyte precursor cells probably contributed to accelerated remyelination and less pronounced axonal damage. Our data indicate that oligodendroglial regeneration and remyelination are enhanced in the maturing rodent brain compared with the young-adult rodent brain.

  3. The aqueous layers within the myelin sheath modulate the membrane properties of simulated hereditary demyelinating neuropathies.

    Science.gov (United States)

    Stephanova, D I; Krustev, S M; Daskalova, M

    2011-03-01

    To expand our studies on the mechanisms underlying the clinical decline of the nerve excitability properties in patients with hereditary demyelinating neuropathies, the contribution of myelin sheath aqueous layers on multiple membrane properties of simulated fiber demyelinations is investigated. Three progressively greater degrees of internodal systematic demyelinations (two mild and one severe termed as ISD1, ISD2 and ISD3, respectively) without/with aqueous layers are simulated using our previous multi-layered model of human motor nerve fiber. The calculated multiple membrane excitability properties are as follows: potentials (intracellular action, electrotonic), strength-duration time constants, rheobasic currents and recovery cycles. They reflect the propagating, accommodative and adaptive processes in the fibers. The results show that all membrane properties, except for the strength-duration time constants and refractoriness, worsen when the myelin lamellae and their corresponding aqueous layers are uniformly reduced along the fiber length. The effect of the aqueous layers is significantly higher on the accommodative and adaptive processes than on the propagating processes in the fibers. Our multi-layered model better approximated some of the functional deficits documented for axons of patients with Charcot-Marie-Tooth disease type 1A. The study provides new and important information on the mechanisms underlying the pathophysiology of hereditary demyelinating neuropathies.

  4. Electrophysiological features of inherited demyelinating neuropathies: A reappraisal in the era of molecular diagnosis.

    Science.gov (United States)

    Lewis, R A; Sumner, A J; Shy, M E

    2000-10-01

    The observation that inherited demyelinating neuropathies have uniform conduction slowing and that acquired disorders have nonuniform or multifocal slowing was made prior to the identification of mutations in myelin-specific genes which cause many of the inherited disorders involving peripheral nerve myelin. It is now clear that the electrophysiological aspects of these disorders are more complex than previously realized. Specifically, certain mutations appear to induce nonuniform slowing of conduction which resemble the findings in acquired demyelinating neuropathies. It is clinically important to recognize the different electrodiagnostic patterns of the various inherited demyelinating neuropathies. In addition, an understanding of the relationship between mutations of specific genes and their associated neurophysiological findings is likely to facilitate understanding of the role of these myelin proteins in peripheral nerve function and of how abnormalities in myelin proteins lead to neuropathy. We therefore review the current information on the electrophysiological features of the inherited demyelinating neuropathies in hopes of clarifying their electrodiagnostic features and to shed light on the physiological consequences of the different genetic mutations.

  5. Incidence of acquired demyelinating syndromes of the CNS in Dutch children : a nationwide study

    NARCIS (Netherlands)

    Ketelslegers, I. A.; Catsman-Berrevoets, C. E.; Neuteboom, R. F.; Boon, M.; van Dijk, K. G. J.; Eikelenboom, M. J.; Gooskens, R. H. J. M.; Niks, E. H.; Overweg-Plandsoen, W. C. G.; Peeters, E. A. J.; Peeters-Scholte, C. M. P. C. D.; Poll-The, B. T.; de Rijk-van Andel, J. F.; Samijn, J. P. A.; Snoeck, I. N.; Stroink, H.; Vermeulen, R. J.; Verrips, A.; Vles, J. S. H.; Willemsen, M. A. A. P.; Pereira, R. Rodrigues; Hintzen, R. Q.

    2012-01-01

    Acquired demyelinating syndromes (ADS) can be a first presentation of multiple sclerosis (MS) in children. The incidence of these disorders in Europe is currently unknown. Children (<18 years old) living in the Netherlands who presented with ADS were included from January 1, 2007 to December 31, 201

  6. Incidence of acquired demyelinating syndromes of the CNS in Dutch children: A nationwide study

    NARCIS (Netherlands)

    Ketelslegers, I.A.; Catsman-Berrevoets, C.E.; Neuteboom, R.F.; Boon, M.; Dijk, K.G.J. van; Eikelenboom, M.J.; Gooskens, R.H.J.M.; Niks, E.H.; Overweg-Plandsoen, W.C.G.; Peeters, E.A.J.; Peeters-Scholte, C.M.P.C.D.; Poll-The, B.T.; Rijk-Van Andel, J.F. de; Samijn, J.P.A.; Snoeck, I.N.; Stroink, H.; Vermeulen, R.J.; Verrips, A.; Vles, J.S.H.; Willemsen, M.A.A.P.; Rodrigues Pereira, R.; Hintzen, R.Q.

    2012-01-01

    Acquired demyelinating syndromes (ADS) can be a first presentation of multiple sclerosis (MS) in children. The incidence of these disorders in Europe is currently unknown. Children (<18 years old) living in the Netherlands who presented with ADS were included from January 1, 2007 to December 31, 201

  7. Incidence of acquired demyelinating syndromes of the CNS in Dutch children: a nationwide study.

    NARCIS (Netherlands)

    Ketelslegers, I.A.; Catsman-Berrevoets, C.E.; Neuteboom, R.F.; Boon, M.; Dijk, K.G.; Eikelenboom, M.J.; Gooskens, R.H.; Niks, E.H.; Overweg-Plandsoen, W.C.; Peeters, E.A.; Peeters-Scholte, C.M.; Poll-The, B.T.; Rijk-van Andel, J.F. de; Samijn, J.P.; Snoeck, I.N.; Stroink, H.; Vermeulen, R.J.; Verrips, A.; Vles, J.S.; Willemsen, M.A.A.P.; Rodrigues Pereira, R.; Hintzen, R.Q.

    2012-01-01

    Acquired demyelinating syndromes (ADS) can be a first presentation of multiple sclerosis (MS) in children. The incidence of these disorders in Europe is currently unknown. Children (<18 years old) living in the Netherlands who presented with ADS were included from January 1, 2007 to December 31,

  8. Incidence of acquired demyelinating syndromes of the CNS in Dutch children: A nationwide study

    NARCIS (Netherlands)

    I.A. Ketelslegers (Immy); C.E. Catsman-Berrevoets (Coriene); R.F. Neuteboom (Rinze); M. Boon (Martin); K.G.J. van Dijk (K. G J); M.J. Eikelenboom (Merijn Judith); R.H.J.M. Gooskens (Rob); E.H. Niks (Erik); W.C.G. Overweg-Plandsoen; E.A. Peeters (Els); C.M.P.C.D. Peeters-Scholte (C. M P C D); B.T. Poll-The; J. De Rijk-Van Andel (Johanneke); J.P. Samijn (Johnny); M.M.J. Snoeck (M. M J); H. Stroink (Hans); R.J. Vermeulen (Jeroen); A. Verrips (Aad); J.S.H. Vles (Johannes); M.A. Willemsen (Michél); R. Rodrigues Pereira; R.Q. Hintzen (Rogier)

    2012-01-01

    textabstractAcquired demyelinating syndromes (ADS) can be a first presentation of multiple sclerosis (MS) in children. The incidence of these disorders in Europe is currently unknown. Children (<18 years old) living in the Netherlands who presented with ADS were included from January 1, 2007 to Dece

  9. MiR-30a inhibits Th17 differentiation and demyelination of EAE mice by targeting the IL-21R.

    Science.gov (United States)

    Qu, Xuebin; Zhou, Jun; Wang, Ting; Han, Jingjing; Ma, Li; Yu, Hongli; Geng, Deqin; Fan, Hongbin; Zhang, Qingshan; Hua, Fang; Yao, Ruiqin

    2016-10-01

    T helper cells 17 (Th17) are recognized as key participants in the pathogenesis of chronic autoimmune diseases such as multiple sclerosis (MS). Regulation of Th17 differentiation is a valuable strategy for diagnosis and treatment of these complicated immune disorders. Here, by genome-wide expression profiling of microRNAs (miRs), we screened miR-30a, whose level was greatly decreased during Th17 differentiation and the process of demyelination disease, both in MS patients and experimental autoimmune encephalomyelitis (EAE) mice. Enforced constitutive expression of miR-30a in naïve T cells inhibited their differentiation into Th17, and in vivo overexpression of miR-30a resulted in fewer Th17 and alleviative EAE. Moreover, target prediction analysis and dual luciferase report assay revealed that interleukin-21 receptor (IL-21R) was a direct target of miR-30a, a finding consistent with the results that miR-30a downregulated the expression of IL-21R, while overexpression of IL-21R alleviated the inhibitory effect of miR-30a on Th17 differentiation. Taken together, our findings imply that miR-30a inhibits Th17 differentiation and the pathogenesis of MS by targeting IL-21R.

  10. HCV-Related Central and Peripheral Nervous System Demyelinating Disorders

    OpenAIRE

    Mariotto, Sara; Ferrari, Sergio; Monaco, Salvatore

    2014-01-01

    Chronic infection with hepatitis C virus (HCV) is associated with a large spectrum of extrahepatic manifestations (EHMs), mostly immunologic/rheumatologic in nature owing to B-cell proliferation and clonal expansion. Neurological complications are thought to be immune-mediated or secondary to invasion of neural tissues by HCV, as postulated in transverse myelitis and encephalopathic forms. Primarily axonal neuropathies, including sensorimotor polyneuropathy, large or small fiber sensory neuro...

  11. Gas6 increases myelination by oligodendrocytes and its deficiency delays recovery following cuprizone-induced demyelination.

    Directory of Open Access Journals (Sweden)

    Michele D Binder

    Full Text Available Multiple sclerosis (MS is a complex demyelinating disease of the central nervous system. Current research has shown that at least in some cases, the primary insult in MS could be directed at the oligodendrocyte, and that the earliest immune responses are primarily via innate immune cells. We have identified a family of receptor protein tyrosine kinases, known as the TAM receptors (Tyro3, Axl and Mertk, as potentially important in regulating both the oligodendrocyte and immune responses. We have previously shown that Gas6, a ligand for the TAM receptors, can affect the severity of demyelination in mice, with a loss of signalling via Gas6 leading to decreased oligodendrocyte survival and increased microglial activation during cuprizone-induced demyelination. We hypothesised TAM receptor signalling would also influence the extent of recovery in mice following demyelination. A significant effect of the absence of Gas6 was detected upon remyelination, with a lower level of myelination after 4 weeks of recovery in comparison with wild-type mice. The delay in remyelination was accompanied by a reduction in oligodendrocyte numbers. To understand the molecular mechanisms that drive the observed effects, we also examined the effect of exogenous Gas6 in in vitro myelination assays. We found that Gas6 significantly increased myelination in a dose-dependent manner, suggesting that TAM receptor signalling could be directly involved in myelination by oligodendrocytes. The reduced rate of remyelination in the absence of Gas6 could thus result from a lack of Gas6 at a critical time during myelin production after injury. These findings establish Gas6 as an important regulator of both CNS demyelination and remyelination.

  12. Neurotrophic ACTH4-9 analogue therapy normalizes electroencephalographic alterations in chronic experimental allergic encephalomyelitis

    NARCIS (Netherlands)

    Gispen, W.H.; Duckers, H.J.; Dokkum, R.P. van; Verhaagen, J.; Luijtelaar, E.L.; Coenen, A.M.; Lopes da Silva, F.H.

    1998-01-01

    Chronic experimental allergic encephalomyelitis (CEAE) is an established experimental model for multiple sclerosis (MS). The demyelinating lesions in the white matter of the central nervous system observed in CEAE and in MS are accompanied by various neurophysiological alterations. Among the best de

  13. Chronic arsenic poisoning masquerading as Landry-Guillain-Barré syndrome.

    Science.gov (United States)

    Goddard, M J; Tanhehco, J L; Dau, P C

    1992-09-01

    Acute arsenic intoxication may present as Landry-Guillain-Barré syndrome because of similarities in clinical symptoms involving the gastrointestinal tract, weakness, and sensory symptoms. Electrodiagnostic findings may be similar with demyelinating changes predominating early in both diseases. A case is presented of repeated arsenic poisoning over two years misdiagnosed as Landry-Guillain-Barré syndrome. Proximal F-loop latency (M-wave latency at wrist + F-wave latency at wrist - 2 M-wave latency at axilla) helped to establish the correct diagnosis. Serial electrodiagnostic studies were done documenting the evolution of chronic repeated arsenic poisoning from a picture showing demyelination to one with severe axonal loss.

  14. Application of the 2012 revised diagnostic definitions for paediatric multiple sclerosis and immune-mediated central nervous system demyelination disorders

    NARCIS (Netherlands)

    van Pelt, E. Danielle; Neuteboom, Rinze F.; Ketelslegers, Immy A.; Boon, Maartje; Catsman-Berrevoets, Coriene E.; Hintzen, Rogier Q.

    2014-01-01

    Background Recently, the International Paediatric Multiple Sclerosis Study Group (IPMSSG) definitions for the diagnosis of immune-mediated acquired demyelinating syndromes (ADS) of the central nervous system, including paediatric multiple sclerosis (MS), have been revised. Objective To evaluate the

  15. Chronic pancreatitis

    Science.gov (United States)

    Chronic pancreatitis - chronic; Pancreatitis - chronic - discharge; Pancreatic insufficiency - chronic; Acute pancreatitis - chronic ... alcohol abuse over many years. Repeated episodes of acute ... chronic pancreatitis. Genetics may be a factor in some cases. ...

  16. Acute Inflammatory Demyelinating Polyneuropathy in Children; Clinical and Electrophysiologic Findings

    Directory of Open Access Journals (Sweden)

    Seyed-Hasan Tonekaboni

    2009-03-01

    Full Text Available Objective:The aim of this study was to evaluate the electrophysiologic findings of Guillain Barre Syndrome (GBS in children and their relation with clinical progress of the disease. Methods:Twenty-three children with GBS were evaluated between 2005 and 2007. Electrophysiologic evaluations were performed at admission and one month later. Findings: Five patients needed respirator, 15 were bedridden, 1 developed recurrence 6 months later, and 2 experienced chronic GBS. The most common findings included: decreased amplitude of muscle action potential (CMAP (96%, increased distal latency (74%, increased F wave latency (69%, and decreased nerve conduction velocity (NCV (61%. Sensory nerve conduction (evaluating sural nerve was normal in 78% of the cases. These measures did not significantly change after 1 month. Conclusion:Electrodiagnostic evaluations are helpful at the primary stages of GBS for diagnosis. Fibrillation potentials and positive sharp waves showing denervation and axonal injury are presentative of longer duration of the disease and a worse prognosis.

  17. [The role of the immune system in hereditary demyelinating neuropathies].

    Science.gov (United States)

    Mäurer, M; Toyka, K V; Martini, R

    2005-06-01

    Hereditary neuropathies, e.g., Charcot-Marie-Tooth (CMT) disease, are inherited diseases of the peripheral nervous system causing chronic progressive motor and sensory dysfunction. Most neuropathies are due to mutations in myelin genes such as PMP22, P0, and the gap junction protein Cx32. Myelin mutant mice are regarded as suitable animal models for several forms of hereditary neuropathies and are important neurobiological tools for the evaluation of pathogenetic and therapeutic concepts in hereditary neuropathies. Using these animal models we could recently show that the immune system is involved in the pathogenesis of hereditary neuropathies. Due to the phenotypic similarities we also consider the immune system important for human inherited neuropathies, in particular since several case reports demonstrate a beneficial effect of immune therapies in patients with hereditary neuropathies. In this review we compare findings from animal models and human disease to elucidate the role of the immune system in hereditary neuropathies.

  18. Effect of noscapine and vincristine combination on demyelination and cell proliferation in vitro.

    Science.gov (United States)

    Hiser, Laree; Herrington, Betty; Lobert, Sharon

    2008-08-01

    Peripheral neuropathy is a common, dose-limiting side effect of vincristine, a frontline therapy for acute lymphoblastic leukemia. Combination chemotherapy that reduces the neurotoxicity without compromising the efficacy of vincristine would improve patient outcomes. We performed in vitro studies using a combination of microtubule-binding antimitotics, noscapine and vincristine. In cell cultures containing neurons, astrocytes, and oligodendrocytes, vincristine caused demyelination as shown by transmission electron microscopy. A combination of vincristine and noscapine protected against demyelination. Human acute lymphoblastic and acute myelogenous leukemia cell lines CCRF-CEM and HL-60, respectively, were used to determine the antiproliferative effect of this novel drug combination. Vincristine and noscapine decreased cell proliferation with IC(50) concentrations of 1 nM and 20 microM, respectively. Analysis of dose-effect relationships using isobolograms and combination indices demonstrated that noscapine acts synergistically with vincristine. Thus, noscapine is a promising candidate for use with vincristine to decrease neurotoxicity and enhance antineoplastic effectiveness.

  19. Loss of Myelin Basic Protein Function Triggers Myelin Breakdown in Models of Demyelinating Diseases

    Directory of Open Access Journals (Sweden)

    Marie-Theres Weil

    2016-07-01

    Full Text Available Breakdown of myelin sheaths is a pathological hallmark of several autoimmune diseases of the nervous system. We employed autoantibody-mediated animal models of demyelinating diseases, including a rat model of neuromyelitis optica (NMO, to target myelin and found that myelin lamellae are broken down into vesicular structures at the innermost region of the myelin sheath. We demonstrated that myelin basic proteins (MBP, which form a polymer in between the myelin membrane layers, are targeted in these models. Elevation of intracellular Ca2+ levels resulted in MBP network disassembly and myelin vesiculation. We propose that the aberrant phase transition of MBP molecules from their cohesive to soluble and non-adhesive state is a mechanism triggering myelin breakdown in NMO and possibly in other demyelinating diseases.

  20. Loss of Myelin Basic Protein Function Triggers Myelin Breakdown in Models of Demyelinating Diseases.

    Science.gov (United States)

    Weil, Marie-Theres; Möbius, Wiebke; Winkler, Anne; Ruhwedel, Torben; Wrzos, Claudia; Romanelli, Elisa; Bennett, Jeffrey L; Enz, Lukas; Goebels, Norbert; Nave, Klaus-Armin; Kerschensteiner, Martin; Schaeren-Wiemers, Nicole; Stadelmann, Christine; Simons, Mikael

    2016-07-12

    Breakdown of myelin sheaths is a pathological hallmark of several autoimmune diseases of the nervous system. We employed autoantibody-mediated animal models of demyelinating diseases, including a rat model of neuromyelitis optica (NMO), to target myelin and found that myelin lamellae are broken down into vesicular structures at the innermost region of the myelin sheath. We demonstrated that myelin basic proteins (MBP), which form a polymer in between the myelin membrane layers, are targeted in these models. Elevation of intracellular Ca(2+) levels resulted in MBP network disassembly and myelin vesiculation. We propose that the aberrant phase transition of MBP molecules from their cohesive to soluble and non-adhesive state is a mechanism triggering myelin breakdown in NMO and possibly in other demyelinating diseases.

  1. Enhanced adenoviral gene delivery to motor and dorsal root ganglion neurons following injection into demyelinated peripheral nerves.

    Science.gov (United States)

    Zhang, Yongjie; Zheng, Yiyan; Zhang, Yi Ping; Shields, Lisa B E; Hu, Xiaoling; Yu, Panpan; Burke, Darlene A; Wang, Heming; Jun, Cai; Byers, Jonathan; Whittemore, Scott R; Shields, Christopher B

    2010-08-15

    Injection of viral vectors into peripheral nerves may transfer specific genes into their dorsal root ganglion (DRG) neurons and motoneurons. However, myelin sheaths of peripheral axons block the entry of viral particles into nerves. We studied whether mild, transient peripheral nerve demyelination prior to intraneural viral vector injection would enhance gene transfer to target DRG neurons and motoneurons. The right sciatic nerve of C57BL/6 mice was focally demyelinated with 1% lysolecithin, and the left sciatic nerve was similarly injected with saline (control). Five days after demyelination, 0.5 microl of Ad5-GFP was injected into both sciatic nerves at the site of previous injection. The effectiveness of gene transfer was evaluated by counting GFP(+) neurons in the DRGs and ventral horns. After peripheral nerve demyelination, there was a fivefold increase in the number of infected DRG neurons and almost a 15-fold increase in the number of infected motoneurons compared with the control, nondemyelinated side. Focal demyelination reduced the myelin sheath barrier, allowing greater virus-axon contact. Increased CXADR expression on the demyelinated axons facilitated axoplasmic viral entry. No animals sustained any prolonged neurological deficits. Increased gene delivery into DRG neurons and motoneurons may provide effective treatment for amyotrophic lateral sclerosis, pain, and spinal cord injury.

  2. Progressive multiple sclerosis cerebrospinal fluid induces inflammatory demyelination, axonal loss, and astrogliosis in mice.

    Science.gov (United States)

    Cristofanilli, Massimiliano; Rosenthal, Hannah; Cymring, Barbara; Gratch, Daniel; Pagano, Benjamin; Xie, Boxun; Sadiq, Saud A

    2014-11-01

    Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demyelination and neurodegeneration throughout the CNS, which lead over time to a condition of irreversible functional decline known as progressive MS. Currently, there are no satisfactory treatments for this condition because the mechanisms that underlie disease progression are not well understood. This is partly due to the lack of a specific animal model that represents progressive MS. We investigated the effects of intracerebroventricular injections of cerebrospinal fluid (CSF) derived from untreated primary progressive (PPMS), secondary progressive (SPMS), and relapsing/remitting (RRMS) MS patients into mice. We found discrete inflammatory demyelinating lesions containing macrophages, B cell and T cell infiltrates in the brains of animals injected with CSF from patients with progressive MS. These lesions were rarely found in animals injected with RRMS-CSF and never in those treated with control-CSF. Animals that developed brain lesions also presented extensive inflammation in their spinal cord. However, discrete spinal cord lesions were rare and only seen in animals injected with PPMS-CSF. Axonal loss and astrogliosis were seen within the lesions following the initial demyelination. In addition, Th17 cell activity was enhanced in the CNS and in lymph nodes of progressive MS-CSF injected animals compared to controls. Furthermore, CSF derived from MS patients who were clinically stable following therapy had greatly diminished capacity to induce CNS lesions in mice. Finally, we provided evidence suggesting that differential expression of pro-inflammatory cytokines present in the progressive MS CSF might be involved in the observed mouse pathology. Our data suggests that the agent(s) responsible for the demyelination and neurodegeneration characteristic of progressive MS is present in patient CSF and is amenable to further characterization in experimental models of the disease.

  3. Effects of deep heating provided by therapeutic ultrasound on demyelinating nerves

    OpenAIRE

    2016-01-01

    [Purpose] Physiotherapeutic heating agents are classified into two groups: superficial-heating agents and deep-heating agents. Therapeutic ultrasound is a deep-heating agent used to treat various musculosketal disorders. Numerous studies have attempted to determine the impact of ultrasound on healthy nerve conduction parameters. However, the instantaneous effects of deep heating via ultrasound on demyelinating nerves do not appear to have been described previously. The present study aimed to ...

  4. Hyperglycemia and downregulation of caveolin-1 enhance neuregulin-induced demyelination.

    Science.gov (United States)

    Yu, Cuijuan; Rouen, Shefali; Dobrowsky, Rick T

    2008-06-01

    Neuregulins (NRGs) are growth factors which bind to Erb receptor tyrosine kinases that localize to Schwann cells (SCs). Although NRGs can promote cell survival, mitogenesis, and myelination in undifferentiated SCs, they also induce demyelination of myelinated co-cultures of SCs and dorsal root ganglion (DRG) neurons. We have shown previously that Erb B2 activity increased in premyelinating SCs in response to hyperglycemia, and that this correlated with the downregulation of the protein caveolin-1 (Cav-1). As myelinated SCs undergo substantial degeneration in diabetic neuropathy, we used myelinated SC/DRG neuron co-cultures to determine if hyperglycemia and changes in Cav-1 expression could enhance NRG-induced demyelination. In basal glucose, NRG1 caused a 2.4-fold increase in the number of damaged myelin segments. This damage reached 3.8-fold under hyperglycemic conditions, and was also associated with a robust decrease in the expression of Cav-1 and compact myelin proteins. The loss of Cav-1 and compact myelin proteins following hyperglycemia and NRG treatment was not due to neuronal loss, since the axons remained intact and there was no loss of PGP 9.5, an axonal marker protein. To examine if changes in Cav-1 were sufficient to alter the extent of NRG-induced demyelination, SC/DRG neurons co-cultures were infected with antisense or dominant-negative Cav-1(P132L) adenoviruses. Either antisense-mediated downregulation or mis-localization of endogenous Cav-1 by Cav-1(P132L) resulted in a 1.5- to 2.4-fold increase in NRG-induced degeneration compared to that present in control cultures. These data support that hyperglycemia and changes in Cav-1 are sufficient to sensitize myelinated SC/DRG co-cultures to NRG-induced demyelination.

  5. Combination of Cerebral Demyelination and Graves Disease in a Case with Miller Fisher Syndrome

    OpenAIRE

    Sibel Güler; Levent Sinan Bir

    2010-01-01

    A 44-year-old male patient with a diagnosis of Miller Fisher syndrome, Graves disease and central nervous system demyelination is presented. Clinical and laboratory findings supported the diagnosis of Miller Fisher syndrome. On T2-weighted sections of cranial magnetic resonance imaging, many ovoid-shaped, hyperintense lesions in bilateral deep white matter were detected. Magnetic resonance imaging spectroscopy demonstrated low N-acetylaspartate to creatine (NAA/Cr) ratio consistent with demye...

  6. Central Nervous System Demyelination in a Charcot-Marie-Tooth Type 1A Patient

    OpenAIRE

    Christos Koros; Maria-Eleftheria Evangelopoulos; Costas Kilidireas; Elisabeth Andreadou

    2013-01-01

    Introduction. Central nervous system involvement, either clinical or subclinical, has been reported mainly in X-linked Charcot-Marie-Tooth (CMT-X) patients. Case Presentation. We present the case of a 31-year-old man with a genetically confirmed history of CMT1A who developed CNS involvement mimicking multiple sclerosis (MS). Clinical, imaging, and laboratory findings suggested an autoimmune CNS demyelination. Discussion. Although the simultaneous existence of CMT1A and MS could be coincident...

  7. THE SPECTRUM OF INFLAMMATORY DEMYELINATING DISEASES OF THE CENTRAL NERVOUS SYSTEM

    OpenAIRE

    Rama Krishna; Naveen; Vengamma; Mohan; Sridhar

    2016-01-01

    INTRODUCTION Idiopathic inflammatory demyelinating diseases (IIDDs) are rare neurological diseases. Their features differ from region to region. We characterize features of these diseases in Chittor. METHODS We describe 100 patients of IDD from Sri Venkateswara Institute of Medical Sciences, Tirupathi from May 2012 – December 2013. RESULTS 10 patients with multiple sclerosis, 14 with ADEM, 6 NMO, 9 with ATM and 9 ON presented with the mean of 32 years wit...

  8. Absence of Multiple Sclerosis and Demyelinating Diseases among Lacandonians, a Pure Amerindian Ethnic Group in Mexico

    Directory of Open Access Journals (Sweden)

    Jose Flores

    2012-01-01

    Full Text Available Multiple Sclerosis (MS is a highly polymorphic disease characterized by different neurologic signs and symptoms. In MS, racial and genetic factors may play an important role in the geographic distribution of this disease. Studies have reported the presence of several protective alleles against the development of autoimmune disorders. In the case of MS, however, they help define MS as a complex disease, and confirm the importance of environmental agents as an independent variable not associated with ethnicity. We carried out an on-site epidemiological study to confirm the absence of MS or NMO among Lacandonians, a pure Amerindian ethnic group in Mexico. We administered a structured interview to 5,372 Lacandonians to assess by family background any clinical data consistent with the presence of a prior demyelinating event. Every participating subject underwent a comprehensive neurological examination by a group of three members of the research team with experience in the diagnosis and treatment of demyelinating disorders to detect clinical signs compatible with a demyelinating disease. We did not find any clinical signs compatible with multiple sclerosis among study participants.

  9. Clemastine rescues behavioral changes and enhances remyelination in the cuprizone mouse model of demyelination.

    Science.gov (United States)

    Li, Zhifang; He, Yangtao; Fan, Shuangyi; Sun, Binbin

    2015-10-01

    Increasing evidence suggests that white matter disorders based on myelin sheath impairment may underlie the neuropathological changes in schizophrenia. But it is unknown whether enhancing remyelination is a beneficial approach to schizophrenia. To investigate this hypothesis, we used clemastine, an FDA-approved drug with high potency in promoting oligodendroglial differentiation and myelination, on a cuprizone-induced mouse model of demyelination. The mice exposed to cuprizone (0.2% in chow) for 6 weeks displayed schizophrenia-like behavioral changes, including decreased exploration of the center in the open field test and increased entries into the arms of the Y-maze, as well as evident demyelination in the cortex and corpus callosum. Clemastine treatment was initiated upon cuprizone withdrawal at 10 mg/kg per day for 3 weeks. As expected, myelin repair was greatly enhanced in the demyelinated regions with increased mature oligodendrocytes (APC-positive) and myelin basic protein. More importantly, the clemastine treatment rescued the schizophrenia-like behavioral changes in the open field test and the Y-maze compared to vehicle, suggesting a beneficial effect via promoting myelin repair. Our findings indicate that enhancing remyelination may be a potential therapy for schizophrenia.

  10. Astrocyte-derived tissue Transglutaminase affects fibronectin deposition, but not aggregation, during cuprizone-induced demyelination

    Science.gov (United States)

    Espitia Pinzon, Nathaly; Sanz-Morello, Berta; Brevé, John J. P.; Bol, John G. J. M.; Drukarch, Benjamin; Bauer, Jan; Baron, Wia; van Dam, Anne-Marie

    2017-01-01

    Astrogliosis as seen in Multiple Sclerosis (MS) develops into astroglial scarring, which is beneficial because it seals off the site of central nervous system (CNS) damage. However, astroglial scarring also forms an obstacle that inhibits axon outgrowth and (re)myelination in brain lesions. This is possibly an important cause for incomplete remyelination in the CNS of early stage MS patients and for failure in remyelination when the disease progresses. In this study we address whether under demyelinating conditions in vivo, tissue Transglutaminase (TG2), a Ca2+ -dependent enzyme that catalyses posttranslational modification of proteins, contributes to extracellular matrix (ECM) deposition and/or aggregation. We used the cuprizone model for de- and remyelination. TG2 immunoreactivity and enzymatic activity time-dependently appeared in astrocytes and ECM, respectively, in the corpus callosum of cuprizone-treated mice. Enhanced presence of soluble monomeric and multimeric fibronectin was detected during demyelination, and fibronectin immunoreactivity was slightly decreased in cuprizone-treated TG2−/− mice. In vitro TG2 overexpression in astrocytes coincided with more, while knock-down of TG2 with less fibronectin production. TG2 contributes, at least partly, to fibronectin production, and may play a role in fibronectin deposition during cuprizone-induced demyelination. Our observations are of interest in understanding the functional implications of TG2 during astrogliosis. PMID:28128219

  11. Syringomyelia in demyelinating disease of the central nervous system: Report of two cases

    Directory of Open Access Journals (Sweden)

    Savić Dejan

    2011-01-01

    Full Text Available Introduction. Syringomyelia is a cavitary extension inside the spinal cord which can be either symptomatic or congenitally-idiopathic. Syringomyelia during the course of the disease in patients presenting with clinically definite multiple sclerosis was described earlier. Syringomyelia in patients presenting with a clinically isolated syndrome suggestive of multiple sclerosis is unusual. Case Outline. We present two patients presenting with demy-elinating disease of the central nervous system with syringomyelia in the cervical and thoracic spinal cord. We did not find classical clinical signs of syringomyelia in our patients, but we disclosed syringomyelia incidentally during magnetic resonance exploration. Magnetic resonance exploration using the gadolinium contrast revealed the signs of active demyelinating lesions in the spinal cord in one patient but not in the other. Conclusion. Syringomyelia in demyelinating disease of the central nervous system opens the question whether it is a coincidental finding or a part of clinical features of the disease. Differentiation of the significance of syringomyelia finding in these patients plays a role in the choice of treatment concept in such patients.

  12. Occurrence and long-term outcome of tumefactive demyelinating lesions in multiple sclerosis.

    Science.gov (United States)

    Totaro, Rocco; Di Carmine, C; Splendiani, A; Torlone, S; Patriarca, L; Carrocci, C; Sciamanna, S; Marini, C; Carolei, A

    2016-07-01

    Although tumefactive multiple sclerosis is a well recognized variant of multiple sclerosis, prognostic uncertainty still exists about long term prognosis. The aim of this study was to estimate the occurrence and long term outcome of tumefactive demyelinating lesions (TDLs) in a cohort of multiple sclerosis patients. We reviewed brain MRI of 443 patients referred to our MS clinic. All patients meeting the McDonald criteria for multiple sclerosis and showing at least one TDL were included. Kaplan-Meier estimates of disease-free survival in patient cohort were compared with control group without TDLs using a log-rank test. Seven cases with TDLs were identified (occurrence 1.58 %). Tumefactive demyelinating lesion recurrence was 16.6 %. Cumulative proportion of patients free from clinical relapse and from new T2 lesions was lower in the control group although not reaching statistical significance (30 vs 50 %; P = 0.666 and 21.7 vs 33.3 %; P = 0.761, respectively). Disability progression analysis showed a not significant trend towards lower probability of remaining progression free for TDL patients (50 vs 61 %; P = 0.295). Occurrence of tumefactive demyelinating lesions in our cohort was higher than those reported in other studies. Overall, TDLs were not predictive of poor outcome in terms of disability progression.

  13. MSX3 Switches Microglia Polarization and Protects from Inflammation-Induced Demyelination.

    Science.gov (United States)

    Yu, Zhongwang; Sun, Dingya; Feng, Jifeng; Tan, Weixing; Fang, Xue; Zhao, Ming; Zhao, Xiaolin; Pu, Yingyan; Huang, Aijun; Xiang, Zhenghua; Cao, Li; He, Cheng

    2015-04-22

    The major challenge for progressive multiple sclerosis therapy is the promotion of remyelination from inflammation-induced demyelination. A switch from an M1- to an M2-dominant polarization of microglia is critical in these repair processes. In this study, we identified the homeobox gene msh-like homeobox-3 (Msx3) as a new pivotal regulator for microglial polarization. MSX3 was induced during microglia M2 polarization and repressed in M1 cells. The expression of MSX3 in microglia was dynamically regulated during experimental autoimmune encephalomyelitis (EAE), which is an animal model of multiple sclerosis. The overexpression of MSX3 in microglia promoted M2 but impeded M1 polarization. Interrupting MSX3 expression in microglia accelerated inflammation-induced demyelination and neurodegeneration. The conditioned medium from MSX3-transduced microglia promoted oligodendrocyte progenitor survival, differentiation, and neurite outgrowth. The adoptive transfer of MSX3-transduced microglia suppressed EAE and facilitated remyelination within the murine CNS in EAE and the LPC model. Mechanically, chromatin immunoprecipitation assays also indicated that MSX3 directly regulated three key genes associated with microglia M2 polarization, including Pparg, Stat6, and Jak3. Importantly, we found that overexpression of MSX3 in human-derived microglia represents the M2 phenotype and ameliorated EAE after intraventricular injection. Our findings suggest a new homeobox protein-dependent mechanism for driving microglia M2 polarization and identify MSX3 as an attractive therapeutic approach for preventing inflammation-induced demyelination and promoting remyelination.

  14. Action potential characteristics of demyelinated rat sciatic nerve following application of 4-aminopyridine.

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    Targ, E F; Kocsis, J D

    1986-01-15

    The sciatic nerves of rats were demyelinated by microinjection of lysophosphatidylcholine. A variety of abnormalities such as conduction slowing and block were present. Application of the potassium channel blocker 4-aminopyridine (4-AP) to the lesion site, led to an increase in area of the compound action potential recorded across the site of demyelination. Single axon recordings revealed three types of changes that may account for the 4-AP-induced increase in the compound response. One group showed broadening of the action potential. Other axons showed hyperexcitability following 4-AP, as manifest by spontaneous firing and multiple spike discharge following a single stimulus. In some of the axons studied, 4-AP led to overcoming of conduction block. Although many axons showed increased excitability properties in the presence of 4-AP, the frequency-following ability of the axons was reduced, and the absolute refractory period of the axons was increased. These results indicate that pharmacological blockade of potassium channels with 4-AP not only leads to action potential broadening in demyelinated axons, but to a variety of excitability changes. These heterogeneous effects of 4-AP should be considered in the rationale for its clinical use.

  15. Absence of Multiple Sclerosis and Demyelinating Diseases among Lacandonians, a Pure Amerindian Ethnic Group in Mexico.

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    Flores, Jose; González, Silvia; Morales, Ximena; Yescas, Petra; Ochoa, Adriana; Corona, Teresa

    2012-01-01

    Multiple Sclerosis (MS) is a highly polymorphic disease characterized by different neurologic signs and symptoms. In MS, racial and genetic factors may play an important role in the geographic distribution of this disease. Studies have reported the presence of several protective alleles against the development of autoimmune disorders. In the case of MS, however, they help define MS as a complex disease, and confirm the importance of environmental agents as an independent variable not associated with ethnicity. We carried out an on-site epidemiological study to confirm the absence of MS or NMO among Lacandonians, a pure Amerindian ethnic group in Mexico. We administered a structured interview to 5,372 Lacandonians to assess by family background any clinical data consistent with the presence of a prior demyelinating event. Every participating subject underwent a comprehensive neurological examination by a group of three members of the research team with experience in the diagnosis and treatment of demyelinating disorders to detect clinical signs compatible with a demyelinating disease. We did not find any clinical signs compatible with multiple sclerosis among study participants.

  16. Demyelination in mild cognitive impairment suggests progression path to Alzheimer's disease.

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    Cristian Carmeli

    Full Text Available The preclinical Alzheimer's disease (AD - amnestic mild cognitive impairment (MCI - is manifested by phenotypes classified into exclusively memory (single-domain MCI (sMCI and multiple-domain MCI (mMCI. We suggest that typical MCI-to-AD progression occurs through the sMCI-to-mMCI sequence as a result of the extension of initial pathological processes. To support this hypothesis, we assess myelin content with a Magnetization Transfer Ratio (MTR in 21 sMCI and 21 mMCI patients and in 42 age-, sex-, and education-matched controls. A conjunction analysis revealed MTR reduction shared by sMCI and mMCI groups in the medial temporal lobe and posterior structures including white matter (WM: splenium, posterior corona radiata and gray matter (GM: hippocampus; parahippocampal and lingual gyri. A disjunction analysis showed the spread of demyelination to prefrontal WM and insula GM in executive mMCI. Our findings suggest that demyelination starts in the structures affected by neurofibrillary pathology; its presence correlates with the clinical picture and indicates the method of MCI-to-AD progression. In vivo staging of preclinical AD can be developed in terms of WM/GM demyelination.

  17. Acute Inflammatory Demyelinating Polyneuropathy and a Unilateral Babinski/Plantar Reflex

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    Davide Cattano

    2008-01-01

    Full Text Available Acquired acute demyelinating peripheral polyneuropathy (AADP is a general classification of pathologies that could affect secondary the peripheral nervous system. They are characterized by an autoimmune process directed towards myelin. Clinically they are characterized by progressive weakness and mild sensory changes. Acute inflammatory demyelinating polyneuropathy often is referred to as Guillain-Barré syndrome (GBS. GBS is the major cause of acute nontraumatic paralysis in healthy people and it is caused by autoimmune response to viral agents (influenza, coxsackie, Epstein-Barr virus, or cytomegalovirus or bacterial infective organisms (Campylobacter jejuni, Mycoplasma pneumoniae. A detailed history, with symptoms of progressive usually bilateral weakness, hyporeflexia, with a typical demyelinating EMG pattern supports the diagnosis. Progressive affection of respiratory muscles and autonomic instability coupled with a protracted and unpredictable recovery normally results in the need for ICU management. We present a case report of a patient with a typical GBS presentation but with a unilateral upgoing plantar reflex (Babinski sign. A unifying diagnosis was made and based on a literature search in Pubmed appears to be the first described case of its kind.

  18. Acute inflammatory demyelinating polyneuropathy and a unilateral babinski/plantar reflex.

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    Cattano, Davide; O'connor, Brian; Shakir, Ra'ad; Giunta, Francesco; Palazzo, Mark

    2008-01-01

    Acquired acute demyelinating peripheral polyneuropathy (AADP) is a general classification of pathologies that could affect secondary the peripheral nervous system. They are characterized by an autoimmune process directed towards myelin. Clinically they are characterized by progressive weakness and mild sensory changes. Acute inflammatory demyelinating polyneuropathy often is referred to as Guillain-Barré syndrome (GBS). GBS is the major cause of acute nontraumatic paralysis in healthy people and it is caused by autoimmune response to viral agents (influenza, coxsackie, Epstein-Barr virus, or cytomegalovirus) or bacterial infective organisms (Campylobacter jejuni, Mycoplasma pneumoniae). A detailed history, with symptoms of progressive usually bilateral weakness, hyporeflexia, with a typical demyelinating EMG pattern supports the diagnosis. Progressive affection of respiratory muscles and autonomic instability coupled with a protracted and unpredictable recovery normally results in the need for ICU management. We present a case report of a patient with a typical GBS presentation but with a unilateral upgoing plantar reflex (Babinski sign). A unifying diagnosis was made and based on a literature search in Pubmed appears to be the first described case of its kind.

  19. Effects of intraventricular methotrexate administration on Cuprizone-induced demyelination in mice

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    Andre Michael Mueller

    2013-10-01

    Full Text Available We previously showed that intrathecal administration of methotrexate slowed disability progression in multiple sclerosis patients with progressive disease. In general MS patients with progressive disease respond poorly to anti-inflammatory therapies. In order to better understand the mechanism by which methotrexate is protective in progressive MS, we analyzed its impact on the non-inflammatory cuprizone-induced demyelination model.When low-dose methotrexate was administered intracerebroventricularly it reduced demyelination and accumulation of GFAP+ reactive astrocytes in the corpus callosum. Administration of methotrexate after the withdrawal of cuprizone neither delayed remyelination nor influenced the number of astrocytes in the corpus callosum suggesting that methotrexate does not interfere with repair processes in the CNS. Moreover, methotrexate increased the expression of IGF1 in vitro and in vivo, a factor known to protect oligodendrocytes and limit the activation of astrocytes. Our studies show that methotrexate has an impact on pathogenic process in a demyelination model whose pathophysiological basis is not primarily related to inflammatory mechanisms, similar to neurodegenerative mechanisms associated with progressive MS. The pronounced inhibitory influence of methotrexate on the accumulation of astrocytes in the corpus callosum suggests that intrathecal methotrexate modulates astroglial activation in progressive MS possibly by promoting CNS production of IGF1.

  20. Human immunodeficiency virus seroconversion presenting with acute inflammatory demyelinating polyneuropathy: a case report

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    Sloan Derek J

    2008-12-01

    Full Text Available Abstract Introduction Acute Human Immunodeficiency Virus infection is associated with a range of neurological conditions. Guillain-Barré syndrome is a rare presentation; acute inflammatory demyelinating polyneuropathy is the commonest form of Guillain-Barré syndrome. Acute inflammatory demyelinating polyneuropathy has occasionally been reported in acute Immunodeficiency Virus infection but little data exists on frequency, management and outcome. Case presentation We describe an episode of Guillain-Barré syndrome presenting as acute inflammatory demyelinating polyneuropathy in a 30-year-old man testing positive for Immunodeficiency Virus, probably during acute seroconversion. Clinical suspicion was confirmed by cerebrospinal fluid analysis and nerve conduction studies. Rapid clinical deterioration prompted intravenous immunoglobulin therapy and early commencement of highly active anti-retroviral therapy. All symptoms resolved within nine weeks. Conclusion Unusual neurological presentations in previously fit patients are an appropriate indication for Immunodeficiency-Virus testing. Highly active anti-retroviral therapy with adequate penetration of the central nervous system should be considered as an early intervention, alongside conventional therapies such as intravenous immunoglobulin.

  1. Tamoxifen accelerates the repair of demyelinated lesions in the central nervous system

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    Gonzalez, Ginez A.; Hofer, Matthias P.; Syed, Yasir A.; Amaral, Ana I.; Rundle, Jon; Rahman, Saifur; Zhao, Chao; Kotter, Mark R. N.

    2016-01-01

    Enhancing central nervous system (CNS) myelin regeneration is recognized as an important strategy to ameliorate the devastating consequences of demyelinating diseases such as multiple sclerosis. Previous findings have indicated that myelin proteins, which accumulate following demyelination, inhibit remyelination by blocking the differentiation of rat oligodendrocyte progenitor cells (OPCs) via modulation of PKCα. We therefore screened drugs for their potential to overcome this differentiation block. From our screening, tamoxifen emerges as a potent inducer of OPC differentiation in vitro. We show that the effects of tamoxifen rely on modulation of the estrogen receptors ERα, ERβ, and GPR30. Furthermore, we demonstrate that administration of tamoxifen to demyelinated rats in vivo accelerates remyelination. Tamoxifen is a well-established drug and is thus a promising candidate for a drug to regenerate myelin, as it will not require extensive safety testing. In addition, Tamoxifen plays an important role in biomedical research as an activator of inducible genetic models. Our results highlight the importance of appropriate controls when using such models. PMID:27554391

  2. Central nervous system Toll-like receptor expression in response to Theiler's murine encephalomyelitis virus-induced demyelination disease in resistant and susceptible mouse strains

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    Turrin Nicolas P

    2008-12-01

    Full Text Available Abstract Background In immunopathological diseases, such as multiple sclerosis (MS, genetic and environmental factors that contribute to the initiation and progression of the disease are often discussed. The Theiler murine encephalomyelitis virus-induced demyelination disease (TMEV-IDD model used to study MS reflects this: genetically susceptible mice infected intra-cerebrally with TMEV develop a chronic demyelination disease. TMEV-IDD can be induced in resistant mouse strains by inducing innate immunity with lipopolysaccharide (LPS. Interestingly, Toll-like receptor 4 (TLR4 is the cognate receptor for LPS and its activation can induces up-regulation of other TLRs, such as TLR7 (the receptor for TMEV and 9, known to be involved in autoimmunity. Up-regulation of TLRs could be involved in precipitating an autoimmune susceptible state. Consequently, we looked at TLR expression in the susceptible (SJL/J and resistant (C57BL/6 strains of mice infected with TMEV. The resistant mice were induced to develop TMEV-IDD by two LPS injections following TMEV infection. Results Both strains were found to up-regulate multiple TLRs (TLR2, 7 and 9 following the TMEV infection. Expression of these TLRs and of viral mRNA was significantly greater in infected SJL/J mice. The susceptible SJL/J mice showed up-regulation of TLR3, 6 and 8, which was not seen in C57BL/6 mice. Conclusion Expression of TLRs by susceptible mice and the up-regulation of the TLRs in resistant mice could participate in priming the mice toward an autoimmune state and develop TMEV-IDD. This could have implications on therapies that target TLRs to prevent the emergence of conditions such as MS in patients at risk for the disease.

  3. White matter changes in paediatric multiple sclerosis and monophasic demyelinating disorders.

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    Longoni, Giulia; Brown, Robert A; MomayyezSiahkal, Parya; Elliott, Colm; Narayanan, Sridar; Bar-Or, Amit; Ann Marrie, Ruth; Ann Yeh, E; Filippi, Massimo; Banwell, Brenda; Arnold, Douglas L

    2017-03-14

    Most children who experience an acquired demyelinating syndrome of the central nervous system will have a monophasic disease course, with no further clinical or radiological symptoms. A subset will be diagnosed with multiple sclerosis, a life-long disorder. Using linear mixed effects models we examined longitudinal diffusion properties of normal-appearing white matter in 505 serial scans of 132 paediatric participants with acquired demyelinating syndromes followed for a median of 4.4 years, many from first clinical presentation, and 106 scans of 80 healthy paediatric participants. Fifty-three participants with demyelinating syndromes eventually received a diagnosis of paediatric-onset multiple sclerosis. Diffusion tensor imaging measures properties of water diffusion through tissue, which normally becomes increasingly restricted and anisotropic in the brain during childhood and adolescence, as fibre bundles develop and myelinate. In the healthy paediatric participants, our data demonstrate the expected trajectory of more restricted and anisotropic white matter diffusivity with increasing age. However, in participants with multiple sclerosis, fractional anisotropy decreased and mean diffusivity of non-lesional, normal-appearing white matter progressively increased after clinical presentation, suggesting not only a failure of age-expected white matter development but also a progressive loss of tissue integrity. Surprisingly, patients with monophasic disease failed to show age-expected changes in diffusion parameters in normal-appearing white matter, although they did not show progressive loss of integrity over time. Further analysis demonstrated that participants with monophasic disease experienced different post-onset trajectories in normal-appearing white matter depending on their presenting phenotype: those with acute disseminated encephalomyelitis demonstrated abnormal trajectories of diffusion parameters compared to healthy paediatric participants, as did

  4. Differential diagnosis of cervical spinal cord demyelinating diseases and cervical intramedullary gliomas

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    Gui-nü HE

    2014-09-01

    Full Text Available Objective To analyze the imaging characteristics of cervical spinal cord demyelinating diseases and cervical intramedullary gliomas, so as to improve the differential diagnosis between them.  Methods A retrospective analysis was conducted using clinical and MRI data from 22 cases of cervical spinal cord demyelinating diseases and 16 cases of cervical intramedullary gliomas.  Results Clinical features in both groups included paresthesia [77.27% (17/22, 12/16], weakness of limbs [72.73% (16/22, 10/16], and dysfunction of autonomic nerve [45.45% (10/22, 4/16]. In cervical MRI, the lesions involving more than 3 vertebras were 63.64% (14/22 in demyelinating group and 15/16 in glioma group, and the average lengths of lesions were (3.41 ± 1.74 and (3.59 ± 1.28 vertebras in 2 groups. The lesions showed long T1 signal [68.18% (15/22, 7/16], equisignal T1 [31.82% (7/22, 6/16] and long T2 signal [100% (22/22, 8/15] in 2 groups. Mixed T1 and T2 signals (3/16, 6/15 could be seen in glioma group. Demyelinating lesions had unclear boundary [90.91% (20/22] with patchy and ribbon-like enhancement (13/16. Limited enlargement of spinal cord (15/16 and thickening spinal meninges (14/16 were more common in glioma group, usually with block and circular enhancement (12/16. Spinal cord involvement around central canal could be seen (14/15, and the cysts or central canal enlargement, hemorrhage and "cap sign" were showed frequently (7/16, 5/16 and 4/16.  Conclusions Although none of one single clinical or MRI feature was sufficient enough to identify cervical spinal demyelinating diseases from cervical glioma, the comprehensive analysis of multiple features could help to make differential diagnosis of these diseases. doi: 10.3969/j.issn.1672-6731.2014.09.008

  5. Protective Effect of a cAMP Analogue on Behavioral Deficits and Neuropathological Changes in Cuprizone Model of Demyelination.

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    Vakilzadeh, Gelareh; Khodagholi, Fariba; Ghadiri, Tahereh; Darvishi, Marzieh; Ghaemi, Amir; Noorbakhsh, Farshid; Gorji, Ali; Sharifzadeh, Mohammad

    2015-08-01

    Multiple sclerosis (MS) is an inflammatory demyelinating disease that leads to neuronal cell loss. Cyclic AMP and its analogs are well known to decrease inflammation and apoptosis. In the present study, we examined the effects of bucladesine, a cell-permeable analogue of cyclic adenosine monophosphate (cAMP), on myelin proteins (PLP, PMP-22), inflammation, and apoptotic, as well as anti-apoptotic factors in cuprizone model of demyelination. C57BL/6J mice were fed with chow containing 0.2% copper chelator cuprizone or vehicle by daily oral gavage for 5 weeks to induce reversible demyelination predominantly of the corpus callosum. Bucladesine was administered intraperitoneally at different doses (0.24, 0.48, or 0.7 μg/kg body weight) during the last 7 days of 5-week cuprizone treatment. Bucladesine exhibited a protective effect on myelination. Furthermore, bucladesine significantly decreased the production of interleukin-6 pro-inflammatory mediator as well as nuclear factor-κB activation and reduced the mean number of apoptotic cells compared to cuprizone-treated mice. Bucladesine also decreased production of caspase-3 as well as Bax and increased Bcl-2 levels. Our data revealed that enhancement of intracellular cAMP prevents demyelination and plays anti-inflammatory and anti-apoptotic properties in mice cuprizone model of demyelination. This suggests the modulation of intracellular cAMP as a potential target for treatment of MS.

  6. Ethidium bromide-induced demyelination of the sciatic nerve of adult Wistar rats

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    Riet-Correa G.

    2002-01-01

    Full Text Available Peripheral nerve ultrastructure was assessed after single or multiple local injections of the intercalating dye ethidium bromide. Thirty-four adult Wistar rats of both sexes were divided into five groups and maintained in a controlled environment with rat chow and water ad libitum throughout the experiment. The experimental animals were injected with 1 µl of 0.1% ethidium bromide in 0.9% saline into the central third of the left sciatic nerve 1 (group 1, 2 (group 2, 4 (group 3, 6 (group 4 or 8 (group 5 times. In groups 2 to 5 the injections were made at 28-day intervals. Control animals received the same amount of 0.9% saline. The animals were killed at different times after injection: group 1 at 7 days (2 rats and 15 days (2 rats; for groups 2, 3, 4 and 5, all rats were killed 10 days after the last injection and the lesions were investigated by light and transmission electron microscopy. In the acute lesions, intoxicated Schwann cells showed a vacuolated cytoplasm and separation of the sheaths from the axon. Myelin sheaths underwent progressive vesiculation and subsequent segmental demyelination. Myelin debris were withdrawn by macrophages and remyelination by Schwann cells was prominent. With the increase in the number of injections collagen fibers also increased in number and progressively enveloped smaller numbers of remyelinated axons composing new fascicles. Wallerian degeneration of fibers apparently not affected by ethidium bromide was more intense in the nerves from groups 4 and 5. The peripheral nerve repairs itself after demyelinating challenges with a profusion of collagen fibers and new fasciculations. This experimental model is valid to mimic recurrent demyelinating neuropathies.

  7. Multifocal acquired demyelinating sensory and motor neuropathy presenting as a peripheral nerve tumor.

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    Allen, David C; Smallman, Clare A; Mills, Kerry R

    2006-09-01

    A man with multifocal acquired demyelinating sensory and motor neuropathy (MADSAM), or Lewis-Sumner syndrome, presented with a progressive left lumbosacral plexus lesion resembling a neurofibroma. After 7 years he developed a left ulnar nerve lesion with conduction block in its upper segment. Treatment with intravenous immunoglobulin improved the symptoms and signs of both lesions. We conclude that inflammatory neuropathy must be considered in the differential diagnosis of peripheral nerve tumors, and that unifocal lesions may precede multifocal involvement in MADSAM by several years. In addition, we discuss the clinical features in 9 patients attending a specialist peripheral nerve clinic and review the literature.

  8. Viral exposures and MS outcome in a prospective cohort of children with acquired demyelination.

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    Makhani, Naila; Banwell, Brenda; Tellier, Raymond; Yea, Carmen; McGovern, Suzanne; O'Mahony, Julia; Ahorro, Jean M; Arnold, Douglas; Sadovnick, A Dessa; Marrie, Ruth A; Bar-Or, Amit

    2016-03-01

    Epstein-Barr virus (EBV) infection is associated with increased multiple sclerosis (MS) risk. Recently, cytomegalovirus (CMV) infection has been proposed as a protective factor against MS development. We determined EBV, herpes simplex virus, varicella-zoster virus and CMV seroprevalence in 247 prospectively followed children with acquired demyelinating syndromes (ADS). Remote EBV infection was more common in children with MS than those with monophasic ADS while CMV infection was more common in children with monophasic ADS. Children displaying evidence of remote EBV without CMV infection were at highest risk of subsequent MS diagnosis. Viral infection repertoire detected at ADS provides important prognostic information.

  9. Central canal ependymal cells proliferate extensively in response to traumatic spinal cord injury but not demyelinating lesions.

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    Lacroix, Steve; Hamilton, Laura K; Vaugeois, Alexandre; Beaudoin, Stéfanny; Breault-Dugas, Christian; Pineau, Isabelle; Lévesque, Sébastien A; Grégoire, Catherine-Alexandra; Fernandes, Karl J L

    2014-01-01

    The adult mammalian spinal cord has limited regenerative capacity in settings such as spinal cord injury (SCI) and multiple sclerosis (MS). Recent studies have revealed that ependymal cells lining the central canal possess latent neural stem cell potential, undergoing proliferation and multi-lineage differentiation following experimental SCI. To determine whether reactive ependymal cells are a realistic endogenous cell population to target in order to promote spinal cord repair, we assessed the spatiotemporal dynamics of ependymal cell proliferation for up to 35 days in three models of spinal pathologies: contusion SCI using the Infinite Horizon impactor, focal demyelination by intraspinal injection of lysophosphatidylcholine (LPC), and autoimmune-mediated multi-focal demyelination using the active experimental autoimmune encephalomyelitis (EAE) model of MS. Contusion SCI at the T9-10 thoracic level stimulated a robust, long-lasting and long-distance wave of ependymal proliferation that peaked at 3 days in the lesion segment, 14 days in the rostral segment, and was still detectable at the cervical level, where it peaked at 21 days. This proliferative wave was suppressed distal to the contusion. Unlike SCI, neither chemical- nor autoimmune-mediated demyelination triggered ependymal cell proliferation at any time point, despite the occurrence of demyelination (LPC and EAE), remyelination (LPC) and significant locomotor defects (EAE). Thus, traumatic SCI induces widespread and enduring activation of reactive ependymal cells, identifying them as a robust cell population to target for therapeutic manipulation after contusion; conversely, neither demyelination, remyelination nor autoimmunity appears sufficient to trigger proliferation of quiescent ependymal cells in models of MS-like demyelinating diseases.

  10. Central canal ependymal cells proliferate extensively in response to traumatic spinal cord injury but not demyelinating lesions.

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    Steve Lacroix

    Full Text Available The adult mammalian spinal cord has limited regenerative capacity in settings such as spinal cord injury (SCI and multiple sclerosis (MS. Recent studies have revealed that ependymal cells lining the central canal possess latent neural stem cell potential, undergoing proliferation and multi-lineage differentiation following experimental SCI. To determine whether reactive ependymal cells are a realistic endogenous cell population to target in order to promote spinal cord repair, we assessed the spatiotemporal dynamics of ependymal cell proliferation for up to 35 days in three models of spinal pathologies: contusion SCI using the Infinite Horizon impactor, focal demyelination by intraspinal injection of lysophosphatidylcholine (LPC, and autoimmune-mediated multi-focal demyelination using the active experimental autoimmune encephalomyelitis (EAE model of MS. Contusion SCI at the T9-10 thoracic level stimulated a robust, long-lasting and long-distance wave of ependymal proliferation that peaked at 3 days in the lesion segment, 14 days in the rostral segment, and was still detectable at the cervical level, where it peaked at 21 days. This proliferative wave was suppressed distal to the contusion. Unlike SCI, neither chemical- nor autoimmune-mediated demyelination triggered ependymal cell proliferation at any time point, despite the occurrence of demyelination (LPC and EAE, remyelination (LPC and significant locomotor defects (EAE. Thus, traumatic SCI induces widespread and enduring activation of reactive ependymal cells, identifying them as a robust cell population to target for therapeutic manipulation after contusion; conversely, neither demyelination, remyelination nor autoimmunity appears sufficient to trigger proliferation of quiescent ependymal cells in models of MS-like demyelinating diseases.

  11. Post-mortem MRI-guided sampling of multiple sclerosis brain lesions: increased yield of active demyelinating and (p)reactive lesions.

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    De Groot, C J; Bergers, E; Kamphorst, W; Ravid, R; Polman, C H; Barkhof, F; van der Valk, P

    2001-08-01

    Macroscopic sampling of multiple sclerosis lesions in the brain tends to find chronic lesions. For a better understanding of the dynamics of the multiple sclerosis disease process, research into new and developing lesions is of great interest. As MRI in vivo effectively demonstrates lesions in multiple sclerosis patients, we have applied it to unfixed post-mortem brain slices to identify abnormalities, in order to obtain a higher yield of active lesions. The Netherlands Brain Bank organized the rapid autopsy of 29 multiple sclerosis patients. The brain was cut in 1 cm coronal slices. One or two slices were subjected to T(1)- and T(2)-weighted MRI, and then cut at the plane of the MRI scan into 5 mm thick opposing sections. Areas of interest were identified based on the MRI findings and excised. One half was fixed in 10% formalin and paraffin-embedded, and the corresponding area in the adjacent half was snap-frozen in liquid nitrogen. In total, 136 out of 174 brain tissue samples could be matched with the abnormalities seen on T(2)-weighted MRIs. The stage of lesional development was determined (immuno) histochemically. For 54 MRI-detectable samples, it was recorded whether they were macroscopically detectable, i.e. visible and/or palpable. Histopathological analysis revealed that 48% of the hyperintense areas seen on T(2)-weighted images represented active lesions, including lesions localized in the normal appearing white matter, without apparent loss of myelin but nevertheless showing a variable degree of oedema, small clusters of microglial cells with enhanced major histocompatibility complex class II antigen, CD45 and CD68 antigen expression and a variable number of perivascular lymphocytes around small blood vessels [designated as (p)reactive lesions]. From the macroscopically not-visible/not-palpable MRI-detected abnormalities, 58% were (p)reactive lesions and 21% contained active demyelinating lesions. In contrast, visible and/or palpable brain tissue samples

  12. Cuprizone inhibits demyelinating leukomyelitis by reducing immune responses without virus exacerbation in an infectious model of multiple sclerosis.

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    Herder, Vanessa; Hansmann, Florian; Stangel, Martin; Schaudien, Dirk; Rohn, Karl; Baumgärtner, Wolfgang; Beineke, Andreas

    2012-03-01

    Multiple sclerosis is one of the most common demyelinating central nervous system diseases in young adults. Theiler's murine encephalomyelitis (TME) is a widely used virus-induced murine model for human myelin disorders. Immunosuppressive approaches generally reduce antiviral immunity and therefore increase virus dissemination with clinical worsening. In the present study, the progressive course of TME was significantly delayed due to a five-week cuprizone feeding period. Cuprizone was able to minimize demyelinating leukomyelitis without virus exacerbation. This phenomenon is supposed to be a consequence of selective inhibition of detrimental inflammatory responses with maintained protective immunity against the virus.

  13. Direct profiling of myelinated and demyelinated regions in mouse brain by imaging mass spectrometry

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    Ceuppens, Ruben; Dumont, Debora; van Brussel, Leen; van de Plas, Babs; Daniels, Ruth; Noben, Jean-Paul; Verhaert, Peter; van der Gucht, Estel; Robben, Johan; Clerens, Stefan; Arckens, Lutgarde

    2007-02-01

    One of the newly developed imaging mass spectrometry (IMS) technologies utilizes matrix-assisted laser desorption/ionization (MALDI) mass spectrometry to map proteins in thin tissue sections. In this study, we evaluated the power of MALDI IMS as we developed it in our (Bruker) MALDI TOF (Reflex IV) and TOF-TOF (Ultraflex II) systems to study myelin patterns in the mouse central nervous system under normal and pathological conditions. MALDI IMS was applied to assess myelin basic protein (MBP) isoform-specific profiles in different regions throughout the mouse brain. The distribution of ions of m/z 14,144 and 18,447 displayed a striking resemblance with white matter histology and were identified as MBP isoform 8 and 5, respectively. In addition, we demonstrated a significant reduction of the MBP-8 peak intensity upon MALDI IMS analysis of focal ethidium bromide-induced demyelinated brain areas. Our MS images were validated by immunohistochemistry using MBP antibodies. This study underscores the potential of MALDI IMS to study the contribution of MBP to demyelinating diseases.

  14. Inflammatory Demyelinating Central Nervous System Diseases in Childhood: Clinical and Paraclinical Profiles in 133 Patients

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    Derya Kaya

    2012-01-01

    Full Text Available In a retrospective review of patients with acquired demyelinating disorders of the central nervous system, 133 patients (5.6% whose diseases started in childhood, were selected from 2369 patients, who had medical records in the Neurology Department of Dokuz Eylul University. Out of 133, 98 had relapsing remitting multiple sclerosis, 21 had secondary progressive multiple sclerosis, 8 had clinically isolated syndrome, 3 had neuromyelitis optica, 2 had Marburg disease, and 1 had radiologically isolated syndrome. In 55 patients (41.3%, disease onset was before age 16. Polysymptomatic presentation (22.6% was the most common initial feature. The EDSS scores ranged from 0 to 9 with a median of 2.0 ( for 126 patients. MRI records of 111 patients were obtained. 97 patients had clinically definite multiple sclerosis. 11 MS patients (11.3% did not initially present the diagnostic MRI features. All of the remaining multiple sclerosis patients fulfilled Barkhof-Tintore criteria (100% and 88.7% fulfilled KIDMUS criteria. Cranial MRI of NMO patients was normal. Our findings demonstrate some important clinical and paraclinical features that can help the literature on acquired demyelinating disorders of childhood by utilizing data from Western Turkey.

  15. Paracaspase MALT1 deficiency protects mice from autoimmune-mediated demyelination.

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    Mc Guire, Conor; Wieghofer, Peter; Elton, Lynn; Muylaert, David; Prinz, Marco; Beyaert, Rudi; van Loo, Geert

    2013-03-15

    The paracaspase MALT 1 is a major player in lymphocyte activation and proliferation. MALT1 mediates Ag-induced signaling to the transcription factor NF-κB by functioning both as a scaffold protein and cysteine protease. We studied the role of MALT1 in the development of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. MALT1-knockout mice did not develop any clinical symptoms of EAE. In addition, lymphocyte and macrophage infiltration into the spinal cord was absent in MALT1-knockout mice, as were demyelination and proinflammatory gene expression. Adoptive transfer experiments showed that MALT1 deficiency in splenocytes is sufficient for EAE resistance. Moreover, autoreactive T cell activation was severely impaired in MALT1-deficient T cells, suggesting the inability of MALT1-deficient effector T cells to induce demyelinating inflammation in the CNS. Finally, the MALT1 substrates A20 and CYLD were completely processed in wild-type T cells during EAE, which was partially impaired in MALT1-deficient T cells, suggesting a contribution of MALT1 proteolytic activity in T cell activation and EAE development. Together, our data indicate that MALT1 may be an interesting therapeutic target in the treatment of multiple sclerosis.

  16. Models of autoimmune demyelination in the central nervous system: on the way to translational medicine

    Directory of Open Access Journals (Sweden)

    Linker Ralf A

    2009-10-01

    Full Text Available Abstract Multiple sclerosis (MS is the most common neurologic disease of young adults. In the recent years, our understanding on disease pathomechanisms has considerably improved and new therapies have emerged. Yet a cure for this devastating disorder is still a far cry away and human resources on ex vivo specimens are limited. More than 70 years after its first description, experimental autoimmune encephalomyelitis (EAE remains an important tool to understand concepts of T cell mediated autoimmunity as well as the roles of the innate and the humoral immune systems. Some EAE models also well reflect mechanisms of tissue damage including demyelination, axonal injury and also cortical changes. A limitation of the classical EAE model is a neglect of CD8 T cell mediated immune mechanisms. Moreover, well characterized models for primary progressive MS or demyelination patterns involving primary oligodendrocyte dystrophy are still not available. Yet many current therapeutic concepts including glatiramer acetate or natalizumab stem from their successful first application in EAE models. New strategies include the widespread use of conditional knockout mice to understand the cell-type specific function of single genes, innovative approaches to establish models on the roles of B cells and CD8 T cells as well as on the relation of inflammation to primary degeneration. In summary, EAE models continue to play an important role in neuroimmunology thereby also stimulating research in other fields of the neurosciences and immunobiology.

  17. Focal Hand Dystonia as a Sign of Demyelinating Attack in Multipl Sclerosis: 'Report of Three Cases’

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    Özge Öcek

    2014-12-01

    Full Text Available Although it is known that dystonia is a basal ganglia disease, dystonic symptoms have been observed in association with lesions of various sites located in sensory and motor pathways. We report three cases of paroxysmal focal hand dystonia, which may be due to the damage of the somatosensorial pathways in the cervical spinal cord. We suggest that the dystonia in our patients may be related to these active demyelinating cervical plaques. Two female and one male patients with definite relapsing remitting MS between the ages of 22 to 45 were admitted with serious disability while using their right hands. In all three cases abnormal posture in the right hand and involuntary sustained contractions together with minor choreiform movements of the fingers were observed. Cervical MRI showed contrast-enhancing demyelinating lesions at the level of C2-3 in all. In one of the patient’s cranial MRI revealed also two new contrast-enhancing plaques on the neighbourhood of right posterior lateral ventricle and parietal cortex. No new or enhancing lesion was detected in the basal ganglia; indicating that the cervical spinal cord lesions were responsible for hand dystonia. In one of the patients, the right median SEP response was absent in accordance with the clinical symptom. All three patients were treated with 1 gram intravenous methylprednisolone a day for 5-10 days. Approximately one month later clinical symptoms have been completely disappeared and control cervical MRI revealed resolution of the active lesions in all.

  18. Physiological Dynamics in Demyelinating Diseases: Unraveling Complex Relationships through Computer Modeling

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    Jay S. Coggan

    2015-09-01

    Full Text Available Despite intense research, few treatments are available for most neurological disorders. Demyelinating diseases are no exception. This is perhaps not surprising considering the multifactorial nature of these diseases, which involve complex interactions between immune system cells, glia and neurons. In the case of multiple sclerosis, for example, there is no unanimity among researchers about the cause or even which system or cell type could be ground zero. This situation precludes the development and strategic application of mechanism-based therapies. We will discuss how computational modeling applied to questions at different biological levels can help link together disparate observations and decipher complex mechanisms whose solutions are not amenable to simple reductionism. By making testable predictions and revealing critical gaps in existing knowledge, such models can help direct research and will provide a rigorous framework in which to integrate new data as they are collected. Nowadays, there is no shortage of data; the challenge is to make sense of it all. In that respect, computational modeling is an invaluable tool that could, ultimately, transform how we understand, diagnose, and treat demyelinating diseases.

  19. The Protective Effects of Areca catechu Extract on Cognition and Social Interaction Deficits in a Cuprizone-Induced Demyelination Model

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    Abulimiti Adilijiang

    2015-01-01

    Full Text Available Schizophrenia is a serious psychiatric illness with an unclear cause. One theory is that demyelination of white matter is one of the main pathological factors involved in the development of schizophrenia. The current study evaluated the protective effects of Areca catechu nut extract (ANE on a cuprizone-induced demyelination mouse model. Two doses of ANE (1% and 2% were administered orally in the diet for 8 weeks. Animals subjected to demyelination showed impaired spatial memory and less social activity. In addition, mice subjected to demyelination displayed significant myelin damage in cortex and demonstrated a higher expression of NG2 and PDGFRα and AMPK activation. ANE treatment not only significantly enhanced cognitive ability and social activity, but also protected myelin against cuprizone toxicity by promoting oligodendrocyte precursor cell (OPC differentiation. In addition, ANE treatment demonstrated significant dephosphorylation of AMPKα, indicating a regulatory role for ANE in schizophrenia. This study showed that ANE treatment may enhance cognitive ability and social activity by facilitating OPC differentiation and protecting against myelin damage in cortex. Results also suggest the AMPK signaling pathway may be involved in this process.

  20. Consensus Statement on medication use in multiple sclerosis by the Spanish Society of Neurology's study group for demyelinating diseases.

    Science.gov (United States)

    García-Merino, A; Fernández, O; Montalbán, X; de Andrés, C; Oreja-Guevara, C; Rodríguez-Antigüedad, A; Arbizu, T

    2013-01-01

    Treatments for multiple sclerosis therapy are rapidly evolving. It is believed that new drugs will be approved in the near future, thereby changing current indications for treatment. In this context, the Spanish Society of Neurology's study group on demyelinating diseases, which evaluates medication use in MS, has decided to draw up a consensus statement on the current indications and guidelines for multiple sclerosis treatment.

  1. Protracted, relapsing and demyelinating experimental autoimmune encephalomyelitis in DA rats immunized with syngeneic spinal cord and incomplete Freund's adjuvant

    DEFF Research Database (Denmark)

    Lorentzen, J C; Issazadeh-Navikas, Shohreh; Storch, M;

    1995-01-01

    , protracted and relapsing EAE (SPR-EAE) after a subcutaneous immunization at the tail base with syngeneic spinal cord and incomplete Freund's adjuvant (IFA). The neurological deficits were accompanied by demyelinating inflammatory lesions in the spinal cord, with infiltrating T lymphocytes and perivascular...

  2. Acute paretic syndrome in juvenile White Leghorn chickens resembles late stages of acute inflammatory demyelinating polyneuropathies in humans

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    Preisinger Rudolf

    2010-01-01

    Full Text Available Abstract Background Sudden limb paresis is a common problem in White Leghorn flocks, affecting about 1% of the chicken population before achievement of sexual maturity. Previously, a similar clinical syndrome has been reported as being caused by inflammatory demyelination of peripheral nerve fibres. Here, we investigated in detail the immunopathology of this paretic syndrome and its possible resemblance to human neuropathies. Methods Neurologically affected chickens and control animals from one single flock underwent clinical and neuropathological examination. Peripheral nervous system (PNS alterations were characterised using standard morphological techniques, including nerve fibre teasing and transmission electron microscopy. Infiltrating cells were phenotyped immunohistologically and quantified by flow cytometry. The cytokine expression pattern was assessed by quantitative real-time PCR (qRT-PCR. These investigations were accomplished by MHC genotyping and a PCR screen for Marek's disease virus (MDV. Results Spontaneous paresis of White Leghorns is caused by cell-mediated, inflammatory demyelination affecting multiple cranial and spinal nerves and nerve roots with a proximodistal tapering. Clinical manifestation coincides with the employment of humoral immune mechanisms, enrolling plasma cell recruitment, deposition of myelin-bound IgG and antibody-dependent macrophageal myelin-stripping. Disease development was significantly linked to a 539 bp microsatellite in MHC locus LEI0258. An aetiological role for MDV was excluded. Conclusions The paretic phase of avian inflammatory demyelinating polyradiculoneuritis immunobiologically resembles the late-acute disease stages of human acute inflammatory demyelinating polyneuropathy, and is characterised by a Th1-to-Th2 shift.

  3. Antibody-Mediated Rejection of the Heart in the Setting of Autoimmune Demyelinating Polyneuropathy: A Case Report and Review of the Literature

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    Kathryn J. Lindley

    2012-01-01

    Full Text Available Background. Antibody-mediated rejection (AMR is caused by the production of donor-specific antibodies (DSA which lead to allograft injury in part via complement activation. The inflammatory demyelinating polyneuropathies (IDP are inflammatory disorders of the nervous system, involving both cellular and humoral immune mechanisms directed against myelin. Case Report. A 58-year-old man five years after heart transplant presented with progressive dyspnea, imbalance, dysphagia, and weakness. Nerve conduction studies and electromyogram were consistent with IDP. Plasmapheresis and high-dose steroids resulted in improvement in neurologic symptoms. Within two weeks, he was readmitted with anasarca and acute renal failure, requiring intravenous furosemide and inotropic support. Echocardiogram and right heart catheterization revealed reduced cardiac function and elevated filling pressures. DSA was positive against HLA DR53, and endomyocardial biopsy revealed grade 1R chronic inflammation, with strong capillary endothelial immunostaining for C4d. Plasmapheresis and intravenous immunoglobulin (IVIG were initiated. His anasarca and renal failure subsequently resolved, echocardiogram showed improved function off inotropes, and anti-DR53 MFI was reduced by 57%. Conclusions. This is an example of a single immune-mediated process causing concurrent IDP and AMR. The improvement in cardiac function and neurologic symptoms with plasmapheresis, IVIG, and high-dose steroids argues for a unifying antibody-mediated mechanism.

  4. Propentofylline treatment on open field behavior in rats with focal ethidium bromide-induced demyelination in the ventral surface of the brainstem.

    Science.gov (United States)

    Martins-Júnior, J L; Bernardi, M M; Bondan, E F

    2016-03-01

    Propentofylline (PPF) is a xanthine derivative with pharmacological effects that are distinct from those of classic methylxanthines. It depresses the activation of microglial cells and astrocytes, which is associated with neuronal damage during neural inflammation and hypoxia. Our previous studies showed that PPF improved remyelination following gliotoxic lesions that were induced by ethidium bromide (EB). In the present study, the long-term effects of PPF on open field behavior in rats with EB-induced focal demyelination were examined. The effects of PPF were first evaluated in naive rats that were not subjected to EB lesions. Behavior in the beam walking test was also evaluated during chronic PPF treatment because impairments in motor coordination can interfere with behavior in the open field. The results showed that PPF treatment in unlesioned rats decreased general activity and caused motor impairment in the beam walking test. Gliotoxic EB injections increased general activity in rats that were treated with PPF compared with rats that received saline solution. Motor incoordination was also attenuated in PPF-treated rats. These results indicate that PPF reversed the effects of EB lesions on behavior in the open field and beam walking test.

  5. Neurotrophic ACTH4-9 analogue therapy normalizes electroencephalographic alterations in chronic experimental allergic encephalomyelitis

    OpenAIRE

    Gispen, W. H.; Duckers, H.J.; van Dokkum, R.P.; Verhaagen, J; Luijtelaar, E.L.; Coenen, A.M.; Lopes da Silva, F.H.

    1998-01-01

    Chronic experimental allergic encephalomyelitis (CEAE) is an established experimental model for multiple sclerosis (MS). The demyelinating lesions in the white matter of the central nervous system observed in CEAE and in MS are accompanied by various neurophysiological alterations. Among the best defined electrophysiological abnormalities are the changes in event-related potentials, in particular evoked potentials involving the spinal cord, i.e. motor and sensory evoked potentials. Less famil...

  6. Spatial and temporal profiles of growth factor expression during CNS demyelination reveal the dynamics of repair priming.

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    Viktoria Gudi

    Full Text Available Demyelination is the cause of disability in various neurological disorders. It is therefore crucial to understand the molecular regulation of oligodendrocytes, the myelin forming cells in the CNS. Growth factors are known to be essential for the development and maintenance of oligodendrocytes and are involved in the regulation of glial responses in various pathological conditions. We employed the well established murine cuprizone model of toxic demyelination to analyze the expression of 13 growth factors in the CNS during de- and remyelination. The temporal mRNA expression profile during demyelination and the subsequent remyelination were analyzed separately in the corpus callosum and cerebral cortex using laser microdissection and real-time PCR techniques. During demyelination a similar pattern of growth factor mRNA expression was observed in both areas with a strong up-regulation of NRG1 and GDNF and a slight increase of CNTF in the first week of cuprizone treatment. HGF, FGF-2, LIF, IGF-I, and TGF-ß1 were up-regulated mainly during peak demyelination. In contrast, during remyelination there were regional differences in growth factor mRNA expression levels. GDNF, CNTF, HGF, FGF-2, and BDNF were elevated in the corpus callosum but not in the cortex, suggesting tissue differences in the molecular regulation of remyelination in the white and grey matter. To clarify the cellular source we isolated microglia from the cuprizone lesions. GDNF, IGF-1, and FGF mRNA were detected in the microglial fraction with a temporal pattern corresponding to that from whole tissue PCR. In addition, immunohistochemical analysis revealed IGF-1 protein expression also in the reactive astrocytes. CNTF was located in astrocytes. This study identified seven different temporal expression patterns for growth factors in white and grey matter and demonstrated the importance of early tissue priming and exact orchestration of different steps during callosal and cortical de

  7. Digesting the emerging role for the gut microbiome in central nervous system demyelination.

    Science.gov (United States)

    Joscelyn, Jennifer; Kasper, Lloyd H

    2014-10-01

    The fields of microbiology, immunology, neurology and nutrition are rapidly converging, as advanced sequencing and genomics-based methodologies have enabled the mapping out of the microbial diversity of humans for the first time. Bugs, guts, brains and behavior were once believed to be separate domains of clinical practice and research; however, recent observations in our understanding of the microbiome indicate that the boundaries between domains are becoming permeable. This permeability is multidirectional: Biological systems are operating simultaneously in a vastly complex and interconnected web. Understanding the microbiome-gut-brain axis will entail fleshing out the mechanisms by which transduction across each domain occurs, allowing us ultimately to appreciate the role of commensal organisms in shaping and modulating host immunity. This article will highlight animal and human research to date, as well as highlight directions for future research. We speculate that the gut microbiome is potentially the premier environmental risk factor mediating inflammatory central nervous system demyelination, in particular multiple sclerosis.

  8. Isolated extra pontine myelinolysis – a rare imaging appearance of osmotic demyelination syndrome

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    D. Rajitha

    2014-01-01

    Full Text Available Rapid correction of hyponatraemia leads to serious neurological complications, like osmotic demyelination syndrome (ODS. In ODS, magnetic resonance imaging (MRI often reveals features of pontine myelinolysis, that may occur in isolation or may, sometimes be associated with extrapontine myelinolysis. Isolated extrapontine myelinolysis is rare. We report the case of a 53-year-old lady brought to the emergency service with vomitings, and altered sensorium. She was found to have profound hyponatraemia (serum sodium 110 meq/L. Correction of hyponatremia was done with slow intravenous infusion of 3% sodium chloride. However, inadvertant, concomitant oral administration of salt led to overcorrection with serum sodium going upto 150 meq/L. She developed quadriplegia, depressed level of consciousness and respiratory failure and required ventilatory support. MRI brain showed features of isolated extrapontine myelinolysis.

  9. Charcot-Marie-Tooth disease masquerading as acute demyelinating encephalomyelitis-like illness.

    Science.gov (United States)

    Kim, Gun-Ha; Kim, Kyoung Min; Suh, Sang-Il; Ki, Chang-Seok; Eun, Baik-Lin

    2014-07-01

    X-linked Charcot-Marie-Tooth disease (CMTX1) is a clinically heterogeneous hereditary motor and sensory neuropathy with X-linked transmission. Common clinical manifestations of CMTX1 disease, as in other forms of Charcot-Marie-Tooth (CMT) disease, are distal muscle wasting and weakness, hyporeflexia, distal sensory disturbance, and foot deformities. Mutations in the connexin-32 gene (gap junction protein β1 [GJB1]) are responsible for CMTX1 disease. In this report, we describe a patient with CMTX1 disease presenting with recurrent attacks of transient and episodic acute demyelinating encephalomyelitis (ADEM)-like symptoms without previous signs of lower extremity weakness or foot deformities; the patient, as well as his asymptomatic mother, exhibited a novel GJB1 mutation (p.Met1Ile). Differential diagnosis of recurrent and transient ADEM-like illness, if unexplained, should include the possibility of CMTX1 disease.

  10. Comparison of electrophysiological findings in axonal and demyelinating Guillain-Barre syndrome.

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    Samira Yadegari

    2014-09-01

    Full Text Available Incidence and predominant subtype of Guillain-Barre syndrome (GBS differs geographically. Electrophysiology has an important role in early diagnosis and prediction of prognosis. This study is conducted to determine the frequent subtype of GBS in a large group of patients in Iran and compare nerve conduction studies in axonal and demyelinating forms of GBS.We retrospectively evaluated the medical records and electrodiagnostic study (EDS of 121 GBS patients who were managed in our hospital during 11 years. After regarding the exclusion criteria, patients classified as three groups: acute inflammatory demyelinating polyneuropathy (AIDP, acute motor axonal neuropathy (AMAN, and acute motor sensory axonal neuropathy (AMSAN. The most frequent subtype and then electrophysiological characteristic based on the time of EDS and their cerebrospinal fluid (CSF profile were assessed.Among 70 patients finally included in the study, 67% were men. About 63%, 23%, and 14% had AIDP, AMAN, and AMSAN, respectively. AIDP patients represented a wider range of ages compared with other groups. Higher levels of CSF protein, abnormal late responses and sural sparing were more frequent in AIDP subtype. Five AMSAN patients also revealed sural sparing. Conduction block (CB was observed in one AMAN patient. Prolonged F-wave latency was observed only in AIDP cases. CB and inexcitable sensory nerves were more frequent after 2 weeks, but reduced F-wave persistency was more prominent in the early phase.AIDP was the most frequent subtype. Although the electrophysiology and CSF are important diagnostic tools, classification should not be made based on a distinct finding.

  11. Brain-derived neurotrophic factor deficiency restricts proliferation of oligodendrocyte progenitors following cuprizone-induced demyelination.

    Science.gov (United States)

    Tsiperson, Vladislav; Huang, Yangyang; Bagayogo, Issa; Song, Yeri; VonDran, Melissa W; DiCicco-Bloom, Emanuel; Dreyfus, Cheryl F

    2015-01-01

    Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors that through its neurotrophic tyrosine kinase, receptor, type 2 (TrkB) receptor, increases 5-bromo-2-deoxyuridine incorporation in oligodendrocyte progenitor cells (OPCs) in culture. Roles in vivo are less well understood; however, increases in numbers of OPCs are restricted in BDNF+/- mice following cuprizone-elicited demyelination. Here, we investigate whether these blunted increases in OPCs are associated with changes in proliferation. BDNF+/+ and BDNF+/- mice were fed cuprizone-containing or control feed. To assess effects on OPC numbers, platelet-derived growth factor receptor alpha (PDGFRα)+ or NG2+ cells were counted. To monitor DNA synthesis, 5-ethynyl-2'-deoxyuridine (EdU) was injected intraperitoneally and colocalized with PDGFRα+ cells. Alternatively, proliferating cell nuclear antigen (PCNA) was colocalized with PDGFRα or NG2. Labeling indices were determined in the BDNF+/+ and BDNF+/- animals. After 4 or 5 weeks of control feed, BDNF+/- mice exhibit similar numbers of OPCs compared with BDNF+/+ animals. The labeling indices for EdU and PCNA also were not significantly different, suggesting that neither the DNA synthesis phase (S phase) nor the proliferative pool size was different between genotypes. In contrast, when mice were challenged by cuprizone for 4 or 5 weeks, increases in OPCs observed in BDNF+/+ mice were reduced in the BDNF+/- mice. This difference in elevations in cell number was accompanied by decreases in EdU labeling and PCNA labeling without changes in cell death, indicating a reduction in the DNA synthesis and the proliferative pool. Therefore, levels of BDNF influence the proliferation of OPCs resulting from a demyelinating lesion.

  12. Acquired CNS Demyelinating Syndrome in Children Referred to Shiraz Pediatric Neurology Ward

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    Soroor INALOO*

    2014-04-01

    Full Text Available How to Cite This Article: Inaloo S, Haghbin S, Moradi M, Dashti H, Safari N. Acquired CNS Demyelinating Syndrome in Children Referred to Shiraz Pediatric Neurology Ward. Iran J Child Neurol. 2014 Spring; 8(2:18-23.ObjectiveIncidence of CNS acquired demyelinating syndrome (ADS, especially multiple sclerosis (MS in children, appears to be on the rise worldwide. The objective of this study was to determine prevalence, clinical presentation, neuroimagingfeatures, and prognosis of different types of ADS in Iranian children.Materials & MethodsDuring the period 2002-2012, all the patients (aged 1-18 years with ADS, such as MS, acute disseminated encephalomyelitis (ADEM, optic neurotic (ON, Devic disease, and transverse myelitis (TM, referred to the pediatric neurology ward, Nemazee Hospital, Shiraz University of Medical Sciences, were includedin this study. Demographic data, clinical signs and symptoms, past and family history, preclinical findings, clinical course, and outcome were obtained.ResultsWe identified 88 patients with ADS in our center. The most prevalent disease was MS with 36.5% (n=32, followed by AEDM 26.1% (n=31, ON 17% (n=13, TM 15.9% (n=14, and Devic disease 4.5% (n=4. MS, ON, TM were morecommon among females while ADEM was more common in males. Children with ADEM were significantly younger than those with other types of ADS.Family history was positive in 10% of patients with MS.Previous history of recent infection was considerably seen in cases with ADEM.Clinical presentation and prognosis in this study was in accordance with those in previous studies on children.ConclusionIn this study, the most common type of ADS was MS, which was more common in female and older age cases. ADEM was more common in male and younger children. ADEM and ON had the best and Devic disease had the worst prognosis.References1. Longer-Gould A, Zhaug JL, Chung J, Yeung Y, Wanbant E, Yao J. Incidence of acquired CNS demyelinating syndrome in a

  13. Chronic myelogenous leukemia (CML)

    Science.gov (United States)

    CML; Chronic myeloid leukemia; Chronic granulocytic leukemia; Leukemia - chronic granulocytic ... Chronic myelogenous leukemia is grouped into phases: Chronic Accelerated Blast crisis The chronic phase can last for ...

  14. Will PEDF Therapy Reverse Chronic Demyelination and Prevent Axon Loss in a Murine Model of Progressive Multiple Sclerosis

    Science.gov (United States)

    2015-12-01

    adult wild-type mice. I, J, Orthogonal images of EYFP /GFAP / Ki67 cell in the SVZ at 120 d post-TM, showing the presence of a fate-mapped mitotic ...the corpus callosum and mitotic labeling of SVZ progenitor cells that subse- quently migrated into the corpus callosum. In contrast, our long-term

  15. Demyelination as a Target for Cell-Based Therapy of Chronic Blast-Induced Traumatic Brain Injury

    Science.gov (United States)

    2014-10-01

    reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching...existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments...imaging and behavioral testing for a post-doctoral fellow – Sujith Sajja. He had also a chance to learn about exosomes , lipidomics and next generation

  16. Inherited demyelinating neuropathies with micromutations of peripheral myelin protein 22 gene.

    Science.gov (United States)

    Taioli, Federica; Cabrini, Ilaria; Cavallaro, Tiziana; Acler, Michele; Fabrizi, Gian Maria

    2011-02-01

    and three sporadic cases, detected mutations caused premature or delayed stop codons and were associated with hereditary neuropathy with liability to pressure palsies; the related pathological pictures ranged from classical tomaculous neuropathy to a mild demyelinating neuropathy with atypical non-tomaculous myelin thickenings. In a single family a c.179-2A> G mutation affecting the splice acceptor site of intron 2 cosegregated with a Charcot-Marie-Tooth disease type 1A-like syndrome and a peculiar pathological picture of demyelinating neuropathy without Charcot-Marie-Tooth disease type 1A-like classical onion bulbs or tomacula. Transcriptional analysis of a novel c.174_178 + 7delAAACGGTGAGGC deletion involving exon 2 and intron 2 demonstrated an unstable mutant transcript leading to a p.Asn59GlyfsX12 change; the mutation represented a null allele and caused a typical tomaculous hereditary neuropathy with liability to pressure palsies. The Charcot-Marie-Tooth disease type 1-like c.179-2A > G allele led to a stable transcript with an in-frame deletion of exon 3 (p.Glu60_Ala106del); the predicted shorter protein could exert variable molecular effects. In conclusion, micromutations of PMP22 cause a clinical and pathological continuum of demyelinating neuropathies that may include atypical phenotypes.

  17. Treatment with metallothionein prevents demyelination and axonal damage and increases oligodendrocyte precursors and tissue repair during experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Penkowa, Milena; Hidalgo, Juan

    2003-01-01

    )beta, neurotrophin-3 (NT-3), NT-4/5, and nerve growth factor (NGF). These beneficial effects of Zn-MT-II treatment could not be attributable to its zinc content per se. The present results support further the use of Zn-MT-II as a safe and successful therapy for multiple sclerosis.......Experimental autoimmune encephalomyelitis (EAE) is an animal model for the human demyelinating disease multiple sclerosis (MS). EAE and MS are characterized by significant inflammation, demyelination, neuroglial damage, and cell death. Metallothionein-I and -II (MT-I + II) are antiinflammatory...... and neuroprotective proteins that are expressed during EAE and MS. We have shown recently that exogenous administration of Zn-MT-II to Lewis rats with EAE significantly reduced clinical symptoms and the inflammatory response, oxidative stress, and apoptosis of the infiltrated central nervous system areas. We show...

  18. Methylcobalamin promotes the differentiation of Schwann cells and remyelination in lysophosphatidylcholine-induced demyelination of the rat sciatic nerve

    Directory of Open Access Journals (Sweden)

    Shunsuke eNishimoto

    2015-08-01

    Full Text Available Schwann cells (SCs are constituents of the peripheral nervous system. The differentiation of SCs in injured peripheral nerves is critical for regeneration after injury. Methylcobalamin (MeCbl is a vitamin B12 analog that is necessary for the maintenance of the peripheral nervous system. In this study, we estimated the effect of MeCbl on SCs. We showed that MeCbl downregulated the activity of Erk1/2 and promoted the expression of the myelin basic protein in SCs. In a dorsal root ganglion neuron–SC coculture system, myelination was promoted by MeCbl. In a focal demyelination rat model, MeCbl promoted remyelination and motor and sensory functional regeneration. MeCbl promoted the in vitro differentiation of SCs and in vivo myelination in a rat demyelination model and may be a novel therapy for several types of nervous disorders.

  19. Relapsing and Progressive Tumefactive Demyelinating Form of Central Nervous System Involvement in a Patient with Progressive Systemic Sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ho Kyun [Dept. of Radiology, Catholic University of Daegu School of Medicine, Daegu (Korea, Republic of); Lee, Hui Joong [Dept. of Kyungpook National University Hospital, Daegu (Korea, Republic of)

    2013-03-15

    White matter hyper intensities (WMHI) on MRI are not rare in patients with progressive systemic sclerosis (PSS). In this presentation, WMHI were developed in both middle cerebellar peduncles and temporal white matter in a patient with PSS, and regressed after medication of high dose steroid. However, new lesions were developed in the subcortices of both precentral gyri, and progressed rapidly to tumefactive hyperintensity on MRI. We report an unusual relapsing and progressive tumefactive demyelinating form of central nervous system involvement in PSS.

  20. Relationship between cerebrospinal fluid biomarkers for inflammation, demyelination and neurodegeneration in acute optic neuritis.

    Directory of Open Access Journals (Sweden)

    Signe Modvig

    Full Text Available BACKGROUND: Various inflammatory biomarkers show prognostic potential for multiple sclerosis (MS-risk after clinically isolated syndromes. However, biomarkers are often examined singly and their interrelation and precise aspects of their associated pathological processes remain unclear. Clarification of these relationships could aid the appropriate implementation of prognostic biomarkers in clinical practice. OBJECTIVE: To investigate the interrelation between biomarkers of inflammation, demyelination and neurodegeneration in acute optic neuritis and to assess their association to measures of MS risk. MATERIAL AND METHODS: A prospective study at a tertiary referral centre from June 2011 to December 2012 of 56 patients with optic neuritis as a first demyelinating symptom and 27 healthy volunteers. Lumbar puncture was performed within 28 (median 16 days of onset. CSF levels of CXCL13, matrix metalloproteinase (MMP-9, CXCL10, CCL-2, osteopontin and chitinase-3-like-1, myelin basic protein (MBP and neurofilament light-chain (NF-L were determined. MS-risk outcome measures were dissemination in space (DIS of white matter lesions on cerebral MRI, CSF oligoclonal bands and elevated IgG-index. RESULTS: IN THE INTERRELATION ANALYSIS THE BIOMARKERS SHOWED CLOSE CORRELATIONS WITHIN TWO DISTINCT GROUPS: Biomarkers of leukocyte infiltration (CXCL13, MMP-9 and CXCL10 were strongly associated (p<0.0001 for all. Osteopontin and chitinase-3-like-1 were also tightly associated (p<0.0001 and correlated strongly to tissue damage markers (NF-L and MBP. The biomarkers of leukocyte infiltration all associated strongly with MS-risk parameters, whereas CHI3L1 and MBP correlated with MRI DIS, but not with CSF MS-risk parameters and osteopontin and NF-L did not correlate with any MS-risk parameters. CONCLUSIONS: OUR FINDINGS SUGGEST TWO DISTINCT INFLAMMATORY PROCESSES: one of leukocyte infiltration, represented by CXCL13, CXCL10 and MMP-9, strongly associated with and

  1. Differentiation and quantification of inflammation, demyelination and axon injury or loss in multiple sclerosis

    Science.gov (United States)

    Wang, Yong; Sun, Peng; Wang, Qing; Trinkaus, Kathryn; Schmidt, Robert E.; Naismith, Robert T.; Song, Sheng-Kwei

    2015-01-01

    Axon injury/loss, demyelination and inflammation are the primary pathologies in multiple sclerosis lesions. Despite the prevailing notion that axon/neuron loss is the substrate of clinical progression of multiple sclerosis, the roles that these individual pathological processes play in multiple sclerosis progression remain to be defined. An imaging modality capable to effectively detect, differentiate and individually quantify axon injury/loss, demyelination and inflammation, would not only facilitate the understanding of the pathophysiology underlying multiple sclerosis progression, but also the assessment of treatments at the clinical trial and individual patient levels. In this report, the newly developed diffusion basis spectrum imaging was used to discriminate and quantify the underlying pathological components in multiple sclerosis white matter. Through the multiple-tensor modelling of diffusion weighted magnetic resonance imaging signals, diffusion basis spectrum imaging resolves inflammation-associated cellularity and vasogenic oedema in addition to accounting for partial volume effects resulting from cerebrospinal fluid contamination, and crossing fibres. Quantitative histological analysis of autopsied multiple sclerosis spinal cord specimens supported that diffusion basis spectrum imaging-determined cellularity, axon and myelin injury metrics closely correlated with those pathologies identified and quantified by conventional histological staining. We demonstrated in healthy control subjects that diffusion basis spectrum imaging rectified inaccurate assessments of diffusion properties of white matter tracts by diffusion tensor imaging in the presence of cerebrospinal fluid contamination and/or crossing fibres. In multiple sclerosis patients, we report that diffusion basis spectrum imaging quantitatively characterized the distinct pathologies underlying gadolinium-enhanced lesions, persistent black holes, non-enhanced lesions and non-black hole lesions, a

  2. Low Prevalence of Sleep Disorders in Demyelinating Disease in a Northern Tenerife Population

    Science.gov (United States)

    González-Platas, Montserrat; González-Platas, Javier; Bermúdez-Hernández, Moises; Pérez-Martín, Maria Yaiza; Croissier-Elías, Cristina; Pérez-Lorensu, Pedro Javier

    2016-01-01

    Study Objectives: Sleep disorders are seen in patients with demyelinating disease (DD) more often than in the general population. Combination of physical and psychological factors such as pain, spasms, nocturia, depression, anxiety, or medication effects could contribute to sleep disruption. Frequently, these disturbances have a major impact on health and quality of life of patients. The aim of this study was to estimate the prevalence of sleep disorders in patients seen in the DD consultation. Methods: 240 patients; mean age 43 years, 187 women; 163 patients with multiple sclerosis (MS): 144 relapsing-remitting, 19 progressive forms, 36 clinically isolated syndrome, 26 radiological isolated syndrome, and 15 patients with others DD. All participants completed questionnaires: Pittsburgh, Epworth, and Stanford scales, indirect symptoms of RLS and Obstructive Sleep Apnea, Fatigue Severity Scale, and Multiple Sclerosis Quality of Life-54. Results: Moderate/severe insomnia 12.5%, OSA 5.8%, RLS 9.6% (confirmed 3 cases), narcolepsy 0, fatigue (> 4) 24.6%. Physical QoL 66.6 ± 19.6, Mental QoL 66.1 ± 21.9. Patients with an established diagnosis showed higher scores on insomnia compared to the group of CIS and RIS (F = 3.85; p = 0.023), no differences were in the other parameters. Fatigue showed high correlation with insomnia (r = 0.443; p < 0.001), RLS (r = 0.513; p < 0.001), and sleepiness (r = 0.211; p = 0.001). None of the variables included in the regression model were shown to be predictors of Physical and Mental QoL. Conclusions: A high percentage of our sample sleeps well. Emphasize the low prevalence of sleep disorders (insomnia, fatigue, RLS, etc). We detected an overestimation in the RLS questionnaire and the low QoL recorded. Citation: González-Platas M, González-Platas J, Bermúdez-Hernández M, Pérez-Martín MY, Croissier-Elías C, Pérez-Lorensu PJ. Low prevalence of sleep disorders in demyelinating disease in a northern tenerife population. J Clin Sleep

  3. Differentiation and quantification of inflammation, demyelination and axon injury or loss in multiple sclerosis.

    Science.gov (United States)

    Wang, Yong; Sun, Peng; Wang, Qing; Trinkaus, Kathryn; Schmidt, Robert E; Naismith, Robert T; Cross, Anne H; Song, Sheng-Kwei

    2015-05-01

    Axon injury/loss, demyelination and inflammation are the primary pathologies in multiple sclerosis lesions. Despite the prevailing notion that axon/neuron loss is the substrate of clinical progression of multiple sclerosis, the roles that these individual pathological processes play in multiple sclerosis progression remain to be defined. An imaging modality capable to effectively detect, differentiate and individually quantify axon injury/loss, demyelination and inflammation, would not only facilitate the understanding of the pathophysiology underlying multiple sclerosis progression, but also the assessment of treatments at the clinical trial and individual patient levels. In this report, the newly developed diffusion basis spectrum imaging was used to discriminate and quantify the underlying pathological components in multiple sclerosis white matter. Through the multiple-tensor modelling of diffusion weighted magnetic resonance imaging signals, diffusion basis spectrum imaging resolves inflammation-associated cellularity and vasogenic oedema in addition to accounting for partial volume effects resulting from cerebrospinal fluid contamination, and crossing fibres. Quantitative histological analysis of autopsied multiple sclerosis spinal cord specimens supported that diffusion basis spectrum imaging-determined cellularity, axon and myelin injury metrics closely correlated with those pathologies identified and quantified by conventional histological staining. We demonstrated in healthy control subjects that diffusion basis spectrum imaging rectified inaccurate assessments of diffusion properties of white matter tracts by diffusion tensor imaging in the presence of cerebrospinal fluid contamination and/or crossing fibres. In multiple sclerosis patients, we report that diffusion basis spectrum imaging quantitatively characterized the distinct pathologies underlying gadolinium-enhanced lesions, persistent black holes, non-enhanced lesions and non-black hole lesions, a

  4. Clinical and radiological characteristics of 17 Chinese patients with pathology confirmed tumefactive demyelinating diseases: follow-up study.

    Science.gov (United States)

    Yao, Jiarui; Huang, Dehui; Gui, Qiuping; Chen, Xiaolei; Lou, Xin; Wu, Lei; Cheng, Chen; Li, Jie; Wu, Weiping

    2015-01-15

    Tumefactive demyelinating disease is a rare inflammatory demyelinating disease (IDD) of the central nervous system (CNS). The literature lacks a clear and consistent description of the clinical and radiological spectrum of this disorder, and few Chinese cases have been studied. Here we report 17 Chinese patients, with pathology confirmed CNS IDD, who had distinct clinical and imaging features from those in previous reports. Median age at onset was 47 years, with a female to male ratio of 1.1:1. Multifocal lesions were present in nine cases (53%) on their pre-biopsy magnetic resonance imagings (MRIs), with locations predominantly involving periventricular white matter (41%), subcortical white matter (41%), juxtacortical regions (41%), and cortical gray matter (35%). Moderate to severe perilesional edema and/or mass effect were present in 35% of cases. A variety of enhancement patterns were observed; most were heterogeneous, including ring-like, patchy, venular-like, nodular, punctate, and diffuse in a decreased frequency. Perilesional restriction on diffusion-weighted images (DWI) were evident in 70% cases. Clinical course prior to biopsy was a first neurological event in 82% cases. During a median follow-up of 4.1 years, 76% of cases remained as isolated demyelinating syndrome, and 70% experienced a total or near-total recovery regardless of whether they received immunotherapy. Further studies are needed, especially concerning series with pathological confirmation and long-term follow-up information.

  5. Administration of Chinpi, a Component of the Herbal Medicine Ninjin-Youei-To, Reverses Age-Induced Demyelination

    Directory of Open Access Journals (Sweden)

    Nanako Sato

    2011-01-01

    Full Text Available The disruption of myelin causes severe neurological diseases. An understanding of the mechanism of myelination and remyelination is essential for the development of therapeutic strategies for demyelination diseases. Our previous findings indicated that the FcRγ/Fyn cascade is a potential therapeutic target for remyelination caused by the Chinese/Japanese traditional herbal (Kampo medicine ninjin’youeito (Ninjin-youei-to, NYT, which is a hot-water extract made from 12 medicinal herbs. To identify which constituents of NYT are involved in the reversal of demyelination and to examine the potential therapeutic effect, we tested several of the chemical constituents of NYT. Here, we report that Chinpi, a constituent of NYT, upregulates the FcRγ/Fyn signaling cascade resulting in a potentially therapeutic effect against age-induced demyelination. In addition, we observed that phosphorylated (activated FcRγ/Fyn upregulated the expression of the 21.5 kDa isoform of myelin basic protein, inducing rapid morphological differentiation, when oligodendrocyte precursor cells (OPCs were cultured in the presence of hesperidin and/or narirutin (the major active constituents of Chinpi. These results suggest that hesperidin and narirutin participate in the FcRγ/Fyn signaling pathway in OPCs causing these cells to differentiate into myelinating oligodendrocytes.

  6. Imaging of demyelinating and neoplastic diseases of the spinal cord; Bildgebung bei demyelinisierenden und tumoroesen Erkrankungen des Rueckenmarks

    Energy Technology Data Exchange (ETDEWEB)

    Mueller-Mang, C. [Institut fuer CT und MRT Gaenserndorf, Gaenserndorf (Austria)

    2010-12-15

    The clinical symptoms of myelopathy are variable and non-specific. Demyelinating as well as neoplastic spinal cord diseases can cause paresthesia, progressive sensomotoric deficits and bowel and bladder dysfunction. Imaging of the spine, especially with magnetic resonance imaging (MRI), is an essential component in the diagnostic assessment of myelopathy and makes a substantial contribution to achieving the correct diagnosis. Although intramedullary neoplasms are far less common than demyelinating spinal cord diseases, radiologists should be familiar with the three most common entities, astrocytoma, ependymoma and hemangioblastoma, which represent over 70% of all spinal cord neoplasms. An early diagnosis and therapy is essential with neoplastic and demyelinating spinal cord diseases to hold residual neurological deficits as low as possible. (orig.) [German] Die klinische Symptomatik von Myelopathien ist aeusserst variabel und unspezifisch. Sowohl demyelinisierende als auch tumoroese Rueckenmarkerkrankungen koennen Paraesthesien, progrediente sensomotorische Ausfaelle und eine Sphinkterdysfunktion hervorrufen. Bildgebende Untersuchungen, und hier allen voran die MRT, sind ein unerlaesslicher Bestandteil zur Abklaerung von Myelopathien und tragen wesentlich zur korrekten Diagnose bei. Intramedullaere Tumoren sind zwar weitaus seltener als demyelinisierende Rueckenmarkerkrankungen, dennoch sollte der Radiologe mit den Bildmerkmalen der 3 haeufigsten Tumorarten, dem Astrozytom, Ependymom und Haemangioblastom vertraut sein, die ueber 70% aller Rueckenmarktumoren verursachen. Eine moeglichst fruehe Diagnostik und Therapie sind bei tumoroesen und demyelinisierenden Rueckenmarkerkrankungen essenziell, um bleibende neurologische Defizite moeglichst gering zu halten. (orig.)

  7. Inhibition of LINGO-1 promotes functional recovery after experimental spinal cord demyelination.

    Science.gov (United States)

    Zhang, Yongjie; Zhang, Yi Ping; Pepinsky, Blake; Huang, Guanrong; Shields, Lisa B E; Shields, Christopher B; Mi, Sha

    2015-04-01

    Blocking LINGO-1 has been shown to enhance remyelination in the rat lysolecithin-induced focal spinal cord demyelination model. We used transcranial magnetic motor-evoked potentials (tcMMEPs) to assess the effect of blocking LINGO-1 on recovery of axonal function in a mouse lysolecithin model at 1, 2 and 4weeks after injury. The role of LINGO-1 was assessed using LINGO-1 knockout (KO) mice and in wild-type mice after intraperitoneal administration of anti-LINGO-1 antagonist monoclonal antibody (mAb3B5). Response rates (at 2 and 4weeks) and amplitudes (at 4weeks) were significantly increased in LINGO-1 KO and mAb3B5-treated mice compared with matched controls. The latency of potentials at 4weeks was significantly shorter in mAb3B5-treated mice compared with controls. Lesion areas in LINGO-1 KO and mAb3B5-treated mice were reduced significantly compared with matched controls. The number of remyelinated axons within the lesions was increased and the G-ratios of the axons were decreased in both LINGO-1 KO and mAb3B5-treated mice compared with matched controls. These data provide morphometric and functional evidence of enhancement of remyelination associated with antagonism of LINGO-1.

  8. Effects of murine and human bone marrow-derived mesenchymal stem cells on cuprizone induced demyelination.

    Directory of Open Access Journals (Sweden)

    Jasmin Nessler

    Full Text Available For the treatment of patients with multiple sclerosis there are no regenerative approaches to enhance remyelination. Mesenchymal stem cells (MSC have been proposed to exert such regenerative functions. Intravenous administration of human MSC reduced the clinical severity of experimental autoimmune encephalomyelitis (EAE, an animal model mimicking some aspects of multiple sclerosis. However, it is not clear if this effect was achieved by systemic immunomodulation or if there is an active neuroregeneration in the central nervous system (CNS. In order to investigate remyelination and regeneration in the CNS we analysed the effects of intravenously and intranasally applied murine and human bone marrow-derived MSC on cuprizone induced demyelination, a toxic animal model which allows analysis of remyelination without the influence of the peripheral immune system. In contrast to EAE no effects of MSC on de- and remyelination and glial cell reactions were found. In addition, neither murine nor human MSC entered the lesions in the CNS in this toxic model. In conclusion, MSC are not directed into CNS lesions in the cuprizone model where the blood-brain-barrier is intact and thus cannot provide support for regenerative processes.

  9. Tissue plasminogen activator-mediated fibrinolysis protects against axonal degeneration and demyelination after sciatic nerve injury.

    Science.gov (United States)

    Akassoglou, K; Kombrinck, K W; Degen, J L; Strickland, S

    2000-05-29

    Tissue plasminogen activator (tPA) is a serine protease that converts plasminogen to plasmin and can trigger the degradation of extracellular matrix proteins. In the nervous system, under noninflammatory conditions, tPA contributes to excitotoxic neuronal death, probably through degradation of laminin. To evaluate the contribution of extracellular proteolysis in inflammatory neuronal degeneration, we performed sciatic nerve injury in mice. Proteolytic activity was increased in the nerve after injury, and this activity was primarily because of Schwann cell-produced tPA. To identify whether tPA release after nerve damage played a beneficial or deleterious role, we crushed the sciatic nerve of mice deficient for tPA. Axonal demyelination was exacerbated in the absence of tPA or plasminogen, indicating that tPA has a protective role in nerve injury, and that this protective effect is due to its proteolytic action on plasminogen. Axonal damage was correlated with increased fibrin(ogen) deposition, suggesting that this protein might play a role in neuronal injury. Consistent with this idea, the increased axonal degeneration phenotype in tPA- or plasminogen-deficient mice was ameliorated by genetic or pharmacological depletion of fibrinogen, identifying fibrin as the plasmin substrate in the nervous system under inflammatory axonal damage. This study shows that fibrin deposition exacerbates axonal injury, and that induction of an extracellular proteolytic cascade is a beneficial response of the tissue to remove fibrin. tPA/plasmin-mediated fibrinolysis may be a widespread protective mechanism in neuroinflammatory pathologies.

  10. bFGF Protects Pre-oligodendrocytes from Oxygen/Glucose Deprivation Injury to Ameliorate Demyelination.

    Science.gov (United States)

    Qu, Xuebin; Guo, Rui; Zhang, Zhenzhong; Ma, Li; Wu, Xiuxiang; Luo, Mengjiao; Dong, Fuxing; Yao, Ruiqin

    2015-10-01

    One of the pathological hallmarks of periventricular white matter injury is the vulnerability of pre-oligodendrocytes (preOLs) to hypoxia-ischemia (HI). There is increasing evidence that basic fibroblast growth factor (bFGF) is an important signaling molecule for neurogenesis and neuroprotection in the central nervous system. However, it is unknown whether bFGF protects preOLs from oxygen/glucose deprivation (OGD) damage in vitro and promotes remyelination in HI-induced rats. In this present study, bFGF exerted a protective effect on myelin by increasing the myelin thickness, the number of myelinated axons, and myelin basic protein expression in the HI-induced demyelinated neonatal rat corpus callosum. In vitro, bFGF ameliorated the impaired mitochondria and cell processes induced by OGD to promote the survival of isolated O4-positive preOLs. Additionally, the expression of fibroblast growth factor receptor 3 (FGFR3) was dramatically up-regulated in the preOLs after bFGF administration in vivo and in vitro. Thus, bFGF-stimulated remyelination in HI-induced rats by protecting the preOLs from hypoxic injury, and the mechanism involved may be mediated by FGFR3.

  11. Transplanted microvascular endothelial cells promote oligodendrocyte precursor cell survival in ischemic demyelinating lesions.

    Science.gov (United States)

    Iijima, Keiya; Kurachi, Masashi; Shibasaki, Koji; Naruse, Masae; Puentes, Sandra; Imai, Hideaki; Yoshimoto, Yuhei; Mikuni, Masahiko; Ishizaki, Yasuki

    2015-11-01

    We previously showed that transplantation of brain microvascular endothelial cells (MVECs) greatly stimulated remyelination in the white matter infarct of the internal capsule (IC) induced by endothelin-1 injection and improved the behavioral outcome. In the present study, we examined the effect of MVEC transplantation on the infarct volume using intermittent magnetic resonance image and on the behavior of oligodendrocyte lineage cells histochemically. Our results in vivo show that MVEC transplantation reduced the infarct volume in IC and apoptotic death of oligodendrocyte precursor cells (OPCs). These results indicate that MVECs have a survival effect on OPCs, and this effect might contribute to the recovery of the white matter infarct. The conditioned-medium from cultured MVECs reduced apoptosis of cultured OPCs, while the conditioned medium from cultured fibroblasts did not show such effect. These results suggest a possibility that transplanted MVECs increased the number of OPCs through the release of humoral factors that prevent their apoptotic death. Identification of such humoral factors may lead to the new therapeutic strategy against ischemic demyelinating diseases.

  12. Targeting insulin-like growth factor 1 leads to amelioration of inflammatory demyelinating disease.

    Directory of Open Access Journals (Sweden)

    Matthew F Cusick

    Full Text Available In patients with multiple sclerosis (MS and in mice with experimental autoimmune encephalomyelitis (EAE, proliferating autoreactive T cells play an important role in the pathogenesis of the disease. Due to the importance of these myelin-specific T cells, these cells have been therapeutic targets in a variety of treatments. Previously we found that Lenaldekar (LDK, a novel small molecule, could inhibit exacerbations in a preclinical model of MS when given at the start of an EAE exacerbation. In those studies, we found that LDK could inhibit human T cell recall responses and murine myelin responses in vitro. In these new studies, we found that LDK could inhibit myelin specific T cell responses through the insulin-like growth factor-1 receptor (IGF-1R pathway. Alteration of this pathway led to marked reduction in T cell proliferation and expansion. Blocking this pathway could account for the observed decreases in clinical signs and inflammatory demyelinating disease, which was accompanied by axonal preservation. Our data indicate that IGF-1R could be a potential target for new therapies for the treatment of autoimmune diseases where autoreactive T cell expansion is a requisite for disease.

  13. Females remyelinate more efficiently than males following demyelination in the aged but not young adult CNS.

    Science.gov (United States)

    Li, Wen-Wu; Penderis, Jacques; Zhao, Chao; Schumacher, Michael; Franklin, Robin J M

    2006-11-01

    To assess the effects of sex on CNS remyelination, demyelinating lesions were induced by injection of ethidium bromide into the caudal cerebellar peduncle of Sprague-Dawley rats divided into the following 8 groups: young adult male, young adult female, old adult male and old adult female and each of these in which the gonads had been removed 4 weeks prior to lesion induction. Remyelination was assessed, blinded to grouping, by a ranking analysis using standard morphological criteria. In young adult animals, where remyelination proceeds rapidly, there was no difference in the remyelination at four weeks after lesion induction in male or females regardless of whether they were intact or castrated/ovariectomised. However, in old adult rats, where remyelination proceeds slowly, the extent of oligodendrocyte remyelination was significantly less in males compared to females at 8 weeks after lesion induction. Removal of gonads did not affect remyelination in old rats of either gender. These results indicate a sex-associated divergence in remyelination efficiency that occurs with ageing that is unaffected by the removal of gonadal sources of sex steroid hormones.

  14. Paeoniflorin inhibits macrophage-mediated lung cancer metastasis.

    Science.gov (United States)

    Wu, Qi; Chen, Gang-Ling; Li, Ya-Juan; Chen, Yang; Lin, Fang-Zhen

    2015-12-01

    Alternatively activated macrophages are more frequently involved in tumor growth, angiogenesis, and immunosuppression. A previous study showed that paeoniflorin, the major active constituent of Paeonia lactiflora Pallas, can inhibit tumor growth and lung metastases of Lewis lung tumor-bearing mice. This study tried to investigate whether paeoniflorin inhibited lung cancer metastasis by inhibiting the alternative activation of macrophages (M2 macrophage). Using a viability assay, the cytotoxicity of paeoniflorin on Lewis lung cancer cells and peritoneal macrophages were investigated. In vitro scratch wound and in vivo lung metastasis experiments were used to test the ability to inhibit the migration of paeoniflorin and the function of M2 macrophages. Flow cytometry was performed to test the cell cycle of Lewis lung cancer cells, and to test the M2 macrophages in peritoneal macrophages and subcutaneous transplantable tumor. It was found that paeoniflorin showed no inhibitory effect on the growth of Lewis lung cancer cells and peritoneal macrophages of mouse in vitro. Paeoniflorin could attenuate the migration of LLC stimulated by alternatively activated macrophages (stimulated for 24 h and 48 h, paeoniflorin 1, 3, 10, 30, 100 μmol·L(-1), P lung cancer cells (paeoniflorin 100 μmol·L(-1), P lung metastasis of Lewis lung cancer cells xenograft and decrease the numbers of M2 macrophages in subcutaneous xenograft tumour in vivo (paeoniflorin 20, 40 mg·kg(-1), P lung metastasis of Lewis lung cancer cells xenograft partly through inhibiting the alternative activation of macrophages.

  15. Macrophage-mediated response to hypoxia in disease

    Directory of Open Access Journals (Sweden)

    Tazzyman S

    2014-11-01

    Full Text Available Simon Tazzyman,1 Craig Murdoch,2 James Yeomans,1 Jack Harrison,1 Munitta Muthana3 1Department of Oncology, 2School of Clinical Dentistry, 3Department of Infection and Immunity, University of Sheffield, Sheffield, UK Abstract: Hypoxia plays a critical role in the pathobiology of various inflamed, diseased tissues, including malignant tumors, atherosclerotic plaques, myocardial infarcts, the synovia of rheumatoid arthritic joints, healing wounds, and sites of bacterial infection. These areas of hypoxia form when the blood supply is occluded and/or the oxygen supply is unable to keep pace with cell growth and/or infiltration of inflammatory cells. Macrophages are ubiquitous in all tissues of the body and exhibit great plasticity, allowing them to perform divergent functions, including, among others, patrolling tissue, combating invading pathogens and tumor cells, orchestrating wound healing, and restoring homeostasis after an inflammatory response. The number of tissue macrophages increases markedly with the onset and progression of many pathological states, with many macrophages accumulating in avascular and necrotic areas, where they are exposed to hypoxia. Recent studies show that these highly versatile cells then respond rapidly to the hypoxia present by altering their expression of a wide array of genes. Here we review the evidence for hypoxia-driven macrophage inflammatory responses in various disease states, and how this influences disease progression and treatment. Keywords: macrophage, hypoxia, inflammation, cytokine

  16. Macrophage mediated PCI enhanced gene-directed enzyme prodrug therapy

    Science.gov (United States)

    Christie, Catherine E.; Zamora, Genesis; Kwon, Young J.; Berg, Kristian; Madsen, Steen J.; Hirschberg, Henry

    2015-03-01

    Photochemical internalization (PCI) is a photodynamic therapy-based approach for improving the delivery of macromolecules and genes into the cell cytosol. Prodrug activating gene therapy (suicide gene therapy) employing the transduction of the E. coli cytosine deaminase (CD) gene into tumor cells, is a promising method. Expression of this gene within the target cell produces an enzyme that converts the nontoxic prodrug, 5-FC, to the toxic metabolite, 5-fluorouracil (5-FU). 5-FC may be particularly suitable for brain tumors, because it can readily cross the bloodbrain barrier (BBB). In addition the bystander effect, where activated drug is exported from the transfected cancer cells into the tumor microenvironment, plays an important role by inhibiting growth of adjacent tumor cells. Tumor-associated macrophages (TAMs) are frequently found in and around glioblastomas. Monocytes or macrophages (Ma) loaded with drugs, nanoparticles or photosensitizers could therefore be used to target tumors by local synthesis of chemo attractive factors. The basic concept is to combine PCI, to enhance the ex vivo transfection of a suicide gene into Ma, employing specially designed core/shell NP as gene carrier.

  17. CNS expression of B7-H1 regulates pro-inflammatory cytokine production and alters severity of Theiler's virus-induced demyelinating disease.

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    D'Anne S Duncan

    Full Text Available The CNS is a unique organ due to its limited capacity for immune surveillance. As macrophages of the CNS, microglia represent a population originally known for the ability to assist neuronal stability, are now appreciated for their role in initiating and regulating immune responses in the brain. Theiler's murine encephalomyelitis virus (TMEV-induced demyelinating disease is a mouse model of multiple sclerosis (MS. In response to TMEV infection in vitro, microglia produce high levels of inflammatory cytokines and chemokines, and are efficient antigen-presenting cells (APCs for activating CD4(+ T cells. However, the regulatory function of microglia and other CNS-infiltrating APCs in response to TMEV in vivo remains unclear. Here we demonstrate that microglia increase expression of proliferating cell nuclear antigen (PCNA, and phenotypically express high levels of major histocompatibility complex (MHC-Class I and II in response to acute infection with TMEV in SJL/J mice. Microglia increase expression of the inhibitory co-stimulatory molecule, B7-H1 as early as day 5 post-infection, while CNS-infiltrating CD11b(+CD11c(-CD45(HIGH monocytes/macrophages and CD11b(+CD11c(+CD45(HIGH dendritic cells upregulate expression of B7-H1 by day 3 post-infection. Utilizing a neutralizing antibody, we demonstrate that B7-H1 negatively regulates TMEV-specific ex vivo production of interferon (IFN-γ, interleukin (IL-17, IL-10, and IL-2 from CD4(+ and CD8(+ T cells. In vivo blockade of B7-H1 in SJL/J mice significantly exacerbates clinical disease symptoms during the chronic autoimmune stage of TMEV-IDD, but only has minimal effects on viral clearance. Collectively, these results suggest that CNS expression of B7-H1 regulates activation of TMEV-specific T cells, which affects protection against TMEV-IDD.

  18. Chronic cholecystitis

    Science.gov (United States)

    Cholecystitis - chronic ... Most of the time, chronic cholecystitis is caused by repeated attacks of acute (sudden) cholecystitis. Most of these attacks are caused by gallstones in the gallbladder. These ...

  19. Chronic Pain

    Science.gov (United States)

    ... pain. Psychotherapy, relaxation and medication therapies, biofeedback, and behavior modification may also be employed to treat chronic pain. × ... pain. Psychotherapy, relaxation and medication therapies, biofeedback, and behavior modification may also be employed to treat chronic pain. ...

  20. Chronic Pain

    Science.gov (United States)

    ... a problem you need to take care of. Chronic pain is different. The pain signals go on ... there is no clear cause. Problems that cause chronic pain include Headache Low back strain Cancer Arthritis ...

  1. Chronic prostatitis

    OpenAIRE

    Le, Brian; Schaeffer, Anthony J.

    2011-01-01

    Chronic prostatitis can cause pain and urinary symptoms, and usually occurs without positive bacterial cultures from prostatic secretions (known as chronic abacterial prostatitis or chronic pelvic pain syndrome [CP/CPPS]). Bacterial infection can result from urinary tract instrumentation, but the cause and natural history of CP/CPPS are unknown.

  2. Chronic prostatitis

    OpenAIRE

    Erickson, Bradley A.; Schaeffer, Anthony J.; Le, Brian

    2008-01-01

    Chronic prostatitis can cause pain and urinary symptoms, and usually occurs without positive bacterial cultures from prostatic secretions (known as chronic abacterial prostatitis or chronic pelvic pain syndrome, CP/CPPS). Bacterial infection can result from urinary tract instrumentation, but the cause and natural history of CP/CPPS are unknown.

  3. 过氧化物酶体增殖物激活受体α(PPARα)对脂多糖刺激巨噬细胞引发炎症反应的影响%Activated peroxisome proliferator-activated receptor αinhibiting the lipopolysaccharide-induced macrophage-mediated inflammatory responses by promoting the autophagy

    Institute of Scientific and Technical Information of China (English)

    杨蓉蓉; 张莉; 张向颖; 时红波; 陈德喜; 段钟平; 任锋; 王琦

    2015-01-01

    Objective To investigate the effects of peroxisome proliferator-activated receptor α( PPARα) on macrophage-mediated inflammatory responses with the interference of lipopolysaccharide and the possible mechanism.Methods The bone marrow stem cells were isolated from the femora of mice.The granulocyte-macrophage colony stimulating factor ( GM-CSF) was used to stimulate the in vitro differentiation from bone marrow stem cells into primary macrophages.An in vitro model with cultured cells expressing in-flammatory cytokines was established by treating the primary macrophages with lipopolysaccharide ( LPS) .A specific chemical agonist, Wy-14643, was used to activate PPARα. Autophagy inhibitors including 3-methyladenine (3-MA) and small interfering RNA against Atg7 ( Atg7 siRNA) were used to inhibit the autophagy.Western blot assay was performed to detect the expression of autophagy-related proteins ( Atg5, Atg7, Beclin-1 and LC3).The transcriptional levels of TNF-α, IL-1β, IL-6, Atg5, Atg7 and Beclin-1 were analyzed by qRT-PCR.Results Compared with the macrophages treated with LPS alone, those pretreated with various concentrations of Wy-14643 (10 μmol/L, 25 μmol/L and 50 μmol/L) showed inhibited ex-pression of proinflammatory cytokines ( TNF-α,IL-1βand IL-6) and enhanced expression of autophagy-relat-ed proteins (Atg5, Atg7 and Beclin-1) at mRNA level in a dose-dependent manner.The expression of auto-phagy-related proteins (Atg5, Atg7, Beclin-1 and LC3) by macrophages was promoted with the pretreatment of Wy-14643 as indicated by Western blot assay.The transcriptional levels of TNF-α, IL-1βand IL-6 were increased in Wy-14643 pretreated-macrophages after stimulation with 3-MA or Atg7 siRNA .Conclusion PPARαsuppressed the macrophage-mediated inflammatory responses by promoting autophagy, suggesting that the PPARα-autophagy pathway might be one of the signaling pathways regulating LPS induced-inflamma-tory responses.%目的:探讨过氧化物酶

  4. Progesterone Enhanced Remyelination in the Mouse Corpus Callosum After Cuprizone Induced Demyelination

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    Iraj Ragerdi Kashani

    2015-11-01

    Full Text Available Background: Progesterone as a sex steroid hormone is thought to affect and prevent demyelination, but its role in promoting myelin repair is far less investigated. In this study, remyelinating potential of progesterone in corpus callosum was evaluated on an experimental model of MS. Methods: In this experimental study, adult male C57BL/6 mice were fed with 0.2% (w/w cuprizone in ground breeder chow ad libitum for 6 weeks. At day zero, after cuprizone removal, mice were divided randomly into two groups: (a placebo group, which received saline pellet implant, (b progesterone group, which received progesterone pellet implant. Some mice of the same age were fed with their normal diet to serve as the healthy control group. Two weeks after progesterone administration, Myelin content was assessed by Luxol-fast blue staining. The myelin basic protein (MBP and proteolipid protein (PLP expression were assessed using Western blot analysis and the changes in the number of oligodendrocytes and oligodendroglial progenitor cells were assessed by immunohistochemistry (IHC and flow cytometry. Results: Luxol-fast blue staining revealed enhanced remyelination in the progesterone group when compared with the placebo group. Densitometry measurements of immunoblots demonstrated that MBP and PLP proteins contents were significantly increased in the progesterone group compared with the placebo group. Flow cytometry and IHC analysis showed increases in Olig2 and O4 cells in the progesterone group compared with the placebo group. Conclusion: Overall, our results indicate that progesterone treatment can stimulate myelin production and that it may provide a feasible and practical way for remyelination in diseases such as multiple sclerosis.

  5. [NMDA receptor encephalitis in the course of recurrent CNS demyelinating disorders: a case report].

    Science.gov (United States)

    Yamamoto, Masanari; Kokubun, Norito; Watanabe, Yuka; Okabe, Ryuta; Nakamura, Toshiki; Hirata, Koichi

    2013-01-01

    We present the case of a 31-year-old woman who developed N-methyl-d-aspartate (NMDA) receptor encephalitis during the course of relapsing and remitting multiple brain lesions. The patient developed a tingling sensation in the left upper and lower extremities, and was first admitted to our hospital at age 27. She was tentatively diagnosed with multiple sclerosis on the basis of multiple lesions with Gd-enhancement in the brainstem, and 2 separate clinical relapses by age 28. At age 31, she developed a headache and pyrexia, followed by confusion and abnormal behavior. Her symptoms acutely progressed to stupor, and subsequently, she developed oral dyskinesia and athetosis-like involuntary movement of the left arm. The stupor state continued over 2 months. However, she had completely recovered by 3 months after the onset of psychiatric symptoms. Her serum and CSF samples tested positive for anti-NMDA receptor antibodies, and she was diagnosed with NMDA receptor encephalitis. Her serum was negative for anti-AQP4 antibody, but showed weak positivity for antinuclear antibody. Between ages 32 and 34, she experienced 2 clinical relapses, including right-hand clumsiness, confusion, aphasia, and dysphagia. FLAIR images showed a high-intensity area in the brain stem, thalamus, and subcortical white matter. No tumors were found throughout the course. A clinical entity of NMDA receptor encephalitis can include various neurologic disorders, such as the development of recurrent demyelinating brain lesions. Further investigation is required to clarify the pathophysiological role of anti-NMDA receptor antibody in our patient.

  6. MRI study of the cuprizone-induced mouse model of multiple sclerosis: demyelination is not found after co-treatment with polyprenols (long-chain isoprenoid alcohols)

    Science.gov (United States)

    Khodanovich, M.; Glazacheva, V.; Pan, E.; Akulov, A.; Krutenkova, E.; Trusov, V.; Yarnykh, V.

    2016-02-01

    Multiple sclerosis is a neurological disorder with poorly understood pathogenic mechanisms and a lack of effective therapies. Therefore, the search for new MS treatments remains very important. This study was performed on a commonly used cuprizone animal model of multiple sclerosis. It evaluated the effect of a plant-derived substance called Ropren® (containing approximately 95% polyprenols or long-chain isoprenoid alcohols) on cuprizone- induced demyelination. The study was performed on 27 eight-week old male CD-1 mice. To induce demyelination mice were fed 0.5% cuprizone in the standard diet for 10 weeks. Ropren® was administered in one daily intraperitoneal injection (12mg/kg), beginning on the 6th week of the experiment. On the 11th week, the corpus callosum in the brain was evaluated in all animals using magnetic resonance imaging with an 11.7 T animal scanner using T2- weighted sequence. Cuprizone treatment successfully induced the model of demyelination with a significant decrease in the size of the corpus callosum compared with the control group (p<0.01). Mice treated with both cuprizone and Ropren® did not exhibit demyelination in the corpus callosum (p<0.01). This shows the positive effect of polyprenols on cuprizone-induced demyelination in mice.

  7. Chronic methylmercurialism in a horse

    Energy Technology Data Exchange (ETDEWEB)

    Seawright, A.A.; Roberts, M.C.; Costigan, P.

    1978-02-01

    Chronic methylmercurialism was produced in a horse given 10 g methylmercury chloride over 10 weeks. Neurological signs, particularly proprioceptive disturbances, were apparent by the final week of dosing and became more severe thereafter. An exudative dermatitis, a reluctance to move, weight loss, reduced appetite and dullness were among the earlier clinical signs, and renal changes characterized by a steadily increasing BUN and glucosuria were detected later. Pathological lesions were confined to the kidneys and the nervous system. There was mild neuronal degeneration in the cerebral cortex and in the cerebellar cortex, axonal demyelination in the dorsal columns of the spinal cord and extensive degeneration of ganglion cells in the dorsal root ganglia. The blood organic mercury level, which had plateaued in the second month, increased rapidly in the last weeks of dosing with a sharp rise terminally. This pattern was repeated for the much lower inorganic mercury levels except for a terminal decrease. The proportion of inorganic mercury was five times greater in the dorsal root ganglia than elsewhere in the CNS, although total mercury levels were similar. Highest tissue mercury levels were found in the liver and kidneys, over 50% being in the form of inorganic mercury. As dealkylation of the methylmercury appeared to be more efficient in the dorsal root ganglia and the kidneys, inorganic mercury derived therefrom may have been responsible for some of the clinical and pathological features of this intoxication in the horse. 21 references, 6 figures, 2 tables.

  8. Gas6 Promotes Oligodendrogenesis and Myelination in the Adult Central Nervous System and After Lysolecithin-Induced Demyelination

    Science.gov (United States)

    Goudarzi, Salman; Rivera, Andrea; Butt, Arthur M.

    2016-01-01

    A key aim of therapy for multiple sclerosis (MS) is to promote the regeneration of oligodendrocytes and remyelination in the central nervous system (CNS). The present study provides evidence that the vitamin K-dependent protein growth arrest specific 6 (Gas6) promotes such repair in in vitro cultures of mouse optic nerve and cerebellum. We first determined expression of Gas6 and TAM (Tyro3, Axl, Mer) receptors in the mouse CNS, with all three TAM receptors increasing in expression through postnatal development, reaching maximal levels in the adult. Treatment of cultured mouse optic nerves with Gas6 resulted in significant increases in oligodendrocyte numbers as well as expression of myelin basic protein (MBP). Gas6 stimulation also resulted in activation of STAT3 in optic nerves as well as downregulation of multiple genes involved in MS development, including matrix metalloproteinase-9 (MMP9), which may decrease the integrity of the blood–brain barrier and is found upregulated in MS lesions. The cytoprotective effects of Gas6 were examined in in vitro mouse cerebellar slice cultures, where lysolecithin was used to induce demyelination. Cotreatment of cerebellar slices with Gas6 significantly attenuated demyelination as determined by MBP immunostaining, and Gas6 activated Tyro3 receptor through its phosphorylation. In conclusion, these results demonstrate that Gas6/TAM signaling stimulates the generation of oligodendrocytes and increased myelin production via Tyro3 receptor in the adult CNS, including repair after demyelinating injury. Furthermore, the effects of Gas6 on STAT3 signaling and matrix MMP9 downregulation indicate potential glial cell repair and immunoregulatory roles for Gas6, indicating that Gas6-TAM signaling could be a potential therapeutic target in MS and other neuropathologies. PMID:27630207

  9. Chronic meningoencephalomyelitis with spastic spinal paralysis. Case report

    Energy Technology Data Exchange (ETDEWEB)

    Mitsuyama, Y.; Thompson, L.R.; Yuki, I.; Tanemori, H.

    1973-01-01

    A case of chronic meningoencephalomyelitis in a 48-year-old housewife is presented. The onset was characterized by spastic paralysis of the lower extremities. The course was progressive with repeated remissions and exacerbations, and the patient died approximately 7 years after the onset of disease. Laboratory tests showed slightly increased cell count in the spinal fluid, accelerated sedimentation rate, positive CRP and RA, and increased ASLO and gamma globulin levels. Neuropathologic examination revealed such changes as perivascular cellular infiltration, glial nodules, poorly demarcated demyelination, and recent necrosis in the spinal cord and basal ganglia. Only mild inflammatory findings were noted in the telencephalon and brain stem. The clinicopathologic findings in this case supported a diagnosis of chronic meningoencepalomyelitis which could not be classified as any known type of encephalomyelitis. (auth)

  10. IL-2 suppression of IL-12p70 by a recombinant HSV-1 expressing IL-2 induces T-cell auto-reactivity and CNS demyelination.

    Directory of Open Access Journals (Sweden)

    Mandana Zandian

    Full Text Available To evaluate the role of cellular infiltrates in CNS demyelination in immunocompetent mice, we have used a model of multiple sclerosis (MS in which different strains of mice are infected with a recombinant HSV-1 expressing IL-2. Histologic examination of the mice infected with HSV-IL-2 demonstrates that natural killer cells, dendritic cells, B cells, and CD25 (IL-2rα do not play any role in the HSV-IL-2-induced demyelination. T cell depletion, T cell knockout and T cell adoptive transfer experiments suggest that both CD8(+ and CD4(+ T cells contribute to HSV-IL-2-induced CNS demyelination with CD8(+ T cells being the primary inducers. In the adoptive transfer studies, all of the transferred T cells irrespective of their CD25 status at the time of transfer were positive for expression of FoxP3 and depletion of FoxP3 blocked CNS demyelination by HSV-IL-2. The expression levels of IL-12p35 relative to IL-12p40 differed in BM-derived macrophages infected with HSV-IL-2 from those infected with wild-type HSV-1. HSV-IL-2-induced demyelination was blocked by injecting HSV-IL-2-infected mice with IL-12p70 DNA. This study demonstrates that suppression of the IL-12p70 function of macrophages by IL-2 causes T cells to become auto-aggressive. Interruption of this immunoregulatory axis results in demyelination of the optic nerve, the spinal cord and the brain by autoreactive T cells in the HSV-IL-2 mouse model of MS.

  11. IL-2 Suppression of IL-12p70 by a Recombinant HSV-1 Expressing IL-2 Induces T-Cell Auto-Reactivity and CNS Demyelination

    Science.gov (United States)

    Zandian, Mandana; Mott, Kevin R.; Allen, Sariah J.; Chen, Shuang; Arditi, Moshe; Ghiasi, Homayon

    2011-01-01

    To evaluate the role of cellular infiltrates in CNS demyelination in immunocompetent mice, we have used a model of multiple sclerosis (MS) in which different strains of mice are infected with a recombinant HSV-1 expressing IL-2. Histologic examination of the mice infected with HSV-IL-2 demonstrates that natural killer cells, dendritic cells, B cells, and CD25 (IL-2rα) do not play any role in the HSV-IL-2-induced demyelination. T cell depletion, T cell knockout and T cell adoptive transfer experiments suggest that both CD8+ and CD4+ T cells contribute to HSV-IL-2-induced CNS demyelination with CD8+ T cells being the primary inducers. In the adoptive transfer studies, all of the transferred T cells irrespective of their CD25 status at the time of transfer were positive for expression of FoxP3 and depletion of FoxP3 blocked CNS demyelination by HSV-IL-2. The expression levels of IL-12p35 relative to IL-12p40 differed in BM-derived macrophages infected with HSV-IL-2 from those infected with wild-type HSV-1. HSV-IL-2-induced demyelination was blocked by injecting HSV-IL-2-infected mice with IL-12p70 DNA. This study demonstrates that suppression of the IL-12p70 function of macrophages by IL-2 causes T cells to become auto-aggressive. Interruption of this immunoregulatory axis results in demyelination of the optic nerve, the spinal cord and the brain by autoreactive T cells in the HSV-IL-2 mouse model of MS. PMID:21364747

  12. Direct angiotensin AT2-receptor stimulation attenuates T-cell and microglia activation and prevents demyelination in experimental autoimmune encephalomyelitis in mice

    DEFF Research Database (Denmark)

    Valero-Esquitino, Verónica; Lucht, Kristin; Namsolleck, Pawel;

    2015-01-01

    in aggregating brain cell cultures and microglia in vitro. In the EAE model, treatment with C21 ameliorated microglia activation and decreased the number of total T-cells and CD4+ T-cells in the spinal cord. Fluorescent myelin staining of spinal cords further revealed a significant reduction of EAE......-induced demyelinated areas in lumbar spinal cord tissue after AT2R-stimulation. C21 treated mice had a significantly better neurological score than vehicle treated controls. In aggregating brain cell cultures challenged with lipopolysaccharide (LPS) plus interferon-γ (IFNγ), AT2R-stimulation prevented demyelination...

  13. Changes of CXCL12, CXCL14 and PDGF levels in the brain of patients with idiopathic demyelinating optic neuritis and neuromyelitis optica.

    Science.gov (United States)

    Tingjun, Chen; Zhaohui, Li; Zhaocai, Jiang; Zihao, Liu; Quangang, Xu; Dehui, Huang; Qing, Lin; Shihui, Wei

    2015-02-15

    The CXC chemokines (CXC-motif ligand 12 and CXC-motif ligand 14) and platelet-derived growth factor are suggested to modulate remyelination in the course of many demyelinating diseases. The present study compared the difference in the brain levels of these chemokines between patients with idiopathic demyelinating optic neuritis (IDON) and neuromyelitis optica (NMO) by measuring their concentrations in the cerebrospinal fluid using an enzyme linked immunosorbent assay. Our data indicate that the prognosis of neuritis depends on the remyelinating process that is impaired due to decreased chemokines. The much lower levels of chemokines would specifically indicate the severe neuritis, such as NMO.

  14. Human induced pluripotent stem cells differentiation into oligodendrocyte progenitors and transplantation in a rat model of optic chiasm demyelination.

    Directory of Open Access Journals (Sweden)

    Alireza Pouya

    Full Text Available BACKGROUND: This study aims to differentiate human induced pluripotent stem cells (hiPSCs into oligodendrocyte precursors and assess their recovery potential in a demyelinated optic chiasm model in rats. METHODOLOGY/PRINCIPAL FINDINGS: We generated a cell population of oligodendrocyte progenitors from hiPSCs by using embryoid body formation in a defined medium supplemented with a combination of factors, positive selection and mechanical enrichment. Real-time polymerase chain reaction and immunofluorescence analyses showed that stage-specific markers, Olig2, Sox10, NG2, PDGFRα, O4, A2B5, GalC, and MBP were expressed following the differentiation procedure, and enrichment of the oligodendrocyte lineage. These results are comparable with the expression of stage-specific markers in human embryonic stem cell-derived oligodendrocyte lineage cells. Transplantation of hiPSC-derived oligodendrocyte progenitors into the lysolecithin-induced demyelinated optic chiasm of the rat model resulted in recovery from symptoms, and integration and differentiation into oligodendrocytes were detected by immunohistofluorescence staining against PLP and MBP, and measurements of the visual evoked potentials. CONCLUSIONS/SIGNIFICANCE: These results showed that oligodendrocyte progenitors generated efficiently from hiPSCs can be used in future biomedical studies once safety issues have been overcome.

  15. Sildenafil (Viagra) Protective Effects on Neuroinflammation: The Role of iNOS/NO System in an Inflammatory Demyelination Model

    Science.gov (United States)

    Raposo, Catarina; Nunes, Ana Karolina de Santana; Luna, Rayana Leal de Almeida; Araújo, Shyrlene Meiry da Rocha; da Cruz-Höfling, Maria Alice; Peixoto, Christina Alves

    2013-01-01

    We recently demonstrated that sildenafil reduces the expression of cytokines, COX-2, and GFAP in a demyelinating model induced in wild-type (WT) mice. Herein, the understandings of the neuroprotective effect of sildenafil and the mediation of iNOS/NO system on inflammatory demyelination induced by cuprizone were investigated. The cerebella of iNOS−/− mice were examined after four weeks of treatment with cuprizone alone or combined with sildenafil. Cuprizone increased GFAP, Iba-1, TNF-α, COX-2, IL-1β, and IFN-γ expression, decreased expression of glutathione S-transferase pi (GSTpi), and damaged myelin in iNOS−/− mice. Sildenafil reduced Iba-1, IFN-γ, and IL-1β levels but had no effect on the expression of GFAP, TNF-α, and COX-2 compared to the cuprizone group. Sildenafil elevated GSTpi levels and improved the myelin structure/ultrastructure. iNOS−/− mice suffered from severe inflammation following treatment with cuprizone, while WT mice had milder inflammation, as found in the previous study. It is possible that inflammatory regulation through iNOS-feedback is absent in iNOS−/− mice, making them more susceptible to inflammation. Sildenafil has at least a partial anti-inflammatory effect through iNOS inhibition, as its effect on iNOS−/− mice was limited. Further studies are required to explain the underlying mechanism of the sildenafil effects. PMID:23970812

  16. Sildenafil (Viagra Protective Effects on Neuroinflammation: The Role of iNOS/NO System in an Inflammatory Demyelination Model

    Directory of Open Access Journals (Sweden)

    Catarina Raposo

    2013-01-01

    Full Text Available We recently demonstrated that sildenafil reduces the expression of cytokines, COX-2, and GFAP in a demyelinating model induced in wild-type (WT mice. Herein, the understandings of the neuroprotective effect of sildenafil and the mediation of iNOS/NO system on inflammatory demyelination induced by cuprizone were investigated. The cerebella of iNOS−/− mice were examined after four weeks of treatment with cuprizone alone or combined with sildenafil. Cuprizone increased GFAP, Iba-1, TNF-α, COX-2, IL-1β, and IFN-γ expression, decreased expression of glutathione S-transferase pi (GSTpi, and damaged myelin in iNOS−/− mice. Sildenafil reduced Iba-1, IFN-γ, and IL-1β levels but had no effect on the expression of GFAP, TNF-α, and COX-2 compared to the cuprizone group. Sildenafil elevated GSTpi levels and improved the myelin structure/ultrastructure. iNOS−/− mice suffered from severe inflammation following treatment with cuprizone, while WT mice had milder inflammation, as found in the previous study. It is possible that inflammatory regulation through iNOS-feedback is absent in iNOS−/− mice, making them more susceptible to inflammation. Sildenafil has at least a partial anti-inflammatory effect through iNOS inhibition, as its effect on iNOS−/− mice was limited. Further studies are required to explain the underlying mechanism of the sildenafil effects.

  17. Demyelinating disease in patients with myasthenia gravis Doenças desmielinizantes em pacientes com miastenia gravis

    Directory of Open Access Journals (Sweden)

    Denis Bernardi Bichuetti

    2008-03-01

    Full Text Available Myasthenia gravis (MG is an autoimmune disease characterized by fluctuating muscle weakness, caused by impaired neuromuscular transmission. Patients with MG can present other autoimmune diseases in association, commonly hypo or hyperthyroidism. The association of MG to demyelinating disease is rare and has been described before. We report on three Brazilian patients with MG that presented distinct demyelinating diseases, two monophasic and one recurrent neuromyelitis optica, several years after the diagnosis of MG, and discuss their clinical courses.Miastenia gravis (MG é doença autoimune caracterizada por episódios de fraqueza muscular alternados com melhora, causada por bloqueio da junção neuromuscular. Pacientes com MG podem apresentar outras doenças autoimunes, comumente hipo ou hipertiroidismo, e a associação de MG com doenças desmielinizantes é raramente descrita. Relatamos três pacientes brasileiros com MG que desenvolveram doenças desmielinizantes, dois monofásicos e um neuromielite óptica recorrente, vários anos após o diagnóstico de MG e discutimos seus cursos clínicos.

  18. Retinitis Pigmentosa and Bilateral Idiopathic Demyelinating Optic Neuritis in a 6-Year-Old Boy with OFD1 Gene Mutation

    Directory of Open Access Journals (Sweden)

    Xun Wang

    2017-01-01

    Full Text Available To identify the cause of a sudden binocular vision decrease in patients with retinitis pigmentosa and bilateral idiopathic demyelinating optic neuritis is difficult, but early diagnosis and treatment significantly improve the prognosis. Here, we report a 6-year-old boy with a progressive binocular vision decrease in 38 days. The patient had a history of night blindness, a mottled retina without pigmentation, extinguished electroretinographic response, tritanopia, and an absent ellipsoid zone outside the macula fovea by optical coherence tomography in both eyes. His condition was diagnosed as retinitis pigmentosa (RP with idiopathic demyelinating optic neuritis (IDON. After corticosteroid therapy, visual acuity recovered to OD: 0.5 and OS: 0.4. Genetic analysis revealed a G985S variant in the oral-facial-digital syndrome 1 gene. Ophthalmologists should pay attention to the existence of other complications in patients with RP who suffer a sudden decrease in vision. A gene survey can help clarify this diagnosis. To our knowledge, this is the first report of a patient with RP and ON, as well as genetic testing results. Nevertheless, the pathogenicity of the variant needs further confirmation.

  19. Retinitis Pigmentosa and Bilateral Idiopathic Demyelinating Optic Neuritis in a 6-Year-Old Boy with OFD1 Gene Mutation

    Science.gov (United States)

    Wang, Xun; Zheng, Cong; Liu, Wen

    2017-01-01

    To identify the cause of a sudden binocular vision decrease in patients with retinitis pigmentosa and bilateral idiopathic demyelinating optic neuritis is difficult, but early diagnosis and treatment significantly improve the prognosis. Here, we report a 6-year-old boy with a progressive binocular vision decrease in 38 days. The patient had a history of night blindness, a mottled retina without pigmentation, extinguished electroretinographic response, tritanopia, and an absent ellipsoid zone outside the macula fovea by optical coherence tomography in both eyes. His condition was diagnosed as retinitis pigmentosa (RP) with idiopathic demyelinating optic neuritis (IDON). After corticosteroid therapy, visual acuity recovered to OD: 0.5 and OS: 0.4. Genetic analysis revealed a G985S variant in the oral-facial-digital syndrome 1 gene. Ophthalmologists should pay attention to the existence of other complications in patients with RP who suffer a sudden decrease in vision. A gene survey can help clarify this diagnosis. To our knowledge, this is the first report of a patient with RP and ON, as well as genetic testing results. Nevertheless, the pathogenicity of the variant needs further confirmation. PMID:28191358

  20. [Chronicity, chronicization, systematization of delusions].

    Science.gov (United States)

    Trapet, P; Fernandez, C; Galtier, M C; Gisselmann, A

    1984-05-01

    Chronicity in psychopathology is indicative of a term, a decay. Chronicization only leads the way to this term. Here, chronicization is taken literally as an inscription in the time course of delusions. The mechanism of systematization seems to be a central mark in the approach to chronic delusions. It is not an alienation or an irreversible closing but an attempted accommodation with reality in the life of psychotic subjects, irrespective of the delusional structure. The role of therapy and drug treatment as a follow-up may in that case assume another meaning.

  1. Chronic pancreatitis

    OpenAIRE

    Kocher, Hemant M.; Froeling, Fieke EM

    2008-01-01

    Chronic pancreatitis is characterised by long-standing inflammation of the pancreas owing to a wide variety of causes, including recurrent acute attacks of pancreatitis. Chronic pancreatitis affects 3–9 people in 100,000; 70% of cases are alcohol-induced.

  2. Chronic pancreatitis

    OpenAIRE

    Kocher, Hemant M.; Kadaba, Raghu

    2011-01-01

    Chronic pancreatitis is characterised by long-standing inflammation of the pancreas due to a wide variety of causes, including recurrent acute attacks of pancreatitis. Chronic pancreatitis affects between 3 and 9 people in 100,000; 70% of cases are alcohol-induced.

  3. 急、慢性炎症性脱髓鞘性多发性神经病神经电生理对比研究%Electrophysiological features of acute inflammatory demyelinating polyneuropathy and chronic inflammatory demyelinating polyneuropathy

    Institute of Scientific and Technical Information of China (English)

    赵东红; 王可人; 朱丹; 赵东辉; 叶玉琴

    2013-01-01

    目的 比较分析急性炎症性脱髓鞘性多发性神经病(AIDP)与慢性炎症性脱髓鞘性多发性神经病(CIDP)的电生理表现.方法 收集2011年1月~2013年1月在吉林大学白求恩第一医院神经内科就诊的19例AIDP患者及15例CIDP患者,分析上下肢周围神经传导检查各项指标.结果 AIDP与CIDP均表现为运动传导速度(MCV)减慢、远端潜伏期延长、波幅降低、传导阻滞、F波及H反射异常,但CIDP组MCV减慢明显,与AIDP组存在显著差异,且CIDP组感觉传导检测异常明显,AIDP组感觉神经传导异常少见.结论 AIDP患者主要以周围神经运动纤维受损为主,存在明显的脱髓鞘及轴索的损伤,但周围神经感觉纤维受损不明显.CIDP患者周围神经运动纤维及感觉纤维受损均非常明显,且脱髓鞘程度明显重于AIDP患者.

  4. Elevation of AQP4 and selective cytokines in experimental autoimmune encephalitis mice provides some potential biomarkers in optic neuritis and demyelinating diseases.

    Science.gov (United States)

    Sun, Li; Weng, Huan; Li, Zhenxin

    2015-01-01

    Idiopathic optic neuritis (ION) is an inflammation of the optic nerve that may result in a complete or partial loss of vision. ION is usually due to the immune attack of the myelin sheath covering the optic nerve. ION acts frequently as the first symptoms of multiple sclerosis (MS) and neuromyelitis optica (NMO), or other inflammatory demyelinating disorders. The pathogenic progression of ION remains unclear. Experimental autoimmune encephalitis (EAE) is a commonly used model of idiopathic inflammatory demyelinating disorders (IIDDs); the optic nerve is affected in EAE as well. The specific mediators of demyelination in optic neuritis are unknown. Recent studies have indicated what T-cell activation in peripheral blood is associated with optic neuritis pathogenesis. The object of the present study was to determine whether certain cytokines (IL-6, IL-17A, and IL-23) and AQP4 contribute to the demyelinating process using EAE model. We have found that IL-6R, AQP4 and IL-23R are significantly increased in mRNA and protein levels in optic nerves in EAE mice compared to control mice; serum AQP4, IL-6, IL-17A, IL-23 are increased whereas transforming growth factor beta (TGF-β) is decreased in EAE mice. These results suggest that AQP4 and selective cytokines in serum are associated with ION pathogenesis in the animal model, and these results shine light for future clinical diagnosis as potential biomarkers in ION patients.

  5. Electromagnetic field stimulation potentiates endogenous myelin repair by recruiting subventricular neural stem cells in an experimental model of white matter demyelination.

    Science.gov (United States)

    Sherafat, Mohammad Amin; Heibatollahi, Motahareh; Mongabadi, Somayeh; Moradi, Fatemeh; Javan, Mohammad; Ahmadiani, Abolhassan

    2012-09-01

    Electromagnetic fields (EMFs) may affect the endogenous neural stem cells within the brain. The aim of this study was to assess the effects of EMFs on the process of toxin-induced demyelination and subsequent remyelination. Demyelination was induced using local injection of lysophosphatidylcholine within the corpus callosum of adult female Sprague-Dawley rats. EMFs (60 Hz; 0.7 mT) were applied for 2 h twice a day for 7, 14, or 28 days postlesion. BrdU labeling and immunostaining against nestin, myelin basic protein (MBP), and BrdU were used for assessing the amount of neural stem cells within the tissue, remyelination patterns, and tracing of proliferating cells, respectively. EMFs significantly reduced the extent of demyelinated area and increased the level of MBP staining within the lesion area on days 14 and 28 postlesion. EMFs also increased the number of BrdU- and nestin-positive cells within the area between SVZ and lesion as observed on days 7 and 14 postlesion. It seems that EMF potentiates proliferation and migration of neural stem cells and enhances the repair of myelin in the context of demyelinating conditions.

  6. Nodes of ranvier and paranodes in chronic acquired neuropathies.

    Directory of Open Access Journals (Sweden)

    Carmen Cifuentes-Diaz

    Full Text Available Chronic acquired neuropathies of unknown origin are classified as chronic inflammatory demyelinating polyneuropathies (CIDP and chronic idiopathic axonal polyneuropathies (CIAP. The diagnosis can be very difficult, although it has important therapeutic implications since CIDP can be improved by immunomodulating treatment. The aim of this study was to examine the possible abnormalities of nodal and paranodal regions in these two types of neuropathies. Longitudinal sections of superficial peroneal nerves were obtained from biopsy material from 12 patients with CIDP and 10 patients with CIAP and studied by immunofluorescence and in some cases electron microscopy. Electron microscopy revealed multiple alterations in the nodal and paranodal regions which predominated in Schwann cells in CIDP and in axons in CIAP. In CIDP paranodin/Caspr immunofluorescence was more widespread than in control nerves, extending along the axon in internodes where it appeared intense. Nodal channels Nav and KCNQ2 were less altered but were also detected in the internodes. In CIAP paranodes, paranodin labeling was irregular and/or decreased. To test the consequences of acquired primary Schwann cells alteration on axonal proteins, we used a mouse model based on induced deletion of the transcription factor Krox-20 gene. In the demyelinated sciatic nerves of these mice we observed alterations similar to those found in CIDP by immunofluorescence, and immunoblotting demonstrated increased levels of paranodin. Finally we examined whether the alterations in paranodin immunoreactivity could have a diagnosis value. In a sample of 16 biopsies, the study of paranodin immunofluorescence by blind evaluators led to correct diagnosis in 70 ± 4% of the cases. This study characterizes for the first time the abnormalities of nodes of Ranvier in CIAP and CIDP, and the altered expression and distribution of nodal and paranodal proteins. Marked differences were observed between CIDP and CIAP

  7. Effects of Reducing Suppressors of Cytokine Signaling-3 (SOCS3 Expression on Dendritic Outgrowth and Demyelination after Spinal Cord Injury.

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    Keun Woo Park

    Full Text Available Suppressors of cytokine signaling-3 (SOCS3 is associated with limitations of nerve growth capacity after injury to the central nervous system. Although genetic manipulations of SOCS3 can enhance axonal regeneration after optic injury, the role of SOCS3 in dendritic outgrowth after spinal cord injury (SCI is still unclear. The present study investigated the endogenous expression of SOCS3 and its role in regulating neurite outgrowth in vitro. Interleukin-6 (IL-6 induces SOCS3 expression at the mRNA and protein levels in neuroscreen-1 (NS-1 cells. In parallel to SOCS3 expression, IL-6 induced tyrosine phosphorylation of signal transducer and activator of transcription 3 (STAT3 in NS-1 cells. Lentiviral delivery of short hairpin RNA (shSOCS3 (Lenti-shSOCS3 to decrease SOCS3 expression into NS-1 cells enhanced IL-6-induced tyrosine phosphorylation of STAT3 (P-STAT3 Tyr705 and promoted neurite outgrowth. In addition, we determined if reduction of SOCS3 expression by microinjection of Lenti-shSOCS3 into spinal cord enhances dendrite outgrowth in spinal cord neurons after SCI. Knocking down of SOCS3 in spinal cord neurons with Lenti-shSOCS3 increased complete SCI-induced P-STAT3 Tyr705. Immunohistochemical analysis showed that complete SCI induced a significant reduction of microtubule association protein 2-positive (MAP-2+ dendrites in the gray and white matter at 1 and 4 weeks after injury. The SCI-induced reduction of MAP-2+ dendrites was inhibited by infection with Lenti-shSOCS3 in areas both rostral and caudal to the lesion at 1 and 4 weeks after complete SCI. Furthermore, shSOCS3 treatment enhanced up-regulation of growth associated protein-43 (GAP-43 expression, which co-localized with MAP-2+ dendrites in white matter and with MAP-2+ cell bodies in gray matter, indicating Lenti-shSOCS3 may induce dendritic regeneration after SCI. Moreover, we demonstrated that Lenti-shSOCS3 decreased SCI-induced demyelination in white matter of spinal cord both

  8. Cortical grey matter demyelination can be induced by elevated pro-inflammatory cytokines in the subarachnoid space of MOG-immunized rats.

    Science.gov (United States)

    Gardner, Christopher; Magliozzi, Roberta; Durrenberger, Pascal F; Howell, Owain W; Rundle, Jon; Reynolds, Richard

    2013-12-01

    A substantial proportion of cases with secondary progressive multiple sclerosis have extensive inflammation in the leptomeninges that is associated with increased subpial demyelination, neuronal loss and an exacerbated disease course. However, the mechanisms underlying this extensive subpial pathology are poorly understood. We hypothesize that pro-inflammatory cytokine production within the meninges may be a key to this process. Post-mortem cerebrospinal fluid and dissected cerebral leptomeningeal tissue from patients with multiple sclerosis were used to study the presence of tumour necrosis factor and interferon gamma protein and messenger RNA levels. A novel model of subpial cortical grey matter demyelination was set up in Dark Agouti rats and analysed using quantitative immunohistochemistry. Increased expression of the pro-inflammatory cytokines tumour necrosis factor and interferon gamma was found in the meninges of cases with secondary progressive multiple sclerosis exhibiting tertiary lymphoid-like structures. Injection of tumour necrosis factor and interferon gamma into the subarachnoid space of female Dark Agouti rats pre-immunized with a subclinical dose of myelin oligodendrocyte glycoprotein mimicked the pathology seen in multiple sclerosis, including infiltration of lymphocytes (CD4+ and CD8+ T cells and CD79+ B cells) into the meninges and extensive subpial demyelination. Extensive microglial/macrophage activation was present in a gradient from the pial surface to deeper cortical layers. Demyelination did not occur in control animals immunized with incomplete Freund's adjuvant and injected with cytokines. These results support the hypothesis that pro-inflammatory molecules produced in the meninges play a major role in cortical demyelination in multiple sclerosis, but also emphasize the involvement of an anti-myelin immune response.

  9. Demyelinating Disease following Anti-TNFa Treatment: A Causal or Coincidental Association? Report of Four Cases and Review of the Literature

    Directory of Open Access Journals (Sweden)

    E. Andreadou

    2013-01-01

    Full Text Available Tumor necrosis factor antagonists (anti-TNFa are an established therapeutic option for several autoimmune and inflammatory bowel diseases. Despite their clinical effectiveness, neurological adverse events have been reported and literature data suggest a potential role of anti-TNFa in the induction of demyelination of the CNS. We present four patients treated with anti-TNFa who developed symptoms suggestive of CNS demyelination. The first patient, a 17-year-old male who received etanercept for psoriatic arthritis for eight months, presented with dysesthesias up to T4 level. The second patient, a 30-year-old male treated with adalimumab for three years due to ankylosing spondylitis, presented with right unilateral tinnitus. The third case, a 47-year-old female, received etanercept for four years because of psoriatic arthritis and developed persistent headache and left-sided face and head numbness. Finally, the fourth patient, a 57-years-old female treated with etanercept for six years due to ankylosing spondylitis, presented with difficulty in speech, swallowing, and ptosis of the right corner of the mouth. In all cases, brain MRI showed lesions suggestive of demyelination, while positive oligoclonal bands were detected in the CSF. Anti-TNFa treatments were discontinued and patients showed clinical improvement with pulsed intravenous corticosteroid therapy. CNS demyelination following anti-TNFa treatment represents a relatively rare but potential serious complication. Close follow-up and MRI monitoring of these patients is mandatory to elucidate whether the clinical manifestations represent adverse events occurring during anti-TNFa therapy or a first demyelinating episode.

  10. Ear infection - chronic

    Science.gov (United States)

    Middle ear infection - chronic; Otitis media - chronic; Chronic otitis media; Chronic ear infection ... up. When this happens, infection can occur. A chronic ear infection develops when fluid or an infection ...

  11. Longitudinal in vivo coherent anti-Stokes Raman scattering imaging of demyelination and remyelination in injured spinal cord

    Science.gov (United States)

    Shi, Yunzhou; Zhang, Delong; Huff, Terry B.; Wang, Xiaofei; Shi, Riyi; Xu, Xiao-Ming; Cheng, Ji-Xin

    2011-10-01

    In vivo imaging of white matter is important for the mechanistic understanding of demyelination and evaluation of remyelination therapies. Although white matter can be visualized by a strong coherent anti-Stokes Raman scattering (CARS) signal from axonal myelin, in vivo repetitive CARS imaging of the spinal cord remains a challenge due to complexities induced by the laminectomy surgery. We present a careful experimental design that enabled longitudinal CARS imaging of de- and remyelination at single axon level in live rats. In vivo CARS imaging of secretory phospholipase A2 induced myelin vesiculation, macrophage uptake of myelin debris, and spontaneous remyelination by Schwann cells are sequentially monitored over a 3 week period. Longitudinal visualization of de- and remyelination at a single axon level provides a novel platform for rational design of therapies aimed at promoting myelin plasticity and repair.

  12. Optimizing the management of neuromyelitis optica and spectrum disorders in resource poor settings: Experience from the Mangalore demyelinating disease registry

    Directory of Open Access Journals (Sweden)

    Lekha Pandit

    2013-01-01

    Full Text Available Background: In resource-poor settings, the management of neuromyelitis optica (NMO and NMO spectrum (NMOS disorders is limited because of delayed diagnosis and financial constraints. Aim: To device a cost-effective strategy for the management of NMO and related disorders in India. Materials and Methods: A cost-effective and disease-specific protocol was used for evaluating the course and treatment outcome of 70 consecutive patients. Results: Forty-five patients (65% had a relapse from the onset and included NMO (n = 20, recurrent transverse myelitis (RTM; n = 10, and recurrent optic neuritis (ROPN; n = 15. In 38 (84.4% patients presenting after multiple attacks, the diagnosis was made clinically. Only 7 patients with a relapsing course were seen at the onset and included ROPN (n = 5, NMO (n = 1, and RTM (n = 1. They had a second attack after a median interval of 1 ± 0.9 years, which was captured through our dedicated review process. Twenty-five patients had isolated longitudinally extensive transverse myelitis (LETM, of which 20 (80% remained ambulant at follow-up of 3 ± 1.9 years. Twelve patients (17% with median expanded disability status scale (EDSS of 8.5 at entry had a fatal outcome. Serum NMO-IgG testing was done in selected patients, and it was positive in 7 of 18 patients (39%. Irrespective of the NMO-IgG status, the treatment compliant patients (44.4% showed significant improvement in EDSS (P ≤ 0.001. Conclusions : Early clinical diagnosis and treatment compliance were important for good outcome. Isolated LETM was most likely a post-infectious demyelinating disorder in our set-up. NMO and NMOS disorders contributed to 14.9% (45/303 of all demyelinating disorders in our registry.

  13. The effect of glia-glia interactions on oligodendrocyte precursor cell biology during development and in demyelinating diseases

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    Diego eClemente

    2013-12-01

    Full Text Available Oligodendrocyte precursor cells (OPCs originate in specific areas of the developing central nervous system (CNS. Once generated, they migrate towards their destinations where they differentiate into mature oligodendrocytes. In the adult, 5-8% of all cells in the CNS are OPCs, cells that retain the capacity to proliferate, migrate and differentiate into oligodendrocytes. Indeed, these endogenous OPCs react to damage in demyelinating diseases, like multiple sclerosis (MS, representing a key element in spontaneous remyelination. In the present work, we review the specific interactions between OPCs and other glial cells (astrocytes, microglia during CNS development and in the pathological scenario of MS. We focus on: i the role of astrocytes in maintaining the homeostasis and spatial distribution of different secreted cues that determine OPC proliferation, migration and differentiation during CNS development; ii the role of microglia and astrocytes in the redistribution of iron, which is crucial for myelin synthesis during CNS development and for myelin repair in MS; iii how microglia secrete different molecules, e.g. growth factors, that favor the recruitment of OPCs in acute phases of MS lesions; and iv how astrocytes modify the extracellular matrix in MS lesions, affecting the ability of OPCs to attempt spontaneous remyelination. Together, these issues demonstrate how both astroglia and microglia influence OPCs in physiological and pathological situations, reinforcing the concept that both development and neural repair are complex and global phenomena. Understanding the molecular and cellular mechanisms that control OPC survival, proliferation, migration and differentiation during development, as well as in the mature CNS, may open new opportunities in the search for reparative therapies in demyelinating diseases like MS.

  14. [Chronic hepatitis].

    Science.gov (United States)

    Figueroa Barrios, R

    1995-01-01

    Medical literature about chronic hepatitis is reviewed. This unresolving disease caused by viruses, drugs or unknown factors may progress to in cirrhosis and hepatocarcinoma. A classification based on liver biopsy histology into chronic persistent and chronic active types has been largely abandoned and emphasis is placed on recognizing the etiology of the various types. One is associated with continuing hepatitis B virus infection; another is related to chronic hepatitis C virus infection and the third is termed autoinmune, because of the association with positive serum autoantibodies. A fourth type with similar clinical functional and morphologic features is found with some drug reactions. Long term corticoesteroid therapy is usually successful in autoinmune type. Associations between antibodies to liver-kidney microsomes and the hepatitis C virus can cause diagnostic difficulties. Antiviral treatment of chronic hepatitis B and C with interpheron alfa is employed, controlling symptoms and abnormal biochemistry and the progression to cirrhosis and liver cancer in 30 to 40% patients. Alternative therapies or combinations with interpheron are being evaluated waiting for final results.

  15. Chronic gastritis.

    Science.gov (United States)

    Sipponen, Pentti; Maaroos, Heidi-Ingrid

    2015-06-01

    Prevalence of chronic gastritis has markedly declined in developed populations during the past decades. However, chronic gastritis is still one of the most common serious pandemic infections with such severe killing sequelae as peptic ulcer or gastric cancer. Globally, on average, even more than half of people may have a chronic gastritis at present. Helicobacter pylori infection in childhood is the main cause of chronic gastritis, which microbial origin is the key for the understanding of the bizarre epidemiology and course of the disease. A life-long and aggressive inflammation in gastritis results in destruction (atrophic gastritis) of stomach mucosa with time (years and decades). The progressive worsening of atrophic gastritis results subsequently in dysfunctions of stomach mucosa. Atrophic gastritis will finally end up in a permanently acid-free stomach in the most extreme cases. Severe atrophic gastritis and acid-free stomach are the highest independent risk conditions for gastric cancer known so far. In addition to the risks of malignancy and peptic ulcer, acid-free stomach and severe forms of atrophic gastritis may associate with failures in absorption of essential vitamins, like vitamin B12, micronutrients (like iron, calcium, magnesium and zinc), diet and medicines.

  16. Chronic Bronchitis

    Science.gov (United States)

    ... breathing. You may also have other tests. Chronic bronchitis is a long-term condition that keeps coming back or never goes away completely. If you smoke, it is important to quit. Treatment can help with your symptoms. It often includes ...

  17. A possible means of monitoring the progress of demyelination in multiple sclerosis: effect of body temperature on visual perception of double light flashes.

    Science.gov (United States)

    Galvin, R J; Regan, D; Heron, J R

    1976-09-01

    The ability to discriminate closely separated pairs of light flashes as being double is impaired in multiple sclerosis. The effects of altering body temperature on double flash resolution and on visual acuity were studied in four multiple sclerosis patients and in control subjects. At demyelinated sites heating impaired and cooling improved double flash resolution. Visual acuity behaved similarly. The double flash test was very sensitive, changing up to 75 ms in response to simple heating and cooling procedures that produced small variations in acuity. Apart from its diagnostic value, the double flash test furnishes a simple in vivo model to study the effect of temperature change (and potential symptomatic therapy) on conduction in partially demyelinated axons in the visual system.

  18. Chronic Pancreatitis in Children

    Science.gov (United States)

    ... Information > Children/Pediatric > Chronic Pancreatitis in Children test Chronic Pancreatitis in Children What symptoms would my child ... pancreatitis will develop diabetes in adolescence. Who gets chronic pancreatitis? Those at risk for chronic pancreatitis are ...

  19. Chronic Beryllium Disease

    Science.gov (United States)

    ... Science Education & Training Home Conditions Chronic Beryllium Disease Chronic Beryllium Disease Make an Appointment Find a Doctor ... MD, MSPH, FCCP (February 01, 2016) What is chronic beryllium disease (CBD)? Chronic beryllium disease (CBD) is ...

  20. Chronic motor tic disorder

    Science.gov (United States)

    Chronic vocal tic disorder; Tic - chronic motor tic disorder ... Chronic motor tic disorder is more common than Tourette syndrome . Chronic tics may be forms of Tourette syndrome. Tics usually start ...

  1. Chronic Pelvic Pain

    Science.gov (United States)

    ... Education & Events Advocacy For Patients About ACOG Chronic Pelvic Pain Home For Patients Search FAQs Chronic Pelvic Pain ... Pelvic Pain FAQ099, August 2011 PDF Format Chronic Pelvic Pain Gynecologic Problems What is chronic pelvic pain? What ...

  2. Electrodiagnostic criteria for polyneuropathy and demyelination: application in 135 patients with Guillain-Barré syndrome. Dutch Guillain-Barré Study Group.

    OpenAIRE

    Meulstee, J.; van der Meché, F G

    1995-01-01

    Since the development of effective but expensive therapeutic strategies for the treatment of Guillain-Barré syndrome, early confirmation of the diagnosis has become very important. Electrodiagnostic criteria were developed for the discrimination of polyneuropathy and in particular for demyelination. The sensitivity and specificity of these criteria were determined in 135 patients with Guillain-Barré syndrome in an early stage of the disease, along with 45 healthy volunteers. The algorithms us...

  3. Chronic thyroiditis (Hashimoto disease)

    Science.gov (United States)

    Hashimoto thyroiditis; Chronic lymphocytic thyroiditis; Autoimmune thyroiditis; Chronic autoimmune thyroiditis; Lymphadenoid goiter - Hashimoto; Hypothyroidism - Hashimoto; Type 2 polyglandular autoimmune ...

  4. Infection with Theiler's murine encephalomyelitis virus directly induces proinflammatory cytokines in primary astrocytes via NF-kappaB activation: potential role for the initiation of demyelinating disease.

    Science.gov (United States)

    Palma, JoAnn P; Kwon, Daeho; Clipstone, Neil A; Kim, Byung S

    2003-06-01

    Theiler's virus infection in the central nervous system (CNS) induces a demyelinating disease very similar to human multiple sclerosis. We have assessed cytokine gene activation upon Theiler's murine encephalomyelitis virus (TMEV) infection and potential mechanisms in order to delineate the early events in viral infection that lead to immune-mediated demyelinating disease. Infection of SJL/J primary astrocyte cultures induces selective proinflammatory cytokine genes (interleukin-12p40 [IL-12p40], IL-1, IL-6, tumor necrosis factor alpha, and beta interferon [IFN-beta]) important in the innate immune response to infection. We find that TMEV-induced cytokine gene expression is mediated by the NF-kappaB pathway based on the early nuclear NF-kappaB translocation and suppression of cytokine activation in the presence of specific inhibitors of the NF-kappaB pathway. Further studies show this to be partly independent of dsRNA-dependent protein kinase (PKR) and IFN-alpha/beta pathways. Altogether, these results demonstrate that infection of astrocytes and other CNS-resident cells by TMEV provides the early NF-kappaB-mediated signals that directly activate various proinflammatory cytokine genes involved in the initiation and amplification of inflammatory responses in the CNS known to be critical for the development of immune-mediated demyelination.

  5. Altered glutamate reuptake in relapsing-remitting and secondary progressive multiple sclerosis cortex: correlation with microglia infiltration, demyelination, and neuronal and synaptic damage.

    Science.gov (United States)

    Vercellino, Marco; Merola, Aristide; Piacentino, Chiara; Votta, Barbara; Capello, Elisabetta; Mancardi, Giovanni Luigi; Mutani, Roberto; Giordana, Maria Teresa; Cavalla, Paola

    2007-08-01

    Cortical involvement in multiple sclerosis (MS) is emerging as an important determinant of disease progression. The mechanisms responsible for MS cortical pathology are not fully characterized. The objective of this study was to assess the role of excitotoxicity in MS cortex, evaluating excitatory amino acid transporter (EAAT) expression and its relationship with demyelination, inflammation, gliosis, and neuronal and synaptic pathology. EAATs are essential in maintaining low extracellular glutamate concentrations and preventing excitotoxicity. Ten MS brains (3 relapsing-remitting MS cases and 7 secondary progressive MS cases) were evaluated by immunohistochemistry for myelin basic protein, CD68, HLA-DR, EAAT1, EAAT2, glial fibrillary acidic protein, phosphorylated c-Jun N-terminal kinase (pJNK), synaptophysin, and neurofilaments. Cortical lesions were frequently observed in MS brains in variable numbers and extensions. In cortical lesions, activated microglia infiltration correlated with focal loss of EAAT1, EAAT2, and synaptophysin immunostaining, and with neuronal immunostaining for pJNK, a protein involved in response to excitotoxic injury. No reduction of EAATs or synaptophysin immunostaining was observed in demyelinated cortex in the absence of activated microglia. Alterations of the mechanisms of glutamate reuptake are found in cortical MS lesions in the presence of activated microglia and are associated with signs of neuronal and synaptic damage suggestive of excitotoxicity. Excitotoxicity may be involved in the pathogenesis of demyelination and of neuronal and synaptic damage in MS cortex.

  6. [Toxic demyelination of the central nervous system. I. Effect of an intercalating gliotoxic drug on the spinal cord in Wistar rats].

    Science.gov (United States)

    Graça, D L

    1989-09-01

    Small volumes of ethidium bromide were injected into the dorsal columns of the spinal cord of Wistar rats. It was induced a demyelinating process, variable in nature and speed of repair according to the dose used. The induced lesions were classified into three groups (type I or fast lesions; type II or slow lesions; type III or intermediate lesions) according to the histological appearance and extension of remyelination. In some lesions or in areas within the same lesion, myelin and glial cell debris were rapidly processed by macrophages and the naked axons soon remyelinated by Schwann cells. In other lesions of similar duration, or areas within the lesions, myelin underwent transformation into mazes of membranes which persisted around the axons for long periods of time. In the lesions which contained such myelin-derived membranes, macrophages were scant and remyelination by Schwann cells was slow and arduous. It may be concluded that the slow resolution of some lesions resulted from the time elapsed between intoxication and disappearance of myelin-related cells. That time difference determined that the cellular responses to demyelination took place in an area devoid of glial cells and therefore without a support for the cellular migration needed for the removal of myelin debris and eventual remyelination. This investigation indicates that the development and outcome of demyelination may be altered by the cellular events that occur during oligodendrocyte degeneration.

  7. Actual Therapeutic Indication of an Old Drug: Urea for Treatment of Severely Symptomatic and Mild Chronic Hyponatremia Related to SIADH

    Directory of Open Access Journals (Sweden)

    Guy Decaux

    2014-09-01

    Full Text Available Oral urea has been used in the past to treat various diseases like gastric ulcers, liver metastases, sickle cell disease, heart failure, brain oedema, glaucoma, Meniere disease, etc. We have demonstrated for years, the efficacy of urea to treat euvolemic (SIADH or hypervolemic hyponatremia. We briefly describe the indications of urea use in symptomatic and paucisymptomatic hyponatremic patients. Urea is a non-toxic, cheap product, and protects against osmotic demyelinating syndrome (ODS in experimental studies. Prospective studies showing the benefit to treat mild chronic hyponatremia due to SIADH and comparing water restriction, urea, high ceiling diuretics, and antivasopressin antagonist antagonist should be done.

  8. The chronic cerebrospinal venous insufficiency syndrome.

    Science.gov (United States)

    Zamboni, P; Galeotti, R

    2010-12-01

    Chronic cerebrospinal venous insufficiency (CCSVI) is a syndrome characterized by stenosies of the internal jugular and/or azygous veins (IJVs-AZ) with opening of collaterals and insufficient drainage proved by reduced cerebral blood flow and increased mean transit time in cerebral MRI perfusional study. The present review is aimed to give a comprehensive overview of the actual status of the art of the diagnosis and treatment of this condition. As far as the origin of venous narrowing is concerned, phlebographic studies of the IJVs and AZ systems demonstrated that venous stenoses were likely to be truncular venous malformations; mostly, they are intraluminal defects such as malformed valve, septa webs. CCSVI condition has been found to be strongly associated with multiple sclerosis (MS), a disabling neurodegenerative and demyelinating disease considered autoimmune in nature. In several epidemiological observations performed at different latitudes on patients with different genetic backgrounds, the prevalence of CCSVI in MS ranges from 56% to 100%. To the contrary, by using venous MR and/or different Doppler protocols, CCSVI was not detected with the same prevalence. Two pilot studies demonstrated the safety and feasibility in Day Surgery of the endovascular treatment of CCSVI by means of balloon angioplasty (PTA). It determines a significant reduction of postoperative venous pressure. Restenosis rate was found out elevated in the IJVs, but negligible in the AZ. However, PTA seems to positively influence clinical and QoL parameters of the associated MS and warrants further randomized control trials.

  9. Patient with neuromyelitis optica and inflammatory demyelinating lesions comprising whole spinal cord from C2 level till conus: case report

    Directory of Open Access Journals (Sweden)

    Pavlisa Goran

    2009-10-01

    Full Text Available Abstract Background Neuromyelitis optica (NMO is an idiopathic, severe, inflammatory demyelinating disease of the central nervous system, that causes severe optic neuritis and myelitis attacks. Early discrimination between multiple sclerosis (MS and NMO is important, as optimum treatment for both diseases may differ considerably. Case Presentation We report a case of a patient who initially presented as longitudinally extensive transverse myelitis (LETM, having spastic upper extremities diparesis and spastic paraplegia, C2/C3 sensory level and urinary incontinence, as well as extensive inflammatory spinal cord lesions from C2 level to conus. After 5 months the patient had another attack of transverse myelitis, had electrophysiological findings consistent with optic neuritis, was seropositive for NMO-IgG (aquaporin-4 IgG and thus fulfilled NMO diagnostic criteria. Following treatment of disease attacks with pulse corticosteroid therapy and intravenous immunoglobulins, we included oral azathioprine in a combination with oral prednisone in the therapy. Since there was no significant clinical improvement, we decided to use cyclophosphamide therapy, which resulted in good clinical improvement and gradual decrease of cord swelling. Conclusion In this NMO case report we wanted to emphasize the extensiveness of inflammatory spinal cord changes in our patient, from C2 level to conus. In the conclusion it is important to say that accurate, early diagnosis and distinction from MS is critical to facilitate initiation of immunosuppressive therapy for attack prevention.

  10. Aquaporin-4 Immuneglobulin G testing in 36 consecutive Jamaican patients with inflammatory central nervous system demyelinating disease

    Directory of Open Access Journals (Sweden)

    Sherri Sandy

    2014-08-01

    Full Text Available Epidemiological studies of neuromyelitis optica (NMO in Jamaica are lacking. Here we reviewed the clinical records of 700 patients undergoing neurological evaluation at the Kingston Public Hospital, the largest tertiary institution in Jamaica over a 4 month period. We investigated the diagnostic utility of Aquaporin-4 ImmuneglobulinG (AQP4-IgG testing in 36 consecutive patients with a diagnosis of an inflammatory demyelinating disorder (IDD of the central nervous system (CNS. Patients were classified into 3 categories: i NMO, n=10; ii multiple sclerosis (MS, n=14 and iii unclassified IDD (n=12. All sera were tested for AQP-IgG status by cell binding assay (Euroimmun. No MS cases were positive. Ninety per cent of NMO cases were positive. Four of 12 patients with unclassified IDD tested positive for AQP4-IgG. AQP4-IgG seropositivity was associated with a lower socioeconomic status, higher EDSS (P=0.04 and lower pulmonary function than the seronegative cases (P=0.007. Aquaporin-4 autoimmunity may account for a significant proportion of Jamaican CNS IDDs.

  11. Quetiapine, an atypical antipsychotic, is protective against autoimmune-mediated demyelination by inhibiting effector T cell proliferation.

    Directory of Open Access Journals (Sweden)

    Feng Mei

    Full Text Available Quetiapine (Que, a commonly used atypical antipsychotic drug (APD, can prevent myelin from breakdown without immune attack. Multiple sclerosis (MS, an autoimmune reactive inflammation demyelinating disease, is triggered by activated myelin-specific T lymphocytes (T cells. In this study, we investigated the potential efficacy of Que as an immune-modulating therapeutic agent for experimental autoimmune encephalomyelitis (EAE, a mouse model for MS. Que treatment was initiated on the onset of MOG(35-55 peptide induced EAE mice and the efficacy of Que on modulating the immune response was determined by Flow Cytometry through analyzing CD4(+/CD8(+ populations and the proliferation of effector T cells (CD4(+CD25(- in peripheral immune organs. Our results show that Que dramatically attenuates the severity of EAE symptoms. Que treatment decreases the extent of CD4(+/CD8(+ T cell infiltration into the spinal cord and suppresses local glial activation, thereby diminishing the loss of mature oligodendrocytes and myelin breakdown in the spinal cord of EAE mice. Our results further demonstrate that Que treatment decreases the CD4(+/CD8(+ T cell populations in lymph nodes and spleens of EAE mice and inhibits either MOG(35-55 or anti-CD3 induced proliferation as well as IL-2 production of effector T cells (CD4(+CD25(- isolated from EAE mice spleen. Together, these findings suggest that Que displays an immune-modulating role during the course of EAE, and thus may be a promising candidate for treatment of MS.

  12. Is it necessary to perform connective tissue disorders laboratory tests when a patient experiences the first demyelinating attack?

    Directory of Open Access Journals (Sweden)

    Masoud Etemadifar

    2013-01-01

    Full Text Available Background: It may be difficult to differentiate between the first demyelinating attack and the neurological manifestations of connective tissue diseases. Materials and Methods: A total of 79 patients with optic neuritis were compared with 79 healthy controls. Their blood samples were tested for erythrocyte sedimentation rate (ESR, C-reactive protein (CRP, antiβ2-Glycoprotein I antibody (IgG, IgM, anticardiolipin antibody (IgM, IgG, lupus anticoagulant, anti-double strand DNA (anri-ds DNA, antinuclear antibody (ANA, anti-myeloperoxidae (p-ANCA, and anti-Proteinase 3 (C-ANCA. Results: In clinically isolated syndrome group β2-Glycoprotein (IgM and lupus anti-coagulant were positive in 1.3% of patients whereas ANA was positive in 1.3% and anti-β2-Glycoprotein I (IgM was positive in 2.5% of control group. No rheumatologic disease was found in objects with positive tests. Conclusion: This study shows no specific difference between two groups.

  13. TLR3 signaling is either protective or pathogenic for the development of Theiler's virus-induced demyelinating disease depending on the time of viral infection

    Directory of Open Access Journals (Sweden)

    Jin Young-Hee

    2011-12-01

    Full Text Available Abstract Background We have previously shown that toll-like receptor 3 (TLR3-mediated signaling plays an important role in the induction of innate cytokine responses to Theiler's murine encephalomyelitis virus (TMEV infection. In addition, cytokine levels produced after TMEV infection are significantly higher in the glial cells of susceptible SJL mice compared to those of resistant C57BL/6 mice. However, it is not known whether TLR3-mediated signaling plays a protective or pathogenic role in the development of demyelinating disease. Methods SJL/J and B6;129S-Tlr3tm1Flv/J (TLR3KO-B6 mice, and TLR3KO-SJL mice that TLR3KO-B6 mice were backcrossed to SJL/J mice for 6 generations were infected with Theiler's murine encephalomyelitis virus (2 × 105 PFU with or without treatment with 50 μg of poly IC. Cytokine production and immune responses in the CNS and periphery of infected mice were analyzed. Results We investigated the role of TLR3-mediated signaling in the protection and pathogenesis of TMEV-induced demyelinating disease. TLR3KO-B6 mice did not develop demyelinating disease although they displayed elevated viral loads in the CNS. However, TLR3KO-SJL mice displayed increased viral loads and cellular infiltration in the CNS, accompanied by exacerbated development of demyelinating disease, compared to the normal littermate mice. Late, but not early, anti-viral CD4+ and CD8+ T cell responses in the CNS were compromised in TLR3KO-SJL mice. However, activation of TLR3 with poly IC prior to viral infection also exacerbated disease development, whereas such activation after viral infection restrained disease development. Activation of TLR3 signaling prior to viral infection hindered the induction of protective IFN-γ-producing CD4+ and CD8+ T cell populations. In contrast, activation of these signals after viral infection improved the induction of IFN-γ-producing CD4+ and CD8+ T cells. In addition, poly IC-pretreated mice displayed elevated PDL-1 and

  14. Subcutaneous immunoglobulins in the treatment of chronic immune-mediated neuropathies

    Science.gov (United States)

    Leussink, Verena I.; Hartung, Hans-Peter; Kieseier, Bernd C.; Stettner, Mark

    2016-01-01

    Intravenous immunoglobulins represent an established therapy for the treatment of chronic immune-mediated neuropathies, specifically chronic inflammatory demyelinating polyradiculoneuropathies (CIDPs) as well as multifocal motor neuropathies (MMNs). For the treatment of antibody deficiency syndromes, subcutaneous immunoglobulins (SCIgs) have represented a mainstay for decades. An emerging body of evidence suggests that SCIg might also exhibit clinical efficacy in CIDP and MMN. This article reviews the current evidence for clinical effectiveness, as well as safety of SCIg for the treatment of immune-mediated neuropathies, and addresses remaining open questions in this context. We conclude that despite the need for controlled long-term studies to demonstrate long-term efficacy of SCIg in immune-mediated neuropathies, SCIg may already represent a potential therapeutic alternative for selected patients. PMID:27366241

  15. Characteristics of Optic Involvement in Central Nervous System Demyelinating Diseases%脱髓鞘性视神经病变的临床特征

    Institute of Scientific and Technical Information of China (English)

    吴茜; 陈博; 柯高潭; 李斌; 卜碧涛

    2015-01-01

    目的:回顾性分析脱髓鞘性视神经病变的临床特征。方法:收集我院特发性视神经炎(IDON)患者71例(IDON 组)、视神经脊髓炎(NMO)患者69例(NMO 组)、有视神经病变的多发性硬化(MS)患者64例(MS 组)共204例患者的临床资料。结果:本组中有17例 MS、26例 NMO 由 IDON 转化而来,但脱髓鞘性视神经病变也可发生在中枢神经系统脱髓鞘事件之后或者同时发生。 NMO 容易合并血清免疫学异常,MS 容易累及双侧视神经且以球后视神经病变多见,IDON 和 NMO 视功能障碍更为严重。随访生存分析表明,合并颅内病灶或血清免疫学异常的 IDON 患者转化为 MS 或 NMO 的风险明显高于其他正常患者。结论:脱髓鞘性视神经病变的诊断要严格遵循诊断流程,正确鉴别这3种疾病对制定治疗方案延缓疾病进展、降低致残率及判断预后具有重要意义。%Objective: To retrospectively analyze clinical features of demyelinating optic neuropathy. Methods:The data of 204 cases with demyelinating optic neuropathy were reviewed, including 71 patients with idiopathic optic neuritis (IDON), 69 cases with neuromyelitis optica (NMO), and 64 multiple sclerosis (MS) patients. Seven-teen cases of MS and 26 cases of NMO were transformed from IDON. Results: Demyelinating optic neuropathy occurred after the CNS demyelinating events or at the same time. Bilateral and retrobulbar optic neuritis were commonly seen in MS while the visual dysfunction in the ON and NMO patients were more severe than that in the MS cases. Follow-up survival analysis showed that the intracranial demyelinating lesions and abnormal serum immunological profiles in IDON were high risk factors for transforming into MS or NMO. Conclusion: Demyeli-nating optic neuropathy needs strict ophthalmological and neurological evaluation. Correct diagnosis is pivotal to the proper treatment and to predicting the outcome of

  16. Neurotrophic ACTH4-9 analogue therapy normalizes electroencephalographic alterations in chronic experimental allergic encephalomyelitis.

    Science.gov (United States)

    Duckers, H J; van Dokkum, R P; Verhaagen, J; van Luijtelaar, E L; Coenen, A M; Lopes da Silva, F H; Gispen, W H

    1998-12-01

    Chronic experimental allergic encephalomyelitis (CEAE) is an established experimental model for multiple sclerosis (MS). The demyelinating lesions in the white matter of the central nervous system observed in CEAE and in MS are accompanied by various neurophysiological alterations. Among the best defined electrophysiological abnormalities are the changes in event-related potentials, in particular evoked potentials involving the spinal cord, i.e. motor and sensory evoked potentials. Less familiar are the changes observed in the electroencephalogram of CEAE-affected animals, which are also encountered in the human equivalent, MS. In the present experiment we evaluated the therapeutic value of a neurotrophic peptide treatment [H-Met(O2)-Glu-His-Phe-D-Lys-Phe-OH, an ACTH4-9 analogue] and its effect on the delayed flash visual evoked potentials (VEP) and power spectra of the electroencephalogram, during a 17-week follow-up of CEAE. CEAE animals treated with the neurotrophic peptide were protected against the development of neurological symptoms during the course of the demyelinating syndrome. VEPs of animals suffering from CEAE showed a delay of the latencies of the late components which was significantly counteracted by peptide treatment. The peak-to-peak amplitude of the VEP afterdischarge recorded from CEAE animals was significantly increased during the course of CEAE and correlated closely with the progression of the myelinopathy. Furthermore, CEAE animals showed an increase of electroencephalogram (EEG) beta activity of up to 500% as compared with the age-matched control group. This increase in beta power mainly consisted of a prevailing 20-21 Hz peak, a frequency that normally is not dominant in control EEG recordings of the rat during passive wakefulness. All these electrophysiological phenomena were absent in ACTH4-9 analogue-treated animals. The present findings underscore the potential importance of a neurotrophic peptide treatment in the pharmacotherapy of

  17. Clinical analysis on 32 cases of chronic inflammatory demyelinating polyradiculoneuropathy%慢性吉兰-巴雷综合征32例临床分析

    Institute of Scientific and Technical Information of China (English)

    崔芳; 黄旭升; 陈朝晖; 刘淑贤

    2005-01-01

    目的总结慢性吉兰-巴雷综合征(CIDP)的临床表现、电生理、病理学等特点.方法对32例CIDP病例进行回顾性分析.结果多为亚急性或慢性起病,首发症状以肢体麻木或感觉异常、肢体无力最为多见,也有以复视、视物模糊、构音障碍和吞咽困难起病.常见的临床表现为进行性或复发性肌无力和感觉障碍,可合并有自主神经、颅神经受损,多数患者临床表现为对称性,少部分为非对称性.肌电图呈神经性受损改变,以运动及感觉神经传导速度减慢为主,部分伴有波幅下降.腓肠神经活检可见髓鞘脱失、髓鞘及胶原纤维增生.静脉滴注人血免疫球蛋白(IVIG)及糖皮质激素治疗有效.结论CIDP为广泛的周围神经损害,多数合并有自主神经损害,颅神经受损者并非少见.神经电生理表现为以脱髓鞘为主,部分伴有轴索变性.腓肠神经活检对CIDP具有重要的诊断价值.IVIG及糖皮质激素是目前治疗CIDP的有效方法.

  18. Improvement of hemoglobin levels after a switch from intravenous to subcutaneous administration of immunoglobulin in chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy

    DEFF Research Database (Denmark)

    Markvardsen, Lars Høj; Christiansen, Ingelise; Jakobsen, Johannes

    2016-01-01

    (Hb) and hemolytic variables. RESULTS: Seventeen patients completed the study. At enrollment, the Hb level was 138 ± 12 g/L, haptoglobin level was 1.4 ± 0.5 g/L, reticulocyte count was 58.7 × 10(9) ± 21.3 × 10(9) /L, and bilirubin level was 6.6 ± 2.3 µmol/L. The average of the two blood samples drawn.......9 × 10(9) ± 35.8 × 10(9) to 54.5 × 10(9) ± 16.3 × 10(9) /L (p = 0.02), and bilirubin decreasing from 7.3 ± 2.8 to 5.8 ± 1.8 µmol/L (p = 0.001). CONCLUSION: A switch from IVIG to SCIG was associated with a slight increase of Hb levels and an improvement of laboratory variables related to hemolytic...

  19. 儿童慢性炎症性脱髓鞘性多发性神经病一例%A child with chronic inflammatory demyelinating polyneuropathy (CIDP)

    Institute of Scientific and Technical Information of China (English)

    沈思翔; 冯建华; 周柏林; 水泉祥

    2003-01-01

    @@ 患儿女,13岁,因下肢乏力1个半月于2001年12月入院.1个半月前无明显诱因出现下肢乏力,上楼困难,步行1 km后觉乏力,有加重趋势,跑、跳困难,无发热、无咳嗽气急、无胸闷心悸、无抽搐、无大小便障碍、无四肢疼痛及麻木等感觉,病前无发热、咳嗽、腹泻等症状.

  20. 慢性炎症性脱髓鞘性多神经病的轴索损害%Axonal lesion in chronic inflammatory demyelinating polyneuropathy

    Institute of Scientific and Technical Information of China (English)

    栾兴华; 王毅敏; 郑日亮; 毕鸿雁; 袁云

    2007-01-01

    目的 探讨慢性炎症性脱髓鞘性多神经病(CIDP)的轴索病理改变.方法 对18例CIDP患者进行电生理和腓肠神经的病理检查,分析不同患者的腓肠神经病理改变特点,并对病理改变不同的两组进行临床、电生理及病理比较.结果 5例以脱髓鞘改变为主者,主要出现薄髓鞘神经纤维和有髓神经纤维的洋葱球样结构,其中3例出现轴索损害.8例以轴索损害为主者,主要出现有髓神经纤维的Wallerian变性和再生簇结构.3例出现有髓神经纤维的髓鞘和轴索混合性损害.2例轻微病理改变.脱髓鞘损害为主者和轴索损害为主者的单核细胞浸润程度无明显差异,且两者可同时存在脱髓鞘和轴索损害的电生理改变特点.结论 轴索损害是CIDP比较常见的病理改变,不应当作为该病的绝对排除标准.单核细胞的浸润是一种普遍改变.