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Sample records for optic neuropathy case

  1. Leber's hereditary optic neuropathy: case report and literature review

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    Hélio Afonso Ghizoni Teive

    Full Text Available CONTEXT: Leber's hereditary optic neuropathy is an important cause of progressive painless visual loss among young male patients. OBJECTIVE: To report on a case of a young patient with a clinical and neurophysiological condition suggestive of Leber's hereditary optic neuropathy, confirmed by genetic testing. CASE REPORT: We describe a 17-year-old male with progressive bilateral visual loss. Two maternal uncles had had similar patterns of visual loss. The patient had a history of smoking and alcohol abuse. Neuro-ophthalmological examination revealed visual acuity of 20/800 in both eyes, with decreased direct and consensual pupillary light reflexes. Fundus examination demonstrated pale optic discs. The visual evoked potential test showed signs of conduction disturbances in both optic nerves and campimetric study showed complete visual loss in all fields of both eyes. A diagnosis of bilateral optic neuropathy with a clinical suspicion of Leber's hereditary optic neuropathy was made. A blood sample was submitted to genetic analysis in relation to the principal mutations of this disorder, and homoplasmic mutation in 11778 was detected, thereby confirming the diagnosis of Leber's hereditary optic neuropathy.

  2. Bilateral optic neuropathy with bilateral putaminal lesions: a case report.

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    Togawa, Jumpei; Ohi, Takekazu

    2015-01-01

    Bilateral optic neuropathy with bilateral putaminal lesions may be caused by methanol or cyanide poisoning or mitochondrial disorders including Leber hereditary optic neuropathy and Leigh syndrome. We report the case of a 34-year-old Japanese man who developed bilateral visual loss 5 days after the development of gastrointestinal symptoms. Magnetic resonance imaging of the brain on admission revealed high-intensity signal areas in the bilateral putamina on diffusion-weighted and T2-weighted images as well as a high-intensity signal area in the left middle cerebellar peduncle that had been identified 3 years previously. We diagnosed bilateral optic neuropathy with bilateral putaminal lesions caused by preceding infection-triggered demyelination. We administered methylprednisolone, but his vision did not recover.

  3. Neuromyelitis optica antibody in Leber hereditary optic neuropathy: case report

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    Luciano Mesquita Simão

    2012-08-01

    Full Text Available Neuromyelitis optica antibody (or aquaporin-4 antibody is a well stablished serum marker associated to high-risk neuromyelitis optica syndrome that presents as an inflammatory demyelinating disease characterized by the occurrence of bilateral and simultaneous optic neuritis without complete visual recovery or it occurs as an isolated episode of transverse myelitis accompanied by longitudinally extensive spinal cord lesions. On the other hand, Leber hereditary optic neuropathy is a primarily hereditary disorder that affects all tissues of the body and its clinical presentation is tissue-specific for the optic nerve and, eventually, it might reach the spinal cord. Overlapping clinical features of neuromyelitis optica and Leber hereditary optic neuropathy may suggest common target organ diseases. The case report described herein emphasizes the coexistence of serum markers of both diseases, and suggests that further investigation of this challenging clinical presentation is warranted to confirm or rule out this association.

  4. Neuromyelitis optica antibody in Leber hereditary optic neuropathy: case report.

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    Simão, Luciano Mesquita

    2012-01-01

    Neuromyelitis optica antibody (or aquaporin-4 antibody) is a well established serum marker associated to high-risk neuromyelitis optica syndrome that presents as an inflammatory demyelinating disease characterized by the occurrence of bilateral and simultaneous optic neuritis without complete visual recovery or it occurs as an isolated episode of transverse myelitis accompanied by longitudinally extensive spinal cord lesions. On the other hand, Leber hereditary optic neuropathy is a primarily hereditary disorder that affects all tissues of the body and its clinical presentation is tissue-specific for the optic nerve and, eventually, it might reach the spinal cord. Overlapping clinical features of neuromyelitis optica and Leber hereditary optic neuropathy may suggest common target organ diseases. The case report described herein emphasizes the coexistence of serum markers of both diseases, and suggests that further investigation of this challenging clinical presentation is warranted to confirm or rule out this association.

  5. Syringomyelia presenting with unilateral optic neuropathy: a case report

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    Ngoo QZ

    2017-03-01

    Full Text Available Qi Zhe Ngoo, Evelyn Li Min Tai, Wan Hazabbah Wan Hitam Department of Ophthalmology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia Purpose: In this case report, we present two cases of syringomyelia with optic neuropathy.Findings: In Case 1, a 36-year-old Malay lady presented to our clinic with acute onset of blurring of vision in her left eye that she experienced since past 1 month. She was diagnosed with syringomyelia 12 years ago and was on conservative management. Her visual acuity was 6/6 in the right eye and counting fingers at 1 m in the left. There was a positive relative afferent pupillary defect in her left eye. Optic nerve functions of her left eye were reduced. Visual field showed a left inferior field defect. Her extraocular muscle movements were full. Magnetic resonance imaging of the brain and spine showed syringomyelia at the level of C2–C6 and T2–T9. Both of her optic nerves were normal. Her condition improved with intravenous and oral corticosteroids. In Case 2, a 44-year-old Malay lady presented to our clinic with a progressive central scotoma in her right eye that she experienced since past 1 month. She had previous history of recurrent episodes of weakness in both of her lower limbs from past 8 months. Visual acuity in her right and left eye was 6/9 and 6/6, respectively. The relative afferent pupillary defect in her right eye was positive. Optic nerve functions of her right eye were affected. Visual field showed a central scotoma in her right eye. Her extraocular muscle movements were full. Fundoscopy of her right eye showed a pale optic disc. Her left eye fundus was normal. Magnetic resonance imaging of the brain and spine showed syringomyelia at T3–T6. Both of her optic nerves were normal. A diagnosis of syringomyelia with right optic atrophy was performed. Her condition improved with intravenous and oral corticosteroids.Conclusion: Optic neuropathy is a rare neuro

  6. Nutritional optic neuropathy.

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    Sawicka-Pierko, Anna; Obuchowska, Iwona; Mariak, Zofia

    2014-01-01

    Nutritional optic neuropathy (aka deficiency optic neuropathy) is a dysfunction of the optic nerve resulting from improper dietary content of certain nutrients essential for normal functioning of the nerve fibers. Most commonly, it results from folic acid and vitamin B complex deficiency associated with malnutrition or poor dietary habits, incorrectly applied vegetarian diet, or chronic alcohol abuse. Obese patients after bariatric surgery constitute another risk group of optic neuropathy. Nutritional optic neuropathy is characterized by painless, gradually progressing, bilateral and symmetrical decrease in visual acuity, which can be accompanied by the color vision dysfunction. Progression of the neuropathy is associated with optic nerve atrophy, manifesting as complete disc pallor. Treatment of nutritional neuropathy includes dietary supplementation, aimed at compensating for the deficient nutrients. The treatment is mostly based on folic acid, vitamin B complex, and protein replacement, as well as eliminating risk factors of neuropathy. Early treatment commencement, prior to irreversible optic nerve atrophy, is a prerequisite of effective treatment. We would like to highlight this problem by presenting the case of a young woman in whom chronic use "water-based" diet resulted in anemia and bilateral nutritional optic neuropathy.

  7. Leber’s hereditary optic neuropathy - case report

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    Mirjana A. Janicijevic Petrovic

    2012-09-01

    Full Text Available Leber’s hereditary optic neuropathy is a neuro-ophthalmological entity characterized by acute or subacute bilateral, not simultaneous visual loss with centro cekal scotoma and occasional further visual improvement. This rare ophthalmological disease can be accompanied with dyschromatopsia. It is associated with a matrilineal inheritance pattern. Its diagnosis used to be solely clini¬cal, aided by imaging and neuro-physiological studies, until the advent of descriptions of mitochondrial biochemical abnormalities and genetic testing. We describe a case of 24 year old male with progressive painless deterioration of visual acuity and positive family history.

  8. Optic neuropathy secondary to cat scratch disease: case report

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    Ricardo Evangelista Marrocos de Aragão

    2010-12-01

    Full Text Available Optic neuropathy due to cat scratch disease is a relatively infrequent occurrence associated with macular star formation and is characterized by sudden painless loss of vision mostly unilateral. Bartonella henselae is well recognized as the etiologic agent in cat scratch disease. Ocular complications of the disease occur in up to 10% of patients and include neuroretinitis. Ocular bartonelosis is usually self-limited with complete or near-complete recovery of vision in otherwise healthy patients. A case of a boy with neuroretinitis caused by B. henselae is reported.

  9. A case of anterior ischemic optic neuropathy associated with uveitis

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    Sugahara M

    2013-05-01

    Full Text Available Michitaka Sugahara, Takayuki Fujimoto, Kyoko Shidara, Kenji Inoue, Masato Wakakura Inouye Eye Hospital, Tokyo, Japan Introduction: Here, we describe a patient who presented with anterior ischemic optic neuropathy (AION and subsequently developed uveitis. Case: A 69-year-old man was referred to our hospital and initially presented with best-corrected visual acuities (BCVA of 20/40 (right eye and 20/1000 (left eye and relative afferent pupillary defect. Slit-lamp examination revealed no signs of ocular inflammation in either eye. Fundus examination revealed left-eye swelling and a pale superior optic disc, and Goldmann perimetry revealed left-eye inferior hemianopia. The patient was diagnosed with nonarteritic AION in the left eye. One week later, the patient returned to the hospital because of vision loss. The BCVA of the left eye was so poor that the patient could only count fingers. Slit-lamp examination revealed 1+ cells in the anterior chamber and the anterior vitreous in both eyes. Funduscopic examination revealed vasculitis and exudates in both eyes. The patient was diagnosed with bilateral panuveitis, and treatment with topical betamethasone was started. No other physical findings resulting from other autoimmune or infectious diseases were found. No additional treatments were administered, and optic disc edema in the left eye improved, and the retinal exudates disappeared in 3 months. The patient's BCVA improved after cataract surgery was performed. Conclusion: Panuveitis most likely manifests after the development of AION. Keywords: anterior ischemic optic neuropathy, uveitis

  10. [Leber's hereditary optic neuropathy after head trauma: a case report].

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    Hayashi, Shintaro; Okamoto, Koichi

    2011-10-01

    A previously healthy 34-year-old man sustained multiple skull fractures in a traffic accident. Radiological findings and visual field examination did not detect any abnormality. Shortly after the accident, he noticed blurred vision in both eyes. Six months after the accident, he gradually developed disturbance of visual acuity in the right eye. His best corrected visual acuity (BCVA) was 0.8 OD and 1.2 OS and brain MRI did not show any abnormality, while Humphrey visual field analysis demonstrated right homonymous hemianopsia. Two months after the initial presentation, his BCVA showed 0.1 OD and 0.08 OS. Visual field examination suggested that both right homonymous hemianopsia and left blind spot had become enlarged. Mitochondrial DNA analysis demonstrated G11,778A mutation and a diagnosis of Leber's hereditary optic neuropathy (LHON) was made. A few reports have documented mild acute insult to the head or blunt optic trauma as triggers of optic neuropathy in subjects with LHON. Although, the precise mechanism of LHON following trauma remains unknown, it appears that an acute insult may be sufficient to precipitate neuropathy in the optic nerve already compromised by mitochondrial dysfunction. Asymptomatic carriers should be advised to avoid possible precipitating factors such as head trauma.

  11. Inherited mitochondrial optic neuropathies

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    Yu-Wai-Man, P; Griffiths, P G; Hudson, G; Chinnery, P F

    2009-01-01

    Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (DOA) are the two most common inherited optic neuropathies and they result in significant visual morbidity among young adults. Both disorders are the result of mitochondrial dysfunction: LHON from primary mitochondrial DNA (mtDNA) mutations affecting the respiratory chain complexes; and the majority of DOA families have mutations in the OPA1 gene, which codes for an inner mitochondrial membrane protein critical for mtDNA maintenance and oxidative phosphorylation. Additional genetic and environmental factors modulate the penetrance of LHON, and the same is likely to be the case for DOA which has a markedly variable clinical phenotype. The selective vulnerability of retinal ganglion cells (RGCs) is a key pathological feature and understanding the fundamental mechanisms that underlie RGC loss in these disorders is a prerequisite for the development of effective therapeutic strategies which are currently limited. PMID:19001017

  12. [Hereditary optic neuropathies].

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    Milea, D; Verny, C

    2012-10-01

    Hereditary optic neuropathies are a group of heterogeneous conditions affecting both optic nerves, with an autosomal dominant, autosomal recessive, X-related or mitochondrial transmission. The two most common non-syndromic hereditary optic neuropathies (Leber's hereditary optic neuropathy and autosomal dominant optic atrophy) are very different in their clinical presentation and their genetic transmission, leading however to a common, non-specific optic nerve atrophy. Beyond the optic atrophy-related visual loss, which is the clinical hallmark of this group of diseases, other associated neurological signs are increasingly recognized.

  13. Genetically determined optic neuropathies

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    Milea, Dan; Amati-Bonneau, Patrizia; Reynier, Pascal

    2010-01-01

    The present review focuses on recent advances in the knowledge of hereditary optic neuropathies resulting from retinal ganglion cell degeneration, mostly due to mitochondrial dysfunctions.......The present review focuses on recent advances in the knowledge of hereditary optic neuropathies resulting from retinal ganglion cell degeneration, mostly due to mitochondrial dysfunctions....

  14. Genetically determined optic neuropathies

    DEFF Research Database (Denmark)

    Milea, Dan; Amati-Bonneau, Patrizia; Reynier, Pascal

    2010-01-01

    The present review focuses on recent advances in the knowledge of hereditary optic neuropathies resulting from retinal ganglion cell degeneration, mostly due to mitochondrial dysfunctions.......The present review focuses on recent advances in the knowledge of hereditary optic neuropathies resulting from retinal ganglion cell degeneration, mostly due to mitochondrial dysfunctions....

  15. [Leber's hereditary optic neuropathy].

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    Leo-Kottler, B; Wissinger, B

    2011-12-01

    Leber's hereditary optic neuropathy (LHON) is a rare disease primarily affecting the retinal ganglion cells. In most cases patients with LHON develop permanent visual loss with a large central scotoma in the visual field of both eyes. The optic disc becomes partially or completely pale. At the onset of the disease many patients are considered to suffer from an optic neuritis and are treated under the diagnostic and therapeutic regimen of optic neuritis. LHON is mostly only considered when high dose cortisone therapy fails to be effective or the second eye is affected. Thereafter, molecular genetic analysis will prove LHON in these cases. Detailed anamnesis including pedigree analysis in combination with observance of the peripapillary microangiopathic alterations at the fundus will help to speed up the diagnosis of LHON, but even after exact clinical and molecular genetic diagnosis of LHON some aspects of the disease still remain a mystery today.

  16. Ophthalmic findings in two cases of methanol optic neuropathy with relapsed vision disturbance

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    Xiu-Juan; Zhao; Lin; Lu; Mei; Li; Hui; Yang

    2015-01-01

    <正>Dear Sir,We hereby report two cases of methanol optic neuropathy with relapsed vision disturbance.Methanol intoxication appears after accidental or suicidal oral ingestion of industrial solvents or cleaning and antifreeze liquids or occasionally is due to fraudulent adulteration of wine or other alcoholic beverages.Its ingestion can cause severe visual disturbances and the outcomes of visual disturbances vary diffusively.Some completely or partially recovered,and some suffered

  17. Molecular screening of 980 cases of suspected hereditary optic neuropathy with a report on 77 novel OPA1 mutations

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    Ferré, Marc; Bonneau, Dominique; Milea, Dan

    2009-01-01

    We report the results of molecular screening in 980 patients carried out as part of their work-up for suspected hereditary optic neuropathies. All the patients were investigated for Leber's hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA), by searching for the ten...... novel OPA1 mutations reported here. The statistical analysis of this large set of mutations has led us to propose a diagnostic strategy that should help with the molecular work-up of optic neuropathies. Our results highlight the importance of investigating LHON-causing mtDNA mutations as well as OPA1...... and OPA3 mutations in cases of suspected hereditary optic neuropathy, even in absence of a family history of the disease....

  18. A Case with Symmetrical Intracranial Calcifications and Systemic Lupus Erythematosus Presenting with Optic Neuropathy

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    Sibel Güler

    2012-06-01

    Full Text Available 53 years old female patient were evaluated for decrease in right eye vision with sudden onset. Neurological examination revealed no characteristics except 20/200 visual acuity in right eye, significant hyperemia and edema findings in optical disc. On cranial CT scans, symmetrical calcifications were evident in bilateral cerebellar peduncles, cerebral hemispheres, both putamens and thalamus. Laboratory examinations showed positive ANA as well as positive anti-DNA and lymphopenia and the case was diagnosed as lupus erythematosus. SLE case with bilaterally diffuse cerebral calcification showed additionally unilateral optic neuropathy clinical presentation. Being the first case in the literature with these two rare associations because of lupus makes it much more interesting to report.

  19. Radiation optic neuropathy after external beam radiation therapy for acromegaly : report of two cases

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    van den Bergh, ACM; Hoving, MA; Links, TP; Dullaart, RPF; Ranchor, AV; ter Weeme, CA; Canrinus, AA; Szabo, BG; Pott, JWR

    2003-01-01

    For diagnosing radiation optic neuropathy (RON) ophthalmological and imaging data were evaluated from 63 acromegalic patients, irradiated between 1967 and 1998. Two patients developed RON: one patient in one optic nerve 10 years and another patient in both optic nerves 5 months after radiation thera

  20. Linezolid-induced optic neuropathy in XDR pulmonary TB: A case series.

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    Srivastava, Anand; Kshetrimayum, Silpa; Gupta, Sanjiv Kumar; Kant, Surya

    2017-04-01

    Optic neuropathy has been reported as a side effect of long-term use of linezolid. This is particularly seen in cases of extensively drug resistant tuberculosis (XDR-TB) where treatment with linezolid may continue for about 24-30 months. We, hereby, report two cases of XDR-TB treated patients with a regimen containing linezolid who developed progressive painless loss of vision during the course of treatment. In both the cases, the visual symptoms resolved completely on withdrawing linezolid. Early recognition of this rare side effect and timely withdrawal may salvage the eyesight of such patients. Copyright © 2016 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

  1. Leber hereditary optic neuropathy mimicking neuromyelitis optica.

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    McClelland, Collin M; Van Stavern, Gregory P; Tselis, Alex C

    2011-09-01

    Leber hereditary optic neuropathy (LHON) is rarely associated with multiple sclerosis-like features. We present a case of a 65-year-old African American woman with LHON masquerading as neuromyelitis optica (NMO). We highlight the features of the clinical examination and MRI that were suggestive of an alternative diagnosis and review the literature regarding LHON and multiple sclerosis. The diagnosis of LHON should be considered in all cases of acute or subacute bilateral optic neuropathy, including presumed seronegative NMO.

  2. Anterior ischaemic optic neuropathy in patient with rheumatoid arthritis--case report.

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    Perić, S; Cerovski, B; Perić, P

    2001-01-01

    This case report presents a patient with long-lasting rheumatoid arthritis (RA) of fourth clinical grade, having ocular complications. RA was diagnosed according to current modified ARA criteria from 1987. Upon admission to the Department of Ophthalmology clinical examination revealed anterior ischaemic optic neuropathy (AION), which is not characteristic manifestation of RA in the eye. The occurrence of AION in patients with RA has been explained in literature as a secondary manifestation of hypertension in these patients or, by the presence of other connective tissue disease apart from RA (for example, MCTD--mixed connective tissue disease). Both mentioned causes were excluded in our case, as well as any other condition that could lead to AION. Therefore, we had concluded that AION presented a late complication of RA.

  3. Restoration of optic neuropathy

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    You SW

    2017-03-01

    Full Text Available Si-Wei You,1 Ming-Mei Wu,2 Fang Kuang,2 Kin-Sang Cho,3 Kwok-Fai So4,5 1Department of Ophthalmology, Xijing Hospital, 2Institute of Neurosciences, The Fourth Military Medical University, Xi’an, China; 3Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA; 4GHM Institute of CNS Regeneration, Key Laboratory of Brain Function and Diseases, Jinan University, Guangzhou, 5Department of Ophthalmology, The State Key laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong SAR, China Abstract: Optic neuropathy refers to disorders involving the optic nerve (ON. Any damage to ON or ON-deriving neurons, the retinal ganglion cells (RGCs, may lead to the breakdown of the optical signal transmission from the eye to the brain, thus resulting in a partial or complete vision loss. The causes of optic neuropathy include trauma, ischemia, inflammation, compression, infiltration, and mitochondrial damages. ON injuries include primary and secondary injuries. During these injury phases, various factors orchestrate injured axons to die back and become unable to regenerate, and these factors could be divided into two categories: extrinsic and intrinsic. Extrinsic inhibitory factors refer to the environmental conditions that influence the regeneration of injured axons. The presence of myelin inhibitors and glial scar, lack of neurotrophic factors, and inflammation mediated by injury are regarded as these extrinsic factors. Extrinsic factors need to trigger the intracellular signals to exert inhibitory effect. Proper regulation of these intracellular signals has been shown to be beneficial to ON regeneration. Intrinsic factors of RGCs are the pivotal reasons that inhibit ON regeneration and are closely linked with extrinsic factors. Intracellular cyclic adenosine monophosphate (cAMP and calcium levels affect axon guidance and growth cone response to guidance molecules

  4. Nonarteritic anterior ischemic optic neuropathy following pars plana vitrectomy for macular hole treatment: case report

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    Leonardo Provetti Cunha

    Full Text Available ABSTRACT Herein, we report a case of nonarteritic anterior ischemic optic neuropathy (NAION following uneventful pars plana vitrectomy for macular hole treatment. A 56-year-old previously healthy woman presented with a full-thickness macular hole in right eye (OD and small cup-to-disc ratios in both eyes. Five days after surgery, she noticed sudden painless loss of vision in OD and was found to have an afferent pupillary defect and intraocular pressure of 29 mmHg. Fundus examination showed right optic disc edema and the resolution of a macular hole with an inferior altitudinal visual field defect. Erythrocyte sedimentation rate, C-reactive protein levels, and general physical examination findings were normal. She was treated with hypotensive eyedrops and oral prednisone, resulting in mild visual improvement and a pale optic disc. A combination of face-down position and increased intraocular pressure due to a small optic disc cup were considered as potential mechanisms underlying NAION in the present case. Vitreoretinal surgeons should be aware of NAION as a potentially serious complication and be able to recognize associated risk factors and clinical findings.

  5. Treatment of hereditary optic neuropathies.

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    Newman, Nancy J

    2012-10-01

    The hereditary optic neuropathies are inherited disorders in which optic nerve dysfunction is a prominent feature in the phenotypic expression of disease. Optic neuropathy may be primarily an isolated finding, such as in Leber hereditary optic neuropathy and dominant optic atrophy, or part of a multisystem disorder. The pathophysiological mechanisms underlying the hereditary optic neuropathies involve mitochondrial dysfunction owing to mutations in mitochondrial or nuclear DNA that encodes proteins essential to mitochondrial function. Effective treatments are limited, and current management includes therapies directed at enhancing mitochondrial function and preventing oxidative damage, as well as genetic counselling, and supportive and symptomatic measures. New therapies, including gene therapy, are emerging via animal models and human clinical trials. Leber hereditary optic neuropathy, in particular, provides a unique model for testing promising treatments owing to its characteristic sequential bilateral involvement and the accessibility of target tissue within the eye. Lessons learned from treatment of the hereditary optic neuropathies may have therapeutic implications for other disorders of presumed mitochondrial dysfunction. In this Review, the natural history of the common inherited optic neuropathies, the presumed pathogenesis of several of these disorders, and the literature to date regarding potential therapies are summarized.

  6. Chronic relapsing inflammatory optic neuropathy: a systematic review of 122 cases reported.

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    Petzold, Axel; Plant, Gordon T

    2014-01-01

    Chronic relapsing inflammatory optic neuropathy (CRION) is an entity that was described in 2003. Early recognition of patients suffering from CRION is relevant because of the associated risk for blindness if treated inappropriately. It seems timely to have a clinical review on this recently defined entity. A systematic literature review, irrespective of language, retrieved 22 case series and single reports describing 122 patients with CRION between 2003 and 2013. We review the epidemiology, diagnostic workup, differential diagnosis, and treatment (acute, intermediate, and long term) in view of the collective data. These data suggest that CRION is a distinct nosological entity, which is seronegative for anti-aquaporin four auto-antibodies and recognized by and managed through its dependency on immuno-suppression. Revised diagnostic criteria are proposed in light of the data compromising a critical discussion of relevant limitations.

  7. Optic neuropathy in familial dysautonomia.

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    Groom, M; Kay, M D; Corrent, G F

    1997-06-01

    Optic atrophy, which is indicative of a CNS disorder, is a rarely described manifestation of familial dysautonomia (Riley-Day syndrome). As these patients are now living longer, the prevalence of optic neuropathy also may be increasing. We present a man with familial dysautonomia and visual loss resulting from optic atrophy and visual field defect suggestive of chiasmal pathology.

  8. Linezolid-induced optic neuropathy

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    Divya Karuppannasamy

    2014-01-01

    Full Text Available Many systemic antimicrobials have been implicated to cause ocular adverse effects. This is especially relevant in multidrug therapy where more than one drug can cause a similar ocular adverse effect. We describe a case of progressive loss of vision associated with linezolid therapy. A 45-year-old male patient who was on treatment with multiple second-line anti-tuberculous drugs including linezolid and ethambutol for extensively drug-resistant tuberculosis (XDR-TB presented to us with painless progressive loss of vision in both eyes. Color vision was defective and fundus examination revealed optic disc edema in both eyes. Ethambutol-induced toxic optic neuropathy was suspected and tablet ethambutol was withdrawn. Deterioration of vision occurred despite withdrawal of ethambutol. Discontinuation of linezolid resulted in marked improvement of vision. Our report emphasizes the need for monitoring of visual function in patients on long-term linezolid treatment.

  9. Infectious optic neuropathies: a clinical update

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    Kahloun, Rim; Abroug, Nesrine; Ksiaa, Imen; Mahmoud, Anis; Zeghidi, Hatem; Zaouali, Sonia; Khairallah, Moncef

    2015-01-01

    Different forms of optic neuropathy causing visual impairment of varying severity have been reported in association with a wide variety of infectious agents. Proper clinical diagnosis of any of these infectious conditions is based on epidemiological data, history, systemic symptoms and signs, and the pattern of ocular findings. Diagnosis is confirmed by serologic testing and polymerase chain reaction in selected cases. Treatment of infectious optic neuropathies involves the use of specific anti-infectious drugs and corticosteroids to suppress the associated inflammatory reaction. The visual prognosis is generally good, but persistent severe vision loss with optic atrophy can occur. This review presents optic neuropathies caused by specific viral, bacterial, parasitic, and fungal diseases. PMID:28539795

  10. Ischaemic optic neuropathy.

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    Hayreh Sohan

    2000-01-01

    Full Text Available Ischaemic optic neuropathy is of two types: anterior (AION and posterior (PION, the first involving the optic nerve head (ONH and the second, the rest of the optic nerve. Pathogenetically AION and PION are very different diseases. AION represents an acute ischaemic disorder of the ONH supplied by the posterior ciliary artery (PCA, while PION has no specific location in the posterior part of the optic nerve and does not represent an ischaemic disorder of any definite artery. The most important step towards a logical understanding of the underlying causes, clinical features, pathogenesis and rational management of AION, is to understand the basic scientific issues involved; these are discussed in some detail. AION clinically is of two types: (1 that due to giant cell arteritis (arteritic AION: A-AION and (2 non-arteritic AION (NA-AION. NA-AION, the more common of the two, is one of the most prevalent and visually crippling diseases in the middle-aged and elderly, and is potentially bilateral. NA-AION is a multifactorial disease, with many risk factors collectively contributing to its development. Although there is no known treatment for NA-AION, reduction of risk factors is important in decreasing chances of involvement of the second eye and of further episodes. Our studies have suggested that nocturnal arterial hypotension is an important risk factor for the development and progression of NA-AION. The role of nocturnal arterial hypotension in the pathogenesis of NA-AION and management of nocturnal hypotension is discussed. Potent antihypertensive drugs, when used aggressively and/or given at bedtime, are emerging as an important risk factor for nocturnal hypotension, and there is some evidence that NA-AION may be occurring as an iatrogenic disease in some individuals. A-AION, by contrast, is an ocular emergency and requires immediate treatment with systemic corticosteroids to prevent further visual loss. The clinical parameters which help to

  11. A case of radiation optic neuropathy after irradiation for pituitary adenoma

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    Ohta, Masahiro; Sasaki, Ushio; Shinohara, Nobuya; Takeda, Tetsuji; Chaki, Takanori; Nishigakiuchi, Keiji; Kusunoki, Katsusuke (Ehime Prefectural Central Hospital, Matsuyama (Japan))

    1992-05-01

    A 60-year-old woman with radiation optic neuropathy 21 months after irradiation is reported. The patient received a total dose of 50 Gy in 25 fractions for 39 days for pituitary adenoma. She presented with bitemporal hemianopsia and loss of recent memory. Gadolinium-enhanced T1-weighted imaging was very useful for detecting lesions in the optic nerves and chiasm to the hypothalamus including mamillary bodies. Two-month steroid therapy was effective in preventing the disease progression, although visual loss and loss of recent memory were not improved. (N.K.).

  12. Radiation-induced optic neuropathy 4 years after radiation: report of a case followed up with MRI

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    Piquemal, R.; Renard, J.P. [Service de Medecine Interne A, Hopital Bretonneau, Tours (France); Cottier, J.P.; Herbreteau, D. [Service de Neuroradiologie, Hopital Bretonneau, Tours (France); Arsene, S.; Rospars, C. [Service d`Ophthalmologie, Hopital Bretonneau, Tpurs (France); Lioret, E.; Jan, M. [Service de Neurochirurgie, Hopital Bretonneau, Tours (France)

    1998-07-01

    We report a case of radiation-induced optic neuropathy in a 32-year-old man with Cushing`s disease and a recurrent tumour of the left cavernous sinus. The patient experienced rapid, painless loss of vision 4 years after treatment without recurrence of tumour or other visual disorder. MRI showed enlargement and contrast enhancement of the optic chiasm. A year later the patient was almost blind and MRI showed atrophy and persistent contrast enhancement of the chiasm. (orig.) With 3 figs., 13 refs.

  13. Anterior ischemic optic neuropathy following dengue fever.

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    Ramakrishnan, Reshma; Shrivastava, Saurabh; Deshpande, Shrikant; Patkar, Priyanka

    2016-01-01

    Dengue fever is caused by a flavivirus. This infection is endemic in the tropics and warm temperate regions of the world. Ocular manifestations of dengue fever include subconjunctival, vitreous, and retinal haemorrhages; posterior uveitis; optic neuritis; and maculopathies, haemorrhage, and oedema. However anterior ischemic optic neuropathy is a rare presentation. Optic nerve ischemia most frequently occurs at the optic nerve head, where structural crowding of nerve fibers and reduction of the vascular supply may combine to impair perfusion to a critical degree and produce optic disc oedema. Here we present a case of anterior ischemic optic neurapathy associated with dengue fever.

  14. Leber's hereditary optic neuropathy and vitamin B12 deficiency

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    Pott, Jan Willem R.; Wong, Kwok H.

    2006-01-01

    Background: Leber's hereditary optic neuropathy (LHON) is a maternally inherited optic neuropathy caused by mutations in mitochondrial DNA (mtDNA). It is also believed that several epigenetic factors have an influence on the development of LHON. Methods: A case series was observed. Results: Three pa

  15. Leber's hereditary optic neuropathy and vitamin B12 deficiency

    NARCIS (Netherlands)

    Pott, Jan Willem R.; Wong, Kwok H.

    2006-01-01

    Background: Leber's hereditary optic neuropathy (LHON) is a maternally inherited optic neuropathy caused by mutations in mitochondrial DNA (mtDNA). It is also believed that several epigenetic factors have an influence on the development of LHON. Methods: A case series was observed. Results: Three

  16. Optic neuropathy associated with periostitis in relapsing polychondritis.

    Science.gov (United States)

    Hirunwiwatkul, Parima; Trobe, Jonathan D

    2007-03-01

    Optic neuropathy is an uncommon manifestation of relapsing polychondritis (RPC), a rare systemic disease affecting cartilaginous and proteoglycan-rich structures. The optic neuropathy has been attributed to ischemia, intrinsic inflammation of the optic nerve, or spread of inflammation to the nerve from adjacent intraconal orbital tissues. We report a case of recurrent corticosteroid-responsive optic neuropathy in which MRI did not show ocular, optic nerve, or intraconal orbital abnormalities but did show periosteal thickening and enhancement in the apical orbit and adjacent intracranial space consistent with periostitis. The periostitis, which is a manifestation of a systemic vasculitis or an autoimmune reaction to progenitors of cartilage, probably caused the optic neuropathy by compression or inflammation. It is important to recognize this mechanism of optic neuropathy as its imaging features may be a subtle yet critical clue to an underlying systemic condition that can be life-threatening if not properly managed.

  17. 视神经疾病165例病因分析%Etiological analysis of 165 cases of optic neuropathy

    Institute of Scientific and Technical Information of China (English)

    童绎; 王剑

    2009-01-01

    目的 探察视神经病变病因.方法 对同仁眼科中心神经眼科2005年1月至12月门诊随机统计165例视神经疾病患者.结果 眶颅外伤最多见,占18%,其次为Lebet视神经萎缩(LHON)占14.5%,颅内占位性病变占10%,前部缺血性视神经病变(AION)占9%,新生儿缺血缺氧脑病占8%.结论 国人视神经病变仍以眶颅外伤、颅内占位及前部缺血性视神经病变多见,感染性少见,LHON有增多趋势,儿童最常见为新生儿缺血缺氧脑病.%Objective To explore the causes of optic neuropathy.Methods One hundred and sixty-five cases of optic neuropathy were analysed in TongRen Eye Center from.Jan to Dec 2005.Results The main cause of optic neuropathy were orbit-cranial trauma(18%), followed by Leber hereditary optic neuropathy(LHON, 14.5%).Intracranial occupational diseases(IOD, 10%), anterior ischemic optic neuropathy(AION, 9 %).Neonatal ischemic encephalopathy(HIE, 8 %).Conclusion Trauma, IOD and AION are the most com-mon causes of optic neuropathy in China, infection caused optic neuropathy is rare.LHON turned to increasing, HIE is the most common optic neuropathy in children.

  18. Is Leber hereditary optic neuropathy treatable? Encouraging results with idebenone in both prospective and retrospective trials and an illustrative case.

    Science.gov (United States)

    Sabet-Peyman, Esfandiar J; Khaderi, Khizer R; Sadun, Alfredo A

    2012-03-01

    A 31-year-old woman developed subacute bilateral visual loss over a 2-week period. Two months later, the diagnosis of Leber hereditary optic neuropathy (LHON) 11778/ND4 was established and the patient was treated with 900 mg of idebenone daily. Over the ensuing 9 months, visual acuity improved from 20/200 to 20/25 in each eye with near-total resolution in visual field abnormalities. Our case report is in agreement with 2 large published series of patients with LHON treated with idebenone, raising hope for treatment of this visually devastating mitochondrial disorder.

  19. Bilateral optic neuropathy in acute cryptococcal meningitis

    Institute of Scientific and Technical Information of China (English)

    Qi Zhe Ngoo; Li Min Evelyn Tai; Wan Hazabbah Wan Hitam; John Tharakan

    2016-01-01

    We reported a case of cryptococcal meningitis presenting with bilateral optic neuropathy in an immunocompetent patient. A 64-year-old Malay gentleman with no medical comorbidities presented with acute bilateral blurring of vision for a week, which was associated with generalised throbbing headache and low grade fever. He also had som-nolence and altered consciousness. Visual acuity in both eyes was no perception of light with poor pupillary reflexes. Extraocular muscle movements were normal. Anterior segments were unremarkable bilaterally. Fundoscopy revealed bilateral optic disc swelling. CT scan of the brain showed multifocal infarct, but no meningeal enhancement or mass. Cerebrospinal fluid opening pressure was normal, while its culture grew Cryptococcus neoformans. A diagnosis of cryptococcal meningitis with bilateral optic neuropathy was made. Patient was treated with a six-week course of intravenous flu-conazole and started concomitantly on a fortnight's course of intravenous amphotericin B. After that, his general condition improved, but there was still no improvement in his visual acuity. On reviewing at two months post-initiation of treatment, fundi showed bilateral optic atrophy. Bilateral optic neuropathy secondary to cryptococcal meningitis was rare. The prognosis was guarded due to the sequelae of optic atrophy. Anti-fungal medication alone may not be sufficient to manage this condition. However, evidence for other treatment modalities is still lacking and further clinical studies are required.

  20. Spheniodal mucocele causing bilateral optic neuropathy and ophthalmoplegia

    Directory of Open Access Journals (Sweden)

    Ambika Selvakumar

    2014-01-01

    Full Text Available Sphenoid sinus mucocele comprises only 2% of all paranasal sinus mucoceles. In literature, there is a case report on sphenoidal mucocele causing bilateral optic neuropathy, with unilateral partial recovery and cranial nerve palsy, but we did not come across any literature with bilateral optic neuropathy and ophthalmoplegia together caused by spheno-ethmoidal mucocele. We present such a rare case of spheno-ethmoidal mucocele causing bilateral optic neuropathy and unilateral sixth nerve palsy who had postsurgery, unilateral good vision recovery, and complete resolution of sixth nerve palsy.

  1. Spheniodal mucocele causing bilateral optic neuropathy and ophthalmoplegia.

    Science.gov (United States)

    Selvakumar, Ambika; Mahalaxmi, Balasubramanyam; Ananth, V; Gautam, Cugati

    2014-04-01

    Sphenoid sinus mucocele comprises only 2% of all paranasal sinus mucoceles. In literature, there is a case report on sphenoidal mucocele causing bilateral optic neuropathy, with unilateral partial recovery and cranial nerve palsy, but we did not come across any literature with bilateral optic neuropathy and ophthalmoplegia together caused by spheno-ethmoidal mucocele. We present such a rare case of spheno-ethmoidal mucocele causing bilateral optic neuropathy and unilateral sixth nerve palsy who had postsurgery, unilateral good vision recovery, and complete resolution of sixth nerve palsy.

  2. Features of mtDNA mutation patterns in European pedigrees and sporadic cases with leber hereditary optic neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Obermaier-Kusser, B.; Schubring, S.; Paprotta, A.; Meitinger, T.; Jaksch, M.; Gerbitz, K.D. [Univ. of Munich (Germany); Lorenz, B. [Univ. of Rogensburgh (Germany); Zerres, K. [Univ. of Bonn (Germany); Meire, F. [Univ. of Ghent (Belgium); Cochaux, P. [Univ. of Brussels (Belgium)] [and others

    1994-11-01

    Leber hereditary optic neuropathy (LHON) is maternally transmitted and is characterized by bilateral loss of central vision in young adults as a result of optic nerve degeneration. Fifteen transition mutations located in different genes for the mitochondrially encoded subunits of respiratory chain complexes have been associated thus far with the disease. Genetic studies have led to the classification of the pathogenic significance of these different mutations. However, more research is required to determine the causality of the mutations and the penetrance of the disease. The present study compares studies of populations of different ethnic origins, namely European LHON pedigrees and sporadic cases, in order to elucidate the pathogenic mechanisms involved. 21 refs., 2 figs., 1 tab.

  3. Diffusion MR Imaging of Postoperative Bilateral Acute Ischemic Optic Neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Kannan, Anusha; Srinivasan, Sivasubramanian [Khoo Teck Puat Hospital, Singapore (Singapore)

    2012-09-15

    We read with great interest, the case report on ischemic optic neuropathy (1). We would like to add a few points concerning the blood supply of the optic nerve and the correlation with the development of post-operative ischemic neuropathy. Actually, the perioperative or post-operative vision loss (postoperative ischemic neuropathy) is most likely due to ischemic optic neuropathy. Ischemic optic neuropathy (2) is classified as an anterior ischemic optic neuropathy (AION) and posterior ischemic optic neuropathy (PION). This classification is based on the fact that blood supply (2) to the anterior segment of the optic nerve (part of the optic nerve in the scleral canal and the optic disc) is supplied by short posterior ciliary vessels or anastamotic ring branches around the optic nerve. The posterior part of the optic canal is relatively less perfused, and is supplied by ophthalmic artery and central fibres are perfused by a central retinal artery. So, in the post-operative period, the posterior part of the optic nerve is more vulnerable for ischemia, especially, after major surgeries (3), one of the theories being hypotension or anaemia (2) and resultant decreased perfusion. The onset of PION is slower than the anterior ischemic optic neuropathy. AION on the other hand, is usually spontaneous (idiopathic) or due to arteritis, and is usually sudden in its onset. The reported case is most likely a case of PION. The role of imaging, especially the diffusion weighted magnetic resonance imaging, is very important because the ophthalmoscopic findings in early stages of PION is normal, and it may delay the diagnosis. On the other hand, edema of the disc is usually seen in the early stages of AION.

  4. [Hereditary optic neuropathies: clinical and molecular genetic characteristics].

    Science.gov (United States)

    Khanakova, N A; Sheremet, N L; Loginova, A N; Chukhrova, A L; Poliakov, A V

    2013-01-01

    The article presents a review of literature on hereditary optic neuropathies: Leber mitochondrial hereditary optic neuropathy, autosomal dominant and autosomal recessive optic neuropathies, X-linked optic atrophy. Clinical and molecular genetic characteristics are covered. Isolated optic neuropathies, as well as hereditary optic disorders, being a part of a complex syndromic disease are described.

  5. Calciphylaxis and bilateral optic neuropathy.

    Science.gov (United States)

    Huerva, V; Sánchez, M C; Ascaso, F J; Craver, L; Fernández, E

    2011-11-01

    A 51-year-old woman on hemodialysis for chronic renal failure complained of visual loss in her right eye. Right optic disc edema was observed on fundus examination. An arteritic optic neuropathy was suspected. However, a first biopsy did not reveal any inflammatory cells. Two months later, the patient experienced sudden visual loss in her left eye and presented with necrotic cutaneous lesions at the distal phalanges of several fingers of the right hand. Necrotic lesions also appeared on the inner aspect of the thighs. Biopsy of the cutaneous lesions revealed calcification in the wall of a small artery. A new biopsy of the temporal artery showed large calcium deposits in the artery's tunica media. The diagnosis of optic neuropathy secondary to calciphylaxis was made. A temporal artery biopsy should be repeated if the first one is inconclusive. An early diagnosis leading to appropriate treatment may help to prevent an irreversible loss of vision in these patients. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  6. Disulfiram neuropathy: two case reports

    OpenAIRE

    2016-01-01

    Background Neuropathy is a rare adverse side effect of disulfiram therapy and is under-recognized. There have been few case reports documenting this side effect. Case presentation Two cases of disulfiram peripheral neuropathy are discussed. The first case is that of a 25-year-old Caucasian woman who was exposed to disulfiram therapy for a total of 8 months and developed pain and stiffness that prevented her from walking. The second case is that of a 46-year-old Caucasian woman who developed s...

  7. [Optic nerve swelling and gadolinium contrast enhancement on magnetic resonance imaging in the subacute stage of Leber's hereditary optic neuropathy: a case report].

    Science.gov (United States)

    Furuki, Misako; Ohkubo, Takuya; Ota, Kiyobumi; Ishikawa, Kinya; Yokota, Takanori; Mizusawa, Hidehiro

    2012-01-01

    We report the case of a 50-year-old man with subacute onset of bilateral visual field loss and visual acuity loss. His visual acuity was 0.07 OD/0.09 OS and Goldmann perimetry showed central scotomas. The optic fundi were normal bilaterally. Magnetic resonance imaging (MRI) showed hyperintensity in the right optic nerve on T(2) weighted imaging and swelling of the optic chiasm with slight enhancement of the bilateral optic nerves and the optic chiasm on gadolinium-enhanced imaging. Since sensory disturbance in the left hand and leg was noted in addition to the visual problem, multiple sclerosis (MS) was suspected initially. The patient was treated with intravenous methylprednisolone (1,000 mg/day), plasma exchange therapy, and immunosuppressant therapy. However, his visual disturbance did not improve. He had a history of deafness and family history of visual disturbance, because of which we performed an analysis of mitochondrial DNA. G11778A point mutation was found, and a diagnosis of Leber's hereditary optic neuropathy (LHON) was made. Although gadolinium contrast enhancement and swelling of the optic nerve are rare, this case shows that these findings are not in conflict with LHON. The present case also suggests that mitochondrial dysfunction may trigger the onset of MS-like extraocular symptoms in patients with LHON.

  8. Demyelinating polyneuropathy in Leber hereditary optic neuropathy.

    NARCIS (Netherlands)

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

    2006-01-01

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

  9. Unilateral anterior ischemic optic neuropathy

    DEFF Research Database (Denmark)

    Herbst, Kristina; Sander, Birgit; Lund-Andersen, Henrik

    2013-01-01

    The intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin, which is sensitive to blue light. Previous chromatic pupillometry studies have shown that the post-illumination response is considered an indicator of the melanopsin activation. The aim......-affected eyes, compared with the non-affected fellow eyes, suggesting dysfunction of the ipRGCs. Compared with the responses of the healthy controls, the blue light post-illumination pupil responses were similar in the affected eyes and increased in the fellow non-affected eyes. This suggests a possible...... of this study was to investigate the ipRGC mediated pupil response in patients with a unilateral non-arteritic anterior ischemic optic neuropathy (NAION). Consensual pupil responses during and after exposure to continuous 20 s blue (470 nm) or red (660 nm) light of high intensity (300 cd/m(2)) were recorded...

  10. Emerging Mitochondrial Therapeutic Targets in Optic Neuropathies.

    Science.gov (United States)

    Lopez Sanchez, M I G; Crowston, J G; Mackey, D A; Trounce, I A

    2016-09-01

    Optic neuropathies are an important cause of blindness worldwide. The study of the most common inherited mitochondrial optic neuropathies, Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA) has highlighted a fundamental role for mitochondrial function in the survival of the affected neuron-the retinal ganglion cell. A picture is now emerging that links mitochondrial dysfunction to optic nerve disease and other neurodegenerative processes. Insights gained from the peculiar susceptibility of retinal ganglion cells to mitochondrial dysfunction are likely to inform therapeutic development for glaucoma and other common neurodegenerative diseases of aging. Despite it being a fast-evolving field of research, a lack of access to human ocular tissues and limited animal models of mitochondrial disease have prevented direct retinal ganglion cell experimentation and delayed the development of efficient therapeutic strategies to prevent vision loss. Currently, there are no approved treatments for mitochondrial disease, including optic neuropathies caused by primary or secondary mitochondrial dysfunction. Recent advances in eye research have provided important insights into the molecular mechanisms that mediate pathogenesis, and new therapeutic strategies including gene correction approaches are currently being investigated. Here, we review the general principles of mitochondrial biology relevant to retinal ganglion cell function and provide an overview of the major optic neuropathies with mitochondrial involvement, LHON and ADOA, whilst highlighting the emerging link between mitochondrial dysfunction and glaucoma. The pharmacological strategies currently being trialed to improve mitochondrial dysfunction in these optic neuropathies are discussed in addition to emerging therapeutic approaches to preserve retinal ganglion cell function.

  11. Chikungunya fever presenting with acute optic neuropathy.

    Science.gov (United States)

    Mohite, Abhijit Anand; Agius-Fernandez, Adriana

    2015-07-28

    Chikungunya fever is a vector borne virus that typically causes a self-limiting systemic illness with fever, skin rash and joint aches 2 weeks after infection. We present the case of a 69-year-old woman presenting with an acute unilateral optic neuropathy as a delayed complication of Chikungunya virus (CHIKV) infection contracted during a recent trip to the West Indies. She presented to our ophthalmology department with acute painless visual field loss in the right eye and a recent flu-like illness. She was found to have a right relative afferent pupillary defect (RAPD) with unilateral optic disc swelling. Serology confirmed recent CHIKV infection. Treatment with intravenous methylprednisolone was delayed while awaiting MRI scans and serology results. At 5-month follow-up, there was a persistent right RAPD and marked optic atrophy with a corresponding inferior scotoma in the visual field. 2015 BMJ Publishing Group Ltd.

  12. [Up to date methods of optic nerve evaluation in patients with optic neuropathy of various etiology].

    Science.gov (United States)

    Sheremet, N L; Ronzina, I A; Galoian, N S; Kazarian, E E

    2011-01-01

    132 patients (188 eyes) with proven optic neuropathy of non-glaucomatous origin were examined using static perimetry, visual evoked potential (flash and pattern types), optic coherent tomography of papilla and thickness of peripapillary nerve fiber layer. Sensitivity/ specificity of methods for identification of optic nerve diseases in acute stage were 92/75%, 92/84%, 90/92% respectively. Combination of these three methods let us identify optic neuropathy in 100% of cases, including latent forms.

  13. Multifocal visual evoked potential in optic neuritis, ischemic optic neuropathy and compressive optic neuropathy

    Directory of Open Access Journals (Sweden)

    Manju Jayaraman

    2014-01-01

    Full Text Available Purpose: To investigate the effect of optic neuritis (ON, ischemic optic neuropathy (ION and compressive optic neuropathy (CON on multifocal visual evoked potential (mfVEP amplitudes and latencies, and to compare the parameters among three optic nerve disorders. Materials and Methods: mfVEP was recorded for 71 eyes of controls and 48 eyes of optic nerve disorders with subgroups of optic neuritis (ON, n = 21 eyes, ischemic optic neuropathy (ION, n = 14 eyes, and compressive optic neuropathy (CON, n = 13 eyes. The size of defect in mfVEP amplitude probability plots and relative latency plots were analyzed. The pattern of the defect in amplitude probability plot was classified according to the visual field profile of optic neuritis treatment trail (ONTT. Results: Median of mfVEP amplitude (log SNR averaged across 60 sectors were reduced in ON (0.17 (0.13-0.33, ION (0.14 (0.12-0.21 and CON (0.21 (0.14-0.30 when compared to controls. The median mfVEP relative latencies compared to controls were significantly prolonged in ON and CON group of 10.53 (2.62-15.50 ms and 5.73 (2.67-14.14 ms respectively compared to ION group (2.06 (-4.09-13.02. The common mfVEP amplitude defects observed in probability plots were diffuse pattern in ON, inferior altitudinal defect in ION and temporal hemianopia in CON eyes. Conclusions: Optic nerve disorders cause reduction in mfVEP amplitudes. The extent of delayed latency noted in ischemic optic neuropathy was significantly lesser compared to subjects with optic neuritis and compressive optic neuropathy. mfVEP amplitudes can be used to objectively assess the topography of the visual field defect.

  14. A case of nonarteritic anterior ischemic optic neuropathy of a male with family history of the disease after receiving sildenafil

    Directory of Open Access Journals (Sweden)

    Felekis T

    2011-10-01

    Full Text Available T Felekis1, I Asproudis1, K Katsanos2, EV Tsianos21University Eye Clinic of Ioannina, Ioannina, Greece; 2First Department of Internal Medicine, University Hospital of Ioannina, Ioannina, GreeceAbstract: A 51-year-old male was referred to the University Eye Clinic of Ioannina with nonarteritic anterior ischemic optic neuropathy (NAION 12 hours after receiving sildenafil citrate (Viagra®. Examination for possible risk factors revealed mild hypercholesterolemia. Family history showed that his father had suffered from bilateral NAION. Although a cause-and-effect relationship is difficult to prove, there are reports indicating an association between the use of erectile dysfunction agents and the development of NAION. Physicians might need to investigate the presence of family history of NAION among systemic or vascular predisposing risk factors before prescribing erectile dysfunction drugs.Keywords: sildenafil, nonarteritic anterior ischemic optic neuropathy, erectile dysfunction drugs, family history

  15. Glaucoma progression associated with Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Nucci, Carlo; Martucci, Alessio; Mancino, Raffaele; Cerulli, Luciano

    2013-02-01

    The purpose of this article is to describe a case of open-angle glaucoma progression associated with Leber's hereditary optic neuropathy. Single case analysis method is used. A 53-year-old woman with a previous diagnosis of glaucoma presented with progressive visual field loss. Complete ophthalmological examination and blood tests were negative for other concomitant diseases. Genetic counseling revealed mitochondrial DNA mutation compatible with the diagnosis of Leber's hereditary optic neuropathy. In conclusion, the case describes the concomitant occurrence of open-angle glaucoma and Leber's optic neuropathy. We hypothesize that the two diseases may have a cumulative effect on oxidative stress and retinal ganglion cell death with the consequent rapid progression of visual impairment. Screening for mitochondrial DNA mutations may be requested in patients with glaucoma who, despite pharmacologically controlled intraocular pressure, show rapid progression of the disease.

  16. The optic nerve head in hereditary optic neuropathies.

    Science.gov (United States)

    O'Neill, Evelyn C; Mackey, David A; Connell, Paul P; Hewitt, Alex W; Danesh-Meyer, Helen V; Crowston, Jonathan G

    2009-05-01

    Hereditary optic neuropathies are a prominent cause of blindness in both children and adults. The disorders in this group share many overlapping clinical characteristics, including morphological changes that occur at the optic nerve head. Accurate and prompt clinical diagnosis, supplemented with imaging when indicated, is essential for optimum management of the relevant optic neuropathy and appropriate counseling of the patient on its natural history. Patient history, visual field assessment, optic disc findings and imaging are the cornerstones of a correct diagnosis. This Review highlights the characteristic optic nerve head features that are common to the various hereditary optic neuropathies, and describes the features that enable the conditions to be differentiated.

  17. Genetic Basis of Mitochondrial Optic Neuropathies.

    Science.gov (United States)

    Maresca, A; Caporali, L; Strobbe, D; Zanna, C; Malavolta, D; La Morgia, C; Valentino, M L; Carelli, V

    2014-01-01

    Over two decades have elapsed since the first mtDNA point mutation was associated with Leber's hereditary optic neuropathy (LHON) in 1988. We have subsequently witnessed a substantial understanding of the molecular basis of hereditary optic neuropathies, as well as of their clinical features and pathogenic mechanisms. It became clear that the large majority of genetic optic neuropathies have a primary or an indirect involvement of mitochondrial functions, justifying the definition of "mitochondrial optic neuropathies". Despite this progress many unsolved features remain to be understood, such as incomplete penetrance and variable clinical expressivity in LHON and dominant optic atrophy (DOA), gender prevalence in LHON, and complex gene/environment interactions in both LHON and DOA. The most recent advancement in our understanding of the molecular basis of mitochondrial optic neuropathies is the topic of this review. In particular, we analyze the role that mitochondrial biogenesis may play in the compensatory mechanisms that underlie incomplete penetrance and clinical expressivity, a scenario relevant for the possible design of future therapeutic approaches. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Retrobulbar optic neuropathy secondary to isolated sphenoid sinus disease

    Directory of Open Access Journals (Sweden)

    Vishal Annaji Chafale

    2015-01-01

    Full Text Available Paranasal sinus disease can cause a condition that mimics optic neuritis. Simultaneous appearance of both diseases would create etiological dilemma .We report two cases of retrobulbar optic neuropathy secondary to isolated sphenoid sinus disease. In the case of a 65-year-old female who had presented with acute loss of vision in the left eye associated with left-sided frontal headache which subsequently turned out to be caused by optic nerve compression at the orbital apex due to collection in abnormally pneumatized left lesser wing of the sphenoid. In another case, a 65-year-old lady had presented with symptoms of bilateral retrobulbar optic neuropathy which was found to be due to direct compression of optic nerves at the orbital apex secondary to metastases from breast carcinoma.

  19. Optic neuropathy after irradiation of meningioma.

    Science.gov (United States)

    Goldsmith, B J; Rosenthal, S A; Wara, W M; Larson, D A

    1992-10-01

    Radiation-induced optic neuropathy (RON) is a rare and catastrophic complication of currently employed radiation therapy regimens for meningiomas that have been partially resected and sampled for biopsy. Between 1972 and 1989, 49 patients received postoperative irradiation for partially resected or biopsy sampled meningiomas, with the optic nerve within the treatment field. One patient experienced RON. The latency period for this case was 23 months. A review of the literature disclosed few cases of RON after treatment for meningioma; however, 42 cases of RON have been reported after radiation therapy for other lesions. The authors constructed two approaches to predict optic nerve radiation tolerance. The first is modeled on a previous proposal for a neural tissue nominal standard dose term and enabled accurate prediction of safe treatment regimens and risk of RON. This approach compared favorably with previously employed nominal standard dose terms. The second approach, based on the linear-quadratic model, proved unsuccessful due to its failure to achieve statistical significance.

  20. [Compressive optic neuropathy related to an anterior clinoid mucocele].

    Science.gov (United States)

    Arnavielle, S; Vignal-Clermont, C; Galatoire, O; Jacomet, P-V; Klap, P; Boissonnet, H; Berges, O; Morax, S

    2010-03-01

    Nasal sinus mucoceles are an uncommon cause of painful optic neuropathy. We report the case of a patient presenting an acute compressive optic neuropathy related to an anterior clinoid mucocele. The diagnosis was mainly made with CT and MRI, and the patient was treated with endoscopic endonasal transseptal surgery 10 days after the beginning of the disorder. Visual recovery was complete 3 days later. We review the literature on the etiologies of this type of pathology, the work-up, and the possible treatments.

  1. Auditory Neuropathy - A Case of Auditory Neuropathy after Hyperbilirubinemia

    Directory of Open Access Journals (Sweden)

    Maliheh Mazaher Yazdi

    2007-12-01

    Full Text Available Background and Aim: Auditory neuropathy is an hearing disorder in which peripheral hearing is normal, but the eighth nerve and brainstem are abnormal. By clinical definition, patient with this disorder have normal OAE, but exhibit an absent or severely abnormal ABR. Auditory neuropathy was first reported in the late 1970s as different methods could identify discrepancy between absent ABR and present hearing threshold. Speech understanding difficulties are worse than can be predicted from other tests of hearing function. Auditory neuropathy may also affect vestibular function. Case Report: This article presents electrophysiological and behavioral data from a case of auditory neuropathy in a child with normal hearing after bilirubinemia in a 5 years follow-up. Audiological findings demonstrate remarkable changes after multidisciplinary rehabilitation. Conclusion: auditory neuropathy may involve damage to the inner hair cells-specialized sensory cells in the inner ear that transmit information about sound through the nervous system to the brain. Other causes may include faulty connections between the inner hair cells and the nerve leading from the inner ear to the brain or damage to the nerve itself. People with auditory neuropathy have OAEs response but absent ABR and hearing loss threshold that can be permanent, get worse or get better.

  2. On the many faces of Leber hereditary optic neuropathy

    NARCIS (Netherlands)

    Oostra, RJ; Tijmes, NT; Cobben, JM; Bolhuis, PA; vanNesselrooij, BPM; Houtman, WA; deKokNazaruk, MM; BleekerWagemakers, EM

    1997-01-01

    Leber hereditary optic neuropathy (LHON) is a maternally inherited disorder, associated with mutations in the mitochondrial DNA, which is notorious for its aspecific presentations. Two pedigrees are described with cases that are atypical for LHON with respect to sex, age of onset, interval between t

  3. On the many faces of Leber hereditary optic neuropathy

    NARCIS (Netherlands)

    Oostra, RJ; Tijmes, NT; Cobben, JM; Bolhuis, PA; vanNesselrooij, BPM; Houtman, WA; deKokNazaruk, MM; BleekerWagemakers, EM

    Leber hereditary optic neuropathy (LHON) is a maternally inherited disorder, associated with mutations in the mitochondrial DNA, which is notorious for its aspecific presentations. Two pedigrees are described with cases that are atypical for LHON with respect to sex, age of onset, interval between

  4. Anterior clinoid mucocele causing optic neuropathy: A case report and review of literature

    Directory of Open Access Journals (Sweden)

    Mohab Abozed

    2017-06-01

    Full Text Available A 66 year old Indian gentleman presented with a 3 days history of headache and gradual progressive loss of vision in his eft eye, ophthalmological assessment showed no light perception in his left eye with papilledema and afferent papillary defect. Computed tomography (CT and Magnetic Resonance Imaging (MRI were done and showed an expanding lesion in the left anterior clinoid process encroaching upon the left orbital apex and optic nerve with features suggestive of a mucocele. Patient was started on dexamethasone, and urgent craniotomy was undertaken, where marsupialization and resection of left anterior clinoid mucocele was done, and histopathologic examination of the operative specimen was consistent with a mucocele. Post-operatively, patient was kept on dexamethasone for few days, with uneventful outcome, and his follow up at 6 months showed complete recovery of his vision from no light perception to 6/12 in the affected eye.

  5. [Designation criteria for Leber's hereditary optic neuropathy].

    Science.gov (United States)

    Nakamura, Makoto; Mimura, Osamu; Wakakura, Masato; Inatani, Masaru; Nakazawa, Toru; Shiraga, Fumio

    2015-05-01

    Designation criteria for Leber's hereditary optic neuropathy (LHON) have been established by a working group for retino-choroidal and optic atrophy funded by the Ministry of Health, Labor, and Welfare (MHLW) of Japan in collaboration with the Japanese Neuro-ophthalmology Society. The criteria are composed of three major symptoms and three ancillary test findings. According to the number and the combination of these symptoms and findings, subjects are classified into definite, probable, and possible LHON cases and asymptomatic carriers. The major symptoms include bilateral involvement with a time-lag, a papillomacular bundle atrophy, both characteristic optic disc findings at the acute phase. In the ancillary testings, mitochondrial DNA mutations specific for LHON are detailed with a table listing the mutation loci being attached. To enhance readers' understanding of description of the major symptoms and ancillary test findings, explanatory remarks on 11 parameters are supplemented. The establishment of the criteria facilitates epidemiological survey of LHON by MHLW and contributes to improvement of welfare for patients with LHON in Japan.

  6. A rare case of toxic optic neuropathy secondary to consumption of neem oil

    Directory of Open Access Journals (Sweden)

    A R Suresha

    2014-01-01

    Full Text Available A 35-year-old female was referred to our hospital with bilateral loss of vision of two days duration. She gave history of consumption of about 150 ml of neem oil five days back.Examination revealed no perception of light in both eyes. Both pupils were dilated and sluggishly reacting to light. Her fundus examination showed bilateral hyperemic, edematous discs and also edema extending along the superior and inferior temporal vascular arcade. Magnetic resonance imaging (MRI scan showed bilateral putaminal regions with altered signal, hypointensities in T1-weighted images, hyperintensities on T2-weighted, images and hyperintense on Fluid Attenuation Inversion Recovery (FLAIR images suggestive of cytotoxic edema due to tissue hypoxia. Her vision improved to 20/200 in both eyes with treatment after two months. This is the first case report of such nature in the literature to the best of our knowledge.

  7. Optic neuropathy secondary to a sphenoid-ethmoidal mucocele: Case report.

    Science.gov (United States)

    Mora-Horna, E R; López, V G; Anaya-Alaminos, R; Ceriotto, A; Salcedo, G

    2015-12-01

    The case is presented of a 51-year old male patient with a history of blunt trauma in the frontal region and a one-year history of vision loss, proptosis and paresis of the lateral rectus muscle of the right eye. A right ethmoid and bilateral sphenoid mucocele was diagnosed. Drainage was performed using an external and endoscopic approach with improvement in symptoms without recurrence at 10 months. Sphenoid mucoceles represent 1% of all mucoceles and may present with different clinical manifestations. Surgical excision is the treatment of choice, and early intervention is indicated to prevent complications. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  8. [Sudden blindness: consider Leber's hereditary optic neuropathy

    NARCIS (Netherlands)

    Schieving, J.H.; Vries, L.B.A. de; Hol, F.A.; Stroink, H.

    2008-01-01

    In 3 young male patients, aged 10, 19 and 21 years respectively, sequential, severe, painless bilateral visual loss occurred. Ophthalmological examination revealed no other abnormalities and this delayed the diagnosis Leber's hereditary optic neuropathy (LHON). LHON is a mitochondrial genetic diseas

  9. Can intramuscular corticosteroid injection cause nonarteritic anterior ischemic optic neuropathy?

    Directory of Open Access Journals (Sweden)

    Bakbak B

    2013-03-01

    Full Text Available Berker Bakbak, Banu Turgut Ozturk, Sansal Gedik, Bengu Ekinci Koktekir, Saban Gonul Selcuk University Medical Faculty, Department of Ophthalmology, Konya, Turkey Abstract: A 56-year-old man noted a sudden decrease of vision in his right eye 4 hours after intramuscular triamcinolone acetonide (TA injection. A diagnosis of unilateral nonarteritic anterior ischemic optic neuropathy (NAION was made, and the patient was counseled to discontinue using TA. Examination for possible risk factors revealed controlled hypertension. Final visual acuity was finger counting at 1 m, and the optic disc was pale in his right eye. This is the first reported case of unilateral NAION that has occurred in a patient after intramuscular corticosteroid injection. Although a cause-and-effect relationship is difficult to prove, the short duration between the TA injection and the NAION is noteworthy. The history of corticosteroid injection should be questioned in cases with predisposing conditions such as hypertension. Keywords: ischemic optic neuropathy, corticosteroids, optic disc edema

  10. Medical management of hereditary optic neuropathies

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    Chiara eLa Morgia

    2014-07-01

    Full Text Available Hereditary optic neuropathies are diseases of the optic nerve. The most common are mitochondrial hereditary optic neuropathies, i.e. the maternally inherited Leber’s Hereditary Optic Neuropathy (LHON and Dominant Optic Atrophy (DOA. They both share a mitochondrial pathogenesis that leads to the selective loss of retinal ganglion cells and axons, in particular of the papillo-macular bundle. Typically, LHON is an acute/subacute loss of central vision associated with impairment of color vision and swelling of retinal nerve fibers followed by optic atrophy. DOA, instead, is characterized by a childhood-onset and slowly progressive loss of central vision, worsening over the years, leading to optic atrophy. The diagnostic workup includes neuro-ophthalmologic evaluation and genetic testing of the three most common mitochondrial DNA mutations affecting complex I (11778/ND4, 3460/ND1 and 14484/ND6 for LHON and sequencing of the nuclear gene OPA1 for DOA. Therapeutic strategies are limited including agents that bypass the complex I defect and exert an antioxidant effect (idebenone. Further strategies are aimed at stimulating compensatory mitochondrial biogenesis. Gene therapy is also a promising venue that still needs to be validated.

  11. Medical Management of Hereditary Optic Neuropathies

    Science.gov (United States)

    La Morgia, Chiara; Carbonelli, Michele; Barboni, Piero; Sadun, Alfredo Arrigo; Carelli, Valerio

    2014-01-01

    Hereditary optic neuropathies are diseases affecting the optic nerve. The most common are mitochondrial hereditary optic neuropathies, i.e., the maternally inherited Leber’s hereditary optic neuropathy (LHON) and dominant optic atrophy (DOA). They both share a mitochondrial pathogenesis that leads to the selective loss of retinal ganglion cells and axons, in particular of the papillo-macular bundle. Typically, LHON is characterized by an acute/subacute loss of central vision associated with impairment of color vision and swelling of retinal nerve fibers followed by optic atrophy. DOA, instead, is characterized by a childhood-onset and slowly progressive loss of central vision, worsening over the years, leading to optic atrophy. The diagnostic workup includes neuro-ophthalmologic evaluation and genetic testing of the three most common mitochondrial DNA mutations affecting complex I (11778/ND4, 3460/ND1, and 14484/ND6) for LHON and sequencing of the nuclear gene OPA1 for DOA. Therapeutic strategies are still limited including agents that bypass the complex I defect and exert an antioxidant effect (idebenone). Further strategies are aimed at stimulating compensatory mitochondrial biogenesis. Gene therapy is also a promising avenue that still needs to be validated. PMID:25132831

  12. Medical management of hereditary optic neuropathies.

    Science.gov (United States)

    La Morgia, Chiara; Carbonelli, Michele; Barboni, Piero; Sadun, Alfredo Arrigo; Carelli, Valerio

    2014-01-01

    Hereditary optic neuropathies are diseases affecting the optic nerve. The most common are mitochondrial hereditary optic neuropathies, i.e., the maternally inherited Leber's hereditary optic neuropathy (LHON) and dominant optic atrophy (DOA). They both share a mitochondrial pathogenesis that leads to the selective loss of retinal ganglion cells and axons, in particular of the papillo-macular bundle. Typically, LHON is characterized by an acute/subacute loss of central vision associated with impairment of color vision and swelling of retinal nerve fibers followed by optic atrophy. DOA, instead, is characterized by a childhood-onset and slowly progressive loss of central vision, worsening over the years, leading to optic atrophy. The diagnostic workup includes neuro-ophthalmologic evaluation and genetic testing of the three most common mitochondrial DNA mutations affecting complex I (11778/ND4, 3460/ND1, and 14484/ND6) for LHON and sequencing of the nuclear gene OPA1 for DOA. Therapeutic strategies are still limited including agents that bypass the complex I defect and exert an antioxidant effect (idebenone). Further strategies are aimed at stimulating compensatory mitochondrial biogenesis. Gene therapy is also a promising avenue that still needs to be validated.

  13. Recovery of Visual Function in a Patient with an Onodi Cell Mucocele Compressive Optic Neuropathy Who Had a 5-Week Interval between Onset and Surgical Intervention: A Case Report

    Directory of Open Access Journals (Sweden)

    Wencan Wu

    2010-01-01

    Full Text Available Purpose. To report on a patient with compressive optic neuropathy secondary to an Onodi cell mucocele, who fully recovered visual function following surgery. Method. Case report. Results. A 28-year-old male was admitted with a right visual acuity of 20/100 following treatment for an initial diagnosis of optic neuritis. Subsequent examination suggested compressive optic neuropathy, and neuroimaging confirmed the presence of an Onodi mucocele compressing the optic nerve. The patient underwent a right endonasal sphenoethmoidectomy with decompression 5 weeks after the initial onset of symptoms. Three weeks following surgery, the visual acuity was 20/20, and there was complete resolution of the visual field defect, which has remained stable at 1 year. Conclusion. Onodi cell mucocele should be included in the differential diagnosis of a young patient with compressive optic neuropathy. Surgical decompression should be considered even when symptoms have been present for over a month.

  14. A case of neuromyelitis optica harboring both anti-aquaporin-4 antibodies and a pathogenic mitochondrial DNA mutation for Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Shiraishi, Wataru; Hayashi, Shintaro; Kamada, Takashi; Isobe, Noriko; Yamasaki, Ryo; Murai, Hiroyuki; Ohyagi, Yasumasa; Kira, Jun-ichi

    2014-02-01

    We report the first case of definite neuromyelitis optica (NMO) with a pathogenic mitochondrial DNA (mtDNA) mutation for Leber's hereditary optic neuropathy (LHON) (G11778A point mutation). A 36-year-old Japanese woman had experienced recurrent neurological symptoms originating from involvements of the optic nerves and spinal cord. She finally lost her bilateral vision, and spastic paraparesis and sensory disturbances below the T6 level remained despite intensive immunotherapies. Brain and spinal magnetic resonance imaging (MRI) revealed T2-high-intensity lesions in the optic nerves and thoracic spinal cord, but no lesions in the brain. A blood examination revealed positivity for both anti-aquaproin-4 antibodies and an LHON mtDNA mutation.

  15. Toxic optic neuropathy: An unusual cause

    Directory of Open Access Journals (Sweden)

    Hema L Ramkumar

    2014-01-01

    Full Text Available A 60-year-old woman with a history of chronic alcoholism and tobacco use presented with the complaint of a painless decrease in vision in both eyes. She lost vision first in the left eye then in the right eye. She admitted consuming at least one 16 ounce bottle of over the counter mouthwash daily and denied consumption of any other alcohols, methanol, or antifreeze. She stated that her vision had been continuing to deteriorate in both eyes. Her best-corrected visual acuity was 4/200 in each eye. Color vision was nil in each eye. Her pupils were sluggish bilaterally, and her optic discs were flat and hyperemic with peripapillary hemorrhages. Her visual fields revealed central scotomas bilaterally. The magnetic resonance imaging of the brain and lumbar puncture were within normal limits. Antinuclear antibody, human leukocyte antigen-B27 genotyping, and B12 were normal; serum thiamine was low. While continuing to ingest mouthwash, her vision decreased to count fingers at 2 feet, and maculopapillary bundle pallor developed. She was started on folate and thiamine supplementation. Once she discontinued mouthwash, her vision improved to 20/400 bilaterally, and her central scotomas improved. This case demonstrates an alcohol-induced toxic optic neuropathy from mouthwash ingestion with some visual recovery after discontinuation of the offending agent.

  16. Disulfiram-induced neuropathy: a case report.

    Science.gov (United States)

    Mohapatra, Satyakam; Sahoo, Manas Ranjan; Rath, Neelmadhav

    2015-01-01

    Disulfiram is widely used for aversive treatment of alcoholism. Neuropathy is one of the most severe side effects of disulfiram therapy. We report the case of a young man who developed a neuropathy following disulfiram administration, with a virtually complete recovery within 2 months.

  17. Anterior ischemic optic neuropathy in association with optic nervehead drusen

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    Bharathi Megur

    2014-01-01

    Full Text Available Optic nerve head drusen (ONHD are incidental ophthalmologic finding in the optic nerve. Patients with ONHD are often asymptomatic, but sometimes present with transient visual obscuration′s (TVO, the reported incidence of which is 8.6%. Optic nerve head drusen are of two types: Superficial; visible and deep. The deep-buried drusen mimic papilledema. Because of the varied presentation deep-buried drusen pose a diagnostic challenge to the ophthalmologists. In young patients, they are mistaken for papilledema as it is clinically difficult to detect a buried drusen in the optic nerve head, but are seen on the surface with aging as the retinal nerve fiber layer thins out. They are observed as pale yellow lesions more often located towards the poles. Clinical examination aided with diagnostic tests like computed tomography (CT orbits and ultrasound B scan can help establish the diagnosis. Herein, we report a rare case of optic nerve head drusen in a young lady, who presented with loss of vision and clinical evaluation and investigations suggested ONHD with anterior ischemic optic neuropathy.

  18. Irreversible optic neuropathy in wernicke encephalopathy and leber hereditary optic neuropathy.

    Science.gov (United States)

    Li, John-Michael; Rucker, Janet C

    2010-03-01

    A 52-year-old woman with alcohol abuse presented with recent worsening of vision, imbalance, and confusion. Examination revealed counting fingers acuity in both eyes with central scotomas, color vision loss, horizontal nystagmus, and gait ataxia. Thiamine was initiated as treatment for a presumptive diagnosis of Wernicke encephalopathy (WE). Brain MRI revealed high T2 signal in the dorsal midbrain and thalami characteristic of WE. The lack of optic disc edema, usually present in patients with WE who have severe optic neuropathy, and lack of visual loss reversibility with thiamine treatment, led to the suspicion of coexisting Leber hereditary optic neuropathy (LHON), which was later confirmed when testing revealed the 14484 mitochondrial DNA mutation. Over the ensuing months, vision did not recover despite improvement of other neurologic findings. Irreversible optic neuropathy in WE should prompt consideration of a coexisting mitochondrial disorder such as LHON.

  19. Bilateral optic neuropathy in acute cr yptococcal meningitis

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    Qi Zhe Ngoo

    2016-11-01

    Full Text Available We reported a case of cryptococcal meningitis presenting with bilateral optic neuropathy in an immunocompetent patient. A 64-year-old Malay gentleman with no medical comorbidities presented with acute bilateral blurring of vision for a week, which was associated with generalised throbbing headache and low grade fever. He also had somnolence and altered consciousness. Visual acuity in both eyes was no perception of light with poor pupillary reflexes. Extraocular muscle movements were normal. Anterior segments were unremarkable bilaterally. Fundoscopy revealed bilateral optic disc swelling. CT scan of the brain showed multifocal infarct, but no meningeal enhancement or mass. Cerebrospinal fluid opening pressure was normal, while its culture grew Cryptococcus neoformans. A diagnosis of cryptococcal meningitis with bilateral optic neuropathy was made. Patient was treated with a six-week course of intravenous fluconazole and started concomitantly on a fortnight's course of intravenous amphotericin B. After that, his general condition improved, but there was still no improvement in his visual acuity. On reviewing at two months post-initiation of treatment, fundi showed bilateral optic atrophy. Bilateral optic neuropathy secondary to cryptococcal meningitis was rare. The prognosis was guarded due to the sequelae of optic atrophy. Anti-fungal medication alone may not be sufficient to manage this condition. However, evidence for other treatment modalities is still lacking and further clinical studies are required.

  20. Toxic optic neuropathy following ingestion of homeopathic medication Arnica-30.

    Science.gov (United States)

    Venkatramani, Devendra V; Goel, Shubhra; Ratra, Vineet; Gandhi, Rashmin Anilkumar

    2013-03-01

    We report a case of acute, bilateral and severe vision loss after inadvertent consumption of a large quantity of the homoeopathic medication Arnica-30. Severe vomiting which required hospitalization preceded visual symptoms. In the acute stage, pupillary responses to light were absent and fundus examination was normal. Vision loss followed a fluctuating course, with profound loss noted after 6 weeks along with bilateral optic disc pallor. Neuro-ophthalmic examination and detailed investigations were performed, including magnetic resonance imaging, electroretinography (ERG) and visual evoked potentials (VEP). Ocular coherence tomography (OCT) showed gross thinning of the retinal nerve fiber layer. While a differential diagnosis of posterior ischemic optic neuropathy was kept in mind, these findings supported a diagnosis of bilateral toxic optic neuropathy. Arnica-30 is popularly used to accelerate wound healing, including after oculoplastic surgery. While homeopathic medicines are generally considered safe due to the very low concentrations involved, Arnica-30 may be neurotoxic if consumed internally in large quantities.

  1. Diagnosis and classification of autoimmune optic neuropathy.

    Science.gov (United States)

    Petzold, Axel; Plant, Gordon T

    2014-01-01

    The spectrum of autoimmune optic neuropathies (ON) is extending. The phenotypic spectrum includes single isolated optic neuritis (SION), relapsing isolated optic neuritis (RION), chronic relapsing inflammatory optic neuropathy (CRION), the neuromyelitis optica (NMO) spectrum disorder, multiple sclerosis associated optic neuritis (MSON) and unclassified optic neuritis (UCON) forms. Epidemiological data suggests a slight female predominance. The ethnic heritage is relevant as Caucasian patients are more likely to suffer from MSON, whilst SION, RION, CRION and NMO are more frequent in non-Caucasian patients. Importantly, prognosis for recovery of visual function is good in MSON, but poorer in NMO and CRION which also have a high chance for recurrent episodes. Testing for serum anti-AQP4 autoantibodies is advised in all patients with severe, atypical or recurrent ON because of the high diagnostic specificity. The diagnostic specificity may be aided by testing for glial biomarkers in the CSF and prognostic accuracy by testing for biomarkers for neuroaxonal degeneration. Optical coherence tomography is a highly accurate tool to document the final outcome. The current clinical classification criteria rely on the phenotype, response to treatment and presence of anti-AQP4 autoantibodies.

  2. Leber hereditary optic neuropathy: current perspectives

    Directory of Open Access Journals (Sweden)

    Meyerson C

    2015-06-01

    Full Text Available Cherise Meyerson, Greg Van Stavern, Collin McClelland Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, MO, USA Abstract: Leber hereditary optic neuropathy (LHON is one of the most common inherited optic neuropathies causing bilateral central vision loss. The disorder results from point mutations in mitochondrial DNA and subsequent mitochondrial dysfunction. The primary cell type that is lost in LHON is the retinal ganglion cell, which is highly susceptible to disrupted ATP production and oxidative stress. Inheritance of LHON follows that of mitochondrial genetics, and it has a highly variable clinical phenotype, as other genetic and environmental factors also play a role. Although LHON usually presents with isolated vision loss, some patients suffer other neurological sequelae. For ill-defined reasons, male LHON mutation carriers are more affected than females. Most LHON patients remain legally blind, but a small proportion can experience spontaneous partial recovery, often within the first year of symptom onset. Unfortunately, at this time there are no established curative interventions and treatment is largely supportive. Patients should be offered low vision services and counseled on mitigating risk factors for additional vision loss, such as smoking and consuming alcohol. Encouraging treatments currently undergoing investigation includes ubiquinone analogs, such as idebenone, as well as gene therapy and stem cells to restore ATP synthesis and provide neuroprotection to surviving retinal ganglion cells. Keywords: Leber hereditary optic neuropathy, mitochondria, neuro-ophthalmology, mitochondrial DNA

  3. Optic neuropathy in a patient with pyruvate dehydrogenase deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Small, Juan E. [Massachusetts General Hospital and Harvard Medical School, Department of Radiology, Boston, MA (United States); Gonzalez, Guido E. [Massachusetts Eye and Ear Infirmary and Harvard Medical School, Department of Radiology, Boston, MA (United States); Clinica Alemana de Santiago, Departmento de Imagenes, Santiago (Chile); Nagao, Karina E.; Walton, David S. [Massachusetts Eye and Ear Infirmary and Harvard Medical School, Department of Ophthalmology, Boston, MA (United States); Caruso, Paul A. [Massachusetts Eye and Ear Infirmary and Harvard Medical School, Department of Radiology, Boston, MA (United States)

    2009-10-15

    Pyruvate dehydrogenase (PDH) deficiency is a genetic disorder of mitochondrial metabolism. The clinical manifestations range from severe neonatal lactic acidosis to chronic neurodegeneration. Optic neuropathy is an uncommon clinical sequela and the imaging findings of optic neuropathy in these patients have not previously been described. We present a patient with PDH deficiency with bilateral decreased vision in whom MRI demonstrated bilateral optic neuropathy and chiasmopathy. (orig.)

  4. Graves' disease presenting as unilateral anterior ischaemic optic neuropathy.

    Science.gov (United States)

    Monigari, Naresh; Deshpande, Anirudda; Nalabothu, Murali; Rao, Shilpa

    2014-03-19

    We report a case of a 28-year-old man who presented with 1-day history of sudden diminution of vision in the right eye. Examination showed unilateral exophthalmos with restricted eyeball movement on upward gaze in the right eye. MRI of the orbit showed no evidence of compression of the optic nerve on the right side. Visual-evoked potential showed prolonged P100 in the right eye. Fundus examination revealed swollen optic disc and para papillary nerve fibre layer splinter haemorrhages with corresponding altitudinal field defect on perimetry suggestive of anterior ischaemic optic neuropathy.

  5. Bilateral Anterior Ischaemic Optic Neuropathy in a Child on Continuous Peritoneal Dialysis; Case report and literature review

    Directory of Open Access Journals (Sweden)

    Abdullah Al-Kaabi

    2016-11-01

    Full Text Available Non-arteritic anterior ischaemic optic neuropathy (NAION is a serious complication of continuous peritoneal dialysis (CPD which can lead to poor vision and blindness. We report a five-year-old girl who had undergone a bilateral nephrectomy at the age of one year and was on home CPD. She was referred to the Paediatric Ophthalmology Unit of Sultan Qaboos University Hospital, Muscat, Oman, in 2013 with acute bilateral vision loss, preceded by a three-day history of poor oral intake. At presentation, the patient had severe systemic hypotension. An ophthalmological examination revealed severe bilateral visual impairment and NAION. She was treated with intravenous methylprednisolone and normal saline boluses. At a five-month follow-up, the visual acuity of the right eye had improved but vision in the left eye remained the same. Acute bilateral blindness due to NAION while on CPD is a rare condition in childhood. Paediatricians should be aware of this complication in order to ensure prompt management.

  6. Incomplete penetrance in mitochondrial optic neuropathies.

    Science.gov (United States)

    Caporali, Leonardo; Maresca, Alessandra; Capristo, Mariantonietta; Del Dotto, Valentina; Tagliavini, Francesca; Valentino, Maria Lucia; La Morgia, Chiara; Carelli, Valerio

    2017-07-14

    Incomplete penetrance characterizes the two most frequent inherited optic neuropathies, Leber's Hereditary Optic Neuropathy (LHON) and dominant optic atrophy (DOA), due to genetic errors in the mitochondrial DNA (mtDNA) and the nuclear DNA (nDNA), respectively. For LHON, compelling evidence has accumulated on the complex interplay of mtDNA haplogroups and environmental interacting factors, whereas the nDNA remains essentially non informative. However, a compensatory mechanism of activated mitochondrial biogenesis and increased mtDNA copy number, possibly driven by a permissive nDNA background, is documented in LHON; when successful it maintains unaffected the mutation carriers, but in some individuals it might be hampered by tobacco smoking or other environmental factors, resulting in disease onset. In females, mitochondrial biogenesis is promoted and maintained within the compensatory range by estrogens, partially explaining the gender bias in LHON. Concerning DOA, none of the above mechanisms has been fully explored, thus mtDNA haplogroups, environmental factors such as tobacco and alcohol, and further nDNA variants may all participate as protective factors or, on the contrary, favor disease expression and severity. Next generation sequencing, complemented by transcriptomics and proteomics, may provide some answers in the next future, even if the multifactorial model that seems to apply to incomplete penetrance in mitochondrial optic neuropathies remains problematic, and careful stratification of patients will play a key role for data interpretation. The deep understanding of which factors impinge on incomplete penetrance may shed light on the pathogenic mechanisms leading to optic nerve atrophy, on their possible compensation and, thus, on development of therapeutic strategies. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Hereditary optic neuropathies share a common mitochondrial coupling defect.

    Science.gov (United States)

    Chevrollier, Arnaud; Guillet, Virginie; Loiseau, Dominique; Gueguen, Naïg; de Crescenzo, Marie-Anne Pou; Verny, Christophe; Ferre, Marc; Dollfus, Hélène; Odent, Sylvie; Milea, Dan; Goizet, Cyril; Amati-Bonneau, Patrizia; Procaccio, Vincent; Bonneau, Dominique; Reynier, Pascal

    2008-06-01

    Hereditary optic neuropathies are heterogeneous diseases characterized by the degeneration of retinal ganglion cells leading to optic nerve atrophy and impairment of central vision. We found a common coupling defect of oxidative phosphorylation in fibroblasts of patients affected by autosomal dominant optic atrophy (mutations of OPA1), autosomal dominant optic atrophy associated with cataract (mutations of OPA3), and Leber's hereditary optic neuropathy, a disorder associated with point mutations of mitochondrial DNA complex I genes. Interestingly, the energetic defect was significantly more pronounced in Leber's hereditary optic neuropathy and autosomal dominant optic atrophy patients with a more complex phenotype, the so-called plus phenotype.

  8. Disseminated histoplasmosis causing reversible gaze palsy and optic neuropathy.

    Science.gov (United States)

    Perry, J D; Girkin, C A; Miller, N R; Mann, R B

    1999-06-01

    Subacute disseminated histoplasmosis is an uncommon entity. Typical neuro-ophthalmologic manifestations are usually secondary to histoplasmomas or encephalitis. A 45-year-old man noted blurred vision while receiving empiric antituberculosis therapy for fever and diffuse granulomatous disease of unknown origin. Vertical-gaze palsy, right horizontal-gaze paresis, and mild right optic neuropathy were found on neuro-ophthalmologic examination. Further questioning revealed a history of frequent contact with fighting cocks from South America. Magnetic resonance images were consistent with multiple hemorrhagic infarcts, areas of inflammation, or both, and cerebral angiography showed changes consistent with vasculitis. A previously obtained biopsy specimen from the duodenum was restained and found to be positive for fungal elements. Serum antigen titers for Histoplasma capsulatum demonstrated evidence of active infection. This case is a rare example of a supranuclear ocular motility disturbance and optic neuropathy secondary to an occlusive vascular process in a patient with subacute disseminated histoplasmosis.

  9. Posterior antebrachial cutaneous neuropathy. Case report.

    Science.gov (United States)

    Chang, C W; Oh, S J

    1990-01-01

    Posterior antebrachial cutaneous (PABC) neuropathy is rare. Two original cases are reported here. In case 1, the neuropathy is probably due to a traction injury in a reduction operation for humeral fracture. In case 2, it is injured associately with an operation in taking a myocutaneous flap. On examination, both cases showed a decreased sensation to pin-prick over the PABC nerve territories and a positive Tinel's sign near the injured sites. Sensory nerve conduction study of the PABC nerves revealed a low amplitude of the compound nerve action potential (CNAP) and a slow sensory nerve conduction velocity (SNCV) in case 1, and absent CNAP in case 2. Our study showed the sensory nerve conduction test is useful in confirming PABC neuropathy.

  10. Leber Hereditary Optic Neuropathy Associated with Bilateral Macular Holes

    Science.gov (United States)

    Shimada, Yoshiaki; Horiguchi, Masayuki

    2016-01-01

    ABSTRACT Leber hereditary optic neuropathy (LHON) causes visual loss, predominantly in healthy young men. We recently examined a patient who previously had bilateral macular holes and subsequently developed LHON at 74 years of age. Although his central scotomas were initially attributed to the macular holes, his visual acuity declined following an initial improvement after operative closure of the macular holes; thus, other diagnoses, including LHON, were considered. Furthermore, macular optical coherence tomography (OCT) images remained unchanged in this time. A mitochondrial genetic analysis identified a 11778G→A mutation. From this case, we propose that LHON remains in the differential diagnosis even in older patients, as has previously been reported. PMID:27335507

  11. Bilateral Retrobulbar Optic Neuropathy in the Setting of Interferon Alpha-2a Therapy

    Directory of Open Access Journals (Sweden)

    Dujon R.W. Fuzzard

    2014-08-01

    Full Text Available The development of biopharmaceutical agents, including the interferons (IFN, offers new treatment options for a wide range of medical conditions. Such advancements, however, have not come without risk to patients. Optic neuropathy in the setting of IFN therapy has been previously documented and is usually attributed to anterior ischaemic optic neuropathy; however, the pathophysiology remains poorly understood. Retrobulbar optic neuropathy associated with IFN treatment has not been described in the medical literature to date. We report the case of a 38-year-old Caucasian female with refractory acute myeloid leukaemia who developed painless bilateral blurred vision within 2 weeks of commencing a course of IFN alpha-2a. Extensive clinical workup demonstrated bilateral retrobulbar optic neuropathy. We report the clinical evaluation of this first documented case and discuss the possible aetiologies of her presentation.

  12. Leber hereditary optic neuropathy: current perspectives.

    Science.gov (United States)

    Meyerson, Cherise; Van Stavern, Greg; McClelland, Collin

    2015-01-01

    Leber hereditary optic neuropathy (LHON) is one of the most common inherited optic neuropathies causing bilateral central vision loss. The disorder results from point mutations in mitochondrial DNA and subsequent mitochondrial dysfunction. The primary cell type that is lost in LHON is the retinal ganglion cell, which is highly susceptible to disrupted ATP production and oxidative stress. Inheritance of LHON follows that of mitochondrial genetics, and it has a highly variable clinical phenotype, as other genetic and environmental factors also play a role. Although LHON usually presents with isolated vision loss, some patients suffer other neurological sequelae. For ill-defined reasons, male LHON mutation carriers are more affected than females. Most LHON patients remain legally blind, but a small proportion can experience spontaneous partial recovery, often within the first year of symptom onset. Unfortunately, at this time there are no established curative interventions and treatment is largely supportive. Patients should be offered low vision services and counseled on mitigating risk factors for additional vision loss, such as smoking and consuming alcohol. Encouraging treatments currently undergoing investigation includes ubiquinone analogs, such as idebenone, as well as gene therapy and stem cells to restore ATP synthesis and provide neuroprotection to surviving retinal ganglion cells.

  13. Leber hereditary optic neuropathy: current perspectives

    Science.gov (United States)

    Meyerson, Cherise; Van Stavern, Greg; McClelland, Collin

    2015-01-01

    Leber hereditary optic neuropathy (LHON) is one of the most common inherited optic neuropathies causing bilateral central vision loss. The disorder results from point mutations in mitochondrial DNA and subsequent mitochondrial dysfunction. The primary cell type that is lost in LHON is the retinal ganglion cell, which is highly susceptible to disrupted ATP production and oxidative stress. Inheritance of LHON follows that of mitochondrial genetics, and it has a highly variable clinical phenotype, as other genetic and environmental factors also play a role. Although LHON usually presents with isolated vision loss, some patients suffer other neurological sequelae. For ill-defined reasons, male LHON mutation carriers are more affected than females. Most LHON patients remain legally blind, but a small proportion can experience spontaneous partial recovery, often within the first year of symptom onset. Unfortunately, at this time there are no established curative interventions and treatment is largely supportive. Patients should be offered low vision services and counseled on mitigating risk factors for additional vision loss, such as smoking and consuming alcohol. Encouraging treatments currently undergoing investigation includes ubiquinone analogs, such as idebenone, as well as gene therapy and stem cells to restore ATP synthesis and provide neuroprotection to surviving retinal ganglion cells. PMID:26170609

  14. Recurrent peroneal neuropathy in adolescent: clinical case

    Directory of Open Access Journals (Sweden)

    V. A. Bulanova

    2012-01-01

    Full Text Available The clinical case of hereditary neuropathy with liability to pressure palsies (HNPP confirmed the results of DNA diagnostics is described. Clinical and electrophysiological features of the course of HNPP in adolescent is analyzed. Many various illnesses require exclusion in case of the foot extensor paresis.

  15. Recurrent peroneal neuropathy in adolescent: clinical case

    OpenAIRE

    V. A. Bulanova; D. S. Druzhinin

    2012-01-01

    The clinical case of hereditary neuropathy with liability to pressure palsies (HNPP) confirmed the results of DNA diagnostics is described. Clinical and electrophysiological features of the course of HNPP in adolescent is analyzed. Many various illnesses require exclusion in case of the foot extensor paresis.

  16. [A case or Leber hereditary optic neuropathy (LHON): differential diagnosis with post inflammatory atrophy of nerve II using the mtDNA analysis].

    Science.gov (United States)

    Lubos, Leszek; Wajgt, Andrzej; Maciejowski, Maciej; Mroczek-Tońska, Katarzyna; Bartnik, Ewa; Dziekanowska, Danuta

    2003-01-01

    The Leber hereditary optic neuropathy (LHON) is a disease due to a mtDNA mutation. The disorder results from enzymatic perturbations in the mitochondrial respiratory chain. Clinically the LHON may present as a progressive axonal atrophy of the optic nerves with or without other neurological symptoms. The process of reaching the diagnosis of the LHON by means of the molecular analysis of mtDNA is discussed.

  17. [Differentiation of concomitant glaucomatous optic neuropathy in optic disc drusen].

    Science.gov (United States)

    Mamikonian, V R; Galoian, N S; Sheremet, N L; Kazarian, E E; Kharlap, S I; Shemeleva-Demir, O A; Tatevosian, A A; Andzhelova, D V; Eksarenko, O V

    2013-01-01

    Characteristics of ocular blood flow (OBF) in primary open-angle glaucoma (POAG) in eyes with optic disc drusen have been investigated. The study enrolled 21 patient (35 eyes) with optic disc drusen, of which 7 (8 eyes) were diagnosed with POAG. Besides the standard tests, the ophthalmological assessment included evaluation of OBF (flowmetry) and an individual normal range of intraocular pressure (IOP). The results showed that optic disc drusen are not associated with OBF changes. Concomitant POAG might be suspected in a patient with optic disc drusen whose OBF is significantly decreased and IOP is above the individual normal range. Differentiation of morphofunctional changes in chronic optic neuropathy, which might be due to either glaucomatous optic neuropathy or optic disc drusen, is complicated when actual IOP lies within the average normal range. Ocular blood flow evaluation by means of flowmetry with calculation of an individual normal range of IOP has been demonstrated as a highly effective predictor of concomitant POAG in patients with optic disc drusen.

  18. Stem Cell Ophthalmology Treatment Study (SCOTS) for retinal and optic nerve diseases:a case report of improvement in relapsing auto-immune optic neuropathy

    Institute of Scientific and Technical Information of China (English)

    Jeffrey N Weiss; Steven Levy; Susan C Benes

    2015-01-01

    We present the results from a patient with relapsing optic neuropathy treated within the Stem Cell Ophthalmology Treatment Study (SCOTS). SCOTS is an Institutional Review Board ap-proved clinical trial and has become the largest ophthalmology stem cell study registered at the National Institutes of Health to date (www.clinicaltrials.gov Identiifer NCT 01920867). SCOTS utilizes autologous bone marrow-derived stem cells (BMSCs) for treatment of retinal and optic nerve diseases. Pre-treatment and post-treatment comprehensive eye exams of a 54 year old female patient were performed both at the Florida Study Center, USA and at The Eye Center of Columbus, USA. As a consequence of a relapsing optic neuritis, the patient’s previously normal visual acuity decreased to between 20/350 and 20/400 in the right eye and to 20/70 in the left eye. Signiifcant visual ifeld loss developed bilaterally. The patient underwent a right eye vitrectomy with injection of BMSCs into the optic nerve of the right eyeand retrobulbar, subtenon and in-travitreal injection of BMSCs in the left eye. At 15 months after SCOTS treatment, the patient’s visual acuity had improved to 20/150 in the right eye and 20/20 in the left eye. Bilateral visual fields improved markedly. Both macular thickness and fast retinal nerve fiber layer thickness were maximally improved at 3 and 6 months after SCOTS treatment. The patient also reduced her mycophenylate dose from 1,500 mg per day to 500 mg per day and required no steroid pulse therapy during the 15-month follow up.

  19. Mitochondrial optic neuropathies – Disease mechanisms and therapeutic strategies

    Science.gov (United States)

    Yu-Wai-Man, Patrick; Griffiths, Philip G.; Chinnery, Patrick F.

    2011-01-01

    Leber hereditary optic neuropathy (LHON) and autosomal-dominant optic atrophy (DOA) are the two most common inherited optic neuropathies in the general population. Both disorders share striking pathological similarities, marked by the selective loss of retinal ganglion cells (RGCs) and the early involvement of the papillomacular bundle. Three mitochondrial DNA (mtDNA) point mutations; m.3460G>A, m.11778G>A, and m.14484T>C account for over 90% of LHON cases, and in DOA, the majority of affected families harbour mutations in the OPA1 gene, which codes for a mitochondrial inner membrane protein. Optic nerve degeneration in LHON and DOA is therefore due to disturbed mitochondrial function and a predominantly complex I respiratory chain defect has been identified using both in vitro and in vivo biochemical assays. However, the trigger for RGC loss is much more complex than a simple bioenergetic crisis and other important disease mechanisms have emerged relating to mitochondrial network dynamics, mtDNA maintenance, axonal transport, and the involvement of the cytoskeleton in maintaining a differential mitochondrial gradient at sites such as the lamina cribosa. The downstream consequences of these mitochondrial disturbances are likely to be influenced by the local cellular milieu. The vulnerability of RGCs in LHON and DOA could derive not only from tissue-specific, genetically-determined biological factors, but also from an increased susceptibility to exogenous influences such as light exposure, smoking, and pharmacological agents with putative mitochondrial toxic effects. Our concept of inherited mitochondrial optic neuropathies has evolved over the past decade, with the observation that patients with LHON and DOA can manifest a much broader phenotypic spectrum than pure optic nerve involvement. Interestingly, these phenotypes are sometimes clinically indistinguishable from other neurodegenerative disorders such as Charcot-Marie-Tooth disease, hereditary spastic

  20. Targeting mitochondrial function to treat optic neuropathy.

    Science.gov (United States)

    Gueven, Nuri; Nadikudi, Monila; Daniel, Abraham; Chhetri, Jamuna

    2016-07-28

    Many reports have illustrated a tight connection between vision and mitochondrial function. Not only are most mitochondrial diseases associated with some form of vision impairment, many ophthalmological disorders such as glaucoma, age-related macular degeneration and diabetic retinopathy also show signs of mitochondrial dysfunction. Despite a vast amount of evidence, vision loss is still only treated symptomatically, which is only partially a consequence of resistance to acknowledge that mitochondria could be the common denominator and hence a promising therapeutic target. More importantly, clinical support of this concept is only emerging. Moreover, only a few drug candidates and treatment strategies are in development or approved that selectively aim to restore mitochondrial function. This review rationalizes the currently developed therapeutic approaches that target mitochondrial function by discussing their proposed mode(s) of action and provides an overview on their development status with regards to optic neuropathies.

  1. [Research progress of Leber hereditary optic neuropathy].

    Science.gov (United States)

    Zhang, A-Mei; Yao, Yong-Gang

    2013-02-01

    Leber hereditary optic neuropathy (LHON; MIM 535000) is one of the most common mitochondrial diseases, with a clinical manifestation of painless, acute or sub-acute bilateral visual loss in young adults leading to blindness and central scotoma. Over 95% of LHON patients were caused by one of three primary mtDNA mutations (m.11778G>A, m.3460G>A and m.14484T>C). Incomplete penetrance and gender bias are two riddles of this disease. Here we summarized recent research progress of LHON, with a focus on the molecular pathogenic mechanisms, clinical features, in vitro experiments and animal models, and prevention and treatment of LHON. In particular, we presented the main findings and challenges in our recent efforts to decipher genetic susceptibility and mechanism of LHON in Chinese patients.

  2. Idebenone for Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Gueven, N

    2016-03-01

    Idebenone is a rapidly absorbed, safe and well-tolerated drug and is currently the only clinically proven treatment option for Leber's hereditary optic neuropathy (LHON) patients. Idebenone (Raxone®) is approved by the European Medicines Agency for the treatment of LHON and has been available on the European market since 2015. Due to its molecular mode of action of bypassing the defective mitochondrial complex I, idebenone leads to improved energy supply and a functional recovery of retinal ganglion cells during the acute stage of the disease, thereby preventing further vision loss and promoting recovery of vision. Thus, commencing treatment shortly after the onset of symptoms is likely to have the best therapeutic effect, a hypothesis that is supported by the available clinical data.

  3. Diagnosis and clinical features of common optic neuropathies.

    Science.gov (United States)

    Biousse, Valérie; Newman, Nancy J

    2016-12-01

    Disorders of the optic nerves (optic neuropathies) are some of the most common causes of visual loss, and can present in isolation or with associated neurological or systemic symptoms and signs. Several optic neuropathies-especially inflammatory optic neuropathies-are associated with neurological disorders and thus are often diagnosed and treated by neurologists. The mechanisms underlying optic neuropathies are diverse and typically manifest with decreased visual acuity, altered colour vision, and abnormal visual field in the affected eye. Diagnosis is made on the basis of clinical history and clinical examination, of which several aspects are particularly important, including the mode of onset of visual loss, the presence of pain with eye movements, the visual acuity, and the retention of colour vision. Advances in optic nerve imaging-particularly retinal digital photography, optical coherence tomography, and MRI techniques-have revolutionised the diagnosis and follow-up of patients with an optic neuropathy. Furthermore, improvement and generalisation of some ancillary tests, such as diagnostic antibodies for neuromyelitis optica, allows better phenotyping of the heterogeneous inflammatory optic neuropathies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Anterior Ischemic Optic Neuropathy as a Manifestation of HELLP Syndrome

    Directory of Open Access Journals (Sweden)

    Boby Varkey Maramattom

    2014-01-01

    Full Text Available Thrombotic microangiopathies (TMAs are a group of disorders characterized by occurrence of thrombi of fibrin and/or platelets with microvascular occlusion and organ ischemia especially the kidney and brain. Hemolysis with a microangiopathic blood smear, elevated liver enzymes, and low platelet count (HELLP syndrome is a type of TMA peculiar to pregnancy and may be associated with neurological complications. Visual complications in HELLP are usually related to cortical blindness. We present the first case of HELLP associated with bilateral anterior ischemic optic neuropathy (AION and blindness which resolved with plasma exchange.

  5. Nonarteritic anterior ischaemic optic neuropathy in Addison's disease.

    Science.gov (United States)

    Ross, A H; Haider, S; Bailey, C C

    2010-10-01

    To report three cases of Nonarteritic anterior ischaemic optic neuropathy (NAAION) in patients with Addison's disease. We present a retrospective review of patients presenting with NAAION with underlying Addison's disease. Three eyes of two young patients presented with NAAION. Both patients had underlying Addison's disease with episodes of prolonged hypotension. To our knowledge, this is the first published report of NAAION associated with Addison's disease. As hypotension may be one of the few situations, in which NAAION may be treatable and the visual loss reversible, it is important to recognize and treat sustained episodes of hypotension in these individuals.

  6. Diffusion MR Imaging of Postoperative Bilateral Acute Ischemic Optic Neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ju Young; Lee, In Ho; Song, Chang June [Chungnam National University Hospital, Daejeon (Korea, Republic of); Hwang, Hee Youn [Eulji University Hospital, Daejeon(Korea, Republic of)

    2012-03-15

    A 57-year-old woman experienced bilateral acute ischemic optic neuropathy after spine surgery. Routine MR imaging sequence, T2-weighted image, showed subtle high signal intensity on bilateral optic nerves. A contrast-enhanced T1 weighted image showed enhancement along the bilateral optic nerve sheath. Moreover, diffusion-weighted image (DWI) and an apparent diffusion coefficient map showed markedly restricted diffusion on bilateral optic nerves. Although MR findings of T2-weighted and contrast enhanced T1-weighted images may be nonspecific, the DWI finding of cytotoxic edema of bilateral optic nerves will be helpful for the diagnosis of acute ischemic optic neuropathy after spine surgery.

  7. Leber遗传性视神经病变24例临床分析%Clinical Analysis of 24 Cases of Lebers Hereditary Optic Neuropathy

    Institute of Scientific and Technical Information of China (English)

    韦企平; 路明; 张丽霞; 杨薇

    2001-01-01

    回顾分析了24例(48眼)Leber遗传性视神经病变的临床特征。患者年龄从12 岁到44岁,平均(20.3±7.2)岁,男性占83%。发病典型者多为1眼无痛性视力下降。视力下降程度从眼前手动到1.2,其中40眼(83%)≤0.1。视野缺损主要为中心暗点或旁中心暗点,色觉障碍严重。本组部分病例发病早期有特征性眼底改变,包括视盘明显充血,视盘周围小血管扩张迂曲,神经纤维层水肿。眼底荧光血管造影视盘及盘缘血管无荧光素渗漏。%A retrospective study on the clinical features of 24 cases of Le ber's hereditary optic neuropathy involving 48 eyes was carried out. The patients aged from 12 to 44 years, with an average age of 20.3±7.2, and the male made up 8 3% of the patients. The typical cases were mostly with painless visual loss in 1 eye. The range of visual loss was from before-the-eye hand sway to 1.2; the vis ual acuity of 40 eyes was equal to or less than 0.1; the visual field defect was chiefly of central or pericentral scotoma; and the color sensation was severely affected. In some patients, at the early stage of the disease, there were fundu s pathological changes characterized by obvious hyperemia of the optic disc, dil ation and tortuosity of the small vessels around the optic disc, edema of the ne rve fiber layer around the optic disc, and no leakage of fluorescein from the op tic disc and the vessels in the marginal region of the optic disc detected by th e fundus fluorescent angiography.

  8. Leber’s Inherited Optic Neuropathy: A Large Family

    Directory of Open Access Journals (Sweden)

    Taylan Pekoz

    2012-04-01

    Full Text Available Leber's hereditary optic neuropathy characterized by loss of central vision is often seen in men and a maternally inherited disease. Here, admitted to our clinic with complaints of unilateral visual loss was diagnosed as Leber's hereditary optic neuropathy which was confirmed by the presence of a mutation at 3460G>A position. [Cukurova Med J 2012; 37(2.000: 121-124

  9. Posterior Ischemic Optic Neuropathy following Herpes Zoster Ophthalmicus

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    Mohammad Pakravan

    2009-01-01

    Full Text Available

    PURPOSE: To report a case of posterior ischemic optic neuropathy (PION following herpes zoster ophthalmicus (HZO. CASE REPORT: A 58-year-old woman with history of recent HZO in her right eye presented with acute painless loss of vision in the same eye to no light perception. Examination revealed a positive relative afferent pupillary defect and a normal appearing optic disc. Inflammatory and infiltrative lesions of the optic nerve were ruled out by laboratory and imaging studies. The patient received systemic acyclovir and prednisolone. Three months later, visual acuity improved to counting fingers, but the optic disc became pale and atrophic leading to a presumptive diagnosis of PION. Considering the positive PCR test for varicella zoster virus and the short time interval between the two presentations, HZO was considered as the most probable cause of the optic neuropathy. CONCLUSION: Herpes zoster ophthalmicus can be associated with PION.

  10. Posterior Ischemic Optic Neuropathy Following Percutaneous Nephrolithotomy

    Directory of Open Access Journals (Sweden)

    Mohammad Pakravan

    2008-12-01

    Full Text Available

    PURPOSE: To report a case of posterior ischemic optic neuropathy (PION following percutaneous nephrolithotomy (PCNL. CASE REPORT: A 57-year-old man with history of diabetes mellitus, hyperlipidemia and mild anemia underwent PCNL for treatment of nephrolithiasis. He noticed painless visual loss in both eyes immediately after the procedure. Visual acuity was light perception, however ophthalmologic examinations were unremarkable and the optic discs were pink with no swelling. Visual fields were severely affected, but neuro-imaging was normal. Within three months, visual acuity and visual fields improved dramatically but the optic discs became slightly pale. CONCLUSION: This is the first report of PION following PCNL. PION is a rare cause of severe visual loss following surgery. Severe blood loss, hypotension, anemia and body position during surgery are the most important risk factors. Ophthalmologists, urologists and anesthesiologists should be aware of this condition and this rare possibility should be considered prior to surgery.

  1. Methylprednisolone pulse therapy in severe dysthyroid optic neuropathy

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    Guy, J.R.; Fagien, S.; Donovan, J.P.; Rubin, M.L. (Univ. of Florida, Gainesville (USA))

    1989-07-01

    Five patients with severe dysthyroid optic neuropathy were treated with intravenous methylprednisolone (1 g daily for 3 consecutive days). Before administration, visual acuity of the more severely affected eyes of each patient was counting fingers at 5 feet, 8/200, 20/400, 20/200, and 20/80. Immediately after completion of pulse therapy, visual acuity improved to 20/25 in four patients and 20/30 in one. Remissions were maintained with oral prednisone and external beam irradiation of the orbit. Pulse methylprednisolone therapy appears to be beneficial in the initial management of severe dysthyroid optic neuropathy.

  2. Secondary post-geniculate involvement in Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Rizzo, Giovanni; Tozer, Kevin R; Tonon, Caterina; Manners, David; Testa, Claudia; Malucelli, Emil; Valentino, Maria Lucia; La Morgia, Chiara; Barboni, Piero; Randhawa, Ruvdeep S; Ross-Cisneros, Fred N; Sadun, Alfredo A; Carelli, Valerio; Lodi, Raffaele

    2012-01-01

    Leber's hereditary optic neuropathy (LHON) is characterized by retinal ganglion cell (RGC) degeneration with the preferential involvement of those forming the papillomacular bundle. The optic nerve is considered the main pathological target for LHON. Our aim was to investigate the possible involvement of the post-geniculate visual pathway in LHON patients. We used diffusion-weighted imaging for in vivo evaluation. Mean diffusivity maps from 22 LHON visually impaired, 11 unaffected LHON mutation carriers and 22 healthy subjects were generated and compared at level of optic radiation (OR). Prefrontal and cerebellar white matter were also analyzed as internal controls. Furthermore, we studied the optic nerve and the lateral geniculate nucleus (LGN) in post-mortem specimens obtained from a severe case of LHON compared to an age-matched control. Mean diffusivity values of affected patients were higher than unaffected mutation carriers (Poptic nerve. The post-geniculate involvement in LHON patients is a downstream post-synaptic secondary phenomenon, reflecting de-afferentation rather than a primary neurodegeneration due to mitochondrial dysfunction of LGN neurons.

  3. Postoperative posterior ischemic optic neuropathy (PION following right pterional meningioma surgery

    Directory of Open Access Journals (Sweden)

    Boby Varkey Maramattom

    2016-01-01

    Full Text Available Postoperative visual loss (POVL is an unpredictable complication of nonocular surgeries. Posterior ischemic optic neuropathy (PION is particularly feared in spinal surgeries in the prone position. We report a rare case of PION occurring after surgery for a pterional meningioma and discuss the various factors implicated in POVL.

  4. Autosomal dominant optic neuropathy and sensorineual hearing loss associated with a novel mutation of WFS1

    NARCIS (Netherlands)

    Hogewind, B.F.T.; Pennings, R.J.E.; Hol, F.A.; Kunst, H.P.M.; Hoefsloot, E.H.; Cruysberg, J.R.M.; Cremers, C.W.R.J.

    2010-01-01

    PURPOSE: To describe the phenotype of a novel Wolframin (WFS1) mutation in a family with autosomal dominant optic neuropathy and deafness. The study is designed as a retrospective observational case series. METHODS: Seven members of a Dutch family underwent ophthalmological, otological, and genetica

  5. Antiretroviral therapy-induced Leber’s hereditary optic neuropathy

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    Anand Moodley

    2014-05-01

    Full Text Available Optic neuropathy in HIV-infected patients results from the HIV infection itself, post-infectious auto-immune disease, opportunistic infections and drugs. Nucleoside reverse transcriptase inhibitors (NRTIs such as zidovudine and stavudine have known mitochondrial toxicity and can cause mitochondrial myopathies, neuropathies, hyperlactataemia, and can induce mitochondrial genetic disorders. Individuals with the mutation for Leber’s hereditary optic neuropathy (LHON, a mitochondrial disorder, are usually asymptomatic but develop visual loss when exposed to external triggers such as smoking. We report on two HIV-infected patients with LHON mutations (m.14484T>C and m.11778G>A who developed profound visual loss with antiretroviral therapy. We postulate that the phenotypic expression of LHON in these genetically predisposed individuals was triggered by NRTI drugs lamivudine and tenofovir when used in combination, despite their relatively weak mitochondrial toxic effects. 

  6. [Leber's hereditary optic neuropathy - phenotype, genetics, therapeutic options].

    Science.gov (United States)

    Gallenmüller, C; Klopstock, T

    2014-03-01

    Leber's hereditary optic neuropathy is a rare genetic disorder affecting the retinal ganglion cells leading to a persistent severe bilateral loss of visual acuity within weeks or months. Males are much more likely to be affected than females, disease onset in most cases takes place between age 15 and 35 years. The disease is caused by point mutations in the mitochondrial DNA. The penetrance of the disease is incomplete, i.e., not all mutation carriers develop clinical symptoms. The phenotype is relatively uniform, but age at onset, severity and prognosis may vary even within the same family. Environmental and endocrine factors, optic disc anatomy as well as mitochondrial and nuclear genetic factors are discussed to influence penetrance as well as interindividual and intrafamilial variability. However, only cigarette smoking and excessive alcohol consumption have been shown to trigger disease onset. The disease is characterised by a central visual field defect, impaired colour vision and fundoscopically a peripapillary microangiopathy in the acute phase. Most patients end up after some months with a severe visual loss below 0.1 and in most cases there is no significant improvement of visual acuity in the course. In rare cases patients experience a mostly partial visual recovery which depends on the type of mutation. For confirmation of the diagnosis a detailed ophthalmological examination with fundoscopy, family history and genetic analysis of the mitochondrial DNA is needed. To date, there is no proven causal therapy, but at early disease stages treatment with idebenone can be tried.

  7. Painful diabetic neuropathies, cases report and diagnostic criteria

    OpenAIRE

    Marco Lacerenza

    2006-01-01

    Painful diabetic neuropathy is a model for the investigation of drug’s efficacy in neuropathic pain. Diabetes, through multiple pathophysiological mechanisms causes several painful neuropathies. In this paper two clinical cases of painful diabetic neuropathic conditions are described and clinical and neurophysiological criteria to make the correct diagnosis are examined. Diabetes causes different painful diabetic neuropathies, at times even in a single patient. Different types of pai...

  8. Endoscopic optic nerve decompression for nontraumatic compressive optic neuropathy

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    Cheng-long REN

    2015-11-01

    Full Text Available Objective To describe the preliminary experience with endoscopic optic nerve decompression (EOND for nontraumatic compressive optic neuropathies (NCONs. Methods The clinical data of 10 patients, male 5 and female 5, with a mean age of 44.3±5.1 years, who underwent EOND for visual loss (n=5 or visual deterioration (n=5 due to tumor compression in General Hospital of Armed Police Forces of China in the period from April 2013 to April 2014 were analyzed retrospectively. Preoperative and 6-month-postoperative clinical and imaging data of these patients were reviewed and analyzed. Results Among 5 patients who lost light perception (including 2 patients with bilateral optic nerve compression before operation, 4 of them showed visual improvement to different degrees on the 7th day after operation (with improvement of bilateral visual acuity. The other 5 patients with visual impairment before operation recovered their visual acuity to different extent after the operation. All of the patients had no obvious post-operative complications. Conclusion EOND is a safe, effective, and minimally invasive surgical technique affording recovery of visual function to NCON patients. DOI: 10.11855/j.issn.0577-7402.2015.11.12

  9. Spastic paraplegia gene 7 in patients with spasticity and/or optic neuropathy.

    Science.gov (United States)

    Klebe, Stephan; Depienne, Christel; Gerber, Sylvie; Challe, Georges; Anheim, Mathieu; Charles, Perrine; Fedirko, Estelle; Lejeune, Elodie; Cottineau, Julien; Brusco, Alfredo; Dollfus, Hélène; Chinnery, Patrick F; Mancini, Cecilia; Ferrer, Xavier; Sole, Guilhem; Destée, Alain; Mayer, Jean-Michel; Fontaine, Bertrand; de Seze, Jérôme; Clanet, Michel; Ollagnon, Elisabeth; Busson, Philippe; Cazeneuve, Cécile; Stevanin, Giovanni; Kaplan, Josseline; Rozet, Jean-Michel; Brice, Alexis; Durr, Alexandra

    2012-10-01

    Mutations in the spastic paraplegia 7 (SPG7) gene encoding paraplegin are responsible for autosomal recessive hereditary spasticity. We screened 135 unrelated index cases, selected in five different settings: SPG7-positive patients detected during SPG31 analysis using SPG31/SPG7 multiplex ligation-dependent probe amplification (n = 7); previously reported ambiguous SPG7 cases (n = 5); patients carefully selected on the basis of their phenotype (spasticity of the lower limbs with cerebellar signs and/or cerebellar atrophy on magnetic resonance imaging/computer tomography scan and/or optic neuropathy and without other signs) (n = 24); patients with hereditary spastic paraparesis referred consecutively from attending neurologists and the national reference centre in a diagnostic setting (n = 98); and the index case of a four-generation family with autosomal dominant optic neuropathy but no spasticity linked to the SPG7 locus. We identified two SPG7 mutations in 23/134 spastic patients, 21% of the patients selected according to phenotype but only 8% of those referred directly. Our results confirm the pathogenicity of Ala510Val, which was the most frequent mutation in our series (65%) and segregated at the homozygous state with spastic paraparesis in a large family with autosomal recessive inheritance. All SPG7-positive patients tested had optic neuropathy or abnormalities revealed by optical coherence tomography, indicating that abnormalities in optical coherence tomography could be a clinical biomarker for SPG7 testing. In addition, the presence of late-onset very slowly progressive spastic gait (median age 39 years, range 18-52 years) associated with cerebellar ataxia (39%) or cerebellar atrophy (47%) constitute, with abnormal optical coherence tomography, key features pointing towards SPG7-testing. Interestingly, three relatives of patients with heterozygote SPG7 mutations had cerebellar signs and atrophy, or peripheral neuropathy, but no spasticity of the lower

  10. Genotype-phenotype correlations in Leber hereditary optic neuropathy.

    Science.gov (United States)

    Tońska, Katarzyna; Kodroń, Agata; Bartnik, Ewa

    2010-01-01

    Leber hereditary optic neuropathy (LHON), acute or subacute vision loss due to retinal ganglion cell death which in the long run leads to optic nerve atrophy is one of the most widely studied maternally inherited diseases caused by mutations in mitochondrial DNA. Although three common mutations, 11778G>A, 14484T>C or 3460G>A are responsible for over 90% of cases and affect genes encoding complex I subunits of the respiratory chain, their influence on bioenergetic properties of the cell is marginal and cannot fully explain the pathology of the disease. The following chain of events was proposed, based on biochemical and anatomical properties of retinal ganglion cells whose axons form the optic nerve: mitochondrial DNA mutations increase reactive oxygen species production in these sensitive cells, leading to caspase-independent apoptosis. As LHON is characterized by low penetrance and sex bias (men are affected about 5 times more frequently than women) the participation of the other factors-genetic and environmental-beside mtDNA mutations was studied. Mitochondrial haplogroups and smoking are some of the factors involved in the complex etiology of this disease.

  11. Oestrogens ameliorate mitochondrial dysfunction in Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Giordano, Carla; Montopoli, Monica; Perli, Elena; Orlandi, Maurizia; Fantin, Marianna; Ross-Cisneros, Fred N; Caparrotta, Laura; Martinuzzi, Andrea; Ragazzi, Eugenio; Ghelli, Anna; Sadun, Alfredo A; d'Amati, Giulia; Carelli, Valerio

    2011-01-01

    Leber's hereditary optic neuropathy, the most frequent mitochondrial disease due to mitochondrial DNA point mutations in complex I, is characterized by the selective degeneration of retinal ganglion cells, leading to optic atrophy and loss of central vision prevalently in young males. The current study investigated the reasons for the higher prevalence of Leber's hereditary optic neuropathy in males, exploring the potential compensatory effects of oestrogens on mutant cell metabolism. Control and Leber's hereditary optic neuropathy osteosarcoma-derived cybrids (11778/ND4, 3460/ND1 and 14484/ND6) were grown in glucose or glucose-free, galactose-supplemented medium. After having shown the nuclear and mitochondrial localization of oestrogen receptors in cybrids, experiments were carried out by adding 100 nM of 17β-oestradiol. In a set of experiments, cells were pre-incubated with the oestrogen receptor antagonist ICI 182780. Leber's hereditary optic neuropathy cybrids in galactose medium presented overproduction of reactive oxygen species, which led to decrease in mitochondrial membrane potential, increased apoptotic rate, loss of cell viability and hyper-fragmented mitochondrial morphology compared with control cybrids. Treatment with 17β-oestradiol significantly rescued these pathological features and led to the activation of the antioxidant enzyme superoxide dismutase 2. In addition, 17β-oestradiol induced a general activation of mitochondrial biogenesis and a small although significant improvement in energetic competence. All these effects were oestrogen receptor mediated. Finally, we showed that the oestrogen receptor β localizes to the mitochondrial network of human retinal ganglion cells. Our results strongly support a metabolic basis for the unexplained male prevalence in Leber's hereditary optic neuropathy and hold promises for a therapeutic use for oestrogen-like molecules.

  12. Gene-environment interactions in Leber hereditary optic neuropathy

    NARCIS (Netherlands)

    M.A. Kirkman; P. Yu-Wai-Man (Patrick); A. Korsten (Alex); M. Leonhardt (Miriam); K. Dimitriadis (Konstantin); I.F.M. de Coo (René); T. Klopstock (Thomas); P.F. Chinnery

    2009-01-01

    textabstractLeber hereditary optic neuropathy (LHON) is a genetic disorder primarily due to mutations of mitochondrial DNA (mtDNA). Environmental factors are thought to precipitate the visual failure and explain the marked incomplete penetrance of LHON, but previous small studies have failed to conf

  13. Visual Rehabilitation of Persons with Leber's Hereditary Optic Neuropathy.

    Science.gov (United States)

    Rudanko, S.-L.

    1995-01-01

    This article presents results of a noncontrolled clinical study of 20 persons with Leber's hereditary optic neuropathy who were treated from 1976 to 1990 at the Low Vision Centre of the Finnish Federation of the Visually Handicapped. The importance of early functional visual rehabilitation is emphasized, as is the use of low vision aids to help…

  14. Painful diabetic neuropathies, cases report and diagnostic criteria

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    Marco Lacerenza

    2006-12-01

    Full Text Available Painful diabetic neuropathy is a model for the investigation of drug’s efficacy in neuropathic pain. Diabetes, through multiple pathophysiological mechanisms causes several painful neuropathies. In this paper two clinical cases of painful diabetic neuropathic conditions are described and clinical and neurophysiological criteria to make the correct diagnosis are examined. Diabetes causes different painful diabetic neuropathies, at times even in a single patient. Different types of pains may originate from different nerve injuries, and harbour different pathophysiological mechanisms. A comprehensive and accurate evaluation of clinical and neurophysiological abnormalities in painful diabetic neuropathies provides insight on the pathophysiological mechanism and directs the clinician towards rational treatment strategies.

  15. Decreased retinal nerve fibre layer thickness detected by optical coherence tomography in patients with ethambutol‐induced optic neuropathy

    Science.gov (United States)

    Chai, Samantha J; Foroozan, Rod

    2007-01-01

    Background It is difficult to assess the degree of optic nerve damage in patients with ethambutol‐induced optic neuropathy, especially just after the onset of visual loss, when the optic disc typically looks normal. Aim To evaluate changes in retinal nerve fibre layer thickness (RNFLT) using optical coherence tomography (OCT) in patients with optic neuropathy within 3 months of cessation of ethambutol treatment. Design A retrospective observational case series from a single neuro‐ophthalmology practice. Methods 8 patients with a history of ethambutol‐induced optic neuropathy were examined within 3 months after stopping ethambutol treatment. All patients underwent a neuro‐ophthalmologic examination, including visual acuity, colour vision, visual fields and funduscopy. OCT was performed on both eyes of each patient using the retinal nerve fibre layer analysis protocol. Results The interval between cessation of ethambutol treatment and the initial visit ranged from 1 week to 3 months. All patients had visual deficits characteristic of ethambutol‐induced optic neuropathy at their initial visit, and the follow‐up examination was performed within 12 months. Compared with the initial RNFLT, there was a statistically significant decrease in the mean RNFLT of the temporal, superior and nasal quadrants (p = 0.009, 0.019 and 0.025, respectively), with the greatest decrease in the temporal quadrant (mean decrease 26.5 μm). Conclusions A decrease in RNFLT is observed in all quadrants in patients with ethambutol‐induced optic neuropathy who have recently discontinued the medication. This decrease is most pronounced in the temporal quadrant of the optic disc. PMID:17215265

  16. Transsynaptic retinal degeneration in optic neuropathies: optical coherence tomography study.

    Science.gov (United States)

    Sriram, Prema; Graham, Stuart L; Wang, Chenyu; Yiannikas, Con; Garrick, Raymond; Klistorner, Alexander

    2012-03-09

    Recently demonstrated neuronal loss in the inner nuclear layer of the retina in multiple sclerosis (MS) and glaucoma raises the question of a primary (possibly immune-mediated) or secondary (transsynaptic) mechanism of retinal damage in these diseases. In the present study we used optical coherence tomography to investigate retrograde retinal transsynaptic degeneration in patients with long-standing and severe loss of ganglion cells due to optic neuropathy. Fifteen eyes of glaucoma patients with visual field defect limited to upper hemifield and 15 eyes of MS patients with previous episode of optic neuritis (ON) and extensive loss of ganglion cells were imaged using spectral-domain optical coherence tomography and compared with two groups of age-matched controls. Combined retinal ganglion cell layer/inner plexiform layer (GCL/IPL) thickness and inner nuclear layer (INL) thickness were analyzed. In the glaucoma group there was a significant (P = 0.0005) reduction of GCL/IPL thickness in the lower (affected) retina compared with normal controls; however INL thickness was not statistically reduced (P = 0.49). In the MS group reduction of GCL/IPL thickness in both hemifields of ON eyes was also significant (P = 0.0001 and P < 0.0001 for inferior and superior retina respectively). However, similar to the glaucomatous eyes, there was no significant reduction of INL thickness in both hemifields (P = 0.25 and P = 0.45). This study demonstrates no significant loss of INL thickness in parts of the retina with long-standing and severe loss of retinal ganglion cells.

  17. Anterior ischemic optic neuropathy precipitated by acute primary angle closure

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    Choudhari Nikhil

    2010-01-01

    Full Text Available A 59-year-old man with a history of longstanding systemic hypotension developed asymmetric non-arteritic anterior ischemic optic neuropathy (NAION apparently precipitated by bilateral sequential acute primary angle closure. NAION is very rarely reported in association with raised intraocular pressure. In contrast to optical coherence tomography, the failure of scanning laser polarimetry to detect axonal swelling was another interesting finding. Possible reasoning for these observations is discussed.

  18. Secondary post-geniculate involvement in Leber's hereditary optic neuropathy.

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    Giovanni Rizzo

    Full Text Available Leber's hereditary optic neuropathy (LHON is characterized by retinal ganglion cell (RGC degeneration with the preferential involvement of those forming the papillomacular bundle. The optic nerve is considered the main pathological target for LHON. Our aim was to investigate the possible involvement of the post-geniculate visual pathway in LHON patients. We used diffusion-weighted imaging for in vivo evaluation. Mean diffusivity maps from 22 LHON visually impaired, 11 unaffected LHON mutation carriers and 22 healthy subjects were generated and compared at level of optic radiation (OR. Prefrontal and cerebellar white matter were also analyzed as internal controls. Furthermore, we studied the optic nerve and the lateral geniculate nucleus (LGN in post-mortem specimens obtained from a severe case of LHON compared to an age-matched control. Mean diffusivity values of affected patients were higher than unaffected mutation carriers (P<0.05 and healthy subjects (P<0.01 in OR and not in the other brain regions. Increased OR diffusivity was associated with both disease duration (B = 0.002; P<0.05 and lack of recovery of visual acuity (B = 0.060; P<0.01. Post-mortem investigation detected atrophy (41.9% decrease of neuron soma size in the magnocellular layers and 44.7% decrease in the parvocellular layers and, to a lesser extent, degeneration (28.5% decrease of neuron density in the magnocellular layers and 28.7% decrease in the parvocellular layers in the LHON LGN associated with extremely severe axonal loss (99% in the optic nerve. The post-geniculate involvement in LHON patients is a downstream post-synaptic secondary phenomenon, reflecting de-afferentation rather than a primary neurodegeneration due to mitochondrial dysfunction of LGN neurons.

  19. Leber's hereditary optic neuropathy mutations associated with infantile-onset myoclonic epilepsy.

    Science.gov (United States)

    Frye, Richard E

    2011-06-01

    Epilepsy syndromes with onset in the first year of life, especially when they include myoclonic features, have special significance since they are associated with long-term developmental and neurological abnormalities. Dravet's severe myoclonic epilepsy in infancy is especially interesting as it is associated with fever-provoked seizures and mutations in the alpha subunit of the sodium channel (SCN1A) in about one-third of the cases. Here, we report 2 children who had clinical features of severe myoclonic epilepsy of infancy without mutations in the SCN1A gene who were found to have mitochondrial DNA mutations associated with Leber's hereditary optic neuropathy. These 2 children demonstrated markers of mitochondrial dysfunction, drug-resistant epilepsy, and dysfunction of nonneurological systems. These cases demonstrate that mitochondrial DNA mutations, especially those associated with Leber's hereditary optic neuropathy, should be considered in cases of myclonic epilepsy starting in infancy, especially when mutations in the SCN1A gene are not found.

  20. Giant Axonal Neuropathy Among Two Siblings - A Case Report

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    John Jhon. K

    2001-01-01

    Full Text Available Giant axonal neuropathy is a rate disorder with an autosomal recessive inheritance. It should be differentiated from toxic neuropathies, and hereditary degenerative disorders of nervous system like Friedreich′s ataxia and HMSN. Thick curly hair, though may not be present always is a useful clinical clue to identify cases. Prognosis is generally poor though course of the illness is variable. We report here a clinically and hisopathologically characteristic familial case of giant axonal neuropathy, which occurred in a 17-year-old boy, and his 21-year-old sister.

  1. Approach to diagnosis and management of optic neuropathy

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    Sharik Mustafa

    2014-01-01

    Full Text Available Visual loss consequent to anterior visual pathway involvement can occur in a variety of clinical settings. In a tropical country like India, apart from the usual suspects, nutritional, infective, and toxic amblyopia have to be considered in the differential diagnosis. The mode of onset (acute/chronic, unilateral versus bilateral involvement, accompanying occular pain or the lack of it, and pattern of visual loss are some of the pointers which help to differentiate optic neuropathy clinically. The presence of concurrent neurological deficits, evidence of other systemic illnesses, and the results of serological and radiological investigations help to confirm the diagnosis. This article briefly describes the important causes of optic neuropathy in the Indian context and outlines a practical approach to management.

  2. Leber's hereditary optic neuropathy associated with multiple sclerosis: Harding's syndrome.

    Science.gov (United States)

    Parry-Jones, A R; Mitchell, J D; Gunarwardena, W J; Shaunak, S

    2008-04-01

    We describe a 32-year-old woman with sequential, severe, painless visual loss in one eye and then the other, and three temporally distinct episodes of neurological disturbance suggestive of demyelination in the spinal cord. She was positive for the T14484C mutation in the mitochondrial genome, one of three common mutations causing Leber's hereditary optic neuropathy. In addition, MRI identified areas of demyelination within the periventricular white matter of the brain and within the spinal cord. The coexistence of multiple sclerosis and Leber's hereditary optic neuropathy (Harding's syndrome) is known to occur more often than would be expected by chance; therefore, screening for the Leber's mutations in multiple sclerosis patients with severe visual loss should be considered because this has important prognostic and genetic implications.

  3. Neuroprotection - new promising treatment for glaucomatous optic neuropathy

    Institute of Scientific and Technical Information of China (English)

    Jian-He Xiao; Mao-Nian Zhang

    2010-01-01

    @@ Glaucoma is the second leading cause of blindness worldwide, and also the most common optic neuropathy, affecting about 60 million people worldwide in its most common forms. This figure is expected to rise to 80 million by 2020[1-2]. In glaucoma, the ultimate cause of vision loss in glaucoma is thought to be retinal ganglion cell (RGC) death. Neuroprotection of RGC is therefore an important goal of glaucoma therapy[3].

  4. Visual loss related to macular subretinal fluid and cystoid macular edema in HIV-related optic neuropathy

    DEFF Research Database (Denmark)

    Gautier, David; Rabier, Valérie; Jallet, Ghislaine;

    2012-01-01

    Optic nerve involvement may occur in various infectious diseases, but is rarely reported after infection by the human immunodeficiency virus (HIV). We report the atypical case of a 38-year-old patient in whom the presenting features of HIV infection were due to a bilateral optic neuropathy associ...... associated with macular subretinal fluid and cystoid macular edema, which responded well to antiretroviral therapy....

  5. Anterior ischemic optic neuropathy after conventional coronary artery bypass graft surgery

    Science.gov (United States)

    Dorecka, Mariola; Miniewicz-Kurkowska, Joanna; Romaniuk, Dorota; Gajdzik-Gajdecka, Urszula; Wójcik-Niklewska, Bogumiła

    2011-01-01

    Summary Background Perioperative optic neuropathy is a disease which can lead to serious, irreversible damage of vision. This complication could be the result of non-ocular surgery, for example, cardiac or spinal procedures. We present a case of anterior ischemic neuropathy (AION) which occurred following a conventional coronary artery bypass graft procedure. Case Report A 57-year-old man, 4 days after Conventional Coronary Artery Bypass Graft surgery as result of multi-vessel stabile coronary artery disease and history of anterolateral wall myocardial infarction, was admitted to the Eye Clinic due to significant loss of vision in his right eye. The patient had hypertension and was a heavy smoker. On admission, the slit lamp examination revealed a relative afferent pupillary defect in the right eye. The fundus examination showed optic disc edema with the presence of flame hemorrhages. Best corrected visual acuity (BCVA) was 0.02. The results of eye examination and fluorescein angiography confirmed the diagnosis of AION. Anti-aggregation and antithrombotic treatment was continued with steroids and vasodilators. After 7 days of this treatment we noticed the improvement of BCVA to 0.2. At 6-month follow-up, the vision was stable, and fundus examination revealed optic disc atrophy. Conclusions After cardiac surgical operations, such as coronary artery bypass graft procedures, anterior ischemic optic neuropathy may occur. In those cases, close cooperation between the various specialists is necessary. PMID:21629193

  6. Successful chemotherapy in a male patient with malignant lymphoma and Leber's hereditary optic neuropathy (LHON).

    Science.gov (United States)

    Zanssen, Stefanie; Buse, Gerhard

    2003-04-01

    Leber's hereditary optic neuropathy (LHON) is a bilateral subacute optic neuropathy caused by hereditary missense mutations of the mitochondrial genome. Primary mutations are located at nucleotide positions 11778, 3460, and 14484 in genes encoding subunits of complex I of the respiratory chain. It has been suggested that degenerative changes in the optic nerve might be mediated by apoptosis. Therefore, we hypothesized that patients affected with LHON might show altered sensitivity to cytotoxic drugs. Here we report the case of a LHON patient carrying the 11778 mutation who required chemotherapy for malignant lymphoma. Using in vitro assays, we found that the patient's peripheral blood mononuclear cells did not show altered vulnerability to cytotoxic drugs. The patient was treated with combination chemotherapy and consolidating radiotherapy, leading to complete remission without inappropriately severe acute or chronic side effects. These data indicate that the 11778 mutation does not change cellular response to cytotoxic drugs in a clinically apparent manner.

  7. Gene-environment interactions in Leber hereditary optic neuropathy.

    Science.gov (United States)

    Kirkman, Matthew Anthony; Yu-Wai-Man, Patrick; Korsten, Alex; Leonhardt, Miriam; Dimitriadis, Konstantin; De Coo, Ireneaus F; Klopstock, Thomas; Chinnery, Patrick Francis

    2009-09-01

    Leber hereditary optic neuropathy (LHON) is a genetic disorder primarily due to mutations of mitochondrial DNA (mtDNA). Environmental factors are thought to precipitate the visual failure and explain the marked incomplete penetrance of LHON, but previous small studies have failed to confirm this to be the case. LHON has no treatment, so identifying environmental triggers is the key to disease prevention, whilst potentially revealing new mechanisms amenable to therapeutic manipulation. To address this issue, we conducted a large, multicentre epidemiological study of 196 affected and 206 unaffected carriers from 125 LHON pedigrees known to harbour one of the three primary pathogenic mtDNA mutations: m.3460G>A, m.11778G>A and m.14484T>C. A comprehensive history of exposure to smoking, alcohol and other putative environmental insults was collected using a structured questionnaire. We identified a strong and consistent association between visual loss and smoking, independent of gender and alcohol intake, leading to a clinical penetrance of 93% in men who smoked. There was a trend towards increased visual failure with alcohol, but only with a heavy intake. Based on these findings, asymptomatic carriers of a LHON mtDNA mutation should be strongly advised not to smoke and to moderate their alcohol intake.

  8. Novel therapeutic approaches for Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Iyer, Shilpa

    2013-03-01

    Many human childhood mitochondrial disorders result from abnormal mitochondrial DNA (mtDNA) and altered bioenergetics. These abnormalities span most of the mtDNA, demonstrating that there are no "unique" positions on the mitochondrial genome that when deleted or mutated produce a disease phenotype. This diversity implies that the relationship between mitochondrial genotype and clinical phenotype is very complex. The origins of clinical phenotypes are thus unclear, fundamentally difficult-to-treat, and are usually clinically devastating. Current treatment is largely supportive and the disorders progress relentlessly causing significant morbidity and mortality. Vitamin supplements and pharmacological agents have been used in isolated cases and clinical trials, but the efficacy of these interventions is unclear. In spite of recent advances in the understanding of the pathogenesis of mitochondrial diseases, a cure remains elusive. An optimal cure would be gene therapy, which involves introducing the missing gene(s) into the mitochondria to complement the defect. Our recent research results indicate the feasibility of an innovative protein-transduction ("protofection") technology, consisting of a recombinant mitochondrial transcription factor A (TFAM) that avidly binds mtDNA and permits efficient targeting into mitochondria in situ and in vivo. Thus, the development of gene therapy for treating mitochondrial disease offers promise, because it may circumvent the clinical abnormalities and the current inability to treat individual disorders in affected individuals. This review aims to focus on current treatment options and future therapeutics in mitochondrial disease treatment with a special emphasis on Leber's hereditary optic neuropathy.

  9. Optic neuropathy in children with Lyme disease.

    Science.gov (United States)

    Rothermel, H; Hedges, T R; Steere, A C

    2001-08-01

    Involvement of the optic nerve, either because of inflammation or increased intracranial pressure, is a rare manifestation of Lyme disease. Of the 4 children reported here with optic nerve abnormalities, 2 had decreased vision months after disease onset attributable to optic neuritis, and 1 had headache and diplopia early in the infection because of increased intracranial pressure associated with Lyme meningitis. In these 3 children, optic nerve involvement responded well to intravenous ceftriaxone therapy. The fourth child had headache and visual loss attributable to increased intracranial pressure and perhaps also to optic neuritis. Despite treatment with ceftriaxone and steroids, he had persistent increased intracranial pressure leading to permanent bilateral blindness. Clinicians should be aware that neuro-ophthalmologic involvement of Lyme disease may have significant consequences. If increased intracranial pressure persists despite antibiotic therapy, measures must be taken quickly to reduce the pressure.

  10. Genetics Home Reference: Leber hereditary optic neuropathy

    Science.gov (United States)

    ... article on PubMed Central Yu-Wai-Man P, Griffiths PG, Hudson G, Chinnery PF. Inherited mitochondrial optic ... Institutes of Health National Library of Medicine Lister Hill National Center for Biomedical Communications 8600 Rockville Pike, ...

  11. Visual Functions and TraceElement Metabolism in Tobacco-toxic Optic Neuropathy

    Institute of Scientific and Technical Information of China (English)

    1992-01-01

    Visual functions and nutrition metabolic characteristics werestudied in 8 subjects(16 eyes)with tobacco-toxic optic neuropathy(TTON).Their visual functions tested by psychophysical and electrophysiologicmethods showed that:1.central vision diminished in 16 eyes,2.dyschromatopsias were found in 14 tested eyes,3.bilateral symmetricalcentral or cecocentral scotomas were the visual field characteristics in allcases,4.PVEP were severe abnormal in 3 spatial frequencies in all cases and56.3% of 15' checkboard ...

  12. Mitochondrial DNA Mutation Associated with Leber's Hereditary Optic Neuropathy

    Science.gov (United States)

    Wallace, Douglas C.; Singh, Gurparkash; Lott, Marie T.; Hodge, Judy A.; Schurr, Theodore G.; Lezza, Angela M. S.; Elsas, Louis J.; Nikoskelainen, Eeva K.

    1988-12-01

    Leber's hereditary optic neuropathy is a maternally inherited disease resulting in optic nerve degeneration and cardiac dysrhythmia. A mitochondrial DNA replacement mutation was identified that correlated with this disease in multiple families. This mutation converted a highly conserved arginine to a histidine at codon 340 in the NADH dehydrogenase subunit 4 gene and eliminated an Sfa NI site, thus providing a simple diagnostic test. This finding demonstrated that a nucleotide change in a mitochondrial DNA energy production gene can result in a neurological disease.

  13. Late-onset Leber hereditary optic neuropathy mimicking Susac's syndrome.

    Science.gov (United States)

    Zoccolella, Stefano; Petruzzella, Vittoria; Prascina, Francesco; Artuso, Lucia; Pacillo, Francesca; Dell'Aglio, Rosa; Avolio, Carlo; Delle Noci, Nicola; Attimonelli, Marcella; Specchio, Luigi Maria

    2010-12-01

    Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder characterized by bilateral painless optic atrophy and blindness. It usually occurs in young men in association with three major mutations in the mitochondrial genome (mtDNA). We report a patient with a history of alcohol abuse who developed at age 63 years visual impairment, sensorineural hearing loss, and memory dysfunction, suggestive of Susac's syndrome. The patient carried the heteroplasmic mt. 11778G>A mutation on the T2e mtDNA haplogroup. It remains unclear if chronic alcohol abuse combined with the mitochondrial genetic background prompted an aged-related neurodegeneration or deferred the onset of the LHON disease.

  14. Hereditary sensory autonomic neuropathy and anaesthesia - a case report

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    Nandini Dave

    2007-01-01

    Full Text Available The hereditary sensory and autonomic neuropathies are a rare group of disorders characterized by progressive loss of function that predominantly affects the peripheral sensory nerves. Autonomic dysfunction is present to a variable degree and can have several implications for anaesthesia. We report the case of a patient with Hereditary sensory and autonomic neuropathy who was posted for a below knee amputation and discuss the anaesthesia management.

  15. Leber′s hereditary optic neuropathy: The mitochondrial connection revisited

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    Khaled K Abu-Amero

    2011-01-01

    Full Text Available Our current understanding of Leber′s hereditary optic neuropathy (LHON-mitochondrial connection falls short of comprehensive. Twenty years of intensive investigation have yielded a wealth of information about mitochondria, the mitochondrial genome, the metabolism of the optic nerve and other structures, and the phenotypic variability of classic LHON. However, we still cannot completely explain how primary LHON mutations injure the optic nerve or why the optic nerve is particularly at risk. We cannot explain the incomplete penetrance or the male predominance of LHON, the typical onset in young adult life without warning, or the synchronicity of visual loss. Moreover, primary LHON mutations clearly are not present in every family with the LHON phenotype (including multigenerational maternal inheritance, and they are present in only a minority of individuals who have the LHON optic neuropathy phenotype without a family history. All lines of evidence point to abnormalities of the mitochondria as the direct or indirect cause of LHON. Therefore, the mitochondria-LHON connection needs to be revisited and examined closely. This review will attempt to do that and provide an update on various aspects of LHON.

  16. Radiation-induced optic neuropathy: A magnetic resonance imaging study

    Energy Technology Data Exchange (ETDEWEB)

    Guy, J.; Mancuso, A.; Beck, R.; Moster, M.L.; Sedwick, L.A.; Quisling, R.G.; Rhoton, A.L. Jr.; Protzko, E.E.; Schiffman, J. (Univ. of Florida, Gainesville (USA))

    1991-03-01

    Optic neuropathy induced by radiation is an infrequent cause of delayed visual loss that may at times be difficult to differentiate from compression of the visual pathways by recurrent neoplasm. The authors describe six patients with this disorder who experienced loss of vision 6 to 36 months after neurological surgery and radiation therapy. Of the six patients in the series, two had a pituitary adenoma and one each had a metastatic melanoma, multiple myeloma, craniopharyngioma, and lymphoepithelioma. Visual acuity in the affected eyes ranged from 20/25 to no light perception. Magnetic resonance (MR) imaging showed sellar and parasellar recurrence of both pituitary adenomas, but the intrinsic lesions of the optic nerves and optic chiasm induced by radiation were enhanced after gadolinium-diethylenetriaminepenta-acetic acid (DTPA) administration and were clearly distinguishable from the suprasellar compression of tumor. Repeated MR imaging showed spontaneous resolution of gadolinium-DTPA enhancement of the optic nerve in a patient who was initially suspected of harboring recurrence of a metastatic malignant melanoma as the cause of visual loss. The authors found the presumptive diagnosis of radiation-induced optic neuropathy facilitated by MR imaging with gadolinium-DTPA. This neuro-imaging procedure may help avert exploratory surgery in some patients with recurrent neoplasm in whom the etiology of visual loss is uncertain.

  17. Leber's Hereditary Optic Neuropathy: The Mitochondrial Connection Revisited.

    Science.gov (United States)

    Abu-Amero, Khaled K

    2011-01-01

    Our current understanding of Leber's hereditary optic neuropathy (LHON)-mitochondrial connection falls short of comprehensive. Twenty years of intensive investigation have yielded a wealth of information about mitochondria, the mitochondrial genome, the metabolism of the optic nerve and other structures, and the phenotypic variability of classic LHON. However, we still cannot completely explain how primary LHON mutations injure the optic nerve or why the optic nerve is particularly at risk. We cannot explain the incomplete penetrance or the male predominance of LHON, the typical onset in young adult life without warning, or the synchronicity of visual loss. Moreover, primary LHON mutations clearly are not present in every family with the LHON phenotype (including multigenerational maternal inheritance), and they are present in only a minority of individuals who have the LHON optic neuropathy phenotype without a family history. All lines of evidence point to abnormalities of the mitochondria as the direct or indirect cause of LHON. Therefore, the mitochondria-LHON connection needs to be revisited and examined closely. This review will attempt to do that and provide an update on various aspects of LHON.

  18. Clinical variability in hereditary optic neuropathies: Two novel mutations in two patients with dominant optic atrophy and Wolfram syndrome.

    Science.gov (United States)

    Galvez-Ruiz, Alberto

    2015-01-01

    Dominant optic atrophy (DOA) and Wolfram syndrome share a great deal of clinical variability, including an association with hearing loss and the presence of optic atrophy at similar ages. The objective of this paper was to discuss the phenotypic variability of these syndromes with respect to the presentation of two clinical cases. We present two patients, each with either DOA or Wolfram syndrome, and contribute to the research literature through our findings of two novel mutations. The overlapping of several clinical characteristics in hereditary optic neuropathies can complicate the differential diagnosis. Future studies are needed to better determine the genotype-phenotype correlation for these diseases.

  19. Potential risk factors for diabetic neuropathy: a case control study

    Directory of Open Access Journals (Sweden)

    Nooraei Mahdi

    2005-12-01

    Full Text Available Abstract Background Diabetes mellitus type II afflicts at least 2 million people in Iran. Neuropathy is one of the most common complications of diabetes and lowers the patient's quality of life. Since neuropathy often leads to ulceration and amputation, we have tried to elucidate the factors that can affect its progression. Methods In this case-control study, 110 diabetic patients were selected from the Shariati Hospital diabetes clinic. Michigan Neuropathic Diabetic Scoring (MNDS was used to differentiate cases from controls. The diagnosis of neuropathy was confirmed by nerve conduction studies (nerve conduction velocity and electromyography. The multiple factors compared between the two groups included consumption of angiotensin converting enzyme inhibitors (ACEI, blood pressure, serum lipid level, sex, smoking, method of diabetes control and its quality. Results Statistically significant relationships were found between neuropathy and age, gender, quality of diabetes control and duration of disease (P values in the order: 0.04, 0.04, Conclusion In this study, hyperglycemia was the only modifiable risk factor for diabetic neuropathy. Glycemic control reduces the incidence of neuropathy, slows its progression and improves the diabetic patient's quality of life. More attention must be paid to elderly male diabetic patients with poor diabetes control with regard to regular foot examinations and more practical education.

  20. Optic atrophy differentially diagnosed as spinocerebellar ataxia from Leber hereditary optic neuropathy by gene mutation analysis.

    Science.gov (United States)

    Song, Y P; Chen, Z S; Mo, G Y; Ding, Q; Zhu, L; Yan, M

    2012-01-01

    Optic atrophy describes a group of diseases of retinal ganglion cells and axons that eventually lead to loss of vision. Optic atrophy has both congenital and acquired causes, and its diagnosis (or differential diagnosis) is complicated. This case report describes a 20-year-old man who presented with a 1-year history of progressive vision loss in both eyes and no obvious systemic symptoms. Fundus examination revealed bilateral optic atrophy. Based on clinical characteristics, visual field analysis and pattern visual evoked potential examination, the presumptive diagnosis was Leber hereditary optic neuropathy (LHON). Analysis of mitochondrial DNA indicated the absence of all of three common mutations associated with LHON (m.3460G>A, m.11778G>A, m.14484T>C). Detailed questioning of the patient revealed a history of prolonged language development and poor balance. Neurological examination indicated abnormal co-ordination, suggesting the presence of inherited spinocerebellar ataxia (SCA). Analysis of the SCA7 gene revealed a high number of trinucleotide repeats [(CAG)(n), n > 64], confirming the diagnosis of SCA. The aetiology of optic atrophies is complicated and the molecular genetic detection approach provides the best information for diagnosing these diseases.

  1. Magnetic resonance imaging of luxury perfusion of the optic nerve head in anterior ischemic optic neuropathy.

    Science.gov (United States)

    Yovel, Oren S; Katz, Miriam; Leiba, Hana

    2012-09-01

    A 49-year-old woman with painless reduction in visual acuity in her left eye was found to have nonarteritic anterior ischemic optic neuropathy (NAION). Fluorescein angiography revealed optic disc capillary leakage consistent with "luxury perfusion." Contrast-enhanced FLAIR magnetic resonance imaging (MRI) showed marked enhancement of the left optic disc. Resolution of the optic disc edema and the MRI abnormalities followed a similar time course. This report appears unique in documenting the MRI findings of luxury perfusion in NAION.

  2. Atypical Leber Hereditary Optic Neuropathy: 18 Year Interval Between Eyes.

    Science.gov (United States)

    Ohden, Kaitlyn L; Tang, Peter H; Lilley, Chrystia C; Lee, Michael S

    2016-09-01

    A 5-year-old boy developed profound loss of vision in his right eye and was found to have a 11778 mitochondrial point mutation consistent with Leber hereditary optic neuropathy (LHON). He maintained 20/20 vision in the left eye for 18 years until age 23, when he experienced loss of vision in that eye. This 18 year interval between eye involvement in LHON is the longest reported to date and reinforces the variability in presentation and progression seen in this disease.

  3. Leber Hereditary Optic Neuropathy: Bringing the Lab to the Clinic.

    Science.gov (United States)

    Rasool, Nailyn; Lessell, Simmons; Cestari, Dean M

    2016-01-01

    Leber hereditary optic neuropathy (LHON) was the first clinically characterized mitochondrial disorder. Since its first description in 1871, much has been discovered regarding the genetics and pathophysiology of the disease. This has enabled the development of in vitro cell and animal models that can be used to try to determine not only the effects of the genetic mutation upon the clinical phenotype but to also test potential novel therapies. Treatments for LHON have ranged from vitamins and minerals to immunosuppressants and, more recently, targeted gene therapy. This article reviews the pathophysiology and clinical features of LHON with a focus on translational research.

  4. [The prevalence of acute vascular optic neuropathies in Donetsk Province].

    Science.gov (United States)

    Antonova, A I

    1989-01-01

    The analysis of the wide-spread nature of acute vascular pathology of the optic nerve in Donetsk Province, according to applications for the period of 10 years--from 1978 to 1987, has shown a continuing growth of this pathology in the general structure of optic nerve diseases, being considerably greater in a young (30-44 years) and a middle-aged (45-59 years) age groups. The highest level of the wide-spread nature of the disease has been and remains in persons above 60 years of age. At the present time, the most critical age for development of acute vascular optic neuropathies is a middle-aged group. Among the patient of this age group women prevail and among men with this pathology prevail unskilled workers and employers.

  5. m.3635G>A mutation as a cause of Leber hereditary optic neuropathy.

    Science.gov (United States)

    Kodroń, Agata; Krawczyński, Maciej R; Tońska, Katarzyna; Bartnik, Ewa

    2014-07-01

    Over 90% of Leber's hereditary optic neuropathy (LHON) is caused by one of three mtDNA mutations (m.11778A>G, m.3460G>A, m.14484T>C). The remaining cases are due to rare mutations in different genes encoding subunits of the respiratory chain. The proband is a 17-year-old male with symptoms of optic nerve atrophy. No common LHON mutations were found, but detailed sequencing identified a rare, homoplasmic mutation m.3635G>A in the ND1 gene.

  6. Bilateral optic neuropathy following bite from brown recluse spider (Loxosceles reclusa).

    Science.gov (United States)

    Mantopoulos, Dimosthenis; Hendershot, Andrew J; Cebulla, Colleen M; Hirsh, David K

    2016-01-01

    A 63-year-old female with history of a resected frontal lobe meningioma presented with bilaterally decreased vision after a bite from a brown recluse spider. The exam was significant for a left relative afferent pupillary defect, bilateral optic nerve pallor, decreased foveal sensitivity in the left eye and new bilateral visual field defects, despite stability of her meningioma. The findings remained stable at 1-year follow-up. To our knowledge, this is the first reported case of optic neuropathy secondary to a brown recluse spider bite. Visual field tests performed prior to the bite allowed us to compare and localize changes related to the bite.

  7. Mucormycoses: serious complication of high-dose corticosteroid therapy for traumatic optic neuropathy.

    Science.gov (United States)

    Dojcinovic, I; Richter, M

    2008-04-01

    Mucormycosis is harmless to a healthy person, but can cause opportunistic infections in immunocompromised patients, and once it has invaded internal organs is frequently fatal. Traumatic optic neuropathy is a rare complication of maxillofacial trauma. Management is controversial, and there are no treatment guidelines in the literature. The main methods of treatment of this condition employed today are high-dose corticosteroids and surgical optic nerve decompression, either alone or in combination. In this case, the patient was in good health, but received high-dose corticosteroids for 2 weeks, which temporarily diminished immune response and permitted the development of mucormycosis.

  8. A MELAS-associated ND1 mutation causing leber hereditary optic neuropathy and spastic dystonia.

    NARCIS (Netherlands)

    Spruijt, L.; Smeets, H.J.M.; Hendrickx, A.; Bettink-Remeijer, M.W.; Maat-Kievit, A.; Schoonderwoerd, K.C.; Sluiter, W.; Coo, I.F.M. de; Hintzen, R.Q.

    2007-01-01

    OBJECTIVE: To report a novel mutation that is associated with Leber hereditary optic neuropathy (LHON) within the same family affected by spastic dystonia. DESIGN: Leber hereditary optic neuropathy is a mitochondrial disorder characterized by isolated central visual loss. Of patients with LHON, 95%

  9. A MELAS-associated ND1 mutation causing leber hereditary optic neuropathy and spastic dystonia.

    NARCIS (Netherlands)

    Spruijt, L.; Smeets, H.J.M.; Hendrickx, A.; Bettink-Remeijer, M.W.; Maat-Kievit, A.; Schoonderwoerd, K.C.; Sluiter, W.; Coo, I.F.M. de; Hintzen, R.Q.

    2007-01-01

    OBJECTIVE: To report a novel mutation that is associated with Leber hereditary optic neuropathy (LHON) within the same family affected by spastic dystonia. DESIGN: Leber hereditary optic neuropathy is a mitochondrial disorder characterized by isolated central visual loss. Of patients with LHON, 95%

  10. Optic neuropathies: characteristic features and mechanisms of retinal ganglion cell loss.

    Science.gov (United States)

    You, Yuyi; Gupta, Vivek K; Li, Jonathan C; Klistorner, Alexander; Graham, Stuart L

    2013-01-01

    Optic neuropathy refers to dysfunction and/or degeneration of axons of the optic nerve with subsequent optic nerve atrophy. A common feature of different optic neuropathies is retinal ganglion cell (RGC) apoptosis and axonal damage. Glaucoma and optic neuritis are the two major degenerative causes of optic nerve damage. Here, we review the anatomy and pathology of the optic nerve, and etiological categories of optic neuropathies, and discuss rodent models that can mimic these conditions. Electrophysiology can reveal signature features of RGC damage using the pattern electroretinogram (PERG), scotopic threshold response (STR) and photopic negative response (PhNR). The amplitude of the visual evoked potential (VEP) also reflects RGC axonal damage. The neurotrophin-mediated survival pathways, as well as the extrinsic and intrinsic cell apoptotic pathways, play a critical role in the pathogenesis of RGC loss. Finally, promising neuroprotective approaches based on the molecular signaling are analyzed for the treatment of optic neuropathies.

  11. Peripheral neuropathy in Whipples disease: a case report.

    Science.gov (United States)

    Rusina, R; Keller, O; Síma, R; Zámečník, J

    2012-04-01

    Whipples disease is a chronic multisystem inflammatory disease with predominantly gastrointestinal manifestations due to Tropheryma whipplei infection. Typical neurological abnormalities include dementia, eye movement abnormalities, hypothalamic dysfunction and oculomasticatory myorhythmias. The literature on peripheral neuropathy in Whipples disease is sparse and the involvement of peripheral nerves in Whipples disease has not been documented convincingly so far. We present a case of Whipples disease presenting by axonal peripheral neuropathy without gastrointestinal involvement. The diagnosis was confirmed by a sural nerve biopsy and consequent PCR of the sample. All clinical signs disappeared progressively during the antibiotic therapy. Two years after the T. whipplei infection, the patient developed dopa-sensitive Parkinson's disease, although these two events seem to be unrelated. This case illustrates the value of peripheral nerve biopsy in cases of axonal neuropathy of unexplained origin and extends the clinical spectrum of Whipples disease to a new modality.

  12. Evidence for retrochiasmatic tissue loss in Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Barcella, Valeria; Rocca, Maria A; Bianchi-Marzoli, Stefania; Milesi, Jacopo; Melzi, Lisa; Falini, Andrea; Pierro, Luisa; Filippi, Massimo

    2010-12-01

    Patients with Leber's hereditary optic neuropathy (LHON) have loss of central vision with severe damage of small-caliber fibers of the papillomacular bundle and optic nerve atrophy. The aim of this study was to define the presence and topographical distribution of brain grey matter (GM) and white matter (WM) injury in LHON patients using voxel-based morphometry (VBM). The correlation of such changes with neuro-ophthalmologic findings and measurements of peripapillary retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT) was also assessed. Dual-echo and fast-field echo scans were acquired from 12 LHON patients and 12 matched controls. VBM analysis was performed using SPM5 and an ANCOVA model. A complete neuro-ophthalmologic examination, including standardized automated Humphrey perimetry as well as average and temporal peripapillary RNFL thickness measurements were obtained in all the patients. Compared with controls, average peripapillary RNFL thickness was significantly decreased in LHON patients. LHON patients also had significant reduced GM volume in the bilateral primary visual cortex, and reduced WM volume in the optic chiasm, optic tract, and several areas located in the optic radiations (OR), bilaterally. Visual cortex and OR atrophy were significantly correlated with average and temporal peripapillary RNFL thickness (P optic nerve or to local mitochondrial dysfunction.

  13. Atypical presentation of Leigh syndrome associated with a Leber hereditary optic neuropathy primary mitochondrial DNA mutation.

    Science.gov (United States)

    Fruhman, Gary; Landsverk, Megan L; Lotze, Timothy E; Hunter, Jill V; Wangler, Michael F; Adesina, Adekunle M; Wong, Lee-Jun C; Scaglia, Fernando

    2011-06-01

    Leber hereditary optic neuropathy (LHON) is caused by point mutations in mitochondrial DNA (mtDNA), and is characterized by bilateral, painless sub-acute visual loss that develops during the second decade of life. Here we report the case of a five year old girl who presented with clinical and neuroradiological findings reminiscent of Leigh syndrome but carried a mtDNA mutation m.11778G>A (p.R340H) in the MTND4 gene usually observed in patients with LHON. This case is unusual for age of onset, gender, associated neurological findings and evolution, further expanding the clinical spectrum associated with primary LHON mtDNA mutations.

  14. An unusual case of suprascapular nerve neuropathy: a case report

    Directory of Open Access Journals (Sweden)

    Kyriakides Theodoros

    2011-08-01

    Full Text Available Abstract Introduction Suprascapular nerve neuropathy constitutes an unusual cause of shoulder weakness, with the most common etiology being nerve compression from a ganglion cyst at the suprascapular or spinoglenoid notch. We present a puzzling case of a man with suprascapular nerve neuropathy that may have been associated with an appendectomy. The case was attributed to nerve injury as the most likely cause that may have occurred during improper post-operative patient mobilization. Case presentation A 23-year-old Caucasian man presented to an orthopedic surgeon with a history of left shoulder weakness of several weeks' duration. The patient complained of pain and inability to lift minimal weight, such as a glass of water, following an appendectomy. His orthopedic clinical examination revealed obvious atrophy of the supraspinatus and infraspinatus muscles and 2 of 5 muscle strength scores on flexion resistance and external rotation resistance. Magnetic resonance imaging showed diffuse high signal intensity within the supraspinatus and infraspinatus muscles and early signs of minimal fatty infiltration consistent with denervation changes. No compression of the suprascapular nerve in the suprascapular or spinoglenoid notch was noted. Electromyographic studies showed active denervation effects in the supraspinatus muscle and more prominent in the left infraspinatus muscle. The findings were compatible with damage to the suprascapular nerve, especially the part supplying the infraspinatus muscle. On the basis of the patient's history, clinical examination, and imaging studies, the diagnosis was suspected to be associated with a possible traction injury of the suprascapular nerve that could have occurred during the patient's transfer from the operating table following an appendectomy. Conclusion Our case report may provide important insight into patient transfer techniques used by hospital personnel, may elucidate the clinical significance of careful

  15. Recurrent painful ophthalmoplegic neuropathy; A case report

    Directory of Open Access Journals (Sweden)

    Semra Saygi

    2014-08-01

    Full Text Available Recurrent painful ophthalmoplegic neuropathy, typically seen as a serious childhood migraine attack which is followed by ptosis and diplopia due to oculomotor nerve palsy. This is regarded as a form of migraine in the previous classifications but according to the latest classification of the International Headache Society has been recognized as cranial neuralgia. Due to the poor pathological and radiological findings of oculomotor nerve during attack, it is difficult to make differential diagnosis. In this manuscript we report 11-year-old female patient with ophtalmoplegic migraine. [Cukurova Med J 2014; 39(4.000: 938-941

  16. 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

  17. Multiple sclerosis associated with Leber's Hereditary Optic Neuropathy.

    Science.gov (United States)

    Palace, Jacqueline

    2009-11-15

    The cause of multiple sclerosis is unknown although it is recognised to involve an inflammatory process associated with demyelinating plaques and more widespread neurodegeneration. It appears to have become progressively more common in females which is further discussed in this issue, and genetic factors, as identified to date, appear to play only a moderate role. One curious observation is that Leber's Hereditary Optic Neuropathy (LHON), a rare genetic syndrome, presents clinically overwhelmingly in males, but can be associated with an MS-like illness and when it does it occurs mainly in females. It is interesting to examine this further to assess if this could give us any clues as to the pathogenesis of MS.

  18. Therapeutic strategies for Leber's hereditary optic neuropathy: A current update.

    Science.gov (United States)

    Gueven, Nuri; Faldu, Dharmesh

    2013-11-01

    Leber's hereditary optic neuropathy (LHON) is a rare mitochondrial retinopathy, caused by mutations in subunits of complex I of the respiratory chain, which leads to elevated levels of oxidative stress and an insufficient energy supply. This molecular pathology is thought to be responsible for the dysfunction and eventual apoptotic loss of retinal ganglion cells in the eye, which ultimately results in blindness. Many strategies, ranging from neuroprotectants, antioxidants, anti-apoptotic- and anti-inflammatory compounds have been tested with mixed results. Currently, the most promising compounds are short-chain quinones that have been shown to protect the vision of LHON patients during the early stages of the disease. This commentary gives a brief overview on the current status of tested therapeutics and also addresses future developments such as the use of gene therapy that hopefully will provide safe and efficient therapy options for all LHON patients.

  19. [Clinical and molecular genetic analysis of hereditary optic neuropathies].

    Science.gov (United States)

    Avetisov, S É; Sheremet, N L; Vorob'eva, O K; Eliseeva, É G; Chukhrova, A L; Loginova, A N; Khanakova, N A; Poliakov, A V

    2013-01-01

    DNA samples of 50 patients with optic neuropathy (ON) associated with congenital cataract were studied to find 3 major mt-DNA mutations (m.11778G>A, m.3460G>A, m.14484T>C), mutations in "hot" regions of OPA 1 gene (exons 8, 14, 15, 16, 18, 27, 28) and in the entire coding sequence of OPA3 gene for molecular genetic confirmation of diagnosis of hereditary Leber and autosomal dominant ON. Primary mutations of mtDNA responsible for hereditary Leber ON were found in 16 patients (32%). Pathogenic mutations of OPAl gene (c.869G>A and c. 2850delT) were identified in 2 patients (4%), these mutations were not found in the literature. OPA3 gene mutations were not revealed.

  20. Evaluation of dysthyroid optic neuropathy using T2-relaxation time of extraocular muscle as parameter

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Fumihiko; Maeda, Toshine; Inoue, Toyoko; Inoue, Yoichi [Olympia Eye Hospital, Tokyo (Japan)

    2001-11-01

    The T2 value of magnetic resonance imaging (MRI) is useful in evaluating the activity of dysthyroid ophthlamopathy. We applied this method in evaluating dysthyroid optic neuropathy in 15 affected eyes of 15 patients. Another group of 40 eyes of 20 patients of dysthyroid opthalmopathy without hypertrophy of extraocular muscles served as control. The T2 value in dysthyroid optic neuropathy significantly decreased following treatment with corticosteroid but the value was still higher than that in control eyes. The findings show that the T2 value of MRI is useful in evaluating the therapeutic effect of dysthyroid optic neuropathy. (author)

  1. Congenital optic nerve anomalies and hereditary optic neuropathies.

    Science.gov (United States)

    Heidary, Gena

    2014-12-01

    Congenital and hereditary optic nerve anomalies represent a significant cause of visual dysfunction. While some optic nerve abnormalities affect the visual system alone, others may be associated with neurologic and systemic findings. Correct identification of the optic nerve disease therefore is crucial both for developing a treatment plan with respect to visual rehabilitation, but also for initiating the appropriate multidisciplinary evaluation. The purpose of this review is to highlight common examples of congenital and inherited optic nerve abnormalities in an effort to familiarize the clinician with salient clinical features of these diseases and to review important systemic testing when relevant.

  2. Endoscopic Decompression for Optic Neuropathy in McCune-Albright Syndrome.

    Science.gov (United States)

    Noh, Jung-Hoon; Kong, Doo-Sik; Seol, Ho Jun; Shin, Hyung Jin

    2014-09-01

    McCune-Albright syndrome (MAS) is characterized by a triad of poly/monostotic fibrous dysplasia, café-au-lait macules and hyperfunctioning endocrinopathies including human growth hormone excess. Acromegaly as a manifestation of endocrine hyperfunction with MAS is uncommon. Surgical excision may be challenging due to the associated severe fibrous dysplasia of the skull base. Through the endoscopic procedures, we treated a case of MAS presenting with compressive optic neuropathy due to fibrous dysplasia and acromegaly caused by growth hormone secreting pituitary adenoma. We reviewed the literature on GH excess in MAS to highlight its surgical and medical challenges.

  3. Myelin vacuolation, optic neuropathy and retinal degeneration after closantel overdosage in sheep and in a goat.

    Science.gov (United States)

    van der Lugt, J J; Venter, I

    2007-01-01

    Toxicity of closantel, a halogenated salicylanilide anthelmintic, is described in 11 sheep and a goat, humanely killed 4-70 days after accidental overdosage. Status spongiosis of the cerebrum and cerebellum was present, its severity decreasing with time after treatment. Ultrastructurally, vacuoles in the cerebral white matter were seen to be intramyelinic due to splitting of myelin lamellae at the intraperiod lines, indicating myelin oedema. In the optic nerves, Wallerian degeneration and eventual fibrosis and atrophy of the nerves followed myelin vacuolation. Lesions in the optic nerves were particularly advanced in the intracanalicular portion, indicating a compressive neuropathy within the optic canal. Acute retinal lesions consisted of papilloedema, necrosis of the outer retinal layers (especially the photoreceptor layer), and retinal separation in tapetal and non-tapetal areas. In more chronic cases, the outer nuclear layer was diffusely attenuated and generally reduced to a single row of cells.

  4. Controversies in neuro-ophthalmology: Steroid therapy for traumatic optic neuropathy

    Directory of Open Access Journals (Sweden)

    Rohit Saxena

    2014-01-01

    Full Text Available Background: There is an increase in the incidence of traumatic optic neuropathy (TON due to increasing urbanization and rapid spurt in the number of motor vehicles on the road. Despite early presentation and ease of diagnosis the visual outcomes in TON are still limited. There is also significant confusion about the timing, dose and efficacy of steroid treatment in its management. Purpose: To provide a clinical update of the pros and cons of steroid therapy for TON. Design: The paper is a retrospective review of the currently available literature in the English language indexed in PubMed. Methods: A PubMed search was conducted by the authors using the following terms: Traumatic optic neuropathy, megadose, steroids, methylprednisolone. Relevant original articles, review articles, and case reports related to the topic of discussion were evaluated and discussed in the paper. Results: There is no prospective randomized control trial evaluating the effect of steroids in TON. There are varying reports on the effect of steroid therapy from significant improvement to no difference compared to observation. Conclusion: The decision to give steroids to patients with TON has to be on an individual case to case basis and must involve informed consent from the patient. There are documented advantages and disadvantages of steroid therapy and a prospective, randomized, controlled trial is necessary comparing steroids, surgery and observation before definitive management can be evolved.

  5. Compressive Optic Neuropathy Caused by Cholesterol Gran-uloma in the Posterior Ethmoid Sinus

    Institute of Scientific and Technical Information of China (English)

    Chun-Chih Lin; Ting-Kuang Chao; Tsu-Hua Chen; Jia-Kang Wang

    2015-01-01

    Purpose:.Cholesterol granuloma is usually associated with chronic middle ear disease..Involvement of the ethmoid sinus by cholesterol granuloma is rare..We describe a case with cholesterol granuloma of the posterior ethmoid sinus causing optic nerve compression..No previous reports were found in our review of the literature. Case report:.A 48-year-old man had impaired visual acuity and a relative afferent pupillary defect in the right eye. Fundus fluorescein angiography showed a swollen optic nerve head and optic disc leakage. Automated perimetry revealed a severe peripheral visual field defect with tunnel vision. Computerized tomography demonstrated an expansile,.isodense mass in the right posterior ethmoid sinus, remodeling of the bony walls of the right sphenoid sinus, and lateral displacement of the optic nerve in the right orbit..Compressive optic neuropathy caused by posterior ethmoid sinus lesion was diagnosed..A transnasal endoscopic exploration of the right ethmoid sinuses demon-strated a soft expansile cystic lesion with a thick yellow cap sule that filled the inside of the posterior ethmoid sinus. Brownish fluid with shiny crystals was drained by fine needle aspiration. The capsule was removed completely, and the mu-cociliary clearance of the sinus was reestablished..The patho-logic pictures confirmed the diagnosis of cholesterol granulo-ma, which included typical cholesterol clefts surrounded by inflammatory cells with focal multi-nucleated giant cells. Visu-al function fully recovered without recurrent lesions after a three-year follow-up. Conclusion:.Compressive optic neuropathy can be rarely caused by cholesterol granuloma in the posterior ethmoid si-nus. The visual prognosis may be good after transnasal endo-scopic decompression in such patients.

  6. Posterior reversible encephalopathy syndrome in a leber hereditary optic neuropathy patient with mitochondrial DNA 11778G>A point mutation.

    Science.gov (United States)

    Da, Yuwei; Zhang, Xuxiang; Li, Fang; Yang, Xiaoping; Zhang, Xinqing; Jia, Jianping

    2013-09-01

    Leber hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disorder that primarily affects the optic nerve. We report a case of reduced visual acuity secondary to optic atrophy in a 13-year-old boy. Transient seizures developed subsequently. Serial magnetic resonance imaging of the brain showed posterior reversible encephalopathy syndrome. Ragged red fibers were not detected on skeletal muscle biopsy. A 11778G>A mitochondrial DNA point mutation was identified in the lymphocytes isolated from peripheral blood. His younger brother was a carrier with the same mutation. The presentation of this case is unusual documenting LHON in association with PRES.

  7. Papilloedema and MRI enhancement of the prechiasmal optic nerve at the acute stage of Leber hereditary optic neuropathy.

    Science.gov (United States)

    Lamirel, Cédric; Cassereau, Julien; Cochereau, Isabelle; Vignal-Clermont, Catherine; Pajot, Olivier; Tanguy, Jean-Yves; Zanlonghi, Xavier; Reynier, Pascal; Amati-Bonneau, Patrizia; Dubas, Frédéric; Bonneau, Dominique; Verny, Christophe

    2010-05-01

    The authors report a case of one patient from a family carrying the homoplasmic Leber hereditary optic neuropathy (LHON) G11778A mitochondrial DNA mutation with papilloedema 9 months prior to the acute stage of LHON and still present at the onset of visual loss. During the vision loss, the MRI demonstrated a T2 hyperintensity and an enhancement of the prechiasmal left optic nerve, suggesting the existence of an inflammatory mechanism. A retrospective review of the chart of two others members of the same family, with bilateral optic disc oedema at onset of the vision loss, suggests that the relationship of papilloedema and acute phase of LHON may not be just a coincidence, at least in this family. The visual loss related to LHON could have been triggered in the setting of the chronic papilloedema, associated with the intracranial hypertension.

  8. Evaluation of retinal nerve fiber layer thickness measurements using optical coherence tomography in patients with tobacco-alcohol-induced toxic optic neuropathy

    Directory of Open Access Journals (Sweden)

    Moura Frederico

    2010-01-01

    Full Text Available Three patients with progressive visual loss, chronic alcoholism and tabagism were submitted to a complete neuro-ophthalmic examination and to retinal nerve fiber layer (RNFL measurements using optical coherence tomography (OCT scanning. Two patients showed marked RNFL loss in the temporal sector of the optic disc. However, a third patient presented RNFL measurements within or above normal limits, based on the Stratus-OCT normative database. Such findings may be due to possible RNFL edema similar to the one that may occur in the acute phase of toxic optic neuropathies. Stratus-OCT was able to detect RNFL loss in the papillomacular bundle of patients with tobacco-alcohol-induced toxic optic neuropathy. However, interpretation must be careful when OCT does not show abnormality in order to prevent diagnostic confusion, since overestimation of RNFL thickness measurements is possible in such cases.

  9. Unilateral Acute Anterior Ischemic Optic Neuropathy in a Patient with an Already Established Diagnosis of Bilateral Optic Disc Drusen

    Science.gov (United States)

    Ayhan, Ziya; Yaman, Aylin; Söylev Bajin, Meltem; Saatci, A. Osman

    2015-01-01

    Optic disc drusen (ODD) are calcific deposits that form in the optic nerve head secondary to abnormalities in axonal metabolism and degeneration. Anterior ischemic optic neuropathy, central retinal artery, and vein occlusion are among the rare vascular complications of disc drusen. We reported the clinical course of a 51-year-old patient with a unilateral acute nonarteritic anterior ischemic optic neuropathy (NAION) who received the diagnosis of bilateral optic disc drusen five years earlier and thereby reiterated the association of ODD and acute NAION. PMID:26550507

  10. Unilateral Acute Anterior Ischemic Optic Neuropathy in a Patient with an Already Established Diagnosis of Bilateral Optic Disc Drusen

    Directory of Open Access Journals (Sweden)

    Ziya Ayhan

    2015-01-01

    Full Text Available Optic disc drusen (ODD are calcific deposits that form in the optic nerve head secondary to abnormalities in axonal metabolism and degeneration. Anterior ischemic optic neuropathy, central retinal artery, and vein occlusion are among the rare vascular complications of disc drusen. We reported the clinical course of a 51-year-old patient with a unilateral acute nonarteritic anterior ischemic optic neuropathy (NAION who received the diagnosis of bilateral optic disc drusen five years earlier and thereby reiterated the association of ODD and acute NAION.

  11. Differential cerebro spinal fluid proteome investigation of Leber hereditary optic neuropathy (LHON) and multiple sclerosis.

    Science.gov (United States)

    D'Aguanno, Simona; Barassi, Alessandra; Lupisella, Santina; d'eril, Gianlodovico Melzi; Del Boccio, Piero; Pieragostino, Damiana; Pallotti, Francesco; Carelli, Valerio; Valentino, Maria Lucia; Liguori, Rocco; Avoni, Patrizia; Bernardini, Sergio; Gambi, Domenico; Urbani, Andrea; Federici, Giorgio

    2008-01-01

    Leber's hereditary optic neuropathy (LHON) is a genetic disease leading to the loss of central vision and optic nerve atrophy. The existence of occasional cases of LHON patients developing a Multiple Sclerosis (MS)-like illness and the hypothesis that mtDNA variants may be involved in MS suggest the possibility of some common molecular mechanisms linking the two diseases. We have pursued a comparative proteomics approach on cerebrospinal fluid (CSF) samples from LHON and MS patients, as well as healthy donors by employing 2-DE gel separations coupled to MALDI-TOF-MS and nLC-MS/MS investigations. 7 protein spots showed significant differential distribution among the three groups. Both CSF of LHON or MS patients are characterized by lower level of transthyretin dimer adduct while a specific up regulation of Apo A-IV was detected in LHON CSF.

  12. Idebenone: A Review in Leber's Hereditary Optic Neuropathy.

    Science.gov (United States)

    Lyseng-Williamson, Katherine A

    2016-05-01

    Idebenone (Raxone(®)), a short-chain benzoquinone, is the only disease-specific drug approved to treat visual impairment in adolescents and adults with Leber's hereditary optic neuropathy (LHON), a rare genetic mitochondrial disease that causes rapid and progressive bilateral vision loss. The mechanism of action of idebenone involves its antioxidant properties and ability to act as a mitochondrial electron carrier. Idebenone overcomes mitochondrial complex I respiratory chain deficiency in patients with LHON by transferring electrons directly to mitochondrial complex III (by-passing complex I), thereby restoring cellular energy (ATP) production and re-activating inactive-but-viable retinal ganglion cells, which ultimately prevents further vision loss and promotes vision recovery. The approval of idebenone in the treatment of LHON was based on the overall data from a randomized clinical trial, a follow-up study and real-world data. Taken together, these studies provide convincing evidence that oral idebenone 900 mg/day for 24 weeks has persistent beneficial effects in preventing further vision impairment and promoting vision recovery in patients with LHON relative to the natural course of the disease. Therefore, idebenone is a valuable agent to treat visual impairment in adolescents and adults with LHON.

  13. [Peculiarities of ocular blood flow in ischemic optic neuropathy and normal tension glaucoma].

    Science.gov (United States)

    Mamikonian, V R; Galoian, N S; Sheremet, N L; Kazarian, E E; Kharlap, S I; Shmeleva-Demir, O A; Andzhelova, D V; Tatevosian, A A

    2013-01-01

    Characteristics of ocular hemodynamics in ischemic optic neuropathy (ION) outcome and normal tension glaucoma (NTG), the conditions that are difficult to be differentially diagnosed, have been investigated. The study enrolled 32 patients (40 eyes) with ION outcome, 26 patients (46 eyes) with NTG, and 20 patients (32 eyes) with no ocular pathology. Besides the standard ophthalmological examination, color Doppler imaging of ocular vessels, evaluation of ocular blood flow volume and individual normal range of intraocular pressure (flowmetry) were performed in all cases. The results showed that an excess of the actual intraocular pressure (IOP) over the individual normal range was much higher in patients with NTG than in patients with ION (39% and 14.5% correspondingly). It was also found that NTG is associated with a more significant decrease of ocular blood flow volume (30.1% in average) in comparison to ION outcome (11%). In both conditions a decrease in velocity parameters of the blood flow in main ocular vessels was registered, however, ocular hemodynamics changes appeared to be more severe in patients with glaucomatous optic neuropathy. A statistically reliable correlation between volumetric and velocity parameters of ocular blood flow has been discovered.

  14. The use of induced pluripotent stem cells for studying and treating optic neuropathies.

    Science.gov (United States)

    Khan, Shahnaz; Hung, Sandy Shen-Chi; Wong, Raymond Ching-Bong

    2016-10-01

    The present review aims to provide an update of applications of induced pluripotent stem cells (iPSCs) for disease modeling, cell/gene therapy, and drug screening for optic neuropathies. Degeneration of retinal ganglion cells (RGCs) is a characteristic of optic neuropathies. Human iPSCs can serve as a model to investigate disease pathology and potential repair mechanisms. In recent years, significant progress has been made in generating RGCs from iPSCs. Various groups have reported the potential of iPSCs for modeling optic neuropathies, such as glaucoma. The literature also highlights the potential to use iPSC-derived cells for high-throughput drug and toxicity screening. The present review summarizes current work in the field of iPSCs in optic neuropathies. Future studies to characterize iPSC-derived RGCs in a more in-depth manner will help expand the use of iPSCs to model and treat optic neuropathic diseases. Furthermore, iPSC modeling can be used in drug development by offering a new avenue to test novel therapeutic drugs for optic neuropathies.

  15. Bilateral Simultaneous Nonarteritic Anterior Ischemic Optic Neuropathy after Ingestion of Sildenafil for Erectile Dysfunction

    Directory of Open Access Journals (Sweden)

    Anna Tarantini

    2012-01-01

    Full Text Available Purpose. To describe a patient who developed bilateral, simultaneous nonarteritic anterior ischemic optic neuropathy (NAION after ingestion of Sildenafil citrate (Viagra for erectile dysfunction. Methods. Observational case report. Results. A 60-year-old diabetic man noted sudden decrease of vision in both eyes 16 hours after his third consecutive 50 mg daily Sildenafil ingestion. A diagnosis of bilateral NAION was made and he was treated for three days with methylprednisolone 1 g/d intravenously, followed by oral prednisone 75 mg/d. Final visual acuity was 20/50 right eye (OD and 20/20 left eye (OS. He had preexisting diabetes. Conclusion. This is the first reported case of simultaneous bilateral NAION occurred in a diabetic patient early after Sildenafil intake. Patients with predisposing conditions such as diabetes have to be warned against the use of PDE inhibitors.

  16. Melanopsin retinal ganglion cells are resistant to neurodegeneration in mitochondrial optic neuropathies

    DEFF Research Database (Denmark)

    La Morgia, C; Ross-Cisneros, F.N.; Sadun, A.A.

    2010-01-01

    Mitochondrial optic neuropathies, that is, Leber hereditary optic neuropathy and dominant optic atrophy, selectively affect retinal ganglion cells, causing visual loss with relatively preserved pupillary light reflex. The mammalian eye contains a light detection system based on a subset of retinal...... for the preservation of pupillary light reaction despite profound visual loss in patients with mitochondrial optic neuropathy, revealing the robustness of melanopsin retinal ganglion cells to a metabolic insult and opening the question of mechanisms that might protect these cells....... ganglion cells containing the photopigment melanopsin. These cells give origin to the retinohypothalamic tract and support the non-image-forming visual functions of the eye, which include the photoentrainment of circadian rhythms, light-induced suppression of melatonin secretion and pupillary light reflex...

  17. EFFICACY OF INTRAVENOUS METHYLPREDNISOLONE THERAPY IN TRAUMATIC OPTIC NEUROPATHY WITH ORBITAL WALL FRACTURES: A PROSPECTIVE COHORT STUDY

    Directory of Open Access Journals (Sweden)

    Srinivasan

    2016-05-01

    Full Text Available BACKGROUND Craniofacial injury due to road traffic accidents, blunt trauma and other accidents leading to traumatic optic neuropathy were managed with high dose of steroids rather than wait and observation and surgical decompression of optic nerve or nerve sheath (in case of sheath hematoma. Motor vehicles and bikes are most frequent causes for traumatic optic neuropathy, accounting for 17%-63% of cases. Our study was conducted to assess the visual loss due to traumatic optic neuropathy in association with orbital bone and wall fracture due to various types of ocular injuries and the response to medical line of management by intravenous methylprednisolone was observed. MATERIALS AND METHODS The prospective cohort study conducted at Department of Ophthalmology, Government Vellore Medical College Hospital, Vellore. Total number of ocular injury cases included in this study were 200. The study period was from November 2014 to December 2015. The ocular injury patients reported as outpatients in eye department as well as referred patients from Trauma Ward. RESULTS In our study, the ocular injuries of age group between 21-40 years is (121/200 60.5%. All cases of traumatic optic neuropathy manifestation individuals fall in that age group with severe form of ocular injuries. But the visual recovery reported with intravenous methylprednisolone and oral prednisolone alone because of neuropraxia and surrounding oedema of tissues as well as incomplete fracture of orbital wall without extending into optic canal level and without impingement of bone chips to the optic nerve. With improvement of colour vision apart from visual acuity improvement, visual field changes disappeared with the treatment. In our study, instead of wait and observation management where there was danger for total loss of vision or surgical decompression which carried the risk of orbital apex structure and other intracranial structure damage, iatrogenic direct and indirect optic nerve

  18. Multiplex MALDI-TOF MS detection of mitochondrial variants in Brazilian patients with hereditary optic neuropathy

    Science.gov (United States)

    Matilde da Silva-Costa, Sueli; Balieiro, Juliane Cristina; Fernandes, Marcela Scabello Amaral; Alves, Rogério Marins; Guerra, Andrea Trevas Maciel; Marcondes, Ana Maria; Sartorato, Edi Lúcia

    2016-01-01

    Purpose Leber hereditary optic neuropathy (LHON) is a mitochondrial disease characterized by bilateral vision loss. More than 95% of LHON cases are associated with one of the three main mtDNA mutations: G11778A, T14484C, and G3460A. The other 5% of cases are due to other rare mutations related to the disease. The aim of this study was to identify the prevalence and spectrum of LHON mtDNA mutations, including the haplogroup, in a cohort of Brazilian patients with optic neuropathy and to evaluate the usefulness of iPLEX Gold/matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) technology in detecting LHON mutations. Methods We analyzed a total of 101 patients; 67 had a clinical diagnosis of LHON and 34 had optic neuropathy of unknown etiology. Direct sequencing and iPLEX Gold/MALDI-TOF MS were used to screen for the most common pathogenic point mutations in LHON, together with the rare mutations G3733A, C4171A, T10663C, G14459A, C14482G, A14495G, C14568T, and C14482A. Results We identified mutations in 36 patients, of whom 83.3% carried the G11778A mutation and 16.7% carried the T14484C mutation. In individuals with mutations, the haplogroups found were L1/L2, L3, C, R, U, D, and H. Rare mutations were not detected in any of the patients analyzed. Conclusions The frequencies of the main LHON mutations were similar to those previously reported for Latin America. A different frequency was found only for the A3460G mutation. The most frequent haplogroups identified were of African origin. The iPLEX Gold/MALDI-TOF MS technology proved to be highly accurate and efficient for screening mutations and identifying the haplogroups related to LHON. The MassArray platform, combined with other techniques, enabled definitive diagnosis of LHON in 36% (36/101) of the cases studied. PMID:27582625

  19. Diagnostic ability of barrett's index to detect dysthyroid optic neuropathy using multidetector computed tomography

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    Mário L. R. Monteiro

    2008-01-01

    Full Text Available OBJECTIVES: The objective of this study was to evaluate the ability of a muscular index (Barrett's Index, calculated with multidetector computed tomography, to detect dysthyroid optic neuropathy in patients with Graves' orbitopathy. METHODS: Thirty-six patients with Graves' orbitopathy were prospectively studied and submitted to neuro-ophthalmic evaluation and multidetector computed tomography scans of the orbits. Orbits were divided into two groups: those with and without dysthyroid optic neuropathy. Barrett's index was calculated as the percentage of the orbit occupied by muscles. Sensitivity and specificity were determined for several index values. RESULTS: Sixty-four orbits (19 with and 45 without dysthyroid optic neuropathy met the inclusion criteria for the study. The mean Barrett's index values (± SD were 64.47% ± 6.06% and 49.44% ± 10.94%in the groups with and without dysthyroid optic neuropathy, respectively (p60% should be carefully examined and followed for the development of dysthyroid optic neuropathy.

  20. A case of hereditary sensory autonomic neuropathy type IV

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    G P Prashanth

    2012-01-01

    Full Text Available Hereditary sensory autonomic neuropathy type IV (HSAN -IV, also known as congenital insensitivity to pain with anhidrosis, is a very rare condition that presents in infancy with anhidrosis, absence of pain sensation and self -mutilation. Developmental delay and mental retardation are usually present. Ultrastructural study of the peripheral nerves demonstrates loss of the unmyelinated and small myelinated fibers. We here report a 8 year -old boy with HSAN IV with typical clinical features where the diagnosis was supported by nerve biopsy findings. However, our case was unusual since mental development was normal.

  1. Hyperbaric oxygen in the treatment of radiation-induced optic neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Guy, J.; Schatz, N.J.

    1986-08-01

    Four patients with radiation-induced optic neuropathies were treated with hyperbaric oxygen. They had received radiation therapy for treatment of pituitary tumors, reticulum cell sarcoma, and meningioma. Two presented with amaurosis fugax before the onset of unilateral visual loss and began hyperbaria within 72 hours after development of unilateral optic neuropathy. Both had return of visual function to baseline levels. The others initiated treatment two to six weeks after visual loss occurred in the second eye and had no significant improvement of vision. Treatment consisted of daily administration of 100% oxygen under 2.8 atmospheres of pressure for 14-28 days. There were no medical complications of hyperbaria. While hyperbaric oxygen is effective in the treatment of radiation-induced optic neuropathy, it must be instituted within several days of deterioration in vision for restoration of baseline function.

  2. Raised intraocular pressure as a potential risk factor for visual loss in Leber Hereditary Optic Neuropathy.

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    Anais Thouin

    Full Text Available Leber Hereditary Optic Neuropathy (LHON is an important cause of inherited mitochondrial blindness among young adults. The majority of patients carry one of three mitochondrial DNA (mtDNA point mutations: m.3460G>A, m.11778G>A and m.14484T>C, all of which affect critical complex I subunits of the mitochondrial respiratory chain. LHON is characterised by marked incomplete penetrance, clearly implying that the mtDNA mutation is insufficient on its own to trigger retinal ganglion cell dysfunction and visual loss. In this case series of three affected patients harbouring the m.11778G>A mutation, we provide evidence suggesting that raised intraocular pressure could be a risk factor triggering visual loss in at-risk LHON carriers.

  3. Raised intraocular pressure as a potential risk factor for visual loss in Leber Hereditary Optic Neuropathy.

    Science.gov (United States)

    Thouin, Anais; Griffiths, Philip G; Hudson, Gavin; Chinnery, Patrick F; Yu-Wai-Man, Patrick

    2013-01-01

    Leber Hereditary Optic Neuropathy (LHON) is an important cause of inherited mitochondrial blindness among young adults. The majority of patients carry one of three mitochondrial DNA (mtDNA) point mutations: m.3460G>A, m.11778G>A and m.14484T>C, all of which affect critical complex I subunits of the mitochondrial respiratory chain. LHON is characterised by marked incomplete penetrance, clearly implying that the mtDNA mutation is insufficient on its own to trigger retinal ganglion cell dysfunction and visual loss. In this case series of three affected patients harbouring the m.11778G>A mutation, we provide evidence suggesting that raised intraocular pressure could be a risk factor triggering visual loss in at-risk LHON carriers.

  4. Clinical and electrophysiological recovery in Leber hereditary optic neuropathy with G3460A mutation.

    Science.gov (United States)

    Sharkawi, Eamon; Oleszczuk, Justyna D; Holder, Graham E; Raina, Joyti

    2012-08-01

    To report a case of clinical and electrophysiological recovery in Leber hereditary optic neuropathy (LHON) with G3460A Mutation. A 10-year-old boy with a three-month history of painless bilateral sequential visual loss upon presentation underwent visual acuity (diminished), anterior and posterior segment examination (normal), fluorescein angiography (normal), Goldman kinetic perimetry (bilateral central scotomata), genetic (a point G3460A mutation) and electrophysiological investigation (undetectable pattern visual evoked potentials (VEP); low amplitude, broadened and reduced flash VEPs and loss of the N95 component in the pattern electroretinograms). Diagnosis of LHON was made. Eighteen months later vision and electrophysiological tests results began spontaneously improving. Kinetic perimetry revealed reduced density and size of scotomata. Two years later, there had been further electrophysiological improvement. This report describes both clinical and electrophysiological improvement in LHON with G3460A mutation.

  5. “Peripheral Neuropathy Crippling Bronchial Asthma”: Two Rare Case Reports of Churg-Strauss Syndrome

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    Kamal Kishore Pandita

    2014-01-01

    Full Text Available Churg-Strauss syndrome (CSS is a rare cause of vasculitic neuropathy. Although rare and potentially fatal, Churg-Strauss syndrome (CSS is easily diagnosable and treatable. The presence of bronchial asthma with peripheral neuropathy in a patient alerts a physician to this diagnosis. This is vividly illustrated by the presented two cases who had neuropathy associated with bronchial asthma, eosinophilia, sinusitis, and positive perinuclear antineutrophil cytoplasmic antibodies (p-ANCA test, which improved with administration of steroids.

  6. Diagnosis and treatment characteristics of radioactive optic neuropathy

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    2014-06-01

    Full Text Available AIM: To explore the diagnosis and treatment methods of radioaction-induced optic neuritis(RIONthrough the clinical dates of 17 patients. METHODS: It was a retrospective case series study. From August 2008 to October 2013, 17 cases(24 eyesof Rion clinical dates from Chinese PLA General Hospital were studied. The diagnosis methods including visual acuity, pupil, fundus, visual field, fundus fluorescein angiography(FFA, visual electrophysiological testing, and head MRI. To analysis the clinical date of patients with diagnosis of RION by statistical description.RESULTS: The deterioration degree of vision: 13 eyes were classified as Ⅳ, 9 eyes as Ⅲ, 2 eyes as Ⅱ. Ten eyes RAPD(+, visual electrophysiology is extinguished. The retina of 5 eyes showed flame hemorrhages and cotton wool spots exudation. Optic nerve head edema in one eye. T1-weighted MRI enhanced in 19 eyes which showed optic nerve of the intracranial and intratubal segments abnormal changed, optic chiasm and pituitary stalk signal abnormalities and enhancement of the optic nerve. Tortuous optic nerves and rough edges were observed in 5 eyes. Treatment effect: 4 eyes of visual acuity improved, 1 eye from blindness to light perception,1 eye from 0.08 to 0.2, 1 eye from 0.4 to 0.6,1 eye from 0.04 to 0.15, the rest of the cases did not see any improvement.CONCLUSION: The unique clinical manifestation of RION can provide objective basis for clinical diagnosis in time, but there have not been proven any effective treatments.

  7. The metabolomic signature of Leber's hereditary optic neuropathy reveals endoplasmic reticulum stress.

    Science.gov (United States)

    Chao de la Barca, Juan Manuel; Simard, Gilles; Amati-Bonneau, Patrizia; Safiedeen, Zainab; Prunier-Mirebeau, Delphine; Chupin, Stéphanie; Gadras, Cédric; Tessier, Lydie; Gueguen, Naïg; Chevrollier, Arnaud; Desquiret-Dumas, Valérie; Ferré, Marc; Bris, Céline; Kouassi Nzoughet, Judith; Bocca, Cinzia; Leruez, Stéphanie; Verny, Christophe; Miléa, Dan; Bonneau, Dominique; Lenaers, Guy; Martinez, M Carmen; Procaccio, Vincent; Reynier, Pascal

    2016-09-15

    Leber's hereditary optic neuropathy (MIM#535000), the commonest mitochondrial DNA-related disease, is caused by mutations affecting mitochondrial complex I. The clinical expression of the disorder, usually occurring in young adults, is typically characterized by subacute, usually sequential, bilateral visual loss, resulting from the degeneration of retinal ganglion cells. As the precise action of mitochondrial DNA mutations on the overall cell metabolism in Leber's hereditary optic neuropathy is unknown, we investigated the metabolomic profile of the disease. High performance liquid chromatography coupled with tandem mass spectrometry was used to quantify 188 metabolites in fibroblasts from 16 patients with Leber's hereditary optic neuropathy and eight healthy control subjects. Latent variable-based statistical methods were used to identify discriminating metabolites. One hundred and twenty-four of the metabolites were considered to be accurately quantified. A supervised orthogonal partial least squares discriminant analysis model separating patients with Leber's hereditary optic neuropathy from control subjects showed good predictive capability (Q(2)cumulated = 0.57). Thirty-eight metabolites appeared to be the most significant variables, defining a Leber's hereditary optic neuropathy metabolic signature that revealed decreased concentrations of all proteinogenic amino acids, spermidine, putrescine, isovaleryl-carnitine, propionyl-carnitine and five sphingomyelin species, together with increased concentrations of 10 phosphatidylcholine species. This signature was not reproduced by the inhibition of complex I with rotenone or piericidin A in control fibroblasts. The importance of sphingomyelins and phosphatidylcholines in the Leber's hereditary optic neuropathy signature, together with the decreased amino acid pool, suggested an involvement of the endoplasmic reticulum. This was confirmed by the significantly increased phosphorylation of PERK and eIF2α, as well as

  8. Vision improvement in a Taiwanese (Han Chinese) family with Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Lin, Hong-Zin; Pang, Cheng-Yoong; Chen, Shee-Ping; Tsai, Rong-Kung

    2012-12-01

    In this report, we describe a Taiwanese (Han Chinese) family with Leber's hereditary optic neuropathy. The family carried a mitochondrial DNA mutation (mtDNA m.14484T>C) associated with spontaneous visual improvement. A 15-year-old boy from this family was diagnosed with Leber's hereditary optic neuropathy 6 months after losing his vision. His vision recovered after 8 months of supportive treatment. His mother, older brother, and two sisters also had the same mutation and had previously experienced vision loss. In this family, there was no male predominance.

  9. Choroidal thickness in Chinese patients with non-arteritic anterior ischemic optic neuropathy.

    Science.gov (United States)

    Jiang, Libin; Chen, Lanlan; Qiu, Xiujuan; Jiang, Ran; Wang, Yaxing; Xu, Liang; Lai, Timothy Y Y

    2016-08-31

    Non-arteritic anterior ischemic optic neuropathy (NA-AION) is one of the most common types of ischemic optic neuropathy. Several recent studies suggested that abnormalities of choroidal thickness might be associated with NA-AION. The main objective of this case-control study was to evaluate whether choroidal thickness is an ocular risk factor for the development of NA-AION by evaluating the peripapillary and subfoveal choroidal thicknesses in affected Chinese patients. Forty-four Chinese patients with unilateral NA-AION were recruited and compared with 60 eyes of 60 normal age and refractive-error matched control subjects. Peripapillary and subfoveal choroidal thicknesses were measured by enhanced depth imaging optical coherence tomography. Choroidal thicknesses of eyes with NA-AION and unaffected fellow eyes were compared with normal controls. Choroidal thicknesses of NA-AION eyes with or without optic disc edema were also compared. The correlation between choroidal thickness and retinal nerve fiber layer (RNFL) thickness, logMAR best-corrected visual acuity (BCVA), and the mean deviation (MD) of Humphrey static perimetry in NA-AION eyes were analyzed. The peripapillary choroidal thicknesses at the nasal, nasal inferior and temporal inferior segments in NA-AION eyes with optic disc edema were significantly thicker compared with that of normal subjects (P choroidal thicknesses between the unaffected fellow eyes of NA-AION patients and normal eyes of healthy controls; or between the NA-AION eyes with resolved optic disc edema and normal eyes (all P > 0.05). No significant correlation between choroidal thickness and RNFL thickness, logMAR BCVA and perimetry MD was found in eyes affected by NA-AION (all P > 0.05). Increase in peripapillary choroid thickness in some segments was found in NA-ION eyes with optic disc edema. However, our findings do not support the hypothesis that choroidal thickness is abnormal in Chinese patients with NA-AION compared with

  10. [Case of chronic progressive encephalo-myelo-radiculo-neuropathy].

    Science.gov (United States)

    Kutoku, Yumiko; Inoue, Ken; Murakami, Tatsufumi; Sunada, Yoshihide

    2010-05-01

    A 65-year-old man developed urinary impairment and gait disturbance over a period of four months. On admission, neurological examinations revealed paraplegia, decreased deep tendon reflexes in the extremities, bilateral positive Babinski and Chaddock signs, superficial and deep sensory disturbances and neurogenic bladder. Cerebrospinal fluid examination disclosed a total cell count of 70/mm3, and protein of 76 mg/dl. Nerve conduction studies and somatosensory evoked potential suggested demyelinating neuropathy and myelopathy. Brain MRI revealed irregular-shaped white matter lesions distributed over the bilateral cerebral hemispheres and the brain stem. In addition spinal MRI disclosed long spinal cord lesions disseminated from the higher cervical to the lower thoracic spine. A 1 microm-thick epon-embedded section and teased fiber preparations of a biopsied sural nerve showed segmental demyelination and remyelination. Treatments using intravenous methylprednisolone and IVIg were both effective. The positive responses to immunological treatment, along with the findings, strongly suggested that the demyelinating lesions occurred in both the central and peripheral nervous systems. We regarded this case as one of chronic progression of Encephalo-myelo-radiculo-neuropathy.

  11. Computer use and ulnar neuropathy: results from a case-referent study

    DEFF Research Database (Denmark)

    Andersen, JH; Frost, P.; Fuglsang-Frederiksen, A.

    2012-01-01

    neuropathy (OR=2.16, 95 % CI; 1.06-4.44).The two outcomes were not associated with daily hours of computer use. Findings suggested specific effects of pressure on the elbow, and might be an explanation for the overweight of left-sided outcomes in this primarily right-handed group. Preventive efforts would......We aimed to evaluate associations between vocational computer use and 1) ulnar neuropathy, and 2) ulnar neuropathy- like symptoms as distinguished by electroneurography. We identified all patients aged 18-65 years, examined at the Department of Neurophysiology on suspicion of ulnar neuropathy, 2001......-2007. We mailed a questionnaire to 546 patients with ulnar neuropathy, 633 patients with ulnar neuropathy-like symptoms, and three community referents per case, matched on sex, age, and primary care centre. From a Job Exposure Matrix we extracted estimates of daily hours of computer use. The analysis...

  12. Hypertrophic Neuropathy Secondary to Hansen's Disease. A Case Report

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    María Octavina Rodríguez Roque

    2016-08-01

    Full Text Available We present the case 49-year-old unmarried woman treated at the hospital of Cienfuegos. The patient complained of weakness in the lower limbs and "numbness" (paresthesia of all four extremities, which improved slightly after treatment. A year later, the muscle weakness and paresthesia worsened, particularly in the upper limbs. She also developed hypopigmented skin lesions on the chest and abdomen. The investigation was initiated due to suspicion of hypertrophic polyneuropathy. A biopsy of the hypochromic lesions was performed, which led to the conclusion that the patient suffered from a hypertrophic polyneuropathy secondary to tuberculoid Hansen's disease. We decided to present this case since a neuropathy is usually slow, insidious and has a long course in these patients; however, leprosy reactions can lead to acute nerve damage, resulting in disabilities and deformities. Consequently, it is important to act quickly in order to avoid them.

  13. Antivascular Endothelial Growth Factor Bevacizumab for Radiation Optic Neuropathy: Secondary to Plaque Radiotherapy

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    Finger, Paul T., E-mail: pfinger@eyecancer.com [New York Eye Cancer Center, New York, NY (United States); Chin, Kimberly J. [New York Eye Cancer Center, New York, NY (United States)

    2012-02-01

    Purpose: To evaluate the intravitreal antivascular endothelial growth factor, bevacizumab, for treatment of radiation optic neuropathy (RON). Methods and Materials: A prospective interventional clinical case series was performed of 14 patients with RON related to plaque radiotherapy for choroidal melanoma. The RON was characterized by optic disc edema, hemorrhages, microangiopathy, and neovascularization. The entry criteria included a subjective or objective loss of vision, coupled with findings of RON. The study subjects received a minimum of two initial injections of intravitreal bevacizumab (1.25 mg in 0.05 mL) every 6-8 weeks. The primary objectives included safety and tolerability. The secondary objectives included the efficacy as measured using the Early Treatment Diabetic Retinopathy Study chart for visual acuity, fundus photography, angiography, and optical coherence tomography/scanning laser ophthalmoscopy. Results: Reductions in optic disc hemorrhage and edema were noted in all patients. The visual acuity was stable or improved in 9 (64%) of the 14 patients. Of the 5 patients who had lost vision, 2 had relatively large posterior tumors, 1 had had the vision decrease because of intraocular hemorrhage, and 1 had developed optic atrophy. The fifth patient who lost vision was noncompliant. No treatment-related ocular or systemic side effects were observed. Conclusions: Intravitreal antivascular endothelial growth factor bevacizumab was tolerated and generally associated with improved vision, reduced papillary hemorrhage, and resolution of optic disc edema. Persistent optic disc neovascularization and fluorescein angiographic leakage were invariably noted. The results of the present study support additional evaluation of antivascular endothelial growth factor medications as treatment of RON.

  14. Diagnostic ability of Humphrey perimetry, Octopus perimetry, and optical coherence tomography for glaucomatous optic neuropathy.

    Science.gov (United States)

    Monsalve, B; Ferreras, A; Calvo, P; Urcola, J A; Figus, M; Monsalve, J; Frezzotti, P

    2016-11-11

    PurposeTo evaluate and compare the diagnostic accuracy of the Humphrey Field Analyzer (HFA), Octopus perimetry, and Cirrus OCT for glaucomatous optic neuropathy.MethodsEighty-eight healthy individuals and 150 open-angle glaucoma patients were consecutive and prospectively selected. Eligibility criteria for the glaucoma group were intraocular pressure ≥21 mm Hg and glaucomatous optic nerve head morphology. All subjects underwent a reliable standard automated perimetry with the HFA and Octopus perimeter, and were imaged with the Cirrus OCT. Receiver-operating characteristic (ROC) curves were plotted for the threshold values and main indices of the HFA and Octopus, the peripapillary retinal nerve fiber layer thicknesses, and the optic nerve head parameters. Sensitivities at 85 and 95% fixed-specificities were also calculated. The best areas under the ROC curves (AUCs) were compared using the DeLong method.ResultsIn the glaucoma group, mean deviation (MD) was -5.42±4.6 dB for HFA and 3.90±3.6 dB for Octopus. The MD of the HFA (0.966; P<0.001), mean sensitivity of the Octopus (0.941; P<0.001), and average cup-to-disc (C/D) ratio measured by the Cirrus OCT (0.958; P<0.001) had the largest AUCs for each test studied. There were no significant differences among them. Sensitivities at 95% fixed-specificity were 82% for pattern standard deviation of the HFA, 81.3% for average C/D ratio of OCT, and 80% for the MD of the Octopus.ConclusionsHFA, Octopus, and Cirrus OCT demonstrated similar diagnostic accuracies for glaucomatous optic neuropathy. Visual field and OCT provide supplementary information and thus these tests are not interchangeable.Eye advance online publication, 11 November 2016; doi:10.1038/eye.2016.251.

  15. Bilateral simultaneous anterior ischemic optic neuropathy, an extrahepatic manifestation of hepatitis C cured with direct acting antivirals

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    Prud’homme, Sylvie

    2016-04-01

    Full Text Available We report a patient with a bilateral optic anterior ischemic neuropathy as an extrahepatic complication of a chronic hepatitis C (HCV infection. The patient presented with a bilateral visual acuity loss and bilateral optic disc oedema. The optic neuropathy was associated with a sudden increase in the viral HCV load after a recent liver transplantation. The stop of the calcineurin inhibitor had no effect on the course of the optic neuropathy. Visual improvement and normalization of HCV viraemia occurred after treatment with sofosbuvir and daclatasvir, which are direct acting antivirals.

  16. Is there alteration in aortic stiffness in Leber hereditary optic neuropathy?

    NARCIS (Netherlands)

    Nemes, A.; Coo, I.F.M. de; Spruijt, L.; Smeets, H.J.; Chinnery, P.F.; Soliman, O.I.; Geleijnse, M.L.; Cate, FJ Ten

    2008-01-01

    PURPOSE: Leber hereditary optic neuropathy (LHON) is recognized as the most common cause of isolated blindness in young men. The current study was designed to test whether LHON as a mitochondrial disease is associated with vascular functional alterations characterized by aortic elastic properties

  17. Clinical expression of Leber hereditary optic neuropathy is affected by the mitochondrial DNA-haplogroup background.

    NARCIS (Netherlands)

    Hudson, G.; Carelli, V.; Spruijt, L.; Gerards, M.; Mowbray, C.; Achilli, A.; Pyle, A.; Elson, J.; Howell, N.; Morgia, C. La; Valentino, M.L.; Huoponen, K.; Savontaus, M.L.; Nikoskelainen, E.; Sadun, A.A.; Salomao, S.R.; Belfort Jr, R.; Griffiths, P.; Man, P.Y.; Coo, R.F. de; Horvath, R.; Zeviani, M.; Smeets, H.J.M.; Torroni, A.; Chinnery, P.F.

    2007-01-01

    Leber hereditary optic neuropathy (LHON) is due primarily to one of three common point mutations of mitochondrial DNA (mtDNA), but the incomplete penetrance implicates additional genetic or environmental factors in the pathophysiology of the disorder. Both the 11778G-->A and 14484T-->C LHON mutation

  18. Patients with Leber hereditary optic neuropathy fail to compensate impaired oxidative phosphorylation.

    NARCIS (Netherlands)

    Korsten, A.; Coo, I.F.M. de; Spruijt, L.; Wit, L.E. de; Smeets, H.J.M.; Sluiter, W.

    2010-01-01

    Ninety-five percent of Leber hereditary optic neuropathy (LHON) patients carry a mutation in one out of three mtDNA-encoded ND subunits of complex I. Penetrance is reduced and more male than female carriers are affected. To assess if a consistent biochemical phenotype is associated with LHON express

  19. LEBERS HEREDITARY OPTIC NEUROPATHY - CORRELATIONS BETWEEN MITOCHONDRIAL GENOTYPE AND VISUAL OUTCOME

    NARCIS (Netherlands)

    OOSTRA, RJ; BOLHUIS, PA; WIJBURG, FA; ZORNENDE, G; BLEEKERWAGEMAKERS, EM

    1994-01-01

    Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease associated with mitochondrial DNA (mtDNA) mutations. We describe the distribution of seven different mtDNA mutations and the clinical findings in 334 LHON patients belonging to 29 families. Mutations described only in LHON

  20. Is there alteration in aortic stiffness in Leber hereditary optic neuropathy?

    NARCIS (Netherlands)

    Nemes, A.; Coo, I.F.M. de; Spruijt, L.; Smeets, H.J.; Chinnery, P.F.; Soliman, O.I.; Geleijnse, M.L.; Cate, FJ Ten

    2008-01-01

    PURPOSE: Leber hereditary optic neuropathy (LHON) is recognized as the most common cause of isolated blindness in young men. The current study was designed to test whether LHON as a mitochondrial disease is associated with vascular functional alterations characterized by aortic elastic properties du

  1. Resistance to the most common optic neuropathy is associated with systemic mitochondrial efficiency.

    Science.gov (United States)

    Lascaratos, Gerassimos; Chau, Kai-Yin; Zhu, Haogang; Gkotsi, Despoina; King, Rosalind; Gout, Ivan; Kamal, Deborah; Luthert, Philip J; Schapira, Anthony H V; Garway-Heath, David F

    2015-10-01

    Glaucomatous optic neuropathy, an important neurodegenerative condition and the commonest optic neuropathy in humans, is the leading cause of irreversible blindness worldwide. Its prevalence and incidence increase exponentially with ageing and raised intraocular pressure (IOP). Using glaucomatous optic neuropathy as an exemplar for neurodegeneration, this study investigates putative factors imparting resistance to neurodegeneration. Systemic mitochondrial function, oxidative stress and vascular parameters were compared from isolated lymphocytes, whole blood and urine samples between 30 patients who have not developed the neuropathy despite being exposed for many years to very high IOP ('resistant'), 30 fast deteriorating glaucoma patients despite having low IOP ('susceptible'), and 30 age-similar controls. We found that 'resistant' individuals showed significantly higher rates of ADP phosphorylation by mitochondrial respiratory complexes I, II and IV, hyperpolarised mitochondrial membrane potential, higher levels of mitochondrial DNA, and enhanced capacity to deal with cytosolic calcium overload and exogenous oxidative stress, as compared to both controls and glaucoma patients. While it has been known for some years that mitochondrial dysfunction is implicated in neurodegeneration, this study provides a fresh perspective to the field of neurodegeneration by providing, for the first time, evidence that systemic mitochondrial efficiency above normal healthy levels is associated with an enhanced ability to withstand optic nerve injury. These results demonstrate the importance of cellular bioenergetics in glaucomatous disease progression, with potential relevance for other neurodegenerative disorders, and raise the possibility for new therapeutic targets in the field of neurodegeneration.

  2. Ethambutol-induced optical neuropathy : risk of overdosing in obese subjects

    NARCIS (Netherlands)

    Hasenbosch, R. E.; Alffenaar, J. W. C.; Koopmans, S. A.; Kosterink, J. G. W.; van der Werf, T. S.; van Altena, R.

    BACKGROUND: Ethambutol (EMB) is one of the first-line drugs in the treatment against tuberculosis (TB). Side-effects are infrequent, but its main adverse effect, optical neuropathy, has long been recognised. The mechanisms of action and predisposing factors have not yet been fully understood.

  3. Influence of mutation type on clinical expression of Leber hereditary optic neuropathy.

    NARCIS (Netherlands)

    Spruijt, L.; Kolbach, D.; Coo, R.F. de; Plomp, A.S.; Bauer, N.J.; Smeets, H.J.M.; Die-Smulders, C.E.M. de

    2006-01-01

    PURPOSE: The aim of this research was to determine the molecular factors of influence on the clinical expression of Leber hereditary optic neuropathy (LHON), which might aid in counseling LHON patients and families. The prevalence of LHON in the Dutch population was determined. DESIGN: Observational

  4. Lack of radiation optic neuropathy in 72 patients treated for pituitary adenoma

    NARCIS (Netherlands)

    van den Bergh, ACM; Dullaart, RPF; van der Vliet, AM; Szabo, BG; ter Weeme, CA; Pott, JWR

    The incidence of radiation optic neuropathy (RON) after external photon beam radiation therapy for nonfunctioning pituitary adenoma (NFA) is not well-studied. Retrospective review of ophthalmological and imaging data in 72 patients with NFA treated between 1985 and 1998 with external beam radiation

  5. Vinca alkaloids induced peripheral neuropathy- case series and review of literature

    Directory of Open Access Journals (Sweden)

    Abdul Hameed

    2016-04-01

    Full Text Available Vinca alkaloids include vincristine, vinblastine and vinorelbine. Peripheral neuropathy is one of the commonest side effects of these agents. Patients with decrease level of serum folate and vitamin B 12 are more prone to develop peripheral neuropathy. Underlying hepatic impairment and concurrent drugs which decreases Vinca alkaloids hepatic metabolism also increases the susceptibility to neuropathy. Peripheral neuropathy can be troublesome for significant number of patients. There is no specific therapy for this complication however; symptoms improve with the use of pyridoxine, pregabalin and NSAIDs in some cases.  Aim of this case study was to review the characteristics and outcomes of patients who suffered from peripheral neuropathy due to vincristine or vinblastine.

  6. Topiramate and visual loss in a patient carrying a Leber hereditary optic neuropathy mutation.

    Science.gov (United States)

    Rinalduzzi, Steno; Cipriani, Anna Maria; Accornero, Neri

    2012-04-01

    We describe a 43-year-old patient who experienced visual loss 4 years after beginning antiepileptic therapy with topiramate. Ophthalmological and neurological examinations led to a preliminary diagnosis of bilateral toxic optic neuritis. Mitochondrial genome sequence analysis detected a Leber hereditary optic neuropathy 11778G>A mutation. The possibility that topiramate might favor a conversion disease, alerts physicians to seek a history of blindness in patients undergoing chronic antiepileptic therapy.

  7. Nonarteritic Anterior Ischemic Optic Neuropathy and Double Thrombophilic Defect: A New Observation

    Directory of Open Access Journals (Sweden)

    Eleni Papageorgiou

    2012-02-01

    Full Text Available We report the first case of nonarteritic anterior ischemic neuropathy (NAION associated with double thrombophilia: protein S deficiency and prothrombin G20210A mutation. A 58-year-old man is presented including the clinical and laboratory findings, cardiovascular profile and thrombophilia screening. The patient presented with 3/10 vision and an inferior altitudinal defect in the right eye. Funduscopic examination of the right eye revealed a hyperemic optic disk with blurred superior optic disk border and sectoral nerve fiber layer edema. Complete blood count, erythrocyte sedimentation rate and C-reactive protein were normal, suggesting a NAION. A workup of cardiovascular risk factors revealed hyperlipidemia, arterial hypertension and high-risk asymptomatic coronary artery disease. Due to the family history of deep vein thrombosis in the patient’s daughter, a thrombophilia screening was additionally performed. The results revealed a double thrombophilic defect, namely congenital protein S deficiency and heterozygosity for prothrombin G20210A mutation, which were also identified in the patient’s daughter. Anticoagulant warfarin therapy was initiated and the patient underwent a triple bypass surgery. At three-month follow-up, the right optic disk edema had resolved, leaving a pale superior optic nerve head. Visual acuity in the right eye had slightly improved to 4/10; however, the dense inferior altitudinal field defect had remained unchanged. The patient is currently treated with warfarin, atorvastatin, irbesartan and metoprolol. This case suggests that the first line of investigation in all patients with NAION involves assessment of cardiovascular risk factors. However, careful history taking will identify NAION patients who are eligible for additional thrombophilia screening: young patients without vasculopathic risk factors, bilateral or recurrent NAION, idiopathic or recurrent venous thromboembolism (VTE, positive family history of VTE

  8. Nonarteritic anterior ischemic optic neuropathy and double thrombophilic defect: a new observation.

    Science.gov (United States)

    Papageorgiou, Eleni; Karamagkiolis, Spyridon; Dimera, Vasiliki

    2012-01-01

    WE REPORT THE FIRST CASE OF NONARTERITIC ANTERIOR ISCHEMIC NEUROPATHY (NAION) ASSOCIATED WITH DOUBLE THROMBOPHILIA: protein S deficiency and prothrombin G20210A mutation. A 58-year-old man is presented including the clinical and laboratory findings, cardiovascular profile and thrombophilia screening. The patient presented with 3/10 vision and an inferior altitudinal defect in the right eye. Funduscopic examination of the right eye revealed a hyperemic optic disk with blurred superior optic disk border and sectoral nerve fiber layer edema. Complete blood count, erythrocyte sedimentation rate and C-reactive protein were normal, suggesting a NAION. A workup of cardiovascular risk factors revealed hyperlipidemia, arterial hypertension and high-risk asymptomatic coronary artery disease. Due to the family history of deep vein thrombosis in the patient's daughter, a thrombophilia screening was additionally performed. The results revealed a double thrombophilic defect, namely congenital protein S deficiency and heterozygosity for prothrombin G20210A mutation, which were also identified in the patient's daughter. Anticoagulant warfarin therapy was initiated and the patient underwent a triple bypass surgery. At three-month follow-up, the right optic disk edema had resolved, leaving a pale superior optic nerve head. Visual acuity in the right eye had slightly improved to 4/10; however, the dense inferior altitudinal field defect had remained unchanged. The patient is currently treated with warfarin, atorvastatin, irbesartan and metoprolol. This case suggests that the first line of investigation in all patients with NAION involves assessment of cardiovascular risk factors. However, careful history taking will identify NAION patients who are eligible for additional thrombophilia screening: young patients without vasculopathic risk factors, bilateral or recurrent NAION, idiopathic or recurrent venous thromboembolism (VTE), positive family history of VTE, and VTE in young age or

  9. Safety and Effects of the Vector for the Leber Hereditary Optic Neuropathy Gene Therapy Clinical Trial

    Science.gov (United States)

    Koilkonda, Rajeshwari D.; Yu, Hong; Chou, Tsung-Han; Feuer, William J.; Ruggeri, Marco; Porciatti, Vittorio; Tse, David; Hauswirth, William W.; Chiodo, Vince; Boye, Sanford L.; Lewin, Alfred S.; Neuringer, Martha; Renner, Lauren; Guy, John

    2014-01-01

    IMPORTANCE We developed a novel strategy for treatment of Leber hereditary optic neuropathy (LHON) caused by a mutation in the nicotinamide adenine dinucleotide dehydrogenase subunit IV (ND4) mitochondrial gene. OBJECTIVE To demonstrate the safety and effects of the gene therapy vector to be used in a proposed gene therapy clinical trial. DESIGN AND SETTING In a series of laboratory experiments, we modified the mitochondrial ND4 subunit of complex I in the nuclear genetic code for import into mitochondria. The protein was targeted into the organelle by agency of a targeting sequence (allotopic expression). The gene was packaged into adeno-associated viral vectors and then vitreally injected into rodent, nonhuman primate, and ex vivo human eyes that underwent testing for expression and integration by immunohistochemical analysis and blue native polyacrylamide gel electrophoresis. During serial follow-up, the animal eyes underwent fundus photography, optical coherence tomography, and multifocal or pattern electroretinography. We tested for rescue of visual loss in rodent eyes also injected with a mutant G11778A ND4 homologue responsible for most cases of LHON. EXPOSURE Ocular infection with recombinant adeno-associated viral vectors containing a wild-type allotopic human ND4 gene. MAIN OUTCOMES AND MEASURES Expression of human ND4 and rescue of optic neuropathy induced by mutant human ND4. RESULTS We found human ND4 expressed in almost all mouse retinal ganglion cells by 1 week after injection and ND4 integrated into the mouse complex I. In rodent eyes also injected with a mutant allotopic ND4, wild-type allotopic ND4 prevented defective adenosine triphosphate synthesis, suppressed visual loss, reduced apoptosis of retinal ganglion cells, and prevented demise of axons in the optic nerve. Injection of ND4 in the ex vivo human eye resulted in expression in most retinal ganglion cells. Primates undergoing vitreal injection with the ND4 test article and followed up for 3

  10. Safety and effects of the vector for the Leber hereditary optic neuropathy gene therapy clinical trial.

    Science.gov (United States)

    Koilkonda, Rajeshwari D; Yu, Hong; Chou, Tsung-Han; Feuer, William J; Ruggeri, Marco; Porciatti, Vittorio; Tse, David; Hauswirth, William W; Chiodo, Vince; Boye, Sanford L; Lewin, Alfred S; Neuringer, Martha; Renner, Lauren; Guy, John

    2014-04-01

    IMPORTANCE We developed a novel strategy for treatment of Leber hereditary optic neuropathy (LHON) caused by a mutation in the nicotinamide adenine dinucleotide dehydrogenase subunit IV (ND4) mitochondrial gene. OBJECTIVE To demonstrate the safety and effects of the gene therapy vector to be used in a proposed gene therapy clinical trial. DESIGN AND SETTING In a series of laboratory experiments, we modified the mitochondrial ND4 subunit of complex I in the nuclear genetic code for import into mitochondria. The protein was targeted into the organelle by agency of a targeting sequence (allotopic expression). The gene was packaged into adeno-associated viral vectors and then vitreally injected into rodent, nonhuman primate, and ex vivo human eyes that underwent testing for expression and integration by immunohistochemical analysis and blue native polyacrylamide gel electrophoresis. During serial follow-up, the animal eyes underwent fundus photography, optical coherence tomography, and multifocal or pattern electroretinography. We tested for rescue of visual loss in rodent eyes also injected with a mutant G11778A ND4 homologue responsible for most cases of LHON. EXPOSURE Ocular infection with recombinant adeno-associated viral vectors containing a wild-type allotopic human ND4 gene. MAIN OUTCOMES AND MEASURES Expression of human ND4 and rescue of optic neuropathy induced by mutant human ND4. RESULTS We found human ND4 expressed in almost all mouse retinal ganglion cells by 1 week after injection and ND4 integrated into the mouse complex I. In rodent eyes also injected with a mutant allotopic ND4, wild-type allotopic ND4 prevented defective adenosine triphosphate synthesis, suppressed visual loss, reduced apoptosis of retinal ganglion cells, and prevented demise of axons in the optic nerve. Injection of ND4 in the ex vivo human eye resulted in expression in most retinal ganglion cells. Primates undergoing vitreal injection with the ND4 test article and followed up for 3

  11. The diagnostic and prognostic value of neurofilament heavy chain levels in immune-mediated optic neuropathies.

    Science.gov (United States)

    Petzold, Axel; Plant, Gordon T

    2012-01-01

    Background. Loss of visual function differs between immune-mediated optic neuropathies and is related to axonal loss in the optic nerve. This study investigated the diagnostic and prognostic value of a biomarker for neurodegeneration, the neurofilament heavy chain (NfH) in three immune-mediated optic neuropathies. Methods. A prospective, longitudinal study including patients with optic neuritis due to multiple sclerosis (MSON, n = 20), chronic relapsing inflammatory optic neuritis (CRION, n = 19), neuromyelitis optica (NMO, n = 9), and healthy controls (n = 28). Serum NfH-SMI35 levels were quantified by ELISA. Findings. Serum NfH-SMI35 levels were highest in patients with NMO (mean 0.79 ± 1.51 ng/mL) compared to patients with CRION (0.13 ± 0.16 ng/mL, P = 0.007), MSON (0.09 ± 0.09, P = 0.008), and healthy controls (0.01 ± 0.02 ng/mL, P = 0.001). High serum NfH-SMI35 levels were related to poor visual outcome. Conclusions. Blood NfH-SMI35 levels are of moderate diagnostic and more important prognostic value in immune-mediated optic neuropathies. We speculate that longitudinal blood NfH levels may help to identify particular disabling events in relapsing conditions.

  12. The Diagnostic and Prognostic Value of Neurofilament Heavy Chain Levels in Immune-Mediated Optic Neuropathies

    Directory of Open Access Journals (Sweden)

    Axel Petzold

    2012-01-01

    Full Text Available Background. Loss of visual function differs between immune-mediated optic neuropathies and is related to axonal loss in the optic nerve. This study investigated the diagnostic and prognostic value of a biomarker for neurodegeneration, the neurofilament heavy chain (NfH in three immune-mediated optic neuropathies. Methods. A prospective, longitudinal study including patients with optic neuritis due to multiple sclerosis (MSON, n=20, chronic relapsing inflammatory optic neuritis (CRION, n=19, neuromyelitis optica (NMO, n=9, and healthy controls (n=28. Serum NfH-SMI35 levels were quantified by ELISA. Findings. Serum NfH-SMI35 levels were highest in patients with NMO (mean 0.79±1.51 ng/mL compared to patients with CRION (0.13±0.16 ng/mL, P=0.007, MSON (0.09±0.09, P=0.008, and healthy controls (0.01±0.02 ng/mL, P=0.001. High serum NfH-SMI35 levels were related to poor visual outcome. Conclusions. Blood NfH-SMI35 levels are of moderate diagnostic and more important prognostic value in immune-mediated optic neuropathies. We speculate that longitudinal blood NfH levels may help to identify particular disabling events in relapsing conditions.

  13. Orbital apex cyst: a rare cause of compressive optic neuropathy post-functional endoscopic sinus surgery

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    Koh YN

    2017-07-01

    Full Text Available Yi Ni Koh,1,2 Shu Fen Ho,2 Letchumanan Pathma,3 Harvinder Singh,3 Embong Zunaina1 1Department of Ophthalmology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia; 2Department of Ophthalmology, 3Department of Otorhinolaryngology, Hospital Raja Permaisuri Bainun, Ipoh, Perak, Malaysia Abstract: There are various causes that can lead to compressive optic neuropathy. We present here orbital apex cyst as an unusual cause of compressive optic neuropathy in a 49-year-old male. He presented with 2 weeks painless loss of vision in the left eye with left-sided headache. He had had left functional endoscopic sinus surgery for left nasal polyps 4 years earlier. Magnetic resonance imaging of brain and orbit revealed a left discrete orbital nodule, possibly orbital cyst or mucocele, which was compressing on the left optic nerve. Left eye vision improved markedly from hand movement to 6/36 pinhole 6/18 after initiation of intravenous dexamethasone. A subsequent endoscopic endonasal left optic nerve decompression found the orbital nodule lesion to be an orbital cyst. Marsupialization was performed instead of excision, as the cyst ruptured intraoperatively. Postoperative vision improved to 6/7.5 with normal optic nerve function postoperatively. Possible cause of orbital apex cyst is discussed. Keywords: orbital cyst, compressive optic neuropathy, functional endoscopic sinus surgery

  14. Pupillometric evaluation of the melanopsin containing retinal ganglion cells in mitochondrial and non-mitochondrial optic neuropathies.

    Science.gov (United States)

    Ba-Ali, Shakoor; Lund-Andersen, Henrik

    2017-07-14

    In recent years, chromatic pupillometry is used in humans to evaluate the activity of melanopsin expressing intrinsic photosensitive retinal ganglion cells (ipRGCs). Blue light is used to stimulate the ipRGCs and red light activates the rod/cone photoreceptors. The late re-dilation phase of pupillary light reflex is primarily driven by the ipRGCs. Optic neuropathies i.e. Leber hereditary optic neuropathy (LHON), autosomal dominant optic atrophy (ADOA), nonarteritic anterior ischemic optic neuropathy (NAION), glaucoma, optic neuritis and idiopathic intracranial hypertension (IIH) are among the diseases, which have been subject to pupillometric studies. The ipRGCs are differentially affected in these various optic neuropathies. In mitochondrial optic neuropathies, the ipRGCs are protected against degeneration, whereas in glaucoma, NAION, optic neuritis and IIH the ipRGCs are damaged. Here, we will review the results of pupillometric, histopathological and animal studies evaluating the ipRGCs in mitochondrial and non-mitochondrial optic neuropathies. Copyright © 2017 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  15. Acute ulnar neuropathy at the wrist: a case report and review of the literature.

    Science.gov (United States)

    Erkin, Gülten; Uysal, Hilmi; Keleş, Işik; Aybay, Canan; Ozel, Sumru

    2006-12-01

    Acute ulnar neuropathy at the wrist is an extremely uncommon condition, at times requiring a high index of suspicion for the diagnosis. Clinical presentations of ulnar nerve lesions at the wrist and hand show variations due to the complex anatomic course of the nerve in distal sites. We report a case of acute ulnar neuropathy at the wrist caused by a ganglion in Guyon's canal, being initially misinterpreted as flexor tenosynovitis. The accurate diagnosis of selective distal motor neuropathy of ulnar nerve was made electrophysiologically. Magnetic resonance imaging revealed a well defined soft tissue mass consistent with a ganglion, compressing the ulnar nerve in Guyon's canal. Entrapment neuropathies are one of the common conditions handled by physiatrists. Ulnar nerve lesions at the wrist should be kept in mind in the differential diagnosis of patients with wrist or hand pain. Magnetic resonance imaging is a useful method in the anatomical evaluation of acute focal neuropathies.

  16. Leber′s hereditary optic neuropathy with molecular characterization in two Indian families

    Directory of Open Access Journals (Sweden)

    Verma I

    2005-01-01

    Full Text Available PURPOSE: Leber′s hereditary optic neuropathy (LHON presents in early adulthood with painless progressive blindness of one or both eyes. Usually there is a positive family history of similar disease on the maternal side. Definitive diagnosis can be established by finding the change in the mitochondrial gene. No molecular studies have been reported from India. MATERIAL AND METHODS: Clinical, ophthalmologic and molecular studies were carried out in two patients from different families and available first degree relatives. The subjects were tested for the three common mutations seen in LHON by molecular techniques of polymerase chain reaction using mutation specific primers. RESULTS: The mutations G3460A and G11778A in the mitochondrial genes MTND1 and MTND4, known to be causative for LHON, were found in one family each. CONCLUSION: Diagnosis of LHON should be considered in familial cases and in young adults with optic atrophy. Confirmation of diagnosis should be sought by molecular gene analysis. Genetic counselling should be offered to all ′at risk′ relatives of a patient harbouring the mutation.

  17. Leber's Hereditary Optic Neuropathy-Gene Therapy: From Benchtop to Bedside

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    Rajeshwari D. Koilkonda

    2011-01-01

    Full Text Available Leber's hereditary optic neuropathy (LHON is a maternally transmitted disorder caused by point mutations in mitochondrial DNA (mtDNA. Most cases are due to mutations in genes encoding subunits of the NADH-ubiquinone oxidoreductase that is Complex I of the electron transport chain (ETC. These mutations are located at nucleotide positions 3460, 11778, or 14484 in the mitochondrial genome. The disease is characterized by apoplectic, bilateral, and severe visual loss. While the mutated mtDNA impairs generation of ATP by all mitochondria, there is only a selective loss of retinal ganglion cells and degeneration of optic nerve axons. Thus, blindness is typically permanent. Half of the men and 10% of females who harbor the pathogenic mtDNA mutation actually develop the phenotype. This incomplete penetrance and gender bias is not fully understood. Additional mitochondrial and/or nuclear genetic factors may modulate the phenotypic expression of LHON. In a population-based study, the mtDNA background of haplogroup J was associated with an inverse relationship of low-ATP generation and increased production of reactive oxygen species (ROS. Effective therapy for LHON has been elusive. In this paper, we describe the findings of pertinent published studies and discuss the controversies of potential strategies to ameliorate the disease.

  18. VISUAL OUTCOME OF TRAUMATIC OPTIC NEUROPATHY IN PATIENTS TREATED WITH INTRAVENOUS MEGADOSE OF STEROIDS

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    A. Sadeghi-Tari

    2005-05-01

    Full Text Available Although uncommon, traumatic optic neuropathy (TON is an important cause of visual loss. Different therapeutic approaches including different dosages of steroids, surgical decompression of optic canal and observation alone have been suggested but there has been no conclusive evidence to establish a standard approach to this devastating cause of visual loss. To determine the effectiveness of intravenous (IV steroids in the treatment of these patients, the medical records of patients with TON, including one bilateral case, treated with IV steroids were reviewed. Twenty-eight patients (22 males, 6 females with mean age of 24.1 (11 to 41 years were enrolled. All patients had received 30 mg/kg loading dose of methylprednisolone succinate followed by 5.4 mg/kg/ hour for 48 hours. Visual acuity (VA was improved by ≥ 1 line in 8 eyes (28.6% immediately after treatment and in 10 eyes (37% after 3 months; however, most of them (6 and 8, respectively were in the range of initial VA of no light perception to hand motion. After adjustment for the baseline VA, these improvements in visual acuities were not considered significant. Neither different orbital fractures, nor various extraocular muscle palsies had any significant effect on the prognosis of ultimate VA. Regarding the natural course of TON, this investigation showed that IV megadose steroids had no clear benefit on the visual outcome of patients with TON.

  19. The Correlation between Subjective and Objective Visual Function Test in Optic Neuropathy Patients

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    Ungsoo Kim

    2012-10-01

    Full Text Available Purpose: To investigate the correlation between visual acuity and quantitative measurements of visual evoked potentials (VEP, optical coherence tomography (OCT, and visual field test (VF in optic neuropathy patients. Methods: We evaluated 28 patients with optic neuropathy. Patients who had pale disc, visual acuity of less than 0.5 and abnormal visual field defect were included. At the first visit, we performed visual acuity and VF as subjective methods and OCT and VEP as objective methods. In the spectral domain OCT, rim volume, average and temporal quadrant retinal nerve fiber layer (RNFL thickness were measured. And pattern VEP (N75, P100, N135 latency, and P100 amplitude and Humphrey 24-2 visual field test (mean deviation and pattern standard deviation were obtained. Using Spearman's correlation coefficient, the correlation between visual acuity and various techniques were assessed. Results: Visual acuity was most correlated with the mean deviation of Humphrey perimetry.

  20. Morphological functional criteria of neuroprotective therapy efficacy in glaucomatous optic neuropathy

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    Tszin Dan

    2015-01-01

    Full Text Available Electrophysiological tests may be used to detect early glaucomatous changes and glaucoma progression risk and to monitor treatment efficacy. Most important pathogenic aspects of glaucomatous process, pathogenesis and multifactorial nature of glaucomatous optic neuropathy are described. Major triggers of glaucomatous optic neuropathy are mechanical and vascular. Principles of neuroprotective therapy, neuroprotective drugs, and mechanisms of action of direct and indirect neuroprotective agents are presented. IOPcc is a basis for neuroprotective therapy selection and its efficacy monitoring. Amongst neuroprotective drugs, NMDA agonists, antioxidants, peptides, and calcium channel blockers are of special importance. Structural damage and functional deficiency (e.g., visual field loss in glaucoma and the most informative and accurate methods of their detection are characterized. Confocal laser microscopy, optical coherence tomography, and scanning laser polarimetry are compared. These techniques are used to study optic nerve head and retinal nerve fiber layer. They are proposed as diagnostic and monitoring tools for glaucoma, glaucoma suspicion, and ocular hypertension. The most sensitive and specific electrophysiological tests for glaucomatous optic neuropathy are pattern electroretinography, multfocal electroretinography, and multifocal visually evoked potentials. 

  1. A Female Patient with Down Syndrome and Low-Penetrance Leber's Hereditary Optic Neuropathy.

    Science.gov (United States)

    Frousiakis, Starleen E; Pouw, Andrew E; Karanjia, Rustum; Sadun, Alfredo A

    2014-09-01

    We present the case of a 19-year-old female with a history of Down syndrome (DS) who was referred to our neuro-ophthalmology clinic for evaluation of Leber's hereditary optic neuropathy (LHON). The patient's family history was significant for a known G11778A mutation in a maternal relative, consistent with LHON. The patient was also positive for the G11778A mutation; however, the genotype demonstrated low penetrance in the pedigree, with only 1 out of 10 adult male offspring showing signs or symptoms of the disease. Mitochondrial mutations implicated in LHON have been shown to impair complex I of the electron transport chain and thereby reducing the effective generation of adenosine triphosphate and increasing the production of toxic reactive oxygen species. Although the partial or complete triplicate of chromosome 21 constitutes the etiology of DS, some of the pleiotropic phenotypes of the syndrome have been attributed to oxidative stress and mitochondrial dysfunction. Given the low penetrance of the mutation and the patient's sex, this case illustrates the possibility that the mitochondrial mutation demonstrated increased penetrance due to pre-existing mitochondrial dysfunction related to DS.

  2. A Female Patient with Down Syndrome and Low-Penetrance Leber's Hereditary Optic Neuropathy

    Directory of Open Access Journals (Sweden)

    Starleen E. Frousiakis

    2014-11-01

    Full Text Available We present the case of a 19-year-old female with a history of Down syndrome (DS who was referred to our neuro-ophthalmology clinic for evaluation of Leber's hereditary optic neuropathy (LHON. The patient's family history was significant for a known G11778A mutation in a maternal relative, consistent with LHON. The patient was also positive for the G11778A mutation; however, the genotype demonstrated low penetrance in the pedigree, with only 1 out of 10 adult male offspring showing signs or symptoms of the disease. Mitochondrial mutations implicated in LHON have been shown to impair complex I of the electron transport chain and thereby reducing the effective generation of adenosine triphosphate and increasing the production of toxic reactive oxygen species. Although the partial or complete triplicate of chromosome 21 constitutes the etiology of DS, some of the pleiotropic phenotypes of the syndrome have been attributed to oxidative stress and mitochondrial dysfunction. Given the low penetrance of the mutation and the patient's sex, this case illustrates the possibility that the mitochondrial mutation demonstrated increased penetrance due to pre-existing mitochondrial dysfunction related to DS.

  3. A case report of congenital sensory neuropathy with anhidrosis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Won Hyong; Chang, Hae Soon; Han, Man Chung; Lee, Suck Hyun; Lee, Duk Yong [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1974-10-15

    Congenital sensory neuropathy with anhidrosis is rare disease and may be confused with other cause of pain insensitivity or indifference. Other cause of pain insensitivity include congenital indifference to pain, congenital sensory neuropathy, hereditary sensory radicular neuropathy, nonprogressive sensory radicular neuropathy, syringomyelia, and hysterical analgesia. It is hereditary disease which is transmitted with autosomal recessive trait. The patient is 8 years old Korean male with complaint of swelling and local heat on right knee joint. Generalized analgesia is noted on physical examination. The skin is dry and coarse with no evidence of sweating. Delayed motor development was noted on early children. Mental development is retarded. On past history, patient showed unpredictable rises of temperature, though the general condition remained good. Multiple painless fracture on right humerus and right metatasal bone was occurred. Rt.knee radiograms show marked swelling of soft tissue and periosteal calcification on distal femru,which are resemble with neurotrophic joint.

  4. Femoral neuropathy due to patellar dislocation in a theatrical and jazz dancer: a case report.

    Science.gov (United States)

    Shin, Chris S; Davis, Brian A

    2005-06-01

    This case report describes a teenage female, high-level modern dancer who suffered multiple left patellar dislocations. Her history is atypical in that after her fifth dislocation, her recovery was hindered secondary to persistent weakness and atrophy of her quadriceps out of proportion to disuse alone. Electrodiagnostic studies and magnetic resonance imaging showed evidence of a subacute femoral neuropathy correlating chronologically with her most recent patellar dislocation. This case suggests that further diagnostic study may be warranted in patients with persistent quadriceps weakness or atrophy after a patellar dislocation, because this may suggest the presence of a femoral neuropathy. This is important because the strength training goals and precautions differ in disuse atrophy and a neuropathy. We believe this is the first reported case of a femoral neuropathy associated with the mechanism of a patellar dislocation.

  5. Disulfiram neuropathy.

    OpenAIRE

    1980-01-01

    Disulfiram (Antabuse) can produce neuropathy in daily doses of less than the usually recommended 500 mg. The four recent cases reported in this paper emphasize the need for greater recognition of this condition. Nerve biopsies showed axonal degeneration. The neuropathy is difficult to distinguish from that associated with ethanol abuse. Disulfiram neuropathy occurs after a variable latent period (mean 5 to 6 months) and progresses steadily. Slow improvement may occur when the drug's use is st...

  6. Efficient mitochondrial biogenesis drives incomplete penetrance in Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Giordano, Carla; Iommarini, Luisa; Giordano, Luca; Maresca, Alessandra; Pisano, Annalinda; Valentino, Maria Lucia; Caporali, Leonardo; Liguori, Rocco; Deceglie, Stefania; Roberti, Marina; Fanelli, Francesca; Fracasso, Flavio; Ross-Cisneros, Fred N; D'Adamo, Pio; Hudson, Gavin; Pyle, Angela; Yu-Wai-Man, Patrick; Chinnery, Patrick F; Zeviani, Massimo; Salomao, Solange R; Berezovsky, Adriana; Belfort, Rubens; Ventura, Dora Fix; Moraes, Milton; Moraes Filho, Milton; Barboni, Piero; Sadun, Federico; De Negri, Annamaria; Sadun, Alfredo A; Tancredi, Andrea; Mancini, Massimiliano; d'Amati, Giulia; Loguercio Polosa, Paola; Cantatore, Palmiro; Carelli, Valerio

    2014-02-01

    Leber's hereditary optic neuropathy is a maternally inherited blinding disease caused as a result of homoplasmic point mutations in complex I subunit genes of mitochondrial DNA. It is characterized by incomplete penetrance, as only some mutation carriers become affected. Thus, the mitochondrial DNA mutation is necessary but not sufficient to cause optic neuropathy. Environmental triggers and genetic modifying factors have been considered to explain its variable penetrance. We measured the mitochondrial DNA copy number and mitochondrial mass indicators in blood cells from affected and carrier individuals, screening three large pedigrees and 39 independently collected smaller families with Leber's hereditary optic neuropathy, as well as muscle biopsies and cells isolated by laser capturing from post-mortem specimens of retina and optic nerves, the latter being the disease targets. We show that unaffected mutation carriers have a significantly higher mitochondrial DNA copy number and mitochondrial mass compared with their affected relatives and control individuals. Comparative studies of fibroblasts from affected, carriers and controls, under different paradigms of metabolic demand, show that carriers display the highest capacity for activating mitochondrial biogenesis. Therefore we postulate that the increased mitochondrial biogenesis in carriers may overcome some of the pathogenic effect of mitochondrial DNA mutations. Screening of a few selected genetic variants in candidate genes involved in mitochondrial biogenesis failed to reveal any significant association. Our study provides a valuable mechanism to explain variability of penetrance in Leber's hereditary optic neuropathy and clues for high throughput genetic screening to identify the nuclear modifying gene(s), opening an avenue to develop predictive genetic tests on disease risk and therapeutic strategies.

  7. Mouse mtDNA mutant model of Leber hereditary optic neuropathy.

    Science.gov (United States)

    Lin, Chun Shi; Sharpley, Mark S; Fan, Weiwei; Waymire, Katrina G; Sadun, Alfredo A; Carelli, Valerio; Ross-Cisneros, Fred N; Baciu, Peter; Sung, Eric; McManus, Meagan J; Pan, Billy X; Gil, Daniel W; Macgregor, Grant R; Wallace, Douglas C

    2012-12-04

    An animal model of Leber hereditary optic neuropathy (LHON) was produced by introducing the human optic atrophy mtDNA ND6 P25L mutation into the mouse. Mice with this mutation exhibited reduction in retinal function by elecroretinogram (ERG), age-related decline in central smaller caliber optic nerve fibers with sparing of larger peripheral fibers, neuronal accumulation of abnormal mitochondria, axonal swelling, and demyelination. Mitochondrial analysis revealed partial complex I and respiration defects and increased reactive oxygen species (ROS) production, whereas synaptosome analysis revealed decreased complex I activity and increased ROS but no diminution of ATP production. Thus, LHON pathophysiology may result from oxidative stress.

  8. Diagnostic ability of Barrett's index to detect dysthyroid optic neuropathy using multidetector computed tomography

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    Monteiro, Mario L.R.; Goncalves, Allan C.P.; Silva, Carla T.M.; Moura, Janete P.; Ribeiro, Carolina S.; Gebrim, Eloisa M.M.S. [Universidade de Sao Paulo (USP), SP (Brazil). Hospital das Clinicas. Division of Ophthalmology; Universidade de Sao Paulo (USP), SP (Brazil). Hospital das Clinicas. Dept. of Endocrinology; Universidade de Sao Paulo (USP), SP (Brazil). Hospital das Clinicas. Division of Radiology]. E-mail: mlrmonteiro@terra.com.br

    2008-07-01

    Objectives: The objective of this study was to evaluate the ability of a muscular index (Barrett's Index), calculated with multidetector computed tomography, to detect dysthyroid optic neuropathy in patients with Graves' orbitopathy. Methods: Thirty-six patients with Graves' orbitopathy were prospectively studied and submitted to neuro-ophthalmic evaluation and multidetector computed tomography scans of the orbits. Orbits were divided into two groups: those with and without dysthyroid optic neuropathy. Barrett's index was calculated as the percentage of the orbit occupied by muscles. Sensitivity and specificity were determined for several index values. Results: Sixty-four orbits (19 with and 45 without dysthyroid optic neuropathy) met the inclusion criteria for the study. The mean Barrett's index values ({+-}SD) were 64.47% {+-} 6.06% and 49.44% {+-} 10.94% in the groups with and without dysthyroid optic neuropathy, respectively (p<0.001). Barrett's index sensitivity ranged from 32% to 100%, and Barrett's index specificity ranged from 24% to 100%. The best combination of sensitivity and specificity was 79%/72% for BI=60% (odds ratio: 9.2). Conclusions: Barrett's Index is a useful indicator of dysthyroid optic neuropathy and may contribute to early diagnosis and treatment. Patients with a Barrett's index >60% should be carefully examined and followed for the development of dysthyroid optic neuropathy. (author)

  9. Prevalence and Genetics of Leber Hereditary Optic Neuropathy in the Danish Population

    DEFF Research Database (Denmark)

    Rosenberg, Niels Thomas; Nørby, Søren; Schwartz, Marianne

    2016-01-01

    PURPOSE: In Denmark, the occurrence of Leber hereditary optic neuropathy (LHON) has continuously been monitored since 1944. We provide here a summary of 70 years of data collection including registered lines and subjects by the end of 2012. METHODS: Affected individuals were identified from a nat...... of other European populations. The genealogic follow-up reveals a relatively high turnover among families with approximately 15 newly affected families per century and the dying out of earlier maternal lines....

  10. A randomized placebo-controlled trial of idebenone in Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Klopstock, Thomas; Yu-Wai-Man, Patrick; Dimitriadis, Konstantinos; Rouleau, Jacinthe; Heck, Suzette; Bailie, Maura; Atawan, Alaa; Chattopadhyay, Sandip; Schubert, Marion; Garip, Aylin; Kernt, Marcus; Petraki, Diana; Rummey, Christian; Leinonen, Mika; Metz, Günther; Griffiths, Philip G; Meier, Thomas; Chinnery, Patrick F

    2011-09-01

    Major advances in understanding the pathogenesis of inherited metabolic disease caused by mitochondrial DNA mutations have yet to translate into treatments of proven efficacy. Leber's hereditary optic neuropathy is the most common mitochondrial DNA disorder causing irreversible blindness in young adult life. Anecdotal reports support the use of idebenone in Leber's hereditary optic neuropathy, but this has not been evaluated in a randomized controlled trial. We conducted a 24-week multi-centre double-blind, randomized, placebo-controlled trial in 85 patients with Leber's hereditary optic neuropathy due to m.3460G>A, m.11778G>A, and m.14484T>C or mitochondrial DNA mutations. The active drug was idebenone 900 mg/day. The primary end-point was the best recovery in visual acuity. The main secondary end-point was the change in best visual acuity. Other secondary end-points were changes in visual acuity of the best eye at baseline and changes in visual acuity for both eyes in each patient. Colour-contrast sensitivity and retinal nerve fibre layer thickness were measured in subgroups. Idebenone was safe and well tolerated. The primary end-point did not reach statistical significance in the intention to treat population. However, post hoc interaction analysis showed a different response to idebenone in patients with discordant visual acuities at baseline; in these patients, all secondary end-points were significantly different between the idebenone and placebo groups. This first randomized controlled trial in the mitochondrial disorder, Leber's hereditary optic neuropathy, provides evidence that patients with discordant visual acuities are the most likely to benefit from idebenone treatment, which is safe and well tolerated.

  11. Dissection of internal carotid artery presenting as isolated ischaemic optic neuropathy

    Directory of Open Access Journals (Sweden)

    Serdar Oruc

    2016-08-01

    Full Text Available Carotid artery dissections are one of the important reasons of cerebrovascular events that are observed before the age of 45. Besides the local findings such as head, neck and face pains, Horner syndrome findings, pulsatile tinnitus and cranial nerve involvements, some other symptoms such as ischemic stroke, transient ischemic attacks and amaurosis fugax can also be observed in the approximately three quarters of patients. Ischemic optic neuropathy may be seen as %4 in the carotid artery dissections and it mostly accompanies other ischemic local symptoms. It is rare to observe the ischemic optic neuropathy as the first and unique finding in the carotid artery dissections. In this study, a 55 year old male patient with carotid artery dissection was represented. He did not have any other complaint, except the sudden unilateral visual loss and he was sent to our clinics from the opthalmology clinics in order to search for the etiology of ischemic optic neuropathy. It should be kept in mind that there can be a possibility to have carotid artery dissections in patients with unilateral visual loss.

  12. [Hereditary optic neuropathies: from clinical signs to diagnosis].

    Science.gov (United States)

    Meunier, I; Lenaers, G; Hamel, C; Defoort-Dhellemmes, S

    2013-12-01

    Inherited optic atrophy must be considered when working up any optic nerve involvement and any systemic disease with signs of optic atrophy, even with a negative family history. There are two classical forms: dominant optic atrophy, characterized by insidious, bilateral, slowly progressive visual loss and temporal disc pallor, and Leber's optic atrophy, characterized by acute loss of central vision followed by the same event in the fellow eye within a few weeks to months, with disc hyperemia in the acute phase. Family history is critical for diagnosis. In the absence of family history, the clinician must rule out an identifiable acquired cause, i.e. toxic, inflammatory, perinatal injury, traumatic or tumoral, with orbital and brain imaging (MRI). Recessive optic atrophies are more rare and more severe and occur as part of multisystemic disorders, particularly Wolfram syndrome (diabetes mellitus, diabetes insipidus, and hearing loss). Effective treatments are limited; alcohol and smoking should be avoided. A cyclosporine trial (taken immediately upon visual loss in the first eye) is in progress in Leber's optic atrophy to prevent involvement of the fellow eye.

  13. Amyloid neuropathies.

    Science.gov (United States)

    Shin, Susan C; Robinson-Papp, Jessica

    2012-01-01

    Peripheral neuropathy is a common complication of many of the systemic amyloidoses. Although the cause of neuropathy is not entirely clear, it is likely related to amyloid deposition within the nerve. This may lead to focal, multifocal, or diffuse neuropathies involving sensory, motor and/or autonomic fibers. The presenting symptoms depend on the distribution of nerves affected. One of the most common phenotypes is sensorimotor polyneuropathy, which is characterized by symptoms of neuropathic pain, numbness, and in advanced cases weakness. Symptoms begin in the feet and ultimately progress to the proximal legs and hands. The most common focal neuropathy is a median neuropathy at the wrist, clinically known as carpal tunnel syndrome. Carpal tunnel symptoms may include pain and sensory disturbances in the lateral palm and fingers; hand weakness may ensue if the focal neuropathy is severe. Autonomic neuropathy may affect a variety of organ systems such as the cardiovascular, gastrointestinal, and genitourinary systems. Symptoms may be non-specific making the diagnosis of autonomic neuropathy more difficult to identify. However, it is important to recognize and distinguish autonomic neuropathy from diseases of the end-organs themselves. This article reviews the inherited and acquired amyloidoses that affect the peripheral nervous system including familial amyloid polyneuropathy, and primary, secondary and senile amyloidosis. We emphasize the clinical presentation of the neurologic aspects of these diseases, physical examination findings, appropriate diagnostic evaluation, treatment and prognosis. © 2012 Mount Sinai School of Medicine.

  14. Bilateral optic neuropathy associated with the tumor necrosis factor-alpha inhibitor golimumab.

    Science.gov (United States)

    Chang, Jessica R; Miller, Neil R

    2014-12-01

    A 62-year-old man developed bilateral blurred vision associated with bilateral optic disc swelling shortly after receiving his third dose of the tumor necrosis factor-alpha (TNF-α) inhibitor golimumab, that he took for psoriatic arthritis. An extensive assessment including magnetic resonance imaging, lumbar puncture, and serologies was negative. He was treated with systemic corticosteroids and the golimumab was stopped, after which his vision improved and his disc swelling resolved. We postulate that the bilateral, simultaneous anterior optic neuropathies in this patient were due to golimumab, representing a rare but well-documented serious adverse event associated with TNF-α inhibitors.

  15. Ethambutol-induced optic neuropathy linked to OPA1 mutation and mitochondrial toxicity.

    Science.gov (United States)

    Guillet, Virginie; Chevrollier, Arnaud; Cassereau, Julien; Letournel, Franck; Gueguen, Naïg; Richard, Laurence; Desquiret, Valérie; Verny, Christophe; Procaccio, Vincent; Amati-Bonneau, Patrizia; Reynier, Pascal; Bonneau, Dominique

    2010-03-01

    Ethambutol (EMB), widely used in the treatment of tuberculosis, has been reported to cause Leber's hereditary optic neuropathy in patients carrying mitochondrial DNA mutations. We study the effect of EMB on mitochondrial metabolism in fibroblasts from controls and from a man carrying an OPA1 mutation, in whom the drug induced the development of autosomal dominant optic atrophy (ADOA). EMB produced a mitochondrial coupling defect together with a 25% reduction in complex IV activity. EMB induced the formation of vacuoles associated with decreased mitochondrial membrane potential and increased fragmentation of the mitochondrial network. Mitochondrial genetic variations may therefore be predisposing factors in EMB-induced ocular injury.

  16. Leber hereditary optic neuropathy - historical report in comparison with the current knowledge.

    Science.gov (United States)

    Piotrowska, Agnieszka; Korwin, Magdalena; Bartnik, Ewa; Tońska, Katarzyna

    2015-01-15

    Leber hereditary optic neuropathy (LHON) is a genetic, maternally inherited disease caused by point mutations in the mitochondrial genome. LHON patients present with sudden, painless and usually bilateral loss of vision caused by optic nerve atrophy. The first clinical description of the disease was made by Theodor Leber, a German ophthalmologist, in 1871. Here we present his thorough notes about members of four families and their pedigrees. We also provide insights into the current knowledge about LHON pathology, genetics and treatment in comparison with Leber's findings.

  17. Vitamin B12-responsive neuropathies: A case series.

    Science.gov (United States)

    Solomon, Lawrence R

    2016-05-01

    Neuropathies often accompany vitamin B12 deficiency. Since many neuropathies are linked to oxidative stress and since B12 has both antioxidant and neurotrophic properties, B12 may also be effective treatment in non-deficient subjects. Thus, the characteristics and predictors of B12-responsive neuropathies and their relationship to disorders associated with increased oxidative stress (oxidant risks) were examined. Retrospective review of 78 subjects with neurological abnormalities treated with B12 and evaluated by the measurement of B12 and the B12-dependent metabolites, methylmalonic acid (MMA), and homocysteine. Sixty-five subjects had neurological improvement (83%), including 35 with other known causes of neuropathy. Only two responders had B12-responsive macrocytosis. Pretherapy B12, MMA, and homocysteine values were normal in 72, 33 and 54% of responders, with all three normal in 23%. Moreover, B12 therapy did not significantly decrease elevated MMA and homocysteine levels in 20 and 37%, respectively, of responders tested but did decrease both metabolites in 75% of evaluable non-responders. At least one oxidant risk was present in 41 of the 46 responders with normal B12 levels (89%). Oral therapy was effective, but parenteral B12 improved responses in four subjects. B12-responsive neuropathies are thus (1) common even when confounding disorders are present; (2) dissociated from the presence of hematological abnormalities; (3) dissociated from the presence of B12-responsive metabolical abnormalities; and (4) associated with the presence of oxidant risks when B12 levels are normal. Since no predictors of responses to B12 therapy were identified, empiric trials with parenteral B12 should be considered in appropriate subjects.

  18. Bilateral optic neuropathy in a patient with familial amyloidotic polyneuropathy

    DEFF Research Database (Denmark)

    Hamann, Steffen; Jensen, Peter Koch; Fledelius, Hans Callø

    2013-01-01

    glaucoma has been reported following intraocular surgery, but optic nerve involvement unrelated to glaucoma has not previously been described. We reported a male patient in his late 40s when deceased, who previously had a liver transplant in order to reduce the abnormal protein synthesis underlying his FAP...

  19. Paraneoplastic neuropathies.

    Science.gov (United States)

    Antoine, Jean-Christophe; Camdessanché, Jean-Philippe

    2017-10-01

    To review recent advances in paraneoplastic neuropathies with emphasis on their definition, different forms and therapeutic development. A strict definition of definite paraneoplastic neuropathies is necessary to avoid confusion. With carcinoma, seronegative sensory neuronopathies and neuronopathies and anti-Hu and anti-CV2/Contactin Response Mediator Protein 5 antibodies are the most frequent. With lymphomas, most neuropathies occur with monoclonal gammopathy including AL amyloidosis, Polyneuropathy-Organomegaly-Endocrinopathy-M component-Skin changes (POEMS) syndrome, type I cryoglobulinemia and antimyelin-associated glycoprotein (MAG) neuropathies and Waldenström's disease. Neuropathies improving with tumor treatment are occasional, occur with a variety of cancer and include motor neuron disease, chronic inflammatory demyelinating neuropathy and nerve vasculitis. If antibodies toward intracellular antigens are well characterized, it is not the case for antibodies toward cell membrane proteins. Contactin-associated protein-2 antibodies occur with neuromyotonia and thymoma with the Morvan's syndrome in addition to Netrin 1 receptor antibodies but may not be responsible for peripheral nerve hyperexcitability. The treatment of AL amyloidosis, POEMS syndrome, anti-MAG neuropathy and cryoglobulinemia is now relatively well established. It is not the case with onconeural antibodies for which the rarity of the disorders and a short therapeutic window are limiting factors for the development of clinical trials. A strict definition of paraneoplastic neuropathies helps their identification and is necessary to allow an early diagnosis of the underlying tumor.

  20. Effect of Maixuekang capsule therapy on optic nerve function, blood coagulation function and cytokines in diabetic optic neuropathy

    Institute of Scientific and Technical Information of China (English)

    Ya-Li Hao

    2016-01-01

    Objective:To analyze the effect of Maixuekang capsule therapy on optic nerve function, blood coagulation function and cytokines in diabetic optic neuropathy.Methods: A total of 55 patients (82 eyes) with diabetic optic neuropathy treated in our hospital between December 2013 and December 2015 were selected, and according to different therapeutic methods, they were divided into observation group (n=38) (49 eyes) who received Maixuekang therapy and control group (n=17) (33 eyes) who received compound vitamin therapy. Differences in optic nerve function, blood coagulation function and cytokine content were compared between two groups after 3 months of treatment.Results:After 3 months of treatment, optic nerve function indexes MS, RNFL thickness and AP100 levels of observation group were higher than those of control group while MD and LP100 levels were lower than those of control group; blood coagulation indexes WBV, PV and FBG levels were lower than those of control group while TT, PT and APTT levels were higher than those of control group; thrombelastogram parameters R value and K value levels were higher than those of control group while α angle, MA and CI levels were lower than those of control group; oxidative stress indexes ROS, MDA and CAT content in serum were lower than those of control group while SOD content was higher than that of control group.Conclusions:Maixuekang capsule can significantly optimize the optic nerve function in patients with DON, which is specifically directly related to its anticoagulation and anti-oxidative stress effect.

  1. Methanol-induced toxic optic neuropathy with diffusion weighted MRI findings.

    Science.gov (United States)

    Tanrivermis Sayit, Asli; Aslan, Kerim; Elmali, Muzaffer; Gungor, Inci

    2016-12-01

    We report a 52-year-old man with methanol intoxication who showed optic nerve damage as assessed by magnetic resonance imaging (MRI). He was admitted to the hospital with blurred vision after the consumption of alcohol (600-700 ml of cologne). He was treated with intravenous ethanol, NaHCO3 and hemodialysis. On admission, a brain and orbital MRI was performed. Bilateral mild contrast enhancement was detected on the contrast-enhanced images in the retrobulbar segment of the optic nerves (RBONs). Also, diffusion-weighted images showed restricted diffusion in the RBONs. Diagnosis was considered as methanol-induced optic neuropathy based on the MRI findings of the optic nerves.

  2. High-dose intravenous pulse steroid therapy for optic disc swelling and subretinal fluid in non-arteritic anterior ischemic optic neuropathy

    Science.gov (United States)

    Takayama, Kei; Kaneko, Hiroki; Kachi, Shu; Ra, Eimei; Ito, Yasuki; Terasaki, Hiroko

    2017-01-01

    ABSTRACT Non-arteritic anterior ischemic optic neuropathy (NAION) is a disease with microvascular abnormality that causes acute optic disc swelling (ODS) and, in severe cases, subretinal fluid (SRF) accumulation. ODS causes compartment syndrome and subsequent axonal degeneration and loss of retinal ganglion cells by apoptosis. No treatment modalities have been effective, although some cases improved after the intake of oral systemic steroids. We reported a case of a 72-year-old man who was referred due to a visual defect in the right eye. At first presentation, visual acuity and visual field were disturbed; critical flicker frequency (CFF) was decreased; and optic coherence tomography (OCT) showed ODS and SRF. Microscopic examination revealed parapapillary hemorrhage and fluorescence angiography showed non-filling, temporal-superior choroidal lesion adjacent to the optic disc at an early phase. After high-dose intravenous steroid treatment, SRF and ODS were decreased, and completely resolved after 30 days. Visual acuity and CFF were improved, and visual field was enlarged. High-dose intravenous steroids could possibly resolve SRF and ODS and improve visual function of patients with NAION. Some cases in NAION improved visual acuity and visual function in natural course, more cases were needed to evaluate the efficiency.

  3. [Hereditary neuropathies].

    Science.gov (United States)

    Vallat, Jean-Michel; Calvo, Judith; Ghorab, Karima; Tazir, Meriem

    2008-11-15

    Although there are many human hereditary neuropathies, most of them with the exception of Charcot-Marie-Tooth disease or hereditary sensorimotor neuropathy, are rare. Irrespective of their type, the mode of transmission may be autosomal dominant or recessive, or X-linked. The most difficult to diagnose, however, are the sporadic forms. It is customary to distinguish the cases in which the neuropathy is the sole clinical expression from multisystemic diseases where neuropathy is one component of multi-organ involvement. The complexity and the multiplicity of genes involved and the lack of understanding of their exact functions hinder logical presentation of these hereditary neuropathies. For understandable technical reasons, the stage of specific treatment, namely the repair of the mutated gene, has yet to be attained.

  4. Optic neuropathy in sheep associated with overdosage of closantel.

    Science.gov (United States)

    Borges, A S; Mendes, L C; de Andrade, A L; Machado, G F; Peiro, J R

    1999-12-01

    This report describes clinical and pathological findings in 2 flocks in Brazil where blindness and deaths in sheep occurred after closantel overdosage. Depression, weakness, and blindness affected 37 animals and 17 died in 2 flocks of 190 animals. Two animals submitted for ophthalmic examination showed no inflammation in the anterior segment of both eyes; posterior segment evaluation by indirect ophthalmoscopy suggested retinal degeneration. One postmortem evaluation local spongy vacuolization was in several regions of the brain and the optical nerves had severe axonal degeneration.

  5. Optic atrophy, cataracts, lipodystrophy/lipoatrophy, and peripheral neuropathy caused by a de novo OPA3 mutation

    Science.gov (United States)

    Bourne, Stephanie C.; Townsend, Katelin N.; Shyr, Casper; Matthews, Allison; Lear, Scott A.; Attariwala, Raj; Lehman, Anna; Wasserman, Wyeth W.; van Karnebeek, Clara; Sinclair, Graham; Vallance, Hilary; Gibson, William T.

    2017-01-01

    We describe a woman who presented with cataracts, optic atrophy, lipodystrophy/lipoatrophy, and peripheral neuropathy. Exome sequencing identified a c.235C > G p.(Leu79Val) variant in the optic atrophy 3 (OPA3) gene that was confirmed to be de novo. This report expands the severity of the phenotypic spectrum of autosomal dominant OPA3 mutations. PMID:28050599

  6. A novel rat model to study the role of intracranial pressure modulation on optic neuropathies.

    Directory of Open Access Journals (Sweden)

    Uttio Roy Chowdhury

    Full Text Available Reduced intracranial pressure is considered a risk factor for glaucomatous optic neuropathies. All current data supporting intracranial pressure as a glaucoma risk factor comes from retrospective and prospective studies. Unfortunately, there are no relevant animal models for investigating this link experimentally. Here we report a novel rat model that can be used to study the role of intracranial pressure modulation on optic neuropathies. Stainless steel cannulae were inserted into the cisterna magna or the lateral ventricle of Sprague-Dawley and Brown Norway rats. The cannula was attached to a pressure transducer connected to a computer that recorded intracranial pressure in real-time. Intracranial pressure was modulated manually by adjusting the height of a column filled with artificial cerebrospinal fluid in relation to the animal's head. After data collection the morphological appearance of the brain tissue was analyzed. Based on ease of surgery and ability to retain the cannula, Brown Norway rats with the cannula implanted in the lateral ventricle were selected for further studies. Baseline intracranial pressure for rats was 5.5 ± 1.5 cm water (n=5. Lowering of the artificial cerebrospinal fluid column by 2 cm and 4 cm below head level reduced ICP to 3.7 ± 1.0 cm water (n=5 and 1.5 ± 0.6 cm water (n=4, a reduction of 33.0% and 72.7% below baseline. Raising the cerebrospinal fluid column by 4 cm increased ICP to 7.5 ± 1.4 cm water (n=2 corresponding to a 38.3% increase in intracranial pressure. Histological studies confirmed correct cannula placement and indicated minimal invasive damage to brain tissues. Our data suggests that the intraventricular cannula model is a unique and viable model that can be used to study the effect of altered intracranial pressure on glaucomatous optic neuropathies.

  7. Evaluation of Leber's hereditary optic neuropathy patients prior to a gene therapy clinical trial

    Science.gov (United States)

    Yang, Shuo; Yang, Hong; Ma, Si-qi; Wang, Shuai-shuai; He, Heng; Zhao, Min-jian; Li, Bin

    2016-01-01

    Abstract Gene therapy may be a promising approach for the treatment of Leber hereditary optic neuropathy. The aim of this study was to evaluate patients with this condition who were recruited into an upcoming gene therapy clinical trial and to assess any changes in the detection parameters to provide support for the clinical trial. Sixteen patients with Leber hereditary optic neuropathy were evaluated using visual function tests 12 months before the initiation of gene therapy. Then, the results of visual acuity (VA), visual field (VF), RNFL (retinal nerve fiber layer) thickness, and Pattern-reversal Visual evoked potential (PR-VEP) were compared and analyzed. A total of 32 eyes of 16 patients were evaluated. Based on the best-corrected visual acuity (BCVA), 24 eyes were relatively stable compared with the baseline evaluation, and 8 eyes had significant changes, including 5 eyes that showed improvement and 3 eyes that showed impairment. In all eyes, the changes in the best-corrected visual acuity were significantly correlated with the changes in the visual field index (VFI), mean defect (MD), and P100 of the visual evoked potential. In the eyes with relatively stable BCVA and those with an obvious improvement in the BCVA, only the visual mean defect showed a significant change; the other indicators were not significantly different. Aside from the patients showing a tendency of spontaneous improvement, the others were in accordance with the requirement. The effects of Leber hereditary optical neuropathy (LHON) gene therapy should be evaluated primarily based on visual acuity. Additionally, visual field, neural fiber thickness, and electrophysiology should be considered in the evaluation. PMID:27749593

  8. Mitochondrial DNA variant associated with Leber hereditary optic neuropathy and high-altitude Tibetans.

    Science.gov (United States)

    Ji, Fuyun; Sharpley, Mark S; Derbeneva, Olga; Alves, Leonardo Scherer; Qian, Pin; Wang, Yaoli; Chalkia, Dimitra; Lvova, Maria; Xu, Jiancheng; Yao, Wei; Simon, Mariella; Platt, Julia; Xu, Shiqin; Angelin, Alessia; Davila, Antonio; Huang, Taosheng; Wang, Ping H; Chuang, Lee-Ming; Moore, Lorna G; Qian, Guisheng; Wallace, Douglas C

    2012-05-08

    The distinction between mild pathogenic mtDNA mutations and population polymorphisms can be ambiguous because both are homoplasmic, alter conserved functions, and correlate with disease. One possible explanation for this ambiguity is that the same variant may have different consequences in different contexts. The NADH dehydrogenase subunit 1 (ND1) nucleotide 3394 T > C (Y30H) variant is such a case. This variant has been associated with Leber hereditary optic neuropathy and it reduces complex I activity and cellular respiration between 7% and 28% on the Asian B4c and F1 haplogroup backgrounds. However, complex I activity between B4c and F1 mtDNAs, which harbor the common 3394T allele, can also differ by 30%. In Asia, the 3394C variant is most commonly associated with the M9 haplogroup, which is rare at low elevations but increases in frequency with elevation to an average of 25% of the Tibetan mtDNAs (odds ratio = 23.7). In high-altitude Tibetan and Indian populations, the 3394C variant occurs on five different macrohaplogroup M haplogroup backgrounds and is enriched on the M9 background in Tibet and the C4a4 background on the Indian Deccan Plateau (odds ratio = 21.9). When present on the M9 background, the 3394C variant is associated with a complex I activity that is equal to or higher than that of the 3394T variant on the B4c and F1 backgrounds. Hence, the 3394C variant can either be deleterious or beneficial depending on its haplogroup and environmental context. Thus, this mtDNA variant fulfills the criteria for a common variant that predisposes to a "complex" disease.

  9. Prevalence and Genetics of Leber Hereditary Optic Neuropathy in the Danish Population

    DEFF Research Database (Denmark)

    Rosenberg, Thomas; Nørby, Søren; Schwartz, Marianne

    2016-01-01

    PURPOSE: In Denmark, the occurrence of Leber hereditary optic neuropathy (LHON) has continuously been monitored since 1944. We provide here a summary of 70 years of data collection including registered lines and subjects by the end of 2012. METHODS: Affected individuals were identified from....... The number of live affected individuals with a verified mitochondrial DNA mutation was 104 on January 1, 2013, which translates to a prevalence rate of 1:54,000 in the Danish population. CONCLUSIONS: Haplogroup distribution as well as mutational spectrum of the Danish LHON cohort do not deviate from those...

  10. Whole mitochondrial genome analysis in South Indian patients with Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Saikia, Bibhuti Ballav; Dubey, Sushil Kumar; Shanmugam, Mahesh Kumar; Sundaresan, Periasamy

    2016-10-28

    Leber's hereditary optic neuropathy (LHON) is a mitochondrial DNA (mtDNA) associated neurodegenerative disorder of retinal ganglion cells. In this study, whole mitochondrial genome sequencing of 75 LHON patients and 40 controls was performed to identify the mutation frequency and haplogroup background of South Indian population. Analysis of mtDNA revealed 559 different variants in LHON patients, including 7 pathogenic mutations, 30 private, and 22 other disease associated variants. A significantly higher (p=0.0008) overall variation load per individual was noted among LHON patients versus controls. We reported for the first time, the association of M haplogroup (p=0.028) with LHON in this cohort.

  11. Identification of small molecules that improve ATP synthesis defects conferred by Leber's hereditary optic neuropathy mutations.

    Science.gov (United States)

    Datta, Sandipan; Tomilov, Alexey; Cortopassi, Gino

    2016-09-01

    Inherited mitochondrial complex I mutations cause blinding Leber's hereditary optic neuropathy (LHON), for which no curative therapy exists. A specific biochemical consequence of LHON mutations in the presence of trace rotenone was observed: deficient complex I-dependent ATP synthesis (CIDAS) and mitochondrial O2 consumption, proportional to the clinical severity of the three primary LHON mutations. We optimized a high-throughput assay of CIDAS to screen 1600 drugs to 2, papaverine and zolpidem, which protected CIDAS in LHON cells concentration-dependently. TSPO and cAMP were investigated as protective mechanisms, but a conclusive mechanism remains to be elucidated; next steps include testing in animal models.

  12. X-inactivation pattern in multiple tissues from two Leber's hereditary optic neuropathy (LHON) patients.

    Science.gov (United States)

    Pegoraro, Elena; Vettori, Andrea; Valentino, Maria L; Molon, Annamaria; Mostacciuolo, Maria L; Howell, Neil; Carelli, Valerio

    2003-05-15

    The more frequent manifestation of ophthalmological abnormalities in males, relative to females, is an unexplained feature of Leber's hereditary optic neuropathy (LHON) that suggests an X-linked modifying gene acting in concert with the pathogenic LHON mitochondrial DNA (mtDNA) mutation. In addition, segregation analysis of the optic neuropathy in LHON pedigrees was compatible with the presence of a recessive-modifying gene on chromosome X. According to this two-locus model, females would be affected only if homozygous or if they were susceptible to skewed X-inactivation. Attempts both to localize the putative LHON-modifying gene by linkage analysis and to find an excess of skewed X-inactivation in affected females were unsuccessful, although the inactivation pattern was only studied in DNA isolated from blood cells. We had the opportunity to analyze a wide range of tissues at autopsy, including the optic nerves and the retina, from two LHON female patients. We found no evidence of skewed X-inactivation in the affected tissues, thus weakening further the hypothesized involvement of a specific X chromosome locus in the pathophysiological expression of LHON.

  13. Oxidative phosphorylation differences between mitochondrial DNA haplogroups modify the risk of Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Gómez-Durán, Aurora; Pacheu-Grau, David; Martínez-Romero, Iñigo; López-Gallardo, Ester; López-Pérez, Manuel J; Montoya, Julio; Ruiz-Pesini, Eduardo

    2012-08-01

    Leber's hereditary optic neuropathy is a maternally inherited optic atrophy caused by mitochondrial DNA point mutations. Previous epidemiological studies have shown that individuals from mitochondrial genetic backgrounds (haplogroups) J/Uk and H have a higher and a lower risk, respectively, of suffering this disorder. To analyze the bases of these associations at cellular and molecular levels, functional studies with cybrids provide high quality evidence. Cybrids from haplogroup J contain less mitochondrial deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) and synthesize a smaller amount of mitochondrial DNA-encoded polypeptides than those from haplogroup H. Haplogroup J cybrids also display lower oxygen consumption, mitochondrial inner membrane potential and total adenosine-5'-triphosphate (ATP) levels. Moreover, mitochondrial DNA levels correlate with many parameters of the oxidative phosphorylation system. These results suggest that the mitochondrial DNA amount determines oxidative phosphorylation capacity and, along with other recently published observations, support the possibility that mitochondrial DNA levels may be responsible for the bias of the disorder toward males, for the incomplete penetrance of mutations causing Leber's hereditary optic neuropathy and for the association of the disease with particular mitochondrial DNA haplogroups.

  14. Reversal of optic neuropathy secondary to voluntary globe luxation.

    Science.gov (United States)

    Yaman, Aylin; Ozturk, Taylan; Soylev, Meltem F

    2009-04-01

    Luxation of the globe is rare in the general population and may be spontaneous, voluntary, or traumatic. Spontaneous or voluntary globe luxation results from shallow orbit, floppy eyelids, lax orbital ligaments, backward displacement of orbital septum, or proptotic eyes due to orbital tumors or infiltrative processes, as in Grave's ophthalmopathy. The authors report a case with unilateral voluntary globe luxation presented with unilateral progressive visual loss.

  15. Neuropathies optiques héréditaires

    DEFF Research Database (Denmark)

    Milea, D; Verny, C

    2012-01-01

    Hereditary optic neuropathies are a group of heterogeneous conditions affecting both optic nerves, with an autosomal dominant, autosomal recessive, X-related or mitochondrial transmission. The two most common non-syndromic hereditary optic neuropathies (Leber's hereditary optic neuropathy...

  16. Organophosphorus agent induced delayed neuropathy: a case report

    Directory of Open Access Journals (Sweden)

    Harshit Acharya

    2016-02-01

    Full Text Available A 40-year old male, was presented with complaint of difficulty in walking with inability to flex foot and toes in bilateral feet ( and ldquo;foot drop and rdquo;, which was acute at the onset and gradually progressive since the past 7 days. The patient's wife and their 2 children had similar complaint with the same period of onset. At home, his family used cottonseed oil as cooking oil with wheat grain mixed with castor oil. On neurological examination, he was found to have lower motor neuron weakness with spasticity. After ruling out other common causes of polyneuropathy and lower motor weakness; due to high suspicion of poisoning by food adulterant, RBC acetyl cholinesterase (AChE and plasma cholinesterase (BuChE were tested at National Institute of Occupational Health (NIOH, which came low and confirmed diagnosis of Organophosphorus (OP poisoning. Nerve conduction study was done; which showed decreased amplitude of conduction in bilateral peroneal and right tibial nerve along with decreased mean nerve conduction velocity of bilateral median nerve. Thus patient was diagnosed with organophosphorus agent induced delayed axonal type of polyneuropathy and physiotherapy was started as treatment. OP compounds are a diverse group of chemicals which are principally used as insecticides in agriculture. Following organophosphate poisoning (OPP, 3 well-defined neurological syndromes are recognised: cholinergic crisis, intermediate syndrome and delayed polyneuropathy. Some organophosphates, particularly triorthocresyl phosphate (TOCP and tricresyl phosphate (TCP, produce delayed neuropathy. On ingestion, they do not produce significant cholinergic crisis, but 7 to 20 days later it leads to a pure motor axonal neuropathy with wrist and foot drop. The mechanism may involve inhibition of neuropathy target esterase (NTE, which is found in the brain, peripheral nerves, and lymphocytes. This form of toxicity has been seen occasionally in small epidemics in

  17. Ischemic optic neuropathy as a model of neurodegenerative disorder: A review of pathogenic mechanism of axonal degeneration and the role of neuroprotection.

    Science.gov (United States)

    Khalilpour, Saba; Latifi, Shahrzad; Behnammanesh, Ghazaleh; Majid, Amin Malik Shah Abdul; Majid, Aman Shah Abdul; Tamayol, Ali

    2017-04-15

    Optic neuropathy is a neurodegenerative disease which involves optic nerve injury. It is caused by acute or intermittent insults leading to visual dysfunction. There are number of factors, responsible for optic neuropathy, and the optic nerve axon is affected in all type which causes the loss of retinal ganglion cells. In this review we will highlight various mechanisms involved in the cell loss cascades during axonal degeneration as well as ischemic optic neuropathy. These mechanisms include oxidative stress, excitotoxicity, angiogenesis, neuroinflammation and apoptosis following retinal ischemia. We will also discuss the effect of neuroprotective agents in attenuation of the negative effect of factors involve in the disease occurrence and progression.

  18. Peripheral neuropathies associated with rheumatoid synovial cysts of the elbow joint: three case reports.

    Science.gov (United States)

    Muramatsu, Keiichi; Kojima, Takanori; Yoshida, Koji; Miyoshi, Tomoyuki; Taguchi, Toshihiko

    2006-12-01

    We present 3 cases with peripheral neuropathies of the median, posterior interosseous, and ulnar nerves associated with rheumatoid synovial cysts of the elbow joint. Magnetic resonance imaging and electrophysiological examination led to the final diagnosis of the relation to synovial cysts of the elbow joint. All patients underwent surgical decompression of these nerves and synovectomy of the elbow joint. Functional recovery was excellent in the 2 patients with median and posterior interosseous nerve palsy but incomplete in the patient with ulnar nerve palsy. Such neuropathies require consideration in the differential diagnosis of wrist and hand disability in patients with rheumatoid arthritis. This awareness should enhance early diagnosis and treatment by surgical decompression.

  19. Intravitreal transplantation of human umbilical cord blood stem cells protects rats from traumatic optic neuropathy.

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    Bing Jiang

    Full Text Available OBJECTIVES: To treat traumatic optic neuropathy (TON with transplantation of human umbilical cord blood stem cells (hUCBSC and explore how transplanted stem cells participate in the neuron repairing process. METHODS: A total of 195 Sprague-Dawley rats were randomly assigned to three groups: sham-surgery, optic nerve injury, and stem cell transplant group. Optic nerve injury was established in rats by directly clamping the optic nerve for 30 seconds. hUCBSC was microinjected into the vitreous cavity of injured rats. Optic nerve function was evaluated by flash visual evoked potentials (F-VEP. Apoptosis in retina tissues was detected by TUNEL staining. GRP78 and CHOP gene expression was measured by RT-PCR. RESULTS: After injury, transplantation of hUCBSC significantly blunted a reduction in optic nerve function indicated by smaller decreases in amplitude and smaller increases in peak latency of F-VEP waveform compared to the injury alone group. Also, significant more in retinal ganglion cell (RGC count and less in RGC apoptosis were detected after transplantation compared to injured rats. The protective effect correlated with upregulated GRP78 and downregulated CHOP mRNA expression. CONCLUSION: Intravitreal transplantation of hUCBSCs significantly blunted a reduction in optic nerve function through increasing RGC survival and decreasing retinal cell apoptosis. The protective role of transplantation was associated with upregulation of GRP78 expression and downregulation of CHOP expression in retinal cells.

  20. Mitochondrial optic neuropathy: In vivo model of neurodegeneration and neuroprotective strategies

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    Julio C Rojas

    2010-03-01

    Full Text Available Julio C Rojas, Francisco Gonzalez-LimaDepartments of Psychology, Pharmacology and Toxicology, University of Texas at Austin, Austin, TX, USAAbstract: This review summarizes the characteristics of a rodent toxicologic model of optic neuropathy induced by the mitochondrial complex I inhibitor rotenone. This model has been developed to fulfill the demand for a drug-screening tool providing a sound mechanistic context to address the role of mitochondrial dysfunction in the pathogenesis of neurodegenerative disorders. It features biochemical, structural, and functional retinal deficits that resemble those of patients with Leber’s hereditary optic neuropathy, a mitochondrial disease characterized by selective degeneration of retinal ganglion cells, and for which an environmental component is believed to play a major triggering role. The available data support the efficiency, sensitivity, and versatility of the model for providing insights into the mechanisms of neurodegeneration, including mitochondrial dysfunction, oxidative stress and excitotoxicity. Screening work with this model has provided proof-of-principle that interventions targeting the electron transport chain, such as USP methylene blue and near-infrared light therapy, are effective at preventing neurodegeneration induced by mitochondrial dysfunction in vivo. Prospective developments of this model include the use of neuronal reporter genes for in vivo non-invasive assessment of retinal degeneration at different time points, and its combination with genetic approaches to elucidate the synergism of environmental and genetic factors in neurodegeneration.Keywords: animal model, neuroprotection, mitochondrial dysfunction, visual function, oxidative stress, cytochrome oxidase

  1. Self-inflicted corneal injuries in a child with congenital sensory neuropathy (A case report

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    Gaonker C

    1991-01-01

    Full Text Available An interesting clinical, report of a rare case of bilateral congeni-tal corneal anaesthesia associated with Congenital Sensory Neuropathy (CSN in a 11sub/2 year old child with corneal ulceration secondary to self-inflicted trauma is reported.

  2. Pyridoxine neuropathy.

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    Waterston, J A; Gilligan, B S

    1987-06-15

    A case of sensory neuropathy in a young woman due to long-term ingestion of pyridoxine, with subsequent recovery, is described. Pyridoxine neuropathy may occur after the long-term ingestion of doses as low as 200 mg a day. Because of its widespread use in the community, both the general public and the medical community need to be aware of this recently described complication of megavitamin therapy.

  3. Long-term evaluation of Leber's hereditary optic neuropathy-like symptoms in rotenone administered rats.

    Science.gov (United States)

    Zhang, Li; Liu, Laura; Philip, Ann L; Martinez, Juan C; Guttierez, Juan C; Marella, Mathieu; Patki, Gaurav; Matsuno-Yagi, Akemi; Yagi, Takao; Thomas, Biju B

    2015-01-12

    Leber's hereditary optic neuropathy (LHON) is an inherited disorder affecting the retinal ganglion cells (RGCs) and their axons that lead to the loss of central vision. This study is aimed at evaluating the LHON symptoms in rats administered with rotenone microspheres into the superior colliculus (SC). Optical coherence tomography (OCT) analysis showed substantial loss of retinal nerve fiber layer (RNFL) thickness in rotenone injected rats. Optokinetic testing in rotenone treated rats showed decrease in head-tracking response. Electrophysiological mapping of the SC surface demonstrated attenuation of visually evoked responses; however, no changes were observed in the ERG data. The progressive pattern of disease manifestation in rotenone administered rats demonstrated several similarities with human disease symptoms. These rats with LHON-like symptoms can serve as a model for future investigators to design and implement reliable tests to assess the beneficial effects of therapeutic interventions for LHON disease.

  4. Results of Mitochondrial DNA Sequence Analysis in Patients with Clinically Diagnosed Leber’s Hereditary Optic Neuropathy

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    Haluk Esgin

    2012-09-01

    Full Text Available Objective: To investigate possible mitochondrial DNA (mtDNA mutations in patients with Leber’s hereditary optic neuropathy (LHON in order to provide a precise diagnosis and genetic counseling.Material and Methods: Between 1982 and 2007, ten patients were clinically diagnosed with LHON and six of these patients agreed to be involved in this study. Six healthy individuals were also included as a control group. mtDNA was isolated from peripheral blood samples and polymerase chain reaction and mtDNA sequence analysis were performed. Results: In one of the six patients, a homoplasmic mutant m.11778G>A mutation was detected. All of the clinically diagnosed LHON patients and the control groups had the m.14212C>T and m.14580G>A single nucleotide polymorphisms (SNPs. The m.11719A>G SNP was detected in three of six patients and four of the controls. Two of the six patients had the m.3197T>C SNP and, in addition, the m.14258G>A SNP was found in one of these two patients, while neither of these mutations were present in the control group.Conclusion: The clinical diagnosis of LHON could be supported by molecular genetics only in one patient by the detection of one mutation. The m.3197T>C and m.14258G>A SNPs should be considered as potential mtDNA mutations due to the fact that they were detected in the patient group. These mutations should be investigated further in large case groups for suspected gene loci that could lead to optic neuropathy.

  5. Disturbed mitochondrial and peroxisomal dynamics due to loss of MFF causes Leigh-like encephalopathy, optic atrophy and peripheral neuropathy.

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    Koch, Johannes; Feichtinger, René G; Freisinger, Peter; Pies, Mechthild; Schrödl, Falk; Iuso, Arcangela; Sperl, Wolfgang; Mayr, Johannes A; Prokisch, Holger; Haack, Tobias B

    2016-04-01

    Mitochondria are dynamic organelles which undergo continuous fission and fusion to maintain their diverse cellular functions. Components of the fission machinery are partly shared between mitochondria and peroxisomes, and inherited defects in two such components (dynamin-related protein (DRP1) and ganglioside-induced differentiation-associated protein 1 (GDAP1)) have been associated with human disease. Deficiency of a third component (mitochondrial fission factor, MFF) was recently reported in one index patient, rendering MFF another candidate disease gene within the expanding field of mitochondrial and peroxisomal dynamics. Here we investigated three new patients from two families with pathogenic mutations in MFF. The patients underwent clinical examination, brain MRI, and biochemical, cytological and molecular analyses, including exome sequencing. The patients became symptomatic within the first year of life, exhibiting seizures, developmental delay and acquired microcephaly. Dysphagia, spasticity and optic and peripheral neuropathy developed subsequently. Brain MRI showed Leigh-like patterns with bilateral changes of the basal ganglia and subthalamic nucleus, suggestive of impaired mitochondrial energy metabolism. However, activities of mitochondrial respiratory chain complexes were found to be normal in skeletal muscle. Exome sequencing revealed three different biallelic loss-of-function variants in MFF in both index cases. Western blot studies of patient-derived fibroblasts indicated normal content of mitochondria and peroxisomes, whereas immunofluorescence staining revealed elongated mitochondria and peroxisomes. Furthermore, increased mitochondrial branching and an abnormal distribution of fission-mediating DRP1 were observed. Our findings establish MFF loss of function as a cause of disturbed mitochondrial and peroxisomal dynamics associated with early-onset Leigh-like basal ganglia disease. We suggest that, even if laboratory findings are not indicative of

  6. Macular Microcysts in Mitochondrial Optic Neuropathies: Prevalence and Retinal Layer Thickness Measurements.

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    Michele Carbonelli

    Full Text Available To investigate the thickness of the retinal layers and to assess the prevalence of macular microcysts (MM in the inner nuclear layer (INL of patients with mitochondrial optic neuropathies (MON.All patients with molecularly confirmed MON, i.e. Leber's Hereditary Optic Neuropathy (LHON and Dominant Optic Atrophy (DOA, referred between 2010 and 2012 were enrolled. Eight patients with MM were compared with two control groups: MON patients without MM matched by age, peripapillary retinal nerve fiber layer (RNFL thickness, and visual acuity, as well as age-matched controls. Retinal segmentation was performed using specific Optical coherence tomography (OCT software (Carl Zeiss Meditec. Macular segmentation thickness values of the three groups were compared by one-way analysis of variance with Bonferroni post hoc corrections.MM were identified in 5/90 (5.6% patients with LHON and 3/58 (5.2% with DOA. The INL was thicker in patients with MON compared to controls regardless of the presence of MM [133.1±7μm vs 122.3±9μm in MM patients (p<0.01 and 128.5±8μm vs. 122.3±9μm in no-MM patients (p<0.05], however the outer nuclear layer (ONL was thicker in patients with MM (101.4±1mμ compared to patients without MM [77.5±8mμ (p<0.001] and controls [78.4±7mμ (p<0.001]. ONL thickness did not significantly differ between patients without MM and controls.The prevalence of MM in MON is low (5-6%, but associated with ONL thickening. We speculate that in MON patients with MM, vitreo-retinal traction contributes to the thickening of ONL as well as to the production of cystic spaces.

  7. Macular Microcysts in Mitochondrial Optic Neuropathies: Prevalence and Retinal Layer Thickness Measurements

    Science.gov (United States)

    Carbonelli, Michele; La Morgia, Chiara; Savini, Giacomo; Cascavilla, Maria Lucia; Borrelli, Enrico; Chicani, Filipe; do V. F. Ramos, Carolina; Salomao, Solange R.; Parisi, Vincenzo; Sebag, Jerry; Bandello, Francesco; Sadun, Alfredo A.; Carelli, Valerio; Barboni, Piero

    2015-01-01

    Purpose To investigate the thickness of the retinal layers and to assess the prevalence of macular microcysts (MM) in the inner nuclear layer (INL) of patients with mitochondrial optic neuropathies (MON). Methods All patients with molecularly confirmed MON, i.e. Leber’s Hereditary Optic Neuropathy (LHON) and Dominant Optic Atrophy (DOA), referred between 2010 and 2012 were enrolled. Eight patients with MM were compared with two control groups: MON patients without MM matched by age, peripapillary retinal nerve fiber layer (RNFL) thickness, and visual acuity, as well as age-matched controls. Retinal segmentation was performed using specific Optical coherence tomography (OCT) software (Carl Zeiss Meditec). Macular segmentation thickness values of the three groups were compared by one-way analysis of variance with Bonferroni post hoc corrections. Results MM were identified in 5/90 (5.6%) patients with LHON and 3/58 (5.2%) with DOA. The INL was thicker in patients with MON compared to controls regardless of the presence of MM [133.1±7μm vs 122.3±9μm in MM patients (p<0.01) and 128.5±8μm vs. 122.3±9μm in no-MM patients (p<0.05)], however the outer nuclear layer (ONL) was thicker in patients with MM (101.4±1mμ) compared to patients without MM [77.5±8mμ (p<0.001)] and controls [78.4±7mμ (p<0.001)]. ONL thickness did not significantly differ between patients without MM and controls. Conclusion The prevalence of MM in MON is low (5-6%), but associated with ONL thickening. We speculate that in MON patients with MM, vitreo-retinal traction contributes to the thickening of ONL as well as to the production of cystic spaces. PMID:26047507

  8. Rare primary mitochondrial DNA mutations and probable synergistic variants in Leber's hereditary optic neuropathy.

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    Alessandro Achilli

    Full Text Available BACKGROUND: Leber's hereditary optic neuropathy (LHON is a maternally inherited blinding disorder, which in over 90% of cases is due to one of three primary mitochondrial DNA (mtDNA point mutations (m.11778G>A, m.3460G>A and m.14484T>C, respectively in MT-ND4, MT-ND1 and MT-ND6 genes. However, the spectrum of mtDNA mutations causing the remaining 10% of cases is only partially and often poorly defined. METHODOLOGY/PRINCIPAL FINDINGS: In order to improve such a list of pathological variants, we completely sequenced the mitochondrial genomes of suspected LHON patients from Italy, France and Germany, lacking the three primary common mutations. Phylogenetic and conservation analyses were performed. Sixteen mitochondrial genomes were found to harbor at least one of the following nine rare LHON pathogenic mutations in genes MT-ND1 (m.3700G>A/p.A132T, m.3733G>A-C/p.E143K-Q, m.4171C>A/p.L289M, MT-ND4L (m.10663T>C/p.V65A and MT-ND6 (m.14459G>A/p.A72V, m.14495A>G/p.M64I, m.14482C>A/p.L60S, and m.14568C>T/p.G36S. Phylogenetic analyses revealed that these substitutions were due to independent events on different haplogroups, whereas interspecies comparisons showed that they affected conserved amino acid residues or domains in the ND subunit genes of complex I. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that these nine substitutions are all primary LHON mutations. Therefore, despite their relative low frequency, they should be routinely tested for in all LHON patients lacking the three common mutations. Moreover, our sequence analysis confirms the major role of haplogroups J1c and J2b (over 35% in our probands versus 6% in the general population of Western Europe and other putative synergistic mtDNA variants in LHON expression.

  9. Auditory Neuropathy in Two Patients with Generalized Neuropathic Disorder: A Case Report

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    P Ahmadi

    2008-06-01

    Full Text Available Background: Although it is not a new disorder, in recent times we have attained a greater understanding of auditory neuropathy (AN. In this type of hearing impairment, cochlear hair cells function but AN victims suffer from disordered neural transmission in the auditory pathway. The auditory neuropathy result profile often occurs as a part of that of the generalized neuropathic disorders, indicated in approximately 30-40% of all reported auditory neuropathy/auditory dyssynchrony (AN/AD cases, with approximately 80% of patients reporting symptom onset over the age of 15 years. In the present report, the results of audiologic tests (behavioral, physiologic and evoked potentials on two young patients with generalized neuropathy are discussed.Case report: Two brothers, 26 and 17 years old, presented with speech perception weakness and movement difficulties that started at 12 years of age and progressed as time passed. In their last examination, there was a moderate to severe flat audiogram in the older patient and mild low tone loss in the younger one. The major difficulty of the patients was severe speech perception impairment that was not compatible with their hearing thresholds. Paresthesia, sural muscle contraction and pain, and balance disorder were the first symptoms of the older brother. Now he can only move with crutches and his finger muscle tonicity has decreased remarkably, with marked fatigue after a short period of walking. Increasing movement difficulties were noted in his last visit. Visual neuropathy had been reported in repeated visual system examinations for the older brother, with similar, albeit less severe, symptoms in the younger brother.In the present study of these patients, behavioral investigations included pure-tone audiometry and speech discrimination scoring. Physiologic studies consisted Transient Evoked Otoacoustic Emission (TEOAE and acoustic reflexes. Electrophysiologic auditory tests were also performed to determine

  10. [A case of localized hypertrophic neuropathy in the sciatic nerve].

    Science.gov (United States)

    Izumi, T; Kusaka, H; Imai, T

    1995-01-01

    A 26-year-old male patient gradually developed muscular atrophy of the right lower leg over a two-year period. Neurological examination revealed absent Achilles tendon reflex and muscular atrophy of the right lower leg and right hamstring muscles. Conduction velocity of the F waves was delayed in the right posterior tibial nerve. A computerized tomography scan and magnetic resonance imaging revealed a mass lesion along the proximal segment of the right sciatic nerve. Exploration revealed a fusiformly swollen sciatic nerve. Histological examination showed that a swollen segment of the sciatic nerve was filled with onion-bulb formations of perineurial cells, consistent with the diagnosis of localized hypertrophic neuropathy. This condition should be added to several etiologies of monomelic amyotrophy. Electrophysiological studies and neuroimaging techniques were useful in obtaining differential diagnosis.

  11. Genetic and Clinical Analyses of DOA and LHON in 304 Chinese Patients with Suspected Childhood-Onset Hereditary Optic Neuropathy

    Science.gov (United States)

    Xiao, Xueshan; Li, Shiqiang

    2017-01-01

    Leber hereditary optic neuropathy (LHON) and dominant optic atrophy (DOA), the most common forms of hereditary optic neuropathy, are easily confused, and it is difficult to distinguish one from the other in the clinic, especially in young children. The present study was designed to survey the mutation spectrum of common pathogenic genes (OPA1, OPA3 and mtDNA genes) and to analyze the genotype-phenotype characteristics of Chinese patients with suspected childhood-onset hereditary optic neuropathy. Genomic DNA and clinical data were collected from 304 unrelated Chinese probands with suspected hereditary optic neuropathy with an age of onset below 14 years. Sanger sequencing was used to screen variants in the coding and adjacent regions of OPA1, OPA3 and the three primary LHON-related mutation sites in mitochondrial DNA (mtDNA) (m.3460G>A, m.11778G>A and m.14484T>C). All patients underwent a complete ophthalmic examination and were compared with age-matched controls. We identified 89/304 (29.3%) primary mtDNA mutations related to LHON in 304 probands, including 76 mutations at m.11778 (76/89, 85.4% of all mtDNA mutations), four at m.3460 (4/89, 4.5%) and nine at m.14484 (9/89, 10.1%). This result was similar to the mutation frequency among Chinese patients with LHON of any age. Screening of OPA1 revealed 23 pathogenic variants, including 11 novel and 12 known pathogenic mutations. This study expanded the OPA1 mutation spectrum, and our results showed that OPA1 mutation is another common cause of childhood-onset hereditary optic neuropathy in Chinese pediatric patients, especially those with disease onset during preschool age. PMID:28081242

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

    Science.gov (United States)

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

    2005-10-01

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

  13. Compound heterozygosity for severe and hypomorphic NDUFS2 mutations cause non-syndromic LHON-like optic neuropathy

    NARCIS (Netherlands)

    Gerber, S.; Ding, M.G.; Gerard, X.; Zwicker, K.; Zanlonghi, X.; Rio, M. del; Serre, V.; Hanein, S.; Munnich, A.; Rotig, A.; Bianchi, L.; Amati-Bonneau, P.; Elpeleg, O.; Kaplan, J.; Brandt, U.; Rozet, J.M.

    2017-01-01

    BACKGROUND: Non-syndromic hereditary optic neuropathy (HON) has been ascribed to mutations in mitochondrial fusion/fission dynamics genes, nuclear and mitochondrial DNA-encoded respiratory enzyme genes or nuclear genes of poorly known mitochondrial function. However, the disease causing gene remains

  14. Heidelberg Retina Tomograph (HRT3) in Population-based Epidemiology : Normative Values and Criteria for Glaucomatous Optic Neuropathy

    NARCIS (Netherlands)

    Ramdas, Wishal D.; Wolfs, Roger C. W.; Hofman, Albert; de Jong, Paulus T. V. M.; Vingerling, Johannes R.; Jansonius, Nomdo M.

    2011-01-01

    Purpose: To establish normative values for Heidelberg Retina Tomograph (HRT3) variables and to develop HRT3-based criteria for glaucomatous optic neuropathy for epidemiological research in a white population. Methods: Consecutive participants in the Rotterdam Study were examined with HRT and

  15. Heidelberg Retina Tomograph (HRT3) in Population-based Epidemiology : Normative Values and Criteria for Glaucomatous Optic Neuropathy

    NARCIS (Netherlands)

    Ramdas, Wishal D.; Wolfs, Roger C. W.; Hofman, Albert; de Jong, Paulus T. V. M.; Vingerling, Johannes R.; Jansonius, Nomdo M.

    2011-01-01

    Purpose: To establish normative values for Heidelberg Retina Tomograph (HRT3) variables and to develop HRT3-based criteria for glaucomatous optic neuropathy for epidemiological research in a white population. Methods: Consecutive participants in the Rotterdam Study were examined with HRT and simulta

  16. [A Case of Albumin-Bound Paclitaxel-Induced Peripheral Neuropathy without Exacerbation].

    Science.gov (United States)

    Uchiyama, Masanobu; Goto, Toshitaka; Ueno, Miho; Kakimoto, Hideki; Mashima, Kouta; Ikari, Yousuke; Takamatsu, Yasushi; Ogata, Kentaro; Kamimura, Hidetoshi

    2017-06-01

    Albumin-bound paclitaxel(nab-PTX)-associated neuropathy decreases the quality of life of cancer patients and leads to dose modification, discontinuation of chemotherapy, and occasionally dose-limiting toxicity. In the present case study, a 92- year-old female patient with peritoneal cancer of carcinomatous peritonitis and carcinomatous ascites was treated with carboplatin plus nab-PTX every 4 weeks as first-line chemotherapy, and a good response was achieved following 4 cycles of this regimen. However, the patient developed Grade 3 peripheral neuropathy and stopped the therapy. As a result, the peripheral neuropathy gradually improved. After 1 year, ascites appeared, and tumor marker(CA125)levels increased. We tried an 8-h infusion of nab-PTX to avoid peripheralneuropathy. After 4 cycles, a positive response was achieved without exacerbation of the peripheralneuropathy. Administering nab-PTX over shorter periods of time has generally led to increased peripheral neuropathy. The severity of peripheralneuropathy can be reduced with a longer infusion time.

  17. Severe acute axonal neuropathy following treatment with arsenic trioxide for acute promyelocytic leukemia: a case report

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    Marcus Kuhn

    2016-05-01

    Full Text Available Peripheral neuropathy is a common complication of arsenic toxicity. Symptoms are usually mild and reversible following discontinuation of treatment. A more severe chronic sensorimotor polyneuropathy characterized by distal axonal-loss neuropathy can be seen in chronic arsenic exposure. The clinical course of arsenic neurotoxicity in patients with coexistence of thiamine deficiency is only anecdotally known but this association may potentially lead to severe consequences. We describe a case of acute irreversible axonal neuropathy in a patient with hidden thiamine deficiency who was treated with a short course of arsenic trioxide for acute promyelocytic leukemia. Thiamine replacement therapy and arsenic trioxide discontinuation were not followed by neurological recovery and severe polyneuropathy persisted at 12-month follow-up. Thiamine plasma levels should be measured in patients who are candidate to arsenic trioxide therapy. Prophylactic administration of vitamin B1 may be advisable. The appearance of polyneuropathy signs early during the administration of arsenic trioxide should prompt electrodiagnostic testing to rule out a pattern of axonal neuropathy which would need immediate discontinuation of arsenic trioxide.

  18. Genetic and biochemical impairment of mitochondrial complex I activity in a family with Leber hereditary optic neuropathy and hereditary spastic dystonia

    NARCIS (Netherlands)

    DeVries, DD; Went, LN; Bruyn, GW; Scholte, HR; Hofstra, RMW; Bolhuis, PA; vanOost, BA

    1996-01-01

    A rare form of Leber hereditary optic neuropathy (LHON) that is associated with hereditary spastic dystonia has been studied in a large Dutch family. Neuropathy and ophthalmological lesions were present together in some family members, whereas only one type of abnormality was found in others. mtDNA

  19. SUR1-Associated Mechanisms Are Not Involved in Ischemic Optic Neuropathy 1 Day Post-Injury.

    Science.gov (United States)

    Nicholson, James D; Guo, Yan; Bernstein, Steven L

    2016-01-01

    Ischemia-reperfusion injury after central nervous system (CNS) injury presents a major health care challenge with few promising treatments. Recently, it has become possible to reduce edema after CNS injury by antagonizing a sulfonylurea receptor 1 (SUR1) regulated ion channel expressed after injury. SUR1 upregulation after injury is a necessary precondition for the formation of this channel, and has been implicated in white matter injury after clinical spinal cord trauma. Glibenclamide, an SUR1 antagonist, appears to have neuroprotective effect against cerebral stroke in an open-label small clinical trial and great effectiveness in reducing damage after varied experimental CNS injury models. Despite its importance in CNS injuries, SUR1 upregulation appears to play no part in rodent anterior ischemic optic neuropathy (rAION) injury as tested by real-time PCR and immunohistochemical staining of rAION-injured rat optic nerve (ON). Furthermore, the SUR1 antagonist glibenclamide administered immediately after rAION injury provided no protection to proximal ON microvasculature 1 day post-injury but may reduce optic nerve head edema in a manner unrelated to ON SUR1 expression. Our results suggest that there may be fundamental differences between rAION optic nerve ischemia and other CNS white matter injuries where SUR1 appears to play a role.

  20. The Retinal Nerve Fiber Layer Defects in Patients with Anterior Ischemic Optic Neuropathy

    Institute of Scientific and Technical Information of China (English)

    HaiLu; QiZang

    1995-01-01

    Purpose:To demonstrate the effects of optic nerve ischemia on retinal nerve fiber layer(RNFL)and the associated visual dysfunction.Methods:23patients(25eyes)wits anterior ischemic optic neuropathy(AION)un derwent fundus fluorescein angiography(FFA),and then red-foree light pic-tures were taken via SE-40exceiter filter.All pictures were printed for RNAFL analysis,Humphrey central field analysis was conducted.All dataobtained fromFFA and visual field defects were analysed statistically.Results:The RNFL defects and the corresponding visual field edfects were pre-sented in 23of 25eyes(92%),The optic disc filling defects,RNAL edfects and visual field defects were found to be highly correspondent to each other.The RNFL defects were mainly the local losses of RNFL which were correspondent to the ischemic regions.Conclusion:The poor optic disc filling or ischemia can result in the RNFL defects which cause the associated visual dysfunction.Because RNFLdefects are irrever-siable changes,the potential values in predicting the prognosis of visual field de-fects caused by RNFL damages were suggested.Eye Science1995;11:165-167.

  1. Analysis of Mitochondrial Gene Mutations in Chinese Pedigrees of Leber's Hereditary Optic Neuropathy

    Institute of Scientific and Technical Information of China (English)

    Ling Lin; Yikai Chen; Yi Tong; Zhihong Zheng; Jianyin Lin

    2002-01-01

    Purpose: To investigate the frequency of common pathogenic primary mitochondrial DNA mutations in Leber's hereditary optic neuropathy (LHON) families.Methods: Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing were used to detect mitochondrial DNA mutations.Sixty-six Chinese examiners from 15 families, including 22 visual affected and their 44 unaffected maternal relatives, underwent molecular genetic evaluation. Eleven normal individuals underwent evaluation as contrl.Results: Of the 15 families with suspicion of LHON, 13 had nucleotide position (nt) Gl1778A mutations, 2 had nt T14484C mutations. All examiners had nt G11719A mutations.Conclusions: The mutations at nucleotides 11778 and 14484 are primary LHON mutations. Molecular genetic findings suggest that the silent mutation at nt G11719A may be a common genetic polymorphism in Chinese.

  2. Clinical Analysis of Leber's Hereditary Optic Neuropathy Harboring mtDNA Mutation at nt11778

    Institute of Scientific and Technical Information of China (English)

    Xinyu Zhang; Qiang Yu; Qingjiong Zhang; Changxian Yi

    2001-01-01

    Purpose: To improve our diagnostic technique through the analysis of clinical features ofLeber's heredita'y optic neuropathy (LHON) harboring mtDNA point mutation at nt11778. Methods: Detection of nt11778 mutation was performed on 38 patients clinically diagnosed as LHON in our ophthalmic center from year 1998 to 2000. Circumstances of onset and family history were obtained and ophthalmoscopy, fundus fluorescein angiography, visual field and visual evoked potential were performed on all 38 patients. Result: 30 In 38 patients (78.95 % ) harbor nt11778 mutation, including 28 male (93.33%) and 2 female (6.67%). The ratio of affected male to female is 14: 1. Patients harboring nt11778 mutation display typical clinical nanifestations. Ccnclusion: Identification of one of the three LHON specifically associated ntDNA mutations is essential to confirm the diagnosis. Eye Science 2001: 17:31 ~ 34.

  3. Single-cell analysis of intercellular heteroplasmy of mtDNA in Leber hereditary optic neuropathy

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    Kobayashi, Y.; Sharpe, H.; Brown, N.

    1994-07-01

    The authors have investigated the distribution of mutant mtDNA molecules in single cells from a patient with Leber hereditary optic neuropathy (LHON). LHON is a maternally inherited disease that is characterized by a sudden-onset bilateral loss of central vision, which typically occurs in early adulthood. More than 50% of all LHON patients carry an mtDNA mutation at nucleotide position 11778. This nucleotide change converts a highly conserved arginine residue to histidine at codon 340 in the NADH-ubiquinone oxidoreductase subunit 4 (ND4) gene of mtDNA. In the present study, the authors used PCR amplification of mtDNA from lymphocytes to investigate mtDNA heteroplasmy at the single-cell level in a LHON patient. They found that most cells were either homoplasmic normal or homoplasmic mutant at nucleotide position 11778. Some (16%) cells contained both mutant and normal mtDNA.

  4. Evidence against an X-linked visual loss susceptibility locus in Leber hereditary optic neuropathy

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    Chalmers, R.M.; Davis, M.B.; Sweeney, M.G.; Wood, N.W.; Harding, A.E. [Inst. of Neurology, London (United Kingdom)

    1996-07-01

    Pedigree analysis of British families with Leber hereditary optic neuropathy (LHON) closely fits a model in which a pathogenic mtDNA mutation interacts with an X-linked visual loss susceptibility locus (VLSL). This model predicts that 60% of affected females will show marked skewing of X inactivation. Linkage analysis in British and Italian families with genetically proven LHON has excluded the presence of such a VLSL over 169 cM of the X chromosome both when all families were analyzed together and when only families with the bp 11778 mutation were studied. Further, there was no excess skewing of X inactivation in affected females. There was no evidence for close linkage to three markers in the pseudoautosomal region of the sex chromosomes. The mechanism of incomplete penetrance and male predominance in LHON remains unclear. 27 refs., 1 fig., 3 tabs.

  5. Gene-Based Therapies for Leber Hereditary Optic Neuropathy. Hype or Hope?

    Science.gov (United States)

    Mackey, David A; Kearns, Lisa S; Hewitt, Alex W

    2016-01-01

    Leber hereditary optic neuropathy has now joined Leber congenital amaurosis in the list of genetic eye diseases undergoing gene therapy clinical trials. Although a dramatic response to treatment would be welcome, a minor improvement in vision is a major challenge in efficacy assessment, given this may occur spontaneously as part of the natural history of minor recovery in some patients. Thus, we must await the outcome of adequately powered clinical trials to know if the treatment is effective, particularly given the likely high cost of such therapeutic interventions in the future. We need global cooperation to ensure that the most suitable patients are enrolled in these trials and that support is provided for participants who need to travel from the Asia-Pacific region to Europe or North America if there are no local arms of these trials.

  6. Changes in Choroidal Thickness follow the RNFL Changes in Leber’s Hereditary Optic Neuropathy

    Science.gov (United States)

    Borrelli, Enrico; Triolo, Giacinto; Cascavilla, Maria Lucia; La Morgia, Chiara; Rizzo, Giovanni; Savini, Giacomo; Balducci, Nicole; Nucci, Paolo; Giglio, Rosa; Darvizeh, Fatemeh; Parisi, Vincenzo; Bandello, Francesco; Sadun, Alfredo A.; Carelli, Valerio; Barboni, Piero

    2016-01-01

    Leber’s hereditary optic neuropathy (LHON) is typically characterized by vascular alterations in the acute phase. The aim of this study was to evaluate choroidal changes occurring in asymptomatic, acute and chronic stages of LHON. We enrolled 49 patients with LHON, 19 with Dominant Optic Atrophy (DOA) and 22 healthy controls. Spectral Domain-Optical Coherence Tomography (SD-OCT) scans of macular and peripapillary regions were performed in all subjects, to evaluate macular and peripapillary choroidal thickness, and retinal nerve fiber layer (RNFL) thicknes. Macular and peripapillary choroidal thicknesses were significantly increased in the acute LHON stage. On the contrary, macular choroidal thickness was significantly reduced in the chronic stage. Furthermore, peripapillary choroidal thickness was decreased in chronic LHON and in DOA. Both RNFL and choroid had the same trend (increased thickness, followed by thinning), but RNFL changes preceded those affecting the choroid. In conclusion, our study quantitatively demonstrated the involvement of the choroid in LHON pathology. The increase in choroidal thickness is a feature of the LHON acute stage, which follows the thickening of RNFL. Conversely, thinning of the choroid is the common outcome in chronic LHON and in DOA. PMID:27853297

  7. Comparison of the Deep Optic Nerve Head Structure between Normal-Tension Glaucoma and Nonarteritic Anterior Ischemic Optic Neuropathy.

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    Eun Ji Lee

    Full Text Available To compare the deep optic nerve head (ONH structure between normal-tension glaucoma (NTG and nonarteritic anterior ischemic optic neuropathy (NAION and also in healthy subjects as a control using enhanced depth imaging (EDI spectral-domain optical coherence tomography (SD-OCT.This prospective cross-sectional study included 21 NAION patients who had been diagnosed as NAION at least 6 months prior to study entry, and 42 NTG patients and 42 healthy controls who were matched with NAION patients in terms of age, intraocular pressure (IOP, and optic disc area. The retinal nerve fiber layer (RNFL thickness in the affected sector was also matched between NAION and NTG patients. The ONH was imaged using SD-OCT with the EDI technique. The anterior lamina cribrosa surface depth (LCD and average prelaminar tissue (PT thickness were measured in a sector of interest in each eye and compared among the three groups.In the sector-matched comparison, LCD was largest in NTG patients, followed by NAION patients, while PT was thinner in NTG patients than in NAION patients (all P < 0.001. NAION patients had a comparable LCD and a thinner PT relative to normal controls (P = 0.170 and < 0.001, respectively.The deep ONH configuration is strikingly different between NTG and NAION. The differing features provide comparative insight into the pathophysiology of the two diseases, and may be useful for differential diagnosis.

  8. Hereditary neuropathies: systematization and diagnostics (clinical case of hereditary motor and sensor neuropathy of the IA type

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    Kolokolova A.M.

    2016-09-01

    Full Text Available Aim: to study the value of routine methods (clinical symptoms, electrophysiological findings and results of DNA analysis in diagnostics of hereditary motor sensory neuropathy type IA in outpatient clinics. Material and Methods. The review of foreign literature is represented. The phenotypic polymorphism, genetic heterogeneity and the difficulties of diagnostics are identified. A family with hereditary motor sensory neuropathy of lAtype is presented, which was diagnosed on the base of available methods in outpatient practice (clinical symptoms, genealogical method, electro-physiological findings and DNA analysis results. Results. Routine algorithm (consistent valuation of clinical symptoms, neurophysiologic findings and the results of DNA analysis helped to verify the diagnosis of hereditary motor sensory neuropathy of lAtype in outpatient practice after more than 20 years of the onset of the disease. Conclusion. The neurologists of outpatient clinics and other specialists must be informed about the availability of diagnostics of hereditary diseases of nervous system.

  9. Incidence and prognostic factor of ethambutol-related optic neuropathy: 10-year experience in southern Taiwan

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    Shih-Chou Chen

    2015-07-01

    Full Text Available To investigate the incidence and prognostic factors of ethambutol-related optic neuropathy (EON in one medical center of southern Taiwan, a retrospective chart review study with 4803 newly diagnosed tuberculosis cases from January 2002 to July 2011 at one medical center hospital in southern Taiwan were reviewed. Of these patients, 1004 had ophthalmic records. Sixty-two cases (1.29% experienced visual impairment and were diagnosed as EON with mean visual acuity of 0.86 ± 0.69 by logMAR. Sixteen of the 62 patients had a follow-up time > 6 months. Of these, eight patients (50% showed visual improvement (an increase in visual acuity of ≥ 2 Snellen lines after ethambutol was discontinued. Another eight patients (50% showed no visual improvement. We analyzed multiple factors between the patients with and without visual improvement by logistic regression, including body weight, daily dose of ethambutol, duration of ethambutol use, cumulative dose of ethambutol, renal function, underlying disease of diabetes mellitus, hypertension, and initial visual acuity showed no statistically significant difference. In conclusion, the incidence of EON was 1.29%. Half of the patients showed visual improvement after discontinuation of ethambutol, and no obvious prognostic factors were found to facilitate the vision recovery. Ethambutol should be discontinued as soon as EON is suspected.

  10. Clinical study of treatment of traumatic optic neuropathy by transcranial approach microscope decompression 30 cases%经颅显微镜下视神经管减压术治疗外伤性视神经损伤30例临床研究

    Institute of Scientific and Technical Information of China (English)

    覃重桥; 陆伟水; 余松祚; 谭适; 陆弘盈

    2011-01-01

    Objective To evaluate the clinical efficacy of treatment of traumatic optic neuropathy by transcranial approach microscope decompression. Methods Totally 36 patients were performed the direct microsurgery to treatment for fracture debris and hematoma and decompression approach with coronal scalp incision. Postoperative supplemented with high - dose steroid impact therapy and nerve nutrition and vasodilators. Results Totally 30 patients were followed - up 3 months and evaluated the efficacy. The visual acuity of 23 patients were improved, and 7 patients were not improve, the total effective rate was 76. 6%. Conclusions It is full exposed, small trauma and completely decompression that traumatic optic neuropathy by transcranial approach microscope decompression, and can be used as an effective way to treat traumatic optic neuropathy.%目的 评价经颅显微镜下视神经管减压术治疗外伤性视神经损伤的临床疗效.方法 30例均作冠状头皮切口,显微镜直视下处理骨折碎片和血肿以及进行视神经管减压,术后辅以大剂量激素冲击和神经营养、扩血管等药物治疗.结果 30例患者术后随访3个月并评价疗效,其中23例视力有不同程度改善,7例视力无提高,总有效率76.6%.结论 经颅显微镜下视神经管减压术具有暴露充分、创伤小、减压彻底等优点,是治疗外伤性视神经损伤的有效方法.

  11. Increased Th17 cells and IL‑17 in rats with traumatic optic neuropathy.

    Science.gov (United States)

    Zheng, Huabin; Zhang, Zhuhong; Luo, Na; Liu, Yuanyuan; Chen, Qingzhong; Yan, Hua

    2014-10-01

    T helper 17 (Th17) cells are strong inducers of numerous autoimmune diseases and inflammation. However, the role of Th17 cells and interleukin (IL)‑17 in traumatic optic neuropathy (TON) are yet to be elucidated. In the present study, a rat model of TON was established using a fluid percussion brain injury device. Th17 cells were found to be upregulated in the spleens of rats in the TON group. In addition, the level of IL‑17 in the retina of rats in the TON group was observed to increase with the upregulation of the Th17 cells. Furthermore, the expression of IL‑17 in the optic nerve was found to be upregulated between one and seven days following injury in the rats in the TON group. These findings strongly suggest that the ratio of Th17 cells and the expression of IL‑17 are upregulated in rats with TON. These findings also provide a rationale for developing therapeutic agents to treat TON.

  12. Leber Hereditary Optic Neuropathy: Do Folate Pathway Gene Alterations Influence the Expression of Mitochondrial DNA Mutation?

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    A Aleyasin

    2010-09-01

    Full Text Available "nBackground: Leber hereditary optic neuropathy (LHON is an inherited form of bilateral optic atrophy leading to the loss of central vision.  The primary cause of vision loss is mutation in the mitochondrial DNA (mtDNA, however, unknown secon­dary genetic and/or epigenetic risk factors are suggested to influence its neuropathology.  In this study folate gene polymor­phisms were examined as a possible LHON secondary genetic risk factor in Iranian patients."nMethods: Common polymorphisms in the MTHFR (C677T and A1298C and MTRR (A66G genes were tested in 21 LHON patients and 150 normal controls."nResults:  Strong associations were observed between the LHON syndrome and C677T (P= 0.00 and A66G (P= 0.00 polymor­phisms.  However, no significant association was found between A1298C (P =0.69 and the LHON syndrome."nConclusion: This is the first study that shows MTHFR C677T and MTRR A66G polymorphisms play a role in the etiology of the LHON syndrome.  This finding may help in the better understanding of mechanisms involved in neural degeneration and vision loss by LHON and hence the better treatment of patients.

  13. Targeting estrogen receptor β as preventive therapeutic strategy for Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Pisano, Annalinda; Preziuso, Carmela; Iommarini, Luisa; Perli, Elena; Grazioli, Paola; Campese, Antonio F; Maresca, Alessandra; Montopoli, Monica; Masuelli, Laura; Sadun, Alfredo A; d'Amati, Giulia; Carelli, Valerio; Ghelli, Anna; Giordano, Carla

    2015-12-15

    Leber's hereditary optic neuropathy (LHON) is a maternally inherited blinding disease characterized by degeneration of retinal ganglion cells (RGCs) and consequent optic nerve atrophy. Peculiar features of LHON are incomplete penetrance and gender bias, with a marked male prevalence. Based on the different hormonal metabolism between genders, we proposed that estrogens play a protective role in females and showed that these hormones ameliorate mitochondrial dysfunction in LHON through the estrogen receptors (ERs). We also showed that ERβ localize to the mitochondria of RGCs. Thus, targeting ERβ may become a therapeutic strategy for LHON specifically aimed at avoiding or delaying the onset of disease in mutation carriers. Here, we tested the effects of ERβ targeting on LHON mitochondrial defective metabolism by treating LHON cybrid cells carrying the m.11778G>A mutation with a combination of natural estrogen-like compounds that bind ERβ with high selectivity. We demonstrated that these molecules improve cell viability by reducing apoptosis, inducing mitochondrial biogenesis and strongly reducing the levels of reactive oxygen species in LHON cells. These effects were abolished in cells with ERβ knockdown by silencing receptor expression or by using specific receptor antagonists. Our observations support the hypothesis that estrogen-like molecules may be useful in LHON prophylactic therapy. This is particularly important for lifelong disease prevention in unaffected LHON mutation carriers. Current strategies attempting to combat degeneration of RGCs during the acute phase of LHON have not been very effective. Implementing a different and preemptive approach with a low risk profile may be very helpful.

  14. Efficacy and Safety of rAAV2-ND4 Treatment for Leber's Hereditary Optic Neuropathy.

    Science.gov (United States)

    Wan, Xing; Pei, Han; Zhao, Min-jian; Yang, Shuo; Hu, Wei-kun; He, Heng; Ma, Si-qi; Zhang, Ge; Dong, Xiao-yan; Chen, Chen; Wang, Dao-wen; Li, Bin

    2016-02-19

    Leber's hereditary optic neuropathy (LHON) is a mitochondrially inherited disease leading to blindness. A mitochondrial DNA point mutation at the 11778 nucleotide site of the NADH dehydrogenase subunit 4 (ND4) gene is the most common cause. The aim of this study was to evaluate the efficacy and safety of a recombinant adeno-associated virus 2 (AAV2) carrying ND4 (rAAV2-ND4) in LHON patients carrying the G11778A mutation. Nine patients were administered rAAV2-ND4 by intravitreal injection to one eye and then followed for 9 months. Ophthalmologic examinations of visual acuity, visual field, and optical coherence tomography were performed. Physical examinations included routine blood and urine. The visual acuity of the injected eyes of six patients improved by at least 0.3 log MAR after 9 months of follow-up. In these six patients, the visual field was enlarged but the retinal nerve fibre layer remained relatively stable. No other outcome measure was significantly changed. None of the nine patients had local or systemic adverse events related to the vector during the 9-month follow-up period. These findings support the feasible use of gene therapy for LHON.

  15. Imaging studies for diagnosing Graves' orbitopathy and dysthyroid optic neuropathy

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    Allan C. Pieroni Gonçalves

    2012-11-01

    Full Text Available Although the diagnosis of Graves' orbitopathy is primarily made clinically based on laboratory tests indicative of thyroid dysfunction and autoimmunity, imaging studies, such as computed tomography, magnetic resonance imaging, ultrasound and color Doppler imaging, play an important role both in the diagnosis and follow-up after clinical or surgical treatment of the disease. Imaging studies can be used to evaluate morphological abnormalities of the orbital structures during the diagnostic workup when a differential diagnosis versus other orbital diseases is needed. Imaging may also be useful to distinguish the inflammatory early stage from the inactive stage of the disease. Finally, imaging studies can be of great help in identifying patients prone to develop dysthyroid optic neuropathy and therefore enabling the timely diagnosis and treatment of the condition, avoiding permanent visual loss. In this paper, we review the imaging modalities that aid in the diagnosis and management of Graves' orbitopathy, with special emphasis on the diagnosis of optic nerve dysfunction in this condition.

  16. Axonal loss and blood flow disturbances in the natural course of indirect traumatic optic neuropathy

    Institute of Scientific and Technical Information of China (English)

    SHI Wei; WANG Huai-zhou; SONG Wei-xian; YANG Wen-li; LI Wei-ye; WANG Ning-li

    2013-01-01

    Background Indirect traumatic optic neuropathy (TON) is an acute injury of the optic nerve associated with severe visual dysfunction,which may be a result of secondary mechanical injury and vascular disorder of the optic nerve due to trauma.We analyzed the natural course of axonal loss and blood flow disturbances in patients with indirect TON to find a possible therapeutic window.Methods A cohort of 54 patients with indirect TON recruited between October 2008 and October 2010 at Beijing Tongren Hospital was retrospectively analyzed.The patients were divided into no light perception group (NLP) and better than NLP (btNLP) group.Specifically,the thickness of the retinal nerve fiber layer (RNFL) measured by spectral domain optical coherence tomography (SD-OCT),and hemodynamic parameters of the ophthalmic artery (OA),central retinal artery (CRA) and posterior ciliary artery (PCA) were determined.Results Two weeks after injury,there was a statistically significant decrease in the thickness of RNFL in the btNLP group as compared with the fellow control eyes (P <0.05).In contrast,in the NLP group,RNFL thickness slightly increased for 2 weeks following injury,then overtly reduced after 4 weeks (P <0.05).Peak systolic velocity (PSV) of CRA was significantly decreased 4 weeks after injury (P <0.05) in both the NLP group and btNLP group (P <0.05).The thickness of RNFL in the NLP group was negatively correlated with PSV of CRA after 1 week of injury (P <0.05,r=-0.962).Conclusions SD-OCT is a useful supplement in detecting the axonal loss in TON.The dynamic change of the thickness of RNFL appears to correlate with the hemodynamic disturbances in the natural course of TON.The first 2 weeks following an injury is critical and should be considered as the therapeutic window for TON patients.

  17. [Determination of the individual normal range of intraocular pressure in differential diagnosis between pseudonormal tension glaucoma and ischemic optic neuropathies].

    Science.gov (United States)

    Mamikonian, V P; Galoian, N S; Sheremet, N L; Kazarian, É É; Shmeleva-Demir, O A; Antonov, A A; Tatevosian, A A

    2014-01-01

    The study investigated the relation between the actual intraocular pressure (IOP) and its individual normal range in normal-tension glaucoma (NTG) and ischemic optic neuropathy (ION) outcome. A total of 39 patients (61 eyes) were examined. Group 1 included 19 patients (35 eyes) with newly diagnosed NTG, group 2--20 patients (26 eyes) with the ION outcome. Besides conventional tests, the ophthalmic assessment in all patients included determination of the individual normal range of IOP and evaluation of biomechanical properties of the cornea. It is showed that determination of the individual normal range of IOP may play a key role in confusing cases of differential diagnosis between NTG and ION. The average actual IOP in patients with NTG generally exceeds the individual normal range by 40% (more than 5 mmHg), whereas in patients with the ION outcome--by only 11.7% (less than 5 mmHg - buffer range). No statistically significant difference in IOP measurements by different tonometry methods was found in either NTG or ION patients with corneal compensated IOP less than 21 mmHg.

  18. Diode Laser 810 Nm as a Potential Treatment to Improve Visual Function in Nonarteritic Anterior Ischemic Optic Neuropathy (NAION

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    Mohammad Hossein Heidari

    2011-01-01

    Full Text Available Nonarteritic anterior ischemic optic neuropathy (NAION is one of the most widespread visually disabling diseases in the middle-aged and elderly population. The optic nerve damage appears to result from a perfusion insufficiency in the short posterior ciliary arteries leading to infarction of the retrolaminar portion of the optic disc. Induced Heat shock protein (Hsp is known to have neuroprotective effects against ischemic injury of the central nervous system in mammals. Transpupillary thermotherapy (TTT application to the optic nerve head induces Hsp70 expression. We hypothesize that Transpupillary thermotherapy (TTT could be a novel method for improving and preserving the function of the optic nerve fibers in the eye with NAION. An 810-nm diode laser beam is focused to the center of the optic nerve head to induce Hsp. Controlled prospective and randomized clinical trial is necessary to confirm conclusively the effectiveness of this method.

  19. Optic Disc and Retinal Nerve Fiber Layer Thickness Evaluation of the Fellow Eyes in Non-Arteritic Ischemic Optic Neuropathy

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    Medine Yılmaz Dağ

    2015-05-01

    Full Text Available Objectives: To examine the fellow eyes in unilateral non-arteritic ischemic optic neuropathy (NAION and to compare their optic disc parameters and peripapillary retinal nerve fiber layer (RNFL thickness with age-and refraction-matched normal controll subjects, using Heidelberg Retinal Tomograph 2 (HRT II. Materials and Methods: The fellow eyes of 40 patients with typical unilateral NAION (study group and one randomly chosen eye of 42 age-, sex-, and refraction-matched normal control subjects were enrolled in the study. Optic disc morphologic features (average disc area, cup area, rim area, disc volume, rim volume, cup/disc area ratio, cup depth and peripapillary RNFL thickness were evaluated using HRT II, a confoal scanning ophtalmoscopy. Results: In the study group, there were 26 (65% men and 14 (35% women, whereas there were 27 (64% men and 15 (36% women in the control group (Chi square test, p=0.89. Mean age of the patients in the study and control groups was 59.4±10.3 and 57.7±9.1 years, respectively (T test, p=0.72. There was not any statistically significant difference regarding mean spheric equivalent between the two groups (Mann-Whitney U-test, p=0.203. The NAION unaffected fellow eyes had significantly smaller disc areas, cup areas, cup volumes, cup-disc area ratios (vertical and lineer, and cup depths than the control eyes (Mann-Whitney U-test; p<0.05, whereas there was no significant difference in the RNFL thickness between the two. Conclusion: A comparison of the fellow eyes in patients with unilateral NAION and the control eyes showed a significant difference in optic disc parameters and the morphology of RNFL. These differences could be important in the pathogenesis of NAION and needs to have further investigated. (Turk J Ophthalmol 2015; 45: 111-114

  20. Optic Nerve Lymphoma. Report of Two Cases and Review of the Literature

    Science.gov (United States)

    Kim, Jennifer L.; Mendoza, Pia; Rashid, Alia; Hayek, Brent; Grossniklaus, Hans E.

    2014-01-01

    Lymphoma may involve the optic nerve as isolated optic nerve lymphoma or in association with CNS or systemic lymphoma. We present two biopsy-proven non-Hodgkin lymphomas of the optic nerve and compare our findings with previously reported cases. We discuss the mechanism of metastasis, classification of optic nerve involvement, clinical features, radiologic findings, optic nerve biopsy indications and techniques, histologic features, and treatments. We propose a classification system of optic nerve lymphoma: isolated optic nerve involvement, optic nerve involvement with CNS disease, optic nerve involvement with systemic disease, and optic nerve involvement with primary intraocular lymphoma. Although it is an uncommon cause of infiltrative optic neuropathy, optic nerve metastasis should be considered in patients with a history of lymphoma. The recommended approach to a patient with presumed optic nerve lymphoma includes neuroimaging, and cerebrospinal fluid evaluation as part of the initial work-up, then judicious use of optic nerve biopsy, depending on the clinical situation. PMID:25595061

  1. Leber’s hereditary optic neuropathy is multiorgan not mono-organ

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    Finsterer J

    2016-11-01

    Full Text Available Josef Finsterer,1 Sinda Zarrouk-Mahjoub2 1Krankenanstalt Rudolfstiftung, Vienna, Austria; 2Genomics Platform, Pasteur Institute of Tunis, Tunisia Abstract: Leber’s hereditary optic neuropathy (LHON is a maternally inherited mitochondrial disorder with bilateral loss of central vision primarily due to mitochondrial DNA (mtDNA mutations in subunits of complex I in the respiratory chain (primary LHON mutations, while other mtDNA mutations can also be causative. Since the first description, it is known that LHON is not restricted to the eyes but is a multisystem disorder additionally involving the central nervous system, ears, endocrinological organs, heart, bone marrow, arteries, kidneys, or the peripheral nervous system. Multisystem involvement may start before or after the onset of visual impairment. Involvement of organs other than the eyes may be subclinical depending on age, ethnicity, and possibly the heteroplasmy rate of the responsible primary LHON mutation. Primary LHON mutations may rarely manifest without ocular compromise but with arterial hypertension, various neurodegenerative diseases, or Leigh syndrome. Patients with LHON need to be closely followed up to detect at which point organs other than the eyes become affected. Multiorgan disease in LHON often responds more favorably to symptomatic treatment than the ocular compromise. Keywords: mitochondrial DNA, heteroplasmy, respiratory chain, LHON, genotype–phenotype correlation

  2. Leber遗传性视神经病变%Hereditary Leber's optic neuropathy

    Institute of Scientific and Technical Information of China (English)

    林玲; 郑志; 陈贻锴

    2001-01-01

    @@ Leber于1871年首次报道了一种遗传性视神经病变的临床症状、体征和遗传特性,该病以急性或亚急性双侧中心视力丧失为主要特征,可通过无临床症状的母亲传递给后代,似乎更好发于年轻男性[1~5],此后该病被称为莱贝视神经萎缩(Leber's hereditary optic neuropathy,LHON).1988年,Wallace等首次发现LHON存在线粒体DNA(mitochondrial DNA,mtDNA)的病理性突变,他们发现在许多LHON家族成员均有mtDNA 11778位点的点突变[6].此后,许多研究证实LHON为母系遗传性疾病, 其主要病因是线粒体基因组某些位点发生突变,是一种最为常见的线粒体遗传病[7].

  3. Mitochondrial ND3 as the novel causative gene for Leber hereditary optic neuropathy and dystonia.

    Science.gov (United States)

    Wang, Kang; Takahashi, Yuji; Gao, Zong-Liang; Wang, Guo-Xiang; Chen, Xian-Wen; Goto, Jun; Lou, Jin-Ning; Tsuji, Shoji

    2009-10-01

    Leber hereditary optic neuropathy and dystonia (LDYT) is a mitochondrial disorder associated with variable combinations of vision loss and progressive generalized dystonia. LDYT is a unique oxidative phosphorylation disorder caused by mutations in mitochondrial ND6 or ND4 gene. In this paper, we describe a Chinese family with 18 LDYT patients. The comprehensive nucleotide sequence analysis of the entire mitochondrial genome using resequencing microarray revealed a mutation (mtND3*10197A (m.10197G>A)) substituting a threonine for a highly conserved alanine at codon 47 of MTND3 on the background of haplogroup D4b. Quantitative analysis of the heteroplasmy of the mutation revealed a homoplasmy in the leukocytes of all the affected individuals on the maternal side. This is the first description of the ND3 mutation causing LDYT. The mtND3*10197A (m.10197G>A) mutation has recently been described in French and Korean patients with Leigh syndrome. These findings suggest that the clinical presentations associated with the mtND3*10197A (m.10197G>A) mutation (ND3) are much wider, encompassing those of LDYT and Leigh syndrome.

  4. Pitfalls in the molecular genetic diagnosis of Leber hereditary optic neuropathy (LHON)

    Energy Technology Data Exchange (ETDEWEB)

    Johns, D.R. (Beth Israel Hospital, Boston, MA (United States)); Neufeld, M.J. (Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States))

    1993-10-01

    Pathogenetic mutations in mtDNA are found in the majority of patients with Leber hereditary optic neuropathy (LHON), and molecular genetic techniques to detect them are important for diagnosis. A false-positive molecular genetic error has adverse consequences for the diagnosis of this maternally inherited disease. The authors found a number of mtDNA polymorphisms that occur adjacent to known LHON-associated mutations and that confound their molecular genetic detection. These transition mutations occur at mtDNA nt 11779 (SfaNI site loss, 11778 mutation), nt 3459 (BsaHI site loss, 3460 mutation), nt 15258 (AccI site loss, 15257 mutation), nt 14485 (mismatch primer Sau3AI site loss, 14484 mutation), and nt 13707 (BstNI site loss, 13708 mutation). Molecular genetic detection of the most common pathogenetic mtDNA mutations in LHON, using a single restriction enzyme, may be confounded by adjacent polymorphisms that occur with a false-positive rate of 2%-7%. 19 refs.

  5. Leber’s hereditary optic neuropathy is multiorgan not mono-organ

    Science.gov (United States)

    Finsterer, Josef; Zarrouk-Mahjoub, Sinda

    2016-01-01

    Leber’s hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disorder with bilateral loss of central vision primarily due to mitochondrial DNA (mtDNA) mutations in subunits of complex I in the respiratory chain (primary LHON mutations), while other mtDNA mutations can also be causative. Since the first description, it is known that LHON is not restricted to the eyes but is a multisystem disorder additionally involving the central nervous system, ears, endocrinological organs, heart, bone marrow, arteries, kidneys, or the peripheral nervous system. Multisystem involvement may start before or after the onset of visual impairment. Involvement of organs other than the eyes may be subclinical depending on age, ethnicity, and possibly the heteroplasmy rate of the responsible primary LHON mutation. Primary LHON mutations may rarely manifest without ocular compromise but with arterial hypertension, various neurodegenerative diseases, or Leigh syndrome. Patients with LHON need to be closely followed up to detect at which point organs other than the eyes become affected. Multiorgan disease in LHON often responds more favorably to symptomatic treatment than the ocular compromise. PMID:27843288

  6. White Matter Changes in Two Leber's Hereditary Optic Neuropathy Pedigrees: 12-Year Follow-Up.

    Science.gov (United States)

    Jančić, Jasna; Dejanović, Ivana; Radovanović, Saša; Ostojić, Jelena; Kozić, Duško; Đurić-Jovičić, Milica; Samardžić, Janko; Ćetković, Mila; Kostić, Vladimir

    2016-01-01

    We are presenting two Leber's hereditary optic neuropathy (LHON) pedigrees with abnormal magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (H-MRS) findings but without neurological manifestation associated with LHON. The study included 14 LHON patients and 41 asymptomatic family members from 12 genealogically unrelated families. MRI showed white matter involvement and H-MRS exhibited metabolic anomalies within 12 LHON families. Main outcome measures were abnormal MRI and H-MRS findings in two pedigrees. MRI of the proband of the first pedigree showed a single demyelinating lesion in the right cerebellar hemisphere, while the proband of the second family displayed multiple supratentorial and infratentorial lesions, compatible with the demyelinating process, and both the absolute choline (Cho) concentration and Cho/creatinine ratio were increased. MRI and H-MRS profiles of both affected and unaffected mitochondrial DNA mutation carriers suggest more widespread central nervous involvement in LHON. Although even after 12 years our patients did not develop neurological symptoms, MRI could still be used to detect possible changes during the disease progression.

  7. Bilateral Anterior Ischaemic Optic Neuropathy in a Child on Continuous Peritoneal Dialysis

    Science.gov (United States)

    Al-Kaabi, Abdullah; Haider, Agha S.; Shafeeq, Mohammed O.; El-Naggari, Mohammed A.; El-Nour, Ibtisam; Ganesh, Anuradha

    2016-01-01

    Non-arteritic anterior ischaemic optic neuropathy (NAION) is a serious complication of continuous peritoneal dialysis (CPD) which can lead to poor vision and blindness. We report a five-year-old girl who had undergone a bilateral nephrectomy at the age of one year and was on home CPD. She was referred to the Paediatric Ophthalmology Unit of Sultan Qaboos University Hospital, Muscat, Oman, in 2013 with acute bilateral vision loss, preceded by a three-day history of poor oral intake. At presentation, the patient had severe systemic hypotension. An ophthalmological examination revealed severe bilateral visual impairment and NAION. She was treated with intravenous methylprednisolone and normal saline boluses. At a five-month follow-up, the visual acuity of the right eye had improved but vision in the left eye remained the same. Acute bilateral blindness due to NAION while on CPD is a rare condition in childhood. Paediatricians should be aware of this complication in order to ensure prompt management. PMID:28003901

  8. Severe manifestation of Leber's hereditary optic neuropathy due to 11778G>A mtDNA mutation in a female with hypoestrogenism due to Perrault syndrome.

    Science.gov (United States)

    Badura-Stronka, Magdalena; Wawrocka, Anna; Zawieja, Krzysztof; Silska, Sylwia; Krawczyński, Maciej Robert

    2013-11-01

    Perrault syndrome (PS) is a rare autosomal recessive condition with ovarian dysgenesis, hearing deficit and neurological abnormalities in female patients. The molecular basis of the syndrome is heterogeneous, mutations in the HSD17B4 gene have been identified in one family and mutations in the HARS2 gene have been found in another one. We have excluded pathogenic changes in the HSD17B4 gene and in the HARS2 gene by a direct sequencing of all coding exons in a female with clinical hallmarks of PS, ataxia and mild mental retardation. In addition, the patient suffers from severe Leber's hereditary optic neuropathy (LHON) due to 11778G>A mtDNA mutation. This case is the first reported patient with PS and LHON. Possible influence of hypoestrogenism on the manifestation of optic neuropathy in this patient is discussed in the context of recent findings concerning the crucial role of estrogens in supporting the vision capacity in LHON-related mtDNA mutation carriers.

  9. Magnetic resonance imaging (MRI) in the diagnosis of optic neuritis and neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Kakisu, Yonetsugu; Adachi-Usami, Emiko; Kojima, Shigeyuki; Hirayama, Keizo

    1989-02-01

    Magnetic resonance imaging (MRI) was performed in thirty patients who had been suffering from optic neuritis (ON). Twenty-one cases were caused by multiple sclerosis (MS) and in 9 cases the causes been defined. In MRI, abnormalities were found in 17 out of 21 MS cases in several places such as near the ventricles, mid-brain, spinal cord etc. Increased signals from the optic chiasm to optic radiation were found in 5 cases. However, abnormal MRI findings did not always correspond to Goldmann visual field defects. In 3 out of 9 cases of ON with unknown causes, high signals in the white matter of the brain were found, and it was suggested that those may develop to MS. MRI was, thus, proved to be very useful for the diagnois of MS.

  10. Neuron-Specific Enolase Is Elevated in Asymptomatic Carriers of Leber's Hereditary Optic Neuropathy

    Science.gov (United States)

    Yee, Kenneth M.; Ross-Cisneros, Fred N.; Lee, Jeong Goo; Da Rosa, Arlon Bastos; Salomao, Solange R.; Berezovsky, Adriana; Belfort, Rubens; Chicani, Filipe; Moraes-Filho, Milton; Sebag, Jerry; Carelli, Valerio; Sadun, Alfredo A.

    2012-01-01

    Purpose. Neuron-specific enolase (NSE) is a biomarker for neuronal stress. Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease affecting retinal ganglion cells (RGC). These RGCs and their axons in the retinal nerve fiber layer (RNFL) and optic nerve head may show subclinical pathology in unaffected mutation carriers, or undergo cell death in affected patients. We hypothesize that increased levels of blood NSE may characterize LHON carriers as a biomarker of ongoing RGC stress. Methods. Serum was obtained from 74 members of a Brazilian pedigree with LHON carrying the homoplasmic 11778/ND4 mitochondrial DNA mutation. Classified by symptoms and psychophysical metrics, 46/74 patients were unaffected mutation “carriers,” 14/74 were “affected,” and 14/74 were “off-pedigree” controls. Serum NSE levels were determined by ELISA specific for the γ subunit of NSE. Results. Serum NSE concentrations in carriers (27.17 ± 39.82 μg/L) were significantly higher than affected (5.66 ± 4.19 μg/L; P = 0.050) and off-pedigree controls (6.20 ± 2.35 μg/L; P = 0.047). Of the 14/46 (30.4 %) carriers with significantly elevated NSE levels (mean = 75.8 ± 42.3 μg/L), 9/14 (64.3%) were male. Furthermore, NSE levels were nearly three times greater in asymptomatic male carriers (40.65 ± 51.21 μg/L) than in asymptomatic female carriers (15.85 ± 22.27 μg/L; P = 0.034). Conclusions. Serum NSE levels are higher in LHON carriers compared with affected and off-pedigree individuals. A subgroup of mostly male carriers had significantly elevated serum NSE levels. Thus, male carriers are at higher risk for LHON-related neuronal stress. PMID:22893673

  11. [Acute Sensory Neuropathies and Acute Autonomic Neuropathies].

    Science.gov (United States)

    Koike, Haruki

    2015-11-01

    From the perspective of neuropathies with an acute onset mimicking that of Guillain-Barré syndrome (GBS), cases with profound sensory and/or autonomic impairment without any significant weakness have been reported. Although the possibility of infectious or toxic etiologies should be carefully excluded, immune mechanisms similar to those in GBS are suggested to be involved in these so-called acute sensory neuropathies and acute autonomic neuropathies. The types of neuropathy include those with predominant sensory manifestations, predominant autonomic manifestations such as autoimmune autonomic ganglionopathy, and both sensory and autonomic manifestations such as acute autonomic and sensory neuropathy. Neuronopathy in the sensory and/or autonomic ganglia (i.e., ganglionopathy) has been commonly suggested in patients with these types of neuropathies. The presence of Anti-GD1b antibodies has been reported in some of the patients with acute sensory neuropathy with deep sensory impairment, whereas anti-ganglionic acetylcholine receptor antibodies are reported to be present in half of the patients with autoimmune autonomic ganglionopathy. The discovery of anti-ganglionic acetylcholine receptor antibodies significantly expanded the spectrum of autoimmune autonomic ganglionopathy. This is because some of the patients with chronic progression mimicking neurodegenerative diseases such as pure autonomic failure were positive for these antibodies. In contrast, pathologically significant autoantibodies have not been identified in acute autonomic and sensory neuropathy. Further studies are needed to clarify the pathogenesis and the spectrum of these types of neuropathies.

  12. [Diabetic neuropathy].

    Science.gov (United States)

    Lechleitner, Monika; Abrahamian, Heidemarie; Francesconi, Claudia; Kofler, Markus

    2016-04-01

    These are the guidelines for diagnosis and treatment of diabetic neuropathy. This diabetic late complication comprises a number of mono- and polyneuropathies, plexopathies, radiculopathies and autonomic neuropathy. The position statement summarizes characteristic clinical symptoms and techniques for diagnostic assessment of diabetic neuropathy. Recommendations for the therapeutic management of diabetic neuropathy, especially for the control of pain in sensorimotor neuropathy, are provided.

  13. Stem Cell Ophthalmology Treatment Study (SCOTS): bone marrow-derived stem cells in the treatment of Leber's hereditary optic neuropathy

    Science.gov (United States)

    Weiss, Jeffrey N.; Levy, Steven; Benes, Susan C.

    2016-01-01

    The Stem Cell Ophthalmology Treatment Study (SCOTS) is currently the largest-scale stem cell ophthalmology trial registered at ClinicalTrials.gov (identifier: NCT01920867). SCOTS utilizes autologous bone marrow-derived stem cells (BMSCs) to treat optic nerve and retinal diseases. Treatment approaches include a combination of retrobulbar, subtenon, intravitreal, intra-optic nerve, subretinal, and intravenous injection of autologous BMSCs according to the nature of the disease, the degree of visual loss, and any risk factors related to the treatments. Patients with Leber's hereditary optic neuropathy had visual acuity gains on the Early Treatment Diabetic Retinopathy Study (ETDRS) of up to 35 letters and Snellen acuity improvements from hand motion to 20/200 and from counting fingers to 20/100. Visual field improvements were noted. Macular and optic nerve head nerve fiber layer typically thickened. No serious complications were seen. The increases in visual acuity obtained in our study were encouraging and suggest that the use of autologous BMSCs as provided in SCOTS for ophthalmologic mitochondrial diseases including Leber's hereditary optic neuropathy may be a viable treatment option. PMID:27904503

  14. Optic nerve histopathology in a case of Wolfram Syndrome

    DEFF Research Database (Denmark)

    Ross-Cisneros, Fred N; Pan, Billy X; Silva, Ruwan A

    2013-01-01

    Mitochondrial dysfunction in Wolfram Syndrome (WS) is controversial and optic neuropathy, a cardinal clinical manifestation, is poorly characterized. We here describe the histopathological features in postmortem retinas and optic nerves (ONs) from one patient with WS, testing the hypothesis...... that mitochondrial dysfunction underlies the pathology. Eyes and retrobulbar ONs were obtained at autopsy from a WS patient, and compared with those of a Leber hereditary optic neuropathy (LHON) patient and one healthy control. Retinas were stained with hematoxylin & eosin for general morphology and ONs were...... of axonal degeneration, involving primarily the papillomacular bundle, closely resembled LHON and other mitochondrial optic neuropathies, supporting that mitochondrial dysfunction underlies its pathogenesis....

  15. Peripheral neuropathy of a forelimb in horses: 27 cases (2000-2013).

    Science.gov (United States)

    Emond, Anne-Laure; Bertoni, Lélia; Seignour, Maeva; Coudry, Virginie; Denoix, Jean-Marie

    2016-11-15

    OBJECTIVE To describe the clinical features, diagnostic procedures, management, and outcome of horses with peripheral neuropathy of a forelimb. DESIGN Retrospective case series. ANIMALS 27 horses. PROCEDURES Records from 2000 to 2013 were reviewed to identify horses with peripheral neuropathy of a forelimb. Horses were grouped as having predominant lesions of a suprascapular nerve, axillary nerve, or radial nerve (alone or in association with other brachial plexus nerves) on the basis of physical examination and diagnostic imaging findings. Treatments were primarily conservative. Signalment, history, lameness characteristics, diagnostic imaging features, case management, and outcomes were evaluated. RESULTS Predominant lesions of a suprascapular nerve, axillary nerve, and radial nerve were identified in 11, 2, and 14 horses, respectively. Eight horses with predominant suprascapular nerve injury and 9 with injury to a radial nerve alone or in association with other nerves returned to their previous activity level or intended use after mean recovery periods of 9.3 and 13.3 months, respectively; 2 horses with a predominant axillary nerve injury had this outcome after a mean 3.5-month recovery period. Ultrasonography was useful for evaluation of muscle atrophy and other injuries during the initial examination (in 27 horses) and the rehabilitation period (in 7 horses). CONCLUSIONS AND CLINICAL RELEVANCE Most horses with peripheral neuropathy of a forelimb returned to athletic soundness following an adequate period of rest. Horses with lesions of a radial nerve alone or in association with other nerves typically required longer recovery times than did those with predominant injuries of a suprascapular nerve.

  16. Ultrasound in the diagnosis of a median neuropathy in the forearm: case report

    Directory of Open Access Journals (Sweden)

    Yoon Joon-Shik

    2007-12-01

    Full Text Available Abstract Background Electrodiagnostic studies are traditionally used in the diagnosis of focal neuropathies, however they lack anatomical information regarding the nerve and its surrounding structures. The purpose of this case is to show that high-resolution ultrasound used as an adjunct to electrodiagnostic studies may complement this lack of information and give insight to the cause. Case presentation A 60-year-old male patient sustained a forearm traction injury resulting in progressive weakness and functional loss in the first three digits of the right hand. High-resolution ultrasound showed the presence of an enlarged nerve and a homogenous soft-tissue structure appearing to engulf the nerve. The contralateral side was normal. Surgery revealed fibrotic bands emanating from the flexor digitorum profundus muscle compressing the median nerve thus confirming the ultrasound findings. Conclusion A diagnostically challenging case of median neuropathy in the forearm is presented in which high-resolution ultrasound was valuable in establishing an anatomic etiology and directing appropriate management.

  17. Vinca alkaloids induced peripheral neuropathy- case series and review of literature

    OpenAIRE

    2016-01-01

    Vinca alkaloids include vincristine, vinblastine and vinorelbine. Peripheral neuropathy is one of the commonest side effects of these agents. Patients with decrease level of serum folate and vitamin B 12 are more prone to develop peripheral neuropathy. Underlying hepatic impairment and concurrent drugs which decreases Vinca alkaloids hepatic metabolism also increases the susceptibility to neuropathy. Peripheral neuropathy can be troublesome for significant number of patients. There is no spec...

  18. Amplitude of sensory nerve action potential in early stage diabetic peripheral neuropathy: an analysis of 500 cases.

    Science.gov (United States)

    Zhang, Yunqian; Li, Jintao; Wang, Tingjuan; Wang, Jianlin

    2014-07-15

    Early diagnosis of diabetic peripheral neuropathy is important for the successful treatment of diabetes mellitus. In the present study, we recruited 500 diabetic patients from the Fourth Affiliated Hospital of Kunming Medical University in China from June 2008 to September 2013: 221 cases showed symptoms of peripheral neuropathy (symptomatic group) and 279 cases had no symptoms of peripheral impairment (asymptomatic group). One hundred healthy control subjects were also recruited. Nerve conduction studies revealed that distal motor latency was longer, sensory nerve conduction velocity was slower, and sensory nerve action potential and amplitude of compound muscle action potential were significantly lower in the median, ulnar, posterior tibial and common peroneal nerve in the diabetic groups compared with control subjects. Moreover, the alterations were more obvious in patients with symptoms of peripheral neuropathy. Of the 500 diabetic patients, neural conduction abnormalities were detected in 358 cases (71.6%), among which impairment of the common peroneal nerve was most prominent. Sensory nerve abnormality was more obvious than motor nerve abnormality in the diabetic groups. The amplitude of sensory nerve action potential was the most sensitive measure of peripheral neuropathy. Our results reveal that varying degrees of nerve conduction changes are present in the early, asymptomatic stage of diabetic peripheral neuropathy.

  19. Clustering of Caucasian Leber hereditary optic neuropathy patients containing the 11778 or 14484 mutations on an mtDNA lineage

    Energy Technology Data Exchange (ETDEWEB)

    Brown, M.D.; Sun, F.; Wallace, D.C. [Emory Univ. School of Medicine, Atlanta, GA (United States)

    1997-02-01

    Leber hereditary optic neuropathy (LHON) is a type of blindness caused by mtDNA mutations. Three LHON mtDNA mutations at nucleotide positions 3460, 11778, and 14484 are specific for LHON and account for 90% of worldwide cases and are thus designated as {open_quotes}primary{close_quotes} LHON mutations. Fifteen other {open_quotes}secondary{close_quotes} LHON mtDNA mutations have been identified, but their pathogenicity is unclear. mtDNA haplotype and phylogenetic analysis of the primary LHON mutations in North American Caucasian patients and controls has shown that, unlike the 3460 and 11778 mutations, which are distributed throughout the European-derived (Caucasian) mtDNA phylogeny, patients containing the 14484 mutation tended to be associated with European mtDNA haplotype J. To investigate this apparent clustering, we performed {chi}{sup 2}-based statistical analyses to compare the distribution of LHON patients on the Caucasian phylogenetic tree. Our results indicate that, unlike the 3460 and 11778 mutations, the 14484 mutation was not distributed on the phylogeny in proportion to the frequencies of the major Caucasian mtDNA haplogroups found in North America. The 14484 mutation was next shown to occur on the haplogroup J background more frequently that expected, consistent with the observation that {approximately}75% of worldwide 14484-positive LHON patients occur in association with haplogroup J. The 11778 mutation also exhibited a moderate clustering on haplogroup J. These observations were supported by statistical analysis using all available mutation frequencies reported in the literature. This paper thus illustrates the potential importance of genetic background in certain mtDNA-based diseases, speculates on a pathogenic role for a subset of LHON secondary mutations and their interaction with primary mutations, and provides support for a polygenic model for LHON expression in some cases. 18 refs., 3 tabs.

  20. Peripheral Neuropathy

    Science.gov (United States)

    ... neuropathy are caused by inborn mistakes in the genetic code or by new genetic mutations. × Definition Peripheral neuropathy ... neuropathy are caused by inborn mistakes in the genetic code or by new genetic mutations. View Full Definition ...

  1. Metabolic neuropathies

    Science.gov (United States)

    Neuropathy - metabolic ... can be caused by many different things. Metabolic neuropathy may be caused by: A problem with the ... one of the most common causes of metabolic neuropathies. People who are at the highest risk for ...

  2. Long-term outcomes of gene therapy for the treatment of Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Yang, Shuo; Ma, Si-Qi; Wan, Xing; He, Heng; Pei, Han; Zhao, Min-Jian; Chen, Chen; Wang, Dao-Wen; Dong, Xiao-Yan; Yuan, Jia-Jia; Li, Bin

    2016-08-01

    Leber's hereditary optic neuropathy (LHON) is a disease that leads to blindness. Gene therapy has been investigated with some success, and could lead to important advancements in treating LHON. This was a prospective, open-label trial involving 9 LHON patients at Tongji Hospital, Wuhan, China, from August 2011 to December 2015. The purpose of this study was to evaluate the long-term outcomes of gene therapy for LHON. Nine LHON patients voluntarily received an intravitreal injection of rAAV2-ND4. Systemic examinations and visual function tests were performed during the 36-month follow-up period to determine the safety and efficacy of this gene therapy. Based on successful experiments in an animal model of LHON, 1 subject also received an rAAV2-ND4 injection in the second eye 12months after gene therapy was administered in the first eye. Recovery of visual acuity was defined as the primary outcome of this study. Changes in the visual field, visual evoked potential (VEP), optical coherence tomography findings, liver and kidney function, and antibodies against AAV2 were defined as secondary endpoints. Eight patients (Patients 2-9) received unilateral gene therapy and visual function improvement was observed in both treated eyes (Patients 4, 6, 7, and 8) and untreated eyes (Patients 2, 3, 4, 6 and 8). Visual regression fluctuations, defined as changes in visual acuity greater than or equal to 0.3 logMAR, were observed in Patients 2 and 9. Age at disease onset, disease duration, and the amount of remaining optic nerve fibers did not have a significant effect on the visual function improvement. The visual field and pattern reversal VEP also improved. The patient (Patient 1) who received gene therapy in both eyes had improved visual acuity in the injected eye after the first treatment. Unfortunately, visual acuity in this eye decreased 3months after he received gene therapy in the second eye. Animal experiments suggested that ND4 expression remains stable in the

  3. Long-term outcomes of gene therapy for the treatment of Leber's hereditary optic neuropathy

    Directory of Open Access Journals (Sweden)

    Shuo Yang

    2016-08-01

    Full Text Available Leber's hereditary optic neuropathy (LHON is a disease that leads to blindness. Gene therapy has been investigated with some success, and could lead to important advancements in treating LHON. This was a prospective, open-label trial involving 9 LHON patients at Tongji Hospital, Wuhan, China, from August 2011 to December 2015. The purpose of this study was to evaluate the long-term outcomes of gene therapy for LHON. Nine LHON patients voluntarily received an intravitreal injection of rAAV2-ND4. Systemic examinations and visual function tests were performed during the 36-month follow-up period to determine the safety and efficacy of this gene therapy. Based on successful experiments in an animal model of LHON, 1 subject also received an rAAV2-ND4 injection in the second eye 12 months after gene therapy was administered in the first eye. Recovery of visual acuity was defined as the primary outcome of this study. Changes in the visual field, visual evoked potential (VEP, optical coherence tomography findings, liver and kidney function, and antibodies against AAV2 were defined as secondary endpoints. Eight patients (Patients 2–9 received unilateral gene therapy and visual function improvement was observed in both treated eyes (Patients 4, 6, 7, and 8 and untreated eyes (Patients 2, 3, 4, 6 and 8. Visual regression fluctuations, defined as changes in visual acuity greater than or equal to 0.3 logMAR, were observed in Patients 2 and 9. Age at disease onset, disease duration, and the amount of remaining optic nerve fibers did not have a significant effect on the visual function improvement. The visual field and pattern reversal VEP also improved. The patient (Patient 1 who received gene therapy in both eyes had improved visual acuity in the injected eye after the first treatment. Unfortunately, visual acuity in this eye decreased 3 months after he received gene therapy in the second eye. Animal experiments suggested that ND4 expression remains

  4. Characterization of retinal nerve fiber layer thickness changes associated with Leber’s hereditary optic neuropathy by optical coherence tomography

    Science.gov (United States)

    ZHANG, YIXIN; HUANG, HOUBIN; WEI, SHIHUI; QIU, HUAIYU; GONG, YAN; LI, HONGYANG; DAI, YANLI; JIANG, ZHAOCAI; LIU, ZIHAO

    2014-01-01

    In the present study, the changes in the retinal nerve fiber layer (RNFL) thickness associated with Leber’s hereditary optic neuropathy (LHON) were examined by Cirrus high definition-optical coherence tomography (OCT), and the correlation between the RNFL thickness and the best corrected visual acuity (BCVA) was evaluated. A cross-sectional study was performed. Sixty-eight eyes from patients with LHON and 30 eyes from healthy individuals were scanned. Affected eyes were divided into 5 groups according to disease duration: Group 1, ≤3 months; group 2, 4–6 months; group 3, 7–9 months; group 4, 10–12 months; and group 5, >12 months. The RNFL thickness of the temporal, superior, nasal and inferior quadrants and the 360° average were compared between the LHON groups and the control group. The eyes in groups 1 and 2 were observed to have a thicker RNFL in the superior, nasal and inferior quadrants and a higher 360°-average RNFL thickness compared with those of the control group (P<0.05), the RNFL was observed to be thinner in the temporal quadrant in groups 1 and 2. The eyes in groups 3 and 4 showed a thinner RNFL in the temporal (P=0.001), superior and inferior (both P<0.05) quadrants, and a lower 360°-average RNFL thickness as compared with controls (P=0.001). No significant correlation was identified between BCVA and RNFL thickness. RNFL thickness was observed to undergo a unique process from thickening to thinning in the patients with LHON. Changes in different quadrants occurred at different time periods and the BCVA was not found to be correlated with RNFL thickness. PMID:24396430

  5. Characterization of retinal nerve fiber layer thickness changes associated with Leber's hereditary optic neuropathy by optical coherence tomography.

    Science.gov (United States)

    Zhang, Yixin; Huang, Houbin; Wei, Shihui; Qiu, Huaiyu; Gong, Yan; Li, Hongyang; Dai, Yanli; Jiang, Zhaocai; Liu, Zihao

    2014-02-01

    In the present study, the changes in the retinal nerve fiber layer (RNFL) thickness associated with Leber's hereditary optic neuropathy (LHON) were examined by Cirrus high definition-optical coherence tomography (OCT), and the correlation between the RNFL thickness and the best corrected visual acuity (BCVA) was evaluated. A cross-sectional study was performed. Sixty-eight eyes from patients with LHON and 30 eyes from healthy individuals were scanned. Affected eyes were divided into 5 groups according to disease duration: Group 1, ≤3 months; group 2, 4-6 months; group 3, 7-9 months; group 4, 10-12 months; and group 5, >12 months. The RNFL thickness of the temporal, superior, nasal and inferior quadrants and the 360° average were compared between the LHON groups and the control group. The eyes in groups 1 and 2 were observed to have a thicker RNFL in the superior, nasal and inferior quadrants and a higher 360°-average RNFL thickness compared with those of the control group (P<0.05), the RNFL was observed to be thinner in the temporal quadrant in groups 1 and 2. The eyes in groups 3 and 4 showed a thinner RNFL in the temporal (P=0.001), superior and inferior (both P<0.05) quadrants, and a lower 360°-average RNFL thickness as compared with controls (P=0.001). No significant correlation was identified between BCVA and RNFL thickness. RNFL thickness was observed to undergo a unique process from thickening to thinning in the patients with LHON. Changes in different quadrants occurred at different time periods and the BCVA was not found to be correlated with RNFL thickness.

  6. Scanning laser polarimetry, but not optical coherence tomography predicts permanent visual field loss in acute nonarteritic anterior ischemic optic neuropathy.

    Science.gov (United States)

    Kupersmith, Mark J; Anderson, Susan; Durbin, Mary; Kardon, Randy

    2013-08-15

    Scanning laser polarimetry (SLP) reveals abnormal retardance of birefringence in locations of the edematous peripapillary retinal nerve fiber layer (RNFL), which appear thickened by optical coherence tomography (OCT), in nonarteritic anterior ischemic optic neuropathy (NAION). We hypothesize initial sector SLP RNFL abnormalities will correlate with long-term regional visual field loss due to ischemic injury. We prospectively performed automated perimetry, SLP, and high definition OCT (HD-OCT) of the RNFL in 25 eyes with acute NAION. We grouped visual field threshold and RNFL values into Garway-Heath inferior/superior disc sectors and corresponding superior/inferior field regions. We compared sector SLP RNFL thickness with corresponding visual field values at presentation and at >3 months. At presentation, 12 eyes had superior sector SLP reduction, 11 of which had inferior field loss. Six eyes, all with superior field loss, had inferior sector SLP reduction. No eyes had reduced OCT-derived RNFL acutely. Eyes with abnormal field regions had corresponding SLP sectors thinner (P = 0.003) than for sectors with normal field regions. During the acute phase, the SLP-derived sector correlated with presentation (r = 0.59, P = 0.02) and with >3-month after presentation (r = 0.44, P = 0.02) corresponding superior and inferior field thresholds. Abnormal RNFL birefringence occurs in sectors corresponding to regional visual field loss during acute NAION when OCT-derived RNFL shows thickening. Since the visual field deficits show no significant recovery, SLP can be an early marker for axonal injury, which may be used to assess recovery potential at RNFL locations with respect to new treatments for acute NAION.

  7. Sequence Analysis of the Mitochondrial Genomes from Dutch Pedigrees with Leber Hereditary Optic Neuropathy

    Science.gov (United States)

    Howell, Neil; Oostra, Roelof-Jan; Bolhuis, Piet A.; Spruijt, Liesbeth; Clarke, Lorne A.; Mackey, David A.; Preston, Gwen; Herrnstadt, Corinna

    2003-01-01

    The complete mitochondrial DNA (mtDNA) sequences for 63 Dutch pedigrees with Leber hereditary optic neuropathy (LHON) were determined, 56 of which carried one of the classic LHON mutations at nucleotide (nt) 3460, 11778, or 14484. Analysis of these sequences indicated that there were several instances in which the mtDNAs were either identical or related by descent. The most striking example was a haplogroup J mtDNA that carried the 14484 LHON mutation. Four different but related mitochondrial genotypes were identified in seven of the Dutch pedigrees with LHON, including six of those described by van Senus. The control region of the founder sequence for these Dutch pedigrees with LHON matches the control-region sequence that Macmillan and colleagues identified in the founder mtDNA of French Canadian pedigrees with LHON. In addition, we obtained a perfect match between the Dutch 14484 founder sequence and the complete mtDNA sequences of two Canadian pedigrees with LHON. Those results indicate that these Dutch and French Canadian 14484 pedigrees with LHON share a common ancestor, that the single origin of the 14484 mutation in this megalineage occurred before the year 1600, and that there is a 14484/haplogroup J founder effect. We estimate that this lineage—including the 14484 LHON mutation—arose 900–1,800 years ago. Overall, the phylogenetic analyses of these mtDNA sequences conservatively indicate that a LHON mutation has arisen at least 42 times in the Dutch population. Finally, analysis of the mtDNA sequences from those pedigrees that did not carry classic LHON mutations suggested candidate pathogenic mutations at nts 9804, 13051, and 14325. PMID:12736867

  8. Extra-visual functional and structural connection abnormalities in Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Rocca, Maria A; Valsasina, Paola; Pagani, Elisabetta; Bianchi-Marzoli, Stefania; Milesi, Jacopo; Falini, Andrea; Comi, Giancarlo; Filippi, Massimo

    2011-02-10

    We assessed abnormalities within the principal brain resting state networks (RSNs) in patients with Leber's hereditary optic neuropathy (LHON) to define whether functional abnormalities in this disease are limited to the visual system or, conversely, tend to be more diffuse. We also defined the structural substrates of fMRI changes using a connectivity-based analysis of diffusion tensor (DT) MRI data. Neuro-ophthalmologic assessment, DT MRI and RS fMRI data were acquired from 13 LHON patients and 13 healthy controls. RS fMRI data were analyzed using independent component analysis and SPM5. A DT MRI connectivity-based parcellation analysis was performed using the primary visual and auditory cortices, bilaterally, as seed regions. Compared to controls, LHON patients had a significant increase of RS fluctuations in the primary visual and auditory cortices, bilaterally. They also showed decreased RS fluctuations in the right lateral occipital cortex and right temporal occipital fusiform cortex. Abnormalities of RS fluctuations were correlated significantly with retinal damage and disease duration. The DT MRI connectivity-based parcellation identified a higher number of clusters in the right auditory cortex in LHON vs. controls. Differences of cluster-centroid profiles were found between the two groups for all the four seeds analyzed. For three of these areas, a correspondence was found between abnormalities of functional and structural connectivities. These results suggest that functional and structural abnormalities extend beyond the visual network in LHON patients. Such abnormalities also involve the auditory network, thus corroborating the notion of a cross-modal plasticity between these sensory modalities in patients with severe visual deficits.

  9. Extra-visual functional and structural connection abnormalities in Leber's hereditary optic neuropathy.

    Directory of Open Access Journals (Sweden)

    Maria A Rocca

    Full Text Available We assessed abnormalities within the principal brain resting state networks (RSNs in patients with Leber's hereditary optic neuropathy (LHON to define whether functional abnormalities in this disease are limited to the visual system or, conversely, tend to be more diffuse. We also defined the structural substrates of fMRI changes using a connectivity-based analysis of diffusion tensor (DT MRI data. Neuro-ophthalmologic assessment, DT MRI and RS fMRI data were acquired from 13 LHON patients and 13 healthy controls. RS fMRI data were analyzed using independent component analysis and SPM5. A DT MRI connectivity-based parcellation analysis was performed using the primary visual and auditory cortices, bilaterally, as seed regions. Compared to controls, LHON patients had a significant increase of RS fluctuations in the primary visual and auditory cortices, bilaterally. They also showed decreased RS fluctuations in the right lateral occipital cortex and right temporal occipital fusiform cortex. Abnormalities of RS fluctuations were correlated significantly with retinal damage and disease duration. The DT MRI connectivity-based parcellation identified a higher number of clusters in the right auditory cortex in LHON vs. controls. Differences of cluster-centroid profiles were found between the two groups for all the four seeds analyzed. For three of these areas, a correspondence was found between abnormalities of functional and structural connectivities. These results suggest that functional and structural abnormalities extend beyond the visual network in LHON patients. Such abnormalities also involve the auditory network, thus corroborating the notion of a cross-modal plasticity between these sensory modalities in patients with severe visual deficits.

  10. Long-term Evaluation of Radiation-Induced Optic Neuropathy After Single-Fraction Stereotactic Radiosurgery

    Energy Technology Data Exchange (ETDEWEB)

    Leavitt, Jacqueline A., E-mail: leavitt.jacqueline@mayo.edu [Department of Ophthalmology, Mayo Clinic and Foundation, Rochester, Minnesota (United States); Stafford, Scott L. [Department of Radiation Oncology, Mayo Clinic and Foundation, Rochester, Minnesota (United States); Link, Michael J. [Department of Neurosurgery, Mayo Clinic and Foundation, Rochester, Minnesota (United States); Pollock, Bruce E. [Department of Radiation Oncology, Mayo Clinic and Foundation, Rochester, Minnesota (United States); Department of Neurosurgery, Mayo Clinic and Foundation, Rochester, Minnesota (United States)

    2013-11-01

    Purpose: To determine the long-term risk of radiation-induced optic neuropathy (RION) in patients having single-fraction stereotactic radiosurgery (SRS) for benign skull base tumors. Methods and Materials: Retrospective review of 222 patients having Gamma Knife radiosurgery for benign tumors adjacent to the anterior visual pathway (AVP) between 1991 and 1999. Excluded were patients with prior or concurrent external beam radiation therapy or SRS. One hundred twenty-nine patients (58%) had undergone previous surgery. Tumor types included confirmed World Health Organization grade 1 or presumed cavernous sinus meningioma (n=143), pituitary adenoma (n=72), and craniopharyngioma (n=7). The maximum dose to the AVP was ≤8.0 Gy (n=126), 8.1-10.0 Gy (n=39), 10.1-12.0 Gy (n=47), and >12 Gy (n=10). Results: The mean clinical and imaging follow-up periods were 83 and 123 months, respectively. One patient (0.5%) who received a maximum radiation dose of 12.8 Gy to the AVP developed unilateral blindness 18 months after SRS. The chance of RION according to the maximum radiation dose received by the AVP was 0 (95% confidence interval [CI] 0-3.6%), 0 (95% CI 0-10.7%), 0 (95% CI 0-9.0%), and 10% (95% CI 0-43.0%) for patients receiving ≤8 Gy, 8.1-10.0 Gy, 10.1-12.0 Gy, and >12 Gy, respectively. The overall risk of RION in patients receiving >8 Gy to the AVP was 1.0% (95% CI 0-6.2%). Conclusions: The risk of RION after single-fraction SRS in patients with benign skull base tumors who have no prior radiation exposure is very low if the maximum dose to the AVP is ≤12 Gy. Physicians performing single-fraction SRS should remain cautious when treating lesions adjacent to the AVP, especially when the maximum dose exceeds 10 Gy.

  11. Ocular neuropathy in peripheral neuropathies.

    Science.gov (United States)

    Evliyaoglu, Ferhat; Karadag, Remzi; Burakgazi, Ahmet Z

    2012-11-01

    Ocular movements and coordination require complex and integrated functions of somatic and autonomic nervous systems. Neurological disorders affecting these nervous systems may cause ocular dysfunction involving extraocular muscles and pupils. In this article, the prevalence, clinical presentations, and management of ocular neuropathy related to certain peripheral neuropathies, including diabetic neuropathy, Guillain-Barré syndrome (GBS), chronic inflammatory neuropathies, human immunodeficiency virus (HIV)-associated neuropathy, and hereditary neuropathies, are examined in detail. Copyright © 2012 Wiley Periodicals, Inc.

  12. [Optic nerve sheath meningioma: diagnosis and new treatment options, a case study of monocular blindness during pregnancy].

    Science.gov (United States)

    Berete, R; Vignal-Clermont, C; Boissonnet, H; Héran, F; Morax, S

    2006-04-01

    Optic nerve sheath meningiomas are challenging lesions to manage. We report here a case of primary optic nerve sheath meningioma in a pregnant woman with sudden unilateral vision loss. Then we review the current literature on the subject, prognosis factors, and report the results of fractionated radiotherapy and current therapeutic guidelines. Pregnancy may accelerate growth of meningiomas and this diagnosis must be considered in all cases of optic neuropathy in pregnant woman.

  13. Trial End Points and Natural History in Patients With G11778A Leber Hereditary Optic Neuropathy

    Science.gov (United States)

    Lam, Byron L.; Feuer, William J.; Schiffman, Joyce C.; Porciatti, Vittorio; Vandenbroucke, Ruth; Rosa, Potyra R.; Gregori, Giovanni; Guy, John

    2014-01-01

    IMPORTANCE Establishing the natural history of G11778A Leber hereditary optic neuropathy (LHON) is important to determine the optimal end points to assess the safety and efficacy of a planned gene therapy trial. OBJECTIVE To use the results of the present natural history study of patients with G11778A LHON to plan a gene therapy clinical trial that will use allotopic expression by delivering a normal nuclear-encoded ND4 gene into the nuclei of retinal ganglion cells via an adeno-associated virus vector injected into the vitreous. DESIGN, SETTING, AND PARTICIPANTS A prospective observational study initiated in 2008 was conducted in primary and referral institutional practice settings. Participants included 44 individuals with G11778A LHON, recruited between September 2008 and March 2012, who were evaluated every 6 months and returned for 1 or more follow-up visits (6–36 months) as of August 2012. EXPOSURES Complete neuro-ophthalmic examination and main measures. MAIN OUTCOMES AND MEASURES Visual acuity, automated visual field testing, pattern electroretinogram, and spectral-domain optical coherence tomography. RESULTS Clinical measures were stable during the follow-up period, and visual acuity was as good as or better than the other visual factors used for monitoring patients. Based on a criterion of 15 or more letters from the Early Treatment Diabetic Retinopathy Study chart, 13 eyes of 8 patients (18%) improved, but 24 months after the onset of symptoms, any further improvements were to no better than 20/100. Acuity recovery occurred in some patients despite continued marked retinal nerve fiber layer thinning indistinguishable from that in patients who did not recover visual acuity. CONCLUSIONS AND RELEVANCE Spontaneous improvement of visual acuity in patients with G11778A LHON is not common and is partial and limited when it occurs, so improvements in vision with adeno-associated virus–mediated gene therapy of a synthetic wild-type ND4 subunit gene should be

  14. Analysis of Retinal Layer Thicknesses and Their Clinical Correlation in Patients with Traumatic Optic Neuropathy.

    Directory of Open Access Journals (Sweden)

    Ju-Yeun Lee

    Full Text Available The aims of this study were 1 To evaluate retinal nerve fiber layer (fRNFL thickness and ganglion cell layer plus inner plexiform layer (GCIPL thickness at the fovea in eyes affected with traumatic optic neuropathy (TON compared with contralateral normal eyes, 2 to further evaluate these thicknesses within 3 weeks following trauma (defined as "early TON", and 3 to investigate the relationship between these retinal layer thicknesses and visual function in TON eyes. Twenty-nine patients with unilateral TON were included. Horizontal and vertical spectral-domain optical coherence tomography (SD-OCT scans of the fovea were taken in patients with unilateral TON. The main outcome measure was thickness of the entire retina, fRNFL, and GCIPL in eight areas. Thickness of each retinal layer was compared between affected and unaffected eyes. The correlation between the thickness of each retinal layer and visual function parameters, including best corrected visual acuity, color vision, P100 latency, and P100 amplitude in visual evoked potential (VEP, mean deviation (MD and visual field index (VFI in Humphrey visual field analysis in TON eyes was analyzed. Thicknesses of the entire retina, fRNFL, and GCIPL in SD-OCT were significantly thinner (3-36% in all measurement areas of TON eyes compared to those in healthy eyes (all p<0.05. Whereas, only GCIPL in the outer nasal, superior, and inferior areas was significantly thinner (5-10% in the early TON eyes than that in the control eyes (all p<0.01. A significant correlation was detected between retinal layer thicknesses and visual function parameters including color vision, P100 latency and P100 amplitude in VEP, MD, and VFI (particularly P100 latency, MD, and VFI (r = -0.70 to 0.84. Among the retinal layers analyzed in this study, GCIPL (particularly in the superior and inferior areas was most correlated with these five visual function parameters (r = -0.70 to 0.71. Therefore, evaluation of morphological change

  15. Hereditary neuropathy with liability to pressure palsies in childhood: Case series and literature update.

    Science.gov (United States)

    Chrestian, Nicolas; McMillan, Hugh; Poulin, Chantal; Campbell, Craig; Vajsar, Jiri

    2015-09-01

    Hereditary Neuropathy with Liability to Pressure Palsy (HNPP) is a rare condition in childhood with a diverse range of clinical presentations. We analyzed the clinical presentation and electrophysiological data of 12 children with a confirmed PMP22 gene deletion and reviewed the published reports of HNPP in children and compared our data with the reports from the literature review. Peroneal palsy was the most common presentation (42%) followed by brachial plexus palsy in 25% of our cases. Nerve conduction studies were always suggestive of the diagnosis demonstrating 3 major patterns: multifocal demyelination at the area of entrapment, generalized sensory-motor polyneuropathy and a combination of the two first patterns in a vast majority (60%). Surprisingly, there was bilateral or unilateral electrophysiological entrapment of the median nerve at the carpal tunnel in all our patients. The clinical presentation of HNPP in childhood is heterogeneous and electrophysiological findings are helpful in establishing the diagnosis. Any unexplained mononeuropathy or multifocal neuropathy should lead to PMP22 gene testing to look for the deletion. Early diagnosis is important in order to facilitate appropriate genetic counseling and also for the appropriate care for these patients. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. A Case of Acute Motor Axonal Neuropathy Mimicking Brain Death and Review of the Literature.

    Science.gov (United States)

    Ravikumar, Sandhya; Poysophon, Poysophon; Poblete, Roy; Kim-Tenser, May

    2016-01-01

    We describe a case report of fulminant Guillain-Barré syndrome (GBS) mimicking brain death. A previously healthy 60-year-old male was admitted to the neurointensive care unit after developing rapidly progressive weakness and respiratory failure. On presentation, the patient was found to have absent brainstem and spinal cord reflexes resembling that of brain death. Acute motor axonal neuropathy, a subtype of GBS, was diagnosed by cerebrospinal fluid and nerve conduction velocity testing. An electroencephalogram showed that the patient had normal, appropriately reactive brain function. Transcranial Doppler (TCD) ultrasound showed appropriate blood flow to the brain. GBS rarely presents with weakness so severe as to mimic brain death. This article provides a review of similar literature. This case demonstrates the importance of performing a proper brain death examination, which includes evaluation for irreversible cerebral injury, exclusion of any confounding conditions, and performance of tests such as electroencephalography and TCDs when uncertainty exists about the reliability of the clinical exam.

  17. Sensory ataxic neuropathy with dysarthria/dysphagia and ophthalmoplegia (SANDO). Two case reports.

    Science.gov (United States)

    Gáti, István; Danielsson, Olof; Jonasson, Jon; Landtblom, Anne-Marie

    2011-12-01

    Case histories of two unrelated patients suffering from sensory ataxic neuropathy, dysarthria/dysphagia and external ophthalmoplegia (SANDO) are reported. Both patients showed compound heterozygosity for POLG1 gene mutations, and presented with symptom of the clinical characteristics of SANDO. A patient with a p.A467T and p.W748S, well-known mutations showed a progressive course with early onset and multisystem involvement, including symptoms characteristics for mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). The second patient showed a less well-known p.T251I and p.G848S mutations with late onset and dysphagia/dysarthria dominated, moderate symptoms. This later is the second published case history, when these POLG1 gene mutations are the possible background of late onset SANDO, dominantly presenting with bulbar symptoms.

  18. Detection of the mtDNA 14484 mutation on an African-specific haplotype: Implications about its role in causing Leber hereditary optic neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Torroni, A.; Petrozzi, M.; Terracina, M. [Universita` di Roma (Italy)] [and others

    1996-07-01

    Leber hereditary optic neuropathy (LHON) is a maternally transmitted disease whose primary clinical manifestation is acute or subacute bilateral loss of central vision leading to central scotoma and blindness. To date, LHON has been associated with 18 mtDNA missense mutations, even though, for many of these mutations, it remains unclear whether they cause the disease, contribute to the pathology, or are nonpathogenic mtDNA polymorphisms. On the basis of numerous criteria, which include the specificity for LHON, the frequency in the general population, and the penetrance within affected pedigrees, the detection of associated defects in the respiratory chain, mutations at three nucleotide positions (nps), 11778 (G{r_arrow}A), 3460 (G{r_arrow}A), and 14484 (T{r_arrow}C) have been classified as high-risk and primary LHON mutations. Overall, these three mutations encompass {ge}90% of the LHON cases. 29 refs., 1 fig.

  19. 外伤性视神经损伤的HRCT及MRI表现%HRCT and MRI manifestations of traumatic optic neuropathy

    Institute of Scientific and Technical Information of China (English)

    李勇; 赵景武; 王振常; 鲜军舫; 李静; 杨本涛; 刘中林

    2011-01-01

    Objective To investigate HRCT and MRI manifestations of traumatic optic neuropathy.Methods HRCT and MRI findings of 19 patients with post-injury visual loss were retrospectively analyzed.Results ① HRCT was performed to all 19 patients.Optic canal fractures were found in 16 cases with 34 lesions, while no fracture was found in the other 3 cases.Fractures on medial and inferior wall of optic canal were common.The vicinal bone structure fractures of optic canal were found in all 19 cases with 77 lesions, including 23 lesions in orbital apex, 15 lesions in greater wing of sphenoid bone near superior and inferior orbital fissure, 11 lesions in sphenoidal planum near chiasmatic sulcus, 2 lesions in lateral wall of sphenoid sinus and 26 lesions in anterior portion of orbit wall, sinusoidal walls of frontal and maxillary sinus.Large diameter of optic nerve was observed in 13 cases.②MRI was obtained in 10 of 19 patients.Abnormal high signal of optic nerve was found in 10 cases with 14 lesions, including 6 lesions in intra-orbital segment, 5 lesions in intra-canal segment and 3 lesions in intracranial segment.③Optic canal decompression surgery was performed to all 19 patients.Improved eyesight of varied degrees was obtained in 13 of 19 cases within 7 days after surgery.Conclusion HRCT can provide detailed information of optic canal and its adjacent structures, while MRI has advantages in the visualization of optic nerve.MRI is helpful to detect the lesions promptly, particularly for traumatic optic neuropathy patients without optic canal fracture.%目的 探讨外伤性视神经损伤的HRCT及MRI表现.方法 对19例外伤致盲患者的HRCT及MRI表现进行回顾性分析.结果 ①19例患者均接受HRCT检查.19例中,16例存在34处视神经管壁骨折,以神经管内侧壁及下壁骨折多见,3例无骨折;视神经管邻近结构骨折共77处,包括眶尖部眼眶骨折23处,蝶骨大翼近眶上裂、眶下裂处骨折15处;蝶骨

  20. A retrospective analysis of characteristics of visual field damage in patients with Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Ran, Ruijin; Yang, Shuo; He, Heng; Ma, Shiqi; Chen, Zhiqi; Li, Bin

    2016-01-01

    The objective of this study is to investigate the characteristics and the evolution of visual field damage caused by Leber's hereditary optic neuropathy (LHON) and to provide clinical data for the diagnosis of LHON. Parameters of visual field in 32 consecutive patients (49 eyes) with LHON who were confirmed by genetic diagnostic tests were retrospectively measured within 1 week, between three to six months, and at six months after onset. Visual field defects revealed central scotoma in 26 eyes (53.1 %), paracentral scotoma in 12 eyes (24.5 %), ceco-central defects in 6 eyes (12.2 %), blind spot enlargenment in 3 eyes (6.1 %), quadrantanopia in 2 eyes (4.1 %) within 1 week after onset. After 3 to 6 months, ceco-central defects were detected in 22 eyes (44.9 %), central isopter constriction in 10 eyes (20.4 %), hemianopia or quadrantanopia in 5 eyes (10.2 %), central scotoma in 4 eyes (8.2 %), and paracentral scotoma in 1 eye (2.0 %). After 6 months, central isopter constriction was observed in 18 eyes (36.7 %), diffuse defects in 21 eyes (42.9 %), ceco-central defects in 3 eyes (6.1 %), hemianopia or quadrantanopia in 5 eyes (10.2 %), and central scotoma in 2 eyes (4.1 %). LHON at different stages was characterized by different focal visual field defects: visual field defects in LHON patients within 1 week after onset were mostly central or paracentral scotoma, which was enlarged around the ceco-central defect, or connected to form a blind spot after 3-6 months. Diffuse and central isopter constriction defects were usually developed after 6 months. Damages firstly appeared in papillomacular bundle and gradually expanded outward. These characteristics of visual field defects reported in this study might provide a clinical basis for better diagnosis of LHON.

  1. A case report of neuromyelitis optica with 37 years' interval between optic neuropathy and spinal cord lesion and literature review%从视神经病变到脊髓损伤间隔37年的视神经脊髓炎一例并文献复习

    Institute of Scientific and Technical Information of China (English)

    李长青; 梁友云; 戚晓昆; 刘建国

    2011-01-01

    目的 提高对从视神经病变到脊髓损伤间隔长的视神经脊髓炎(NMO)的认识,以减少误诊.方法 对1例从视神经病变到脊髓损伤间隔37年的NMO患者行血、脑脊液化验及脊髓、头颅MRI等检查,分析临床资料、随访并文献复习.结果 患者脑脊液碱性髓鞘蛋白及IgG合成率均偏高,寡克隆区带阳性,视觉诱发电位异常,脊髓MRI可见T1-7髓内长T2异常信号,诊断明确后经过糖皮质类固醇和丙种球蛋白治疗后患者症状明显好转.目前随访病情稳定.结论 从视神经病变到脊髓损伤可以间隔相当长的时间.当患者出现视神经炎时,要注意亚临床脊髓及头颅病变的筛查,注意是否有转变成为NMO或多发性硬化的可能性.%Objective To improve the recognization of long term interval between optic neuropathy and spinal cord injury of neuromyelitis optica. Methods One 51-year old male patient with 37 years'interval between optic neuropathy and spinal cord injury of neuromyelitis optica underwent the examination of plasma and cerebrospinal fluid and head and spinal MRI examinations, who was also followed up. His clinical data were analyzed and related literature was reviewed. Results The myelin basic protein and IgG index in his cerebrospinal fluid was high, his oligoclonal band of cerebrospinal fluid was positive, and abnormal finding in visual evoked potential. Abnormal intramedullary long T2 signals was showed in spinal cord MRI at T1-7 segment. When dignosed as neuromyelitis optica, the clinical symptom and signs was improved with corticosteroid and gamma globulin therapy. The patient was in stable condition at present.Conclusions There could be a long term interval between optic neuritis and myelitis. One should pay attention to clinical features and imaging examination of subclinical lesion in spinal cord and brain and conoide the possibility of developing neuromyelitis optica or multiple sclerosis.

  2. Radiation optic neuropathy and retinopathy with low dose (20 Gy radiation treatment

    Directory of Open Access Journals (Sweden)

    Crandall E. Peeler

    2016-10-01

    Conclusions and importance: Though cumulative radiation doses to the anterior visual pathway of less than 50 Gy are traditionally felt to be safe, it is important to consider not just the total exposure but also the size of individual fractions. The single-dose threshold for RON in proton beam treatment has yet to be defined. Our case suggests that fractions of less than 10 Gy should be delivered to minimize the risk of optic nerve injury.

  3. Optic Neuropathy from Cobalt Toxicity in a Patient who Ingested Cattle Magnets

    OpenAIRE

    Bhardwaj, Namita; Perez, Javier; Peden, Marc

    2011-01-01

    Cobalt is a widely used in the industrial production of hard metals. Cobalt ingestion has been reported to cause widespread systemic toxicity, but its effects on vision have been sparsely reported. The authors report the case of a patient who ingested cattle magnets, which remained in his stomach for an unknown duration of time. These magnets largely consist of cobalt that gradually leached into his blood stream, resulting in protean systemic manifestations, which included optic atrophy.

  4. 外伤性视神经病变手术治疗之我见%Current situation of surgery for traumatic optic neuropathy

    Institute of Scientific and Technical Information of China (English)

    程金伟; 魏锐利

    2011-01-01

    大剂量糖皮质激素冲击治疗是外伤性视神经病变的首选治疗方案,但仍有许多患者对糖皮质激素治疗无效.视神经管减压术成为治疗外伤性视神经病变的重要选择.但是,问题接踵而来:何种情况应该采取视神经管减压?视神经管减压的手术时机是什么?如何才能达到视神经管减压的目的 ?这些问题长期以来一直是眼科界争论的焦点.因此,综合已有的临床资料和证据,我们提出视神经管减压术须慎重掌握适应证,迟发性或进行性视力障碍是较佳适应证,而原发性视力丧失者不宜手术治疗.另外,应在7 d以内尽早实施手术并达到充分的骨性视神经管及视神经鞘减压.%Although corticosteroid therapy remains the mainstream of various treatment procedures in traumatic optic neuropathy,some patients are still unable to benefit by this procedure. Therefore,optic nerve decompression has become an important choice for treating traumatic optic neuropathy. However,several problems have been raised on optic nerve decompression,such as who is suitable for this operation;as well as when to do and how to do this operation. The answers to these questions are controversial. We systematically review the current clinical evidence,and suggest that surgical decompression is indicated in cases with late onset and progressive visual loss;it is not indicated in primary complete loss of vision.Furthermore,it has been recommended that an adequate decompression requires the addition of an optic nerve sheath incision to the osseous optic canal,and it must be undertaken within seven days after the injury.

  5. Successful amelioration of mitochondrial optic neuropathy using the yeast NDI1 gene in a rat animal model.

    Directory of Open Access Journals (Sweden)

    Mathieu Marella

    Full Text Available BACKGROUND: Leber's hereditary optic neuropathy (LHON is a maternally inherited disorder with point mutations in mitochondrial DNA which result in loss of vision in young adults. The majority of mutations reported to date are within the genes encoding the subunits of the mitochondrial NADH-quinone oxidoreductase, complex I. Establishment of animal models of LHON should help elucidate mechanism of the disease and could be utilized for possible development of therapeutic strategies. METHODOLOGY/PRINCIPAL FINDINGS: We established a rat model which involves injection of rotenone-loaded microspheres into the optic layer of the rat superior colliculus. The animals exhibited the most common features of LHON. Visual loss was observed within 2 weeks of rotenone administration with no apparent effect on retinal ganglion cells. Death of retinal ganglion cells occurred at a later stage. Using our rat model, we investigated the effect of the yeast alternative NADH dehydrogenase, Ndi1. We were able to achieve efficient expression of the Ndi1 protein in the mitochondria of all regions of retinal ganglion cells and axons by delivering the NDI1 gene into the optical layer of the superior colliculus. Remarkably, even after the vision of the rats was severely impaired, treatment of the animals with the NDI1 gene led to a complete restoration of the vision to the normal level. Control groups that received either empty vector or the GFP gene had no effects. CONCLUSIONS/SIGNIFICANCE: The present study reports successful manifestation of LHON-like symptoms in rats and demonstrates the potential of the NDI1 gene therapy on mitochondrial optic neuropathies. Our results indicate a window of opportunity for the gene therapy to be applied successfully after the onset of the disease symptoms.

  6. Clinical analysis on 12 cases of syphilitic optic neuritis

    Directory of Open Access Journals (Sweden)

    Lin LI

    2016-08-01

    Full Text Available Objective To explore the clinical characteristics and pathophysiological mechanism of syphilitic optic neuritis.  Methods The clinical signs and symptoms, laboratory tests, electrophysiological examinations, imaging features, treatment and prognosis of 12 cases with syphilitic optic neuritis admitted in our hospital from January 2014 to March 2016 were retrospectively analyzed.  Results The main clinical manifestation was vision loss in 12 patients (18 eyes, with acute or subacute onset, monocular attack or one after other. Degrees of visual loss differed among these patients. They also presented visual field defect and ocular fundus changes. Cerebrospinal fluid (CSF examination showed increased white blood cell and protein. Rapid plasma reagin (RPR assay and Treponema pallidum hemagglutination assay (TPHA in serum were positive. RPR assay/toluidine red unheated serum test (TRUST and TPHA in CSF were positive. Visual-evoked potential (VEP showed prolonged latency and declined amplitude of P100 wave. MRI revealed optic atrophy, abnormal signs in medial orbital part or overall length of optic nerve. The vision was improved after intravenous injection of aqueous penicillin and muscular injection of benzathine benzylpenicillin.  Conclusions Neurosyphilis is a rare cause of optic neuritis. Differential diagnosis should be paid attention on syphilitic optic neuritis from idiopathic optic neuritis and ischemic optic neuropathy. Serologic test and CSF examination will be helpful for a clear diagnosis. Besides, early diagnosis and standard therapy are essential for vision recovery. DOI: 10.3969/j.issn.1672-6731.2016.07.007

  7. Very high penetrance and occurrence of Leber's hereditary optic neuropathy in a large Han Chinese pedigree carrying the ND4 G11778A mutation.

    Science.gov (United States)

    Zhou, Xiangtian; Zhang, Hongxing; Zhao, Fuxin; Ji, Yanchun; Tong, Yi; Zhang, Juanjuan; Zhang, Yu; Yang, Li; Qian, Yaping; Lu, Fan; Qu, Jia; Guan, Min-Xin

    2010-08-01

    We report here the clinical, genetics and molecular characterization of a five-generation Han Chinese family with Leber's hereditary optic neuropathy (LHON). Strikingly, this family exhibits very high penetrance and occurrence of optic neuropathy. In particular, 25 (10 males/15 females) of 30 matrilineal relatives exhibited the variable severity, ranging from profound to mild of visual impairment. This penetrance of optic neuropathy in this Chinese family is much higher than those in many families with LHON worldwide. The age-at-onset for visual impairment in matrilineal relatives in this Chinese family varied from 7 to 24years old, with the average of 15 years old. Furthermore, the ratio between affected male and female matrilineal relatives is 1:1.5 in the Chinese family. This observation is in contrast with the typical features in LHON pedigrees that there was predominance of affected males in LHON in many families from different ethnic origins. Molecular analysis of mitochondrial genome identified the known ND4 G11778A mutation and 51 variants, belonging to Asian haplogroup C4a1. The absence of other known secondary LHON-associated and functionally significant mtDNA mutations in this Chinese family suggested that mitochondrial variants may not play an important role in the phenotypic manifestation of the G11778A mutation in this Chinese family. Therefore, nuclear modifier gene(s) may be responsible for very high penetrance and occurrence of optic neuropathy in this Chinese pedigree.

  8. N-hexane neuropathy with vertigo and cold allodynia in a silk screen printer: A case study.

    Science.gov (United States)

    Pradhan, Sunil; Tandon, Ruchika

    2015-01-01

    N-hexane neuropathy is an occupational disease caused by exposure to n-hexane, which is used as a solvent in silk screen printing. Here, we describe a 35-year-old man, a silk screen printer by profession, who presented with dizziness, distal swelling of both lower limbs for 10 months and tingling and burning sensation in both feet for 9.5 months along with cold allodynia. The patient had normal results of a motor and sensory system examination, apart from an impaired temperature sense. Nerve conduction tests showed a conduction block in bilateral common peroneal nerves and absence of conduction in bilateral sural nerves. These symptoms resolved when further exposure to n-hexane was ceased but cold allodynia remained. Thus, cold allodynia and impaired temperature sense can be a manifestation of n-hexane neuropathy. Hence, abnormalities on nerve conduction studies can be detected in n-hexane neuropathy patients, even before clinical examination detects any such abnormalities. In the case of the patients presenting with sensory motor neuropathy, history of occupational exposure to n-hexane becomes important, as the sooner the disease is detected, the better the chances of recovery.

  9. Cell therapy using retinal progenitor cells shows therapeutic effect in a chemically-induced rotenone mouse model of Leber hereditary optic neuropathy.

    Science.gov (United States)

    Mansergh, Fiona C; Chadderton, Naomi; Kenna, Paul F; Gobbo, Oliviero L; Farrar, G Jane

    2014-11-01

    Primary mitochondrial disorders occur at a prevalence of one in 10 000; ∼50% of these demonstrate ocular pathology. Leber hereditary optic neuropathy (LHON) is the most common primary mitochondrial disorder. LHON results from retinal ganglion cell pathology, which leads to optic nerve degeneration and blindness. Over 95% of cases result from one of the three common mutations in mitochondrial genes MTND1, MTND4 and MTND6, which encode elements of the complex I respiratory chain. Various therapies for LHON are in development, for example, intravitreal injection of adeno-associated virus carrying either the yeast NDI1 gene or a specific subunit of mammalian Complex I have shown visual improvement in animal models. Given the course of LHON, it is likely that in many cases prompt administration may be necessary before widespread cell death. An alternative approach for therapy may be the use of stem cells to protect visual function; this has been evaluated by us in a rotenone-induced model of LHON. Freshly dissected embryonic retinal cells do not integrate into the ganglion cell layer (GCL), unlike similarly obtained photoreceptor precursors. However, cultured retinal progenitor cells can integrate in close proximity to the GCL, and act to preserve retinal function as assessed by manganese-enhanced magnetic resonance imaging, optokinetic responses and ganglion cell counts. Cell therapies for LHON therefore represent a promising therapeutic approach, and may be of particular utility in treating more advanced disease.

  10. Error diagnóstico en la neuropatía óptica epidémica Diagnostic error in epidemic optic neuropathy

    Directory of Open Access Journals (Sweden)

    Rosaralis Santiesteban Freixas

    2005-12-01

    Full Text Available La forma óptica de la epidemia de neuropatía, aparecida en el decenio pasado en Cuba, ha sido motivo de discusión por el posible hiperdiagnóstico, de los más de 22 000 casos notificados. El propósito principal de este trabajo es profundizar en la caracterización de esta enfermedad y dar a conocer la congruencia que debe de existir entre la agudeza visual y la visión de colores en las neuropatías de este tipo; además, estimar sobre la base de este elemento la posible cifra de errores diagnósticos de dos grupos de pacientes con neuropatía optica epidérmica y en un tercer grupo de pacientes que no mejoraron con tratamiento, donde se reunieron 78 casos remitidos porque no mejoraban con tratamiento vitamínico. Los resultados demostraron congruencia entre el estado de afectación de la agudeza visual y la visión de colores en más del 90 % de los 960 casos de los grupos 1 y 2, con diagnóstico de neuropatía óptica epidémica comprobados por expertos, a diferencia de los casos del tercer grupo, en los que se detectó que el 96,1 % tuvieron de inicio falsos diagnósticos de esta enfermedad p The optic form of the neuropathy epidemic that appeared in the last decade in Cuba has been discussed due to the possible hyperdiagnosis of the more than 22 000 notified cases. The main objective of this paper was to go deep into the characterization of this disease, to make known the congruency that should exist between the visual acuity and the vision of colors in the neuropathies of this type, and to estimate, on the basis of this element, the possible figure of diagnostic errors in 2 groups of patients with EON and of a third group of patients that did not improve with the treatment. In this group, there were 78 cases that were referred because they did not respond to vitamin therapy. The results showed congruency between the state of affection of visual acuity and the vision of colors in more than 90 % of the 960 cases from groups 1 and 2 with

  11. Peripheral Neuropathy

    Science.gov (United States)

    ... can be associated with peripheral neuropathy. Metabolic and endocrine disorders impair the body’s ability to transform nutrients into ... to neuropathies as a result of chemical imbalances. Endocrine disorders that lead to hormonal imbalances can disturb normal ...

  12. Vasculitic neuropathy.

    Science.gov (United States)

    Sampaio, Luzia; Silva, Lã Gia; Terroso, Georgina; Nadais, Goreti; Mariz, Eva; Ventura, Francisco

    2011-01-01

    Vasculitic neuropathy corresponds to the occurrence of vasculitis at the level of vasa nervorum, resulting in ischemic damage of the peripheral nerve and axonal degeneration. Vasculitic neuropathy commonly occurs in association with systemic diseases and may be the initial manifestation or arise in the course of established disease. Although rare, vasculitis can be confined to the peripheral nervous system - non-systemic vasculitic neuropathy. This paper aims to review the classification, diagnosis and treatment of vasculitic neuropathy.

  13. [Peripheral neuropathy in relation to LAV/HTLV III retrovirus infection. A clinical, anatomical and immunological study. 5 cases].

    Science.gov (United States)

    Leport, C; Chaunu, M P; Sicre, J; Brun-Vezinet, F; Hauw, J J; Vildé, J L

    1987-01-24

    An unexplained peripheral neuropathy was observed in five patients with positive serology for LAV/HTLV III. Three of them presented with polyneuropathy, one with chronic meningitis and oculomotor palsies, and one with a mononeuropathy. CSF was abnormal in 5/5, with elevated protein content (0.4-4 g/l) and abnormal cell count (29-65/mm3). Intrathecal production of LAV-specific IgG was demonstrated in 3/4 cases. Electromyographic examination showed reduced nerve conduction velocity in 4/5. Neuromuscular biopsy revealed microvasculitis with mononuclear cell infiltrates in 3/4 cases; characterization of these cells showed that they were predominantly non monoclonal T8 lymphocytes. Other symptoms of "AIDS-related complex" were present in all five patients. None had other causes of peripheral neuropathy. Thus, peripheral neuropathy can be the initial manifestation of LAV/HTLV III infection. Isolation of the virus from the nerve in one published case, and arguments for intrathecal synthesis of LAV-specific IgG suggest the direct role of this agent; however, the lymphocytic infiltration seen in three of our cases favours an indirect immune mechanism, as in other organs, such as lungs and lymph nodes.

  14. Optic nerve involvement in childhood onset systemic lupus erythematosus: Three cases and a review of the literature.

    Science.gov (United States)

    Suri, D; Abujam, B; Gupta, A; Rawat, A; Saikia, B; Walker Minz, R; Gupta, V; Bansal, R; Kaushik, S; Singh, S

    2016-01-01

    The ocular system can be affected in systemic lupus erythematosus (SLE) in one third of patients. However, optic nerve involvement is relatively uncommon, but is more so in pediatric SLE patients, where it can occur in 1% of cases. We report three children with SLE who presented with optic nerve involvement. Two children had optic neuritis, with optic neuritis being the first manifestation in one child. The third child had ischaemic optic neuropathy secondary to antiphospholipid syndrome. A careful work up for SLE should be performed in every child with optic nerve disease. Prompt diagnosis and early treatment results in a better prognosis.

  15. Small Fiber Neuropathy in Children: Two Case Reports Illustrating the Importance of Recognition.

    Science.gov (United States)

    Hoeijmakers, Janneke G J; Faber, Catharina G; Miedema, Carien J; Merkies, Ingemar S J; Vles, Johan S H

    2016-10-01

    Small fiber neuropathy (SFN) is a debilitating condition that often leads to pain and autonomic dysfunction. In the last few decades, SFN has been gaining more attention, particularly in adults. However, literature about SFN in children remains limited. The present article reports the cases of 2 adolescent girls diagnosed with SFN. The first patient (14 years of age) complained about painful itch and tingling in her legs, as well as dysautonomia symptoms for years. She also reported a red/purple-type discoloration of her legs aggravated by warmth and standing, compatible with erythromelalgia. The diagnosis of SFN was confirmed by a reduced intraepidermal nerve fiber density (IENFD) in skin biopsy sample. No underlying conditions were found. Symptomatic neuropathic pain treatment was started with moderate effect. The second patient (16 years of age) developed painful sensations in both feet and hands 6 weeks after an ICU admission for diabetic ketoacidosis, which included dysautonomia symptoms. She also exhibited some signs of erythromelalgia. The patient was diagnosed with predominant SFN (abnormal IENFD and quantitative sensory testing) as well as minor large nerve fiber involvement. Treatment with duloxetine, combined with a rehabilitation program, resulted in a marked improvement in her daily functioning. Although the SFN diagnosis in these 2 cases could be established according to the definition of SFN used in adults, additional diagnostic tools are needed that may be more appropriate for children. Additional information about the course of SFN in children may result in better treatment options. Copyright © 2016 by the American Academy of Pediatrics.

  16. A Case of Acute Motor Axonal Neuropathy Mimicking Brain Death and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Sandhya eRavikumar

    2016-04-01

    Full Text Available We describe a case report of fulminant Guillain-Barré syndrome mimicking brain death. A previously healthy 60-year-old male was admitted to the neurointensive care unit after developing rapidly progressive weakness and respiratory failure. On presentation, the patient was found to have absent brainstem and spinal cord reflexes resembling that of brain death. Acute motor axonal neuropathy (AMAN, a subtype of Guillain-Barré syndrome, was diagnosed by cerebrospinal fluid and nerve conduction velocity testing. An electroencephalogram showed that the patient had normal, appropriately reactive brain function. Transcranial Doppler ultrasound showed appropriate blood flow to the brain. Guillain-Barré syndrome rarely presents with weakness so severe as to mimic brain death. This article provides a review of similar literature. This case demonstrates the importance of performing a proper brain death examination, which includes evaluation for irreversible cerebral injury, exclusion of any confounding conditions, and performance of tests such as electroencephalography and transcranial dopplers when uncertainty exists about the reliability of the clinical exam.

  17. Giant iliopectineal bursitis presenting as neuropathy and severe edema of the lower limb: case illustration and review of the literature.

    Science.gov (United States)

    Iwata, Takahiro; Nozawa, Satoshi; Ohashi, Minoru; Sakai, Hiroshi; Shimizu, Katsuji

    2013-05-01

    We report a 61-year-old woman with rheumatoid arthritis (RA: Steinblocker stage III, class 3) who developed severe swelling and neuropathy of the right lower limb caused by an iliopectineal bursa associated with destruction of the hip joint. Physical examination revealed an inguinal mass and groin pain. X-ray examination indicated destruction of the hip joint. Contrast-enhanced computed tomography showed the bursa connected with the hip joint and a markedly compressed external iliac vein among the inguinal ligament, pubis, and bursa. The patient underwent partial synovial resection and total hip arthroplasty for recovery of hip function, and this led to successful resolution of the symptoms and bursa. We present the characteristic images from this case and review all previously reported cases of RA iliopsoas bursitis causing leg swelling or neuropathy, and summarize the background. Since this lesion may cause various symptoms, clinical awareness that iliopsoas bursitis may present with unique clinical symptoms may aid correct diagnosis.

  18. Respiratory function in cybrid cell lines carrying European mtDNA haplogroups: implications for Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Carelli, Valerio; Vergani, Lodovica; Bernazzi, Barbara; Zampieron, Claudia; Bucchi, Laura; Valentino, Maria; Rengo, Chiara; Torroni, Antonio; Martinuzzi, Andrea

    2002-10-09

    The possibility that some combinations of mtDNA polymorphisms, previously associated with Leber's hereditary optic neuropathy (LHON), may affect mitochondrial respiratory function was tested in osteosarcoma-derived transmitochondrial cytoplasmic hybrids (cybrids). In this cellular system, in the presence of the same nuclear background, different exogenous mtDNAs are used to repopulate a parental cell line previously devoid of its original mtDNA. No detectable differences in multiple parameters exploring respiratory function were observed when mtDNAs belonging to European haplogroups X, H, T and J were used. Different possible explanations for the previously established association between haplogroup J and LHON 11778/ND4 and 14484/ND6 pathogenic mutations are discussed, including the unconventional proposal that mtDNA haplogroup J may exert a protective rather than detrimental effect.

  19. Mitochondrial dysfunction due to Leber's hereditary optic neuropathy as a cause of visual loss during assessment for epilepsy surgery.

    Science.gov (United States)

    Niehusmann, Pitt; Surges, Rainer; von Wrede, Randi D; Elger, Christian E; Wellmer, Jörg; Reimann, Jens; Urbach, Horst; Vielhaber, Stefan; Bien, Christian G; Kunz, Wolfram S

    2011-01-01

    Assessment for epilepsy surgery may require invasive measures such as implantation of intracranial electrodes or the Wada test. These investigations are commonly well tolerated. However, complications, including visual disturbances of various etiologies, have been reported. Here we describe two patients with pharmacoresistant temporal lobe epilepsy (TLE) who displayed loss of vision in the context of presurgical assessment and in whom mutations associated with Leber's hereditary optic neuropathy (LHON) were detected. Genetic analysis revealed in one patient the frequent mitochondrial G11778A LHON mutation in ND4. In the second patient, the mitochondrial C4640A mutation in ND2 was detected. This rare LHON mutation enhanced the sensitivity of the patient's muscle and brain tissue to amobarbital, a known blocker of the mitochondrial respiratory chain. Mitochondrial dysfunction has been reported in epilepsy. Thus, the presence of LHON mutations can be a rare cause of visual disturbances in patients with epilepsy and may have predisposed to development of epilepsy.

  20. Deep sequencing unearths nuclear mitochondrial sequences under Leber's hereditary optic neuropathy-associated false heteroplasmic mitochondrial DNA variants.

    Science.gov (United States)

    Petruzzella, Vittoria; Carrozzo, Rosalba; Calabrese, Claudia; Dell'Aglio, Rosa; Trentadue, Raffaella; Piredda, Roberta; Artuso, Lucia; Rizza, Teresa; Bianchi, Marzia; Porcelli, Anna Maria; Guerriero, Silvana; Gasparre, Giuseppe; Attimonelli, Marcella

    2012-09-01

    Leber's hereditary optic neuropathy (LHON) is associated with mitochondrial DNA (mtDNA) ND mutations that are mostly homoplasmic. However, these mutations are not sufficient to explain the peculiar features of penetrance and the tissue-specific expression of the disease and are believed to be causative in association with unknown environmental or other genetic factors. Discerning between clear-cut pathogenetic variants, such as those that appear to be heteroplasmic, and less penetrant variants, such as the homoplasmic, remains a challenging issue that we have addressed here using next-generation sequencing approach. We set up a protocol to quantify MTND5 heteroplasmy levels in a family in which the proband manifests a LHON phenotype. Furthermore, to study this mtDNA haplotype, we applied the cybridization protocol. The results demonstrate that the mutations are mostly homoplasmic, whereas the suspected heteroplasmic feature of the observed mutations is due to the co-amplification of Nuclear mitochondrial Sequences.

  1. Language skills in a child with Leber hereditary optic neuropathy following intrathecal chemotherapy for acute lymphoblastic leukemia.

    Science.gov (United States)

    Lewis, Fiona M; Coman, David J; Murdoch, Bruce E

    2010-11-01

    The language skills of a male child with Leber hereditary optic neuropathy (LHON) and coincidentally treated for acute lymphoblastic leukemia (ALL) with intrathecal chemotherapy at the age of 3 years 8 months were comprehensively evaluated twice over a 6-month period approximately 5½ years after diagnosis of ALL. Despite marked chemotherapy-related leukoencephalopathic changes documented on magnetic resonance imaging, the child presented with stable language skills, which were generally average to above-average based on the normative data from a comprehensive language test battery. In light of the coincidental presentation in the child of a diagnosis of LHON, which may lead to serious vision impairment and increased vulnerability to drug neurotoxicity, coupled with a history of central nervous system (CNS)-directed treatment for ALL resulting in progressive white matter pathology, the study highlights the importance of ongoing monitoring of the child's language development throughout his adolescent years.

  2. Evidence for Detrimental Cross Interactions between Reactive Oxygen and Nitrogen Species in Leber's Hereditary Optic Neuropathy Cells

    Science.gov (United States)

    Santini, Paolo

    2016-01-01

    Here we have collected evidence suggesting that chronic changes in the NO homeostasis and the rise of reactive oxygen species bioavailability can contribute to cell dysfunction in Leber's hereditary optic neuropathy (LHON) patients. We report that peripheral blood mononuclear cells (PBMCs), derived from a female LHON patient with bilateral reduced vision and carrying the pathogenic mutation 11778/ND4, display increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS), as revealed by flow cytometry, fluorometric measurements of nitrite/nitrate, and 3-nitrotyrosine immunodetection. Moreover, viability assays with the tetrazolium dye MTT showed that lymphoblasts from the same patient are more sensitive to prolonged NO exposure, leading to cell death. Taken together these findings suggest that oxidative and nitrosative stress cooperatively play an important role in driving LHON pathology when excess NO remains available over time in the cell environment. PMID:26881022

  3. Previously Unclassified Mutation of mtDNA m.3472T>C: Evidence of Pathogenicity in Leber's Hereditary Optic Neuropathy.

    Science.gov (United States)

    Sheremet, N L; Nevinitsyna, T A; Zhorzholadze, N V; Ronzina, I A; Itkis, Y S; Krylova, T D; Tsygankova, P G; Malakhova, V A; Zakharova, E Y; Tokarchuk, A V; Panteleeva, A A; Karger, E M; Lyamzaev, K G; Avetisov, S E

    2016-07-01

    Leber's hereditary optic neuropathy (LHON) refers to a group of mitochondrial diseases and is characterized by defects of the mitochondrial electron transport chain and decreased level of oxidative phosphorylation. The list of LHON primary mtDNA mutations is regularly updated. In this study, we describe the homoplasmic nucleotide substitution m.3472T>C in the MT-ND1 (NADH-ubiquinone oxidoreductase chain 1) gene and specific changes in cell metabolism in a patient with LHON and his asymptomatic sister. To confirm the presence of mutation-related mitochondrial dysfunction, respiration of skin fibroblasts and platelets from the patient and his sister was studied, as well as the mitochondrial potential and production of reactive oxygen species in the skin fibroblasts. In addition, based on characteristics of the toxic effect of paraquat, a new approach was developed for detecting the functional activity of complex I of the mitochondrial respiratory chain.

  4. Evidence for Detrimental Cross Interactions between Reactive Oxygen and Nitrogen Species in Leber's Hereditary Optic Neuropathy Cells.

    Science.gov (United States)

    Falabella, Micol; Forte, Elena; Magnifico, Maria Chiara; Santini, Paolo; Arese, Marzia; Giuffrè, Alessandro; Radić, Kristina; Chessa, Luciana; Coarelli, Giulia; Buscarinu, Maria Chiara; Mechelli, Rosella; Salvetti, Marco; Sarti, Paolo

    2016-01-01

    Here we have collected evidence suggesting that chronic changes in the NO homeostasis and the rise of reactive oxygen species bioavailability can contribute to cell dysfunction in Leber's hereditary optic neuropathy (LHON) patients. We report that peripheral blood mononuclear cells (PBMCs), derived from a female LHON patient with bilateral reduced vision and carrying the pathogenic mutation 11778/ND4, display increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS), as revealed by flow cytometry, fluorometric measurements of nitrite/nitrate, and 3-nitrotyrosine immunodetection. Moreover, viability assays with the tetrazolium dye MTT showed that lymphoblasts from the same patient are more sensitive to prolonged NO exposure, leading to cell death. Taken together these findings suggest that oxidative and nitrosative stress cooperatively play an important role in driving LHON pathology when excess NO remains available over time in the cell environment.

  5. Evidence for Detrimental Cross Interactions between Reactive Oxygen and Nitrogen Species in Leber’s Hereditary Optic Neuropathy Cells

    Directory of Open Access Journals (Sweden)

    Micol Falabella

    2016-01-01

    Full Text Available Here we have collected evidence suggesting that chronic changes in the NO homeostasis and the rise of reactive oxygen species bioavailability can contribute to cell dysfunction in Leber’s hereditary optic neuropathy (LHON patients. We report that peripheral blood mononuclear cells (PBMCs, derived from a female LHON patient with bilateral reduced vision and carrying the pathogenic mutation 11778/ND4, display increased levels of reactive oxygen species (ROS and reactive nitrogen species (RNS, as revealed by flow cytometry, fluorometric measurements of nitrite/nitrate, and 3-nitrotyrosine immunodetection. Moreover, viability assays with the tetrazolium dye MTT showed that lymphoblasts from the same patient are more sensitive to prolonged NO exposure, leading to cell death. Taken together these findings suggest that oxidative and nitrosative stress cooperatively play an important role in driving LHON pathology when excess NO remains available over time in the cell environment.

  6. Neuropatía óptica hereditaria de Leber Leber´s hereditary optic neuropathy

    Directory of Open Access Journals (Sweden)

    Yannara Elina Columbié Garbey

    2012-06-01

    Full Text Available La neuropatía óptica hereditaria de Leber es una enfermedad de herencia materna que se caracteriza por la pérdida subaguda, indolora y bilateral, aunque por lo general no siempre al unísono de la visión central. Predomina en hombres jóvenes y es causada por mutaciones puntuales del ADN mitocondrial. Esta es una de las neuropatías ópticas hereditarias más frecuentes y altamente invalidante, cuyo diagnóstico de certeza lo constituyen los estudios moleculares. El propósito de esta revisión es alertar en cuanto a su diagnóstico y posible incremento en condiciones ambientales favorecedoras. Se realizó una búsqueda automatizada de artículos científicos relacionados con el tema, en PUBMED e Hinari, que resultó en 37 publicaciones realizadas durante los años 1988-2010. Se estudiaron y discutieron aspectos de la enfermedad tales como antecedentes históricos, factores de riesgo, epidemiología, genética, características clínicas, diagnóstico y tratamiento; además de profundizar en su estado actual en nuestro contexto. En Cuba actualmente se conoce de la existencia de varias familias que padecen la neuropatía óptica hereditaria de Leber. El alza de la incidencia probablemente se debió a las condiciones medioambientales que favorecen o son factores de riesgo de esta entidad, como ocurrió durante la pasada epidemia de neuropatía óptica en Cuba. Cada día se producen más avances en el campo de la genética, que permiten identificar un número mayor de mutaciones asociadas a esta entidad. Esto unido al conocimiento de las características clínicas de la enfermedad ha permitido identificar las familias afectadas y actuar sobre los factores de riesgo.Leber´s hereditary optic neuropathy is a maternally inherited disease characterized by subacute, painless and bilateral loss of the central vision, although not always at the same time. It predominates in young men and is caused by mitochondrial DNA spot mutations. This is one of

  7. Measurement of Systemic Mitochondrial Function in Advanced Primary Open-Angle Glaucoma and Leber Hereditary Optic Neuropathy.

    Directory of Open Access Journals (Sweden)

    Nicole J Van Bergen

    Full Text Available Primary Open Angle Glaucoma (POAG is a common neurodegenerative disease characterized by the selective and gradual loss of retinal ganglion cells (RGCs. Aging and increased intraocular pressure (IOP are glaucoma risk factors; nevertheless patients deteriorate at all levels of IOP, implying other causative factors. Recent evidence presents mitochondrial oxidative phosphorylation (OXPHOS complex-I impairments in POAG. Leber Hereditary Optic Neuropathy (LHON patients suffer specific and rapid loss of RGCs, predominantly in young adult males, due to complex-I mutations in the mitochondrial genome. This study directly compares the degree of OXPHOS impairment in POAG and LHON patients, testing the hypothesis that the milder clinical disease in POAG is due to a milder complex-I impairment. To assess overall mitochondrial capacity, cells can be forced to produce ATP primarily from mitochondrial OXPHOS by switching the media carbon source to galactose. Under these conditions POAG lymphoblasts grew 1.47 times slower than controls, whilst LHON lymphoblasts demonstrated a greater degree of growth impairment (2.35 times slower. Complex-I enzyme specific activity was reduced by 18% in POAG lymphoblasts and by 29% in LHON lymphoblasts. We also assessed complex-I ATP synthesis, which was 19% decreased in POAG patients and 17% decreased in LHON patients. This study demonstrates both POAG and LHON lymphoblasts have impaired complex-I, and in the majority of aspects the functional defects in POAG were milder than LHON, which could reflect the milder disease development of POAG. This new evidence places POAG in the spectrum of mitochondrial optic neuropathies and raises the possibility for new therapeutic targets aimed at improving mitochondrial function.

  8. Measurement of Systemic Mitochondrial Function in Advanced Primary Open-Angle Glaucoma and Leber Hereditary Optic Neuropathy.

    Science.gov (United States)

    Van Bergen, Nicole J; Crowston, Jonathan G; Craig, Jamie E; Burdon, Kathryn P; Kearns, Lisa S; Sharma, Shiwani; Hewitt, Alex W; Mackey, David A; Trounce, Ian A

    2015-01-01

    Primary Open Angle Glaucoma (POAG) is a common neurodegenerative disease characterized by the selective and gradual loss of retinal ganglion cells (RGCs). Aging and increased intraocular pressure (IOP) are glaucoma risk factors; nevertheless patients deteriorate at all levels of IOP, implying other causative factors. Recent evidence presents mitochondrial oxidative phosphorylation (OXPHOS) complex-I impairments in POAG. Leber Hereditary Optic Neuropathy (LHON) patients suffer specific and rapid loss of RGCs, predominantly in young adult males, due to complex-I mutations in the mitochondrial genome. This study directly compares the degree of OXPHOS impairment in POAG and LHON patients, testing the hypothesis that the milder clinical disease in POAG is due to a milder complex-I impairment. To assess overall mitochondrial capacity, cells can be forced to produce ATP primarily from mitochondrial OXPHOS by switching the media carbon source to galactose. Under these conditions POAG lymphoblasts grew 1.47 times slower than controls, whilst LHON lymphoblasts demonstrated a greater degree of growth impairment (2.35 times slower). Complex-I enzyme specific activity was reduced by 18% in POAG lymphoblasts and by 29% in LHON lymphoblasts. We also assessed complex-I ATP synthesis, which was 19% decreased in POAG patients and 17% decreased in LHON patients. This study demonstrates both POAG and LHON lymphoblasts have impaired complex-I, and in the majority of aspects the functional defects in POAG were milder than LHON, which could reflect the milder disease development of POAG. This new evidence places POAG in the spectrum of mitochondrial optic neuropathies and raises the possibility for new therapeutic targets aimed at improving mitochondrial function.

  9. A variant of Leber hereditary optic neuropathy characterized by recovery of vision and by an unusual mitochondrial genetic etiology

    Energy Technology Data Exchange (ETDEWEB)

    Mackey, D. (Royal Children' s Hospital, Melbourne (Australia)); Howell, N. (Univ. of Texas, Galveston (United States))

    1992-12-01

    The Tas2 and Vic2 Australian families are affected with a variant of Leber hereditary optic neuropathy (LHON). The risk of developing the optic neuropathy shows strict maternal inheritance, and the opthalmological changes in affected family members are characteristic of LHON. However, in contrast to the common form of the disease, members of these two families show a high frequency of vision recovery. To ascertain the mitochondrial genetic etiology of the LHON in these families, both (a) the nucleotide sequences of the seven mitochondrial genes encoding subunits of respiratory-chain complex I and (b) the mitochondrial cytochrome b gene were determined for representatives of both families. Neither family carries any of the previously identified primary mitochondrial LHON mutations: ND4/11778, ND1/3460, or ND1/4160. Instead, both LHON families carry multiple nucleotide changes in the mitochondrial complex I genes, which produce conservative amino acid changes. From the available sequence data, it is inferred that the Vic2 and Tas2 LHON families are phylogenetically related to each other and to a cluster of LHON families in which mutations in the mitochondrial cytochrome b gene have been hypothesized to play a primary etiological role. However, sequencing analysis establishes that the Vic2 and Tas2 LHON families do not carry these cytochrome b mutations. There are two hypotheses to account for the unusual mitochondrial genetic etiology of the LHON in the Tas2 and Vic2 LHON families. One possibility is that there is a primary LHON mutation within the mitochondrial genome but that it is at a site that was not included in the sequencing analyses. Alternatively, the disease in these families may result from the cumulative effects of multiple secondary LHON mutations that have less severe phenotypic consequences. 29 refs., 3 figs., 3 tabs.

  10. Measurement of Systemic Mitochondrial Function in Advanced Primary Open-Angle Glaucoma and Leber Hereditary Optic Neuropathy

    Science.gov (United States)

    Van Bergen, Nicole J; Crowston, Jonathan G.; Craig, Jamie E.; Burdon, Kathryn P.; Kearns, Lisa S.; Sharma, Shiwani; Hewitt, Alex W.; Mackey, David A.; Trounce, Ian A.

    2015-01-01

    Primary Open Angle Glaucoma (POAG) is a common neurodegenerative disease characterized by the selective and gradual loss of retinal ganglion cells (RGCs). Aging and increased intraocular pressure (IOP) are glaucoma risk factors; nevertheless patients deteriorate at all levels of IOP, implying other causative factors. Recent evidence presents mitochondrial oxidative phosphorylation (OXPHOS) complex-I impairments in POAG. Leber Hereditary Optic Neuropathy (LHON) patients suffer specific and rapid loss of RGCs, predominantly in young adult males, due to complex-I mutations in the mitochondrial genome. This study directly compares the degree of OXPHOS impairment in POAG and LHON patients, testing the hypothesis that the milder clinical disease in POAG is due to a milder complex-I impairment. To assess overall mitochondrial capacity, cells can be forced to produce ATP primarily from mitochondrial OXPHOS by switching the media carbon source to galactose. Under these conditions POAG lymphoblasts grew 1.47 times slower than controls, whilst LHON lymphoblasts demonstrated a greater degree of growth impairment (2.35 times slower). Complex-I enzyme specific activity was reduced by 18% in POAG lymphoblasts and by 29% in LHON lymphoblasts. We also assessed complex-I ATP synthesis, which was 19% decreased in POAG patients and 17% decreased in LHON patients. This study demonstrates both POAG and LHON lymphoblasts have impaired complex-I, and in the majority of aspects the functional defects in POAG were milder than LHON, which could reflect the milder disease development of POAG. This new evidence places POAG in the spectrum of mitochondrial optic neuropathies and raises the possibility for new therapeutic targets aimed at improving mitochondrial function. PMID:26496696

  11. [The mitochondrial ND5 T12338C mutation may be associated with Leber's hereditary optic neuropathy in two Chinese families].

    Science.gov (United States)

    Ji, Yan-Chun; Liu, Xiao-Ling; Zhao, Fu-Xin; Zhang, Juan-Juan; Zhang, Yu; Zhou, Xiang-Tian; Qu, Jia; Guan, Min-Xin

    2011-04-01

    Leber's hereditary optic neuropathy (LHON) associated with mitochondrial DNA mutation is a maternally inherited eye disease. We reported here the clinical, genetic and molecular characterization of two Han Chinese families with Leber's hereditary optic neuropathy. Ophthalmologic examinations revealed that the variable severity and age-of-onset in visual impairment among probands and other matrilineal relatives of these families. Strikingly, there were extremely low penetrances of visual impairment in these families. Sequence analysis of complete mitochondrial genomes in these pedigrees identified the homoplasmic ND4 G11696A and ND5 T12338C mutation and distinct sets of polymorphism belonging to haplogroups F2. It is well known that mitochondrial DNA ND4 G11696A is associated with LHON. The ND5 T12338C mutation resulted in replacement of the first amino acid, translation-initiating methionine with a threonine, and shortening two amino acids of ND5. This mutation also locates in two nucleotides adjacent to the 3' end of the tRNALeu(Cun). Thus, this mutation may alter structural formation and stabilization of functional tRNA, thereby leading to a failure in protein synthesis and mitochondrial dysfunction involved in visual impairment. Therefore, the ND4 G11696A and ND5 T12338C mutation is likely associated with LHON in these two Chinese families. But these families exhibited extremely low penetrances of visual impairment. It suggests that other factors, such as nuclear modifier gene(s) or environmental factor(s), may play a role in the phenotypic expression of the LHON-associated ND4 G11696A and ND5 T12338C mutation.

  12. Pediatric sciatic neuropathy presenting as painful leg: A case report and review of literature

    Directory of Open Access Journals (Sweden)

    Manish Prasad

    2013-01-01

    Full Text Available Introduction: Mononeuropathies, in general, are very uncommon in childhood. Sciatic neuropathy (SN is probably underappreciated in childhood and likely to represent nearly one quarter of childhood mononeuropathies. Materials and Methods: We present a 7-year-old girl who presented with painful right lower limb and abnormal gait. Detailed investigation revealed transient eosinophilia, abnormal neurophysiology, and magnetic resonance imaging (MRI suggestive of isolated sciatic neuropathy. Results: She has responded very well to physiotherapy and has made a complete motor recovery, although she is left with an area of abnormal sensation affecting the lateral border of her right leg and the dorsum of her foot. Discussion: Differential diagnoses for pediatric SN have been discussed including compressive neuropathies in children and various hyper-eosinophilia syndromes. Compressive neuropathies in childhood are very rare and compression of the sciatic nerve is the second most common group after peroneal nerve lesion.

  13. A review of nerve conduction studies in cases of suspected compression neuropathies of the upper limb.

    LENUS (Irish Health Repository)

    Neligan, A

    2010-01-01

    Entrapment neuropathies, particularly those affecting upper limbs, are common reasons for referral for nerve conduction studies (NCS). However, concordance between clinical findings and NCS findings, especially in patients being considered for intervention including decompressive surgery, has not been assessed.

  14. Leber's遗传性视神经病变患者的线粒体DNA检测%Diagnostic and differential diagnostic potent6ial of mitochondrial DNA assessment in patients with Leber's hereditary optic neuropathy

    Institute of Scientific and Technical Information of China (English)

    冯雪梅; 濮伟; 高殿文; 伊佐敷靖; 大庭纪雄

    2001-01-01

    Objective To study the primary mutations of mitochondrial DNA (mtDNA) associated with Leber′s hereditary optic neuropathy (LHON) in patients with optic neuropathy. Methods Seventy-nine patients with a variety of bilateral optic neuropathy were examined. Mutations at np 3 460, np 11 778 and np 14 484 of mtDNA were tested by PCR-restriction fregment length polymorphism technique to detect DNA in peripheral blood. The samples were taken from 16 cases of clinically diagnosed LHON, 44 cases of suspected LHON, two cases of alcohol amblyopia, four cases of multiple sclerosis, five cases of autosomal dominant hereditary optic atrophy, 4 cases with primary open-angle glaucoma, three cases of spinocerebellar degeneration, and one case of ethambutol-induced optic neuropathy. Results The mutation at np 11 778 was identified in 31 cases (39.2%), consisting of all the 16 clinically diagnosed LHON cases, thirteen cases (29.5%) of the suspected LHON, and the two cases of alcohol amblyopia. The remaining 48 cases were negative for mtDNA mutations at np 3 460, np 11 778, or np 14 484. Conclusion Assessment of mtDNA provides a useful diagnsotic aid in confirming and excluding the diagnosis of LHON, particularly useful in cases without a family hereditary history and cases with cause unknown bilateral optic neuritis.%目的探讨与Leber's遗传性视神经病变(Leber's hereditary optic neuropathy,LHON)相关的线粒体DNA原发位点突变在视神经疾病中的诊断意义。方法 79例各种原因引起的双侧视神经疾病中,16例为临床诊断的LHON患者,44例为可疑LHON患者,2例为酒精性弱视患者,4例为多发性硬化症患者,5例为常染色体显性遗传的视神经萎缩患者,4例为原发性开角型青光眼患者,3例为脊髓小脑退行性变和1例乙胺丁醇引起的视神经萎缩患者。用聚合酶链反应(polymerase chain reaction, PCR)及限制性片段长度多态性技术,检测外

  15. Patterns of white matter diffusivity abnormalities in Leber's hereditary optic neuropathy: a tract-based spatial statistics study.

    Science.gov (United States)

    Milesi, Jacopo; Rocca, Maria A; Bianchi-Marzoli, Stefania; Petrolini, Melissa; Pagani, Elisabetta; Falini, Andrea; Comi, Giancarlo; Filippi, Massimo

    2012-09-01

    Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease characterized by retinal ganglion cell degeneration and optic nerve atrophy, leading to a loss of central vision. The aim of this study was to explore the topographical pattern of damage to the brain white matter (WM) tracts from patients with chronic LHON using diffusion tensor (DT) MRI and tract-based spatial statistics (TBSS). Brain dual-echo and DT MRI scans were acquired from 13 patients with chronic LHON and 25 matched controls using a 3.0 T scanner. TBSS analysis was performed using the FMRIB's Diffusion Toolbox. A complete neuro-ophthalmologic examination, including standardized automated Humphrey perimetry as well as average and temporal peripapillary retinal nerve fiber layer thickness (PRNFL) measurements, was obtained in all patients. Mean average and temporal PRNFL thicknesses were decreased significantly in LHON patients. Compared to controls, TBSS analysis revealed significant diffusivity abnormalities in these patients, which were characterized by a decreased fractional anisotropy (FA) and an increased mean diffusivity and radial diffusivity, affecting exclusively the optic tracts and optic radiations (OR). In patients, a significant correlation was found between optic tract average FA and mean visual acuity (r = 0.57, p = 0.04). In LHON patients, DT MRI reveals a microstructural alteration of the WM along the entire visual pathways, with a sparing of the other main WM tracts of the brain. Damage to the OR may be secondary either to trans-synaptic degeneration, which in turn is due to neuroaxonal loss in the retina and optic nerve, or to local mitochondrial dysfunction.

  16. Impending anterior ischemic optic neuropathy with elements of retinal vein occlusion in a patient on interferon for polycythemia vera

    Directory of Open Access Journals (Sweden)

    Rue KS

    2012-10-01

    Full Text Available Kelly S Rue, Louis K Hirsch, Alfredo A SadunDepartment of Neuro-Ophthalmology, Doheny Eye Institute and Keck School of Medicine, University of Southern California, Los Angeles, CA, USAAbstract: We describe the course and likely pathophysiology of impending anterior ischemic optic neuropathy (AION and retinal vein occlusion in a 56-year-old man with polycythemia vera managed with interferon alpha for 2 years. Our patient presented with decreased vision, scintillating scotomata, and floaters. Fundus examination findings and results of a fluorescein angiogram led to the diagnosis of impending AION and retinal vein occlusion. Considering that both polycythemia vera and interferon have possible influences on vascular occlusion and optic disc edema, we stopped interferon treatment and immediately attempted to treat the polycythemia vera empirically with pentoxifylline and any interferon-associated inflammation with prednisone. Our patient experienced complete resolution of fundus abnormalities and return of normal vision within 3 weeks, which may be attributed to our successful treatment of both etiologies. Thus, further study is warranted to elucidate the treatment of both polycythemia vera and interferon-induced impending AION.Keywords: optic disc edema, interferon alpha, vascular occlusion, Roth spot, autoantibody, pentoxifylline

  17. Painful neuropathy caused by compression of the inferior alveolar nerve by focal osteosclerotic lesion of the mandible: A case report.

    Science.gov (United States)

    Debevc, David; Hitij, Tomaž; Kansky, Andrej

    2017-01-01

    Osteosclerotic lesions are a common finding on dental radiographs. They are considered developmental variants of a normal bone architecture and they usually do not need any treatment. The purpose of this article is to present a rare case of osteosclerotic lesion of the mandible causing trigeminal neuropathy by compression of the alveolar nerve. The pain started with dental hypersensitivity of the mandibular right first molar. Later on, signs of irreversible molar tooth pulpitis developed. Endodontic therapy and apicoectomy did not resolve the pain, which later intensified, and painful neuropathy localized to inferior alveolar nerve developed; therefore, surgical decompression was indicated. Treating a dental patient with neuralgic pain is always a challenge, especially if there is no obvious source or reason for this type of pain. A clear evaluation and treatment protocol are important to minimize the patient's morbidity and avoid unnecessary overtreatment.

  18. Two Cases of Elderly-Onset Hereditary Neuropathy with Liability to Pressure Palsy Manifesting Bilateral Peroneal Nerve Palsies

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    Norihiko Kawaguchi

    2012-10-01

    Full Text Available Hereditary neuropathy with liability to pressure palsy (HNPP is characterized by recurrent focal neuropathies, which usually become symptomatic in the second or third decade of life. However, clinical phenotypic heterogeneity among patients with HNPP has recently been reported. Certain patients show polyneuropathy-type diffuse nerve injuries, whereas others remain asymptomatic at older ages. We present two cases of elderly-onset bilateral peroneal nerve palsies with diffuse muscle weakness in the lower limbs and glove-and-stocking type sensory disturbance. Both patients were diagnosed with HNPP by genetic analyses that detected deletions of chromosome 17p11.2 in peripheral myelin protein 22 genes. Their clinical courses suggested that the Japanese sitting style termed ‘seiza’, a way of sitting on the floor with the lower legs crossed under the thighs, was a precipitating factor for the bilateral peroneal nerve palsies.

  19. Drug-induced peripheral neuropathy

    DEFF Research Database (Denmark)

    Vilholm, Ole Jakob; Christensen, Alex Alban; Zedan, Ahmed;

    2014-01-01

    Peripheral neuropathy can be caused by medication, and various descriptions have been applied for this condition. In this MiniReview, the term 'drug-induced peripheral neuropathy' (DIPN) is used with the suggested definition: Damage to nerves of the peripheral nervous system caused by a chemical...... substance used in the treatment, cure, prevention or diagnosis of a disease. Optic neuropathy is included in this definition. A distinction between DIPN and other aetiologies of peripheral neuropathy is often quite difficult and thus, the aim of this MiniReview is to discuss the major agents associated...

  20. Effective intravenous immunoglobulin therapy for Churg-Strauss syndrome (allergic granulomatous angiitis complicated by neuropathy of the eighth cranial nerve: a case report

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    Ozaki Yoshio

    2012-09-01

    Full Text Available Abstract Introduction We report the case of a patient with Churg-Strauss syndrome with eighth cranial nerve palsy. Vestibulocochlear nerve palsy is extremely rare in Churg-Strauss syndrome. To the best of our knowledge, only one case of complicated neuropathy of the eighth cranial nerve has been described in a previous report presenting an aggregate calculation, but no differentiation between polyarteritis nodosa and Churg-Strauss syndrome was made. High-dose immunoglobulin was administered to our patient, and her neuropathy of the eighth cranial nerve showed improvement. Case presentation At the age of 46, a Japanese woman developed Churg-Strauss syndrome that later became stable with low-dose prednisolone treatment. At the age of 52, she developed sudden difficulty of hearing in her left ear, persistent severe rotary vertigo, and mononeuritis multiplex. At admission, bilateral perceptive deafness of about 80dB and eosinophilia of 4123/μL in peripheral blood were found. A diagnosis of cranial neuropathy of the eighth cranial nerve associated with exacerbated Churg-Strauss syndrome was made. Although high doses of steroid therapy alleviated the inflammatory symptoms and markers, the vertigo and bilateral hearing loss remained. Addition of a high-dose immunoglobulin finally resulted in marked alleviation of the symptoms associated with neuropathy of the eighth cranial nerve. Conclusions A high dose of immunoglobulin therapy shows favorable effects in neuropathy of the eighth cranial nerve, but no reports regarding its efficacy in cranial neuropathy have been published.

  1. Pupil responses derived from outer and inner retinal photoreception are normal in patients with hereditary optic neuropathy.

    Science.gov (United States)

    Kawasaki, Aki; Collomb, Sylvie; Léon, Lorette; Münch, Mirjam

    2014-03-01

    We compared the pupil responses originating from outer versus inner retinal photoreception between patients with isolated hereditary optic neuropathy (HON, n = 8) and healthy controls (n = 8). Three different testing protocols were used. For the first two protocols, a response function of the maximal pupil contraction versus stimulus light intensity was generated and the intensity at which half of the maximal pupil contraction, the half-max intensity, was determined. For the third protocol, the pupil size after light offset, the re-dilation rate and re-dilation amplitude were calculated to assess the post-light stimulus response. Patients with HON had bilateral, symmetric optic atrophy and significant reduction of visual acuity and visual field compared to controls. There were no significant mean differences in the response curve and pupil response parameters that reflect mainly rod, cone or melanopsin activity between patients and controls. In patients, there was a significant correlation between the half-max intensity of the red light sequence and visual field loss. In conclusion, pupil responses derived from outer or inner retinal photoreception in HON patients having mild-to moderate visual dysfunction are not quantitatively different from age-matched controls. However, an association between the degree of visual field loss and the half-max intensity of the cone response suggests that more advanced stages of disease may lead to impaired pupil light reflexes.

  2. Idebenone protects against retinal damage and loss of vision in a mouse model of Leber's hereditary optic neuropathy.

    Directory of Open Access Journals (Sweden)

    Fabrice D Heitz

    Full Text Available Leber's hereditary optic neuropathy (LHON is an inherited disease caused by mutations in complex I of the mitochondrial respiratory chain. The disease is characterized by loss of central vision due to retinal ganglion cell (RGC dysfunction and optic nerve atrophy. Despite progress towards a better understanding of the disease, no therapeutic treatment is currently approved for this devastating disease. Idebenone, a short-chain benzoquinone, has shown promising evidence of efficacy in protecting vision loss and in accelerating recovery of visual acuity in patients with LHON. It was therefore of interest to study suitable LHON models in vitro and in vivo to identify anatomical correlates for this protective activity. At nanomolar concentrations, idebenone protected the rodent RGC cell line RGC-5 against complex I dysfunction in vitro. Consistent with the reported dosing and observed effects in LHON patients, we describe that in mice, idebenone penetrated into the eye at concentrations equivalent to those which protected RGC-5 cells from complex I dysfunction in vitro. Consequently, we next investigated the protective effect of idebenone in a mouse model of LHON, whereby mitochondrial complex I dysfunction was caused by exposure to rotenone. In this model, idebenone protected against the loss of retinal ganglion cells, reduction in retinal thickness and gliosis. Furthermore, consistent with this protection of retinal integrity, idebenone restored the functional loss of vision in this disease model. These results support the pharmacological activity of idebenone and indicate that idebenone holds potential as an effective treatment for vision loss in LHON patients.

  3. Efficacy and Safety of rAAV2-ND4 Treatment for Leber’s Hereditary Optic Neuropathy

    Science.gov (United States)

    Wan, Xing; Pei, Han; Zhao, Min-jian; Yang, Shuo; Hu, Wei-kun; He, Heng; Ma, Si-qi; Zhang, Ge; Dong, Xiao-yan; Chen, Chen; Wang, Dao-wen; Li, Bin

    2016-01-01

    Leber’s hereditary optic neuropathy (LHON) is a mitochondrially inherited disease leading to blindness. A mitochondrial DNA point mutation at the 11778 nucleotide site of the NADH dehydrogenase subunit 4 (ND4) gene is the most common cause. The aim of this study was to evaluate the efficacy and safety of a recombinant adeno-associated virus 2 (AAV2) carrying ND4 (rAAV2-ND4) in LHON patients carrying the G11778A mutation. Nine patients were administered rAAV2-ND4 by intravitreal injection to one eye and then followed for 9 months. Ophthalmologic examinations of visual acuity, visual field, and optical coherence tomography were performed. Physical examinations included routine blood and urine. The visual acuity of the injected eyes of six patients improved by at least 0.3 log MAR after 9 months of follow-up. In these six patients, the visual field was enlarged but the retinal nerve fibre layer remained relatively stable. No other outcome measure was significantly changed. None of the nine patients had local or systemic adverse events related to the vector during the 9-month follow-up period. These findings support the feasible use of gene therapy for LHON. PMID:26892229

  4. Intravitreal delivery of AAV-NDI1 provides functional benefit in a murine model of Leber hereditary optic neuropathy.

    Science.gov (United States)

    Chadderton, Naomi; Palfi, Arpad; Millington-Ward, Sophia; Gobbo, Oliverio; Overlack, Nora; Carrigan, Matthew; O'Reilly, Mary; Campbell, Matthew; Ehrhardt, Carsten; Wolfrum, Uwe; Humphries, Peter; Kenna, Paul F; Farrar, G Jane

    2013-01-01

    Leber hereditary optic neuropathy (LHON) is a mitochondrially inherited form of visual dysfunction caused by mutations in several genes encoding subunits of the mitochondrial respiratory NADH-ubiquinone oxidoreductase complex (complex I). Development of gene therapies for LHON has been impeded by genetic heterogeneity and the need to deliver therapies to the mitochondria of retinal ganglion cells (RGCs), the cells primarily affected in LHON. The therapy under development entails intraocular injection of a nuclear yeast gene NADH-quinone oxidoreductase (NDI1) that encodes a single subunit complex I equivalent and as such is mutation independent. NDI1 is imported into mitochondria due to an endogenous mitochondrial localisation signal. Intravitreal injection represents a clinically relevant route of delivery to RGCs not previously used for NDI1. In this study, recombinant adenoassociated virus (AAV) serotype 2 expressing NDI1 (AAV-NDI1) was shown to protect RGCs in a rotenone-induced murine model of LHON. AAV-NDI1 significantly reduced RGC death by 1.5-fold and optic nerve atrophy by 1.4-fold. This led to a significant preservation of retinal function as assessed by manganese enhanced magnetic resonance imaging and optokinetic responses. Intraocular injection of AAV-NDI1 overcomes many barriers previously associated with developing therapies for LHON and holds great therapeutic promise for a mitochondrial disorder for which there are no effective therapies.

  5. Inner retinal contributions to the multifocal electroretinogram: patients with Leber's hereditary optic neuropathy (LHON). Multifocal ERG in patients with LHON.

    Science.gov (United States)

    Kurtenbach, Anne; Leo-Kottler, Beate; Zrenner, Eberhart

    2004-05-01

    In this study we examine the multifocal electroretinogram (mfERG) recorded from patients suffering from Leber's hereditary optic neuropathy (LHON), a degeneration of the ganglion cell and nerve fibre layers of the retina. We compared the mfERGs recorded from 11 patients with LHON, to those from 11 control subjects. The pattern ERG (PERG) was additionally performed with 9 of the patients. MfERGs were recorded and analysed using the VERIS 3.01 system with a stimulus of 103 equal-sized hexagons. For analysis, hexagons were grouped according to distance from the optic nerve head (ONH) and according to distance from the fovea. Two significant differences were found between the waveforms of the two groups: In the first order kernel, the control group showed a component around 34 ms that decreased with distance from the ONH. This component was reduced in the LHON group of subjects. In the second order (first slice) kernel, the patient group was missing features that decrease with distance from the fovea in the control group. PERG amplitudes showed a significant correlation with the amplitude of the second order mfERG kernel. The results show that the damage to ganglion cells and nerve fibres caused by LHON can be detected in mfERG recordings and indicate that activity from the inner retina can contribute significantly to first and second order waveforms.

  6. Idebenone protects against retinal damage and loss of vision in a mouse model of Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Heitz, Fabrice D; Erb, Michael; Anklin, Corinne; Robay, Dimitri; Pernet, Vincent; Gueven, Nuri

    2012-01-01

    Leber's hereditary optic neuropathy (LHON) is an inherited disease caused by mutations in complex I of the mitochondrial respiratory chain. The disease is characterized by loss of central vision due to retinal ganglion cell (RGC) dysfunction and optic nerve atrophy. Despite progress towards a better understanding of the disease, no therapeutic treatment is currently approved for this devastating disease. Idebenone, a short-chain benzoquinone, has shown promising evidence of efficacy in protecting vision loss and in accelerating recovery of visual acuity in patients with LHON. It was therefore of interest to study suitable LHON models in vitro and in vivo to identify anatomical correlates for this protective activity. At nanomolar concentrations, idebenone protected the rodent RGC cell line RGC-5 against complex I dysfunction in vitro. Consistent with the reported dosing and observed effects in LHON patients, we describe that in mice, idebenone penetrated into the eye at concentrations equivalent to those which protected RGC-5 cells from complex I dysfunction in vitro. Consequently, we next investigated the protective effect of idebenone in a mouse model of LHON, whereby mitochondrial complex I dysfunction was caused by exposure to rotenone. In this model, idebenone protected against the loss of retinal ganglion cells, reduction in retinal thickness and gliosis. Furthermore, consistent with this protection of retinal integrity, idebenone restored the functional loss of vision in this disease model. These results support the pharmacological activity of idebenone and indicate that idebenone holds potential as an effective treatment for vision loss in LHON patients.

  7. Gene therapy for mitochondrial diseases: Leber Hereditary Optic Neuropathy as the first candidate for a clinical trial.

    Science.gov (United States)

    Cwerman-Thibault, Hélène; Augustin, Sébastien; Ellouze, Sami; Sahel, José-Alain; Corral-Debrinski, Marisol

    2014-03-01

    Mitochondrial disorders cannot be ignored anymore in most medical disciplines; indeed their minimum estimated prevalence is superior to 1 in 5000 births. Despite the progress made in the last 25 years on the identification of gene mutations causing mitochondrial pathologies, only slow progress was made towards their effective treatments. Ocular involvement is a frequent feature in mitochondrial diseases and corresponds to severe and irreversible visual handicap due to retinal neuron loss and optic atrophy. Interestingly, three clinical trials for Leber Congenital Amaurosis due to RPE65 mutations are ongoing since 2007. Overall, the feasibility and safety of ocular Adeno-Associated Virus delivery in adult and younger patients and consistent visual function improvements have been demonstrated. The success of gene-replacement therapy for RPE65 opens the way for the development of similar approaches for a broad range of eye disorders, including those with mitochondrial etiology such as Leber Hereditary Optic Neuropathy (LHON). Copyright © 2013 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  8. Inflammatory neuropathies.

    Science.gov (United States)

    Whitesell, Jackie

    2010-09-01

    Inflammatory neuropathies are acquired disorders of peripheral nerves and occasionally of the central nervous system that can affect individuals at any age. The course can be monophasic, relapsing, or progressive. Inflammatory neuropathies are classified as acute or chronic. The acute form reaches a nadir by 4 weeks and the chronic form over 8 weeks or greater. The most common example of an acute inflammatory neuropathy is acute inflammatory demyelinating polyradiculoneuropathy (AIDP), which is part of the Guillain-Barré syndrome (GBS). The most common chronic inflammatory neuropathy is chronic inflammatory demyelinating polyradiculopathy (CIDP). Other chronic inflammatory neuropathies are multifocal motor neuropathy (MMN) and the Lewis-Sumner syndrome. The Fisher syndrome and Bickerstaff brainstem encephalitis occur acutely and have clinical overlap with AIDP.

  9. Autonomic neuropathy

    DEFF Research Database (Denmark)

    Hilsted, J

    1980-01-01

    In order to elucidate the physiological significance of autonomic neuropathy in juvenile diabetics, cardiovascular, hormonal and metabolic functions have been investigated in three groups of juvenile diabetics: One group had no signs of neuropathy, one group had presumably slight autonomic...... neuropathy (reduced beat-to-beat variation in heart rate during hyperventilation) and one group had clinically severe autonomic neuropathy, defined by presence of orthostatic hypotension. In all three experimental situations we found sympathetic dysfunction causing cardiovascular and/or hormonal...... maladjustments in patients with autonomic neuropathy. Regarding metabolic functions we found normal responses to graded exercise and insulin-induced hypoglycemia in patients with autonomic neuropathy in spite of blunted catecholamine responses, suggesting increased sensitivity of glycogen stores and adipose...

  10. P-ANCA vasculitic neuropathy with 12-year latency between onset of neuropathy and systemic symptoms

    Directory of Open Access Journals (Sweden)

    Greenberg Steven A

    2002-10-01

    Full Text Available Abstract Background The differential diagnosis of chronic progressive multifocal asymmetric neuropathies is challenging. Vasculitic neuropathies, multifocal forms of chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathies, and asymmetric lower motor neuron disorders are important considerations. Case presentation We report a patient with an unusually long 12-year course of nonsystemic vasculitic neuropathy prior to the development of systemic manifestations. Conclusion We discuss some of the difficulties involved in the diagnosis of chronic progressive multifocal asymmetric neuropathies.

  11. Bilateral paraneoplastic optic neuropathy and unilateral retinal compromise in association with prostate cancer: a differential diagnostic challenge in a patient with unexplained visual loss.

    Science.gov (United States)

    Carboni, Giovannella; Forma, Gina; Bond, April D; Adamus, Grazyna; Iannaccone, Alessandro

    2012-08-01

    We report a 77-year-old Caucasian man with a 1-year complaint of unexplained visual loss and a 4-year history of prostate cancer. A complete ophthalmologic exam, Goldmann visual fields (GVFs), intravenous fluorescein angiography (IVFA), macular and disc optical coherence tomography (OCT), pattern-reversal visual evoked potentials (PVEPs), and flash electroretinograms (ERGs) were performed. On examination, visual acuity was reduced bilaterally. Fundus exam showed juxtapapillary changes (OS > OD) and, in OS, disc pallor, peripheral RPE dropout and whitish retinal discoloration along the arcades. OCTs were normal OU. Cancer-associated retinopathy (CAR) was suspected. A flash ERG was normal OD and markedly reduced and electronegative OS. An IVFA showed bilateral juxtapapillary staining and changes highly suggestive of sequelae of central retinal artery occlusion (CRAO) OS , in which a cilioretinal artery existed along the papillomacular bundle. GVFs showed bilateral blind spot enlargement and centrocecal scotomas, and PVEPs were delayed. These findings suggested cancer-associated optic neuropathy (CAON), confirmed by presence of anti-optic nerve autoantibodies (auto-Abs). No anti-retinal auto-Abs were found. CAON is a less common paraneoplastic manifestation than CAR and it is rarely observed in association with prostate cancer. A combination of visual function testing methods permitted the recognition, in this highly unusual case, of the concurrent presence of unilateral ERG changes most likely attributable to CRAO complications in OS, in all likelihood unrelated to CAON, and not to be confused with unilateral CAR. Auto-Ab testing in combination with visual function tests helps achieve a better understanding of the pathophysiology of vision loss in paraneoplastic visual syndromes.

  12. [Autonomic neuropathies].

    Science.gov (United States)

    Siepmann, T; Penzlin, A I; Illigens, B M W

    2013-07-01

    Autonomic neuropathies are a heterogeneous group of diseases that involve damage of small peripheral autonomic Aδ- and C-fibers. Causes of autonomic nerve fiber damage are disorders such as diabetes mellitus and HIV-infection. Predominant symptoms of autonomic neuropathy are orthostatic hypotension, gastro-intestinal problems, urogenital dysfunction, and cardiac arrhythmia, which can severely impair the quality of life in affected patients. Furthermore, autonomic neuropathies can be induced by autoimmune diseases such as acute inflammatory demyelinating polyneuropathy, hereditary disorders such as the lysosomal storage disorder Fabry disease and hereditary sensory and autonomic neuropathies, as well as certain toxins and drugs.

  13. Thalidomide neuropathy in childhood.

    Science.gov (United States)

    Fleming, Fiona J; Vytopil, Michal; Chaitow, Jeffrey; Jones, H Royden; Darras, Basil T; Ryan, Monique M

    2005-02-01

    Thalidomide was withdrawn from world markets in 1961 following recognition of its teratogenic effects. More recently, however, thalidomide treatment has been reintroduced to adult and paediatric practice for a variety of dermatologic, immunologic, rheumatologic and neoplastic disorders. Neuropathy is a significant side effect of thalidomide therapy, which may limit its clinical use. We report four cases of sensorimotor axonal neuropathy in children aged 10-15 years, treated with thalidomide for myxopapillary ependymoma, Crohn's disease and recurrent giant aphthous ulceration. Thalidomide neuropathy is often associated with proximal weakness and may progress even after discontinuation of treatment, in the phenomenon of 'coasting'. Children treated with thalidomide should undergo regular neurophysiologic studies in order to detect presymptomatic or progressive peripheral neuropathy.

  14. X-inactivation patterns in female Leber`s hereditary optic neuropathy patients do not support a strong X-linked determinant

    Energy Technology Data Exchange (ETDEWEB)

    Pegoraro, E.; Hoffman, E.P. [Univ. of Pittsburgh School of Medicine, PA (United States); Carelli, V.; Cortelli, P. [Univ. of Bologna (Italy)] [and others

    1996-02-02

    Leber`s hereditary optic neuropathy (LHON) accounts for about 3% of the cases of blindness in young adult males. The underlying mitochondrial pathogenesis of LHON has been well studied, with specific mitochondrial DNA (mtDNA) mutations of structural genes described and well characterized. However, enigmatic aspects of the disease are not explained by mutation data, such as the higher proportion of affected males, the later onset of the disease in females, and the presence of unaffected individuals with a high proportion of mutant mtDNA. A hypothesis which has been put forward to explain the unusual disease expression is a dual model of mtDNA and X-linked nuclear gene inheritance. If a nuclear X-linked modifier gene influences the expression of the mitochondrial-linked mutant gene then the affected females should be either homozygous for the nuclear determinant, or if heterozygous, lyonization should favor the mutant X. In order to determine if an X-linked gene predisposes to LHON phenotype we studied X-inactivation patterns in 35 females with known mtDNA mutations from 10 LHON pedigrees. Our results do not support a strong X-linked determinant in LHON cause: 2 of the 10 (20%) manifesting carriers showed skewing of X-inactivation, as did 3 of the 25 (12%) nonmanifesting carriers. 39 refs., 2 figs., 1 tab.

  15. Pure motor axonal neuropathy triggered by antituberculous therapy in an undiagnosed case of acute intermittent porphyria.

    Science.gov (United States)

    Babar, Masood Uz Zaman; Hakeem, Haris; Khan, Sara

    2017-03-27

    A man aged 22 years misdiagnosed as suffering from recurrent abdominal tuberculosis, in view of recurrent abdominal pain was treated for abdominal tuberculosis in the past. The patient was prescribed antituberculous therapy. 2 months after starting treatment, he developed progressive weakness of all 4 limbs. Electrodiagnostic examination revealed an acute severe motor axonal neuropathy. Further workup revealed elevated porphyrin precursors in urine.

  16. Clinical pathological and genetic analysis of 2 cases of mitochondrial myopathy presented as acute motor axonal neuropathy

    Directory of Open Access Journals (Sweden)

    Hou-min YIN

    2014-06-01

    Full Text Available Background The main clinical manifestations of mitochondrial myopathy are chronic limb weakness and muscular soreness. Subclinical peripheral nerve injury is also reported, but acute axonal neuropathy.like syndrome concurrent with lactic acidosis is rare. In this paper the clinical features of 2 patients presenting as acute lactic acidosis and sudden muscle weakness were analyzed. Pathological changes and genetic mutations were detected.  Methods Electromyography (EMG and muscle biopsy were performed. Modified Gomori trichrome (MGT and succinodehydrogenase (SDH staining were used to identify pathological changes. Changes of ultra microstructure of muscular tissue were observed under electron microscope. Mitochondrial DNA (mtDNA full length sequencing was performed using 24 pairs of partially overlapping primers.  Results EMG showed a coexistence of neurogenic and myogenic changes. Dramatic decrease of motor nerve amplitude and moderately reduced sensory nerve amplitude were observed but nerve conduction velocity was normal in both patients. Impressive ragged red fibers were seen on MGT staining. Electron microscope showed dramatic mitochondrial abnormalities in Case 1 and paracrystaline inclusions in Case 2. mtDNA sequencing showed 3243A > G mutation in Case 1 and 8344A > G mutation in Case 2. Conclusions Mitochondrial myopathy can present as metabolic crisis like acute lactic acidosis, dyspnea and acute motor axonal neuropathy.like syndrome. It is a life.threatening phenotype that needs more attention. doi: 10.3969/j.issn.1672-6731.2014.06.007

  17. [A case of sensory ataxic neuropathy, dysarthria, and ophthalmoparesis with multiple mitochondrial DNA deletions].

    Science.gov (United States)

    Tanaka, Koji; Tateishi, Takahisa; Kawamura, Nobutoshi; Ohyagi, Yasumasa; Urata, Michiyo; Kira, Jun-ichi

    2013-01-01

    We report the case of a 62-year-old man with sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO). He developed gait disturbance at 54 years of age, muscle weakness at 56 years, and difficulty hearing at 58 years. His brother had muscle weakness in both legs from age 20 years, and was diagnosed with Charcot-Marie-Tooth disease because he had muscle weakness of the four extremities, decreased CMAP and SNAP amplitudes on peripheral nerve conduction tests, and loss of large myelinated fibers and onion-bulb formations on sural nerve biopsy. His brother died aged 46 years, but no accurate cause of death was identified. Neurological examination of the present patient revealed bilateral ptosis, external ophthalmoparesis, dysarthria, dysphagia, sensorineural hearing loss, mild weakness and atrophy of proximal muscles in all four limbs, severe sensory ataxia, and disturbance of deep sensation in his legs. He showed elevation of lactate and pyruvate levels in cerebrospinal fluid and serum. An aerobic exercise test disclosed a marked increase in lactate and pyruvate levels in serum. On nerve conduction study, amplitudes of CMAP and SNAP, and F wave-evoked frequency were decreased. Needle electromyography showed chronic neurogenic patterns with fibrillation potentials in the extremity muscles. Head MRI demonstrated T2 prolonged lesions in the bilateral basal ganglia, while brain MRS revealed a small lactate peak. Biopsy of his left lateral vastus muscle showed ragged-red fibers and group atrophy, and some muscle fibers had decreased cytochrome c activity. Left sural nerve biopsy revealed a marked loss of large myelinated fibers, and some onion-bulb formations. Genetic testing disclosed a large mtDNA deletion in the biopsied muscle. Among nuclear genes, we found point mutations in ANT-1 (exon 1 c.105G>A, 5' untranslated region) and POLG-1 (exon 4, c.1218G>A, p. and exon 23 c.3920C>T, p.A1217V). We diagnosed SANDO. This is the first case of SANDO with large

  18. Ulnar nerve compression neuropathy at Guyon's canal caused by crutch walking: case report with ultrasonographic nerve imaging.

    Science.gov (United States)

    Ginanneschi, Federica; Filippou, Georgios; Milani, Paolo; Biasella, Alessia; Rossi, Alessandro

    2009-03-01

    This report is the first account of Guyon's syndrome after the bilateral use of forearm crutches. Crutch palsy is usually neuropraxic in nature and associated with clinical and electrophysiologic recovery of nerve function, especially if patients are instructed to not bear excessive weight on the wrist. The present case history follows this pattern. In establishing the diagnosis of a focal compression neuropathy, a combination of clinical assessment and neurophysiologic studies are typically used. This report describes the additional application of ultrasound imaging to verify the diagnosis and to track changes in the appearance of the nerve during follow-up.

  19. Isolated sciatic neuropathy as an initial manifestation of a high grade B-cell lymphoma: A case report and literature review.

    Science.gov (United States)

    He, Wenzhuan; Wang, Weizhen; Gustas, Cristy; Malysz, Jozef; Kaur, Divpreet

    2016-10-01

    Sciatic nerve neuropathy due to infiltrating of a high grade B-cell lymphoma is a very rare situation and has not often been reported. We report a case with a previous history of indolent lymphoma who presented with isolated sciatic nerve neuropathy and was found to have diffuse large B cell lymphoma involving the sciatic nerve. Although the current case is not a primary sciatic nerve lymphoma given the systematic involvement shown on MRI and PET/CT scan, the case represents a neurolymphomatosis of the sciatic nerve given the direct invasion of the lymphoma cells into the sciatic nerve. Due to the rarity of this condition, we subsequently reviewed related literatures.

  20. [Diabetic neuropathy].

    Science.gov (United States)

    Chudzik, Wiesław; Kaczorowska, Beata; Przybyła, Monika; Chudzik, Bartosz; Gałka, Małgorzata

    2007-01-01

    Diabetic neuropathy is most common chronic complication of diabetes mellitus. It is responsible for substantial morbidity, increased mortality and impaired quality of life. Patogenesis of diabetic neuropathy is complex. Chronic hyperglycemia is a major factor induces nerve fibers injury. High level of glucose stimulate the polyol pathway causing osmotic stress and enhance reactive oxygen species generation, as well as it play an important role in diabetic angiopathy development. Distal symmetric polineuropathy is most common type of diabetic neuropathy. Many patient may develop combinations of neuropathies concerning somatic and autonomic system. Early diagnosis and administered suitable treatment are necessary to reduce severe complication of diabetic neuropathy as well as strict glycemic control and risk factor increased.

  1. Mitochondrial variants may influence the phenotypic manifestation of Leber's hereditary optic neuropathy-associated ND4 G11778A mutation

    Institute of Scientific and Technical Information of China (English)

    Wanshi Cai; Qun Fu; Xiangtian Zhou; Jia Qu; Yi Tong; Min-Xin Guan

    2008-01-01

    We report here the characterization of a five-generation Han Chinese family with Leber's hereditary optic neuropathy (LHON). Strik-ingly, this Chinese family displayed high penetrance and expressivity of visual loss. The average age-of-onset of vision loss was 18 years in this family. Nineteen (11 males/8 females) of 29 matrilineal relatives in this family developed visual loss with a wide range of severity,ranging from blindness to normal vision. Sequence analysis of mitochondrial genome in this pedigree revealed the presence of the ND4 G11778A mutation and 44 other variants belonging to Asian haplogroup M7b. The G11778A mutation is present at homoplasmy in matri-lineal relatives of this Chinese family. Of other variants, the CO1 G6480A, ND5 T12811C and Cytb A15395G located at highly conserved residues of corresponding polypeptides. In fact, these variants were implicated to be involved in other clinical abnormalities. Here, these variants may act in synergy with the primary LHON-associated Gl1778A mutation. Thus, the mitochondrial dysfunction caused by the primary ND4 G11778A mutation may be worsened by these mitochondrial variants. The results imply that the G6480A, T12811C and A15395G variants might have a potential modifier role in increasing the penetrance and expressivity of the primary LHON-associated G11778A mutation in this Chinese family.

  2. Leber's hereditary optic neuropathy is associated with mitochondrial ND6 T14502C mutation

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Fuxin [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Guan, Minqiang [Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Zhou, Xiangtian [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Yuan, Meixia; Liang, Ming [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Liu, Qi [Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Liu, Yan; Zhang, Yongmei [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Yang, Li [Division of Human Genetics, Cincinnati Children' s Hospital Medical Center, Cincinnati, OH 45229 (United States); Tong, Yi [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350005 (China); Wei, Qi-Ping; Sun, Yan-Hong [Department of Ophthalmology, Dongfang Hospital, Beijing University of Chinese Medicine and Pharmacology, Beijing 100078 (China); Qu, Jia, E-mail: jqu@wzmc.net [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); and others

    2009-11-20

    We report here the clinical, genetic, and molecular characterization of three Chinese families with Leber's hereditary optic neuropathy (LHON). There were variable severity and age of onset in visual impairment among these families. Strikingly, there were extremely low penetrances of visual impairment in these Chinese families. Sequence analysis of complete mitochondrial genomes in these pedigrees showed the homoplasmic T14502C (I58V) mutation, which localized at a highly conserved isoleucine at position 58 of ND6, and distinct sets of mtDNA polymorphisms belonging to haplogroups M10a, F1a1, and H2. The occurrence of T14502C mutation in these several genetically unrelated subjects affected by visual impairment strongly indicates that this mutation is involved in the pathogenesis of visual impairment. Here, mtDNA variants I187T in the ND1, A122V in CO1, S99A in the A6, and V254I in CO3 exhibited an evolutionary conservation, indicating a potential modifying role in the development of visual impairment associated with T14502C mutation in those families. Furthermore, nuclear modifier gene(s) or environmental factor(s) may play a role in the phenotypic manifestation of the LHON-associated T14502C mutation in these Chinese families.

  3. Leber's hereditary optic neuropathy is associated with mitochondrial ND1 T3394C mutation

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Min [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Guan, Minqiang [Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Zhao, Fuxing; Zhou, Xiangtian [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Yuan, Meixia [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Tong, Yi [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350005 (China); Yang, Li [Division of Human Genetics, Cincinnati Children' s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 (United States); Wei, Qi-Ping; Sun, Yan-Hong [Department of Ophthalmology, Dongfang Hospital, Beijing University of Chinese Medicine and Pharmacology, Beijing 100078 (China); Lu, Fan [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Qu, Jia, E-mail: jqu@wzmc.net [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); and others

    2009-06-05

    We report here the clinical, genetic and molecular characterization of four Chinese families with Leber's hereditary optic neuropathy (LHON). There were variable severity and age-of-onset in visual impairment among these families. Strikingly, there were extremely low penetrances of visual impairment in these Chinese families. Sequence analysis of complete mitochondrial genomes in these pedigrees showed the homoplasmic T3394C (Y30H) mutation, which localized at a highly conserved tyrosine at position 30 of ND1, and distinct sets of mtDNA polymorphisms belonging to haplogroups D4b and M9a. The occurrence of T3394C mutation in these several genetically unrelated subjects affected by visual impairment strongly indicates that this mutation is involved in the pathogenesis of visual impairment. However, there was the absence of functionally significant mtDNA mutations in these four Chinese pedigrees carrying the T3394C mutation. Therefore, nuclear modifier gene(s) or environmental factor(s) may play a role in the phenotypic expression of the LHON-associated T3394C mutation.

  4. Leber氏病的线粒体研究%Research on Leber's Hereditary Optic Neuropathy in Two Strips

    Institute of Scientific and Technical Information of China (English)

    肖文玮; 郭锋; 李春霞; 王颖; 陈良君; 于晓莉

    2005-01-01

    目的了解Leber氏遗传性视神经病变(Leber's hereditary optic neuropathy,LHON)相关的线粒体DNA原发性突变基因检测结果,探讨该项检查的临床意义.方法采用聚合酶链反应(polymerase chain reaction,PCR),检测先证者及其母系血缘亲属外周血DNA中提取的线粒体DNA的3 460位点,11778位点.结果本组临床确诊患者的DNA均表现为11 778位点突变,未发现3 460位点突变.结论Leber病发病机制为mtDNA点突变,线粒体DNA的检测分析为确立LHON提供了诊断依据,尤其对无家族史或原因不明的双侧性视神经炎的患者更具有诊断价值.并为其它神经性遗传病的研究提供了技术支撑.

  5. Leber's hereditary optic neuropathy (LHON) pathogenic mutations induce mitochondrial-dependent apoptotic death in transmitochondrial cells incubated with galactose medium.

    Science.gov (United States)

    Ghelli, Anna; Zanna, Claudia; Porcelli, Anna Maria; Schapira, Anthony H V; Martinuzzi, Andrea; Carelli, Valerio; Rugolo, Michela

    2003-02-01

    Leber's hereditary optic neuropathy (LHON), a maternally inherited form of central vision loss, is associated with mitochondrial DNA pathogenic point mutations affecting different subunits of complex I. We here report that osteosarcoma-derived cytoplasmic hybrids (cybrid) cell lines harboring one of the three most frequent LHON pathogenic mutations, at positions 11778/ND4, 3460/ND1, and 14484/ND6, undergo cell death when galactose replaces glucose in the medium, contrary to control cybrids that maintain some growth capabilities. This is a well known way to produce a metabolic stress, forcing the cells to rely on the mitochondrial respiratory chain to produce ATP. We demonstrate that LHON cybrid cell death is apoptotic, showing chromatin condensation and nuclear DNA laddering. Moreover, we also document the mitochondrial involvement in the activation of the apoptotic cascade, as shown by the increased release of cytochrome c into the cytosol in LHON cybrid cells as compared with controls. Cybrids bearing the 3460/ND1 and 14484/ND6 mutations seemed more readily prone to undergo apoptosis as compared with the 11778/ND4 mutation. In conclusion, LHON cybrid cells forced by the reduced rate of glycolytic flux to utilize oxidative metabolism are sensitized to an apoptotic death through a mechanism involving mitochondria.

  6. Minocycline, a possible neuroprotective agent in Leber's hereditary optic neuropathy (LHON): studies of cybrid cells bearing 11,778 mutation.

    Science.gov (United States)

    Haroon, Mohammad Fahad; Fatima, Ambrin; Schöler, Susanne; Gieseler, Anne; Horn, Thomas F W; Kirches, Elmar; Wolf, Gerald; Kreutzmann, Peter

    2007-12-01

    Leber's hereditary optic neuropathy (LHON) is a retinal neurodegenerative disorder caused by mitochondrial DNA point mutations. Complex I of the respiratory chain affected by the mutation results in a decrease in ATP and an increase of reactive oxygen species production. Evaluating the efficacy of minocycline in LHON, the drug increased the survival of cybrid cells in contrast to the parental cells after thapsigargin-induced calcium overload. Similar protection was observed by treatment with cyclosporine A, a blocker of the mitochondrial permeability transition pore (mPTP). Ratiometric Ca(2+) imaging reveals that acetylcholine/thapsigargin triggered elevation of the cytosolic calcium concentration is alleviated by minocycline and cyclosporine A. The mitochondrial membrane potential of LHON cybrids was significantly conserved and the active-caspase-3/procaspase-3 ratio was decreased in both treatments. Our observations show that minocycline inhibits permeability transition induced by thapsigargin in addition to its antioxidant effects. In relation with its high safety profile, these results would suggest minocycline as a promising neuroprotective agent in LHON.

  7. Mitochondrial tRNA(Thr) A15951G mutation may not be associated with Leber's Hereditary Optic Neuropathy.

    Science.gov (United States)

    Zhang, Xi; Yu, Shuaishuai; Tu, Yunhai; Huang, Wenjie

    2016-07-01

    Mutation in mitochondrial DNA (mtDNA) has been found to play an important role in the pathogenesis of Leber's Hereditary Optic Neuropathy (LHON). Three primary mutations, the ND4 G11778A, ND6 T14484C, and ND1 G3460A, have been found to account more than 90% of LHON patients in many families worldwide. In addition to the mutations in genes encoding the respiratory chain complex I, reports concerning the mt-tRNA gene mutations associated with LHON have increased, some pathogenic mutations caused the failure in mt-tRNA metabolism, thereby worsened the mitochondrial dysfunction that is responsible for LHON. Recently, the A15951G mutation in mt-tRNA(Thr) gene has been reported to be a "modified" factor in increasing the penetrance and expressivity of LHON-associated ND4 G11778A mutation in three Chinese families. However, evolutionary conservation analysis of this mutation suggested a poor conservation index and the pathogenicity scoring system showed that this mutation was a neutral polymorphism.

  8. Non-Invasive Cell-Based Therapy for Traumatic Optic Neuropathy

    Science.gov (United States)

    2013-10-01

    3. Work out protocols for creating TAI with our customized forceps; cholera toxin B (CTB) to anterogradely labeling optic nerves and...Association for Research in Vision and Ophthalmology Society for Neuroscience Editorial member of Transplantation & technology and research

  9. Optic nerve atrophy

    Science.gov (United States)

    Optic atrophy; Optic neuropathy ... There are many causes of optic atrophy. The most common is poor blood flow. This is called ischemic optic neuropathy. The problem most often affects older adults. The optic ...

  10. A Simple Oligonucleotide Biochip Capable of Rapidly Detecting Known Mitochondrial DNA Mutations in Chinese Patients with Leber’S Hereditary Optic Neuropathy (LHON

    Directory of Open Access Journals (Sweden)

    Wei-Dong Du

    2011-01-01

    Full Text Available Leber's hereditary optic neuropathy (LHON is a maternally transmitted disease. Clinically, no efficient assay protocols have been available. In this study, we aimed to develop an oligonucleotide biochip specialized for detection of known base substitution mutations in mitochondrial DNA causing LHON and to investigate frequencies of LHON relevant variants in Anhui region of China. Thirty-two pairs of oligonucleotide probes matched with the mutations potentially linked to LHON were covalently immobilized. Cy5-lablled targets were amplified from blood DNA samples by a multiplex PCR method. Two kinds of primary mutations 11778 G > A and 14484 T > C from six confirmed LHON patients were interrogated to validate this biochip format. Further, fourteen Chinese LHON pedigrees and twenty-five unrelated healthy individuals were investigated by the LHON biochip, direct sequencing and pyrosequencing, respectively. The biochip was found to be able efficiently to discriminate homoplasmic and heteroplasmic mtDNA mutations in LHON. Biochip analysis revealed that twelve of eighteen LHON symptomatic cases from the 14 Chinese pedigree harbored the mutations either 11778G > A, 14484T > C or 3460G > A, respectively, accounting for 66.7%. The mutation 11778G > A in these patients was homoplasmic and prevalent (55.5%, 10 of 18 cases. The mutations 3460G > A and 3394T > C were found to co-exist in one LHON case. The mutation 13708G > A appeared in one LHON pedigree. Smaller amount of sampling and reaction volume, easier target preparation, fast and high-throughput were the main advantages of the biochip over direct DNA sequencing and pyrosequencing. Our findings suggested that primary mutations of 11778G > A, 14484T > C or 3460G > A are main variants of mtDNA gene leading to LHON in China. The biochip would easily be implemented in clinical diagnosis.

  11. A simple oligonucleotide biochip capable of rapidly detecting known mitochondrial DNA mutations in Chinese patients with Leber's hereditary optic neuropathy (LHON).

    Science.gov (United States)

    Du, Wei-Dong; Chen, Gang; Cao, Hui-Min; Jin, Qing-Hui; Liao, Rong-Feng; He, Xiang-Cheng; Chen, Da-Ben; Huang, Shu-Ren; Zhao, Hui; Lv, Yong-Mei; Tang, Hua-Yang; Tang, Xian-Fa; Wang, Yong-Qing; Sun, Song; Zhao, Jian-Long; Zhang, Xue-Jun

    2011-01-01

    Leber's hereditary optic neuropathy (LHON) is a maternally transmitted disease. Clinically, no efficient assay protocols have been available. In this study, we aimed to develop an oligonucleotide biochip specialized for detection of known base substitution mutations in mitochondrial DNA causing LHON and to investigate frequencies of LHON relevant variants in Anhui region of China. Thirty-two pairs of oligonucleotide probes matched with the mutations potentially linked to LHON were covalently immobilized. Cy5-lablled targets were amplified from blood DNA samples by a multiplex PCR method. Two kinds of primary mutations 11778 G > A and 14484 T > C from six confirmed LHON patients were interrogated to validate this biochip format. Further, fourteen Chinese LHON pedigrees and twenty-five unrelated healthy individuals were investigated by the LHON biochip, direct sequencing and pyrosequencing, respectively. The biochip was found to be able efficiently to discriminate homoplasmic and heteroplasmic mtDNA mutations in LHON. Biochip analysis revealed that twelve of eighteen LHON symptomatic cases from the 14 Chinese pedigree harbored the mutations either 11778G > A, 14484T > C or 3460G A, respectively, accounting for 66.7%. The mutation 11778G > A in these patients was homoplasmic and prevalent (55.5%, 10 of 18 cases). The mutations 3460G > A and 3394T > C were found to co-exist in one LHON case. The mutation 13708G > A appeared in one LHON pedigree. Smaller amount of sampling and reaction volume, easier target preparation, fast and high-throughput were the main advantages of the biochip over direct DNA sequencing and pyrosequencing. Our findings suggested that primary mutations of 11778G > A, 14484T > C or 3460G > A are main variants of mtDNA gene leading to LHON in China. The biochip would easily be implemented in clinical diagnosis.

  12. Fifteen novel mutations in the mitochondrial NADH dehydrogenase subunit 1, 2, 3, 4, 4L, 5 and 6 genes from Iranian patients with Leber's hereditary optic neuropathy (LHON).

    Science.gov (United States)

    Rezvani, Zahra; Didari, Elmira; Arastehkani, Ahoura; Ghodsinejad, Vadieh; Aryani, Omid; Kamalidehghan, Behnam; Houshmand, Massoud

    2013-12-01

    Leber's hereditary optic neuropathy (LHON) is an optic nerve dysfunction resulting from mutations in mitochondrial DNA (mtDNA), which is transmitted in a maternal pattern of inheritance. It is caused by three primary point mutations: G11778A, G3460A and T14484C; in the mitochondrial genome. These mutations are sufficient to induce the disease, accounting for the majority of LHON cases, and affect genes that encode for the different subunits of mitochondrial complexes I and III of the mitochondrial respiratory chain. Other mutations are secondary mutations associated with the primary mutations. The purpose of this study was to determine MT-ND variations in Iranian patients with LHON. In order to determine the prevalence and distribution of mitochondrial mutations in the LHON patients, their DNA was studied using PCR and DNA sequencing analysis. Sequencing of MT-ND genes from 35 LHON patients revealed a total of 44 nucleotide variations, in which fifteen novel variations-A14020G, A13663G, C10399T, C4932A, C3893G, C10557A, C12012A, C13934T, G4596A, T12851A, T4539A, T4941A, T13255A, T14353C and del A 4513-were observed in 27 LHON patients. However, eight patients showed no variation in the ND genes. These mutations contribute to the current database of mtDNA polymorphisms in LHON patients and may facilitate the definition of disease-related mutations in human mtDNA. This research may help to understand the disease mechanism and open up new diagnostic opportunities for LHON.

  13. Genetic and biochemical impairment of mitochondrial complex I activity in a family with Leber hereditary optic neuropathy and hereditary spastic dystonia

    Energy Technology Data Exchange (ETDEWEB)

    De Vries, D.D.; Oost, B.A. van [Univ. Hospital Nijmegen (Netherlands); Went, L.N.; Bruyn, G.W. [Univ. of Leiden (Netherlands)] [and others

    1996-04-01

    A rare form of Leber hereditary optic neuropathy (LHON) that is associated with hereditary spastic dystonia has been studied in a large Dutch family. Neuropathy and ophthalmological lesions were present together in some family members, whereas only one type of abnormality was found in others. mtDNA mutations previously reported in LHON were not present. Sequence analysis of the protein-coding mitochondrial genes revealed two previously unreported mtDNA mutations. A heteroplasmic A{yields}G transition at nucleotide position 11696 in the ND4 gene resulted in the substitution of an isoleucine for valine at amino acid position 312. A second mutation, a homoplasmic T{yields}A transition at nucleotide position 14596 in the ND6 gene, resulted in the substitution of a methionine for the isoleucine at amino acid residue 26. Biochemical analysis of a muscle biopsy revealed a severe complex I deficiency, providing a link between these unique mtDNA mutations and this rare, complex phenotype including Leber optic neuropathy. 80 refs., 2 figs., 3 tabs.

  14. A clinical study of Leber hereditary optic neuropathy%Leber遗传性视神经病变临床研究

    Institute of Scientific and Technical Information of China (English)

    韦企平; 孙艳红; 周翔天; 周剑; 宫晓红; 贾小云

    2012-01-01

    ,Intraocular pressure (IOP),virual field and visual evoked potential (VEP) were tested for all the patients.Some(64 cases) had optical coherence tomography (OCT) measurement.Mutations of mtDNA were detected for all the groups,and clinical analysis were carried out emphatically in the patients with the 11778 mutation confirmed by gene assessment.T paired test was used to evaluate two group patients of different Mitochondrial DNA mutation.Results Gene mutations were found in 215 of the 414 patients (52%).Approximately 93% (199/255) of the patients were caused by the common primary mutations (11778,14484,3460 mutation),in which 100% mutation (106/106) in group A,65% (91/139) in group B,and 11% (18/169) in group C.No cases were diagnosed with confirmed LHON in the patients with unilateral optic neuropathy.Fundus examination in 334 eyes of 167 cases showed pseudo papilledema (54 eyes),normal (67 eyes),pale disc or plae on the teperal side of the optic disc (213 eyes).On the basis data of OCT from 64 patients and 84 normal person,RNFL was found thickening at the early stage and thinning gradually at the later stage in the LHON patients.But,the RNFL thickness of patients with 1-2 years history was not significantly different from the patients with over 2 years history(P =0.051),and there was no difference among the patients with different mitochondrial DNA mutations.The initial mean VA of patients with the 14484 mutation and 11778 mutation were 3.6±0.65,3.75 ± 0.54(t=0.536,P>0.05),but the follow-up VA were 4.29 ± 0.55 (t =4.034,P < 0.001) and 3.93 ± 0.49 respectively (t =1.857,P >0.05).Conclusions The symptoms and fundus manifestation were similar in the LHOH patients with different primary site muation.Gene mutation analysis is helpful to assess the prognosis of visual acuity.

  15. Acute Motor Axonal Neuropathy (Aman) With Motor Conduction Blocks In Childhood; Case Report

    OpenAIRE

    Yildirim, Serhan; Adviye, Rahşan; Gül, Hakan Levent; Türk Börü, Ülkü

    2016-01-01

    Objective Acute motor axonal neuropathy (AMAN), characterized with decreased compound muscle action potentials (CMAP) and absence of demyelinating findings in electrophysiological studies, is a subtype of Guillain-Barre Syndrome (GBS). A 4 yr-old male patient presented with ascending weakness, dysarthria and dysphagia to İstanbul Dr. Lütfi Kırdar Kartal Training and Research Hospital Neurology outpatient for three days to in 2012. Dysphonia, restricted eye movements, flaccid tetraplegia and a...

  16. Pseudohypertrophy of the calf muscles in a patient with diabetic neuropathy: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Jin; Lee, Young Hwan; Jung, Kyung Jae; Park, Young Chan; Kim, Ho Kyun; Kim, Ok Dong [School of Medicine, Catholic University of Daegu, Daegu (Korea, Republic of)

    2007-09-15

    Partial or complete loss of innervation of skeletal muscle leads to muscle weakness and atrophic changes, resulting in decreased muscle volume with fatty replacement. Rarely, enlargement of the affected muscle may occur, related to two processes: true hypertrophy and pseudohypertrophy. We report CT and MR findings of the pseudohypertrophy of calf muscles, especially the soleus and gastrocnemius muscles, in a patient with diabetic neuropathy that showed increased muscle volume with diffuse fatty replacement and the presence of scanty muscle fibers.

  17. Stem Cell Ophthalmology Treatment Study (SCOTS: bone marrow-derived stem cells in the treatment of Leber′s hereditary optic neuropathy

    Directory of Open Access Journals (Sweden)

    Jeffrey N Weiss

    2016-01-01

    Full Text Available The Stem Cell Ophthalmology Treatment Study (SCOTS is currently the largest-scale stem cell ophthalmology trial registered at ClinicalTrials.gov (identifier: NCT01920867. SCOTS utilizes autologous bone marrow-derived stem cells (BMSCs to treat optic nerve and retinal diseases. Treatment approaches include a combination of retrobulbar, subtenon, intravitreal, intra-optic nerve, subretinal, and intravenous injection of autologous BMSCs according to the nature of the disease, the degree of visual loss, and any risk factors related to the treatments. Patients with Leber′s hereditary optic neuropathy had visual acuity gains on the Early Treatment Diabetic Retinopathy Study (ETDRS of up to 35 letters and Snellen acuity improvements from hand motion to 20/200 and from counting fingers to 20/100. Visual field improvements were noted. Macular and optic nerve head nerve fiber layer typically thickened. No serious complications were seen. The increases in visual acuity obtained in our study were encouraging and suggest that the use of autologous BMSCs as provided in SCOTS for ophthalmologic mitochondrial diseases including Leber′s hereditary optic neuropathy may be a viable treatment option.

  18. Stem Cell Ophthalmology Treatment Study (SCOTS):bone marrow-derived stem cells in the treatment of Leber’s hereditary optic neuropathy

    Institute of Scientific and Technical Information of China (English)

    Jeffrey N Weiss; Steven Levy; Susan C Benes

    2016-01-01

    hTe Stem Cell Ophthalmology Treatment Study (SCOTS) is currently the largest-scale stem cell ophthal-mology trial registered at ClinicalTrials.gov (identiifer: NCT01920867). SCOTS utilizes autologous bone marrow-derived stem cells (BMSCs) to treat optic nerve and retinal diseases. Treatment approaches include a combination of retrobulbar, subtenon, intravitreal, intra-optic nerve, subretinal, and intravenous injection of autologous BMSCs according to the nature of the disease, the degree of visual loss, and any risk factors related to the treatments. Patients with Leber’s hereditary optic neuropathy had visual acuity gains on the Early Treatment Diabetic Retinopathy Study (ETDRS) of up to 35 letters and Snellen acuity improvements from hand motion to 20/200 and from counting ifngers to 20/100. Visual ifeld improvements were noted. Macular and optic nerve head nerve ifber layer typically thickened. No serious complications were seen. hTe increases in visual acuity obtained in our study were encouraging and suggest that the use of autolo-gous BMSCs as provided in SCOTS for ophthalmologic mitochondrial diseases including Leber’s hereditary optic neuropathy may be a viable treatment option.

  19. Bilateral optic neuropathy and intraretinal deposits after pars plana vitrectomy in amyloidosis

    Directory of Open Access Journals (Sweden)

    Rossetti Alberto

    2015-01-01

    Full Text Available Pathological examination of material from a nonextensive pars plana vitrectomy (PPV in the right eye provided a diagnosis of nonfamilial amyloidosis in a 68-year-old woman, who presented with bilateral glass wool-like vitreous opacities. Genetic testing revealed a Tyr114Cys mutation in the transthyretin gene. Six months after PPV, perimetry showed intense constriction with a temporal island and central scotoma in the right eye. An extensive PPV was performed in the left eye. Spectral domain optical coherence tomography evidenced bilateral epimacular amyloid deposits and unreported reflective spots within the inner retina. One year later, visual acuity had decreased to 20/400 in the left eye, with mild vitreous opacity, pale cupped optic disc and inferior altitudinal field defect. Bilateral diurnal intraocular pressure, transiently increased after PPV, never exceeded 16 mmHg with medication. Our patient presented optic nerve blood supply impairment, due to amyloidosis, which caused optic atrophy. Epiretinal and intraretinal deposit detection could aid in diagnosing patients with suspected amyloidosis.

  20. Autonomic neuropathies

    Science.gov (United States)

    Low, P. A.

    1998-01-01

    A limited autonomic neuropathy may underlie some unusual clinical syndromes, including the postural tachycardia syndrome, pseudo-obstruction syndrome, heat intolerance, and perhaps chronic fatigue syndrome. Antibodies to autonomic structures are common in diabetes, but their specificity is unknown. The presence of autonomic failure worsens prognosis in the diabetic state. Some autonomic neuropathies are treatable. Familial amyloid polyneuropathy may respond to liver transplantation. There are anecdotal reports of acute panautonomic neuropathy responding to intravenous gamma globulin. Orthostatic hypotension may respond to erythropoietin or midodrine.

  1. Diffusion-Weighted Imaging of Traumatic Optic Neuropathy: Diagnosis and Predicting the Prognosis

    Science.gov (United States)

    2014-01-01

    protocols at the Shock Trauma Center usually involve early facial fracture fixation with metallic plates (often in the initial 1 or 2 days). Performing...such as signs of major facial trauma involving swollen shut eyes, orbital bone fractures, and muscle entrapment, then justification of enrollment...fibers and occurs from a number of mechanisms both in blunt and penetrating trauma . Out of all the types of ocular injuries, traumatic optic

  2. Vasculitic neuropathies.

    Science.gov (United States)

    Gwathmey, Kelly Graham; Burns, Ted Michael; Collins, Michael Paul; Dyck, P James Bonham

    2014-01-01

    The vasculitic neuropathies are a diverse group of disorders characterised by the acute-to-subacute onset of painful sensory and motor deficits that result from inflammatory destruction of nerve blood vessels and subsequent ischaemic injury. They are common in patients with primary systemic vasculitis and are seen in vasculitis secondary to disorders such as rheumatoid arthritis, viral infections, and diabetic inflammatory neuropathies. It is imperative that neurologists recognise these disorders to initiate treatment promptly and thereby prevent morbidity and mortality. To simplify the approach to patients with vasculitis of the peripheral nerves, a straightforward, dichotomous classification scheme can be used in which the vasculitic neuropathies are divided into two groups-nerve large arteriole vasculitis and nerve microvasculitis-on the basis of the size of the involved vessels. The size of the affected blood vessels correlates with the clinical course and prognosis in patients with vasculitic neuropathy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Autonomic Neuropathy

    Science.gov (United States)

    ... harm. Alpha-lipoic acid Preliminary research suggests this antioxidant may be helpful in slowing or even reversing ... electrical waves transmitted through electrodes placed on the skin, may help ease pain associated with diabetic neuropathy. ...

  4. Mitochondrial DNA mutation m.10680G > A is associated with Leber hereditary optic neuropathy in Chinese patients

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    Zhang A-Mei

    2012-03-01

    Full Text Available Abstract Background Leber hereditary optic neuropathy (LHON is a mitochondrial disorder with gender biased and incomplete penetrance. The majority of LHON patients are caused by one of the three primary mutations (m.3460G > A, m.11778G > A and m.14484T > C. Rare pathogenic mutations have been occasionally reported in LHON patients. Methods We screened mutation m.10680G > A in the MT-ND4L gene in 774 Chinese patients with clinical features of LHON but lacked the three primary mutations by using allele specific PCR (AS-PCR. Patients with m.10680G > A were further determined entire mtDNA genome sequence. Results The optimal AS-PCR could detect as low as 10% heteroplasmy of mutation m.10680G > A. Two patients (Le1263 and Le1330 were identified to harbor m.10680G > A. Analysis of the complete mtDNA sequences of the probands suggested that they belonged to haplogroups B4a1 and D6a1. There was no other potentially pathogenic mutation, except for a few private yet reported variants in the MT-ND1 and MT-ND5 genes, in the two lineages. A search in reported mtDNA genome data set (n = 9277; excluding Chinese LHON patients identified no individual with m.10680G > A. Frequency of m.10680G > A in Chinese LHON patients analyzed in this study and our previous studies (3/784 was significantly higher than that of the general populations (0/9277 (P = 0.0005. Conclusion Taken together, we speculated that m.10680G > A may be a rare pathogenic mutation for LHON in Chinese. This mutation should be included in future clinical diagnosis.

  5. Longitudinal study of a heteroplasmic 3460 Leber hereditary optic neuropathy family by multiplexed primer-extension analysis and nucleotide sequencing

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, S.S.; Fahy, E. [Applied Genetics, San Diego, CA (United States); Bodis-Wollner, I. [State Univ. of New York College of Optometry, New York, NY (United States)] [and others

    1996-02-01

    Nucleotide-sequencing and multiplexed primer-extension assays have been used to quantitate the mutant-allele frequency in 14 maternal relatives, spanning three generations, from a family that is heteroplasmic for the primary Leber hereditary optic neuropathy (LHON) mutation at nucleotide 3460 of the mitochondrial genome. There was excellent agreement between the values that were obtained with the two different methods. The longitudinal study shows that the mutant-allele frequency was constant within individual family members over a sampling period of 3.5 years. Second, although there was an overall increase in the mutant-allele frequency in successive generations, segregation in the direction of the mutant allele was not invariant, and there was one instance in which there was a significant decrease in the frequency from parent to offspring. From these two sets of results, and from previous studies of heteroplasmic LHON families, we conclude that there is no evidence for a marked selective pressure that determines the replication, segregation, or transmission of primary LHON mutations to white blood cells and platelets. Instead, the mtDNA molecules are most likely to replicate and segregate under conditions of random drift at the cellular level. Finally, the pattern of transmission in this maternal lineage is compatible with a developmental bottleneck model in which the number of mitochondrial units of segregation in the female germ line is relatively small in relation to the number of mtDNA molecules within a cell. However, this is not an invariant pattern for humans, and simple models of mitochondrial gene transmission are inappropriate at the present time. 37 refs., 4 figs., 1 tab.

  6. Unilateral anterior ischemic optic neuropathy: chromatic pupillometry in affected, fellow non-affected and healthy control eyes

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    Kristina eHerbst

    2013-05-01

    Full Text Available The intrinsically photosensitive retinal ganglion cells (ipRGCs express the photopigment melanopsin, which is sensitive to blue light. Previous chromatic pupillometry studies have shown that the post-illumination response is considered an indicator of the melanopsin activation. The aim of this study was to investigate the ipRGC mediated pupil response in patients with a unilateral non-arteritic anterior ischemic optic neuropathy (NAION. Consensual pupil responses during and after exposure to continuous 20 s blue (470 nm or red (660 nm light of high intensity (300 cd/m2 were recorded in each eye for 10 patients. Comparisons were performed both intra-individually (affected versus non-affected eyes and inter-individually (compared with healthy controls. The pupil response was calculated both during the illumination and during the post-illumination phase. The pupil responses to blue and red colours were significantly reduced in the NAION-affected eyes, compared with the fellow non-affected eyes. When comparing the affected eyes with the healthy control eyes, the post-illumination responses were not significantly different. In addition, the post-illumination pupil responses after blue light exposure were increased in the fellow non-affected patients’ eyes, compared with the healthy controls. However, significance was only reached for the late post-illumination response. In conclusion, chromatic pupillometry disclosed reduced post-illumination pupil responses in the NAION-affected eyes, compared with the non-affected fellow eyes, suggesting dysfunction of the ipRGCs. Compared with the responses of the healthy controls, the blue light post-illumination pupil responses were similar in the affected eyes and increased in the fellow non-affected eyes. This suggests a possible adaptive phenomenon, involving the ipRGCs of both eyes after unilateral NAION.

  7. Cigarette toxicity triggers Leber's hereditary optic neuropathy by affecting mtDNA copy number, oxidative phosphorylation and ROS detoxification pathways

    Science.gov (United States)

    Giordano, L; Deceglie, S; d'Adamo, P; Valentino, M L; La Morgia, C; Fracasso, F; Roberti, M; Cappellari, M; Petrosillo, G; Ciaravolo, S; Parente, D; Giordano, C; Maresca, A; Iommarini, L; Del Dotto, V; Ghelli, A M; Salomao, S R; Berezovsky, A; Belfort, R; Sadun, A A; Carelli, V; Loguercio Polosa, P; Cantatore, P

    2015-01-01

    Leber's hereditary optic neuropathy (LHON), the most frequent mitochondrial disease, is associated with mitochondrial DNA (mtDNA) point mutations affecting Complex I subunits, usually homoplasmic. This blinding disorder is characterized by incomplete penetrance, possibly related to several genetic modifying factors. We recently reported that increased mitochondrial biogenesis in unaffected mutation carriers is a compensatory mechanism, which reduces penetrance. Also, environmental factors such as cigarette smoking have been implicated as disease triggers. To investigate this issue further, we first assessed the relationship between cigarette smoke and mtDNA copy number in blood cells from large cohorts of LHON families, finding that smoking was significantly associated with the lowest mtDNA content in affected individuals. To unwrap the mechanism of tobacco toxicity in LHON, we exposed fibroblasts from affected individuals, unaffected mutation carriers and controls to cigarette smoke condensate (CSC). CSC decreased mtDNA copy number in all cells; moreover, it caused significant reduction of ATP level only in mutated cells including carriers. This implies that the bioenergetic compensation in carriers is hampered by exposure to smoke derivatives. We also observed that in untreated cells the level of carbonylated proteins was highest in affected individuals, whereas the level of several detoxifying enzymes was highest in carriers. Thus, carriers are particularly successful in reactive oxygen species (ROS) scavenging capacity. After CSC exposure, the amount of detoxifying enzymes increased in all cells, but carbonylated proteins increased only in LHON mutant cells, mostly from affected individuals. All considered, it appears that exposure to smoke derivatives has a more deleterious effect in affected individuals, whereas carriers are the most efficient in mitigating ROS rather than recovering bioenergetics. Therefore, the identification of genetic modifiers that

  8. Cigarette toxicity triggers Leber's hereditary optic neuropathy by affecting mtDNA copy number, oxidative phosphorylation and ROS detoxification pathways.

    Science.gov (United States)

    Giordano, L; Deceglie, S; d'Adamo, P; Valentino, M L; La Morgia, C; Fracasso, F; Roberti, M; Cappellari, M; Petrosillo, G; Ciaravolo, S; Parente, D; Giordano, C; Maresca, A; Iommarini, L; Del Dotto, V; Ghelli, A M; Salomao, S R; Berezovsky, A; Belfort, R; Sadun, A A; Carelli, V; Loguercio Polosa, P; Cantatore, P

    2015-12-17

    Leber's hereditary optic neuropathy (LHON), the most frequent mitochondrial disease, is associated with mitochondrial DNA (mtDNA) point mutations affecting Complex I subunits, usually homoplasmic. This blinding disorder is characterized by incomplete penetrance, possibly related to several genetic modifying factors. We recently reported that increased mitochondrial biogenesis in unaffected mutation carriers is a compensatory mechanism, which reduces penetrance. Also, environmental factors such as cigarette smoking have been implicated as disease triggers. To investigate this issue further, we first assessed the relationship between cigarette smoke and mtDNA copy number in blood cells from large cohorts of LHON families, finding that smoking was significantly associated with the lowest mtDNA content in affected individuals. To unwrap the mechanism of tobacco toxicity in LHON, we exposed fibroblasts from affected individuals, unaffected mutation carriers and controls to cigarette smoke condensate (CSC). CSC decreased mtDNA copy number in all cells; moreover, it caused significant reduction of ATP level only in mutated cells including carriers. This implies that the bioenergetic compensation in carriers is hampered by exposure to smoke derivatives. We also observed that in untreated cells the level of carbonylated proteins was highest in affected individuals, whereas the level of several detoxifying enzymes was highest in carriers. Thus, carriers are particularly successful in reactive oxygen species (ROS) scavenging capacity. After CSC exposure, the amount of detoxifying enzymes increased in all cells, but carbonylated proteins increased only in LHON mutant cells, mostly from affected individuals. All considered, it appears that exposure to smoke derivatives has a more deleterious effect in affected individuals, whereas carriers are the most efficient in mitigating ROS rather than recovering bioenergetics. Therefore, the identification of genetic modifiers that

  9. The Mitochondrial DNA Mutation at Position 11778 in Chinese Families with Leber's Hereditary Optic Neuropathy

    Institute of Scientific and Technical Information of China (English)

    1994-01-01

    We amplified the 340 bp of mitochondrial DMA (mtDNA) by PCR including the recognized sequence of restriction enzyme of SfaN I . After amplification and digestion of SfaN I , two bands of 190 bp and 150 bp appeared in the mtDNA of four normal individuals but only one band of 340 bp appeared in the mtDNA with the mutation of G to A at the site of the nucleotide 11778 because such mutation destroyed the recognized sequence of SfaN I . We studied the mtDNAs of the patients with Leber's hereditary optic neur...

  10. ORAL MANIFESTATIONS AND PROSTHETIC REHABILITATION IN HEREDITARY SENSORY AND AUTONOMIC NEUROPATHY (HSANTYPE IV:A CASE REPORT*

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    Duygu OFLUOĞLU

    2016-04-01

    Full Text Available Hereditary sensory and autonomic neuropathies (HSAN are rare genetic syndromes of unknown etiology. They are seen in early childhood and are categorized into six different types by their symptoms. HSAN type 4 demonstrates autosomal recessive transmission pattern, with such major characteristics as loss of sense of pain, self-mutilation, anhydrosis and mental retardation. Sympathetic innervations are deficient despite the existence of sweat glands. Sufferers are hypotonic without any tendon reflexes, and neuro-motor development is retarded. In some cases tactile sensation and vibration may be intact. Biting injuries due to lack of pain sensation cause laceration, ulceration and scarring of the tongue, lips and other parts of oral mucosa. Tooth luxation and severe dental attrition have been observed. This case report presents oral and dental findings, surgical treatments and prosthetic rehabilitation of an 11- year-old boy with HSAN type 4.

  11. Organophosphate-induced delayed neuropathy: case report Neuropatia tardia por organofosforado: relato de caso

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    Luiz Felipe R Vasconcellos

    2002-12-01

    Full Text Available Organophosphate induced delayed neuropathy (OPIDN is an uncommon clinical condition. It occurs in association with the ingestion of great amounts of organophosphate after the stimulation of cholinergic receptor. The clinical picture is characterized by a distal paresis in lower limbs associated with sensitive symptoms. Electrodiagnostic studies show a motor axonal neuropathy. Involvement of the central nervous system may occur. We describe a 39 years-old female patient who developed hyperesthesia associated with lower limbs paresis, fourteen days after she had ingested a Dichlorvos-based insecticide. Electrophysiological study was characterized by an axonal polyneuropathy pattern. Pyramidal tract dysfunction was observed later in upper limbs. Considering that both peripheral and central nervous systems are involved we believe that the more appropriated term would be organophosphate induced delayed neuropathy (OPIDN instead of organophosphate induced delayed polyneuropathy (OPIDP.A neuropatia tardia dos organofosforados (NTOF é condição clinica incomum. Geralmente ocorre após a intoxicação aguda por organofosforados, seguindo-se a fase de hiperestimulação colinérgica. O quadro clínico é caracterizado por déficit motor distal nos membros inferiores associado a sintomas sensitivos. O estudo eletroneuromiográfico tem demonstrado padrão axonal motor na maioria dos casos. Podem ocorrer sinais de comprometimento do sistema nervoso central. Descrevemos o caso de uma paciente de 39 anos que ingeriu inseticida a base de Dichlorvos e quatorze dias após apresentou quadro de hiperestesia associado a paresia distal nos membros inferiores. Realizou eletroneuromiografia que se caracterizou por padrão compatível com polineuropatia axonal. Sinais piramidais, de aparecimento mais tardio, foram observados nos membros superiores. Diante do comprometimento do sistema nervoso periférico e central, também consideramos o termo neuropatia tardia por

  12. Aortitis requiring aortic repair associated with glaucoma, thyroiditis, glaucoma, and neuropathy: case report

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    Bayer Günther

    2011-05-01

    Full Text Available Abstract Aortitis may be due to infectious and non-infectious causes. We observed aortitis, associated with glaucoma, thyroiditis, pericarditis, pleural effusion and neuropathy in a 63-years old woman. Despite antibiotic therapy, inflammatory signs persisted and resolved only after initiation of glucocorticoid therapy. Increasing aortic ectasia necessitated resection of the ascending aorta and implantation of a Vascutek 30 mm prosthesis. Histologically a granulomatous aortitis was diagnosed. Since all other possible causes were excluded, an immunological mechanism of the aortitis is suspected and possible triggering factors are discussed.

  13. Pyridoxine neuropathy. A four-year electrophysiological and clinical follow-up of a severe case.

    Science.gov (United States)

    Santoro, L; Ragno, M; Nucciotti, R; Barbieri, F; Caruso, G

    1991-02-01

    In a 54-year-old male a severe sensory neuropathy was observed during treatment for pulmonary tuberculosis with isoniazid (400 mg/day) and pyridoxine (600 mg/day). Eight months after withdrawal from isoniazid the sensory symptomatology was still progressing, although muscle strength was never reduced. A sural nerve biopsy revealed marked loss of large myelinated fibres. Only when pyridoxine treatment was interrupted did a slow improvement begin. A clinical and electrophysiologic follow-up showed a very slow and still incomplete recovery after four years. The possibility of an unusual individual susceptibility to toxic effects of pyridoxine is considered.

  14. Leber遗传性视神经萎缩病外显率的影响因素研究进展%Progress of the factors influencing the penetrance of Leber’s hereditary optic neuropathy

    Institute of Scientific and Technical Information of China (English)

    仲俊维; 陈鼎; 余新平; 童绎; 谷峰

    2015-01-01

    Abstract• Leber’s hereditary optic neuropathy ( LHON ) is a maternally inherited blinding disease. The clinical phenotype of LHON is the degeneration of retinal ganglion cells ( RGCs) and a progressive degeneration of the optic nerve. Three common mutations, G11778A, T14484C and G3460A are responsible for over 90% of cases. Differences in penetrance indicate the additional modifier genes influencing penetrance of the mitochondrial DNA mutation for LHON patients. Different types of mitochondrial haplogroups, environmental factors also have different effects on the penetrance of the mitochondrial DNA mutations. ln the present paper, here the progress of the factors influencing the penetrance of Leber’s hereditary optic neuropathy will be summarized.%Leber 遗传性视神经萎缩病( Leber’s Hereditary Optic Neuropathy, LHON)的发生是由于视网膜神经节细胞死亡进而导致视神经萎缩,表现为急性或亚急性双眼视力下降,是目前研究最为广泛的由线粒体基因突变引起的母系遗传病之一。超过90%的LHON是由线粒体基因组的3个原发致病突变之一所致,即 G11778 A、T14484 C 和G3460 A。 LHON临床表型不同,外显率的不同以及发病率的性别差异都提示可能存在其他相关基因(核基因和线粒体基因组)在其发挥着重要作用。本文主要对近二十年来该病的分子遗传学,特别是可能的外显率影响因素的研究进展作一阐述,为该病预防与临床治疗提供参考。

  15. [The analysis of mitochondrial DNA haplogroups and variants for Leber's hereditary optic neuropathy in Chinese families carrying the m.14484T >C mutation].

    Science.gov (United States)

    Meng, Xiangjuan; Zhu, Jinping; Gao, Min; Zhang, Sai; Zhao, Fuxin; Zhang, Juanjuan; Liu, Xiaoling; Wei, Qiping; Tong, Yi; Zhang, Minglian; Qu, Jia; Guan, Minxin

    2014-04-01

    The m.14484T>C mutation in mitochondrial ND6 gene (MT-ND6) is a primary mutation underlying the development of Leber's hereditary optic neuropathy (LHON) , but by itself not enough to cause visual loss. To explore the role of mitochondrial haplogroups on the expression of LHON for the people carrying the m.14484T>C mutation, we performed systematic and extended mutational screening of MT-ND6 gene in a cohort of 1177 Han Chinese patients with LHON. A total of 67 affected subjects carried the homoplasmic m.14484T>C mutation, accounting for 5.7% of this LHON population. The penetrances of optic neuropathy among 51 pedigrees carrying the m.14484T>C mutation ranged from 5.6% to 100.0%, with the average of 21.5%. The sequence analysis of entire mitochondrial genomes of 51 probands exhibited distinct sets of polymorphisms belonging to 18 Eastern Asian haplogroups. The frequencies of haplogroup A and haplogroup F were sig-nificantly less in the LHON mtDNA samples than those in 106 Chinese controls. On the other hand, the haplogroup M10a accounted for 9.8% of the patient's mtDNA samples but was absent in 106 Chinese controls. Strikingly, the average pene-trance (46.13%) of optic neuropathy for the pedigrees carrying mitochondrial haplogroup M10a was higher than those car-rying other mtDNA haplogroups. These observations indicated that mitochondrial haplogroup M10a may increase the risk of visual loss.

  16. Crowdsourcing as a screening tool to detect clinical features of glaucomatous optic neuropathy from digital photography.

    Directory of Open Access Journals (Sweden)

    Danny Mitry

    Full Text Available Crowdsourcing is the process of simplifying and outsourcing numerous tasks to many untrained individuals. Our aim was to assess the performance and repeatability of crowdsourcing in the classification of normal and glaucomatous discs from optic disc images.Optic disc images (N = 127 with pre-determined disease status were selected by consensus agreement from grading experts from a large cohort study. After reading brief illustrative instructions, we requested that knowledge workers (KWs from a crowdsourcing platform (Amazon MTurk classified each image as normal or abnormal. Each image was classified 20 times by different KWs. Two study designs were examined to assess the effect of varying KW experience and both study designs were conducted twice for consistency. Performance was assessed by comparing the sensitivity, specificity and area under the receiver operating characteristic curve (AUC.Overall, 2,540 classifications were received in under 24 hours at minimal cost. The sensitivity ranged between 83-88% across both trials and study designs, however the specificity was poor, ranging between 35-43%. In trial 1, the highest AUC (95%CI was 0.64(0.62-0.66 and in trial 2 it was 0.63(0.61-0.65. There were no significant differences between study design or trials conducted.Crowdsourcing represents a cost-effective method of image analysis which demonstrates good repeatability and a high sensitivity. Optimisation of variables such as reward schemes, mode of image presentation, expanded response options and incorporation of training modules should be examined to determine their effect on the accuracy and reliability of this technique in retinal image analysis.

  17. Crowdsourcing as a screening tool to detect clinical features of glaucomatous optic neuropathy from digital photography.

    Science.gov (United States)

    Mitry, Danny; Peto, Tunde; Hayat, Shabina; Blows, Peter; Morgan, James; Khaw, Kay-Tee; Foster, Paul J

    2015-01-01

    Crowdsourcing is the process of simplifying and outsourcing numerous tasks to many untrained individuals. Our aim was to assess the performance and repeatability of crowdsourcing in the classification of normal and glaucomatous discs from optic disc images. Optic disc images (N = 127) with pre-determined disease status were selected by consensus agreement from grading experts from a large cohort study. After reading brief illustrative instructions, we requested that knowledge workers (KWs) from a crowdsourcing platform (Amazon MTurk) classified each image as normal or abnormal. Each image was classified 20 times by different KWs. Two study designs were examined to assess the effect of varying KW experience and both study designs were conducted twice for consistency. Performance was assessed by comparing the sensitivity, specificity and area under the receiver operating characteristic curve (AUC). Overall, 2,540 classifications were received in under 24 hours at minimal cost. The sensitivity ranged between 83-88% across both trials and study designs, however the specificity was poor, ranging between 35-43%. In trial 1, the highest AUC (95%CI) was 0.64(0.62-0.66) and in trial 2 it was 0.63(0.61-0.65). There were no significant differences between study design or trials conducted. Crowdsourcing represents a cost-effective method of image analysis which demonstrates good repeatability and a high sensitivity. Optimisation of variables such as reward schemes, mode of image presentation, expanded response options and incorporation of training modules should be examined to determine their effect on the accuracy and reliability of this technique in retinal image analysis.

  18. Hereditary Neuropathy with Liability to Pressure Palsy: A Recurrent and Bilateral Foot Drop Case Report

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    Filipa Flor-de-Lima

    2013-01-01

    Full Text Available Hereditary neuropathy with liability to pressure palsy is characterized by acute, painless, recurrent mononeuropathies secondary to minor trauma or compression. A 16-year-old boy had the first episode of right foot drop after minor motorcycle accident. Electromyography revealed conduction block and slowing velocity conduction of the right deep peroneal nerve at the fibular head. After motor rehabilitation, he fully recovered. Six months later he had the second episode of foot drop in the opposite site after prolonged squatting position. Electromyography revealed sensorimotor polyneuropathy of left peroneal, sural, posterior tibial, and deep peroneal nerves and also of ulnar, radial, and median nerves of both upper limbs. Histological examination revealed sensory nerve demyelination and focal thickenings of myelin fibers. The diagnosis of hereditary neuropathy with liability to pressure palsy was confirmed by PMP22 deletion of chromosome 17p11.2. He started motor rehabilitation and avoidance of stressing factors with progressive recovery. After one-year followup, he was completely asymptomatic. Recurrent bilateral foot drop history, “sausage-like” swellings of myelin in histological examination, and the results of electromyography led the authors to consider the diagnosis despite negative family history. The authors highlight this rare disease in pediatric population and the importance of high index of clinical suspicion for its diagnosis.

  19. Yeast NDI1 Improve Oxidative Phosphorylation Capacity and Increases Protection Against Oxidative Stress and Cell Death in Cells Carrying a Leber’s Hereditary Optic Neuropathy Mutation

    OpenAIRE

    Park, Jeong Soon; Li, You-Fen; Bai, Yidong

    2007-01-01

    G11778A in the subunit ND4 gene of NADH dehydrogenase complex is the most common primary mutation found in Leber’s hereditary optic neuropathy (LHON) patients. The NDI1 gene, which encodes the internal NADH -quinone oxidoreductase in Saccharomyces cerevisiae, was introduced into the nuclear genome of a mitochondrial defective human cell line, Le1.3.1, carrying the G11778A mutation. In transformant cell lines, LeNDI1-1 and -2, total and complex I-dependent respiration were fully restored and l...

  20. Non-arteritic anterior ischaemic optic neuropathy: evaluation of the brain and optic pathway by conventional MRI and magnetisation transfer imaging

    Energy Technology Data Exchange (ETDEWEB)

    Argyropoulou, Maria I.; Zikou, Anastasia K.; Tzovara, Ioanna; Margariti, Persefoni [University of Ioannina, Department of Radiology, Medical School, Ioannina (Greece); Nikas, Alexios; Asproudis, Ioannis [University of Ioannina, Ophthalmologic Clinic, Medical School, Ioannina (Greece); Blekas, Kostandinos; Galatsanos, Nikolaos [University of Ioannina, Department of Informatics, Ioannina (Greece)

    2007-07-15

    The purpose of the study was to examine the brain and the visual pathway of patients with non-arteritic anterior ischaemic optic neuropathy (NAION) by using conventional MRI (cMRI) and volumetric magnetisation transfer imaging (MTI). Thirty NAION patients, aged 67.5 {+-} 8.14 years, and 28 age- and gender-matched controls were studied. MTI was used to measure the magnetisation transfer ratio (MTR) of the chiasm and for MTR histograms of the brain. The presence of areas of white matter hyperintensity (WMH) was evaluated on fluid-attenuated inversion recovery (FLAIR) images. Area of the optic nerves (ONs) and volume of the chiasm were assessed, as were coronal short-tau inversion recovery (STIR) and MTI images, respectively. More areas of WMH were observed in patients (total 419; mean 14.4; SD 19) than in controls (total 127; mean 4.7; SD 5.7), P < 0.001. Area (in square millimetres) of the affected ONs, volume(in cubic millimetres) and MTR (in percent) of the chiasm (10.7 {+-} 4.6), (75.8 {+-} 20.2), (56.4 {+-} 6.5), respectively, were lower in patients than in controls (13.6 {+-} 4.3), (158.2 {+-} 75.3) (62.1 {+-} 6.2), respectively, P < 0.05. Mean MTR of brain histograms was lower in patients (53.0 {+-} 8.0) than in controls (58.0 {+-} 5.6), P < 0.05. NAION is characterised by decreased ON and chiasmatic size. The low MTR of the chiasm and brain associated with increased areas of WMH may be suggestive of demyelination and axonal damage due to generalised cerebral vascular disease. (orig.)

  1. Short segment incremental study in ulnar neuropathy at the wrist: report of three cases and review of the literature.

    Science.gov (United States)

    Yalinay Dikmen, Pinar; Oge, A Emre; Yazici, Jale

    2010-03-01

    Ulnar nerve lesions may occur at different sublocations at wrist and may involve various branches of the nerve. Standard neurophysiological studies are generally insufficient in revealing these lesions. Demonstration of conduction block and/or focal slowing of nerve conduction is the most definitive electrodiagnostic evidence for the localization of segmental demyelination. Short-segment incremental study (SSIS) is a sensitive technique for detecting the ulnar neuropathy at the wrist (UNW). We report 3 cases of UNW caused by ganglion cysts in Guyon's canal which were studied by using SSIS across the wrist. Even though SSIS is a time-consuming and technically demanding method, it increases the electrodiagnostic potential of detecting segmental demyelination in this location.

  2. Radio frequency ablation in drug resistant chemotherapy-induced peripheral neuropathy: A case report and review of literature

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    Naveen Yadav

    2010-01-01

    Full Text Available Chemotherapy-induced peripheral neuropathy (CIPN is a frequently encountered complication. It can result from a host of agents. Various modalities of treatment have been advocated, of which a novel method is radio frequency ablation. A 63-year-old male, a case of carcinoma prostrate with bone metastases, presented with tingling and numbness in right upper limb. He was given morphine, gabapentin and later switched to pregabalin, but medications provided only minor relief. Initially he was given stellate ganglion block, then radiofrequency ablation of dorsal root ganglion was done, but it failed to provide complete relief. Pulsed radiofrequency ablation (PRF was then done for 90 seconds; two cycles each in both ulnar and median nerve. After the procedure the patient showed improvement in symptoms within four to five hours and 80% relief in symptoms. We conclude that PRF can be used for the treatment of drug resistant CIPN.

  3. Blunt Facial Trauma Causing Isolated Optic Nerve Hematoma

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    R. Parab

    2013-01-01

    Full Text Available Traumatic optic neuropathy is an uncommon, yet serious, result of facial trauma. The authors present a novel case of a 59-year-old gentleman who presented with an isolated blunt traumatic left optic nerve hematoma causing vision loss. There were no other injuries or fractures to report. This case highlights the importance of early recognition of this rare injury and reviews the current literature and management of traumatic optic neuropathy.

  4. n-HEXANE NEUROPATHY DUE TO SHOEMAKING: REPORT OF FIVE CASES

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    K. Sadeghniat

    2005-04-01

    Full Text Available n-hexane neuropathy has been described after glue sniffing and industrial exposure. Onset may be subacute and reminiscent of Guillain-Barre' syndrome. Five patients (15-18 years old presented with paresthesia, severe weakness of the extremities particularly lower extremities, as well as muscular atrophy, total areflexia and gait disturbances were admitted in hospital in March 2003. All of these boys were workers of a small footwear production unit. They worked as gluers of leather pieces. Nerve conduction velocity studies showed latency prolongation and cerebrospinal fluid (CSF analysis showed normal protein. In the workplace assessment, it was found that hexacarbone-containing adhesives were used in an inappropriate ventilated place and without any personal protective devices. These patients were re-examined 8 months later. Sensory and autonomic symptoms were alleviated but two of them still had gait disturbance and decreased reflexes.

  5. Hereditary sensory and autonomic neuropathy type V: Report of a rare case

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    Ritesh Kalaskar

    2015-01-01

    Full Text Available Hereditary sensory and autonomic neuropathy (HSAN type V is a rare inherited disease caused by a mutation in the neurotrophic tyrosine kinase receptor, type 1 gene located on chromosome 1 (1q21-q22. It is characterized by pain insensitivity, partial anhydrosis without mental retardation and unimpaired touch and pressure sensitivity. Self-mutilation injury involving the teeth, lips, tongue, ears, eyes, nose, and fingers are invariable feature of this disorder. The purpose of this paper was to discuss the diagnosis and oral management of 18-month-old girl with HSAN type V, having typical oral manifestation of bitten tongue and auto-extraction of primary teeth. Modified bite guard was given to the patient to prevent further self-mutilating injuries to the tongue.

  6. Diabetic Neuropathies.

    Science.gov (United States)

    Izenberg, Aaron; Perkins, Bruce A; Bril, Vera

    2015-08-01

    Diabetes mellitus is a common condition and diabetics are prone to develop a spectrum of neuropathic complications ranging from symmetric and diffuse to asymmetric and focal neuropathies that may be associated with significant morbidity. Diabetic sensorimotor polyneuropathy is the most common of these complications, occurring in patients with type 1 and 2 diabetes mellitus, as well as in those with prediabetes and glucose intolerance. In this review, the authors discuss the wide variety of neuropathies that can present in the context of diabetes, including the clinical manifestations, diagnostic features, and approach to management. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  7. Leber遗传性视神经病变研究进展%Research progress of Leber hereditary optic neuropathy

    Institute of Scientific and Technical Information of China (English)

    张阳阳

    2015-01-01

    Leber hereditary optic neuropathy (LHON) is one of the most common maternally transmitted hereditary retinal diseases,which is mainly caused by one of the three point mutations in mitochondrial DNA(mt DNA) (G11778A,G3460A and G14484C).LHON is characterized by painless,acute or sub-acute bilateral visual loss in young men with central scotoma.Incomplete dominance and gender bias are two puzzles of this disease.Although currently there is no effective therapy to prevent or cure the LHON,the ongoing clinical trials of gene therapy have showed initial success in some LHON patients with G11778A mutation.Here we summarized recent research progress of LHON,focusing on the clinical features,molecular and pathogenic mechanisms,animal models,and gene therapy of it.%Leber遗传性视神经病变(LHON)是临床上常见的遗传性视神经病变,是一种以母系遗传为特征的线粒体疾病,主要由线粒体DNA (mtDNA)3个原发突变G11778A、G3460A和G14484C引起.LHON多见于青壮年男性,主要临床表现为无痛性双侧视力下降或丧失和中心盲点.不完全外显和性别偏好是该病亟待解决的两大难题.虽然目前尚无有效的预防及治疗措施,但在美国进行的LHON基因治疗临床试验已取得初步成功.本文就LHON的临床表现、发病机制、分子遗传学特点、动物模型、基因治疗等进行介绍,进一步加强对本病的认识.

  8. The research progress of leber's hereditary optic neuropathy%Leber遗传性视神经病变的研究进展

    Institute of Scientific and Technical Information of China (English)

    张娟娟; 冀延春; 周翔天; 瞿佳; 管敏鑫

    2016-01-01

    Leber遗传性视神经病变(Leber's hereditary optic neuropathy,LHON)是一种主要累及青壮年男性,导致视神经退行性变的母系遗传病.线粒体DNA(mitochondrial DNA,mtDNA)突变为LHON发病的主要分子基础.LHON不完全外显和男性好发的特征表明,其他因素(如mtDNA单体型、核修饰基因和/或环境因素等)在LHON发病中起着重要作用.%Leber's hereditary optic neuropathy (LHON) is a maternally-inherited eye disease that generally affects young adults.Mutations in mtDNA are the molecular bases for this disorder.The incomplete penetrancc and male bias of LHON indicate that other factors,including mitochondrial haplogroup,nuclear modified genes and/or environmental factors,play an important role in the incidence of LHON.

  9. Leber遗传性视神经病变分子遗传学研究进展%Molecule Genetic Research Advances of Leber's Hereditary Optic Neuropathy

    Institute of Scientific and Technical Information of China (English)

    赵福新; 管敏鑫

    2008-01-01

    Leber hereditary optic neuropathy(LHON)is a maternally inherited disorder leading to rapid,painless,bilateral loss of central vision.Point mutation of mitochondrial DNA(mtDNA)results in LHON.This paper makes a brief introduction of primary,secondary mutations and other mutations,and elucidates the role of nuclear modified gene;haplogroup and surroundings factor(smoking,alcohol,etc.)in the penetrance and phenotypic expression of the LHON,respectively.%Leber遗传性视神经病变(Leber hereditary optic neuropathy,LHON)是一种导致双眼快速的、无痛性的中心视力丧失的母系遗传性疾病.主要是由线粒体DNA(mitochondrial DNA,mtDNA)发生点突变所致.本文主要介绍LHON原发性、继发性和其他相关位点突变,阐述核修饰基因、mtDNA单体型及环境因素(吸烟、饮酒等)对LHON外显率和发病严重程度的影响.

  10. Simultaneous occurrence of the 11778 (ND4) and the 9438 (COX III) mtDNA mutations in Leber hereditary optic neuropathy: Molecular, biochemical, and clinical findings

    Energy Technology Data Exchange (ETDEWEB)

    Oostra, R.J.; Bleeker-Wagemakers, E.M.; Zwart, R. [Ophthalmic Research Institute, Amsterdam (Netherlands)] [and others

    1995-10-01

    Three mtDNA point mutations at nucleotide position (np) 3460, at np 11778 and at np 14484, are thought to be of primary importance in the pathogenesis of Leber hereditary optic neuropathy (LHON), a maternally inherited disease characterized by subacute central vision loss. These mutations are present in genes coding for subunits of complex I (NADH dehydrogenase) of the respiratory chain, occur exclusively in LHON maternal pedigrees, and have never been reported to occur together. Johns and Neufeld postulated that an mtDNA mutation at np 9438, in the gene coding for one of the subunits (COX III) of complex IV (cytochrome c oxidase), was also of primary importance. Johns and Neufeld (1993) found this mutation, which changed a conserved glycine to a serine, in 5 unrelated LHON probands who did not carry one of the presently known primary mutations, but they did not find it in 400 controls. However, the role of this sequence variant has been questioned in the Journal when it has been found to occur in apparently healthy African and Cuban individuals. Subsequently, Johns et al. described this mutation in two Cuban individuals presenting with optic and peripheral neuropathy. 22 refs., 1 fig., 1 tab.

  11. Autonomic neuropathy

    DEFF Research Database (Denmark)

    Hilsted, J

    1983-01-01

    The diagnosis of autonomic neuropathy is often difficult to establish, since clinical symptoms generally appear late in the course of the disease, and may be non-specific. A number of recently developed quantifiable and reproducible autonomic nerve function tests are reviewed, with emphasis on th...

  12. [Hereditary peripheral neuropathies].

    Science.gov (United States)

    Vallat, Jean-Michel; Tazir, Mériem; Calvo, Judith; Funalot, Benoît

    2009-09-01

    Currently more than 30 genes are known to be responsible for genetically determined neuropathies. Charcot-Marie-Tooth (CMT) disease is the most frequent of these hereditary neuropathies, with a prevalence of 4.7 to 36 per 100 000. In its demyelinating forms (CMT1), approximately 70% of cases are associated with a duplication of the PMP22gene. In its axonal forms (CMT2), 10-20% of the cases may be associated with a mutation of the MFN2gene. For North African patients with recessive transmission, a mutation of the LMNA gene must be sought. It is essential to stress the great variability of the phenotype--clinical, electrophysiological, and histologic--between and within families. A detailed analysis of these criteria, together with consideration of ethnic origin, may guide the search for the causal mutation. Whether the case involves certainly hereditary transmission or a sporadic form, it is desirable to be able to examine the maximum number of the patient's kin, both clinically and electrophysiologically. The forms with recessive transmission usually have a very early onset and are more serious than the dominant forms. The early- and very early-onset forms of CMT are increasingly better distinguished: congenital hypomyelination neuropathy (mutations of PMP22, MPZ or EGR2), or more axonal forms, including SMARD1 (Spinal muscle atrophy with respiratory distress; mutations of IGHMBP2) and EOHMSN (Early-onset hereditary motor and sensory neuropathy; mutations of MFN2). The prevention of cutaneous (ulcerations), bone, and amputation complications is very important in patients with hereditary sensory and autonomic neuropathies, because of the severity of the sensory disorders.

  13. Peripheral neuropathies.

    Science.gov (United States)

    Hanewinckel, R; Ikram, M A; Van Doorn, P A

    2016-01-01

    Peripheral neuropathies are diseases of the peripheral nervous system that can be divided into mononeuropathies, multifocal neuropathies, and polyneuropathies. Symptoms usually include numbness and paresthesia. These symptoms are often accompanied by weakness and can be painful. Polyneuropathies can be divided into axonal and demyelinating forms, which is important for diagnostic reasons. Most peripheral neuropathies develop over months or years, but some are rapidly progressive. Some patients only suffer from mild, unilateral, slowly progressive tingling in the fingers due to median nerve compression in the wrist (carpal tunnel syndrome), while other patients can be tetraplegic, with respiratory insufficiency within 1-2 days due to Guillain-Barré syndrome. Carpal tunnel syndrome, with a prevalence of 5% and incidence of 1-2 per 1000 person-years, is the most common mononeuropathy. Population-based data for chronic polyneuropathy are relatively scarce. Prevalence is estimated at 1% and increases to 7% in persons over 65 years of age. Incidence is approximately 1 per 1000 person-years. Immune-mediated polyneuropathies like Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy are rare diseases, with an annual incidence of approximately 1-2 and 0.2-0.5 per 100 000 persons respectively. Most peripheral neuropathies are more prevalent in older adults and in men, except for carpal tunnel syndrome, which is more common in women. Diabetes is a common cause of peripheral neuropathy and is associated with both mono- and polyneuropathies. Among the group of chronic polyneuropathies, in about 20-25% no direct cause can be found. These are slowly progressive axonal polyneuropathies. © 2016 Elsevier B.V. All rights reserved.

  14. Hepatitis C virus infection, cryoglobulinemia, and peripheral neuropathy: a case report

    Directory of Open Access Journals (Sweden)

    Vigani A.G.

    2005-01-01

    Full Text Available Hepatitis C virus (HCV is essentially hepatotropic but its manifestations can extend beyond the liver. It can be associated with autoimmune diseases, such as mixed cryoglobulinemia, membranoproliferative glomerulonephritis, autoimmune thyroiditis, and lymphoproliferative disorders. The mechanisms that trigger these manifestations are not completely understood. We describe a 48-year-old man with chronic HCV infection (circulating HCV RNA and moderate hepatitis as indicated by liver biopsy, cryoglobulinemia, and sensory and motor peripheral neuropathy. The diagnosis of multineuropathy was confirmed by clinical examination and electromyographic tests. A nerve biopsy revealed an inflammatory infiltrate in the perineurial space and signs of demyelination and axonal degeneration. The patient had no improvement of neurological symptoms with the use of analgesics and neuro-modulators. He was then treated with interferon-alpha (3 million units subcutaneously, 3 times per week and ribavirin (500 mg orally, twice a day for 48 weeks. Six months after the end of therapy, the patient had sustained viral response (negative HCV RNA and remission of neurological symptoms, but cryoglobulins remained positive. A review of the literature on the pathogenesis and treatment of neurological manifestations associated with HCV infection is presented. This report underscores the need for a thorough evaluation of HCV-infected patients because of the possibility of extrahepatic manifestations. Antiviral treatment with interferon and ribavirin can be effective and should be considered in patients with neurological complications associated with HCV infection.

  15. [A case of brachial plexus neuropathy who presented with acute paralysis of the hand after sleep].

    Science.gov (United States)

    Iijima, Makiko; Okuma, Yasuyuki; Ohizumi, Hideki; Fujishima, Kenji; Goto, Keigo; Mizuno, Yoshikuni

    2002-09-01

    We report a 46-year-old woman who presented with acute paresis of the right hand and arm. She was well until when she noted a paresis and dysesthesia in her right hand in the morning. Neurological examination revealed weakness in the muscles which were supplied by lower cervical segments, with increased deep tendon reflexes in the right arm. Allen's test and Wright's test were positive. The nerve conduction studies disclosed a reduced CMAPs more severely by right median than ulnar nerve stimulation. The frequency and amplitude of the F waves was also reduced. Needle electromyogram showed a mild neurogenic pattern in the right hand muscles. Digital subtraction angiography revealed a tapering of the subclavian artery when the right arm was abducted. She underwent decompression surgery. A remarkable improvement of the symptoms was observed after surgery. Our patient suggests that brachial plexus neuropathy should be considered in the acute paresis of the hand after sleep, and that surgical procedure would lead to a successful outcome.

  16. Optic neuropathy, cardiomyopathy, cognitive disability in patients with a homozygous mutation in the nuclear MTO1 and a mitochondrial MT-TF variant.

    Science.gov (United States)

    Charif, Majida; Titah, Salah Mohamed Cherif; Roubertie, Agathe; Desquiret-Dumas, Valérie; Gueguen, Naig; Meunier, Isabelle; Leid, Jean; Massal, Frédéric; Zanlonghi, Xavier; Mercier, Jacques; Raynaud de Mauverger, Eric; Procaccio, Vincent; Mousson de Camaret, Bénédicte; Lenaers, Guy; Hamel, Christian P

    2015-10-01

    We report on clinical, genetic and metabolic investigations in a family with optic neuropathy, non-progressive cardiomyopathy and cognitive disability. Ophthalmic investigations (slit lamp examination, funduscopy, OCT scan of the optic nerve, ERG and VEP) disclosed mild or no decreased visual acuity, but pale optic disc, loss of temporal optic fibers and decreased VEPs. Mitochondrial DNA and exome sequencing revealed a novel homozygous mutation in the nuclear MTO1 gene and the homoplasmic m.593T>G mutation in the mitochondrial MT-TF gene. Muscle biopsy analyses revealed decreased oxygraphic Vmax values for complexes I+III+IV, and severely decreased activities of the respiratory chain complexes (RCC) I, III and IV, while muscle histopathology was normal. Fibroblast analysis revealed decreased complex I and IV activity and assembly, while cybrid analysis revealed a partial complex I deficiency with normal assembly of the RCC. Thus, in patients with a moderate clinical presentation due to MTO1 mutations, the presence of an optic atrophy should be considered. The association with the mitochondrial mutation m.593T>G could act synergistically to worsen the complex I deficiency and modulate the MTO1-related disease.

  17. Chronic idiopathic intestinal pseudo-obstruction caused by acquired visceral neuropathy localised in the left colon: report of two cases.

    Science.gov (United States)

    Suzuki, H; Amano, S; Matsumoto, K; Kitagawa, T; Masuda, T

    1987-07-01

    Two cases of chronic idiopathic intestinal pseudo-obstruction (CIIP) are reported. One is a 51-year-old man, and the other is a 47-year-old woman. Both patients presented with severe constipation and barium enema showed a marked dilation of the right colon, and a narrowing in the left colon. Studies done on the motility of the colon and anorectum revealed normal resting pressure profiles of the anorectom, a normal recto-anal reflex, and a normal resting tone of the collapsed colon. Administration of methacholine chloride, however, provoked large, non-propulsive movements in the collapsed colon, which were inhibited by the administration of atropin sulfate. Histologic examination disclosed a marked decrease in neurons and an increase of Schwann cells in the myenteric plexus of the collapsed colon. CIIP due to acquired visceral neuropathy localised in the left colon, was diagnosed as a result of manometric and histologic findings. One case was cured surgically, by a left hemi-colectomy, and the other was cured medically using choline antagonists and laxatives.

  18. A successful case on traditional Chinese fumigation-soaking therapy in treating diabetic peripheral neuropathy

    Institute of Scientific and Technical Information of China (English)

    Hongfang Liu; Huayang Wu; Lizhong Zhang; Jinxi Zhao

    2006-01-01

    AIM: To investigate the scheme of inducing the diabetic peripheral neuropathy (DNP) symptoms by combine Chinese traditional medicine with modern medicine. METHODS: Patient hospitalized on April 1, 2005. Main symptoms in hospitalization: His bilateral fingers and toe tips felt stabbing pain, numb, cold, assuming a type of sock set which alleviated after he had a rest and aggravated after exercise. He had also got the symptom of dizziness, asthenia, eating little food, very thin bowel and body pain which had influence on his sleeping. Physical examination in hospital: The bilateral lower limbs which got a hyperpathia did not swell. The bilateral dorsum pedis artery pulsation was atlenuarive. The skin temperature was not high. Other nerve system examination had been discovered abnormal. Diagnosis: Traditional Chinese medical diagnosis: Xiaokebing (blood stasis for insufficiency of qi, blockage of meridian and collaterals). Modern medical diagnosis: Diabetes type 2, DNP, diabetic lower limbs artery obliteration, diabetic foot (0 level), diabetic retinopathy, coronary atherosclerotic heart disease, hypertension, chronic bronchitis, chronic obstructive pulmonary emphysema. Carried on the former therapy plan that continued to use insulin to control blood glucose, depressed blood pressure and total plasma lipoprotein etc. Meanwhile used the therapy of bilateral feet medicinal bath (Sanling 30 g, Ezhu 30 g, Ruxiang 30 g, Moyao 30 g, Zhichuanwu 30 g, Zhicaowu 30 g, Weilingxian 30 g, Mugua 30 g, Sangzhi 30 g), boiled in water, 1 dose everyday, soak feet twice a day, 20-30 minutes once, < 37 ℃. RESULTS: Seven days later, the pain of bilateral feet alleviated obviously, and the bilateral dorsum pedis artery pulsation enhanced. Blood glucose and total plasma lipoprotein had no changes. CONCLUSION: The symptoms of DNP such as pain, coldness, numbness of the lower limbs can be induced by combining feet medicinal bath (fumigation-soaking) treatment with modern medicine.

  19. OPTIC DISC MELANOCYTOMA: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Sahiba Bedi

    2016-08-01

    Full Text Available Melanocytoma of the optic disc is a rare ophthalmic tumour that arises from melanocytes and is a variant of the melanocytic nevus. It occurs on the optic disc and often extends into the peripapillary retina and choroid. It appears as a dark brown or black lesion, typically small and is almost always unilateral. Although traditionally believed to be a relatively stationary lesion, it is now known to exhibit minor enlargement in 10–15% of cases and can cause minor visual loss by a variety of mechanisms. 1-2% cases can transform to malignant melanoma. We present a case report of a 65-year-old female whose dilated fundus examination of the right eye revealed a circular, pigmented and elevated lesion about 1.5 mm in size covering almost whole of the optic nerve head except for the superior rim, suggestive of optic disc melanocytoma.

  20. Pediatric sciatic neuropathies due to unusual vascular causes

    NARCIS (Netherlands)

    Srinivasan, Jayashri; Escolar, Diane; Ryan, Monique; Darras, Basil; Jones, H. Royden

    2008-01-01

    Four cases of pediatric sciatic neuropathies due to unusual vascular mechanisms are reported. Pediatric sciatic neuropathies were seen after umbilical artery catheterization, embolization of arteriovenous malformation, meningococcemia, and hypereosinophilic vasculitis. Electrophysiologic studies dem

  1. Pediatric sciatic neuropathies due to unusual vascular causes

    NARCIS (Netherlands)

    Srinivasan, Jayashri; Escolar, Diane; Ryan, Monique; Darras, Basil; Jones, H. Royden

    Four cases of pediatric sciatic neuropathies due to unusual vascular mechanisms are reported. Pediatric sciatic neuropathies were seen after umbilical artery catheterization, embolization of arteriovenous malformation, meningococcemia, and hypereosinophilic vasculitis. Electrophysiologic studies

  2. Penicillamin-induced neuropathy in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Pedersen, P B; Hogenhaven, H

    1990-01-01

    A case of penicillamin-induced severe polyradiculopathy in rheumatoid arthritis is presented. The neuropathy was of demyelinating type, purely motor, proximal and clinically fully reversible when the drug ceased. In case of a progressive neuropathy, during penicillamin treatment, this adverse...

  3. Molecular pathogenetic mechanism of Leber's hereditary optic neuropathy%Leber's遗传性视神经病变分子致病机制研究

    Institute of Scientific and Technical Information of China (English)

    瞿佳; 管敏鑫

    2006-01-01

    Leber's遗传性视神经病变(Leber's hereditary optic neuropathy,LHON)是一种较常见的引起视神经萎缩的遗传性疾病.该病主要引起双侧中心视力丧失,造成永久性的严重视觉障碍,常常发生在一些即将或已工作或上学的年轻人身上,以及在对该病患者家系中其他成员进行遗传病检查时发现.在一些LHON家系中,视觉障碍的患者呈现母系遗传方式,这表明线粒体DNA(mitochondrial DNA,mtDNA)是该病的分子遗传基础.至今为止,在世界各地不同家系报道中已经发现大约有35个与LHON相关的灾变位点,其中ND1 G3460A、ND4 G11778A、ND6 T14484C为三个公认的原发突变位点,均参与呼吸链复合体I的亚基编码.在不同种族发病统计中,其中大约50%的LHON由三个原发致病突变中的一个所致,尤为G11778A突变为主.引人注意的是,LHON家系携带相同突变的母系成员表现出不同的外显率、表现度(如发病严重程度、发病年龄、视力丧失进展程度).不完全和不同的外显率以及轻度的生化影响说明mtDNA突变本身不足以产生临床表型,其他因素(如环境、核修饰基因、线粒体单体型等)可能影响LHON的外显率和表型表达.%Leber's hereditary optic neuropathy (LHON) is the most common hereditary optic atrophies. The disease causes the bilateral loss of central vision. The importance of LHON lies in it ability to cause such severe and usually permanent vision loss in young adults who are about to start or have recently begun employrent or higher education, and the ramification of diagnosing an inherited disease to other members of the patient's family. The maternal transmission of visual dysfunction in families with LHON suggested the mutations in mitochondrial DNA (mtDNA) are the molecular bases of this disorder. Up to date, 35 LHON-associated mtDNA mutations have been identified in many pedigrees worldwide. Of these, three primary mutations: ND1 G3460A, ND4 G11778A

  4. Acquired inflammatory demyelinating neuropathies.

    Science.gov (United States)

    Ensrud, E R; Krivickas, L S

    2001-05-01

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

  5. Sensory correlates of pain in peripheral neuropathies.

    Science.gov (United States)

    Ng Wing Tin, Sophie; Ciampi de Andrade, Daniel; Goujon, Colette; Planté-Bordeneuve, Violaine; Créange, Alain; Lefaucheur, Jean-Pascal

    2014-05-01

    To characterize sensory threshold alterations in peripheral neuropathies and the relationship between these alterations and the presence of pain. Seventy-four patients with length-dependent sensory axonal neuropathy were enrolled, including 38 patients with painful neuropathy (complaining of chronic, spontaneous neuropathic pain in the feet) and 36 patients with painless neuropathy. They were compared to 28 age-matched normal controls. A standardized quantitative sensory testing protocol was performed in all individuals to assess large and small fiber function at the foot. Large fibers were assessed by measuring mechanical (pressure and vibration) detection thresholds and small fibers by measuring pain and thermal detection thresholds. Between patients with neuropathy and controls, significant differences were found for mechanical and thermal detection thresholds but not for pain thresholds. Patients with painful neuropathy and those with painless neuropathy did not differ regarding mechanical or thermal thresholds, but only by a higher incidence of thermal or dynamic mechanical allodynia in case of painful neuropathy. Pain intensity correlated with the alteration of thermal detection and mechanical pain thresholds. Quantitative sensory testing can support the diagnosis of sensory neuropathy when considering detection threshold measurement. Thermal threshold deterioration was not associated with the occurrence of pain but with its intensity. There is a complex relationship between the loss or functional deficit of large and especially small sensory nerve fibers and the development of pain in peripheral neuropathy. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  6. Evidence against an X-linked locus close to DXS7 determining visual loss susceptibility in British and Italian families with Leber hereditary optic neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Sweeney, M.G.; Davis, M.B.; Lashwood, A.; Brockington, M.; Harding, A.E. (Institute of Neurology, Queen Square, London (United Kingdom)); Toscano, A. (Clinica Neurologica, Messina (Italy))

    1992-10-01

    Leber hereditary optic neuropathy (LHON) is associated with mutations of mtDNA, but two features of LHON pedigrees are not explicable solely on the basis of mitochondrial inheritance. There is a large excess of affected males, and not all males at risk develop the disease. These observations could be explained by the existence of an X-linked visual loss susceptibility gene. This hypothesis was supported by linkage studies in Finland, placing the susceptibility locus at DXS7, with a maximum lod score of 2.48 at a recombination fraction of 0. Linkage studies in 1 Italian and 12 British families with LHON, analyzed either together or separately depending on the associated mtDNA mutation, have excluded the presence of such a locus from an interval of about 30 cM around DXS7 in these kindreds, with a total lod score of -26.51 at a recombination fraction of 0. 17 refs., 2 figs., 1 tab.

  7. Partial mitochondrial complex I inhibition induces oxidative damage and perturbs glutamate transport in primary retinal cultures. Relevance to Leber Hereditary Optic Neuropathy (LHON).

    Science.gov (United States)

    Beretta, Simone; Wood, John P M; Derham, Barry; Sala, Gessica; Tremolizzo, Lucio; Ferrarese, Carlo; Osborne, Neville N

    2006-11-01

    Leber Hereditary Optic Neuropathy (LHON) is a maternally inherited form of visual loss, due to selective degeneration of retinal ganglion cells. Despite the established aetiological association between LHON and mitochondrial DNA mutations affecting complex I of the electron transport chain, the pathophysiology of this disorder remains obscure. Primary rat retinal cultures were exposed to increasing concentrations of rotenone to titrate complex I inhibition. Neural cells were more sensitive than Müller glial cells to rotenone toxicity. Rotenone induced an increase in mitochondrial-derived free radicals and lipid peroxidation. Sodium-dependent glutamate uptake, which is mostly mediated by the glutamate transporter GLAST expressed by Müller glial cells, was reduced dose-dependently by rotenone with no changes in GLAST expression. Our findings suggest that complex I-derived free radicals and disruption of glutamate transport might represent key elements for explaining the selective retinal ganglion cell death in LHON.

  8. Mitochondrial gene therapy improves respiration, biogenesis, and transcription in G11778A Leber's hereditary optic neuropathy and T8993G Leigh's syndrome cells.

    Science.gov (United States)

    Iyer, Shilpa; Bergquist, Kristen; Young, Kisha; Gnaiger, Erich; Rao, Raj R; Bennett, James P

    2012-06-01

    Many incurable mitochondrial disorders result from mutant mitochondrial DNA (mtDNA) and impaired respiration. Leigh's syndrome (LS) is a fatal neurodegenerative disorder of infants, and Leber's hereditary optic neuropathy (LHON) causes blindness in young adults. Treatment of LHON and LS cells harboring G11778A and T8993G mutant mtDNA, respectively, by >90%, with healthy donor mtDNA complexed with recombinant human mitochondrial transcription factor A (rhTFAM), improved mitochondrial respiration by ∼1.2-fold in LHON cells and restored >50% ATP synthase function in LS cells. Mitochondrial replication, transcription, and translation of key respiratory genes and proteins were increased in the short term. Increased NRF1, TFAMB1, and TFAMA expression alluded to the activation of mitochondrial biogenesis as a mechanism for improving mitochondrial respiration. These results represent the development of a therapeutic approach for LHON and LS patients in the near future.

  9. Searching the co-occurrence of pathogenic mutations for Leber's hereditary optic neuropathy and hearing loss in more than 26,000 whole mitochondrial genomes.

    Science.gov (United States)

    Yang, Haixin; Liu, Rui; Wang, Chuan-Chao

    2016-09-01

    The co-occurrence of pathogenic or candidate mutations for Leber's hereditary optic neuropathy (LHON) and hearing loss has long been suggested to be a rare incident. The "rare" is probably caused by inadequate database searches. In this study, we created and released a comprehensive database with detailed information of haplogroup, variants, coding sites, and potential pathogenic mutations for more than 26,000 whole mitochondrial genomes. We found the co-occurrence in more than 200 individuals including not only LHON or hearing loss patients but also individuals sampled from general populations with various haplogroup backgrounds. The results highlighted the significant importance of adequate database searching in the genetic analysis of mitochondrial disorders.

  10. Differential Diagnosis for Multiple Sclerosis-related Optic Neuritis

    Institute of Scientific and Technical Information of China (English)

    Yan Zhang; Xiaolei Liang; Shihui Wei; Hongyang Li

    2015-01-01

    Purpose:.To analyze clinical features and main causes of multiple sclerosis-related optic neuritis (MS-ON), providing evidence for the differential diagnosis of MS-ON. Methods: Clinical data were collected from 527 patients, 123 males and 404 females, diagnosed with MS-ON between June 2008 and June 2013. Visual acuity, optometry, visual field, slit-lamp microscopy, indirect ophthalmoscopy (20D), opti-cal coherence tomography (OCT) and magnetic resonance imaging (MRI) were performed. Venous blood was sampled for detection of autoimmune antibodies and Aquaporin (AQP-4). Results:.Fifty nine cases were diagnosed with neuromyelitis optica-related optic neuritis. (NMO-ON),.27 Sjogren's syn-drome-related optic neuropathy,.22 tumors,.21 anterior is-chemic optic neuropathy, 15 radiation-induced optic neuropa-thy, 14 optic neuropathy-related infection, 17 genetic eye dis-eases and 10 open angle glaucoma. Among168 MS-ON pa-tients undergoing optic nerve MRI,90 cases (53.57%) had a lesion 30 mm in two (1.19%). Conclusion:.MS-ON is more commonly misdiagnosed with NMO-ON and Sjogren's syndrome, when compared to optic neuropathy, tumors and ischemic optic neuropathy.

  11. Lyme borreliosis in southern United Kingdom and a case for a new syndrome, chronic arthropod-borne neuropathy.

    Science.gov (United States)

    Dryden, M S; Saeed, K; Ogborn, S; Swales, P

    2015-02-01

    This series of serologically confirmed Lyme disease is the largest reported in the UK and represents 508 patients who presented to one hospital in the South of England between 1992 and 2012. The mean rate of borreliosis throughout this period was 9·8/100,000 population, much higher than the reported national rate of 1·7/100,000. The actual rate increased each year until 2009 when it levelled off. Patients clinically presented with rash (71%), neurological symptoms (16%, of whom half had VII cranial nerve palsies), arthropathy (8%), pyrexia (5%), cardiac abnormalities (1%) or other manifestations (chronic Lyme disease. These patients have a different disease from Lyme disease and therefore an alternative name, chronic arthropod-borne neuropathy (CAN), and case definition for this condition is proposed. We suggest that this chronic condition needs to be distinguished from Lyme disease, as calling the chronic illness 'Lyme disease' causes confusion to patients and physicians. We recommend research initiatives to investigate the aetiology, diagnosis and therapy of CAN.

  12. Clinical and cytogenetic study of a case with familial chromosomal translocation presenting with facial dysmorphism and axial neuropathy.

    Science.gov (United States)

    El-Bassyouni, H T; Shehab, M; Kora, H M; Temtamy, S A

    2012-01-01

    We report on a 9-year-old female patient presenting with muscle weakness, facial dysmorphism and mild mental retardation. She had low birth weight, developmental delay, hypotonia and hyporeflexia and difficulties in climbing the stairs. EMG revealed axonal polyneuropathy affecting both upper and lower limbs. She was the child of non-consanguineous parents, her cytogenetic findings revealed 46,XX,t(12;14)(q14;q23). The mother's karyotype was normal 46,XX while the father's karyotype was 46,XY,t(12;14)(q14;q23) the same as his daughter. Her normal sister's karyotype was also 46,XX,t(12; 14) (q14;q23). Fluorescence in situ hybridization (FISH) was used to elucidate the breakpoints and Array-CGH was done for the patient to confirm the balanced translocation. This observation is of interest because it represents a rare case of a balanced translocation with abnormal phenotype. Mutant genes causing axonal neuropathy have been located on various chromosomes other than 12q14 or 14q24. This report shows the importance of molecular cytogenetics and its correlation with abnormal phenotype and the possibility of another gene locus at the presently studied chromosomal breakpoints. Detailed correlations between chromosome aberrations and their phenotypes are of invaluable help in localising genes for axonal polyneuropathy.

  13. Leber's hereditary optic neuropathy caused by the homoplasmic ND1 m.3635G>A mutation in nine Han Chinese families.

    Science.gov (United States)

    Zhang, Juanjuan; Jiang, Pingping; Jin, Xiaofen; Liu, Xiaoling; Zhang, Minglian; Xie, Shipeng; Gao, Min; Zhang, Sai; Sun, Yan-Hong; Zhu, Jinping; Ji, Yanchun; Wei, Qi-Ping; Tong, Yi; Guan, Min-Xin

    2014-09-01

    In this report, we investigated the molecular mechanism underlying Leber's hereditary optic neuropathy (LHON)-associated mitochondrial m.3635G>A (p.S110N, ND1) mutation. A mutational screening of ND1 gene in a cohort of 1070 Han Chinese subjects LHON identified the m.3635G>A mutation in nine Chinese families with suggestively maternally transmitted LHON. Thirty-eight (22 males/16 females) of 162 matrilineal relatives in these families exhibited the variable severity and age-at-onset of optic neuropathy. Molecular analysis of their mitochondrial genomes identified the homoplasmic m.3635G>A mutation and distinct sets of polymorphisms belonging to the Asian haplogroups G2a1, R11a, D4, R11a, M7b2, G1a, F1a1, B4, and N9a3, respectively. Using cybrids constructed by transferring mitochondria from lymphoblastoid cell lines derived from one Chinese family into mtDNA-less (ρ(0)) cells, we showed ~27% decrease in the activity of NADH:ubiquinone oxidoreductase (complex I) in mutant cybrids carrying the m.3635G>A mutation, compared with control cybrids. The respiratory deficiency caused by the m.3635G>A mutation results in decreased efficiency of mitochondrial ATP synthesis. These mitochondrial dysfunctions caused an increase in the production of reactive oxygen species in the mutant cybrids. The data provide the direct evidence for the m.3635G>A mutation leading to LHON. Our findings may provide new insights into the understanding of pathophysiology of LHON.

  14. Biochemical evidence for a mitochondrial genetic modifier in the phenotypic manifestation of Leber's hereditary optic neuropathy-associated mitochondrial DNA mutation.

    Science.gov (United States)

    Jiang, Pingping; Liang, Min; Zhang, Chaofan; Zhao, Xiaoxu; He, Qiufen; Cui, Limei; Liu, Xiaoling; Sun, Yan-Hong; Fu, Qun; Ji, Yanchun; Bai, Yidong; Huang, Taosheng; Guan, Min-Xin

    2016-08-15

    Leber's hereditary optic neuropathy (LHON) is the most common mitochondrial disease. Mitochondrial modifiers are proposed to modify the phenotypic expression of primary LHON-associated mitochondrial DNA (mtDNA) mutations. In this study, we demonstrated that the LHON susceptibility allele (m.14502T > C, p. 58I > V) in the ND6 gene modulated the phenotypic expression of primary LHON-associated m.11778G > A mutation. Twenty-two Han Chinese pedigrees carrying m.14502T > C and m.11778G > A mutations exhibited significantly higher penetrance of optic neuropathy than those carrying only m.11778G > A mutation. We performed functional assays using the cybrid cell models, generated by fusing mtDNA-less ρ(o) cells with enucleated cells from LHON patients carrying both m.11778G > A and m.14502T > C mutations, only m.14502T > C or m.11778G > A mutation and a control belonging to the same mtDNA haplogroup. These cybrids cell lines bearing m.14502T > C mutation exhibited mild effects on mitochondrial functions compared with those carrying only m.11778G > A mutation. However, more severe mitochondrial dysfunctions were observed in cell lines bearing both m.14502T > C and m.11778G > A mutations than those carrying only m.11778G > A or m.14502T > C mutation. In particular, the m.14502T > C mutation altered assemble of complex I, thereby aggravating the respiratory phenotypes associated with m.11778G > A mutation, resulted in a more defective complex I. Furthermore, more reductions in the levels of mitochondrial ATP and increasing production of reactive oxygen species were also observed in mutant cells bearing both m.14502T > C and m.11778G > A mutation than those carrying only 11778G > A mutation. Our findings provided new insights into the pathophysiology of LHON that were manifested by interaction between primary and secondary mtDNA mutations.

  15. Very low penetrance of Leber's hereditary optic neuropathy in five Han Chinese families carrying the ND1 G3460A mutation.

    Science.gov (United States)

    Tong, Yi; Sun, Yan-Hong; Zhou, Xiangtian; Zhao, Fuxin; Mao, Yijian; Wei, Qi-ping; Yang, Li; Qu, Jia; Guan, Min-Xin

    2010-04-01

    We report here the clinical, genetic, and molecular characterization of five Han Chinese families with Leber's hereditary optic neuropathy (LHON). Strikingly, there were very low penetrances of visual impairment in these Chinese families, ranging from 4.2% to 22.2%, with an average of 10.2%. In particular, only 7 (4 males/3 females) of 106 matrilineal relatives in these families exhibited the variable severity and age-at-onset in visual dysfunction. The age-at-onset for visual impairment in matrilineal relatives in these families, varied from 20 to 25 years, with an average of 21.8 years old. Molecular analysis of mitochondrial genomes identified the homoplasmic ND1 G3460A mutation and distinct sets of variants, belonging to the Asian haplogroups B5b, C4a1, D5, F1, and R9, respectively. This suggests that the G3640A mutation occurred sporadically and multiplied through evolution of the mtDNA in China. However, there was the absence of known secondary LHON-associated mtDNA mutations in these Chinese families. Very low penetrance of visual loss in these five Chinese pedigrees strongly indicated that the G3640A mutation was itself insufficient to develop the optic neuropathy. The absence of secondary LHON mtDNA mutations suggest that these mtDNA haplogroup-specific variants may not play an important role in the phenotypic expression of the G3640A mutation in those Chinese families with low penetrance of vision loss. However, nuclear modifier genes, epigenetic and environmental factors appear to be modifier factors for the phenotypic manifestation of the G3640A mutation in these Chinese families.

  16. Peripheral neuropathy associated with mitochondrial disease in children.

    Science.gov (United States)

    Menezes, Manoj P; Ouvrier, Robert A

    2012-05-01

    Mitochondrial diseases in children are often associated with a peripheral neuropathy but the presence of the neuropathy is under-recognized because of the overwhelming involvement of the central nervous system (CNS). These mitochondrial neuropathies are heterogeneous in their clinical, neurophysiological, and histopathological characteristics. In this article, we provide a comprehensive review of childhood mitochondrial neuropathy. Early recognition of neuropathy may help with the identification of the mitochondrial syndrome. While it is not definite that the characteristics of the neuropathy would help in directing genetic testing without the requirement for invasive skin, muscle or liver biopsies, there appears to be some evidence for this hypothesis in Leigh syndrome, in which nuclear SURF1 mutations cause a demyelinating neuropathy and mitochondrial DNA MTATP6 mutations cause an axonal neuropathy. POLG1 mutations, especially when associated with late-onset phenotypes, appear to cause a predominantly sensory neuropathy with prominent ataxia. The identification of the peripheral neuropathy also helps to target genetic testing in the mitochondrial optic neuropathies. Although often subclinical, the peripheral neuropathy may occasionally be symptomatic and cause significant disability. Where it is symptomatic, recognition of the neuropathy will help the early institution of rehabilitative therapy. We therefore suggest that nerve conduction studies should be a part of the early evaluation of children with suspected mitochondrial disease.

  17. Glioblastoma multiforme of the optic chiasm: A rare case of common pathology

    Science.gov (United States)

    Lyapichev, Kirill A.; Bregy, Amade; Cassel, Adrienne; Handfield, Chelsea; Velazquez-Vega, Jose; Kay, Matthew D.; Basil, Gregory; Komotar, Ricardo J.

    2016-01-01

    Background: Malignant optic and chiasmatic gliomas are extremely rare, and are classified pathologically as anaplastic astrocytoma or glioblastoma multiforme (GBM). Approximately 40 cases of optic GBM in adults have been reported in the literature, and only five of them were described to originate from the optic chiasm. Case Description: An 82-year-old male patient with a past medical history of diabetes mellitus type 2, melanoma, and bladder cancer presented with gradual vision loss of the left eye in a period of 1 month. After neuro-ophthalmological examination, the decision of thither magnetic resonance imaging (MRI) studies was made. It showed a contrast enhancing mass in the region of the optic chiasm. In this case, imaging study was not enough to establish an accurate diagnosis and a left pterional craniotomy for biopsy and resection of the optic chiasmal mass was performed. After histological evaluation of the mass tissue, the diagnosis of GBM was made. Taking into account the patient's poor condition and unfavorable prognosis he was moved to inpatient hospice. The patient deceased within 2 months after surgery. Conclusion: Chiasmal GBM is an extremely rare condition where a biopsy is necessary for accurate diagnosis and optimal treatment. Differential diagnosis for such lesions can be very difficult and include demyelinating optic neuritis and non-demyelinating inflammatory optic neuropathy (e.g., sarcoid), vascular lesions (e.g., cavernoma), compressive lesions of the optic apparatus, metastatic malignancy, and primary tumors of the anterior optic pathway. The role of chemotherapy and radiotherapy including novel stereotaxic radiosurgery methods is still unclear and will need to be evaluated. PMID:27512611

  18. [Inflammatory neuropathies and multineuritis].

    Science.gov (United States)

    Kuntzer, Thierry; Chofflon, Michel

    2009-12-02

    Inflammatory neuropathies include those neuropathies in which the diagnosis, outcome and type of treatment are badly known, the reason of this review. They are expressed as diffuse (such as CIDP and ganglionopathies), multifocal (vasculitic neuropathy) or focal (MMN; plexopathies; immune reconstitution inflammatory syndrome). These forms of neuropathies are important to be known because the beneficial therapeutic possibilities of immunosuppression.

  19. A pedigree of Leber's hereditary optic neuropathy with mtDNA14484 mutation%伴有mtDNA14484位点突变的Leber病一大家系

    Institute of Scientific and Technical Information of China (English)

    童绎; 王影; 姜枫; 刘斌; 张守康; 杨薇

    2008-01-01

    Objective To analyze a pedigree of Leber' s hereditary optic neuropathy, and its penetrance, anticipation, and spontaneous eyesight improvement, and its relationship with mitochondrial DNA mutation. Methods Eighteen members in the tinnily were undergone routine visual check. Five cases were taken visual evoked potential and visual field examination. DNA sequencing was performed on6 eases to check the mtDNA11778,3460 and 14484 loci.Results (1)The offsprings from the first wife in the first generation showed decreased acuity of the two eyes, which was optic atrophy identified by funduseopy. (2) The mtDNA had mutation at position 14484, but not at positions 11778 and 3460. Conclusion The pedigree showed a typical maternal inheritance of Leber' s hereditary optic neuropathy. It was eaused by mtDNA 14484 mutation.%目的 研究Leber病一大家系的遗传因素,探讨其外显率、遗传早现、自发视力恢复,以及与mtDNA的关联性.方法 对家系中18例患者进行调查,并行视力、眼底等常规检查;5例患者作了视觉诱发电位(visual evoked potential,VEP)及视野检查;应用聚合酶链反应对6例患者外周血液进行mtDNA11778、3460及144843个位点检查.结果 (1)本家系第Ⅰ代娶二妻,前妻后代皆无明显诱因出现双眼视力下降,经眼底镜检查符合视神经萎缩诊断.后妻无眼病,其后代均无眼病.(2)6例患者的mtDNA检查显示11778、3460位点未发现突变,而在14484位点出现同质性突变.结论 该家系Leber病呈典型母系遗传,该病的临床表现可能与mtDNA14484位点突变密切关联.

  20. 视觉诱发电位在外伤性视神经病变治疗中的临床应用%VEP clinical application in the treatment of traumatic optic neuropathy

    Institute of Scientific and Technical Information of China (English)

    赵玲; 冯秀艳

    2012-01-01

    Objective To observe the effect of treating traumatic optic neuropathy(TON)through the visual evoked potential(VEP).Methods 35cases of traumatic optic neuropathy were devided into three groups randomly,treated with routine management,routine management plus methyl-prednisone and hyperbaric oxygen(HBO)combined with methyl-prednisone,observed the difference of the latent period and amplitudes of VEP after treatment.Results The amplitudes of VEP was significant differently in methyl-prednisone and HBO combined with methyl-prednisone treatment groups compared with the routine management group(P < 0.05).Conclusion The VEP determination has certain clinical value in the injury of the optive nerve.The VEP results show that the treatment with the basic management plus methyl-prednisone and HBO early can improve the function of the optic nerve.%目的 通过视觉诱发电位(VEP)检测来评价外伤性视神经病变(TON)的临床治疗效果.方法 TON 33例(35眼)随机分成3组,分别采用常规治疗、常规加甲基强的松龙(甲强龙)治疗及甲强龙联合高压氧(HBO)治疗3种方法,对治疗前后VEP的P波振幅及潜伏期进行比较.结果 甲强龙治疗组和甲强龙联合HBO治疗组VEP的P波振幅改善分别与常规治疗组比较差异有统计学意义(t=2.41,P<0.05;t =4.69,P<0.01).结论 VEP在外伤性视神经病变中对视神经损伤的判定有较高的临床参考价值.