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Sample records for charcot marie tooth

  1. Charcot-Marie-Tooth disease.

    LENUS (Irish Health Repository)

    Reilly, Mary M

    2011-03-01

    Charcot-Marie-Tooth (CMT) disease is the commonest inherited neuromuscular disorder affecting at least 1 in 2,500. Over the last two decades, there have been rapid advances in understanding the molecular basis for many forms of CMT with more than 30 causative genes now described. This has made obtaining an accurate genetic diagnosis possible but at times challenging for clinicians. This review aims to provide a simple, pragmatic approach to diagnosing CMT from a clinician\\'s perspective.

  2. Early Onset Charcot-Marie-Tooth Disease

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2005-06-01

    Full Text Available The clinical signs and genetic analysis of early-onset Charcot-Marie-Tooth disease (CMT in a 2-year-old boy and members of his family are reported from the Academic Medical Center, Amsterdam, and Sophia Children’s Hospital, Rotterdam, the Netherlands.

  3. Pediatric Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Jani-Acsadi, Agnes; Ounpuu, Sylvia; Pierz, Kristan; Acsadi, Gyula

    2015-06-01

    Heritable diseases of the peripheral nerves (Charcot-Marie-Tooth disease [CMT]) affect the motor units and sensory nerves, and they are among the most prevalent genetic conditions in the pediatric patient population. The typical clinical presentation includes distal muscle weakness and atrophy, but the severity and progression are largely variable. Improvements in supportive treatment have led to better preservation of patients' motor functions. More than 80 genes have been associated with CMT. These genetic discoveries, along with the developments of cellular and transgenic disease models, have allowed clinicians to better understand the disease mechanisms, which should lead to more specific treatments.

  4. Diagnosis of Charcot-Marie-Tooth Disease

    Directory of Open Access Journals (Sweden)

    Isabel Banchs

    2009-01-01

    Full Text Available Charcot-Marie-Tooth (CMT disease or hereditary motor and sensory neuropathy (HMSN is a genetically heterogeneous group of conditions that affect the peripheral nervous system. The disease is characterized by degeneration or abnormal development of peripheral nerves and exhibits a range of patterns of genetic transmission. In the majority of cases, CMT first appears in infancy, and its manifestations include clumsiness of gait, predominantly distal muscular atrophy of the limbs, and deformity of the feet in the form of foot drop. It can be classified according to the pattern of transmission (autosomal dominant, autosomal recessive, or X linked, according to electrophysiological findings (demyelinating or axonal, or according to the causative mutant gene. The classification of CMT is complex and undergoes constant revision as new genes and mutations are discovered. In this paper, we review the most efficient diagnostic algorithms for the molecular diagnosis of CMT, which are based on clinical and electrophysiological data.

  5. [Pathology of Charcot-Marie-Tooth Disease].

    Science.gov (United States)

    Oka, Nobuyuki

    2016-01-01

    Although genetic testing is available, nerve biopsy is useful in selected patients for the diagnosis of Charcot-Marie-Tooth disease (CMT). These are sporadic cases of hereditary neuropathy, or familial cases in which genetic testing is negative. CMT is caused by mutations of various genes. The pathological features of CMT have mostly been investigated using nerve biopsy, which may shed light on the presumed functions of mutated gene products. PMP22 duplication in CMT1A induces numerous large onion bulb lesions (OB). Compared to chronic inflammatory demyelinating polyradiculoneuropathy, the differential features of CMT1A are patchy distribution of OB and non-inflammatory lesions. CMT1B also manifests as OB, but presents abnormal compaction of myelin sheaths caused by uncompacted myelin or excessive myelin folding. CMT2 includes axonal neuropathies and many causative genes have been found. CMT2A (MFN2 mutation) shows abnormal mitochondria with a spherical morphology instead of tubular in the longitudinal direction. CMT4 consists of autosomal recessive forms with demyelinating pathology. Most subtypes have mutations of genes relating to myelin maintenance, and pathologically, they show abnormal folding of the myelin structure.

  6. ANESTHESIA FOR CHARCOT-MARIE-TOOTH DISEASE: CASE REPORT.

    Science.gov (United States)

    Alzaben, Khalid R; Samarah, Omar Q; Obeidat, Salameh S; Halhouli, Oday; Al Kharabsheh, Murad

    2016-06-01

    Charcot-Marie-Tooth disease comprises a group of disorders characterized by progressive muscle weakness and wasting. Reviewing the anaesthetic literature produced conflicting reports about the best anaesthetic options for patients with CMTD; as they are at increased risk of prolonged response to muscle relaxants, malignant hyperthermia and risks of regional anaesthesia. We present a case of the successful use of total intravenous anaesthesia with dexmedetomidine and propofol combined with caudal block using bupivacaine mixed with dexmedetomidine without any complications, for a 17 year old male patient with Charcot Marie-Tooth disease who underwent a lower limb orthopedic surgery.

  7. An Analysis of the Symptomatic Domains Most Relevant to Charcot Marie Tooth Neuropathy (CMT) Patients

    Science.gov (United States)

    2015-04-28

    Charcot Marie Tooth Disease (CMT); Hereditary Sensory and Motor Neuropathy; Nerve Compression Syndromes; Tooth Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Heredodegenerative Disorders, Nervous System

  8. Molecular Diagnosis of Charcot-Marie Tooth Disease

    Directory of Open Access Journals (Sweden)

    J. Gordon Millichap

    2002-02-01

    Full Text Available The frequency of mutations in certain genes in 153 unrelated patients with Charcot-Marie-Tooth disease (CMT was determined by DNA sequencing before clinical testing at the Departments of Molecular and Human Genetics and Pediatrics, Baylor College of Medicine, Houston, TX, and other centers.

  9. Quality-of-life in Charcot-Marie-Tooth disease: the patient's perspective.

    Science.gov (United States)

    Johnson, Nicholas E; Heatwole, Chad R; Dilek, Nuran; Sowden, Janet; Kirk, Callyn A; Shereff, Denise; Shy, Michael E; Herrmann, David N

    2014-11-01

    This study determines the impact of symptoms associated with Charcot-Marie-Tooth disease on quality-of-life. Charcot-Marie-Tooth patients in the Inherited Neuropathies Consortium Rare Diseases Clinical Research Network Contact Registry were surveyed. The survey inquired about 214 symptoms and 20 themes previously identified as important to Charcot-Marie-Tooth patients through patient interviews. Symptom population impact was calculated as the prevalence multiplied by the relative importance of each symptom identified. Prevalence and symptom impact were analyzed by age, symptom duration, gender, Charcot-Marie-Tooth type, and employment status. 407 participants returned the survey, identifying foot and ankle weakness (99.7%) and impaired balance (98.6%) as the most prevalent themes. Foot and ankle weakness and limitations with mobility were the themes with the highest impact. Both symptom prevalence and impact gradually increased with age and symptom duration. Several themes were more prevalent in women with Charcot-Marie-Tooth, including activity limitations, pain, fatigue, hip-thigh weakness, and gastrointestinal issues. All of the themes, except emotional or body image issues, were more prevalent among unemployed individuals. There were minimal differences in symptom prevalence between Charcot-Marie-Tooth types. There are multiple symptoms that impact Charcot-Marie-Tooth quality-of-life in adults. These symptoms have different levels of importance, are readily recognized by patients, and represent critical areas of Charcot-Marie-Tooth health.

  10. Phenotypic spectrum of dynamin 2 mutations in Charcot-Marie-Tooth neuropathy

    NARCIS (Netherlands)

    K.G. Claeys; S. Züchner; M. Kennerson; J. Berciano; A. Garcia; K. Verhoeven; E. Storey; J.R. Merory; H.M.E. Bienfait; M. Lammens; E. Nelis; J. Baets; E. de Vriendt; Z.N. Berneman; I. de Veuster; J.M. Vance; G. Nicholson; V. Timmerman; P. de Jonghe

    2009-01-01

    Dominant intermediate Charcot-Marie-Tooth neuropathy type B is caused by mutations in dynamin 2. We studied the clinical, haematological, electrophysiological and sural nerve biopsy findings in 34 patients belonging to six unrelated dominant intermediate Charcot-Marie-Tooth neuropathy type B familie

  11. Phenotypic spectrum of dynamin 2 mutations in Charcot-Marie-Tooth neuropathy.

    NARCIS (Netherlands)

    Claeys, K.G.; Zuchner, S.; Kennerson, M.; Berciano, J.; Garcia, A.; Verhoeven, K.; Storey, E.; Merory, J.R.; Bienfait, H.M.; Lammens, M.M.Y.; Nelis, E.; Baets, J.; Vriendt, E. De; Berneman, Z.N.; Veuster, I. De; Vance, J.M.; Nicholson, G.; Timmerman, V.; Jonghe, P. de

    2009-01-01

    Dominant intermediate Charcot-Marie-Tooth neuropathy type B is caused by mutations in dynamin 2. We studied the clinical, haematological, electrophysiological and sural nerve biopsy findings in 34 patients belonging to six unrelated dominant intermediate Charcot-Marie-Tooth neuropathy type B familie

  12. Charcot-Marie-Tooth disease complicating type 2 diabetes.

    LENUS (Irish Health Repository)

    Win, Htet Htet Ne

    2012-02-01

    Although both conditions are relatively common, there are very few descriptions of type 2 diabetes mellitus coexisting with Charcot-Marie-Tooth disease (CMT). This case report and literature review describes a 53-year-old Irish man who presented with type 2 diabetes and significant neuropathy, and who was subsequently diagnosed with CMT type 1A. This case report will also discuss how to differentiate diabetic neuropathy from a progressive hereditary neuropathy and how coexistence aggravates the progression of neuropathy thus necessitating early diagnosis.

  13. Charcot-marie-tooth disease complicating type 2 diabetes.

    LENUS (Irish Health Repository)

    Win, Htet Htet Ne

    2011-07-01

    Although both conditions are relatively common, there are very few descriptions of type 2 diabetes mellitus coexisting with Charcot-Marie-Tooth disease (CMT). This case report and literature review describes a 53-year-old Irish man who presented with type 2 diabetes and significant neuropathy, and who was subsequently diagnosed with CMT type 1A. This case report will also discuss how to differentiate diabetic neuropathy from a progressive hereditary neuropathy and how coexistence aggravates the progression of neuropathy thus necessitating early diagnosis.

  14. Charcot-Marie-Tooth disease type 1A

    DEFF Research Database (Denmark)

    Hertz, Jens Michael; Børglum, A D; Brandt, C A

    1994-01-01

    Charcot-Marie-Tooth disease type 1A (CMT1A) is an autosomal dominant peripheral neuropathy associated with a DNA duplication on chromosome 17p11.2-p12 in the majority of cases. Most of the sporadic cases are due to a de novo duplication. We have screened for this duplication in 11 Danish patients...... with CMT type 1, using four different techniques, and identified a de novo duplication in a sporadic case. Analysis of the fully informative pVAW409R3a alleles in this family showed the duplication to be of paternal origin....

  15. Charcot-Marie-Tooth and Related Diseases

    Science.gov (United States)

    ... of France, and Howard Henry Tooth of the United Kingdom. Although most people have never heard of CMT, ... CMT provided by patients and families. (See http://neurology.med. wayne.edu/neurogenetics/na_database. php.) MDA ...

  16. Charcot-Marie-Tooth disease: genetic and rehabilitation aspects

    Directory of Open Access Journals (Sweden)

    Mariana CEVEI

    2008-05-01

    Full Text Available Charcot-Marie-Tooth hereditary motor and sensory neuropathy refers to a group of disorders characterized by a chronic motor and sensory polyneuropathy. Typical cases have distal muscle weakness and peroneal atrophy often associated with mild to moderate sensory loss, depressed tendon reflexes, and pes cavus. Hereditary neuropathies are categorized by mode of inheritance and chromosomal locus. The diagnosis is based on family history, characteristic findings on physical examination, EMG, nerve conduction velocity testing, and occasionally on nerve biopsy. The disorder shows allelic and non-allelic genetic heterogeneity, thus mutations of different genes leading to the same clinical features. Also, different mutations of the same gene may lead to different phenotypes. Molecular genetic testing is available in clinical laboratories for diagnosis of 7 subtypes of the disease. Genetic counseling and risk assessment depend on the inheritance. We present two cases with Charcot-Marie-Tooth type 1 and type 2 respectively. There is no cure for the disorder, although physical therapy and moderate activity are often recommended to maintain muscle strength and endurance.

  17. Hand weakness in Charcot-Marie-Tooth disease 1X.

    LENUS (Irish Health Repository)

    Arthur-Farraj, P J

    2012-07-01

    There have been suggestions from previous studies that patients with Charcot-Marie-Tooth disease (CMT) have weaker dominant hand muscles. Since all studies to date have included a heterogeneous group of CMT patients we decided to analyse hand strength in 43 patients with CMT1X. We recorded handedness and the MRC scores for the first dorsal interosseous and abductor pollicis brevis muscles, median and ulnar nerve compound motor action potentials and conduction velocities in dominant and non-dominant hands. Twenty-two CMT1X patients (51%) had a weaker dominant hand; none had a stronger dominant hand. Mean MRC scores were significantly higher for first dorsal interosseous and abductor pollicis brevis in non-dominant hands compared to dominant hands. Median nerve compound motor action potentials were significantly reduced in dominant compared to non-dominant hands. We conclude that the dominant hand is weaker than the non-dominant hand in patients with CMT1X.

  18. Noncompaction Cardiomyopathy with Charcot-Marie-Tooth Disease

    Directory of Open Access Journals (Sweden)

    Sherif Ali Eltawansy

    2015-01-01

    Full Text Available We report a case of a 53-year-old female presenting with a new-onset heart failure that was contributed secondary to noncompaction cardiomyopathy. The diagnosis was made by echocardiogram and confirmed by cardiac MRI. Noncompaction cardiomyopathy (also known as ventricular hypertrabeculation is a newly discovered disease. It is considered to be congenital (genetic cardiomyopathy. It is usually associated with genetic disorders and that could explain the genetic pathogenesis of the non-compaction cardiomyopathy. Our case had a history of Charcot-Marie-Tooth disease. There is a high incidence of arrhythmia and embolic complications. The treatment usually consists of the medical management, defibrillator placement, and lifelong anticoagulation. Heart transplantation will be the last resort.

  19. Therapeutic options in Charcot-Marie-Tooth diseases.

    Science.gov (United States)

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

    2015-04-01

    Charcot-Marie-Tooth (CMT) diseases represent a heterogeneous genetic disorder (more than 80 genes are implicated in these inherited neuropathies), but sharing a similar phenotype. In recent years, advances in molecular genetics and molecular biology, and also the development of various animal models of CMT, have led to a better understanding. Taken together, this knowledge represents a prerequisite for the development of future therapies in CMT, and in peripheral nervous system disorders in general. The efficacy of various substances has been shown in vitro and also in vivo (in animal models); but, no significant positive effect has yet been confirmed in humans. However, some of these trials are still in development, and we may expect positive results in the future. Although CMT is still an incurable disease, symptomatic treatments (physiotherapy, surgery, analgesic, etc.) are crucial to improve the quality of life of CMT patients.

  20. De novo PMP2 mutations in families with type 1 Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Motley, William W; Palaima, Paulius; Yum, Sabrina W; Gonzalez, Michael A; Tao, Feifei; Wanschitz, Julia V; Strickland, Alleene V; Löscher, Wolfgang N; De Vriendt, Els; Koppi, Stefan; Medne, Livija; Janecke, Andreas R; Jordanova, Albena; Zuchner, Stephan; Scherer, Steven S

    2016-06-01

    We performed whole exome sequencing on a patient with Charcot-Marie-Tooth disease type 1 and identified a de novo mutation in PMP2, the gene that encodes the myelin P2 protein. This mutation (p.Ile52Thr) was passed from the proband to his one affected son, and segregates with clinical and electrophysiological evidence of demyelinating neuropathy. We then screened a cohort of 136 European probands with uncharacterized genetic cause of Charcot-Marie-Tooth disease and identified another family with Charcot-Marie-Tooth disease type 1 that has a mutation affecting an adjacent amino acid (p.Thr51Pro), which segregates with disease. Our genetic and clinical findings in these kindred demonstrate that dominant PMP2 mutations cause Charcot-Marie-Tooth disease type 1.

  1. Charcot-Marie-Tooth disease and intracellular traffic.

    Science.gov (United States)

    Bucci, Cecilia; Bakke, Oddmund; Progida, Cinzia

    2012-12-01

    Mutations of genes whose primary function is the regulation of membrane traffic are increasingly being identified as the underlying causes of various important human disorders. Intriguingly, mutations in ubiquitously expressed membrane traffic genes often lead to cell type- or organ-specific disorders. This is particularly true for neuronal diseases, identifying the nervous system as the most sensitive tissue to alterations of membrane traffic. Charcot-Marie-Tooth (CMT) disease is one of the most common inherited peripheral neuropathies. It is also known as hereditary motor and sensory neuropathy (HMSN), which comprises a group of disorders specifically affecting peripheral nerves. This peripheral neuropathy, highly heterogeneous both clinically and genetically, is characterized by a slowly progressive degeneration of the muscle of the foot, lower leg, hand and forearm, accompanied by sensory loss in the toes, fingers and limbs. More than 30 genes have been identified as targets of mutations that cause CMT neuropathy. A number of these genes encode proteins directly or indirectly involved in the regulation of intracellular traffic. Indeed, the list of genes linked to CMT disease includes genes important for vesicle formation, phosphoinositide metabolism, lysosomal degradation, mitochondrial fission and fusion, and also genes encoding endosomal and cytoskeletal proteins. This review focuses on the link between intracellular transport and CMT disease, highlighting the molecular mechanisms that underlie the different forms of this peripheral neuropathy and discussing the pathophysiological impact of membrane transport genetic defects as well as possible future ways to counteract these defects.

  2. Systematic review of exercise for Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Sman, Amy D; Hackett, Daniel; Fiatarone Singh, Maria; Fornusek, Ché; Menezes, Manoj P; Burns, Joshua

    2015-12-01

    Charcot-Marie-Tooth disease (CMT) is a slowly progressive hereditary degenerative disease and one of the most common neuromuscular disorders. Exercise may be beneficial to maintain strength and function for people with CMT, however, no comprehensive evaluation of the benefits and risks of exercise have been conducted. A systematic review was completed searching numerous electronic databases from earliest records to February 2015. Studies of any design including participants of any age with confirmed diagnosis of CMT that investigated the effects of exercise were eligible for inclusion. Of 13,301 articles identified following removal of duplicates, 11 articles including 9 unique studies met the criteria. Methodological quality of studies was moderate, sample sizes were small, and interventions and outcome measures used varied widely. Although the majority of the studies identified changes in one or more outcome measurements across exercise modalities, the majority were non-significant, possibly due to Type II errors. Significant effects described included improvements in strength, functional activities, and physiological adaptations following exercise. Despite many studies showing changes in strength and function following exercise, findings of this review should be met with caution due to the few studies available and moderate quality of evidence. Well-powered studies, harmonisation of outcome measures, and clearly described interventions across studies would improve the quality and comparability of the evidence base. The optimal exercise modality and intensity for people with CMT as well as the long-term safety of exercise remain unclear.

  3. The shifting paradigm of Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Echaniz-Laguna, A

    2015-01-01

    Molecular studies have created a paradigm shift in our perception of Charcot-Marie-Tooth disease (CMT). Indeed, CMT has evolved from the concept of a rather homogeneous hereditary disease exclusively involving peripheral nerves to the concept of a highly heterogeneous clinical and genetic syndrome mainly - but sometimes not exclusively - involving the peripheral nervous system. The phenotypic spectrum of CMT overlaps with other inherited neuropathies such as distal hereditary motor neuropathy (dHMN), hereditary sensory and autonomic neuropathy (HSAN), spinal muscular atrophy (SMA) subtypes, and the neuropathies of mitochondrial disorders. At a molecular level, mutations in one given gene may alternatively provoke CMT, HSAN, dHMN or SMA variants. Over the last years, there have been dramatic advances in deciphering the molecular basis for many CMT subtypes and more than 900 different mutations in more than 60 causative genes are now described. However, as 75% of CMT causative genes apparently remain unknown and as disease-specific therapies are not available, major advances are yet to come in the field of CMT.

  4. Mouse model for Charcot Marie-Tooth as a tool to better understand the disease

    OpenAIRE

    Barneo Muñoz, Manuela

    2016-01-01

    Introducción La enfermedad de Charcot-Marie-Tooth (CMT) es uno de los trastornos neurológicos hereditarios más comunes que afecta a 17-40 de cada 100.000 personas según poblaciones; concretamente esta cifra se sitúa en 28 personas de cada 100.000 en España. La enfermedad recibe el nombre de los tres médicos que la identificaron por primera vez en 1886; Jean-Marie Charcot y Pierre Marie en París, Francia y Howard Henry Tooth en Cambridge, Inglaterra. La enfermedad de CMT, también conocida c...

  5. Cx32 gene mutation associated with X-linked recessive Charcot-Marie-Tooth disease

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    The form of Charcot-Marie-Tooth (CMT) neuropathy that maps to Xq13 is X-linked dominant, or X-linked intermediate. Heterozygous females are more mildly affected than hemizygous males. It has been known that this type of CMT is caused by mutations of connexin32 (Cx32) gene. A typical X-linked recessive Charcot-Marie-Tooth Chinese family was analyzed with single strand conformation polymorphism method. A Cx32 gene point mutation, Arg15Gln, in exon 2 was identified in all affected family members, suggesting that this mutation is responsible for the CMT incidence of this family.

  6. A novel mutation in VCP causes Charcot-Marie-Tooth Type 2 disease.

    Science.gov (United States)

    Gonzalez, Michael A; Feely, Shawna M; Speziani, Fiorella; Strickland, Alleene V; Danzi, Matt; Bacon, Chelsea; Lee, Youjin; Chou, Tsui-Fen; Blanton, Susan H; Weihl, Conrad C; Zuchner, Stephan; Shy, Michael E

    2014-11-01

    Mutations in VCP have been reported to account for a spectrum of phenotypes that include inclusion body myopathy with Paget's disease of the bone and frontotemporal dementia, hereditary spastic paraplegia, and 1-2% of familial amyotrophic lateral sclerosis. We identified a novel VCP mutation (p.Glu185Lys) segregating in an autosomal dominant Charcot-Marie-Tooth disease type 2 family. Functional studies showed that the Glu185Lys variant impaired autophagic function leading to the accumulation of immature autophagosomes. VCP mutations should thus be considered for genetically undefined Charcot-Marie-Tooth disease type 2.

  7. A Rasch Analysis of the Charcot-Marie-Tooth Neuropathy Score (CMTNS) in a Cohort of Charcot-Marie-Tooth Type 1A Patients

    Science.gov (United States)

    Guedj, Mickaël; Bertrand, Viviane; Foucquier, Julie; Jouve, Elisabeth; Commenges, Daniel; Proust-Lima, Cécile; Murphy, Niall P.; Blin, Olivier; Magy, Laurent; Cohen, Daniel; Attarian, Shahram

    2017-01-01

    The Charcot-Marie-Tooth Neuropathy Score (CMTNS) was developed as a main efficacy endpoint for application in clinical trials of Charcot-Marie-Tooth disease type 1A (CMT1A). However, the sensitivity of the CMTNS for measuring disease severity and progression in CMT1A patients has been questioned. Here, we applied a Rasch analysis in a French cohort of patients to evaluate the psychometrical properties of the CMTNS. Overall, our analysis supports the validity of the CMTNS for application to CMT1A patients though with some limitations such as certain items of the CMTNS being more suitable for moderate to severe forms of the disease, and some items being disordered. We suggest that additional items and/or categories be considered to better assess mild-to-moderate patients. PMID:28095456

  8. Connexin32 gene mutations in X-linked dominant Charcot-Marie-Tooth disease (CMTX1)

    NARCIS (Netherlands)

    Janssen, EAM; Kemp, S; Hensels, GW; Sie, OG; deDieSmulders, CEM; Hoogendijk, JE; deVisser, M; Bolhuis, PA

    1997-01-01

    Single-strand conformational polymorphisms (SSCP) of the connexin32 gene were analyzed in 121 patients possibly affected by Charcot-Marie-Tooth (CMT) disease. The 121 patients were selected from 443 possible CMT/HNPP (hereditary neuropathy with liability to pressure palsies) patients based on geneti

  9. Charcot-Marie-Tooth disease: frequency of genetic subtypes and guidelines for genetic testing.

    LENUS (Irish Health Repository)

    Murphy, Sinead M

    2012-07-01

    Charcot-Marie-Tooth disease (CMT) is a clinically and genetically heterogeneous group of diseases with approximately 45 different causative genes described. The aims of this study were to determine the frequency of different genes in a large cohort of patients with CMT and devise guidelines for genetic testing in practice.

  10. Nerve Excitability Properties in Charcot-Marie-Tooth Disease Type 1A

    Science.gov (United States)

    Nodera, Hiroyuki; Bostock, Hugh; Kuwabara, Satoshi; Sakamoto, Takashi; Asanuma, Kotaro; Jia-Ying, Sung; Ogawara, Kazue; Hattori, Naoki; Hirayama, Masaaki; Kaji, Ryuji

    2004-01-01

    Charcot-Marie-Tooth disease type 1A (CMT1A) is commonly considered a prototype of a hereditary demyelinating polyneuropathy. Apart from the myelin involvement, there has been little information on axonal membrane properties in this condition. Taking advantage of the uniform nature of the disease process, we undertook the "in vivo" assessment of…

  11. Neuromuscular Hip Dysplasia in Charcot-Marie-Tooth Disease Type 1A

    Science.gov (United States)

    Bamford, Nigel S.; White, Klane K.; Robinett, Stephanie A.; Otto, Randolph K.; Gospe, Sidney M., Jr.

    2009-01-01

    Charcot-Marie-Tooth disease (CMT) is one of the most common inherited neurological disorders, affecting 36 in 100,000 people. CMT type 1A (hereditary motor and sensory neuropathy) is the most frequent form of this disease, affecting 60 to 80% of the CMT population, but its diagnosis may be delayed because of inconsistent clinical signs and…

  12. Effective cauda equina decompression in two siblings with Charcot-Marie-Tooth disease type 1B

    NARCIS (Netherlands)

    van Doormaal, Tristan P C; van Ruissen, Fred; Miller, Kai J; Hoogendijk, Jessica E

    2016-01-01

    Two siblings with Charcot-Marie-Tooth (CMT) 1B due to a c.517G>C (p.Gly173Arg) mutation in the MPZ gene both developed an acute cauda syndrome with unbearable back pain radiating to both legs, progressive muscle weakness of the legs, and saddle hypesthesia with fecal and urinary incontinence. MRI sh

  13. Charcot-Marie-Tooth disease: The development of a diagnostic platform using next generation sequencing

    DEFF Research Database (Denmark)

    Christensen, Rikke; Væth, Signe; Thorsen, Kasper;

    Background: Charcot-Marie-Tooth Disease (CMT) is one of the most common inherited neurological diseases. Today, more than 70 CMT related genes are known to cause inherited neuropathy. The diagnostic strategy in most laboratories is based on Sanger-sequencing of few genes. In our patient cohort...

  14. [PREGNANCY AND DELIVERY IN A PATIENT WITH CHARCOT-MARIE-TOOTH DISEASE].

    Science.gov (United States)

    Pehlivanov, B; Matev, M

    2016-01-01

    We report a case of a 34 years old primigravida with Charcot-Marie-Tooth disease (CMTD). The course of pregnancy was uneventful with no deterioration of symptoms due to the disease. Performed amniocentesis showed healthy fetus. Planned cesarean section with spinal anesthesia was performed because of the restricted pelvis. The possible issues of combination pregnancy and CMTD are discussed.

  15. Hand involvement in children with Charcot-Marie-Tooth disease type 1A

    NARCIS (Netherlands)

    Burns, Joshua; Bray, Paula; Cross, Lauren A.; North, Kathryn N.; Ryan, Monique M.; Ouvrier, Robert A.

    2008-01-01

    Charcot-Marie-Tooth disease type 1A (CMT1A), a demyelinating neuropathy characterised by progressive length-dependent muscle weakness and atrophy, is thought to affect the foot and leg first followed some time later by hand weakness and dysfunction. We aimed to characterise hand Strength, function a

  16. Dysfunction in the hip joints in children with Charcot-Marie-Tooth syndrome (literature review

    Directory of Open Access Journals (Sweden)

    Иван Юрьевич Поздникин

    2015-09-01

    Full Text Available A review of the literature on the treatment of children with dysfunction in the hip joints in motor-sensory neuropathy Charcot-Marie-Tooth is presented. Peculiarities of disease diagnosis and the approach used in the treatment of patients are described. The Charcot-Marie-Tooth syndrome is a hereditary neuromuscular disease characterized by progressive atrophy of the distal muscle group of the lower limbs. According to international authors, the incidence of hip joint dysfunction in this condition is at least 10%, ranking second only to foot deformities. In the Russian literature, the problem has not been adequately interpreted. Early diagnosis of dysfunction in the hip joints during Charcot-Marie-Tooth syndrome is complicated by the child's age and is characterized by progression. Conflicting clinical signs and trivial symptoms of the disease also confuse diagnosis, until it becomes clearer in adolescence or the second or third decade of life. Surgical reconstructive operations on the hip joint often occur too late, and they are accompanied by a greater frequency of neurological complications. Practitioner awareness coupled with an early diagnosis of hip subluxation and decentration and complex orthopedic and neurological examinations of children with the disease of Charcot-Marie-Tooth should result in more favorable outcomes.

  17. Mutations in the MORC2 gene cause axonal Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Sevilla, Teresa; Lupo, Vincenzo; Martínez-Rubio, Dolores; Sancho, Paula; Sivera, Rafael; Chumillas, María J; García-Romero, Mar; Pascual-Pascual, Samuel I; Muelas, Nuria; Dopazo, Joaquín; Vílchez, Juan J; Palau, Francesc; Espinós, Carmen

    2016-01-01

    Charcot-Marie-Tooth disease (CMT) is a complex disorder with wide genetic heterogeneity. Here we present a new axonal Charcot-Marie-Tooth disease form, associated with the gene microrchidia family CW-type zinc finger 2 (MORC2). Whole-exome sequencing in a family with autosomal dominant segregation identified the novel MORC2 p.R190W change in four patients. Further mutational screening in our axonal Charcot-Marie-Tooth disease clinical series detected two additional sporadic cases, one patient who also carried the same MORC2 p.R190W mutation and another patient that harboured a MORC2 p.S25L mutation. Genetic and in silico studies strongly supported the pathogenicity of these sequence variants. The phenotype was variable and included patients with congenital or infantile onset, as well as others whose symptoms started in the second decade. The patients with early onset developed a spinal muscular atrophy-like picture, whereas in the later onset cases, the initial symptoms were cramps, distal weakness and sensory impairment. Weakness and atrophy progressed in a random and asymmetric fashion and involved limb girdle muscles, leading to a severe incapacity in adulthood. Sensory loss was always prominent and proportional to disease severity. Electrophysiological studies were consistent with an asymmetric axonal motor and sensory neuropathy, while fasciculations and myokymia were recorded rather frequently by needle electromyography. Sural nerve biopsy revealed pronounced multifocal depletion of myelinated fibres with some regenerative clusters and occasional small onion bulbs. Morc2 is expressed in both axons and Schwann cells of mouse peripheral nerve. Different roles in biological processes have been described for MORC2. As the silencing of Charcot-Marie-Tooth disease genes have been associated with DNA damage response, it is tempting to speculate that a deregulation of this pathway may be linked to the axonal degeneration observed in MORC2 neuropathy, thus adding a

  18. ALS5/SPG11/KIAA1840 mutations cause autosomal recessive axonal Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Montecchiani, Celeste; Pedace, Lucia; Lo Giudice, Temistocle; Casella, Antonella; Mearini, Marzia; Gaudiello, Fabrizio; Pedroso, José L; Terracciano, Chiara; Caltagirone, Carlo; Massa, Roberto; St George-Hyslop, Peter H; Barsottini, Orlando G P; Kawarai, Toshitaka; Orlacchio, Antonio

    2016-01-01

    Charcot-Marie-Tooth disease is a group of hereditary peripheral neuropathies that share clinical characteristics of progressive distal muscle weakness and atrophy, foot deformities, distal sensory loss, as well as diminished tendon reflexes. Hundreds of causative DNA changes have been found, but much of the genetic basis of the disease is still unexplained. Mutations in the ALS5/SPG11/KIAA1840 gene are a frequent cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum and peripheral axonal neuropathy, and account for ∼ 40% of autosomal recessive juvenile amyotrophic lateral sclerosis. The overlap of axonal Charcot-Marie-Tooth disease with both diseases, as well as the common autosomal recessive inheritance pattern of thin corpus callosum and axonal Charcot-Marie-Tooth disease in three related patients, prompted us to analyse the ALS5/SPG11/KIAA1840 gene in affected individuals with autosomal recessive axonal Charcot-Marie-Tooth disease. We investigated 28 unrelated families with autosomal recessive axonal Charcot-Marie-Tooth disease defined by clinical, electrophysiological, as well as pathological evaluation. Besides, we screened for all the known genes related to axonal autosomal recessive Charcot-Marie-Tooth disease (CMT2A2/HMSN2A2/MFN2, CMT2B1/LMNA, CMT2B2/MED25, CMT2B5/NEFL, ARCMT2F/dHMN2B/HSPB1, CMT2K/GDAP1, CMT2P/LRSAM1, CMT2R/TRIM2, CMT2S/IGHMBP2, CMT2T/HSJ1, CMTRID/COX6A1, ARAN-NM/HINT and GAN/GAN), for the genes related to autosomal recessive hereditary spastic paraplegia with thin corpus callosum and axonal peripheral neuropathy (SPG7/PGN, SPG15/ZFYVE26, SPG21/ACP33, SPG35/FA2H, SPG46/GBA2, SPG55/C12orf65 and SPG56/CYP2U1), as well as for the causative gene of peripheral neuropathy with or without agenesis of the corpus callosum (SLC12A6). Mitochondrial disorders related to Charcot-Marie-Tooth disease type 2 were also excluded by sequencing POLG and TYMP genes. An additional locus for autosomal recessive Charcot-Marie-Tooth

  19. De Novo duplication in Charcot-Marie-Tooth Type 1A

    Energy Technology Data Exchange (ETDEWEB)

    Mandich, P.; Bellone, E.; Ajmar, F. [and others

    1996-09-01

    We read with interest the paper on {open_quotes}Prevalence and Origin of De Novo Duplications in Charcot-Marie-Tooth Disease Type 1A: First Report of a De Novo Duplication with a Maternal Origin,{close_quotes}. They reported their experience with 10 sporadic cases of Charcot-Marie-Tooth type 1A (CMT1A) in which it was demonstrated that the disease had arisen as the result of a de novo duplication. They analyzed the de novo-duplication families by using microsatellite markers and identified the parental origin of the duplication in eight cases. In one family the duplication was of maternal origin, whereas in the remaining seven cases it was of paternal origin. The authors concluded that their report was the first evidence of a de novo duplication of maternal origin, suggesting that this is not a phenomenon associated solely with male meiosis. 7 refs.

  20. 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.

  1. Refined genetic mapping of X-linked Charcot-Marie-Tooth neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Fain, P.R.; Barker, D.F.; Chance, P.F. (Univ. of Utah, School of Medicine, Salt Lake City, UT (United States))

    1994-02-01

    Genetic linkage studies were conducted in four multigenerational families with X-linked Charcot-Marie-Tooth disease (CMTX), using 12 highly polymorphic short-tandem-repeat markers for the pericentromeric region of the X Chromosome. Pairwise linkage analysis with individual markers confirmed tight linkage of CMTX to the pericentromeric region in each family. Multipoint analyses strongly support the order DXS337-CMTX-DXS441-(DXS56, PGK1). 38 refs., 2 figs., 1 tab.

  2. Laparoscopic appendectomy in a pediatric patient with type 1 Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Heller, Joshua A; Marn, Richard Y

    2015-12-01

    A pediatric patient with type 1 Charcot-Marie-Tooth disease-a disorder associated with a demyelinating polyneuropathy-presented for laparoscopic appendectomy in the setting of acute appendicitis. Induction and maintenance of anesthesia were successfully managed without the use of any depolarizing or nondepolarizing neuromuscular blocking agents. The patient was successfully extubated at the completion of the procedure without any respiratory or neuromuscular sequelae, with excellent pain control and no postoperative nausea or vomiting.

  3. Surgical Treatment of Scoliosis in Patients with Charcot-Marie-Tooth Disease

    Institute of Scientific and Technical Information of China (English)

    Farzad Omidi Kashani; Ibrahim Ghayem Hasankhani; Mahdi Banaii

    2009-01-01

    Objective: Apparently, scoliosis occurs in approximately one-third of patients with Charcot-Marie-Tooth disease. Little is known about the response of these curves to treatment. The purpose of this study was to evaluate the results of spinal surgery in these peculiar patients. Methods: We retrospectively evaluated the results of spinal surgery in eight patients who had scoliosis due to clinically and electrophysiologically proven Charcot-Marie-Tooth disease. Radiographs were reviewed. The location and direction of the curve pattern, the age at the time of surgery, type of surgery, number of levels fused, instrumentations used, intra or postoperative complications, and results and need for reoperation were recorded. Results: Eight patients associated with Charcot-Marie-Tooth disease who underwent scoliotic surgery were identified. The average age and curve at the time of surgery were 21.1 years and 56.4° respectively. 62.5% of the curves had left thoracic component and more than one third was associated with thoracic hyperkyphosis. Long posterior spinal fusion was performed most often, with an average of 11.5 spinal segments fused. Instrumentation was used in all posterior fusions. At an average of 39 months (range, 24 to 72 months) postoperatively, the fusion appeared to be solid in all patients. Conclusion: Scoliosis in patients with Charcot-Marie-Tooth disease differs from that in patients with idiopathic scoliosis in regarding to the etiology and the prevalence of thoracic hyperkyphosis, but the surgical management appears to be similar. Spondylodesis does not appear to be associated with a high rate of complications.

  4. Overlapping molecular pathological themes link Charcot-Marie-Tooth neuropathies and hereditary spastic paraplegias.

    Science.gov (United States)

    Timmerman, Vincent; Clowes, Virginia E; Reid, Evan

    2013-08-01

    In this review we focus on Charcot-Marie-Tooth (CMT) neuropathies and hereditary spastic paraplegias (HSPs). Although these diseases differ in whether they primarily affect the peripheral or central nervous system, both are genetically determined, progressive, long axonopathies that affect motor and sensory pathways. This commonality suggests that there might be similarities in the molecular pathology underlying these conditions, and here we compare the molecular genetics and cellular pathology of the two groups.

  5. 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...

  6. Charcot-Marie-Tooth disease and posterior scleritis: a case report Doença de Charcot-Marie-Tooth e esclerite posterior: relato de caso

    Directory of Open Access Journals (Sweden)

    Elisabeth N. Martins

    2000-10-01

    Full Text Available Purpose: To describe the unusual association of Charcot-Marie-Tooth disease (CMTD and posterior scleritis. Methods: Case report of a 16-year-old female with decreased visual acuity and pain in both eyes. Results: Ophthalmologic examination showed a posterior scleritis, confirmed by ultrasound and angiofluoresceinography. Foot deformities and sensory dysfunction were identified in the patient and some of her relatives. The diagnosis of CMTD in this patient was confirmed by eletrophysiologic studies. Conclusions: The association of posterior scleritis in a patient with CMTD has never been reported. This is also the first description of an inflammatory ocular disease in these patients.Objetivo: Descrever a associação entre doença de Charcot-Marie-Tooth (DCMT e esclerite posterior. Metodologia: Relato de caso de uma paciente do sexo feminino, 16 anos de idade, com baixa de acuidade visual e dor em ambos os olhos. Resultados: O exame oftalmológico revelou esclerite posterior, observada também por ultra-som e angiofluoresceinografia. Deformidades de pernas e pés foram identificadas na paciente e em seus familiares. O diagnóstico de DCMT na paciente estudada foi confirmado por estudos eletrofisiológicos. Conclusões: A presença de esclerite posterior em paciente com DCMT não é descrita na literatura, não se encontrando também relatos de outras doenças oculares inflamatórias, nestes pacientes.

  7. Charcot-Marie-Tooth Disease Type 2B

    Directory of Open Access Journals (Sweden)

    Şenay Durdu

    2009-06-01

    Full Text Available Chatcot-Marie-Tooth (CMT is also known as peroneal muscular atrophy and hereditary motor-sensory neuropathy (HMSN. It is the most commonly encountered inherited peripheral neuropathy. Actually, CMT is not a single disease, but is a group of disorders with similar symptoms. CMT type 2 is the second most common form after CMT type1. Symptoms usually begin in childhood or early adulthood. Mostly the peripheral nerves of the lower extremities and occasionaly upper extremities may be affected. Motor nerve involvoment induces distal muscle weakness and atrophy in the lower extremities that may result in foot deformities known as foot drop, pes cavus, pes planus, hammer toe etc. As a result of sensorial nevre degeneration, callus, recurrent foot ulcers, osteonecrosis, osteolysis and spontaneous amputation may accompany the disease. The speed of nerve conduction is not changed in the EMG, but axonal type sensorymotor semptoms that lead to a decrease of amplitude. We report here a 55 year old man with recurrent foot ulcers for 33 years and self amputations, whose EMG findings suggest acsonal neuropathy and who also has a 20 year - old son with similar complaints.

  8. A novel transgenic mouse model of Chinese Charcot-Marie-Tooth disease type 2L

    Institute of Scientific and Technical Information of China (English)

    Ruxu Zhang; Qian Pan; Beisha Tang; Fufeng Zhang; Xiaobo Li; Shunxiang Huang; Xiaohong Zi; Ting Liu; Sanmei Liu; Xuning Li; Kun Xia

    2014-01-01

    We previously found that the K141N mutation in heat shock protein B8 (HSPB8) was respon-sible for Charcot-Marie-Tooth disease type 2L in a large Chinese family. The objective of the present study was to generate a transgenic mouse model bearing the K141N mutation in the human HSPB8 gene, and to determine whether this K141NHSPB8 transgenic mouse model would manifest the clinical phenotype of Charcot-Marie-Tooth disease type 2L, and consequently be suitable for use in studies of disease pathogenesis. Transgenic mice overexpressing K141NHSPB8 were generated using K141N mutant HSPB8 cDNA cloned into a pCAGGS plasmid driven by a human cytomegalovirus expression system. PCR and western blot analysis conifrmed integra-tion of the K141NHSPB8 gene and widespread expression in tissues of the transgenic mice. The K141NHSPB8 transgenic mice exhibited decreased muscle strength in the hind limbs and impaired motor coordination, but no obvious sensory disturbance at 6 months of age by behavioral assess-ment. Electrophysiological analysis showed that the compound motor action potential amplitude in the sciatic nerve was signiifcantly decreased, but motor nerve conduction velocity remained normal at 6 months of age. Pathological analysis of the sciatic nerve showed reduced myelinated ifber density, notable axonal edema and vacuolar degeneration in K141NHSPB8 transgenic mice, suggesting axonal involvement in the peripheral nerve damage in these animals. These ifndings indicate that the K141NHSPB8 transgenic mouse successfully models Charcot-Marie-Tooth disease type 2L and can be used to study the pathogenesis of the disease.

  9. The Gdap1 knockout mouse mechanistically links redox control to Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Niemann, Axel; Huber, Nina; Wagner, Konstanze M; Somandin, Christian; Horn, Michael; Lebrun-Julien, Frédéric; Angst, Brigitte; Pereira, Jorge A; Halfter, Hartmut; Welzl, Hans; Feltri, M Laura; Wrabetz, Lawrence; Young, Peter; Wessig, Carsten; Toyka, Klaus V; Suter, Ueli

    2014-03-01

    The ganglioside-induced differentiation-associated protein 1 (GDAP1) is a mitochondrial fission factor and mutations in GDAP1 cause Charcot-Marie-Tooth disease. We found that Gdap1 knockout mice (Gdap1(-/-)), mimicking genetic alterations of patients suffering from severe forms of Charcot-Marie-Tooth disease, develop an age-related, hypomyelinating peripheral neuropathy. Ablation of Gdap1 expression in Schwann cells recapitulates this phenotype. Additionally, intra-axonal mitochondria of peripheral neurons are larger in Gdap1(-/-) mice and mitochondrial transport is impaired in cultured sensory neurons of Gdap1(-/-) mice compared with controls. These changes in mitochondrial morphology and dynamics also influence mitochondrial biogenesis. We demonstrate that mitochondrial DNA biogenesis and content is increased in the peripheral nervous system but not in the central nervous system of Gdap1(-/-) mice compared with control littermates. In search for a molecular mechanism we turned to the paralogue of GDAP1, GDAP1L1, which is mainly expressed in the unaffected central nervous system. GDAP1L1 responds to elevated levels of oxidized glutathione by translocating from the cytosol to mitochondria, where it inserts into the mitochondrial outer membrane. This translocation is necessary to substitute for loss of GDAP1 expression. Accordingly, more GDAP1L1 was associated with mitochondria in the spinal cord of aged Gdap1(-/-) mice compared with controls. Our findings demonstrate that Charcot-Marie-Tooth disease caused by mutations in GDAP1 leads to mild, persistent oxidative stress in the peripheral nervous system, which can be compensated by GDAP1L1 in the unaffected central nervous system. We conclude that members of the GDAP1 family are responsive and protective against stress associated with increased levels of oxidized glutathione.

  10. Atypical presentation of Charcot-Marie-Tooth disease 1A: A case report.

    Science.gov (United States)

    Kulkarni, Shilpa D; Sayed, Rafat; Garg, Meenal; Patil, Varsha A

    2015-11-01

    Charcot-Marie-Tooth (CMT) 1A is the most common form of CMT disease and is characterized by duplication of Peripheral myelin protein 22 (PMP22) gene. We report a boy with genetically confirmed CMT1A disease having clinical involvement of hypoglossal and glossopharyngeal nerves, as well as asymmetrical and primarily upper limb involvement. These atypical features widen the clinical spectrum of CMT1A, leading to interesting observations about PMP22 gene related disorders and varied clinical expression of similar genetic mutations.

  11. Malignant melanoma and Charcot-Marie-Tooth disease: A further case

    Energy Technology Data Exchange (ETDEWEB)

    Manoukian, S.; Briscioli, V.; Lalatta, F. [Instituti Clinici di Perfezionamento, Milan (Italy)

    1997-01-20

    In a previous issue of this journal, Greene et al. described 2 patients with Charcot-Marie-Tooth (CMT) disease who later developed cutaneous malignant melanoma. Although the development of the two diseases in the same patient may have occurred by chance, the authors raised the possibility of a shared neural crest defect or a genetic linkage. Among the patients reported by Greene et al., one had a dominant form of CMT. The patient`s mother and brother were similarly affected. A paternal aunt died of melanoma. The second patient had a neuronal type of CMT. His brother showed the same disease, but the parents were not examined. 7 refs.

  12. Sport activity in Charcot-Marie-Tooth disease: A case study of a Paralympic swimmer.

    Science.gov (United States)

    Vita, Giuseppe; La Foresta, Stefania; Russo, Massimo; Vita, Gian Luca; Messina, Sonia; Lunetta, Christian; Mazzeo, Anna

    2016-09-01

    This study reports the positive physical, emotional and psychosocial changes induced by sport activity in a Paralympic swimmer with Charcot-Marie-Tooth (CMT) type 4A. When we compared evaluations before initiating sport activity with those after five years of competitive activity, we found: i) increased proximal muscles strength of upper limbs; ii) augmented ability to propel wheelchair independently; iii) improved quality of life; iv) reduced trait anxiety and striking improvement of depression; v) enhanced self-esteem. Longitudinal studies in large cohorts to evaluate the positive effects of sport activity are needed to support provision of evidence-based advice to patients and families.

  13. Pes Cavus and Charcot Marie Tooth Disease: A Case Report and Brief Review of the Literature

    Directory of Open Access Journals (Sweden)

    Levent Ediz

    2011-09-01

    Full Text Available Charcot-Marie-Tooth (CMT is a disease that is highly heterogeneous, both clinically and genetically. Clinical and electrophysiological data are essential for diagnosis. Children with CMT experience acquired foot weakness, contracture and deformity (pes cavus and hammer toes from an early age. Early intervention targeting the foot and ankle may prevent long-term disability in CMT. Here we present a CMT patient with acquired pes cavus and hammer toes and review the literature briefly for diagnosis, treatment, and rehabilitation of CMT. As a result we conclude that CMT should also come into mind in the differential diagnosis of acquired pes cavus and hammer toes.

  14. Assignment of a second Charcot-Marie-Tooth type II locus to chromosome 3q

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, J.M.; Elliott, J.L.; Yee, W.C. [Washington Univ. School of Medicine, St. Louis, MO (United States)] [and others

    1995-10-01

    Charcot-Marie-Tooth disease (CMT) is the most common inherited motor and sensory neuropathy. The neuronal form of this disorder is referred to as Charcot-Marie-Tooth type II disease (CMT2). CMT2 is usually inherited as an autosomal dominant trait with a variable age at onset of symptoms associated with progressive axonal neuropathy. In some families, the locus that predisposes to CMT2 has been demonstrated to map to the distal portion of the short arm of chromosome 1. Other families with CMT2 do not show linkage with 1p markers, suggesting genetic heterogeneity in CMT2. We investigated linkage in a single large kindred with autosomal dominant CMT2. The gene responsible for CMT2 in this kindred (CMT2B) was mapped to the interval between the microsatellite markers D3S1769 and D3S1744 in the 3q13-22 region. Study of additional CMT2 kindreds should serve to further refine the disease gene region and may ultimately lead to the identification of a gene defect that underlies the CMT2 phenotype. 21 refs., 3 figs., 1 tab.

  15. Copy Number Variations in a Population-Based Study of Charcot-Marie-Tooth Disease

    Directory of Open Access Journals (Sweden)

    Helle Høyer

    2015-01-01

    Full Text Available Copy number variations (CNVs are important in relation to diversity and evolution but can sometimes cause disease. The most common genetic cause of the inherited peripheral neuropathy Charcot-Marie-Tooth disease is the PMP22 duplication; otherwise, CNVs have been considered rare. We investigated CNVs in a population-based sample of Charcot-Marie-Tooth (CMT families. The 81 CMT families had previously been screened for the PMP22 duplication and point mutations in 51 peripheral neuropathy genes, and a genetic cause was identified in 37 CMT families (46%. Index patients from the 44 CMT families with an unknown genetic diagnosis were analysed by whole-genome array comparative genomic hybridization to investigate the entire genome for larger CNVs and multiplex ligation-dependent probe amplification to detect smaller intragenomic CNVs in MFN2 and MPZ. One patient had the pathogenic PMP22 duplication not detected by previous methods. Three patients had potentially pathogenic CNVs in the CNTNAP2, LAMA2, or SEMA5A, that is, genes related to neuromuscular or neurodevelopmental disease. Genotype and phenotype correlation indicated likely pathogenicity for the LAMA2 CNV, whereas the CNTNAP2 and SEMA5A CNVs remained potentially pathogenic. Except the PMP22 duplication, disease causing CNVs are rare but may cause CMT in about 1% (95% CI 0–7% of the Norwegian CMT families.

  16. Reliability of the CMT neuropathy score (second version) in Charcot-Marie-Tooth disease.

    LENUS (Irish Health Repository)

    Murphy, Sinéad M

    2011-09-01

    The Charcot-Marie-Tooth neuropathy score (CMTNS) is a reliable and valid composite score comprising symptoms, signs, and neurophysiological tests, which has been used in natural history studies of CMT1A and CMT1X and as an outcome measure in treatment trials of CMT1A. Following an international workshop on outcome measures in Charcot-Marie-Tooth disease (CMT), the CMTNS was modified to attempt to reduce floor and ceiling effects and to standardize patient assessment, aiming to improve its sensitivity for detecting change over time and the effect of an intervention. After agreeing on the modifications made to the CMTNS (CMTNS2), three examiners evaluated 16 patients to determine inter-rater reliability; one examiner evaluated 18 patients twice within 8 weeks to determine intra-rater reliability. Three examiners evaluated 63 patients using the CMTNS and the CMTNS2 to determine how the modifications altered scoring. For inter- and intra-rater reliability, intra-class correlation coefficients (ICCs) were ≥0.96 for the CMT symptom score and the CMT examination score. There were small but significant differences in some of the individual components of the CMTNS compared with the CMTNS2, mainly in the components that had been modified the most. A longitudinal study is in progress to determine whether the CMTNS2 is more sensitive than the CMTNS for detecting change over time.

  17. A family with Charcot-Marie-Tooth disease (type 1: evaluating diagnostic role of nerve conduction studies

    Directory of Open Access Journals (Sweden)

    Sangeeta Gupta

    2014-06-01

    Full Text Available We aimed to report a case history of a family with Charcot-Marie-Tooth disease and to assess the role of nerve conduction studies in the diagnosis. A 10-year-old girl presented with difficulty in walking with a history of delayed motor milestones and slowly progressive weakness in distal muscles of both the lower limbs, with similar group of complaints in her father and a younger brother. Clinical examination of the patients was done and nerve conduction studies were performed. Clinical features and nerve conduction studies suggested the diagnosis as Charcot-Marie-Tooth disease with characteristic electro-diagnostic findings of Charcot-Marie-Tooth disease type-1. Charcot-Marie-Tooth disease is a rare disorder found in India. Although genetic tests form the basis of accurate diagnosis, yet nerve conduction studies, to a great extent, prove to be remarkable in approaching the diagnosis and distinguishing the common subtypes of this rare condition. [Int J Res Med Sci 2014; 2(3.000: 1147-1150

  18. Postural instability in Charcot-Marie-Tooth type 1A patients is strongly associated with reduced somatosensation.

    NARCIS (Netherlands)

    Linden, M.H. van der; Linden, S.C. van der; Hendricks, H.T.; Engelen, B.G.M. van; Geurts, A.C.H.

    2010-01-01

    In order to determine the influence of somatosensory impairments, due to the loss of large myelinated fibres, on the postural stability of Charcot-Marie-Tooth 1A (CMT) patients, a cross-sectional balance assessment was done. Nine CMT patients were compared with eight patients with a distal type of S

  19. Spine deformities in Charcot-Marie-Tooth 4C caused by SH3TC2 gene mutations.

    NARCIS (Netherlands)

    Azzedine, H.; Ravise, N.; Verny, C.; Gabreëls-Festen, A.A.W.M.; Lammens, M.M.Y.; Grid, D.; Vallat, J.M.; Durosier, G.; Senderek, J.; Nouioua, S.; Hamadouche, T.; Bouhouche, A.; Guilbot, A.; Stendel, C.; Ruberg, M.; Brice, A.; Birouk, N.; Dubourg, O.; Tazir, M.; LeGuern, E.

    2006-01-01

    BACKGROUND: Charcot-Marie-Tooth (CMT) disease is a heterogeneous group of inherited peripheral motor and sensory neuropathies with several modes of inheritance: autosomal dominant, X-linked, and autosomal recessive (AR) CMT. A locus responsible for the demyelinating form of ARCMT was assigned to the

  20. Targeting the colony stimulating factor 1 receptor alleviates two forms of Charcot-Marie-Tooth disease in mice.

    Science.gov (United States)

    Klein, Dennis; Patzkó, Ágnes; Schreiber, David; van Hauwermeiren, Anemoon; Baier, Michaela; Groh, Janos; West, Brian L; Martini, Rudolf

    2015-11-01

    See Scherer (doi:10.1093/awv279) for a scientific commentary on this article.Charcot-Marie-Tooth type 1 neuropathies are inherited disorders of the peripheral nervous system caused by mutations in Schwann cell-related genes. Typically, no causative cure is presently available. Previous preclinical data of our group highlight the low grade, secondary inflammation common to distinct Charcot-Marie-Tooth type 1 neuropathies as a disease amplifier. In the current study, we have tested one of several available clinical agents targeting macrophages through its inhibition of the colony stimulating factor 1 receptor (CSF1R). We here show that in two distinct mouse models of Charcot-Marie-Tooth type 1 neuropathies, the systemic short- and long-term inhibition of CSF1R by oral administration leads to a robust decline in nerve macrophage numbers by ∼70% and substantial reduction of the typical histopathological and functional alterations. Interestingly, in a model for the dominant X-linked form of Charcot-Marie-Tooth type 1 neuropathy, the second most common form of the inherited neuropathies, macrophage ablation favours maintenance of axonal integrity and axonal resprouting, leading to preserved muscle innervation, increased muscle action potential amplitudes and muscle strengths in the range of wild-type mice. In another model mimicking a mild, demyelination-related Charcot-Marie-Tooth type 1 neuropathy caused by reduced P0 (MPZ) gene dosage, macrophage blockade causes an improved preservation of myelin, increased muscle action potential amplitudes, improved nerve conduction velocities and ameliorated muscle strength. These observations suggest that disease-amplifying macrophages can produce multiple adverse effects in the affected nerves which likely funnel down to common clinical features. Surprisingly, treatment of mouse models mimicking Charcot-Marie-Tooth type 1A neuropathy also caused macrophage blockade, but did not result in neuropathic or clinical improvements

  1. Charcot-Marie-Tooth病的诊治%Progress of the diagnosis and treatment of Charcot-Marie-Tooth disease

    Institute of Scientific and Technical Information of China (English)

    洪道俊; 张玉生

    2014-01-01

    Charcot-Marie-Tooth病(CMT)是最常见的一种遗传性周围神经病,是一组具有显著临床异质性和遗传异质性的疾病,主要表现为肢体远端肌肉进行性无力和萎缩,伴有轻到中度感觉减退,腱反射减弱和足部畸形等.近20年CMT致病基因的不断被克隆,其疾病分型、临床表型和基因表型的关系发生了巨大变化.本文主要阐述CMT的疾病分型演变、基因诊断策略、临床治疗进展.

  2. Next-generation sequencing and genetic diagnosis of Charcot-Marie-Tooth disease

    Directory of Open Access Journals (Sweden)

    Ashok Verma

    2014-01-01

    Full Text Available Over 70 different Charcot-Marie-Tooth disease (CMT–associated genes have now been discovered and their number is growing. Conventional genetic testing for all CMT genes is cumbersome, expensive, and impractical in an individual patient. Next-generation sequencing (NGS technology allows cost-effective sequencing of large scale DNA, even entire exome (coding sequences or whole genome and thus, NGS platform can be employed to effectively target a large number or all CMT-related genes for accurate diagnosis. This overview discusses how NGS can be strategically used for genetic diagnosis in patients with CMT or unexplained neuropathy. A comment is made to combine simple clinical and electrophysiological algorithm to assign patients to major CMT subtypes and then employ NGS to screen for all known mutations in the subtype-specific CMT gene panel.

  3. Charcot-Marie-Tooth disease and pathways to molecular based therapies.

    Science.gov (United States)

    Harel, T; Lupski, J R

    2014-11-01

    The discovery in 1991 that chromosome 17p12 duplication is associated with Charcot-Marie-Tooth (CMT) disease marked the beginning of an era of molecular insight into this disorder, which encompasses the peripheral motor and sensory neuropathies. A mere two decades later, over 40 subtypes of CMT have been molecularly defined and many have been extensively studied in vitro and in animal models, providing the framework for a more comprehensive understanding of the biological pathways dictating myelination, axonal dynamics, and axon-glia interactions. The advent of next-generation sequencing technologies offers opportunities in both research and clinical settings for gene discovery, further molecular understanding and diagnosis, and calls for modifications of the existing algorithms guiding genetic testing. Although treatment is mainly supportive at this time, advances in this field are anticipated as the molecular basis of CMT is unraveled.

  4. A Review of X-linked Charcot-Marie-Tooth Disease.

    Science.gov (United States)

    Wang, Ying; Yin, Fei

    2016-05-01

    X-linked Charcot-Marie-Tooth disease (CMTX) is the second common genetic variant of CMT. CMTX type 1 causes 90% of CMTX. The most important clinical features of CMTX are similar with other types of CMT; however, a few patients get the central nervous system involved with or without white matter lesions; males are more severely and earlier affected than females. In this review, the authors focus on the origin and classification of CMTX, the central nervous system manifestations of CMTX1, the possible mechanism by which GJB1 mutations cause CMT1X, and the emerging therapeutic strategies for CMTX. Moreover, several cases are presented to illustrate the central nervous system manifestations.

  5. Connexin mutations in X-linked Charcot-Marie-Tooth disease

    Energy Technology Data Exchange (ETDEWEB)

    Bergoffen, J. (Univ. of Pennsylvania Medical School, Philadelphia, PA (United States)); Scherer, S.S.; Wang, S.; Scott, M.; Bone, L.J.; Chen, K.; Lensch, M.W.; Fischbeck, K.H. (Univ. of Pennsylvania Medical School, PA (United States)); Paul, D.L. (Harvard Medical School, Boston, MA (United States)); Change, P.F. (Univ. of Pennsylvania Medical School and Neurology Division, Philadelphia, PA (United States))

    1993-12-24

    X-linked Charcot-Marie-Tooth disease (CMTX) is a form of hereditary neuropathy with demyelination. Recently, this disorder was mapped to chromosome Xq13.1. The gene for the gap junction protein connexin32 is located in the same chromosomal segment, which led to its consideration as a candidate gene for CMTX. With the use of Northern (RNA) blot and immunohistochemistry techniques, it was found that connexin32 is normally expressed in myelinated peripheral nerve. Direct sequencing of the connexin32 gene showed seven different mutations in affected persons from eight CMTX families. These findings, a demonstration of inherited defects in a gap junction protein, suggest that connexin32 plays an important role in peripheral nerve.

  6. Diagnóstico clínico de la enfermedad Charcot-Marie-Tooth

    Directory of Open Access Journals (Sweden)

    Yuselis Pérez Cid

    2014-08-01

    Full Text Available La enfermedad de Charcot-Marie-Tooth es un trastorno polineuropático genéticamente heterogéneo, en la que se han identificado más de 30 genes responsables; sin embargo, el diagnóstico es posible establecerlo sobre las bases de los estudios clínicos y electrofisiológicos. Constituye un reto en la práctica médica de los países del tercer mundo contar con la realización sistemática de estudios genéticos moleculares de las neuropatías hereditarias, por lo que en este trabajo se enfatiza en los estudios clínico-electrofisiológicos para la clasificación de la CMT

  7. [Therapy for Charcot-Marie-Tooth Disease: From the Standpoint of Neurologists].

    Science.gov (United States)

    Nakagawa, Masanori

    2016-01-01

    To date, there is no approved pharmacologic treatment for any form of Charcot-Marie-Tooth disease (CMT). However, some clinical or preclinical trials for CMT1A have been undertaken, for example Neurotrophin-3, PXT3003, and neuregulin-1. Gene therapy for CMT1X, CMT2F and Giant axonal neuropathy using animal model or culture cells have been reported with some interesting results. Stem cell research for example iPS cells derived from patients with CMT2A or CMT2E, is being conducted to clarify the mechanism of CMT and find therapeutic clues. The development of new surrogate markers for clinical trials is also needed. Additionally, steps should be taken to improve the quality of life of patients with CMT, including pain control and life style enhancement.

  8. Anesthetic Management of a Patient With Charcot-Marie-Tooth Disease.

    Science.gov (United States)

    Ohshita, Naohiro; Oka, Saeko; Tsuji, Kaname; Yoshida, Hiroaki; Morita, Shosuke; Momota, Yoshihiro; Tsutsumi, Yasuo M

    2016-01-01

    Charcot-Marie-Tooth disease (CMTD) is a hereditary peripheral neuropathy and is characterized by progressive muscle atrophy and motor-sensory disorders in all 4 limbs. Most reports have indicated that major challenges with general anesthetic administration in CMTD patients are the appropriate use of nondepolarizing muscle relaxants and preparation for malignant hyperthermia in neuromuscular disease. Moderate sedation may be associated with the same complications as those of general anesthesia, as well as dysfunction of the autonomic nervous system, reduced perioperative respiratory function, difficulty in positioning, and sensitivity to intravenous anesthetic agents. We decided to use intravenous sedation in a CMTD patient and administered midazolam initially and propofol continuously, with total doses of 1.5 mg and 300 mg, respectively. Anesthesia was completed in 3 hours and 30 minutes without adverse events. We suggest that dental anesthetic treatment with propofol and midazolam may be effective for patients with CMTD.

  9. Unusual manifestations of Charcot-Marie-Tooth disease: A clinical observation

    Directory of Open Access Journals (Sweden)

    Akhila Kumar Panda

    2014-01-01

    Full Text Available Charcot-Marie-Tooth disease (CMT is the most common hereditary neuromuscular disorder. Careful assessment of clinical presentations, mode of inheritance, electrophysiological studies, and genetic analysis form the basis for the diagnosis of CMT. CMT4 is a group of progressive motor and sensory axonal demyelinating neuropathies. It is distinguished from other forms of CMT by autosomal recessive pattern of inheritance, variable clinical manifestations, electrophysiological study, nerve biopsy, and specific genetic studies. Here, we report an interesting case of hereditary neuropathy with recessive inheritance pattern who presented with combined clinical phenotypes of 4B1, 4C, and 4D subtypes. The histopathological study revealed onion bulb appearance suggestive of demyelination and remyelination phenomenon. The overlapping clinical manifestation may create a diagnostic challenge which would be confirmed by specific molecular analysis.

  10. Genetic dysfunction of MT-ATP6 causes axonal Charcot-Marie-Tooth disease.

    LENUS (Irish Health Repository)

    Pitceathly, Robert D S

    2012-09-11

    Charcot-Marie-Tooth (CMT) disease is the most common inherited neuromuscular disorder, affecting 1 in 2,500 individuals. Mitochondrial DNA (mtDNA) mutations are not generally considered within the differential diagnosis of patients with uncomplicated inherited neuropathy, despite the essential requirement of ATP for axonal function. We identified the mtDNA mutation m.9185T>C in MT-ATP6, encoding the ATP6 subunit of the mitochondrial ATP synthase (OXPHOS complex V), at homoplasmic levels in a family with mitochondrial disease in whom a severe motor axonal neuropathy was a striking feature. This led us to hypothesize that mutations in the 2 mtDNA complex V subunit encoding genes, MT-ATP6 and MT-ATP8, might be an unrecognized cause of isolated axonal CMT and distal hereditary motor neuropathy (dHMN).

  11. Charcot-Marie-Tooth disease and dilated cardiomyopathy. A rare combination.

    Directory of Open Access Journals (Sweden)

    Rafael Pila Pérez

    2011-07-01

    Full Text Available Se presenta el caso de un paciente de 50 años de edad, con 14 años de evolución de manifestaciones clínicas, destacándose las alteraciones musculoesqueléticas de los cuatro miembros con atrofia de las prominencias tenar e hipotenar y de la musculatura de ambas piernas. Se destacó la presencia de alteraciones sensitivas en miembros inferiores con distribución en calcetín, atrofia, atonía, arreflexia y marcha equina. Desde el punto de vista cardiaco, el paciente presentaba un fibriloaleteo. La radiografía de tórax mostró un aumento marcado del área cardiaca y la ecocardiografía puso de manifiesto una miocardiopatía dilatada. El estudio histopatológico confirmó la presencia de la enfermedad de Charcot-Marie-Tooth asociada a miocardiopatía dilatada. El diagnóstico se basó en las características clínicas, la velocidad de conducción motora, y el estudio histopatológico, que demostró desmielinización con lesiones en “cebolla”, si bien faltaron los estudios genéticos. La enfermedad de Charcot-Marie-Tooth es una enfermedad rara; aproximadamente un 60 % de los pacientes que la padecen, son portadores de una duplicación del cromosoma 17. Por ello, se consideró oportuno transmitir la experiencia de este caso.

  12. Charcot-Marie-Tooth病的研究与诊断进展%Progress of Research and Diagnosis of Charcot-Marie-Tooth Disease

    Institute of Scientific and Technical Information of China (English)

    朱琳; 胡静

    2011-01-01

    Charcot-Marie-Tooth disease(CMT) is % group of the most common familial peripheral neuropathies with highly genetic and clinical heterogeneity. CMT accounts for aboul 90% of hereditary neuropathies. CMT has similar clinical manifestations. Now there are at least .15 subtypes, which makes great difficulties in diagnosiing the disease. Therefore, this arliclc review;, the effective diagnostic methods of detailing the phenotypes and screening disease-related geres bused on the analysis of the clinical presentations, electrophysiology. Peripheral nerve pathology and causative genes of the subtypes of CMT.%Charcot-Marie-Tooth病,是一组最常见的在遗传和临床上都具有高度异质性的家族性周围神经病,约占全部遗传性神经病的90%.其基本临床表现相似,目前已知的亚型多达35种,为该病的确诊带来极大困难.因此,本文综述该病各亚型的临床、电生理、周围神经病理、致病基因及有效诊断方法.

  13. Pé cavo adquirido na doença de Charcot-Marie-Tooth Acquired pes cavus in Charcot-Marie-Tooth disease

    Directory of Open Access Journals (Sweden)

    Daniel Augusto Carvalho Maranho

    2009-01-01

    Full Text Available As neuropatias sensitivomotoras hereditárias, principalmente a doença de Charcot-Marie-Tooth, manifestam-se frequentemente com o aparecimento de pé cavovaro, deformidade caracterizada pela acentuação fixa do arco plantar e inversão do retropé. O diagnóstico da doença de base e a cuidadosa avaliação do paciente fornecem os elementos-chave para decisão do tratamento. O cavo pode situar-se no antepé, retropé ou ser o resultado da associação das duas localizações. Deformidades combinadas, principalmente varismo e garras dos artelhos, devem ser bem avaliadas; as características clínicas como grau das alterações, acometimento da força muscular, flexibilidade e idade são fatores importantes para a decisão da conduta. O tratamento conservador do pé cavovaro por meio de fisioterapia, palmilhas e adaptação nos calçados é reservado ao paciente mais jovem ou casos levemente acometidos. Entretanto, há tendência de agravamento das deformidades devido à característica progressiva da doença neurológica de base. Assim, o tratamento cirúrgico pelas técnicas clássicas é indicado precocemente, sendo importante identificar as alterações primárias, diferenciá-las das secundárias e corrigi-las, se possível. As transferências musculares são usadas no sentido de minimizar o desequilíbrio, estruturas retraídas são seccionadas ou alongadas e osteotomias localizadas devem ser preferíveis às artrodeses, que são reservadas para pés rígidos e muito deformados de pacientes adultos.Hereditary motor and sensory neuropathies, especially Charcot-Marie-Tooth disease, are frequently expressed with an acquired cavusvarus foot which is characterized by a fixed increase of the plantar arch and hindfoot inversion. Diagnosis of the underlying condition achieved through careful patient assessment and local evaluations is the keystone for decision-making about the adequate treatment. The cavus may present as an isolated deformity of

  14. Factors associated with foot and ankle strength in healthy preschool-age children and age-matched cases of Charcot-Marie-Tooth disease type 1A.

    Science.gov (United States)

    Rose, Kristy J; Burns, Joshua; North, Kathryn N

    2010-04-01

    Charcot-Marie-Tooth disease affects foot and ankle strength from the earliest stages of the disease; however, little is known about factors influencing normal strength development or the pathogenesis of foot weakness and deformity in Charcot-Marie-Tooth disease. The authors investigated factors associated with foot and ankle strength in healthy preschool-age children and compared to age-matched cases of Charcot-Marie-Tooth disease type 1A. In healthy children, ankle dorsiflexion range of motion was one of the strongest independent correlates of foot and ankle strength. Compared with healthy children, those with Charcot-Marie-Tooth disease type 1A had significantly less dorsiflexion strength and range as well as imbalance in inversion-to-eversion and plantarflexion-to-dorsiflexion strength ratios. Given the association between ankle dorsiflexion strength and range in the healthy children, and the abnormality of these parameters in Charcot-Marie-Tooth disease, investigation of the cause-effect relationship is warranted to identify more targeted therapy and further understand the pathogenesis of foot deformity in Charcot-Marie-Tooth disease.

  15. Charcot-Marie-Tooth type 4F disease caused by S399fsx410 mutation in the PRX gene.

    Science.gov (United States)

    Kabzinska, D; Drac, H; Sherman, D L; Kostera-Pruszczyk, A; Brophy, P J; Kochanski, A; Hausmanowa-Petrusewicz, I

    2006-03-14

    Charcot-Marie-Tooth type 4F disease (CMT4F) is an autosomal recessive neuropathy caused by mutations in the PRX gene. To date, only seven mutations have been identified in the PRX gene. In this study, the authors report a novel S399fsX410 mutation in the PRX gene and its effects at the protein level, which was identified in an 8-year-old patient with early-onset CMT disease.

  16. Resetting translational homeostasis restores myelination in Charcot-Marie-Tooth disease type 1B mice.

    Science.gov (United States)

    D'Antonio, Maurizio; Musner, Nicolò; Scapin, Cristina; Ungaro, Daniela; Del Carro, Ubaldo; Ron, David; Feltri, M Laura; Wrabetz, Lawrence

    2013-04-01

    P0 glycoprotein is an abundant product of terminal differentiation in myelinating Schwann cells. The mutant P0S63del causes Charcot-Marie-Tooth 1B neuropathy in humans, and a very similar demyelinating neuropathy in transgenic mice. P0S63del is retained in the endoplasmic reticulum of Schwann cells, where it promotes unfolded protein stress and elicits an unfolded protein response (UPR) associated with translational attenuation. Ablation of Chop, a UPR mediator, from S63del mice completely rescues their motor deficit and reduces active demyelination by half. Here, we show that Gadd34 is a detrimental effector of CHOP that reactivates translation too aggressively in myelinating Schwann cells. Genetic or pharmacological limitation of Gadd34 function moderates translational reactivation, improves myelination in S63del nerves, and reduces accumulation of P0S63del in the ER. Resetting translational homeostasis may provide a therapeutic strategy in tissues impaired by misfolded proteins that are synthesized during terminal differentiation.

  17. Myelin protein zero gene mutated in Charcot-Marie-Tooth type 1B patients

    Energy Technology Data Exchange (ETDEWEB)

    Su, Ying; Li, Lanying; Lepercq, J.; Lebo, R.V. (Univ. of California, San Francisco, CA (United States)); Brooks, D.G.; Ravetch, J.V. (Sloan-Kettering Institute, New York, NY (United States)); Trofatter, J.A. (Massachusetts General Hospital, Boston, MA (United States))

    1993-11-15

    The autosomal dominant of Charcot-Marie-Tooth disease (CMT), whose gene is type 1B (CMT1B), has slow nerve conduction with demyelinated Schwann cells. In this study the abundant peripheral myelin protein zero (MPZ) gene, MPZ, was mapped 130 kb centromeric to the Fc receptor immunoglobulin gene cluster in band 1q22, and a major MPZ point mutation was found to cosegregate with CMT1B in one large CMT1B family. The MPZ point mutation in 18 of 18 related CMT1B pedigree 1 patients converts a positively charged lysine in codon 96 to a negatively charged glutamate. The same MPZ locus cosegregates with the CMT1B disease gene in a second CMT1B family [total multipoint logarithm of odds (lod) = 11.4 at [theta] = 0.00] with a splice junction mutation. Both mutations occur in MPZ protein regions otherwise conserved identically in human, rat, and cow since these species diverged 100 million years ago. MPZ protein, expressed exclusively in myelinated peripheral nerve Schwann cells, constitutes >50% of myelin protein. These mutations are anticipated to disrupt homophilic MPZ binding and result in CMT1B peripheral nerve demyelination.

  18. Quality of life in patients with Charcot-Marie-Tooth disease type 1A

    Directory of Open Access Journals (Sweden)

    Juliana B. Taniguchi

    2013-06-01

    Full Text Available We assessed the functional impairment in Charcot-Marie-Tooth resulting from 17p11.2-p12 duplication (CMT1A patients using the Short-Form Health Survey (SF-36, which is a quality of life questionnaire. Twenty-five patients of both genders aged ≥10 years with a positive molecular diagnosis of CMT1A were selected. Age- and gender-matched Control Group (without family history of neuropathy, and the sociodemographic and professional conditions similar to the patients' group were selected to compare the SF-36 results between them. The results showed that the majority quality of life impairments in CMT1A patients occurred in the social and emotional domains. Functional capacity also tended to be significantly affected; other indicators of physical impairment were preserved. In conclusion, social and emotional aspects are mostly neglected in the assistance provided to CMT1A Brazilian patients, and they should be better understood in order to offer global health assistance with adequate quality of life as a result.

  19. Mutational studies in X-linked Charcot-Marie-Tooth disease (CMTX)

    Energy Technology Data Exchange (ETDEWEB)

    Cherryson, A.K.; Yeung, L.; Kennerson, M.L.; Nicholson, G.A. [Univ. of Syndey, Concord (Australia)

    1994-09-01

    Charcot-Marie-Tooth disease, also known as hereditary motor and sensory neuropathy (HMSN), is a heterogeneous group of slowly progressive disorders of the peripheral nerve. X-linked CMT (CMTX) is characterized by slow motor nerve conduction velocities in affected males and the presence of mildly affected or normal carrier females with intermediate or normal nerve conduction velocities. CMTX, which has an incidence of 3.1 per 100,000 and accounts for approximately 10% of CMT cases, has been mapped to Xq13. One of the genes lying in this region, connexin 32, has been found to contain alterations in individuals affected with X-linked CMT. We have identified our X-linked families from dominant type 1 CMT families using the clinical criteria given above. These families were screened for point mutations in connexin 32. We have identified three missense mutations, a G{r_arrow}A transition at amino acid 35 (valine to methionine), a C{r_arrow}G transition at amino acid 158 (proline to alanine) and a T{r_arrow}A transition at amino acid 182 (serine to threonine). Another family showed a 18 bp deletion, which removed the amino acid 111 to 116 inclusive (histidine, glycine, aspartic acid, proline, leucine, histidine).

  20. Mild phenotype of Charcot-Marie-Tooth disease type 4B1.

    Science.gov (United States)

    Murakami, Tatsufumi; Kutoku, Yumiko; Nishimura, Hirotake; Hayashi, Makiko; Abe, Akiko; Hayasaka, Kiyoshi; Sunada, Yoshihide

    2013-11-15

    Charcot-Marie-Tooth type 4B1 (CMT4B1) is a rare autosomal recessive demyelinating neuropathy caused by mutation of the myotubularin-related 2 (MTMR2) gene. It is characterized by a severe early-onset motor and sensory neuropathy, and myelin outfoldings on nerve biopsy. We describe a mild phenotype of CMT4B1 in a Japanese patient. She noticed difficulty in walking as an initial symptom at age 13. Her symptoms progressed slowly, and she could still walk at age 34. There was no cranial neuropathy. A nerve conduction study demonstrated demyelinating neuropathy. Sural nerve biopsy revealed a moderate-to-severe loss of myelinated fibers, and many focally folded myelin sheaths. Electron micrographs showed myelin outfoldings and infoldings. DNA tests for CMT showed that she is a homozygote for the MTMR2 p.R628PfsX18 mutation. The mild phenotype in our patient is probably due to the C-terminal position of the frame-shift mutation in MTMR2.

  1. Linkage localization of X-linked Charcot-Marie-Tooth disease

    Energy Technology Data Exchange (ETDEWEB)

    Bergoffen, J. (Children' s Hospital, Philadelphia, PA (United States) Univ. of Pennsylvania, Philadelphia (United States)); Trofatter, J.; Haines, J.L. (Massachusetts General Hospital, Boston (United States)); Pericak-Vance, M.A. (Duke Univ., Durham, NC (United States)); Chance, P.F. (Univ. of Utah, Salt Lake City (United States)); Fischbeck, K.H. (Univ. of Pennsylvania, Philadelphia (United States))

    1993-02-01

    Charcot-Marie-Tooth disease (CMT), also known as hereditary motor and sensory neuropathy, is a heterogeneous group of slowly progressive, degenerative disorders of peripheral nerve. X-linked CMT (CMTX) (McKusick 302800), a subdivision of type I, or demyelinating, CMT is an X-linked dominant condition with variable penetrance. Previous linkage analysis using RFLPs demonstrated linkage to markers on the proximal long and short arms of the X chromosome, with the more likely localization on the proximal long arm of the X chromosome. Available variable simple-sequence repeats (VSSRs) broaden the possibilities for linkage analysis. This paper presents new linkage data and recombination analysis derived from work with four VSSR markers - AR, PGKP1, DXS453, and DXYS1X - in addition to analysis using RFLP markers described elsewhere. These studies localize the CMTX gene to the proximal Xq segment between PGKP1 (Xq11.2-12) and DXS72 (Xq21.1), with a combined maximum multipoint lod score of 15.3 at DXS453 ([theta] = 0). 32 refs., 3 figs., 2 tabs.

  2. GDAP1 mutations in Italian axonal Charcot-Marie-Tooth patients: Phenotypic features and clinical course.

    Science.gov (United States)

    Pezzini, I; Geroldi, A; Capponi, S; Gulli, R; Schenone, A; Grandis, M; Doria-Lamba, L; La Piana, C; Cremonte, M; Pisciotta, C; Nolano, M; Manganelli, F; Santoro, L; Mandich, P; Bellone, E

    2016-01-01

    Mutations in the ganglioside-induced differentiation associated-protein 1 (GDAP1) gene have been associated with both autosomal recessive (AR) and dominant (AD) Charcot-Marie-Tooth (CMT) axonal neuropathy. The relative frequency of heterozygous, dominant mutations in Italian CMT is unknown. We investigated the frequency of dominant mutations in GDAP1 in a cohort of 109 axonal Italian patients by sequencing genomic DNA and search for copy number variations. We also explored correlations with clinical features. All cases had already been tested for variants in common axonal AD genes. Eight patients (7.3%) harbored five already reported heterozygous mutations in GDAP1 (p.Arg120Gly, p.Arg120Trp, p.His123Arg, p.Gln218Glu, p.Arg226Ser). Mutations had different penetrances in the families; the onset of symptoms is in the first decade and progression is slower than usually seen in GDAP1-related AR-CMT. We show that the relative frequency of mutations in GDAP was slightly higher than those observed in MFN2 and MPZ (7.3% vs 6.3% and 5.0%). The relatively milder clinical features and the quite indolent course observed are relevant for prognostic assessment. On the basis of our experience and the data reported here, we suggest GDAP1 as the first gene that should be analysed in Italian patients affected by CMT2.

  3. Exacerbation of Charcot-Marie-Tooth type 2E neuropathy following traumatic nerve injury.

    Science.gov (United States)

    Villalón, Eric; Dale, Jeffrey M; Jones, Maria; Shen, Hailian; Garcia, Michael L

    2015-11-19

    Charcot-Marie-Tooth disease (CMT) is the most commonly inherited peripheral neuropathy. CMT disease signs include distal limb neuropathy, abnormal gait, sensory defects, and deafness. We generated a novel line of CMT2E mice expressing hNF-L(E397K), which displayed muscle atrophy of the lower limbs without denervation, proximal reduction in large caliber axons, and decreased nerve conduction velocity. In this study, we challenged wild type, hNF-L and hNF-L(E397K) mice with crush injury to the sciatic nerve. We analyzed functional recovery by measuring toe spread and analyzed gait using the Catwalk system. hNF-L(E397K) mice demonstrated reduced recovery from nerve injury consistent with increased susceptibility to neuropathy observed in CMT patients. In addition, hNF-L(E397K) developed a permanent reduction in their ability to weight bear, increased mechanical allodynia, and premature gait shift in the injured limb, which led to increasingly disrupted interlimb coordination in hNF-L(E397K). Exacerbation of neuropathy after injury and identification of gait alterations in combination with previously described pathology suggests that hNF-L(E397K) mice recapitulate many of clinical signs associated with CMT2. Therefore, hNF-L(E397K) mice provide a model for determining the efficacy of novel therapies.

  4. Perk Ablation Ameliorates Myelination in S63del-Charcot-Marie-Tooth 1B Neuropathy.

    Science.gov (United States)

    Musner, Nicolò; Sidoli, Mariapaola; Zambroni, Desireè; Del Carro, Ubaldo; Ungaro, Daniela; D'Antonio, Maurizio; Feltri, Maria L; Wrabetz, Lawrence

    2016-01-01

    In peripheral nerves, P0 glycoprotein accounts for more than 20% of myelin protein content. P0 is synthesized by Schwann cells, processed in the endoplasmic reticulum (ER) and enters the secretory pathway. However, the mutant P0 with S63 deleted (P0S63del) accumulates in the ER lumen and induces a demyelinating neuropathy in Charcot-Marie-Tooth disease type 1B (CMT1B)-S63del mice. Accumulation of P0S63del in the ER triggers a persistent unfolded protein response. Protein kinase RNA-like endoplasmic reticulum kinase (PERK) is an ER stress sensor that phosphorylates eukaryotic initiation factor 2 alpha (eIF2alpha) in order to attenuate protein synthesis. We have shown that increasing phosphophorylated-eIF2alpha (P-eIF2alpha) is a potent therapeutic strategy, improving myelination and motor function in S63del mice. Here, we explore the converse experiment:Perkhaploinsufficiency reduces P-eIF2alpha in S63del nerves as expected, but surprisingly, ameliorates, rather than worsens S63del neuropathy. Motor performance and myelin abnormalities improved in S63del//Perk+/- compared with S63del mice. These data suggest that mechanisms other than protein translation might be involved in CMT1B/S63del neuropathy. In addition,Perkdeficiency in other cells may contribute to demyelination in a non-Schwann-cell autonomous manner.

  5. Charcot-Marie-Tooth type 1A disease from patient to laboratory.

    Science.gov (United States)

    Perveen, Shazia; Mannan, Shazia; Hussain, Abrar; Kanwal, Sumaira

    2015-02-01

    Charcot-Marie-Tooth (CMT) disease is a well-known neural or spinal type of muscular atrophy. It is the most familiar disease within a group of conditions called Hereditary Motor and Sensory Neuropathies (HMSN). The disease was discovered by three scientists several years ago. Several genes are involved as the causative agents for the disease. Hundreds of causative mutations have been found and research work for the identification of a novel locus and for the treatment of CMT1A is going on. This review article was planned to gather information on CMT disease and updates on its treatment.National Center for Biotechnology Information (NCBI) and PubMed were searched for data retrieval. Molgen database, which is the exclusive site for CMT mutation, was the other source of articles. Different aspects of the CMT disease were compared.Advancements in the finding of the causative gene, discovery of the novel Loci are the current issues in this regard.CMT disease is incurable, but researchers are trying to get some benefits from different natural compounds and several therapeutic agents.Various groups are working on the treatment projects of CMT1A. Major step forward in CMT research was taken in 2004 when ascorbic acid was used for transgenic mice treatment. Gene therapy for constant neurotrophin-3 (NT- 3) delivery by secretion by muscle cells for the CMT1A is also one of the possible treatments under trial.

  6. Clinical and genetic spectra in a series of Chinese patients with Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Wang, Rui; He, Jin; Li, Jin-Jing; Ni, Wang; Wu, Zhi-Ying; Chen, Wan-Jin; Wang, Yi

    2015-12-01

    The aim of this study was to determine the clinical features and frequencies of genetic subtypes in a series of patients with Charcot-Marie-Tooth (CMT) disease from Eastern China. Patients were divided into three subtypes, CMT1, CMT2 and hereditary neuropathy with liability to pressure palsy (HNPP), according to their electrophysiological manifestations. Multiplex ligation-dependent probe analysis (MLPA) was performed to detect duplications/deletions in the PMP22 gene. The coding regions and splice sites of the GJB1, MPZ, MFN2 and GDAP-1 genes were determined by direct sequencing. Among the 148 patients in the study, 37.2% of the cases had mutations in genes assessed. The mutation detection rate was higher in patients with family histories than in spontaneous cases. PMP22 duplication (13.5%) was predominant in this group of patients, followed by PMP22 deletion (11.5%), and point mutations in GJB1 (8.8%), MPZ (2.0%) and MFN2 (0.7%). Three novel mutations (c.151T>C and c.310 A>G in GJB1 and c.1516 C>G in MFN2) were detected. A small deletion in PMP22 exon 4 was detected in a patient with severe CMT1. Genetic tests have great value in CMT patients with family histories. The frequency of PMP22 duplications was lower in Asian patients than in others. We suggest that genetic testing strategies in CMT patients should be primarily based on electromyography data.

  7. X inactivation in females with X-linked Charcot-Marie-Tooth disease.

    LENUS (Irish Health Repository)

    Murphy, Sinéad M

    2012-07-01

    X-linked Charcot-Marie-Tooth disease (CMT1X) is the second most common inherited neuropathy, caused by mutations in gap junction beta-1 (GJB1). Males have a uniformly moderately severe phenotype while females have a variable phenotype, suggested to be due to X inactivation. We aimed to assess X inactivation pattern in females with CMT1X and correlate this with phenotype using the CMT examination score to determine whether the X inactivation pattern accounted for the variable phenotype in females with CMT1X. We determined X inactivation pattern in 67 females with CMT1X and 24 controls using the androgen receptor assay. We were able to determine which X chromosome carried the GJB1 mutation in 30 females. There was no difference in X inactivation pattern between patients and controls. In addition, there was no correlation between X inactivation pattern in blood and phenotype. A possible explanation for these findings is that the X inactivation pattern in Schwann cells rather than in blood may explain the variable phenotype in females with CMT1X.

  8. Postural stabilization and balance assessment in Charcot-Marie-Tooth 1A subjects.

    Science.gov (United States)

    Lencioni, T; Rabuffetti, M; Piscosquito, G; Pareyson, D; Aiello, A; Di Sipio, E; Padua, L; Stra, F; Ferrarin, M

    2014-09-01

    The aim of the present study was to assess postural stabilization skill in adult subjects affected by Charcot-Marie-Tooth disease (CMT) type 1A. For this purpose ground reaction force (GRF) was measured by means of a piezoelectric force platform during the sit-to-stand (STS) movement, until a steady state erect posture was achieved. Specific indexes to quantify Centre of Mass acceleration, both during postural stabilization and during quiet standing, were computed using a mathematical model. Forty-seven CMT1A subjects were recruited for the study, and the control group was formed by forty-one age- and sex-matched healthy subjects. The results show that CMT1A subjects are less stable than controls during the quiet stance. Greater difficulty (high values of Yinf, the final instability rate) to maintain erect posture appears to be mainly associated with plantar-flexor muscle weakness, rather than to damage of the proprioceptive system. The worst performances shown by CMT1A subjects in the stabilization phase (high values of I, the global index of postural stabilization performance) seem to be associated with reduced muscle strength and the loss of large sensory nerve fibres. Distal muscle weakness appears to affect both postural stabilization and quiet erect posture. The presented protocol and the analysis of postural stabilization parameters provide useful information on CMT1A balance disorders.

  9. Oral Health, Temporomandibular Disorder, and Masticatory Performance in Patients with Charcot-Marie-Tooth Type 2

    Directory of Open Access Journals (Sweden)

    Rejane L. S. Rezende

    2013-01-01

    Full Text Available Background. The aim of this study was to evaluate the oral health status of temporomandibular disorders (TMD and bruxism, as well as to measure masticatory performance of subjects with Charcot-Marie-Tooth type 2 (CMT2. Methods and Results. The average number of decayed, missing, and filled teeth (DMFT for both groups, control (CG and CMT2, was considered low (CG = 2.46; CMT2 = 1.85, P=0.227. The OHIP-14 score was considered low (CG = 2.86, CMT2 = 5.83, P=0.899. The prevalence of self-reported TMD was 33.3% and 38.9% (P=0.718 in CG and CMT2 respectively and for self-reported bruxism was 4.8% (CG and 22.2% (CMT2, without significant difference between groups (P=0.162. The most common clinical sign of TMD was masseter (CG = 38.1%; CMT2 = 66.7% and temporalis (CG = 19.0%; GCMT2 = 33.3% muscle pain. The geometric mean diameter (GMD was not significantly different between groups (CG = 4369; CMT2 = 4627, P=0.157. Conclusion. We conclude that the CMT2 disease did not negatively have influence either on oral health status in the presence and severity of TMD and bruxism or on masticatory performance.

  10. Characterization of gait parameters in patients with Charcot-Marie-Tooth disease.

    Directory of Open Access Journals (Sweden)

    Kuruvilla A

    2000-01-01

    Full Text Available The gait of five patients with Charcot-Marie-Tooth(CMT disease was analyzed using light-emitting diodes and a force plate. The flexion-extension motions of the hips, knees, and ankles, as well as their moments (vector sums of forces acting at the joints in the flexion-extension and abduction-adduction planes, were quantified. The gait of the CMT patients showed abnormalities consistent with both distal weakness (ankle dorsi- and plantar-flexors and weakness of the hip abductor muscles. The latter weakness appeared to produce asymmetric hip moments and truncal instability in the mediolateral plane during ambulation. However, the extent to which the gait was abnormal appeared not to be exclusively related to the severity of the sensorimotor conduction deficits in the peripheral nerves. In the four patients for whom nerve conduction velocity studies were available, decrease in the lower-extremity distal conduction velocities and evoked motor amplitude potentials did not correlate with the severity and extent of the gait abnormalities.

  11. Charcot-Marie-Tooth Disease and Related Hereditary Neuropathies: From Gene Function to Associated Phenotypes.

    Science.gov (United States)

    Pareyson, D; Saveri, P; Piscosquito, G

    2014-10-10

    Charcot-Marie-Tooth disease (CMT) and related neuropathies are a genetically highly heterogeneous group of neurodegenerative disorders. CMT affects both the sensory and motor nerves, distal Hereditary Motor Neuropathies (dHMN) are phenotypically similar disorders involving only motor nerves, while Hereditary Sensory and Autonomic Neuropathies (HSAN) are rare distinct disorders affecting sensory and sometimes autonomic nerves. Almost 70 genes have been identified as responsible for these disorders. It is astonishing to learn how diverse are the cellular sublocalisation and the functional roles of the encoded proteins of CMT-associated genes which all lead to similar disorders of the peripheral nervous system. Myelin formation and maintenance, mitochondrial dynamics, cytoskeleton organization, axonal transport, and vesicular trafficking are the most frequently involved pathways. However, dysfunction of several activities from the nucleus to the neuromuscular junction forms the basis for these hereditary neuropathies, making it challenging predicting the functions of newly identified mutated genes. In this review we will discuss the function and related phenotypes of all the genes thus far associated with CMT, dHMN, and HSAN.

  12. Hereditary motor and sensory neuropathies or Charcot-Marie-Tooth diseases: an update.

    Science.gov (United States)

    Tazir, Meriem; Hamadouche, Tarik; Nouioua, Sonia; Mathis, Stephane; Vallat, Jean-Michel

    2014-12-15

    Hereditary motor and sensory neuropathies (HMSN) or Charcot-Marie-Tooth (CMT) diseases are the most common degenerative disorders of the peripheral nervous system. However, the frequency of the different subtypes varies within distinct populations. Although more than seventy clinical and genetic forms are known to date, more than 80% of CMT patients in Western countries have genetic abnormalities associated with PMP22, MPZ, MFN2 and GJB1. Given the considerable genetic heterogeneity of CMT, we emphasize the interest of both clinical and pathological specific features such that focused genetic testing could be performed. In this regard, peripheral nerve lesions in GDAP1 mutations (AR CMT1A), such as mitochondrial abnormalities, have been newly demonstrated. Otherwise, while demyelinating autosomal recessive CMT used to be classified as CMT4 (A, B, C …), we propose a simplified classification such as AR CMT1 (A, B, C …), and AR CMT2 for axonal forms. Also, we stress that next generation sequencing techniques, now considered to be the most efficient methods of genetic testing in CMT, will be helpful in molecular diagnosis and research of new genes involved. Finally, while no effective therapy is known to date, ongoing new therapeutic trials such as PXT3003 (a low dose combination of the three already approved drugs baclofen, naltrexone, and D-sorbitol) give hopes for potential curative treatment.

  13. Charcot-Marie-Tooth disease and dilated cardiomyopathy. A rare combination. Enfermedad de Charcot-Marie-Tooth y miocardiopatía dilatada. Una rara asociación.

    Directory of Open Access Journals (Sweden)

    Rafael Pila Pérez

    2011-07-01

    Full Text Available

    Se presenta el caso de un paciente de 50 años de edad, con 14 años de evolución de manifestaciones clínicas, destacándose las alteraciones musculoesqueléticas de los cuatro miembros con atrofia de las prominencias tenar e hipotenar y de la musculatura de ambas piernas. Se destacó la presencia de alteraciones sensitivas en miembros inferiores con distribución en calcetín, atrofia, atonía, arreflexia y marcha equina. Desde el punto de vista cardiaco, el paciente presentaba un fibriloaleteo. La radiografía de tórax mostró un aumento marcado del área cardiaca y la ecocardiografía puso de manifiesto una miocardiopatía dilatada. El estudio histopatológico confirmó la presencia de la enfermedad de Charcot-Marie-Tooth asociada a miocardiopatía dilatada. El diagnóstico se basó en las características clínicas, la velocidad de conducción motora, y el estudio histopatológico, que demostró desmielinización con lesiones en “cebolla”, si bien faltaron los estudios genéticos. La enfermedad de Charcot-Marie-Tooth es una enfermedad rara; aproximadamente un 60 % de los pacientes que la padecen, son portadores de una duplicación del cromosoma 17. Por ello, se consideró oportuno transmitir la experiencia de este caso.

    The case of a 50 years old male patient is presented. Along 14 years of clinical evolution, four limbs musculoskeletal disorders with atrophy of the thenar and hypothenar prominences and muscles of both legs had been emphasized. The presence of sensory impairment in lower limbs with stocking distribution, atrophy, weakness, areflexia and equine gait were very peculiar in this case. From the cardiac point of view, the patient presented a fibrillation/flutter. Chest radiography showed a marked increase in the cardiac area and echocardiography revealed dilated cardiomyopathy. Histopathological examination confirmed the presence of Charcot-Marie-Tooth disease associated with dilated cardiomyopathy. While genetic

  14. Minimally Invasive Early Operative Treatment of Progressive Foot and Ankle Deformity Associated With Charcot-Marie-Tooth Disease.

    Science.gov (United States)

    Boffeli, Troy J; Tabatt, Jessica A

    2015-01-01

    Charcot-Marie-Tooth disease is a neuromuscular disorder that commonly results in a predictable pattern of progressive bilateral lower extremity weakness, numbness, contracture, and deformity, including drop foot, loss of ankle eversion strength, dislocated hammertoes, and severe cavus foot deformity. Late stage reconstructive surgery will be often necessary if the deformity becomes unbraceable or when neuropathic ulcers have developed. Reconstructive surgery for Charcot-Marie-Tooth deformity is generally extensive and sometimes staged. Traditional reconstructive surgery involves a combination of procedures, including tendon lengthening or transfer, osteotomy, and arthrodesis. The described technique highlights our early surgical approach, which involves limited intervention before the deformity becomes rigid, severe, or disabling. We present 2 cases to contrast our early minimally invasive technique with traditional late stage reconstruction. Charcot-Marie-Tooth disease affects different muscles at various stages of disease progression. As 1 muscle becomes weak, the antagonist will overpower it and cause progressive deformity. The focus of the early minimally invasive approach is to decrease the forces that cause progressive deformity yet maintain function, where possible. Our goal has been to maintain a functional and braceable foot and ankle, with the hope of avoiding or limiting the extent of future major reconstructive surgery. The presented cases highlight the patient selection criteria, the ideal timing of early surgical intervention, the procedure selection criteria, and operative pearls. The early minimally invasive approach includes plantar fasciotomy, Achilles tendon lengthening, transfer of the peroneus longus to the fifth metatarsal, Hibbs and Jones tendon transfer, and hammertoe repair of digits 1 to 5.

  15. Clinical, neurophysiological and morphological study of dominant intermediate Charcot-Marie-Tooth type C neuropathy.

    Science.gov (United States)

    Thomas, Florian P; Guergueltcheva, Velina; Gondim, Francisco A A; Tournev, Ivailo; Rao, Chitharanjan V; Ishpekova, Boryana; Kinsella, Laurence J; Pan, Yi; Geller, Thomas J; Litvinenko, Ivan; De Jonghe, Peter; Scherer, Steven S; Jordanova, Albena

    2016-03-01

    Dominant intermediate Charcot-Marie-Tooth neuropathy subtype C (DI-CMTC) was associated with mutations in the YARS gene, encoding tyrosyl-tRNA synthetase, in two large unrelated Bulgarian and US pedigrees and one sporadic case. Here for the first time we describe the clinical, neurophysiological and histopathological features, and phenotypic differences between these two DI-CMTC families. Twenty-one affected individuals from the US family and 27 from the Bulgarian family were evaluated. The mean age of onset in US subjects was 10.7 years in men and 7.3 years in women, while in the Bulgarian participants it was 18.2 years in men and 33.7 years in women. The course was slowly progressive. Extensor digitorum brevis atrophy was uniform. Atrophy and/or weakness of upper and lower limb muscles were found in over 50 % of the subjects. Nerve conduction studies (NCS) were abnormal in all US adults and five of six children and all Bulgarian patients except one asymptomatic 25-year-old man. Median motor NCS were in the range of 29.5-45.6 m/s in the US family and 24.7-57.8 m/s in the Bulgarian family. Sural sensory nerve action potentials were absent in 14/21 and 4/12 NCS from adult US and Bulgarian participants, respectively. Analysis of sural nerve biopsies from US patients revealed age-dependent morphological changes of axonal degeneration, absence of onion bulbs, and <10 % fibers with segmental remyelination. Our findings provide further insights into the diagnosis and pathology of intermediate CMT. They also extend the phenotypic spectrum of peripheral neuropathies associated with aminoacyl-tRNA synthetase mutations.

  16. Myelin protein zero gene sequencing diagnoses Charcot-Marie-Tooth Type 1B disease

    Energy Technology Data Exchange (ETDEWEB)

    Su, Y.; Zhang, H.; Madrid, R. [Univ. of California, San Francisco, CA (United States)] [and others

    1994-09-01

    Charcot-Marie-Tooth disease (CMT), the most common genetic neuropathy, affects about 1 in 2600 people in Norway and is found worldwide. CMT Type 1 (CMT1) has slow nerve conduction with demyelinated Schwann cells. Autosomal dominant CMT Type 1B (CMT1B) results from mutations in the myelin protein zero gene which directs the synthesis of more than half of all Schwann cell protein. This gene was mapped to the chromosome 1q22-1q23.1 borderline by fluorescence in situ hybridization. The first 7 of 7 reported CMT1B mutations are unique. Thus the most effective means to identify CMT1B mutations in at-risk family members and fetuses is to sequence the entire coding sequence in dominant or sporadic CMT patients without the CMT1A duplication. Of the 19 primers used in 16 pars to uniquely amplify the entire MPZ coding sequence, 6 primer pairs were used to amplify and sequence the 6 exons. The DyeDeoxy Terminator cycle sequencing method used with four different color fluorescent lables was superior to manual sequencing because it sequences more bases unambiguously from extracted genomic DNA samples within 24 hours. This protocol was used to test 28 CMT and Dejerine-Sottas patients without CMT1A gene duplication. Sequencing MPZ gene-specific amplified fragments identified 9 polymorphic sites within the 6 exons that encode the 248 amino acid MPZ protein. The large number of major CMT1B mutations identified by single strand sequencing are being verified by reverse strand sequencing and when possible, by restriction enzyme analysis. This protocol can be used to distringuish CMT1B patients from othre CMT phenotypes and to determine the CMT1B status of relatives both presymptomatically and prenatally.

  17. [Molecular diagnosis of axonal forms of Charcot-Marie-Tooth disease].

    Science.gov (United States)

    Latour, P; Vial, C

    2009-12-01

    Charcot-Marie-Tooth (CMT) disease is the most common cause of inherited peripheral neuropathies with a frequency estimated at 1/2500. Electroneuromyographic examination distinguishes a myelinic form (CMT1) and an axonal form of the disease (CMT2). Significant genetic heterogeneity is found in CMT, with 15 genes or loci for CMT2. To date, a molecular diagnosis has not been established for most CMT2 patients and the distribution of identified mutations is wide spreading over nearly all genes. Simple guidelines for daily practice are difficult to establish from compilation of mutation reports or consultation of databases; little simplification can be expected from future findings. We present our results of molecular diagnosis for 251 CMT2 index cases characterized by their mode of inheritance (217 dominant and 34 recessive cases), and a motor conduction velocity in median nerve equal to or above to 38m/s. For each case, at least one of the genes known to date for CMT2 (MFN2, RAB7, GARS, NF-L, HSPB1, GDAP1, MPZ, HSPB8, GJB1, DNM2, YARS, LMNA, and MED25) was studied. Around 22% of diagnoses were established and efficiency was comparable for dominant or recessive cases. For dominant cases, the first objective was to search for mutations of proteins connexin32, mitofusin2 and P0. For recessive cases, GDAP1 provided the key to molecular diagnosis; lamin A/C mutations were only found for patients with an ethnic background from North Africa. Heat shock proteins HSPB1 and HSPB8 were implicated in a significant proportion of "spinal" (or pure motor) CMT2. NF-L or RAB7 mutations were rare. We did not identify any deleterious mutations in GARS, DNM2, YARS orMED2. We propose a simple decision tree for molecular diagnosis of CMT2.

  18. Junctophilin-1 is a modifier gene of GDAP1-related Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Pla-Martín, David; Calpena, Eduardo; Lupo, Vincenzo; Márquez, Celedonio; Rivas, Eloy; Sivera, Rafael; Sevilla, Teresa; Palau, Francesc; Espinós, Carmen

    2015-01-01

    Mutations in the GDAP1 gene cause different forms of Charcot-Marie-Tooth (CMT) disease, and the primary clinical expression of this disease is markedly variable in the dominant inheritance form (CMT type 2K; CMT2K), in which carriers of the GDAP1 p.R120W mutation can display a wide range of clinical severity. We investigated the JPH1 gene as a genetic modifier of clinical expression variability because junctophilin-1 (JPH1) is a good positional and functional candidate. We demonstrated that the JPH1-GDAP1 cluster forms a paralogon and is conserved in vertebrates. Moreover, both proteins play a role in Ca(2+) homeostasis, and we demonstrated that JPH1 is able to restore the store-operated Ca(2+) entry (SOCE) activity in GDAP1-silenced cells. After the mutational screening of JPH1 in a series of 24 CMT2K subjects who harbour the GDAP1 p.R120W mutation, we characterized the JPH1 p.R213P mutation in one patient with a more severe clinical picture. JPH1(p.R213P) cannot rescue the SOCE response in GDAP1-silenced cells. We observed that JPH1 colocalizes with STIM1, which is the activator of SOCE, in endoplasmic reticulum-plasma membrane puncta structures during Ca(2+) release in a GDAP1-dependent manner. However, when GDAP1(p.R120W) is expressed, JPH1 seems to be retained in mitochondria. We also established that the combination of GDAP1(p.R120W) and JPH1(p.R213P) dramatically reduces SOCE activity, mimicking the effect observed in GDAP1 knock-down cells. In summary, we conclude that JPH1 and GDAP1 share a common pathway and depend on each other; therefore, JPH1 can contribute to the phenotypical consequences of GDAP1 mutations.

  19. Balance and muscle power of children with Charcot-Marie-Tooth

    Directory of Open Access Journals (Sweden)

    Tais R. Silva

    2014-08-01

    Full Text Available BACKGROUND: In certain diseases, functional constraints establish a greater relationship with muscle power than muscle strength. However, in hereditary peripheral polyneuropathies, no such relationship was found in the literature. OBJECTIVE: In children with Charcot-Marie-Tooth (CMT, to identify the impact of muscle strength and range of movement on the static/dynamic balance and standing long jump based on quantitative and functional variables. METHOD: The study analyzed 19 participants aged between 6 and 16 years, of both genders and with clinical diagnoses of CMT of different subtypes. Anthropometric data, muscle strength of the lower limbs (hand-held dynamometer, ankle and knee range of movement, balance (Pediatric Balance Scale and standing long jump distance were obtained by standardized procedures. For the statistical analysis, Pearson and Spearman correlation coefficients were used. RESULTS: There was a strong positive correlation between balance and the muscle strength of the right plantar flexors (r=0.61 and dorsiflexors (r=0.59 and a moderate correlation between balance and the muscle strength of inversion (r=0.41 and eversion of the right foot (r=0.44. For the long jump and range of movement, there was a weak positive correlation with right and left plantar flexion (r=0.20 and r=0.12, respectively and left popliteal angle (r=0.25, and a poor negative correlation with left dorsiflexion (r=-0.15. CONCLUSIONS: The data on the patients analyzed suggests that the maintenance of distal muscle strength favors performance during balance tasks, while limitations in the range of movement of the legs seem not to be enough to influence the performance of the horizontal long jump.

  20. Moléstia de Charcot-Marie-Tooth: conceito clínico-patológico atual

    Directory of Open Access Journals (Sweden)

    José Antonio Levy

    1962-06-01

    Full Text Available Após considerações sobre o quadro anátomo-patológico da moléstia de Charcot-Marie-Tooth, o autor relata 4 casos, chegando à conclusão de que esta moléstia pode ser considerada como uma neuromiopatia em virtude de algumas alterações histopatológicas musculares serem primárias, ao passo que outras são secundárias à lesão do neurônio motor periférico.

  1. Coexistent Charcot-Marie-Tooth type 1A and type 2 diabetes mellitus neuropathies in a Chinese family

    OpenAIRE

    A-ping Sun; Lu Tang; Qin Liao; Hui Zhang; Ying-shuang Zhang; Jun Zhang(UT Austin)

    2015-01-01

    Charcot-Marie-Tooth disease type 1A (CMT1A) is caused by duplication of the peripheral myelin protein 22 (PMP22) gene on chromosome 17. It is the most common inherited demyelinating neuropathy. Type 2 diabetes mellitus is a common metabolic disorder that frequently causes predominantly sensory neuropathy. In this study, we report the occurrence of CMT1A in a Chinese family affected by type 2 diabetes mellitus. In this family, seven individuals had duplication of the PMP22 gene, although only ...

  2. Misunderstanding of foot drop in a patient with charcot-marie-tooth disease and lumbar disk herniation.

    Science.gov (United States)

    Han, Youngmin; Kim, Kyoung-Tae; Cho, Dae-Chul; Sung, Joo-Kyung

    2015-04-01

    We report the case of 57-year-old woman diagnosed with Charcot-Marie-Tooth (CMT) disease and lumbar disk herniation (LDH). She had left leg weakness and foot numbness, foot deformity (muscle atrophy, high arch, and clawed toes). The lumbar spine MRI showed LDH at L4-5. Additionally, electrophysiology results were consistent with chronic peripheral motor-sensory polyneuropathy (axonopathy). In genetic testing, 17p11.2-p12 duplication/deletions characteristic of CMT disease were observed. We confirmed the patient's diagnosis as CMT disease and used conservative treatment.

  3. Novel mutations in the PRX and the MTMR2 genes are responsible for unusual Charcot-Marie-Tooth disease phenotypes.

    Science.gov (United States)

    Nouioua, Sonia; Hamadouche, Tarik; Funalot, Benoit; Bernard, Rafaëlle; Bellatache, Nora; Bouderba, Radia; Grid, Djamel; Assami, Salima; Benhassine, Traki; Levy, Nicolas; Vallat, Jean-Michel; Tazir, Meriem

    2011-08-01

    Autosomal recessive Charcot-Marie-Tooth diseases, relatively common in Algeria due to high prevalence of consanguineous marriages, are clinically and genetically heterogeneous. We report on two consanguineous families with demyelinating autosomal recessive Charcot-Marie-Tooth disease (CMT4) associated with novel homozygous mutations in the MTMR2 gene, c.331dupA (p.Arg111LysfsX24) and PRX gene, c.1090C>T (p.Arg364X) respectively, and peculiar clinical phenotypes. The three patients with MTMR2 mutations (CMT4B1 family) had a typical phenotype of severe early onset motor and sensory neuropathy with typical focally folded myelin on nerve biopsy. Associated clinical features included vocal cord paresis, prominent chest deformities and claw hands. Contrasting with the classical presentation of CMT4F (early-onset Dejerine-Sottas phenotype), the four patients with PRX mutations (CMT4F family) had essentially a late age of onset and a protracted and relatively benign evolution, although they presented marked spine deformities. These observations broaden the spectrum of clinical phenotypes associated with these two CMT4 forms.

  4. Rapid genetic screening of Charcot-Marie-Tooth disease type 1A and hereditary neuropathy with liability to pressure palsies patients

    Institute of Scientific and Technical Information of China (English)

    Xiaobo Li; Kun Xia; Beisha Tang; Ruxu Zhang; Xiaohong Zi; Lin Li; Yajing Zhan; Shunxiang Huang; Jin Li; Xuning Li; Xigui Li; Zhengmao Hu

    2012-01-01

    We used the allele-specific PCR-double digestion method on peripheral myelin protein 22 (PMP22) to determine duplication and deletion mutations in the proband and family members of one family with Charcot-Marie-Tooth disease type 1 and one family with hereditary neuropathy with liability to pressure palsies. The proband and one subclinical family member from the Charcot-Marie-Tooth disease type 1 family had a PMP22 gene duplication; one patient from the hereditary neuropathy with liability to pressure palsies family had a PMP22 gene deletion. Electron microscopic analysis of ultrathin sections of the superficial peroneal nerve from the two probands demonstrated demyelination and myelin sheath hyperplasia, as well as an ‘onion-like’ structure in the Charcot-Marie-Tooth disease type 1A patient. We observed an irregular thickened myelin sheath and ‘mouse-nibbled’-like changes in the patient with hereditary neuropathy with liability to pressure palsies. In the Charcot-Marie-Tooth disease type 1A patient, nerve electrophysiological examination revealed moderate-to-severe reductions in the motor and sensory conduction velocities of the bilateral median nerve, ulnar nerve, tibial nerve, and sural nerve. Moreover, the compound muscle action potential amplitude was decreased. In the patient with hereditary neuropathy with liability to pressure palsies, the nerve conduction velocity of the bilateral tibial nerve and sural nerve was moderately reduced, and the nerve conduction velocity of the median nerve and ulnar nerve of both upper extremities was slightly reduced.

  5. Tripod pinch strength and thumb opposition are the major determinants of manual dexterity in Charcot-Marie-Tooth disease type 1A

    NARCIS (Netherlands)

    Videler, A.J.; Beelen, A.; van Schaik, I.N.; Verhamme, C.; van den Berg, L.H.; Visser, M.; Nollet, F.

    2010-01-01

    BACKGROUND: Clinical features of Charcot-Marie-Tooth disease type 1A (CMT1A) include slowly progressive distal muscle weakness, atrophy and sensory loss. Upper-limb involvement results in reduced manual dexterity interfering with the execution of daily activities. OBJECTIVE: To identify which hand f

  6. Doença de Charcot-Marie-Tooth: estudo da biópsia do nervo sural em 41 pacientes Charcot-Marie-Tooth disease: sural nerve biopsy findings in 41 patients

    OpenAIRE

    Freitas,Marcos R. G.; Osvaldo J. M. Nascimento; Leila Chimelli; Freitas,Gabriel R. de

    1995-01-01

    São apresentados os resultados da biópsia do nervo sural à microscopia óptica e eletrônica (ME) em 41 pacientes com doença de Charcot-Marie-Tooth (CMT) Por estudos de neurocondução prévios nove eram do tipo I e 32 do tipo II. No tipo I, todos tinham grande diminuição do número de fibras, sendo os histogramas do tipo unimodal. Encontramos imagens de desmielinização, remielinização, formação de bulbos de cebola e de regeneração. Um paciente apresentava espessamento da bainha de mielina (atrofia...

  7. Correlation between connexin 32 gene mutations and clinical phenotype in X-linked dominant Charcot-Marie-Tooth neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Ionasescu, V.; Ionasescu, R.; Searby, C. [Univ. of Iowa Hospitals and Clinics, Iowa City, IA (United States)

    1996-06-14

    We studied the relationship between the genotype and clinical phenotype in 27 families with dominant X-linked Charcot-Marie-Tooth (CMTX1) neuropathy. Twenty-two families showed mutations in the coding region of the connexin32 (cx32) gene. The mutations include four nonsense mutations, eight missense mutations, two medium size deletions, and one insertion. Most missense mutations showed a mild clinical phenotype (five out of eight), whereas all nonsense mutations, the larger of the two deletions, and the insertion that produced frameshifts showed severe phenotypes. Five CMTX1 families with mild clinical phenotype showed no point mutations of the cx32 gene coding region. Three of these families showed positive genetic linkage with the markers of the Xq13.1 region. The genetic linkage of the remaining two families could not be evaluated because of their small size. 25 refs., 1 fig., 1 tab.

  8. Coexistent Charcot-Marie-Tooth type 1A and type 2 diabetes mellitus neuropathies in a Chinese family

    Directory of Open Access Journals (Sweden)

    A-ping Sun

    2015-01-01

    Full Text Available Charcot-Marie-Tooth disease type 1A (CMT1A is caused by duplication of the peripheral myelin protein 22 (PMP22 gene on chromosome 17. It is the most common inherited demyelinating neuropathy. Type 2 diabetes mellitus is a common metabolic disorder that frequently causes predominantly sensory neuropathy. In this study, we report the occurrence of CMT1A in a Chinese family affected by type 2 diabetes mellitus. In this family, seven individuals had duplication of the PMP22 gene, although only four had clinical features of polyneuropathy. All CMT1A patients with a clinical phenotype also presented with type 2 diabetes mellitus. The other three individuals had no signs of CMT1A or type 2 diabetes mellitus. We believe that there may be a genetic link between these two diseases.

  9. A novel mitofusin 2 gene mutation causing Charcot-Marie-Tooth type 2A disease in a Chinese family

    Institute of Scientific and Technical Information of China (English)

    CHEING Chor Kwan; LAU Kwok Kwong; YU Kwok Wai; CHAN Yan Wo Albert; MAK Miu Chloe

    2010-01-01

    @@ Charcot-Marie-Tooth disease (CMT), also known as hereditary motor and sensory neuropathies, comprises a genetically heterogeneous group of inherited peripheral neuropathies. Clinically it is characterized by progressive distal weakness, muscle atrophy, distal sensory loss and loss of deep tendon reflexes. Following electrophysiological criteria, CMT is divided into two main forms: the primarily demyelinating neuropathy CMT1 with severely decreased nerve conduction velocity (NCV) (38 m/s) but decreased amplitudes.1 CMT2A, an autosomal dominant disease caused by mitofusin 2 gene (MFN2) mutations, is the most common type of CMT2, accounting for up to 33% of familial CMT2 cases.2 We reported a patient with clinical diagnosis of CMT2 caused by a novel MFN2 mutation. To our knowledge, this is a relatively early report of genetically confirmed CMT2A in Chinese.

  10. [Current Status of Genetic Diagnosis of Charcot-Marie-Tooth Disease: Variety of the Disease-causing Genes].

    Science.gov (United States)

    Hashiguchi, Akihiro; Higuchi, Yujiro; Takashima, Hiroshi

    2016-01-01

    At least 40 genes have been associated with Charcot-Marie-Tooth disease (CMT) and the related inherited neuropathies. Genetic studies have revealed the following factors as causes of inherited neuropathies: myelin components, transcription factors for myelination, myelin maintenance systems, differentiation factors of the peripheral nerve, neurofilaments, protein transfer systems, mitochondrial proteins, DNA repair, RNA/protein synthesis, ion channels, and aminoacyl-tRNA synthetases. Since 2007, we have tried to screen for mutations in CMT patients using microarrays or next generation sequencers. As a result, the detection rate of gene mutations has improved to about 25%. In this study, we applied target resequencing to 72 genes. From the negative examples, we identified the cases based on clinical course, family history, and electrophysiological findings, and then performed exome analysis. We then tried to identify novel causative genes by analyzing the enormous data obtained from our exome analysis.

  11. Dynamic pedobarography and radiographic evaluation of surgically treated cavovarus foot deformity in children with Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Erickson, Steven; Hosseinzadeh, Pooya; Iwinski, Henry J; Muchow, Ryan C; Talwalkar, Vishwas R; Walker, Janet L; Milbrandt, Todd A

    2015-07-01

    Pedobarography is a common tool for the evaluation of foot deformity. We describe our radiographic and pedobarographic outcomes of surgical treatment of cavovarus foot deformity in children with Charcot-Marie-Tooth disease. Nineteen patients for a total of 30 feet were included. Preoperative and postoperative dynamic pedobarographic measurements were made and analyzed using the five-mask technique. Pedobarographic measures showed statistical significance for increased contact area and decreased peak forces in most mask areas after surgical treatment. Peak pressure and redistribution of varus pressure patterns trended toward improvement. We found pedobarographic studies helpful; however, pedobarographic data are somewhat difficult to interpret and should be used in addition to clinical and radiographic examination.

  12. Analysis of the benefits of vitamin cocktails in treating Charcot-Marie-Tooth disease type 1A.

    Science.gov (United States)

    Kaya, Ferdinand; Belin, Sophie; Micallef, Joelle; Blin, Olivier; Fontés, Michel

    2008-08-01

    We recently proposed that the use of high doses of ascorbic acid (AA) could constitute the first potential treatment for Charcot-Marie-Tooth disease type 1A (CMT1A).4 We investigated the potential benefits of using cocktails of vitamins for CMT1A therapy. We used transient transfection of Schwann cells with a construction placing the expression of a reporter gene under the control of the Schwann cell-specific promoter of PMP22. Transfected cells were cultured with or without addition of ascorbic acid, vitamin A, vitamin E, or a cocktail of these vitamins. Adding vitamin A or E counteracts the effect of ascorbic acid in inhibiting PMP22 expression. We thus recommend that vitamins A and E should not be included in combination with AA in clinical trials.

  13. [Case of Charcot-Marie-Tooth disease type 1A with increased cerebrospinal fluid proteins and nerve root hypertrophy].

    Science.gov (United States)

    Ishigami, Noriko; Kondo, Masaki; Nakagawa, Masanori

    2008-06-01

    We report herein a 54-year-old man who first noticed muscle weakness of the hands and legs and hypesthesia of the legs at 20-years-old. Symptoms gradually worsened. Charcot-Marie-Tooth disease type 1A (CMT 1A) was diagnosed on the basis of a nerve conduction study and PMP22 gene duplication. Increased levels of cerebrospinal fluid proteins were identified and cervical and lumbosacral nerve root hypertrophy was evident on magnetic resonance imaging (MRI). CMT 1A with increased CSF proteins and nerve root hypertrophy was carefully evaluated clinically and electrophysiologically to rule out other motor sensory neuropathies such as CIDP. Increased levels of CSF proteins in this case might have resulted from circulatory disturbance of CSF in hypertrophic nerve roots.

  14. Clinical and neurophysiological investigation of a large family with dominant Charcot-Marie-Tooth type 2 disease with pyramidal signs

    Directory of Open Access Journals (Sweden)

    Eduardo Luis de Aquino Neves

    2011-06-01

    Full Text Available Charcot-Marie-Tooth (CMT disease is a hereditary neuropathy of motor and sensory impairment with distal predominance. Atrophy and weakness of lower limbs are the first signs of the disease. It can be classified, with the aid of electromyography and nerve conduction studies, as demyelinating (CMT1 or axonal (CMT2. OBJECTIVE: Clinical and neurophysiological investigation of a large multigenerational family with CMT2 with autosomal dominant mode of transmission. METHOD: Fifty individuals were evaluated and neurophysiological studies performed in 22 patients. RESULTS: Thirty individuals had clinical signs of motor-sensory neuropathy. Babinski sign was present in 14 individuals. Neurophysiological study showed motor-sensory axonal polyneuropathy. CONCLUSION: The clinical and neurophysiological characteristics of this family does not differ from those observed with other forms of CMT, except for the high prevalence of Babinski sign.

  15. Charcot-Marie-Tooth syndrome and neurofibromatosis type 1 with multiple neurofibromas of the entire spinal nerve roots.

    Science.gov (United States)

    Onu, David O; Hunn, Andrew W; Peters-Willke, Jens

    2013-07-13

    The coexistence of polyneuropathy which has the definite clinical and electromyographical findings consistent with Charcot-Marie-Tooth (CMT) syndrome and neurofibromatosis type 1 (NF1) has infrequently been reported. We describe a patient with both CMT and NF1, who had multiple neurofibromas involving the entire spinal neural axis. In addition, he had multiple neurofibromas distributed within the ileopsoas and gluteus muscles and subcutaneous tissues. These lesions were detected readily by MRI and the patient underwent successful surgical resection of the largest tumours compressing bilateral C2 nerve roots. To our knowledge, this is the first reported case of CMT syndrome coexisting with NF1 in which multiple neurofibromas involved the entire spinal nerve roots. We discuss the diagnostic and therapeutic challenges, emphasising the role of MRI and electrophysiology in such cases and provide a literature review.

  16. Amiotrofia neuro-medular de Charcot-Marie-Tooth associada a artrogripose multipla congenita: registro de um caso e revisão da literatura

    Directory of Open Access Journals (Sweden)

    James Pitagoras de Mattos

    1982-09-01

    Full Text Available Os autores registram a associação da amiotrofia neuro-medular de Charcot-Marie-Tooth com artrogripose múltipla congênita. Mostram as associações com as duas condições em apreço na literatura, assim como acrescentam outras alterações observadas nos diversos exames radiológicos realizados.

  17. The central nervous system phenotype of X-linked Charcot-Marie-Tooth disease: a transient disorder of children and young adults.

    Science.gov (United States)

    Al-Mateen, Majeed; Craig, Alexa Kanwit; Chance, Phillip F

    2014-03-01

    We describe 2 patients with X-linked Charcot-Marie-Tooth disease, type 1 (CMTX1) disease and central nervous system manifestations and review 19 cases from the literature. Our first case had not been previously diagnosed with Charcot-Marie-Tooth disease, and the second case, although known to have Charcot-Marie-Tooth disease, was suspected of having CMTX1 after presentation with central nervous system manifestations. The most common central nervous system manifestations were transient and included dysarthria, ataxia, hemiparesis, and tetraparesis resembling periodic paralysis. Of the 21 patients, 19 presented at 21 years of age or younger, implicating CMTX1 with transient central nervous system manifestations as a disorder that predominantly affects children and adolescents. CMTX1 should be included in the differential diagnosis of patients who present with transient central nervous system phenomena, including stroke-like episodes, tetraparesis suggestive of periodic paralysis, dysarthria, ataxia, or combinations of these deficits. Reversible, bilateral, nonenhancing white matter lesions and restricted diffusion on magnetic resonance imaging are characteristic features of the central nervous system phenotype of CMTX1.

  18. Assessment of Targeted Next-Generation Sequencing as a Tool for the Diagnosis of Charcot-Marie-Tooth Disease and Hereditary Motor Neuropathy.

    Science.gov (United States)

    Lupo, Vincenzo; García-García, Francisco; Sancho, Paula; Tello, Cristina; García-Romero, Mar; Villarreal, Liliana; Alberti, Antonia; Sivera, Rafael; Dopazo, Joaquín; Pascual-Pascual, Samuel I; Márquez-Infante, Celedonio; Casasnovas, Carlos; Sevilla, Teresa; Espinós, Carmen

    2016-03-01

    Charcot-Marie-Tooth disease is characterized by broad genetic heterogeneity with >50 known disease-associated genes. Mutations in some of these genes can cause a pure motor form of hereditary motor neuropathy, the genetics of which are poorly characterized. We designed a panel comprising 56 genes associated with Charcot-Marie-Tooth disease/hereditary motor neuropathy. We validated this diagnostic tool by first testing 11 patients with pathological mutations. A cohort of 33 affected subjects was selected for this study. The DNAJB2 c.352+1G>A mutation was detected in two cases; novel changes and/or variants with low frequency (A mutation was also detected in three additional families. On haplotype analysis, all of the patients from these five families shared the same haplotype; therefore, the DNAJB2 c.352+1G>A mutation may be a founder event. Our gene panel allowed us to perform a very rapid and cost-effective screening of genes involved in Charcot-Marie-Tooth disease/hereditary motor neuropathy. Our diagnostic strategy was robust in terms of both coverage and read depth for all of the genes and patient samples. These findings demonstrate the difficulty in achieving a definitive molecular diagnosis because of the complexity of interpreting new variants and the genetic heterogeneity that is associated with these neuropathies.

  19. SENSITIVITY OF COMPUTER ESTHESIOMETRY ON DISTAL PARTS OF THE UPPER EXTREMITIES AT PATIENTS WITH HEREDITARY NEUROPATHY CHARCOT-MARIE-TOOTH

    Directory of Open Access Journals (Sweden)

    NATALIA SHNAYDER

    2011-11-01

    Full Text Available The purpose: to define the diagnostic importance of computer esthesiometry for use in diagnostics of hereditary neuropathy with primary defeat of myelin sheath of peripheral nerves of the upper extremities. Materials and methods: 47 individuals in a condition of relative health (control group from 21 to 50 years, comparable group % 40 patients from 6 to 81 years, with hereditary neuropathy Charcot%Marie%Tooth (CMT. Vibrating sensitivity was investigated by means of computer vibrometer “Vibrotester MBN” VТ%02%1 (MBN, RF in a wide strip of frequencies of vibration (8, 16, 32, 64, 125, 250, 500 Hz. Statistical data processing of research was lead by means of programs STATISTICA v. 7.0 (StatSoft, USA. Results and discussion: We compared received corridors vibrating sensitivity on the upper extremities for healthy volunteers with those at patients with CMT. Statistically significant increase of vibration sensitivity thresholds in a wide range of vibration frequencies on upper extremities and at patients with CMT versus healthy volunteers is shown. Computer esthesiometry method demonstrates high sensitivity in diagnostics of hereditary neuropathy with primary damage of myelin sheath of peripheral nerves of upper extremities on an example of CMT.

  20. Multicolor in situ hybridization and linkage analysis order Charcot-Marie-Tooth type I (CMTIA) gene-region markers

    Energy Technology Data Exchange (ETDEWEB)

    Lebo, R.V.; Lynch, E.D.; Golbus, M.S. (Univ. of California, San Francisco (United States)); Bird, T.D. (Univ. of Washington, Seattle (United States)); Barker, D.F.; O' Connell, P.; Chance, P.F. (Univ. of Utah, Salt Lake City (United States))

    1992-01-01

    This study demonstrates a clear and current role for multicolor in situ hybridization in expediting positional cloning studies of unknown disease genes. Nine polymorphic DNA cosmids have been mapped to eight ordered locations spanning the Charcot-Marie-Tooth type 1 (CMT1A) disease gene region in distal band 17p11.2, by multicolor in situ hybridization. When used with linkage analysis, these methods have generated a fine physical map and have firmly assigned the CMT1A gene to distal band 17p11.2. Linkage analysis with four CMT1A pedigrees mapped the CMT1A gene with respect to two flanking markers. Additional loci were physically mapped and ordered by in situ hybridization and analysis of phase-known recombinants in CMT1A pedigrees. These data demonstrate the ability of in situ hybridization to resolve loci within 0.5 Mb on early-metaphase chromosomes. Multicolor in situ hybridization also excluded the possibility of pericentric inversions in two unrelated patients with CMT1 and neurofibromatosis type 1. When used with pulsed-field gel electrophoresis, multicolor in situ hybridization can establish physical location, order, and distance in closely spaced chromosome loci.

  1. Mapping of the chromosome 1p36 region surrounding the Charcot-Marie-Tooth disease type 2A locus

    Energy Technology Data Exchange (ETDEWEB)

    Denton, P.; Gere, S.; Wolpert, C. [Duke Univ., Durham, NC (United States)] [and others

    1994-09-01

    Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral neuropathy. Although CMT2 is clinically indistinguishable from CMT1, the two forms can be differentiated by pathological and neurophysiological methods. We have established one locus, CMT2A on chromosome 1p36, and have established genetic heterogeneity. This locus maps to the region of the deletions associated with neuroblastoma. We have now identified an additional 11 CMT2 families. Three families are linked to chromosome 1p36 while six families are excluded from this region. Another six families are currently under analysis and collection. To date the CMT2A families represent one third of those CMT2 families examined. We have established a microdissection library of the 1p36 region which is currently being characterized for microsatellite repeats and STSs using standard hybridization techniques and a modified degenerate primer method. In addition, new markers (D1S253, D1S450, D1S489, D1S503, GATA27E04, and GATA4H04) placed in this region are being mapped using critical recombinants in the CEPH reference pedigrees. Fluorescent in situ hybridization (FISH) has been used to confirm mapping. A YAC contig is being assembled from the CEPH megabase library using STSs to isolate key YACs which are extended by vectorette end clone and Alu-PCR. These findings suggest that the CMT2 phenotype is secondary to at least two different genes and demonstrates further heterogeneity in the CMT phenotype.

  2. DGAT2 Mutation in a Family with Autosomal-Dominant Early-Onset Axonal Charcot-Marie-Tooth Disease.

    Science.gov (United States)

    Hong, Young Bin; Kang, Junghee; Kim, Ji Hyun; Lee, Jinho; Kwak, Geon; Hyun, Young Se; Nam, Soo Hyun; Hong, Hyun Dae; Choi, Yu-Ri; Jung, Sung-Chul; Koo, Heasoo; Lee, Ji Eun; Choi, Byung-Ok; Chung, Ki Wha

    2016-05-01

    Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy and is a genetically and clinically heterogeneous disorder. We examined a Korean family in which two individuals had an autosomal-dominant axonal CMT with early-onset, sensory ataxia, tremor, and slow disease progression. Pedigree analysis and exome sequencing identified a de novo missense mutation (p.Y223H) in the diacylglycerol O-acyltransferase 2 (DGAT2) gene. DGAT2 encodes an endoplasmic reticulum-mitochondrial-associated membrane protein, acyl-CoA:diacylglycerol acyltransferase, which catalyzes the final step of the triglyceride (TG) biosynthesis pathway. The patient showed consistently decreased serum TG levels, and overexpression of the mutant DGAT2 significantly inhibited the proliferation of mouse motor neuron cells. Moreover, the variant form of human DGAT2 inhibited the axonal branching in the peripheral nervous system of zebrafish. We suggest that mutation of DGAT2 is the novel underlying cause of an autosomal-dominant axonal CMT2 neuropathy. This study will help provide a better understanding of the pathophysiology of axonal CMT and contribute to the molecular diagnostics of peripheral neuropathies.

  3. Absence of Dystrophin Related Protein-2 disrupts Cajal bands in a patient with Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Brennan, Kathryn M; Bai, Yunhong; Pisciotta, Chiara; Wang, Suola; Feely, Shawna M E; Hoegger, Mark; Gutmann, Laurie; Moore, Steven A; Gonzalez, Michael; Sherman, Diane L; Brophy, Peter J; Züchner, Stephan; Shy, Michael E

    2015-10-01

    Using exome sequencing in an individual with Charcot-Marie-Tooth disease (CMT) we have identified a mutation in the X-linked dystrophin-related protein 2 (DRP2) gene. A 60-year-old gentleman presented to our clinic and underwent clinical, electrophysiological and skin biopsy studies. The patient had clinical features of a length dependent sensorimotor neuropathy with an age of onset of 50 years. Neurophysiology revealed prolonged latencies with intermediate conduction velocities but no conduction block or temporal dispersion. A panel of 23 disease causing genes was sequenced and ultimately was uninformative. Whole exome sequencing revealed a stop mutation in DRP2, c.805C>T (Q269*). DRP2 interacts with periaxin and dystroglycan to form the periaxin-DRP2-dystroglycan complex which plays a role in the maintenance of the well-characterized Cajal bands of myelinating Schwann cells. Skin biopsies from our patient revealed a lack of DRP2 in myelinated dermal nerves by immunofluorescence. Furthermore electron microscopy failed to identify Cajal bands in the patient's dermal myelinated axons in keeping with ultrastructural pathology seen in the Drp2 knockout mouse. Both the electrophysiologic and dermal nerve twig pathology support the interpretation that this patient's DRP2 mutation causes characteristic morphological abnormalities recapitulating the Drp2 knockout model and potentially represents a novel genetic cause of CMT.

  4. Bicyclic-Capped Histone Deacetylase 6 Inhibitors with Improved Activity in a Model of Axonal Charcot-Marie-Tooth Disease.

    Science.gov (United States)

    Shen, Sida; Benoy, Veronick; Bergman, Joel A; Kalin, Jay H; Frojuello, Mariana; Vistoli, Giulio; Haeck, Wanda; Van Den Bosch, Ludo; Kozikowski, Alan P

    2016-02-17

    Charcot-Marie-Tooth (CMT) disease is a disorder of the peripheral nervous system where progressive degeneration of motor and sensory nerves leads to motor problems and sensory loss and for which no pharmacological treatment is available. Recently, it has been shown in a model for the axonal form of CMT that histone deacetylase 6 (HDAC6) can serve as a target for the development of a pharmacological therapy. Therefore, we aimed at developing new selective and activity-specific HDAC6 inhibitors with improved biochemical properties. By utilizing a bicyclic cap as the structural scaffold from which to build upon, we developed several analogues that showed improved potency compared to tubastatin A while maintaining excellent selectivity compared to HDAC1. Further screening in N2a cells examining both the acetylation of α-tubulin and histones narrowed down the library of compounds to three potent and selective HDAC6 inhibitors. In mutant HSPB1-expressing DRG neurons, serving as an in vitro model for CMT2, these inhibitors were able to restore the mitochondrial axonal transport deficits. Combining structure-based development of HDAC6 inhibitors, screening in N2a cells and in a neuronal model for CMT2F, and preliminary ADMET and pharmacokinetic profiles, resulted in the selection of compound 23d that possesses improved biochemical, functional, and druglike properties compared to tubastatin A.

  5. Charcot-Marie-Tooth-linked mutant GARS is toxic to peripheral neurons independent of wild-type GARS levels.

    Directory of Open Access Journals (Sweden)

    William W Motley

    2011-12-01

    Full Text Available Charcot-Marie-Tooth disease type 2D (CMT2D is a dominantly inherited peripheral neuropathy caused by missense mutations in the glycyl-tRNA synthetase gene (GARS. In addition to GARS, mutations in three other tRNA synthetase genes cause similar neuropathies, although the underlying mechanisms are not fully understood. To address this, we generated transgenic mice that ubiquitously over-express wild-type GARS and crossed them to two dominant mouse models of CMT2D to distinguish loss-of-function and gain-of-function mechanisms. Over-expression of wild-type GARS does not improve the neuropathy phenotype in heterozygous Gars mutant mice, as determined by histological, functional, and behavioral tests. Transgenic GARS is able to rescue a pathological point mutation as a homozygote or in complementation tests with a Gars null allele, demonstrating the functionality of the transgene and revealing a recessive loss-of-function component of the point mutation. Missense mutations as transgene-rescued homozygotes or compound heterozygotes have a more severe neuropathy than heterozygotes, indicating that increased dosage of the disease-causing alleles results in a more severe neurological phenotype, even in the presence of a wild-type transgene. We conclude that, although missense mutations of Gars may cause some loss of function, the dominant neuropathy phenotype observed in mice is caused by a dose-dependent gain of function that is not mitigated by over-expression of functional wild-type protein.

  6. Recurrent Episodes of Stroke-Like Symptoms in a Patient with Charcot-Marie-Tooth Neuropathy X Type 1

    Directory of Open Access Journals (Sweden)

    Ning Wu

    2015-12-01

    Full Text Available Charcot-Marie-Tooth disease (CMT, also known as hereditary motor sensory neuropathy, is a heterogeneous group of disorders best known for causing inherited forms of peripheral neuropathy. The X-linked form, CMTX1, is caused by mutations in the gap junction protein beta 1 (GJB1 gene, expressed both by peripheral Schwann cells and central oligodendrocytes. Central manifestations are known but are rare, and there are few case reports of leukoencephalopathy with transient or persistent neurological deficits in patients with this CMT subtype. Here, we report the case of a man with multiple male and female family members affected by neuropathy who carries a pathologic mutation in GJB1. He has experienced three transient episodes with variable neurological deficits over the course of 7 years with corresponding changes on magnetic resonance imaging (MRI. This case illustrates CMT1X as a rare cause of transient neurological deficit and demonstrates the evolution of associated reversible abnormalities on MRI over time. To the best of our knowledge, this report provides the longest period of serial imaging in a single patient with this condition in the English language literature.

  7. Improving molecular diagnosis of Chinese patients with Charcot-Marie-Tooth by targeted next-generation sequencing and functional analysis.

    Science.gov (United States)

    Li, Li-Xi; Zhao, Shao-Yun; Liu, Zhi-Jun; Ni, Wang; Li, Hong-Fu; Xiao, Bao-Guo; Wu, Zhi-Ying

    2016-05-10

    Charcot-Marie-Tooth (CMT) disease is the most common hereditary peripheral neuropathy. More than 50 causative genes have been identified. The lack of genotype-phenotype correlations in many CMT patients make it difficult to decide which genes are affected. Recently, targeted next-generation sequencing (NGS) has been introduced as an alternative approach for diagnosis of genetic disorders. Here, we applied targeted NGS in combination with PMP22 duplication/deletion analysis to screen causative genes in 22 Chinese CMT families. The novel variants detected by targeted NGS were then further studied in cultured cells. Of the 22 unrelated patients, 8 had PMP22 duplication. The targeted NGS revealed 10 possible pathogenic variants in 11 patients, including 7 previously reported variants and 3 novel heterozygous variants (GJB1: p.Y157H; MFN2: p.G127S; YARS: p.V293M). Further classification of the novel variants according to American College of Medical Genetics and Genomics (ACMG) standards and guidelines and functional analysis in cultured cells indicated that p.Y157H in GJB1 was pathogenic, p.G127S in MFN2 was likely pathogenic, while p.V293M in YARS was likely benign. Our results suggest the potential for targeted NGS to make a more rapid and precise diagnosis in CMT patients. Moreover, the functional analysis is required when the novel variants are indistinct.

  8. Occurrence of Optic Neuritis and Cervical Cord Schwannoma with Charcot-Marie-Tooth Type 4B1 Disease.

    Science.gov (United States)

    Scott, Patrick; Bruwer, Zandre; Al-Kharusi, Khalsa; Meftah, Douja; Al-Murshedi, Fathiya

    2016-05-01

    Charcot-Marie-Tooth neuropathy type 4B1 (CMT4B1) disease is a rare subtype of CMT4 with reported association of facial weakness, vocal cord paresis, chest deformities, and claw hands. We report the unusual occurrence of optic neuritis and cervical cord schwannoma in a male individual with confirmed CMT4B1 disease. Sequencing of the MTMR2 gene revealed a novel nonsense homozygous mutation c.1768C>T (p.Gln590*). The mutation was identified in affected relatives of the proband and a second, apparently unrelated, family. The rare association of optic neuritis or schwannoma with genetically confirmed CMT1A has been individually observed, but never with recessive CMT. To the best of our knowledge, the occurrence of optic neuritis and cervical cord schwannoma in the same patient has never been reported with any form of CMT including CMT4B1. In similar cases, we recommend immediate medical attention to rule out the possibility of schwannomas in patients with all demyelinating CMT subtypes in case of the development of focal neurological signs or acute worsening of clinical status.

  9. A cohort study of MFN2 mutations and phenotypic spectrums in Charcot-Marie-Tooth disease 2A patients.

    Science.gov (United States)

    Choi, B-O; Nakhro, K; Park, H J; Hyun, Y S; Lee, J H; Kanwal, S; Jung, S-C; Chung, K W

    2015-06-01

    Charcot-Marie-Tooth disease 2A (CMT2A) is the most common axonal form of peripheral neuropathy caused by a defect in the mitofusin 2 (MFN2) gene, which encodes an outer mitochondrial membrane GTPase. MFN2 mutations result in a large range of phenotypes. This study analyzed the prevalence of MFN2 mutation in Korean families with their assorted phenotypes (607 CMT families and 160 CMT2 families). Direct sequencing of the MFN2 coding exons or whole-exome sequencing has been applied to identify causative mutations. A total of 21 mutations were found in 36 CMT2 families. Comparative genotype-phenotype correlations impacting severity, onset age, and specific symptoms were assessed. Most mutations were seen in the GTPase domain (∼86%). A deletion mutation found in the transmembrane helices is reported for the first time, as well as five novel mutations at other domains. MFN2 mutations made up 5.9% of total CMT families, whereas 22.9% in CMT2 families, of which 27.8% occurred de novo. Interestingly, patient phenotypes ranged from mild to severe even for the same mutation, suggesting other factors influenced phenotype and penetrance. This CMT2A cohort study will be useful for molecular diagnosis and treatment of axonal neuropathy.

  10. Charcot-Marie-Tooth Disease Type 4H Resulting from Compound Heterozygous Mutations in FGD4 from Nonconsanguineous Korean Families.

    Science.gov (United States)

    Hyun, Young Se; Lee, Jinho; Kim, Hye Jin; Hong, Young Bin; Koo, Heasoo; Smith, Alec S T; Kim, Deok-Ho; Choi, Byung-Ok; Chung, Ki Wha

    2015-11-01

    Charcot-Marie-Tooth disease type 4H (CMT4H) is an autosomal recessive demyelinating subtype of peripheral enuropathies caused by mutations in the FGD4 gene. Most CMT4H patients are in consanguineous Mediterranean families characterized by early onset and slow progression. We identified two CMT4H patients from a Korean CMT cohort, and performed a detailed genetic and clinical analysis in both cases. Both patients from nonconsanguineous families showed characteristic clinical manifestations of CMT4H including early onset, scoliosis, areflexia, and slow disease progression. Exome sequencing revealed novel compound heterozygous mutations in FGD4 as the underlying cause in both families (p.Arg468Gln and c.1512-2A>C in FC73, p.Met345Thr and c.2043+1G>A (p.Trp663Trpfs*30) in FC646). The missense mutations were located in highly conserved RhoGEF and PH domains which were predicted to be pathogenic in nature by in silico modeling. The CMT4H occurrence frequency was calculated to 0.7% in the Korean demyelinating CMT patients. This study is the first report of CMT4H in Korea. FGD4 assay could be considered as a means of molecular diagnosis for sporadic cases of demyelinating CMT with slow progression.

  11. Autosomal recessive MFN2-related Charcot-Marie-Tooth disease with diaphragmatic weakness: Case report and literature review.

    Science.gov (United States)

    Tan, Christopher A; Rabideau, Marina; Blevins, Amy; Westbrook, Marjorie Jody; Ekstein, Tali; Nykamp, Keith; Deucher, Anne; Harper, Amy; Demmer, Laurie

    2016-06-01

    Pathogenic variants in the mitofusin 2 gene (MFN2) are the most common cause of autosomal dominant Charcot-Marie-Tooth (CMT2) disease, which is typically characterized by axonal sensorimotor neuropathy. We report on a 7-month-old white female with hypotonia, motor delay, distal weakness, and motor/sensory axonal neuropathy in which next-generation sequencing analysis identified compound heterozygous pathogenic variants (c.2054_2069_1170del and c.392A>G) in MFN2. A review of the literature reveals that sporadic and familial cases of compound heterozygous or homozygous pathogenic MFN2 variants have been infrequently described, which indicates that MFN2 can also be inherited in a recessive manner. This case highlights several clinical findings not typically associated with MFN2 pathogenic variants, including young age of onset and rapidly progressing diaphragmatic paresis that necessitated tracheostomy and mechanical ventilation, and adds to the growing list of features identified in autosomal recessive MFN2-related CMT2. Our patient with MFN2-related CMT2 expands the clinical and mutational spectrum of individuals with autosomal recessive CMT2 and identifies a new clinical feature that warrants further observation. © 2016 Wiley Periodicals, Inc.

  12. A Novel Mutation of GDAP1 Associated with Charcot-Marie-Tooth Disease in An Iranian Family

    Directory of Open Access Journals (Sweden)

    Esmaeel MOHAMMADI PARGOO

    2012-06-01

    Full Text Available As a result of higher distributed consanguinity in the Mediterranean region and the Middle East, autosomal-recessive forms of Charcot-Marie-Tooth (ARCMT are more common in these areas. CMT disease caused by mutations in the ganglioside-induced differentiation-associated protein 1 (GDAP1 gene is a severe autosomal recessive neuropathy resulting in either demyelinating CMT4A neuropathy or axonal neuropathy with vocal cord paresis. The patient was an 8-year-old boy with AR inheritance that showed some delayed achievement of motor milestones, including walking, also bilateral foot drop, wasting of distal muscles in the legs, pes cavus and marked weakness of the foot dorsiflexors. He had no hoarseness or vocal cord paralysis. Total genomic DNA was extracted from whole peripheral blood of the patient and his family by using standard procedures. PCR- sequencing method were used to analysis the whole coding regions of the GDAP1 gene. A novel homozygote insertion of T nucleotide in codon 34 was detected (c.100_101insT that probably led to an early stop codon. This mutation may be associated with a common haplotype, suggesting a common ancestor that needs further investigation in the Iranian population.

  13. Improving molecular diagnosis of Chinese patients with Charcot-Marie-Tooth by targeted next-generation sequencing and functional analysis

    Science.gov (United States)

    Liu, Zhi-Jun; Ni, Wang; Li, Hong-Fu; Xiao, Bao-Guo; Wu, Zhi-Ying

    2016-01-01

    Charcot-Marie-Tooth (CMT) disease is the most common hereditary peripheral neuropathy. More than 50 causative genes have been identified. The lack of genotype-phenotype correlations in many CMT patients make it difficult to decide which genes are affected. Recently, targeted next-generation sequencing (NGS) has been introduced as an alternative approach for diagnosis of genetic disorders. Here, we applied targeted NGS in combination with PMP22 duplication/deletion analysis to screen causative genes in 22 Chinese CMT families. The novel variants detected by targeted NGS were then further studied in cultured cells. Of the 22 unrelated patients, 8 had PMP22 duplication. The targeted NGS revealed 10 possible pathogenic variants in 11 patients, including 7 previously reported variants and 3 novel heterozygous variants (GJB1: p.Y157H; MFN2: p.G127S; YARS: p.V293M). Further classification of the novel variants according to American College of Medical Genetics and Genomics (ACMG) standards and guidelines and functional analysis in cultured cells indicated that p.Y157H in GJB1 was pathogenic, p.G127S in MFN2 was likely pathogenic, while p.V293M in YARS was likely benign. Our results suggest the potential for targeted NGS to make a more rapid and precise diagnosis in CMT patients. Moreover, the functional analysis is required when the novel variants are indistinct. PMID:27027447

  14. Misclassification and linkage of hereditary sensory and autonomic neuropathy type 1 as Charcot-Marie-Tooth disease, Type 2B

    Energy Technology Data Exchange (ETDEWEB)

    Vance, J.M.; Speer, M.C.; Stajich, J.M. [Duke Univ. Medical Center, Durham, NC (United States)

    1996-07-01

    Recently Kwon et al. published in the Journal their work describing linkage of a single large family with an inherited axonal neuropathy to chromosome 3, which they suggest is a second locus for Charcot-Marie-Tooth (CMT) type 2 and subsequently named {open_quotes}CMT2B.{close_quotes} We think that the diagnostic classification of this family as CMT2 is incorrect, since the subjects have a severe sensory neuropathy that fits within the hereditary sensory and autonomic neuropathy (HSAN) type 1 classification of Dyck (1993). Abnormal sensory findings in CMT2 separate it from distal spinal muscular atrophy but are a minor component of clinical symptoms in most CMT patients, as CMT is primarily a motor neuropathy. When Kwon et al. state that {open_quotes}all [patients] had characteristic findings in their physical examinations, including... evidence of foot sores that were slow to heal, or amputated limbs related to the poorly healing foot ulcers,{close_quotes} it suggests that a different diagnosis is more appropriate. In our experience collecting data on >950 individuals in >60 CMT1, CMT2, CMTX and CMT4 families, we have not seen foot ulcers, osteomyelitis, or amputations. Ulcerations leading to osteomyelitis and amputations are usually associated with severe sensory neuropathies. 16 refs., 1 tab.

  15. Genetics of Charcot-Marie-Tooth (CMT Disease within the Frame of the Human Genome Project Success

    Directory of Open Access Journals (Sweden)

    Vincent Timmerman

    2014-01-01

    Full Text Available Charcot-Marie-Tooth (CMT neuropathies comprise a group of monogenic disorders affecting the peripheral nervous system. CMT is characterized by a clinically and genetically heterogeneous group of neuropathies, involving all types of Mendelian inheritance patterns. Over 1,000 different mutations have been discovered in 80 disease-associated genes. Genetic research of CMT has pioneered the discovery of genomic disorders and aided in understanding the effects of copy number variation and the mechanisms of genomic rearrangements. CMT genetic study also unraveled common pathomechanisms for peripheral nerve degeneration, elucidated gene networks, and initiated the development of therapeutic approaches. The reference genome, which became available thanks to the Human Genome Project, and the development of next generation sequencing tools, considerably accelerated gene and mutation discoveries. In fact, the first clinical whole genome sequence was reported in a patient with CMT. Here we review the history of CMT gene discoveries, starting with technologies from the early days in human genetics through the high-throughput application of modern DNA analyses. We highlight the most relevant examples of CMT genes and mutation mechanisms, some of which provide promising treatment strategies. Finally, we propose future initiatives to accelerate diagnosis of CMT patients through new ways of sharing large datasets and genetic variants, and at ever diminishing costs.

  16. Two novel mutations in the GDAP1 and PRX genes in early onset Charcot-Marie-Tooth syndrome.

    Science.gov (United States)

    Auer-Grumbach, M; Fischer, C; Papić, L; John, E; Plecko, B; Bittner, R E; Bernert, G; Pieber, T R; Miltenberger, G; Schwarz, R; Windpassinger, C; Grill, F; Timmerman, V; Speicher, M R; Janecke, A R

    2008-02-01

    Autosomal recessive Charcot-Marie-Tooth syndrome (AR-CMT) is often characterised by an infantile disease onset and a severe phenotype. Mutations in the ganglioside-induced differentiation-associated protein 1 (GDAP1) gene are thought to be a common cause of AR-CMT. Mutations in the periaxin (PRX) gene are rare. They are associated with severe demyelination of the peripheral nerves and sometimes lead to prominent sensory disturbances. To evaluate the frequency of GDAP1 and PRX mutations in early onset CMT, we examined seven AR-CMT families and 12 sporadic CMT patients, all presenting with progressive distal muscle weakness and wasting. In one family also prominent sensory abnormalities and sensory ataxia were apparent from early childhood. In three families we detected four GDAP1 mutations (L58LfsX4, R191X, L239F and P153L), one of which is novel and is predicted to cause a loss of protein function. In one additional family with prominent sensory abnormalities a novel homozygous PRX mutation was found (A700PfsX17). No mutations were identified in 12 sporadic cases. This study suggests that mutations in the GDAP1 gene are a common cause of early-onset AR-CMT. In patients with early-onset demyelinating AR-CMT and severe sensory loss PRX is one of the genes to be tested.

  17. Efeitos do uso de órteses na Doença de Charcot-Marie-Tooth: atualização da literatura Orthoses effects in Charcot-Marie-Tooth Disease: update

    Directory of Open Access Journals (Sweden)

    Rouse Barbosa Pereira

    2012-12-01

    Full Text Available A Doença de Charcot-Marie-Tooth (DCMT é a neuropatia periférica hereditária mais comum em seres humanos, apresentando incidência de 1:2.500 pessoas. A fraqueza distal crural na DCMT provoca inúmeras alterações na marcha, como, por exemplo, na velocidade, no comprimento, na largura e cadência dos passos. Vários recursos em reabilitação têm sido propostos para gerenciar os problemas de deambulação, dentre eles, destaca-se a utilização de órteses. O objetivo deste estudo é apresentar e discutir os resultados de estudos sobre os efeitos da utilização de órteses nos padrões de marcha na DCMT. Neste estudo foi utilizada atualização da literatura através das principais bases de dados nacionais/internacionais (SciELO, LILACS e MEDLINE, publicados entre os anos de 2006-2012. O tratamento da DCMT consiste em fisioterapia e utilização de equipamentos de assistência, visto que ainda não há fármacos ou terapia gênica capaz de atenuar os danos clínicos e funcionais. Tal associação busca maximizar a função e melhorar a qualidade de vida desses pacientes, na tentativa de evitar agravos adicionais relativos à incapacidade física. A partir de atualização de literatura é possível concluir que existe consenso sobre a utilização de órteses nos membros inferiores para promover a estabilização das articulações do tornozelo e um padrão de deambulação mais funcional, evitando sinergias inadequadas de movimento e atenuando o risco de quedas.Charcot-Marie-Tooth (CMT disease is the most common hereditary peripheral neuropathy in humans, presenting incidence of 1:2.500 people. The distal crural weakness of the CMT causes numerous gait impairment changes, for example, velocity, length, width and cadence of the steps. Several rehabilitation resources have been proposed to manage the walking problems, among them, the use of orthoses is highlighted. The objective of this study was to present and discuss the results of

  18. Enfermedad de Charcot Marie Tooth (CMT4A por mutacion en el gen GDAP1: reporte de una familia colombiana

    Directory of Open Access Journals (Sweden)

    Angela Milena Martin

    2015-12-01

    Full Text Available Antecedentes:Las mutaciones del gen GDAP1 son causantes de la enfermedad de Charcot Marie Tooth tanto autosómica dominante como recesiva, y se han reportado más de 40 mutaciones distintas. La mutación recesiva Q163X ha sido descrita en pacientes de ascendencia española y se ha demostrado una mutación fundadora originaria de España en pacientes de origen suramericano. Describimos las características físicas e histológicas y el impacto molecular de la mutación Q163X en una familia colombiana.Objetivo:Se describe el impacto de la mutación Q163X en las características físicas, histológicas y moleculares en una familia colombiana.Métodos:Se describe dos pacientes de sexo femenino, hijas de padres consanguíneos, quienes presentaron inicio de síntomas en los dos primeros años de vida, mostrando deterioro funcional severo, sin evidencia de dismorfía, disfonía o parálisis diafragmática. Los estudios de electrofisiología mostraron una neuropatía sensitiva y motora con patrón axonal. Se solicitó la secuenciación del gen GDAP1, y el estudio identificó una mutación homocigota puntual (c. 487 C>T en el exón 4, causando un codón de parada prematuro (p. Q163X. Este resultado confirma el diagnóstico de Enfermedad de Charcot Marie Tooth, tipo 4A (recesiva, tipo axonal.Resultados:Las pacientes fueron remitidas al servicio de Fisiatría para evaluación de métodos de asistencia para deambulación. Ellas reciben seguimiento por el servicio de Neumología, quienes vigilan la función pulmonar y el desarrollo de parálisis diafragmática. Se brindó asesoramiento genético. La genealogía del paciente, las características fenotípicas y los hallazgos en los estudios electrofisiológicos son herramientas valiosas en el enfoque clínico del paciente con CMT, de forma que se pueda plantear una posible mutación causal. Se debe considerar la presencia de mutaciones en el gen GDAP1 en pacientes de origen suramericano, en especial la

  19. Surgical treatment of cavus foot in Charcot-Marie-tooth disease: a review of twenty-four cases: AAOS exhibit selection.

    Science.gov (United States)

    Faldini, Cesare; Traina, Francesco; Nanni, Matteo; Mazzotti, Antonio; Calamelli, Carlotta; Fabbri, Daniele; Pungetti, Camilla; Giannini, Sandro

    2015-03-18

    Charcot-Marie-Tooth disease is the single most common diagnosis associated with cavus foot. The imbalance involving intrinsic and extrinsic muscles has been suggested as the main pathogenetic cause of cavus foot in this disease. The goal of surgical treatment is to correct the deformity to obtain a plantigrade foot. In the presence of a flexible deformity and the absence of degenerative arthritis, preserving as much as possible of the overall range of motion of the foot and ankle is advisable. Twenty-four cavus feet in twelve patients with Charcot-Marie-Tooth disease were included in the study. Clinical evaluation was summarized with the Maryland Foot Score. Radiographic evaluation assessed calcaneal pitch, Meary angle, Hibb angle, and absence of degenerative joint changes. Only patients who had a flexible deformity, with varus of the heel reducible in the Coleman-Andreasi test, and did not have degenerative joint arthritis were included in this study. Surgical treatment consisted in plantar fasciotomy, midtarsal osteotomy, extensor hallucis longus tendon transfer to the first metatarsal (Jones procedure), and dorsiflexion osteotomy of the first metatarsal. Mean follow-up was six years (range, two to thirteen years). The mean Maryland Foot Score was 72 preoperatively and 86 postoperatively. The postoperative result was rated as excellent in twelve feet (50%), good in ten (42%), and fair in two (8%). Mean calcaneal pitch was 34° preoperatively and 24° at the time of the latest follow-up, the mean Hibb angle was 121° preoperatively and 136° postoperatively, and the mean Meary angle was 25° preoperatively and 2° postoperatively. Plantar fasciotomy, midtarsal osteotomy, the Jones procedure, and dorsiflexion osteotomy of the first metatarsal yielded adequate correction of flexible cavus feet in patients with Charcot-Marie-Tooth disease in the absence of fixed hindfoot deformity. The fact that the improvement in the outcome score was only modest may be attributable

  20. Muscle pathology without severe nerve pathology in a new mouse model of Charcot-Marie-Tooth disease type 2E.

    Science.gov (United States)

    Shen, Hailian; Barry, Devin M; Dale, Jeffrey M; Garcia, Virginia B; Calcutt, Nigel A; Garcia, Michael L

    2011-07-01

    Mutations in neurofilament light (NF-L) have been linked to Charcot-Marie-Tooth disease type 2E (CMT2E) in humans. To provide insight into disease pathogenesis, we developed a novel line of CMT2E mice that constitutively express human NF-L (hNF-L) with a glutamic acid to lysine mutation at position 397 (hNF-L(E397K)). This new line of mice developed signs consistent with CMT2E patients. Disease signs were first observed at 4 months in hNF-L(E397K) mice, and consisted of aberrant hind limb posture, digit deformities, reduced voluntary locomotor activity, reduced motor nerve conduction velocities (MNCVs) and muscle atrophy. Reduced voluntary locomotor activity and muscle pathology occurred without significant denervation, and hNF-L(E397K) mice showed relatively mild signs of nerve pathology. Nerve pathology in hNF-L(E397K) mice was characterized by ectopic accumulations of phosphorylated NFs in motor neuron cell bodies as early as 1 month. Moreover, NF organization was altered in motor and sensory roots, with small motor axons being most affected. Peak axonal diameter was reduced for small motor axons prior to and after the onset of overt phenotypes, whereas large motor axons were affected only after onset, which correlated with reduced MNCVs. Additionally, there was a small reduction in the number of sensory axons in symptomatic hNF-L(E397K) mice. hNF-L(E397K) mice are a novel line of CMT2E mice that recapitulate many of the overt phenotypes observed in CMT2E patients and hNF-L(P22S) mice. The cellular pathology observed in hNF-L(E397K) mice differed from that recently reported in hNF-L(P22S) mice, suggesting that overt CMT2E phenotypes may arise through different cellular mechanisms.

  1. Mutational analysis of the myelin protein zero (MPZ) gene associated with Charcot-Marie-Tooth neuropathy type 1B

    Energy Technology Data Exchange (ETDEWEB)

    Roa, B.B.; Warner, L.E.; Lupski, J.R. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1994-09-01

    The MPZ gene that maps to chromosome 1q22q23 encodes myelin protein zero, which is the most abundant peripheral nerve myelin protein that functions as a homophilic adhesion molecule in myelin compaction. Association of the MPZ gene with the dysmyelinating peripheral neuropathies Charcot-Marie-Tooth disease type 1B (CMT1B) and the more severe Dejerine-Sottas syndrome (DSS) was previously demonstrated by MPZ mutations identified in CMT1B and in rare DSS patients. In this study, the coding region of the MPZ gene was screened for mutations in a cohort of 74 unrelated patients with either CMT type 1 or DSS who do not carry the most common CMT1-associated molecular lesion of a 1.5 Mb DNA duplication on 17p11.2-p12. Heteroduplex analysis detected base mismatches in ten patients that were distributed over three exons of MPZ. Direct sequencing of PCR-amplified genomic DNA identified a de novo MPZ mutation associated with CMT1B that predicts an Ile(135)Thr substitution. This finding further confirms the role of MPZ in the CMT1B disease process. In addition, two polymorphisms were identified within the Gly(200) and Ser(228) codons that do not alter the respective amino acid residues. A fourth base mismatch in MPZ exon 3 detected by heteroduplex analysis is currently being characterized by direct sequence determination. Previously, four unrelated patients in this same cohort were found to have unique point mutations in the coding region of the PMP22 gene. The collective findings on CMT1 point mutations could suggest that regulatory region mutations, and possibly mutations in CMT gene(s) apart from the MPZ, PMP22 and Cx32 genes identified thus far, may prove to be significant for a number of CMT1 cases that do not involve DNA duplication.

  2. Novel mutations in the connexin 32 gene associated with X-linked Charcot-Marie-Tooth disease

    Energy Technology Data Exchange (ETDEWEB)

    Tan, C.; Ainsworth, P. [Victoria Hospital, Ontario (Canada)]|[Childrens Hospital of Western Ontario (Canada)

    1994-09-01

    Charcot-Marie-Tooth disease is a pathologically and genetically hetergenous group of disorders that cause a progressive neuropathy, defined pathologically by degeneration of the myelin (CMT 1) of the axon (CMT 2) of the peripheral nerves. An X-linked type of the demyelinating form of this disorder (CMT X) has recently been linked to mutations in the connexin 32 (Cx32) gene, which codes for a 284 amino acid gap junction protein found in myelinated peripheral nerve. To date some 7 different mutations in this gene have been identified as being responsible for CMT X. The majority of these predict nonconservative amino acid substitutions, while one is a frameshift mutation which predicts a premature stop at codon 21. We report the results of molecular studies on three further local CMT X kindreds. The Cx32 gene was amplified by PCR in three overlapping fragments 300-450 bp in length using leukocyte-derived DNA as template. These were either sequenced directly using a deaza dGTP sequencing protocol, or were cloned and sequenced using a TA vector. In two of the kindreds the affected members carried a point mutation which was predicted to effect a non-conservative amino acid change within the first transmembrane domain. Both of these mutations caused a restriction site alteration (the loss of an Nla III and the creation of a Pvu II, respectively), and the former mutation was observed to segregate with the clinicial phenotype in affected family members. Affected members of the third kindred, which was a very large multigenerational family that had been extensively studied previously, were shown to carry a point mutation predicted to cause a premature truncation of the Cx32 gene product in the intracellular carboxy terminus. This mutation obliterated an Rsa I site which allowed a rapid screen of several other family members.

  3. Genetic interaction between MTMR2 and FIG4 phospholipid phosphatases involved in Charcot-Marie-Tooth neuropathies.

    Directory of Open Access Journals (Sweden)

    Ilaria Vaccari

    2011-10-01

    Full Text Available We previously reported that autosomal recessive demyelinating Charcot-Marie-Tooth (CMT type 4B1 neuropathy with myelin outfoldings is caused by loss of MTMR2 (Myotubularin-related 2 in humans, and we created a faithful mouse model of the disease. MTMR2 dephosphorylates both PtdIns3P and PtdIns(3,5P(2, thereby regulating membrane trafficking. However, the function of MTMR2 and the role of the MTMR2 phospholipid phosphatase activity in vivo in the nerve still remain to be assessed. Mutations in FIG4 are associated with CMT4J neuropathy characterized by both axonal and myelin damage in peripheral nerve. Loss of Fig4 function in the plt (pale tremor mouse produces spongiform degeneration of the brain and peripheral neuropathy. Since FIG4 has a role in generation of PtdIns(3,5P(2 and MTMR2 catalyzes its dephosphorylation, these two phosphatases might be expected to have opposite effects in the control of PtdIns(3,5P(2 homeostasis and their mutations might have compensatory effects in vivo. To explore the role of the MTMR2 phospholipid phosphatase activity in vivo, we generated and characterized the Mtmr2/Fig4 double null mutant mice. Here we provide strong evidence that Mtmr2 and Fig4 functionally interact in both Schwann cells and neurons, and we reveal for the first time a role of Mtmr2 in neurons in vivo. Our results also suggest that imbalance of PtdIns(3,5P(2 is at the basis of altered longitudinal myelin growth and of myelin outfolding formation. Reduction of Fig4 by null heterozygosity and downregulation of PIKfyve both rescue Mtmr2-null myelin outfoldings in vivo and in vitro.

  4. Efficacy of focal mechanic vibration treatment on balance in Charcot-Marie-Tooth 1A disease: a pilot study.

    Science.gov (United States)

    Pazzaglia, Costanza; Camerota, F; Germanotta, M; Di Sipio, E; Celletti, C; Padua, L

    2016-07-01

    Patients affected by Charcot-Marie-Tooth (CMT) disease experience an impaired balance. Although the causes of the postural instability are not fully understood, somatosensory system seems to play a key role. Mechanical vibration seems to act on the somatosensory system and to improve its function. The aim of our study was to evaluate the effects of focal mechanical vibration (fMV) on the balance of CMT 1A patients. We enrolled 14 genetically confirmed CMT 1A patients (8 female and 6 male, mean age 492 years, range 32-74, mean duration of disease: 13 years, range 1-30). Patients underwent a 3-day fMV treatment on quadriceps and triceps surae and were evaluated before the treatment as well as 1 week and 1 month after the end of the treatment. The primary outcome measure was the Berg Balance Scale (BBS) and the secondary were the Dynamic Gait Index (DGI), the 6 Min Walking Test (6MWT), the muscular strength of lower limbs, the Quality of Life (QoL) questionnaire and the stabilometric variables. The statistical analysis showed a significant modification of the BBS due to the effect of treatment (p treatment applied on lower limbs of CMT 1A patients determined an improvement of balance as detected by the BBS. The concurrent improvement of stabilometric variables in the eyes closed condition only suggests that fMV acts mostly on somatosensory afferences. Further studies are needed to confirm these data on a larger sample of CMT patients.

  5. PMP22 related neuropathies: Charcot-Marie-Tooth disease type 1A and Hereditary Neuropathy with liability to Pressure Palsies.

    Science.gov (United States)

    van Paassen, Barbara W; van der Kooi, Anneke J; van Spaendonck-Zwarts, Karin Y; Verhamme, Camiel; Baas, Frank; de Visser, Marianne

    2014-03-19

    PMP22 related neuropathies comprise (1) PMP22 duplications leading to Charcot-Marie-Tooth disease type 1A (CMT1A), (2) PMP22 deletions, leading to Hereditary Neuropathy with liability to Pressure Palsies (HNPP), and (3) PMP22 point mutations, causing both phenotypes. Overall prevalence of CMT is usually reported as 1:2,500, epidemiological studies show that 20-64% of CMT patients carry the PMP22 duplication. The prevalence of HNPP is not well known. CMT1A usually presents in the first two decades with difficulty walking or running. Distal symmetrical muscle weakness and wasting and sensory loss is present, legs more frequently and more severely affected than arms. HNPP typically leads to episodic, painless, recurrent, focal motor and sensory peripheral neuropathy, preceded by minor compression on the affected nerve. Electrophysiological evaluation is needed to determine whether the polyneuropathy is demyelinating. Sonography of the nerves can be useful. Diagnosis is confirmed by finding respectively a PMP22 duplication, deletion or point mutation. Differential diagnosis includes other inherited neuropathies, and acquired polyneuropathies. The mode of inheritance is autosomal dominant and de novo mutations occur. Offspring of patients have a chance of 50% to inherit the mutation from their affected parent. Prenatal testing is possible; requests for prenatal testing are not common. Treatment is currently symptomatic and may include management by a rehabilitation physician, physiotherapist, occupational therapist and orthopaedic surgeon. Adult CMT1A patients show slow clinical progression of disease, which seems to reflect a process of normal ageing. Life expectancy is normal.

  6. Conduction block and tonic pupils in Charcot-Marie-Tooth disease caused by a myelin protein zero p.Ile112Thr mutation.

    LENUS (Irish Health Repository)

    Murphy, Sinéad M

    2011-03-01

    We report a patient with Charcot-Marie-Tooth disease (CMT) due to the p.Ile112Thr mutation in myelin protein zero (MPZ) who presented with a patchy neuropathy with conduction block and tonic pupils. Conduction block is unusual in inherited neuropathies, while pupil abnormalities are recognised to occur in CMT especially due to MPZ mutations. This case highlights that patchy demyelinating neuropathy with conduction block may occur in p.Ile112Thr MPZ mutations. Involvement of the pupils, as in this case, may be a pointer towards a genetic rather than inflammatory cause of neuropathy.

  7. Irmandade afetada pela atrofia muscular peroneal de Charcot-Marie-Tooth com possível variante do fenômeno da antecipação

    Directory of Open Access Journals (Sweden)

    Aguinaldo Gonçalves

    1977-06-01

    Full Text Available Considerando-se a peculiaridade genética da atrofia peroneal de Charcot-Marie-Tooth, é feita a descrição clínica de família com três irmãos afetados, com idade de aparecimento progressivamente antecipada, refletindo possível variante do fenômeno da antecipação, condição inusitada na literatura, não só para esta doença, mas também, de modo geral, em Genética Humana.

  8. First reported case of Charcot Marie Tooth disease type 4C in a child from India with SH3TC2 mutation but absent spinal deformities

    Directory of Open Access Journals (Sweden)

    Umesh Dinkar Kalane

    2015-01-01

    Full Text Available Charcot Marie Tooth (CMT disease is a group of hereditary motor sensory neuropathies with significant genetic heterogeneity. This disorder has been scarcely reported in the Indian literature. Here, we report a case of the rare but relatively more severe autosomal recessive CMT type 4C disease with a few features that are distinct from its regular presentation. Our patient was proven to have one of the common mutations in the SH3TC2 gene, which has so far not been described in Indian patients.

  9. 进行性腓肌萎缩症的神经电生理学研究%Study of electroneurophysiology on Charcot-Marie-Tooth disease

    Institute of Scientific and Technical Information of China (English)

    陈菁华; 林丽丽; 魏丽玲

    2007-01-01

    Objective To explore the diagnostic value of electroneurophisology in patients with charcot-Ma-rie-Tooth disease(CMT).Methods Electromyogram(EMG),Motor nerve conduction velocity(MCV),Sensory nenre conduction velocity(SCV) and F wave were measured in 31 cases with Charcot-Marie-Tooth disease(CMT).Resuits The abnormality rate of EMG was 90%,MCV was 100%,SCV was 90%,and F wave was 34%.Conclu-sion The electroneurophysiology is very practical and valuable in diagnosing Charcot-Marie-Tooth disease.%目的 研究进行性腓肌萎缩症患者的肌电图、周围神经传导速度及F反应特点,探讨神经电生理检查对诊断该病的价值.方法 对31例进行性腓肌萎缩症患者的肌电图(EMG)、运动神经传导速度(MCV)、感觉神经传导速度(SCV)及F波进行检测.结果 肌电图异常率90%,运动神经传导速度异常率100%,感觉神经传导速度异常率90%,F波检测异常率34%.结论 神经电生理检查是诊断进行性腓肌萎缩症的可靠方法.

  10. Lower extremity muscles activity in standing and sitting position with use of sEMG in patients suffering from Charcot-Marie-Tooth syndrome.

    Science.gov (United States)

    Kuciel, Natalia Maria; Konieczny, Grzegorz Krzysztof; Oleksy, Łukasz; Wrzosek, Zdzisława

    2016-01-01

    There is very limited, evidenced data about movement possibilities in patients with high level of lower limb muscles atrophy and fatigue in patients suffering from Charcot-Marie-Tooth syndrome. Patient (age 46) suffering from Charcot-Marie-Tooth disease for 30 years with multiple movement restrictions and muscles atrophy above knees took part into the study. Tests were performed for 8 muscles of the lower limb and pelvis. Muscles electrical activity was tested in sitting and standing position (for knees extended and hyperextended). In the right leg rectus femoris, vastus lateralis obliquus, gluteus medius and semitendinosus muscles activated at first and were working the longest time. The highest activity was observed in standing position with knees extended. In the left leg rectus femoris and biceps femoris muscles activated at first and biceps femoris was working the longest time. Activity level in left lower limb is much lower than in the right one. Muscles weakness is asymmetric. Left leg is much weaker and engages antagonists and synergists muscles to compensate weaker rectus femoris, vastus medialis obliquus and vastus lateralis obliquus.

  11. A novel mutation in GJB1 (c.212T>G) in a Chinese family with X-linked Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Xiao, Fei; Tan, Jia-ze; Zhang, Xu; Wang, Xue-Feng

    2015-03-01

    Gap junction protein beta 1 (GJB1) gene mutations lead to X-linked Charcot-Marie-Tooth (CMTX) disease. We investigated a Chinese family with CMTX and identified a novel GJB1 point mutation. Clinical and electrophysiological features of the pedigree were examined, and sequence alterations of the coding region of GJB1 that encode connexin32 were determined by direct sequencing. Sequence alignment of the mutation site was performed using Clustal W. Mutation effects were analysed using PolyPhen-2, SIFT and Mutation Taster software. The three-dimensional structures of the mutant and wild-type proteins were predicted by modeling with SWISS MODEL online software. The affected family members displayed typical Charcot-Marie-Tooth phenotypes, but phenotypic heterogeneity was observed. Nerve conduction velocities of all affected patients were slow. Sequencing of GJB1 revealed a heterozygous T>G missense mutation at nucleotide 212 in the proband, the proband's mother and the proband's daughter. The affected male sibling of the proband displayed a hemizygous missense mutation with T>G transition at the identical position on the GJB1 gene. This mutation resulted in an amino acid change from isoleucine to serine that was predicted to lead to tertiary structural alterations that would disrupt the function of the GJB1 protein. A novel point mutation in GJB1 was detected, expanding the spectrum of GJB1 mutations known to be associated with CMTX.

  12. Spinal and bulbar muscular atrophy and Charcot-Marie-Tooth type 1A: Co-existence of two rare neuromuscular genetic diseases in the same patient.

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    Sagnelli, Anna; Scaioli, Vidmer; Piscosquito, Giuseppe; Salsano, Ettore; Dalla Bella, Eleonora; Gellera, Cinzia; Pareyson, Davide

    2015-10-01

    Spinal and bulbar muscular atrophy is an X-linked neuromuscular disease caused by a trinucleotide CAG repeat expansion in the androgen receptor gene; it is clinically characterized by adult-onset, slowly progressive weakness and atrophy mainly affecting proximal limb and bulbar muscles. Charcot-Marie-Tooth disease type 1A is an autosomal dominant polyneuropathy due to peripheral myelin protein 22 gene duplication and characterized by slowly progressive distal limb muscle weakness, atrophy and sensory loss with foot deformities. Here we report the co-occurrence of both neuromuscular genetic diseases in the same male patient. Difficulties in climbing stairs and jaw weakness were presenting symptoms consistent with SBMA. However, predominant distal weakness and bilateral pes cavus were rather suggestive of a hereditary polyneuropathy. The combination of two diseases, even if extremely rare, should be considered in the presence of atypical symptoms; in the case of genetic diseases this event may have important implications on family members' counseling.

  13. Multiplex Detection and Genotyping of Point Mutations Involved in Charcot-Marie-Tooth Disease Using a Hairpin Microarray-Based Assay

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    Yasser Baaj

    2009-01-01

    Full Text Available We previously developed a highly specific method for detecting SNPs with a microarray-based system using stem-loop probes. In this paper we demonstrate that coupling a multiplexing procedure with our microarray method is possible for the simultaneous detection and genotyping of four point mutations, in three different genes, involved in Charcot-Marie-Tooth disease. DNA from healthy individuals and patients was amplified, labeled with Cy3 by multiplex PCR; and hybridized to microarrays. Spot signal intensities were 18 to 74 times greater for perfect matches than for mismatched target sequences differing by a single nucleotide (discrimination ratio for “homozygous” DNA from healthy individuals. “Heterozygous” mutant DNA samples gave signal intensity ratios close to 1 at the positions of the mutations as expected. Genotyping by this method was therefore reliable. This system now combines the principle of highly specific genotyping based on stem-loop structure probes with the advantages of multiplex analysis.

  14. Mitochondrial defects and neuromuscular degeneration caused by altered expression of Drosophila Gdap1: implications for the Charcot-Marie-Tooth neuropathy.

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    López Del Amo, Víctor; Seco-Cervera, Marta; García-Giménez, José Luís; Whitworth, Alexander J; Pallardó, Federico V; Galindo, Máximo Ibo

    2015-01-01

    One of the genes involved in Charcot-Marie-Tooth (CMT) disease, an inherited peripheral neuropathy, is GDAP1. In this work, we show that there is a true ortholog of this gene in Drosophila, which we have named Gdap1. By up- and down-regulation of Gdap1 in a tissue-specific manner, we show that altering its levels of expression produces changes in mitochondrial size, morphology and distribution, and neuronal and muscular degeneration. Interestingly, muscular degeneration is tissue-autonomous and not dependent on innervation. Metabolic analyses of our experimental genotypes suggest that alterations in oxidative stress are not a primary cause of the neuromuscular degeneration but a long-term consequence of the underlying mitochondrial dysfunction. Our results contribute to a better understanding of the role of mitochondria in CMT disease and pave the way to generate clinically relevant disease models to study the relationship between mitochondrial dynamics and peripheral neurodegeneration.

  15. Crystallization and preliminary X-ray analysis of a native human tRNA synthetase whose allelic variants are associated with Charcot-Marie-Tooth disease.

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    Xie, Wei; Schimmel, Paul; Yang, Xiang-Lei

    2006-12-01

    Glycyl-tRNA synthetase (GlyRS) is one of a group of enzymes that catalyze the synthesis of aminoacyl-tRNAs for translation. Mutations of human and mouse GlyRSs are causally associated with Charcot-Marie-Tooth disease, the most common genetic disorder of the peripheral nervous system. As the first step towards a structure-function analysis of this disease, native human GlyRS was expressed, purified and crystallized. The crystal belonged to space group P4(3)2(1)2 or its enantiomorphic space group P4(1)2(1)2, with unit-cell parameters a = b = 91.74, c = 247.18 A, and diffracted X-rays to 3.0 A resolution. The asymmetric unit contained one GlyRS molecule and had a solvent content of 69%.

  16. Metabolite profile of a mouse model of Charcot-Marie-Tooth type 2D neuropathy: implications for disease mechanisms and interventions.

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    Bais, Preeti; Beebe, Kirk; Morelli, Kathryn H; Currie, Meagan E; Norberg, Sara N; Evsikov, Alexei V; Miers, Kathy E; Seburn, Kevin L; Guergueltcheva, Velina; Kremensky, Ivo; Jordanova, Albena; Bult, Carol J; Burgess, Robert W

    2016-01-01

    Charcot-Marie-Tooth disease encompasses a genetically heterogeneous class of heritable polyneuropathies that result in axonal degeneration in the peripheral nervous system. Charcot-Marie-Tooth type 2D neuropathy (CMT2D) is caused by dominant mutations in glycyl tRNA synthetase (GARS). Mutations in the mouse Gars gene result in a genetically and phenotypically valid animal model of CMT2D. How mutations in GARS lead to peripheral neuropathy remains controversial. To identify putative disease mechanisms, we compared metabolites isolated from the spinal cord of Gars mutant mice and their littermate controls. A profile of altered metabolites that distinguish the affected and unaffected tissue was determined. Ascorbic acid was decreased fourfold in the spinal cord of CMT2D mice, but was not altered in serum. Carnitine and its derivatives were also significantly reduced in spinal cord tissue of mutant mice, whereas glycine was elevated. Dietary supplementation with acetyl-L-carnitine improved gross motor performance of CMT2D mice, but neither acetyl-L-carnitine nor glycine supplementation altered the parameters directly assessing neuropathy. Other metabolite changes suggestive of liver and kidney dysfunction in the CMT2D mice were validated using clinical blood chemistry. These effects were not secondary to the neuromuscular phenotype, as determined by comparison with another, genetically unrelated mouse strain with similar neuromuscular dysfunction. However, these changes do not seem to be causative or consistent metabolites of CMT2D, because they were not observed in a second mouse Gars allele or in serum samples from CMT2D patients. Therefore, the metabolite 'fingerprint' we have identified for CMT2D improves our understanding of cellular biochemical changes associated with GARS mutations, but identification of efficacious treatment strategies and elucidation of the disease mechanism will require additional studies.

  17. Early-onset osteoarthritis, Charcot-Marie-Tooth like neuropathy, autoimmune features, multiple arterial aneurysms and dissections: an unrecognized and life threatening condition.

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    Mélodie Aubart

    Full Text Available BACKGROUND: Severe osteoarthritis and thoracic aortic aneurysms have recently been associated with mutations in the SMAD3 gene, but the full clinical spectrum is incompletely defined. METHODS: All SMAD3 gene mutation carriers coming to our centre and their families were investigated prospectively with a structured panel including standardized clinical workup, blood tests, total body computed tomography, joint X-rays. Electroneuromyography was performed in selected cases. RESULTS: Thirty-four SMAD3 gene mutation carriers coming to our centre were identified and 16 relatives were considered affected because of aortic surgery or sudden death (total 50 subjects. Aortic disease was present in 72%, complicated with aortic dissection, surgery or sudden death in 56% at a mean age of 45 years. Aneurysm or tortuosity of the neck arteries was present in 78%, other arteries were affected in 44%, including dissection of coronary artery. Overall, 95% of mutation carriers displayed either aortic or extra-aortic arterial disease. Acrocyanosis was also present in the majority of patients. Osteoarticular manifestations were recorded in all patients. Joint involvement could be severe requiring surgery in young patients, of unusual localization such as tarsus or shoulder, or mimicking crystalline arthropathy with fibrocartilage calcifications. Sixty eight percent of patients displayed neurological symptoms, and 9 suffered peripheral neuropathy. Electroneuromyography revealed an axonal motor and sensory neuropathy in 3 different families, very evocative of type II Charcot-Marie-Tooth (CMT2 disease, although none had mutations in the known CMT2 genes. Autoimmune features including Sjogren's disease, rheumatoid arthritis, Hashimoto's disease, or isolated autoantibodies- were found in 36% of patients. INTERPRETATION: SMAD3 gene mutations are associated with aortic dilatation and osteoarthritis, but also autoimmunity and peripheral neuropathy which mimics type II

  18. Doença de Charcot-Marie-Tooth associada a malformação de Klippel-Feil: registro de um caso e revisão da literatura

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    Carlos A. de Assis Viegas

    1980-06-01

    Full Text Available Depois de caracterizar a doença de Charcot-Marie-Tooth e a malformação de Klippel-Feil, o autor relata um caso em que ambas estão associadas e procede a uma revisão da literatura pertinente, apresentando múltiplas possibilidades de associação de uma e outra com diversos entidades mórbidas.

  19. Clinical classification and gene mutation of Chinese probands with Charcot-Marie-Tooth disease Analysis of 57 cases

    Institute of Scientific and Technical Information of China (English)

    Ruxu Zhang; Xiaobo Li; Xiaohong Zi; Shunxiang Huang; Fufeng Zhang; Kun Xia; Qian Pan; Beisha Tang

    2011-01-01

    Charcot-Mafie-Tooth (CMT) disease is the most common inherited peripheral neuropathic disorder.CMT is clinically and genetically heterogeneous. To date, 27 genes associated with the disease have been cloned. The present study carried out clinical classification according to clinical,electrophysiological and pathological features, conducted inheritance classification according to inheritance patterns, and performed mutation analysis of 13 CMT disease genes (PMP22, CX32,HSPB1, MNF2, MPZ, HSPB8, GDAP1, NFL, EGR2, SIMPLE, RAB7, LMNA, MTMR2) in 57 Chinese probands with CMT. Five cases of AD-CMT1 and 13 cases of sporadic CMT1 were diagnosed as CMT1A; five cases of X-CMT1, one case of X-CMT2 and one case of sporadic CMT1 were diagnosed as CMTX1; four cases of AD-CMT2 were diagnosed as CMT2F; one case of AD-CMT2 and one case of sporadic CMT2 were diagnosed as CMT2A2; one case of AD-CMT2 was diagnosed as CMT2L; one case of AD-CMT2 was diagnosed as CMT2J; one case of AR-CMT1 was diagnosed as CMT4A. Among the 57 CMT probands, seven genotypes were determined among 34 patients, with a detection rate of 59.6%. The results indicated that the clinical classification and inheritance classification are indispensable for selecting potential disease genes for mutation detection, and for efficient molecular diagnosis.

  20. Charcot-Marie-Tooth病1X型的临床与分子遗传学研究进展%Advance in Clinical and Molecular Genetics Study of Charcot-Marie-Tooth Disease 1X Type (review)

    Institute of Scientific and Technical Information of China (English)

    乔晓会; 李越星

    2009-01-01

    Charcot-Marie-Tooth病(CMT)中,1X型发病率居于第2位,它由GJB1基因突变致Connexin32蛋白结构或功能异常,引起细胞间通道缺陷导致发病.文章综述了CMT1X的典型临床特征和分子遗传学进展,总结了CMT发病机制的研究.

  1. [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.

  2. MRI findings, patterns of disease distribution, and muscle fat fraction calculation in five patients with Charcot-Marie-Tooth type 2 F disease

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    Gaeta, Michele; Mileto, Achille; Minutoli, Fabio; Settineri, Nicola; Donato, Rocco; Ascenti, Giorgio; Blandino, Alfredo [Policlinico ' ' G. Martino' ' , Dipartimento di Scienze Radiologiche, Messina (Italy); Mazzeo, Anna; Di Leo, Rita [Policlinico ' ' G. Martino' ' , Dipartimento di Neuroscienze, Scienze Psichiatriche ed Anestesiologiche, Messina (Italy)

    2012-05-15

    To describe the magnetic resonance imaging (MRI) pattern of muscle involvement and disease progression in five patients with late-onset Charcot-Marie-Tooth (CMT) disease type 2 F, due to a previously unknown mutation. Five patients (three males, two females) underwent MRI of the lower limbs to define the pattern of muscle involvement and evaluate the muscle fat fraction (MFF) of residual thigh muscle with gradient-echo (GRE) dual-echo dual-flip angle technique. Evaluation of fatty infiltration both by visual inspection and MFF calculation was performed. A proximal-to-distal gradient of muscle involvement was depicted in male patients with extensive muscle wasting of lower legs, less severe impairment of distal thigh muscles, and sparing of proximal thigh muscles. A peculiar phenotype finding was that no or only slight muscle abnormalities could be found in the two female patients. We described the pattern of muscle involvement and disease progression in a family with CMT disease type 2 F. GRE dual-echo dual-flip angle MRI technique is a valuable technique to obtain a rapid quantification of MFF. (orig.)

  3. A brief review of recent Charcot-Marie-Tooth research and priorities [v1; ref status: indexed, http://f1000r.es/53g

    Directory of Open Access Journals (Sweden)

    Sean Ekins

    2015-02-01

    Full Text Available This brief review of current research progress on Charcot-Marie-Tooth (CMT disease is a summary of discussions initiated at the Hereditary Neuropathy Foundation (HNF scientific advisory board meeting on November 7, 2014. It covers recent published and unpublished in vitro and in vivo research. We discuss recent promising preclinical work for CMT1A, the development of new biomarkers, the characterization of different animal models, and the analysis of the frequency of gene mutations in patients with CMT. We also describe how progress in related fields may benefit CMT therapeutic development, including the potential of gene therapy and stem cell research. We also discuss the potential to assess and improve the quality of life of CMT patients. This summary of CMT research identifies some of the gaps which may have an impact on upcoming clinical trials. We provide some priorities for CMT research and areas which HNF can support. The goal of this review is to inform the scientific community about ongoing research and to avoid unnecessary overlap, while also highlighting areas ripe for further investigation. The general collaborative approach we have taken may be useful for other rare neurological diseases.

  4. A novel Lys141Thr mutation in small heat shock protein 22 (HSPB8) gene in Charcot-Marie-Tooth disease type 2L.

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    Nakhro, Khriezhanuo; Park, Jin-Mo; Kim, Ye Jin; Yoon, Bo Ram; Yoo, Jeong Hyun; Koo, Heasoo; Choi, Byung-Ok; Chung, Ki Wha

    2013-08-01

    Charcot-Marie-Tooth disease (CMT) is a group of clinically and genetically heterogeneous peripheral neuropathies. HSPB8 gene encodes heat shock protein 22 (HSP22) which belongs to the superfamily of small stress induced proteins. Mutations in HSPB8 are implicated to CMT2L and distal hereditary motor neuropathy 2A (dHMN2A). All three reported HSPB8 mutations are interestingly located in the Lys141 residue. In the present study, we examined a Korean axonal CMT patient who presented distal limb atrophy, sensory loss, areflexia, and axonal loss of large myelinated fibers. Whole exome sequencing identified a novel missense mutation c.422A>C (p.Lys141Thr) in HSPB8 as the underlying cause of the CMT2 patient. The mutation was regarded as a de novo case because both unaffected parents have no such mutation. The patient with HSPB8 mutation is the first case in Koreans. Clinical heterogeneities have been revealed in patients with Lys141 mutation; the present patient revealed similar phenotype of CMT2L. In addition, the lower limb MRI revealed a similarity between our HSPB8 and HSPB1 patients. It seems that the Lys141 site in the alpha-crystallin domain of HSPB8 is regarded as a mutational hot spot for peripheral neuropathy development, and mutations even in the same codon can exhibit different CMT phenotypes.

  5. Long-Range Structural Effects of a Charcot-Marie-Tooth Disease-Causing Mutation in Human Glycyl-TRNA Synthetase

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    Xie, W.; Nangle, L.A.; Zhang, W.; Schimmel, P.; Yang, X.-L.

    2009-06-04

    Functional expansion of specific tRNA synthetases in higher organisms is well documented. These additional functions may explain why dominant mutations in glycyl-tRNA synthetase (GlyRS) and tyrosyl-tRNA synthetase cause Charcot-Marie-Tooth (CMT) disease, the most common heritable disease of the peripheral nervous system. At least 10 disease-causing mutant alleles of GlyRS have been annotated. These mutations scatter broadly across the primary sequence and have no apparent unifying connection. Here we report the structure of wild type and a CMT-causing mutant (G526R) of homodimeric human GlyRS. The mutation is at the site for synthesis of glycyl-adenylate, but the rest of the two structures are closely similar. Significantly, the mutant form diffracts to a higher resolution and has a greater dimer interface. The extra dimer interactions are located {approx}30 {angstrom} away from the G526R mutation. Direct experiments confirm the tighter dimer interaction of the G526R protein. The results suggest the possible importance of subtle, long-range structural effects of CMT-causing mutations at the dimer interface. From analysis of a third crystal, an appended motif, found in higher eukaryote GlyRSs, seems not to have a role in these long-range effects.

  6. Diagnostic algorithms in Charcot-Marie-Tooth neuropathies: experiences from a German genetic laboratory on the basis of 1206 index patients.

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    Rudnik-Schöneborn, S; Tölle, D; Senderek, J; Eggermann, K; Elbracht, M; Kornak, U; von der Hagen, M; Kirschner, J; Leube, B; Müller-Felber, W; Schara, U; von Au, K; Wieczorek, D; Bußmann, C; Zerres, K

    2016-01-01

    We present clinical features and genetic results of 1206 index patients and 124 affected relatives who were referred for genetic testing of Charcot-Marie-Tooth (CMT) neuropathy at the laboratory in Aachen between 2001 and 2012. Genetic detection rates were 56% in demyelinating CMT (71% of autosomal dominant (AD) CMT1/CMTX), and 17% in axonal CMT (24% of AD CMT2/CMTX). Three genetic defects (PMP22 duplication/deletion, GJB1/Cx32 or MPZ/P0 mutation) were responsible for 89.3% of demyelinating CMT index patients in whom a genetic diagnosis was achieved, and the diagnostic yield of the three main genetic defects in axonal CMT (GJB1/Cx32, MFN2, MPZ/P0 mutations) was 84.2%. De novo mutations were detected in 1.3% of PMP22 duplication, 25% of MPZ/P0, and none in GJB1/Cx32. Motor nerve conduction velocity was uniformly 40 m/s in MFN2, and more variable in GJB1/Cx32, MPZ/P0 mutations. Patients with CMT2A showed a broad clinical severity regardless of the type or position of the MFN2 mutation. Out of 75 patients, 8 patients (11%) with PMP22 deletions were categorized as CMT1 or CMT2. Diagnostic algorithms are still useful for cost-efficient mutation detection and for the interpretation of large-scale genetic data made available by next generation sequencing strategies.

  7. Identification of a novel SBF2 frameshift mutation in charcot-marie-tooth disease type 4B2 using whole-exome sequencing.

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    Chen, Meiyan; Wu, Jing; Liang, Ning; Tang, Lihui; Chen, Yanhua; Chen, Huishuang; Wei, Wei; Wei, Tianying; Huang, Hui; Yi, Xin; Qi, Ming

    2014-10-01

    Charcot-Marie-Tooth disease type 4B2 with early-onset glaucoma (CMT4B2, OMIM 604563) is a genetically-heterogeneous childhood-onset neuromuscular disorder. Here, we report the case of a 15-year-old male adolescent with lower extremity weakness, gait abnormalities, foot deformities and early-onset glaucoma. Since clinical diagnosis alone was insufficient for providing pathogenetic evidence to indicate that the condition belonged to a consanguineous family, we applied whole-exome sequencing to samples from the patient, his parents and his younger brother, assuming that the patient's condition is transmitted in an autosomal recessive pattern. A frame-shift mutation, c.4571delG (P.Gly1524Glufs∗42), was revealed in the CMT4B2-related gene SBF2 (also known as MTMR13, MIM 607697), and this mutation was found to be homozygous in the proband and heterozygous in his parents and younger brother. Together with the results of clinical diagnosis, this case was diagnosed as CMT4B2. Our finding further demonstrates the use of whole-exome sequencing in the diagnosis and treatment of rare diseases.

  8. Screening for SH3TC2 gene mutations in a series of demyelinating recessive Charcot-Marie-Tooth disease (CMT4).

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    Piscosquito, Giuseppe; Saveri, Paola; Magri, Stefania; Ciano, Claudia; Gandioli, Claudia; Morbin, Michela; Bella, Daniela D; Moroni, Isabella; Taroni, Franco; Pareyson, Davide

    2016-09-01

    Charcot-Marie-Tooth disease type 4C (CMT4C) is an autosomal recessive (AR) demyelinating neuropathy associated to SH3TC2 mutations, characterized by early onset, spine deformities, and cranial nerve involvement. We screened 43 CMT4 patients (36 index cases) with AR inheritance, demyelinating nerve conductions, and negative testing for PMP22 duplication, GJB1 and MPZ mutations, for SH3TC2 mutations. Twelve patients (11 index cases) had CMT4C as they carried homozygous or compound heterozygous mutations in SH3TC2. We found six mutations: three nonsense (p.R1109*, p.R954*, p.Q892*), one splice site (c.805+2T>C), one synonymous variant (p.K93K) predicting altered splicing, and one frameshift (p.F491Lfs*32) mutation. The splice site and the frameshift mutations are novel. Mean onset age was 7 years (range: 1-14). Neuropathy was moderate-to-severe. Scoliosis was present in 11 patients (severe in 4), and cranial nerve deficits in 9 (hearing loss in 7). Scoliosis and cranial nerve involvement are frequent features of this CMT4 subtype, and their presence should prompt the clinician to look for SH3TC2 gene mutations. In our series of undiagnosed CMT4 patients, SH3TC2 mutation frequency is 30%, confirming that CMT4C may be the most common AR-CMT type.

  9. The influence of somatosensory and muscular deficits on postural stabilization: Insights from an instrumented analysis of subjects affected by different types of Charcot-Marie-Tooth disease.

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    Lencioni, Tiziana; Piscosquito, Giuseppe; Rabuffetti, Marco; Bovi, Gabriele; Calabrese, Daniela; Aiello, Alessia; Di Sipio, Enrica; Padua, Luca; Diverio, Manuela; Pareyson, Davide; Ferrarin, Maurizio

    2015-08-01

    Charcot-Marie-Tooth (CMT) disease is the most common hereditary neuromuscular disorder. CMT1 is primarily demyelinating, CMT2 is primarily axonal, and CMTX1 is characterized by both axonal and demyelinating abnormalities. We investigated the role of somatosensory and muscular deficits on quiet standing and postural stabilization in patients affected by different forms of CMT, comparing their performances with those of healthy subjects. Seventy-six CMT subjects (CMT1A, CMT2 and CMTX1) and 41 healthy controls were evaluated during a sit-to-stand transition and the subsequent quiet upright posture by means of a dynamometric platform. All CMT patients showed altered balance and postural stabilization compared to controls. Multivariate analysis showed that in CMT patients worsening of postural stabilization was related to vibration sense deficit and to dorsi-flexor's weakness, while quiet standing instability was related to the reduction of pinprick sensibility and to plantar-flexor's weakness. Our results show that specific sensory and muscular deficits play different roles in balance impairment of CMT patients, both during postural stabilization and in static posture. An accurate evaluation of residual sensory and muscular functions is therefore necessary to plan for the appropriate balance rehabilitation treatment for each patient, besides the CMT type.

  10. 腓骨肌萎缩症分子突变研究现状%An overview of molecular mutations of charcot marie tooth disease

    Institute of Scientific and Technical Information of China (English)

    范晓博

    2010-01-01

    腓骨肌萎缩症(charcot marie tooth disease,CMT)是一组高发病率的周围神经系统的单基因遗传病,具有临床和遗传异质性.可分为CMT1型,CMT2型,CMTX型和CMT4型.近些年随着分子遗传学和分子生物学的快速发展,已经发现了很多CMT的相关致病基因.主要包括外周髓鞘蛋白22基因、髓鞘蛋白零蛋白基因、间隙连接蛋白-32基因、驱动蛋白1B基因、Ras相关蛋白7基因、小分子热休克蛋白27基因等.本文就CMT相关致病基因研究现状作一综述.

  11. Whole Genome Sequencing Identifies a 78 kb Insertion from Chromosome 8 as the Cause of Charcot-Marie-Tooth Neuropathy CMTX3

    Science.gov (United States)

    Brewer, Megan H.; Chaudhry, Rabia; Qi, Jessica; Kidambi, Aditi; Drew, Alexander P.; Ryan, Monique M.; Subramanian, Gopinath M.; Young, Helen K.; Zuchner, Stephan; Reddel, Stephen W.; Nicholson, Garth A.; Kennerson, Marina L.

    2016-01-01

    With the advent of whole exome sequencing, cases where no pathogenic coding mutations can be found are increasingly being observed in many diseases. In two large, distantly-related families that mapped to the Charcot-Marie-Tooth neuropathy CMTX3 locus at chromosome Xq26.3-q27.3, all coding mutations were excluded. Using whole genome sequencing we found a large DNA interchromosomal insertion within the CMTX3 locus. The 78 kb insertion originates from chromosome 8q24.3, segregates fully with the disease in the two families, and is absent from the general population as well as 627 neurologically normal chromosomes from in-house controls. Large insertions into chromosome Xq27.1 are known to cause a range of diseases and this is the first neuropathy phenotype caused by an interchromosomal insertion at this locus. The CMTX3 insertion represents an understudied pathogenic structural variation mechanism for inherited peripheral neuropathies. Our finding highlights the importance of considering all structural variation types when studying unsolved inherited peripheral neuropathy cases with no pathogenic coding mutations. PMID:27438001

  12. Expression of a dynamin 2 mutant associated with Charcot-Marie-Tooth disease leads to aberrant actin dynamics and lamellipodia formation.

    Science.gov (United States)

    Yamada, Hiroshi; Kobayashi, Kinue; Zhang, Yubai; Takeda, Tetsuya; Takei, Kohji

    2016-08-15

    Specific mutations in dynamin 2 are linked to Charcot-Marie-Tooth disease (CMT), an inherited peripheral neuropathy. However, the effects of these mutations on dynamin function, particularly in relation to the regulation of the actin cytoskeleton remain unclear. Here, selected CMT-associated dynamin mutants were expressed to examine their role in the pathogenesis of CMT in U2OS cells. Ectopic expression of the dynamin CMT mutants 555Δ3 and K562E caused an approximately 50% decrease in serum stimulation-dependent lamellipodia formation; however, only K562E caused aberrations in the actin cytoskeleton. Immunofluorescence analysis showed that the K562E mutation resulted in the disappearance of radially aligned actin bundles and the simultaneous appearance of F-actin clusters. Live-cell imaging analyses showed F-actin polymers of decreased length assembled into immobile clusters in K562E-expressing cells. The K562E dynamin mutant colocalized with the F-actin clusters, whereas its colocalization with clathrin-coated pit marker proteins was decreased. Essentially the same results were obtained using another cell line, HeLa and NG108-15 cells. The present study is the first to show the association of dynamin CMT mutations with aberrant actin dynamics and lamellipodia, which may contribute to defective endocytosis and myelination in Schwann cells in CMT.

  13. [A case of Charcot-Marie-Tooth disease 1 B with Val 146Phe mutation of myelin protein zero showing a severe clinical phenotype].

    Science.gov (United States)

    Ohnishi, A; Aoki, A; Yamamoto, T; Tsuji, S

    2000-03-01

    A 15-year-old boy had complaints of progressive gait disturbance and foot deformity. He started to walk at the age of 18 months. Since two years of age, he had noticed unstable gait. He showed evident scoliosis and enlarged great auricular nerves. Moderate to slight degrees of muscular atrophy and weakness of distal upper, and proximal and distal lower limbs were observed. Pes equinovarus deformity of both feet was obvious. Muscle stretch reflexes were absent in both limbs except decreased triceps brachii reflex. Vibratory sensation was decreased severely in the toes and mildly in the fingers. In cerebrospinal fluid, protein was mildly elevated. Median nerve motor conduction velocity was 5.0 m/sec. On sural nerve biopsy, both demyelinated and remyelinated axons and onion-bulbs without hypomyelination were observed. Therefore, the diagnosis of Charcot-Marie-Tooth disease 1 was made. The direct sequencing of the genomic DNA encoding the Po gene revealed a mutant allele, a guanine to thymine substitution of nucleotide position 436, which caused a substitution of phenylalanine for valine at amino acid position 146. This type of Po mutation is different from any type of Po mutation reported in the literature.

  14. A novel mutation in the nerve-specific 5'UTR of the GJB1 gene causes X-linked Charcot-Marie-Tooth disease.

    LENUS (Irish Health Repository)

    Murphy, Sinéad M

    2011-03-01

    X-linked Charcot-Marie-Tooth disease (CMT1X) is the second most common cause of CMT, and is usually caused by mutations in the gap junction protein beta 1 (GJB1) gene which codes for connexin 32 (CX32). CX32 has three tissue-specific promoters, P1 which is specific for liver and pancreas, P1a specific for liver, oocytes and embryonic stem cells, and P2 which is nerve-specific. Over 300 mutations have been described in GJB1, spread throughout the coding region. We describe two families with X-linked inheritance and a phenotype consistent with CMT1X who did not have mutations in the GJB1 coding region. The non-coding region of GJB1 was sequenced and an upstream exon-splicing variant found at approximately - 373G>A which segregated with the disease in both families and was not present in controls. This substitution is located at the last base of the nerve-specific 5\\'UTR and thus may disrupt splicing of the nerve-specific transcript. Online consensus splice-site programs predict a reduced score for the mutant sequence vs. the normal sequence. It is likely that other mutations within the GJB1 non-coding regions account for the CMT1X families who do not have coding region mutations.

  15. NEFL N98S mutation: another cause of dominant intermediate Charcot-Marie-Tooth disease with heterogeneous early-onset phenotype.

    Science.gov (United States)

    Berciano, José; Peeters, Kristien; García, Antonio; López-Alburquerque, Tomás; Gallardo, Elena; Hernández-Fabián, Arantxa; Pelayo-Negro, Ana L; De Vriendt, Els; Infante, Jon; Jordanova, Albena

    2016-02-01

    The purpose of this study was to describe a pedigree with NEFL N98S mutation associated with a dominant intermediate Charcot-Marie-Tooth disease (DI-CMT) and heterogeneous early-onset phenotype. The pedigree comprised two patients, the proband and her son, aged 38 and 5 years. The proband, evaluated at age 31, showed delayed motor milestones that, as of the second decade, evolved into severe phenotype consisting of sensorimotor neuropathy, pes cavus, clawing hands, gait and kinetic cerebellar ataxia, nystagmus and dysarthria, she being wheelchair bound. By then, a working diagnosis of sporadic early onset cerebellar ataxia with peripheral neuropathy was established. Screening of mutations associated with SCA and autosomal recessive cerebellar ataxias was negative. Her son showed a mild phenotype characterized by delayed motor milestones, and lower-limb hypotonia and areflexia. Electrophysiology in both patients showed nerve conduction slowing in the intermediate range, both in proximal and distal nerve segments, but where compound muscle action potentials exhibited severe attenuation there was conduction slowing down to the demyelinating range. In the proband, cranial magnetic resonance imaging (MRI) showed cerebellar atrophy, electromyography disclosed active denervation in tibialis anterior, and MRI of lower-limb musculature demonstrated widespread and distally accentuated muscle fatty atrophy; furthermore, on water sensitive MRI sequences there was edema of calf muscles. We conclude that the NEFL N98S mutation is associated with a DI-CMT phenotype characterized by early-onset sensorimotor neuropathy delaying motor milestones, which may evolve into a severe and complex clinical picture including cerebellar ataxia.

  16. Analysis of mutations in 17p 11.2 region in patients with Charcot-Marie-Tooth type 1 disease and patients with tomaculose neuropathy

    Directory of Open Access Journals (Sweden)

    Zamurović Nataša

    2002-01-01

    Full Text Available Charcot-Marie-Tooth type 1Α disease (CMT1A and hereditary neuropathy with liability to pressure palsies (HNPP are common inherited disorders of the peripheral nervous system associated with duplication and deletion respectively, of the 17p11.2 segment including the gene of peripheral myelin protein 22. We studied 48 subjects belonging to 29 families with clinical and electrophysiological signs of definite CMT1, 20 patients with suspected CMT phenotype, and 17 patients and healthy members of their families with HNPP. Blood sampling and DNA isolation, PCR, restriction analysis, southern blotting were performed using standard procedures. Of 48 patients with diagnosis of definite CMT1 in 25 (52% we found a 1.5 Mb tandem duplication in chromosome 17p11.2. These duplications were not found in any of 20 sporadic cases with the clinical phenotype of CMT but without reliable electrophysiological data. Only 13 (44.8%of 29 unrelated CMT1 patients from the first group had 17p11.2 duplications. Three of 4 sporadic cases (75% with definite CMT1 had 17p11.2 duplications. Of 17 patients from 6 families with HNPP deletion of 17p11.2 segment was found in 15 (88.2%, as well as in 5 (83.3% of six unrelated cases. Detection of CMT1A/HNPP recombination hotspot is a simple and reliable DNA diagnostic method, which is useful only for the patients with clinically already verified CMT1, and HNPP for further genetic counseling of patients and members of their families.

  17. Localization of a gene (CMT2A) for autosomal dominant Charcot-Marie-Tooth disease type 2 to chromosome 1p and evidence of genetic heterogeneity

    Energy Technology Data Exchange (ETDEWEB)

    Othmane, K.B.; Loprest, L.J.; Wilkinson, K.M. (Duke Univ. Medical Center, Durham, NC (United States)); Middleton, L.T. (Cyprus Institute of Neurology and Genetics, Nicosia (Cyprus)) (and others)

    1993-08-01

    Charcot-Marie-Tooth (CMT) disease type 2 (CMT2) is an inherited peripheral neuropathy characterized by variable age of onset and normal or slightly diminished nerve conduction velocity. CMT2 is pathologically and genetically distinct from CMT type 1 (CMT1). While CMT1 has been shown to be genetically heterogeneous, no chromosomal localization has been established for CMT2. The authors have performed pedigree linkage analysis in six large autosomal dominant CMT2 families and have demonstrated linkage and heterogeneity to a series of microsatellites (D1S160, D1S170, D1S244, D1S228 and D1S199) in the distal region of the short arm of chromosome 1. Significant evidence for heterogeneity was found using admixture analyses and the two-point lod scores. Admixture analyses using the multipoint results for the markers D1S244, D1S228, and D1S199 supported the two-point findings. Three families, DUK662, DUK1241, and 1523 gave posterior probabilities of 1.0, 0.98, and 0.88 of being of the linked type. Multipoint analysis examining the [open quotes]linked[close quotes] families showed that the most favored location for the CMT2A gene is within the interval flanked by D1S244 and D1S228 (odds approximately 70:1 of lying within versus outside that interval). These findings suggest that the CMT2 phenotype is secondary to at least two different genes and demonstrate further heterogeneity in the CMT phenotype.

  18. Molecular analyses of unrelated Charcot-Marie-Tooth (CMT) disease patients suggest a high frequency of the CMT1A duplication

    Energy Technology Data Exchange (ETDEWEB)

    Wise, C.A.; Davis, S.N.; Heju, Z.; Pentao, L.; Patel, P.I.; Lupski, J.R. (Baylor College of Medicine, Houston, TX (United States)); Garcia, C.A. (Louisiana State Univ. School of Medicine, New Orleans, LA (United States))

    1993-10-01

    Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy. One form of CMT, CMT type 1A, is characterized by uniformly decreased nerve conduction velocities, usually shows autosomal dominant inheritance, and is associated with a large submicroscopic duplication of the p11.2-p12 region of chromosome 17. A cohort of 75 unrelated patients diagnosed clinically with CMT and evaluated by electrophysiological methods were analyzed molecularly for the presence of the CMT1A DNA duplication. Three methodologies were used to assess the duplication: Measurement of dosage differences between RFLP alleles, analysis of polymorphic (GT)[sub n] repeats, and detection of a junction fragment by pulsed-field gel electrophoresis. The CMT1A duplication was found in 68% of the 63 unrelated CMT patients with electrophysiological studies consistent with CMT type 1 (CMT1). The CMT1A duplication was detected as a de novo event in two CMT1 families. Twelve CMT patients who did not have decreased nerve conduction velocities consistent with a diagnosis of CMT type 2 (CMT2) were found not to have the CMT1A duplication. The most informative molecular method was the detection of the CMT1A duplication-specific junction fragment. Given the high frequency of the CMT1A duplication in CMT patients and the high frequency of new mutations, the authors conclude that a molecular test for the CMT1A DNA duplication is very useful in the differential diagnosis of patients with peripheral neuropathies. 61 refs., 4 figs.

  19. LITAF mutations associated with Charcot-Marie-Tooth disease 1C show mislocalization from the late endosome/lysosome to the mitochondria.

    Directory of Open Access Journals (Sweden)

    Andressa Ferreira Lacerda

    Full Text Available Charcot-Marie-Tooth (CMT disease is one of the most common heritable neuromuscular disorders, affecting 1 in every 2500 people. Mutations in LITAF have been shown to be causative for CMT type 1C disease. In this paper we explore the subcellular localization of wild type LITAF and mutant forms of LITAF known to cause CMT1C (T49M, A111G, G112S, T115N, W116G, L122V and P135T. The results show that LITAF mutants A111G, G112S, W116G, and T115N mislocalize from the late endosome/lysosome to the mitochondria while the mutants T49M, L122V, and P135T show partial mislocalization with a portion of the total protein present in the late endosome/lysosome and the remainder of the protein localized to the mitochondria. This suggests that different mutants of LITAF will produce differing severity of disease. We also explored the effect of the presence of mutant LITAF on wild-type LITAF localization. We showed that in cells heterozygous for LITAF, CMT1C mutants T49M and G112S are dominant since wild-type LITAF localized to the mitochondria when co-transfected with a LITAF mutant. Finally, we demonstrated how LITAF transits to the endosome and mitochondria compartments of the cell. Using Brefeldin A to block ER to Golgi transport we demonstrated that wild type LITAF traffics through the secretory pathway to the late endosome/lysosome while the LITAF mutants transit to the mitochondria independent of the secretory pathway. In addition, we demonstrated that the C-terminus of LITAF is necessary and sufficient for targeting of wild-type LITAF to the late endosome/lysosome and the mutants to the mitochondria. Together these data provide insight into how mutations in LITAF cause CMT1C disease.

  20. Prevalence and origin of De Novo duplications in Charcot-Marie-Tooth disease type 1A: First report of a De Novo duplication with a maternal origin

    Energy Technology Data Exchange (ETDEWEB)

    Blair, I.P.; Nash, J.; Gordon, M.J.; Nicholson, G.A. [Univ. of Sydney, New South Wales (United Kingdom)

    1996-03-01

    Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy. Sporadic cases of CMT have been described since the earliest reports of the disease. The most frequent form of the disorder, CMT1A, is associated with a 1.5-Mb DNA duplication on chromosome 17p11.2, which segregates with the disease. In order to investigate the prevalence of de novo CMT1A duplications, this study examined 118 duplication-positive CMT1A families. In 10 of these families it was demonstrated that the disease had arisen as the result of a de novo mutation. By taking into account the ascertainment of families, it can be estimated that {>=}10% of autosomal dominant CMT1 families are due to de novo duplications. The CMT1A duplication is thought to be the product of unequal crossing over between parental chromosome 17 homologues during meiosis. Polymorphic markers from within the duplicated region were used to determine the parental origin of these de novo duplications in eight informative families. Seven were of paternal and one of maternal origin. This study represents the first report of a de novo duplication with a maternal origin and indicates that it is not a phenomenon associated solely with male meioses. Recombination fractions for the region duplicated in CMT1A are larger in females than in males. That suggests that oogenesis may be afforded greater protection from misalignment during synapsis, and/or that there may be lower activity of those factors or mechanisms that lead to unequal crossing over at the CMT1A locus. 41 refs., 2 figs.

  1. Mutation Analysis of Gap Junction Protein Beta 1 and Genotype-Phenotype Correlation in X-linked Charcot-Marie-Tooth Disease in Chinese Patients

    Institute of Scientific and Technical Information of China (English)

    Bo Sun; Zhao-Hui Chen; Li Ling; Yi-Fan Li; Li-Zhi Liu; Fei Yang; Xu-Sheng Huang

    2016-01-01

    Background:Among patients with Charcot-Marie-Tooth disease (CMT),the X-linked variant (CMTX) caused by gap junction protein beta 1 (GJB1) gene mutation is the second most frequent type,accounting for approximately 90% of all CMTX.More than 400 mutations have been identified in the GJB1 gene that encodes connexin 32 (CX32).CX32 is thought to form gap junctions that promote the diffusion pathway between cells.GJB1 mutations interfere with the formation of the functional channel and impair the maintenance of peripheral myelin,and novel mutations are continually discovered.Methods:We included 79 unrelated patients clinically diagnosed with CMT at the Department of Neurology of the Chinese People's Liberation Army General Hospital from December 20,2012,to December 31,2015.Clinical examination,nerve conduction studies,and molecular and bioinformatics analyses were performed to identify patients with CMTX 1.Results:Nine GJB1 mutations (c.283G>A,c.77C>T,c.643C>T,c.515C>T,c.191G>A,c.610C>T,c.490C>T,c.491G>A,and c.44G>A) were discovered in nine patients.Median motor nerve conduction velocities of all nine patients were < 38 m/s,resembling CMT Type 1.Three novel mutations,c.643C>T,c.191G>A,and c.610C>T,were revealed and bioinformatics analyses indicated high pathogenicity.Conclusions:The three novel missense mutations within the GJB1 gene broaden the mutational diversity of CMT 1 X.Molecular analysis of family members and bioinformatics analyses of the afflicted patients confirmed the pathogenicity of these mutations.

  2. Peria xin and Charcot-Marie-Tooth DiseaseS ubtype 4F%Periaxin与腓骨肌萎缩症4 F亚型

    Institute of Scientific and Technical Information of China (English)

    任页玫(综述); 石亚伟(审校)

    2015-01-01

    Periaxin是施万细胞特异表达的一种蛋白,在维持髓鞘稳定性方面起重要作用,该基因突变将导致脱髓鞘型常染色体隐性遗传的腓骨肌萎缩症4F 亚型发生。从分子遗传学角度探讨腓骨肌萎缩症4F亚型发病的机制已成为目前研究的热点。从 periaxin的分布、结构与功能开展研究,寻找与其相互作用的蛋白质并揭示其互作的生物学意义,从蛋白质水平上研究腓骨肌萎缩症的发病机制具有重要意义。%Periaxin is expressed by myelinating Schwann cells ,which plays an essential role in stabiliza-tion of the myeline sheath.Periaxin mutations cause autosomal recessive,demyelination neuropathy,Charcot-Marie-Tooth 4F(CMT4F) subtype.Molecular genetics mechanism of CMT4F subtype has been one of the hot spots in the research field.The study of periaxin distribution,structures and functions,finding the interacting proteins with periaxin will reveal its biological function ,and lay the foundation for the research of CMT patho-genesis on the protein level.

  3. Lack of GDAP1 induces neuronal calcium and mitochondrial defects in a knockout mouse model of charcot-marie-tooth neuropathy.

    Science.gov (United States)

    Barneo-Muñoz, Manuela; Juárez, Paula; Civera-Tregón, Azahara; Yndriago, Laura; Pla-Martin, David; Zenker, Jennifer; Cuevas-Martín, Carmen; Estela, Anna; Sánchez-Aragó, María; Forteza-Vila, Jerónimo; Cuezva, José M; Chrast, Roman; Palau, Francesc

    2015-04-01

    Mutations in GDAP1, which encodes protein located in the mitochondrial outer membrane, cause axonal recessive (AR-CMT2), axonal dominant (CMT2K) and demyelinating recessive (CMT4A) forms of Charcot-Marie-Tooth (CMT) neuropathy. Loss of function recessive mutations in GDAP1 are associated with decreased mitochondrial fission activity, while dominant mutations result in impairment of mitochondrial fusion with increased production of reactive oxygen species and susceptibility to apoptotic stimuli. GDAP1 silencing in vitro reduces Ca2+ inflow through store-operated Ca2+ entry (SOCE) upon mobilization of endoplasmic reticulum (ER) Ca2+, likely in association with an abnormal distribution of the mitochondrial network. To investigate the functional consequences of lack of GDAP1 in vivo, we generated a Gdap1 knockout mouse. The affected animals presented abnormal motor behavior starting at the age of 3 months. Electrophysiological and biochemical studies confirmed the axonal nature of the neuropathy whereas histopathological studies over time showed progressive loss of motor neurons (MNs) in the anterior horn of the spinal cord and defects in neuromuscular junctions. Analyses of cultured embryonic MNs and adult dorsal root ganglia neurons from affected animals demonstrated large and defective mitochondria, changes in the ER cisternae, reduced acetylation of cytoskeletal α-tubulin and increased autophagy vesicles. Importantly, MNs showed reduced cytosolic calcium and SOCE response. The development and characterization of the GDAP1 neuropathy mice model thus revealed that some of the pathophysiological changes present in axonal recessive form of the GDAP1-related CMT might be the consequence of changes in the mitochondrial network biology and mitochondria-endoplasmic reticulum interaction leading to abnormalities in calcium homeostasis.

  4. Lack of GDAP1 induces neuronal calcium and mitochondrial defects in a knockout mouse model of charcot-marie-tooth neuropathy.

    Directory of Open Access Journals (Sweden)

    Manuela Barneo-Muñoz

    2015-04-01

    Full Text Available Mutations in GDAP1, which encodes protein located in the mitochondrial outer membrane, cause axonal recessive (AR-CMT2, axonal dominant (CMT2K and demyelinating recessive (CMT4A forms of Charcot-Marie-Tooth (CMT neuropathy. Loss of function recessive mutations in GDAP1 are associated with decreased mitochondrial fission activity, while dominant mutations result in impairment of mitochondrial fusion with increased production of reactive oxygen species and susceptibility to apoptotic stimuli. GDAP1 silencing in vitro reduces Ca2+ inflow through store-operated Ca2+ entry (SOCE upon mobilization of endoplasmic reticulum (ER Ca2+, likely in association with an abnormal distribution of the mitochondrial network. To investigate the functional consequences of lack of GDAP1 in vivo, we generated a Gdap1 knockout mouse. The affected animals presented abnormal motor behavior starting at the age of 3 months. Electrophysiological and biochemical studies confirmed the axonal nature of the neuropathy whereas histopathological studies over time showed progressive loss of motor neurons (MNs in the anterior horn of the spinal cord and defects in neuromuscular junctions. Analyses of cultured embryonic MNs and adult dorsal root ganglia neurons from affected animals demonstrated large and defective mitochondria, changes in the ER cisternae, reduced acetylation of cytoskeletal α-tubulin and increased autophagy vesicles. Importantly, MNs showed reduced cytosolic calcium and SOCE response. The development and characterization of the GDAP1 neuropathy mice model thus revealed that some of the pathophysiological changes present in axonal recessive form of the GDAP1-related CMT might be the consequence of changes in the mitochondrial network biology and mitochondria-endoplasmic reticulum interaction leading to abnormalities in calcium homeostasis.

  5. Enfermedad de Charcot-Marie-Tooth: Estudio clínico y molecular de los genes GJB-1 y MFN2 en la población española.

    OpenAIRE

    Casasnovas Pons, Carlos

    2010-01-01

    [spa] La enfermedad de Charcot-Marie-Tooth (CMT) es un grupo heterogéneo de enfermedades que afectan el sistema nervioso periférico. Su prevalencia se estima entre los 10 y 30 casos por cada 100,000 habitantes. La clasificación más frecuente empleada en la actualidad combina los hallazgos clínicos con el patrón de herencia y los hallazgos electrofisiológicos o de anatomía patológica.

  6. 有TIA样表现的Charcot-Marie-Tooth病:病例报告及文献复习%Case report about Charcot-Marie-Tooth disease with manifestation of TIA and literature review

    Institute of Scientific and Technical Information of China (English)

    俞羚; 李建萍; 李焰生

    2007-01-01

    @@ 腓骨肌萎缩症又称为Charcot-Marie-Tooth病(CMT),是人类最常见的遗传性周围神经病,其发病率在美国约为1/2500,国内亦有不少报道.其主要表现为足内侧肌、腓骨肌和大腿肌远端进行性无力和萎缩,典型者呈弓形足和"鹤腿",也可累及手或前臂肌肉,形成爪形手;腱反射(特别是踝反射)减弱或消失;可伴有轻到中度感觉减退,主要累及深感觉.目前将CMT分为CMT1、CMT2、CMT3、CMT4和CMTX等5型.CMTX占其中10%~15%,并不少见,但有类似短暂性缺血发作(TIA)样表现的极少,容易漏诊或误诊.现报道一例初诊为有TIA样表现的CMTX.

  7. Progress of surgical treatment for foot and ankle deformities due to the Charcot-Marie-Tooth disease%Charcot-Marie-Tooth病足踝畸形与外科治疗进展

    Institute of Scientific and Technical Information of China (English)

    梁喜斌; 秦泗河

    2014-01-01

    Charcot-Marie-Tooth病(CMT)是一种进行性、神经性肌萎缩综合征,是周围神经系统最常见的遗传性疾病,易引起下肢足踝畸形,尤以高弓内翻足多见.由于CMT病涉及多学科,临床表现多样,临床医生对此病的治疗熟悉甚少,使此类患者就医时出现较大困惑.本文参考近年文献,归纳认为对于CMT引起的足踝畸形的外科治疗,应根据患者年龄、畸形类别与程度、肌力失衡的范围及程度、患者对矫形治疗的期望值等因素确定手术指征、制定矫形方案.

  8. Molecular genetic analysis of a Chinese family with Charcot-Marie-Tooth disease%一个Charcot-Marie-Tooth病家系的分子遗传学分析

    Institute of Scientific and Technical Information of China (English)

    杨莹韵; 从杨; 孙之星; 田原; 刘辰; 杨威

    2010-01-01

    目的 鉴定一个Charcot-Marie-Tooth病(CMT)家系的致病突变.方法 根据家族史、临床表现和肌电图检查结果判断家系CMT分型.采集16名家系成员外周血,提取基因组DNA.针对CMT1的6个亚型,选择微卫星标记进行连锁分析.针对PMP22基因重复突变,采用实时定量PCR检测家系成员.结果 本家系疾病呈常染色体显性遗传.患者均有青少年发病、缓慢进展的下肢无力症状.部分患者经查体发现下肢腱反射减弱、痛触觉减弱,下肢神经传导速度均小于30 m/s,提示为CMT1型.通过连锁分析排除了CMT1A、CMT1E以外的其他4个亚型,证实患者基因组内PMP22基因存在重复突变.结论 此家系患者表型为CMT1A,其致病突变为染色体17p11.2区域内PMP22基因的重复.

  9. Recombination hot spot in 3.2-kb region of the Charcot-Marie Tooth type 1A repeat sequences: New tools for molecular diagnosis of hereditary neuropathy with liability to pressure palsies and of Charcot-Marie-Tooth type 1A

    Energy Technology Data Exchange (ETDEWEB)

    Lopes, J.; LeGuern, E.; Gouider, R.; Tardieu, S.; Abbas, N. [Hopital de la Salpetriere, Paris (France)] [and others

    1996-06-01

    Charcot-Marie-Tooth type 1A (CMT1A) disease and hereditary neuropathy with liability to pressure palsies (HNPP) are autosomal dominant neuropathies, associated, respectively, with duplications and deletions of the same 1.5-Mb region on 17p11.2-p12. These two rearrangements are the reciprocal products of an unequal meiotic crossover between the two chromosome 17 homologues, caused by the misalignment of the CMT1A repeat sequences (CMT1A-REPs), the homologous sequences flanking the 1.5-Mb CMT1A/HNPP monomer unit. In order to map recombination breakpoints within the CMT1A-REPs, a 12.9-kb restriction map was constructed from cloned EcoRI fragments of the proximal and distal CMT1A-REPs. Only 3 of the 17 tested restriction sites were present in the proximal CMT1A-REP but absent in the distal CMT1A-REP, indicating a high degree of homology between these sequences. The rearrangements were mapped in four regions of the CMT1A-REPs by analysis of 76 CMT1A index cases and 38 HNPP patients, who were unrelated. A hot spot of crossover breakpoints located in a 3.2-kb region accounted for three-quarters of the rearrangements, detected after EcoRI/SacI digestion, by the presence of 3.2-kb and 7.8-kb junction fragments in CMT1A and HNPP patients, respectively. These junction fragments, which can be detected on classical Southern blots, permit molecular diagnosis. Other rearrangements can also be detected by gene dosage on the same Southern blots. 25 refs., 4 figs., 2 tabs.

  10. Charcot-Marie-Tooth Disease

    Science.gov (United States)

    ... as the hormone androgen, to prevent nerve degeneration. Vitamin C has been studied in CMT1A and the ... Complications of AIDS Information Page Neurological Complications of Lyme Disease Information Page Neuromyelitis Optica Information Page Neuronal Migration ...

  11. Charcot-Marie-Tooth Disease

    Science.gov (United States)

    ... of symptoms is very gradual. The degeneration of motor nerves results in muscle weakness and atrophy in the ... of symptoms is very gradual. The degeneration of motor nerves results in muscle weakness and atrophy in the ...

  12. 腓骨肌萎缩症的分子遗传学研究%Molecular genetics of Charcot-Marie-Tooth disease

    Institute of Scientific and Technical Information of China (English)

    章远志; Nanbert ZHONG

    2005-01-01

    腓骨肌萎缩症也称为Charcot-Marie-Tooth病(CMT),是一类高发病率的周围神经系统单基因遗传病,可发生于世界范围的各个种族之中,发病率为1/25000遗传方式主要为常染色体显性遗传(AD),也可见常染色体隐性遗传(AR)及X连锁显性或隐性遗传(XD或XR)。即使是同一家庭中的患者,其患病的严重程度也会不同。

  13. Research progress in molecular genetics of Charcot-Marie-Tooth disease type 2%腓骨肌萎缩症2型分子遗传学研究进展

    Institute of Scientific and Technical Information of China (English)

    肖智权; 张付峰; 唐北沙

    2007-01-01

    腓骨肌萎缩症(Charcot-Marie-Tooth disease,CMT)是一类最常见的遗传性周围神经病之一,发病率为1/2500。主要呈常染色体显性(autosomal dominant,AD)遗传,也可呈常染色体隐性遗传(autosomal recessive,AR)及连锁显性(x-linked dominant,XD)或隐性遗传(X-linked recessive,XR)。随着分子遗传学研究的进展,近几年对CMT2型的研究已经取得很大的进展,相继克隆了多个基因并不断发现新的致病基因(表1)。

  14. Selected items from the Charcot-Marie-Tooth (CMT) Neuropathy Score and secondary clinical outcome measures serve as sensitive clinical markers of disease severity in CMT1A patients.

    Science.gov (United States)

    Mannil, Manoj; Solari, Alessandra; Leha, Andreas; Pelayo-Negro, Ana L; Berciano, José; Schlotter-Weigel, Beate; Walter, Maggie C; Rautenstrauss, Bernd; Schnizer, Tuuli J; Schenone, Angelo; Seeman, Pavel; Kadian, Chandini; Schreiber, Olivia; Angarita, Natalia G; Fabrizi, Gian Maria; Gemignani, Franco; Padua, Luca; Santoro, Lucio; Quattrone, Aldo; Vita, Giuseppe; Calabrese, Daniela; Young, Peter; Laurà, Matilde; Haberlová, Jana; Mazanec, Radim; Paulus, Walter; Beissbarth, Tim; Shy, Michael E; Reilly, Mary M; Pareyson, Davide; Sereda, Michael W

    2014-11-01

    This study evaluates primary and secondary clinical outcome measures in Charcot-Marie-Tooth disease type 1A (CMT1A) with regard to their contribution towards discrimination of disease severity. The nine components of the composite Charcot-Marie-Tooth disease Neuropathy Score and six additional secondary clinical outcome measures were assessed in 479 adult patients with genetically proven CMT1A and 126 healthy controls. Using hierarchical clustering, we identified four significant clusters of patients according to clinical severity. We then tested the impact of each of the CMTNS components and of the secondary clinical parameters with regard to their power to differentiate these four clusters. The CMTNS components ulnar sensory nerve action potential (SNAP), pin sensibility, vibration and strength of arms did not increase the discriminant value of the remaining five CMTNS components (Ulnar compound motor action potential [CMAP], leg motor symptoms, arm motor symptoms, leg strength and sensory symptoms). However, three of the six additional clinical outcome measures - the 10m-timed walking test (T10MW), 9 hole-peg test (9HPT), and foot dorsal flexion dynamometry - further improved discrimination between severely and mildly affected patients. From these findings, we identified three different composite measures as score hypotheses and compared their discriminant power with that of the CMTNS. A composite of eight components CMAP, Motor symptoms legs, Motor symptoms arms, Strength of Legs, Sensory symptoms), displayed the strongest power to discriminate between the clusters. As a conclusion, five items from the CMTNS and three secondary clinical outcome measures improve the clinical assessment of patients with CMT1A significantly and are beneficial for upcoming clinical and therapeutic trials.

  15. 腓骨肌萎缩症1型18例电生理分析%Electrophysiological analysis of Charcot-Marie-Tooth disease type

    Institute of Scientific and Technical Information of China (English)

    张家良; 梅翠红

    2006-01-01

    目的 分析腓骨肌萎缩症1型(Charcot-Marie-Tooth病,CMT1)电生理特点.方法 应用肌电图仪检测和分析来自12家系18例CMT1型病人的电生理特征,包括肌电图(EMG)、运动神经传导速度(MCV)和感觉神经传导速度(SCV).结果 15例的病人肌电图上出现纤颤、正相电位,15例病人有运动电位时限延长.正中神经SCV有13例未测出,而对应的MCV只有1例未测出.腓总神经、胫神经的MCV分别有9、10例未测出而正中神经MCV只有1例未测出.结论 电生理特点为下肢神经病变重于上肢,感觉神经病变重于运动神经.感觉、运动神经均受累,不同病人受累程度不一致;CMT1型病人同一家系,表现存在差异.

  16. 中国人中发现一例Charcot-Marie-Tooth病连接蛋白32基因新突变%A new mutation in the connexin 32 gene was found in Charcot-Marie-Tooth disease in Chinese patients

    Institute of Scientific and Technical Information of China (English)

    笪宇威; 沈定国

    2000-01-01

    目的了解中国人进行性腓骨肌萎缩症(Charcot-Marie-Tooth disease, CMT)连接蛋白32(connexin 32,Cx32)基因外显子2的突变情况.方法对6例无亲缘关系的、无重复的CMT1患者和10例无亲缘关系的CMT2患者进行SSCP分析,对有异常者进行测序,根据突变点序列设计合适的内切酶,对50名正常对照进行酶切分析.结果在1例CMT1患者发生了Gly21Asp(62G→A)错义突变.用限制性内切酶H-aeⅡ酶切50名正常对照未见异常,表明该突变为致病性突变.结论 Gly21Asp是未报道过的新型突变,中国人CMT1患者中CMTX患者可能占一定比例.

  17. 剔除小鼠神经微管运动蛋白Kif1b基因导致类似Charcot-Marie-Tooth病动物模型%Neuronal microtubule motor protein Kif1b gene knockout mice as animal model of Charcot-Marie-Tooth disease

    Institute of Scientific and Technical Information of China (English)

    董铭; 于澎; 饶明俐; 田中庸介

    2007-01-01

    目的 研究杂合子小鼠Kif1b基因剔除后导致的表现型,探讨其作为类似Charcot-Marie-Tooth(CMT)病动物模型的可行性.方法 用Southern blotting和PCR检测同源重组和基因型,Western blotting测定杂合子KIF1B蛋白表达量,行为学实验观察其表现型.结果 杂合子Kif1b基因剔除小鼠的KIF1B蛋白表达量减少了一半以上,行为学实验结果表明,杂合子基因剔除小鼠在运动和感觉方面均有异常.Rota-rod实验,Rod walking实验和Wire hanging实验中,野生型小鼠的停留时间均明显长于Kif1b基因剔除小鼠.同时,杂合子Kif1b基因剔除小鼠在热板实验和福尔马林实验中,表现出对温度觉和痛觉反应的迟钝,其反应时间与野生型小鼠相比明显延长,反应强度降低.结论 杂合子Kif1b基因剔除小鼠的表现型与人类腓骨肌萎缩症相似,作为疾病模型具备可行性.

  18. ELECTRONEUROPHYSIOLOGICAL CHARACTERISTIC ANALYSIS WITH CHARCOT-MARIE-TOOTH DISEASE%腓骨肌萎缩症患者神经电生理检测特征性分析

    Institute of Scientific and Technical Information of China (English)

    张鸿雁

    2014-01-01

    目的:探讨腓骨肌萎缩症(Charcot-Marie-Tooth disease,CMT)患者的神经电生理改变特点;方法:应用肌电诱发电位仪对6例腓骨肌萎缩症患者进行电生理检测,对检查结果进行回顾性总结和分析.结果:6例患者运动或感觉神经传导速度均存在不同程度的减慢、消失或波幅降低,且下肢重于上肢;6例患者被检肌肉均呈现不同程度神经源性损害.结论:CMT的神经电生理特点是神经源性损害,神经电生理检查是发现和诊断CMT的可靠方法.

  19. 腓骨肌萎缩症2型(CMT2)小鼠模型的研究进展%Research progress in the mouse models of Charcot-Marie-Tooth disease type 2 (CMT2)

    Institute of Scientific and Technical Information of China (English)

    于珍; 栾春杰; 顾鸣敏

    2014-01-01

    腓骨肌萎缩症(Charcot-Marie-Tooth disease,CMT)是人类最常见的遗传性运动和感觉神经疾病之一,全球群体发病率约为1/2500.CMT主要分为脱髓鞘型(包括CMT1,CMT3,CMT4和CMTX1)和轴索型(CMT2).迄今为止,先后已有17个CMT2的致病基因被定位和克隆,然而对这些基因的致病机制所知甚少.建立CMT2小鼠模型是从动物水平研究突变基因致病机制的有效手段.目前已成功构建了近10种CMT2的转基因小鼠、基因敲除小鼠或基因敲入小鼠模型,其中尤以带有人源致病基因的转基因小鼠模型为多.文章简要介绍了CMT2小鼠模型构建策略,着重阐述了CMT2小鼠模型的研究进展,并对个别小鼠模型进行了剖析.

  20. Genetic heterogeneity and clinical variability of charcot-Marie-Tooth disease%腓骨肌萎缩症的遗传异质性和临床变异性

    Institute of Scientific and Technical Information of China (English)

    王国相; 段晓慧; 顾卫红

    2010-01-01

    @@ 一、前言 夏科-马里-图斯病(Charcot-Marie-Tooth disease,CMT),又名腓骨肌萎缩症,是一组最常见的周围神经单基因遗传病,患病率约为1/2500,遗传方式有常染色体显性遗传、常染色体隐性遗传和X连锁遗传.其典型临床表现为青年期起病,缓慢进展的远端肌力减退及肌肉萎缩,弓形足,锤状趾,腱反射消失,四肢远端深感觉障碍.临床上依据电生理和病理的改变主要分为脱髓鞘型(CMT1/HMSN1)和轴索型(CMT2/HMSN2),此外还存在一些特殊类型,如CMT3、CMT4、CMTX和显性遗传中间型CMT(CMTDI,表1).

  1. Exclusive expression of the Rab11 effector SH3TC2 in Schwann cells links integrin-α6 and myelin maintenance to Charcot-Marie-Tooth disease type 4C.

    Science.gov (United States)

    Vijay, Sauparnika; Chiu, Meagan; Dacks, Joel B; Roberts, Rhys C

    2016-07-01

    Charcot-Marie-Tooth disease type 4C (CMT4C) is one of the commonest autosomal recessive inherited peripheral neuropathies and is associated with mutations in the Rab11 effector, SH3TC2. Disruption of the SH3TC2-Rab11 interaction is the molecular abnormality underlying this disease. However, why SH3TC2 mutations cause an isolated demyelinating neuropathy remains unanswered. Here we show that SH3TC2 is an exclusive Schwann cell protein expressed late in myelination and is downregulated following denervation suggesting a functional role in myelin sheath maintenance. We support our data with an evolutionary cell biological analysis showing that the SH3TC2 gene, and its paralogue SH3TC1, are derived from an ancestral homologue, the duplication of which occurred in the common ancestor of jawed vertebrates, coincident with the appearance of Schwann cells and peripheral axon myelination. Furthermore, we report that SH3TC2 associates with integrin-α6, suggesting that aberrant Rab11-dependent endocytic trafficking of this critical laminin receptor in myelinated Schwann cells is connected to the demyelination seen in affected nerves. Our study therefore highlights the inherent evolutionary link between SH3TC2 and peripheral nerve myelination, pointing also towards a molecular mechanism underlying the specific demyelinating neuropathy that characterizes CMT4C.

  2. Mutation analysis of neurofilament-light gene in Chinese Charcot-Marie-Tooth disease%神经丝轻链基因在腓骨肌萎缩症中的突变分析

    Institute of Scientific and Technical Information of China (English)

    罗巍; 唐北沙; 赵国华; 李崎; 萧剑锋; 杨期东; 夏家辉

    2003-01-01

    目的探讨神经丝轻链基因(neurofilament-light gene, NF-L)在中国人腓骨肌萎缩症(Charcot-Marie-Tooth disease,CMT)中的突变特点. 方法应用聚合酶链反应-单链构象多态性技术结合DNA序列分析方法,对32个来自全国5省汉族的CMT家系先证者进行了NF-L基因的突变分析. 结果32例先证者中只有1例患者出现异常条带,经DNA测序证实该患者在NF-L基因的外显子3发生了1329C→T碱基改变,由于编码的氨基酸未改变,均为酪氨酸(Tyr),为一种同义突变. 结论 NF-L基因突变可能在中国人的腓骨肌萎缩症患者中少见.

  3. A locus-specific database for mutations in GDAP1 allows analysis of genotype-phenotype correlations in Charcot-Marie-Tooth diseases type 4A and 2K

    Directory of Open Access Journals (Sweden)

    Cassereau Julien

    2011-12-01

    Full Text Available Abstract Background The ganglioside-induced differentiation-associated protein 1 gene (GDAP1, which is involved in the Charcot-Marie-Tooth disease (CMT, the most commonly inherited peripheral neuropathy, encodes a protein anchored to the mitochondrial outer membrane. The phenotypic presentations of patients carrying GDAP1 mutations are heterogeneous, making it difficult to determine genotype-phenotype correlations, since the majority of the mutations have been found in only a few unrelated patients. Locus-specific databases (LSDB established in the framework of the Human Variome Project provide powerful tools for the investigation of such rare diseases. Methods and Results We report the development of a publicly accessible LSDB for the GDAP1 gene. The GDAP1 LSDB has adopted the Leiden Open-source Variation Database (LOVD software platform. This database, which now contains 57 unique variants reported in 179 cases of CMT, offers a detailed description of the molecular, clinical and electrophysiological data of the patients. The usefulness of the GDAP1 database is illustrated by the finding that GDAP1 mutations lead to primary axonal damage in CMT, with secondary demyelination in the more severe cases of the disease. Conclusion Findings of this nature should lead to a better understanding of the pathophysiology of CMT. Finally, the GDAP1 LSDB, which is part of the mitodyn.org portal of databases of genes incriminated in disorders involving mitochondrial dynamics and bioenergetics, should yield new insights into mitochondrial diseases.

  4. Silencing of the Charcot-Marie-Tooth disease-associated gene GDAP1 induces abnormal mitochondrial distribution and affects Ca2+ homeostasis by reducing store-operated Ca2+ entry.

    Science.gov (United States)

    Pla-Martín, David; Rueda, Carlos B; Estela, Anna; Sánchez-Piris, Maribel; González-Sánchez, Paloma; Traba, Javier; de la Fuente, Sergio; Scorrano, Luca; Renau-Piqueras, Jaime; Alvarez, Javier; Satrústegui, Jorgina; Palau, Francesc

    2013-07-01

    GDAP1 is an outer mitochondrial membrane protein that acts as a regulator of mitochondrial dynamics. Mutations of the GDAP1 gene cause Charcot-Marie-Tooth (CMT) neuropathy. We show that GDAP1 interacts with the vesicle-organelle trafficking proteins RAB6B and caytaxin, which suggests that GDAP1 may participate in the mitochondrial movement within the cell. GDAP1 silencing in the SH-SY5Y cell line induces abnormal distribution of the mitochondrial network, reduces the contact between mitochondria and endoplasmic reticulum (ER) and alters the mobilization of mitochondria towards plasma membrane upon depletion of ER-Ca(2+) stores. GDAP1 silencing does not affect mitochondrial Ca(2+) uptake, ER-Ca(2+), or Ca(2+) flow from ER to mitochondria, but reduces Ca(2+) inflow through store-operated Ca(2+) entry (SOCE) following mobilization of ER-Ca(2+) and SOCE-driven Ca(2+) entry in mitochondria. Our studies suggest that the pathophysiology of GDAP1-related CMT neuropathies may be associated with abnormal distribution and movement of mitochondria throughout cytoskeleton towards the ER and subplasmalemmal microdomains, resulting in a decrease in SOCE activity and impaired SOCE-driven Ca(2+) uptake in mitochondria.

  5. 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.

  6. Advances in the study of genetic characteristics and molecular mechanisms in Charcot-Marie-Tooth disease%腓骨肌萎缩症的遗传特征及致病机制的研究进展

    Institute of Scientific and Technical Information of China (English)

    徐汪洋; 孙莲花; 顾鸣敏

    2010-01-01

    腓骨肌萎缩症(Charcot-Marie-Tooth disease,CMT)是一类常见的遗传性周围神经病,发病率约为1/2500.该病主要呈AD遗传,也可呈AR遗传及XD或XR遗传.据统计,与CMT相关的基因有33个[1],已确定的致病基因至少有27个,其中外周髓鞘蛋白22(peripheral myelin protein 22,PMP22)、髓鞘蛋白零(myelin protein zero,MPZ)和间隙连接蛋白32(connexin-32,Cx32)异常最受关注.近年来在突变基因特征及其致病机制方面取得的研究进展为该病的基因诊断和基因治疗奠定了基础.本文主要就上述内容作一综述.%Charcot-Marie-Tooth disease (CMT) is a kind of common hereditary peripheral neuropathy which incidence is estimated 1/2 500. The genetic pattern of this disease mainly shows autosomal dominant (AD) , also shows autosomal recessive inheritance ( AR) and X-linked dominant ( XD) , or recessive inheritance (XR). It was reported that there were 33 CMT-related genes[1]. Twenty-seven disease-causing genes were defined, including peripheral myelin protein 22 ( PMP22) , myelin protein zero ( MPZ) , and connexin 32 ( Cx32) , which had more relevant reports. In recent years, lots of new disease-causing genes have been defined, which laid the foundation for exploring neural degeneration and the pathogenesis of muscle atrophy and for the prevention or treatment of the disease through gene diagnosis and gene therapy. In this paper, the features of mutation genes and the mechanisms of disease-causing genes in CMT are reviewed.

  7. 中国汉族人群腓骨肌萎缩症Cx32基因突变分析%Mutation screening of Cx32 in Han Chinese patients with Charcot-Marie-Tooth disease

    Institute of Scientific and Technical Information of China (English)

    张如旭; 罗巍; 资晓宏; 夏昆; 蔡芳; 萧剑峰; 赵国华; 张付峰; 沈潞; 江泓; 唐北沙

    2005-01-01

    Objective: To investigate the Cx32 mutation features and the clinical manifestations of Chinese patients with Charcot-Marie-Tooth disease(CMT). Methods: Twenty-four of 65 unrelated CMT patients were selected for Cx32 mutation screening after the exclusion of the CMT1A 1.5 Mb duplication and male-to-male transmission. The motor and sensory nerve conduction studies were performed in all probands and most of their affected family members to establish the clinical CMT1 ,CMT2 or CMT intermediate diagnosis. The presence of mutations in the coding region of Cx32 was detected by single-strand conformation polymorphism analysis combined with direct sequencing. Results: We found 7 different point mutations in the coding region of Cx32 in a total of 7 families. All the patients were mildly to moderately affected with a clinical CMT1 or CMT intermediate diagnosis. The mutation Arg15Gln was inherited with X-linked recessive trait in family 1 involved in our study. The Arg75Trp mutation was detected in a family with X-linked dominant CMT and autosomal recessive nonsydromic hearing loss. The clinical phenotype of the Thr188Ala mutation was firstly reported. Conclusion: Seven different Cx32 point mutations were detected and the percentage of Chinese CMT families with Cx32 mutation is about 10% in our study. The inheritance model of CMT secondary to Cx32 mutation could be X-linked dominant, X-linked recessive or sporadic. Male patients are usually more severely affected than females with slower nerve conduction velocities. Cx32 mutation screening should be firstly performed in those CMT families without male-to-male transmission and CMT1A duplication.

  8. 腓骨肌萎缩症患者的临床与神经电生理特征分析%THE CLINICAL ANALYISI AND NEUROELECTROPHYSIOLOGICAL CHARACTERISTICS IN PATIENTS WITH CHARCOT-MARIE-TOOTH DISEASE(CMT)

    Institute of Scientific and Technical Information of China (English)

    黄献; 宋治; 郑文; 黄顺祥

    2010-01-01

    目的:探讨腓骨肌萎缩症(Charcot-Marie-Tooth disease,CMT)的临床与神经电生理特征;方法:应用肌电图仪检测和分析21例腓骨肌萎缩症患者的电生理特征,包括肌电图和运动、感觉神经传导速度;分析电生理特征与临床之间的关系;结果:16例患者肌电图出现纤颤电位和(或)正锐波,17例患者运动单位(MUP)时限延长.11例腓总神经、13例胫神经运动传导速度(MCV)未引出,1例正中神经、2例尺神经MCV未引出,3例正中神经、2例尺神经MCV正常,其余均有不同程度减慢;15例腓肠神经感觉神经传导速度(SCV)未引出,3例正中神经、6例尺神经SCV未引出,7例正中神经、5例尺神经SCV正常,其余均有不同程度减慢.结论:CMT患者的神经电生理特征大多数呈神经原性损害,运动和感觉神经传导速度有不同程度的受累,下肢的神经病变重于上肢,临床表现结合神经肌电图检查有助于CMT的确诊.

  9. 腓骨肌萎缩症1型临床与电生理分析%Clinical and Electrophysiological Analysis of Charcot-Marie-Tooth Disease Type 1

    Institute of Scientific and Technical Information of China (English)

    张家良; 常建军

    2005-01-01

    目的:分析腓骨肌萎缩症1型(charcot-marie-tooth disease,CMT1)患者的临床与电生理特点. 方法:对1家系24人(已故2例)中7例(已故1例)CMT1患者临床特点进行总结,分析其中6例的电生理特征,包括肌电图(EMG)、运动神经传导速度(MCV)和感觉神经传导速度(SCV). 结果:4例于青少年期发病,有肢体远端肌无力和萎缩、腱反射减弱或消失、足畸形等典型的临床症状;3例EMG出现纤颤、正相电位,6例有运动电位时限延长;3例下肢SCV引不出,1例MCV引不出.结论:同一家系的CMT1型患者,临床表现亦差异较大;电生理特点为下肢神经病变重于上肢,感觉神经病变重于运动神经,且受累的严重程度不一致.

  10. 腓骨肌萎缩症4型遗传学研究进展%Advances in genetic studies of Charcot-Marie-Tooth disease type 4 (CMT4)

    Institute of Scientific and Technical Information of China (English)

    许烨; 张嘉莹; 杨博宇; 何志宏; 张慕晨; 于珍; 顾鸣敏

    2015-01-01

    腓骨肌萎缩症也称夏科-马利-杜斯氏病(Charcot-Marie-Tooth disease,CMT),是人类最常见的遗传性周围神经病之一,其遗传方式以常染色体显性遗传为主,也有部分呈常染色体隐性遗传或X连锁显性或隐性遗传.根据临床表型将CMT分为脱髓鞘型(CMT1)、轴突型(CMT2)和中间型(DI-CMT).常染色体隐性遗传的CMT1(AR-CMT1,也称CMT4型)临床表现除了CMT常见的四肢远端进行性肌无力和萎缩,以及高足弓和爪形手外,常起病早,进展迅速,并有不同程度的感觉障碍和脊柱畸形(以脊柱侧凸为主).近年来的研究显示,CMT4有11种亚型,其中有些亚型的致病机制较明确,有些亚型存在建立者突变,有些亚型还局限在临床描述和突变检出上.文章综述了CMT4的最新研究进展,包括各亚型的临床表现、致病机制和小鼠模型等.

  11. An analysis of electroneurophysiological and clinical characteristics in patients with charcot- Marie-Tooth disease%腓骨肌萎缩症的临床及神经电生理特点分析

    Institute of Scientific and Technical Information of China (English)

    邹艺; 刘英; 李素荣; 胥勋成; 高国勋

    2008-01-01

    目的:探讨腓骨肌萎缩症即夏科-马里-图思病(Charcot-Marie-Tooth disease, CMT)的临床及神经电生理特点.方法:应用肌电图仪检测和分析28例CMT患者的电生理特征,包括肌电图(EMG)、运动神经传导速度(MCV)、感觉神经传导速度(SCV).结果:主要症状有弓形足、垂足、鹤腿和腱反射消失;21例患者EMG出现纤颤电位、正锐波,25例患者运动单位电位(MUP)时限延长.14例患者下肢SCV未引出,12例患者下肢MCV未引出,正中神经SCV有6例未引出,而对应的MCV只有2例未引出.结论:该组CMT患者电生理特点为EMG呈神经原性损害.下肢神经病变重于上肢.感觉、运动神经均受累,感觉神经病变重于运动神经.神经电生理检查是诊断腓骨肌萎缩症的可靠方法.

  12. 腓骨肌萎缩症患者致病基因突变特点的研究%The characteristics of gene mutations in Chinese patients with Charcot-Marie-Tooth disease

    Institute of Scientific and Technical Information of China (English)

    张付峰; 张成; 潘乾; 蔡芳; 郭鹏; 唐北沙; 赵国华; 罗巍; 夏昆; 刘小民; 肖剑锋; 张如旭; 陈彪

    2005-01-01

    目的探讨腓骨肌萎缩症(Charcot-Marie-Tooth disease,CMT)致病基因的突变特点.方法应用实时荧光定量PCR方法、聚合酶链反应-单链构象多态性分析(PCR-SSCP)或PCR直接测序等方法对113个确诊的CMT家系进行了PMP22、MPZ、CX32、EGR2、GDAP1、NEFL、HSP22、HSP27等致病基因进行突变检测.结果发现有36个家系为PMP22重复突变所致,7个家系为CX32基因突变所致,1个家系为MPZ基因突变所致,1个家系为GDAP1基因突变所致,1个家系为HSP22基因突变所致,1个家系为HSP27基因突变所致,未发现PMP22、EGR2和NEFL基因点突变.结论 CMT的PMP22基因重复突变所占比例为31.9%, CX32基因突变所占比例为6.2%, HSP22、HSP27、MPZ和GDAP1基因点突变所占比例均为0.9%,PMP22、EGR2和NEFL基因点突变少见.

  13. Muscle-specific function of the centronuclear myopathy and Charcot-Marie-Tooth neuropathy-associated dynamin 2 is required for proper lipid metabolism, mitochondria, muscle fibers, neuromuscular junctions and peripheral nerves.

    Science.gov (United States)

    Tinelli, Elisa; Pereira, Jorge A; Suter, Ueli

    2013-11-01

    The ubiquitously expressed large GTPase Dynamin 2 (DNM2) plays a critical role in the regulation of intracellular membrane trafficking through its crucial function in membrane fission, particularly in endocytosis. Autosomal-dominant mutations in DNM2 cause tissue-specific human disorders. Different sets of DNM2 mutations are linked to dominant intermediate Charcot-Marie-Tooth neuropathy type B, a motor and sensory neuropathy affecting primarily peripheral nerves, or autosomal-dominant centronuclear myopathy (CNM) presenting with primary damage in skeletal muscles. To understand the underlying disease mechanisms, it is imperative to determine to which degree the primary affected cell types require DNM2. Thus, we used cell type-specific gene ablation to examine the consequences of DNM2 loss in skeletal muscle cells, the major relevant cell type involved in CNM. We found that DNM2 function in skeletal muscle is required for proper mouse development. Skeletal muscle-specific loss of DNM2 causes a reduction in muscle mass and in the numbers of muscle fibers, altered muscle fiber size distributions, irregular neuromuscular junctions (NMJs) and isolated degenerating intramuscular peripheral nerve fibers. Intriguingly, a lack of muscle-expressed DNM2 triggers an increase of lipid droplets (LDs) and mitochondrial defects. We conclude that loss of DNM2 function in skeletal muscles initiates a chain of harmful parallel and serial events, involving dysregulation of LDs and mitochondrial defects within altered muscle fibers, defective NMJs and peripheral nerve degeneration. These findings provide the essential basis for further studies on DNM2 function and malfunction in skeletal muscles in health and disease, potentially including metabolic diseases such as diabetes.

  14. Recommendations to enable drug development for inherited neuropathies: Charcot-Marie-Tooth and Giant Axonal Neuropathy [v1; ref status: indexed, http://f1000r.es/33n

    Directory of Open Access Journals (Sweden)

    Lori Sames

    2014-04-01

    Full Text Available Approximately 1 in 2500 Americans suffer from Charcot-Marie-Tooth (CMT disease. The underlying disease mechanisms are unique in most forms of CMT, with many point mutations on various genes causing a toxic accumulation of misfolded proteins. Symptoms of the disease often present within the first two decades of life, with CMT1A patients having reduced compound muscle and sensory action potentials, slow nerve conduction velocities, sensory loss, progressive distal weakness, foot and hand deformities, decreased reflexes, bilateral foot drop and about 5% become wheelchair bound. In contrast, the ultra-rare disease Giant Axonal Neuropathy (GAN is frequently described as a recessively inherited condition that results in progressive nerve death. GAN usually appears in early childhood and progresses slowly as neuronal injury becomes more severe and leads to death in the second or third decade. There are currently no treatments for any of the forms of CMTs or GAN. We suggest that further clinical studies should analyse electrical impedance myography as an outcome measure for CMT. Further, additional quality of life (QoL assessments for these CMTs are required, and we need to identify GAN biomarkers as well as develop new genetic testing panels for both diseases. We propose that using the Global Registry of Inherited Neuropathy (GRIN could be useful for many of these studies. Patient advocacy groups and professional organizations (such as the Hereditary Neuropathy Foundation (HNF, Hannah's Hope Fund (HHF, The Neuropathy Association (TNA and the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM can play a central role in educating clinicians and patients. Undertaking these studies will assist in the correct diagnosis of disease recruiting patients for clinical studies, and will ultimately improve the endpoints for clinical trials. By addressing obstacles that prevent industry investment in various forms of inherited neuropathies

  15. Recommendations to enable drug development for inherited neuropathies: Charcot-Marie-Tooth and Giant Axonal Neuropathy [v2; ref status: indexed, http://f1000r.es/3am

    Directory of Open Access Journals (Sweden)

    Lori Sames

    2014-04-01

    Full Text Available Approximately 1 in 2500 Americans suffer from Charcot-Marie-Tooth (CMT disease. The underlying disease mechanisms are unique in most forms of CMT, with many point mutations on various genes causing a toxic accumulation of misfolded proteins. Symptoms of the disease often present within the first two decades of life, with CMT1A patients having reduced compound muscle and sensory action potentials, slow nerve conduction velocities, sensory loss, progressive distal weakness, foot and hand deformities, decreased reflexes, bilateral foot drop and about 5% become wheelchair bound. In contrast, the ultra-rare disease Giant Axonal Neuropathy (GAN is frequently described as a recessively inherited condition that results in progressive nerve death. GAN usually appears in early childhood and progresses slowly as neuronal injury becomes more severe and leads to death in the second or third decade. There are currently no treatments for any of the forms of CMTs or GAN. We suggest that further clinical studies should analyse electrical impedance myography as an outcome measure for CMT. Further, additional quality of life (QoL assessments for these CMTs are required, and we need to identify GAN biomarkers as well as develop new genetic testing panels for both diseases. We propose that using the Global Registry of Inherited Neuropathy (GRIN could be useful for many of these studies. Patient advocacy groups and professional organizations (such as the Hereditary Neuropathy Foundation (HNF, Hannah's Hope Fund (HHF, The Neuropathy Association (TNA and the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM can play a central role in educating clinicians and patients. Undertaking these studies will assist in the correct diagnosis of disease recruiting patients for clinical studies, and will ultimately improve the endpoints for clinical trials. By addressing obstacles that prevent industry investment in various forms of inherited neuropathies

  16. Irradiação contralateral de força para a ativação do músculo tibial anterior em portadores da doença de Charcot-Marie-Tooth: efeitos de um programa de intervenção por FNP Contralateral force irradiation for the activation of tibialis anterior muscle in carriers of Charcot-Marie-Tooth disease: effect of PNF intervention program

    Directory of Open Access Journals (Sweden)

    Paula C. Meningroni

    2009-10-01

    Full Text Available OBJETIVO: Avaliar a resposta do músculo tibial anterior (TA após um protocolo de cinco semanas com irradiação contralateral de força através de diagonais de facilitação neuromuscular proprioceptiva (FNP em pacientes com polineuropatia desmielinizante associada à doença de Charcot-Marie-Tooth do tipo 1A (CMT-1A. MÉTODOS: Participaram deste estudo 12 pacientes, de ambos os sexos. Eles foram tratados em uma frequência de duas vezes por semana, durante cinco semanas. Em cada sessão, foram utilizadas as diagonais de Chopping, extensão-adução com rotação interna (EARI e flexão-abdução com rotação interna (FARI. As diagonais foram repetidas quatro vezes, em ambos os membros superiores e inferiores; cada diagonal tinha duração média de 6 segundos. Durante as execuções, a resposta muscular do TA foi registrada por um eletromiógrafo de superfície, desprezando-se os 2 segundos iniciais e finais de cada diagonal. A média dos valores de Root Mean Square (RMS das quatro repetições foi normalizada em porcentagem. Os dados iniciais e finais foram submetidos ao teste em t para amostras pareadas com valores de p significativos OBJECTIVE: To evaluate the response of the tibialis anterior (TA muscle following a five-week protocol with contralateral irradiation force through Proprioceptive Neuromuscular Facilitation (PNF diagonals in patients with demyelinating polyneuropathy associated with Charcot-Marie-Tooth disease type 1A (CMT-1A. METHODS: The study included 12 patients of both sexes. They were treated twice-weekly for 5 weeks. At each session, they performed the following diagonal patterns: chopping, extension-adduction with internal rotation (EAIR and flexion-abduction with internal rotation (FAIR. The diagonals were repeated four times, in both upper and lower limbs, with each repetition lasting six seconds on average. During execution, the response of the TA muscle was recorded by a surface electromyograph disregarding the

  17. Charcot-Marie-Tooth病研究进展

    Institute of Scientific and Technical Information of China (English)

    郭晓强; 王江雁; 时兰春; 王仁杰

    2006-01-01

    Charcot-Marie-Tooth disease(CMT病)是一种进行性神经性肌萎缩综合征,又称遗传性运动和感觉神经性疾病(HMSN)和腓骨肌萎缩症(PMA),CMT病本身并不会危害患者的生命,但却严重影响患者的身体状况,给他们的日常生活带来不便。CMT病的进展比较缓慢,患者的临床表现主要是控制脚/小腿或手,前臂的感觉信息和肌肉萎缩为特征,伴感觉障碍、脊柱及足畸形、植物神经功能紊乱等症状。CMT病是最普遍的遗传性神经疾病之一,至今仍没有有效的治疗方法。但随着研究的深入,人们逐渐对CMT病有了更为全面的认识,在治疗上也开始出现一些新的选择,从而为这种疾病的症状改善和最终的治愈带来了希望。

  18. Pathologic and genetic features in 6 Chinese X-linked Charcot-Marie-Tooth disease type 1 families%X连锁Charcot-Marie-Tooth病1型六个家系的病理和基因突变特点

    Institute of Scientific and Technical Information of China (English)

    栾兴华; 乔晓会; 吕鹤; 王朝霞; 李越星; 袁云

    2012-01-01

    Objectives To report pathological and genetic features of 6 Chinese families with Xlinked Charcot-Marie-Tooth disease type 1 ( CMTX1 ).Methods The index cases from 6 families with CMTX1 are males with onset of disease between 11 and 24 years old.All of them had distal leg muscle weakness,accompanied with areflexia and sensory loss in the feet.Additionally,the index 1 presented with recurrent encephalopathy and the index case 5 with cerebellar ataxia.Peripheral neuropathy was found in 12 family members,while other 7 members showed talipescavus and hyporeflexia.Sural nerve biopsies were performed in all index cases.Connexin 32(Cx32) gene was analyzed in the index cases,8 affected and 10unaffected family members as well as 50 healthy women control subjects.Results Mild to moderate loss of myelinated fiber with axonal degeneration and regeneration clusters were found in all index cases. Thin myelin fibers were found in 5,small onion bulbs in 3 and inflammatory infiltrates in 2.Five novel mutations (I20T,I127F,D178G,A197V,403_404insT) and one L10L synonymous mutation were detected in the 6index cases and their affected family members.The same mutations,in heterozygous state,were detected in 4 female family members without clinical symptoms,but not found in 6 male unaffected family members.The same mutations were not found in healthy control subjects.Conclusions The CMTX1 patients in our study present predominantly axonal lesions.Frequent novel Cx32 gene mutations indicated that private mutations may be common in Chinese CMTX1 patients.%目的 报道6个X连锁Charcot-Marie-Tooth病1型(CMTX1)家系的神经病理和基因型改变特点.方法 6个CMTX1家系的先证者均为男性,发病年龄11 ~24岁,出现下肢远端为主的肌无力、腱反射减低和轻度感觉减退.先证者1伴随发作性白质脑病,先证者5伴随小脑性共济失调.12名家系成员也出现周围神经损害症状,另7名存在高弓足或腱反射减低.对6例先证者行腓

  19. 突变缝隙连接蛋白32在X连锁Charcot-Marie-Tooth病1型患者的外周血管内皮细胞异常表达%Mutant connexin 32 abnormally distributed in the vascular endothelial cells of X-linked Charcot-Marie-Tooth disease type 1 patients

    Institute of Scientific and Technical Information of China (English)

    栾兴华; 洪道俊; 乔晓会; 吕鹤; 王朝霞; 袁云

    2011-01-01

    Objective To investigate expression distribution of mutant connexin 32 (Cx32) protein in human endothelial cells in patients with X-linked Charcot-Marie-Tooth disease type 1 ( CMTX1 ) .Methods Nerve biopsies were performed in 3 patients with CMTX1 and in 3 non-CMTX1 controls. Cx32 mutations of c. 379A > T( I127F), c. 533A > G(D178G) and c. 590C > T(A197V) were identified in these 3 patients respectively. Immunofluorescent (IMF) staining of nerve blood vessel was processed with antibodies against Cx32, Yon Willebrand factor and Cx40. The mutant Cx32 was constructed in pEGFP-N plasmid (pEGFP-N1-Cx32) and was transfected in HeLa cells. Cx32 and GRP78, a marker of endoplasmic reticulum ( ER), were stained by IMF in HeLa cells to investigate expression of mutant Cx32. Results In 3 control cases, Cx32 was visualized by IMF staining as dots along gap junction of vascular endothelial cells,and it was coexisted with Cx40. However, immunoreactivity of Cx32 in 3 patients was predominantly decreased and was not located in endothelial gap junction. The transfection of 3 Cx32 mutants into HeLa cells demonstrated the pathogenic changes. The cells with the mutation c. 379A >T found Cx32 accumulations in the cytoplasm; the cells with mutation c. 533A >G showed few staining positive dots surrounding the nuclear and the cells with c. 590C > T showed dot-like expression of Cx32 both in the cytoplasmicand cell membrane. The mutant Cx32 was not overlapped with expression of the marker of ER.ConclusionsMutant Cx32 might cause dysfunction of endothelial gap-junctions due to the abnormal expression of Cx32 in level and location in the vascular endothelial cells of CMTX1 patients.%目的 观察突变缝隙连接蛋白32( Cx32)在X连锁的Charcot-Marie-Tooth病1型(CMTX1)患者血管内皮细胞的表达规律。方法 对3例经Cx32基因检查证实的CMTX1患者(突变位点分别为c.379A>T、c.533A>G和c.590C>T点突变)进行腓肠神经活体组织检查,同

  20. Clinical research of one family with Charcot-Marie-Tooth disease%一家系人群遗传性神经源性腓骨肌萎缩症的临床研究

    Institute of Scientific and Technical Information of China (English)

    邢军卫; 高颂轶; 刘小红; 谭璐; 张晓莉; 徐曼

    2011-01-01

    目的 探讨婴儿期起病的腓骨肌萎缩症(Charcot-Marie-Tooth disease,CMT)一家系的遗传方式、临床特征、实验室及相关辅助检查、染色体核型及基因诊断等.方法 按照遗传学标准家系分析纲要对患者家族成员作调查,分析临床特征,做详细的体格检查,部分行血常规、血生化、头颅CT、染色体核型检查.绘制家系发病图谱,并进行遗传学分析和基因诊断.结果 先证者谱系代号为Ⅲ7,男性,5岁半.以发现双下肢进行性变细4年半就诊.家系4代41人中患病3人,死亡1例,均为男性,起病年龄为10月至1岁,所有患者均有肌肉萎缩,肢体无力,腱反射减弱或消失,跨阈步态.症状和体征随着年龄增长进行性加重.无明显智力低下.2名CMT患者及5名家系内表型正常者均发现17p11.2-p12区域内包含PMP22基因的重复突变,其亚型为CMT1A.结论 CMT是一种临床表型相似、由不同遗传方式引起的复杂性遗传性疾病,不同的临床表型由不同的基因突变引起;该家系遗传方式为常染色体显性遗传,临床分型为CMT1A;致病基因为17p11.2-p12区域内包含PMP22基因的重复突变.

  1. Neuroelectrophysiological and pathological features of Charcot-Marie-Tooth disease ( report of 2 cases)%腓骨肌萎缩症的神经电生理及病理学特点(附2例报告)

    Institute of Scientific and Technical Information of China (English)

    刘艳; 黄辉; 王超; 赵玉红

    2012-01-01

    目的 探讨腓骨肌萎缩症(CMT)的神经电生理及病理学特点.方法 回顾性分析2例腓骨肌萎缩症患者的神经电生理及病理学资料.结果 本组患者主要表现为慢性进行性双下肢远端肌无力和肌萎缩,弓形足,伴有双上肢受累,腱反射消失,四肢感觉障碍.神经电生理检查显示神经传导速度减慢,神经源性损害;神经活检显示节段性脱髓鞘,部分区域“洋葱球样”改变;电镜显示有髓神经密度中度减少,髓鞘破坏;肌活检显示肌纤维萎缩呈角形.结论 CMT的神经电生理特点为神经源性损害;病理学特点为周围神经节段性脱髓鞘和神经源性肌萎缩.%Objective To explore the features of neuroelectrophysiological and pathological of Charcot-Marie-Tooth disease (CMT). Methods The neuroelectrophysiological and pathological datas of 2 CMT patients were analyzed retrospectively. Results The clinical manifestations of the 2 cases were chronic progressive of lower limbs distal muscle weakness and muscle atrophy, bow foot, and with double upper limbs involved, the tendon reflexes were disappeared and sensory disturbance in limbs. Electrophysiological examination showed nerve conduction velocity decreased and neurogenic damages. Nerve biopsy showed that there were segmental demyelination and "onion ball" structure in some lesion. Electron microscope showed that the density of myelinated nerve fibers was moderate reduced and myelin damage. Muscle biopsy showed the muscle fibers atrophy with angle type. Conclusions The neuroelectrophysiology feature of CMT is neurogenic damages. The pathological features are segmental demyelination of peripheral nerve and neural atrophy.

  2. Identification of A Novel SBF2 Frameshift Mutation in Charcot-Marie-Tooth Disease Type 4B2 Using Whole-exome Sequencing

    Institute of Scientific and Technical Information of China (English)

    Meiyan Chen; Xin Yi; Ming Qi; Jing Wu; Ning Liang; Lihui Tang; Yanhua Chen; Huishuang Chen; Wei Wei; Tianying Wei; Hui Huang

    2014-01-01

    Charcot–Marie–Tooth disease type 4B2 with early-onset glaucoma (CMT4B2, OMIM 604563) is a genetically-heterogeneous childhood-onset neuromuscular disorder. Here, we report the case of a 15-year-old male adolescent with lower extremity weakness, gait abnormalities, foot deformities and early-onset glaucoma. Since clinical diagnosis alone was insufficient for providing pathogenetic evidence to indicate that the condition belonged to a consanguineous family, we applied whole-exome sequencing to samples from the patient, his parents and his younger brother, assuming that the patient’s condition is transmitted in an autosomal recessive pattern. A frame-shift mutation, c.4571delG (P.Gly1524Glufs*42), was revealed in the CMT4B2-related gene SBF2 (also known as MTMR13, MIM 607697), and this mutation was found to be homozygous in the proband and heterozygous in his parents and younger brother. Together with the results of clinical diagnosis, this case was diagnosed as CMT4B2. Our finding further demonstrates the use of whole-exome sequencing in the diagnosis and treatment of rare diseases.

  3. Charcot-Marie-Tooth病的特殊类型

    Institute of Scientific and Technical Information of China (English)

    马永才; 李太伟

    2003-01-01

    @@ Charcot-Marie-Tooth病(CMT)又名腓骨肌萎缩症或遗传性运动、感觉神经病(HMSN)是一组影响周围神经系统临床、亚临床的遗传多型性疾病.以首先出现腓骨肌萎缩,继以远端肌萎缩为特征,伴感觉障碍、脊柱及足畸形、植物神经功能紊乱等.

  4. Learning about Charcot-Marie-Tooth Disease

    Science.gov (United States)

    ... function and balance, occasional lower leg and forearm muscle cramping, loss of some normal reflexes, occasional partial sight and/or hearing loss, and, in some individuals, scoliosis (curvature of the ... to the muscles - lose their protective outer coverings, their myelin sheaths. ...

  5. Clinical and pathological differences in common subtypes of Charcot-Marie-Tooth disease%常见腓骨肌萎缩症亚型的临床和神经病理改变差异分析

    Institute of Scientific and Technical Information of China (English)

    刘菁菁; 吕鹤; 王朝霞; 刘靖; 左越焕; 贺茂林; 袁云

    2016-01-01

    目的 探讨腓骨肌萎缩症(Charcot-Marie-Tooth disease,CMT)常见亚型的临床表现和周围神经病理改变.方法 收集2005-2015年就诊于我院神经内科门诊并经基因检查证实的81例CMT患者,其中CMT1A型31例(38.3%),CMTX1型19例(23.5%),CMT2A2型16例(19.8%),其他9种少见CMT亚型患者合计15例(1.2%~4.9%).比较其中48例3种常见类型患者在平均发病年龄、病程、下肢远端肌力、高弓足出现率之间的差异,同时比较其腓肠神经病理改变的差异.结果 CMT1A型患者的发病年龄为(12.00 ±6.77)岁,CMTX1型(11.81±4.65)岁,CMT2A2型(5.00±2.68)岁(Brown-Forsythe检验,P=0.001).CMT1A型病程为(12.00±6.75)年,CMTX1型为(8.50±4.75)年,CMT2A2型为(5.00±2.73)年(Brown-Forsythe检验,P=0.001).下肢足背伸肌力在CMT1A为Ⅳ(0,Ⅴ)级,CMTX1为Ⅲ+(0,Ⅳ)级,CMT2A2为0(0,Ⅳ)级(H=11.359,P=0.020).高弓足出现在15/23的CMT1A型、10/16的CMTX1型和1/9的CMT2A2型患者(Fisher检验,P=0.017).3例出现脑部症状患者均为CMTX1型.3例伴随有视力下降的患者均为CMT2A2型.腓肠神经有髓神经纤维的洋葱球样结构出现在23/23的CMT1A、5/16的CMTX1和2/9的CMT2A2患者(Fisher检验,P=0.000);再生簇出现在16/23的CMT1A、16/16的CMTX1和9/9的CMT2A2患者(x2=7.666,P=0.016).上述指标在3组间差异均具有统计学意义.结论 CMT1A型、CMTX1型和CMT2A2型是本组患者最常见的CMT亚型,关注发病年龄、病程、肌力下降程度、高弓足出现率、脑部以及视神经损害的出现有助于三者的临床区分,注意有髓神经纤维洋葱球样结构和再生簇出现程度也有助于其病理分型.%Objective To analyze the differences of the clinical and neuropathological features among the common Charcot-Marie-Tooth disease (CMT) subtypes.Methods There were 81 CMT patients confirmed by genetic testing from 2005 to 2015 in Department of Neurology,Peking University First Hospital,including 31 cases of CMT1A (38.3%),19

  6. The same mutation Glu208Lys in the GJB1 gene was detected in 2 families with X-linked Charcot-Marie-Tooth Disease%在两个X连锁显性腓骨肌萎缩症家系中发现同一GJB1基因突变Glu208Lys

    Institute of Scientific and Technical Information of China (English)

    宋书娟; 闫明; 王小竹; 章远志; 邹俊华; 钟南

    2007-01-01

    在两个X连锁显性腓骨肌萎缩症(Charcot-Marie-Tooth disease,CMT)家系中进行了GJB1基因的突变分析.提取基因组DNA,PCR(polymerase chain reaction)反应扩增GJBl基因编码序列,进行单链构象多态性(singlestrand conformational polymorphism,SSCP)分析,对有差异SSCP带型的PCR产物进行测序,结果在两家系中发现同一GJBl基因c.622G→A(GIu208Lys)突变.所发现的突变位点在国内尚未报道.

  7. 小热休克蛋白22基因在腓骨肌萎缩症中的突变分析%Mutation analysis of small heat-shock protein 22 gene in Chinese patients with Charcot-Marie-Tooth disease

    Institute of Scientific and Technical Information of China (English)

    张付峰; 胡正茂; 严新翔; 张如旭; 郭鹏; 唐北沙; 赵国华; 陈彪; 张成; 罗巍; 刘小民; 夏昆; 蔡芳

    2005-01-01

    Objective To study the characteristics of the mutation of small heat-shock protein 22 (HSP22) gene in Chinese patients with Charcot-Marie-Tooth (CMT)disease. Methods A CMT2L proband with 423(G→T) mutation in HSP22 gene had been studied and reported by the present authors. In this study, mutation analysis of HSP22 gene was performed using polymerase chain reaction and DNA direct sequencing in 114 CMT probands. Results In the 114 CMT probands, a 582(C→T)(T194T) samesense mutation was found in two unrelated families. Conclusion The rate of HSP22 gene mutation in Chinese patients with CMT is as low as 0.87%(1/115).%目的探讨小热休克蛋白22(small heat-shock protein 22, HSP22)基因在中国人腓骨肌萎缩症(Charcot-Marie-Tooth disease,CMT)中的突变特点.方法应用聚合酶链反应和DNA直接测序方法,对1个发现HSP22基因423(G→T)突变的CMT2L家系外的114个CMT家系先证者进行了HSP22基因的突变分析.结果114个先证者中有2例患者在 HSP22基因的第3外显子发生了582(C→T)碱基改变,由于编码的氨基酸未改变,均为色氨酸(Thr),为一种同义突变.结论HSP22基因突变在中国人的腓骨肌萎缩症患者中少见,突变率为0.87%(1/115).

  8. 周围髓鞘蛋白22基因重复异常的Charcot-Marie-Tooth病患者临床表型分析%Clinical Phenotype of Peripheral Myelin Protein 22 Gene Duplication Abnormality in Charcot-Marie-Tooth Disease

    Institute of Scientific and Technical Information of China (English)

    叶静; 翟红珍; 廖张原; 李存江

    2009-01-01

    目的 分析Charcot-Marie-Tooth病(CMT)周嗣髓鞘蛋白22(PMP22)基因重复异常患者临床症状、体征和电生理特点.方法 61例CMT患者,14例为有家族史的先证者,47例为散发患者,PCR-双酶切方法检测周围髓鞘蛋白22(PMP22)基因重复异常片断,详细问病史和神经系统查体、部分患者行腰穿和腓肠神经病理检查.结果 检出PMP22基因重复异常患者41例,主要临床特点为以双足背屈力弱为主的双下肢无力,伴双侧小腿为主的四肢远端萎缩,80%伴上肢远端肌萎缩,97%踝反射减弱或消失,68%伴有深浅感觉障碍,少数脑脊液蛋白增高,神经电生理和腓肠神经病理提示为脱髓鞘伴有轴索变性.结论 PMP22基因重复异常的CMT患者的临床表现为以下肢远端肌萎缩和肌无力为主,伴有感觉异常;周围神经髓鞘和轴索均有病变.

  9. Tripod pinch strength and thumb opposition are the major determinants of manual dexterity in CharcoteMarieeTooth disease type 1A

    NARCIS (Netherlands)

    Videler, Annemieke J.; Beelen, Anita; van Schaik, Ivo N.; Verhamme, Camiel; van den Berg, Leonard H.; de Visser, Marianne; Nollet, Frans

    2010-01-01

    Background Clinical features of Charcot-Marie-Tooth disease type 1A (CMT1A) include slowly progressive distal muscle weakness, atrophy and sensory loss. Upper-limb involvement results in reduced manual dexterity interfering with the execution of daily activities. Objective To identify which hand fun

  10. 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.

  11. @@%Charcot-Marie-Tooth病一家族分析

    Institute of Scientific and Technical Information of China (English)

    孙明周

    2014-01-01

    目的 通过对1家族Charcot-Marie-Tooth病(cMT)系谱分析,探讨其遗传特点、临床表现及预后,为遗传咨询提供依据.方法 分析家族中患者的性别分布规律,临床表现特点进行分析.结果 家族中男女均可发病,男性患病率明显高于女性.男性患者症状典型,典型症状表现为慢性进展性四肢远端肌肉无力和消瘦肌萎缩呈典型的“鹤腿”,双足骨骼畸形呈“弓形足”;家族中女性患者少见,除Ⅱ8症状表现典型外,其余女性无受累;感觉主诉不显著,无中枢神经受累表现.结论 本例家族CMT呈常染色体显性遗传,男性受累多且症状典型,女性受累少.由于患者症状特征显著,遗传模式明确,预后良好,对于遗传咨询具有指导意义.

  12. 缝隙连接蛋白B1基因I20T新突变导致伴有短暂性脑白质损害的X连锁Charcot-Marie-Tooth病1型%Transient white matter lesions in X-linked Charcot-Marie-Tooth disease type 1 with novel I20T mutation of gap junction protein beta 1 gene

    Institute of Scientific and Technical Information of China (English)

    栾兴华; 陈彬; 郑日亮; 张巍; 王朝霞; 袁云

    2009-01-01

    目的 报道1个伴有短暂性脑白质损害的X连锁Charcot-Marie-Tooth病1型(CMT1x)家系的临床、影像学和基因改变特点.方法 先证者为14岁男孩,出现短暂发作性言语不能和轻度肢体麻木无力2年5个月.其母亲存在弓形足.对先证者进行头颅MRI、神经电生理检查和腓肠神经活体组织检查;对先证者及其父母,50名女性无周围神经病及脑病对照者进行缝隙连接蛋白B1(GJB1)基因检测.结果 先证者周围神经的运动神经动作电位波幅显著下降,传导速度轻度减慢.听觉和体感诱发电位潜伏期明显延长.MRI显示胼胝体和大脑后部白质对称性异常信号,6个月后病变显著减轻.病理检查提示慢性轴索性周围神经病,电镜检查还可见有髓神经纤维的髓鞘施兰切迹加宽.先证者及其母亲GJB1基因存在I20T突变,其父和50名女性对照者无此突变.结论 伴短暂性脑白质损害的CMT1X可能与GJB1基因I20T新突变有关,其大脑白质的MR1改变具有可逆性.%Objective To describe the clinical, radiological and genetic features in a family with X-linked Charot-Marie-Tooth disease type 1 (CMT1X) with transient white matter lesions.Methods The proband is a 14-year-old boy who presented transient and recurrent dysarthria, mild numbness and weakness of the limbs for 2 years and 5 months.Later he developed leg weakness.His mother only presented pes cavus.MRI, electrophysiology and nerve biopsy were performed in the proband.Gap junction protein beta 1 (GJB1) gene was analyzed by PCR-sequencing on the proband, his parents and 50 non-illness control women.Results Electremyography showed marked reduced amplitude of the distal compound muscle action potentials and mild decrease of conduction velocities.MRI showed bilateral white matter lesions in centrum semiovale and corpus callnsum, which improved significantly after 6 months.Pathological examination revealed chronic axonal neuropathy and widened Schmidt

  13. Mutation analysis of small heat-shock protein 27 gene in Chinese patients with Charcot-Marie-Tooth disease%中国人腓骨肌萎缩症小热休克蛋白27基因突变分析

    Institute of Scientific and Technical Information of China (English)

    刘小民; 唐北沙; 赵国华; 夏昆; 张付峰; 潘乾; 蔡芳; 胡正茂; 张成; 陈彪; 沈璐; 张如旭; 江泓

    2005-01-01

    目的探讨中国人腓骨肌萎缩症(Charcot-Marie-Tooth disease, CMT)小热休克蛋白27基因(small heat-shock protein 27, HSP27)的突变特点.方法应用聚合酶链反应结合DNA序列分析方法,对114个CMT家系的先证者进行 HSP27基因突变研究,并进一步对基因突变家系进行单体型分析.结果在4个常染色体显性遗传CMT2家系中发现一个 HSP27基因错义突变C379T,单体型分析提示这4个家系很可能具有共同祖先.结论中国人CMT患者存在 HSP27基因突变,但突变率较低(0.90%). HSP27基因C397T突变除引起远端型遗传性运动神经病外尚可导致CMT2,进一步证实同一CMT疾病基因的同一突变可引起不同的表现型.

  14. Mutation analysis for a family affected with Charcot-Marie-Tooth disease type 4C%一个腓骨肌萎缩症4C型家系的SH3TC2基因突变分析

    Institute of Scientific and Technical Information of China (English)

    于珍; 张嘉莹; 许烨; 杨博宇; 何志宏; 张慕晨; 沈薇; 顾鸣敏

    2016-01-01

    目的 明确1个腓骨肌萎缩症(Charcot-Marie-Tooth disease,CMT)家系的分子遗传发病机制.方法 抽提家系成员外周血基因组DNA;应用目标外显子捕获及二代测序技术对先证者的72个候选基因进行基因突变筛查,并对可疑基因进行Sanger测序验证;用PyMOL-1软件对突变基因的蛋白质结构进行分子模拟.结果 先证者SH3TC2基因第11外显子中检出c.1894G>A纯合错义突变(p.E632K);先证者父母及女儿均为c.1894G>A杂合突变携带者,其他家系成员及300名正常对照者中均未检测到该突变.经检索NCBI、HGMD、1000 genome等数据库,c.1894G>A突变为未报道过的新突变.分子模拟显示该基因突变改变了SH3TC2蛋白的三维构象.结论 SH3TC2基因突变可能与该CMT4C型家系先证者的发病有关.新发现的c.1894G>A突变(p.E632K)扩展了SH3TC2基因的突变谱.%Objective To identify potential mutation in a Chinese family affected with Charcot-Marie-Tooth disease(CMT).Methods Clinical data of the family was collected,and genomic DNA was extracted from peripheral blood samples of the family members.Seventy-two candidate genes of the proband were captured and sequenced by targeted next-generation sequencing,and the results were confirmed by Sanger sequencing.The protein structure was predicted with PyMOL-1 software.Results A homozygous missense mutation c.1894G>A(p.E632K) was identified in the exon 11 of the SH3TC2 gene in the proband.Heterozygous c.1894G>A mutation was also detected in the proband's father,mother and daughter,but not in the healthy family members and 300 normal controls.Retrieval of the NCBI,HGMD and 1000 genome databases has verified the c.1894G> A to be as a novel mutation.Computer simulation has suggested that the mutation has altered the 3D structure of the SH3TC2 protein.Conclusion The proband was diagnosed as CMT4C,for which the underlying gene was SH3TC2.This finding has expanded the spectrum of SH3TC2 mutation

  15. The effect of HSPB8 gene mutation on cell viability in Charcot-Marie-Tooth disease type 2L%腓骨肌萎缩症2L热休克蛋白B8过表达对细胞相对活力的影响

    Institute of Scientific and Technical Information of China (English)

    李书剑; 唐北沙; 赵国华; 张如旭; 夏昆; 潘乾

    2011-01-01

    Objective To study the effect of Charcot-Marie-Tooth 2L disease causing gene K141N mutation in heat shock protein B8 gene (HSPB8)on cell viability.Methods By using liposome transfection technique,wt HSPB8,K141N HSPB8 eukaryotic expression vector and green fluorescent protein (GFP) vector were transfected into SHSY-5Y cell,respectively.Twenty-four hours later,the cells were treated with 44℃ lethal heat shock for 40 minutes.The relative viability of SHSY-5Y cells in each group was tested by using tetrazole blue colorimetric method (methyl thiazolyl tetrazolium,MTT).Results There were significant differences among the light absorption value of GFP,pEGFP-wt HSPB8 and pEGFP-K141N HSPB8 transfected groups after heat shock (P < 0.05 ),indicating that the relative viability of cells overexpressed with wt HSPB8 and K141N HSPB8 was different from that of control cells.The viability of cells overexpressing wt HSPB8 was highest,followed by cells overexpressed with K141N HSPB8.The viability of cells tranfected with GFP only was the lowest.Conclusion HSPB8 may play an important role in the protection of cells under lethal heat shock treatment,and the K141N mutation can impair the protective effect.%目的 探讨轴索型腓骨肌萎缩症2L(axonal Charcot-Marie-Tooth disease type 2L,CMT2L)K141N突变的热休克蛋白B8(heat shock protein B8,HSPB8)对细胞相对活力的影响.方法 应用脂质体转染技术,将野生型HSPB8(wt HSPB8)和K141N突变型HSPB8( K141N HSPB8)分别转染SHSY-5Y细胞,使其过量表达上述蛋白,以表达绿色荧光蛋白(green fluorescent protein,GFP)为阴性对照,转染24 h后用44℃致死性热休克处理40 min,用四甲基偶氮唑蓝(methyl thiazolyl tetrazolium,MTT)比色法检测SHSY-5Y细胞的相对活力.结果 未处理组pEGFP-wt HSPB8与pEGFP-K141N HSPB8组间吸光度值比较P>0.05,而热休克处理组pEGFP-wt HSPB8与pEGFP-K141N HSPB8组间吸光度值比较P<0.05,表明热休克处理后各组细胞相对活力

  16. 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

  17. LITAF、RAB7、LMNA和MTMR2基因在中国人腓骨肌萎缩症患者的突变分析%Mutation analysis of LITAF,RAB7,LMNA and MTMR2 genes in Chinese Charcot-Marie-Tooth disease

    Institute of Scientific and Technical Information of China (English)

    张如旭; 唐北沙; 郭鹏; 任志军; 赵国华; 刘三妹; 刘婷; 资晓宏; 胡正茂; 夏昆

    2010-01-01

    为了分析LITAF、RAB7、LMNA和MTMR2基因在中国人腓骨肌萎缩症(Charcot-Marie-Tooth disease,CMT)的突变特点,文章分别应用PCR结合DNA序列分析方法和PCR-单链构象多态性(PCR-SSCP)结合DNA序列分析方法对6个常染色体显性遗传家系先证者和27个散发病例进行LITAF和RAB7基因突变分析;应用PCR-SSCP结合DNA序列分析方法对14个常染色体遗传的CMT家系先证者和27个散发患者进行LMNA和MTMR2基因突变分析.结果发现:LITAF基因c.269G→A、c.274A→G序列变异和LMNA基因c.1243G→A、c.1910C→T序列变异.未发现RAB7和MTMR2基因的序列变异.其中LITAF基因c.269G→A,LMNA基因c.1243G→A和c.1910C→T为新发现的单核苷酸多态;LITAF基因c.274A→G为已知多态.说明LITAF、RAB7、LMNA和MTMR2基因突变在中国人CMT患者中罕见.

  18. 伴有脑干听觉诱发电位异常的腓骨肌萎缩症发现连接蛋白32基因新突变%A new mutation in the connexin 32 gene of a Chinese family with Charcot-Marie-Tooth disease associated with central conduction slowing

    Institute of Scientific and Technical Information of China (English)

    罗巍; 唐北沙; 赵国华; 夏昆; 羊毅; 萧剑锋; 严新翔; 杨期东; 夏家辉

    2002-01-01

    目的报告一个脑干听觉诱发电位有异常改变的腓骨肌萎缩症(Charcot-Marie-Tooth disease,CMT)家系,并探讨与连接蛋白32(connexin 32,Cx32)基因突变的关系.方法对整个家系进行临床检查,对先证者进行肌电图及脑干听觉诱发电位检查,并应用聚合酶链式反应-单链构象多态(polymerase chain reaction-single strand conformation polymorphism, PCR-SSCP)技术结合DNA序列分析方法检测了先证者、家系内8人及家系外50名无血缘关系的正常人. 结果先证者肌电图检查示神经传导速度明显减慢,脑干听觉诱发电位示中枢传导延长,该家系中先证者及另3人均出现异常SSCP条带,经测序证实为392T→C(Leu131Pro)突变. 结论 Leu131Pro是未报道过的突变,腓骨肌萎缩症患者可以出现脑干听觉诱发电位异常.

  19. Analysis of the clinical, electrophysiological and histopathological features of Chinese Charcot-Marie Tooth disease patients with small heat-shock protein 27 gene mutation%小热休克蛋白27基因突变所致腓骨肌萎缩症患者的临床、电生理和病理特点

    Institute of Scientific and Technical Information of China (English)

    刘小民; 唐北沙; 赵国华; 夏昆; 张付峰; 严新翔; 肖岚

    2005-01-01

    目的探讨小热休克蛋白27基因(small heat-shock protein 27,Hsp27)突变所致腓骨肌萎缩症(Charcot-Marie-Tooth disease,CMT)患者的临床、电生理和病理特点.方法对发现Hsp27基因同一突变(C379T)的4个常染色体显性遗传CMT2家系的7例患者的临床表现、电生理和病理检查进行回顾性分析.结果患者主要临床特点为35~60岁发病,平均病程(17.6±6.6)年,发病后平均(12.6±4.9)年需要扶拐杖行走,平均(20.7±5.7)年完全丧失行走能力;患者感觉障碍轻,神经电生理示下肢神经传导速度呈中至重度减慢,但上肢正常或轻度减慢,神经活检证实为慢性轴突性神经病,肌肉活检显示神经原性肌萎缩.结论Hsp27基因C397T突变可引起CMT2表现型,突变家系的临床表现与文献报道的该基因突变CMT2F家系有所不同.

  20. A new mutation in the GJB1 gene of a Chinese family with Charcot-Marie-Tooth disease associated with vocal cord paresis%伴声带麻痹的X连锁腓骨肌萎缩症GJB1基因新突变

    Institute of Scientific and Technical Information of China (English)

    李清华; 蒋静子; 刘开祥; 俸军林; 曾爱源; 李浩; 吴岚; 唐永刚; 陈梅玲; 林小慧

    2010-01-01

    Objective To report an X-linked dominant Charcot-Marie-Tooth disease (CMTX) Chinese family with vocal cord paresis and to identify the mutation of gap junction protein beta 1 gene (GJB1). Methods Part of the family members with dysphagia, dysphonia and lethal respiratory failure were studied through flexible laryngoscope, clinical, brain MRI and electrophysiological examinations. After excluding large fragment tandem duplication containing peripheral myelin protein 22 gene (PMP22), direct sequencing was performed to analyze the mutation of the GJB1 gene in 5 patients including the proband, 5 unaffected family members and 50 unrelated healthy individuals. Results Eight members spanning 3 generations in this family were affected with CMTX characterized by progressive atrophy and weakness of the anterior tibial and peroneal muscles, especially in the proband. Vocal cord paresis was observed through flexible laryngoscope in total of 4 affected members with dysarthria and dysphagia, 2 of them died of severe respiratory failure due to complete bilateral vocal cord involvement. Normal brain MRI was observed in the proband. The electrophysiological data showed predominant demyelization involving the motor and sensory nerves in the proband. DNA sequencing revealed a de novo c. 186 C>G missense mutation in exon 2 of the GJB1 gene, the mutation cosegregated with phenotype. Conclusion Respiratory failure associated with vocal cord involvement may be a rare and severe symptom in CMTX. The present report provides further evidence for clinical and genetic heterogeneity in the X-linked Charcot-Marie-Tooth disease.%目的 报告1个临床可疑的伴声带麻痹的X连锁显性遗传腓骨肌萎缩症(X-1inked Charcot-Marie-Tooth disease,CMTX)家系,并探讨与连接蛋白(gap jurction protein beta 1,GJB1)基因突变的关系.方法 对1个具有声音嘶哑、吞咽困难、致死性呼吸衰竭的临床可疑的CMTX家系进行临床、纤维喉镜、头部MRI及电生理检

  1. Charcot-Marine-Tooth CMT-2 Polyneuropathy Syndrome A Case Study.

    Directory of Open Access Journals (Sweden)

    Arbind Kumar Choudhary

    2015-06-01

    Full Text Available Abstract Charcot-Marie-Tooth disease CMT refers to the inherited peripheral neuropathies affect approximately one in 2500 people they are among the most common inherited neurological disorders. The majority of CMT patients have autosomal dominant inheritance although X-linked dominant and autosomal recessive forms also exist. The majority of cases are demyelinating although up to one third appear to be primary axonal or neuronal disorders. A patient of 9-year-old girl visited our hospital because of began to suffer from an insidious onset of progressive distal weakness and numbness and muscle twitching in both in her upper and lower limbs. Nerve conduction studies showed sensory nerve conduction SNCV of bilateral median and ulnar nerve was reduced in upper limb and bilateral sural nerve was reduced in lower limb While in case of motor nerve conduction MNCV bilateral median and ulnar nerve was reduced in upper limb and common peroneal nerve CPN as well as posterior tibial nerve was decreased leg. F response latencies were markedly prolonged in patient. Family history along with electrophysiological studied showed It was typical case of autosomal dominant CMT 2 axonal neuropathy. CMT is currently an untreatable disorder and at the moment the treatment of CMT is only supportive as there are no drugs available that would halt the disease symptoms. The care of a CMT patient is challenging for the health care team.

  2. Clinical features and gene mutations of patients with Charcot-Marie-Tooth disease type 1 and type 2%腓骨肌萎缩症1型和2型的临床与基因突变特点

    Institute of Scientific and Technical Information of China (English)

    郭鹏; 张保刚; 王相斌; 宋福聪; 冯文霞; 唐北沙; 夏昆

    2011-01-01

    Objective To investigate the clinical and genetic mutation characteristics of patients with Charcot-Marie-Tooth disease type 1 and type 2. Methods The clinical manifestations, electrophysiological and pathological characteristics were retrospectively analyzed in patients with Charcot-Marie-Tooth ( CMT) disease type 1 and type 2 and 91 CMT pedigrees,and the PMP22 large fragment duplication mutation and the gene mutation of PMP22,MPZ.SIMPLE,EGR2, RAB7, NEFL, MFN2, Hsp27, Hsp22 were analyzed. Results The age of onset in patients with CMT 1 was earlier, and most frequently first symptoms were weakness and atrophy in distal end of lower limbs with hypesthesia, and neurogenic examination showed obvious atrophy in leg muscle with weakness or vanishing of reflection of knee and ankle,and there was talipes cavus in all the patients. Neuro-electrophysiological examination showed that nerve conduction velocity was decreased. Pathological examination showed the pathological changes of demyelination, and gene mutation analysis showed large fragment duplication mutation and the MPZ gene mutation,in contrast to that,the incidence of CMT1 was lower,the age of onset was later,and the pathological changes of locomotor system were more obvious than those in sensing system, nerve conductive velocity was within normal range, pathological changes presented axonal degeneration, and gene mutation analysis showed gene mutation in MFN2, Hsp27and Hsp22. Conclusion The clinical manifestations of CMTlare different from those of CMT2,and the analysis results for gene mutation are coincident with clinical characteristics,with high accuracy, little injury,earlier diagmosis, which is worth being applied generally in clinic, especially for the patients with family history or their relatives with high risk factors.%目的 探讨腓骨肌萎缩症(CMT)1型和2型患者的临床与基因突变的特点.方法 对临床诊断为CMT1型和CMT2型91个家系先证者的临床表现、电生理和病理

  3. Clinical features and gene mutations of Chinese patients with autosomal dominant Charcot-Marie-Tooth disease%常染色体显性遗传腓骨肌萎缩症的临床与基因突变特点

    Institute of Scientific and Technical Information of China (English)

    郭鹏; 宋福聪; 王相斌; 冯文霞; 胡志强; 唐北沙; 夏昆

    2011-01-01

    Objective To analyze the characteristics of the clinical features and the gene mutations between Chinese patients with autosomal dominant Charcot-Marie-Tooth disease. Methods The clinical manifestations, electrophysiological and pathological investigations of patients with autosomal dominant Charcot-Marie-Tooth were analyzed retrospectively. One hundred and six CMT patients underwent mutation analysis of PMP22 duplication and PMP22, MPZ, SIMPLE, EGR2, RAB7,NEFL,MFN2,Hsp27 and Hsp22. Results CMT1A was caused by PMP22 duplication,and CMT1B was caused by MPZ mutation. In those patients,the age of onset were earlier. The most frequently first symptom was weakness and atrophy in lower limbs with hypesthesia. Physical examination showed distal limb weakness and wasting,and taplipes cavus in all of them. Electromyogram and nerve conduction velocity showed slow nerve conduction. Pathological examination showed demye-lination. CMT2A2 was caused by MFN2 mutation,CMT2F wag caused by Hsp27 mutation,and CMT2L was caused by Hsp22 mutation. Compared with CMT1 ,patients of CMT2 were less frequent,the age of onset were later,motor disability was more sever than sensory disability. Electromyogram and nerve conduction velocity was normal. Pathological examination showed axonal denaturation. Conclusions In this study, the results of the mutation screening were consistent with the clinical features. Mutation screening has the character of high accuracy,little harm and can help to diagnosis earlier,so it suggestes to be performed widely in the clinic especially to the patients who has family history or to the lineal relatives.%目的:探讨常染色体显性遗传腓骨肌萎缩症(CMT)患者的临床与基因突变的特点。方法:对43个常染色体显性遗传CMT家系共106例患者的临床表现、电生理和病理特点进行回顾性分析,并进行PMP22的大片段重复突变和PMP22、MPZ、SIMPLE、EGR2、RAB7、NEFL、MFN2、Hsp27及Hsp22

  4. 基因重复的进行性腓骨肌萎缩症1A型临床与电生理研究%Clinical and electrophysiological study on charcot-Marie-Tooth disease type 1A with gene duplication.

    Institute of Scientific and Technical Information of China (English)

    笪宇威; 沈定国; 苏凤霞; 刘淑贤

    2001-01-01

    Objective  To study the clinical and electrophysiological features in Charcot-Marie-Tooth disease type 1A with gene duplication.Methods Clinical symptoms and signs were summarized in 22 patients from 21 unrelated families. Electromyography (EMG) as well as motor conduction velocities (MCV) and sensory conduction velocities (SCV) examinations were performed in all patients. Results Evidence of CMT was initially detected within the second decade in 18 patients. Nearly half of patients were sporadic cases. The typical clinical manifestations of CMT1A were weakness and atrophy in the distal limbs, weakness or absence of the tendon reflexes, talipes equinovarus and postural tremor the upper limb. Additionally, some special symptoms and signs were also observed occasionally, including brisk tendon reflexes, extensor plantar responses, scoliosis, foot ulcers and nystagmus. EMG revealed that 77.3% of the patients had fibrillation and positive sharp potentials. 81.8% of them had prolonged motor unit potential limit. Median MCV showed there was no significant difference between CMT1A patients and CMT1 patients without duplication (t=1.63, P>0.05). Values of SCV and MCV for the lower limbs were not obtained in 20 patients and more than 2/3 of the patients respectively. Conclusions The clinical features of CMT1A included high frequent of sporadic cases, early onset in the second decade and various manifestations. The electrophysiological features were that the damages of nerves for the lower limbs were more severer than those in the upper limbs and the damages of the sensory nerves were more severer than those of the motor nerves. The phenotype was variable although the genotype was the same in CMT1A patients with PMP22 duplication.%目的研究有基因重复的进行性腓骨肌萎缩症1A型(Charcot-Marie-Tooth病1A,CMT1A)临床与电生理特点。方法对来自21个家系的22名CMT1A病人临床特点进行总结,同时分析其电

  5. Auditory Function in Children with Charcot-Marie-Tooth Disease

    Science.gov (United States)

    Rance, Gary; Ryan, Monique M.; Bayliss, Kristen; Gill, Kathryn; O'Sullivan, Caitlin; Whitechurch, Marny

    2012-01-01

    The peripheral manifestations of the inherited neuropathies are increasingly well characterized, but their effects upon cranial nerve function are not well understood. Hearing loss is recognized in a minority of children with this condition, but has not previously been systemically studied. A clear understanding of the prevalence and degree of…

  6. Causes of Charcot-Marie-Tooth Disease (CMT)

    Science.gov (United States)

    ... axons , extend from sensory nerve cells in the body's periphery back toward the spinal cord, and from muscle-controlling nerve cells in the spinal cord out toward the muscles. Axons transmit electrical signals for sensation and movement to and from the ...

  7. Genetics Home Reference: Charcot-Marie-Tooth disease

    Science.gov (United States)

    ... SBF2 (CMT4B2), SH3TC2 (CMT4C), NDRG1 (CMT4D), EGR2 (CMT4E), PRX (CMT4F), FGD4 (CMT4H), and FIG4 (CMT4J). Intermediate forms ... MED25 MFN2 MPZ MTMR2 NDRG1 NEFL PMP22 PRPS1 PRX RAB7A SBF2 SH3TC2 TRPV4 YARS Related Information What ...

  8. 周围髓鞘蛋白22基因重复突变致夏科-马里-图斯病1A亚型的临床变异性%Clinical variability of Charcot-Marie-Tooth disease type 1A patients with PMP22 duplication mutation

    Institute of Scientific and Technical Information of China (English)

    段晓慧; 顾卫红; 王国相; 郝莹; 王康; 汪仁斌; 孙少杰; 杨斯柳

    2010-01-01

    目的 探讨夏科-马里-图斯病(CMT)患者周围髓鞘蛋白22(PMP22)基因重复突变特征及临床变异性.方法 联合应用改良的等位基因特异性PCR-双酶切和基于荧光标记毛细管电泳短串联重复序列(STR)分析对45例临床拟诊CMT患者进行PMP22基因重复突变的检测,详细分析其中阳性病例的临床特征.结果 在45例拟诊CMT患者中共检测出PMP22基因重复病例21例,包括10例临床特征符合四肢远端萎缩无力的典型CMT1型患者和11例不典型的CMT患者,后者具有特殊表型:1例仅以轻度头晕就诊;1例合并听力障碍;2例以反复发作性肢体无力起病;2例伴有上肢姿势性震颤;4例伴有小脑性共济失调;1例伴有癫(癎)发作.结论 PMP22基因重复突变为CMT病最常见的病因,改良的等位基因特异性PCR-双酶切提供了一种准确、可靠并易于操作的检测方法,有助于该病的诊断和鉴别.同时,通过综合分析PMP22重复突变阳性的CMT1A患者临床表现、电生理及病理特征,提示该组疾病具有高度的临床变异性.%Objective To investigate the characteristics of PMP22 duplication mutation and the clinical variability of Charcot-Marie-Tooth disease type 1A (CMT1A) patients. Methods PMP22 duplication mutation analysis were performed in 45 cases diagnosed probably CMT by combination of improved allele-specific PCR-restriction enzyme digestion and short tandem repeat (STR) analysis based on laser-induced fluorescence detection in capillary electrophoresis. The clinical features of the positive cases were precisely analyzed. Results With the combined use of two methods, PMP22 duplication was detected in 21 cases, i.e. 10 CMT1 cases with typical presentations including weakness and atrophy in the distal limbs, and 11 atypical cases with special phenotypes including 1 case with mild dizziness, 1 case with hearing loss, 2 cases with recurrent limbs weakness, 2 cases with postural tremor in the upper limbs, 4

  9. The comparative study on electrophysiological changes in patients with hereditary neuropathy with liability to pressure palsy and patients with Charcot-Marie-Tooth 1 A type disease%CMT1A型与遗传性压迫易感性周围神经病的神经电生理对比研究

    Institute of Scientific and Technical Information of China (English)

    宋春莉; 王哲; 刘丽波; 周丽娜; 唐攀; 梁战华; 韩杰; 孙大勇

    2013-01-01

    目的 探讨腓骨肌萎缩症1A型(CMT1A)与遗传性压力易感性神经病(HNPP)在神经电生理检测的不同特点.方法 记录9例CMT1A型和12例HNPP患者的临床特点,对两组患者进行了正中神经、尺神经、胫神经、腓总神经运动神经传导速度检测和正中神经、尺神经、胫神经、腓浅神经、腓肠神经感觉神经传导速度检测.结果 CMT1A型患者存在广泛的电生理异常,四肢周围神经NCV都明显减慢或消失,而且感觉和运动减慢程度一致,并且对任何节段周围神经的影响程度相同;HNPP患者的电生理特点是广泛的SCV不同程度减慢,而MCV减慢相对较轻且不同节段程度不同,主要是末端潜伏期值延长,以及明显的运动神经易卡压部位传导阻滞.结论 神经电生理检测是该两种疾病诊断及鉴别诊断的重要手段,短节段电位检测可证实HNPP的嵌压部位.%Objective To investigate different feature of electrophysiology in patients with hereditary neuropathy with liability to pressure palsy ( HNPP) and patients with Charcot-Marie-Tooth disease. Methods Record clinical features from 9 patients of CMT1A and 12 patients of HNPP,compare two groups of patients with motor nerve conduction velocity testing in median nerve,ulnar nerve,tibial nerve,peroneal nerve,as well as the sensory nerve conduction velocity in median nerve,ulnar nerve,tibial nerve,superficial peroneal nerve and sural nerve. Result Limb peripheral nerve NCV of CMT1A type patients are slowed down or disappeared, degree in SCV and MCV also decreased, suggest a wide range of electrophysiological abnormalities impacting on every segment. HNPP patients display extensive SCV decreases with different degree. At the same time MCV slow down relatively mild and vary different degrees in different segments, distal latency values display prolonged as well as motor nerve conduction block in easily entrapment site. Conclusion Nerve electrophysiological testing is

  10. 腓骨肌萎缩症(CMT)1型的临床、神经电生理及CMT1A型基因诊断方法的研究%Study on the clinic, neuro-electrophysiology of Charcot-Marie-Tooth disease type 1 and the gene diagnosis methods of CMT1 A

    Institute of Scientific and Technical Information of China (English)

    史磊; 曹秉振

    2013-01-01

    目的 观察腓骨肌萎缩症(CMT)1型患者的临床表现及神经电生理特点,同时利用两种不同方法检测CMT1A型相关基因是否存在突变,并分析两种方法的临床应用价值以进一步确定CMT1A型的诊断.方法 对临床确诊为CMT1型的5例患者进行详细的临床及神经电生理检查,同时对所有患者利用等位基因特异性PCR及MLPA两种方法进行PMP22基因重复突变检测.结果 4例患者20岁前发病,其中2例有家族史,1例患者30岁左右发病.临床特点为进行性四肢远端无力伴肌萎缩,四肢远端感觉减退,腱反射均减弱或消失,2例患者出现弓型足.神经电生理检查示神经传导速度减慢,波幅轻度降低.两种基因检测均发现1例患者存在PMP22基因重复突变.结论 CMT1型发病年龄较早,主要表现为进行性四肢无力伴肌萎缩,神经电生理可见神经传导速度明显降低,波幅略有降低.等位基因特异性PCR和MLPA两种方法检测基因突变结果一致.%Objective To study the clinical and neuro-electrophysiological features of Charcot-Marie-Tooth type 1. Two methods were combined to detect mutations in CMT 1A - related genes and comparison of the two methods was performed to determine the clinical value for further diagnosis of CMT1 A. Methods 5 cases of patients with CMT1 underwent detailed clinical and neuro-electrophysiology examinations. Allele-specific PCR and multiplex ligation-dependent probe amplification type CMT1 ( MLPA-CMT1) were respectively used to detect PMP22 gene duplication mutation in 5 cases. Results Two cases has a family history. age at onset was in the first or second decade except one patient. The clinical features were slowly progressive distalmuscle weakness , atrophy and end - brush form sensory decrement, diminshed or absent tendon reflexes. There are foot deformity in 2 patients. EMG showed conduction velocities highly decreased and volatility decreased slightly. One patient was detected

  11. Clinical and electrophysiological characteristics of Charcot-Marie-Tooth disease type 1A patients with PMP22 duplication mutation%周围髓鞘蛋白22基因重复突变致夏科-马里-图斯病1A亚型的临床和神经电生理特征

    Institute of Scientific and Technical Information of China (English)

    汪仁斌; 严莉; 段晓慧; 毛坤; 孙少杰; 董明睿; 焦劲松; 王国相

    2012-01-01

    目的 探讨周围髓鞘蛋白22(PMP22)基因重复突变阳性的夏科-马里-图斯病(CMT) 1A亚型患者临床和神经电生理改变特点.方法 总结21例PMP22基因重复突变阳性的CMT1A患者的临床特点,并分析其神经电生理特征.结果 21例患者中,10例临床特征符合四肢远端萎缩无力的典型CMT1型表现,另外11例呈不典型性,如仅有头晕、合并听力障碍、上肢姿势性震颤、反复发作性肢体无力、伴有小脑性共济失调及癫(痢)等.10例患者肌电图出现纤颤电位和(或)正锐波,15例患者运动单位电位时限延长.神经传导存在广泛异常,所有患者被检的运动或感觉神经传导速度存在不同程度的减慢或消失.结论 PMP22重复突变阳性的CMT1A患者具有较高的临床异质性,其电生理特点为肌电图呈神经源性损害,感觉神经病变重于运动神经,下肢受累程度重于上肢,神经电生理检查对CMT1A的诊断很重要.%Objective To investigate the clinical and electrophysiological characteristics in Charcot-Marie-Tooth disease(CMT ) type 1A patients with (peripheral myetin protein22,PMP22) duplication mutation. Methods Twenty one patients with CMT 1A were retrospectively studied. Routine electromyography ( EMG) and nerve conduction had been performed in all patients. Hie clinical and electrophysiological features were analyzed. Results 10 of 21 patients showed typical presentations including weakness and atrophy in the distal parts of limbs, and 11 atypical cases with special phenotypes including mild dizziness, hearing loss, postural tremor in the upper limbs, recurrent limbs weakness , cerebellar ataxia and epilepsy. EMG detected fibrillation potentials and positive sharp waves in 10 patients and prolonged duration of motor unit potentials in 15 patients respectively. Nerve conduction studies revealed decreased nerve conductive velocity or unelicited potentials in all detected nerves in the patients. Conclusion The CMT 1

  12. Assessment of upper motor neuron dysfunction by triple stimulation technique in patients with Charcot-Marie-Tooth disease%三重刺激技术对腓骨肌萎缩症上运动神经元损害的评估

    Institute of Scientific and Technical Information of China (English)

    徐迎胜; 张朔; 刘小璇; 孙阿萍; 樊东升

    2016-01-01

    目的 对腓骨肌萎缩症(CMT)患者进行三重刺激技术(TST)检测,探索其上运动神经元(UMN)损害的亚临床证据,以期为致病基因的筛选提供依据.方法 分析2013年8月至2015年8月于北京大学第三医院神经内科就诊的经基因检测确诊的CMT患者65例.对其进行临床查体、神经电生理检测,主要观察锥体束征和TST检测(包括经颅磁刺激、外周神经刺激、对冲技术等)结果,计算TST test/TST control波幅比,判断其上运动神经元功能状况.结果 临床查体发现7例患者下肢腱反射亢进,Babinski征阳性,肌张力增高,其中2例合并上肢腱反射亢进,Hoffmann征阳性.10例患者TST test/TST control波幅比下降(其中5例下肢腱反射亢进,Babinski征阳性,2例合并上肢腱反射亢进,Hoffmann征阳性).对应的致病基因:MFN2基因突变5例,BSCL2基因突变1例,3例GJB1基因突变,GDAP基因突变1例.根据临床查体和TST结果,18.5%(12例)的患者存在上运动神经元损害.结论 CMT患者可存在上运动神经元损害,据此可进行相关致病基因检测.%Objective To investigate the presence of upper motor neuron dysfunction in patients with Charcot-Marie-Tooth disease (CMT) by triple stimulation technique (TST) to provide evidence for gene diagnosis.Methods A total of 65 CMT patients confirmed by genetic testing from Peking University Third Hospital between August 2013 and August 2015,underwent physical examination and routine electrophysiological tests and triple stimulation technique.The TST combined transcranial magnetic stimulation (TMS) of the motor cortex with peripheral collision studies.The results were expressed by the TST amplitude ratio (TST test/TST control).Based on the result of physical examination and the ratio of TST,the function of upper motor neuron was assessed.Results All of the CMT patients had typical presentations and were confirmed genetically.Hyperreflexia,Babinski sign and muscular hypertonia were

  13. Charcot-Marie-Tooth病Ⅰ型的免疫学机制研究进展(综述)

    Institute of Scientific and Technical Information of China (English)

    笪宇威; 贾建平

    2005-01-01

    Charcot-Marie-Tooth病(CMT)即进行性腓骨肌萎缩症,是神经系统常见的遗传病之一,目前已报道11个致病基因与Ⅰ型相关.近来研究发现,CMT1(脱髓鞘型)动物模型中髓鞘损害伴随T淋巴细胞和巨噬细胞增加,部分CMT患者周围血中活化的T细胞增加,MHC-Ⅱ分子在腓肠神经中表达增高以及一些病例对激素治疗效果好,均提示该病可能与免疫因素有关.

  14. Classification and molecular diagnostic procedure for Chacort-Marie-Tooth disease%腓骨肌萎缩症的分型与分子诊断流程

    Institute of Scientific and Technical Information of China (English)

    张如旭; 唐北沙

    2012-01-01

    Charcot-Marie-Tooth disease (CMT) is the most common form of hereditary neuropathy with significant clinical and genetic heterogeneity.So far 28 genes have been cloned.The main clinical manifestations of CMT include progressive distal muscle wasting and weakness,impaired distal sensation,and diminishing or loss of tendon reflex.Patients may be classified into demyelinating type (CMT1) and axonal type (CMT2) according to electrophysiological and pathological characteristics.Establishment of a standard diagnostic procedure based on clinical,electrophysiological and pathological findings will enable accurate diagnosis in most CMT patients and provide guidance for gene consulting and prognosis.%腓骨肌萎缩症(Charcot-Marie-Tooth disease,CMT)是一组最常见的具有高度临床和遗传异质性的周围神经单基因遗传病,目前已有28个疾病基因被克隆.主要临床症状包括进行性对称性肢体远端肌无力和肌萎缩,感觉障碍和腱反射减退或消失.根据电生理和病理特点,CMT可分为脱髓鞘型和轴突型.通过临床表现、电生理病理特点进行临床和遗传学分型,选择可能的疾病基因进行突变分析等一系列具有逻辑性的诊断流程,可明确分子诊断,为疾病预后和遗传咨询提供指导性意见.

  15. 腓骨肌萎缩症1型患者肌电图及PMP22基因特点分析%Electromyography and PMP22 gene analysis in patients with type 1 Charcot-Marie-Tooth disease

    Institute of Scientific and Technical Information of China (English)

    潘晓丽; 潘志宏; 张楠楠; 高红

    2015-01-01

    目的:探讨和研究腓骨肌萎缩症1型(Charcot‐Marie‐Tooth disease 1,CMT1)患者肌电图和 PMP22基因改变特点。方法对43例CM T1患者进行常规神经传导速度和肌电图检查,应用PCR双酶切方法对其中33例CM T1患者及15名健康志愿者(对照组)检测17p11.2‐12 PM P22基因重复序列(即1760 bp片段)。33例CM T1患者依有无17p11.2‐12 PM P22基因特异性片段分为 PM P22基因特异性片段阳性组与阴性组,比较两组患者神经传导改变有无差异。结果43例患者均行肌电图检测,均表现为运动或感觉神经传导速度存在明显减慢(100%),感觉神经病变重于运动神经,下肢受累程度重于上肢;所检129块肌肉中,88块(68.2%)呈神经源性损害。经 PM P22基因学检测的33例中20例(60.6%)检测出1760 bp片断,对照组均未检测到此片段。PM P22基因特异性片段阳性组感觉神经传导速度、运动神经传导速度及远端潜伏期与阴性组比较差异均无统计学意义(P>0.05)。结论 CMT1患者肌电图改变具有其特异性,结合PCR‐双酶切法检测 PMP22特异性基因重复序列可提高诊断CM T1的准确性及敏感性。%Objective To study the electromyography and PM P22 gene features in patients with type 1 Charcot‐Marie‐Tooth (CMT ) disease . Methods Routine electromyography and nerve conduction were performed in 43 patients with CMT 1 .Polymerase chain reaction (PCR) combined with restriction enzyme digestion was used to detect PMP22 gene duplication on chromosome 17p11.2‐12 (1760 bp) in 33 CMT 1 patients and 15 healthy volunteers (the control group) .According to the presence or absence of 17 p11.2‐12 PMP22 gene segments ,33 CMT 1 patients were divided into the positive group and the negative group . Parameters of nerve conduction were compared between two groups .Results All of the patients had the nerve conduction velocities slower or disappeared

  16. Hereditaer motorisk sensorisk neuropati (Charcot-Marie-Tooths sygdom). Molekyloergenetiske aspekter

    DEFF Research Database (Denmark)

    Hertz, M J; Børglum, Anders; Brandt, C A

    1995-01-01

    -Sottas disease, is a hypertrophic neuropathy with markedly reduced nerve conduction velocity. HMSN type I is genetically heterogenous with at least four autosomal loci and at least two X-linked loci. The most frequent form, HMSN type Ia, is associated with a specific duplication on chromosome 17, which can...... be detected by DNA-analysis. The genes for HMSN type Ia, Ib and an X-linked dominant form have been identified as PMP22, MPZ and GJB1 respectively. Analysis for these molecular defects will become important in the differential diagnosis of peripheral neuropathies and will surely prove invaluable...

  17. Narcolepsy with cataplexy in a child with Charcot-Marie-Tooth disease. Case Report.

    Science.gov (United States)

    Zheng, Feixia; Wang, Shuang

    2016-09-01

    We report an 8-year-old boy diagnosed with both CMT1 and narcolepsy, which were not reported simultaneously presenting in one person. The boy presented with a history of increased suddenly falling frequency and excessive daytime sleepiness for 3 months. CMT1 was diagnosed by electrophysiology and genetic testing. Narcolepsy had not been diagnosed until the frequently falling caused by sudden and transient episodes of legs weakness triggered by emotion was found. Multiple sleep latency test showed multiple sleep onset REM periods with reduced sleep latency. When CMT1 and narcolepsy were coexist in an individual, the latter might be overlooked. Cataplexy caused by narcolepsy might be disregard as distal muscle weakness of CMT1. The daytime sleepiness might also be ignored. Therefore, we recommend that patients with sleep disorders should be queried about the symptoms of narcolepsy.

  18. Dynamin 2 mutations in Charcot–Marie–Tooth neuropathy highlight the importance of clathrin-mediated endocytosis in myelination

    DEFF Research Database (Denmark)

    Sidiropoulos, Páris; Miehe, Michaela; Bock, Thomas

    2016-01-01

    and neurons from the peripheral nervous system expressing dominant intermediate Charcot-Marie-Tooth neuropathy mutants showed defects in clathrin-mediated endocytosis. We demonstrate that, as a consequence, protein surface levels are altered in Schwann cells. Furthermore, we discovered that myelination...

  19.  Hypertelorism in Charcot-Marie-Tooth disease 1A from the common PMP22 duplication: A Case Report

    Directory of Open Access Journals (Sweden)

    Josef Finsterer

    2012-03-01

    Full Text Available  The 1.4Mb tandem-duplication in the PMP22 gene at 17p11.2 usually manifests as hereditary sensorimotor polyneuropathy with foot deformity, sensorineural hearing-loss, moderate developmental delay, and gait disturbance. Hypertelorism and marked phenotypic variability within a single family has not been reported. In a single family, the PMP22 tandem-duplication manifested as short stature, sensorimotor polyneuropathy, tremor, ataxia, sensorineural hearing-loss, and hypothyroidism in the 27 years-old index case, as mild facial dysmorphism, muscle cramps, tinnitus, intention tremor, bradydiadochokinesia, and sensorimotor polyneuropathy in the 31 year-old half-brother of the index-patient, and as sensorimotor polyneuropathy and foot deformityin the father of the two. The half-brother additionally presented with hypertelorism, not previously reported in PMP22tandem-duplication carriers. The presented cases show that the tandem-duplication 17p11.2 may present with marked intra-familialphenotype variability and that mild facial dysmorphism with stuck-out ears and hypertelorism may be a rare phenotypic feature of this mutation. The causal relation between facial dysmorphism and the PMP22 tandem-duplication, however, remains speculative.

  20. X-linked Charcot-Marie-Tooth (CMT) neuropathies (CMTX1, CMTX2, CMTX3) show different clinical phenotype and molecular genetics

    Energy Technology Data Exchange (ETDEWEB)

    Ionasescu, V.V.; Searby, C.C.; Ionasescu, R. [Univ. of Iowa Hospitals and Clinics, Iowa City, IA (United States)

    1994-09-01

    The purpose of this study was to compare the X-linked dominant type CMTX1 (20 families) with X-linked recessive types CMTX2 and CMTX3 (2 families). The clinical phenotype was consistent with CMT peripheral neuropathy in all cases including distal weakness, atrophy and sensory loss, pes cavus and areflexia. Additional clinicial involvement of the central nervous system was present in one family with CMTX2 (mental retardation) and one family with CMTX3 (spastic paraparesis). Tight genetic linkage to Xq13.1 was present in 20 families with CMTX1 (Z=34.07 at {theta}=0) for the marker DXS453. Fifteen of the CMTX1 families showed point mutations of the connexin 32 coding region (5 nonsense mutations, 8 missense mutations, 2 deletions). Five CMTX1 neuropathy families showed no evidence of point mutations of the CX32 coding sequence. These findings suggest that the CMTX1 neuropathy genotype in these families may be the result of promoter mutations, 3{prime}-untranslated region mutations or exon/intron splice site mutations or a mutation with a different type of connexin but which has close structural similarities to CX32. No mutations of the CX32 coding region were found in the CMTX2 or CMTX3 families. Linkage to Xq13.1 was excluded in both families. Genetic linkage to Xp22.2 was present in the CMTX2 family (Z=3.54 at {theta}=0) for the markers DXS987 and DXS999. Suggestion of linkage to Xq26 (Z=1.81 at {theta}=0) for the marker DXS86 was present in the CMTX3 family.

  1. Is the extracellular ATP a key in X-linked Charcot-Marie-Tooth disease and in inherited non-syndromic deafness?

    OpenAIRE

    Mas del Molino, Ezequiel

    2011-01-01

    [spa] El ATP es una molécula ampliamente conocida por su papel en muchas funciones como la homeostasis celular, el mantenimiento de gradientes iónicos, el mantenimiento del pH en gránulos secretores, el almacenamiento energético, regulador de la interacción actina-miosina, etc. Además, el ATP puede actuar como molécula señalizadora a través de los receptores purinérgicos P2. De receptores P2 hay de dos tipos, los P2X, que son ionotrópicos, y los P2Y que son metabotrópicos. Los primeros son un...

  2. Charcot in contemporary literature.

    Science.gov (United States)

    Goetz, Christopher G

    2006-03-01

    Charcot and his medical observations remain an enduring topic of scientific study in neurology, but he is also the topic of modern literary works. This essay examines the depiction of Jean-Martin Charcot (1825-1893) as a character in late-twentieth-century literature as an index of the contemporary nonmedical literary public's interest in neurology and Charcot. It focuses on three contemporary works that involve Charcot as a central figure with comparison between primary source documents and the rendered context, character development, and plot lines of these literary works. The two French novels [Slumbers of Indiscretion and Dr. Charcot of the Salpêtrière] and one American play [Augustine (Big Hysteria)] approach Charcot and neurology with differing levels of historical accuracy. All create a figure of authority, each with a different coloration of the balance between power and its abuse. Two focus almost exclusively on his work with hysteria and inaccurately amplify Charcot's concern with symbolic sexual conflict as the origin of hysteria and fictionalize more extensive interactions with Freud than historical documents support. The three works demonstrate that Charcot retains an enduring fascination with an enigmatic personality, a controversial career, and a pivotal role in the development of studies involving the brain and behavior. Neurologists should not look to these works as replacements for more seriously composed historical studies, but as enrichments anchored in the imaginative possibilities of Charcot and his fin de siècle era.

  3. Yeast Interacting Proteins Database: YGR185C, YPL013C [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available associated with Charcot-Marie-Tooth (CMT) neuropathies Rows with this bait as bait (1) Rows with this bait ... anticodon; mutations in human ortholog YARS are associated with Charcot-Marie-Tooth (CMT) neuropathies Rows

  4. [Charcot and hysteria].

    Science.gov (United States)

    Widlöcher, D; Dantchev, N

    1994-01-01

    Charcot's work on hysteria has always been controversial. All his attitudes, whether on the theory of the ovary, the hysteroepileptic seizure or the use of hypnosis, have always been charicatured, misunderstood and separated from the wider context of his overall approach. Rereading Charcot's works shows that he developed his approach progressively over a period of more than 20 years before coming to his psychological model of hysteria. This model explains the formation of the symptom and the hysterical conversion via a mechanism of being ignorant of the motor representation. This concept has never been disproven and remains the only theory explaining the formation of the hysteria symptom. Based on Charcot's fundamental contribution, Freud and Janet further developed their work on the psychopathology of hysteria.

  5. 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

  6. [Jean-martin charcot].

    Science.gov (United States)

    Sakuta, Manabu

    2014-11-01

    Charcot created a system for the classification and diagnosis of neurological patients in the 1850s. His methodology consisted of listening to a patient's family history and present history, observing the patient scrupulously, and confirming lesions by autopsy once the patient was dead. He compared two different diseases in order to make their differences clear. Once he understood the fundamental form of a disease, he proceeded to study less perfect forms that had a single symptom. By this process, Charcot developed many new symptomatologies in Neurology.

  7. Marie Curie; Marie Curie

    Energy Technology Data Exchange (ETDEWEB)

    Trotereau, J.

    2011-07-01

    The legend has only retained from Marie Curie (1867-1934) the image of a hard and brilliant worker, pioneer in the radioactivity domain, and who awarded twice the Nobel Price. Behind the scientist, there is a women, Marya Salomea Sklodowska, the 'Polish', who was considered during some time as an 'alien', an 'atheistic intellectual', an 'emancipated women'. When she died alone in July 1934, after an exhausting life of labour, her funeral led to no official ceremony or speech. This small book summarizes the biography of the most famous female scientist in the world

  8. Den diabetiske Charcots fod

    DEFF Research Database (Denmark)

    Christensen, Tomas Møller; Yderstraede, Knud; Ejskjaer, Niels

    2008-01-01

    Charcot's arthropathy is a rare complication to diabetes with peripheral neuropathy. The diagnosis is based on a red, oedematous foot with 2 degrees C difference in skin temperature between the affected foot compared to the unaffected foot. The condition is characterised by fractures, dislocation...

  9. Charcot foot syndrome.

    Science.gov (United States)

    Jeffcoate, W J

    2015-06-01

    Charcot foot syndrome is an uncommon complication of diabetes but is potentially devastating in its consequences. Outcome is made worse by widespread professional ignorance leading to delayed diagnosis, but it is also hampered by lack of understanding of its causes and lack of treatments with proven effectiveness, other than offloading. There remains a desperate need for studies into its causes as well as comparative audit and trials designed to determine the best treatment for this difficult condition. Such work can probably only be effectively carried out through the establishment of multicentre networks. Nevertheless, improved understanding in recent years of the likely role of inflammatory pathways has raised awareness of the multiple ways in which the effects of neuropathy may be manifest in the development of the Charcot foot. This awareness is also leading to the realization that similar processes may conceivably contribute to the refractoriness of other foot diseases in diabetes, including both chronic unhealing ulcers and osteomyelitis.

  10. Charcot and vascular Parkinsonism

    Directory of Open Access Journals (Sweden)

    Hélio A. G. Teive

    Full Text Available ABSTRACT Jean-Martin Charcot (1825-1893, recognized as the founder of Neurology and the first formal teacher of nervous system diseases, died on August 16, 1893, from acute pulmonary edema secondary to myocardial infarction. In his last years, there were several descriptions of his gait and posture disorders, suggesting the diagnosis of “lower-half parkinsonism” due to cerebrovascular disease.

  11. Den diabetiske Charcots fod

    DEFF Research Database (Denmark)

    Christensen, T.M.; Yderstraede, K.; Ejskjaer, N.;

    2008-01-01

    Charcot's arthropathy is a rare complication to diabetes with peripheral neuropathy. The diagnosis is based on a red, oedematous foot with 2 degrees C difference in skin temperature between the affected foot compared to the unaffected foot. The condition is characterised by fractures, dislocation...... of joints and deformity. The treatment is off-loading. When the off-loading treatment is completed, the patient should gradually adjust to wearing bespoken shoes. Lifelong control of the feet and shoes is necessary Udgivelsesdato: 2008/8/11...

  12. Progress in molecular diagnosis of Charcot-Marie-Tooth-disease type 1 (CMT 1, HMSN I) and hereditary neuropathy with liability to pressure palsies (HNPP) by fluorescence in situ hybridization (FISH)-detection of a potential genetic mosaicism

    Energy Technology Data Exchange (ETDEWEB)

    Bathke, K.; Liehr. T.; Ekici, A. [Institute for Human Genetics, Erlange (Germany)] [and others

    1994-09-01

    We tested 20 CMT 1 patients characterized according to the criteria of the European CMT consortium by Southern hybridization of MspI restricted genomic DNA with probes pVAW409R1, pVAW412Hec and pEW401HE. In 11 of the 20 CMT 1 cases (55%), we observed a duplication in 17q11.2; one patient had a dinucleotide insertion in exon 6 of the PO-gene (5%). One HNPP case had a typical 17p11.2 deletion. Analysis of CA-repeats was performed with primers RM11GT and Mfd41; SSCP-analysis of the PO, PMP22 and Cx32-genes is in progress. FISH was carried out with probe pVAW409R1. 125 interphase nuclei were analyzed for each proband by counting the signals per nucleus. Normal cells show a characteristic distribution of signals: 1 signal in 5.9% of nuclei, 2 in 86.3% and 3 in 7.8%. A duplication is indicated by a shift to 3 signals in more than approximately 60% and 2 in less than 25% of the nuclei. In contrast, the 17p11.2 deletion of the HNPP patient shifts to 82.4% of nuclei with a single hybridization signal versus 14.4% with 2 signals. We detected one case with significantly abnormal distribution of interphase nuclei hybridization signals compared to cultures of normal cells and to those with 17p11.2 duplication or deletion: 3.2% nuclei revealed 1 signal, 48.0% two signals and 48.8% 3 signals, indicating a pathogenic but moderate dosis increase compared to the throughout duplicated cases. FISH with probe pVAW409R1 is a versatile tool to detect the HNPP deletion both in interphase nuclei and in metaphase chromosomes. In CMT 1 disease interphase nuclei are required for FISH analysis due to the small duplication of 1.5 Mbp. In contrast to Southern techniques, FISH is able to detect genetic mosaicism.

  13. 1例腓骨肌萎缩症亚急性进展误诊分析%Analysis on misdiagnosis in one case of charcot marie tooth disease in subacute progress

    Institute of Scientific and Technical Information of China (English)

    郭洁; 王亚萍

    2010-01-01

    @@ 1病例介绍 患者,男性,51岁.主因四肢无力伴麻木进行性加重1年转入我院.患者于入院前1年开始出现四肢无力伴麻木,以双下肢为著,呈进行性加重,经常摔倒,需要轮椅帮助日常活动.当地医院以慢性炎性脱髓鞘性周围神经病(CIDP)收入院.

  14. No mutation was detected in the LMNA gene among sporadic Charcot-Marie-Tooth patients%在散发型腓骨肌萎缩症患者中未检测出LMNA基因突变

    Institute of Scientific and Technical Information of China (English)

    宋书娟; 章远志; 陈彪; 王曼捷; 王越英; 张远锦; 闫明; Nanbert ZHONG

    2006-01-01

    Objective: To intensively investigate sporadic CMT patients, we have analyzed the LMNA gene in this study in a series of 32 unrelated CMT patients. Methods: Twelve exons of the LMNA gene were amplified from genetomic DNA. PCR products of each exon were analyzed by single strand conformational polymorphism (SSCP). Results: No abnormal SSCP pattern, suggesting no mutation in our CMT patients, was detected. Conclusion: The CMT diseases resulted from the mutations of LMNA gene were rare.

  15. Contribución del estudio neurofisiológico al diagnóstico y control evolutivo de la enfermedad de Charcot-Marie-Tooth en la provincia de Las Palmas

    OpenAIRE

    Navarro Rivero, Beatriz

    2015-01-01

    Programa de doctorado: Patología Quirúrgica [ES]En la presente tesis se estudian los diferentes tipos gnéticos de CMT en la provincia de Las Palmas mediante un estudio transversal, descriptivo y retrospectivo entre los años 2008-2012; valorando la importancia del estudio neurofisiológico y su posible correlación de los parámetros neurofiosológicos con diferentes nervios respecto a discapacidad clínica, tiempos de evolución de la enfer...

  16. Disease: H00264 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H00264 Charcot-Marie-Tooth disease (CMT); Hereditary motor and sensory neuropathy; ...Peroneal muscular atrophy Charcot-Marie-Tooth disease is a genetically heterogeneous group of inherited peri...52 613353 PMID:18215208 Barisic N, Claeys KG, Sirotkovic-Skerlev M, Lofgren A, Nelis E, De Jonghe P, Timmerman V Charcot-Marie-Too...378 Niemann A, Berger P, Suter U Pathomechanisms of mutant proteins in Charcot-Marie-Tooth disease. Neuromol...ecular Med 8:217-42 (2006) PMID:15518599 Bertorini T, Narayanaswami P, Rashed H Charcot-Marie-Too

  17. The seminal role played by Pierre Marie in Neurology and Internal Medicine

    Directory of Open Access Journals (Sweden)

    Gustavo M Almeida

    2015-10-01

    Full Text Available The authors review the most important contributions of Pierre Marie to the elucidation and description of several neurological diseases, such as Charcot-Marie-Tooth’s disease and hereditary cerebellar ataxia, as well as his contributions to Internal Medicine, including his pioneering studies on acromegaly, ankylosing spondylitis, and hypertrophic pulmonary osteoarthropathy. His works led to incontestable advances in the medical sciences that transcended his time.

  18. Charcot foot and ankle with osteomyelitis

    Directory of Open Access Journals (Sweden)

    Ryan Donegan

    2013-10-01

    Full Text Available This paper presents a review of the current literature discussing topics of Charcot osteoarthropathy, osteomyelitis, diagnosing osteomyelitis, antibiotic management of osteomyelitis, and treatment strategies for management of Charcot osteoarthropathy with concurrent osteomyelitis.

  19. The Charcot foot in diabetes.

    Science.gov (United States)

    Rogers, Lee C; Frykberg, Robert G; Armstrong, David G; Boulton, Andrew J M; Edmonds, Michael; Van, Georges Ha; Hartemann, Agnes; Game, Frances; Jeffcoate, William; Jirkovska, Alexandra; Jude, Edward; Morbach, Stephan; Morrison, William B; Pinzur, Michael; Pitocco, Dario; Sanders, Lee; Wukich, Dane K; Uccioli, Luigi

    2011-09-01

    The diabetic Charcot foot syndrome is a serious and potentially limb-threatening lower-extremity complication of diabetes. First described in 1883, this enigmatic condition continues to challenge even the most experienced practitioners. Now considered an inflammatory syndrome, the diabetic Charcot foot is characterized by varying degrees of bone and joint disorganization secondary to underlying neuropathy, trauma, and perturbations of bone metabolism. An international task force of experts was convened by the American Diabetes Association and the American Podiatric Medical Association in January 2011 to summarize available evidence on the pathophysiology, natural history, presentations, and treatment recommendations for this entity.

  20. Charcot's son, commander Jean-Baptiste Charcot: from neurology to "Pourquoi Pas?".

    Science.gov (United States)

    Teive, Hélio A G; Munhoz, Renato P; Simões, Jefferson C

    2012-04-01

    Charcot name became very famous around the world, firstly because of the work of Professor Jean-Martin Charcot, the founder of Clinical Neurology, and, secondly, because of his son, Jean-Baptiste, the world famous maritime explorer.

  1. An overview of the Charcot foot pathophysiology

    OpenAIRE

    Öğüt, Tahir; Kaynak, Gökhan; Birsel, Olgar; Güven, Mehmet Fatih

    2013-01-01

    Charcot arthropathy of the foot is a rare but devastating complication of diabetes that remains to be a challenging issue for the foot and ankle surgeons. Charcot foot fails to be an obvious diagnostic option that comes to mind, even in a pathognomonic clinical appearance. The rarity of the disorder, more common pathologies that mimic the condition, and the self-limiting prognosis deviate the clinician from the right diagnosis. The clinical challenges in the diagnosis of Charcot foot require ...

  2. Charcot foot and ankle with osteomyelitis

    OpenAIRE

    Donegan, Ryan; Sumpio, Bauer; Peter A. Blume

    2013-01-01

    This paper presents a review of the current literature discussing topics of Charcot osteoarthropathy, osteomyelitis, diagnosing osteomyelitis, antibiotic management of osteomyelitis, and treatment strategies for management of Charcot osteoarthropathy with concurrent osteomyelitis.Keywords: Charcot foot; osteomyelitis; diabetes mellitus; infection; neuropathy(Published: 1 October 2013)Citation: Diabetic Foot & Ankle 2013, 4: 21361 - http://dx.doi.org/10.3402/dfa.v4i0.21361

  3. MARIE CURIE

    Directory of Open Access Journals (Sweden)

    EDGAR SERNA MONTOYA

    2011-12-01

    Full Text Available María Sklodowska ‒Marie Curie‒ fue pionera en la ciencia de la radiactividad; es mejor conocida como la descubridora de los elementos radiactivos polonio y radio, y como el primer científico en ganar dos premios Nobel: Física y Química. Para sus colegas y el público en general, el radio fue la clave para un cambio fundamental en nuestra comprensión de la materia y la energía. Su trabajo no sólo influyó en el desarrollo de la ciencia fundamental, sino que también marcó el comienzo de una nueva era en la investigación y los tratamientos médicos.

  4. Imaging of Charcot foot; Bildgebung des Charcot-Fusses

    Energy Technology Data Exchange (ETDEWEB)

    Erlemann, Rainer; Schmitz, Annette [Helios Klinikum Duisburg, Helios St. Johannes Klinik, Duisburg (Germany). Inst. fuer Radiologie

    2014-03-15

    The onset of a Charcot foot ist a feared complication of a long lasting diabetes mellitus. A peripheral neuropathy and continuous weight bearing of the foot subsequent to repeated traumas depict the conditions. There exist three types of a Charcot foot, an atrophic, a hypertophic and a mixed type. In early stages a differentiation from osteoarthritis is difficult. Subluxation or luxation within the Lisfranc's joint is typical. The joints of the foot could rapidly and extensively be destroyed or may present the morphology of a 'superosteoarthritis'. Often, soft tissue infections or osteomyelitis evolve from ulcers of the skin as entry points. Diagnosis of osteomyelitis necessitate MR imaging as plain radiography offers only low sensitivity for detection of an osteomyelitis. The existence of periosteal reactions is not a proof for osteomyelitis. Bone marrow edema and soft tissue edema also appear in a non infected Charcot foot. The range of soft tissue infections goes from cellulitis over phlegmon to abscesses. The ghost sign is the most suitable diagnostic criterion for osteomyelitis. In addition, the penumbra sign or the existence of a sinus tract between a skin ulcer and the affected bone may be helpful. (orig.)

  5. Tooth extraction

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007630.htm Tooth extraction To use the sharing features on this page, please enable JavaScript. A tooth extraction is a procedure to remove a tooth from ...

  6. [Charcot, Freud and the unconscious].

    Science.gov (United States)

    Lellouch, Alain

    2004-01-01

    The aim of this work is to assess, on an historical and critical point of view, the new psychological perspective, introduced by Charcot (1825-1893), during the ten last years (1882-1892) of his life to explain hysteria symptomas. From clinical examples (hypnosis and hypnotherapy, "hystero-traumatism", "psychological theory of hysteria", "faith healing"), the paper shows how psychological dimension went back into the Parisian Hospital Medicine. This occurred on the late XIXth century, just one century after Mesmer, when Freud was Charcot's intern, at La Salpêtrière hospital, during years 1885-1886. The return of a non-rational thought into hospital medicine upset the organicist concepts of the Parisian "Ecole anatomo-clinique".

  7. Tooth anatomy

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/002214.htm Tooth anatomy To use the sharing features on this page, ... upper jawbone is called the maxilla. Images Tooth anatomy References Lingen MW. Head and neck. In: Kumar ...

  8. Charcot Spine and Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Philippe Loriaut

    2014-01-01

    Full Text Available Charcot spine is rare condition whose association with Parkinson’s disease (PD has not been reported yet. The authors reported the cases of two patients with PD who developed Charcot spine. Both patients presented with a history of back pain and bilateral radicular leg pain. They had complete clinical and radiological assessment. Lumbar spine was involved in both patients. Clinical features and response to treatment were described. In the first case, circumferential fusion and stabilization were performed on the dislocated vertebral levels. A solid and stable fusion of the spine was obtained with satisfactory clinical outcome. Surgical treatment has been recommended to the other patient. In both cases, no other neurological etiology was found to account for Charcot spine. In conclusion, Charcot spine is associated with several neurological affections but has not previously been reported in association with Parkinson’s disease.

  9. An overview of the Charcot foot pathophysiology.

    Science.gov (United States)

    Kaynak, Gökhan; Birsel, Olgar; Güven, Mehmet Fatih; Oğüt, Tahir

    2013-01-01

    Charcot arthropathy of the foot is a rare but devastating complication of diabetes that remains to be a challenging issue for the foot and ankle surgeons. Charcot foot fails to be an obvious diagnostic option that comes to mind, even in a pathognomonic clinical appearance. The rarity of the disorder, more common pathologies that mimic the condition, and the self-limiting prognosis deviate the clinician from the right diagnosis. The clinical challenges in the diagnosis of Charcot foot require in-depth investigations of its enigmatic nature to establish useful guidelines. Yet, this goal seems to be beyond reach, without a holistic view of the immense literature concerning the pathophysiology of the disorder. The primary objective of this article is to put together and review the recent advancements about the etiology and intrinsic mechanisms of diabetic Charcot foot.

  10. [Charcot-arthropathy in diabetes mellitus

    NARCIS (Netherlands)

    Schoonbeek, A.; Ottens, R.L.J.M.; Lutterman, J.A.

    2002-01-01

    Charcot's arthropathy is a relative uncommon complication of diabetic neuropathy. The aetiology remains poorly understood. According to the neurotraumatic theory, the foot, which has become insensitive through neuropathy, is subjected to extensive (micro)trauma through continuation of use. Ultimatel

  11. Intramedullary foot fixation for midfoot Charcot neuroarthropathy.

    Science.gov (United States)

    Lamm, Bradley M; Siddiqui, Noman A; Nair, Ajitha K; LaPorta, Guido

    2012-01-01

    Midfoot Charcot collapse commonly occurs through the tarsometatarsal and/or midtarsal joints, which creates the characteristic "rocker bottom" deformity. Intramedullary metatarsal fixation spanning the tarsus into the talus and/or calcaneus is a recently developed method for addressing unstable midfoot Charcot deformity. The intramedullary foot fixation technique has various advantages when addressing midfoot Charcot deformity in the neuropathic patient. These advantages include anatomical realignment, minimally invasive fixation technique, formal multiple joint fusion, adjacent joint fixation beyond the level of Charcot collapse, rigid interosseus fixation, and preservation of foot length. The goals of the intramedullary foot fixation procedure are to create a stable, plantigrade, and ulcer-free foot, which allows the patient to ambulate with custom-molded orthotics and shoes.

  12. An overview of the Charcot foot pathophysiology

    Directory of Open Access Journals (Sweden)

    Gökhan Kaynak

    2013-08-01

    Full Text Available Charcot arthropathy of the foot is a rare but devastating complication of diabetes that remains to be a challenging issue for the foot and ankle surgeons. Charcot foot fails to be an obvious diagnostic option that comes to mind, even in a pathognomonic clinical appearance. The rarity of the disorder, more common pathologies that mimic the condition, and the self-limiting prognosis deviate the clinician from the right diagnosis. The clinical challenges in the diagnosis of Charcot foot require in-depth investigations of its enigmatic nature to establish useful guidelines. Yet, this goal seems to be beyond reach, without a holistic view of the immense literature concerning the pathophysiology of the disorder. The primary objective of this article is to put together and review the recent advancements about the etiology and intrinsic mechanisms of diabetic Charcot foot.

  13. Charcot's son, commander Jean-Baptiste Charcot: from neurology to "Pourquoi Pas?"

    Directory of Open Access Journals (Sweden)

    Hélio A. G. Teive

    2012-04-01

    Full Text Available Charcot name became very famous around the world, firstly because of the work of Professor Jean-Martin Charcot, the founder of Clinical Neurology, and, secondly, because of his son, Jean-Baptiste, the world famous maritime explorer.

  14. Kaks Mari Vaalas / Eha Komissarov

    Index Scriptorium Estoniae

    Komissarov, Eha, 1947-

    1999-01-01

    9. nov.-st galeriis 'Vaal' Mari Roosvaldi maalinäitus 'Persoon'; 10. nov.-st galerii keldrisaalis Mari Kurismaa 'Matemaatika ja metafüüsika'. Mari Roosvaldi kollaazhides on ühendatud maal ja foto.

  15. Hysteria after Charcot: back to the future.

    Science.gov (United States)

    Bogousslavsky, Julien

    2011-01-01

    The studies on hysteria and hypnotism probably constitute the most important long-term work of Jean-Martin Charcot and his school, starting around 1870 until Charcot's death in 1893. Désiré Bourneville, Charcot's sixth interne at La Salpêtrière, was probably instrumental in stimulating his mentor's interest in hysteria, while Charles Richet's 1875 article on somnambulism was the trigger for Charcot to introduce hypnotism into the management of hysterics. Albert Pitres, Paul Richer, Georges Gilles de la Tourette, Paul Sollier, Joseph Babinski, Sigmund Freud and Pierre Janet became the most famous of Charcot's collaborators on hysteria, either as 'guardians of the temple' (Richer, Gilles de la Tourette, who defended their mentor's concepts against Hippolyte Bernheim and the Nancy school in the dispute during the 1880-1890s), or in renewing the field in psychology (Janet and Freud, in the 1890s) or clinical neurology (Babinski in the 1900s). In 1908, a 'quarrel of hysteria' led several of Charcot's pupils into opposition with each other, from which Babinski was considered victorious against Charcot's successor Fulgence Raymond, despite the weaknesses of his theory on 'pithiatism'. During World War I, there was a new surge of interest in hysteria associated with war psycho-neuroses, and several students of Charcot became actively involved in medical military care (Sollier, Babinski, Gilbert Ballet, Achille Souques). Babinski's pupil Clovis Vincent developed a treatment called torpillage (torpedoing) against war hysteria, associating painful galvanic current discharges with 'persuasion', but this was dismissed after the soldiers, considering it as torture, rebelled. After World War I, the neurological and psychiatric interest in hysteria again faded away, and this condition largely went back to the no-man's land, where it had been before Charcot initiated his studies. A comprehensive look at the evolution of ideas on hysteria in the followers of Charcot shows that

  16. Charcot-like joints in calcium pyrophosphate dihydrate deposition disease

    Energy Technology Data Exchange (ETDEWEB)

    Helms, C.A.; Chapman, G.S.; Wild, J.H.

    1981-10-01

    Two cases of Charcot-like joints in patients with pseudogout who were otherwise neurologically intact are presented. The arthropathy of pseudogout should include Charcot-like joints and it is emphasized that an apparent Charcot joint should raise the question of pseudogout.

  17. Jean-Martin Charcot and his legacy.

    Science.gov (United States)

    Bogousslavsky, Julien

    2014-01-01

    Jean-Martin Charcot (1825-1893) rightly is considered the father of both modern neurology and psychiatry in France and much beyond. While he never was interested in mental disease and what was called 'alienism' at the time, his career at La Salpêtrière Hospital over 30 years was mainly marked by the development of a huge group of students which focused on the study and management of hysteria. When Charcot took office at the beginning of 1862, hysteria was a 'no-man's land', medically speaking, since neither the alienists nor the internists had much interest in this condition. At La Salpêtrière, these chronic patients were largely left to themselves before Désiré Bourneville, one of Charcot's first students, convinced his chief to care for them. Subsequently, the studies of Charcot with Paul Richer, Joseph Babinski, Georges Gilles de la Tourette, Paul Sollier, Pierre Janet, and many others allowed the condition to be addressed in detail. During his stay with Charcot in 1885-1866, Sigmund Freud, a young neuropathologist at the time, became fascinated by hysteria, an interest which probably was the main start of his interest in psychology. Charcot emphasized the concept of mental factors in hysteria, along with that of a 'dynamic' lesion, which accounted for the lack of neuropathological findings in the patients. While his ideas on hysteria and hypnotism were criticized after his death even by former pupils, such as Babinski, recent findings from functional studies using magnetic resonance imaging show how accurate and often visionary Charcot's thinking was in this field.

  18. Jean-Baptiste Charcot and Brazil.

    Science.gov (United States)

    Teive, Hélio Afonso Ghizoni; Lima, Carlos Frederico Leite de Souza; Lima, Plínio Marcos Garcia de; Germiniani, Francisco Manoel Branco; Munhoz, Renato Puppi

    2014-08-01

    Jean-Baptiste Charcot, a neurologist from the famous Salpêtrière school and a renowned maritime explorer, visited Brazil twice. The first visit was in 1903, when the first French Antarctic expedition, traveling aboard the ship Français, made a very short stopover in Recife, in the state of Pernambuco. The second took place in 1908, during the famous voyage of the Pourquoi Pas? to the Antarctic, when Charcot and his crew stayed in the city of Rio de Janeiro for eight days.

  19. Jean-Baptiste Charcot and Brazil

    Directory of Open Access Journals (Sweden)

    Hélio Afonso Ghizoni Teive

    2014-06-01

    Full Text Available Jean-Baptiste Charcot, a neurologist from the famous Salpêtrière school and a renowned maritime explorer, visited Brazil twice. The first visit was in 1903, when the first French Antarctic expedition, traveling aboard the ship Français, made a very short stopover in Recife, in the state of Pernambuco. The second took place in 1908, during the famous voyage of the Pourquoi Pas? to the Antarctic, when Charcot and his crew stayed in the city of Rio de Janeiro for eight days.

  20. Surgical treatment of the Charcot foot.

    Science.gov (United States)

    Pinzur, Michael S

    2016-01-01

    With the increased number of diabetics worldwide and the increased incidence of morbid obesity in more prosperous cultures, there has become an increased awareness of Charcot arthropathy of the foot and ankle. Outcome studies would suggest that patients with deformity associated with Charcot Foot arthropathy have impaired health related quality of life. This awareness has led reconstructive-minded foot and ankle surgeons to develop surgical strategies to treat these acquired deformities. This article outlines the current clinical approach to this disabling medical condition.

  1. The pathogenesis of Charcot neuroarthropathy: current concepts

    Directory of Open Access Journals (Sweden)

    Shelly A. M. Larson

    2012-01-01

    Full Text Available The pathogenesis of Charcot neuroarthropathy (CN has been poorly understood by clinicians and scientists alike. Current researchers have made progress toward understanding the cause of CN and possible treatment options. The authors review the current literature on the pathogenesis of this debilitating disorder and attempt to explain the roles of inflammation, bone metabolism, and advanced glycation end products.

  2. Jean-Martin Charcot's house officers at La Salpêtrière Hospital.

    Science.gov (United States)

    Walusinski, Olivier

    2011-01-01

    From the time he became chef de service at La Salpêtrière Hospital in 1866 until his death in 1893, Jean-Martin Charcot oversaw 32 house officers. Some of them became famous, such as D.M. Bourneville, E. Brissaud, P. Marie and G. Gilles de la Tourette. Others are less well known. The fact remains that Charcot knew how to surround himself with fine students and leverage their talents in order to make the neurological discoveries by which he would become famous throughout the world. Here, we present the biographies of H. Soulier (1862), J. Cotard (1865), R. Lépine (1867), A. Gombault (1872), A. Pierret (1874), A. Pitres (1876), P. Oulmont (1877), G. Guinon (1885), P. Blocq(1887), E. Huet (1888), E. Parmentier (1890) and A. Souques(1893). Each of these men with their unique paths and interests helped lay the foundations for the birth of neurology at the end of the 19th century in Paris. As Emile Littré said: 'La science de la Médecine, si elle ne veut pas être rabaissée au rang de métier, doit s'occuper de son histoire et soigner les vieux monuments que les temps passés lui ont légués', which could be translated as 'to avoid being reduced to a trade, the science of medicine must attend to its history and take care of the old monuments handed down by time'.

  3. Jean-Martin Charcot Pathologist, Neurologist, Psychiatrist and Physician

    Directory of Open Access Journals (Sweden)

    Sanjay Pandey

    2012-01-01

    Full Text Available Jean-Martin Charcot is known as father of modern neurology. Before him, neurology was only limited to select disorders like chorea. His contributions were not limited to neurology only, as he was instrumental in many new developments in the field of pathology, psychiatry, and internal medicine. Even after 100 years, Charcot`s clinical methods remain the pillar of modern neurology.

  4. Oral high dose ascorbic acid treatment for one year in young CMT1A patients: a randomised, double-blind, placebo-controlled phase II trial

    NARCIS (Netherlands)

    Verhamme, C.; de Haan, R.J.; Vermeulen, M.; Baas, F.; de Visser, M.; van Schaik, I.N.

    2009-01-01

    ABSTRACT: BACKGROUND: High dose oral ascorbic acid substantially improved myelination and locomotor function in a Charcot-Marie-Tooth type 1A mouse model. A phase II study was warranted to investigate whether high dose ascorbic acid also has such a substantial effect on myelination in Charcot-Marie-

  5. Rosalie: the brazilian female monkey of Charcot Rosalie: a pequenina macaca brasileira de Charcot

    Directory of Open Access Journals (Sweden)

    Hélio A.G. Teive

    2005-09-01

    Full Text Available Jean-Martin Charcot, the father of Neurology, a very austere and reserved man that did not express affection freely for human being, had a profound affection to animals, particularly to a small female monkey, called "Rosalie", which came from Brazil and was a gift of Dom Pedro II to Charcot.Jean-Martin Charcot, considerado o pai da Neurologia, foi um homem de aspecto austero e reservado, que tinha dificuldades de expressar os seus sentimentos para outros seres humanos. Contudo ele tinha profunda afeição por animais, particularmente por uma pequena macaca, chamada de "Rosalie", oriunda do Brasil e que foi um presente dado a ele por Dom Pedro II.

  6. [Charcot and his legacy to medicine].

    Science.gov (United States)

    Camacho Aguilera, José Francisco

    2012-01-01

    Jean-Martin Charcot (1825-1893) was a French physician whose professional life is divided into two phases: the first dedicated to neurology, and the second dedicated to the psychiatry area. Charcot is considered the father of modern neurology. In the Hospice de la Salpêtrière he began his research on neurological diseases, founded a laboratory of pathology (including microscopy and photography), and gave hospital classes based on pathological anatomy related to clinical manifestations based in the field of neurology. His research led to the description and study of different neurological diseases, such as multiple sclerosis, lateral amyotrophic sclerosis, hereditary motor and sensory neuropathy, motor ataxia, Parkinson`s disease, Gilles de la Tourette syndrome, epilepsy, visual aphasia and agnosia, to name a few. Some signs and diseases took their name as an eponym, and some are still mentioned in the current medicine, while others are left in oblivion.

  7. The Charcot foot: pathophysiology, diagnosis and classification.

    Science.gov (United States)

    Trieb, K

    2016-09-01

    Neuropathic changes in the foot are common with a prevalence of approximately 1%. The diagnosis of neuropathic arthropathy is often delayed in diabetic patients with harmful consequences including amputation. The appropriate diagnosis and treatment can avoid an extensive programme of treatment with significant morbidity for the patient, high costs and delayed surgery. The pathogenesis of a Charcot foot involves repetitive micro-trauma in a foot with impaired sensation and neurovascular changes caused by pathological innervation of the blood vessels. In most cases, changes are due to a combination of both pathophysiological factors. The Charcot foot is triggered by a combination of mechanical, vascular and biological factors which can lead to late diagnosis and incorrect treatment and eventually to destruction of the foot. This review aims to raise awareness of the diagnosis of the Charcot foot (diabetic neuropathic osteoarthropathy and the differential diagnosis, erysipelas, peripheral arterial occlusive disease) and describe the ways in which the diagnosis may be made. The clinical diagnostic pathways based on different classifications are presented. Cite this article: Bone Joint J 2016;98-B:1155-9.

  8. Avangardistid Moskvas / Mari Sobolev

    Index Scriptorium Estoniae

    Sobolev, Mari, 1968-

    2000-01-01

    Valdek Alberi ja Taave Tuutma videoinstallatsioonist "Think different" näitusel "Salon 2000" Moskva Kunstnike Keskmajas 16.-26. III. Kuraator Mari Sobolev. Eesti väljapaneku vastukajast ja Jüri Arrakust, kelle maalid olid näitusel "Balti meistrid", ajalehes "Kommersant". Moskva kunstinäitustest.

  9. Significance of Charcot Leyden crystals in hepatic aspirates

    Directory of Open Access Journals (Sweden)

    Misra Vatsala

    2009-01-01

    Full Text Available Charcot Leyden crystals are hexagonal bipyramidal structures localised in the primary granules of the cytoplasm of eosinophils and basophils. Their presence, along with eosinophilic infiltrate, is an indirect evidence of parasitic infestation particularly with Toxocara, Capilliriasis, Ascariasis, or Fasciola. We report here two cases where Charcot Leyden crystals with eosinophilic infiltrate were found in the smears prepared from hepatic abscess.

  10. Clinical management of acute diabetic Charcot foot in Denmark

    DEFF Research Database (Denmark)

    Jansen, Rasmus Bo; Svendsen, Ole Lander; Kirketerp-Møller, Klaus

    2016-01-01

    INTRODUCTION: Charcot foot is a severe complication to diabetes mellitus and treatment involves several different clinical specialities. Our objective was to describe the current awareness, knowledge and treatment practices of Charcot foot among doctors who handle diabetic foot disorders. METHODS......: This study is based on a questionnaire survey sent out to healthcare professionals, primarily doctors, working with diabetic foot ulcers and Charcot feet in the public sector of the Danish healthcare system. RESULTS: The survey obtained a 52% response rate. A temperature difference of > 2 °C between the two...... and treatment practices of acute diabetic Charcot foot at diabetes foot clinics in Denmark. The responders seem to follow the international recommendations and guidelines on management of the acute diabetic Charcot foot, despite a lack of Danish guidelines. FUNDING: none. TRIAL REGISTRATION: not relevant....

  11. A case report of Charcot's joint%Charcot's关节病一例报道

    Institute of Scientific and Technical Information of China (English)

    李灿; 孙娟娟; 王朝夫

    2015-01-01

    Objective To investigate the clinicopathologic features and main points of diagnosis and differential diagnosis of Charcot's joint.Methods A case of Charcot's joint was studied and the related literatures were reviewed.Its clinical manifestations and pathomorphological characteristics were analyzed.Results A 41-year-old male was admitted to the hospital due to loss of range of motion ( ROM ) of the left shoulder joint progressively and painlessly.The X-ray showed the humeral head was partially missing.The CT represent ed irregular soft tissue mass es in high density with an indistinct edge,and discontiguous left scapulabone.The MRI showed changes of syringomyelia was presented in the glenoid cavity of the left shoulder joint,humeral head,proximal humerus and spinal cord of thoracic segments.According to the histological ifndings,free bone detritus accumulationswere microscopicallyseen in the lesions and adjacent soft tissues at an early stage,andthe secondary changes due to the reactions of osteoclast-likemultinucleated giant cells and inlfammatory cells and proliferation of ifbrous tissues.The formation of pannusacted as an important basisfor distinguishing Charcot's joint and other kinds of arthritis.Conclusions Charcot's joint is a kind of neuropathic arthropathy which lacks distinctive histopathologic features.So it is necessary to combine clinical features,pathological manifestations with radiographic examination results in clarifying the diagnosis.Only based on typical clinical symptoms,clear imaging features and mixed pathological changes of injury and repair,can a deifnitediagnosis be made.

  12. Klassika & ekskremendid / Mari Sobolev

    Index Scriptorium Estoniae

    Sobolev, Mari, 1968-

    2002-01-01

    20.-21. aprillil toimus Pärnus 8. Fideo- ja Vilmifestival alapealkirjaga "Eksperimendid ja klassika". Peakorraldaja Rael Artel. Rami Raski filmist "Legowitz 1999" (soome rühmitus Vivid), läti filmist "Love, death & television", Concordia ülikooli ("Ülemus") ja Academia Grata (portreefilmid Asta Isakist, Andrus Joonasest jm.) programmist, Kadriann Kibuse ja Liina Paakspuu filmist "Urban Obsessions", Mirja-Mari Smidti ja Allan Tõnissoo videost, Marianne Männi koomiksitest kataloogis

  13. Organization experience of diagnostic and medicosocial services for patients with Charcot—Marie—Tooth disease in Krasnoyarsk region

    Directory of Open Access Journals (Sweden)

    E. V. Glushchenko

    2012-01-01

    Full Text Available Hereditary neuropathy Charcot-Marie-Tooth (CMT is the most common form of hereditary polyneuropathies. Goal of the study was the development of evidence-based diagnostic and treatment algorithms using patients with CMT (for example, in Krasnoyarsk Territory.Materials and methods: A total of 324 people. (probands and their relatives 1 and 2 lines of kinship. We analyzed 125 (38,5 % clinical cases of CMT, 64/125 (51,2 % clinical cases were include to statistical analysis (probands and their family trees, past the full range of clinical and laboratory findings according to the protocol this study. Age ranged from 6 to 81 years, median age — 30,5 years, including women 24 (37,5 %, median age — 33,5 years; males 40 (62,5 %, median age — 28,5 years. Methods of diagnosis: clinical, genetic, neurophysiological, molecular genetic, assessment of quality of life assessment of anxiety and depression.Results: The family history of CMT noted in 53/57 (93,0 % cases, with a predominance of autosomal dominant type of inheritance —52 (91,2 % cases. As a result of DNA testing duplication of peripheral myelin protein gene (RMR22 on chromosome 17, held 34 survey, this mutation was found in 17 (50,0 % patients. Modified method of computer esthesiometry for CMT diagnosis using domestic diagnostic equipment “Vibrotester-MBN” BT-02-1 has a high sensitivity in the early stages of the disease and can be recommended for more widespread adoption of on par with other subjects of the Russian Federation.

  14. A Charcot-Marie-Tooth disease resembling to chronic inflammatory demyelinating polyradiculoneuropathy: a report of two cases%慢性炎性脱髓鞘性周围神经病样表现的腓骨肌萎缩症二例

    Institute of Scientific and Technical Information of China (English)

    王毅; 乔凯; 吕传真

    2005-01-01

    目的观察亚急性病程的慢性炎性脱髓鞘性周围神经病(CIDP)样表现的腓骨肌萎缩症(CMT)的临床、病理和电生理特点.方法报道2例亚急性的CIDP样表现的CMT患者的临床、神经电生理及周围神经活检的病理特点.结果 2例证实为17p12重复突变的CMT1A患者,慢性病程中亚急性加重,临床表现类似于CIDP.肌电图示运动神经传导速度(MNCV)减慢、阻滞;神经活检见洋葱头样改变,髓鞘脱失,有炎性细胞的浸润,证明有炎性脱髓鞘的CMT1A存在,且免疫治疗有效.结论慢性病程的CMT1A可有类似于CIDP的病程和临床表现,免疫治疗可改善症状.

  15. Did Jean-Martin Charcot contribute to stroke?

    Science.gov (United States)

    Bogousslavsky, Julien; Paciaroni, Maurizio

    2010-01-01

    Stroke was never identified as a significant, autonomous field of activity of the emerging school of neurology at La Salpêtrière, which developed after the appointment of Jean-Martin Charcot (1825-1893) during the last days of 1861. However, stroke was already present in Charcot's first paper (1851), which dealt with a case of multiple organ cardiac embolism, including middle cerebral artery infarction, at a time when the studies of Rudolf Virchow on thromboembolism were unknown in France. A few years later, Charcot made a still up-to-date description of vascular intermittent claudication, which had only been reported in the horse. In the 1860s, Charcot and his pupils presented several major works dealing with cerebrovascular disease, including famous studies on miliary aneurysms in cerebral hemorrhage. This work was done with Charles Bouchard, at the time Charcot's 'interne', but who would become one of his 'political' opponents 2 decades later, when in 1892, as president of the 'agrégation' jury, he rejected the professorship application of 4 protégés of Charcot, including Joseph Babinski and Georges Gilles de la Tourette. Further work on cerebrovascular disease by Charcot included histological studies of brain 'softening', paraneoplastic cerebral arterial occlusion and consequences of stroke (e.g. arthropathies, vegetative changes, contractures and abnormal movements). Brain localization, one of Charcot's major neurological topics, was also largely based on stroke case studies. Charcot's work on stroke remains poorly recognized, but it demonstrates his unique skills in stimulating scientific work in younger colleagues, many of whom subsequently became major figures of neurology and psychiatry.

  16. Confronting a dramatic situation: the charcot foot complicated by osteomyelitis.

    Science.gov (United States)

    Dalla Paola, Luca

    2014-12-01

    Charcot osteoarthropathy is a serious complication of diabetic neuropathy. Its prevalence in the diabetic population varies in the literature in relation to certain variables, such as the method of assessment, clinical or instrumental; the population studied; and the scope of the selection. This article is intended as a review of the recent literature concerning Charcot osteoarthropathy in its evolution and complications characterized by the development of ulceration and subsequent bone infection. Diagnosis and treatment strategies--either medical or surgical--are discussed both for Charcot arthropathy and osteomyelitis.

  17. Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases

    Science.gov (United States)

    2015-08-24

    Spinal Muscular Atrophy; Charcot-Marie-Tooth Disease; Muscular Dystrophy; Spinal Muscular Atrophy With Respiratory Distress 1; Amyotrophic Lateral Sclerosis; Motor Neuron Disease; Neuromuscular Disease; Peroneal Muscular Atrophy; Fragile X Syndrome

  18. [Hereditary sensory and motor neuropathy and hereditary sensory and autonomic neuropathies: recent advances].

    Science.gov (United States)

    Stojkovic, T

    2011-12-01

    This review summarizes the recent genetic advances in hereditary sensorimotor neuropathy also called Charcot-Marie-Tooth disease. The different new genes discovered in 2010 and their underlying phenotypes will be presented.

  19. Mary, dogma, and psychoanalysis.

    Science.gov (United States)

    Todd, E H

    1985-06-01

    Why does Mary hold her prominent place in Catholic theology to the extent that five specific dogmas have developed around her? Psychoanalytic theory suggests dogma arises out of the psychic needs of people and psychic needs of people are expressed in dogma. The early views of Erich Fromm, a disciple of Freud, are presented to demonstrate that Marian dogma arose from the psychic needs of the people. The views of both Catholic and Protestant thinkers are presented, as well as theological and psychiatric views.

  20. AN ELECTRICAL HAIL MARY.

    Science.gov (United States)

    Neubert, David

    2016-05-01

    Double sequential defibrillation is currently being employed in a number of EMS systems across the United States, including Wake County, N.C.; Fort Worth, Texas; and New Orleans. Even though there isn't a large body of literature surrounding this technique, it's been demonstrated successful in the electrophysiology lab, ED and prehospital settings. Since access to procainamide--another treatment for refractory v fib--is limited, this may be the only available option when faced with a patient who's failed standard ACLS defibrillation and medication administration. It's an intervention that has little chance to do harm, and it may represent the "hail Mary" pass to a successful ROSC touchdown.

  1. On Source of Mary's Tragedy

    Institute of Scientific and Technical Information of China (English)

    胡杰

    2016-01-01

    Long Day's Journey into Night is a great work of American dramatist Eugene O'Neill. As the only female protagonist fully portrayed in the play, Mary's tragedy generated a hot debate. In this thesis, through detailed analysis, it is found that Mary is the victim of male-dominated society and men are the source of her tragedy.

  2. Jean-Baptiste Charcot, the French Antarctic expedition and scurvy.

    Science.gov (United States)

    Teive, Hélio Afonso Ghizoni; Germiniani, Francisco Manoel Branco; Munhoz, Renato Puppi

    2014-07-01

    During the second expedition to the South Pole, Commander Jean-Baptiste Charcot and some members of the crew of "Pourquoi Pas?" developed symptoms suggestive of scurvy. The clinical picture was totally reversed after dietary changes.

  3. Exostectomy for chronic midfoot plantar ulcer in Charcot deformity

    DEFF Research Database (Denmark)

    Laurinaviciene, R.; Kirketerp-Moeller, K.; Holstein, Per Evald

    2008-01-01

    Charcot midfoot ulcers are rare and very difficult to heal, with surgery being an option. This retrospective study assessed healing rates, complications, and the incidence of re-ulceration and other foot ulcer problems following exostectomies Udgivelsesdato: 2008/2......Charcot midfoot ulcers are rare and very difficult to heal, with surgery being an option. This retrospective study assessed healing rates, complications, and the incidence of re-ulceration and other foot ulcer problems following exostectomies Udgivelsesdato: 2008/2...

  4. Jean-Martin Charcot: neurologist by avocation, nephrologist by yearning.

    Science.gov (United States)

    Eknoyan, Garabed

    2011-01-01

    In an age of medical advances and specialization, Jean-Martin Charcot (1825-1893) helped found the discipline of neurology and in 1882 was appointed the first Professor of Diseases of the Nervous System in France. As an investigator with broad interests and vast knowledge, Charcot contributed to several other disciplines. An early mentor and dominant figure in Charcot's formative years was Pierre Rayer (1793-1867), famous for his seminal contributions to the study of the kidney, who gifted to Charcot his passion for clinical pathological correlations and likely a yearning for the study of kidney diseases. Famous for the clarity and incisiveness of his formal teaching presentations, Charcot lectured on the kidney at the Faculty of Medicine in Paris in 1877. Translated into English and published as a book titled Lectures on Bright's Disease, those lectures became widely accessible and quoted in the literature through the 1940s. In addition, at a time when he was already concentrating on the study of neurological disorders, Charcot maintained his life-long interest in the kidney and published original studies on the pathological changes of the kidney in gout and experimental lead poisoning, as well as supporting a study of hysterical ischuria by his students.

  5. Charcot neuroarthropathy of the foot and ankle: diagnosis and management strategies.

    Science.gov (United States)

    Blume, Peter A; Sumpio, Bauer; Schmidt, Brian; Donegan, Ryan

    2014-01-01

    This article reviews current literature discussing the etiology, pathophysiology, diagnosis and imaging, and conservative and surgical treatment of Charcot osteoarthropathy. The treatment of Charcot osteoarthropathy with concurrent osteomyelitis is also discussed.

  6. Bone mineral density in diabetes mellitus patients with and without a Charcot foot

    DEFF Research Database (Denmark)

    Christensen, Tomas M; Bülow, Jens; Simonsen, Lene

    2010-01-01

    To measure bone mineral density in patients with diabetes mellitus and the complication Charcot osteoarthropathy (CA).......To measure bone mineral density in patients with diabetes mellitus and the complication Charcot osteoarthropathy (CA)....

  7. Victor Hugo, Marie Tudor

    OpenAIRE

    Sabourin, Lise

    2016-01-01

    Dans la collection de poche qui rend aisément accessibles les grandes pièces du répertoire français, Clélia Anfray donne, avec une introduction (pp. 7-42), une notice sur la genèse, la rédaction et la parution, un historique des représentations, une chronologie, des indications bibliographiques et des notes, le texte du drame consacré par Hugo à cette «reine qui soit une femme. Grande comme une reine, vraie comme une femme» qu’il veut voir en Marie Tudor («Préface», p. 47). La documentation h...

  8. Jean-Martin Charcot's Role in the 19th Century Study of Music Aphasia

    Science.gov (United States)

    Johnson, Julene K.; Lorch, Marjorie; Nicolas, Serge; Graziano, Amy

    2013-01-01

    Jean-Martin Charcot (1825-93) was a well-known French neurologist. Although he is widely recognized for his discovery of several neurological disorders and his research into aphasia, Charcot's ideas about how the brain processes music are less well known. Charcot discussed the music abilities of several patients in the context of his "Friday…

  9. Freud with Charcot: Freud's discovery and the question of diagnosis.

    Science.gov (United States)

    Lepoutre, Thomas; Villa, François

    2015-04-01

    Although Charcot's seminal role in influencing Freud is widely stated, although Freud's trip to Paris to study with Charcot is well recognized as pivotal in his shift from neurological to psychopathological work, a key fact of the Freudian heuristic remains largely underestimated: namely, that Freud's psychopathological breakthrough, which gave birth to psychoanalysis, cannot be separated from his 'diagnostic preoccupation', which is a crucial and at times the first organizing principle of his earliest writings. The purpose of this article is therefore to reopen the question of diagnosis by following its development along the path leading from Charcot to Freud. The authors demonstrate that Freud's careful attention to diagnostic distinctions follows strictly in the direction of Charcot's 'nosological method'. More importantly, the article intends to identify the precise way in which his ideas operate in Freud's own work, in order to understand how Freud reinvests them to forge his own nosological system. If the authors trace the destiny of Charcot's lessons as they reach Freud's hands, it is the importance granted to mixed neuroses in Freud's psychopathology that allows them to pinpoint the role played by the diagnostic process in the rationality of psychoanalysis.

  10. Etiology, pathophysiology and classifications of the diabetic Charcot foot

    Directory of Open Access Journals (Sweden)

    Nikolaos Papanas

    2013-05-01

    Full Text Available In people with diabetes mellitus, the Charcot foot is a specific manifestation of peripheral neuropathy that may involve autonomic neuropathy with high blood flow to the foot, leading to increased bone resorption. It may also involve peripheral somatic polyneuropathy with loss of protective sensation and high risk of unrecognized acute or chronic minor trauma. In both cases, there is excess local inflammatory response to foot injury, resulting in local osteoporosis. In the Charcot foot, the acute and chronic phases have been described. The former is characterized by local erythema, edema, and marked temperature elevation, while pain is not a prominent symptom. In the latter, signs of inflammation gradually recede and deformities may develop, increasing the risk of foot ulceration. The most common anatomical classification describes five patterns, according to the localization of bone and joint pathology. This review article aims to provide a brief overview of the diabetic Charcot foot in terms of etiology, pathophysiology, and classification.

  11. Surgical reconstruction of charcot foot neuroarthropathy, a case based review.

    Science.gov (United States)

    Kučera, Tomáš; Šponer, Pavel; Šrot, Jaromír

    2014-01-01

    Our case-based review focuses on limb salvage through operative management of Charcot neuroarthropathy of the diabetic foot. We describe a case, when a below-knee amputation was considered in a patient with chronic Charcot foot with a rocker-bottom deformity and chronic plantar ulceration. Conservative treatment failed. Targeted antibiotic therapy and operative management (Tendo-Achilles lengthening, resectional arthrodesis of Lisfranc and midtarsal joints, fixation with large-diameter axial screws, and plaster cast) were performed. On the basis of this case, we discuss options and drawbacks of surgical management. Our approach led to healing of the ulcer and correction of the deformity. Two years after surgery, we observed a significant improvement in patient's quality of life. Advanced diagnostic and imaging techniques, a better understanding of the biomechanics and biology of Charcot neuroarthropathy, and suitable osteosynthetic material enables diabetic limb salvage.

  12. Etiology, pathophysiology and classifications of the diabetic Charcot foot.

    Science.gov (United States)

    Papanas, Nikolaos; Maltezos, Efstratios

    2013-01-01

    In people with diabetes mellitus, the Charcot foot is a specific manifestation of peripheral neuropathy that may involve autonomic neuropathy with high blood flow to the foot, leading to increased bone resorption. It may also involve peripheral somatic polyneuropathy with loss of protective sensation and high risk of unrecognized acute or chronic minor trauma. In both cases, there is excess local inflammatory response to foot injury, resulting in local osteoporosis. In the Charcot foot, the acute and chronic phases have been described. The former is characterized by local erythema, edema, and marked temperature elevation, while pain is not a prominent symptom. In the latter, signs of inflammation gradually recede and deformities may develop, increasing the risk of foot ulceration. The most common anatomical classification describes five patterns, according to the localization of bone and joint pathology. This review article aims to provide a brief overview of the diabetic Charcot foot in terms of etiology, pathophysiology, and classification.

  13. Tooth sensitivity and whitening.

    Science.gov (United States)

    Swift, Edward J

    2005-09-01

    This article presents a review of the basic concepts of tooth sensitivity and how those concepts apply to cervical dentin hypersensitivity and the sensitivity frequently associated with tooth whitening. The etiology and treatment of cervical dentin hypersensitivity are described. The clinical presentation, incidence, and predisposing factors for sensitivity associated with tooth whitening also are discussed.

  14. Multistate Aquatic Resources Information System (MARIS)

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — MARIS is an internet-based information sharing network that allows multiple states to provide a common set of variables via a single web interface. MARIS is not a...

  15. Mary Shelley: Teaching and Learning through "Frankenstein"

    Science.gov (United States)

    Girard, Theresa M.

    2009-01-01

    In the writing of "Frankenstein", Mary Shelley was able to change the course of women's learning, forever. Her life started from an elite standpoint as the child of Mary Wollstonecraft and William Godwin. As such, she was destined to grow to be a major influence in the world. Mary Shelley's formative years were spent with her father and his many…

  16. Plantar Temperature Response to Walking in Diabetes with and without Acute Charcot: The Charcot Activity Response Test

    Directory of Open Access Journals (Sweden)

    Bijan Najafi

    2012-01-01

    Full Text Available Objective. Asymmetric plantar temperature differences secondary to inflammation is a hallmark for the diagnosis and treatment response of Charcot foot syndrome. However, little attention has been given to temperature response to activity. We examined dynamic changes in plantar temperature (PT as a function of graduated walking activity to quantify thermal responses during the first 200 steps. Methods. Fifteen individuals with Acute Charcot neuroarthropathy (CN and 17 non-CN participants with type 2 diabetes and peripheral neuropathy were recruited. All participants walked for two predefined paths of 50 and 150 steps. A thermal image was acquired at baseline after acclimatization and immediately after each walking trial. The PT response as a function of number of steps was examined using a validated wearable sensor technology. The hot spot temperature was identified by the 95th percentile of measured temperature at each anatomical region (hind/mid/forefoot. Results. During initial activity, the PT was reduced in all participants, but the temperature drop for the nonaffected foot was 1.9 times greater than the affected side in CN group (P=0.04. Interestingly, the PT in CN was sharply increased after 50 steps for both feet, while no difference was observed in non-CN between 50 and 200 steps. Conclusions. The variability in thermal response to the graduated walking activity between Charcot and non-Charcot feet warrants future investigation to provide further insight into the correlation between thermal response and ulcer/Charcot development. This stress test may be helpful to differentiate CN and its response to treatment earlier in its course.

  17. An overview of conservative treatment options for diabetic Charcot foot neuroarthropathy

    Directory of Open Access Journals (Sweden)

    Crystal L. Ramanujam

    2011-05-01

    Full Text Available Conservative management of Charcot foot neuroarthropathy remains efficacious for certain clinical scenarios. Treatment of the patient should take into account the stage of the Charcot neuroarthopathy, site(s of involvement, presence or absence of ulceration, presence or absence of infection, overall medical status, and level of compliance. The authors present an overview of evidence-based non-operative treatment for diabetic Charcot neuroarthropathy with an emphasis on the most recent developments in therapy.

  18. Mortality Risk of Charcot Arthropathy Compared With That of Diabetic Foot Ulcer and Diabetes Alone

    OpenAIRE

    Sohn, Min-Woong; Lee, Todd A.; Stuck, Rodney M; Frykberg, Robert G.; Budiman-Mak,Elly

    2009-01-01

    OBJECTIVE The purpose of this study was to compare mortality risks of patients with Charcot arthropathy with those of patients with diabetic foot ulcer and those of patients with diabetes alone (no ulcer or Charcot arthropathy). RESEARCH DESIGN AND METHODS A retrospective cohort of 1,050 patients with incident Charcot arthropathy in 2003 in a large health care system was compared with patients with foot ulcer and those with diabetes alone. Mortality was determined during a 5-year follow-up pe...

  19. Osteotomies for the Management of Charcot Neuroarthropathy of the Foot and Ankle.

    Science.gov (United States)

    Scott, Ryan T; DeCarbo, William T; Hyer, Christopher F

    2015-07-01

    Patients with diabetic neuropathy that develop unstable Charcot neuroarthropathy not only have an autoimmune disease that prolongs the healing process, they also often have an inability to maintain a non-weight bearing status. Charcot neuroarthopathy is often devastating to the structure and stability of the foot and ankle. This disease may require permanent bracing, reconstructive surgical stabilization, and in some cases lower leg amputation. Successful management of Charcot neuroarthopathy requires diligence and surveillance by physician and patient alike.

  20. Charcots artropati som årsag til hypoparatyroid hyperkalcæmi

    DEFF Research Database (Denmark)

    Engberg, Susanne; Jensen, Jens-Erik Beck; Kønig, Karen Bay

    2012-01-01

    A 45-year-old woman with type 2 diabetes and multiple diabetic complications was diagnosed with hypoparathyroid hypercalcaemia. The bone scintigraphy showed Charcots arthropathy. Blood tests, computer tomography and mammography did not give any indication of malignancy, vitamin-D intoxication nor...... hyperthyroidism. Charcots arthropathy is not a recognized cause of hypoparathyroid hypercalcaemia, but the mechanism might be increased boneresorption. We recommend that Charcots arthropathy is considered a cause of hypoparathyroid hypercalcaemia in patients with diabetic neuropathy....

  1. To Tell the Tooth

    Science.gov (United States)

    ... To Tell the Tooth Print and Take a Quiz + Watch Videos Dudley and Friends Sesame Street + For Preteens Healthy Habits Nutrition Be a Dentist + For Educators Career Resources Presentations and Resources Smile Smarts Dental Health Curriculum MouthHealthy Kids > Games and Quizzes > To Tell the Tooth To Tell ...

  2. Nasal tooth: case report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Si Hyun; Kim, Ji Hye; Hwang, Hee Young; Yang, Dal Mo; Kim, Hyung Sik; Park, Chol Heui [Gachon Medical School, Inchon (Korea, Republic of)

    2002-12-01

    Ectopic tooth is not uncommon and usually occurs in the palate and maxillary sinus. We report a case of ectopic tooth located in the nasal cavity, a rare site. The mass depicted by CT was highly attenuated, and central lucency was observed.

  3. Mary Rudenberg, Music Therapist Pioneer

    Directory of Open Access Journals (Sweden)

    Christine Neugebauer

    2010-03-01

    Full Text Available It was during my training when I came to understand and appreciate the knowledge base and experience that Mary Rudenberg has contributed to the field of music therapy. Medical music therapy was still in its infancy and the music therapy internship program at the University of Texas Medical Branch in Galveston, Texas was one of a few internships in the nation offering music therapy training in a medical setting.

  4. Neuropathic arthropathy (Charcot's joint) in dialysis patients

    Energy Technology Data Exchange (ETDEWEB)

    Meneghello, A.; Bertoli, M.

    1984-08-01

    To the author's knowledge, uraemic neuropathy has not been previously reported as a cause of Charcot's joint. In this paper they present three cases in which the association between clinical and radiographic patterns suggest the diagnosis of neuropathic arthropathy. The features of uraemic neuropathy are stressed and the role of secondary hyperparathyroidism in the development of this type of arthropathy is discussed. The extremely severe hyperparathyroidism reported here, may cause tendon and ligament disease, especially at the site of their bone insertion. Uraemic tendon and ligament failures weaken joints and produce further instability, which may be a precipitating factor of uraemic Charcot's joint in patients undergoing chronic haemodialysis. 5 figs.

  5. Current concepts of Charcot foot in diabetic patients.

    Science.gov (United States)

    La Fontaine, Javier; Lavery, Lawrence; Jude, Edward

    2016-03-01

    The Charcot foot is an uncommon complication of neuropathy in diabetes. It is a disabling and devastating condition. The etiology of the Charcot foot is unknown, but it is characterized by acute inflammation with collapse of the foot and/or the ankle. Although the cause of this potentially debilitating condition is not known, it is generally accepted that the components of neuropathy that lead to foot complications must exist. When it is not detected early, a severe deformity will result in a secondary ulceration, infection, and amputation. Immobilization in the early stages is the key for success, but severe deformity may still develop. When severe deformity is present, bracing may be attempted but often patients will need surgical intervention. Good success has been shown with internal and external fixation. In patients with concomitant osteomyelitis, severe deformity, and/or soft tissue infection, a high amputation may be the best treatment of choice.

  6. MODERN APPROACHES TO SURGICAL TREATMENT OF CHARCOT NEUROARTHROPATHY (review

    Directory of Open Access Journals (Sweden)

    S. V. Pavlyuchenko

    2016-01-01

    Full Text Available The present review addresses a pressing orthopaedic issue of surgical treatment for patients with severe foot deformities occurring as consequence to Charcot neuroarthropathy. Described pathology is a severe threatening condition causing high risk of infections and potential limb loss. The paper describes main foot reconstructive procedures employed depending on pathology stage and localization as well as identifies ways to improve surgical treatment of affected patients.

  7. Incidence and management of ulcers in diabetic Charcot feet.

    Science.gov (United States)

    Larsen, K; Fabrin, J; Holstein, P E

    2001-09-01

    This study followed 115 patients with diabetes--who between them had 140 feet with Charcot's arthropathy--over six to 114 months (median: 48). A total of 43 patients (37%) developed ulcers in 53 feet. Their treatment was multifactorial. An offloading regimen was adopted, with the use of crutches and therapeutic sandals with soft, individually moulded insoles, followed by adjusted or bespoke shoes. Recalcitrant ulcers were treated with surgery in 16 patients (37%). Antibiotics were needed by 21 patients (49%). The incidence of ulceration was 17% per year. The median time interval between the acute component of Charcot's arthropathy and ulcer development was 36 months (range: 0-120 months). In seven patients, the ulcer developed during the acute phase. In 12 patients the ulcers were localised to the rockerbottom deformity in the mid-foot region, but in 31 patients other regions were affected. Dynamic footprint analysis was used to help adjust the offloading shoe/insole on the rockerbottom deformity. Such ulcers took twice as long to heal as other ulcers. Surgical treatment comprised: major amputation (two patients), arthrodesis for unstable ankle (three patients), toe amputations (seven patients), resection of the rockerbottom deformity (one patient) and other revisions (three patients). One patient died with an unhealed ulcer. There is a four-fold risk of ulcers in diabetic Charcot deformity compared with the overall risk of foot ulcers in diabetic feet. Healing was achieved in 40 patients (93%). The surgical intervention rate of 37% in ulcer cases in Charcot feet was low compared with the literature.

  8. Charcot arthropathy in ultrasound examination - a case report.

    Science.gov (United States)

    Płaza, Mateusz; Nowakowska-Płaza, Anna; Walentowska-Janowicz, Marta; Chojnowski, Marek; Sudoł-Szopińska, Iwona

    2016-06-01

    This article presents a patient with a long history of type 1 diabetes mellitus complicated with neuropathy and Charcot disease. The most common cause of neuropathic osteoarthropathy, called Charcot osteoarthropathy, is poorly controlled diabetes. The clinical picture is characterized by considerable edema, redness and increased skin temperature with relatively slight pain due to injury to nerve fibers responsible for pain sensation. The differential diagnosis should include bacterial or autoimmune arthritis, arthritis associated with gout as well as venous thrombosis and injury. The contribution of a local inflammatory reaction and abnormal bone turnover with excessive osteoclast activity might play a role in the etiopathogenesis of this disease. As a result, osseous and articular destruction progresses rapidly leading to irreversible deformity of the foot. Avoiding weight-bearing and resting the foot in a specially selected plaster cast is the most important part of treatment. Patients with the aforementioned complaints are referred to radiologists for imaging examinations. An ultrasonographer should pay attention to changes typical of Charcot arthropathy, such as: inflammatory and destructive changes in joints of the foot, uneven contour of bones with thickening and periosteal hyperemia as well as soft tissue swelling.

  9. Charcot arthropathy in ultrasound examination – a case report

    Directory of Open Access Journals (Sweden)

    Mateusz Płaza

    2016-06-01

    Full Text Available This article presents a patient with a long history of type 1 diabetes mellitus complicated with neuropathy and Charcot disease. The most common cause of neuropathic osteoarthropathy, called Charcot osteoarthropathy, is poorly controlled diabetes. The clinical picture is characterized by considerable edema, redness and increased skin temperature with relatively slight pain due to injury to nerve fibers responsible for pain sensation. The differential diagnosis should include bacterial or autoimmune arthritis, arthritis associated with gout as well as venous thrombosis and injury. The contribution of a local inflammatory reaction and abnormal bone turnover with excessive osteoclast activity might play a role in the etiopathogenesis of this disease. As a result, osseous and articular destruction progresses rapidly leading to irreversible deformity of the foot. Avoiding weight-bearing and resting the foot in a specially selected plaster cast is the most important part of treatment. Patients with the aforementioned complaints are referred to radiologists for imaging examinations. An ultrasonographer should pay attention to changes typical of Charcot arthropathy, such as: inflammatory and destructive changes in joints of the foot, uneven contour of bones with thickening and periosteal hyperemia as well as soft tissue swelling.

  10. Charcot joints as chronic complications of diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Peter Andrea

    2002-01-01

    Full Text Available Introduction Charcot joints are considered to be chronic complications of diabetes mellitus. Although it is not a common disease, due to its progressive character, it can lead to permanent immobility and reduces quality of life in these patients. It is known that evolution of Charcot joints has three stages and the best results of therapy can only be achieved in the first stage. Later, only surgical treatment can be considered with very poor results. Case report This is a case report of a young patient with a very severe form of diabetic arthropathy and other complications of diabetes. This 27-year old woman suffered from diabetes for 10 years and her family history showed that her grandfather and uncle had diabetes too. During physical examination severe deformities of the foot and malleolus were detected. Detection of chronic complications required evaluation of the level of neuropathy. Discussion Chronic complications of diabetes are very frequent. A severe form of complications are Charcot joints that can lead to permanent immobility. That is why it is important to recognize the early signs and symptoms of these changes in order to treat them in the early phase when best results are expected.

  11. Charcot arthropathy in ultrasound examination – a case report

    Science.gov (United States)

    Nowakowska-Płaza, Anna; Walentowska-Janowicz, Marta; Chojnowski, Marek; Sudoł-Szopińska, Iwona

    2016-01-01

    This article presents a patient with a long history of type 1 diabetes mellitus complicated with neuropathy and Charcot disease. The most common cause of neuropathic osteoarthropathy, called Charcot osteoarthropathy, is poorly controlled diabetes. The clinical picture is characterized by considerable edema, redness and increased skin temperature with relatively slight pain due to injury to nerve fibers responsible for pain sensation. The differential diagnosis should include bacterial or autoimmune arthritis, arthritis associated with gout as well as venous thrombosis and injury. The contribution of a local inflammatory reaction and abnormal bone turnover with excessive osteoclast activity might play a role in the etiopathogenesis of this disease. As a result, osseous and articular destruction progresses rapidly leading to irreversible deformity of the foot. Avoiding weight-bearing and resting the foot in a specially selected plaster cast is the most important part of treatment. Patients with the aforementioned complaints are referred to radiologists for imaging examinations. An ultrasonographer should pay attention to changes typical of Charcot arthropathy, such as: inflammatory and destructive changes in joints of the foot, uneven contour of bones with thickening and periosteal hyperemia as well as soft tissue swelling. PMID:27446605

  12. [Charcot and Babinski: beyond a simple teacher-student relationship].

    Science.gov (United States)

    Massie, Rami

    2004-08-01

    Jean-Martin Charcot (1825-1893) is now considered to be the father of clinical neurology in France. He trained a generation of eminent neurologists, among them Joseph Babinski, with whom he had a special relationship. Babinski was undoubtedly Charcot's favorite pupil and they enjoyed an excellent collaboration at la Salpétrière. Even though both men felt tremendous respect for each other, it is sad that this relationship may, in one instance, have been detrimental to Babinski. This is probably the reason why Bouchard denied him full professorship, a decision with eventual consequences for both men. In spite of this, the neurologist of Polish origin held his master in tremendous admiration, even as he pursued Charcot's research on hysteria after his death. Even though Babinski eventually contradicted his master on many fundamental issues, it did not affect his devotion to him. The relationship between the two men can be considered as more than a simple relationship between a teacher and his pupil and may be compared to a father-son relationship, which is a reminder of the original model of Hippocratic teaching.

  13. Decellularized Tooth Bud Scaffolds for Tooth Regeneration.

    Science.gov (United States)

    Zhang, W; Vazquez, B; Oreadi, D; Yelick, P C

    2017-01-01

    Whole tooth regeneration approaches currently are limited by our inability to bioengineer full-sized, living replacement teeth. Recently, decellularized organ scaffolds have shown promise for applications in regenerative medicine by providing a natural extracellular matrix environment that promotes cell attachment and tissue-specific differentiation leading to full-sized organ regeneration. We hypothesize that decellularized tooth buds (dTBs) created from unerupted porcine tooth buds (TBs) can be used to guide reseeded dental cell differentiation to form whole bioengineered teeth, thereby providing a potential off-the-shelf scaffold for whole tooth regeneration. Porcine TBs were harvested from discarded 6-mo-old pig jaws, and decellularized by successive sodium dodecyl sulfate/Triton-X cycles. Four types of replicate implants were used in this study: 1) acellular dTBs; 2) recellularized dTBs seeded with porcine dental epithelial cells, human dental pulp cells, and human umbilical vein endothelial cells (recell-dTBs); 3) dTBs seeded with bone morphogenetic protein (BMP)-2 (dTB-BMPs); and 4) freshly isolated nondecellularized natural TBs (nTBs). Replicate samples were implanted into the mandibles of host Yucatan mini-pigs and grown for 3 or 6 mo. Harvested mandibles with implanted TB constructs were fixed in formalin, decalcified, embedded in paraffin, sectioned, and analyzed via histological methods. Micro-computed tomography (CT) analysis was performed on harvested 6-mo samples prior to decalcification. All harvested constructs exhibited a high degree of cellularity. Significant production of organized dentin and enamel-like tissues was observed in dTB-recell and nTB implants, but not in dTB or dTB-BMP implants. Micro-CT analyses of 6-mo implants showed the formation of organized, bioengineered teeth of comparable size to natural teeth. To our knowledge, these results are the first to describe the potential use of dTBs for functional whole tooth regeneration.

  14. Jean-Baptiste Charcot in Rio de Janeiro: glamorous trip and celebrity in 1908.

    Science.gov (United States)

    Teive, Hélio A G; Munhoz, Renato P; Lima, Plínio G de; Germiniani, Francisco M B

    2015-09-01

    The authors review the visit of Commander Charcot and the crew of his ship, the "Pourquoi Pas?", to Rio de Janeiro, Brazil, in 1908, where he stayed for eight days, while en-route as part of the second French expedition to the Antarctic. It was a glamorous stay as Commander Charcot was treated as a true star and international celebrity, befitting his position.

  15. Charcot Neuropathic Arthropathy of the Foot: A Literature Review and Single-Center Experience

    Science.gov (United States)

    Shaikh, Haroun Hassan

    2016-01-01

    Charcot neuropathic osteoarthropathy of the foot is a relatively common complication of diabetic neuropathy. Incorrect diagnosis and improper treatment often result in the extremity having to be amputated. This paper summarises the current view on the etiology, diagnostics, and treatment of diabetic Charcot neuropathic osteoarthropathy, with particular focus on preserving the extremity through surgical intervention from our own experiences. PMID:27656656

  16. Charcot Neuropathic Arthropathy of the Foot: A Literature Review and Single-Center Experience

    OpenAIRE

    Tomas Kucera; Haroun Hassan Shaikh; Pavel Sponer

    2016-01-01

    Charcot neuropathic osteoarthropathy of the foot is a relatively common complication of diabetic neuropathy. Incorrect diagnosis and improper treatment often result in the extremity having to be amputated. This paper summarises the current view on the etiology, diagnostics, and treatment of diabetic Charcot neuropathic osteoarthropathy, with particular focus on preserving the extremity through surgical intervention from our own experiences.

  17. Charcot Neuropathic Arthropathy of the Foot: A Literature Review and Single-Center Experience

    Directory of Open Access Journals (Sweden)

    Tomas Kucera

    2016-01-01

    Full Text Available Charcot neuropathic osteoarthropathy of the foot is a relatively common complication of diabetic neuropathy. Incorrect diagnosis and improper treatment often result in the extremity having to be amputated. This paper summarises the current view on the etiology, diagnostics, and treatment of diabetic Charcot neuropathic osteoarthropathy, with particular focus on preserving the extremity through surgical intervention from our own experiences.

  18. Autogenous tooth transplantation for replacing a lost tooth: case reports

    OpenAIRE

    Kang, Ji-Youn; Chang, Hoon-Sang; Hwang,Yun-Chan; Hwang, In-Nam; Oh, Won-Mann; LEE, Bin-Na

    2013-01-01

    The autogenous tooth transplantation is an alternative treatment replacing a missing tooth when a suitable donor tooth is available. It is also a successful treatment option to save significant amount of time and cost comparing implants or conventional prosthetics. These cases, which required single tooth extraction due to deep caries and severe periodontal disease, could have good results by transplanting non-functional but sound donor tooth to the extraction site.

  19. [Jean-Martin Charcot (1825-1893): a physician with multiple facets].

    Science.gov (United States)

    Lellouch, Alain

    2013-12-01

    This work is registered in the year (2013) commemorating the 120 years since Jean-Martin Charcot's (1825-1893) death. Presently, the event takes place during 2013, in France, in Paris, at Hôpital de la Salpêtrière where Charcot practiced as medical chief of l'Hospice de la Vieillesse-Femmes, from 1862 until he died in 1893. The aim of the research is to show, from various examples and sources (printed and handwritten: fonds d'archives Charcot de la Salpêtrière) how talented Charcot was as a clinician, pathologist and microscopist, researcher and experimenter, teacher, artist, designer, cartoonist, polyglot and traveller), how varied his medical career was and how innovative his scientific method was. All this permitted Charcot to make an impressive number of medical discoveries in various fields which are today known as geriatrics and rheumatology, internal medicine, cardiology, neurology, psychiatry and paranormal processes.

  20. Episodic central nervous system symptoms with reversible white matter involvement in Chinese patients with X-linked Charcot-Marie-Tooth disease and literatures review%伴一过性中枢神经障碍的3个X连锁显性夏科-马里-图斯病家系的临床和遗传学研究及文献复习

    Institute of Scientific and Technical Information of China (English)

    张海华; 高利国; 王静敏; 高志杰; 姜玉武; 王爽; 熊晖; 常杏芝; 吴晔

    2013-01-01

    Objective To analyze the phenotype and genotype of CMTX1 patients with episodic transient reversible white matter involvement,and delineate the features of brain MRI in the episode and the possible mechanisms.Method Three Chinese probands and their family members were sequenced in the coding regions of GJB1.With the other 16 reported CMTX1 patients with episodic transient reversible white matter involvement,the clinical feature of the episodic central nervous system symptoms and the genotypes were reviewed.Result Missense mutations in GJB1 were identified in all 3 probands.In 19 patients with transient reversible white matter involvement,the episodes were manifested as weakness of the limbs,dysarthria,and dysphagia,without disturbance of consciousness or seizures.The episodes lasted for 13 hours (10 min-72 hours) with complete remission in all patients; There were multiple episodes in 9 patients.During the episode,brain MRI showed symmetrical high signals in T2 weighted,Flair and DWI images in periventricular white matter,with predominance in posterior region including splenium of corpus callosum.These changes in imaging were most prominent during or within 1 week after the clinical episode.Significant improvements occurred within 1 month,with complete remission within 4-6 months.No specific locations of mutant amino acids in GJB1 protein were found in these patients with episodic transient reversible white matter involvement.Conclusion Episodic transient reversible white matter involvement may present in a small number of patients with CMTX1.Transient edema of oligodendrocytes due to the dysfunction of gap junction may be involved in the pathogenesis.There is no correlation between the location of the mutant amino acids in GJB1 and the occurrence of the episodes.%目的 分析伴有短暂可逆性脑白质病变的X连锁显性夏科-马里-图斯病(CMTX1)患者临床和头颅核磁(MRI)特点及可能的发生机制,探讨GJB1基因型与患者脑白质病变的相关关系.方法 以临床诊断为CMTX1且伴短暂可逆性脑白质病变的3个先证者及其家庭成员为研究对象,对其进行GJB1基因检测分析.并收集国际已报道的16例患者,对连同本研究3例共19例进行临床特征及突变类型的总结分析.结果 3例先证者均发现GJB1基因编码区的错义突变.19例伴短暂可逆性脑白质病变的CMXT1患者发作期表现为:四肢无力、构音障碍、吞咽困难等,无意识障碍及惊厥;平均发作持续时间13 h(10 min~72 h),发作均可自行完全缓解;9例病程中有多次发作;发作期头颅MRI表现为脑室周围白质对称性长T1、长T2、Flair高信号,DWI高信号,后头部显著,常累及胼胝体压部,发作期及发作后1周内脑白质异常最为明显,1个月明显好转,4~6个月完全恢复.发生可逆性脑白质病变的CMTX1患者的突变位点在GJB1蛋白上无特定分布区域.结论 少数CMTX1患者可出现短暂可逆性的脑白质病变,推测可能与细胞间通道功能障碍导致胶质细胞一过性水肿有关.GJB1基因型与患者是否出现脑白质病变临床表型无明确相关性.

  1. Näitused / Mari Sobolev

    Index Scriptorium Estoniae

    Sobolev, Mari, 1968-

    1998-01-01

    Rotermanni soolaladu. "Elektrokardiogramm" (tegevuskunsti üritus); Vaal-galerii. Antoni T̉pies "Litograafiaid aastatest 1973-1995"; Mari Kadanik, Eero Barndõk, Rain Ader "Pildid" (maalid); Paldiski Põhikool. "Niemenlautta ja Hugo Simbergi fotod" (soome kunstniku fotode koopiad, pildistatud enne 1915. a.; Kullo lastegalerii. Neli uut näitust.(lastekunst); Arhitektuurimuuseum. Arnold Matteus - Tartu linna arhitekt (juubelinäitus), Alvar Aalto "Kolm objekti Eestis"; Linnagalerii Tallinnas. "Valge" (ruumi- ja moekunsti näitus); Sammas-galerii. Jüri Jegorow "Insect" (arvutigraafika); Endla Teatri palmisaal. "Muzik in der Kunst" (Tallinna kunstitudengite näitus); Eesti Rahvusraamatukogu. Õie Kütt "Uued ja vanad ehted"

  2. [Review] Mary Toft's Rabbit Tale

    OpenAIRE

    Jones, Emrys

    2013-01-01

    Originally broadcast in April 2011 and aired again by BBC Radio 4 this November, Mary Toft’s Rabbit Tale is a radio drama retelling the story of its titular fraudster’s brief notoriety. With a high-profile cast – including singer Will Young as Toft’s husband and Rupert Graves as man-midwife, John Howard – the play explores a number of issues related to the alleged rabbit births of 1726 and their impact on public discourse of the time.

  3. Tooth in oropharynx

    Directory of Open Access Journals (Sweden)

    D Nagarajappa

    2011-01-01

    Full Text Available The incidence of ectopic teeth has increased. In many cases, the etiology of ectopic teeth cannot be identified. Ectopic tooth in deciduous dentition period is very rare and information is limited about its causes and characteristics. The conditions commonly associated with an increased prevalence of ectopic teeth include cleft lip and palate, cleidocranial dysplasia, and Gardner syndrome. The diagnosis is made by the clinical and radiological examinations. The indication for extraction in ectopic teeth cases is in general determined by the presence of symptomatology, or by the need for preventing future complications. We present a case of an ectopic maxillary tooth in a 4 year-old boy. In addition, this report also addresses a young patient with a tooth in the oropharynx with the objective of non traumatic etiology, and such a clinical presentation is extremely rare. The authors believe the case presented here is the first documented case of an ectopic supernumerary tooth seen in the oropharynx.

  4. Tooth in oropharynx.

    Science.gov (United States)

    Nagarajappa, D; Manjunatha, Bs

    2011-09-01

    The incidence of ectopic teeth has increased. In many cases, the etiology of ectopic teeth cannot be identified. Ectopic tooth in deciduous dentition period is very rare and information is limited about its causes and characteristics. The conditions commonly associated with an increased prevalence of ectopic teeth include cleft lip and palate, cleidocranial dysplasia, and Gardner syndrome. The diagnosis is made by the clinical and radiological examinations. The indication for extraction in ectopic teeth cases is in general determined by the presence of symptomatology, or by the need for preventing future complications. We present a case of an ectopic maxillary tooth in a 4 year-old boy. In addition, this report also addresses a young patient with a tooth in the oropharynx with the objective of non traumatic etiology, and such a clinical presentation is extremely rare. The authors believe the case presented here is the first documented case of an ectopic supernumerary tooth seen in the oropharynx.

  5. Colour Symbols in Mari Songs

    Directory of Open Access Journals (Sweden)

    Natalia Glukhova

    2016-06-01

    Full Text Available This article presents a system of colour symbols in Mari folk songs based on the results of a multifold investigation. The research was carried out with the help of a complex technique applied to 2100 songs from different song collections. Mari colour symbols have never before been the object of research. The process of investigation included several steps. The most important of these was the semantic analysis that helped to discern 2000 mentions of four main spectre colours as well as white, black, silver, and golden. Quantitative data evaluation singled out a dominant group by a dichotomous method, applying the principle of simple majority employed in mathematical statistics. The same technique divided the other colour symbols into complementary, auxiliary, and insignificant groups. The results of an investigation into ethnic symbology are also shown graphically. The main reconstructed meanings of colour in the analysed songs denote such emotions as joy, wonder, astonishment, grief, melancholy, some aesthetic ideals, ethical vices, as well as people’s character and appearance.

  6. Functional tooth regenerative therapy: tooth tissue regeneration and whole-tooth replacement.

    Science.gov (United States)

    Oshima, Masamitsu; Tsuji, Takashi

    2014-07-01

    Oral and general health is compromised by irreversible dental problems, including dental caries, periodontal disease and tooth injury. Regenerative therapy for tooth tissue repair and whole-tooth replacement is currently considered a novel therapeutic concept with the potential for the full recovery of tooth function. Several types of stem cells and cell-activating cytokines have been identified in oral tissues. These cells are thought to be candidate cell sources for tooth tissue regenerative therapies because they have the ability to differentiate into tooth tissues in vitro and in vivo. Whole-tooth replacement therapy is regarded as an important model for the development of an organ regenerative concept. A novel three-dimensional cell-manipulation method, designated the organ germ method, has been developed to recapitulate organogenesis. This method involves compartmentalisation of epithelial and mesenchymal cells at a high cell density to mimic multicellular assembly conditions and epithelial-mesenchymal interactions. A bioengineered tooth germ can generate a structurally correct tooth in vitro and erupt successfully with the correct tooth structure when transplanted into the oral cavity. We have ectopically generated a bioengineered tooth unit composed of a mature tooth, periodontal ligament and alveolar bone, and that tooth unit was successfully engrafted into an adult jawbone through bone integration. Such bioengineered teeth were able to perform normal physiological tooth functions, such as developing a masticatory potential in response to mechanical stress and a perceptive potential for noxious stimuli. In this review, we describe recent findings and technologies underpinning tooth regenerative therapy.

  7. [The Salpêtrière from Mazarin to Charcot].

    Science.gov (United States)

    Bonduelle, M

    1997-01-01

    The edict of 1656 creating the Hôpital Général for sheltering the incapacitated and beggars assigned women to the Salpêtrière which kept its name of Petit-Arsenal (1636). Mazarin contributed generously to the construction. The completion of the facade (1756) imparted a final shape to the overall plan that had been uncertain for a long time. The Infirmerie générale (1780-1787) made a start toward medicalization, while the loges housed the insane under better conditions. For the Salpêtrière (named in 1837 Hospice de la Vieillesse-Femmes [Hospice for old Women]), it was the era of the alienists, renown for Pinel, his students and successors. In 1862 Charcot undertook the cultivation of its "inexhaustable resources". A laboratory in the avant-garde of microscopy became the basis for the anatomo-clinical method. In ten years Charcot laid the foundations of neurology: multiple sclerosis, locomotor ataxia, physiological anatomy of the cord, amyotrophic lateral sclerosis, etc. After his work on motor localization (1875), hysteria became his prime subject. Between 1877 and 1881, he built a service that became a model: laboratories, related clinical departments, a polyclinic (an putpatient department, a short-term hospital). The creation in 1882 of the clinical chair for diseases of the nervous system crowned the enterprise. The formal lectures on Fridays and the Tuesday clinical conferences attracted an audience from around the world. Charcot and his school made the Salpêtrière synonomous with neurology.

  8. Vibration therapy for Parkinson's disease: Charcot's studies revisited.

    Science.gov (United States)

    Kapur, Sachin S; Stebbins, Glenn T; Goetz, Christopher G

    2012-01-01

    The 19th century neurologist, J-M Charcot, used a vibration chair for treating Parkinson's disease (PD). He documented improvement, but few subsequent studies examined vibration treatment. Using a specialized lounge chair, we conducted a rater blinded, randomized trial of body vibration vs. no vibration in 23 PD patients. The primary outcome measure was change from baseline in the motor section of the MDS-UPDRS. Both vibration and no vibration groups significantly improved after one month of daily treatments. However, there was no significant difference between the two treatment groups, suggesting that non-specific or placebo factors had an effect on PD motor function.

  9. Diabetic charcot neuroarthropathy of the foot and ankle with osteomyelitis.

    Science.gov (United States)

    Ramanujam, Crystal L; Stapleton, John J; Zgonis, Thomas

    2014-10-01

    One of the most devastating foot and/or ankle complications in the diabetic population with peripheral neuropathy is the presence of Charcot neuroarthropathy (CN). In recent years, diabetic limb salvage has been attempted more frequently as opposed to major lower extremity amputation for CN of the foot and ankle with ulceration and/or deep infection. Treatment strategies for osteomyelitis in the diabetic population have evolved. This article reviews some of the most common surgical strategies recommended for the diabetic patient with CN of the foot and/or ankle and concomitant osteomyelitis.

  10. Sarcopenia and body composition in diabetic Charcot osteoarthropathy

    DEFF Research Database (Denmark)

    Jansen, Rasmus Bo; Christensen, Tomas Møller; Bülow, Jens

    2015-01-01

    : Cross-sectional case-control study of people with diabetes with acute or chronic Charcot osteoarthropathy, matched with otherwise healthy people with diabetes. A total of 49 subjects (distribution ~1:1) had a total body DXA-scanning, measuring appendicular lean mass, android/gynoid and truncal...... (24.5-31.9%), whereas there were no significant differences found between the groups (P=0.065). Neither truncal/total fat percent nor android/gynoid fat percent ratios showed differences between the groups. CONCLUSION: To our knowledge, this is the first published dataset investigating body...

  11. Chapter 15: Jean-Martin Charcot and the anatomo-clinical method of neurology.

    Science.gov (United States)

    Goetz, Christopher G

    2010-01-01

    Jean-Martin Charcot (1825-1893) was the premier clinical neurologist of the 19th century. Charcot's research was anchored in the anatomo-clinical method, a two-part methodology that linked clinical signs with anatomical lesions. The first step of this method involved the careful documentation of clinical signs with longitudinal observation. At the time of death, the second step involved autopsy examination of the brain and spinal cord. With combined clinical and anatomical data, Charcot was able to suggest concrete clinical-anatomical correlations. This method helped to define the tracts and nuclei responsible for normal and abnormal neurological signs and was pivotal to a new classification of neurological diseases based on anatomy. The best-developed example of this method was Charcot's work with motor system degenerative disorders, specifically amyotrophic lateral sclerosis. These studies led to the international designation of amyotrophic lateral sclerosis as Charcot's disease. Other examples of the fruits of the anatomo-clinical method included several stroke syndromes and the linkage of specific signs to specific lesions in multiple sclerosis. The discipline fostered cortical localization theory, which moved neurologists away from the concept of the brain as a homogenous organ in preference to the concept that brain regions controlled specific motor, sensory and language functions. Charcot's attempts to apply his anatomo-clinical method to the knotty neurological diagnosis of hysteria led him to experiments and conclusions that drew criticism and even scorn from colleagues. These events tarnished Charcot's reputation at the close of his career. In the context of Charcot's extensive discoveries and lasting contributions, the anatomo-clinical method remains the anchor of modern neurological diagnosis and is Charcot's most important contribution to clinical neurology.

  12. Jean-Marie Dufour 1937-2007

    CERN Multimedia

    2007-01-01

    Jean-Marie Dufour, who was head of the CERN Legal Service from 1974 until his retirement in 2001, passed away on 8 July. Following his arrival at CERN in 1966 during the crucial phase of expansion of the Laboratory’s site, Jean-Marie Dufour ensured that CERN’s rules were applied while taking part in essential stages of the Organization’s development. With his fine mind and erudition, Jean-Marie Dufour, a staunch European devoted to the CERN cause, has left his mark on the Legal Service. The Service will publish a tribute to him in a forthcoming issue of the Bulletin.

  13. Mary Priestley interviewed by Leslie Bunt

    Directory of Open Access Journals (Sweden)

    Leslie Bunt

    2004-07-01

    Full Text Available I interviewed Mary Priestley at her London flat in May 2004. Mary is a well-known figure throughout the world of music therapy. At the Ninth World Congress, held in Washington in 1999, her work in Analytical Music Therapy was celebrated as one of the five universally acknowledged approaches in music therapy. Before training as a music therapist Mary also worked as a writer, artist, illustrator and secretary. Born in 1925, she was the daughter of the English playwright and author J.B. Priestley and Jane Lewis who became his second wife.

  14. Marie Curie during ORT4

    Science.gov (United States)

    2003-01-01

    Marie Curie rover drives down the rear ramp during Operational Readiness Test (ORT) 4.Pathfinder, a low-cost Discovery mission, is the first of a new fleet of spacecraft that are planned to explore Mars over thenext ten years. Mars Global Surveyor, already en route, arrives at Mars on September 11 to begin a two year orbital reconnaissance of the planet's composition, topography, and climate. Additional orbiters and landers will follow every 26 months.The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C. JPL is an operating division of the California Institute of Technology (Caltech). The Imager for Mars Pathfinder (IMP) was developed by the University of Arizona Lunar and Planetary Laboratory under contract to JPL. Peter Smith is the Principal Investigator.

  15. Marie Curie during ORT6

    Science.gov (United States)

    2003-01-01

    Marie Curie sits on the lander petal prior to deployment during the pre launch Operations Readiness Test (ORT) 6.Pathfinder, a low-cost Discovery mission, is the first of a new fleet of spacecraft that are planned to explore Mars over thenext ten years. Mars Global Surveyor, already en route, arrives at Mars on September 11 to begin a two year orbital reconnaissance of the planet's composition, topography, and climate. Additional orbiters and landers will follow every 26 months.The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C. JPL is an operating division of the California Institute of Technology (Caltech). The Imager for Mars Pathfinder (IMP) was developed by the University of Arizona Lunar and Planetary Laboratory under contract to JPL. Peter Smith is the Principal Investigator.

  16. Biomaterial selection for tooth regeneration.

    Science.gov (United States)

    Yuan, Zhenglin; Nie, Hemin; Wang, Shuang; Lee, Chang Hun; Li, Ang; Fu, Susan Y; Zhou, Hong; Chen, Lili; Mao, Jeremy J

    2011-10-01

    Biomaterials are native or synthetic polymers that act as carriers for drug delivery or scaffolds for tissue regeneration. When implanted in vivo, biomaterials should be nontoxic and exert intended functions. For tooth regeneration, biomaterials have primarily served as a scaffold for (1) transplanted stem cells and/or (2) recruitment of endogenous stem cells. This article critically synthesizes our knowledge of biomaterial use in tooth regeneration, including the selection of native and/or synthetic polymers, three-dimensional scaffold fabrication, stem cell transplantation, and stem cell homing. A tooth is a complex biological organ. Tooth loss represents the most common organ failure. Tooth regeneration encompasses not only regrowth of an entire tooth as an organ, but also biological restoration of individual components of the tooth including enamel, dentin, cementum, or dental pulp. Regeneration of tooth root represents perhaps more near-term opportunities than the regeneration of the whole tooth. In the adult, a tooth owes its biological vitality, arguably more, to the root than the crown. Biomaterials are indispensible for the regeneration of tooth root, tooth crown, dental pulp, or an entire tooth.

  17. Tooth regeneration: current status.

    Science.gov (United States)

    Dadu, Shifali S

    2009-01-01

    Regeneration of a functional tooth has the potential to be a promising therapeutic strategy. Experiments have shown that with the use of principles of bioengineering along with adult stem cells, scaffold material, and signaling molecules, tooth regeneration is possible. Research work is in progress on creating a viable bioroot with all its support. A new culture needs to be created that can possibly provide all the nutrients to the stem cells. With the ongoing research, tissue engineering is likely to revolutionize dental health and well-being of people by regenerating teeth over the next decade.

  18. Tooth regeneration: Current status

    Directory of Open Access Journals (Sweden)

    Dadu Shifali

    2009-01-01

    Full Text Available Regeneration of a functional tooth has the potential to be a promising therapeutic strategy. Experiments have shown that with the use of principles of bioengineering along with adult stem cells, scaffold material, and signaling molecules, tooth regeneration is possible. Research work is in progress on creating a viable bioroot with all its support. A new culture needs to be created that can possibly provide all the nutrients to the stem cells. With the ongoing research, tissue engineering is likely to revolutionize dental health and well-being of people by regenerating teeth over the next decade.

  19. Charcot neuroarthropathy of the foot and ankle: a review.

    Science.gov (United States)

    Varma, Ajit Kumar

    2013-01-01

    Charcot neuroarthropathy is a limb-threatening, destructive process that occurs in patients with neuropathy associated with medical diseases such as diabetes mellitus. Clinicians' treating diabetic patients should be vigilant in recognizing the early signs of acute Charcot neuroarthropathy, such as pain, warmth, edema, or pathologic fracture in a neuropathic foot. Early detection and prompt treatment can prevent joint and bone destruction, which, if untreated, can lead to morbidity and high-level amputation. A high degree of suspicion is necessary. Once the early signs have been detected, prompt immobilization and offloading are important. Treatment should be determined on an individual basis, and it must be determined whether a patient can be treated conservatively or will require surgical intervention when entering the chronic phase. If diagnosed early, medical and conservative measures only will be required. Surgery is indicated for patients with severe or unstable deformities that, if untreated, will result in major amputations. A team approach that includes a foot and ankle surgeon, a diabetologist, a physiotherapist, a medical social councilor, and, most importantly, the patient and immediate family members is vital for successful management of this serious condition.

  20. Pierre Janet, Sigmund Freud and Charcot's psychological and psychiatric legacy.

    Science.gov (United States)

    Pérez-Rincón, Héctor

    2011-01-01

    A key moment in the history of psychiatry occurred during Charcot's time at La Salpêtriere. Though his studies on hysteria and hypnotism, the founder of neurology inspired the work of two of his alumni: a Viennese Nervenartz and a French philosopher interested in the dissociation of personality. Even though neither of them was originally an alienist, their respective work allowed the field of neurosis--then belonging to internal medicine--to pass to psychiatry. The parallel lives of these frères enemis, both of whom were treated differently by fame, developed inside a very complex cultural and scientific milieu. Therefore, it is necessary to consider them together with other physicians, some of whom are much less well-known nowadays, who one way or another carried Charcot's influence into psychiatry, psychology and psychotherapy. The fates of the Dioscuri have been reversed--the fame and success of Freudian psychoanalysis ran parallel to Janet's oblivion and his long 'purgatory', but now the 'renaissance' of his work coincides with the decline of psychoanalysis as a theoretical explanation for mental pathology.

  1. Radium, Marie Curie and modern science.

    Science.gov (United States)

    Langevin-Joliot, H

    1998-11-01

    In 1898, the discovery of two new elements, polonium and radium, reawakened interest in the topic of uranic rays discovered 2 years before by H. Becquerel. Radioactivity, a name coined by Marie Curie, became a major research field for decades. The contrasting personalities of Pierre Curie, already a first-rank physicist, and of the young Marie Curie-Sklodowska as they undertook their common work are described. It is shown how a well-chosen quantitative method and a systematic approach combining physics and chemistry led to the discovery within less than 1 year. The special role of radium and the determination of its atomic weight by Marie Curie followed by her long-term program for accumulating pure radium salts are emphasized. The first woman with a full professorship at a French University, Marie Curie created and managed the Radium Institute.

  2. Radikaalsus muuseumi kaitsva teki all / Mari Sobolev

    Index Scriptorium Estoniae

    Sobolev, Mari, 1968-

    2004-01-01

    Rotermanni soolalaos avatud Marco (Marko) Laimre isiknäituse "Küsimused ja vastused" puhul 13. IV toimunud konverentsist. Johannes Saare, Eha Komissarovi, Hanno Soansi, Anders Härmi ja Mari Sobolevi ettekannetest

  3. Pneumomediastinum after Tooth Extraction

    OpenAIRE

    Ilhan Ocakcioglu; Serhat Koyuncu; Mustafa Kupeli; Oguzhan Bol

    2016-01-01

    Pneumomediastinum is defined as the presence of air in mediastinum. Pneumomediastinum can sometimes occur after surgery. Pneumomediastinum seen after dental procedures is rare. We presented the case of subcutaneous emphysema developed in the neck and upper chest after tooth extraction and discussed the possible mechanisms of pneumomediastinum.

  4. Beaming the columns for Charcot diabetic foot reconstruction: a retrospective analysis.

    Science.gov (United States)

    Grant, William P; Garcia-Lavin, Silvia; Sabo, Roy

    2011-01-01

    This study explored the concept of "beaming" the medial and lateral longitudinal columns as a variation of the current technique for hindfoot and Lisfranc Charcot reconstruction. We reviewed radiographic changes and outcomes for patients who underwent Charcot foot reconstruction at our facility over the 14-year period from January 1994 to January 2008. Beaming was performed on 71 Charcot foot deformities in 70 patients, 22 (31%) of which displayed an isolated hindfoot deformity, 20 (28%) an isolated Lisfranc deformity, and 29 (41%) with a combination of hindfoot and Lisfranc deformities. The average radiographic follow up was 31.00 ± 22.97 months. Group 1 consisted of reconstructions that involved only medial and lateral column beams and showed significant improvements in radiographic alignment between the preoperative and postoperative measurements, including Meary's angle (P Charcot reconstruction. Complications included pin tract infections, broken pin, osteomyelitis, transfer lesions, and ulcerations.

  5. Sympathetic neuropathy in diabetes mellitus patients does not elicit Charcot osteoarthropathy

    DEFF Research Database (Denmark)

    Christensen, Tomas M; Simonsen, Lene; Holstein, Per E

    2011-01-01

    AIM: The aim of the study was to determine the degree of neuropathy (autonomic and somatic) in patients with diabetes mellitus with or without Charcot osteoarthropathy (CA). METHODS: Forty-nine patients with diabetes mellitus type 1 or 2 were investigated. The patient population of interest...... was the patients with acute Charcot foot (n=17) or chronic Charcot foot (n=7). The inclusion criterion for an acute Charcot foot was a temperature difference of more than 2° between the two feet, oedema of the affected foot, typical hotspots in a bone scintigram and a typical clinical course. In addition, patients...... with first toe amputation (n=5), a high-risk group for development of CA, and two control groups consisting of diabetes patients with (n=9) or without somatic neuropathy (n=11) were investigated. Regional blood flow in the feet was measured by venous occlusion plethysmography. Quantitation of somatic...

  6. Jean-Baptiste Charcot in Rio de Janeiro: glamorous trip and celebrity in 1908

    Directory of Open Access Journals (Sweden)

    Hélio A. G. Teive

    2015-09-01

    Full Text Available The authors review the visit of Commander Charcot and the crew of his ship, the “Pourquoi Pas?”, to Rio de Janeiro, Brazil, in 1908, where he stayed for eight days, while en-route as part of the second French expedition to the Antarctic. It was a glamorous stay as Commander Charcot was treated as a true star and international celebrity, befitting his position.

  7. Circular External Fixation as a Primary or Adjunctive Therapy for the Podoplastic Approach of the Diabetic Charcot Foot.

    Science.gov (United States)

    Short, Daniel J; Zgonis, Thomas

    2017-01-01

    Numerous techniques have been described for surgical management of the diabetic Charcot foot. External fixation has become a main surgical tool for the reconstructive foot and ankle surgeon when dealing with the ulcerated diabetic Charcot foot. In the presence of an open wound and/or osteomyelitis, staged reconstruction with circular external fixation becomes ideal for salvage of the diabetic lower extremity. Also, circular external fixation can provide simultaneous compression and stabilization, correct the underlying osseous or soft tissue deformities, and surgically offload the diabetic Charcot foot. This article describes a variety of circular external fixation applications for the diabetic Charcot foot.

  8. Mari e-raamatukogu / Tatjana Verina ; vene keelest tõlkinud Ene Riet

    Index Scriptorium Estoniae

    Verina, Tatjana

    2011-01-01

    Mari e-raamatukogu loomise aluseks on Mari-Eli Vabariigi etnokultuuriliste ja rahvusvaheliste suhete arendamise projekt, hetkel on elektroonilises raamatukogus 52 täistekstilist teavikut Tšavaini nimelise Mari Rahvusraamatukogu haruldaste raamatute kogust

  9. Charcot foot in diabetes and an update on imaging

    Directory of Open Access Journals (Sweden)

    Fatma Bilge Ergen

    2013-11-01

    Full Text Available Charcot neuroarthropathy (CN is a serious complication of diabetes mellitus that can cause major morbidity including limb amputation. Since it was first described in 1883, and attributed to diabetes mellitus in 1936, the diagnosis of CN has been very challenging even for the experienced practitioners. Imaging plays a central role in the early and accurate diagnosis of CN, and in distinction of CN from osteomyelitis. Conventional radiography, computed tomography, nuclear medicine scintigraphy, magnetic resonance imaging, and positron emission tomography are the imaging techniques currently in use for the evaluation of CN but modalities other than magnetic resonance imaging appeared to be complementary. This study focuses on imaging findings of acute and chronic neuropathic osteoarthropathy in diabetes and discrimination of infected vs. non-infected neuropathic osteoarthropathy.

  10. Saw-tooth cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Karatza Ageliki A

    2009-12-01

    Full Text Available Abstract We present an unusual case of cardiomyopathy in a two month old male infant with a grade-I systolic murmur. Echocardiographic examination disclosed left ventricular (LV, dysplasia with saw-tooth like inwards myocardial projections extending from the lateral walls towards the LV cavity. There was mild LV systolic dysfunction with apical hypokinesia. Cardiovascular magnetic resonance demonstrated in detail these cross bridging muscular projections originating from the inferior interventricular septum and lateral LV wall, along with areas of hypokinesis at the LV septum and apex in a noncoronary distribution, without any late gadolinium enhancement. We have termed this condition saw-tooth cardiomyopathy because of the very characteristic appearance.

  11. 牙仙女%The Tooth Fairy

    Institute of Scientific and Technical Information of China (English)

    李世荣

    2009-01-01

    @@ The American children’s ritual of hiding a lost tooth under a pillow stems from an old German tradition of placing a lost tooth in a mouse or rat hole SO that when a new tooth grew in,it would possess the strong dental qualities of a rodent’S tooth.In America the “tooth rat”was replaced by the“tooth fairy”,who would compensate the child with money for surrendering a tooth to her.

  12. Solving tooth sensitivity.

    Science.gov (United States)

    Miller, Michael B

    2010-01-01

    Solving tooth sensitivity requires both you and the patients to be resilient and to understand that if one approach doesn't work, you can try another one that is non-invasive or, at worst, minimally invasive. Much like the clinician who posted the original question, I strongly believe that it is our responsibility to convince patients that jumping to a radical solution could be totally unnecessary--and expensive-- and still might not solve the problem.

  13. Tooth in oropharynx

    OpenAIRE

    Nagarajappa, D; B S Manjunatha

    2011-01-01

    The incidence of ectopic teeth has increased. In many cases, the etiology of ectopic teeth cannot be identified. Ectopic tooth in deciduous dentition period is very rare and information is limited about its causes and characteristics. The conditions commonly associated with an increased prevalence of ectopic teeth include cleft lip and palate, cleidocranial dysplasia, and Gardner syndrome. The diagnosis is made by the clinical and radiological examinations. The indication for extraction in ec...

  14. Engineering international relations / Maris Riekstins ; interv. Talis Saule Archdeacon

    Index Scriptorium Estoniae

    Riekstins, Maris

    2008-01-01

    Läti annab peatselt Läänemeremaade Nõukogu eesistuja teatepulga üle Taanile. Läti välisminister Maris Riekstins Läänemeremaade Nõukogu teemadest ning suhetest Venemaaga. Maris Riekstins'i CV

  15. Meet EPA Scientist Marie O'Shea, Ph.D.

    Science.gov (United States)

    EPA Scientist Dr. Marie O'Shea is Region 2's Liaison to the Agency's Office of Research and Development (ORD). Marie has a background in research on urban watershed management, focused on characterizing and controlling nutrients in stormwater runoff.

  16. MaRIE Undulator & XFEL Systems

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Dinh Cong [Los Alamos National Laboratory; Marksteiner, Quinn R. [Los Alamos National Laboratory; Anisimov, Petr Mikhaylovich [Los Alamos National Laboratory; Buechler, Cynthia Eileen [Los Alamos National Laboratory

    2015-03-23

    The 22 slides in this presentation treat the subject under the following headings: MaRIE XFEL Performance Parameters, Input Electron Beam Parameters, Undulator Design, Genesis Simulations, Risks, and Summary It is concluded that time-dependent Genesis simulations show the MaRIE XFEL can deliver the number of photons within the required bandwidth, provided a number of assumptions are met; the highest risks are associated with the electron beam driving the XFEL undulator; and risks associated with the undulator and/or distributed seeding technique may be evaluated or retired by performing early validation experiments.

  17. Mary Shelly and Her "Hideous Progeny"

    Institute of Scientific and Technical Information of China (English)

    谌英

    2011-01-01

    Mary Shelly's representative work Frankenstein has spawned innumerable interpretations since its first publication in 1818.This thesis explores Mary Shelly's motivation of creating the monster.Mary Shelly's "hideous progeny" to some degree is her "shadow"

  18. Autogenous tooth transplantation: an alternative to replace extracted tooth

    Directory of Open Access Journals (Sweden)

    David B. Kamadjaja

    2015-09-01

    Full Text Available Background: The gold standard treatment to replace missing tooth is dental implants, however, in certain cases, such as in young patients its placement is contraindicated. Autogenous tooth transplantation, which has been widely done in Scandinavian countries for many years, may become a good alternative to overcome this problem. Purpose: This article attempted to provide information about the indication, treatment planning, surgical technique and the successful result of autogenous tooth transplantation. Case: A fifteen year old male patient presented with large caries and periapical disease of his lower left first molar, which was partially erupted and the roots was not fully formed in radiograph. Case management: Autogenous tooth transplantation procedure was performed consisting of extraction of #36, odontectomy of #38 followed by its implantation to socket #36 and fixation of the transplanted tooth to the adjacent teeth. Post operative evaluation was done on regular basis within 18 months period. There was no complaint, the tooth was clinically stable and no evidence of periodontal problem. Serial radiographs showed healing of alveolar bone and periodontal tissue, and the complete root formation was evident by 18 months post operatively. Conclusion: Autogenous tooth transplantation is a potential alternative to replace extracted tooth. Provided that the case be properly planned and operation carefully performed, successful result of this treatment can be achieved.

  19. Charcot, la salpêtrière, and hysteria as represented in European literature.

    Science.gov (United States)

    Koehler, Peter J

    2013-01-01

    In this chapter, I describe the influence of Jean-Martin Charcot (1825-1893), his neurological school at the Salpêtrière (Paris), and his teaching of hysteria on European literature. Many references to Charcot and descriptions of hysterical attacks are found not only in French naturalistic literature but also subsequently in naturalistic novels from other European countries (the Netherlands, Russia, Scandinavian countries, Spain, Italy, and Germany) and furthermore in novels written in new literary movements that followed naturalism. At first, objective descriptions were presented, but in the periods that followed, in particular during the past decades, criticism, rather than objective descriptions, became the motivation for continuing to use Charcot and his teaching of hysteria as inspiration for novels and plays, although Charcot as an admired founder of neurology did not quite disappear, even in recent novels. It is quite impressive to observe how Charcot and his demonstrations of hysterical attacks still resound throughout European literature, even after more than a century.

  20. Pressure pain perception in the diabetic Charcot foot: facts and hypotheses

    Directory of Open Access Journals (Sweden)

    Ernst A. Chantelau

    2013-05-01

    Full Text Available Background:Reduced traumatic and posttraumatic (nociceptive pain is a key feature of diabetic neuropathy. Underlying condition is a gradual degeneration of endings of pain nerves (A-delta fibers and C-fibers, which operate as receivers of noxious stimuli (nociceptors. Hence, the absence of A-delta fiber mediated sharp pain (“first” pain, and of C-fiber mediated dull pain (“second” pain. However, patients with diabetic neuropathy and acute Charcot foot often experience deep dull aching in the Charcot foot while walking on it. Aim: To create a unifying hypothesis on the kind of pain in an acute Charcot foot. Result: Absence of punctuate (pinprick pain perception at the sole of a Charcot foot, as was shown recently, likely corresponds to vanished intraepidermal A-delta fiber endings. C-fiber nociceptors are reduced, according to histopathology studies. Both types of fibers contribute to posttraumatic hyperalgesia at the skin level, as studies show. Their deficiencies likely impact on posttraumatic hyperalgesia at the skin level and, probably, also at the skeletal level. Conclusion: It is hypothesised that deep dull aching in an acute diabetic Charcot foot may represent faulty posttraumatic hyperalgesia involving cutaneous and skeletal tissues.

  1. On the early history of male hysteria and psychic trauma. Charcot's influence on Freudian thought.

    Science.gov (United States)

    Libbrecht, K; Quackelbeen, J

    1995-10-01

    This paper discusses the influence of Jean-Martin Charcot's views on Sigmund Freud's early theory of hysteria and the notion of psychical trauma. We consider the early history of both psychical trauma and male hysteria, for in Charcot's view traumatic hysteria and male hysteria are identical. Freud's two 1886 lectures on male hysteria, delivered after his return from Paris, are crucial to the subject because they present Freud's first impressions of Charcot and his teaching. Some of the ideas presented in the two lectures foreshadow Freud's later generalization of the etiological role of trauma and his theory of the role of psychical trauma in the genesis of hysteria; that is, each hysterical symptom is due to a psychical trauma reviving an earlier traumatic event--the so-called principle of deferred action (Nachträglichkeit). Several arguments substantiate the thesis that Freud's notion of psychical (sexual) trauma was developed in reference to Charcot's notion of traumatic hysteria, and that the early psychoanalytic theory of psychical trauma is clearly indebted to Freud's encounter with Charcot's male traumatic hysterical patients. The discussed Freudian development points out the major role of (physical) traumata in eliciting psychopathological pictures and in this way is of definite historical relevance for the present-day discussion on the traumatic nature of the so-called multiple personality syndrome and other dissociative disorders, and post-traumatic stress disorders.

  2. Mary Elizabeth Hickox Mandels, 90, bioenergy leader

    Directory of Open Access Journals (Sweden)

    Eveleigh Douglas E

    2009-09-01

    Full Text Available Abstract Mary E H Mandels, who spearheaded the US Army's national bioconversion studies for four decades and was an early proponent of conversion of waste biomass to readily bioconvertible sugars for the production of chemicals and transportation fuels such as ethanol, died 17 February 2008 at Natick, MA, USA. She was 90.

  3. Bon appetite! / Mari-Liis Rebane

    Index Scriptorium Estoniae

    Rebane, Mari-Liis

    2009-01-01

    Pimedate Ööde 13. filmifestivali alafestivali Animated Dreams täispikki animafilme: Austraalia "Mary ja Max" (režissöör Elliot, Adam), Rootsi-Taani-Norra "Metropia" (režissöör Tarik Saleh), Iisraeli-Austraalia "9,99 dollarit" (režissöör Tatia Rosenthal)

  4. Mari Trentinjan : Muzhtshina jejo smerti / Bernard Lavillier

    Index Scriptorium Estoniae

    Lavillier, Bernard

    2003-01-01

    Prantsuse näitlejanna Marie Trintignant'iga (41) suri 1. augustil Prantsusmaal oma elukaaslase, ansambli "Noir Desire" liidri Bertrand Cantat' poolt Vilniuses talle tekitatud trauma tagajärjel. Näitlejanna eludraama. Järgneb 5. jaan. 2004, lk. 16-18 : ill

  5. Classroom Instruction: The Influences of Marie Clay

    Science.gov (United States)

    McNaughton, Stuart

    2014-01-01

    Marie Clay's body of work has influenced classroom instruction in direct and indirect ways, through large overarching themes in our pedagogical content knowledge as well as specific smart practices. This paper focuses on her the contributions to our thinking about instruction which come from two broad theoretical concepts; emergent literacy…

  6. The effectiveness of non-surgical interventions in the treatment of Charcot foot.

    Science.gov (United States)

    Smith, Caroline; Kumar, Saravana; Causby, Ryan

    2007-12-01

    Background  Charcot neuropathic osteoarthropathy is commonly known as 'Charcot foot'. It is a serious foot complication of diabetes mellitus that can frequently lead to foot ulceration, gangrene, hospital admission and foot amputation. A multidisciplinary approach to the management of Charcot foot is taken involving medical and allied health professionals. The management approach may also differ between different countries. To date, there is no systematic review of the literature undertaken to identify the clinical effectiveness of non-operative interventions in the treatment of acute Charcot foot. Objective  The objective of this review was to identify the effectiveness of non-surgical interventions with reducing lesions, ulceration, the rate of surgical intervention, reducing hospital admissions and improve the quality of life of subjects with Charcot foot. Search strategy  A comprehensive search strategy was undertaken on databases available from University of South Australia from their inception to November 2006. Selection criteria  Randomised controlled trials or clinical controlled trials were primarily sought. Critical appraisal of study quality and data extraction was undertaken using Joanna Briggs Institute instruments. Review Manager software was used to calculate comparative statistics. Results  This review identified 11 trials and five trials were included in the review. Three trials involved the use of bisphosphonate, a pharmacological agent. Two experimental treatments were also included, evaluating palliative radiology and magnetic fields. No trials were found using immobilisation and off-loading interventions for acute Charcot foot. The overall methodological quality score of the five studies was moderate. Owing to heterogeneous data, meta-analysis could not be performed. The trials did not report on reducing lesions, ulceration, rate of surgical intervention, hospital admissions and the quality of life of subjects with Charcot foot. The

  7. Combined Internal and External Fixation for Diabetic Charcot Reconstruction: A Retrospective Case Series.

    Science.gov (United States)

    Hegewald, Kenneth W; Wilder, Megan L; Chappell, Todd M; Hutchinson, Byron L

    2016-01-01

    Diabetic Charcot neuroarthropathy is a complex, limb-threatening disease process with major lifestyle-altering repercussions for patients. When Charcot neuroarthropathy leads to unstable deformity, ulceration, and potential infection despite conservative therapies, foot and ankle surgeons often consider reconstructive limb salvage procedures to restore function. The purpose of the present study was to evaluate the clinical and radiographic outcomes of diabetic Charcot reconstruction using combined internal and external fixation. A total of 22 patients were reviewed; 16 (72.73%) midfoot and 6 (27.27%) tibiotalocalcaneal arthrodesis procedures were consecutively performed from March 2009 to May 2013. All surgical procedures were performed in nonacute phases of the Charcot process in patients with diagnosed diabetes mellitus and documented peripheral neuropathy. Patients were excluded from the study if they were not diabetic despite having undergone Charcot reconstruction, regardless of the fixation method, or if they did not complete radiographic imaging. During a mean follow-up period of 58.60 ± 42.37 (range 16 to 164) weeks, limb salvage was achieved in 20 patients (90.91%), and 2 (9.09%) required below-the-knee amputation at a mean of 42 ± 14.14 weeks. Wound dehiscence occurred in 8 (36.36%), pin tract infection in 10 (45.45%), and superficial wound infection in 9 (40.91%) and peaked in bimodal fashion at 4 and 8 weeks postoperatively. Radiographic analysis of the pre- versus postoperative alignment showed statistically significant changes in the lateral talo-first metatarsal angle (p = .02) and lateral talar declination angle (p = .01). The limb salvage rates with diabetic Charcot reconstruction are improving in part because of the continued development of increasingly superior modalities for both internal and external fixation.

  8. On the centenary of Charcot: hysteria, suggestibility and hypnosis.

    Science.gov (United States)

    Chertok, L

    1984-06-01

    In studying hysteria by means of hypnosis, Charcot placed emphasis on the psychological aetiology of the neuroses. Among his pupils, Freud alone grasped this epistemological turning-point, from which he made his great discoveries. But hysteria and hypnosis still remain today largely unknown. We have not yet elucidated the 'mysterious leap' between the psychological and the somatic for the former, and between the relational and the instrumental for the latter. While psychoanalysts have constantly concerned themselves with hysteria, they have shown a lack of interest in hypnosis after Freud abandoned its practice. According to Freud, thanks to transference, affect would be controlled by cognition, a viewpoint eminently suited to satisfy his rationalistic outlook. Affect, however, remains an unknown realm. The affective relationship has, at all events, acquired an ever-increasing importance in psychoanalysis during the last few years, with the emphasis on the early mother-child relationship. The 'affective locus' remains the basic, as well as the most obscure, element in the hypno-suggestive relationship. The behaviourist approach, which quantifies the 'vertical' dimension in depth, is a limited one. The study of the 'horizontal' dimension of subjective experience represents a new line of research, which may make it possible to distinguish different forms of hypnosis. The understanding of hypno-suggestion may throw light on psychoanalysis, psychotherapy, and the human sciences in general.

  9. Charcot foot reconstruction with combined internal and external fixation: case report

    Directory of Open Access Journals (Sweden)

    Zgonis Thomas

    2010-02-01

    Full Text Available Abstract Charcot neuroarthropathy is a destructive and often-limb threatening process that can affect patients with peripheral neuropathy of any etiology. Early recognition and appropriate management is crucial to prevention of catastrophic outcomes. Delayed diagnosis and subsequent pedal collapse often preclude successful conservative management of these deformities and necessitate surgical intervention for limb salvage. We review the current literature on surgical reconstruction of Charcot neuroarthropathy and present a case report of foot reconstruction with combined internal and external fixation methods.

  10. Negative-pressure wound therapy in the management of diabetic Charcot foot and ankle wounds.

    Science.gov (United States)

    Ramanujam, Crystal L; Stapleton, John J; Zgonis, Thomas

    2013-09-23

    As the prevalence of diabetes mellitus continues to rise, innovative medical and surgical treatment options have increased dramatically to address diabetic-related foot and ankle complications. Among the most challenging clinical case scenarios is Charcot neuroarthropathy associated with soft tissue loss and/or osteomyelitis. In this review article, the authors present a review of the most common utilizations of negative-pressure wound therapy as an adjunctive therapy or combined with plastic surgery as it relates to the surgical management of diabetic Charcot foot and ankle wounds.

  11. Negative-pressure wound therapy in the management of diabetic Charcot foot and ankle wounds

    Directory of Open Access Journals (Sweden)

    Crystal L. Ramanujam

    2013-09-01

    Full Text Available As the prevalence of diabetes mellitus continues to rise, innovative medical and surgical treatment options have increased dramatically to address diabetic-related foot and ankle complications. Among the most challenging clinical case scenarios is Charcot neuroarthropathy associated with soft tissue loss and/or osteomyelitis. In this review article, the authors present a review of the most common utilizations of negative-pressure wound therapy as an adjunctive therapy or combined with plastic surgery as it relates to the surgical management of diabetic Charcot foot and ankle wounds.

  12. Surgical Correction of the Achilles Tendon for Diabetic Foot Ulcerations and Charcot Neuroarthropathy.

    Science.gov (United States)

    Ramanujam, Crystal L; Zgonis, Thomas

    2017-04-01

    Achilles tendon pathologic conditions are implicated in contributing to the development of many diabetic foot complications including diabetic foot ulceration and Charcot neuroarthropathy. Surgical correction of the diabetic equinus deformity has been studied as an isolated or adjunctive treatment when dealing with difficult-to-close diabetic foot ulcerations or when surgically addressing the diabetic Charcot neuroarthropathy foot or ankle. This article reviews the most common indications, complications, and surgical procedures for equinus correction by either a tendo-Achilles lengthening or gastrocnemius recession for the management of diabetic foot conditions.

  13. Partial tooth gear bearings

    Science.gov (United States)

    Vranish, John M. (Inventor)

    2010-01-01

    A partial gear bearing including an upper half, comprising peak partial teeth, and a lower, or bottom, half, comprising valley partial teeth. The upper half also has an integrated roller section between each of the peak partial teeth with a radius equal to the gear pitch radius of the radially outwardly extending peak partial teeth. Conversely, the lower half has an integrated roller section between each of the valley half teeth with a radius also equal to the gear pitch radius of the peak partial teeth. The valley partial teeth extend radially inwardly from its roller section. The peak and valley partial teeth are exactly out of phase with each other, as are the roller sections of the upper and lower halves. Essentially, the end roller bearing of the typical gear bearing has been integrated into the normal gear tooth pattern.

  14. Marked loss of sympathetic nerve fibers in chronic Charcot foot of diabetic origin compared to ankle joint osteoarthritis.

    Science.gov (United States)

    Koeck, Franz-Xaver; Bobrik, Verena; Fassold, Alexander; Grifka, Joachim; Kessler, Sigurd; Straub, Rainer H

    2009-06-01

    The pathogenesis of Charcot foot is based on three disputed factors: (1) loss of neurotrophic influence, (2) microtraumatic lesions, and (3) neurovascular disturbances. These etiological causes were uncovered by clinicophysiological tests. However, no results of quantitative nerve density studies of sympathetic and sensory substance P-positive (SP+) nerve fibers are available. We studied the density of sympathetic and SP+ nerve fibers in three distinct areas of the tarsus. Fifteen patients with ankle osteoarthritis (OA) and 15 patients with diabetic Charcot foot were included. Patients with OA did not differ from those with Charcot foot in SP+ sensory nerve fiber density. However, at all three areas, the density of sympathetic nerve fibers was significantly lower in patients with Charcot foot compared to OA (p = 0.006). In addition, we found that the sympathetic nerve repellent factor semaphorin 3C was highly expressed in inflamed tissue in Charcot patients. In Charcot foot of diabetic origin a severe loss of sympathetic nerve fibers was observed. These findings in chronically inflamed Charcot foot lend support to the neurovascular theory in the late chronic phase, which probably depends on the inflammatory upregulation of nerve repellent factors.

  15. Jean-Martin Charcot and art: relationship of the "founder of neurology" with various aspects of art.

    Science.gov (United States)

    Bogousslavsky, Julien; Boller, François

    2013-01-01

    Jean-Martin Charcot (1825-1893), the "father of neurology" in France and much beyond, was also the man who established academic psychiatry in Paris, differentiating it from clinical alienism. In his teaching, he used artistic representations from previous centuries to illustrate the historical developments of hysteria, mainly with the help of his pupil Paul Richer. Charcot liked to draw portraits (in particular, sketches of colleagues during boring faculty meetings and students' examinations), caricatures of himself and others, church sculptures, landscapes, soldiers, etc. He also used this skill in his clinical and scientific work; he drew histological or anatomic specimens, as well as patients' features and demeanor. His most daring artistic experiments were drawing under the influence of hashish. Charcot's tastes in art were conservative; he displayed no affinity for the avant-gardes of his time, including impressionism, or for contemporary musicians, such as César Franck or Hector Berlioz. Léon Daudet, son of Charcot's former friend and famous writer Alphonse Daudet, described Charcot's home as a pseudo-gothic kitsch accumulation of heteroclite pieces of furniture and materials. However, as Henry Meige wrote a few years after his mentor's death, Charcot the artist remains "inseparable from Charcot the physician."

  16. Mary Somerville and the world of science

    CERN Document Server

    Chapman, Allan

    2015-01-01

    Mary Somerville (1780-1872), after whom Somerville College Oxford was named, was the first woman scientist to win an international reputation entirely in her own right, rather than through association with a scientific brother or father. She was active in astronomy, one of the most demanding areas of science of the day, and flourished in the unique British tradition of Grand Amateurs, who paid their own way and were not affiliated with any academic institution. Mary Somerville was to science what Jane Austen was to literature and Frances Trollope to travel writing. Allan Chapman’s vivid account brings to light the story of an exceptional woman, whose achievements in a field dominated by men deserve to be very widely known.

  17. Mechanisms for Nonrecurrent Genomic Rearrangements Associated with CMT1A or HNPP: Rare CNVs as a Cause for Missing Heritability

    NARCIS (Netherlands)

    F. Zhang; P. Seeman; P. Liu; M.A.J. Weterman; C. Gonzaga-Jauregui; C.F. Towne; S.D. Batish; E. de Vriendt; P. de Jonghe; B. Rautenstrauss; K.H. Krause; M. Khajavi; J. Posadka; A. Vandenberghe; F. Palau; L. van Maldergem; F. Baas; V. Timmerman; J.R. Lupski

    2010-01-01

    Genomic rearrangements involving the peripheral myelin protein gene (PMP22) in human chromosome 17p12 are associated with neuropathy: duplications cause Charcot-Marie-Tooth disease type IA (CMT1A), whereas deletions lead to hereditary neuropathy with liability to pressure palsies (HNPP). Our previou

  18. Thrombotic Microangiopathy in Inverted Formin 2-Mediated Renal Disease

    DEFF Research Database (Denmark)

    Challis, Rachel C; Ring, Troels; Xu, Yaobo;

    2016-01-01

    and her mother also had Charcot-Marie-Tooth disease. Using whole-exome sequencing, we identified a mutation in the inverted formin 2 gene (INF2) in the mutational hotspot for FSGS. Subsequent analysis of the Newcastle aHUS cohort identified another family with a functionally-significant mutation in INF2...

  19. A frameshift mutation in LRSAM1 is responsible for a dominant hereditary polyneuropathy.

    NARCIS (Netherlands)

    Weterman, M.A.J.; Sorrentino, V.; Kasher, P.R.; Jakobs, M.E.; Engelen, B.G.M. van; Fluiter, K.; Wissel, M.B. de; Sizarov, A.; Nurnberg, G.; Nurnberg, P.; Zelcer, N.; Schelhaas, H.J.; Baas, F.

    2012-01-01

    Despite the high number of genes identified in hereditary polyneuropathies/Charcot-Marie-Tooth (CMT) disease, the genetic defect in many families is still unknown. Here we report the identification of a new gene for autosomal dominant axonal neuropathy in a large three-generation family. Linkage ana

  20. Studies of cellular radiosensitivity in hereditary disorders of nervous system and muscle

    Energy Technology Data Exchange (ETDEWEB)

    Brennan, S.; Lewis, P.D. (Royal Postgraduate Medical School, London (UK))

    1983-12-01

    Skin fibroblasts from patients with familial dysautonomia, Duchenne muscular dystrophy and Charcot-Marie-Tooth disease show normal sensitivity to ionising radiation, as measured by post-irradiation clonal growth. Previous reports of cellular hypersensitivity to ionising radiation and other DNA-damaging agents in familial dysautonomia and Duchenne muscular dystrophy have not been confirmed.

  1. Comparison of CMT1A and CMT2: similarities and differences.

    NARCIS (Netherlands)

    Bienfait, H.M.; Verhamme, C.; Schaik, I.N. van; Koelman, J.H.; Visser, B.W. de; Haan, R.J. de; Baas, F.; Engelen, B.G.M. van; Visser, M. de

    2006-01-01

    To evaluate the clinical and electrophysiological similarities and differences between two large groups of patients with Charcot-Marie-Tooth disease, i.e. CMT1A and CMT2, we performed a post hoc comparison of clinical and electrophysiological data.Most CMT1A and CMT2 patients had the classical CMT p

  2. Abnormal interaction of motor neuropathy-associated mutant HspB8 (Hsp22) forms with the RNA helicase Ddx20 (gemin3)

    NARCIS (Netherlands)

    Sun, Xiankui; Fontaine, Jean-Marc; Hoppe, Adam D.; Carra, Serena; DeGuzman, Cheryl; Martin, Jody L.; Simon, Stephanie; Vicart, Patrick; Welsh, Michael J.; Landry, Jacques; Benndorf, Rainer

    2010-01-01

    A number of missense mutations in the two related small heat shock proteins HspB8 (Hsp22) and HspB1 (Hsp27) have been associated with the inherited motor neuron diseases (MND) distal hereditary motor neuropathy and Charcot-Marie-Tooth disease. HspB8 and HspB1 interact with each other, suggesting tha

  3. Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2

    NARCIS (Netherlands)

    S. Zuchner; P. de Jonghe; A. Jordanova; K.G. Claeys; V. Guergueltcheva; S. Cherninkova; S.R. Hamilton; G. van Stavern; K.M. Krajewski; J. Stajich; I. Tournev; K. Verhoeven; C.T. Langerhorst; M. de Visser; F. Baas; T. Bird; V. Timmerman; M. Shy; J.M. Vance

    2006-01-01

    Objective: Charcot-Marie-Tooth (CMT) neuropathy with visual impairment due to optic atrophy has been designated as hereditary motor and sensory neuropathy type VI (HMSN VI). Reports of affected families have indicated autosomal dominant and recessive forms, but the genetic cause of this disease has

  4. Women who Worked with Marie Curie.

    Science.gov (United States)

    Pigeard-Micault, Natalie

    2015-06-01

    Marie Curie directed a research laboratory for 28 years. Between 1906 and 1934, forty five women worked under her guidance. Some were, and are, well-known in their own countries as their first woman full professor such as Ellen Gleditsch or Margaret von Wrangel, but for twenty eight of them, who were often French, nothing has ever been written. The strong presence of women in Marie Curie's laboratory has often been highlighted and has been considered as an exception, and the result of deliberate choice. Of course, these women did not choose this workplace by accident. They knew its director was a woman, a laureate of one, and after 1911, two Nobel Prizes, who was leading a well-equipped laboratory with an important radioactive source. But how did Marie Curie selected her collaborators among the many applications she received? Was her choice influenced by gender? A prosopographical research based on genealogical researches and new sources explains this presence contextually and sheds light on several questions : where did these women come from, what were their social and geographic origins, did they occupy any specific cultural or technical area inside Curie's lab, what future did they have after the laboratory? Through their lives, we can question the existence, or not, of a one profile of the female researcher in scientific areas in France.

  5. Mary Grant Seacole: the first nurse practitioner.

    Science.gov (United States)

    Messmer, P R; Parchment, Y

    1998-01-01

    Mary Grant Seacole was born in 1805, in Kingston, Jamaica, to a Jamaican doctress (medicine woman) and a Scottish naval officer. Later Seacole became a doctress, nursing British soldiers during epidemics of cholera, dysentery, and yellow fever in Jamaica, Cuba, and Panama. After refusals by both the British government and Florence Nightingale to be allowed to practice in Scutari, she financed her own way to the scene of the Crimean War and then established the British Hotel to serve both the comfort and medical needs of the wounded soldiers. At night, Seacole worked side by side with Nightingale at Scutari as a volunteer nurse. Seacole's fame grew proportionately after she was seen helping wounded soldiers on the battlefields even while the battles were still raging. Seacole died on May 14, 1881, in London. One hundred years later, many members of the London black community, a few members of the Nurses Association of Jamaica and the Friends of Mary Seacole marched to her grave, honoring her as one of the greatest women of all times. Mary Grant Seacole rose above the barriers of racial prejudice and demonstrated the determinism, compassion, and caring that have became the hallmark of nurse practitioners.

  6. Mary Katrantzou 真实之美

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    3月27日,Mary Katrantzou时装发布会将在751D·PARK第一车间举行。Mary Katrantzou的主题发布围绕奢华的代名词展开,意在寻找过滤奢华之后的美丽;一件源于艺术或设计的作品如果过于真实,女性是无法穿戴的。前几季主要基于香水瓶,艺术内饰和的艺术实体,例如花田,日常物品,古董邮票,风景的设计系列以及最近的鞋子系列,均以印花图案为其审美核心。Mary Katrantzou在伦敦时装周2009春夏系列上首次展出了她的成衣系列,并得到了BFC公司和New Gen Scheme的支持。

  7. Jean-Marie Dufour 1937-2007

    CERN Multimedia

    2007-01-01

    Picture taken by Rudiger Voss in the Legal Service LibraryJean-Marie Dufour, CERN Legal Advisor from 1974 until his retirement in 2001, passed away on 8 July. For us, his colleagues in the Legal Service, Jean-Marie was a tutor and a reference, who passed on to us his passion for the practice of law in an intergovernmental organisation. As a boss, his abiding managerial quality was his unstinting loyalty to his collaborators. Jean-Marie joined CERN in 1966 and for the next 35 years was to be the guardian of the Laboratory’s rules. This was his view of the Organization: "...I have discovered [at CERN] a fascinating universe driven by two forces: science and Europe; a world of physicists and engineers who, encouraged by the States of Europe, run a remarkable Laboratory, where Europeans have achieved reconciliation and restored the grand tradition of European physics, attracting physicists from around the world; a Laboratory that transcends not only the fro...

  8. Atypical Odontalgia (Phantom Tooth Pain)

    Science.gov (United States)

    ... atypical facial pain, phantom tooth pain, or neuropathic orofacial pain, is characterized by chronic pain in a ... such as a specialist in oral medicine or orofacial pain. The information contained in this monograph is ...

  9. Piet Mondrian's trees and the evolution in understanding multiple sclerosis, Charcot Prize Lecture 2011

    NARCIS (Netherlands)

    Steinman, L.; Axtell, R.C.; Barbieri, D.; Bhat, R.; Brownell, S.E.; Jong, B.A. de; Dunn, S.E.; Grant, J.L.; Han, M.H.; Ho, P.P.; Kuipers, H.F.; Kurnellas, M.P.; Ousman, S.S.; Rothbard, J.B.

    2013-01-01

    Four questions were posed about multiple sclerosis (MS) at the 2011 Charcot Lecture, Oct. 22, 2011. 1. The Male/Female Disparity: Why are women developing MS so much more frequently than men? 2. Neuronal and Glial Protection: Are there guardian molecules that protect the nervous system in MS? 3. Pre

  10. Charcot, Mitchell and Lees: neurology free thinkers and their experiences of psychoactive drugs

    Directory of Open Access Journals (Sweden)

    Hélio A. G. Teive

    Full Text Available ABSTRACT Three world-famous neurologists, Charcot and Mitchell, in the 19th century, and Lees, in this century, all of whom had great scientific curiosity, experimented with the psychoactive drugs hashish, mescal and yagé, respectively, in an attempt to increase their knowledge of neurological diseases and how the brain works.

  11. Charcot arthropathy of the elbow joint as a presenting feature of Chiari malformation with syringomyelia.

    Science.gov (United States)

    Sahoo, Sushanta K; Salunke, Pravin

    2014-12-01

    Charcot arthropathy of the elbow joint is occasionally seen with Chiari malformation with syringomyelia, but rarely as a presenting feature as in the reported case. The treatment is directed toward its underlying cause to halt its progression. Thus, it is important to diagnose the cause as early as possible.

  12. Data mining for identifying novel associations and temporal relationships with Charcot foot.

    Science.gov (United States)

    Munson, Michael E; Wrobel, James S; Holmes, Crystal M; Hanauer, David A

    2014-01-01

    INTRODUCTION. Charcot foot is a rare and devastating complication of diabetes. While some risk factors are known, debate continues regarding etiology. Elucidating other associated disorders and their temporal occurrence could lead to a better understanding of its pathogenesis. We applied a large data mining approach to Charcot foot for elucidating novel associations. METHODS. We conducted an association analysis using ICD-9 diagnosis codes for every patient in our health system (n = 1.6 million with 41.2 million time-stamped ICD-9 codes). For the current analysis, we focused on the 388 patients with Charcot foot (ICD-9 713.5). RESULTS. We found 710 associations, 676 (95.2%) of which had a P value for the association less than 1.0 × 10⁻⁵ and 603 (84.9%) of which had an odds ratio > 5.0. There were 111 (15.6%) associations with a significant temporal relationship (P Charcot foot in the context of pathogenesis models that include neurotrophic, neurovascular, and microtraumatic factors mediated through inflammatory cytokines. Future work should focus on confirmatory analyses. These novel areas of investigation could lead to prevention or earlier diagnosis.

  13. Increased spasticity from a fracture in the baclofen catheter caused by Charcot spine: case report.

    Science.gov (United States)

    Ravindra, Vijay M; Ray, Wilson Z; Sayama, Christina M; Dailey, Andrew T

    2015-04-01

    In patients with Charcot spine, a loss of normal feedback response from the insensate spine results in spinal neuropathy. Increasing deformity, which can manifest as sitting imbalance, crepitus, or increased back pain, can result. We present the case of a patient with a high-thoracic spinal cord injury (SCI) who subsequently developed a Charcot joint at the T10-11 level that resulted in a dramatic increase in previously controlled spasticity after fracture of an existing baclofen catheter. The 68-year-old man with T4 paraplegia presented with increasing baclofen requirements and radiographic evidence of fracture of the intrathecal baclofen catheter with an associated Charcot joint with extensive bony destruction. The neuropathic spinal arthropathy caused mechanical baclofen catheter malfunction and resulting increased spasticity. The patient was found to have transected both his spinal cord and the baclofen catheter. Treatment consisted of removal of the catheter and stabilization with long-segment instrumentation and fusion from T6 to L2. Follow-up radiographs obtained a year and a half after surgery showed no evidence of hardware failure or significant malalignment. The patient has experienced resolution of symptoms and does not require oral or intrathecal baclofen. This is the only reported case of a Charcot spine causing intrathecal catheter fracture, leading to increased spasticity. This noteworthy case suggests that late spinal instability should be considered in the setting of SCI and increased spasticity.

  14. A two-stage percutaneous approach to charcot diabetic foot reconstruction.

    Science.gov (United States)

    Lamm, Bradley M; Gottlieb, H David; Paley, Dror

    2010-01-01

    The goals of Charcot deformity correction are to restore osseous alignment, regain pedal stability, and prevent ulceration. Traditional reconstructive surgical approaches involve large, open incisions to remove bone and the use of internal fixation to attempt to fuse dislocated joints. Such operations can result in shortening of the foot and/or incomplete deformity correction, fixation failure, incision healing problems, infection, and the longterm use of casts or braces. We recommend a minimally invasive surgical technique for the treatment of Charcot deformity, which we performed on 11 feet in 8 patients. Osseous realignment was achieved through gradual distraction of the joints with external fixation, after which minimally invasive arthrodesis was performed with rigid internal fixation. Feet were operated on at various stages of Charcot deformity: Eichenholtz stage I (1 foot), Eichenholtz stage II (6 feet), and Eichenholtz stage III (4 feet). When comparing the average change in preoperative and postoperative radiographic angles, the transverse plane talar-first metatarsal angle (P = .02), sagittal plane talar-first metatarsal angle (P = .008), and calcaneal pitch angle (P = .001) were all found to be statistically significant. Complications included 3 operative adjustments of external or internal fixation, 4 broken wires or half-pins, 2 broken rings, and 11 pin tract infections. Most notably, no deep infection, no screw failure, and no recurrent ulcerations occurred and no amputations were necessary during an average follow-up of 22 months. Gradual Charcot foot correction with the Taylor spatial frame plus minimally invasive arthrodesis is an effective treatment.

  15. Data Mining for Identifying Novel Associations and Temporal Relationships with Charcot Foot

    Directory of Open Access Journals (Sweden)

    Michael E. Munson

    2014-01-01

    Full Text Available Introduction. Charcot foot is a rare and devastating complication of diabetes. While some risk factors are known, debate continues regarding etiology. Elucidating other associated disorders and their temporal occurrence could lead to a better understanding of its pathogenesis. We applied a large data mining approach to Charcot foot for elucidating novel associations. Methods. We conducted an association analysis using ICD-9 diagnosis codes for every patient in our health system (n=1.6 million with 41.2 million time-stamped ICD-9 codes. For the current analysis, we focused on the 388 patients with Charcot foot (ICD-9 713.5. Results. We found 710 associations, 676 (95.2% of which had a P value for the association less than 1.0×10−5 and 603 (84.9% of which had an odds ratio > 5.0. There were 111 (15.6% associations with a significant temporal relationship P<1.0×10−3. The three novel associations with the strongest temporal component were cardiac dysrhythmia, pulmonary eosinophilia, and volume depletion disorder. Conclusion. We identified novel associations with Charcot foot in the context of pathogenesis models that include neurotrophic, neurovascular, and microtraumatic factors mediated through inflammatory cytokines. Future work should focus on confirmatory analyses. These novel areas of investigation could lead to prevention or earlier diagnosis.

  16. Biomaterial Selection for Tooth Regeneration

    OpenAIRE

    2011-01-01

    Biomaterials are native or synthetic polymers that act as carriers for drug delivery or scaffolds for tissue regeneration. When implanted in vivo, biomaterials should be nontoxic and exert intended functions. For tooth regeneration, biomaterials have primarily served as a scaffold for (1) transplanted stem cells and/or (2) recruitment of endogenous stem cells. This article critically synthesizes our knowledge of biomaterial use in tooth regeneration, including the selection of native and/or s...

  17. Farewell Jean-Marie Good Luck Eva Welcome back Franz

    CERN Document Server

    2001-01-01

    At the farewell reception offered by the Director-General, Professor Luciano Maiani, on the occasion of Jean-Marie Dufour's retirement from CERN, three generations of CERN Legal Counsel met. From right to left: Jean-Marie Dufour, who retires on 30 November 2001, after 35 years of service. Eva-Maria Gröniger-Voss, who takes over from Jean-Marie Dufour on 1st December 2001. Ambassador Franz Schmid, CERN Legal Counsel from 1971 to 1974.

  18. Marie and Pierre Curie. Life in extremes; Marie and Pierre Curie. Leben in Extremen

    Energy Technology Data Exchange (ETDEWEB)

    Roethlein, Brigitte

    2008-07-01

    In Paris in 1894, two young physicists fall in love: Marie Sklodowska and Pierre Curie. They get married and make great contributions to science, research radioactivity and discover new chemical elements. The marriage of Marie and Pierre Curie is quite modern: They work together as equals, share their thoughts and pursue their plans together as partners. They share an absolute interest in science, a love of nature, and a sceptic attitude towards the sophisticated society of the Belle Epoque. They are together 24 hours a day with hardly ever any disagreement. Whenever one of them is ill - which is quite often because of the high level of radioactivity in their laboratory -, the other will nurse him or her. After only twelve years of mutual love, Pierre Curie dies. Marie raises their two daughters on her own and continues her research. In 1911, she will be the first scientist that ever gets a second Nobel Prize. (orig.) [German] Im Paris des Jahres 1894 verlieben sich zwei junge Physiker: Marie Sklodowska und Pierre Curie. Sie heiraten und leisten gemeinsam Grosses fuer die Wissenschaft, erforschen die Radioaktivitaet und entdecken neue chemische Elemente. Zusammen erhalten sie den Nobelpreis. Marie und Pierre Curie fuehren eine Ehe, die ihrer Zeit weit voraus ist: Sie arbeiten gleichberechtigt miteinander, teilen ihre Gedanken und verfolgen ihre Plaene gemeinsam. Beiden eigen ist die absolute wissenschaftliche Neugier, die Liebe zur Natur und die Skepsis gegenueber der mondaenen Gesellschaft der Belle Epoque. Fast jeden Tag sind sie rund um die Uhr zusammen, dabei gibt es selten Spannungen. Wenn einer von beiden gesundheitliche Probleme hat - und das haben sie wegen der radioaktiven Belastung im Labor oft - ist der andere fuer ihn da und pflegt ihn. Nach nur zwoelf gemeinsamen Jahren der Liebe und Arbeit stirbt Pierre Curie. Marie zieht ihre beiden Toechter alleine gross und fuehrt die Forschungen weiter. 1911 erhaelt sie als erster Mensch zum zweiten Mal den

  19. Analysis of split tooth as an unstudied reason for tooth extraction

    OpenAIRE

    Osaghae, Ifueko Patience; Azodo, Clement Chinedu

    2014-01-01

    Background Split tooth is an unstudied reason for tooth extraction. The purpose of this study was to determine and analyze split tooth as a reason for extraction in a dental clinic in Benin City. Methods The prospective study was carried out on 669 patients having tooth extraction between May, 2005 and December, 2012. Over the period of the study, diagnosis and tooth extraction were done by three dentists of more five years practice experience. The indications for tooth extraction were noted ...

  20. Tooth wear patterns in the deciduous dentition.

    Science.gov (United States)

    Warren, John J; Yonezu, Takuro; Bishara, Samir E

    2002-12-01

    Tooth wear is common in the deciduous dentition. A recent study suggests that tooth wear in the deciduous dentition is related to subsequent tooth wear in adults, so that early identification of factors related to tooth wear could be of long-term benefit. The purposes of this study were to describe patterns of tooth wear in the deciduous dentition and to relate tooth wear to occlusal characteristics and longitudinal dietary patterns. Data were collected as part of a longitudinal study of a cohort of children recruited at birth from Iowa hospitals. Stone casts were obtained in the deciduous dentition stage, and 355 children, 4 to 5 years old, met the selection criteria. Tooth wear was categorized for each tooth as none, mild, moderate, or severe, and related to occlusal characteristics and longitudinal data on fruit juice and soft drink consumption. All children exhibited some tooth wear on at least 1 tooth, and nearly 16% of them had at least 1 tooth with severe wear. Tooth wear was generally more severe in the maxillary arch and the anterior teeth. Severe tooth wear on the molars was significantly related to posterior crossbites, but severe tooth wear on the incisors was related to Class III canine relationships. There were no statistically significant relationships between tooth wear and soft drink or fruit juice consumption. Based on our results, we concluded that mild tooth wear is universal in the deciduous dentition, but only a few occlusal factors are related to severe tooth wear. Tooth wear was not related to any dietary patterns we investigated.

  1. Mari Martin - vahelüli looja ja kandja vahel / Mari Martin ; intervjueerinud Tanel Veenre

    Index Scriptorium Estoniae

    Martin, Mari, 1983-

    2009-01-01

    Kalamari Promotioni tegevjuht, Tartu Ülikoolis majandust õppiv Mari Martin oma esimestest sammudest moemaailmas, kaubamärkide ReUse RePublic (premeeriti noorte äriideede võistlusel "Ajujaht 2009" 175000 krooniga) ja Tallinn Dolls loomisest, eesti disaineritest, unistustest seoses eesti disainiga

  2. Risk factors of diabetic foot Charcot arthropathy: a case-control study at a Malaysian tertiary care centre

    Science.gov (United States)

    Fauzi, Aishah Ahmad; Chung, Tze Yang; Latif, Lydia Abdul

    2016-01-01

    INTRODUCTION This study aimed to determine the risk factors of diabetic Charcot arthropathy of the foot among diabetic patients with and without foot problems. METHODS This was a case-control study involving diabetic patients attending the Diabetic Foot Care and Wound Management Clinic at University Malaya Medical Centre, Kuala Lumpur, Malaysia, from June 2010 to June 2011. Data on sociodemographic profiles, foot factors and diabetes characteristics was collected and analysed. RESULTS A total of 48 diabetic patients with Charcot arthropathy of the foot were identified. Data from these 48 patients was compared with those of 52 diabetic patients without foot problems. Up to 83.3% of patients with diabetic Charcot arthropathy presented with unilateral Charcot foot, most commonly located at the midfoot (45.8%). Patients with a history of foot problems, including foot ulcer, amputation, surgery or a combination of problems, had the highest (26-time) likelihood of developing Charcot arthropathy (odds ratio 26.4; 95% confidence interval 6.4–109.6). Other significant risk factors included age below 60 years, more than ten years’ duration of diabetes mellitus and the presence of nephropathy. CONCLUSION A history of prior diabetic foot problems is the greatest risk factor for developing diabetic Charcot arthropathy, compared with other risk factors such as diabetes characteristics and sociodemographic profiles. Preventive management of diabetic foot problems in the primary care setting and multidisciplinary care are of paramount importance, especially among chronic diabetic patients. PMID:27075668

  3. Marie Curie's contribution to Medical Physics.

    Science.gov (United States)

    Jean-Claude, Rosenwald; Nüsslin, Fridtjof

    2013-09-01

    On occasion of its 50th anniversary, the International Organization for Medical Physics (IOMP) from now on is going to celebrate annually an International Day of Medical Physics for which the 7th November, the birthday of Marie Sklodowska Curie, a most exceptional character in science at all and a pioneer of medical physics, has been chosen. This article briefly outlines her outstanding personality, sketches her fundamental discovery of radioactivity and emphasizes the impact of her various achievements on the development of medical physics at large.

  4. Marie and Pierre Curie and radium: history, mystery, and discovery.

    Science.gov (United States)

    Mould, R F

    1999-09-01

    Commencing with Marie Curie's early life in Poland and the discovery of radium in the rue l'Homond "shed" in Paris in 1898, this paper includes some little known facts. It ends with some unusual uses of and claims for radium, and finally, because Medical Physics is an American journal, details are included of Marie Curie's two visits to the USA.

  5. Eisma sadamahoone = Eisma port building / Mari Kurismaa ; kommenteerinud Krista Aren

    Index Scriptorium Estoniae

    Kurismaa, Mari, 1956-

    2015-01-01

    Eluruumid Eisma sadamahoones (Eisma küla, Vihula vald, Lääne-Virumaa). Sisekujunduse autorid Mari Kurismaa, Indrek Allmann; arhitekt Indrek Allmann (AB Pluss). Eesti Sisearhitektide Liidu aastapreemia 2014/2015 parima kodu eest. Lühidalt Mari Kurismaast ja Indrek Allmannist

  6. Mari Koger : "Arhitekte on palju. Tuleb leida õige" / Gitte Hint

    Index Scriptorium Estoniae

    Hint, Gitte

    2003-01-01

    Mari Koger (sünd. 1973) kodu kujundamisest, planeerimisest, valgustusest, värvidest, suhtlemisest kliendiga. Mari Kogerist, loetletud tema tehtud ühiskondlike ruumide sisekujundused aastast 2002. M. Koger töötab Boom.ee OÜ-s. Ill.: M. Kogeri värv. portree

  7. 33 CFR 117.653 - St. Mary's Falls Canal.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false St. Mary's Falls Canal. 117.653 Section 117.653 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Michigan § 117.653 St. Mary's Falls Canal. The draw...

  8. Tooth polishing: The current status

    Directory of Open Access Journals (Sweden)

    Madhuri Alankar Sawai

    2015-01-01

    Full Text Available Healthy teeth and gums make a person feel confident and fit. As people go about their daily routines and with different eating and drinking habits, the tooth enamel turns yellowish or gets stained. Polishing traditionally has been associated with the prophylaxis procedure in most dental practices, which patients know and expect. However, with overzealous use of polishing procedure, there is wearing of the superficial tooth structure. This would lead to more accumulation of local deposits. Also, it takes a long time for the formation of the fluoride-rich layer of the tooth again. Hence, now-a-days, polishing is not advised as a part of routine oral prophylaxis procedure but is done selectively based on the patients′ need. The article here, gives an insight on the different aspects of the polishing process along with the different methods and agents used for the same.

  9. Tooth polishing: The current status.

    Science.gov (United States)

    Sawai, Madhuri Alankar; Bhardwaj, Ashu; Jafri, Zeba; Sultan, Nishat; Daing, Anika

    2015-01-01

    Healthy teeth and gums make a person feel confident and fit. As people go about their daily routines and with different eating and drinking habits, the tooth enamel turns yellowish or gets stained. Polishing traditionally has been associated with the prophylaxis procedure in most dental practices, which patients know and expect. However, with overzealous use of polishing procedure, there is wearing of the superficial tooth structure. This would lead to more accumulation of local deposits. Also, it takes a long time for the formation of the fluoride-rich layer of the tooth again. Hence, now-a-days, polishing is not advised as a part of routine oral prophylaxis procedure but is done selectively based on the patients' need. The article here, gives an insight on the different aspects of the polishing process along with the different methods and agents used for the same.

  10. Primary culprit for tooth loss!!

    Directory of Open Access Journals (Sweden)

    Sailavanya Nuvvula

    2016-01-01

    Full Text Available Aim: In order to facilitate planning for dental health services and to progress strategies to continue the reduction in tooth loss, it is important to identify the factors that result in such loss. therefore the aim of the study is to investigate the major cause for tooth extraction. Objective: to examine whether the major reason for tooth extraction is dental caries or periodontal disease. Materials and Methods: The study is carried out among the dental practitioners in our district. A questionnaire containing 10 items was distributed to the dental practitioners, which included age, gender, no of teeth indicated for extraction, the reason for extraction, and the periodontal parameters that are involved with the extracted tooth and were requested to complete the form on every extraction they were to undertake. the study form was collected at the end of the study period and data was subjected to statistical analysis. Results: A total of 502 patients were enrolled during the study period, and a total of 1055 teeth were extracted for several reasons. we found that 51.14%extractions are due to dental caries in case of 20-30years age groups, which is more when compared to tooth loss due to periodontal diseases in this age group. whereas in case of >40years of age group periodontal diseases account for 54.11%, and dental caries accounts for only 29.11%. Showing more teeth were lost due to periodontal disease. Conclusion: therefore we concluded that, caries is the dominant reason for extraction in patients with 20–30 years of age while periodontal disease accounts for the majority of tooth extraction in patients older than 40 years.

  11. On gear tooth stiffness evaluation

    DEFF Research Database (Denmark)

    Pedersen, Niels Leergaard; Jørgensen, Martin Felix

    2014-01-01

    The estimation of gear stiffness is important for determining the load distribution between the gear teeth when two sets of teeth are in contact. Two factors have a major influence on the stiffness; firstly the boundary condition through the gear rim size included in the stiffness calculation...... and secondly the size of the contact. In the FE calculation the true gear tooth root profile is applied. The meshing stiffnesses of gears are highly non-linear, it is however found that the stiffness of an individual tooth can be expressed in a linear form assuming that the contact width is constant. © 2014...

  12. Roadmap to MaRIE March 2015

    Energy Technology Data Exchange (ETDEWEB)

    Barnes, Cris William [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-03-30

    Los Alamos National Laboratory’s proposed MaRIE facility is slated to introduce the world’s highest energy hard x-ray free electron laser (XFEL). As the light source for the Matter-Radiation Interactions in Extremes experimental facility (MaRIE), the 42-keV XFEL, with bursts of x-ray pulses at gigahertz repetition for studying fast dynamical processes, will help accelerate discovery and design of the advanced materials needed to meet 21st-century national security and energy security challenges. Yet the science of free-electron lasers has a long and distinguished history at Los Alamos National Laboratory (LANL), where for nearly four decades Los Alamos scientists have been performing research, design, development, and collaboration work in FEL science. The work at Los Alamos has evolved from low-gain amplifier and oscillator FEL development to highbrightness photoinjector development, and later, self-amplified spontaneous emission (SASE) and high-gain amplifier FEL development.

  13. Evolution and developmental diversity of tooth regeneration.

    Science.gov (United States)

    Tucker, Abigail S; Fraser, Gareth J

    2014-01-01

    This review considers the diversity observed during both the development and evolution of tooth replacement throughout the vertebrates in a phylogenetic framework from basal extant chondrichthyan fish and more derived teleost fish to mammals. We illustrate the conservation of the tooth regeneration process among vertebrate clades, where tooth regeneration refers to multiple tooth successors formed de novo for each tooth position in the jaws from a common set of retained dental progenitor cells. We discuss the conserved genetic mechanisms that might be modified to promote morphological diversity in replacement dentitions. We review current research and recent progress in this field during the last decade that have promoted our understanding of tooth diversity in an evolutionary developmental context, and show how tooth replacement and dental regeneration have impacted the evolution of the tooth-jaw module in vertebrates.

  14. Orthodontic Tooth Movement: A Historic Prospective.

    Science.gov (United States)

    Will, Leslie A

    2016-01-01

    The earliest report on orthodontic tooth movement in the English literature was published in 1911. Oppenheim carried out studies on baboons to determine what histologic changes occurred during tooth movement. Reitan and many others carried out research into the nature of tooth movement. The pressure-tension model of tooth movement developed from these studies, whereby the two sides of the tooth responded to forces as if in isolation. A second theory, proposed by Stuteville in 1938, was the hydraulic theory of tooth movement. In this theory, fluid from the vasculature, lymphatic system and intercellular spaces responds to the forces of tooth movement, damping the force and limiting movement. Bien and Baumrind expanded on this theory with their own studies in the 1960s. It is clear that both the pressure-tension and fluid flow concepts have merit, but considerable work needs to be done to ascertain the details so that tooth movement can be managed and controlled.

  15. Tooth Retained Implant: No More an Oxymoron

    OpenAIRE

    Divya Bhat

    2011-01-01

    Introduction: Periodontally af-fected teeth are treated in one of the two ways. (1) Tooth retention after periodontal surgery, in which the degree of regeneration achieved is unpredictable. (2) Tooth extrac-tion and implant placement. Implants have an osseointegrated surface which does not provide adequate shock absorption. Regeneration can be achieved by resecting the crown of the affected tooth and submerging the root. This technique has not had a clinical application so far as the tooth be...

  16. Biology of tooth replacement in amniotes

    Institute of Scientific and Technical Information of China (English)

    John A Whitlock; Joy M Richman

    2013-01-01

    Tooth replacement is a common trait to most vertebrates, including mammals. Mammals, however, have lost the capacity for continuous tooth renewal seen in most other vertebrates, and typically have only 1–2 generations of teeth. Here, we review the mechanisms of tooth replacement in reptiles and mammals, and discuss in detail the current and historical theories on control of timing and pattern of tooth replacement and development.

  17. Charcot neuroarthropathy in simultaneous kidney–pancreas transplantation: report of two cases

    Directory of Open Access Journals (Sweden)

    Jorge Javier del Vecchio

    2013-08-01

    Full Text Available Charcot neuroarthropathy (CN is considered a major complication in diabetes mellitus (DM, and it is estimated that 1% of diabetic patients may develop this complication. Simultaneous kidney–pancreas transplantation (SKPT is one of the most effective therapies for patients with type 1 DM and end-stage diabetic nephropathy. Some cases with a Charcot-modified clinical presentation during the postoperative convalescence period after SKPT have been described. The clinical presentation may condition severe destructive lesions, and good practices include systematic follow-up. Based on the cases described, SKPT is one more entity that might lead to CN ‘foot-at-risk’. The aim of this article is to describe two cases of neuropathic arthropathy with rapid progression in the short term after SKPT.

  18. Current Approaches to Diagnosis and Classification Features of Neuroosteoarthropathy Charcot (literature review

    Directory of Open Access Journals (Sweden)

    Balatiuk Irina

    2016-12-01

    Full Text Available The article provides the analysis of the publications of domestic and foreign authors on such complication of diabetes as diabetic Charcot osteoarthropathy. It formulates modern domestic classification of diabetic foot syndrome. It has been stated that diabetic foot syndrome is a serious medical and social problem, due to the high level of disability of patients, it causes significant social and economic losses to society. Pathogenetic basis for the development of diabetic osteoarthropathy is a combination of uncontrolled bone resorption and the lack of sensitivity of the defense, which leads to the destruction of joints. The gold standard for diagnosis of Charcot osteoarthropathy is X-ray densitometry that allows you to objectively assess the state of bone mineral density.

  19. [Tooth regeneration--dream to reality].

    Science.gov (United States)

    Wang, Song-Ling; Wang, Xue-Jiu

    2008-04-01

    Tooth or dentition missing compromises human health physically and psychiatrically. Although several prosthesis methods are used to restore tooth loss, these restorations are still non-biological methods. It is a dream for human being to regenerate a real tooth for hundreds years. There are two ways to regenerate the tooth. One is application of conventional tissue engineering techniques including seed cells and scaffold. The other is regeneration tooth using dental epithelium and dental mesenchymal cells based on the knowledge of tooth initiation and development. Marked progress has been achieved in these two ways, while there is still a long way to go. Recently a new concept has been proposed for regeneration of a biological tooth root based on tooth-related stem cells and tissue engineering technique. A biological tooth root has been regenerated in swine. It may be a valuable method for restoration of tooth loss before successful whole tooth regeneration. A latest research showed that a subpopulation in bone marrow cells can give rise to ameloblast-like cells when mixed with embryonic epithelium and reassociation with integrated mesenchyme, which may provide a new seed cell source for tooth regeneration.

  20. 21 CFR 872.3920 - Porcelain tooth.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Porcelain tooth. 872.3920 Section 872.3920 Food... DEVICES DENTAL DEVICES Prosthetic Devices § 872.3920 Porcelain tooth. (a) Identification. A porcelain tooth is a prefabricated device made of porcelain powder for clinical use (§ 872.6660) intended for...

  1. 自拟柴胡四金汤治疗夏科(Charcot)综合征

    Institute of Scientific and Technical Information of China (English)

    韩美荣

    2002-01-01

    @@ 笔者在2001年临床中遇到2例夏科(Charcot)综合征患者,2例均表现为典型的上腹痛、发热、黄疸,B超检查均提示胆总管呈泥沙样结石伴有胆管炎.笔者自拟柴胡四金汤治疗,疗效显著,兹介绍如下.

  2. Birth of modern psychiatry and the death of alienism: the legacy of Jean-Martin Charcot.

    Science.gov (United States)

    Bogousslavsky, Julien; Moulin, Thierry

    2011-01-01

    At the time of Jean-Martin Charcot, Paris--the main center for studies on the nervous system and its disorders--was home to critical exchanges between the developing discipline of neurology and psychiatry. Contrary to the commonly held view, and in spite of an established tradition concerning mental diseases, emerging neurology had a much stronger influence on psychiatry ('alienism') than the reverse. This was largely due to the school built up by Jean-Martin Charcot himself, which was organized around the study and management of hysteria. Although Charcot always claimed to be uninterested in mental medicine, he stimulated the development of an original scientific approach to nervous system conditions, based on Claude Bernard's method, along with structured academic teaching. Conversely, alienism paradoxically remained stuck in organicism, after Antoine Bayle's report in 1822 of 'arachnitis' as the substratum of general paresis of the insane. Contrary to alienism, the young neurological school was capable of self-criticism, and progressively highlighted mental factors in hysteria. This led to the paradox that neurologists were active in a disease with no organic cerebral lesion, while alienists were postulating brain lesions in all mental disorders. Pushed by Charcot, the academic evolution led to the launch of a faculty chair of mental and brain diseases in 1875, which was taken over for nearly half a century by his direct pupils Benjamin Ball, Alix Joffroy and Gilbert Ballet, who held the position until 1916, supporting the development of modern psychiatry in general hospitals, while alienism progressively disappeared at the turn of the century.

  3. Bilateral Charcot arthropathy of shoulder secondary to syringomyelia: An unusual case report

    Directory of Open Access Journals (Sweden)

    Ashok Panagariya

    2012-01-01

    Full Text Available Neuropathic arthropathy of the shoulder is a relatively rare disorder characterized by destruction of joint secondary to loss of sensory innervation. Bilateral Charcot arthropathy is an even rarer disorder, with very few cases reported in the English literature. We herein present a case of bilateral shoulder arthropathy secondary to syringomyelia with classical clinical and radiological findings. Radiological finding on one side was of resorptive type and resorptive mixed with productive on the other side.

  4. Abductor hallucis muscle flap with circular external fixation for Charcot foot osteomyelitis: a case report

    Directory of Open Access Journals (Sweden)

    Crystal L. Ramanujam

    2011-05-01

    Full Text Available Complicated soft tissue defects of the diabetic foot often call for alternative methods to traditional primary closure. Despite the popularity of microvascular free flaps, local muscle flaps can offer reliable reconstruction for these challenging wounds with shorter surgical times and reduced complication rates. In this article, the authors describe the successful use of the abductor hallucis muscle flap and external fixation for soft tissue reconstruction of a chronic Charcot foot wound and osteomyelitis in a diabetic patient.

  5. Conservative and surgical treatment of the chronic Charcot foot and ankle

    Directory of Open Access Journals (Sweden)

    Mehmet Fatih Güven

    2013-08-01

    Full Text Available Charcot neuroarthropathy (CN is a severe joint disease in the foot and ankle that can result in fracture, permanent deformity, and limb loss. It is a serious and potentially limb-threatening lower-extremity late complication of diabetes mellitus. The aim of this manuscript was to evaluate modern concepts of chronic CN through a review of the available literature and to integrate a perspective of management from the authors’ extensive experience.

  6. Abductor hallucis muscle flap with circular external fixation for Charcot foot osteomyelitis: a case report

    OpenAIRE

    Zgonis, Thomas; Ramanujam, Crystal L.; Facaros, Zacharia

    2011-01-01

    Complicated soft tissue defects of the diabetic foot often call for alternative methods to traditional primary closure. Despite the popularity of microvascular free flaps, local muscle flaps can offer reliable reconstruction for these challenging wounds with shorter surgical times and reduced complication rates. In this article, the authors describe the successful use of the abductor hallucis muscle flap and external fixation for soft tissue reconstruction of a chronic Charcot foot wound and ...

  7. Osteomyelitis or Charcot neuro-osteoarthropathy? Differentiating these disorders in diabetic patients with a foot problem

    OpenAIRE

    Bulent M. Ertugrul; Lipsky, Benjamin A.; Savk, Oner

    2013-01-01

    Both osteomyelitis and Charcot neuro-osteoarthropathy (CN) are potentially limb-threatening complications of diabetic neuropathy, but they require quite different treatments. Almost all bone infections in the diabetic foot originate from an infected foot ulcer while diabetic osteoarthropathy is a non-infectious process in which peripheral neuropathy plays the critical role. Differentiating between diabetic foot osteomyelitis and CN requires careful evaluation of the patient, including the med...

  8. Novel use of a Dektak 150 surface profiler unmasks differences in resorption pit profiles between control and Charcot patient osteoclasts.

    Science.gov (United States)

    Petrova, Nina L; Petrov, Peter K; Edmonds, Michael E; Shanahan, Catherine M

    2014-04-01

    We hypothesized that newly formed osteoclasts from patients with acute Charcot osteoarthropathy can resorb surfaces of bone more extensively compared with controls. Peripheral blood monocytes, isolated from eight Charcot patients and nine controls, were cultured in vitro on 24-well plates and bovine bone discs in duplicate with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor κβ ligand (RANKL). Osteoclast formation was assessed by tartrate-resistant acid phosphatase staining (TRAcP) at day 17. Resorption was measured at day 21 after toluidine blue staining by two methods: (1) area of resorption at the surface by image analysis (%) and (2) area of resorption under the surface (μm(2)) measured by a Dektak 150 Surface Profiler. Ten 1,000 μm-long scans were performed per disc. Pits were classified as unidented, bidented, and multidented according to their shape. Although the number of newly formed TRAcP positive multinucleated cells (>3 nuclei) was similar in M-CSF + RANKL-treated cultures between controls and Charcot patients, the latter exhibited increased resorbing activity. The area of resorption on the surface by image analysis was significantly greater in Charcot patients compared with controls (21.1 % [14.5-26.2] vs. 40.8 % [35.4-46.0], median [25-75th percentile], p Charcot patients pits were deeper and wider and more frequently presented as multidented pits. This application of the Dektak 150 Surface Profiler revealed novel differences in resorption pit profile from osteoclasts derived from Charcot patients compared with controls. Resorption in Charcot patients was mediated by highly aggressive newly formed osteoclasts from monocytes eroding large and deep areas of bone.

  9. Moved by Mary: The power of pilgrimage in the modern world

    NARCIS (Netherlands)

    Hermkens, A.K.; Jansen, W.H.M.; Notermans, C.D.

    2009-01-01

    The Virgin Mary continues to attract devotees to her images and shrines. In Moved by Mary, anthropologists, geographers and historians explore how people and groups around the world identify and join with Mary in their struggle against social injustice, and how others mobilize Mary to impose ideas a

  10. Syringomyelia with Chiari I Malformation Presenting as Hip Charcot Arthropathy: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Roya Memarpour

    2015-01-01

    Full Text Available Neuroarthropathy (neuropathic osteoarthropathy, also known as Charcot joint, is a condition characterized by a progressive articular surface destruction in the setting of impaired nociceptive and proprioceptive innervation of the involved joint. It is seen most commonly in the foot and ankle secondary to peripheral neuropathy associated with diabetes mellitus. Cases of hip (Charcot neuroarthropathy are rare and almost exclusively reported in patients with neurosyphilis (tabes dorsalis. We report a case of a 36-year-old man who presented to the emergency department complaining of right hip pain. On physical examination, pain and thermal sensory deficits were noted in the upper torso with a cape-like distribution, as well as signs of an upper motor neuron lesion in the left upper and lower extremities. A magnetic resonance imaging study (MRI of the right hip showed evidence of early articular surface destruction and periarticular edema consistent with hip Charcot arthropathy. An MRI of the spine revealed an Arnold-Chiari type I malformation with extensive syringohydromyelia of the cervical and thoracic spine.

  11. The pathogenesis of Charcot osteoarthropathy: the role of the peripheral nervous system

    Directory of Open Access Journals (Sweden)

    Galstyan Gagik Radikovich

    2015-01-01

    Full Text Available Neuroosteoarthropathy is a rare, but devastating complication affecting patients with peripheral neuropathy. It is a progressive, destructive condition that is characterised by progressive bone and joint deterioration of the foot leading to permanent incapacity. Nowadays, diabetes mellitus is by far the most common etiology of CNO (Charcot neuro-osteoarthropathy, especially if it affects the foot or ankle.The cause of the condition is still controversial among experts. In particular, new data have emerged on the central role of RANK/RANKL/OPG in the pathogenesis of this complication, also known as Charcot foot. No pharmacological methods of therapy have proven effective to date. Very little progress has been made in treating this condition since the days of Jean-Martin Charcot. Today, the universally accepted treatment involves completely relieving pressure from the limb using a polymer retaining bandage. The aim of this review is to analyze research into the pathogenesis of CNO and our potential to better understand the nature of this condition.Particular attention is paid to modern concept of neuroosteopathology, according to which neuropathy is crucial to developing acute osseous pathology. Revealing new aspects of CNO pathogenesis can help extend therapeutic resources for treating this patient group.

  12. Is the Eichenholtz classification still valid for the diabetic Charcot foot?

    Science.gov (United States)

    Chantelau, Ernst Adolf; Grützner, Gotthard

    2014-01-01

    In his 1966 monograph "Charcot joints", Sidney N. Eichenholtz (1909-2000) described "three well defined stages … in the course and development of a Charcot joint", based on plain X-rays of 68 patients. Since then, medical imaging has advanced very much: computed tomography and magnetic resonance imaging (MRI) scans exceed plain X-ray by far in detecting foot fractures and other injuries. The earliest, nondeforming, X-ray-negative inflammatory stage of the acute Charcot joint of the diabetic foot can be visualised only by use of MRI. This stage, which Eichenholtz evidently failed to recognise, will heal without significant arthropathy, if treated in time. By contrast, the stages considered by Eichenholtz inevitably result in major arthropathy and foot deformity. Hence, superseding the Eichenholtz classification is overdue. We propose an MRI-based classification comprising two severity grades (0 and 1, according to absence/presence of cortical fractures) and two stages (active/inactive, according to presence/absence of skeletal inflammation).

  13. Comparison of Complications for Internal and External Fixation for Charcot Reconstruction: A Systematic Review.

    Science.gov (United States)

    Dayton, Paul; Feilmeier, Mindi; Thompson, Mitchell; Whitehouse, Paul; Reimer, Rachel A

    2015-01-01

    The surgical reconstruction of Charcot deformity can be a challenge for foot and ankle surgeons. Consensus is lacking among surgeons regarding the best method of surgical fixation to be used in reconstruction, and clear strong evidence is also lacking in published studies. We undertook a systematic review of electronic databases and other relevant sources in an attempt to better understand the complications and outcomes associated with internal and external fixation for Charcot foot and ankle reconstruction. A total of 23 level 4 studies with 616 procedures were identified. Of these, 12 studies with 275 procedures used internal fixation, and 11 studies with 341 procedures used external fixation. The odds of a successful outcome with internal fixation was 6.86. The odds of a successful outcome with external fixation was 13.20 (odds ratio 0.52, 95% confidence interval 0.30 to 0.90). The odds of success for internal fixation was 0.52 times as likely as the odds of success with external fixation. Because the odds ratio did not include 1, this difference was statistically significant at the p foot and ankle surgeons when making decisions regarding fixation for Charcot reconstruction.

  14. The life and legacy of Marie Curie.

    Science.gov (United States)

    Rockwell, Sara

    2003-01-01

    Marie Curie was a remarkable woman whose discoveries broke new ground in physics and chemistry and also opened the door for advances in engineering, biology, and medicine. She broke new ground for women in science: she was, for example, the first woman to receive a doctor of science degree in France, the first woman to win Nobel Prize, the first woman to lecture at the Sorbonne, the first person to win two Nobel Prizes, and the first Nobel Laureate whose child also won a Nobel Prize. Her life offers insights into the changing role of women in science and academia over the past century. It also offers examples of many ways in which scientists can, and should, work to improve the educational programs and career opportunities available to those who follow in their footsteps.

  15. Mary Wigman: the coreography of Carmina Burana

    Directory of Open Access Journals (Sweden)

    Elena Randi

    2012-11-01

    Full Text Available This essay analyses the choreography of Mary Wigman’s Carmina Burana (1955, music by Orff, whose substantial outline Randi can reconstruct primarily through the drawings, partially unpublished, Wigman made to write down the different passages of her dance score. Randi thinks that the characters must not be seen as realistic and that they are the projections of the Vagabond, whose quest is supposed to be the theme underlining the story. The theme of destiny – a destiny on which man has very little or no control – is dominant. The end of the choreography seems to clarify that the self’s quest consists in piétiner sur place: our actions are inevitably sucked under by a whirlpool (represented by the wheel of Fortune choreographically rendered by the figure of the circle and they are unable to bring any significant change. 

  16. COMPUTED TOMOGRAPHY OF TOOTH RESORPTION IN CATS.

    Science.gov (United States)

    Lang, Linda G; Wilkinson, Thomas E; White, Tammy L; Farnsworth, Raelynn K; Potter, Kathleen A

    2016-09-01

    Tooth resorption is the most common dental disease in cats and can be a source of oral pain. The current clinical gold standard for diagnosis includes a combination of oral exam and dental radiography, however early lesions are not always detected. Computed tomography (CT) of the skull, including the dental arches, is a commonly performed diagnostic procedure, however the appearance of tooth resorption on CT and the diagnostic ability of CT to detect tooth resorption have not been evaluated. The purpose of this prospective, descriptive, diagnostic accuracy study was to characterize the CT appearance of tooth resorption in a sample of affected cats and to evaluate the sensitivity and specificity of CT for tooth resorption compared to the clinical gold standard of oral exam and intraoral dental radiography. Twenty-eight cat cadaver specimens were recruited for inclusion. Each specimen was evaluated using oral exam, intraoral dental radiography, and computed tomography (four different slice thicknesses). Each tooth was evaluated for the presence or absence of tooth resorption. Teeth with lesions and a subset of normal teeth were evaluated with histopathology. On CT, tooth resorption appeared as irregularly marginated hypoattenuating defects in the mineral attenuating tooth components, most commonly involving the root or cementoenamel junction. Sensitivity for CT detection of tooth resorption was fair to poor (42.2-57.7%) and specificity was good to excellent (92.8-96.3%). Findings from this study indicated that CT has high specificity but low sensitivity for detection of tooth resorption in cats.

  17. Fluoridation and tooth wear in Irish adults.

    LENUS (Irish Health Repository)

    Burke, F M

    2010-10-01

    The aim of this study was to determine the prevalence of tooth wear in adults in Ireland and its relationship with water fluoridation. The National Survey of Adult Oral Health was conducted in 2000\\/2001. Tooth wear was determined using a partial mouth examination assessing the upper and lower anterior teeth. A total of 2456 subjects were examined. In this survey, increasing levels and severity of tooth wear were associated with ageing. Men were more affected by tooth wear and were more likely to be affected by severe tooth wear than women. It was found that age, and gender were significant predictors of tooth wear (P < 0.01). Overall, there was no significant relationship between fluoridation and tooth wear in this study.

  18. Ilizarov External Fixator Versus Retrograde Intramedullary Nailing for Ankle Joint Arthrodesis in Diabetic Charcot Neuroarthropathy.

    Science.gov (United States)

    ElAlfy, Barakat; Ali, Ayman M; Fawzy, Sallam I

    Charcot neuroarthropathy of the ankle joint is a destructive process that leads to instability and significant morbidity that can end with amputation. Surgical arthrodesis in Charcot neuroarthropathy has a high failure rate. The aim of the present prospective study was to compare the outcomes of an Ilizarov external fixator and retrograde intramedullary nailing (IMN) for tibiotalar arthrodesis in Charcot neuroarthropathy. From February 2010 to October 2013, 27 patients (16 males and 11 females) with Charcot neuropathy of the ankle joint were treated in our department. Their ages ranged from 32 to 75 (average 54) years. Of the 27 patients, 14 received an Ilizarov external fixator and 13 underwent IMN. A preoperative clinical and radiologic assessment of all patients was performed. The outcomes were measured for bone union, development of complications, and clinical follow-up. The mean score of modified American Orthopaedic Foot and Ankle Society ankle hindfoot scale was 80 ± 2.7 points in the Ilizarov group and 75 ± 1.9 points in the IMN group. In the Ilizarov group, 12 of 14 patients achieved union, and in the IMN group, 10 of 13 patients achieved union. The complication rate was significantly greater in the external fixator group than in the IMN group. The complications in the Ilizarov group included nonunion in 2 patients (14%), pin tract infection in 8 (57%), pin tract loosening in 3 (21%), surgical wound infection in 3 (21%), and wound breakdown in 1 patient (7%). In the IMN group, nonunion occurred in 3 patients (23.1%), back-out of a distal locking bolt in 2 (15.4 %), and a superficial wound infection that resolved with antibiotics in 1 patient (7.7%). In conclusion, retrograde IMN and the Ilizarov external fixator both yielded better union for tibiotalar arthrodesis in Charcot neuroarthropathy. The Ilizarov external fixator resulted in a greater union rate than IMN but the complications with external fixation were significantly greater than those

  19. Sudeck's disease stage 1, or diabetic Charcot's foot stage 0? Case report and assessment of the diagnostic value of MRI

    Directory of Open Access Journals (Sweden)

    Poll Ludger W

    2010-10-01

    Full Text Available Abstract Background The diagnosis of Sudeck's syndrome stage 1 (nowadays termed complex regional pain syndrome I, abbreviated CRPS I is based on clinical features, namely swelling and pain in a limb. Plain X-ray may be normal. In the absence of pain sensitivity, e.g. in diabetic neuropathy, CRPS I of the foot can be mistaken for Charcot's foot stage 0 (so-called neuro-osteoarthropathy. Case presentation The case of a type-1 diabetic woman is reported, in whom CRPS I following a calcaneal fracture was mistaken for Charcot's osteoarthropathy (because of bone marrow edema displayed by conventional MR imaging. In addition, a review is presented on 6 consecutive cases with CRPS I of the foot, and on 20 cases with Charcot's foot stage 0, with particular emphasis on MR imaging findings. The number of bones per foot affected with marrow edema was similar in either condition, with a tendency towards a more patchy, diffuse distribution of bone marrow edema in CRPS I. Bone marrow edema apparently regressed more promptly in response to treatment in Charcot's foot stage 0. Conclusion Differentiation of CRPS I from Charcot's foot stage 0 remains a diagnostic dilemma in patients with pain insensitivity. Conventional MRI may be helpful, when repeated for monitoring the treatment response.

  20. Inhibition of TNF-α Reverses the Pathological Resorption Pit Profile of Osteoclasts from Patients with Acute Charcot Osteoarthropathy

    Directory of Open Access Journals (Sweden)

    Nina L. Petrova

    2015-01-01

    Full Text Available We hypothesised that tumour necrosis factor-α (TNF-α may enhance receptor activator of nuclear factor-κβ ligand- (RANKL- mediated osteoclastogenesis in acute Charcot osteoarthropathy. Peripheral blood monocytes were isolated from 10 acute Charcot patients, 8 diabetic patients, and 9 healthy control subjects and cultured in vitro on plastic and bone discs. Osteoclast formation and resorption were assessed after treatment with (1 macrophage-colony stimulating factor (M-CSF and RANKL and (2 M-CSF, RANKL, and neutralising antibody to TNF-α (anti-TNF-α. Resorption was measured on the surface of bone discs by image analysis and under the surface using surface profilometry. Although osteoclast formation was similar in M-CSF + RANKL-treated cultures between the groups (p>0.05, there was a significant increase in the area of resorption on the surface (p<0.01 and under the surface (p<0.01 in Charcot patients compared with diabetic patients and control subjects. The addition of anti-TNF-α resulted in a significant reduction in the area of resorption on the surface (p<0.05 and under the surface (p<0.05 only in Charcot patients as well as a normalisation of the aberrant erosion profile. We conclude that TNF-α modulates RANKL-mediated osteoclastic resorption in vitro in patients with acute Charcot osteoarthropathy.

  1. Anne-Marie Sargueil: ilu on kasulik / intervjueerinud Emilie Toomela

    Index Scriptorium Estoniae

    Sargueil, Anne-Marie

    2015-01-01

    Prantsuse Disainiinstituudi juht Anne-Marie Sargueil rääkis prantsuse ja skandinaavia disainist, prantslaste disainieelistustest, uutest suundadest disaini valdkonnas, Eesti Tarbekunsti- ja Disainimuuseumis avatud näitusest "20 prantsuse disainiikooni"

  2. Marie Curie: In the Laboratory and on the Battlefield

    Science.gov (United States)

    Badash, Lawrence

    2003-07-01

    This year is the centennial of the Nobel Prize in Physics shared by Henri Becquerel and the Curies for their pioneering work on radioactivity. But Marie Curie's contribution to the medical use of x rays is not widely known.

  3. Deployment of Autonomous GPS Stations in Marie Byrd Land, Antartica

    Science.gov (United States)

    Donnellan, A.; Luyendyk, B.; Smith, M.; Dace, G.

    1999-01-01

    During the 1998-1999 Antarctic field season, we installed three autonomous GPS stations in Marie Byrd Land, West Antarctica to measure glacio-isostatic rebound and rates of spreading across the West Antartic Rift System.

  4. Marie Curie's Doctoral Thesis: Prelude to a Nobel Prize.

    Science.gov (United States)

    Wolke, Robert L.

    1988-01-01

    Traces the life and research techniques of Marie Curie's doctoral dissertation leading to the discovery and purification of radium from ore. Reexamines the discoveries of other scientists that helped lead to this separation. (ML)

  5. A bust of Marie Sklodowska Curie at CERN

    CERN Multimedia

    1979-01-01

    The Polish Deputy Minister of Energy and Nuclear Power, J. Felicki, presented the Directors General with a bust of Mme Marie Sklodowska Curie on behalf of physicists of Poland (CERN Courier 19 (1979) 164).

  6. Mary Tyler Moore Helps Launch NIH MedlinePlus Magazine

    Science.gov (United States)

    ... Issues Mary Tyler Moore Helps Launch NIH MedlinePlus Magazine Past Issues / Winter 2007 Table of Contents For ... Javascript on. Among those attending the NIH MedlinePlus magazine launch on Capitol Hill were (l-r) NIH ...

  7. Mary Carpenter: 19th Century English Correctional Education Hero.

    Science.gov (United States)

    Gehring, Thom; Bowers, Fredalene B.

    2003-01-01

    Describes Mary Carpenter's (1807-1877) work in prison reform and correctional education. Provides biographical information and selections from her writings. (Contains 11 references and a chronology of her work.) (JOW)

  8. Anneli Remme soovitab : Kuninganna Mary elu ja surm / Anneli Remme

    Index Scriptorium Estoniae

    Remme, Anneli, 1968-

    2002-01-01

    Kontserdisarja "Hingemuusika" teist kontserti raamivad Henry Purcelli teosed, millest esimene on loodud kuninganna Mary sünnipäevaks, viimane matusetseremooniaks. Barokkansambli Corelli Consort esituses 26., 27., ja 28. apr. Viljandi, Tartu ja Tallinna kirikutes

  9. Raamatukogu esisele kerkib kevadel Marie Underi kuju / Andres Eilart

    Index Scriptorium Estoniae

    Eilart, Andres

    2009-01-01

    Skulptor Mati Karminil ja arhitekt Tiit Trummalil valmib valgest marmorist mälestusmärk Marie Underile. Kuju püstitatakse 2010. a. kevadel Eesti Rahvusraamatukogu ette. Alale on kavandatud ka veekaskaadid

  10. Mari Koger : seina sisse ehitatud akvaariumiga poissmehekodu / Gitte Hint

    Index Scriptorium Estoniae

    Hint, Gitte

    2003-01-01

    80-ruutmeetrine poissmehekorter Viimsi uues elamus. Elutoa ja vannitoa vahelises seinas paikneb kahelt poolt vaadeldav akvaarium. Magamistoa üks seintest on ehitatud vanadest tellistest. Sisearhitekt Mari Koger, tema kommentaarid. Ill.: plaan, 9 värv. vaadet

  11. Ämari baas sobib USA-le ja brittidele

    Index Scriptorium Estoniae

    2013-01-01

    Eelmisel nädalal Eestit külastanud USA ja Ühendkuningriigi sõjalised esindajad NATO juures kindralleitnandid David R. Hogg ja Christopher Harper kinnitasid, et on valmis oma lennukeid Ämari baasist opereerima

  12. A jolly good call for Marie Curie Fellows

    CERN Multimedia

    2009-01-01

    A new funding opportunity to train young researchers has just been announced by the European Commission. One of the calls within FP7 Marie Curie Actions requests proposals for Initial Training Network (ITN) projects, with a deadline of 22 December 2009. Project proposals are strongly encouraged at CERN and authors can receive support and guidance from the Marie Curie Steering Group. Winnie Wong: "I wouldn’t have considered a PhD if I hadn’t been a Marie Curie fellow" Dan Savu: "It’s the best of both worlds: training plus working in an international organisation" ITN projects have one key aim: training. Academic and industrial partners work together to form a network to recruit and train Marie Curie Fellows. Fellows are young researchers (typically PhD-level) from any country who combine project-based research with tailor-made training programmes, ...

  13. Tooth sensitivity: mechanisms and management.

    Science.gov (United States)

    Markowitz, K

    1993-08-01

    Tooth sensitivity is a common complaint encountered in clinical practice. Exposed superficial dentin is free of nerve endings, yet sensitive. Experimental evidence indicates that stimuli, such as probing the dentin surface and air blasts, induce fluid movements in the dentinal tubules and these fluid movements, in turn, activate the intradental nerves. The condition of the dentin surface is critically important in allowing this process. In addition, the internal environment of the pulp may influence nerve excitability. Therapies for tooth sensitivity include both agents that obstruct the dentinal tubules and agents that can decrease the excitability of the intradental nerves. The exact treatment used depends on the etiology of the individual's problem and the extent of dentinal tissue damage.

  14. Towards tooth friendly soft drinks.

    Science.gov (United States)

    Kolahi, Jafar; Fazilati, Mohamad; Kadivar, Mahdi

    2009-10-01

    Most soft drinks contain high concentration of simple carbohydrates and have a pH of 3 or even lower. Therefore, they are harmful for tooth structure. A tooth friendly soft drink (T.F.S.D) should have the following characteristics and elements; fluoride (approximately 1 ppm), casein phosphopeptide-amorphous calcium phosphate (2%), xylitol (4-6g/serving), tea polyphenols (2-4 mg/ml), cranberry extract (250 mg/ml of the flavonoids quercetin and myricetin), sugar free, pH close to 5.5 and super oxygenation (240,000 ppm) vs. carbonation. T.F.S.D can be packaged in a container which gaseous oxygen is dissolved in a liquid in the form of bubbles. However, looking at opportunities for so-called sophisticated soft drinks, T.F.S.D will be an example for a functional and health oriented soft drink.

  15. Optical spectroscopy and tooth decay

    Science.gov (United States)

    Misra, P.; De, T.; Singh, R.

    2005-11-01

    Optical spectroscopy in the ultraviolet, visible and mid-infrared spectral regions has been used to discriminate between healthy and diseased teeth of patients in the age range 15-75 years. Spectral scans of absorbance versus wavenumber and fluorescence intensity versus wavelength have been recorded and investigated for caries and periodontal disease. Such optical diagnostics can prove very useful in the early detection and treatment of tooth decay.

  16. Supernumerary Jawbone Tooth: Clinical Case

    OpenAIRE

    Rivas Gutiérrez, Jesús; Carlos Sánchez, María Dolores

    2016-01-01

    Introduction: supernumerary teeth are dental development anomalies, alsoknown as hyperdontia or extra teeth. Their prevalence ranges between 0.3% and 3.8%.Their morphology may be normal or dismorphic and are associated to the etiology ofocclusal alterations. It is important to make an early diagnostic through a radiographicalstudy. Case presentation:this article presents a clinical case of a supernumerary tooth thatcaused rotation and crowding of the anterior bottom teeth, which was addressed...

  17. 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

    The peripheral myelin protein 22 gene (PMP22) encodes an intrinsic membrane protein of compact myelin. Duplication or deletion of PMP22 causes the most common autosomal dominant neuropathies, Charcot-Marie-Tooth disease type 1A or hereditary neuropathy with liability to pressure palsies. Charcot-Marie-Tooth disease type 1A is a hypertrophic de-remyelinating neuropathy manifesting with peroneal muscular atrophy and uniform, marked, slowing of nerve conduction velocities. Hereditary neuropathy with liability to pressure palsies is a recurrent focal neuropathy with sausage-like myelin thickening (tomacula) and non-uniform nerve conduction velocity changes. Missense or nonsense mutations also cause more severe Charcot-Marie-Tooth disease type 1A forms of infancy or hereditary neuropathy with liability to pressure palsies, but they are presumably very rare. We performed a mutational scanning of PMP22 in 229 index patients (46 familial, 183 isolated) referred for suspected inherited neuropathy. The series included 125 cases with hereditary neuropathy with liability to pressure palsies (mean age 42.5 years), 47 cases with Charcot-Marie-Tooth disease type 1A (motor nerve conduction velocities at median nerve below 38 m/s) (mean age 40.7 years) and 57 cases with Charcot-Marie-Tooth with unknown nerve conduction velocities (mean age 43 years). Preliminary molecular studies ruled out PMP22 duplication or deletion or mutations in a comprehensive panel of Charcot-Marie-Tooth genes. Mutational scanning of PMP22 was done by denaturing high performance liquid chromatography and automated nucleotide sequencing. To investigate the molecular basis of phenotype-to-genotype correlations, we performed a transcriptional analysis of PMP22 using reverse-transcriptase polymerase chain reaction and quantitative real-time polymerase chain reaction in two phenotypically divergent nerve biopsies. Ten patients harboured eight micromutations of PMP22 including four novel changes. In six familial

  18. Referrals to the Marie Curie nursing service in North Yorkshire.

    Science.gov (United States)

    Hanratty, B; Feather, J; Ward, C

    2000-01-01

    District and Marie Curie nurses participated in a small-scale study to describe referrals to a Marie Curie service in one English health district over a 3-month period. The number of new patients referred was small; they were geographically clustered and had widely differing life expectancies. Anecdotal reports of difficulties with the 'Nurselink' referral system were not confirmed, and in situations where the system was in operation, Marie Curie nurses were more likely to speak directly to the referring nurse. The most frequently cited reason for referral was general nursing needs; however, Marie Curie nurses felt that they were most often involved to provide family support. These findings suggest that there may not be a shared understanding of the Marie Curie nurse's role, and that equity in community palliative nursing care merits examination. Defining and publicizing the role of the Marie Curie nurse, providing guidance for referrals and prioritizing communication between professionals are proposed not only to enhance the service locally but to ensure that the service is available to all. This article illustrates the value of research to identify ways to improve service delivery.

  19. Preoperative imaging of charcot neuroarthropathy. Does the additional application of {sup 18}F-FDG-PET make sense?

    Energy Technology Data Exchange (ETDEWEB)

    Hoepfner, S. [Abt. fuer Diagnostische Radiologie, Universitaetsklinikum Giessen und Marburg, Standort Giessen (Germany); Krolak, C. [Inst. fuer Klinische Radiologie, Klinikum der Ludwig-Maximilians-Univ. Muenchen (Germany); Kessler, S. [Chirurgische Klinik und Poliklinik, Klinikum der Ludwig-Maximilians-Univ. Muenchen (Germany); Tiling, R. [Klinik und Poliklinik fuer Nuklearmedizin, Klinikum der Ludwig-Maximilians-Univ. Muenchen (Germany)

    2006-07-01

    With about 4 million diabetics in Germany and presumed inclination over the following years the treatment of diabetic complications like diabetic foot will become an even more important point. The management of Charcot's foot has undergone fundamental change in the last few years. Formerly, treatment was almost exclusively limited to non surgical measures; since the late 1990's, however, current practice has shifted to early, stage-appropriate surgical therapy. The aim of the present prospective study was to investigate the value of positron emission tomography (PET) in the pre-operative work-up of Charcot's foot. PET were compared to magnetic resonance tomography (MRI). Patients, methods: MRI and PET imaging were used as part of the preoperative work-up in 18 patients with Type II diabetes mellitus. The diagnosis of Charcot's foot requiring surgical treatment were made on the basis of clinical and radiologic criteria. Results: of 46 Charcot's lesions confirmed at surgery, 44 and 35 were detected by means of PET and MRI, respectively. PET can be used in the work-up of patients with metal implants where the MRI does not show adequate findings. PET shows the areas of detritus formation exhibit only moderately increased glucose metabolism and at visual interpretation do not usually impress as typical for acute osteomyelitis. Average SUV values stood at 1.2 (range: 0.5-2.9). Conclusions: the differentiation between Charcot's lesions and floride osteomyelitis provides the surgeon with important additional information, which is often unavailable from MRI. Because of this important additional data, PET could be considered preferable to morphologic imaging (CT, projection radiography) in the preoperative work-up of Charcot's foot. (orig.)

  20. Automating digital leaf measurement: the tooth, the whole tooth, and nothing but the tooth.

    Science.gov (United States)

    Corney, David P A; Tang, H Lilian; Clark, Jonathan Y; Hu, Yin; Jin, Jing

    2012-01-01

    Many species of plants produce leaves with distinct teeth around their margins. The presence and nature of these teeth can often help botanists to identify species. Moreover, it has long been known that more species native to colder regions have teeth than species native to warmer regions. It has therefore been suggested that fossilized remains of leaves can be used as a proxy for ancient climate reconstruction. Similar studies on living plants can help our understanding of the relationships. The required analysis of leaves typically involves considerable manual effort, which in practice limits the number of leaves that are analyzed, potentially reducing the power of the results. In this work, we describe a novel algorithm to automate the marginal tooth analysis of leaves found in digital images. We demonstrate our methods on a large set of images of whole herbarium specimens collected from Tilia trees (also known as lime, linden or basswood). We chose the genus Tilia as its constituent species have toothed leaves of varied size and shape. In a previous study we extracted c.1600 leaves automatically from a set of c.1100 images. Our new algorithm locates teeth on the margins of such leaves and extracts features such as each tooth's area, perimeter and internal angles, as well as counting them. We evaluate an implementation of our algorithm's performance against a manually analyzed subset of the images. We found that the algorithm achieves an accuracy of 85% for counting teeth and 75% for estimating tooth area. We also demonstrate that the automatically extracted features are sufficient to identify different species of Tilia using a simple linear discriminant analysis, and that the features relating to teeth are the most useful.