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Sample records for optic neuropathy accompanying

  1. Infectious optic neuropathy.

    PubMed

    Golnik, Karl C

    2002-03-01

    A wide variety of infectious agents are known to cause optic neuropathy. This article will consider the bacteria, spirochetes, fungi, and viruses that most commonly affect the optic nerve. Clinical presentation is variable, but some pathogens often produce a characteristic funduscopic pattern. Diagnosis is usually made on the basis of clinical suspicion and serologic testing. Polymerase chain reaction is also increasingly utilized. Most infectious agents can be effectively treated but visual recovery is highly variable. PMID:15513450

  2. Dysthyroid optic neuropathy (DON).

    PubMed

    Ebner, Roberto

    2002-03-01

    Dysthyroid Optic Neuropathy (DON) affects a small percentage of patients with Graves disease, but, when it occurs, it can cause significant and permanent loss of vision. DON is treatable if recognized early. Systemic steroids can be effective, but may cause side affects. Orbital injection of steroids may play a role in selected patients. Orbital radiation has a more permanent effect and has gained wide acceptance as a relatively non-invasive method of reversing DON. Surgery to decompress crowded orbits has been used for years and continues to be a viable approach for those patients with optic neuropathy, especially when there is significant proptosis. Optic nerve decompression can also be achieved through a transethmoidal approach. PMID:15513451

  3. Genetics Home Reference: Leber hereditary optic neuropathy

    MedlinePlus

    ... Conditions Leber hereditary optic neuropathy Leber hereditary optic neuropathy Enable Javascript to view the expand/collapse boxes. ... Open All Close All Description Leber hereditary optic neuropathy (LHON) is an inherited form of vision loss. ...

  4. Radiation optic neuropathy

    SciTech Connect

    Kline, L.B.; Kim, J.Y.; Ceballos, R.

    1985-08-01

    Following surgery for pituitary adenoma, radiation therapy is an accepted treatment in reducing tumor recurrence. However, a potential therapeutic complication is delayed radionecrosis of perisellar neural structures, including the optic nerves and chiasm. This particular cause of visual loss, radiation optic neuropathy (RON), has not been emphasized in the ophthalmologic literature. Four cases of RON seen in the past five years are reported. Diagnostic criteria include: (1) acute visual loss (monocular or binocular), (2) visual field defects indicating optic nerve or chiasmal dysfunction, (3) absence of optic disc edema, (4) onset usually within three years of therapy (peak: 1-1 1/2 years), and (5) no computed tomographic evidence of visual pathway compression. Pathologic findings, differential diagnosis and therapy will be discussed in outlining the clinical profile of RON.

  5. Management of ischemic optic neuropathies

    PubMed Central

    Hayreh, Sohan Singh

    2011-01-01

    Ischemic optic neuropathies (IONs) consist primarily of two types: anterior ischemic optic neuropathy (AION) and posterior ischemic optic neuropathy (PION). AION comprises arteritic AION (A-AION: due to giant cell arteritis) and non-arteritic AION (NA-AION: due to other causes). PION consists of arteritic PION (A-PION: due to giant cell arteritis), non-arteritic PION (NA-PION: due to other causes), and surgical PION (a complication of several systemic surgical procedures). These five types of ION are distinct clinical entities etiologically, pathogenetically, clinically and from the management point of view. In the management of AION, the first crucial step with patients aged 50 and over is to identify immediately whether it is arteritic or not because A-AION is an ophthalmic emergency and requires urgent treatment with high-dose steroid therapy to prevent any further visual loss in one or both eyes. Patients with NA-AION, when treated with systemic corticosteroid therapy within first 2 weeks of onset, had significantly better visual outcome than untreated ones. Systemic risk factors, particularly nocturnal arterial hypotension, play major roles in the development of NA-AION; management of them is essential in its prevention and management. NA-PION patients, when treated with high-dose systemic steroid therapy during the very early stages of the disease, showed significant improvement in visual acuity and visual fields, compared to untreated eyes. A-PION, like A-AION, requires urgent treatment with high-dose steroid therapy to prevent any further visual loss in one or both eyes. There is no satisfactory treatment for surgical PION, except to take prophylactic measures to prevent its development. PMID:21350282

  6. Traumatic Optic Neuropathy: A Review

    PubMed Central

    Kumaran, Arjunan Muthu; Sundar, Gangadhara; Chye, Lim Thiam

    2014-01-01

    The aim of this article is to evaluate current literature on investigation and management of traumatic optic neuropathy (TON), propose recommendations for diagnosis and management, and explore novel future treatments. TON, though uncommon, causes substantial visual loss. Without clear guidelines, there is much ambiguity regarding its diagnosis and management. Investigation and treatment (conservative, medical, surgical, and combined) vary widely between centers. Electronic databases PubMed, MEDLINE, PROSPERO, CENTRAL, and EMBASE were searched for content that matched “Traumatic optic neuropathy.” Articles with abstracts and full text available, published in the past 10 years, written English and limited to human adults, were selected. All study designs were acceptable except case reports and case series with fewer 10 patients. All abstracts were then evaluated for relevance. References of these studies were evaluated and if also relevant, included. A total of 2,686 articles were retrieved and 43 examined for relevance. Of these, 23 articles were included. TON is a clinical diagnosis. Visual-evoked potential is useful in diagnosis and prognosis. Computed tomography demonstrates canal fractures and concomitant injuries. Magnetic resonance images should be reserved for select and stable patients. Conservative treatment is appropriate in mild TON. Steroids are of questionable benefit and may be harmful. Surgery should be reserved for patients with radiological evidence of compression and individualized. PMID:25709751

  7. Optic neuropathy associated with systemic sarcoidosis

    PubMed Central

    Burton, Ben J.; Graham, Elizabeth M.; Plant, Gordon T.

    2016-01-01

    Objective: To identify and follow a series of 52 patients with optic neuropathy related to sarcoidosis. Methods: Prospective observational cohort study. Results: The disorder was more common in women and affected a wide age range. It was proportionately more common in African and Caribbean ethnic groups. Two clinical subtypes were identified: the more common was a subacute optic neuropathy resembling optic neuritis; a more slowly progressive optic neuropathy arose in the remaining 17%. Sixteen (31%) were bilateral. Concurrent intraocular inflammation was seen in 36%. Pain arose in only 27% of cases. An optic perineuritis was seen in 2 cases, and predominate involvement of the chiasm in one. MRI findings showed optic nerve involvement in 75% of cases, with adjacent and more widespread inflammation in 31%. Treatment with corticosteroids was helpful in those with an inflammatory optic neuropathy, but not those with mass lesions. Relapse of visual signs arose in 25% of cases, necessitating an increase or escalation of treatment, but relapse was not a poor prognostic factor. Conclusions: This is a large prospective study of the clinical characteristics and outcome of treatment in optic neuropathy associated with sarcoidosis. Patients who experience an inflammatory optic neuropathy respond to treatment but may relapse. Those with infiltrative or progressive optic neuropathies improve less well even though the inflammatory disorder responds to therapy. PMID:27536707

  8. Emerging Mitochondrial Therapeutic Targets in Optic Neuropathies.

    PubMed

    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. PMID:27288727

  9. Traumatic Optic Neuropathy - A Conundrum.

    PubMed

    Selvaraj, Vinoth Kanna; Viswanathan, Ramachandran; Devanathan, Vasudevan

    2016-03-01

    Visual impairment following head injury may be an enigma especially if the onset of symptoms were to be few days after the actual trauma and the bias arising out of the initial normal ophthalmological examination is not neutralised by unbiased repeated formal clinical evaluation aided with electrophysiology. We report and discuss here a 32-year-old lady with delayed onset of indirect traumatic visual loss with anaemia who failed to improve after blood transfusion but improved immediately following steroid therapy seven days after trauma. Though steroids have not been shown to have a significant contribution on outcomes following Traumatic optic neuropathy, this report rekindles its role in delayed progressive visual loss following head trauma and the need to re-analyse the role of steroids in patients with delayed progressive visual disturbance following head injury excluding those with acute onset symptoms in view of different pathologies in both these presentations. This paper also highlights potential mechanisms for the two major types of presentation. PMID:27134913

  10. Toxic optic neuropathies: an updated review.

    PubMed

    Grzybowski, Andrzej; Zülsdorff, Magdalena; Wilhelm, Helmut; Tonagel, Felix

    2015-08-01

    Toxic optic neuropathy (TON) is caused by the damage to the optic nerve through different toxins, including drugs, metals, organic solvents, methanol and carbon dioxide. A similar clinical picture may also be caused by nutritional deficits, including B vitamins, folic acid and proteins with sulphur-containing amino acids. This review summarizes the present knowledge on disease-causing factors, clinical presentation, diagnostics and treatment in TON. It discusses in detail known and hypothesized relations between drugs, including tuberculostatic drugs, antimicrobial agents, antiepileptic drugs, antiarrhythmic drugs, disulfiram, halogenated hydroquinolones, antimetabolites, tamoxifen and phosphodiesterase type 5 inhibitors and optic neuropathy. PMID:25159832

  11. Pegylated Interferon Alpha–Associated Optic Neuropathy

    PubMed Central

    Berg, Kathleen T.; Nelson, Bruce; Harrison, Andrew R.; McLoon, Linda K.; Lee, Michael S.

    2013-01-01

    A 52-year-old man with chronic hepatitis C presented with painless, bilateral, simultaneous non-arteritic anterior ischemic optic neuropathy (NAION) and peripheral neuropathy. Symptoms began 19 weeks after starting peginterferon alpha-2a. The peripheral neuropathy and vision of the right eye improved, but the vision of the left eye worsened after stopping interferon. We identified 23 additional cases of NAION during interferon alpha therapy. At least 12 of these patients suffered bilateral NAION. Patients lost vision 1–40 weeks after initiating therapy. Of 21 eyes that had documented initial and follow-up acuities, 8 improved, 1 worsened, and the rest remained stable. One patient had a painful peripheral neuropathy. Treatment with interferon alpha may result in NAION. Discontinuation of therapy deserves consideration after weighing individual risks and benefits. PMID:20351572

  12. [Optic neuropathy in acute poisoning with methanol].

    PubMed

    Sekkat, A; Maillard, P; Dupeyron, G; Bensouda, J; Arne, J L; Bec, P

    1982-01-01

    The authors report four cases of methanol poisoning, two of which suffering acute bilateral optic neuropathy which secondarily leads to optic atrophy. The report the main clinical features of such a poisoning and the actual basis of its physiopathology and treatment. According to the four cases reported, they underline the importance of early diagnosis and specific treatment. PMID:7169508

  13. Magnetic resonance imaging of radiation optic neuropathy

    SciTech Connect

    Zimmerman, C.F.; Schatz, N.J.; Glaser, J.S. )

    1990-10-15

    Three patients with delayed radiation optic neuropathy after radiation therapy for parasellar neoplasms underwent magnetic resonance imaging. The affected optic nerves and chiasms showed enlargement and focal gadopentetate dimeglumine enhancement. The magnetic resonance imaging technique effectively detected and defined anterior visual pathway changes of radionecrosis and excluded the clinical possibility of visual loss because of tumor recurrence.

  14. Systemic corticosteroids in nonarteritic ischemic optic neuropathy

    PubMed Central

    Al-Zubidi, Nagham; Zhang, Jason; Spitze, Arielle; Lee, Andrew G

    2014-01-01

    Nonarteritic ischemic optic neuropathy (NAION) is one of the most prevalent optic nerve disorders seen in ophthalmic practice. The role of corticosteroid therapy in NAION remains a highly controversial area of debate in ophthalmology. This brief review will provide an overview of the current clinical evidence on this topic as well as some comment on the medical debate. PMID:25449939

  15. Diabetic Peripheral Neuropathy: Should a Chaperone Accompany Our Therapeutic Approach?

    PubMed Central

    Farmer, Kevin L.; Li, Chengyuan

    2012-01-01

    Diabetic peripheral neuropathy (DPN) is a common complication of diabetes that is associated with axonal atrophy, demyelination, blunted regenerative potential, and loss of peripheral nerve fibers. The development and progression of DPN is due in large part to hyperglycemia but is also affected by insulin deficiency and dyslipidemia. Although numerous biochemical mechanisms contribute to DPN, increased oxidative/nitrosative stress and mitochondrial dysfunction seem intimately associated with nerve dysfunction and diminished regenerative capacity. Despite advances in understanding the etiology of DPN, few approved therapies exist for the pharmacological management of painful or insensate DPN. Therefore, identifying novel therapeutic strategies remains paramount. Because DPN does not develop with either temporal or biochemical uniformity, its therapeutic management may benefit from a multifaceted approach that inhibits pathogenic mechanisms, manages inflammation, and increases cytoprotective responses. Finally, exercise has long been recognized as a part of the therapeutic management of diabetes, and exercise can delay and/or prevent the development of painful DPN. This review presents an overview of existing therapies that target both causal and symptomatic features of DPN and discusses the role of up-regulating cytoprotective pathways via modulating molecular chaperones. Overall, it may be unrealistic to expect that a single pharmacologic entity will suffice to ameliorate the multiple symptoms of human DPN. Thus, combinatorial therapies that target causal mechanisms and enhance endogenous reparative capacity may enhance nerve function and improve regeneration in DPN if they converge to decrease oxidative stress, improve mitochondrial bioenergetics, and increase response to trophic factors. PMID:22885705

  16. [Ischemic optic neuropathy after lumbar spine surgery].

    PubMed

    Bermejo-Alvarez, M A; Carpintero, M; García-Carro, G; Acebal, G; Fervienza, P; Cosío, F

    2007-12-01

    Ischemic optic neuropathy is the most common cause of visual complications after non-ophthalmic surgery. The incidence has varied in different case series, but prone-position spine surgery appears to be involved in most of the reports. We present the case of a 47-year-old woman who developed near total blindness in the left eye following lumbar spine fusion surgery involving the loss of 900 mL of blood. An ophthalmic examination including inspection of the ocular fundus, fluorescein angiography, and visual evoked potentials returned a diagnosis of retrolaminar optic neuropathy. Outcome was poor. PMID:18200998

  17. Late onset Leber's optic neuropathy: a case confused with ischaemic optic neuropathy.

    PubMed Central

    Borruat, F X; Green, W T; Graham, E M; Sweeney, M G; Morgan-Hughes, J A; Sanders, M D

    1992-01-01

    A case is reported of a 63-year-old man with progressive central visual loss in one eye followed 11 months later by involvement of the fellow eye. A diagnosis of chronic ischaemic optic neuropathy was considered. However, despite a negative family history, the absence of electrocardiographic abnormalities, and minimal fundus changes a diagnosis of Leber's optic neuropathy was made on the basis of magnetic resonance imaging findings and the mitochondrial DNA mutation at base pair 11778. Images PMID:1420066

  18. Postirradiation optic neuropathy in antral carcinoma

    SciTech Connect

    Singh, J.; Vashist, S.

    1984-06-01

    A case is described of a patient who developed radiation-induced optic neuropathy 18 months following cobalt-60 irradiation for carcinoma of the left maxillary antrum and ethmoid sinus. This case is unusual because of the early onset of the optic nerve damage following radiation therapy and the ultimate emergence of the eye involved by tumor compression as the better eye in terms of visual acuity.

  19. Methanol optic neuropathy: a histopathological study.

    PubMed

    Sharpe, J A; Hostovsky, M; Bilbao, J M; Rewcastle, N B

    1982-10-01

    The histopathologic effects of methanol on the optic nerve were studied in four patients. Circumscribed myelin damage occurred behind the lamina cribrosa in each nerve. Axons were preserved. Demyelination also occurred in cerebral hemispheric white matter in one patient. This selective myelinoclastic effect of methanol metabolism is probably caused by histotoxic anoxia in watershed areas of the cerebral and distal optic nerve circulations. Juxtabulbar demyelination may cause optic disk edema in methanol poisoning by compressive obstruction of orthograde axoplasmic flow. Visual loss may be due to disruption of saltatory conduction. Retrolaminar demyelinating optic neuropathy is an early morphologic correlate of visual loss in methanol intoxication. PMID:6889696

  20. Mutations for Leber hereditary optic neuropathy in patients with alcohol and tobacco optic neuropathy

    PubMed Central

    Amaral-Fernandes, Marcela Scabello; Marcondes, Ana Maria; Miranda, Paulo Maurício do Amor Divino; Maciel-Guerra, Andréa Trevas

    2011-01-01

    Purpose There are many similarities in the clinical presentation of Leber hereditary optic neuropathy (LHON) and in patients who have optic neuropathy and a history of heavy tobacco and alcohol consumption. The main objective of this study is to investigate the frequency of primary and secondary mitochondrial DNA (mtDNA) mutations for LHON in patients diagnosed as having alcohol and tobacco optic neuropathy (ATON). Methods Twenty-six patients who had a history of heavy alcohol and tobacco consumption and who developed bilateral optic neuropathy were tested for primary mutations (G11778A, T14484C, and G3460A) by restriction analysis, and 14 secondary mutations in the genes mitochondrially encoded NADH dehydrogenase 1 (MT-ND1), mitochondrially encoded NADH dehydrogenase 4 (MT-ND4), mitochondrially encoded NADH dehydrogenase 4L (MT-ND4L), mitochondrially encoded NADH dehydrogenase 5 (MT-ND5), mitochondrially encoded NADH dehydrogenase 6 (MT-ND6), and mitochondrially encoded cytochrome B (MT-CYB) by direct sequencing. Results Four (15.4%) of 26 patients tested positive for LHON primary mutations, two for the G11778A mutation, and two for the T14484C mutation. No patient tested positive for any of the 14 secondary mutations. Familial recurrence was present in four patients, and only three of these patients have presented the LHON mutation. Conclusions The diagnosis of LHON should be considered in all patients diagnosed as having optic neuropathy, particularly those with familial recurrence of vision loss. PMID:22194643

  1. Magnetic resonance imaging in Leber's optic neuropathy.

    PubMed Central

    Kermode, A G; Moseley, I F; Kendall, B E; Miller, D H; MacManus, D G; McDonald, W I

    1989-01-01

    Thirteen males with Leber's optic neuropathy had magnetic resonance imaging (MRI) of the brain, and in eight the optic nerves were imaged using STIR (Short Time Inversion Recovery) sequences. All optic nerve scans were abnormal. In seven with bilateral visual loss four showed bilateral increased optic nerve signal and three unilateral increase. The involvement was of the mid and posterior intra-orbital sections over three 5 mm slices or more with sparing of the anterior portion. One patient with unilateral visual loss had increased signal only on the affected side. Brain MRI was normal, in marked contrast to the findings in clinically isolated optic neuritis in which multiple white matter lesions are seen in the majority. Images PMID:2732742

  2. Leber hereditary optic neuropathy: current perspectives

    PubMed Central

    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

  3. Optic neuropathy following an altitude exposure.

    PubMed

    Steigleman, Allan; Butler, Frank; Chhoeu, Austin; O'Malley, Timothy; Bower, Eric; Giebner, Stephen

    2003-09-01

    This case report describes a 20-yr-old man who presented with retro-orbital pain and blurred vision in his left eye 3 wk after an altitude exposure in a hypobaric chamber. He was found to have significant deficits in color vision and visual fields consistent with an optic neuropathy in his left eye. The patient was diagnosed with decompression sickness and treated with hyperbaric oxygen with a U.S. Navy Treatment Table VI. All signs and symptoms resolved with a single hyperbaric oxygen treatment but recurred. A head MRI revealed a left frontoethmoid sinus opacity. A concomitant sinusitis was diagnosed. The patient had full resolution of symptoms after a total of four hyperbaric oxygen treatments and antibiotic therapy at 6-wk follow-up. Although a para-infectious etiology for this patient's optic neuropathy cannot be excluded, his history of altitude exposure and significant, rapid response to hyperbaric oxygen treatment strongly implies decompression sickness in this case. PMID:14503679

  4. Idebenone for Leber's hereditary optic neuropathy.

    PubMed

    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. PMID:27186591

  5. Spheniodal mucocele causing bilateral optic neuropathy and ophthalmoplegia

    PubMed Central

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

    2014-01-01

    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. PMID:23571243

  6. The clinical spectrum of amiodarone-associated optic neuropathy.

    PubMed Central

    Johnson, Lenworth N.; Krohel, Gregory B.; Thomas, Eric R.

    2004-01-01

    PURPOSE: To describe the clinical spectrum of amiodarone-associated optic neuropathy. METHODS: Observational cases series and review. RESULTS: Of 55 cases, the median interval for onset of optic neuropathy was four months after initiating amiodarone; 88% occurred within 12 months. Seven (13%) patients were asymptomatic. Twenty-two (40%) patients presented with sudden visual loss, while 26 (47%) had insidious loss of vision. Visual acuity ranged from 20/15 to light perception; 10 (18%) patients had legal blindness with visual acuity of 20/200 or worse. Visual field loss was present in 91% of cases. Color vision loss was present in eight (40%) of 20 cases. Optic disc edema was present in 85% of cases, while eight (15%) patients had retrobulbar optic neuropathy, without evidence of disc edema. Optic disc edema resolved over a median time of three months. Five patients had raised intracranial pressure on lumbar puncture. CONCLUSION: We were able to classify amiodarone-associated optic neuropathy into five clinical categories with respect to temporal characteristics and optic nerve appearance: insidious-onset (43%), acute-onset (28%), retrobulbar (13%), increased intracranial pressure (8%), and delayed-progressive onset (8%). Most cases of optic neuropathy commenced within 12 months of initiating amiodarone, with the median onset being four months. Over 10% of patients will have no visual symptoms at the onset. Ophthalmologic examinations within the first 12 months--and particularly within four months of initiating amiodarone--should improve early detection of amiodarone-associated optic neuropathy. PMID:15586652

  7. Dysthyroid optic neuropathy. The crowded orbital apex syndrome.

    PubMed

    Neigel, J M; Rootman, J; Belkin, R I; Nugent, R A; Drance, S M; Beattie, C W; Spinelli, J A

    1988-11-01

    The authors have reviewed the clinical presentation, visual fields, color vision testing, visual-evoked potentials, and computed tomographic (CT) findings of 58 patients (95 eyes) with dysthyroid optic neuropathy. The authors compared these findings to a control group of 60 patients (119 eyes) with thyroid eye disease who underwent CT scanning and did not exhibit evidence of optic neuropathy. Clinically, dysthyroid optic neuropathy is an insidious disease; when compared with the usual Graves' orbitopathy patient, the optic neuropathy group presented at a later age and with a later onset of thyroid eye disease. The patients in this group were more likely to be male and/or diabetic, and often presented with desaturation of color vision. Asymmetrical extraocular muscle restriction and vertical tropias were more frequent in the optic neuropathy group. The most sensitive indicators of optic nerve dysfunction appeared to be visual-evoked potentials and color vision. Computed tomographic studies confirmed that apical orbital crowding was a characteristic feature of optic neuropathy. These findings should alert the clinician to a more aggressive approach to these patients. PMID:3211460

  8. Toxic optic neuropathy: an unusual cause.

    PubMed

    Ramkumar, Hema L; Savino, Peter J

    2014-10-01

    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. PMID:25449946

  9. Traumatic Optic Neuropathy – A Conundrum

    PubMed Central

    Selvaraj, Vinoth Kanna; Devanathan, Vasudevan

    2016-01-01

    Visual impairment following head injury may be an enigma especially if the onset of symptoms were to be few days after the actual trauma and the bias arising out of the initial normal ophthalmological examination is not neutralised by unbiased repeated formal clinical evaluation aided with electrophysiology. We report and discuss here a 32-year-old lady with delayed onset of indirect traumatic visual loss with anaemia who failed to improve after blood transfusion but improved immediately following steroid therapy seven days after trauma. Though steroids have not been shown to have a significant contribution on outcomes following Traumatic optic neuropathy, this report rekindles its role in delayed progressive visual loss following head trauma and the need to re-analyse the role of steroids in patients with delayed progressive visual disturbance following head injury excluding those with acute onset symptoms in view of different pathologies in both these presentations. This paper also highlights potential mechanisms for the two major types of presentation. PMID:27134913

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

    PubMed Central

    Megur, Bharathi; Megur, Deepak; Megur, Umesh; Reddy, Sandeep

    2014-01-01

    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. PMID:25116784

  11. Deficiency of thiosulphate sulphurtransferase (rhodanese) in Leber's hereditary optic neuropathy.

    PubMed Central

    Poole, C J; Kind, P R

    1986-01-01

    Leber's hereditary optic neuropathy is a rare cause of progressive visual failure. Its cause is unknown, but one hypothesis is that patients have a defect in the detoxication of cyanide. One of the enzymes used in this detoxication is thiosulphate sulphurtransferase (rhodanese). The activity of this enzyme was measured in the rectal mucosa of a group of subjects with Leber's hereditary optic neuropathy, and it was found to be considerably reduced compared with that in a group of controls (p less than 0.001). This finding supports the hypothesis of an inborn error of cyanide detoxication in this condition. PMID:3085790

  12. Methylprednisolone pulse therapy in severe dysthyroid optic neuropathy

    SciTech Connect

    Guy, J.R.; Fagien, S.; Donovan, J.P.; Rubin, M.L. )

    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.

  13. Radial optic neurotomy as a treatment for anterior ischemic optic neuropathy secondary to optic disc drusen

    PubMed Central

    Pinxten, Isabel; Stalmans, Peter

    2014-01-01

    Importance: Radial optic neurotomy (RON) was first described by Opremcak as a treatment for patients with central retinal vein occlusion (CRVO). The most common cause of visual loss in patients with optic disc drusen is nonarteritic anterior ischemic optic neuropathy (NAION). The pathogenesis of nonarteritic anterior ischemic optic neuropathy associated with optic disc drusen is assumed to be similar to the compartment-like syndrome described by Opremcak in the case of central retinal vein occlusion. Observation: An 82-year-old male with bilateral optic disc drusen presented with bilateral visual loss and severe visual field defects consistent with nonarteritic anterior ischemic optic neuropathy. A radial optic neurotomy was performed to treat the most affected eye. Postoperatively, significant and persistent improvement of visual acuity and improved automated perimetry were observed in the operated eye. Conclusion: Optic nerve head decompression by radial optic neurotomy could be a treatment option in patients with nonarteritic anterior ischemic optic neuropathy associated with optic disc drusen and severe visual field defects.

  14. Comparison of Optic Disc Morphology of Optic Nerve Atrophy between Compressive Optic Neuropathy and Glaucomatous Optic Neuropathy

    PubMed Central

    Hata, Masayuki; Miyamoto, Kazuaki; Oishi, Akio; Makiyama, Yukiko; Gotoh, Norimoto; Kimura, Yugo; Akagi, Tadamichi; Yoshimura, Nagahisa

    2014-01-01

    Objectives To compare the optic nerve head (ONH) structure between compressive optic neuropathy (CON) and glaucomatous optic neuropathy (GON), and to determine whether selected ONH quantitative parameters effectively discriminate between GON and CON, especially CON cases presenting with a glaucoma-like disc. Methods We prospectively assessed 34 patients with CON, 34 age-matched patients with moderate or severe GON, and 34 age-matched healthy control subjects. The quantitative parameters of ONH structure were compared using the Heidelberg Retina Tomograph 2 (HRT2) and Spectralis optical coherence tomography with an enhanced depth imaging method. Results The mean and maximum cup depths of CON were significantly smaller than those with GON (P<0.001 and P<0.001, respectively). The distance between Bruch's membrane opening and anterior surface of the lamina cribrosa (BMO-anterior LC) of CON was also significantly smaller than that of glaucoma but was similar to that of the healthy group (P<0.001 and P = 0.47, respectively). Based on Moorfields regression analysis of the glaucoma classification of HRT2, 15 eyes with CON were classified with a glaucoma-like disc. The cup/disc area ratio did not differ between cases of CON with a glaucoma-like disc and cases of GON (P = 0.16), but the BMO-anterior LC and mean and maximum cup depths of CON cases with a glaucoma-like disc were smaller than those in GON (P = 0.005, P = 0.003, and P = 0.001, respectively). Conclusions Measurements of the cup depths and the LC depth had good ability to differentiate between CON with a glaucoma-like disc and glaucoma. There was no laminar remodeling detected by laminar surface position in the patients with CON compared to those with GON. PMID:25375855

  15. Bilateral optic disc oedema and associated optic neuropathy in the setting of FOLFOX chemotherapy

    PubMed Central

    2013-01-01

    Background To report a case of bilateral optic disc oedema and associated optic neuropathy in the setting of FOLFOX chemotherapy. Case presentation A case of a 57-year-old male being treated with FOLFOX chemotherapy for stage 3B colorectal cancer, who developed bilateral optic disc oedema and associated left sided optic neuropathy is described. The patient presented following cycles 7, 8 and 9 of chemotherapy with a history of bilateral simultaneous intermittent inferior altitudinal field defects. These episodes progressed to bilateral optic nerve oedema and a subsequent left sided optic neuropathy. The patient’s symptoms and oedema regressed with discontinuation of chemotherapy. Conclusion This is the first report suggesting a vasospastic role of 5-fluoruracil in 5-FU associated optic neuropathy. It highlights that 5-FU may have the potential to cause arterial vasospasm outside the cardiac vasculature, resulting in end-organ optic nerve ischaemia. PMID:23926927

  16. Retrobulbar optic neuropathy secondary to isolated sphenoid sinus disease

    PubMed Central

    Chafale, Vishal Annaji; Lahoti, Satish Arunkumar; Pandit, Alak; Gangopadhyay, Goutam; Biswas, Atanu

    2015-01-01

    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. PMID:25883489

  17. Investigation-Directed Approach to Inflammatory Optic Neuropathies.

    PubMed

    Boudreault, Katherine; Durand, Marlene L; Rizzo, Joseph F

    2016-01-01

    Any presentation of an optic neuropathy with features that suggest inflammation should be addressed promptly because of blindness and the potential for effective treatment in some cases. A step-wise approach, including laboratory testing and imaging, is often informative, although the diagnosis may remain elusive despite detailed investigation. PMID:26959137

  18. [An Undeniable Case of Optic Neuropathy Due to Cabazitaxel].

    PubMed

    Noguchi, Yusuke; Kawashima, Yugo; Kawara, Hiroko; Kaneko, Masatomo; Nakauchi, Hiroo; Tokuyama, Yoko

    2016-06-01

    Cabazitaxelis a taxane-type antineoplastic agent used for treating prostate cancer. Although typical side effects include neutropenia and fatigue, no studies have investigated eye disorders as a possible side effect, and the details are not clear. Herein, we report our experience of an undeniable case of optic neuropathy caused by cabazitaxel. A 78-year-old man had been diagnosed with prostate cancer (cT3aN1M1b, stage IV) 3 years previously, with a treatment history of bicalutamide, leuprorelin, flutamide, docetaxel, abiraterone, and enzalutamide. Because of a decline in vision during the second and third administration cycles of cabazitaxel, the patient visited an ophthalmologist. He was found to have reduced visual acuity, reduced central critical flicker frequency, narrowed field of vision, and impaired color vision, and was diagnosed with optic neuropathy. Although cabazitaxel administration was continued through 6 cycles, the symptoms were unchanged, and no drastic exacerbation was seen. This patient undeniably developed optic neuropathy due to cabazitaxel. Optic neuropathy due to taxane-type antineoplastic agents has also been reported with paclitaxel or docetaxel, and all precautions should be taken when administering such drugs. Detailed studies that include data from a larger number of facilities should be conducted in the future. PMID:27306820

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

    ERIC Educational Resources Information Center

    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…

  20. Finger prick blood testing in Leber hereditary optic neuropathy.

    PubMed Central

    Mackey, D; Nasioulas, S; Forrest, S

    1993-01-01

    Individuals from 33 unrelated Australian families with optic atrophy were screened for 10 different single base alterations in mitochondrial DNA (mtDNA) associated with Leber hereditary optic neuropathy (LHON) using direct polymerase chain reaction amplification of blood spots collected on Guthrie cards. This method using blood spots allows easily accessible screening for LHON mtDNA mutations with minimal biohazard risk and reduced expense in the storage and transport of specimens. PMID:8318469

  1. Psychophysical testing in rodent models of glaucomatous optic neuropathy.

    PubMed

    Grillo, Stephanie L; Koulen, Peter

    2015-12-01

    Processing of visual information begins in the retina, with photoreceptors converting light stimuli into neural signals. Ultimately, signals are transmitted to the brain through signaling networks formed by interneurons, namely bipolar, horizontal and amacrine cells providing input to retinal ganglion cells (RGCs), which form the optic nerve with their axons. As part of the chronic nature of glaucomatous optic neuropathy, the increasing and irreversible damage and ultimately loss of neurons, RGCs in particular, occurs following progressive damage to the optic nerve head (ONH), eventually resulting in visual impairment and visual field loss. There are two behavioral assays that are typically used to assess visual deficits in glaucoma rodent models, the visual water task and the optokinetic drum. The visual water task can assess an animal's ability to distinguish grating patterns that are associated with an escape from water. The optokinetic drum relies on the optomotor response, a reflex turning of the head and neck in the direction of the visual stimuli, which usually consists of rotating black and white gratings. This reflex is a physiological response critical for keeping the image stable on the retina. Driven initially by the neuronal input from direction-selective RGCs, this reflex is comprised of a number of critical sensory and motor elements. In the presence of repeatable and defined stimuli, this reflex is extremely well suited to analyze subtle changes in the circuitry and performance of retinal neurons. Increasing the cycles of these alternating gratings per degree, or gradually reducing the contrast of the visual stimuli, threshold levels can be determined at which the animal is no longer tracking the stimuli, and thereby visual function of the animal can be determined non-invasively. Integrating these assays into an array of outcome measures that determine multiple aspects of visual function is a central goal in vision research and can be realized, for

  2. Skin biopsies in the evaluation of atypical optic neuropathies.

    PubMed

    Bielory, L; Kupersmith, M; Warren, F; Bystryn, J; Frohman, L

    1993-01-01

    Patients with atypical clinical presentations of common optic neuropathies such as optic neuritis (ON), anterior ischemic optic neuropathy (AION), or optic neuropathy of unknown etiology (UON) are difficult to distinguish from inflammatory autoimmune optic neuropathy (AON) which is typically associated with a poor visual prognosis, unless treated with high doses of corticosteroids and/or immunosuppressive agents. The authors retrospectively evaluated 34 patients [AON (n = 12); AION (n = 5); ON (n = 9); UON (n = 8)] with visual loss which deteriorated over weeks to months or followed an atypical course, for the presence of immunological markers suggestive of AON. These markers included serological testing for antiphospholipid (APA) and antinuclear (ANA) antibodies, and evaluation of histopathologic and immunofluorescent staining of skin biopsies. All patients underwent a skin biopsy. Four of the 12 patients with AON had urticarial cutaneous lesions which revealed leukocytoclastic and/or lymphohistiocytic vasculitis. Seven of the remaining eight AON patients had skin biopsies of non-lesional skin which revealed immunoreactant deposition. Seven of the 21 skin biopsies obtained from the non-AON patients had findings of vacuolization or mild perivascular infiltration of lymphocytes (n = 5) and immunofluorescent deposits (n = 2). Abnormal skin biopsies (92%;p = 0.0009) and circulating APA (82%; p = 0.013) were common in AON patients while ANA was not statistically increased in AON patients (p = 0.06) when compared to the remaining patients as a whole. AON patients typically demonstrate evidence of systemic autoimmune involvement, as manifested by cutaneous abnormalities such as urticarial vasculitis and/or immunoreactant deposition and circulating APA. These may serve as markers for identifying AON patients who may be treated with immunomodulatory agents. PMID:22822778

  3. Amiodarone-Associated Optic Neuropathy: A Critical Review

    PubMed Central

    Passman, Rod S.; Bennett, Charles L.; Purpura, Joseph M.; Kapur, Rashmi; Johnson, Lenworth N.; Raisch, Dennis W.; West, Dennis P.; Edwards, Beatrice J.; Belknap, Steven M.; Liebling, Dustin B.; Fisher, Mathew J.; Samaras, Athena T.; Jones, Lisa-Gaye A.; Tulas, Katrina-Marie E.; McKoy, June M.

    2011-01-01

    Although amiodarone is the most commonly prescribed antiarrhythmic drug, its use is limited by serious toxicities, including optic neuropathy. Current reports of amiodarone associated optic neuropathy identified from the Food and Drug Administration's Adverse Event Reporting System (FDA-AERS) and published case reports were reviewed. A total of 296 reports were identified: 214 from AERS, 59 from published case reports, and 23 from adverse events reports for patients enrolled in clinical trials. Mean duration of amiodarone therapy before vision loss was 9 months (range 1-84 months). Insidious onset of amiodarone associated optic neuropathy (44%) was the most common presentation, and nearly one-third were asymptomatic. Optic disc edema was present in 85% of cases. Following drug cessation, 58% had improved visual acuity, 21% were unchanged, and 21% had further decreased visual acuity. Legal blindness (< 20/200) was noted in at least one eye in 20% of cases. Close ophthalmologic surveillance of patients during the tenure of amiodarone administration is warranted. PMID:22385784

  4. A Novel Rodent Model of Posterior Ischemic Optic Neuropathy

    PubMed Central

    Wang, Yan; Brown, Dale P.; Duan, Yuanli; Kong, Wei; Watson, Brant D.; Goldberg, Jeffrey L.

    2014-01-01

    Objectives To develop a reliable, reproducible rat model of posterior ischemic optic neuropathy (PION) and study the cellular responses in the optic nerve and retina. Methods Posterior ischemic optic neuropathy was induced in adult rats by photochemically induced ischemia. Retinal and optic nerve vasculature was examined by fluorescein isothiocyanate–dextran extravasation. Tissue sectioning and immunohistochemistry were used to investigate the pathologic changes. Retinal ganglion cell survival at different times after PION induction, with or without neurotrophic application, was quantified by fluorogold retrograde labeling. Results Optic nerve injury was confirmed after PION induction, including local vascular leakage, optic nerve edema, and cavernous degeneration. Immunostaining data revealed microglial activation and focal loss of astrocytes, with adjacent astrocytic hypertrophy. Up to 23%, 50%, and 70% retinal ganglion cell loss was observed at 1 week, 2 weeks, and 3 weeks, respectively, after injury compared with a sham control group. Experimental treatment by brain-derived neurotrophic factor and ciliary neurotrophic factor remarkably prevented retinal ganglion cell loss in PION rats. At 3 weeks after injury, more than 40% of retinal ganglion cells were saved by the application of neurotrophic factors. Conclusions Rat PION created by photochemically induced ischemia is a reproducible and reliable animal model for mimicking the key features of human PION. Clinical Relevance The correspondence between the features of this rat PION model to those of human PION makes it an ideal model to study the pathophysiologic course of the disease, most of which remains to be elucidated. Furthermore, it provides an optimal model for testing therapeutic approaches for optic neuropathies. PMID:23544206

  5. Fasudil alleviates traumatic optic neuropathy by inhibiting Rho signaling pathway

    PubMed Central

    Yu, Jianglong; Lan, Shiying; Wang, Ruijia; Maier, Aba; Luan, Xinping

    2015-01-01

    Objectives: The present study is to investigate the pathological changes in rabbits with traumatic optic neuropathy (TON), as well as the effect of fasudil on the lesions. Methods: A total of 144 New Zealand rabbits were successfully established as TON models. Twelve hours after surgery, the rabbits in control, dexamethasone, and fasudil groups were administrated with saline, dexamethasone, and fasudil via ear veins, respectively. Then, retinas of the rabbits were obtained at 72 h and on days 7, 14 and 21 after surgery. The pathological changes in retina and optic nerves were observed by hematoxylin and eosin staining and transmission electron microscopy. The expression levels of Rho-associated genes were measured using quantitative real-time polymerase chain reaction. Results: In control group, the axons were swelling, and mitochondria showed vacuolation after optic nerve crush. Mitochondria were swelled slightly in dexamethasone group. By contrast, nerves in fasudil group were repaired. Retinal ganglion cells in control group were reduced significantly due to optic nerve crush. The loss of retinal ganglion cells was alleviated in fasudil group. Quantitative real-time polymerase chain reaction showed that the expression of Rho-associated genes were down-regulated. Conclusions: The present study demonstrates that fasudil inhibits the apoptosis of retinal ganglion cells and ameliorates damages of optic nerves in traumatic optic neuropathy. PMID:26550269

  6. Optic neuropathy resulting from indirect trauma.

    PubMed

    Ginifer, Corinne; Scharapow, David

    2002-09-01

    Minor blunt injury to the head and face may result in optic nerve contusion with secondary optic atrophy. The resulting visual loss is devastating for the individual. We report an uncommon but important complication that may result from an apparently trivial injury. Early identification and initiation of appropriate management may restore the individual's vision. Emergency physicians are often the first to see patients at risk of this complication yet there is little discussion of this injury in the emergency medicine literature. PMID:12487050

  7. Leber Hereditary Optic Neuropathy Associated with Bilateral Macular Holes

    PubMed Central

    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

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

    NASA Astrophysics Data System (ADS)

    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.

  9. Mitochondrial optic neuropathies – Disease mechanisms and therapeutic strategies

    PubMed Central

    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

  10. Leber’s Hereditary Optic Neuropathy: The Mitochondrial Connection Revisited

    PubMed Central

    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. PMID:21572729

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

    SciTech Connect

    Guy, J.; Mancuso, A.; Beck, R.; Moster, M.L.; Sedwick, L.A.; Quisling, R.G.; Rhoton, A.L. Jr.; Protzko, E.E.; Schiffman, J. )

    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.

  12. Automated Peripheral Neuropathy Assessment Using Optical Imaging and Foot Anthropometry.

    PubMed

    Siddiqui, Hafeez-U R; Spruce, Michelle; Alty, Stephen R; Dudley, Sandra

    2015-08-01

    A large proportion of individuals who live with type-2 diabetes suffer from plantar sensory neuropathy. Regular testing and assessment for the condition is required to avoid ulceration or other damage to patient's feet. Currently accepted practice involves a trained clinician testing a patient's feet manually with a hand-held nylon monofilament probe. The procedure is time consuming, labor intensive, requires special training, is prone to error, and repeatability is difficult. With the vast increase in type-2 diabetes, the number of plantar sensory neuropathy sufferers has already grown to such an extent as to make a traditional manual test problematic. This paper presents the first investigation of a novel approach to automatically identify the pressure points on a given patient's foot for the examination of sensory neuropathy via optical image processing incorporating plantar anthropometry. The method automatically selects suitable test points on the plantar surface that correspond to those repeatedly chosen by a trained podiatrist. The proposed system automatically identifies the specific pressure points at different locations, namely the toe (hallux), metatarsal heads and heel (Calcaneum) areas. The approach is generic and has shown 100% reliability on the available database used. The database consists of Chinese, Asian, African, and Caucasian foot images. PMID:26186748

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

    PubMed

    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. PMID:26959136

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

    PubMed

    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. PMID:26819093

  15. A retrospective review of 26 cases of dysthyroid optic neuropathy

    SciTech Connect

    Panzo, G.J.; Tomsak, R.L.

    1983-08-01

    Sixteen patients (14 women and two men) with dysthyroid optic neuropathy (26 involved eyes) were treated with either oral corticosteroids, orbital irradiation, surgical orbital decompression, combined corticosteroids and irradiation, or combined corticosteroids and surgical decompression. Thirteen of 16 eyes responded favorably to corticosteroid therapy but eight of the 13 relapsed upon discontinuation of treatment. Two of four eyes responded to irradiation initially but later relapsed. The response to orbital decompression was almost uniformly beneficial (eight of nine eyes responded) and lasting in all. Combined modes of therapy offered no additional advantage.

  16. Macular infarction and traumatic optic neuropathy following blunt ocular trauma.

    PubMed

    Goel, Neha; Rajput, Metu; Sawhney, Amrita; Sardana, Tushar

    2016-01-01

    Macular infarction is a visually disabling condition caused by a variety of reasons. It has rarely been described in association with blunt ocular trauma. We describe the case of a young healthy male who sustained injury with a bull's leg and presented with severe visual loss owing to macular infarction and traumatic optic neuropathy. This report of an angiographically documented macular infarct secondary to ocular contusion highlights an additional feature in the spectrum of ocular findings following blunt trauma that might lead to a severe and permanent affliction of vision. PMID:26949360

  17. Macular infarction and traumatic optic neuropathy following blunt ocular trauma

    PubMed Central

    Goel, Neha; Rajput, Metu; Sawhney, Amrita; Sardana, Tushar

    2015-01-01

    Macular infarction is a visually disabling condition caused by a variety of reasons. It has rarely been described in association with blunt ocular trauma. We describe the case of a young healthy male who sustained injury with a bull’s leg and presented with severe visual loss owing to macular infarction and traumatic optic neuropathy. This report of an angiographically documented macular infarct secondary to ocular contusion highlights an additional feature in the spectrum of ocular findings following blunt trauma that might lead to a severe and permanent affliction of vision. PMID:26949360

  18. Biomechanical assessment in models of glaucomatous optic neuropathy.

    PubMed

    Nguyen, Thao D; Ethier, C Ross

    2015-12-01

    The biomechanical environment within the eye is of interest in both the regulation of intraocular pressure and the loss of retinal ganglion cell axons in glaucomatous optic neuropathy. Unfortunately, this environment is complex and difficult to determine. Here we provide a brief introduction to basic concepts of mechanics (stress, strain, constitutive relationships) as applied to the eye, and then describe a variety of experimental and computational approaches used to study ocular biomechanics. These include finite element modeling, direct experimental measurements of tissue displacements using optical and other techniques, direct experimental measurement of tissue microstructure, and combinations thereof. Thanks to notable technical and conceptual advances in all of these areas, we are slowly gaining a better understanding of how tissue biomechanical properties in both the anterior and posterior segments may influence the development of, and risk for, glaucomatous optic neuropathy. Although many challenging research questions remain unanswered, the potential of this body of work is exciting; projects underway include the coupling of clinical imaging with biomechanical modeling to create new diagnostic tools, development of IOP control strategies based on improved understanding the mechanobiology of the outflow tract, and attempts to develop novel biomechanically-based therapeutic strategies for preservation of vision in glaucoma. PMID:26115620

  19. Leber's hereditary optic neuropathy with 3460 mitochondrial DNA mutation.

    PubMed Central

    Hwang, Jeong-Min; Chang, Bong Leen; Koh, Hyoung Jun; Kim, Ji Yeon; Park, Sung Sup

    2002-01-01

    Leber's hereditary optic neuropathy (LHON) is a maternally transmitted disease causing acute or subacute, bilateral optic atrophy mainly in young men. It is found to be a mitochondrial disorder with the primary mitochondrial DNA (mtDNA) mutations at 11,778, 3460, and 14,484. The incidence of each mutation is reported to be race-dependent. Point mutations at mtDNA nucleotide position 11,778 and 14,484 have been reported in Korean patients with LHON, however there has been no report of mtDNA mutation at nucleotide position 3460. Molecular genetic analyses at four primary sites (11,778, 14,484, 15,257, and 3460) of mitochondrial DNA using the polymerase chain reaction, restriction enzyme digestion, and direct sequencing were performed in a 35-yr-old man with severe visual loss. A point mutation in the mtDNA at nucleotide position 3460 was identified and a conversion of a single alanine to a threonine was confirmed. To our knowledge, this is the first report confirming mtDNA mutation at nucleotide position 3460 in Korean patients with LHON. Detailed molecular analyses would be very helpful for the correct diagnosis of optic neuropathy of unknown etiology and for genetic counseling. PMID:11961321

  20. Bilateral Glaucomatous Optic Neuropathy Caused by Eye Rubbing.

    PubMed

    Savastano, Alfonso; Savastano, Maria Cristina; Carlomusto, Laura; Savastano, Silvio

    2015-01-01

    In this report, we describe a particular condition of a 52-year-old man who showed advanced bilateral glaucomatous-like optic disc damage, even though the intraocular pressure resulted normal during all examinations performed. Visual field test, steady-state pattern electroretinogram, retinal nerve fiber layer and retinal tomographic evaluations were performed to evaluate the optic disc damage. Over a 4-year observational period, his visual acuity decreased to 12/20 in the right eye and counting fingers in the left eye. Visual fields were severely compromised, and intraocular pressure values were not superior to 14 mm Hg during routine examinations. An accurate anamnesis and the suspicion of this disease represent a crucial aspect to establish the correct diagnosis. In fact, our patient strongly rubbed his eyes for more than 10 h per day. Recurrent and continuous eye rubbing can induce progressive optic neuropathy, causing severe visual field damage similar to the pathology of advanced glaucoma. PMID:26483667

  1. Evaluation of acute radiation optic neuropathy by B-scan ultrasonography

    SciTech Connect

    Lovato, A.A.; Char, D.H.; Quivey, J.M.; Castro, J.R. )

    1990-09-15

    We studied the accuracy of B-scan ultrasonography to diagnose radiation-induced optic neuropathy in 15 patients with uveal melanoma. Optic neuropathy was diagnosed by an observer masked as to clinical and photographic data. We analyzed planimetry area measurements of the retrobulbar nerve before and after irradiation. The retrobulbar area of the optic nerve shadow on B-scan was quantitated with a sonic digitizer. Increased optic nerve shadow area was confirmed in 13 of 15 patients who had radiation optic neuropathy (P less than .004). The correct diagnosis was confirmed when the results of ultrasound were compared to fundus photography and fluorescein angiography. In 13 patients there was acute radiation optic neuropathy. Two patients did not show an enlarged retrobulbar optic nerve, and the clinical appearance suggested early progression to optic atrophy. Ultrasonography documents the enlargement of the optic nerve caused by acute radiation changes.

  2. Treatment strategies for inherited optic neuropathies: past, present and future

    PubMed Central

    Yu-Wai-Man, P; Votruba, M; Moore, A T; Chinnery, P F

    2014-01-01

    Bilateral visual loss secondary to inherited optic neuropathies is an important cause of registrable blindness among children and young adults. The two prototypal disorders seen in clinical practice are Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (DOA). About 90% of LHON cases are due to one of three mitochondrial DNA (mtDNA) point mutations: m.3460G>A, m.11778G>A, and m.14484T>C, which affect critical complex I subunits of the mitochondrial respiratory chain. The majority of patients with DOA harbour pathogenic mutations within OPA1, a nuclear gene that codes for a multifunctional inner mitochondrial membrane protein. Despite their contrasting genetic basis, LHON and DOA share overlapping pathological and clinical features that serve to highlight the striking tissue-specific vulnerability of the retinal ganglion cell (RGC) layer to disturbed mitochondrial function. In addition to severe visual loss secondary to progressive optic nerve degeneration, a subgroup of patients will also develop a more aggressive syndromic phenotype marked by significant neurological deficits. The management of LHON and DOA remains largely supportive, but major advances in our understanding of the mechanisms underpinning RGC loss in these two disorders are paving the way for novel forms of treatment aimed at halting or reversing visual deterioration at different stages of the disease process. In addition to neuroprotective strategies for rescuing RGCs from irreversible cell death, innovative in vitro fertilisation techniques are providing the tantalising prospect of preventing the germline transmission of pathogenic mtDNA mutations, eradicating in so doing the risk of disease in future generations. PMID:24603424

  3. Auditory function in individuals within Leber's hereditary optic neuropathy pedigrees.

    PubMed

    Rance, Gary; Kearns, Lisa S; Tan, Johanna; Gravina, Anthony; Rosenfeld, Lisa; Henley, Lauren; Carew, Peter; Graydon, Kelley; O'Hare, Fleur; Mackey, David A

    2012-03-01

    The aims of this study are to investigate whether auditory dysfunction is part of the spectrum of neurological abnormalities associated with Leber's hereditary optic neuropathy (LHON) and to determine the perceptual consequences of auditory neuropathy (AN) in affected listeners. Forty-eight subjects confirmed by genetic testing as having one of four mitochondrial mutations associated with LHON (mt11778, mtDNA14484, mtDNA14482 and mtDNA3460) participated. Thirty-two of these had lost vision, and 16 were asymptomatic at the point of data collection. While the majority of individuals showed normal sound detection, >25% (of both symptomatic and asymptomatic participants) showed electrophysiological evidence of AN with either absent or severely delayed auditory brainstem potentials. Abnormalities were observed for each of the mutations, but subjects with the mtDNA11778 type were the most affected. Auditory perception was also abnormal in both symptomatic and asymptomatic subjects, with >20% of cases showing impaired detection of auditory temporal (timing) cues and >30% showing abnormal speech perception both in quiet and in the presence of background noise. The findings of this study indicate that a relatively high proportion of individuals with the LHON genetic profile may suffer functional hearing difficulties due to neural abnormality in the central auditory pathways. PMID:21887510

  4. Nutritional Optic Neuropathy Caused by Copper Deficiency After Bariatric Surgery.

    PubMed

    Rapoport, Yuna; Lavin, Patrick J M

    2016-06-01

    A 47-year-old woman developed severe bilateral visual loss 4 years after a Roux-en-Y gastric bypass and 24 years after vertical banded gastroplasty. Her serum copper level was 35 μg/dL (normal, 80-155 μg/dL). She was prescribed elemental copper tablets. Because her methylmalonic acid was slightly elevated, she received vitamin B12 injections as well. Five weeks later, she reported that her vision had improved and, at 10 months, her vision had recovered from 20/400 bilaterally to 20/25 in each eye. This case highlights the importance of checking copper levels in addition to the "more routine" vitamin levels, such as B1, B6, B12, E, and serum folate in patients with suspected nutritional optic neuropathy after bariatric surgery, particularly if it involved a bypass procedure. PMID:26828841

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

    PubMed

    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. PMID:25343117

  6. Macular thickness as a predictor of loss of visual sensitivity in ethambutol-induced optic neuropathy

    PubMed Central

    Peng, Chun-xia; Zhang, Ai-di; Chen, Bing; Yang, Bing-jian; Wang, Qiu-hong; Yang, Mo; Wei, Shi-hui

    2016-01-01

    Ethambutol is a common cause of drug-related optic neuropathy. Prediction of the onset of ethambutol-induced optic neuropathy and consequent drug withdrawal may be an effective method to stop visual loss. Previous studies have shown that structural injury to the optic nerve occurred earlier than the damage to visual function. Therefore, we decided to detect structural biomarkers marking visual field loss in early stage ethambutol-induced optic neuropathy. The thickness of peripapillary retinal nerve fiber layer, macular thickness and visual sensitivity loss would be observed in 11 ethambutol-induced optic neuropathy patients (22 eyes) using optical coherence tomography. Twenty-four healthy age- and sex-matched participants (48 eyes) were used as controls. Results demonstrated that the temporal peripapillary retinal nerve fiber layer thickness and average macular thickness were thinner in patients with ethambutol-induced optic neuropathy compared with healthy controls. The average macular thickness was strongly positively correlated with central visual sensitivity loss (r2 =0.878, P=0.000). These findings suggest that optical coherence tomography can be used to efficiently screen patients. Macular thickness loss could be a potential factor for predicting the onset of ethambutol-induced optic neuropathy. PMID:27127488

  7. Macular thickness as a predictor of loss of visual sensitivity in ethambutol-induced optic neuropathy.

    PubMed

    Peng, Chun-Xia; Zhang, Ai-di; Chen, Bing; Yang, Bing-Jian; Wang, Qiu-Hong; Yang, Mo; Wei, Shi-Hui

    2016-03-01

    Ethambutol is a common cause of drug-related optic neuropathy. Prediction of the onset of ethambutol-induced optic neuropathy and consequent drug withdrawal may be an effective method to stop visual loss. Previous studies have shown that structural injury to the optic nerve occurred earlier than the damage to visual function. Therefore, we decided to detect structural biomarkers marking visual field loss in early stage ethambutol-induced optic neuropathy. The thickness of peripapillary retinal nerve fiber layer, macular thickness and visual sensitivity loss would be observed in 11 ethambutol-induced optic neuropathy patients (22 eyes) using optical coherence tomography. Twenty-four healthy age- and sex-matched participants (48 eyes) were used as controls. Results demonstrated that the temporal peripapillary retinal nerve fiber layer thickness and average macular thickness were thinner in patients with ethambutol-induced optic neuropathy compared with healthy controls. The average macular thickness was strongly positively correlated with central visual sensitivity loss (r (2) =0.878, P=0.000). These findings suggest that optical coherence tomography can be used to efficiently screen patients. Macular thickness loss could be a potential factor for predicting the onset of ethambutol-induced optic neuropathy. PMID:27127488

  8. Peripapillary Pachychoroid in Nonarteritic Anterior Ischemic Optic Neuropathy

    PubMed Central

    Nagia, Lina; Huisingh, Carrie; Johnstone, John; Kline, Lanning B.; Clark, Mark; Girard, Michael J. A.; Mari, Jean Martial; Girkin, Christopher A.

    2016-01-01

    Purpose This study examined the peripapillary choroidal thickness (PCT) in nonarteritic ischemic optic neuropathy (NAION) in comparison to contralateral eyes and normal eyes. Methods We used enhanced depth imaging spectral-domain optical coherence tomography to image the optic nerve head of 20 NAION, 10 contralateral eyes, and 102 normal eyes. Following compensation, the scans were manually delineated to identify relevant surfaces including Bruch's membrane opening (BMO), Bruch's membrane, and anterior sclera. The PCT was defined as the measurement between Bruch's membrane and the anterior sclera and was measured at increasing distance from BMO. Models adjusted for age, BMO area, and axial length were used to compare the mean PCT between NAION and normal eyes, and contralateral eyes and normal eyes. Paired t-tests were used to compare the PCT between NAION and contralateral eyes. Results The mean PCT was thicker in NAION and contralateral eyes when compared with normal eyes at all distances from BMO (P < 0.001). The PCT was not significantly thicker in contralateral eyes when compared with affected NAION eyes. Choroidal thickness was thinnest in the inferior quadrant in all eyes regardless of the group. Conclusions Increased peripapillary choroidal thickness was noted in both NAION and contralateral eyes. The thicker choroid may be an associated feature or a result of the disorder. Although further longitudinal study is required to determine causation, these findings may suggest that a thickened peripapillary choroid may be a component of the disk-at-risk clinical phenotype. PMID:27583829

  9. High doses of cobalt induce optic and auditory neuropathy.

    PubMed

    Apostoli, Pietro; Catalani, Simona; Zaghini, Anna; Mariotti, Andrea; Poliani, Pietro Luigi; Vielmi, Valentina; Semeraro, Francesco; Duse, Sarah; Porzionato, Andrea; Macchi, Veronica; Padovani, Alessandro; Rizzetti, Maria Cristina; De Caro, Raffaele

    2013-09-01

    The adverse biological effects of continuous exposure to cobalt and chromium have been well defined. In the past, this toxicity was largely an industrial issue concerning workers exposed in occupational setting. Nevertheless, recent reports have described a specific toxicity mediated by the high levels of cobalt and chromium released by metallic prostheses, particularly in patients who had received hip implants. Clinical symptoms, including blindness, deafness and peripheral neuropathy, suggest a specific neurotropism. However, little is known about the neuropathological basis of this process, and experimental evidence is still lacking. We have investigated this issue in an experimental setting using New Zealand White rabbits treated with repeated intravenous injections of cobalt and chromium, alone or in combination. No evident clinical or pathological alterations were associated after chromium administration alone, despite its high levels in blood and tissue while cobalt-chromium and cobalt-treated rabbits showed clinical signs indicative of auditory and optic system toxicity. On histopathological examination, the animals showed severe retinal and cochlear ganglion cell depletion along with optic nerve damage and loss of sensory cochlear hair cells. Interestingly, the severity of the alterations was related to dosages and time of exposure. These data confirmed our previous observation of severe auditory and optic nerve toxicity in patients exposed to an abnormal release of cobalt and chromium from damaged hip prostheses. Moreover, we have identified the major element mediating neurotoxicity to be cobalt, although the molecular mechanisms mediating this toxicity still have to be defined. PMID:23069009

  10. Congenital optic nerve anomalies and hereditary optic neuropathies

    PubMed Central

    Heidary, Gena

    2014-01-01

    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.

  11. Post-traumatic optic neuropathy: our surgical and medical protocol.

    PubMed

    Emanuelli, E; Bignami, M; Digilio, E; Fusetti, S; Volo, T; Castelnuovo, P

    2015-11-01

    Post-traumatic optic neuropathy (TON) is a rare, but very much feared event. It is a traumatic injury of the optic nerve at any level along its course (often inside the optic canal), with partial or total loss of visual acuity, temporarily or permanently. Until now, an univocal treatment strategy does not exist. The clinical records of 26 patients, treated from 2002 to 2013, were reviewed. The most frequent cause of injury was road traffic accident (63%), followed by iatrogenic damage, work injuries, sport or home accidents. All patients underwent pre-operative ophthalmological evaluation, neuro-imaging (angio-CT or angio-MRI scans) and systemic corticosteroid therapy. All patients required a surgical treatment, due to poor response to medical therapy; it consisted of an endonasal endoscopic decompression of the intracanalicular segment of the optic nerve, performed by removing the bony wall of the optical canal and releasing the perineural sheath. Improvement of visual acuity was reached in 65% of cases. No minor or major complication occurred intra- or post-operative, with a maximum follow-up time of 41 months. An improvement in visual acuity was achieved, although very limited in some cases, when surgery was performed as close as possible to the traumatic event. In the literature, there is no evidence-based data evaluating both of the two main treatment options (medical therapy versus surgical decompression), to state which is the gold standard in the treatment for TON. We discuss the pro and cons of our protocol: medical endovenous steroid treatment, within 8 h of injury, and endoscopic surgical decompression within 12-24 since the beginning of medical therapy, represent the best solution in terms of risk-benefit ratio for the patients. PMID:25472815

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

    PubMed Central

    Gonçalves, Allan C. Pieroni; Gebrim, Eloísa M. M. S.; Monteiro, Mário L. R.

    2012-01-01

    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. PMID:23184212

  13. Nonarteritic anterior ischemic optic neuropathy (NAION) and its experimental models

    PubMed Central

    Bernstein, Steven L.; Johnson, Mary A.; Miller, Neil R.

    2011-01-01

    Anterior ischemic optic neuropathy (AION) can be divided into nonarteritic (NAION) and arteritic (AAION) forms. NAION makes up ~85% of all cases of AION, and until recently was poorly understood. There is no treatment for NAION, and its initiating causes are poorly understood, in part because NAION is not lethal, making it difficult to obtain fresh, newly affected tissue for study. In-vivo electrophysiology and post-mortem studies reveal specific responses that are associated with NAION. New models of NAION have been developed which enable insights into the pathophysiological events surrounding this disease. These models include both rodent and primate species, and the power of a `vertically integrated' multi-species approach can help in understanding the common cellular mechanisms and physiological responses to clinical NAION, and to identify potential approaches to treatment. The models utilize laser light to activate intravascular photoactive dye to induce capillary vascular thrombosis, while sparing the larger vessels. The observable optic nerve changes associated with rodent models of AION (rAION) and primate NAION (pNAION) are indistinguishable from that seen in clinical disease, including sectoral axonal involvement, and in-vivo electrophysiological data from these models are consistent with clinical data. Early post-infarct events reveal an unexpected inflammatory response, and changes in intraretinal gene expression for both stress response, while sparing outer retinal function, which occurs in AAION models. Histologically, the NAION models reveal an isolated loss of retinal ganglion cells by apoptosis. There are changes detectable by immunohistochemistry suggesting that other retinal cells mount a brisk response to retinal ganglion cell distress without themselves dying. The optic nerve ultimately shows axonal loss and scarring. Inflammation is a prominent early histological feature. This suggests that clinically, specific modulation of inflammation may

  14. Acute and Bilateral Blindness Due to Optic Neuropathy Associated With Copper Deficiency

    PubMed Central

    Naismith, Robert T.; Shepherd, James B.; Weihl, Conrad C.; Tutlam, Nhial T.; Cross, Anne H.

    2010-01-01

    Background Acquired copper deficiency in adults is associated with a subacute to chronic progressive myeloneuropathy and optic neuropathy. Objective To describe an individual after gastric bypass surgery who developed a chronic progressive myeloneuropathy, an acute optic neuropathy, along with anemia and leukopenia. Design Case report. Setting Academic center. Patient A 55-year-old woman, following gastric bypass surgery 22 years earlier, developed progressive numbness, weakness, and sphincter disturbance over 6 years. She awoke one morning with bilateral blindness. Examination findings showed evidence of severe myelopathy and peripheral neuropathy. Main Outcome Measures Magnetic resonance imaging, optical coherence tomography, electrophysiologic studies, nerve and muscle biopsy specimens, and vision testing. Results Over 1 year of follow-up, copper infusion therapy seemed to stabilize the progressive myeloneuropathy and improved leukopenia and anemia. It had no effect on the optic neuropathy. Optic nerve tissue injury was observed on magnetic resonance diffusion tensor imaging and on optical coherence tomography. Conclusions Copper deficiency should be considered in cases of atypical optic neuropathy. Serum copper levels should be monitored in patients with a compatible neurologic syndrome who have undergone gastric bypass surgery. Although visual acuity did not improve after copper infusion in our patient, prompt recognition of copper deficiency may prevent further deterioration. PMID:19667226

  15. Ultrasonography in distinguishing optic neuritis from nonarteritic anterior ischemic optic neuropathy

    PubMed Central

    Dehghani, Alireza; Giti, Masoomeh; Akhlaghi, Mohamad Reza; Karami, Mehdi; Salehi, Fatemeh

    2012-01-01

    Background and Objectives: Optic neuritis (ON) and nonarteritic anterior ischemic optic neuropathy (NAION) have some overlapping clinical profiles. We evaluated the usefulness of B-scan ultrasonography in distinguishing ON from NAION by measuring diameter of the optic nerve. Materials and Methods: Consecutive patients with an acute noncompressive unilateral optic neuropathy with relative afferent pupillary defect and onset of visual loss during the last 2 weeks were included. Diagnosis of ON was based on age ≤ 35 years, orbital pain associated with eye movement, and no disk edema, and diagnosis of NAION was based on age ≥ 60 years, no orbital pain associated with eye movement, and presence of disk edema. Age- and gender-matched subjects without ocular disease were selected for comparison. The diameter of the optic nerve was measured by a single radiologist with B-scan ultrasonography. Results: In ON patients, the mean diameter of the affected nerve was significantly larger than that of the unaffected nerve and also larger than that of the right nerve of young controls; P < 0.05. In NAION patients, however, there was no significant difference between the mean diameter of the affected nerve and of the unaffected nerve or the right nerve of elderly controls; P > 0.05. Also, the diameter of the affected nerve was significantly larger in ON than in AION patients; P < 0.05. Conclusion: B-scan ultrasonography is helpful in the early stages of optic neuropathy to distinguish ON from NAION in those cases for which the diagnosis is still uncertain after clinical evaluation. PMID:23210062

  16. Ischemic optic neuropathies and their models: disease comparisons, model strengths and weaknesses

    PubMed Central

    Miller, Neil R.

    2015-01-01

    Ischemic optic neuropathies (IONs) describe a group of diseases that specifically target the optic nerve and result in sudden vision loss. These include nonarteritic and arteritic anterior ischemic optic neuropathy (NAION and AAION) and posterior ischemic optic neuropathy (NPION, APION). Until recently, little was known of the mechanisms involved in ION damage, due to a lack of information about the mechanisms associated with these diseases. This review discusses the new models that closely mimic these diseases (rodent NAION, primate NAION, rodent PION). These models have enabled closer dissection of the mechanisms involved with the pathophysiology of these disorders and enable identification of relevant mechanisms and potential pathways for effective therapeutic intervention. Descriptions of the different models are included, and comparisons between the models, their relative similarities with the clinical disease, as well as differences are discussed. PMID:25690987

  17. Methylene blue provides behavioral and metabolic neuroprotection against optic neuropathy.

    PubMed

    Rojas, Julio C; John, Joseph M; Lee, Jung; Gonzalez-Lima, F

    2009-04-01

    Methylene blue (MB) is a diaminophenothiazine with potent antioxidant and unique redox properties that prevent morphologic degenerative changes in the mouse retina induced by rotenone, a specific mitochondrial complex I inhibitor. This study evaluated pigmented rats to determine whether MB's neuroprotective effects against rotenone-mediated retinal neurotoxicity have functional relevance and whether these effects are mediated by an improvement in neuronal energy metabolism in vivo. Visual function was behaviorally assessed by determining differences in the illuminance sensitivity threshold pre- and post-bilateral intravitreal injection of rotenone (200 microg/kg) or rotenone plus MB (70 microg/kg). Retinal degeneration was morphologically studied using unbiased stereological tools. Changes in histochemically determined cytochrome oxidase activity in the visual pathway were used to evaluate the impact of treatments on neuronal energy metabolism. Rotenone induced a 1.4 log unit increase in the illumination threshold compared to baseline, as well as a 32% decrease in ganglion cell layer cell (GCL) density, and a 56% decrease in GCL layer + nerve fiber layer thickness. Co-administration of MB prevented the changes in visual function and the retinal histopathology. Furthermore, rotenone induced a functional deafferentation of the visual system, as revealed by decreases in the metabolic activity of the retina, superior colliculus, and visual cortex. These metabolic changes were also prevented by MB. The results provided the first demonstration of MB's behavioral and metabolic neuroprotection against optic neuropathy, and implicate MB as a candidate neuroprotective agent with metabolic-enhancing properties that may be used in the treatment of neurodegenerative diseases associated with mitochondrial dysfunction. PMID:19384599

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

    SciTech Connect

    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.

  19. Unilateral Optic Neuropathy and Acute Angle-Closure Glaucoma following Snake Envenomation

    PubMed Central

    Olcaysu, Osman Okan; Cadirci, Kenan; Durur Karakaya, Afak; Bayramlar, Huseyin

    2015-01-01

    Purpose. We aimed to describe a unique case in which a patient developed unilateral optic neuritis and angle-closure glaucoma as a result of snake envenomation. Case Report. Approximately 18 hours after envenomation, a 67-year-old female patient described visual impairment and severe pain in her left eye (LE). The patient's best corrected visual acuity was 10/10 in the RE and hand motion in the LE. Cranial magnetic resonance imaging showed signs of neuropathy in the left optic nerve. In the LE, corneal haziness, closure of the iridocorneal angle, and mild mydriasis were observed and pupillary light reflex was absent. Intraocular pressure was 25 mmHg and 57 mmHg in the RE and LE, respectively. The patient was diagnosed with acute angle-closure glaucoma in the LE. Optic neuropathy was treated with intravenous pulse methylprednisolone. Left intraocular pressure was within normal range starting on the fourth day. One month after the incident, there was no sign of optic neuropathy; relative afferent pupillary defect and optic nerve swelling disappeared. Conclusions. Patients with severe headache and visual loss after snake envenomation must be carefully examined for possible optic neuropathy and angle-closure glaucoma. Early diagnosis and treatment of these cases are necessary to prevent permanent damage to optic nerves. PMID:25705536

  20. Radiation optic neuropathy after megavoltage external-beam irradiation: Analysis of time-dose factors

    SciTech Connect

    Parsons, J.T.; Bova, F.J.; Million, R.R.

    1994-11-15

    To investigate the risk of radiation-induced optic neuropathy according to total radiotherapy dose and fraction size, based on both retrospective and prospectively collected data. Between October 1964 and May 1989, 215 optic nerves in 131 patients received fractionated external-beam irradiation during the treatment of primary extracranial head and neck tumors. All patients had a minimum of 3 years of ophthalmologic follow-up (range, 3 to 21 years). The clinical end point was visual acuity of 20/100 or worse as a result of optic nerve injury. Anterior ischemic optic neuropathy developed in five nerves (at mean and median times of 32 and 30 months, respectively, and a range of 2-4 years). Retrobulbar optic neuropathy developed in 12 nerves (at mean and median times of 47 and 28 months, respectively, and a range of 1-14 years). No injuries were observed in 106 optic nerves that received a total dose of <59 Gy. Among nerves that received doses of {ge} 60 Gy, the dose per fraction was more important than the total dose in producing optic neuropathy. The 15-year actuarial risk of optic compared with 47% when given in fraction sizes {ge}1.9 Gy. The data also suggest an increased risk of optic nerve injury with increasing age. As there is no effective treatment of radiation-induced optic neuropathy, efforts should be directed at its prevention by minimizing the total dose, paying attention to the dose per fraction to the nerve, and using reduced field techniques where appropriate to limit the volume of tissues that receive high-dose irradiation. 32 refs., 5 figs., 5 tabs.

  1. Isolated optic neuropathy in a case of Behçet's disease.

    PubMed

    Cetin, Ebru N; Yaylali, Volkan; Yildirim, Cem

    2011-04-01

    A 57-year-old male with a 1-year history of recurrent oral ulceration and papulopustular lesions presented with acute visual loss in his left eye. He had an oedematous disc without any signs of uveitis. Laboratory work-up regarding infectious diseases was negative. The patient was diagnosed with acute optic neuropathy secondary to Behçet's disease. Systemic steroid and colchicine treatments were started but his vision did not improve. Isolated optic neuropathy is rare in Behçet's disease and early treatment with high-dose steroids may not be successful in some cases. PMID:21264492

  2. Unilateral compressive optic neuropathy due to skull hyperostosis secondary to nutritional vitamin A deficiency.

    PubMed

    Zayed, Mohammed G; Hickman, Simon J; Batty, Ruth; McCloskey, Eugene V; Pepper, Irene M

    2015-01-01

    We report a 17-year-old boy who presented with a chronic left unilateral optic neuropathy. Computerized tomography and magnetic resonance imaging demonstrated compression of the left optic nerve due to skull hyperostosis. He was found to be profoundly vitamin A deficient secondary to an unusual diet consisting predominantly of potato chips and crisps. Skull hyperostosis with cranial neuropathies and other neurological abnormalities has been described in growing animals fed vitamin A deficient diets but has not been previously reported in humans. PMID:26136803

  3. Complicated hereditary spastic paraplegia with peripheral neuropathy, optic atrophy and mental retardation.

    PubMed

    Miyama, S; Arimoto, K; Kimiya, S; Tomi, H

    2000-08-01

    An 8-year old girl with a not previously described type of complicated hereditary spastic paraplegia (HSP) is presented. Spasticity in her lower limbs had already been recognized during infancy and worsened progressively. Severe delay in mental development was observed. Peripheral neuropathy and optic atrophy developed at 5 years of age. On brain magnetic resonance imaging, an abnormally thin corpus callosum was observed. Involvement of the fasciculus gracilis was suggested by somatosensory evoked potentials. To our knowledge, there has been no reported case of complicated HSP with peripheral neuropathy, optic atrophy and mental retardation so far. We postulate that our patient is a sporadic case of not previously described complicated HSP. PMID:11071149

  4. Unilateral compressive optic neuropathy due to skull hyperostosis secondary to nutritional vitamin A deficiency

    PubMed Central

    Zayed, Mohammed G.; Hickman, Simon J.; Batty, Ruth; McCloskey, Eugene V.; Pepper, Irene M.

    2015-01-01

    Summary We report a 17-year-old boy who presented with a chronic left unilateral optic neuropathy. Computerized tomography and magnetic resonance imaging demonstrated compression of the left optic nerve due to skull hyperostosis. He was found to be profoundly vitamin A deficient secondary to an unusual diet consisting predominantly of potato chips and crisps. Skull hyperostosis with cranial neuropathies and other neurological abnormalities has been described in growing animals fed vitamin A deficient diets but has not been previously reported in humans. PMID:26136803

  5. [Nonarteritic ischemic optic neuropathy animal model and its treatment applications].

    PubMed

    Chuman, Hideki

    2014-04-01

    Nonarteritic ischemic optic neuropathy (NAION) is one of the most common acute unilaterally onset optic nerve diseases. One management problem in terms of NAION is the difficulty of differential diagnosis between NAION and anterior optic neuritis (ON). A second problem is that there is no established treatment for the acute stage of NAION. A third problem is that there is no preventive treatment for a subsequent attack on the fellow eye, estimated to occur in 15 to 25% of patients with NAION. For differentiation of acute NAION from anterior optic neuritis, we investigated the usefulness of laser speckle flowgraphy (LSFG). In the normal control group, the tissue blood flow did not significantly differ between the right and left eyes. In the NAION group, all 6 patients had 29.5% decreased mean blur rate (MBR), which correlates to optic disc blood flow, of the NAION eye compared with the unaffected eye. In the anterior ON group, all 6 cases had 15.9% increased MBR of the anterior ON eye compared with the unaffected eye. Thus, LSFG showed a difference of the underlying pathophysiology between NAION and anterior ON despite showing disc swelling in both groups and could be useful for differentiating both groups. For the treatment of acute stage of NAION, we tried to reproduce the rodent model of NAION (rNAION) developed by Bernstein and colleagues. To induce rNAION, after the administration of rose bengal(RB) (2.5 mM) into the tail vein of SD rats, the small vessels of the left optic nerve were photoactivated using a 514 nm argon green laser (RB-laser-induction). In the RB-laser-induction eyes, the capillaries within the optic disc were reduced markedly, the optic disc became swollen, and fluorescein angiography showed filling defect in the choroid and the optic disc at an early stage, followed by hyperfluorescence at a late stage. Electrophysiological evaluation revealed that visual evoked potential (VEP) amplitude was significantly decreased but an electroretinogram

  6. Color Doppler imaging of orbital venous flow in dysthyroid optic neuropathy.

    PubMed

    Nakase, Y; Osanai, T; Yoshikawa, K; Inoue, Y

    1994-01-01

    Color Doppler imaging was performed to evaluate the venous stasis in 39 orbits, including 9 optic neuropathy orbits, of 20 patients with dysthyroid ophthalmopathy and 22 orbits of 11 healthy subjects. The superior ophthalmic vein (SOV) was detected in 26 dysthyroid ophthalmopathy orbits and in 13 control orbits. The blood flow in the SOV was in the anteroposterior direction in 20 dysthyroid ophthalmopathy orbits and in 13 control orbits. Reversed flow, ie, the flow in the posteroanterior direction, was seen in 6 dysthyroid ophthalmopathy orbits and in none of the control orbits. In dysthyroid ophthalmopathy orbits, the blood flow in the SOV was reversed in 5 (36%) of the 14 orbits with apical orbital crowding observed on computed tomography, which means there was compression of the optic nerve by enlarged extraocular muscles, as compared to in 1 (4%) of the 25 orbits without apical orbital crowding (P < 0.05). The percentage of the orbits having reversed flow in SOV was 44% of dysthyroid ophthalmopathy orbits with optic neuropathy as opposed to 7% of those without optic neuropathy (P < 0.05). Reversed blood flow in the SOV strongly supported the existence of severe venous stasis in the orbits, which may be related to the development of dysthyroid optic neuropathy. PMID:7933702

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

    PubMed

    Prud'homme, Sylvie; Nevens, Frederik; Casteels, Ingele

    2016-01-01

    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. PMID:27625964

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

    PubMed Central

    Prud’homme, Sylvie; Nevens, Frederik; Casteels, Ingele

    2016-01-01

    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. PMID:27625964

  9. Evidence for preserved direct pupillary light response in Leber's hereditary optic neuropathy.

    PubMed Central

    Wakakura, M; Yokoe, J

    1995-01-01

    AIMS/BACKGROUND--Pupillary light response is usually defective in all types of optic neuropathy. However, the authors have observed in patients with Leber's hereditary optic neuropathy (LHON) relatively normal light response, with consequent misdiagnosis psychogenic visual loss in some cases. To confirm this clinical impression, afferent pupillary defect was assessed by measurement of adjusted constriction amplitude (CA) and escape rate (ER) by infrared videopupillography (Iriscorder-C 2515). METHODS--Thirteen consecutive patients (26 eyes) with LHON (average age 27.2 years) were examined; 12 had the mitochondrial DNA 11778 mutation and one the 14484 mutation. Seven of these patients had a positive family history. For comparison, the above rates were determined in 19 patients (23 eyes) with idiopathic optic neuritis (ON; average age 35.1 years), 18 patients (19 eyes) with anterior ischaemic optic neuropathy (AION; average age 58.1 years), and 25 volunteers (50 eyes) with healthy eyes (average age 39.6 years). RESULTS--The distribution of visual acuity was essentially the same in all optic neuropathy groups. Reduction in CA and increase in ER were significant in patients with ON and AION, but not in those with LHON. Only slight afferent pupillary defect was evident even 2 years after the onset of LHON. CA in AION and ER in ON were correlated statistically with visual acuity and Humphrey mean threshold deviation, while CA and ER in LHON were not. CONCLUSION--Pupillary light response in patients with LHON obviously differs from that in patients with other types of optic neuropathy. LHON appears to be pathophysiologically characterised by well preserved afferent fibres for pupillary light response (probably from W cells). Besides being of pathogenetic interest, the detection of clinical features should facilitate the diagnosis of LHON particularly when family history provides no indication. PMID:7612556

  10. Oestrogens ameliorate mitochondrial dysfunction in Leber’s hereditary optic neuropathy

    PubMed Central

    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

    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. PMID:20943885

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

    PubMed Central

    Maramattom, Boby Varkey; Sundar, Shyam; Thomas, Dalvin; Panikar, Dilip

    2016-01-01

    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.

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

    PubMed

    Maramattom, Boby Varkey; Sundar, Shyam; Thomas, Dalvin; Panikar, Dilip

    2016-01-01

    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. PMID:27570391

  13. Bilateral Blindness due to Ischemic Optic Nerve Neuropathy After Abdominal Surgery.

    PubMed

    Geis, Alexander B U; Höfert, Anke; Silvanus, Marie-Therese; Bornfeld, Norbert; Peters, Jürgen

    2015-08-15

    Postoperative blindness is an unpredictable, devastating, and yet not-uncommon complication of anesthesia. We present the case of a patient who suffered bilateral loss of eyesight after surgery. The diagnostic evidence led us to believe that it was bilateral posterior ischemic optic neuropathy; however, the true mechanisms of damage remain a matter of speculation. PMID:26275307

  14. Should steroids be offered to patients with nonarteritic anterior ischemic optic neuropathy (NAION)?

    PubMed Central

    Lee, Andrew G.; Biousse, Valérie

    2010-01-01

    The treatment of nonarteritic anterior optic neuropathy remains very limited and disappointing. Recent publications have suggested that oral steroids as well as intravitreal injections of steroids might be helpful to accelerate resolution of disc edema and improve visual outcome. However, the use of steroids to treat acute NAION remains largely debated. PMID:20523196

  15. Management of traumatic optic neuropathy--a study of 23 patients.

    PubMed Central

    Mauriello, J. A.; DeLuca, J.; Krieger, A.; Schulder, M.; Frohman, L.

    1992-01-01

    Twenty three patients with traumatic optic neuropathy were managed by medical and surgical treatment as follows. High dose intravenous steroids were initiated in all patients. If visions did not improve significantly after 24 to 48 hours decompression of an optic nerve sheath haematoma by medial orbitotomy and neurosurgical decompression of the optic canal were considered based on computed tomographic scan findings. Nine of 16 patients who received steroids only showed significant improvement. One of three showed improvement on optic nerve decompression after steroid failure; three or four showed improvement on optic nerve decompression after steroid failure; three or four showed improvement with combined optic nerve sheath decompression by the medial orbitotomy and decompression of the optic canal by frontal craniotomy. A lucid interval of vision after injury and an enlarged optic nerve sheath were associated with an improved prognosis. Five of the 23 patients had a lucid interval and all five had a final improved vision, while only five of 18 patients without a lucid interval improved. Similarly seven of the nine with an enlarged optic nerve sheath showed improvement while only three of 10 patients (three bilateral cases) who presented with no light perception improved with medical and surgical treatment. While a prospective controlled study of the management of traumatic optic neuropathy is necessary this preliminary study suggests that treatment of traumatic optic nerve sheath haematoma by optic nerve sheath decompression should be considered in selected patients. Images PMID:1622947

  16. Traumatic Optic Neuropathy: A Potentially Unrecognized Diagnosis after Sports-Related Concussion.

    PubMed

    Ellis, Michael J; Ritchie, Lesley; Cordingley, Dean; Essig, Marco; Mansouri, Behzad

    2016-01-01

    Traumatic optic neuropathy is a rare cause of visual disturbance after head injury that can be difficult to distinguish from coexisting vestibulo-ocular dysfunction because of the overlap in presenting symptoms in patients with these conditions. We present a case report of a 13-year-old girl who sustained a head injury during a ringette game leading to blurred vision and diplopia persisting 5 months after injury. Clinical history and physical examination findings were consistent with a traumatic optic neuropathy, convergence insufficiency, and postconcussion syndrome. Neuroimaging was normal. The patient was managed using a multidisciplinary approach. At 6 months of follow-up, neuro-ophthalmological examination demonstrated evidence of permanent partial optic nerve injury, and formal neuropsychological testing fell primarily within normal limits. The patient was advised to retire from collision sports. The authors discuss the value of a comprehensive multidisciplinary approach to the evaluation and management of concussion patients presenting with persistent visual symptoms. PMID:26745167

  17. Toxic optic neuropathy in the setting of docetaxel chemotherapy: a case report

    PubMed Central

    2014-01-01

    Background To describe the first reported case of toxic optic neuropathy secondary to docetaxel (Taxotere®) chemotherapy. Case presentation A 53-year-old female presented with predominantly unilateral visual loss, but extensive bilateral visual field defects and bilateral optic nerve head swelling 2 weeks after first dose of docetaxel (Taxotere®) and trastuzumab (Herceptin®) chemotherapy for a left sided node-positive, HER2 positive breast cancer. Extensive investigation ruled out other causes of optic neuropathy. She was treated with high dose corticosteroids intravenously for 1 week then a tapering oral dose over 8 weeks. Visual field defects gradually resolved and visual acuity improved. Docetaxel chemotherapy was discontinued but targeted therapy with trastuzumab continued without further complication. Conclusion Docetaxel can cause a toxic optic neuropathy possibly due to an ischemic or neurotoxic mechanism at the optic nerve head. With cessation of docetaxel therapy and treatment with systemic corticosteroids, visual recovery can occur without significant residual visual deficit. PMID:24564293

  18. Subacute myelo‑optic neuropathy, beriberi, and HTLV‑I‑associated myelopathy: elucidation of some neurological diseases in Japan.

    PubMed

    Igata, Akihiro

    2012-01-01

    Personal experience of the discovery of the cause, pathophysiology, and treatment as well as prevention of subacute myelo‑optic neuropathy, beriberi, and HTLV‑I‑associated myelopathy were described. PMID:23222550

  19. Recessive Mutations in RTN4IP1 Cause Isolated and Syndromic Optic Neuropathies

    PubMed Central

    Angebault, Claire; Guichet, Pierre-Olivier; Talmat-Amar, Yasmina; Charif, Majida; Gerber, Sylvie; Fares-Taie, Lucas; Gueguen, Naig; Halloy, François; Moore, David; Amati-Bonneau, Patrizia; Manes, Gael; Hebrard, Maxime; Bocquet, Béatrice; Quiles, Mélanie; Piro-Mégy, Camille; Teigell, Marisa; Delettre, Cécile; Rossel, Mireille; Meunier, Isabelle; Preising, Markus; Lorenz, Birgit; Carelli, Valerio; Chinnery, Patrick F.; Yu-Wai-Man, Patrick; Kaplan, Josseline; Roubertie, Agathe; Barakat, Abdelhamid; Bonneau, Dominique; Reynier, Pascal; Rozet, Jean-Michel; Bomont, Pascale; Hamel, Christian P.; Lenaers, Guy

    2015-01-01

    Autosomal-recessive optic neuropathies are rare blinding conditions related to retinal ganglion cell (RGC) and optic-nerve degeneration, for which only mutations in TMEM126A and ACO2 are known. In four families with early-onset recessive optic neuropathy, we identified mutations in RTN4IP1, which encodes a mitochondrial ubiquinol oxydo-reductase. RTN4IP1 is a partner of RTN4 (also known as NOGO), and its ortholog Rad8 in C. elegans is involved in UV light response. Analysis of fibroblasts from affected individuals with a RTN4IP1 mutation showed loss of the altered protein, a deficit of mitochondrial respiratory complex I and IV activities, and increased susceptibility to UV light. Silencing of RTN4IP1 altered the number and morphogenesis of mouse RGC dendrites in vitro and the eye size, neuro-retinal development, and swimming behavior in zebrafish in vivo. Altogether, these data point to a pathophysiological mechanism responsible for RGC early degeneration and optic neuropathy and linking RTN4IP1 functions to mitochondrial physiology, response to UV light, and dendrite growth during eye maturation. PMID:26593267

  20. Genetic heterogeneity and mitochondrial DNA heteroplasmy in Leber's hereditary optic neuropathy.

    PubMed Central

    Holt, I J; Miller, D H; Harding, A E

    1989-01-01

    Analysis of mitochondrial DNA from patients with Leber's hereditary optic neuropathy and their relatives showed that the previously reported mutation at base pair (bp) 11778, shown by loss of a recognition site for the restriction endonuclease SfaNI, was present in only four out of eight families. This mutation was associated with a poor prognosis for visual recovery, whereas four of five affected males without the 11778 bp mutation followed for four years or more had regained useful vision. All but one of the subjects showing the SfaNI site loss had a variable mixture of mutant and normal mitochondrial DNA in peripheral blood, and the relative proportions appeared to be correlated with the risk of developing or transmitting Leber's hereditary optic neuropathy. Images PMID:2575667

  1. Optic neuropathy secondary to dasatinib in the treatment of a chronic myeloid leukemia case

    PubMed Central

    Monge, Katia Sotelo; Gálvez-Ruiz, Alberto; Alvárez-Carrón, Alberto; Quijada, César; Matheu, Anna

    2015-01-01

    The drug dasatinib is a new therapeutic option for patients with chronic myeloid leukemia (CML) as well as acute lymphocytic lymphoblastic leukemia (ALL). However, the scientific literature has not reached a consensus regarding the types of secondary ophthalmologic effects that this drug may have. In this study, we present the case of a 36-year-old male patient who was treated with dasatinib. Two and a half months later, this patient began to experience progressive visual loss in the superior visual field of both eyes. After ruling out various diagnostic options and performing extensive complementary tests, the suspected diagnosis was compatible with optic neuropathy secondary to dasatinib. The patient partially improved after stopping this medication and receiving oral corticosteroid treatment. Although secondary ophthalmological effects related to dasatinib are practically non-existent, our case is the first to report optic neuropathy secondary to this drug. PMID:26155085

  2. [Not only optic neuropathy: new molecular and clinical aspects of OPA1 gene mutations].

    PubMed

    Ołdak, Monika; Sciezyńska, Aneta; Szulborski, Kamil; Szaflik, Jacek P; Szaflik, Jerzy

    2014-01-01

    Autosomal dominant optic nerve atrophy is the most frequent dominantly inherited optic neuropathy. The main causesof the disease are OPA1 gene mutations, which are detected in about 60% of patients. Encoded by the nuclear genome the OPA1 protein plays an important role in a wide variety of processes crucial to the proper functioning of mitochondria, the role of OPAl in many of them has been discovered recently. A detailed study of patients with mutations in the OPA1 gene has shown that about 20% of them present symptoms of a multiple system disease, which may include hearing loss, progressive external ophthalmoplegia, ataxia, myopathy, peripheral neuropathy, spastic paraparesis and multiple sclerosis-like illness. This clinical manifestation is difficult to differentiate from other neurodegenerative diseases, that is why genetic testing is very important in order to determine the molecular basis of the disease in these patients. PMID:25137924

  3. Combined endoscopic and subciliary orbital decompression for thyroid-related compressive optic neuropathy.

    PubMed

    Graham, S M; Carter, K D

    1997-09-01

    Compressive optic neuropathy is a feared, although unusual, complication of thyroid-related orbitopathy. A variety of surgical approaches have been described to achieve orbital decompression and alleviate the hallmark apical orbital crowding of this condition. We describe a subciliary anterior orbitotomy approach to the floor combined with an endoscopic medial wall resection. The anterior orbitotomy allows removal of the bones of the orbital floor both medial and lateral to the canal of the infraorbital nerve. The anterior orbital floor is retained for globe support. This combined approach retains the low morbidity of the endoscopic operation while achieving increased apical medial orbital wall and orbital floor decompression. We describe two illustrative cases where this approach produced a dramatic improvement in visual function. The surgical refinements associated with this combined approach offer technical advantages over other operations in the treatment of thyroid-related compressive optic neuropathy. PMID:9403938

  4. A randomized placebo-controlled trial of idebenone in Leber’s hereditary optic neuropathy

    PubMed Central

    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

    2011-01-01

    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. PMID:21788663

  5. Analysis of Fundus Photography and Fluorescein Angiography in Nonarteritic Anterior Ischemic Optic Neuropathy and Optic Neuritis

    PubMed Central

    Kim, Min Kyung

    2016-01-01

    Purpose We evaluated fundus and fluorescein angiography (FAG) findings and characteristics that can help distinguish nonarteritic anterior ischemic optic neuropathy (NAION) from optic neuritis (ON). Methods Twenty-three NAION patients and 17 ON with disc swelling patients were enrolled in this study. We performed fundus photography and FAG. The disc-swelling pattern, hyperemia grade, presence of splinter hemorrhages, cotton-wool spots, artery/vein ratio and degree of focal telangiectasia were investigated. The FAG findings for each patient were compared with respect to the following features: the pattern of disc leakage in the early phase, arteriovenous (artery/vein) transit time (second), and the presence and pattern of the filling delay. Results Cotton-wool spots, focal telangiectasia, and venous congestion were more common in the affected eyes of NAION patients. Upon FAG, 76.5% of the patients in the ON group exhibited normal choroidal circulation. However, 56.5% of patients in the NAION group demonstrated abnormal filling defects, such as peripapillary, generalized, or watershed zone filling delays. Conclusions Fundus findings, including cotton-wool spots, focal telangiectasia, and venous congestion in the affected eye, may be clues that can be used to diagnose NAION. In addition, choroidal insufficiencies on FAG could be also helpful in differentiating NAION from ON. PMID:27478356

  6. Preserved Visual Acuity in Anterior Ischemic Optic Neuropathy Secondary to Giant Cell (temporal) Arteritis

    PubMed Central

    Antonio-Santos, Aileen A.; Murad-Kejbou, Sally J.; Foroozan, Rod; Yedavally, Sunita; Kaufman, David I.; Eggenberger, Eric R.

    2016-01-01

    OBJECTIVE To evaluate the prevalence and clinical profile of patients with biopsy-proven arteritic anterior ischemic optic neuropathy presenting with preserved visual acuity of 20/40 or better and those with an initial poor visual acuity of 20/50 or worse through a retrospective chart review RESULTS Nine of 37 patients with arteritic anterior ischemic optic neuropathy presented with a preserved visual acuity of 20/40 or better in the affected eye. All patients with preserved visual acuity had initial visual field defects that spared the central field. All 37 patients immediately received high-dose corticosteroid therapy. Visual acuity worsened by > 2 lines in one of nine patients (11%) with preserved visual acuity, with a corresponding progression of visual field constriction. CONCLUSION Although preserved visual acuity of 20/40 or better has traditionally been associated with the nonarteritic form of anterior ischemic optic neuropathy, giant cell arteritis should still be strongly considered, especially if they have giant cell arteritis systemic symptoms. PMID:26958148

  7. Recessive optic atrophy, sensorimotor neuropathy and cataract associated with novel compound heterozygous mutations in OPA1.

    PubMed

    Lee, Jinho; Jung, Sung-Chul; Hong, Young Bin; Yoo, Jeong Hyun; Koo, Heasoo; Lee, Ja Hyun; Hong, Hyun Dae; Kim, Sang-Beom; Chung, Ki Wha; Choi, Byung-Ok

    2016-07-01

    Mutations in the optic atrophy 1 gene (OPA1) are associated with autosomal dominant optic atrophy and 20% of patients demonstrate extra-ocular manifestations. In addition to these autosomal dominant cases, only a few syndromic cases have been reported thus far with compound heterozygous OPA1 mutations, suggestive of either recessive or semi‑dominant patterns of inheritance. The majority of these patients were diagnosed with Behr syndrome, characterized by optic atrophy, ataxia and peripheral neuropathy. The present study describes a 10-year-old boy with Behr syndrome presenting with early‑onset severe optic atrophy, sensorimotor neuropathy, ataxia and congenital cataracts. He had optic atrophy and was declared legally blind at six years old. Electrophysiological, radiological, and histopathological findings were compatible with axonal sensorimotor polyneuropathy. At birth, he presented with a congenital cataract, which has not been previously described in patients with OPA1 mutations. Whole exome sequencing indicated a pair of novel compound heterozygous mutations: p.L620fs*13 (c.1857‑1858delinsT) and p.R905Q (c.G2714A). Neither mutation was observed in controls (n=300), and thus, they were predicted to be pathogenic by multiple in silico analyses. The mutation sites were highly conserved throughout different vertebrate species. The patients parents did not have any ophthalmic or neurologic symptoms and the results of electrophysiological studies were normal, suggestive of an autosomal recessive pattern of inheritance. The present study identified novel compound heterozygous OPA1 mutations in a patient with recessive optic atrophy, sensorimotor neuropathy and congenital cataracts, indicating an expansion of the clinical spectrum of pathologies associated with OPA1 mutations. Thus, OPA1 gene screening is advisable in the workup of patients with recessive optic atrophy, particularly with Behr syndrome and cataracts. PMID:27150940

  8. Recessive optic atrophy, sensorimotor neuropathy and cataract associated with novel compound heterozygous mutations in OPA1

    PubMed Central

    LEE, JINHO; JUNG, SUNG-CHUL; HONG, YOUNG BIN; YOO, JEONG HYUN; KOO, HEASOO; LEE, JA HYUN; HONG, HYUN DAE; KIM, SANG-BEOM; CHUNG, KI WHA; CHOI, BYUNG-OK

    2016-01-01

    Mutations in the optic atrophy 1 gene (OPA1) are associated with autosomal dominant optic atrophy and 20% of patients demonstrate extra-ocular manifestations. In addition to these autosomal dominant cases, only a few syndromic cases have been reported thus far with compound heterozygous OPA1 mutations, suggestive of either recessive or semi-dominant patterns of inheritance. The majority of these patients were diagnosed with Behr syndrome, characterized by optic atrophy, ataxia and peripheral neuropathy. The present study describes a 10-year-old boy with Behr syndrome presenting with early-onset severe optic atrophy, sensorimotor neuropathy, ataxia and congenital cataracts. He had optic atrophy and was declared legally blind at six years old. Electrophysiological, radiological, and histopathological findings were compatible with axonal sensorimotor polyneuropathy. At birth, he presented with a congenital cataract, which has not been previously described in patients with OPA1 mutations. Whole exome sequencing indicated a pair of novel compound heterozygous mutations: p.L620fs*13 (c.1857–1858delinsT) and p.R905Q (c.G2714A). Neither mutation was observed in controls (n=300), and thus, they were predicted to be pathogenic by multiple in silico analyses. The mutation sites were highly conserved throughout different vertebrate species. The patients parents did not have any ophthalmic or neurologic symptoms and the results of electrophysiological studies were normal, suggestive of an autosomal recessive pattern of inheritance. The present study identified novel compound heterozygous OPA1 mutations in a patient with recessive optic atrophy, sensorimotor neuropathy and congenital cataracts, indicating an expansion of the clinical spectrum of pathologies associated with OPA1 mutations. Thus, OPA1 gene screening is advisable in the workup of patients with recessive optic atrophy, particularly with Behr syndrome and cataracts. PMID:27150940

  9. Mitochondrial EFTs defects in juvenile-onset Leigh disease, ataxia, neuropathy, and optic atrophy

    PubMed Central

    Ahola, Sofia; Isohanni, Pirjo; Euro, Liliya; Brilhante, Virginia; Palotie, Aarno; Pihko, Helena; Lönnqvist, Tuula; Lehtonen, Tanita; Laine, Jukka; Tyynismaa, Henna

    2014-01-01

    Objective: We report novel defects of mitochondrial translation elongation factor Ts (EFTs), with high carrier frequency in Finland and expand the manifestations of this disease group from infantile cardiomyopathy to juvenile neuropathy/encephalopathy disorders. Methods: DNA analysis, whole-exome analysis, protein biochemistry, and protein modeling. Results: We used whole-exome sequencing to find the genetic cause of infantile-onset mitochondrial cardiomyopathy, progressing to juvenile-onset Leigh syndrome, neuropathy, and optic atrophy in 2 siblings. We found novel compound heterozygous mutations, c.944G>A [p.C315Y] and c.856C>T [p.Q286X], in the TSFM gene encoding mitochondrial EFTs. The same p.Q286X variant was found as compound heterozygous with a splice site change in a patient from a second family, with juvenile-onset optic atrophy, peripheral neuropathy, and ataxia. Our molecular modeling predicted the coding-region mutations to cause protein instability, which was experimentally confirmed in cultured patient cells, with mitochondrial translation defect and lacking EFTs. Only a single TSFM mutation has been previously described in different populations, leading to an infantile fatal multisystem disorder with cardiomyopathy. Sequence data from 35,000 Finnish population controls indicated that the heterozygous carrier frequency of p.Q286X change was exceptionally high in Finland, 1:80, but no homozygotes were found in the population, in our mitochondrial disease patient collection, or in an intrauterine fetal death material, suggesting early developmental lethality of the homozygotes. Conclusions: We show that in addition to early-onset cardiomyopathy, TSFM mutations should be considered in childhood and juvenile encephalopathies with optic and/or peripheral neuropathy, ataxia, or Leigh disease. PMID:25037205

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

    PubMed

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

    2016-06-01

    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. PMID:25869060

  11. Optic neuropathy secondary to syphilis in an HIV negative patient.

    PubMed

    Berrozpe-Villabona, C; Santos-Bueso, E; Bañeros-Rojas, P; Aguilar Munoa, S; Saenz-Francés, F; Díaz-Valle, D; Martínez-de-la-Casa, J M; García-Feijoo, J

    2016-02-01

    Ocular syphilis is a resurgent clinical condition due to unsafe sexual practices. It has been reported in both immunocompromised and immunocompetent patients, but in HIV positive patients, it is more likely to exhibit a more aggressive course and adopt atypical clinical patterns such as optic nerve involvement. Herein we report an atypical case of optic neuritis secondary to syphilis in an HIV negative patient. This case highlights the importance of considering syphilis in the differential diagnosis of ocular inflammation and of obtaining HIV serology, since both diseases share common risk factors. PMID:26868532

  12. Current concepts in the diagnosis, pathogenesis and management of nonarteritic anterior ischaemic optic neuropathy

    PubMed Central

    Miller, N R; Arnold, A C

    2015-01-01

    Nonarteritic anterior ischaemic optic neuropathy (NAION) is the most common acute optic neuropathy in patients over the age of 50 and is the second most common cause of permanent optic nerve-related visual loss in adults after glaucoma. Patients typically present with acute, painless, unilateral loss of vision associated with a variable visual field defect, a relative afferent pupillary defect, a swollen, hyperaemic optic disc, and one or more flame-shaped peripapillary retinal haemorrhages. The pathogenesis of this condition is unknown, but it occurs primarily in patients with structurally small optic discs that have little or no cup and a variety of underlying vascular disorders that may or may not be known at the time of visual loss. There is no consistently beneficial medical or surgical treatment for the condition, but there are now animal models that allow testing of various potential therapies. About 40% of patients experience spontaneous improvement in visual acuity. Patients in whom NAION occurs in one eye have a 15–19% risk of developing a similar event in the opposite eye over the subsequent 5 years. PMID:24993324

  13. Leber's Hereditary Optic Neuropathy Affects Only Female Matrilineal Relatives in Two Chinese Families

    PubMed Central

    Qu, Jia; Wang, Ying; Tong, Yi; Zhou, Xiangtian; Zhao, Fuxin; Yang, Li; Zhang, Shoukang; Zhang, Juanjuan; West, Constance E.; Guan, Min-Xin

    2010-01-01

    Purpose. The purpose of this study was to investigate the role of modifier factors in the expression of Leber's hereditary optic neuropathy (LHON). Methods. Thirty-five subjects from two Han Chinese families with maternally transmitted LHON underwent a clinical and genetic evaluation and molecular analysis of mitochondrial (mt)DNA. Results. Matrilineal relatives in the two Chinese families exhibited a wide range of severity in visual impairment, from blindness to nearly normal vision. Very strikingly, all nine affected individuals of 21 matrilineal relatives (13 females/8 males) were female, which translates to 33% and 57% of penetrance for optic neuropathy in the two families. The average age at onset was 22 and 25 years. These observations were in contrast with typical features in many LHON pedigrees that have a predominance of affected males. Molecular analysis of their mtDNAs identified the homoplasmic ND4 G11778A mutation and distinct sets of variants belonging to the Asian haplogroups M1 and M10a. Of other variants, the L175F variant in CO3; the I58V variant in ND6; and the I189V, L292R, and S297A variants in CYTB were located at highly conserved residues of polypeptides. Conclusions. Only female matrilineal relatives with a wide range of penetrance, severity, and age at onset of optic neuropathy in these two Chinese pedigrees showed the involvement of X-linked or autosomal recessive modifier genes in the phenotypic manifestation of the G11778A mutation. Furthermore, mitochondrial haplogroup-specific variants, together with epigenetic and environmental factors, may contribute to the phenotypic manifestation of the primary LHON-associated G11778A mutation in these pedigrees. PMID:20435583

  14. Autosomal recessive hereditary motor and sensory neuropathy with mental retardation, optic atrophy and pyramidal signs.

    PubMed Central

    MacDermot, K D; Walker, R W

    1987-01-01

    A syndrome is described, consisting of severe neurogenic distal wasting, generalised muscle weakness, absent ankle reflexes, pyramidal signs, mental retardation, optic atrophy and retinal colloid bodies. A sural nerve biopsy from one case showed loss of nerve fibres suggesting the diagnosis of hereditary motor and sensory neuropathy. Progression of the disorder was very slow, all patients still being able to walk more than 20 years after the onset. The persons affected with this syndrome were two brothers and their female cousin from a large Gujerati pedigree where consanguinity was high. Autosomal recessive inheritance is therefore suggested. Images PMID:3479531

  15. Bilateral simultaneous optic neuropathy in adults: clinical, imaging, serological, and genetic studies.

    PubMed Central

    Morrissey, S P; Borruat, F X; Miller, D H; Moseley, I F; Sweeney, M G; Govan, G G; Kelly, M A; Francis, D A; Harding, A E; McDonald, W I

    1995-01-01

    To elucidate the cause(s) of acute or subacute bilateral simultaneous optic neuropathy (BSON) in adult life, a follow up study of 23 patients was performed with clinical assessment, brain MRI, HLA typing, and mitochondrial DNA analysis. The results of CSF electrophoresis were available from previous investigations in 11 patients. At follow up, five (22%) had developed clinically definite multiple sclerosis, four (17%) had mitochondrial DNA point mutations indicating a diagnosis of Leber's hereditary optic neuropathy (LHON). The remaining 14 patients (61%) still had clinically isolated BSON a mean of 50 months after the onset of visual symptoms: three of 14 (21%) had multiple MRI white matter lesions compatible with multiple sclerosis, three of 14 (21%) had the multiple sclerosis associated HLA-DR15/DQw6 haplotype, and one of seven tested had CSF oligoclonal IgG bands; in total only five (36%) had one or more of these risk factors. The low frequency of risk factors for the development of multiple sclerosis in these 14 patients suggests that few will develop multiple sclerosis with more prolonged follow up. It is concluded that: (a) about 20% of cases of BSON without affected relatives are due to LHON; (b) multiple sclerosis develops after BSON in at least 20% of cases, but the long term conversion rate is likely to be considerably less than the rate of over 70% seen after an episode of acute unilateral optic neuritis in adult life. PMID:7823072

  16. [Interferon-alpha toxicity and reversible bilateral optical neuropathy: a timely withdrawal of the drug].

    PubMed

    Pérez-Carro, G; Fernández-Alonso, R; González-Diéguez, M L; Rodríguez-García, M; Junceda-Moreno, J

    2014-04-01

    Clinical case A patient with chronic, painless, bilateral loss of vision, after significant intake of interferon (IFNα) and ribavirina due to liver transplant. Ocular fundus is normal. A suspected retrobulbar optic neuropathy is confirmed by a prolongation of the latency of the patient's visual evoked potential. There being no prior record of risk factors and with the patient's systemic analysis giving normal results, the clinical improvement and the electro-physiological tests conducted after the drug was withdrawn point to interferon as negatively affecting the bilateral optic nerve. Discussion Interferon-α is used in the treatment of viral and neoplastic illnesses. Currently the drug is formulated as Interferon alfa pegilado (IFNα-p) in order to reduce toxicity and increase tolerance. The most common secondary effects are flu symptoms, asthenia and weigh loss. Affected ocular tissue is rare and optic neuropathy is also an infrequent complication: retinopathy at the beginning of treatment is, however, more frequent. The most widely accepted hypothesis as to the cause of toxicity is the presence of circulating immune complexes. It is, therefore, essential for ophthalmologists to be aware of the toxicity of this drug in order to be able to withdraw it in good time, thus preventing potentially irreversible sight loss. PMID:24269470

  17. Does altered fractionation influence the risk of radiation-induced optic neuropathy?

    SciTech Connect

    Bhandare, Niranjan; Monroe, Alan T.; Morris, Christopher G.; Bhatti, M. Tariq; Mendenhall, William M. . E-mail: mendewil@shands.ufl.edu

    2005-07-15

    Purpose: To analyze the parameters that influence the risk of radiation-induced optic neuropathy (RION) after radiotherapy for head-and-neck tumors. Methods and Materials: Between 1964 and 2000, 273 patients with tumors of the nasopharynx, paranasal sinuses, nasal cavity, and hard palate adenoid cystic carcinomas were treated with curative intent and had radiation fields that included the optic nerves and/or chiasm. Patients were followed for at least 1 year after radiotherapy. Results: Radiation-induced optic neuropathy developed in 32 eyes of 24 patients (9%). The 5-year rates of freedom from RION according to the total dose and once- vs. twice-daily fractionation were as follows: {<=}63 Gy once daily, 95%; {<=}63 Gy twice daily, 98%; >63 Gy once daily, 78%; and >63 Gy twice daily, 91%. Multivariate analysis revealed that the total dose affected the risk of RION (p = 0.0047), with patient age (p = 0.0909), once-daily vs. twice-daily fractionation (p = 0.0684), and overall treatment time (p = 0.0972) were marginally significant. The use of adjuvant chemotherapy did not significantly influence the likelihood of developing RION. Conclusion: The likelihood of developing RION is primarily influenced by the total dose. Hyperfractionation may reduce the risk of experiencing this complication.

  18. Electrophysiological changes in optic neuropathy of streptozotocin induced diabetic rats

    PubMed Central

    Ghita, AM; Parvu, D; Sava, R; Georgescu, L; Zagrean, L

    2013-01-01

    The visually evoked potentials are electrical signals generated by the occipital cortex due to electrical stimulus. The clinical importance of VEP is to diagnose the functional changes of the optic nerve in different diseases such as diabetic mellitus. Our study sought latency of VEP changes depending on glycemic value and duration of diabetes in Wistar rats. Methods: this study evaluated the VEP of 25 rats in three groups: control group, diabetic group 1 with glycemic values between 200-400mg/dl and diabetic group 2 with glycemic values between 400 and 600mg/dl. These rats from diabetic group 2 were followed for 4 months and the ones in control group and diabetic group 1 for 5 months. Results: the latency of VEP shows slight changes without any statistical significance in the control group. In diabetic group 1 and 2 similar changes occurred, with statistical significance and the amplitude of the changes was proportional with the glycemic value. The rats had a rapid increase of VEP latency after the induction of diabetes and returned to a normal range in the first month. After a time, when the latencies of VEP were in normal range, a new growth appeared faster and larger as the glycemic values were higher. Conclusion: diabetes brings changes to the visual signal transmission and to the central processing, this being revealed by the examination of the visually evoked potential. Increased VEP latency is statistically correlated with the changes that occur at the level of the values of glucose in blood. A rapid growth in blood sugar lowers the visual signal transmission. This change is temporary despite the persistence of elevated blood glucose values, probably by adjusting to the new condition. However, maintaining high glycemic values remotely produces a progressive increase of the delay of the visual signal. This progressive increase is faster as blood glucose levels are higher. PMID:24155786

  19. In vivo imaging methods to assess glaucomatous optic neuropathy.

    PubMed

    Fortune, Brad

    2015-12-01

    The goal of this review is to summarize the most common imaging methods currently applied for in vivo assessment of ocular structure in animal models of experimental glaucoma with an emphasis on translational relevance to clinical studies of the human disease. The most common techniques in current use include optical coherence tomography and scanning laser ophthalmoscopy. In reviewing the application of these and other imaging modalities to study glaucomatous optic neuropathy, this article is organized into three major sections: 1) imaging the optic nerve head, 2) imaging the retinal nerve fiber layer and 3) imaging retinal ganglion cell soma and dendrites. The article concludes with a brief section on possible future directions. PMID:26048475

  20. Leber's "plus": neurological abnormalities in patients with Leber's hereditary optic neuropathy.

    PubMed Central

    Nikoskelainen, E K; Marttila, R J; Huoponen, K; Juvonen, V; Lamminen, T; Sonninen, P; Savontaus, M L

    1995-01-01

    Previous studies suggest that Leber's hereditary optic neuropathy (LHON) may be a systemic disorder with manifestations in organs other than the optic nerves. To evaluate nervous system involvement 38 men and eight women with LHON were re-examined. The patients were divided into three groups according to mtDNA analysis--namely, patients with the 11778 or with the 3460 mutation and patients without these primary mutations. Fifty nine per cent of patients had neurological abnormalities but there was no significant difference between the three groups. Movement disorders were the most common finding; nine patients had constant postural tremor, one chronic motor tic disorder, and one parkinsonism with dystonia. Four patients had peripheral neuropathy with no other evident cause. Two patients had a multiple sclerosis-like syndrome; in both patients MRI showed changes in the periventricular white matter. Thoracic kyphosis occurred in seven patients, five of whom had the 3460 mutation. In one patient the 3460 mutation was associated with involvement of the brain stem. It is suggested that various movement disorders, multiple sclerosis-like illness, and deformities of the vertebral column may associate pathogenetically with LHON. Images PMID:7629530

  1. Unilateral optic neuropathy from possible sphenoidal sinus barotrauma after recreational scuba diving: a case report.

    PubMed

    Gunn, David J; O'Hagan, Stephen

    2013-01-01

    A case report is presented of a 35-year-old woman who developed a progressive right optic neuropathy while surfacing from a series of four recreational dives on the Great Barrier Reef, Queensland, Australia. The patient reported severe sudden onset blurred vision in the right eye associated with a mild headache and epistaxis on surfacing from diving. The patient had her first medical review the day after returning from her trip. At this time visual acuity in the right eye was 20/80, with left eye 20/20. There was a relative afferent pupillary defect in the right eye. A high-resolution computed tomography scan showed fluid in the right sphenoid sinus. Computed perimetry revealed patchy visual field loss in the right eye. The provisional diagnosis of sphenoidal sinus barotrauma-induced optic neuropathy was made. Over 10 days of observation, the visual acuity returned to 20/20 in the right eye and visual field changes resolved. This case highlights a very unusual cause of visual loss associated with diving. PMID:23397871

  2. The 14th Hoyt Lecture: Ischemic Optic Neuropathy: The Evolving Profile, 1966-2015.

    PubMed

    Arnold, Anthony C

    2016-06-01

    Since the first English language description by Miller and Smith in 1966 of ischemic optic neuropathy as a distinct ophthalmic syndrome, a long series of studies has refined the clinical profile to what we consider to be accurate today. From the specifics of pathogenesis to the clinical appearance to the effect of therapy, the basic tenets of diagnosis and management have evolved over 5 decades. What we thought we knew about the following topics has changed: location of vasculopathy; incidence; age at onset; optic disc appearance; risk factors for development; natural history; rate of fellow eye involvement; ischemia as an all-or-none phenomenon; and treatment. A look back at these discoveries shows both how far we have come and how far we have to go in managing this disorder. PMID:27176556

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

    PubMed Central

    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

  4. Hereditary Neuropathies

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Hereditary Neuropathies Information Page Synonym(s): Neuropathy - Hereditary Table of Contents ( ... and Information Publicaciones en Español What are Hereditary Neuropathies? Hereditary neuropathies are a group of inherited disorders ...

  5. Peripheral Neuropathy

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Peripheral Neuropathy Information Page Condensed from Peripheral Neuropathy Fact Sheet ... Español Additional resources from MedlinePlus What is Peripheral Neuropathy? Peripheral neuropathy describes damage to the peripheral nervous ...

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

    PubMed Central

    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

  7. Bilateral non-arteritic ischemic optic neuropathy in a transsexual woman using excessive estrogen dosage.

    PubMed

    Wierckx, Katrien; De Zaeytijd, Julie; Elaut, Els; Heylens, Gunter; T'Sjoen, Guy

    2014-02-01

    We present a case report on a 53-year-old transsexual woman who developed acute painless vision loss in both eyes during cross-sex hormone treatment. After 10 months of cross-sex hormone treatment, she experienced total vision loss of the right eye and, 6 months later, vision loss to 20/63 in the left eye. After a full ophthalmic exam, bilateral sequential non-arteritic ischemic optic neuropathy (NA-ION) was diagnosed. Extensive etiological work-up revealed no cardiac abnormalities or inherited blood-clotting disorders. A manifest self-administered overdose of transdermal estrogen treatment with serum estradiol levels of 5,765 pg/ml was possibly related to the sequential bilateral NA-ION resulting in nearly total vision loss in this transsexual woman. PMID:24057212

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

    PubMed Central

    Tarantini, Anna; Faraoni, Alessandra; Menchini, Francesca; Lanzetta, Paolo

    2012-01-01

    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. PMID:22481954

  9. Nonarteritic anterior ischemic optic neuropathy as the presenting manifestation of primary antiphospholipid syndrome

    PubMed Central

    Tugcu, Betul; Acar, Nur; Coskun, Cigdem Tanrıverdi; Celik, Selda; Yigit, Fadime Ulviye

    2014-01-01

    Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by vascular thrombosis or pregnancy morbidity. Ocular involvement in APS includes a broad spectrum of manifestations involving anterior and posterior segment or the presence of neuroophthalmologic features. Nonarteritic anterior ischemic optic neuropathy (NAION) is a very rare finding, and in this report a case having NAION as the prevailing sign of APS is presented. A middle-aged women who presented with visual disturbances in her left eye (LE) and turned out to have the diagnosis of primary APS with the help of rheumatological investigations is discussed. She was treated with oral steroids for NAION in her LE. With systemic and rheumatological work-up, primary APS was diagnosed, and hydroxychloroquine, coumadin, and aspirin were started, after which she remained stable under control. Due to the important diagnostic and therapeutic implications of APS, it should be considered in the differential diagnosis of NAION, particularly when the etiology is uncertain. PMID:23571268

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

    SciTech Connect

    Chalmers, R.M.; Davis, M.B.; Sweeney, M.G.; Wood, N.W.; Harding, A.E.

    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.

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

    SciTech Connect

    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.

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

    PubMed

    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. PMID:21414825

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

    PubMed

    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. PMID:27488066

  14. Crystallins Are Regulated Biomarkers for Monitoring Topical Therapy of Glaucomatous Optic Neuropathy

    PubMed Central

    Prokosch, Verena; Schallenberg, Maurice; Thanos, Solon

    2013-01-01

    Optic nerve atrophy caused by abnormal intraocular pressure (IOP) remains the most common cause of irreversible loss of vision worldwide. The aim of this study was to determine whether topically applied IOP-lowering eye drugs affect retinal ganglion cells (RGCs) and retinal metabolism in a rat model of optic neuropathy. IOP was elevated through cauterization of episcleral veins, and then lowered either by the daily topical application of timolol, timolol/travoprost, timolol/dorzolamide, or timolol/brimonidine, or surgically with sectorial iridectomy. RGCs were retrogradely labeled 4 days prior to enucleation, and counted. Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), matrix-assisted laser desorption ionization mass spectrometry, Western blotting, and immunohistochemistry allowed the identification of IOP-dependent proteomic changes. Genomic changes were scrutinized using microarrays and qRT-PCR. The significant increase in IOP induced by episcleral vein cauterization that persisted until 8 weeks of follow-up in control animals (p<0.05) was effectively lowered by the eye drops (p<0.05). As anticipated, the number of RGCs decreased significantly following 8 weeks of elevated IOP (p<0.05), while treatment with combination compounds markedly improved RGC survival (p<0.05). 2D-PAGE and Western blot analyses revealed an IOP-dependent expression of crystallin cry-βb2. Microarray and qRT-PCR analyses verified the results at the mRNA level. IHC demonstrated that crystallins were expressed mainly in the ganglion cell layer. The data suggest that IOP and either topically applied antiglaucomatous drugs influence crystallin expression within the retina. Neuronal crystallins are thus suitable biomarkers for monitoring the progression of neuropathy and evaluating any neuroprotective effects. PMID:23468831

  15. Inhibition of adenosine kinase attenuates inflammation and neurotoxicity in traumatic optic neuropathy.

    PubMed

    Ahmad, Saif; Elsherbiny, Nehal M; Bhatia, Kanchan; Elsherbini, Ahmed M; Fulzele, Sadanand; Liou, Gregory I

    2014-12-15

    Traumatic optic neuropathy (TON) is associated with apoptosis of retinal ganglion cells. Local productions of reactive oxygen species and inflammatory mediators from activated microglial cells have been hypothesized to underlie apoptotic processes. We previously demonstrated that the anti-inflammatory effect of adenosine, through A2A receptor activation had profound protective influence against retinal injury in traumatic optic neuropathy. This protective effect is limited due to rapid cellular re-uptake of adenosine by equilibrative nucleotside transporter-1 (ENT1) or break down by adenosine kinase (AK), the key enzyme in adenosine clearance pathway. Further, the use of adenosine receptors agonists are limited by systemic side effects. Therefore, we seek to investigate the potential role of amplifying the endogenous ambient level of adenosine by pharmacological inhibition of AK. We tested our hypothesis by comparing TON-induced retinal injury in mice with and without ABT-702 treatment, a selective AK inhibitor (AKI). The retinal-protective effect of ABT-702 was demonstrated by significant reduction of Iba-1, ENT1, TNF-α, IL-6, and iNOS/nNOS protein or mRNA expression in TON as revealed by western blot and real time PCR. TON-induced superoxide anion generation and nitrotyrosine expression were reduced in ABT-702 treated mice retinal sections as determined by immunoflourescence. In addition, ABT-702 attenuated p-ERK1/2 and p-P38 activation in LPS induced activated mouse microglia cells. The results of the present investigation suggested that ABT-702 had a protective role against marked TON-induced retinal inflammation and damage by augmenting the endogenous therapeutic effects of site- and event-specific accumulation of extracellular adenosine. PMID:25457840

  16. A Case of Decreased Visual Field after Uneventful Cataract Surgery: Nonarteritic Anterior Ischemic Optic Neuropathy

    PubMed Central

    Lee, Hun; Kim, Chan Yun; Seong, Gong Je

    2010-01-01

    The purpose of this article is to report a case of nonarteritic anterior ischemic optic neuropathy (NAION) after uneventful cataract surgery. A 53-year-old Filipina underwent cataract surgery. She had a small optic disc with cup-to-disc ratio of 0.2 in the left eye and 0.3 in the right eye. On the first postoperative day, the uncorrected visual acuity (UCVA) was 20/20, with an intraocular pressure (IOP) of 20 mmHg in the left eye. At one week after operation, the UCVA was 20/20 and the IOP was 15 mmHg. Three weeks later, she underwent cataract surgery in the right eye. On the first postoperative day, her UCVA was 20/20 in both eyes, but she complained of a visual field decrease in the left eye. A relative afferent pupillary defect (RAPD) was noted and the optic disc was pallid and swollen diffusely. A red-free photo showed defect surrounding the optic disc. A visual field test showed tunnel vision sparing the central vision. In this report, the authors hypothesize an association between cataract extraction and delayed NAION. Since the risk of NAION in the fellow eye is 30-50%, visual acuity, visual field, fundus exam and RAPD should be routinely checked. PMID:20157417

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

    PubMed Central

    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. PMID:27560494

  18. A case of decreased visual field after uneventful cataract surgery: nonarteritic anterior ischemic optic neuropathy.

    PubMed

    Lee, Hun; Kim, Chan Yun; Seong, Gong Je; Ma, Kyoung Tak

    2010-02-01

    The purpose of this article is to report a case of nonarteritic anterior ischemic optic neuropathy (NAION) after uneventful cataract surgery. A 53-year-old Filipina underwent cataract surgery. She had a small optic disc with cup-to-disc ratio of 0.2 in the left eye and 0.3 in the right eye. On the first postoperative day, the uncorrected visual acuity (UCVA) was 20/20, with an intraocular pressure (IOP) of 20 mmHg in the left eye. At one week after operation, the UCVA was 20/20 and the IOP was 15 mmHg. Three weeks later, she underwent cataract surgery in the right eye. On the first postoperative day, her UCVA was 20/20 in both eyes, but she complained of a visual field decrease in the left eye. A relative afferent pupillary defect (RAPD) was noted and the optic disc was pallid and swollen diffusely. A red-free photo showed defect surrounding the optic disc. A visual field test showed tunnel vision sparing the central vision. In this report, the authors hypothesize an association between cataract extraction and delayed NAION. Since the risk of NAION in the fellow eye is 30-50%, visual acuity, visual field, fundus exam and RAPD should be routinely checked. PMID:20157417

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

    PubMed

    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. PMID:27560494

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

    SciTech Connect

    Finger, Paul T.; Chin, Kimberly J.

    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.

  1. Clioquinol-zinc chelate: a candidate causative agent of subacute myelo-optic neuropathy.

    PubMed Central

    Arbiser, J. L.; Kraeft, S. K.; van Leeuwen, R.; Hurwitz, S. J.; Selig, M.; Dickersin, G. R.; Flint, A.; Byers, H. R.; Chen, L. B.

    1998-01-01

    BACKGROUND: 5-chloro-7-iodo-8-hydroxyquinoline (clioquinol) was used clinically three decades ago as an oral antiparasitic agent and to increase intestinal absorption of zinc in patients with acrodermatitis enteropathica, a genetic disorder of zinc absorption. Use of clioquinol was epidemiologically linked to subacute myelo-optic neuropathy (SMON), characterized by peripheral neuropathy and blindness, which affected 10,000 patients in Japan. Discontinuation of oral clioquinol use led to elimination of SMON, however, the mechanism of how clioquinol induces neurotoxicity is unclear. MATERIALS AND METHODS: We tested the effect of clioquinol-metal chelates on neural crest-derived melanoma cells. The effect of clioquinol chelates on cells was further studied by electron microscopy and by a mitochondrial potential-sensitive fluorescent dye. RESULTS: Of the ions tested, only clioquinol-zinc chelate demonstrated cytotoxicity. The cytotoxicity of clioquinol-zinc chelate was extremely rapid, suggesting that its primary effect was on the mitochondria. Electron microscopic analysis demonstrated that clioquinol-zinc chelate caused mitochondrial damage. This finding was further confirmed by the observation that clioquinol-zinc chelate caused a decrease in mitochondrial membrane potential. CONCLUSIONS: We demonstrate that clioquinol, in the presence of zinc, is converted to a potent mitochondrial toxin. The phenomenon of clioquinol mediated toxicity appears to be specific to zinc and is not seen with other metals tested. Since clioquinol has been shown to cause increased systemic absorption of zinc in humans, it is likely that clioquinol-zinc chelate was present in appreciable levels in patients with SMON and may be the ultimate causative toxin of SMON. Images Fig. 2 Fig. 3 PMID:9848083

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

    PubMed Central

    Kim, Tae-Woo; Hwang, Jeong-Min

    2016-01-01

    Purpose 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). Methods 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. Results 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). Conclusion 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. PMID:27035660

  3. Metabolic neuropathies

    MedlinePlus

    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 ...

  4. Diabetic Neuropathy

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Diabetic Neuropathy Information Page Table of Contents (click to jump ... Organizations Additional resources from MedlinePlus What is Diabetic Neuropathy? Diabetic neuropathy is a peripheral nerve disorder caused ...

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

    PubMed

    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

  6. Visual evoked potentials to multiple temporal frequencies. Use in the differential diagnosis of optic neuropathy.

    PubMed

    Bobak, P; Friedman, R; Brigell, M; Goodwin, J; Anderson, R

    1988-07-01

    The usefulness of the visual evoked potential (VEP) in differential diagnosis increases when stimulus parameters such as check size and grating orientation are varied. In this study we varied the stimulation frequency. Temporal frequency-specific abnormalities were compared in three patient categories, including retrobulbar optic neuritis (eight patients), pseudotumor cerebri (11 patients), and thyroid eye disease (seven patients). All patients had minimal clinical evidence of optic nerve damage when tested. A 2.3 cycle-per-degree sinusoidal grating of 55% contrast was phase reversed at either 1 or 4 Hz. The P1 latency of the 1-Hz data and the phase at 8 Hz, the second harmonic of the 4-Hz input frequency, were measured. In retrobulbar neuritis, latency (phase) was severely abnormal at both temporal frequencies. In thyroid eye disease, VEP phase was abnormal at 8 Hz while the P1 latency was normal at 1 Hz. The P1 latency and phase were normal in most cases of pseudotumor cerebri. The results suggest differing mechanisms for damage in compressive vs primary demyelinating neuropathies. PMID:3390057

  7. [Immune-mediated neuropathies].

    PubMed

    Stoll, G; Reiners, K

    2016-08-01

    The Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are the most common immune-mediated polyneuropathies, which can show variable clinical and electrophysiological manifestations. Rarer immune-mediated neuropathies encompass paraproteinemic neuropathies (PPN), multifocal motor neuropathy (MMN) and vasculitic neuropathies. The diagnosis usually relies on the history of symptom evolution, distribution of nerve dysfunction and particularly on characteristic features in nerve conduction studies, aided by cerebrospinal fluid (CSF) examination and nerve biopsy findings. The therapeutic toolbox encompasses corticosteroids, immunoglobulins and plasmapheresis often accompanied by long-term immunosuppression. It is important to note that immune-mediated neuropathies selectively respond to treatment and contraindications need to be considered. Despite treatment a considerable number of patients suffer from permanent neurological deficits. PMID:27474733

  8. Peripheral neuropathy

    MedlinePlus

    Peripheral neuritis; Neuropathy - peripheral; Neuritis - peripheral; Nerve disease; Polyneuropathy ... Neuropathy is very common. There are many types and causes. Often, no cause can be found. Some ...

  9. Predictive value of visual evoked potentials, relative afferent pupillary defect, and orbital fractures in patients with traumatic optic neuropathy

    PubMed Central

    Tabatabaei, Seyed Ali; Soleimani, Mohammad; Alizadeh, Mahdi; Movasat, Morteza; Mansoori, Mohammad Reza; Alami, Zakieh; Foroutan, Alireza; Joshaghani, Mahmood; Safari, Saeid; Goldiz, Arzhang

    2011-01-01

    Background: The purpose of this study was to determine the predictive value of flash visual-evoked potentials (VEP), relative afferent pupillary defect, and presence of orbital fractures in patients with traumatic optic neuropathy. Methods: A prospective study was conducted in 15 patients with indirect traumatic optic neuropathy. All patients underwent a thorough ophthalmic examination. Initial visual acuity, final visual acuity, and relative afferent pupillary defect were determined, and visual acuity was converted into logMAR units. We performed flash VEP and an orbital computed tomography scan in all patients. Results: There was a good correlation between relative afferent pupillary defect and final visual acuity (r = −0.83), and better initial visual acuity could predict better final visual acuity (r = 0.92). According to findings from flash VEP parameters, there was a relationship between final visual acuity and amplitude ratio of the wave (r = 0.59) and latency ratio of the wave (r = −0.61). Neither primary visual acuity nor final visual acuity was related to the presence of orbital fractures in the orbital CT scan. Conclusion: Patients with traumatic optic neuropathy often present with severe vision loss. Flash VEP, poor initial visual acuity, and higher grade of relative afferent pupillary defect could predict final visual acuity in these patients. Presence of orbital fracture was not a predictive factor for primary visual acuity or final visual acuity. PMID:21845028

  10. Second-order bosonic Kadanoff-Baym equations for plasmon-accompanied optical absorption

    NASA Astrophysics Data System (ADS)

    Schüler, Michael; Pavlyukh, Yaroslav

    2016-03-01

    The availability of ultra-short and strong light sources opens the door for a variety of new experiments such as transient absorption, where optical properties of systems can be studied in extreme nonequilibrium situations. The nonequilibrium Green's function formalism is an efficient approach to investigate these processes theoretically. Here we apply the method to the light-matter interaction of the magnesium 2p core level accompanied by electron-plasmon interaction due to collective excitations in the conduction band. The plasmons are described as massive bosonic quasi-particle excitations, leading to a second-order equations of motion, requiring a new approach for their propagation.

  11. Dendrimers Target the Ischemic Lesion in Rodent and Primate Models of Nonarteritic Anterior Ischemic Optic Neuropathy

    PubMed Central

    Guo, Yan; Johnson, Mary A.; Mehrabian, Zara; Mishra, Manoj K.; Kannan, Rangaramanujam; Miller, Neil R.; Bernstein, Steven L.

    2016-01-01

    Introduction Polyamidoamine dendrimer nanoparticles (~ 4 nanometers) are inert polymers that can be linked to biologically active compounds. These dendrimers selectively target and accumulate in inflammatory cells upon systemic administration. Dendrimer-linked compounds enable sustained release of therapeutic compounds directly at the site of damage. The purpose of this study was to determine if dendrimers can be used to target the optic nerve (ON) ischemic lesion in our rodent and nonhuman primate models of nonarteritic anterior ischemic optic neuropathy (NAION), a disease affecting >10,000 individuals in the US annually, and for which there currently is no effective treatment. Methods NAION was induced in male Long-Evans rats (rNAION) and in one adult male rhesus monkey (pNAION) using previously described procedures. Dendrimers were covalently linked to near-infrared cyanine-5 fluorescent dye (D-Cy5) and injected both intravitreally and systemically (in the rats) or just systemically (in the monkey) to evaluate D-Cy5 tissue accumulation in the eye and optic nerve following induction of NAION. Results Following NAION induction, Cy-5 dendrimers selectively accumulated in astrocytes and circulating macrophages. Systemic dendrimer administration provided the best penetration of the ON lesion site when injected shortly after induction. Systemic administration 1 day post-induction in the pNAION model gave localization similar to that seen in the rats. Conclusions Dendrimers selectively target the ischemic ON lesion after induction of both rNAION and pNAION. Systemic nanoparticle-linked therapeutics thus may provide a powerful, targeted and safe approach to NAION treatment by providing sustained and focused treatment of the cells directly affected by ischemia. PMID:27128315

  12. The Epidemiology of Leber Hereditary Optic Neuropathy in the North East of England

    PubMed Central

    Man, P. Y. W.; Griffiths, P. G.; Brown, D. T.; Howell, N.; Turnbull, D. M.; Chinnery, P. F.

    2003-01-01

    We performed the first population-based clinical and molecular genetic study of Leber hereditary optic neuropathy (LHON) in a population of 2,173,800 individuals in the North East of England. We identified 16 genealogically unrelated families who harbor one of the three primary mitochondrial DNA (mtDNA) mutations that cause LHON. Two of these families were found to be linked genetically to a common maternal founder. A de novo mtDNA mutation (G3460A) was identified in one family. The minimum point prevalence of visual failure due to LHON within this population was 3.22 per 100,000 (95% CI 2.47–3.97 per 100,000), and the minimum point prevalence for mtDNA LHON mutations was 11.82 per 100,000 (95% CI 10.38–13.27 per 100,000). These results indicate that LHON is not rare but has a population prevalence similar to autosomally inherited neurological disorders. The majority of individuals harbored only mutant mtDNA (homoplasmy), but heteroplasmy was detected in ∼12% of individuals. Overall, however, ∼33% of families with LHON had at least one heteroplasmic individual. The high incidence of heteroplasmy in pedigrees with LHON raises the possibility that a closely related maternal relative of an index case may not harbor the mtDNA mutation, highlighting the importance of molecular genetic testing for each maternal family member seeking advice about their risks of visual failure. PMID:12518276

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

    PubMed Central

    Johns, D R; Neufeld, M J

    1993-01-01

    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 the diagnosis. A false-positive molecular genetic error has adverse consequences for the diagnosis of this maternally inherited disease. We 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%. PMID:8213820

  14. Phylogenetic Analysis of the Mitochondrial Genomes from Leber Hereditary Optic Neuropathy Pedigrees

    PubMed Central

    Howell, N.; Kubacka, I.; Halvorson, S.; Howell, B.; McCullough, D. A.; Mackey, D.

    1995-01-01

    The nucleotide sequences of the mitochondrial genomes from patients with Leber hereditary optic neuropathy (LHON) were used for phylogenetic analysis to study the origin and population history of pathogenic mitochondrial mutations. Sequences of both the coding region (8300 bp) and the more rapidly evolving noncoding control region (1300 bp) were analyzed. Patients with the primary LHON mutations at nucleotides 3460, 11,778, and 14,484 were included in this study, as were LHON patients and non-LHON controls that lacked these primary mutations; some of the subjects also carried secondary LHON mutations. The phylogenetic analyses demonstrate that primary LHON mutations arose and were fixed multiple times within the population, even for the small set of LHON patients that was analyzed in these initial studies. In contrast, the secondary LHON mutations at nucleotides 4216, 4917, and 13,708 arose once: the mitochondrial genomes that carried these secondary mutations formed a well supported phylogenetic cluster that apparently arose 60,000 to 100,000 years ago. Previous studies found secondary LHON mutations at a higher frequency among LHON patients than among control subjects. However, this finding does not prove a pathogenetic role of these mutations in LHON. Instead, the increased frequency is more likely to reflect the population genetic history of secondary mutations relative to that of primary LHON mutations. PMID:7635294

  15. MRI in Leber's hereditary optic neuropathy: the relationship to multiple sclerosis

    PubMed Central

    Matthews, Lucy; Enzinger, Christian; Fazekas, Franz; Rovira, Alex; Ciccarelli, Olga; Dotti, Maria Teresa; Filippi, Massimo; Frederiksen, Jette L; Giorgio, Antonio; Küker, Wilhelm; Lukas, Carsten; Rocca, Maria A; De Stefano, Nicola; Toosy, Ahmed; Yousry, Tarek; Palace, Jacqueline

    2015-01-01

    Background Leber's hereditary optic neuropathy (LHON) and a multiple sclerosis (MS)-like illness appear to coexist 50 times more frequently than would be expected by chance. This association of LHON and MS (LMS) raises an important question about whether there could be a common pathophysiological mechanism involving mitochondrial dysfunction. Objective The primary aim was to define MRI features of LMS and LHON, and to assess the proportions of individuals displaying features typical of MS. Secondarily, we investigated the effect of gender on the risk of developing white matter lesions in the context of LHON. Methods A blinded standardised review of conventional brain MRIs of 30 patients with MS, 31 patients with LHON and 11 patients with LMS was conducted by three independent experts in the field. MS-like MRI features were assessed. Results All patients with LMS and 26% of patients with LHON had white matter lesions. Of these, all patients with LMS and 25% with LHON were found to have an MRI appearance typical of MS. Female patients with LHON had a significantly greater risk of having white matter lesions consistent with MS compared with male patients (relative risk 8.3). Conclusions A blinded review of conventional brain MRIs shows that patients with LMS have a scan appearance indistinguishable from MS. Mitochondrial dysfunction could be a common pathophysiological pathway in the formation of white matter lesions. There appears to be a strong female influence on the radiological appearance as well as clinical development of MS in patients with LHON. PMID:25053773

  16. Obstructive sleep apnea syndrome and non-arteritic anterior ischemic optic neuropathy: a case control study

    PubMed Central

    Ghaleh Bandi, Mir Farhad; Naserbakht, Morteza; Tabasi, Abdolreza; Marghaiezadeh, Azin; Riazee Esfahani, Mohammad; Golzarian, Zohre

    2015-01-01

    Background: Sleep apnea is temporary cessation or absence of breathing during sleep. Significant increase in blood pressure is clinically seen in apneic episodes. The aim of this study was to examine sleep apnea syndrome as a risk factor for non- arthritic anterior ischemic optic neuropathy (NAION) in a case control study. Methods: Nineteen NAION patients (9 men and 10 women) and 31 age and sex matched control participants (18 men and 13 women) were evaluated for obstructive sleep apnea syndrome (OSAS). Full night polysomnography was performed and proportion of OSAS was compared between the NAION patients and the control group. Other risk factors for NAION such as hypertension, diabetes, hyperlipidemia, ischemic heart disease and tobacco consumption were also evaluated. Chi square test and independent samples t-test were used for statistical analysis. Results: OF the 19 NAION patients, 18 (95%) had OSAS, and of the control group 13 (41.9%) had OSAS. The frequency of OSAS was significantly higher among NAION patients compared to the controls (p< 0.001). The Mean Respiratory Disturbance Index (RDI) was 37.65/h SD= 37.61/h in NAION patients and it was 15.05/h SD= 11.97/h (p= 0.018) in controls. The frequency of diabetes and hypertension was significantly higher in the NAION patients than in controls. Conclusion: based on the results of this study, it seems that there is an association between NAION and OSAS. PMID:26913263

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

    SciTech Connect

    Johns, D.R. ); Neufeld, M.J. )

    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.

  18. Leber's hereditary optic neuropathy is associated with mitochondrial ND1 T3394C mutation

    SciTech Connect

    Liang, Min; Guan, Minqiang; Zhao, Fuxing; Zhou, Xiangtian; Yuan, Meixia; Tong, Yi; Yang, Li; Wei, Qi-Ping; Sun, Yan-Hong; Lu, Fan; Qu, Jia; 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.

  19. Leber's hereditary optic neuropathy is associated with mitochondrial ND6 T14502C mutation

    SciTech Connect

    Zhao, Fuxin; Guan, Minqiang; Zhou, Xiangtian; Yuan, Meixia; Liang, Ming; Liu, Qi; Liu, Yan; Zhang, Yongmei; Yang, Li; Tong, Yi; Wei, Qi-Ping; Sun, Yan-Hong; Qu, Jia; 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.

  20. Optic neuropathy in a patient with vitamin B12 deficiency: a case report.

    PubMed

    Areekul, S; Roongpisuthipong, C; Churdchu, K; Thanomsak, W

    1992-12-01

    A 19-year-old man presented with blurring of vision for 2 weeks. He also complained of anorexia with weight loss during the past 4 months. Eight years ago, his small bowel from midportion of the jejunum, ileum, ascending colon and transverse colon were resected because of gangrene. He gave no history of exposure to tobacco, alcohol or other toxins. The bone marrow aspiration showed hypocellular with panhypoplasia. Serum vitamin B12 level was low while serum and red cell folate were within normal limits. His visual acuity was 5/200 in both eyes with centrocecal scotomas in both eyes. Other neurologic and ophthalmic examinations were found to be normal. The patient was given intramuscular injections of 1,000 micrograms of cyanocobalamin. Four months later, his visual acuity improved, serum vitamin B12 level and the bone marrow returned to be normal. This is a frank case of optic neuropathy in a patient with vitamin B12 deficiency due to a massive small bowel resection. PMID:1308541

  1. Mean Platelet Volume in Patients with Nonarteritic Anterior Ischemic Optic Neuropathy

    PubMed Central

    Şahin, Muhammed; Şahin, Alparslan; Elbey, Bilal; Yüksel, Harun; Türkcü, Fatih Mehmet; Cingü, Abdullah Kürşat

    2016-01-01

    Objective. We aimed to investigate the mean platelet volume (MPV) of the patients with nonarteritic anterior ischemic optic neuropathy (NAION). Methods. The medical records of 46 patients with the diagnosis of NAION and 90 control subjects were retrospectively evaluated. All participants underwent complete ocular examination including intraocular pressure (IOP) measurement. Hematocrit, MPV, hemoglobin, and platelet levels of the patients with NAION were compared with those of control subjects. Results. There was no significant difference between the groups in platelet counts (p = 0.76). NAION group had significantly higher MPV values (8.25 ± 1.26 fL) than that of control subjects (7.64 ± 1.01 fL) (p < 0.001). Multivariate logistic regression analysis showed that MPV is an independent predictor of NAION (odds ratio = 1.61; 95% confidence interval (CI) = 1.13–2.28; p = 0.007). The mean IOP was significantly higher in NAION group (p < 0.001). IOP was also found as an independent predictor of NAION according to the regression analysis (OR = 1.27; 95% CI = 1.08–1.48; p = 0.003). Conclusion. Our results demonstrated that the MPV values were significantly higher in NAION patients, suggesting that larger platelets may contribute to the pathogenesis of the NAION. PMID:26966556

  2. Simultaneous Bilateral Nonarteritic Anterior Ischemic Optic Neuropathy in a Patient with a History of Diffuse Large B-Cell Lymphoma

    PubMed Central

    Lazar, David B.; Lemor, Daniel; Brown, Archie; Nussdorf, Jonathan D.

    2015-01-01

    Background Nonarteritic anterior ischemic optic neuropathy (NAAION) has a poorly understood etiology, and the onset of simultaneous bilateral NAAION in a patient <50 years without identifiable systemic risk factors is rare. Case Report We present the case of a patient with acute painless monocular vision loss and bilateral optic disc edema who subsequently developed painless vision loss in the fellow eye. The patient's history was significant for diffuse large B-cell lymphoma, and our pressing diagnostic concern was to determine if his vision loss and bilateral optic disc changes represented lymphomatous infiltrates. A complete ocular exam demonstrated findings consistent with simultaneous bilateral NAAION. After an extensive systemic workup for malignancy with central nervous system involvement, vasculitis, and other entities associated with NAAION, we determined that the patient's primary risk factor for developing bilateral ischemic optic neuropathies was his crowded optic discs. Conclusion This case supports the hypothesis that a crowded optic disc is a sufficient primary risk factor for developing NAAION. PMID:25829891

  3. Functional rescue of experimental ischemic optic neuropathy with αB-crystallin

    PubMed Central

    Pangratz-Fuehrer, S; Kaur, K; Ousman, S S; Steinman, L; Liao, Y J

    2011-01-01

    Purpose Anterior ischemic optic neuropathy (AION) is an important cause of acute vision loss in adults, and there is no effective treatment. We studied early changes following experimental AION and tested the benefit of a potential treatment. Materials and Methods We induced experimental AION in adult mice and tested the effects of short-term (daily for 3 days) and long-term (every other day for 3 weeks) αB-crystallin (αBC) treatment using histological and serial intracranial flash visual evoked potential recordings. Results One day after experimental AION, there was swelling at the optic nerve (ON) head and increased expression of αBC, a small heat shock protein important in ischemia and inflammation. This upregulation coincided with microglial and astrocytic activation. Our hypothesis was that αBC may be part of the endogenous protective mechanism against injury, thus we tested the effects of αBC on experimental AION. Daily intraveneous or intravitreal αBC injections did not improve visual evoked potential amplitude or latency at days 1–2. However, αBC treatment decreased swelling and dampened the microglial and astrocytic activation on day 3. Longer treatment with intravenous αBC led to acceleration of visual evoked potential latency over 3 weeks, without improving amplitude. This latency acceleration did not correlate with increased retinal ganglion cell survival but did correlate with complete rescue of the ON oligodendrocytes, which are important for myelination. Conclusions We identified αBC as an early marker following experimental AION. Treatment with αBC enhanced this endogenous, post-ischemic response by decreasing microglial activation and promoting ON oligodendrocyte survival. PMID:21475310

  4. Orbital Volumetry in Graves' Orbitopathy: Muscle and Fat Involvement in relation to Dysthyroid Optic Neuropathy.

    PubMed

    Al-Bakri, Moug; Rasmussen, Ase Krogh; Thomsen, Carsten; Toft, Peter Bjerre

    2014-01-01

    Purpose. We wanted to investigate the relative significance of fat and muscle enlargement in the development of dysthyroid optic neuropathy (DON) in Graves' orbitopathy (GO). Methods. Preoperative coronal CT scans of 13 patients with and without DON who subsequently underwent orbital decompression were retrospectively analyzed. Thirteen patients imaged for unilateral orbital fractures served as controls. Results. The retrobulbar muscle volume was 2.1 ± 0.5 cm(3) (mean ± SD) in controls, 4.3 ± 1.5 cm(3) in GO without DON, and 4.7 ± 1.7 cm(3) in GO with DON. The retrobulbar fat volume was 5.4 ± 1.6 cm(3) in controls, 8.7 ± 8.0 cm(3) in GO without DON, and 9.4 ± 3.1 cm(3) in GO with DON. The muscle and fat volumes were higher in patients with GO than in controls (P < 0.001), but the volumes in orbits with and without DON were not significantly different. The volume of the optic nerve were similar in the 3 groups. The number of apical, coronal 2 mm thick slices with no fat was 2.9 ± 0.9 in normal orbits, it was 4.1 ± 1.0 in GO orbits without DON and 5.3 ± 0.8 in GO orbits with DON (P = 0.007). Conclusion. Apical muscle enlargement may be more important than orbital fat enlargement in the development of DON. However, the fact that apical crowding and muscle enlargement also occur in orbits without DON suggests that other factors also play a role in the development of DON. PMID:25101183

  5. Leber hereditary optic neuropathy: identification of the same mitochondrial ND1 mutation in six pedigrees.

    PubMed Central

    Howell, N; Bindoff, L A; McCullough, D A; Kubacka, I; Poulton, J; Mackey, D; Taylor, L; Turnbull, D M

    1991-01-01

    Biochemical and molecular genetic evidence is presented that in six independent pedigrees the development of Leber hereditary optic neuropathy (LHON) is due to the same primary mutation in the mitochondrial ND1 gene. A LHON family from the Newcastle area of Great Britain was analyzed in depth to determine the mitochondrial genetic etiology of their disease. Biochemical assays of mitochondrial electron transport in organelles isolated from the platelet/white-blood-cell fraction have established that the members of this family have a substantial and specific lowering of flux through complex I (NADH-ubiquinone oxidoreductase). To determine the site of the primary mitochondrial gene mutation in this pedigree, all seven mitochondrial complex I genes were sequenced, in their entirety, from two family members. The primary mutation was identified as a homoplasmic transition at nucleotide 3460, which results in the substitution of threonine for alanine at position 52 of the ND1 protein. This residue occurs within a very highly conserved hydrophilic loop, is invariantly alanine or glycine in all ND1 proteins, and is adjacent to an invariant aspartic acid residue. This is only the second instance in which both a biochemical abnormality and a mitochondrial gene mutation have been identified in an LHON pedigree. The sequence analysis of the ND81 gene was extended to a further 11, unrelated LHON pedigrees that had been screened previously and found not to carry the mitochondrial ND4/R340H mutation. The ND1/A52T mutation at nucleotide 3460 was found in five of these 11 pedigrees. In contrast, this sequence change was not found in any of the 47 non-LHON controls. The possible role of secondary complex I mutations in the etiology of LHON is also addressed in these studies. PMID:1928099

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

    SciTech Connect

    Leavitt, Jacqueline A.; Stafford, Scott L.; Link, Michael J.; Pollock, Bruce E.

    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.

  7. Nonarteritic anterior ischemic optic neuropathy: associations with homozygosity for the C677T methylenetetrahydrofolate reductase mutation.

    PubMed

    Glueck, Charles J; Wang, Ping; Bell, Howard; Rangaraj, Venkat; Goldenberg, Naila

    2004-03-01

    The association between nonarteritic anterior ischemic optic neuropathy (NAION) and coagulation disorders was prospectively assessed at least 3 months after the occurrence of ocular vascular events in 12 white patients in an outpatient clinical research center. Two community-based ophthalmologists evaluated the 12 NAION patients in the consecutive order of their referral. Polymerase chain reaction-complementary DNA assays of gene mutations associated with coagulation disorders and serologic coagulation measurements in study patients were compared with those in 36 healthy, normal race-, sex-, and age-matched controls, with 3 controls matched for each case. Of the 12 patients, 4 men and 8 women (mean age 62 +/- 15 years, 3 of them 55 years or older), 8 had unilateral NAION (bilateral in 4). The 12 patients with NAION were more likely than controls to demonstrate homozygosity for the methylenetetrahydrofolate reductase (MTHFR) C677T mutation (50% vs 11 %; Fisher's P =.009, with the likelihood of a type I error quite small, 0.9%). Our sample size had a power of 80% to detect this case-control difference in C677T MTHFR homozygosity at an alpha value of.05. Of the 12 NAION patients, 7 (58%) had at least 1 gene mutation in the C677T MTHFR, G1691A V Leiden, or G20210A prothrombin gene, compared with 5 of 36 controls (14%) (chi(2) = 9.48, P =. 002, with the likelihood of a type I error quite small, 0.2%). Our sample size had a power of 85% to detect this case-control difference at alpha =. 05. Of the 8 women with NAION, 5 (63%) first experienced the condition while taking hormone replacement therapy (n = 4) or during pregnancy (n = 1), with superposition of estrogen-induced thrombophilia on heritable thrombophilia and hypofibrinolysis. Confirmation of a causal relationship between coagulation disorders and NAION should facilitate its prevention and treatment and help protect against thrombi in other vascular beds. PMID:15007309

  8. Neuromyelitis optica (Devic's syndrome): no association with the primary mitochondrial DNA mutations found in Leber hereditary optic neuropathy.

    PubMed Central

    Cock, H; Mandler, R; Ahmed, W; Schapira, A H

    1997-01-01

    Devic's neuromyelitis optica is a rare syndrome characterised by the combination of acute or subacute optic neuritis and transverse myelitis, in some cases considered to be a variant of multiple sclerosis. Mutations of mitochondrial DNA (mtDNA) associated with Leber hereditary optic neuropathy (LHON) have been identified in some patients with multiple sclerosis in whom optic neuritis is a prominent early feature. Using restriction enzyme digestion of mtDNA products amplified by the polymerase chain reaction, the primary LHON mtDNA mutations at positions 3460 bp, 11,778 bp, and 14,484 bp have been excluded in four women with Devic's neuromyelitis optica. A mutation at 4160 bp associated in some LHON families with more widespread neurological disease was also not detected. It is concluded that the primary mtDNA mutations currently associated with LHON are not responsible for the prominence of optic nerve disease in Devic's neuromyelitis optica. PMID:9010406

  9. Interaction of heritable and estrogen-induced thrombophilia: possible etiologies for ischemic optic neuropathy and ischemic stroke.

    PubMed

    Glueck, C J; Fontaine, R N; Wang, P

    2001-02-01

    Our specific aim was to assess how thrombophilic exogenous estrogens interacted with heritable thrombophilias leading to non-arteritic ischemic optic neuropathy (NAION) and ischemic stroke. Coagulation measures were performed in a 74 year old patient and her immediate family. The proband had a 47 year history of 9 previous thrombotic episodes, and developed unilateral NAION 4 years after starting estrogen replacement therapy (ERT). The proband was heterozygous for two thrombophilic gene mutations (G20210A prothrombin gene, platelet glycoprotein IIIa P1A1/A2 polymorphism), and homozygous for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene. Of 238 normal controls, none had these 3 gene mutations together. The proband's mother and brother had deep venous thrombosis (DVT). The proband's brother, sister, nephew, daughter, and two granddaughters were homozygous for the C677T MTHFR mutation. The proband's brother was heterozygous for the G20210A prothrombin gene mutation. The proband's niece was heterozygous for the G20210A prothrombin gene mutation, homozygous for the C677T MTHFR mutation, homozygous for the hypofibrinolytic 4G polymorphism of the plasminogen activator inhibitor-1 (PAI-1) gene, and heterozygous for the platelet glycoprotein IIIa P1A1/A2 polymorphism. Of 238 normal controls, none had the niece's combination of 4 gene mutations. When ERT-mediated thrombophilia was superimposed on the proband's heritable thrombophilias, unilateral ischemic optic neuropathy developed, her tenth thrombotic event over a 5 decade period. When estrogen-progestin oral contraceptives were given to the proband's niece, she had an ischemic stroke at age 22. Exogenous estrogen-mediated thrombophilia superimposed on heritable thrombophilia and hypofibrinolysis is associated with arterial and venous thrombi, and appears to be a preventable, and potentially reversible etiology for ischemic optic neuropathy and ischemic stroke. PMID:11246543

  10. Assessment of retinal ganglion cell damage in glaucomatous optic neuropathy: Axon transport, injury and soma loss.

    PubMed

    Nuschke, Andrea C; Farrell, Spring R; Levesque, Julie M; Chauhan, Balwantray C

    2015-12-01

    Glaucoma is a disease characterized by progressive axonal pathology and death of retinal ganglion cells (RGCs), which causes structural changes in the optic nerve head and irreversible vision loss. Several experimental models of glaucomatous optic neuropathy (GON) have been developed, primarily in non-human primates and, more recently and commonly, in rodents. These models provide important research tools to study the mechanisms underlying glaucomatous damage. Moreover, experimental GON provides the ability to quantify and monitor risk factors leading to RGC loss such as the level of intraocular pressure, axonal health and the RGC population. Using these experimental models we are able to gain a better understanding of GON, which allows for the development of potential neuroprotective strategies. Here we review the advantages and disadvantages of the relevant and most often utilized methods for evaluating axonal degeneration and RGC loss in GON. Axonal pathology in GON includes functional disruption of axonal transport (AT) and structural degeneration. Horseradish peroxidase (HRP), rhodamine-B-isothiocyanate (RITC) and cholera toxin-B (CTB) fluorescent conjugates have proven to be effective reporters of AT. Also, immunohistochemistry (IHC) for endogenous AT-associated proteins is often used as an indicator of AT function. Similarly, structural degeneration of axons in GON can be investigated via changes in the activity and expression of key axonal enzymes and structural proteins. Assessment of axonal degeneration can be measured by direct quantification of axons, qualitative grading, or a combination of both methods. RGC loss is the most frequently quantified variable in studies of experimental GON. Retrograde tracers can be used to quantify RGC populations in rodents via application to the superior colliculus (SC). In addition, in situ IHC for RGC-specific proteins is a common method of RGC quantification used in many studies. Recently, transgenic mouse models

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

    PubMed Central

    Lee, Ju-Yeun; Cho, Kyuyeon; Park, Kyung-Ah; Oh, Sei Yeul

    2016-01-01

    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

  12. A “Fille du Roy” Introduced the T14484C Leber Hereditary Optic Neuropathy Mutation in French Canadians

    PubMed Central

    Laberge, Anne-Marie; Jomphe, Michèle; Houde, Louis; Vézina, Hélène; Tremblay, Marc; Desjardins, Bertrand; Labuda, Damian; St-Hilaire, Marc; Macmillan, Carol; Shoubridge, Eric A.; Brais, Bernard

    2005-01-01

    The predominance of the T14484C mutation in French Canadians with Leber hereditary optic neuropathy is due to a founder effect. By use of genealogical reconstructions of maternal lineages, a woman married in Quebec City in 1669 is identified as the shared female ancestor for 11 of 13 affected individuals, who were previously not known to be related. These individuals carry identical mitochondrial haplogroups. The current geographic distribution of French Canadian cases overlaps with that of the founder’s female descendants in 1800. This is the first example of genealogical reconstruction to identify the introduction of a mitochondrial mutation by a woman in a founder population. PMID:15954041

  13. Peripheral Neuropathy

    MedlinePlus

    ... 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 ...

  14. Alcoholic neuropathy

    MedlinePlus

    Neuropathy - alcoholic; Alcoholic polyneuropathy ... The exact cause of alcoholic neuropathy is unknown. It likely includes both a direct poisoning of the nerve by the alcohol and the effect of poor nutrition ...

  15. Neuropathy Tests

    MedlinePlus

    ... be limited. Home Visit Global Sites Search Help? Neuropathy Share this page: Was this page helpful? Overview | ... of testing are: To diagnose the presence of neuropathy and distinguish it from other conditions that may ...

  16. Risk of Nonarteritic Anterior Ischemic Optic Neuropathy Following End-Stage Renal Disease.

    PubMed

    Chang, Yuh-Shin; Weng, Shih-Feng; Chang, Chun; Wang, Jhi-Joung; Su, Shih-Bin; Huang, Chien-Cheng; Wang, Jiu-Yao; Jan, Ren-Long

    2016-03-01

    To investigate the risk of nonarteritic anterior ischemic optic neuropathy (NAION) following end-stage renal disease (ESRD).A retrospective, nationwide, matched cohort study.ESRD patients identified by the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 585.The study cohort included 93,804 ESRD patients registered with the Taiwan National Health Insurance Research Database between January 2000 and December 2009. An age- and sex-matched control group comprised 93,804 patients (case:control = 1:1) selected from the Taiwan Longitudinal Health Insurance Database 2000. Information for each patient was collected from the index date until December 2011. The incidence and risk of NAION were compared between the ESRD and control groups. The adjusted hazard ratio (HR) for NAION after adjustment for potential confounders was obtained by a Cox proportional hazard regression analysis. A Kaplan-Meier analysis was used to calculate the cumulative incidence rate of NAION.The incidence of NAION following ESRD.In total, 133 ESRD patients (0.14%) and 51 controls (0.05%) had NAION (P < 0.001) during the follow-up period, leading to a significantly elevated risk of NAION in the ESRD patients compared with the controls (incidence rate ratio = 3.14, 95% confidence interval [CI] = 2.11-4.67). After adjustment for potential confounders including diabetes mellitus, hypertension, hypotension, hyperlipidemia, and 2-way interaction terms between any 2 factors, ESRD patients were 3.12 times more likely to develop NAION than non-ESRD patients in the full cohort (adjusted HR = 3.12, 95% CI = 2.10-4.64). Additionally, patients with hypertension and hyperlipidemia showed higher incidence rates of NAION in the ESRD group compared with the controls: 2.31 (95% CI = 1.40-3.82) for hypertension and 2.72 (95% CI = 1.14-6.50) for hyperlipidemia.ESRD increased the risk of NAION, which is an interdisciplinary emergency. Close

  17. Levodopa-carbidopa may improve vision loss in indirect traumatic optic neuropathy.

    PubMed

    Razeghinejad, M Reza; Rahat, Feisal; Bagheri, Mohammadhadi

    2010-10-01

    To compare the effect of levodopa-carbidopa on the visual outcome of patients with indirect traumatic optic neuropathy (ITON), this randomized, double-blind, placebo-controlled study was conducted on 32 patients with ITON within 6 days after trauma. Patients underwent a complete ocular examination, pattern visual evoked potential (PVEP) testing, and high-resolution orbital computed tomography (CT) scanning. All patients received high-dose intravenous methylprednisolone, and levodopa was also administered to the levodopa group. The main outcome measures were best corrected visual acuity and PVEP results at the last-completed examination. The study was completed on 16 patients in the levodopa group and 10 patients in the placebo group because the others were lost to follow-up. There were no statistically significant differences for age, sex, involved eye, ocular and CT scan findings, pretreatment visual acuity, frequency of recordable PVEPs, and follow-up. In the levodopa group the visual acuity improved significantly after treatment (p = 0.009), but not in the placebo group (p = 0.34). After treatment the visual acuity in the levodopa group was 2.1 ± 2.1, and in the placebo group was 3.9 ± 1.2 (p = 0.008). In those who had visual acuity less than or equal to figure count, significant improvement in visual acuity was observed in the levodopa group (p = 0.03), but not in the placebo group (p = 0.34). However, the final visual acuity in these patients was comparable after treatment (p = 0.21). Nine patients (56.2%) in the levodopa group, and 1 (10%) in the placebo group, experienced improvement in visual acuity (p = 0.02). The frequency of unrecordable PVEPs were comparable in both groups (p = 0.09). Patients treated with levodopa within 6 days of onset of ITON were more likely to experience improvement in visual acuity than those in the placebo group. PMID:20649490

  18. An example of Leber hereditary optic neuropathy not involving a mutation in the mitochondrial ND4 gene.

    PubMed Central

    Howell, N; McCullough, D

    1990-01-01

    A large Australian family afflicted with Leber's Hereditary Optic Neuropathy (LHON) is analyzed at the nucleotide sequence level in this report. Biochemical assays of platelet mitochondria isolated from members of this family have demonstrated a significant decrease in the specific activity of Complex I (NADH-ubiquinol oxidoreductase) of the electron transport chain. It is shown here, however, that neither this biochemical lesion nor the optic neuropathy are due to the mutation at nucleotide position 11,778 of the mitochondrial ND4 gene first identified by Wallace et al. in several LHON pedigrees. Furthermore, extensive DNA sequencing studies reveal no candidate mutations within the mitochondrial ND3 gene, the ND4L/ND4 genes, or the contiguous tRNA genes. These studies provide the first direct evidence that not all LHON lineages--even those associated with a biochemical defect in mitochondrial respiratory chain Complex I--carry a mutation in the ND4 gene. Members of the Australian LHON family exhibit neurological abnormalities in addition to the well-characterized ophthalmological changes. It is hypothesized that LHON may be a syndrome or set of related diseases in which the clinical abnormalities are a function, at least in part, of the mitochondrial Complex I gene in which the proximate mutation occurs. Images Figure 2 PMID:2121024

  19. Quantum walks accompanied by spin flipping in one-dimensional optical lattices

    NASA Astrophysics Data System (ADS)

    Wang, Li; Liu, Na; Chen, Shu; Zhang, Yunbo

    2015-11-01

    We investigate continuous-time quantum walks of two fermionic atoms loaded in one-dimensional optical lattices with on-site interaction and subjected to a Zeeman field. The quantum walks are accompanied by spin-flipping processes. We calculate the time-dependent density distributions of the two fermions with opposite spins which are initially positioned at the center site by means of an exact numerical method. Besides the usual fast linear expansion behavior, we find an interesting spin-flipping-induced localization in the time evolution of density distributions. We show that the fast linear expansion behavior can be restored by simply ramping up the Zeeman field or further increasing the spin-flipping strength. The intrinsic origin of this exotic phenomenon is attributed to the emergence of a flat band in the single-particle spectrum of the system. Furthermore, we investigate the effect of on-site interaction on the dynamics of the quantum walkers. The two-particle correlations are calculated and the signal of localization is also shown therein. A simple potential experimental application of this interesting phenomenon is proposed.

  20. Axonal degeneration, regeneration and ganglion cell death in a rodent model of anterior ischemic optic neuropathy (rAION).

    PubMed

    Zhang, Cheng; Guo, Yan; Slater, Bernard J; Miller, Neil R; Bernstein, Steven L

    2010-08-01

    Using laser-induced photoactivation of intravenously administered rose Bengal in rats, we generated an ischemic infarction of the intrascleral portion of the optic nerve (ON) comparable to that which occurs in humans to investigate optic nerve axon degenerative events following optic nerve infarct and the potential for axon re-growth. Animals were euthanized at different times post infarct. Axon degeneration was evaluated with SMI312 immunolabeling, and GAP-43 immunostaining was used to identify axon regeneration. Terminal dUTP nick end labeling (TUNEL) was used to evaluate retinal ganglion cell (RGC) death. There was significant axon structural disruptinot ion at the anterior intrascleral portion of the ON by 3d post-infarct, extending to the posterior ON by 7d post-stroke. Destruction of normal axon structure and massive loss of axon fibers occurred by 2 weeks. GAP-43 immunoreactivity occurred in the anterior ON by 7d post-infarct, lasting 3-4 weeks, without extension past the primary ischemic lesion. TUNEL-positive cells in the RGC layer appeared by 7d post-insult. These results indicate that following induction of ischemic optic neuropathy, significant axon damage occurs by 3d post-infarct, with later neuronal death. Post-stroke adult rat retinal ganglion cells attempt to regenerate their axons, but this effort is restricted to the unmyelinated region of the anterior ON. These responses are important in understanding pathologic process that underlies human non-arteritic anterior ischemic optic neuropathy (NAION) and may guide both the appropriate treatment of NAION and the window of opportunity for such treatment. PMID:20621651

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

    SciTech Connect

    Obermaier-Kusser, B.; Schubring, S.; Paprotta, A.; Meitinger, T.; Jaksch, M.; Gerbitz, K.D.; Lorenz, B.; Zerres, K.; Meire, F.; Cochaux, P.

    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.

  2. Lack of differences among mitochondrial DNA in family members with Leber's hereditary optic neuropathy and differing visual outcomes.

    PubMed

    Mashima, Y; Hiida, Y; Oguchi, Y

    1995-03-01

    Investigation of a maternal family of three generations of Leber's hereditary optic neuropathy (LHON) showed four affected and three unaffected individuals. Two of the four patients had recovered near-normal vision, one spontaneously, and one following treatment with idebenone, a quinol compound. One patient whose visual impairment persisted was a heavy consumer of alcohol and tobacco. Molecular genetic analysis of 12 known primary or secondary mutations in mitochondrial DNA (mtDNA) associated with LHON revealed only the 11778 mutation in a homoplasmic fashion with no secondary mutations. The variations in clinical outcome thus could not be explained by synergistically interacting secondary mutations in mtDNA. Environmental factors may play an etiologic role in the development of optic atrophy. PMID:7780566

  3. High resolution magnetic resonance imaging of the anterior visual pathway in patients with optic neuropathies using fast spin echo and phased array local coils.

    PubMed Central

    Gass, A; Barker, G J; MacManus, D; Sanders, M; Riordan-Eva, P; Tofts, P S; Thorpe, J; McDonald, W I; Moseley, I F; Miller, D H

    1995-01-01

    High resolution MRI of the anterior visual pathways was evaluated using frequency selective fat suppressed fast spin echo (FSE) sequences in conjunction with phased array local coils in patients with optic neuropathies. Fifteen normal controls and 57 patients were examined. Coronal T2 weighted fat suppressed FSE images were obtained in 11 minutes with an in plane resolution of 0.39 x 0.39 mm. The optic nerve and its sheath containing CSF were clearly differentiated. Central retinal vessels were often visible. In demyelinating optic neuritis and in anterior ischaemic optic neuropathy high signal within the nerve was readily delineated. Meningiomas and gliomas involving the optic nerve were precisely visualised both in the orbit and intracranially. Extrinsic compression of the optic nerves was readily visualised in carotid artery ectasia and dysthyroid eye disease. Enlarged subarachnoid spaces around the optic nerves were demonstrated in benign intracranial hypertension. High resolution MRI of the anterior visual pathway represents an advance in the diagnosis and management of patients presenting with optic neuropathy. Images PMID:7745403

  4. Evidence for Detrimental Cross Interactions between Reactive Oxygen and Nitrogen Species in Leber's Hereditary Optic Neuropathy Cells

    PubMed Central

    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

  5. A variant of Leber hereditary optic neuropathy characterized by recovery of vision and by an unusual mitochondrial genetic etiology.

    PubMed Central

    Mackey, D; Howell, N

    1992-01-01

    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 ophthalmological 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 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. PMID:1463007

  6. Measurement of Systemic Mitochondrial Function in Advanced Primary Open-Angle Glaucoma and Leber Hereditary Optic Neuropathy

    PubMed Central

    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

  7. A variant of Leber hereditary optic neuropathy characterized by recovery of vision and by an unusual mitochondrial genetic etiology

    SciTech Connect

    Mackey, D. ); Howell, N. )

    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.

  8. [New insights into the pathogenesis of glaucomatous optic neuropathy and refinement of the objective assessment of its functional damage].

    PubMed

    Nakamura, Makoto

    2012-03-01

    Glaucomatous optic neuropathy is a primary pathological condition responsible for visual dysfunction due to glaucoma. However, how intraocular pressure and other risk factors lead to glaucomatous optic neuropathy is not fully understood. Given that static or kinetic visual field tests for evaluating visual dysfunction in glaucomatous optic neuropathy are a subjective assessments based on a psychophysical principle, the development of a tool for objective assessment of the visual field is needed. In this study, we attempt to elucidate the pathophysiology of glaucomatous optic neuropathy and to refine a modality for the objective assessment of the visual dysfunction due to it. Aquaporin (AQP) water channels are located primarily in the plasma membrane. These proteins form either a homo- or hetero-tetramer and allow water to cross the plasma membrane bi-directionally. The transmembrane water movement through AQPs is critically involved in the maintenance of normal neuronal activity. Among the 13 isoforms indentified so far, AQP-4 is known to be expressed in the retrobulbar portion of the optic nerve. However, the optic nerve head, the primary pathological site of glaucomatous optic neuropathy, reportedly does not express AQP-4. We found that in control rats, astrocytes throughout the optic nerve express AQP-9. The chronic elevation of intraocular pressure due to cauterization of three episcleral veins substantially reduced both gene expression and immunoreactivity of AQP-9, whereas it did not change the AQP-4 gene or protein expression in the retrobulbar portion of the optic nerve. These findings are implicated in the chronic elevation of intraocular pressure in astrocytes. Similar findings were also observed in the eyes of a monkey with angle-laser-induced ocular hypertension and of a human with primary open-angle glaucoma. AQP-9 was also expressed in the cell bodies of retinal ganglion cells in control rats and its expression was significantly reduced in the eyes of

  9. Diabetic Neuropathies

    PubMed Central

    Russell, James W.; Zilliox, Lindsay A.

    2014-01-01

    Purpose of Review: This article provides an overview for understanding the diagnosis, pathogenesis, and management of diabetic neuropathy. Recent Findings: New information about the pathogenesis of diabetic neuropathy continues to emerge, which will lead to identifying new drug targets. It is clear that the natural history of diabetic neuropathy is changing and the rate of progression is slowing. This is likely because of a combination of earlier diagnosis, improved glycemic management, and improved control of related complications such as hyperlipidemia and hypertension. Early diagnosis is critical, and small fiber neuropathy or subclinical diabetic neuropathy may be reversed or significantly improved with appropriate intervention. The American Academy of Neurology recently published guidelines for the treatment of painful diabetic neuropathy. Summary: Diabetic neuropathy is common and can present with varied clinical presentations discussed in this article. Although treatment currently focuses on pain management, attention should be paid to potential risk factors for neuropathy. For example, glycemic control, hyperlipidemia, and hypertension should be managed with diet, exercise, and medications. Class I or II clinical studies indicate that pregabalin, duloxetine, amitriptyline, gabapentin, and opioids are effective in the management of diabetic neuropathic pain. PMID:25299279

  10. Differences between Non-arteritic Anterior Ischemic Optic Neuropathy and Open Angle Glaucoma with Altitudinal Visual Field Defect

    PubMed Central

    Han, Sangyoun; Jung, Jong Jin

    2015-01-01

    Purpose To investigate the differences in retinal nerve fiber layer (RNFL) change and optic nerve head parameters between non-arteritic anterior ischemic optic neuropathy (NAION) and open angle glaucoma (OAG) with altitudinal visual field defect. Methods Seventeen NAION patients and 26 OAG patients were enrolled prospectively. The standard visual field indices (mean deviation, pattern standard deviation) were obtained from the Humphrey visual field test and differences between the two groups were analyzed. Cirrus HD-OCT parameters were used, including optic disc head analysis, average RNFL thickness, and RNFL thickness of each quadrant. Results The mean deviation and pattern standard deviation were not significantly different between the groups. In the affected eye, although the disc area was similar between the two groups (2.00 ± 0.32 and 1.99 ± 0.33 mm2, p = 0.586), the rim area of the OAG group was smaller than that of the NAION group (1.26 ± 0.56 and 0.61 ± 0.15 mm2, respectively, p < 0.001). RNFL asymmetry was not different between the two groups (p = 0.265), but the inferior RNFL thickness of both the affected and unaffected eyes were less in the OAG group than in the NAION group. In the analysis of optic disc morphology, both affected and unaffected eyes showed significant differences between two groups. Conclusions To differentiate NAION from OAG in eyes with altitudinal visual field defects, optic disc head analysis of not only the affected eye, but also the unaffected eye, by using spectral domain optical coherence tomography may be helpful. PMID:26635459

  11. Peripapillary Retinal Nerve Fiber Layer Swelling Predicts Peripapillary Atrophy in a Primate Model of Nonarteritic Anterior Ischemic Optic Neuropathy

    PubMed Central

    Johnson, Mary A.; Miller, Neil R.; Nolan, Theresa; Bernstein, Steven L.

    2016-01-01

    Purpose To determine the relationship between peripapillary retinal nerve fiber layer (PRNFL) swelling and eventual PRNFL atrophy, and between PRNFL swelling/atrophy and neural function, in a nonhuman primate model of nonarteritic anterior ischemic optic neuropathy (pNAION). Methods pNAION was induced in five normal, adult male rhesus monkeys by laser activation of intravenously injected rose bengal at the optic nerve head. Spectral-domain optical coherence tomography measurements of the PRNFL were performed at baseline; 1 day; 1, 2, and 4 weeks; and several later times over a period of an additional 2 to 3 months. Simultaneous pattern-reversal electroretinograms (PERGs) and visual evoked potentials (VEPs) were recorded and color fundus photographs taken at the same time points. Results In all cases, initial PRNFL swelling was associated with atrophy, and the greater the initial swelling, the greater the degree of eventual atrophy (r = 0.65, P = 0.0002). The change in PRNFL thickness closely correlated with VEP amplitude loss (r = 0.90), although this relationship was only a strong trend (P = 0.083). Furthermore, VEP amplitude loss closely correlated with PERG N95 amplitude loss (r = 0.80, P = 0.00002) Conclusions In our model of human NAION, the degree of initial PRNFL swelling correlated with the severity of atrophy. Areas that did not swell developed little to no atrophy. The amount of PRNFL loss was reflected in VEP and PERG N95 amplitude reductions. PMID:26868755

  12. Autonomic neuropathies

    NASA Technical Reports Server (NTRS)

    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.

  13. The transcorneal electrical stimulation as a novel therapeutic strategy against retinal and optic neuropathy: a review of experimental and clinical trials

    PubMed Central

    Tao, Ye; Chen, Tao; Liu, Bei; Wang, Li-Qiang; Peng, Guang-Hua; Qin, Li-Min; Yan, Zhong-Jun; Huang, Yi-Fei

    2016-01-01

    Transcorneal electrical stimulation (TES) is a novel therapeutic approach to activate the retina and related downstream structures. TES has multiple advantages over traditional treatments, such as being minimally invasive and readily applicable in a routine manner. Series of animal experiments have shown that TES protects the retinal neuron from traumatic or genetic induced degeneration. These laboratory evidences support its utilization in ophthalmological therapies against various retinal and optical diseases including retinitis pigmentosa (RP), traumatic optic neuropathy, anterior ischemic optic neuropathy (AION), and retinal artery occlusions (RAOs). Several pioneering explorations sought to clarify the functional mechanism underlying the neuroprotective effects of TES. It seems that the neuroprotective effects should not be attributed to a solitary pathway, on the contrary, multiple mechanisms might contribute collectively to maintain cellular homeostasis and promote cell survival in the retina. More precise evaluations via functional and morphological techniques would determine the exact mechanism underlying the remarkable neuroprotective effect of TES. Further studies to determine the optimal parameters and the long-term stability of TES are crucial to justify the clinical significance and to establish TES as a popularized therapeutic modality against retinal and optic neuropathy. PMID:27366697

  14. The transcorneal electrical stimulation as a novel therapeutic strategy against retinal and optic neuropathy: a review of experimental and clinical trials.

    PubMed

    Tao, Ye; Chen, Tao; Liu, Bei; Wang, Li-Qiang; Peng, Guang-Hua; Qin, Li-Min; Yan, Zhong-Jun; Huang, Yi-Fei

    2016-01-01

    Transcorneal electrical stimulation (TES) is a novel therapeutic approach to activate the retina and related downstream structures. TES has multiple advantages over traditional treatments, such as being minimally invasive and readily applicable in a routine manner. Series of animal experiments have shown that TES protects the retinal neuron from traumatic or genetic induced degeneration. These laboratory evidences support its utilization in ophthalmological therapies against various retinal and optical diseases including retinitis pigmentosa (RP), traumatic optic neuropathy, anterior ischemic optic neuropathy (AION), and retinal artery occlusions (RAOs). Several pioneering explorations sought to clarify the functional mechanism underlying the neuroprotective effects of TES. It seems that the neuroprotective effects should not be attributed to a solitary pathway, on the contrary, multiple mechanisms might contribute collectively to maintain cellular homeostasis and promote cell survival in the retina. More precise evaluations via functional and morphological techniques would determine the exact mechanism underlying the remarkable neuroprotective effect of TES. Further studies to determine the optimal parameters and the long-term stability of TES are crucial to justify the clinical significance and to establish TES as a popularized therapeutic modality against retinal and optic neuropathy. PMID:27366697

  15. Efficacy and Safety of rAAV2-ND4 Treatment for Leber’s Hereditary Optic Neuropathy

    PubMed Central

    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

  16. Differential visual system organization and susceptibility to experimental models of optic neuropathies in three commonly used mouse strains.

    PubMed

    De Groef, Lies; Dekeyster, Eline; Geeraerts, Emiel; Lefevere, Evy; Stalmans, Ingeborg; Salinas-Navarro, Manuel; Moons, Lieve

    2016-04-01

    Mouse disease models have proven indispensable in glaucoma research, yet the complexity of the vast number of models and mouse strains has also led to confusing findings. In this study, we evaluated baseline intraocular pressure, retinal histology, and retinofugal projections in three mouse strains commonly used in glaucoma research, i.e. C57Bl/6, C57Bl/6-Tyr(c), and CD-1 mice. We found that the mouse strains under study do not only display moderate variations in their intraocular pressure, retinal architecture, and retinal ganglion cell density, also the retinofugal projections to the dorsal lateral geniculate nucleus and the superior colliculus revealed striking differences, potentially underlying diverging optokinetic tracking responses and visual acuity. Next, we reviewed the success rate of three models of (glaucomatous) optic neuropathies (intravitreal N-methyl-d-aspartic acid injection, optic nerve crush, and laser photocoagulation-induced ocular hypertension), looking for differences in disease susceptibility between these mouse strains. Different genetic backgrounds and albinism led to differential susceptibility to experimentally induced retinal ganglion cell death among these three mouse strains. Overall, CD-1 mice appeared to have the highest sensitivity to retinal ganglion cell damage, while the C57Bl/6 background was more resistant in the three models used. PMID:26791081

  17. Alcoholic neuropathy

    MedlinePlus

    ... objects in the shoes Guarding the extremities to prevent injury from pressure Alcohol must be stopped to prevent the damage from ... The only way to prevent alcoholic neuropathy is not to drink excessive amounts of alcohol.

  18. Handcuff neuropathies.

    PubMed

    Stone, D A; Laureno, R

    1991-01-01

    Compressive neuropathy due to tight application of handcuffs occurred in 5 patients. The superficial radial nerve was affected in 8 hands and the median nerve in two. Neurologic deficits persisted as long as 3 years after handcuffing. Nerve conduction studies helped to exclude malingering and other diagnoses. All patients had been intoxicated when handcuffed or had been arrested with force. The handcuff mechanism, which allows accidental overtightening after application, is an unrecognized factor in these neuropathies. PMID:1985280

  19. Leber hereditary optic neuropathy: involvement of the mitochondrial ND1 gene and evidence for an intragenic suppressor mutation.

    PubMed Central

    Howell, N; Kubacka, I; Xu, M; McCullough, D A

    1991-01-01

    A large Queensland family has an extreme form of Leber hereditary optic neuropathy (LHON) in which several neurological abnormalities and an infantile encephalopathy are present in addition to the characteristic ophthalmological changes. Sequence analysis of the seven mitochondrial genes encoding subunits of respiratory chain complex I (NADH-ubiquinone oxidoreductase) reveals two novel features of the etiology of this mitochondrial genetic disease. The first conclusion from these studies is that the ophthalmological and neurological deficits in this family are produced by a mutation at nucleotide 4160 of the ND1 gene. This nucleotide alteration results in the substitution of proline for the highly conserved leucine residue at position 285 of the ND1 protein. Secondary-structure analysis predicts that the proline replacement disrupts a small alpha helix in a hydrophilic loop. All nine family members analyzed were homoplasmic for this mutation. The second major result from these studies is that the members of one branch of this family carry, at nucleotide 4136 of the same gene, a second mutation, also homoplasmic, which produces a cysteine-for-tyrosine replacement at position 277. The clinical and biochemical phenotypes of the family members indicate that this second nucleotide substitution may function as an intragenic suppressor mutation which ameliorates the neurological abnormalities and complex I deficiency. PMID:2018041

  20. Mitochondrial tRNA(Thr) A15951G mutation may not be associated with Leber's Hereditary Optic Neuropathy.

    PubMed

    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. PMID:26000946

  1. Radiation-induced optic neuropathy following external beam radiation therapy for nasopharyngeal carcinoma: A retrospective case-control study

    PubMed Central

    WANG, WEI; YANG, HUI; GUO, LING; SU, HONGYU; WEI, SHIHUI; ZHANG, XIULAN

    2016-01-01

    Radiation-induced optic neuropathy (RION) is a severe ocular complication in patients with nasopharyngeal carcinoma (NPC) following external beam radiation therapy. However, the systemic risk factors for this condition remain unclear. Therefore, patients with NPC who received radiotherapy between 2004 and 2007 at the Sun Yat-Sen University Cancer Center were retrospectively reviewed in this case-control study. The study included 40 RION patients and 40 patients in the control group, who were strictly matched to the RION patients by tumor histopathology, location, Union for International Cancer Control-Tumor Node Metastasis classification and radiotherapy protocol. Univariate and multivariate statistical regression analyses were performed to identify factors predictive of RION. The univariate analysis demonstrated that age (>60 years), gender (female) and chemotherapy significantly affected the risk of RION, whereas diabetes, hypertension and hepatitis B virus infection did not exert a significant effect. The results of the multivariate analysis suggested that only gender and chemotherapy were significantly associated with an increased incidence of RION. Therefore, the results of the present study suggested that female gender and chemotherapy constitute risk factors for the development of RION following radiotherapy for NPC. The ocular symptoms of high-risk patients should be carefully investigated and reported by ophthalmologists. PMID:27123298

  2. Leber's hereditary optic neuropathy is associated with the mitochondrial ND6 T14484C mutation in three Chinese families

    SciTech Connect

    Sun Yanhong; Wei Qiping; Zhou Xiangtian; Qian Yaping; Zhou Jian; Lu Fan; Qu Jia . E-mail: jqu@wzmc.net; Guan Minxin . E-mail: min-xin.guan@cchmc.org

    2006-08-18

    We report here the clinical, genetic, and molecular characterization of three Chinese families with maternally transmitted Leber's hereditary optic neuropathy (LHON). Clinical and genetic evaluations revealed the variable severity and age-of-onset in visual impairment in these families. In the affected matrilineal relatives, the loss of central vision is bilateral, the fellow eye becoming affected either simultaneously (45%) or sequentially (55%). The penetrances of vision loss in these pedigrees were 27%, 50%, and 60%, respectively. The age-at-onset of vision loss in these families was 14, 19, and 24 years, respectively. Furthermore, the ratios between affected male and female matrilineal relatives were 1:1, 1:1.2, and 1:2, respectively. Mutational analysis of mitochondrial DNA revealed the presence of homoplasmic ND6 T14484C mutation, which has been associated with LHON. The incomplete penetrance and phenotypic variability implicate the involvement of nuclear modifier gene(s), environmental factor(s) or mitochondrial haplotype(s) in the phenotypic expression of the LHON-associated T14484C mutation in these Chinese pedigrees.

  3. Leber's hereditary optic neuropathy is associated with the mitochondrial ND4 G11696A mutation in five Chinese families

    SciTech Connect

    Zhou Xiangtian |; Wei Qiping; Yang Li; Tong Yi |; Zhao Fuxin; Lu Chunjie; Qian Yaping; Sun Yanghong; Lu Fan; Qu Jia |. E-mail: jqu@wzmc.net; Guan Minxin ||. E-mail: min-xin.guan@cchmc.org

    2006-02-03

    We report here the clinical, genetic, and molecular characterization of five Chinese families with Leber's hereditary optic neuropathy (LHON). Clinical and genetic evaluations revealed the variable severity and age-of-onset in visual impairment in these families. Strikingly, there were extremely low penetrances of visual impairment in these Chinese families. Sequence analysis of the complete mitochondrial genomes in these pedigrees showed the distinct sets of mtDNA polymorphism, in addition to the identical ND4 G11696A mutation associated with LHON. Indeed, this mutation is present in homoplasmy only in the maternal lineage of those pedigrees but not other members of these families. In fact, the occurrence of the G11696A mutation in these several genetically unrelated subjects affected by visual impairment strongly indicates that this mutation is involved in the pathogenesis of visual impairment. Furthermore, the N405D in the ND5 and G5820A in the tRNA{sup Cys}, showing high evolutional conservation, may contribute to the phenotypic expression of G11696A mutation in the WZ10 pedigree. However, there was the absence of functionally significant mtDNA mutations in other four Chinese pedigrees carrying the G11696A mutation. Therefore, nuclear modifier gene(s) or environmental factor(s) may play a role in the phenotypic expression of the LHON-associated G11696A mutation in these Chinese pedigrees.

  4. Visual outcome of mega-dose intravenous corticosteroid treatment in non-arteritic anterior ischemic optic neuropathy – retrospective analysis

    PubMed Central

    2014-01-01

    Background To date, non arteritic anterior ischemic optic neuropathy (NAION) is still incurable. We wish to evaluate the effect of intravenous (IV) corticosteroids on the visual outcome of NAION patients. Methods Visual parameters were retrospectively compared between NAION patients treated with IV corticosteroids and untreated NAION patients (control). Visual acuity (VA) and Humphrey automated static perimetry visual field (VF) defects of the affected eye were compared between groups at baseline, 1, 3, 6 months, and end of follow-up visits. The VF analysis consisted of number of quadrant involvements and mean deviation (MD). Results Each group comprised 23 patients (24 eyes). Mean initial VA was similar in the control and treatment groups (p = 0.8). VA at end of follow-up did not improve in either groups (p = 0.8 treated group, p = 0.1 control group). No improvement and no difference in VF defects were found by either quadrant analysis (p = 0.1 treated group, p = 0.5 control group) or MD analysis (p = 0.2, treated group, p = 0.9 control group). VA and VF parameters tended to be worse in the treated group, although without statistical significance. Conclusions Our results suggest that IV corticosteroids may not improve the visual outcome of NAION patients. Since intravenous corticosteroids could potentially cause serious adverse effects, this treatment for NAION is questionable. PMID:24886579

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

    SciTech Connect

    De Vries, D.D.; Oost, B.A. van; Went, L.N.; Bruyn, G.W.

    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.

  6. [A case of hereditary motor and sensory neuropathy with pyramidal tract sign, optic nerve atrophy and mental retardation].

    PubMed

    Adachi, T; Imaoka, K; Shirasawa, A; Yamaguchi, S; Kobayashi, S

    1998-12-01

    The patient was a 61-year-old man who suffered from gait disturbance since childhood. He also had mental retardation. Gait disturbance was slowly progressive. His mother, sister, brother and son of his sister suffered from gait disturbance. On neurological examination, he showed mental retardation, optic nerve atrophy and neural deafness. He also showed severe muscle atrophy and weakness of bilateral lower limbs associated with pes cavus. Muscle tonus of lower limbs and patellar tendon reflex were increased bilaterally. Achilles tendon reflex was absent. Babinski and Chaddock signs were positive. Superficial and deep sensations were almost normal. There were no cerebellar signs. Blood chemistry was normal. On nerve conduction studies, motor nerve conduction velocity of the upper limbs was normal and that of the posterior tibial nerve was decreased; right 36.0m/sec, left 29.7m/sec. Sensory nerve conduction velocity of the median nerve was slightly decreased; right 36.5m/sec, left 45.2m/sec and sural nerve did not respond to electric stimuli. On sural nerve biopsy, the density of myelinated fibers was severely decreased. Onion bulb formation was not observed. We classified this case as hereditary motor and sensory neuropathy (HMSN) type II based on nerve conduction studies and findings from sural nerve biopsy. HMSN with pyramidal tract sign has been classified as type V and HMSN with optic nerve atrophy as type VI. This case had characteristic symptoms as type V and VI. Histopathological findings of HMSN type V and VI have not been established yet. This case might provide an important clue for classification of HMSN. PMID:10349345

  7. Optical properties of ITO films obtained by high-frequency magnetron sputtering with accompanying ion treatment

    SciTech Connect

    Krylov, P. N. Zakirova, R. M.; Fedotova, I. V.

    2013-10-15

    A variation in the properties of indium-tin-oxide (ITO) films obtained by the method of reactive magnetron sputtering with simultaneous ion treatment is reported. The ITO films feature the following parameters in the optical range of 450-1100 nm: a transmission coefficient of 80%, band gap of 3.50-3.60 eV, and a refractive index of 1.97-2.06. All characteristics of the films depend on the ion-treatment current. The latter, during the course of deposition, reduces the resistivity of the ITO films with the smallest value of the resistivity being equal to 2 Multiplication-Sign 10{sup -3} {Omega} cm. The degradation of films with a high resistivity when kept in air is observed.

  8. Optic neuropathy in a herd of beef cattle in Alberta associated with consumption of moldy corn

    PubMed Central

    Sandmeyer, Lynne S.; Vujanovic, Vladimir; Petrie, Lyall; Campbell, John R.; Bauer, Bianca S.; Allen, Andrew L.; Grahn, Bruce H.

    2015-01-01

    A group of beef cattle in eastern Alberta was investigated due to sudden onset of blindness after grazing on standing corn in mid-winter. Fumonisin-producing Fusarium spp. were isolated from the corn. Blindness was due to an optic nerve degeneration suspected to be secondary to fumonisin mycotoxin. PMID:25750444

  9. Bilateral optic neuropathy and intraretinal deposits after pars plana vitrectomy in amyloidosis.

    PubMed

    Rossetti, Alberto; Alberto, Rossetti; Spedicato, Luigi; Luigi, Spedicato; Fassina, Ambrogio; Ambrogio, Fassina; Doro, Daniele; Daniele, Doro

    2015-01-01

    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. PMID:25686071

  10. Improved Vision from Severe Compressive Optic Neuropathy by Apical Cavernous Hemangioma.

    PubMed

    Kang, Hyera; Takahashi, Yasuhiro; Nishimura, Kunihiro; Yasuda, Muneyoshi; Akutsu, Hiroyoshi; Kakizaki, Hirohiko

    2016-01-01

    A 59-year-old woman had a 1-year history of right vision loss. Her visual acuity was then 0.01 OD, and the critical flicker frequency (CFF) was 8 Hz OD. Goldmann perimetry examination showed inferior suppression of the right visual field center. Funduscopic examination revealed normal coloring of the right optic disc. Imaging studies showed an apical oval tumor. The optic nerve was compressed by both the tumor and the superior rectus muscle/levator palpebrae superioris complex. The tumor was dissected from the surrounding tissues and completely extracted. Histopathologic examination confirmed a cavernous hemangioma. The patient underwent three cycles of postoperative steroid pulse therapy. One year after the surgery, her visual acuity and CFF improved to 1.0 and 32 Hz OD, respectively. Her right visual field was within the normal range. PMID:27099610

  11. Improved Vision from Severe Compressive Optic Neuropathy by Apical Cavernous Hemangioma

    PubMed Central

    Kang, Hyera; Takahashi, Yasuhiro; Nishimura, Kunihiro; Yasuda, Muneyoshi; Akutsu, Hiroyoshi; Kakizaki, Hirohiko

    2016-01-01

    A 59-year-old woman had a 1-year history of right vision loss. Her visual acuity was then 0.01 OD, and the critical flicker frequency (CFF) was 8 Hz OD. Goldmann perimetry examination showed inferior suppression of the right visual field center. Funduscopic examination revealed normal coloring of the right optic disc. Imaging studies showed an apical oval tumor. The optic nerve was compressed by both the tumor and the superior rectus muscle/levator palpebrae superioris complex. The tumor was dissected from the surrounding tissues and completely extracted. Histopathologic examination confirmed a cavernous hemangioma. The patient underwent three cycles of postoperative steroid pulse therapy. One year after the surgery, her visual acuity and CFF improved to 1.0 and 32 Hz OD, respectively. Her right visual field was within the normal range. PMID:27099610

  12. Inherited neuropathies.

    PubMed

    Chance, P F; Reilly, M

    1994-10-01

    Charcot-Marie-Tooth neuropathy (CMT) type 1 is a genetically heterogeneous group of chronic demyelinating polyneuropathies with loci mapping to chromosome 17 (CMT1A), chromosome 1 (CMT1B), the X chromosome (CMTX), and to another unknown autosome (CMT1C). CMT1A is most often associated with a tandem 1.5-Mb duplication in chromosome 17p11.2-12, or in rare patients may result from a point mutation in the peripheral myelin protein-22 (PMP22) gene. CMT1B is associated with point mutations in the myelin protein zero (P0) gene. The molecular defect in CMT1C is unknown. CMTX is associated with mutations in the connexin 32 gene. CMT2 is an axonal neuropathy of undetermined cause. One form of CMT2 maps to chromosome 1p36 (CMT2A). Dejerine-Sottas disease is a severe, infantile-onset demyelinating polyneuropathy that may be associated with point mutations in either the PMP22 gene or the P0 gene. Hereditary neuropathy with liability to pressure palsies (HNPP) is a recurrent, episodic demyelinating neuropathy. HNPP is associated with a 1.5-Mb deletion in chromosome 17p11.2-12 and may result from reduced expression of the PMP22 gene. Most examples of CMT1A and HNPP are reciprocal duplication or deletion syndromes originating from unequal crossover during germ cell meiosis. Familial amyloid polyneuropathy (FAP) is an autosomal dominant disorder that classically presents with a sensory peripheral neuropathy and early autonomic involvement. Transthyretin (TTR) is the most common constituent amyloid fibril protein deposited in FAP, and there are now 28 point mutations in the TTR gene described in TTR-related FAP. Liver transplantation looks promising as a treatment for TTR-related FAP. PMID:7804455

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

    PubMed

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

    2015-09-01

    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 approved clinical trial and has become the largest ophthalmology stem cell study registered at the National Institutes of Health to date (www.clinicaltrials.gov Identifier 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. Significant visual field 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 intravitreal 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. PMID:26604914

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

    PubMed Central

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

    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 approved clinical trial and has become the largest ophthalmology stem cell study registered at the National Institutes of Health to date (www.clinicaltrials.gov Identifier 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. Significant visual field 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 intravitreal 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. PMID:26604914

  15. Cigarette toxicity triggers Leber's hereditary optic neuropathy by affecting mtDNA copy number, oxidative phosphorylation and ROS detoxification pathways

    PubMed Central

    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

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

    SciTech Connect

    Brown, M.D.; Sun, F.; Wallace, D.C.

    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.

  17. Longitudinal study of a heteroplasmic 3460 Leber hereditary optic neuropathy family by multiplexed primer-extension analysis and nucleotide sequencing

    SciTech Connect

    Ghosh, S.S.; Fahy, E.; Bodis-Wollner, I.

    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.

  18. Unilateral Anterior Ischemic Optic Neuropathy: Chromatic Pupillometry in Affected, Fellow Non-Affected and Healthy Control Eyes

    PubMed Central

    Herbst, Kristina; Sander, Birgit; Lund-Andersen, Henrik; Wegener, Marianne; Hannibal, Jens; Milea, Dan

    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 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 colors 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. PMID:23717301

  19. Intravitreal Injection of a Rho-Kinase Inhibitor (Fasudil) for Recent-Onset Nonarteritic Anterior Ischemic Optic Neuropathy.

    PubMed

    Sanjari, Nasrin; Pakravan, Mohammad; Nourinia, Ramin; Esfandiari, Hamed; Hafezi-Moghadam, Ali; Zandi, Souska; Nakao, Shintaro; Shah-Heidari, Mohamamad-Hassan; Jamali, Arsia; Yaseri, Mehdi; Ahmadieh, Hamid

    2016-06-01

    This study evaluated the effects of intravitreal injection of fasudil (IVF), a Rho-kinase inhibitor, in cases of recent-onset nonarteritic anterior ischemic optic neuropathy (NAION). In this interventional case series, 13 eyes of 13 patients diagnosed with NAION within 14 days of onset were included. The affected eyes received a 0.025 mg/0.05 mL IVF. Functional and structural outcomes were assessed 1 and 3 months following treatment. Best corrected visual acuity (BCVA) was the main outcome measured, with mean deviation (MD) index of the VF test and peripapillary retinal nerve fiber layer thickness as secondary measures. There was a statistically significant improvement in the patients' BCVA 1 and 3 months following IVF; BCVA improved from 1.69 ± 0.55 logMAR at baseline to 0.98 ± 0.47 and 0.93 ± 0.51 logMAR at 1 and 3 months, respectively (P = .004). The change in BCVA was not significant between month 1 and month 3 (P = .22). Peripapillary retinal nerve fiber layer thickness decreased from 173.5 ± 29.28 µm in the baseline evaluation to 85.8 ± 8.8 µm at 1 month, and 62.9 ± 5.97 µm at 3 months (P = .003). MD values changed from 24.60 ± 3.80 to 21.0 ± 6.10 and 20.5 ± 6.50 at 1 and 3 months, respectively (P = .007 and .005, respectively). This pilot study suggests that IVF may be an effective treatment for patients with recent-onset NAION. Larger studies are required to establish the therapeutic role of fasudil for NAION. PMID:26444290

  20. Plasma Exchange and Immunoadsorption in Pediatric Inflammatory Optic Neuropathy Resistant to Corticosteroid Therapy: Four French Cases.

    PubMed

    Jacquet, Coralie; Garnier, Arnaud; Cheuret, Emmanuel

    2016-06-01

    Steroids as a foremost therapy are widely used in pediatric optic neuritis (ON). Yet, this treatment is not standardized to date. Some children show a resistance to the classic treatment by steroids. Although plasma exchange (PE) and immunoadsorption (IA) techniques are increasingly being adopted and lead to good results in resistant cases in adult patients, very few studies have shown interest in treating ON when steroids have failed. In this study, we report four observations of children, two of whom are treated by PE and two by IA techniques, describing the treatment protocols together with the side effects observed. PMID:26926073

  1. Transient vision loss at depth due to presumed barotraumatic optic neuropathy.

    PubMed

    Hexdall, Eric J; Butler, Frank K

    2012-01-01

    Pressure-related vision loss has been reported during ascent to altitude. We report the case of an otherwise healthy diver who suffered painless, sudden-onset binocular vision loss at depth, followed by complete recovery immediately upon surfacing. We examine the dive and briefly discuss the differential diagnosis of transient vision loss in the setting of ambient pressure changes. We conclude that the diver likely suffered from sphenoid sinus barotrauma, possibly in association with dehiscence of the bony canals of the optic nerves as they travel in close proximity to the walls of the sphenoid sinus. PMID:23045919

  2. Leber's Hereditary Optic Neuropathy Is Associated with the T3866C Mutation in Mitochondrial ND1 Gene in Three Han Chinese Families

    PubMed Central

    Zhou, Xiangtian; Qian, Yaping; Zhang, Juanjuan; Tong, Yi; Jiang, Pingping; Liang, Min; Dai, Xianning; Zhou, Huihui; Zhao, Fuxin; Ji, Yanchun; Mo, Jun Qin; Qu, Jia; Guan, Min-Xin

    2012-01-01

    Purpose. To investigate the pathophysiology of Leber's hereditary optic neuropathy (LHON). Methods. Seventy-one subjects from three Chinese families with LHON underwent clinical, genetic, molecular, and biochemical evaluations. Biochemical characterizations included the measurements of the rates of endogenous, substrate-dependent respirations, the adenosine triphosphate (ATP) production and generation of reactive oxygen species using lymphoblastoid cell lines derived from five affected matrilineal relatives of these families and three control subjects. Results. Ten of 41 matrilineal relatives exhibited variable severity and age at onset of optic neuropathy. The average age at onset of optic neuropathy in matrilineal relatives of the three families was 5, 11, and 24 years, respectively. Molecular analysis identified the ND1 T3866C (I187T) mutation and distinct sets of polymorphisms belonging to the Eastern Asian haplogroups D4a, M10a, and R, respectively. The I187T mutation is localized at the highly conserved isoleucine at a transmembrane domain of the ND1 polypeptide. The marked reductions in the rate of endogenous, malate/glutamate-promoted and succinate/glycerol-3-phosphate-promoted respiration were observed in mutant cell lines carrying the T3866C mutation. The deficient respiration is responsible for the reduced ATP synthesis and increased generation of reactive oxygen species. Conclusions. Our data convincingly show that the ND1 T3866C mutation leads to LHON. This mutation may be insufficient to produce a clinical phenotype. Other modifier factors may contribute to the phenotypic manifestation of the T3866C mutation. The T3866C mutation should be added to the list of inherited factors for molecular diagnosis of LHON. Thus, our findings may provide new insights into the understanding of pathophysiology and valuable information on the management of LHON. PMID:22577081

  3. [The analysis of mitochondrial DNA haplogroups and variants for Leber's hereditary optic neuropathy in Chinese families carrying the m.14484T >C mutation].

    PubMed

    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. PMID:24846978

  4. Nab-paclitaxel-induced cystoid macular edema in a patient with pre-existing optic neuropathy.

    PubMed

    Park, Elizabeth; Goldberg, Naomi R; Adams, Sylvia

    2016-07-01

    Paclitaxel is a widely used chemotherapy agent that has rarely been associated with ophthalmic toxicities. Cystoid macular edema is one such rare side effect of paclitaxel therapy. Its pathophysiology remains poorly understood. Here, we report on a 69-year-old woman who developed cystoid macular edema associated with the albumin-bound formulation of paclitaxel after several months of therapy for breast cancer. After 2 months of drug withdrawal, her vision improved and there was a significant improvement in the macular edema by imaging with spectral-domain optical coherence tomography. Oncologists using taxane agents should be aware of this rare adverse outcome for timely patient referral to an ophthalmologist and appropriate treatment to preserve a patient's visual acuity. PMID:26982237

  5. Crowdsourcing as a Screening Tool to Detect Clinical Features of Glaucomatous Optic Neuropathy from Digital Photography

    PubMed Central

    Mitry, Danny; Peto, Tunde; Hayat, Shabina; Blows, Peter; Morgan, James; Khaw, Kay-Tee; Foster, Paul J.

    2015-01-01

    Aim 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. Methods 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). Results 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. Conclusions 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. PMID:25692287

  6. Time Course of Macular and Peripapillary Inner Retinal Thickness in Non-arteritic Anterior Ischaemic Optic Neuropathy Using Spectral-Domain Optical Coherence Tomography

    PubMed Central

    Goto, Katsutoshi; Miki, Atsushi; Araki, Syunsuke; Mizukawa, Kenichi; Nakagawa, Masaki; Takizawa, Go; Ieki, Yoshiaki; Kiryu, Junichi

    2016-01-01

    ABSTRACT To report a time course of the ganglion cell complex (GCC) and circumpapillary retinal nerve fibre layer (cpRNFL) thicknesses using spectral-domain optical coherence tomography in patients with non-arteritic anterior ischaemic optic neuropathy (NAION), five patients with unilateral NAION were studied (the average age of 66.8 ± 7.8 years old). Forty-one age-matched normal controls were also enrolled. The GCC and cpRNFL thicknesses were measured at the initial visit and at 1, 3, 6, and 12 months using RTVue-100. The GCC thickness and the cpRNFL thickness of the patients were compared with those of the normal controls. The GCC thickness in the NAION patients was 96.49 μm at the initial visit, 84.28 μm at 1 month, 74.26 μm at 3 months, 71.23 μm at 6 months, and 69.51 μm at 12 months. The values at 1, 3, 6, and 12 months were significantly reduced (p < 0.01). The cpRNFL thickness at the initial visit was significantly increased, whereas the values at 6 and 12 months were significantly reduced (p < 0.01). The GCC thickness is more useful for the detection of retinal ganglion cell loss at an early stage than the cpRNFL thickness, because the GCC thickness is unaffected by optic disc swelling at the initial visit, unlike the cpRNFL thickness. PMID:27110047

  7. Hereditary neuropathy.

    PubMed

    Heidenreich, Wayne F

    2010-01-01

    A 58-year-old male presented with a history of slowly progressive bilateral hand weakness manifested by decreased grip strength and pinch strength associated with some pain in the first metacarpal-carpal joints with atrophy of the muscles of the web space. An evaluation based on history, physical exam, and judicious diagnostic testing yielded a finding of motor and sensory peripheral polyneuropathy and a working diagnosis of hereditary nerve pressure palsy syndrome (HNPP) or hereditary neuropathy with liability to pressure palsies. The clinical findings and diagnostic tests for sensory and motor peripheral neuropathy are discussed. The case details over time, hereditary features, and the natural history of this disorder lead to a favorable clinical and insurance medicine prognosis. PMID:21290997

  8. Giant Axonal Neuropathy

    MedlinePlus

    ... Diversity Find People About NINDS NINDS Giant Axonal Neuropathy Information Page Table of Contents (click to jump ... done? Clinical Trials Organizations What is Giant Axonal Neuropathy? Giant axonal neuropathy (GAN) is a rare inherited ...

  9. Multifocal Motor Neuropathy

    MedlinePlus

    ... Diversity Find People About NINDS NINDS Multifocal Motor Neuropathy Information Page Table of Contents (click to jump ... done? Clinical Trials Organizations What is Multifocal Motor Neuropathy? Multifocal motor neuropathy is a progressive muscle disorder ...

  10. Additional Types of Neuropathy

    MedlinePlus

    ... A A Listen En Español Additional Types of Neuropathy Charcot's Joint Charcot's Joint, also called neuropathic arthropathy, ... can stop bone destruction and aid healing. Cranial Neuropathy Cranial neuropathy affects the 12 pairs of nerves ...

  11. Generalized pruritus preceding paraneoplastic neuropathy.

    PubMed

    Hébant, Benjamin; Miret, Nicolas; Berthelot, Lucile; Jaafar, Mohamad; Maltête, David; Lefaucheur, Romain

    2016-04-01

    Paraneoplastic syndromes are a group of rare disorders involving non-metastatic systemic effects accompanying malignancies, and occur remotely from the tumor itself. Chronic pruritus lasting more than 6 weeks can be from paraneoplastic origin. A 65-year-old woman was admitted for generalized pruritus lasting for 1 month, despite treatment with prednisolone, levocetirizine and hydroxyzine. General examination was normal. Biological data and gastroscopy were normal. One month later, the patient was readmitted for worsening of her pruritus and walking impairment, revealing a severe sensory neuropathy. Blood anti-Hu antibodies returned positive at a level of 400 (normal <100). Bronchoscopy and bronchial biopsies revealed small-cell lung carcinoma. To our knowledge, the association of generalized pruritus and paraneoplastic neuropathy has been rarely reported. Our observation raises the question of a pathophysiological continuum between pruritus and neuropathy in a paraneoplastic context. PMID:26633089

  12. Automatic quantitative analysis of experimental primary and secondary retinal neurodegeneration: implications for optic neuropathies

    PubMed Central

    Davis, B M; Guo, L; Brenton, J; Langley, L; Normando, E M; Cordeiro, M F

    2016-01-01

    Secondary neurodegeneration is thought to play an important role in the pathology of neurodegenerative disease, which potential therapies may target. However, the quantitative assessment of the degree of secondary neurodegeneration is difficult. The present study describes a novel algorithm from which estimates of primary and secondary degeneration are computed using well-established rodent models of partial optic nerve transection (pONT) and ocular hypertension (OHT). Brn3-labelled retinal ganglion cells (RGCs) were identified in whole-retinal mounts from which RGC density, nearest neighbour distances and regularity indices were determined. The spatial distribution and rate of RGC loss were assessed and the percentage of primary and secondary degeneration in each non-overlapping segment was calculated. Mean RGC number (82 592±681) and RGC density (1695±23.3 RGC/mm2) in naïve eyes were comparable with previous studies, with an average decline in RGC density of 71±17 and 23±5% over the time course of pONT and OHT models, respectively. Spatial analysis revealed greatest RGC loss in the superior and central retina in pONT, but significant RGC loss in the inferior retina from 3 days post model induction. In comparison, there was no significant difference between superior and inferior retina after OHT induction, and RGC loss occurred mainly along the superior/inferior axis (~30%) versus the nasal–temporal axis (~15%). Intriguingly, a significant loss of RGCs was also observed in contralateral eyes in experimental OHT. In conclusion, a novel algorithm to automatically segment Brn3a-labelled retinal whole-mounts into non-overlapping segments is described, which enables automated spatial and temporal segmentation of RGCs, revealing heterogeneity in the spatial distribution of primary and secondary degenerative processes. This method provides an attractive means to rapidly determine the efficacy of neuroprotective therapies with implications for any

  13. Analysis of Vision Loss Caused by Radiation-Induced Optic Neuropathy After Particle Therapy for Head-and-Neck and Skull-Base Tumors Adjacent to Optic Nerves

    SciTech Connect

    Demizu, Yusuke; Murakami, Masao; Miyawaki, Daisuke; Niwa, Yasue; Akagi, Takashi; Sasaki, Ryohei; Terashima, Kazuki; Suga, Daisaku; Kamae, Isao; Hishikawa, Yoshio

    2009-12-01

    Purpose: To assess the incident rates of vision loss (VL; based on counting fingers or more severe) caused by radiation-induced optic neuropathy (RION) after particle therapy for tumors adjacent to optic nerves (ONs), and to evaluate factors that may contribute to VL. Methods and Materials: From August 2001 to August 2006, 104 patients with head-and-neck or skull-base tumors adjacent to ONs were treated with carbon ion or proton radiotherapy. Among them, 145 ONs of 75 patients were irradiated and followed for greater than 12 months. The incident rate of VL and the prognostic factors for occurrence of VL were evaluated. The late effects of carbon ion and proton beams were compared on the basis of a biologically effective dose at alpha/beta = 3 gray equivalent (GyE{sub 3}). Results: Eight patients (11%) experienced VL resulting from RION. The onset of VL ranged from 17 to 58 months. The median follow-up was 25 months. No significant difference was observed between the carbon ion and proton beam treatment groups. On univariate analysis, age (>60 years), diabetes mellitus, and maximum dose to the ON (>110 GyE{sub 3}) were significant, whereas on multivariate analysis only diabetes mellitus was found to be significant for VL. Conclusions: The time to the onset of VL was highly variable. There was no statistically significant difference between carbon ion and proton beam treatments over the follow-up period. Based on multivariate analysis, diabetes mellitus correlated with the occurrence of VL. A larger study with longer follow-up is warranted.

  14. Pan-American mDNA haplogroups in Chilean patients with Leber’s hereditary optic neuropathy

    PubMed Central

    Romero, Pablo; Fernández, Verónica; Slabaugh, Mark; Seleme, Nicolás; Reyes, Nury; Gallardo, Patricia; Herrera, Luisa; Peña, Luis; Pezo, Patricio; Moraga, Mauricio

    2014-01-01

    Purpose The clinical impact of mDNA mutations on the development of Leber hereditary optic neuropathy (LHON) may be modulated by mitochondrial haplogroups, which vary across populations. The aim of this research was to determine the clinical spectrum and molecular characteristics, including the haplogroup, of 15 South American families with LHON. Methods This study was a prospective, observational study conducted between March 2006 and August 2012. All patients were referred to the Clinical Hospital of the University of Chile, where the clinical study was conducted. Molecular studies were conducted at the Biomedical Sciences Institute (ICBM) of the University of Chile. Fifteen index cases were identified with molecular analysis after initial neuroophthalmic examination at different centers throughout Chile. Clinical features of patients with LHON and maternal relatives of the 15 families (75 individuals: 26 affected and 49 healthy carriers) were evaluated. The primary mDNA mutations (m.3460G>A, m.11778G>A, or m.14484T>C) were determined with restriction fragment length polymorphism analysis in all individuals. Mitochondrial haplogroups were determined with direct sequencing of two hypervariable regions (HV1 and HV2) and compared with reference sequences. Results The m.11778G>A mutation was found in 59 subjects (78.7%), the m.14484T>C mutation was found in 12 subjects (16.0%), and the m.3460G>A mutation was found in four (5.3%) subjects. The average age of onset of symptoms in affected subjects was 22.2 years old (range 3 to 53 years); 21 (80.7%) were male, and five (19.3%) were female. Twelve families (80%) had Amerindian haplogroups: One family had the A2 haplogroup, four families had the B2i2 haplogroup, six families had the C1b haplogroup, and one family had the D1g haplogroup. Conclusions In this limited sample size, the Amerindian haplogroup A2 was associated with delayed onset of disease in this population. Patients with haplogroup C retained better vision

  15. Simultaneous occurrence of the 11778 (ND4) and the 9438 (COX III) mtDNA mutations in Leber hereditary optic neuropathy: Molecular, biochemical, and clinical findings

    SciTech Connect

    Oostra, R.J.; Bleeker-Wagemakers, E.M.; Zwart, R.

    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.

  16. Management of Diabetic Neuropathy

    PubMed Central

    Ali, Raymond Azman

    2003-01-01

    Diabetes mellitus is the commonest cause of neuropathy worldwide. Diabetic neuropathy (DN) develops in about 4–10% of diabetic patients after 5 years and in 15% after 20 years. Four main mechanisms have been postulated to underlie the pathogenesis of DN. Diabetic neuropathy can be divided into symmetrical and asymmetrical neuropathies. Diabetic Autonomic Neuropathy (DAN) parallels the severity of DSN, and affects primarily the cardiovascular, gastrointestinal, genitourinary and integumentary systems. The cornerstone of treatment of diabetic neuropathy is optimization of glycaemic control. Future treatments for diabetic neuropathy should address the underlying pathogenesis. PMID:23386794

  17. Subacute diabetic proximal neuropathy

    NASA Technical Reports Server (NTRS)

    Pascoe, M. K.; Low, P. A.; Windebank, A. J.; Litchy, W. J.

    1997-01-01

    OBJECTIVE: To evaluate the clinical, electrophysiologic, autonomic, and neuropathologic characteristics and the natural history of subacute diabetic proximal neuropathy and its response to immunotherapy. MATERIAL AND METHODS: For the 12-year period from 1983 to 1995, we conducted a retrospective review of medical records of Mayo Clinic patients with diabetes who had subacute onset and progression of proximal weakness. The responses of treated versus untreated patients were compared statistically. RESULTS: During the designated study period, 44 patients with subacute diabetic proximal neuropathy were encountered. Most patients were middle-aged or elderly, and no sex preponderance was noted. The proximal muscle weakness often was associated with reduced or absent lower extremity reflexes. Associated weight loss was a common finding. Frequently, patients had some evidence of demyelination on nerve conduction studies, but it invariably was accompanied by concomitant axonal degeneration. The cerebrospinal fluid protein concentration was usually increased. Diffuse and substantial autonomic failure was generally present. In most cases, a sural nerve biopsy specimen suggested demyelination, although evidence of an inflammatory infiltrate was less common. Of 12 patients who received treatment (with prednisone, intravenous immune globulin, or plasma exchange), 9 had improvement of their conditions, but 17 of 29 untreated patients (59%) with follow-up also eventually had improvement, albeit at a much slower rate. Improvement was usually incomplete. CONCLUSION: We suggest that the entity of subacute diabetic proximal neuropathy is an extensive and severe variant of bilateral lumbosacral radiculoplexopathy, with some features suggestive of an immune-mediated cause. It differs from chronic inflammatory demyelinating polyradiculoneuropathy in that most cases have a more restricted distribution and seem to be monophasic and self-limiting. The efficacy of immunotherapy is unproved

  18. Optic nerve atrophy

    MedlinePlus

    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. ...

  19. COMPUTERIZED EXPERT SYSTEM FOR EVALUATION OF AUTOMATED VISUAL FIELDS FROM THE ISCHEMIC OPTIC NEUROPATHY DECOMPRESSION TRIAL: METHODS, BASELINE FIELDS, AND SIX-MONTH LONGITUDINAL FOLLOW-UP

    PubMed Central

    Feldon, Steven E

    2004-01-01

    ABSTRACT Purpose To validate a computerized expert system evaluating visual fields in a prospective clinical trial, the Ischemic Optic Neuropathy Decompression Trial (IONDT). To identify the pattern and within-pattern severity of field defects for study eyes at baseline and 6-month follow-up. Design Humphrey visual field (HVF) change was used as the outcome measure for a prospective, randomized, multi-center trial to test the null hypothesis that optic nerve sheath decompression was ineffective in treating nonarteritic anterior ischemic optic neuropathy and to ascertain the natural history of the disease. Methods An expert panel established criteria for the type and severity of visual field defects. Using these criteria, a rule-based computerized expert system interpreted HVF from baseline and 6-month visits for patients randomized to surgery or careful follow-up and for patients who were not randomized. Results A computerized expert system was devised and validated. The system was then used to analyze HVFs. The pattern of defects found at baseline for patients randomized to surgery did not differ from that of patients randomized to careful follow-up. The most common pattern of defect was a superior and inferior arcuate with central scotoma for randomized eyes (19.2%) and a superior and inferior arcuate for nonrandomized eyes (30.6%). Field patterns at 6 months and baseline were not different. For randomized study eyes, the superior altitudinal defects improved (P = .03), as did the inferior altitudinal defects (P = .01). For nonrandomized study eyes, only the inferior altitudinal defects improved (P = .02). No treatment effect was noted. Conclusions A novel rule-based expert system successfully interpreted visual field defects at baseline of eyes enrolled in the IONDT. PMID:15747764

  20. N-hexane neuropathy in offset printers.

    PubMed Central

    Chang, C M; Yu, C W; Fong, K Y; Leung, S Y; Tsin, T W; Yu, Y L; Cheung, T F; Chan, S Y

    1993-01-01

    In an offset printing factory with 56 workers, 20 (36%) developed symptomatic peripheral neuropathy due to exposure to n-hexane. Another 26 workers (46%) were found to have subclinical neuropathy. The initial change in the nerve conduction study was reduced amplitude of the sensory action potentials, followed by reduced amplitude of the motor action potentials, reduction in motor conduction velocities and increase in distal latencies. These changes indicate primary axonal degeneration with secondary demyelination. Sural nerve biopsy in a severe case showed giant axonal swellings due to accumulation of 10nm neurofilaments, myelin sheath attenuation and widening of nodal gaps. The development of neuropathy bore no direct relationship to the duration of exposure, hence factors such as individual susceptibility may be important. Optic neuropathy and CNS involvement were uncommon and autonomic neuropathy was not encountered. Images PMID:8505647

  1. Searching the co-occurrence of pathogenic mutations for Leber's hereditary optic neuropathy and hearing loss in more than 26,000 whole mitochondrial genomes.

    PubMed

    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. PMID:25714144

  2. Evidence against an X-linked locus close to DXS7 determining visual loss susceptibility in British and Italian families with Leber hereditary optic neuropathy

    SciTech Connect

    Sweeney, M.G.; Davis, M.B.; Lashwood, A.; Brockington, M.; Harding, A.E. ); Toscano, A. )

    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.

  3. A mitochondrial DNA variant, identified in Leber hereditary optic neuropathy patients, which extends the amino acid sequence of cytochrome c oxidase subunit I.

    PubMed Central

    Brown, M D; Yang, C C; Trounce, I; Torroni, A; Lott, M T; Wallace, D C

    1992-01-01

    A G-to-A transition at nucleotide pair (np) 7444 in the mtDNA was found to correlate with Leber hereditary optic neuropathy (LHON). The mutation eliminates the termination codon of the cytochrome c oxidase subunit I (COI) gene, extending the COI polypeptide by three amino acids. The mutation was discovered as an XbaI restriction-endonuclease-site loss present in 2 (9.1%) of 22 LHON patients who lacked the np 11778 LHON mutation and in 6 (1.1%) of 545 unaffected controls. The mutant polypeptide has an altered mobility on SDS-PAGE, suggesting a structural alteration, and the cytochrome c oxidase enzyme activity of patient lymphocytes is reduced approximately 40% relative to that in controls. These data suggest that the np 7444 mutation results in partial respiratory deficiency and thus contributes to the onset of LHON. Images Figure 1 Figure 3 PMID:1322638

  4. Detection of the mtDNA 14484 mutation on an African-specific haplotype: Implications about its role in causing Leber hereditary optic neuropathy

    SciTech Connect

    Torroni, A.; Petrozzi, M.; Terracina, M.

    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.

  5. Genetic heterogeneity of primary open angle glaucoma and ocular hypertension: linkage to GLC1A associated with an increased risk of severe glaucomatous optic neuropathy.

    PubMed Central

    Brézin, A P; Béchetoille, A; Hamard, P; Valtot, F; Berkani, M; Belmouden, A; Adam, M F; Dupont de Dinechin, S; Bach, J F; Garchon, H J

    1997-01-01

    The GLC1A locus for autosomal dominant juvenile and middle age onset primary open angle glaucoma (OAG) has been mapped to chromosome 1q21-q31. OAG, however, is a heterogeneous disease. We tested linkage of OAG and ocular hypertension (OHT), a major risk factor for OAG, to GLC1A in eight French families with multiple cases of juvenile and middle age onset OAG. There was strong evidence of genetic heterogeneity, four families being linked to GLC1A and two or three others being unlinked, depending on whether the complete OAG phenotype was analysed alone or jointly with OHT. Peak intraocular pressure (IOP) did not differ significantly between the two groups of families, while linkage to GLC1A conferred a highly increased risk of developing OAG and of having severe glaucomatous optic neuropathy. Testing linkage of familial OAG to GLC1A may therefore have prognostic value too. PMID:9222961

  6. Neuropathy secondary to drugs

    MedlinePlus

    Neuropathy secondary to drugs is a loss of sensation or movement in a part of the body ... weakness. Many medicines may affect the development of neuropathy, including: Heart or blood pressure drugs: Amiodarone Hydralazine ...

  7. Neuropathy secondary to drugs

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000700.htm Neuropathy secondary to drugs To use the sharing features on this page, please enable JavaScript. Neuropathy secondary to drugs is a loss of sensation ...

  8. A Single Intravitreal Injection of Ranibizumab Provides No Neuroprotection in a Nonhuman Primate Model of Moderate-to-Severe Nonarteritic Anterior Ischemic Optic Neuropathy

    PubMed Central

    Miller, Neil R.; Johnson, Mary A.; Nolan, Theresa; Guo, Yan; Bernstein, Steven L.

    2015-01-01

    Purpose Ranibizumab, a vascular endothelial growth factor-antagonist, is said to be neuroprotective when injected intravitreally in patients with nonarteritic anterior ischemic optic neuropathy (NAION). We evaluated the efficacy of a single intravitreal (IVT) injection of ranibizumab in a nonhuman primate model of NAION (pNAION). Methods We induced pNAION in one eye of four adult male rhesus monkeys using a laser-activated rose Bengal induction method. We then immediately injected the eye with either ranibizumab or normal saline (NS) intravitreally. We performed a clinical assessment, optical coherence tomography, electrophysiological testing, fundus photography, and fluorescein angiography in three of the animals (one animal developed significant retinal hemorrhages and, therefore, could not be analyzed completely) prior to induction, 1 day and 1, 2, and 4 weeks thereafter. Following the 4-week analysis of the first eye, we induced pNAION in the contralateral eye and then injected either ranibizumab or NS, whichever substance had not been injected in the first eye. We euthanized all animals 5 to 12 weeks after the final assessment of the second eye and performed both immunohistochemical and light and electron microscopic analyses of the retina and optic nerves of both eyes. Results A single IVT dose of ranibizumab administered immediately after induction of pNAION resulted in no significant reduction of clinical, electrophysiological, or histologic damage compared with vehicle-injected eyes. Conclusions A single IVT dose of ranibizumab is not neuroprotective when administered immediately after induction of pNAION. PMID:26624498

  9. Treatment of gastrointestinal autonomic neuropathy.

    PubMed

    Törnblom, Hans

    2016-03-01

    The symptoms caused by gastrointestinal autonomic neuropathy in diabetes mellitus is important to highlight since it affects a large proportion of people with diabetes, regardless of whether this is type 1 or type 2. Gastroparesis and general signs of bowel dysfunction, such as constipation, diarrhoea and abdominal pain are most often encountered and involve both pharmacological and non-pharmacological treatment options. This mini-review summarises a presentation given at the 'Diagnosis and treatment of autonomic diabetic neuropathy in the gut' symposium at the 2015 annual meeting of the EASD. It is accompanied by another mini-review on a topic from this symposium (by Azpiroz and Malagelada, DOI: 10.1007/s00125-015-3831-1 ) and a commentary by the Session Chair, Péter Kempler (DOI: 10.1007/s00125-015-3826-y ). PMID:26634570

  10. Peripheral neuropathies 1988

    SciTech Connect

    Assal, J.P.; Liniger, C.

    1990-01-01

    The authors present results and experience in sixteen specific disciplines related to the study of nerve physiopathology, diagnosis and treatment. Twenty-two different peripheral neuropathies are presented, and different models related to health care strategies are discussed. The authors report on Inflammatory and autoimmune neuropathies and Genetic neuropathies.

  11. Entrapment neuropathies III: lower limb.

    PubMed

    Beltran, Luis S; Bencardino, Jenny; Ghazikhanian, Varand; Beltran, Javier

    2010-11-01

    Clinicians frequently encounter compressive neuropathies of the lower extremity. The clinical history and physical examination, along with electrodiagnostic testing and imaging studies, lead to the correct diagnosis. The imaging characteristics of the compression neuropathies can include acute and chronic changes in the nerves and the muscles they innervate. We provide a detailed review of compression neuropathies of the lower extremity with an emphasis on magnetic resonance (MR) imaging characteristics. We discuss the clinical presentation, etiology, anatomical location, and MR imaging appearance of these neuropathies, including the piriformis syndrome, iliacus syndrome, saphenous neuropathy, obturator neuropathy, lateral femoral cutaneous neuropathy (meralgia paresthetica), proximal tibial neuropathy, common peroneal neuropathy, deep peroneal neuropathy, superficial peroneal neuropathy, tarsal tunnel syndrome, Baxter's neuropathy, jogger's foot, sural neuropathy, and Morton's neuroma. PMID:21072728

  12. Giant axonal neuropathy: visual and oculomotor deficits.

    PubMed

    Kirkham, T H; Guitton, D; Coupland, S G

    1980-08-01

    Giant axonal neuropathy, a generalised disorder or neurofilaments, presents as a chronic, progressive peripheral neuropathy in childhood. Evidence for central nervous system involvement is demonstrated in this study of four male patients with giant axonal neuropathy who had defective visual function and abnormal ocular motility. The visual system was studied by electroretinography, which showed normal retinal function, and by visual evoked potentials, which showed disease of both optic nerves and retrochiasmal visual pathways. The ocular motility disorder, studied by electrooculography, comprised defective pursuit, inability to maintain eccentric gaze with gaze paretic and rebound nystagmus, abnormal optokinetic responses and failure of suppression of the vestibulo-ocular reflex by fixation. These findings suggested involvement by giant axonal neuropathy of the cerebellar and brain stem pathways important in the control of ocular motility. PMID:7192592

  13. Protective effects of systemic treatment with methylprednisolone in a rodent model of non-arteritic anterior ischemic optic neuropathy (rAION).

    PubMed

    Huang, Tzu-Lun; Huang, Shun-Ping; Chang, Chung-Hsing; Lin, Kung-Hung; Chang, Shu-Wen; Tsai, Rong-Kung

    2015-02-01

    This study investigated the protective effects of the administration of steroids on optic nerves (ON) and retinal ganglion cells (RGCs) in a rodent model of non-arteritic anterior ischemic optic neuropathy (rAION). We induced rAION using rose bengal and argon laser irradiation in a photodynamic procedure on the optic discs of rats. The treated groups received methylprednisolone (MP) via peritoneal injection for 2 weeks. The control group received intraperitoneal injections of phosphate-buffered saline (PBS) post-rAION. At the 4th week post-infarct, MP treatments significantly rescued the RGCs (mm(2)) in the central retinas (1920 ± 210, p < 0.001) and mid-peripheral retinas (950 ± 240, respectively, p = 0.018) compared with those of the PBS-treated rats (central: 900 ± 210 and mid-peripheral: 440 ± 180). Functional assessment with flash visual-evoked potentials demonstrated that P1 latency (ms) was shortened in the MP group compared to the PBS group (108 ± 14 and 147 ± 9, respectively, p < 0.001). In addition, the P1 amplitude (uV) was enhanced in the MP group compared to the PBS group (55 ± 12 and 41 ± 13, respectively, p < 0.05). TUNEL assays showed a decrease in the number of apoptotic cells in the RGC layers of MP-treated retinas compared to the PBS-treated group (p < 0.05). ED1 positive cells (/HPF) were significantly decreased in the ONs of the MP group compared to the PBS group (p < 0.001). In conclusion, systemic administration of MP had neuroprotective effects on RGC survival and ON function in the rAION animal model. PMID:25543054

  14. Two families with Leber's hereditary optic neuropathy carrying G11778A and T14502C mutations with haplogroup H2a2a1 in mitochondrial DNA.

    PubMed

    Qiao, Chen; Wei, Tanwei; Hu, Bo; Peng, Chunyan; Qiu, Xueping; Wei, Li; Yan, Ming

    2015-08-01

    The mitochondrial haplogroup has been reported to affect the clinical expression of Leber's hereditary optic neuropathy (LHON). The present study aimed to investigate the interaction between mutations and the haplogroup of mitochondrial DNA (mtDNA) in families. Two unrelated families with LHON were enrolled in the study, and clinical, genetic and molecular characterizations were determined in the affected and unaffected family members. Polymerase chain reaction direct sequencing was performed using 24 pairs of overlapping primers for whole mtDNA to screen for mutations and haplogroup. Bioinformatics analysis was performed to evaluate the pathogenic effect of these mtDNA mutations and the haplogroup. The G11778A mutation was identified in the two families. In addition, the members of family 2 exhibited the T14502C mutation and those in family 1 exhibited the T3394C and T14502C mutations, which were regarded as secondary mutations. The penetrance of visual loss in families 1 and 2 were 30.8 and 33.3%, respectively. In addition, the two families were found to be in the H2a2a1 haplogroup. In this limited sample size, it was demonstrated that the H2a2a1 haplogroup had a possible protective effect against LHON. Additional modifying factors, including environmental factors, lifestyle, estrogen levels and nuclear genes may also be important in LHON. PMID:25936877

  15. X chromosome-linked and mitochondrial gene control of Leber hereditary optic neuropathy: evidence from segregation analysis for dependence on X chromosome inactivation.

    PubMed Central

    Bu, X D; Rotter, J I

    1991-01-01

    Leber hereditary optic neuropathy (LHON) has been shown to involve mutation(s) of mitochondrial DNA, yet there remain several confusing aspects of its inheritance not explained by mitochondrial inheritance alone, including male predominance, reduced penetrance, and a later age of onset in females. By extending segregation analysis methods to disorders that involve both a mitochondrial and a nuclear gene locus, we show that the available pedigree data for LHON are most consistent with a two-locus disorder, with one responsible gene being mitochondrial and the other nuclear and X chromosome-linked. Furthermore, we have been able to extend the two-locus analytic method and demonstrate that a proportion of affected females are likely heterozygous at the X chromosome-linked locus and are affected due to unfortunate X chromosome inactivation, thus providing an explanation for the later age of onset in females. The estimated penetrance for a heterozygous female is 0.11 +/- 0.02. The calculated frequency of the X chromosome-linked gene for LHON is 0.08. Among affected females, 60% are expected to be heterozygous, and the remainder are expected to be homozygous at the responsible X chromosome-linked locus. PMID:1896469

  16. Mitochondrial tRNAThr 15891C>G mutation was not associated with Leber's hereditary optic neuropathy in Han Chinese patients.

    PubMed

    Jiang, Zhaochang; Yu, Jinfang; Xia, Bohou; Zhuo, Guangchao

    2016-01-01

    Mutations in mitochondrial DNA (mtDNA) were the most important causes of Leber's hereditary optic neuropathy (LHON). To date, approximately 25 LHON-associated mtDNA mutations have been identified in various ethnic populations. Three primary mutations, the 3460G > A, 11778G > A and 14484T > C, in genes encoding the subunits of respiratory chain complex I, were the most common LHON-associated mtDNA mutations. Moreover, secondary mutations in mt-tRNA genes have been reported increasingly to be associated with LHON, simply due to the high mutation rates of mt-tRNAs. There is a lack of functional analysis and a poor genetic evaluation of a certain mt-tRNA mutation, which failed to meet the classic pathogenicity scoring system. As a result, how to classify a pathogenic mutation in mt-tRNA gene became important for both geneticist and clinician to diagnosis the LHON or the suspicious of LHON. In this study, we reassessed the role of a point mutation in mt-tRNA(Thr) gene which had been reported to be a mutation associated with LHON, the pathogenicity of this mutation has been discussed in this context. PMID:25186221

  17. X chromosome-linked and mitochondrial gene control of Leber hereditary optic neuropathy: Evidence from segregation analysis for dependence on X chromosome inactivation

    SciTech Connect

    Xiangdong Bu; Rotter, J.I. Univ. of California, Los Angeles )

    1991-09-15

    Leber hereditary optic neuropathy (LHON) has been shown to involve mutation(s) of mitochondrial DNA, yet there remain several confusing aspects of its inheritance not explained by mitochondrial inheritance alone, including male predominance, reduced penetrance, and a later age of onset in females. By extending segregation analysis methods to disorders that involve both a mitochondrial and a nuclear gene locus, the authors show that the available pedigree data for LHON are most consistent with a two-locus disorder, with one responsible gene being mitochondrial and the other nuclear and X chromosome-linked. Furthermore, they have been able to extend the two-locus analytic method and demonstrate that a proportion of affected females are likely heterozygous at the X chromosome-linked locus and are affected due to unfortunate X chromosome inactivation, thus providing an explanation for the later age of onset in females. The estimated penetrance for a heterozygous female is 0.11{plus minus}0.02. The calculated frequency of the X chromosome-linked gene for LHON is 0.l08. Among affected females, 60% are expected to be heterozygous, and the remainder are expected to be homozygous at the responsible X chromosome-linked locus.

  18. X-inactivation patterns in female Leber`s hereditary optic neuropathy patients do not support a strong X-linked determinant

    SciTech Connect

    Pegoraro, E.; Hoffman, E.P.; Carelli, V.; Cortelli, P.

    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.

  19. Peripheral Neuropathy: Symptoms and Signs

    MedlinePlus

    ... Research News Make a Difference Symptoms of Peripheral Neuropathy Print This Page Peripheral Neuropathy symptoms usually start ... slowly over many years. The symptoms of peripheral neuropathy often include: A sensation of wearing an invisible “ ...

  20. Inherited mitochondrial neuropathies.

    PubMed

    Finsterer, Josef

    2011-05-15

    Mitochondrial disorders (MIDs) occasionally manifest as polyneuropathy either as the dominant feature or as one of many other manifestations (inherited mitochondrial neuropathy). MIDs in which polyneuropathy is the dominant feature, include NARP syndrome due to the transition m.8993T>, CMT2A due to MFN2 mutations, CMT2K and CMT4A due to GDAP1 mutations, and axonal/demyelinating neuropathy with external ophthalmoplegia due to POLG1 mutations. MIDs in which polyneuropathy is an inconstant feature among others is the MELAS syndrome, MERRF syndrome, LHON, Mendelian PEO, KSS, Leigh syndrome, MNGIE, SANDO; MIRAS, MEMSA, AHS, MDS (hepato-cerebral form), IOSCA, and ADOA syndrome. In the majority of the cases polyneuropathy presents in a multiplex neuropathy distribution. Nerve conduction studies may reveal either axonal or demyelinated or mixed types of neuropathies. If a hereditary neuropathy is due to mitochondrial dysfunction, the management of these patients is at variance from non-mitochondrial hereditary neuropathies. Patients with mitochondrial hereditary neuropathy need to be carefully investigated for clinical or subclinical involvement of other organs or systems. Supportive treatment with co-factors, antioxidants, alternative energy sources, or lactate lowering agents can be tried. Involvement of other organs may require specific treatment. Mitochondrial neuropathies should be included in the differential diagnosis of hereditary neuropathies. PMID:21402391

  1. Inherited Peripheral Neuropathies

    PubMed Central

    Saporta, Mario A.; Shy, Michael E.

    2013-01-01

    SYNOPSIS Charcot Marie Tooth disease (CMT) is a heterogeneous group of inherited peripheral neuropathies in which the neuropathy is the sole or primary component of the disorder, as opposed to diseases in which the neuropathy is part of a more generalized neurological or multisystem syndrome. Due to the great genetic heterogeneity of this condition, it can be challenging for the general neurologist to diagnose patients with specific types of CMT. Here, we review the biology of the inherited peripheral neuropathies, delineate major phenotypic features of the CMT subtypes and suggest strategies for focusing genetic testing. PMID:23642725

  2. Treatment of peripheral neuropathies.

    PubMed Central

    Hallett, M; Tandon, D; Berardelli, A

    1985-01-01

    There are three general approaches to treatment of peripheral neuropathy. First, an attempt should be made to reverse the pathophysiological process if its nature can be elucidated. Second, nerve metabolism can be stimulated and regeneration encouraged. Third, even if the neuropathy itself cannot be improved, symptomatic therapy can be employed. This review outlines the options available for each approach. PMID:3003254

  3. Propylthiouracil and peripheral neuropathy.

    PubMed

    Van Boekel, V; Godoy, J M; Lamy, L A; Assuf, S; Meyer Neto, J G; Balassiano, S L; Prata, L E

    1992-06-01

    Peripheral neuropathy is a rare manifestation in hyperthyroidism. We describe the neurological manifestations of a 38 year old female with Graves' disease who developed peripheral neuropathy in the course of her treatment with propylthiouracil. After the drug was tapered off, the neurological signs disappeared. Therefore, we call attention for a possible toxic effect on peripheral nervous system caused by this drug. PMID:1339201

  4. Painful Traumatic Trigeminal Neuropathy.

    PubMed

    Rafael, Benoliel; Sorin, Teich; Eli, Eliav

    2016-08-01

    This article discusses neuropathic pain of traumatic origin affecting the trigeminal nerve. This syndrome has been termed painful traumatic trigeminal neuropathy by the International Headache Society and replaces atypical odontalgia, deafferentation pain, traumatic neuropathy, and phantom toothache. The discussion emphasizes the diagnosis and the early and late management of injuries to the trigeminal nerve and subsequent painful conditions. PMID:27475512

  5. Immunotherapy in Peripheral Neuropathies.

    PubMed

    Léger, Jean-Marc; Guimarães-Costa, Raquel; Muntean, Cristina

    2016-01-01

    Immunotherapy has been investigated in a small subset of peripheral neuropathies, including an acute one, Guillain-Barré syndrome, and 3 chronic forms: chronic inflammatory demyelinating polyradiculoneuropathy, multifocal motor neuropathy, and neuropathy associated with IgM anti-myelin-associated glycoprotein. Several experimental studies and clinical data are strongly suggestive of an immune-mediated pathogenesis. Either cell-mediated mechanisms or antibody responses to Schwann cell, compact myelin, or nodal antigens are considered to act together in an aberrant immune response to cause damage to peripheral nerves. Immunomodulatory treatments used in these neuropathies aim to act at various steps of this pathogenic process. However, there are many phenotypic variants and, consequently, there is a significant difference in the response to immunotherapy between these neuropathies, as well as a need to improve our knowledge and long-term management of chronic forms. PMID:26602549

  6. Inverted optical intrinsic response accompanied by decreased cerebral blood flow are related to both neuronal inhibition and excitation

    PubMed Central

    Ma, Zengguang; Cao, Pengjia; Sun, Pengcheng; Zhao, Linna; Li, Liming; Tong, Shanbao; Lu, Yiliang; Yan, Yan; Chen, Yao; Chai, Xinyu

    2016-01-01

    Negative hemodynamic response has been widely reported in blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging studies, however its origin is still controversial. Optical intrinsic signal (OIS) imaging can be used to study brain activity by simultaneously recording hemodynamic signals at different wavelengths with high spatial resolution. In this study, we found transcorneal electrical stimulation (TcES) could elicit both positive OIS response (POR) and negative OIS response (NOR) in cats’ visual cortex. We then investigated the property of this negative response to TcES and its relationship with cerebral blood flow (CBF) and neuronal activity. Results from laser speckle contrast imaging showed decreased CBF in the NOR region while increased CBF in the POR region. Both planar and laminar electrophysiological recordings in the middle (500–700 μm) cortical layers demonstrated that decreased and increased neuronal activities were coexisted in the NOR region. Furthermore, decreased neuronal activity was also detected in the deep cortical layers in the NOR region. This work provides evidence that the negative OIS together with the decreased CBF should be explained by mechanisms of both neuronal inhibition and excitation within middle cortical layers. Our results would be important for interpreting neurophysiological mechanisms underlying the negative BOLD signals. PMID:26860040

  7. Sustained Neuroprotection From a Single Intravitreal Injection of PGJ2 in a Nonhuman Primate Model of Nonarteritic Anterior Ischemic Optic Neuropathy

    PubMed Central

    Miller, Neil R.; Johnson, Mary A.; Nolan, Theresa; Guo, Yan; Bernstein, Alexander M.; Bernstein, Steven L.

    2014-01-01

    Purpose. Prostaglandin J2 (PGJ2) is neuroprotective in a murine model of nonarteritic anterior ischemic optic neuropathy (NAION). After assessing for potential toxicity, we evaluated the efficacy of a single intravitreal (IVT) injection of PGJ2 in a nonhuman primate model of NAION (pNAION). Methods. We assessed PGJ2 toxicity by administering it as a single high-dose intravenous (IV) injection, consecutive daily high-dose IV injections, or a single IVT injection in one eye of five adult rhesus monkeys. To assess efficacy, we induced pNAION in one eye of five adult male rhesus monkeys using a laser-activated rose bengal induction method. We then injected the eye with either PGJ2 or phosphate-buffered saline (PBS) intravitreally immediately or 5 hours post induction. We performed a clinical assessment, optical coherence tomography, electrophysiological testing, fundus photography, and fluorescein angiography in all animals prior to induction and at 1 day, 1 week, 2 weeks, and 4 weeks after induction. Following analysis of the first eye, we induced pNAION in the contralateral eye and then injected either PGJ2 or PBS. We euthanized all animals 5 weeks after final assessment of the fellow eye and performed both immunohistochemical and light and electron microscopic analyses of the retina and optic nerves. Results. Toxicity: PGJ2 caused no permanent systemic toxicity regardless of the amount injected or route of delivery, and there was no evidence of any ocular toxicity with the dose of PGJ2 used in efficacy studies. Transient reduction in the amplitudes of the visual evoked potentials and the N95 component of the pattern electroretinogram (PERG) occurred after both IV and IVT administration of high doses of PGJ2; however, the amplitudes returned to normal in all animals within 1 week. Efficacy: In all eyes, a single IVT dose of PGJ2 administered immediately or shortly after induction of pNAION resulted in a significant reduction of clinical, electrophysiological, and

  8. [Chemotherapy induced peripheral neuropathy].

    PubMed

    Kolak, Agnieszka; Starosławska, Elzbieta; Kubiatowski, Tomasz; Kieszko, Dariusz; Cisek, Paweł; Patyra, Krzysztof Ireneusz; Surdyka, Dariusz; Mocarska, Agnieszka; Burdan, Franciszek

    2013-11-01

    Modern cancer therapy prolongs patients life but commonly increases incidence of treatment-related complications. One of such adverse effect is a neurotoxicity, which usually manifestates as peripheral neuropathies (CIPN), characterised by various sensory (tingling, numbness, pain), motor (foot and hands drop, fastening buttons difficulties) and autonomic (constipation, arythmia) abnormalities as well as pain. Despite of intensive epidemiological and clinical studies, standardized diagnostic criteria and methods of the neuropathy prevention and treatment have not been fully established. The most commonly used form of treatment is symptomatic therapy, including anticonvulsant and antidepressant drugs. Proper education of patients and their families of symptoms and neuropathy consequences is desirable to reduce anxiety and stress. PMID:24575651

  9. HIV peripheral neuropathy.

    PubMed

    Gabbai, Alberto Alain; Castelo, Adauto; Oliveira, Acary Souza Bulle

    2013-01-01

    Peripheral neuropathies are the most common neurological manifestations occurring in HIV-infected individuals. Distal symmetrical sensory neuropathy is the most common form encountered today and is one of the few that are specific to HIV infection or its treatment. The wide variety of other neuropathies is akin to the neuropathies seen in the general population and should be managed accordingly. In the pre-ART era, neuropathies were categorized according to the CD4 count and HIV viral load. In the early stages of HIV infection when CD4 count is high, the inflammatory demyelinating neuropathies predominate and in the late stages with the decline of CD4 count opportunistic infection-related neuropathies prevail. That scenario has changed with the present almost universal use of ART (antiretroviral therapy). Hence, HIV-associated peripheral neuropathies are better classified according to their clinical presentations: distal symmetrical polyneuropathy, acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), mononeuropathies, mononeuropathies multiplex and cranial neuropathies, autonomic neuropathy, lumbosacral polyradiculomyelopathy, and amyotrophic lateral sclerosis (ALS)-like motor neuropathy. Treated with ART, HIV-infected individuals are living longer and are at a higher risk of metabolic and age-related complications; moreover they are also prone to the potentially neurotoxic effects of ART. There are no epidemiological data regarding the incidence and prevalence of the peripheral neuropathies. In the pre-ART era, most data were from case reports, series of patients, and pooled autopsy data. At that time the histopathological evidence of neuropathies in autopsy series was almost 100%. In large prospective cohorts presently being evaluated, it has been found that 57% of HIV-infected individuals have distal symmetrical sensory neuropathy and 38% have neuropathic pain. It is now clear that

  10. Temperature sensitive auditory neuropathy.

    PubMed

    Zhang, Qiujing; Lan, Lan; Shi, Wei; Yu, Lan; Xie, Lin-Yi; Xiong, Fen; Zhao, Cui; Li, Na; Yin, Zifang; Zong, Liang; Guan, Jing; Wang, Dayong; Sun, Wei; Wang, Qiuju

    2016-05-01

    Temperature sensitive auditory neuropathy is a very rare and puzzling disorder. In the present study, we reported three unrelated 2 to 6 year-old children who were diagnosed as auditory neuropathy patients who complained of severe hearing loss when they had fever. Their hearing thresholds varied from the morning to the afternoon. Two of these patients' hearing improved with age, and one patient received positive results from cochlear implant. Genetic analysis revealed that these three patients had otoferlin (OTOF) homozygous or compound heterozygous mutations with the genotypes c.2975_2978delAG/c.4819C>T, c.4819C>T/c.4819C>T, or c.2382_2383delC/c.1621G>A, respectively. Our study suggests that these gene mutations may be the cause of temperature sensitive auditory neuropathy. The long term follow up results suggest that the hearing loss in this type of auditory neuropathy may recover with age. PMID:26778470

  11. Cerebral involvement in axonal Charcot-Marie-Tooth neuropathy caused by mitofusin2 mutations.

    PubMed

    Brockmann, Knut; Dreha-Kulaczewski, Steffi; Dechent, Peter; Bönnemann, Carsten; Helms, Gunther; Kyllerman, Marten; Brück, Wolfgang; Frahm, Jens; Huehne, Kathrin; Gärtner, Jutta; Rautenstrauss, Bernd

    2008-07-01

    Mutations in the mitofusin 2 (MFN2) gene are a major cause of primary axonal Charcot- Marie-Tooth (CMT) neuropathy. This study aims at further characterization of cerebral white matter alterations observed in patients with MFN2 mutations. Molecular genetic, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and diffusion tensor imaging (DTI) investigations were performed in four unrelated patients aged 7 to 38 years with early onset axonal CMT neuropathy. Three distinct and so far undescribed MFN2 mutations were detected. Two patients had secondary macrocephaly and mild diffuse predominantly periventricular white matter alterations on MRI. In addition, one boy had symmetrical T2-hyperintensities in both thalami. Two patients had optic atrophy, one of them with normal MRI. In three patients proton MRS revealed elevated concentrations of total N-acetyl compounds (neuronal marker), total creatine (found in all cells) and myo-inositol (astrocytic marker) in cerebral white and gray matter though with regional variation. These alterations were most pronounced in the two patients with abnormal MRI. DTI of these patients revealed mild reductions of fractional anisotropy and mild increase of mean diffusivity in white matter. The present findings indicate an enhanced cellular density in cerebral white matter of MFN2 neuropathy which is primarily due to a reactive gliosis without axonal damage and possibly accompanied by mild demyelination. PMID:18425620

  12. Permanent Peripheral Neuropathy

    PubMed Central

    Higgins, Elizabeth

    2014-01-01

    The health risks and side effects of fluoroquinolone use include the risk of tendon rupture and myasthenia gravis exacerbation, and on August 15, 2013, the Food and Drug Administration updated its warning to include the risk of permanent peripheral neuropathy. We present a case of fluoroquinolone-induced peripheral neuropathy in a patient treated for clinically diagnosed urinary tract infection with ciprofloxacin antibiotic. PMID:26425618

  13. The Background of Mitochondrial DNA Haplogroup J Increases the Sensitivity of Leber's Hereditary Optic Neuropathy Cells to 2,5-Hexanedione Toxicity

    PubMed Central

    Ghelli, Anna; Porcelli, Anna Maria; Zanna, Claudia; Vidoni, Sara; Mattioli, Stefano; Barbieri, Anna; Iommarini, Luisa; Pala, Maria; Achilli, Alessandro; Torroni, Antonio; Rugolo, Michela; Carelli, Valerio

    2009-01-01

    Leber's hereditary optic neuropathy (LHON) is a maternally inherited blinding disease due to mitochondrial DNA (mtDNA) point mutations in complex I subunit genes, whose incomplete penetrance has been attributed to both genetic and environmental factors. Indeed, the mtDNA background defined as haplogroup J is known to increase the penetrance of the 11778/ND4 and 14484/ND6 mutations. Recently it was also documented that the professional exposure to n-hexane might act as an exogenous trigger for LHON. Therefore, we here investigate the effect of the n-hexane neurotoxic metabolite 2,5-hexanedione (2,5-HD) on cell viability and mitochondrial function of different cell models (cybrids and fibroblasts) carrying the LHON mutations on different mtDNA haplogroups. The viability of control and LHON cybrids and fibroblasts, whose mtDNAs were completely sequenced, was assessed using the MTT assay. Mitochondrial ATP synthesis rate driven by complex I substrates was determined with the luciferine/luciferase method. Incubation with 2,5-HD caused the maximal loss of viability in control and LHON cells. The toxic effect of this compound was similar in control cells irrespective of the mtDNA background. On the contrary, sensitivity to 2,5-HD induced cell death was greatly increased in LHON cells carrying the 11778/ND4 or the 14484/ND6 mutation on haplogroup J, whereas the 11778/ND4 mutation in association with haplogroups U and H significantly improved cell survival. The 11778/ND4 mutation on haplogroup U was also more resistant to inhibition of complex I dependent ATP synthesis by 2,5-HD. In conclusion, this study shows that mtDNA haplogroups modulate the response of LHON cells to 2,5-HD. In particular, haplogroup J makes cells more sensitive to its toxic effect. This is the first evidence that an mtDNA background plays a role by interacting with an environmental factor and that 2,5-HD may be a risk element for visual loss in LHON. This proof of principle has broad implications for

  14. Determination of potential role of antioxidative status and circulating biochemical markers in the pathogenesis of ethambutol induced toxic optic neuropathy among diabetic and non-diabetic patients.

    PubMed

    Rasool, Mahmood; Malik, Arif; Manan, Abdul; Aziz, Khuram; Mahmood, Amna; Zaheer, Saima; Shuja, Naveed; Qazi, Mahmood Husain; Kamal, Mohammad Amjad; Karim, Sajjad

    2015-11-01

    The present study was designed to explore the antioxidative status and circulating biochemical markers having a potential role in the pathogenesis of ethambutol (EMB) induced toxic optic neuropathy (TON) among diabetic and non-diabetic patients. Fifty patients under complete therapy of EMB for tuberculosis were included in the present study. Inclusion criteria for patients were to receive EMB everyday during treatment, a dose of 25 mg/kg for initial 2 months and 15 mg/kg during the rest of therapy period. We conducted color vision and visual acuity test for all patients. Fifteen out of fifty EMB induced TON patients, were found to be diabetic. Color vision and visual acuity test results were evaluated for diabetic and non-diabetic as well as twenty age matched controls. The results demonstrated a significant pattern of circulating biochemical markers between the studied groups. Data regarding hematological (RBC, p value = 0.02; Hemoglobin, p value = 0.02), hepatic (total bilirubin, p value = 0.01), renal (urea, p value = 0.03; creatinine, p value = 0.007), lipid (total cholesterol, p value = 0.01; total triglycerides, p value = 0.03) and antioxidative (superoxide dismutase, p value = 0.005; glutathione, p value = 0.02; catalase, p value = 0.02) profile showed a highly significant difference among the studied groups specially patients with diabetes. Malondialdehyde (MDA) level had gone significantly up in diabetic TON patients (p value = 0.02), in comparison to other antioxidants and vitamins (Vit). Vit-A, E, B1, B12 and Zinc seem to be playing a major role in the pathogenesis of TON, specially Vit-E and B1 surpassed all the antioxidants as having highly significant inverse relationships with MDA (MDA vs Vit-E, r = -0.676(**) and MDA vs Vit-B1, r = -0.724(**) respectively). We conclude that during the ethambutol therapy the decreased levels of Vit-E and Vit-B1 possibly play a role in the development of TON and may be used as therapeutic

  15. [Ultrasonographic diagnosis of inflammatory neuropathies].

    PubMed

    Sugimoto, Takamichi; Ochi, Kazuhide; Hosomi, Naohisa; Matsumoto, Masayasu

    2014-03-01

    Ultrasonographic nerve enlargement has primarily been reported in patients with inflammatory neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy, Guillain-Barre syndrome, vasculitic neuropathy and leprosy. Nerve ultrasonography is a promising diagnostic supportive tool for inflammatory neuropathies. The ultrasonographic findings that are currently useful are 1) nerve enlargement primarily suggests the existence of inflammatory or demyelinating neuropathies and 2) for patients with CIDP or demyelinating Charcot-Marie-Tooth disease, the pattern of nerve enlargement is noted, and this pattern is useful for discriminating between these diseases. More precise evidence of ultrasonographic findings for inflammatory neuropathies should be established in the future. PMID:24607946

  16. Peripheral neuropathies during biologic therapies.

    PubMed

    Yagita, Masato; Hamano, Toshiaki; Hatachi, Saori; Fujita, Masaaki

    2016-01-01

    Peripheral neuropathies should be recognized as the adverse effects of biological agents, especially anti-TNF agents. However, no solid clinical databases for biological agent-associated peripheral neuropathies (BAPN) have been established in Japan. Here we report two cases of peripheral neuropathy associated with anti-TNF agents. One was peroneal motor neuropathy. The other case was chronic inflammatory demyelinating polyradiculoneuropathy. In addition, we summarize the previous reports on BAPN and discuss their prevalence rate, pathogenesis and management. PMID:24313920

  17. Multifocal motor neuropathy.

    PubMed

    Muley, Suraj Ashok; Parry, Gareth J

    2012-09-01

    Multifocal motor neuropathy (MMN) was first described in 1988 as a purely motor neuropathy affecting multiple motor nerves. The diagnosis was based entirely on demonstrating electrophysiological evidence of a conduction block (CB) that selectively affected motor axons, with sparing of sensory axons even through the site of motor CB. Subsequently, a similar disorder was reported but with absence of demonstrable CB on routine nerve conduction studies and there is still some debate as to whether MMN without CB is related to MMN. MMN is thought to be an inflammatory neuropathy related to an immune attack on motor nerves. The conventional hypothesis is that the primary pathology is segmental demyelination, but recent research raises the possibility of a primary axonopathy. Anti-GM1 antibodies can be found in some patients but it is unclear whether these antibodies are pathogenic. Intravenous immunoglobulin is the mainstay of treatment but other immunosuppressive treatments can also be effective. PMID:22743043

  18. Nitrated poly(4-hydroxystyrene) microspheres for optical pH and potassium ion sensing based on turbidity changes accompanying polymer sweller

    NASA Astrophysics Data System (ADS)

    Wang, Hongming

    2000-10-01

    Porous poly(4-acetoxystyrene) swellable microspheres with diameters approximately 1~2 μm were prepared by seeded emulsion polymerization. Toluene was used as the porogenic solvent and divinylbenzene was used as the crosslinker. The seed particles with diameters approximately 0.5~1 μm were prepared by dispersion polymerization without adding porogenic solvent and crosslinker. Functionality was introduced by two derivatization reactions, hydrolysis and nitration, to form nitrated poly(4-hydroxystyrene). These polymer microspheres swell at high pH due to the deprotonation of the hydroxyl group on the polymer backbone. Swelling is accompanied by an increase in water content which causes the polymer refractive index to decrease. These microspheres, were embedded in a hydrogel for pH sensing. When either dibenzo-18-crown-6 or valinomycin was co- immobilized on the polymer, they were then used to sense potassium ion. Poly(2-hydroxyethylmethacrylate) or poly(vinylalcohol) hydrogel membranes with embedded nitrated poly(4- hydroxystyrene) microspheres were prepared by photopolymerization. These membranes possess desirable optical properties for pH sensing. The refractive index of the hydrated hydrogel is constant and not affected by pH, but the refractive index of the microspheres does vary with pH. When the membrane is in contact with a buffer at high pH, the membrane turbidity decreases because the refractive index difference between the microspheres and the hydrogel decreases. The apparent pKa values can be adjusted by varying the nitrogen percentage of the microspheres, by controlling the conditions of the nitration reaction. The observed pK a value can be as low as 5.6 or as high as 10.2. The response time of the membrane with microspheres prepared by seeded emulsion polymerization utilizing PVA as the membrane matrix was 10~15 seconds. Response times were longer for the poly(HEMA) matrix with embedded microspheres synthesized by dispersion polymerization. A very

  19. Diabetic Neuropathy: Mechanisms to Management

    PubMed Central

    Edwards, James L.; Vincent, Andrea; Cheng, Thomas; Feldman, Eva L.

    2014-01-01

    Neuropathy is the most common and debilitating complication of diabetes and results in pain, decreased motility, and amputation. Diabetic neuropathy encompasses a variety of forms whose impact ranges from discomfort to death. Hyperglycemia induces oxidative stress in diabetic neurons and results in activation of multiple biochemical pathways. These activated pathways are a major source of damage and are potential therapeutic targets in diabetic neuropathy. Though therapies are available to alleviate the symptoms of diabetic neuropathy, few options are available to eliminate the root causes. The immense physical, psychological, and economic cost of diabetic neuropathy underscores the need for causally targeted therapies. This review covers the pathology, epidemiology, biochemical pathways, and prevention of diabetic neuropathy, as well as discusses current symptomatic and causal therapies and novel approaches to identify therapeutic targets. PMID:18616962

  20. Genetics Home Reference: ataxia neuropathy spectrum

    MedlinePlus

    ... Genetics Home Health Conditions ataxia neuropathy spectrum ataxia neuropathy spectrum Enable Javascript to view the expand/collapse ... Download PDF Open All Close All Description Ataxia neuropathy spectrum is part of a group of conditions ...

  1. Genetics Home Reference: small fiber neuropathy

    MedlinePlus

    ... Home Health Conditions small fiber neuropathy small fiber neuropathy Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Small fiber neuropathy is a condition characterized by severe pain attacks ...

  2. Autoimmune peripheral neuropathies.

    PubMed

    Bourque, Pierre R; Chardon, Jodi Warman; Massie, Rami

    2015-09-20

    Peripheral nervous system axons and myelin have unique potential protein, proteolipid, and ganglioside antigenic determinants. Despite the existence of a blood-nerve barrier, both humoral and cellular immunity can be directed against peripheral axons and myelin. Molecular mimicry may be triggered at the systemic level, as was best demonstrated in the case of bacterial oligosaccharides. The classification of immune neuropathy has been expanded to take into account specific syndromes that share unique clinical, electrophysiological, prognostic and serological features. Guillain-Barré syndrome encompasses a classical syndrome of acute demyelinating polyradiculoneuropathy and many variants: axonal motor and sensory, axonal motor, Miller-Fisher, autonomic, and sensory. Similarly, chronic immune neuropathy is composed of classic chronic inflammatory demyelinating polyradiculoneuropathy and variants characterized as multifocal (motor or sensorimotor), sensory, distal symmetric, and syndromes associated with monoclonal gammopathy. Among putative biomarkers, myelin associated glycoprotein and several anti-ganglioside autoantibodies have shown statistically significant associations with specific neuropathic syndromes. Currently, the strongest biomarker associations are those linking Miller-Fisher syndrome with anti-GQ1b, multifocal motor neuropathy with anti-GM1, and distal acquired symmetric neuropathy with anti-MAG antibodies. Many other autoantibody associations have been proposed, but presently lack sufficient specificity and sensitivity to qualify as biomarkers. This field of research has contributed to the antigenic characterization of motor and sensory functional systems, as well as helping to define immune neuropathic syndromes with widely different clinical presentation, prognosis and response to therapy. Serologic biomarkers are likely to become even more relevant with the advent of new targeted forms of immunotherapy, such as monoclonal antibodies. PMID:25748038

  3. Diabetic autonomic neuropathy.

    PubMed

    Clarke, B F; Ewing, D J; Campbell, I W

    1979-10-01

    This review attempts to outline the present understanding of diabetic autonomic neuropathy. The clinical features have been increasinly recognised but knowledge of the localization and morphology of the lesions and their pathogenesis remains fragmentary. A metabolic causation as postulated in somatic nerves accords best with clinical observations. Most bodily systems, particularly the cardiovascular, gastrointestinal and urogenital, are involved with added disturbances of thermoregulatory function and pupillary reflexes. Possible effects on neuroendocrine and peptidergic secretion and respiratory control await definition. Current interest centres around the development of a new generation of tests of autonomic nerve function that are simple, non-invasive, reproducible and allow precision in diagnosis and accurate quantitation. Most are based on cardiovascular reflexes and abnormality in them is assumed to reflect autonomic damage elsewhere. Probably no single test suffices and a battery of tests reflecting both parasympathetic and sympathetic function is preferable. Little is known of the natural history. The prevalence may be greater than previously suspected and although symptoms are mild in the majority, a few develop florid features. The relation of control and duration of diabetes to the onset and progression of autonomic neuropathy is not clearly established. Once tests of autonomic function become abnormal they usually remain abnormal. Symptomatic autonomic neuropathy carries a greatly increased mortality rate possibly due to indirect mechanisms such as renal failure and direct mechanisms such as cardio-resiratory arrest. Improved treatment of some of the more disabling symptoms has been possible in recent years. PMID:387501

  4. [Radiation-induced neuropathy].

    PubMed

    Kolak, Agnieszka; Starosławska, Elzbieta; Kieszko, Dariusz; Cisek, Paweł; Patyra, Krzysztof Ireneusz; Surdyka, Dariusz; Dobrzyńska-Rutkowska, Aneta; Łopacka-Szatan, Karolina; Burdan, Franciszek

    2013-12-01

    Radiation-induced neuropathy is commonly observed among oncological patients. Radiation can affect the nervous tissue directly or indirectly by inducing vasculopathy or dysfunction of internal organs. Symptoms may be mild and reversible (e.g., pain, nausea, vomiting, fever, drowsiness, fatigue, paresthesia) or life-threatening (cerebral oedema, increased intracranial pressure, seizures). Such complications are clinically divided into peripheral (plexopathies, neuropathies of spinal and cranial nerves) and central neuropathy (myelopathy, encephalopathy, cognitive impairment). The degree of neuronal damages primarily depends on the total and fractional radiation dose and applied therapeutic methods. The conformal and megavoltage radiotherapy seems to be the safeties ones. Diagnostic protocol includes physical examination, imaging (in particular magnetic resonance), electromyography, nerve conduction study and sometimes histological examination. Prevention and early detection of neurological complications are necessary in order to prevent a permanent dysfunction of the nervous system. Presently their treatment is mostly symptomatic, but in same cases a surgical intervention is required. An experimental and clinical data indicates some effectiveness of different neuroprotective agents (e.g. anticoagulants, vitamin E, hyperbaric oxygen, pentoxifylline, bevacizumab, methylphenidate, donepezil), which should be administered before and/or during radiotherapy. PMID:24490474

  5. An Early Diagnostic Tool for Diabetic Peripheral Neuropathy in Rats

    PubMed Central

    Kambiz, Shoista; van Neck, Johan W.; Cosgun, Saniye G.; van Velzen, Marit H. N.; Janssen, Joop A. M. J. L.; Avazverdi, Naim; Hovius, Steven E. R.; Walbeehm, Erik T.

    2015-01-01

    The skin’s rewarming rate of diabetic patients is used as a diagnostic tool for early diagnosis of diabetic neuropathy. At present, the relationship between microvascular changes in the skin and diabetic neuropathy is unclear in streptozotocin (STZ) diabetic rats. The aim of this study was to investigate whether the skin rewarming rate in diabetic rats is related to microvascular changes and whether this is accompanied by changes observed in classical diagnostic methods for diabetic peripheral neuropathy. Computer-assisted infrared thermography was used to assess the rewarming rate after cold exposure on the plantar skin of STZ diabetic rats’ hind paws. Peripheral neuropathy was determined by the density of intra-epidermal nerve fibers (IENFs), mechanical sensitivity, and electrophysiological recordings. Data were obtained in diabetic rats at four, six, and eight weeks after the induction of diabetes and in controls. Four weeks after the induction of diabetes, a delayed rewarming rate, decreased skin blood flow and decreased density of IENFs were observed. However, the mechanical hyposensitivity and decreased motor nerve conduction velocity (MNCV) developed 6 and 8 weeks after the induction of diabetes. Our study shows that the skin rewarming rate is related to microvascular changes in diabetic rats. Moreover, the skin rewarming rate is a non-invasive method that provides more information for an earlier diagnosis of peripheral neuropathy than the classical monofilament test and MNCV in STZ induced diabetic rats. PMID:25984949

  6. Painful Peripheral Neuropathies

    PubMed Central

    Marchettini, P; Lacerenza, M; Mauri, E; Marangoni, C

    2006-01-01

    Peripheral neuropathies are a heterogeneous group of diseases affecting peripheral nerves. The causes are multiple: hereditary, metabolic, infectious, inflammatory, toxic, traumatic. The temporal profile includes acute, subacute and chronic conditions. The majority of peripheral neuropathies cause mainly muscle weakness and sensory loss, positive sensory symptoms and sometimes pain. When pain is present, however, it is usually extremely intense and among the most disabling symptoms for the patients. In addition, the neurological origin of the pain is often missed and patients receive inadequate or delayed specific treatment. Independently of the disease causing the peripheral nerve injury, pain originating from axonal pathology or ganglionopathy privileges neuropathies affecting smaller fibres, a clinical observation that points towards abnormal activity within nociceptive afferents as a main generator of pain. Natural activation of blood vessels or perineurial nociceptive network by pathology also causes intense pain. Pain of this kind, i.e. nerve trunk pain, is among the heralding symptoms of inflammatory or ischemic mononeuropathy and for its intensity represents itself a medical emergency. Neuropathic pain quality rekindles the psychophysical experience of peripheral nerves intraneural microstimulation i.e. a combination of large and small fibres sensation temporally distorted compared to physiological perception evoked by natural stimuli. Pins and needles, burning, cramping mixed with numbness, and tingling are the wording most used by patients. Nociceptive pain instead is most often described as aching, deep and dull. Good command of peripheral nerve anatomy and pathophysiology allows timely recognition of the different pain components and targeted treatment, selected according to intensity, type and temporal profile of the pain. PMID:18615140

  7. Cardiovascular autonomic neuropathy

    PubMed Central

    McCarty, Niamh

    2016-01-01

    Cardiovascular autonomic neuropathy often goes unrecognized. We present a case of a 22-year-old man with multiple manifestations of this disease, including weakness, dizziness, fatigue, tachycardia, abnormal QTc, and orthostasis, which occurred 2 years after his type 1 diabetes diagnosis. He exhibited parasympathetic denervation with resting tachycardia and exercise intolerance but also had evidence of orthostatic hypotension, which suggests sympathetic denervation. He did not have complete cardiovascular autonomic reflex testing, which would have been helpful, but improved with aggressive diabetes treatment and the increase of beta-blockade. It is important to identify these patients to understand their signs and symptoms and consider appropriate therapies. PMID:27034552

  8. Cardiovascular autonomic neuropathy.

    PubMed

    McCarty, Niamh; Silverman, Barry

    2016-04-01

    Cardiovascular autonomic neuropathy often goes unrecognized. We present a case of a 22-year-old man with multiple manifestations of this disease, including weakness, dizziness, fatigue, tachycardia, abnormal QTc, and orthostasis, which occurred 2 years after his type 1 diabetes diagnosis. He exhibited parasympathetic denervation with resting tachycardia and exercise intolerance but also had evidence of orthostatic hypotension, which suggests sympathetic denervation. He did not have complete cardiovascular autonomic reflex testing, which would have been helpful, but improved with aggressive diabetes treatment and the increase of beta-blockade. It is important to identify these patients to understand their signs and symptoms and consider appropriate therapies. PMID:27034552

  9. Metabolic neuropathies and myopathies.

    PubMed

    D'Amico, Adele; Bertini, Enrico

    2013-01-01

    Inborn errors of metabolism may impact on muscle and peripheral nerve. Abnormalities involve mitochondria and other subcellular organelles such as peroxisomes and lysosomes related to the turnover and recycling of cellular compartments. Treatable causes are β-oxidation defects producing progressive neuropathy; pyruvate dehydrogenase deficiency, porphyria, or vitamin B12 deficiency causing recurrent episodes of neuropathy or acute motor deficit mimicking Guillain-Barré syndrome. On the other hand, lysosomal (mucopolysaccharidosis, Gaucher and Fabry diseases), mitochondriopathic (mitochondrial or nuclear mutations or mDNA depletion), peroxisomal (adrenomyeloneuropathy, Refsum disease, sterol carrier protein-2 deficiency, cerebrotendinous xanthomatosis, α-methylacyl racemase deficiency) diseases are multisystemic disorders involving also the heart, liver, brain, retina, and kidney. Pathophysiology of most metabolic myopathies is related to the impairment of energy production or to abnormal production of reactive oxygen species (ROS). Main symptoms are exercise intolerance with myalgias, cramps and recurrent myoglobinuria or limb weakness associated with elevation of serum creatine kinase. Carnitine palmitoyl transferase deficiency, followed by acid maltase deficiency, and lipin deficiency, are the most common cause of isolated rhabdomyolysis. Metabolic myopathies are frequently associated to extra-neuromuscular disorders particularly involving the heart, liver, brain, retina, skin, and kidney. PMID:23622366

  10. Diabetic corneal neuropathy.

    PubMed Central

    Schultz, R O; Peters, M A; Sobocinski, K; Nassif, K; Schultz, K J

    1983-01-01

    Corneal epithelial lesions can be found in approximately one-half of asymptomatic patients with diabetes mellitus. These lesions are transient and clinically resemble the keratopathy seen in staphylococcal keratoconjunctivitis. Staphylococcal organisms, however, can be isolated in equal percentages from diabetic patients without keratopathy. Diabetic peripheral neuropathy was found to be related to the presence of diabetic keratopathy after adjusting for age with analysis of covariance. The strongest predictor of both keratopathy and corneal fluorescein staining was vibration perception threshold in the toes (P less than 0.01); and the severity of keratopathy was directly related to the degree of diminution of peripheral sensation. Other predictors of keratopathy were: reduced tear breakup time (P less than 0.03), type of diabetes (P less than 0.01), and metabolic status as indicated by c-peptide fasting (P less than 0.01). No significant relationships were found between the presence of keratopathy and tear glucose levels, endothelial cell densities, corneal thickness measurements, the presence of S epidermidis, or with duration of disease. It is our conclusion that asymptomatic epithelial lesions in the nontraumatized diabetic cornea can occur as a manifestation of generalized polyneuropathy and probably represent a specific form of corneal neuropathy. Images FIGURE 1 FIGURE 2 FIGURE 3 PMID:6676964

  11. Pediatric sciatic neuropathies

    PubMed Central

    Ryan, M.M.; Escolar, D.M.; Darras, B.; Jones, H.R.

    2011-01-01

    Objective: The incidence, cause, and prognosis of sciatic neuropathy in children is not well understood. We report our 30-year experience of 53 patients with pediatric sciatic neuropathies (SN). Methods: Prospective review of the history, physical examination, electrophysiologic findings, and clinical course of children with SN. Results: The etiology of SN injury was varied and included trauma (13), iatrogenic causes (13) (8 orthopedic surgeries and 5 miscellaneous surgeries), prolonged extrinsic compression and immobilization (6), tumors (7), vascular (5), idiopathic and progressive (4), infantile and nonprogressive (2), and unknown, presumed postviral (3). Electrophysiologic studies demonstrated abnormalities in motor conduction studies of the peroneal nerve in 44/53 (83%) or tibial nerve in 35/51 (67%). Sensory conduction studies were abnormal in sural nerve in 34 of 43 cases (79%), and superficial peroneal nerves in 15/25 (60%). Needle EMG was abnormal in peroneal innervated muscles in all subjects, in tibial nerve innervated muscles in 43/51 (84%), and in the hamstrings in 18/29 (62%). Prognosis for recovery was variable and depended on the etiology and the severity of the nerve injury. Conclusions: SN is an uncommon mononeuropathy in children. The causes of SN are varied in children compared to adults. Electrophysiologic studies in children may be limited by poor tolerance but play an important role in establishing the diagnosis. PMID:21403109

  12. Diagnostic approach to peripheral neuropathy

    PubMed Central

    Misra, Usha Kant; Kalita, Jayantee; Nair, Pradeep P.

    2008-01-01

    Peripheral neuropathy refers to disorders of the peripheral nervous system. They have numerous causes and diverse presentations; hence, a systematic and logical approach is needed for cost-effective diagnosis, especially of treatable neuropathies. A detailed history of symptoms, family and occupational history should be obtained. General and systemic examinations provide valuable clues. Neurological examinations investigating sensory, motor and autonomic signs help to define the topography and nature of neuropathy. Large fiber neuropathy manifests with the loss of joint position and vibration sense and sensory ataxia, whereas small fiber neuropathy manifests with the impairment of pain, temperature and autonomic functions. Electrodiagnostic (EDx) tests include sensory, motor nerve conduction, F response, H reflex and needle electromyography (EMG). EDx helps in documenting the extent of sensory motor deficits, categorizing demyelinating (prolonged terminal latency, slowing of nerve conduction velocity, dispersion and conduction block) and axonal (marginal slowing of nerve conduction and small compound muscle or sensory action potential and dennervation on EMG). Uniform demyelinating features are suggestive of hereditary demyelination, whereas difference between nerves and segments of the same nerve favor acquired demyelination. Finally, neuropathy is classified into mononeuropathy commonly due to entrapment or trauma; mononeuropathy multiplex commonly due to leprosy and vasculitis; and polyneuropathy due to systemic, metabolic or toxic etiology. Laboratory investigations are carried out as indicated and specialized tests such as biochemical, immunological, genetic studies, cerebrospinal fluid (CSF) examination and nerve biopsy are carried out in selected patients. Approximately 20% patients with neuropathy remain undiagnosed but the prognosis is not bad in them. PMID:19893645

  13. Auditory Neuropathy/Dyssynchrony in Biotinidase Deficiency

    PubMed Central

    Yaghini, Omid

    2016-01-01

    Biotinidase deficiency is a disorder inherited autosomal recessively showing evidence of hearing loss and optic atrophy in addition to seizures, hypotonia, and ataxia. In the present study, a 2-year-old boy with Biotinidase deficiency is presented in which clinical symptoms have been reported with auditory neuropathy/auditory dyssynchrony (AN/AD). In this case, transient-evoked otoacoustic emissions showed bilaterally normal responses representing normal function of outer hair cells. In contrast, acoustic reflex test showed absent reflexes bilaterally, and visual reinforcement audiometry and auditory brainstem responses indicated severe to profound hearing loss in both ears. These results suggest AN/AD in patients with Biotinidase deficiency. PMID:27144235

  14. The coexistence of mitochondrial ND6 T14484C and 12S rRNA A1555G mutations in a Chinese family with Leber's hereditary optic neuropathy and hearing loss

    SciTech Connect

    Wei Qiping; Zhou Xiangtian; Yang Li; Sun Yanhong; Zhou Jian; Li Guang; Jiang, Robert; Lu Fan; Qu Jia . E-mail: jqu@wzmc.net; Guan Minxin . E-mail: min-xin.guan@cchmc.org

    2007-06-15

    We report here the clinical, genetic and molecular characterization of one three-generation Han Chinese family with Leber's hereditary optic neuropathy (LHON) and hearing loss. Four of 14 matrilineal relatives exhibited the moderate central vision loss at the average age of 12.5 years. Of these, one subject exhibited both LHON and mild hearing impairment. Sequence analysis of the complete mitochondrial genomes in the pedigree showed the presence of homoplasmic LHON-associated ND6 T14484C mutation, deafness-associated 12S rRNA A1555 mutation and 47 other variants belonging to Eastern Asian haplogroup H2. None of other mitochondrial variants was evolutionarily conserved and functional significance. Therefore, the coexistence of the A1555G mutation and T14484C mutations in this Chinese family indicate that the A1555G mutation may play a synergistic role in the phenotypic manifestation of LHON associated ND6 T14484C mutation. However, the incomplete penetrance of vision and hearing loss suggests the involvement of nuclear modifier genes and environmental factors in the phenotypic expression of these mtDNA mutations.

  15. Inflammatory demyelinating neuropathies.

    PubMed

    Muley, Suraj Ashok; Parry, Gareth J

    2009-05-01

    Early and effective treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) is important to minimize axonal degeneration that occurs secondary to demyelination. The disease course is invariably chronic, so long-term treatment is often required, and adverse effects and costs are important considerations in devising a treatment plan. CIDP responds to prednisone, but long-term treatment can result in significant adverse effects. Azathioprine, mycophenolate mofetil, and cyclosporine can be used as steroid-sparing agents and may facilitate more rapid and successful tapering of prednisone. Intravenous immunoglobulin (IVIg) and plasma exchange are also effective in the treatment of CIDP and can be used in patients who are unresponsive to prednisone or develop steroid-related adverse effects. IVIg may also be used as a first-line treatment, but its cost can be a limiting factor. A few uncontrolled studies have suggested that pulsed weekly methylprednisolone is both effective and well tolerated in the long-term treatment of CIDP. Treatments based on rituximab or cyclophosphamide have also been used in resistant disease. Variants of CIDP have been described on the basis of their association with specific antibodies or immunoglobulins and their response to specific immunomodulatory treatments. Multifocal motor neuropathy with conduction block responds to IVIg in the majority of patients. However, weakness may slowly worsen over time, and some patients become unresponsive. Anecdotal reports suggest that rituximab may be useful in patients who develop progressive disease. Placebo-controlled trials in anti-myelin-associated glycoprotein neuropathy suggest that rituximab is effective and, with a combination of prednisone and cyclophosphamide, numbness and strength may improve. Other treatments that may be effective include plasma exchange and IVIg. Treatment is generally started with prednisone, IVIg, or plasma exchange. Rituximab and cyclophosphamide are used only

  16. Peripheral Neuropathy and Agent Orange

    MedlinePlus

    ... registry health exam . Research on peripheral neuropathy and herbicides The Health and Medicine Division (HMD) (formally known ... acute or subacute onset may be associated with herbicide exposure. Based on this evidence, VA presumed an ...

  17. Vasculitic neuropathy following exposure to minocycline

    PubMed Central

    Baratta, John M.; Dyck, P. James B.; Brand, Patricio; Thaisetthawatkul, Pariwat; Dyck, Peter J.; Engelstad, JaNean K.; Goodman, Brent

    2015-01-01

    Objective: To report 3 patients with minocycline-induced autoimmunity resulting in peripheral nerve vasculitis. Methods: We report 3 patients who, during minocycline treatment for acne vulgaris, developed subacute onset of pain and weakness caused by vasculitis in single and multiple mononeuropathy patterns. Results: Each patient underwent either a nerve or muscle biopsy that confirmed vasculitis. One patient additionally developed systemic symptoms (including fever, fatigue, and night sweats) and another had a posterior circulation stroke. Symptoms developed with either early or prolonged use of minocycline. Despite withdrawal of minocycline, patients needed long-term immunotherapy to gain neurologic improvement. Conclusions: Our findings suggest that the typical neuropathy associated with minocycline use is painful single or multiple mononeuropathy due to peripheral nerve vasculitis, which may also be accompanied by presumed CNS vasculitis (presenting as stroke). PMID:26601119

  18. Partial regeneration and long-term survival of rat retinal ganglion cells after optic nerve crush is accompanied by altered expression, phosphorylation and distribution of cytoskeletal proteins.

    PubMed

    Dieterich, Daniela C; Trivedi, Niraj; Engelmann, Ralf; Gundelfinger, Eckart D; Gordon-Weeks, Phillip R; Kreutz, Michael R

    2002-05-01

    In a screen to identify genes that are expressed differentially in the retina after partial optic nerve crush, we identified MAP1B as an up-regulated transcript. Western blot analysis of inner retina protein preparations confirmed changes in the protein composition of the microtubule-associated cytoskeleton of crushed vs. uncrushed nerve. MAP1B immunoreactivity and transcript levels were elevated for two weeks after crush. Immunostaining and Western blots with monoclonal antibodies directed against developmentally regulated phosphorylation sites on MAP1B revealed a gradient of MAP1B phosphorylation from the proximal optic nerve stump to the soma of retinal ganglion cells. Most interestingly, using antibodies directed against developmentally regulated phosphorylation sites on MAP1B, we observed that a significant number of crushed optic nerve axons develop MAP1B-immunopositive growth cones, which cross the crush site and migrate along the distal nerve fragment. In parallel, an abnormal distribution of highly phosphorylated neurofilament protein (pNF-H) in the cell soma and dendrites of presumably axotomized retinal ganglion cells was observed following partial nerve crush. This redistribution is present for the period between day 7 and 28 postcrush and is not seen in cells that stay connected to the superior colliculus. Axotomized ganglion cells, which contain pNF-H in soma and dendrites appear to have been disconnected from the colliculus at an early stage but survive axonal trauma for long periods. PMID:12028353

  19. Crucifixion and median neuropathy

    PubMed Central

    Regan, Jacqueline M; Shahlaie, Kiarash; Watson, Joseph C

    2013-01-01

    Crucifixion as a means of torture and execution was first developed in the 6th century B.C. and remained popular for over 1000 years. Details of the practice, which claimed hundreds of thousands of lives, have intrigued scholars as historical records and archaeological findings from the era are limited. As a result, various aspects of crucifixion, including the type of crosses used, methods of securing victims to crosses, the length of time victims survived on the cross, and the exact mechanisms of death, remain topics of debate. One aspect of crucifixion not previously explored in detail is the characteristic hand posture often depicted in artistic renditions of crucifixion. In this posture, the hand is clenched in a peculiar and characteristic fashion: there is complete failure of flexion of the thumb and index finger with partial failure of flexion of the middle finger. Such a “crucified clench” is depicted across different cultures and from different eras. A review of crucifixion history and techniques, median nerve anatomy and function, and the historical artistic depiction of crucifixion was performed to support the hypothesis that the “crucified clench” results from proximal median neuropathy due to positioning on the cross, rather than from direct trauma of impalement of the hand or wrist. PMID:23785656

  20. Evaluation and prevention of diabetic neuropathy.

    PubMed

    Aring, Ann M; Jones, David E; Falko, James M

    2005-06-01

    Diabetic neuropathy is a debilitating disorder that occurs in nearly 50 percent of patients with diabetes. It is a late finding in type 1 diabetes but can be an early finding in type 2 diabetes. The primary types of diabetic neuropathy are sensorimotor and autonomic. Patients may present with only one type of diabetic neuropathy or may develop combinations of neuropathies (e.g., distal symmetric polyneuropathy and autonomic neuropathy). Distal symmetric polyneuropathy is the most common form of diabetic neuropathy. Diabetic neuropathy also can cause motor deficits, silent cardiac ischemia, orthostatic hypotension, vasomotor instability, hyperhidrosis, gastroparesis, bladder dysfunction, and sexual dysfunction. Strict glycemic control and good daily foot care are key to preventing complications of diabetic neuropathy. PMID:15952441

  1. Profiling the Mitochondrial Proteome of Leber’s Hereditary Optic Neuropathy (LHON) in Thailand: Down-Regulation of Bioenergetics and Mitochondrial Protein Quality Control Pathways in Fibroblasts with the 11778G>A Mutation

    PubMed Central

    Tun, Aung Win; Chaiyarit, Sakdithep; Kaewsutthi, Supannee; Katanyoo, Wanphen; Chuenkongkaew, Wanicha; Kuwano, Masayoshi; Tomonaga, Takeshi; Peerapittayamongkol, Chayanon; Thongboonkerd, Visith; Lertrit, Patcharee

    2014-01-01

    Leber’s Hereditary Optic Neuropathy (LHON) is one of the commonest mitochondrial diseases. It causes total blindness, and predominantly affects young males. For the disease to develop, it is necessary for an individual to carry one of the primary mtDNA mutations 11778G>A, 14484T>C or 3460G>A. However these mutations are not sufficient to cause disease, and they do not explain the characteristic features of LHON such as the higher prevalence in males, incomplete penetrance, and relatively later age of onset. In order to explore the roles of nuclear encoded mitochondrial proteins in development of LHON, we applied a proteomic approach to samples from affected and unaffected individuals from 3 pedigrees and from 5 unrelated controls. Two-dimensional electrophoresis followed by MS/MS analysis in the mitochondrial lysate identified 17 proteins which were differentially expressed between LHON cases and unrelated controls, and 24 proteins which were differentially expressed between unaffected relatives and unrelated controls. The proteomic data were successfully validated by western blot analysis of 3 selected proteins. All of the proteins identified in the study were mitochondrial proteins and most of them were down regulated in 11778G>A mutant fibroblasts. These proteins included: subunits of OXPHOS enzyme complexes, proteins involved in intermediary metabolic processes, nucleoid related proteins, chaperones, cristae remodelling proteins and an anti-oxidant enzyme. The protein profiles of both the affected and unaffected 11778G>A carriers shared many features which differed from those of unrelated control group, revealing similar proteomic responses to 11778G>A mutation in both affected and unaffected individuals. Differentially expressed proteins revealed two broad groups: a cluster of bioenergetic pathway proteins and a cluster involved in protein quality control system. Defects in these systems are likely to impede the function of retinal ganglion cells, and may

  2. Diabetic neuropathy in the gut: pathogenesis and diagnosis.

    PubMed

    Azpiroz, Fernando; Malagelada, Carolina

    2016-03-01

    The activity of the digestive tract is usually regulated to match its content: physiological stimuli in the gut induce modulatory reflexes that control digestive function so that digestion is normally not perceived. However, under certain circumstances, digestive stimuli may activate sensory afferents and give rise to conscious sensations. Both reflex and sensory signals are modulated by a balance of excitatory and inhibitory mechanisms. Patients with diabetes may develop a neuropathy affecting the control of gastric and/or intestinal motor function and the sensory innervation as well. During fasting the stomach is contracted and relaxes to accommodate a meal. After ingestion the stomach progressively recontracts and this contraction gently produces gastric emptying. Impairment of excitatory pathways affects the contraction of the stomach, which may result in delayed gastric emptying and vomiting of retained food. Conversely, alteration of the inhibitory neural pathways results in impaired relaxation of the stomach in response to a meal; in this case increased wall tension may produce early satiation, fullness and nausea. Diabetic neuropathy may distort the control of intestinal motility, which can lead to diverse symptoms such as diarrhoea, constipation, intestinal distension and abdominal pain. Neuropathy in diabetes may also affect the sensory nerves of the gut, and depending on which pathways are involved, perception may be increased or reduced. In summary, in patients with diabetic neuropathy, disorders of gut motor function are associated with sensory abnormalities, and the combination of impaired pathways determines the clinical consequences. This review summarises a presentation given at the 'Diagnosis and treatment of autonomic diabetic neuropathy in the gut' symposium at the 2015 annual meeting of the EASD. It is accompanied by another mini-review on a topic from this symposium (by Hans Törnblom, DOI: 10.1007/s00125-015-3829-9 ) and a commentary by the

  3. Disruptive SCYL1 Mutations Underlie a Syndrome Characterized by Recurrent Episodes of Liver Failure, Peripheral Neuropathy, Cerebellar Atrophy, and Ataxia

    PubMed Central

    Schmidt, Wolfgang M.; Rutledge, S. Lane; Schüle, Rebecca; Mayerhofer, Benjamin; Züchner, Stephan; Boltshauser, Eugen; Bittner, Reginald E.

    2015-01-01

    Hereditary ataxias comprise a group of genetically heterogeneous disorders characterized by clinically variable cerebellar dysfunction and accompanied by involvement of other organ systems. The molecular underpinnings for many of these diseases are widely unknown. Previously, we discovered the disruption of Scyl1 as the molecular basis of the mouse mutant mdf, which is affected by neurogenic muscular atrophy, progressive gait ataxia with tremor, cerebellar vermis atrophy, and optic-nerve thinning. Here, we report on three human individuals, from two unrelated families, who presented with recurrent episodes of acute liver failure in early infancy and are affected by cerebellar vermis atrophy, ataxia, and peripheral neuropathy. By whole-exome sequencing, compound-heterozygous mutations within SCYL1 were identified in all affected individuals. We further show that in SCYL1-deficient human fibroblasts, the Golgi apparatus is massively enlarged, which is in line with the concept that SCYL1 regulates Golgi integrity. Thus, our findings define SCYL1 mutations as the genetic cause of a human hepatocerebellar neuropathy syndrome. PMID:26581903

  4. Disruptive SCYL1 Mutations Underlie a Syndrome Characterized by Recurrent Episodes of Liver Failure, Peripheral Neuropathy, Cerebellar Atrophy, and Ataxia.

    PubMed

    Schmidt, Wolfgang M; Rutledge, S Lane; Schüle, Rebecca; Mayerhofer, Benjamin; Züchner, Stephan; Boltshauser, Eugen; Bittner, Reginald E

    2015-12-01

    Hereditary ataxias comprise a group of genetically heterogeneous disorders characterized by clinically variable cerebellar dysfunction and accompanied by involvement of other organ systems. The molecular underpinnings for many of these diseases are widely unknown. Previously, we discovered the disruption of Scyl1 as the molecular basis of the mouse mutant mdf, which is affected by neurogenic muscular atrophy, progressive gait ataxia with tremor, cerebellar vermis atrophy, and optic-nerve thinning. Here, we report on three human individuals, from two unrelated families, who presented with recurrent episodes of acute liver failure in early infancy and are affected by cerebellar vermis atrophy, ataxia, and peripheral neuropathy. By whole-exome sequencing, compound-heterozygous mutations within SCYL1 were identified in all affected individuals. We further show that in SCYL1-deficient human fibroblasts, the Golgi apparatus is massively enlarged, which is in line with the concept that SCYL1 regulates Golgi integrity. Thus, our findings define SCYL1 mutations as the genetic cause of a human hepatocerebellar neuropathy syndrome. PMID:26581903

  5. Paraproteinemic neuropathy: a practical review.

    PubMed

    Rison, Richard A; Beydoun, Said R

    2016-01-01

    The term paraproteinemic neuropathy describes a heterogeneous set of neuropathies characterized by the presence of homogeneous immunoglobulin in the serum. An abnormal clonal proliferation of B-lymphocytes or plasma cells, which may or may not occur in the context of a hematologic malignancy, produces the immunoglobulins in excess. If malignancy is identified, treatment should be targeted to the neoplasm. Most cases, however, occur as monoclonal gammopathy of undetermined significance. Few prospective, randomized, placebo-controlled trials are available to inform the management of paraproteinemic neuropathies. Clinical experience combined with data from smaller, uncontrolled studies provide a basis for recommendations, which depend on the specific clinical setting in which the paraprotein occurs. In this review, we provide a clinically practical approach to diagnosis and management of such patients. PMID:26821540

  6. Ulnar neuropathy: evaluation and management.

    PubMed

    Dy, Christopher J; Mackinnon, Susan E

    2016-06-01

    Ulnar neuropathy is commonly encountered, both acutely after elbow trauma and in the setting of chronic compression neuropathy. Careful clinical evaluation and discerning evaluation of electrodiagnostic studies are helpful in determining the prognosis of recovery with nonoperative and operative management. Appreciation of the subtleties in clinical presentation and thoughtful consideration of the timing and type of surgical intervention are critical to optimizing outcomes after treatment of ulnar neuropathy. The potential need for decompression at both the cubital tunnel and Guyon's canal must be appreciated. Supplementation of decompression with supercharged end-to-side nerve transfer can expedite motor recovery of the ulnar intrinsic muscles in the appropriately selected patient. The emergence of nerve transfer techniques has also changed the management of acute ulnar nerve injuries. PMID:27080868

  7. Vascular Steal Syndrome, Optic Neuropathy, and Foreign Body Granuloma Reaction to Onyx-18 Embolization for Congenital Orbito-Facial Vascular Malformation.

    PubMed

    Liu, Catherine Y; Yonkers, Marc A; Liu, Tiffany S; Minckler, Don S; Tao, Jeremiah P

    2016-04-01

    A 34-year-old patient presented with a right orbito-facial mass since childhood, consistent with a congenital arteriovenous (AV) malformation. Prior to presentation, she had multiple incomplete surgical resections and embolizations with N-butyl acetyl acrylate and Onyx-18. The patient reported gradual, progressive vision loss shortly after Onyx-18 embolization. Five months after embolization, she presented with decreased vision, disfigurement and mechanical ptosis relating to a large subcutaneous mass affecting the medial right upper eyelid and forehead. Significant exam findings included a visual acuity of 20/400 (20/60 prior to embolization), an afferent pupillary defect, and optic disc pallor. MRI and angiography revealed a persistent AV malformation with feeders from the ophthalmic artery and an absent choroidal flush to the right eye. Pathology from surgical resection showed a significant foreign body giant cell reaction to the embolization material adjacent to the vessels. We suggest that an incomplete embolization with Onyx-18 may have caused vascular steal syndrome from the ophthalmic artery. PMID:27239463

  8. Vascular Steal Syndrome, Optic Neuropathy, and Foreign Body Granuloma Reaction to Onyx-18 Embolization for Congenital Orbito-Facial Vascular Malformation

    PubMed Central

    Liu, Catherine Y.; Yonkers, Marc A.; Liu, Tiffany S.; Minckler, Don S.; Tao, Jeremiah P.

    2016-01-01

    A 34-year-old patient presented with a right orbito-facial mass since childhood, consistent with a congenital arteriovenous (AV) malformation. Prior to presentation, she had multiple incomplete surgical resections and embolizations with N-butyl acetyl acrylate and Onyx-18. The patient reported gradual, progressive vision loss shortly after Onyx-18 embolization. Five months after embolization, she presented with decreased vision, disfigurement and mechanical ptosis relating to a large subcutaneous mass affecting the medial right upper eyelid and forehead. Significant exam findings included a visual acuity of 20/400 (20/60 prior to embolization), an afferent pupillary defect, and optic disc pallor. MRI and angiography revealed a persistent AV malformation with feeders from the ophthalmic artery and an absent choroidal flush to the right eye. Pathology from surgical resection showed a significant foreign body giant cell reaction to the embolization material adjacent to the vessels. We suggest that an incomplete embolization with Onyx-18 may have caused vascular steal syndrome from the ophthalmic artery. PMID:27239463

  9. Chemotherapy-induced peripheral neuropathy.

    PubMed

    Fehrenbacher, Jill C

    2015-01-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is common in patients receiving anticancer treatment and can affect survivability and long-term quality of life of the patient following treatment. The symptoms of CIPN primarily include abnormal sensory discrimination of touch, vibration, thermal information, and pain. There is currently a paucity of pharmacological agents to prevent or treat CIPN. The lack of efficacious therapeutics is due, at least in part, to an incomplete understanding of the mechanisms by which chemotherapies alter the sensitivity of sensory neurons. Although the clinical presentation of CIPN can be similar with the various classes of chemotherapeutic agents, there are subtle differences, suggesting that each class of drugs might induce neuropathy via different mechanisms. Multiple mechanisms have been proposed to underlie the development and maintenance of neuropathy; however, most pharmacological agents generated from preclinical experiments have failed to alleviate the symptoms of CIPN in the clinic. Further research is necessary to identify the specific mechanisms by which each class of chemotherapeutics induces neuropathy. PMID:25744683

  10. Hereditary sensory neuropathy type I

    PubMed Central

    Auer-Grumbach, Michaela

    2008-01-01

    Hereditary sensory neuropathy type I (HSN I) is a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset. The exact prevalence is unknown, but is estimated as very low. Disease onset varies between the 2nd and 5th decade of life. The main clinical feature of HSN I is the reduction of sensation sense mainly distributed to the distal parts of the upper and lower limbs. Variable distal muscle weakness and wasting, and chronic skin ulcers are characteristic. Autonomic features (usually sweating disturbances) are invariably observed. Serious and common complications are spontaneous fractures, osteomyelitis and necrosis, as well as neuropathic arthropathy which may even necessitate amputations. Some patients suffer from severe pain attacks. Hypacusis or deafness, or cough and gastrooesophageal reflux have been observed in rare cases. HSN I is a genetically heterogenous condition with three loci and mutations in two genes (SPTLC1 and RAB7) identified so far. Diagnosis is based on the clinical observation and is supported by a family history. Nerve conduction studies confirm a sensory and motor neuropathy predominantly affecting the lower limbs. Radiological studies, including magnetic resonance imaging, are useful when bone infections or necrosis are suspected. Definitive diagnosis is based on the detection of mutations by direct sequencing of the SPTLC1 and RAB7 genes. Correct clinical assessment and genetic confirmation of the diagnosis are important for appropriate genetic counselling and prognosis. Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN), especially HSAN II, as well as diabetic foot syndrome, alcoholic neuropathy, neuropathies caused by other neurotoxins/drugs, immune mediated neuropathy, amyloidosis, spinal cord diseases, tabes dorsalis, lepra neuropathy, or decaying skin

  11. The exome sequencing identified the mutation in YARS2 encoding the mitochondrial tyrosyl-tRNA synthetase as a nuclear modifier for the phenotypic manifestation of Leber's hereditary optic neuropathy-associated mitochondrial DNA mutation.

    PubMed

    Jiang, Pingping; Jin, Xiaofen; Peng, Yanyan; Wang, Meng; Liu, Hao; Liu, Xiaoling; Zhang, Zengjun; Ji, Yanchun; Zhang, Juanjuan; Liang, Min; Zhao, Fuxin; Sun, Yan-Hong; Zhang, Minglian; Zhou, Xiangtian; Chen, Ye; Mo, Jun Qin; Huang, Taosheng; Qu, Jia; Guan, Min-Xin

    2016-02-01

    Leber's hereditary optic neuropathy (LHON) is the most common mitochondrial disorder. Nuclear modifier genes are proposed to modify the phenotypic expression of LHON-associated mitochondrial DNA (mtDNA) mutations. By using an exome sequencing approach, we identified a LHON susceptibility allele (c.572G>T, p.191Gly>Val) in YARS2 gene encoding mitochondrial tyrosyl-tRNA synthetase, which interacts with m.11778G>A mutation to cause visual failure. We performed functional assays by using lymphoblastoid cell lines derived from members of Chinese families (asymptomatic individuals carrying m.11778G>A mutation, or both m.11778G>A and heterozygous p.191Gly>Val mutations and symptomatic subjects harboring m.11778G>A and homozygous p.191Gly>Val mutations) and controls lacking these mutations. The 191Gly>Val mutation reduced the YARS2 protein level in the mutant cells. The aminoacylated efficiency and steady-state level of tRNA(Tyr) were markedly decreased in the cell lines derived from patients both carrying homozygous YARS2 p.191Gly>Val and m.11778G>A mutations. The failure in tRNA(Tyr) metabolism impaired mitochondrial translation, especially for polypeptides with high content of tyrosine codon such as ND4, ND5, ND6 and COX2 in cells lines carrying homozygous YARS2 p.191Gly>Val and m.11778G>A mutations. The YARS2 p.191Gly>Val mutation worsened the respiratory phenotypes associated with m.11778G>A mutation, especially reducing activities of complexes I and IV. The respiratory deficiency altered the efficiency of mitochondrial ATP synthesis and increased the production of reactive oxygen species. Thus, mutated YARS2 aggravates mitochondrial dysfunctions associated with the m.11778G>A mutation, exceeding the threshold for the expression of blindness phenotype. Our findings provided new insights into the pathophysiology of LHON that were manifested by interaction between mtDNA mutation and mutated nuclear-modifier YARS2. PMID:26647310

  12. Non-Systemic Vasculitic Neuropathy: An Enigmatic Clinical Entity

    PubMed Central

    Lubana, Sandeep Singh; Singh, Navdeep; Sanelli-Russo, Susan; Abrudescu, Adriana

    2015-01-01

    Patient: Female, 63 Final Diagnosis: Non-systemic vasculitic peripheral neuropathy Symptoms: Paresthesia Medication: — Clinical Procedure: Sural nerve biopsy Specialty: Rheumatology Objective: Challenging differential diagnosis Background: Non-systemic vasculitic peripheral neuropathy is a rare condition characterized by necrotizing inflammation resulting in luminal narrowing of the vasa nervorum, leading to ischemic injury to peripheral nerves. Here, we present the case of 63-year-old woman with subacute onset of severe hyperesthesia of the lower extremities accompanied by foot drop. Case Report: A 63-year-old woman with prolonged history of uncontrolled diabetes mellitus presented with subacute onset of severe bilateral lower extremity hyperesthesia and motor weakness along with left-sided foot drop. She had multiple emergency room visits with no relief of her symptoms. High doses of analgesics were insufficient to control pain. Laboratory tests were positive only for high erythrocyte sedimentation rate and C-reactive protein. A skin biopsy obtained 5 cm above the left lateral malleolus revealed medium-sized dermal vasculitis with dense mononuclear infiltrate. Electromyography showed peripheral neuropathy. A nerve biopsy was needed to reveal the exact diagnosis. Conclusions: Diagnosis of non-systemic vasculitic peripheral neuropathy can be delayed or missed in patients with uncontrolled diabetes mellitus, leading to significant morbidity. Elevated markers of inflammation in the absence of a possible explanation should prompt the clinician to perform a nerve biopsy; however, it is an invasive procedure and is associated with complications of post-neuropathic pain and delayed wound healing. Magnetic resonance angiography of the lower limbs, if combined with skin biopsy, can save the patient from undergoing nerve biopsy. PMID:26167722

  13. Effects of Semelil (ANGIPARS™) on diabetic peripheral neuropathy: A randomized, double-blind Placebo-controlled clinical trial

    PubMed Central

    Bakhshayeshi, S.; Madani, SP.; Hemmatabadi, M.; Heshmat, R.; Larijani, B.

    2011-01-01

    Background and the purpose of the study Diabetic neuropathy is the most common diabetic complication that often is accompanied by significant morbidity, mortality and economic burden. The purpose of this study was evaluation of effect of Semelil (ANGIPARS™), a new herbal drug for treatment of diabetic foot ulcers or diabetic peripheral neuropathy. Methods In this double blind clinical trial, 49 type 2 diabetes patients with different degrees of neuropathy were evaluated in two groups (ANGIPARS™ and placebo groups). All patients were assessed at the start and 12 weeks after treatment, with laboratory tests, United Kingdom screening test, Michigan neuropathy screening score, Michigan diabetic neuropathy score, vibration perception thresholds, nerve conduction study, monofilament test and visual analog scale. Results Michigan diabetic neuropathy score was decreased notably in ANGIPARS™ group. In the nerve conduction study, appropriate meaningful changes were observed in the distal latency and amplitude in the motor Ulnar nerve in ANGIPARS™ group. Conclusion The results showed limited evidence of efficacy of ANGIPARS™ in diabetic neuropathy treatment and more studies with a larger sample size and longer duration are required. PMID:22615641

  14. Animal Models of Autoimmune Neuropathy

    PubMed Central

    Soliven, Betty

    2014-01-01

    The peripheral nervous system (PNS) comprises the cranial nerves, the spinal nerves with their roots and rami, dorsal root ganglia neurons, the peripheral nerves, and peripheral components of the autonomic nervous system. Cell-mediated or antibody-mediated immune attack on the PNS results in distinct clinical syndromes, which are classified based on the tempo of illness, PNS component(s) involved, and the culprit antigen(s) identified. Insights into the pathogenesis of autoimmune neuropathy have been provided by ex vivo immunologic studies, biopsy materials, electrophysiologic studies, and experimental models. This review article summarizes earlier seminal observations and highlights the recent progress in our understanding of immunopathogenesis of autoimmune neuropathies based on data from animal models. PMID:24615441

  15. Electrophysiological investigation of toxic neuropathies.

    PubMed

    Le Quesne, P M

    1982-01-01

    Electrophysiological changes are correlated with pathological processes. Marked slowing of conduction is found in segmental demyelination due to delayed nodal excitation or short lengths of continuous conduction. Secondary demyelination causes slow conduction in hexacarbon neuropathy. Slight reduction in maximal conduction velocity is attributable to selective damage to large fibres in acrylamide neuropathy. Sensory nerve action potential amplitude is a sensitive measure of peripheral nerve function and comparison of abnormalities in different nerve segments may indicate the nature of the underlying pathological change. Other abnormalities may be elucidated by double stimuli; eg repetitive activity due to cholinesterase inhibition only occurs after the first of two closely spaced stimuli. Activity-related excitability changes may be detected by measuring the amplitude of the response to a submaximal stimulus at varying times after a maximal shock and is increased and prolonged by the pyrethroid deltamethrin. PMID:6962658

  16. Genetics Home Reference: hereditary neuropathy with liability to pressure palsies

    MedlinePlus

    ... hereditary neuropathy with liability to pressure palsies hereditary neuropathy with liability to pressure palsies Enable Javascript to ... Download PDF Open All Close All Description Hereditary neuropathy with liability to pressure palsies is a disorder ...

  17. Genetics Home Reference: distal hereditary motor neuropathy, type II

    MedlinePlus

    ... hereditary motor neuropathy, type II distal hereditary motor neuropathy, type II Enable Javascript to view the expand/ ... Open All Close All Description Distal hereditary motor neuropathy, type II is a progressive disorder that affects ...

  18. Genetics Home Reference: distal hereditary motor neuropathy, type V

    MedlinePlus

    ... hereditary motor neuropathy, type V distal hereditary motor neuropathy, type V Enable Javascript to view the expand/ ... Open All Close All Description Distal hereditary motor neuropathy, type V is a progressive disorder that affects ...

  19. Genetics Home Reference: hereditary sensory neuropathy type IA

    MedlinePlus

    ... Conditions hereditary sensory neuropathy type IA hereditary sensory neuropathy type IA Enable Javascript to view the expand/ ... PDF Open All Close All Description Hereditary sensory neuropathy type IA is a condition characterized by nerve ...

  20. Neuromyotonia in hereditary motor neuropathy.

    PubMed Central

    Hahn, A F; Parkes, A W; Bolton, C F; Stewart, S A

    1991-01-01

    Two siblings with a distal motor neuropathy experienced cramping and difficulty in relaxing their muscles after voluntary contraction. Electromyographic recordings at rest revealed repetitive high voltage spontaneous electrical discharges that were accentuated after voluntary contraction and during ischaemia. Regional neuromuscular blockage with curare indicated hyperexcitability of peripheral nerve fibres and nerve block suggested that the ectopic activity originated in proximal segments of the nerve. Symptoms were improved with diphenylhydantoin, carbamazepine and tocainide. Images PMID:1851512

  1. Peripheral Neuropathy Associated withHypereosinophilic Syndrome

    PubMed Central

    Lee, Kyung Ho; Kim, Jung Eun

    2008-01-01

    The idiopathic hypereosinophilic syndrome (HES) represents a leukoproliferative disorder, characterized by unexplained prolonged eosinophilia (>6 months) and evidence of specific organ damage. So far, the peripheral neuropathy associated with skin manifestations of HES has not been reported in the dermatologic literature although the incidence of peripheral neuropathy after HES ranges from 6~52%. Herein, we report the peripheral neuropathy associated with HES, documented by clinical, histopathological, and electrodiagnostic criteria. PMID:27303181

  2. Management of oxaliplatin-induced peripheral neuropathy

    PubMed Central

    Saif, M Wasif; Reardon, John

    2005-01-01

    Neurotoxicity is the most frequent dose-limiting toxicity of oxaliplatin. Acute sensory neurotoxicity manifests as rapid onset of cold-induced distal dysesthesia and/or paresthesia, sometimes accompanied by cold-dependent muscular contractions of the extremities or the jaw. The symptoms, often occurring during or shortly after infusion, are usually transient and mild. A cumulative sensory peripheral neuropathy may also develop with prolonged treatment with oxaliplatin, eventually causing superficial and deep sensory loss, sensory ataxia, and functional impairment. Studies have shown patients with acute sensory symptoms to display little or no axonal degeneration. The similarity of acute symptoms induced by oxaliplatin to those caused by several drugs or toxins acting on neuronal or muscular ion channels suggests that these symptoms may result from a specific interaction of oxaliplatin with voltage-gated sodium (Na+) channels. The current recommendations for the management of the acute and cumulative neurotoxicity from oxaliplatin include education about exposure to cold, dose modification, “stop and go”, and use of neuromodulatory agents, in particular, intravenous calcium and magnesium infusion. Upon the approval of oxaliplatin-based regimens both for adjuvant and metastatic treatment of colon cancer, it is crucial to compile knowledge about the recognition and management of neurotoxicity from oxaliplatin. PMID:18360567

  3. Clinical and electrodiagnostic features of sciatic neuropathies.

    PubMed

    Distad, B Jane; Weiss, Michael D

    2013-02-01

    Sciatic neuropathy is the second most common neuropathy of the lower extremity and a common cause of foot drop. This article reviews the anatomy, clinical features, pathophysiology, and electrodiagnostic assessment of sciatic neuropathies. There are multiple potential sites of pathology, determined in part by the mechanism of insult, including trauma, compression, masses, inflammation, and vascular lesions. Diagnosis is augmented by careful electrodiagnostic studies and imaging to help distinguish sciatic neuropathy from other sources of pathology. Electrodiagnostic studies may also help in assessing for early recovery and in determining prognosis. PMID:23177034

  4. Imaging of neuropathies about the hip.

    PubMed

    Martinoli, Carlo; Miguel-Perez, Maribel; Padua, Luca; Gandolfo, Nicola; Zicca, Anna; Tagliafico, Alberto

    2013-01-01

    Neuropathies about the hip may be cause of chronic pain and disability. In most cases, these conditions derive from mechanical or dynamic compression of a segment of a nerve within a narrow osteofibrous tunnel, an opening in a fibrous structure, or a passageway close to a ligament or a muscle. Although the evaluation of nerve disorders primarily relies on neurological examination and electrophysiology, diagnostic imaging is currently used as a complement to help define the site and aetiology of nerve compression and exclude other disease possibly underlying the patient' symptoms. Diagnosis of entrapment neuropathies about the hip with US and MR imaging requires an in-depth knowledge of the normal imaging anatomy and awareness of the anatomic and pathologic factors that may predispose or cause a nerve injury. Accordingly, the aim of this article is to provide a comprehensive review of hip neuropathies with an emphasis on the relevant anatomy, aetiology, clinical presentation, and their imaging appearance. The lateral femoral cutaneous neuropathy (meiralgia paresthetica), femoral neuropathy, sciatic neuropathy, obturator neuropathy, superior and inferior gluteal neuropathies and pudendal neuropathy will be discussed. PMID:21549536

  5. Alternative Quantitative Tools in the Assessment of Diabetic Peripheral and Autonomic Neuropathy.

    PubMed

    Vinik, A I; Casellini, C; Névoret, M-L

    2016-01-01

    Here we review some seldom-discussed presentations of diabetic neuropathy, including large fiber dysfunction and peripheral autonomic dysfunction, emphasizing the impact of sympathetic/parasympathetic imbalance. Diabetic neuropathy is the most common complication of diabetes and contributes additional risks in the aging adult. Loss of sensory perception, loss of muscle strength, and ataxia or incoordination lead to a risk of falling that is 17-fold greater in the older diabetic compared to their young nondiabetic counterparts. A fall is accompanied by lacerations, tears, fractures, and worst of all, traumatic brain injury, from which more than 60% do not recover. Autonomic neuropathy has been hailed as the "Prophet of Doom" for good reason. It is conducive to increased risk of myocardial infarction and sudden death. An imbalance in the autonomic nervous system occurs early in the evolution of diabetes, at a stage when active intervention can abrogate the otherwise relentless progression. In addition to hypotension, many newly recognized syndromes can be attributed to cardiac autonomic neuropathy such as orthostatic tachycardia and bradycardia. Ultimately, this constellation of features of neuropathy conspire to impede activities of daily living, especially in the patient with pain, anxiety, depression, and sleep disorders. The resulting reduction in quality of life may worsen prognosis and should be routinely evaluated and addressed. Early neuropathy detection can only be achieved by assessment of both large and small- nerve fibers. New noninvasive sudomotor function technologies may play an increasing role in identifying early peripheral and autonomic neuropathy, allowing rapid intervention and potentially reversal of small-fiber loss. PMID:27133153

  6. Sensory neuropathy in two Border collie puppies.

    PubMed

    Vermeersch, K; Van Ham, L; Braund, K G; Bhatti, S; Tshamala, M; Chiers, K; Schrauwen, E

    2005-06-01

    A peripheral sensory neuropathy was diagnosed in two Border collie puppies. Neurological, electrophysiological and histopathological examinations suggested a purely sensory neuropathy with mainly distal involvement. Urinary incontinence was observed in one of the puppies and histological examination of the vagus nerve revealed degenerative changes. An inherited disorder was suspected. PMID:15971901

  7. Peripheral Neuropathy – Clinical and Electrophysiological Considerations

    PubMed Central

    Chung, Tae; Prasad, Kalpana; Lloyd, Thomas E.

    2013-01-01

    This article is a primer on the pathophysiology and clinical evaluation of peripheral neuropathy for the radiologist. Magnetic resonance neurography (MRN) has utility in the diagnosis of many focal peripheral nerve lesions. When combined with history, examination, electrophysiology, and laboratory data, future advancements in high-field MRN may play an increasingly important role in the evaluation of patients with peripheral neuropathy. PMID:24210312

  8. Animal models of HIV peripheral neuropathy

    PubMed Central

    Burdo, Tricia H; Miller, Andrew D

    2014-01-01

    The use of animal models in the study of HIV and AIDS has advanced our understanding of the underlying pathophysiologic mechanisms of infection. Of the multitude of HIV disease manifestations, peripheral neuropathy remains one of the most common long-term side effects. Several of the most important causes of peripheral neuropathy in AIDS patients include direct association with HIV infection with or without antiretroviral medication and infection with opportunistic agents. Because the pathogeneses of these diseases are difficult to study in human patients, animal models have allowed for significant advancement in the understanding of the role of viral infection and the immune system in disease genesis. This review focuses on rodent, rabbit, feline and rhesus models used to study HIV-associated peripheral neuropathies, focusing specifically on sensory neuropathy and antiretroviral-associated neuropathies. PMID:25214880

  9. Giant axonal neuropathy: MRS findings.

    PubMed

    Alkan, Alpay; Kutlu, Ramazan; Sigirci, Ahmet; Baysal, Tamer; Altinok, Tayfun; Yakinci, Cengiz

    2003-10-01

    Giant axonal neuropathy (GAN) is a rare genetic disease of childhood involving the central and peripheral nervous systems. Axonal loss with several giant axons filled with neurofilaments is the main histopathological feature of peripheral nerve biopsies in this disease. Routine neuroimaging studies reveal diffuse hyperintensities in cerebral and cerebellar white matter. In this case report, the authors present the brain magnetic resonance spectroscopic features (normal N-acetylaspartate/creatine and increased choline/creatine and myoinositol/creatine ratios), which might indicate the absence of neuroaxonal loss and the presence of significant demyelination and glial proliferation in white matter, of an 11-year-old boy diagnosed with GAN. PMID:14569833

  10. [Automated imaging of the optic nerve and optic nerve fibers is essential to daily clinical practice].

    PubMed

    Lachkar, Y

    2004-06-01

    Chronic open-angle glaucoma is a progressive optical neuropathy. Automated imaging of the optic disc and optic nerve fibers provides reliable analysis of the optic nerve as well as long-term follow-up of neuropathy patients. HRT, GDX-VCC, and OCT, which analyze the optic disc and optical fibers, provide indisputable assistance in improving screening techniques and the follow-up of progressive glaucoma. PMID:15319758

  11. Current understanding of auditory neuropathy.

    PubMed

    Boo, Nem-Yun

    2008-12-01

    Auditory neuropathy is defined by the presence of normal evoked otoacoustic emissions (OAE) and absent or abnormal auditory brainstem responses (ABR). The sites of lesion could be at the cochlear inner hair cells, spiral ganglion cells of the cochlea, synapse between the inner hair cells and auditory nerve, or the auditory nerve itself. Genetic, infectious or neonatal/perinatal insults are the 3 most commonly identified underlying causes. Children usually present with delay in speech and language development while adult patients present with hearing loss and disproportionately poor speech discrimination for the degree of hearing loss. Although cochlear implant is the treatment of choice, current evidence show that it benefits only those patients with endocochlear lesions, but not those with cochlear nerve deficiency or central nervous system disorders. As auditory neuropathy is a disorder with potential long-term impact on a child's development, early hearing screen using both OAE and ABR should be carried out on all newborns and infants to allow early detection and intervention. PMID:19904452

  12. Autonomic Neuropathy in Diabetes Mellitus

    PubMed Central

    Verrotti, Alberto; Prezioso, Giovanni; Scattoni, Raffaella; Chiarelli, Francesco

    2014-01-01

    Diabetic autonomic neuropathy (DAN) is a serious and common complication of diabetes, often overlooked and misdiagnosed. It is a systemic-wide disorder that may be asymptomatic in the early stages. The most studied and clinically important form of DAN is cardiovascular autonomic neuropathy defined as the impairment of autonomic control of the cardiovascular system in patients with diabetes after exclusion of other causes. The reported prevalence of DAN varies widely depending on inconsistent definition, different diagnostic method, different patient cohorts studied. The pathogenesis is still unclear and probably multifactorial. Once DAN becomes clinically evident, no form of therapy has been identified, which can effectively stop or reverse it. Prevention strategies are based on strict glycemic control with intensive insulin treatment, multifactorial intervention, and lifestyle modification including control of hypertension, dyslipidemia, stop smoking, weight loss, and adequate physical exercise. The present review summarizes the latest knowledge regarding clinical presentation, epidemiology, pathogenesis, and management of DAN, with some mention to childhood and adolescent population. PMID:25520703

  13. Peroneal neuropathy after weight loss.

    PubMed

    Cruz-Martinez, A; Arpa, J; Palau, F

    2000-06-01

    The objectives of this study were to evaluate the clinical and electrophysiological findings in peroneal mononeuropathies following a weight-reduction diet. Thirty patients with acute peroneal palsy and weight loss were studied. Complete nerve conduction studies (NCS) were performed in upper and lower limbs. NCS showed conduction block (CB) of the peroneal nerve at the fibular head that recovered in 29 patients within 3 weeks to 3 months. Severity of CB was correlated with clinical weakness. Three patients had abnormalities consistent with polyneuropathy (PNP). NCS in asymptomatic relatives confirmed familial neuropathy. Nerve biopsy and molecular study were consistent with hereditary neuropathy with liability to pressure palsies (HNPP). One of these peroneal palsies (6 months) recovered after neurolysis. Weight loss might be a risk factor in peroneal mononeuropathies. NCS is a tool in the diagnosis of the site and severity of the nerve injury. Testing should be considered for relatives of patients with PNP because peroneal mononeuropathies may be the first expression of HNPP. PMID:10905469

  14. Drugs for the treatment of peripheral neuropathies.

    PubMed

    Marmiroli, Paola; Cavaletti, Guido

    2016-01-01

    Peripheral neuropathies are frequent in association with systemic diseases as well as isolated disorders. Recent advances in the therapy of specific neuropathies led to the approval of new drugs/treatments. This review selected those peripheral neuropathies where the most recent approvals were provided and revised the potential future developments in diabetic and toxic-induced neuropathies, although they do not have a currently available causal therapy in view of their epidemiological and social relevance. Data have been extracted from the most important published trials and from clinical experience. In addition, data from the Food and Drug Administration and European Medicine Agency indications on the treatment of the selected peripheral neuropathies and from recently updated international guidelines have also been included. The website of the U.S. National Institutes of Health www.clinicaltrials.gov registry has been used as the reference database for phase III clinical trials not yet published or ongoing. This review gives a general overview of the most recent advances in the treatment of amyloid, inflammatory, and paraproteinemic peripheral neuropathies. Moreover, it briefly describes the unmet medical need in disabling and frequent conditions, such as diabetic and chemotherapy-induced neuropathy, highlighting the most promising therapeutic approaches to their treatment. PMID:26567516

  15. Compressive neuropathy in the upper limb

    PubMed Central

    Thatte, Mukund R.; Mansukhani, Khushnuma A.

    2011-01-01

    Entrampment neuropathy or compression neuropathy is a fairly common problem in the upper limb. Carpal tunnel syndrome is the commonest, followed by Cubital tunnel compression or Ulnar Neuropathy at Elbow. There are rarer entities like supinator syndrome and pronator syndrome affecting the Radial and Median nerves respectively. This article seeks to review comprehensively the pathophysiology, Anatomy and treatment of these conditions in a way that is intended for the practicing Hand Surgeon as well as postgraduates in training. It is generally a rewarding exercise to treat these conditions because they generally do well after corrective surgery. Diagnostic guidelines, treatment protocols and surgical technique has been discussed. PMID:22022039

  16. Chronic demyelinating peripheral neuropathy in cerebrotendinous xanthomatosis.

    PubMed

    Argov, Z; Soffer, D; Eisenberg, S; Zimmerman, Y

    1986-07-01

    Three siblings with chemically proved cerebrotendinous xanthomatosis presented with typical neurological manifestations of dementia and spinocerebellar disorder. Electrodiagnostic tests revealed demyelinating neuropathy in all three. Sural nerve biopsies showed loss of myelinated large fibers, marked Schwann cell proliferation, and onion bulb formation. Teased-fiber preparations confirmed the occurrence of segmental demyelination and remyelination. We suggest that demyelinating neuropathy is part of the neurological spectrum of cerebrotendinous xanthomatosis and should be considered in the differential diagnosis of a recessively inherited motor and sensory neuropathy. PMID:3017187

  17. Familial multiple symmetric lipomatosis with peripheral neuropathy.

    PubMed

    Chalk, C H; Mills, K R; Jacobs, J M; Donaghy, M

    1990-08-01

    We describe coexisting peripheral neuropathy and multiple symmetric lipomatosis in 4 of 7 siblings. The absence of either condition in 3 other generations of this family suggests autosomal recessive inheritance. None of the affected siblings were alcoholic, a factor some have proposed to explain the frequent occurrence of peripheral neuropathy in sporadic multiple symmetric lipomatosis. Serum lipid studies, including apoprotein A levels, were normal. Sural nerve biopsy from 1 patient showed nerve fiber loss, predominantly affecting large myelinated fibers. The relationship between myelin sheath thickness and axon diameter was normal, arguing that this neuropathy is not due to primary axonal atrophy. PMID:2166247

  18. [Peripheral neuropathy occurring soon after cord blood transplantation].

    PubMed

    Harada, Sakiko; Hayashi, Hiromi; Tadera, Noriyuki; Iwama, Kannichi; Kajiwara, Kouichi; Kouzai, Yasuji; Koudo, Hideki

    2016-04-01

    We experienced two cases of peripheral neuropathy in the early phase following cord blood transplantation. Case 1 was a 66-year-old man with recurrent T-ALL. On day 8, he experienced a sharp pain originating in both the palms and the soles, which worsened spreading to the knees, and was accompanied by muscle weakness. The neurological symptom progressed to the point of being unable to walk. A nerve conduction velocity test showed demyelination and axonopathy. In the CSF analysis, albuminocytologic dissociation and a rise in myelin basic protein were detected. These findings met the diagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP). The symptoms improved with intravenous immunoglobulin (IVIG). He is now able to walk and continues to visit our department. Case 2 was a 42-year-old man with primary mediastinal large B-cell lymphoma. As the disease was refractory, he underwent reduced intensity cord blood transplantation (RICBT). Flare and numbness started in the palms and soles on day 26, with the symptoms progressing thereafter. A nerve conduction velocity test showed demyelination and axonopathy. The symptoms improved after IVIG administration. The diagnosis of peripheral neuropathy after transplantation is often difficult, but when an immunologic disorder is suspected to be the cause, early administration of IVIG may be effective. PMID:27169453

  19. Updates in diabetic peripheral neuropathy

    PubMed Central

    Juster-Switlyk, Kelsey; Smith, A. Gordon

    2016-01-01

    Diabetes has become one of the largest global health-care problems of the 21 st century. According to the Centers for Disease Control and Prevention, the population prevalence of diabetes in the US is approaching 10% and is increasing by 5% each year. Diabetic neuropathy is the most common complication associated with diabetes mellitus. Diabetes causes a broad spectrum of neuropathic complications, including acute and chronic forms affecting each level of the peripheral nerve, from the root to the distal axon. This review will focus on the most common form, distal symmetric diabetic polyneuropathy. There has been an evolution in our understanding of the pathophysiology and the management of diabetic polyneuropathy over the past decade. We highlight these new perspectives and provide updates from the past decade of research. PMID:27158461

  20. The neuropathy of erectile dysfunction.

    PubMed

    Bleustein, C B; Arezzo, J C; Eckholdt, H; Melman, A

    2002-12-01

    These studies were intended to explore the relationship between autonomic neuropathy and erectile dysfunction (ED). Sensory thresholds reflecting the integrity of both large diameter, myelinated neurons (ie pressure, touch, vibration) and small diameter axons (ie hot and cold thermal sensation) were determined on the penis and finger. Data were compared across subjects with and without ED, controlling for age, hypertension and diabetes. The correlation of specific thresholds scores and IIEF values were also examined. Seventy-three patients who visited the academic urology clinics at Montefiore hospital were evaluated. All patients were required to complete the erectile function domain of the International Index of Erectile Function (IIEF) questionnaire: 20 subjects had no complaints of ED and scored within the 'normal' range on the IIEF. Patients were subsequently tested on their index finger and glans penis for vibration (Biothesiometer), pressure (Semmes-Weinstein monofilaments), spatial perception (Tactile Circumferential Discriminator), and warm and cold thermal thresholds (Physitemp NTE-2). Sensation of the glans penis, as defined by the examined sensory thresholds, was significantly diminished in patients with ED and these differences remained significant when controlling for age, diabetes and hypertension. In contrast, thresholds on the index finger were equivalent in the ED and non-ED groups. Threshold and IIEF scores were highly correlated, consistent with an association between diminished sensation and decreasing IIEF score (worse erectile functioning). These relations also remained significant when controlling for age, diabetes and hypertension. The findings demonstrate dysfunction of large and small diameter nerve fibers in patients with ED of all etiologies. Further, the neurophysiologic measures validate the use of the IIEF as an index of ED, as objective findings of sensory neuropathy were highly correlated with worse IIEF scores. The sensory

  1. Hereditary Neuropathy with Liability to Pressure Palsies.

    PubMed

    Choi, Hyoung Won; Kuntz, Nancy L

    2015-11-01

    Investigators from 4 pediatric hospitals in Canada analyzed the clinical presentation and electrophysiological data of 12 children with hereditary neuropathy with liability to pressure palsies (HNPP), caused by PMP22 gene deletion. PMID:26933540

  2. Vitamin B supplementation for diabetic peripheral neuropathy

    PubMed Central

    Jayabalan, Bhavani; Low, Lian Leng

    2016-01-01

    Vitamin B12 deficiency has been associated with significant neurological pathology, especially peripheral neuropathy. This review aims to examine the existing evidence on the effectiveness of vitamin B12 supplementation for the treatment of diabetic peripheral neuropathy. A search of PubMed and the Cochrane Central Register of Controlled Trials for all relevant randomised controlled trials was conducted in December 2014. Any type of therapy using vitamin B12 or its coenzyme forms was assessed for efficacy and safety in diabetics with peripheral neuropathy. Changes in vibration perception thresholds, neuropathic symptoms and nerve conduction velocities, as well as the adverse effects of vitamin B12 therapy, were assessed. Four studies comprising 363 patients met the inclusion criteria. This review found no evidence that the use of oral vitamin B12 supplements is associated with improvement in the clinical symptoms of diabetic neuropathy. Furthermore, the majority of studies reported no improvement in the electrophysiological markers of nerve conduction. PMID:26892473

  3. INHERITED NEUROPATHIES: CLINICAL OVERVIEW AND UPDATE

    PubMed Central

    KLEIN, CHRISTOPHER J.; DUAN, XIAOHUI; SHY, MICHAEL E.

    2014-01-01

    Inherited neuropathy is a group of common neurologic disorders with heterogeneous clinical presentations and genetic causes. Detailed neuromuscular evaluations, including nerve conduction studies, laboratory testing, and histopathologic examination, can assist in identification of the inherited component beyond family history. Genetic testing increasingly enables definitive diagnosis of specific inherited neuropathies. Diagnosis, however, is often complex, and neurologic disability may have both genetic and acquired components in individual patients. The decision of which genetic test to order or whether to order genetic tests is often complicated, and the strategies to maximize the value of testing are evolving. Apart from rare inherited metabolic neuropathies, treatment approaches remain largely supportive. We provide a clinical update of the various types of inherited neuropathies, their differential diagnoses, and distinguishing clinical features (where available). A framework is provided for clinical evaluations, including the inheritance assessment, electrophysiologic examinations, and specific genetic tests. PMID:23801417

  4. Surgical treatment of a tomaculous neuropathy.

    PubMed

    Taggart, T F; Allen, T R

    2001-08-01

    Compressive neuropathy of the ulnar nerve at the elbow is the second most common nerve entrapment in the upper limb. Eight possible anatomical points of constriction have been identified. The most common constriction being the intermuscular septum proximally or between the two heads of the flexor carpi ulnaris in the cubital canal distally. Surgical release is successful in 80-90% of cases. Certain rare genetic conditions can predispose susceptible peripheral nerves to similar compressive neuropathies but there is no literature on surgical treatment of such patients. We present a case of hereditary neuropathy with liability to pressure palsy (HNPP) often known as 'tomaculous' neuropathy, in a patient with ulnar nerve symptoms who underwent a surgical release. PMID:11523718

  5. Bicycling induced pudendal nerve pressure neuropathy.

    PubMed

    Silbert, P L; Dunne, J W; Edis, R H; Stewart-Wynne, E G

    1991-01-01

    Pudendal neuropathies are well recognised as part of more generalised peripheral neuropathies; however, focal abnormalities of the pudendal nerve due to cycling-related injuries have been infrequently reported. We describe two patients who developed pudendal neuropathies secondary to pressure effects on the perineum from racing-bicycle saddles. Both were male competitive athletes, one of whom developed recurrent numbness of the penis and scrotum after prolonged cycling; the other developed numbness of the penis, an altered sensation of ejaculation, with disturbance of micturition and reduced awareness of defecation. Both patients improved with alterations in saddle position and riding techniques. We conclude that pudendal nerve pressure neuropathy can result from prolonged cycling, particularly when using a poor riding technique. PMID:1821826

  6. Peripheral Neuropathy in Mouse Models of Diabetes.

    PubMed

    Jolivalt, Corinne G; Frizzi, Katie E; Guernsey, Lucie; Marquez, Alex; Ochoa, Joseline; Rodriguez, Maria; Calcutt, Nigel A

    2016-01-01

    Peripheral neuropathy is a frequent complication of chronic diabetes that most commonly presents as a distal degenerative polyneuropathy with sensory loss. Around 20% to 30% of such patients may also experience neuropathic pain. The underlying pathogenic mechanisms are uncertain, and therapeutic options are limited. Rodent models of diabetes have been used for more than 40 years to study neuropathy and evaluate potential therapies. For much of this period, streptozotocin-diabetic rats were the model of choice. The emergence of new technologies that allow relatively cheap and routine manipulations of the mouse genome has prompted increased use of mouse models of diabetes to study neuropathy. In this article, we describe the commonly used mouse models of type 1 and type 2 diabetes, and provide protocols to phenotype the structural, functional, and behavioral indices of peripheral neuropathy, with a particular emphasis on assays pertinent to the human condition. © 2016 by John Wiley & Sons, Inc. PMID:27584552

  7. [Auditory synaptopathy/neuropathy: clinical findings and diagnosis].

    PubMed

    Walger, M; Foerst, A; Beutner, D; Streicher, B; Stürmer, K; Lang-Roth, R

    2011-05-01

    Auditory synaptopathy/neuropathy (AS/AN) is a special subtype of sensorineural hearing disorders with heterogeneous phenotypes and underestimated incidence. AS/AN generally develops in infancy, occasionally in adulthood. Symptoms include fluctuating, mostly bilateral hearing loss and abnormally reduced speech comprehension, especially in noisy environments. Within audiological assessments, patients with AS/AN present otoacoustic emissions (TEOAE; DPOAE) and cochlear microphonics (CM), absence of stapedius reflexes (SR) as well as absent or pathologically altered auditory evoked brainstem potentials (ABR). Children with AS/AN cannot be identified within OAE-based newborn hearing screening programs. Clinical findings, transtympanic electrocochleography (ECoG) and further diagnostic tools permit further identification of individual characteristics. In individual cases conventional amplification and the use of FM systems may improve hearing and communication skills. If these interventions, accompanied by intensive hearing, speech and language therapy are unsuccessful, cochlear implants (CI) or alternative forms of communication may be useful options for rehabilitation. PMID:21505928

  8. Multiple cranial neuropathies following etanercept administration.

    PubMed

    Hunter, Jacob B; Rivas, Alejandro

    2016-01-01

    There have been recent reports of sarcoid-like granulomatosis development following the administration of tumor necrosis factor (TNF) inhibitors. To date, only four cases of neurosarcoidosis have been reported in association with TNF inhibitors, two of which were attributed to etanercept. We present the first case of etanercept-induced neurosarcoidosis involving multiple cranial neuropathies, including the trigeminal, facial, and vestibulocochlear nerves, while also highlighting the differential diagnoses of multiple cranial neuropathies and the association of TNF inhibitors and neurosarcoidosis. PMID:27178520

  9. Pattern Recognition Approach to Neuropathy and Neuronopathy

    PubMed Central

    Barohn, Richard J; Amato, Anthony A.

    2014-01-01

    Synopsis Neuropathic disorders encompass those that affect the neuron’s cell body or neuronopathies, those affecting the peripheral process, or peripheral neuropathies. The peripheral neuropathies can be broadly subdivided into the myelinopathies and axonopathies. These conditions can be hereditary or acquired. Each of these disorders has distinct clinical features that enable neurologists to recognize the various patterns of presentation. Once a particular pattern is established, further laboratory studies can be performed to confirm the clinical impression. PMID:23642713

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

    PubMed

    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. PMID:16318371

  11. Mouse Models of Diabetic Neuropathy

    PubMed Central

    Sullivan, Kelli A.; Hayes, John M.; Wiggin, Timothy D.; Backus, Carey; Oh, Sang Su; Lentz, Stephen I.; Brosius, Frank; Feldman, Eva L.

    2007-01-01

    Diabetic neuropathy (DN) is a debilitating complication of type 1 and type 2 diabetes. Rodent models of DN do not fully replicate the pathology observed in human patients. We examined DN in streptozotocin (STZ)-induced [B6] and spontaneous type 1 diabetes [B6Ins2Akita] and spontaneous type 2 diabetes [B6-db/db, BKS-db/db]. DN was defined using the criteria of the Animal Models of Diabetic Complications Consortium (http://www.amdcc.org). Despite persistent hyperglycemia, the STZ-treated B6 and B6Ins2Akita mice were resistant to the development of DN. In contrast, DN developed in both type 2 diabetes models: the B6-db/db and BKS-db/db mice. The persistence of hyperglycemia and development of DN in the B6-db/db mice required an increased fat diet while the BKS-db/db mice developed severe DN and remained hyperglycemic on standard mouse chow. Our data support the hypothesis that genetic background and diet influence the development of DN and should be considered when developing new models of DN. PMID:17804249

  12. Treatment of painful diabetic neuropathy.

    PubMed

    Javed, Saad; Petropoulos, Ioannis N; Alam, Uazman; Malik, Rayaz A

    2015-01-01

    Painful diabetic neuropathy (PDN) is a debilitating consequence of diabetes that may be present in as many as one in five patients with diabetes. The objective assessment of PDN is difficult, making it challenging to diagnose and assess in both clinical practice and clinical trials. No single treatment exists to prevent or reverse neuropathic changes or to provide total pain relief. Treatment of PDN is based on three major approaches: intensive glycaemic control and risk factor management, treatments based on pathogenetic mechanisms, and symptomatic pain management. Clinical guidelines recommend pain relief in PDN through the use of antidepressants such as amitriptyline and duloxetine, the γ-aminobutyric acid analogues gabapentin and pregabalin, opioids and topical agents such as capsaicin. Of these medications, duloxetine and pregabalin were approved by the US Food and Drug Administration (FDA) in 2004 and tapentadol extended release was approved in 2012 for the treatment of PDN. Proposed pathogenetic treatments include α-lipoic acid (stems reactive oxygen species formation), benfotiamine (prevents vascular damage in diabetes) and aldose-reductase inhibitors (reduces flux through the polyol pathway). There is a growing need for studies to evaluate the most potent drugs or combinations for the management of PDN to maximize pain relief and improve quality of life. A number of agents are potential candidates for future use in PDN therapy, including Nav 1.7 antagonists, N-type calcium channel blockers, NGF antibodies and angiotensin II type 2 receptor antagonists. PMID:25553239

  13. Small fiber neuropathy: Getting bigger!

    PubMed

    Chan, Amanda C Y; Wilder-Smith, Einar P

    2016-05-01

    Etiological and clinical heterogeneity of small fiber neuropathy (SFN) precludes a unifying approach and necessitates reliance on recognizable clinical syndromes. Symptoms of SFN arise from dysfunction in nociception, temperature, and autonomic modalities. This review focuses on SFN involving nociception and temperature, examining epidemiology, etiology, clinical presentation, diagnosis, pathophysiology, and management. Prevalence of SFN is 52.95 per 100,000 population, and diabetes and idiopathic are the most common etiologies. Dysesthesia, allodynia, pain, burning, and coldness sensations frequently present in a length-dependent pattern. Additional autonomic features in gastrointestinal, urinary, or cardiovascular systems are frequent but poorly objectified. SFN is diagnosed by intraepidermal nerve fiber density and quantitative sensory and autonomic tests in combination with normal nerve conduction. Pathophysiological understanding centers on sodium channel dysfunction, and genetic forms are beginning to be understood. Treatment is directed at the underlying etiology supported by symptomatic treatment using antidepressants and anticonvulsants. Little is known about long-term outcomes, and systematic cohort studies are needed. PMID:26872938

  14. Treatment of painful diabetic neuropathy

    PubMed Central

    Petropoulos, Ioannis N.; Alam, Uazman; Malik, Rayaz A.

    2015-01-01

    Painful diabetic neuropathy (PDN) is a debilitating consequence of diabetes that may be present in as many as one in five patients with diabetes. The objective assessment of PDN is difficult, making it challenging to diagnose and assess in both clinical practice and clinical trials. No single treatment exists to prevent or reverse neuropathic changes or to provide total pain relief. Treatment of PDN is based on three major approaches: intensive glycaemic control and risk factor management, treatments based on pathogenetic mechanisms, and symptomatic pain management. Clinical guidelines recommend pain relief in PDN through the use of antidepressants such as amitriptyline and duloxetine, the γ-aminobutyric acid analogues gabapentin and pregabalin, opioids and topical agents such as capsaicin. Of these medications, duloxetine and pregabalin were approved by the US Food and Drug Administration (FDA) in 2004 and tapentadol extended release was approved in 2012 for the treatment of PDN. Proposed pathogenetic treatments include α-lipoic acid (stems reactive oxygen species formation), benfotiamine (prevents vascular damage in diabetes) and aldose-reductase inhibitors (reduces flux through the polyol pathway). There is a growing need for studies to evaluate the most potent drugs or combinations for the management of PDN to maximize pain relief and improve quality of life. A number of agents are potential candidates for future use in PDN therapy, including Nav 1.7 antagonists, N-type calcium channel blockers, NGF antibodies and angiotensin II type 2 receptor antagonists. PMID:25553239

  15. Molecular study of patients with auditory neuropathy.

    PubMed

    Carvalho, Guilherme Machado De; Ramos, Priscila Zonzini; Castilho, Arthur Menino; Guimarães, Alexandre Caixeta; Sartorato, Edi Lúcia

    2016-07-01

    Auditory neuropathy is a type of hearing loss that constitutes a change in the conduct of the auditory stimulus by the involvement of inner hair cells or auditory nerve synapses. It is characterized by the absence or alteration of waves in the examination of brainstem auditory evoked potentials, with otoacoustic and/or cochlear microphonic issues. At present, four loci associated with non‑syndromic auditory neuropathy have been mapped: Autosomal recessive deafness‑9 [DFNB9; the otoferlin (OTOF) gene] and autosomal recessive deafness‑59 [DFNB59; the pejvakin (PJVK) gene], associated with autosomal recessive inheritance; the autosomal dominant auditory neuropathy gene [AUNA1; the diaphanous‑3 (DIAPH3) gene]; and AUNX1, linked to chromosome X. Furthermore, mutations of connexin 26 [the gap junction β2 (GJB2) gene] have also been associated with the disease. OTOF gene mutations exert a significant role in auditory neuropathy. In excess of 80 pathogenic mutations have been identified in individuals with non‑syndromic deafness in populations of different origins, with an emphasis on the p.Q829X mutation, which was found in ~3% of cases of deafness in the Spanish population. The identification of genetic alterations responsible for auditory neuropathy is one of the challenges contributing to understand the molecular bases of the different phenotypes of hearing loss. Thus, the present study aimed to investigate molecular changes in the OTOF gene in patients with auditory neuropathy, and to develop a DNA chip for the molecular diagnosis of auditory neuropathy using mass spectrometry for genotyping. Genetic alterations were investigated in 47 patients with hearing loss and clinical diagnosis of auditory neuropathy, and the c.35delG mutation in the GJB2 gene was identified in three homozygous patients, and the heterozygous parents of one of these cases. Additionally, OTOF gene mutations were tracked by complete sequencing of 48 exons, although these results

  16. PHENYLMETHYLSULFONYL FLUORIDE PROTECTS RATS FROM MIPAFOX-INDUCED DELAYED NEUROPATHY

    EPA Science Inventory

    Initiation of organophosphorus-induced delayed neuropathy (OPIDN) is thought to consist of two molecular events involving the phosphorylation of the target enzyme, neurotoxic esterase or neuropathy target enzyme (NTE), and a subsequent 'aging' reaction which transforms the inhibi...

  17. Pathogenesis of immune-mediated neuropathies.

    PubMed

    Dalakas, Marinos C

    2015-04-01

    Autoimmune neuropathies occur when immunologic tolerance to myelin or axonal antigens is lost. Even though the triggering factors and the underling immunopathology have not been fully elucidated in all neuropathy subsets, immunological studies on the patients' nerves, transfer experiments with the patients' serum or intraneural injections, and molecular fingerprinting on circulating autoantibodies or autoreactive T cells, indicate that cellular and humoral factors, either independently or in concert with each other, play a fundamental role in their cause. The review is focused on the main subtypes of autoimmune neuropathies, mainly the Guillain-Barré syndrome(s), the Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), the Multifocal Motor Neuropathy (MMN), and the IgM anti-MAG-antibody mediated neuropathy. It addresses the factors associated with breaking tolerance, examines the T cell activation process including co-stimulatory molecules and key cytokines, and discusses the role of antibodies against peripheral nerve glycolipids or glycoproteins. Special attention is given to the newly identified proteins in the nodal, paranodal and juxtaparanodal regions as potential antigenic targets that could best explain conduction failure and rapid recovery. New biological agents against T cells, cytokines, B cells, transmigration and transduction molecules involved in their immunopathologic network, are discussed as future therapeutic options in difficult cases. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis. PMID:24949885

  18. Peripheral Neuropathy in Rats Exposed to Dichloroacetate

    PubMed Central

    Calcutt, Nigel A.; Lopez, Veronica L.; Bautista, Arjel D.; Mizisin, Leah M.; Torres, Brenda R.; Shroads, Albert L.; Mizisin, Andrew P.; Stacpoole, Peter W.

    2009-01-01

    The use of dichloroacetate (DCA) for treating patients with mitochondrial diseases is limited by the induction of peripheral neuropathy. The mechanisms of DCA-induced neuropathy are not known. Oral DCA treatment (50–500 mg/kg/day for up to 16 weeks) induced tactile allodynia in both juvenile and adult rats; concurrent thermal hypoalgesia developed at higher doses. Both juvenile and adult rats treated with DCA developed nerve conduction slowing that was more pronounced in adult rats. No overt axonal or glial cell abnormalities were identified in peripheral nerves or spinal cord of any DCA-treated rats but morphometric analysis identified a reduction of mean axonal caliber of peripheral nerve myelinated fibers. DCA treatment also caused accumulation of oxidative stress markers in the nerves. These data indicate that behavioral, functional and structural indices of peripheral neuropathy may be induced in both juvenile and adult rats treated with DCA at doses similar to those in clinical use. DCA-induced peripheral neuropathy primarily afflicts axons and involves both metabolic and structural disorders. The DCA-treated rat may provide insight into the pathogenesis of peripheral neuropathy and facilitate development of adjuvant therapeutics to prevent this disorder that currently restricts the clinical use of DCA. PMID:19680144

  19. Abnormal calcium homeostasis in peripheral neuropathies

    PubMed Central

    Fernyhough, Paul; Calcutt, Nigel A.

    2010-01-01

    Abnormal neuronal calcium (Ca2+) homeostasis has been implicated in numerous diseases of the nervous system. The pathogenesis of two increasingly common disorders of the peripheral nervous system, namely neuropathic pain and diabetic polyneuropathy, has been associated with aberrant Ca2+ channel expression and function. Here we review the current state of knowledge regarding the role of Ca2+ dyshomeostasis and associated mitochondrial dysfunction in painful and diabetic neuropathies. The central impact of both alterations of Ca2+ signalling at the plasma membrane and also intracellular Ca2+ handling on sensory neuron function is discussed and related to abnormal endoplasmic reticulum performance. We also present new data highlighting sub-optimal axonal Ca 2+ signalling in diabetic neuropathy and discuss the putative role for this abnormality in the induction of axonal degeneration in peripheral neuropathies. The accumulating evidence implicating Ca2+ dysregulation with both painful and degenerative neuropathies, along with recent advances in understanding of regional variations in Ca2+ channel and pump structures, makes modulation of neuronal Ca2+ handling an increasingly viable approach for therapeutic interventions against the painful and degenerative aspects of many peripheral neuropathies. PMID:20034667

  20. Delayed neuropathy after organophosphorus insecticide (Dipterex) poisoning: a clinical, electrophysiological and nerve biopsy study.

    PubMed

    Vasilescu, C; Alexianu, M; Dan, A

    1984-05-01

    Clinical, electrophysiological and histological findings in four patients accidentally poisoned with the organophosphorus insecticide Dipterex are reported. Three to five weeks after insecticide ingestion signs of a distal sensorimotor (preponderantly motor) neuropathy occurred. The patients complained of paraesthesia in the lower limbs, and two of them of very disagreeable pricking sensation in the soles of the feet, responsive to carbamazepine. They showed distal weakness mainly of the legs, footdrop , difficult gait and muscle hypotonia. Ankle jerk was abolished while other tendon reflexes persisted. Two months or even later after poisoning, knee jerks in all the patients were very brisk and more and less accompanied by other pyramidal signs (patellar clonus, abolishment of abdominal cutaneous reflexes, Babinski's sign). Clinical, electrophysiological and nerve biopsy data revealed a "dying-back" neuropathy in our patients. Distal muscle fatigue was confirmed by failure of neuromuscular transmission on repetitive nerve stimulation. PMID:6736986

  1. Auditory Neuropathy Spectrum Disorder Masquerading as Social Anxiety

    PubMed Central

    Rao, Mukund G.; Mishra, Shree; Varambally, Shivarama; Nagarajarao, Shivashankar; Gangadhar, Bangalore N.

    2015-01-01

    The authors report a case of a 47-year-old man who presented with treatment-resistant anxiety disorder. Behavioral observation raised clinical suspicion of auditory neuropathy spectrum disorder. The presence of auditory neuropathy spectrum disorder was confirmed on audiological investigations. The patient was experiencing extreme symptoms of anxiety, which initially masked the underlying diagnosis of auditory neuropathy spectrum disorder. Challenges in diagnosis and treatment of auditory neuropathy spectrum disorder are discussed. PMID:26351622

  2. Rheumatoid neuropathy: a histological and electrophysiological study

    PubMed Central

    Weller, R. O.; Bruckner, F. E.; Chamberlain, M. Anne

    1970-01-01

    Peripheral nerves in five patients with rheumatoid neuropathy were examined electrophysiologically and by sural nerve biopsy. There was close correlation between the clinical severity of the disease and the degree of nerve damage found histologically and by EMG. Group 1 patients with a mild distal sensory neuropathy showed varying degrees of axonal degeneration in the large myelinated fibres and some segmental demyelination. Group 2 patients with a severe, rapidly progressive sensori-motor neuropathy had extensive loss of myelinated fibres. In one case all the large fibres had degenerated. The second case had lost both large and small myelinated fibres together with many of the non-myelinated axons. The major nerve damage in both groups appeared to be axonal degeneration but some segmental demyelination was detected. Occlusive vascular disease in the vasa nervorum was considered to be the major cause of the nerve damage. Images PMID:4320255

  3. Expenditures in the elderly with peripheral neuropathy

    PubMed Central

    Callaghan, Brian C.; Burke, James F.; Rodgers, Ann; McCammon, Ryan; Langa, Kenneth M.; Feldman, Eva L.; Kerber, Kevin A.

    2013-01-01

    Summary To optimize care in the evaluation of peripheral neuropathy, we sought to define which tests drive expenditures and the role of the provider type. We investigated test utilization and expenditures by provider type in those with incident neuropathy in a nationally representative elderly, Medicare population. Multivariable logistic regression was used to determine predictors of MRI and electrodiagnostic utilization. MRIs of the neuroaxis and electrodiagnostic tests accounted for 88% of total expenditures. Mean and aggregate diagnostic expenditures were higher in those who saw a neurologist. Patients who saw a neurologist were more likely to receive an MRI and an electrodiagnostic test. MRIs and electrodiagnostic tests are the main contributors to expenditures in the evaluation of peripheral neuropathy, and should be the focus of future efficiency efforts. PMID:24175158

  4. [Wernicke encephalopathy accompanying linitis plastica].

    PubMed

    Soós, Zsuzsanna; Salamon, Mónika; Oláh, Roland; Czégeni, Anna; Salamon, Ferenc; Folyovich, András; Winkler, Gábor

    2014-01-01

    Wernicke encephalopathy (or Wernicke-Korsakoff encephalopathy) is a rarely diagnosed neurological disorder, which is caused by vitamin B1 deficiency. In the classical form it is characterized by a typical triad (confusion, oculomotor disturbance and ataxia), however, in the majority of the cases only confusion is present. It can be frequently observed in subjects with chronic alcohol consumption, but it may accompany different pathological states of which end stage malignant diseases are the most importants, where confusion may have different backgrounds. The authors present the case of an old male patient with advanced gastric cancer recognised and treated vitamin B1 deficiency, and they draw attention to difficulties of the diagnosis of Wernicke's disease. PMID:24379094

  5. Early Electrophysiological Abnormalities and Clinical Neuropathy

    PubMed Central

    Hyllienmark, Lars; Alstrand, Nils; Jonsson, Björn; Ludvigsson, Johnny; Cooray, Gerald; Wahlberg-Topp, Jeanette

    2013-01-01

    OBJECTIVE The aim of this study was to elucidate whether subclinical nerve dysfunction as reflected by neurophysiological testing predicts the development of clinical neuropathy in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS Fifty-nine patients were studied twice with neurophysiological measurements at baseline and at follow-up. At baseline, patients were 15.5 ± 3.22 years (range 7–22 years) of age, and duration of diabetes was 6.8 ± 3.3 years. At follow-up, patients were 20–35 years of age, and disease duration was 20 ± 5.3 years (range 10–31 years). RESULTS At baseline, patients showed modestly reduced nerve conduction velocities and amplitudes compared with healthy subjects, but all were free of clinical neuropathy. At follow-up, clinical neuropathy was present in nine (15%) patients. These patients had a more pronounced reduction in peroneal motor nerve conduction velocity (MCV), median MCV, and sural sensory nerve action potential at baseline (P < 0.010–0.003). In simple logistic regression analyses, the predictor with the strongest association with clinical neuropathy was baseline HbA1c (R2 = 48%, odds ratio 7.9, P < 0.002) followed by peroneal MCV at baseline (R2 = 38%, odds ratio 0.6, P < 0.006). With the use of a stepwise forward analysis that included all predictors, first baseline HbA1c and then only peroneal MCV at baseline entered significantly (R2 = 61%). Neuropathy impairment assessment showed a stronger correlation with baseline HbA1c (ρ = 0.40, P < 0.002) than with follow-up HbA1c (ρ = 0.034, P < 0.007). CONCLUSIONS Early defects in nerve conduction velocity predict the development of diabetic neuropathy. However, the strongest predictor was HbA1c during the first years of the disease. PMID:23723354

  6. Diagnosis and therapeutic options for peripheral vasculitic neuropathy.

    PubMed

    Blaes, Franz

    2015-04-01

    Vasculitis can affect the peripheral nervous system alone (nonsystemic vasculitic neuropathy) or can be a part of primary or secondary systemic vasculitis. In cases of pre-existing systemic vasculitis, the diagnosis can easily be made, whereas suspected vasculitic neuropathy as initial or only manifestation of vasculitis requires careful clinical, neurophysiological, laboratory and histopathological workout. The typical clinical syndrome is mononeuropathia multiplex or asymmetric neuropathy, but distal-symmetric neuropathy can frequently be seen. Standard treatments include steroids, azathioprine, methotrexate and cyclophosphamide. More recently the B-cell antibody rituximab and intravenous immunoglobulins have shown to be effective in some vasculitic neuropathy types. PMID:25829955

  7. Diagnosis and therapeutic options for peripheral vasculitic neuropathy

    PubMed Central

    2015-01-01

    Vasculitis can affect the peripheral nervous system alone (nonsystemic vasculitic neuropathy) or can be a part of primary or secondary systemic vasculitis. In cases of pre-existing systemic vasculitis, the diagnosis can easily be made, whereas suspected vasculitic neuropathy as initial or only manifestation of vasculitis requires careful clinical, neurophysiological, laboratory and histopathological workout. The typical clinical syndrome is mononeuropathia multiplex or asymmetric neuropathy, but distal-symmetric neuropathy can frequently be seen. Standard treatments include steroids, azathioprine, methotrexate and cyclophosphamide. More recently the B-cell antibody rituximab and intravenous immunoglobulins have shown to be effective in some vasculitic neuropathy types. PMID:25829955

  8. DIABETIC NEUROPATHY PART 2: PROXIMAL AND ASSYMMETRIC PHENOTYPES

    PubMed Central

    Pasnoor, Mamatha; Dimachkie, Mazen M.; Barohn, Richard J.

    2014-01-01

    Diabetic neuropathies consist of a variety of syndromes resulting from different types of damage to peripheral or cranial nerves. Although distal symmetric polyneuropathy is most common type of diabetic neuropathy, there are many other subtypes of diabetic neuropathies which have been defined since the 1800’s. Included in these descriptions are patients with proximal diabetic, truncal, cranial, median, and ulnar neuropathies. Various theories have been proposed for the pathogenesis of these neuropathies. The treatment of most of these requires tight and stable glycemic control. Spontaneous recovery is seen in most of these conditions with diabetic control Immunotherapies have been tried in some of these conditions but are quite controversial. PMID:23642718

  9. Hereditary neuropathy with liability to pressure palsies presenting with sciatic neuropathy.

    PubMed

    Topakian, Raffi; Wimmer, Sibylle; Pischinger, Barbara; Pichler, Robert

    2014-01-01

    Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal-dominant disorder associated with recurrent mononeuropathies following compression or trivial trauma. Reports on sciatic neuropathy as the presenting manifestation of HNPP are very scarce. We report on a 21-year-old previously healthy man who was admitted with sensorimotor deficits in his left leg. He had no history of preceding transient episodes of weakness or sensory loss. Clinical and electrophysiological examinations were consistent with sciatic neuropathy. Cerebrospinal fluid investigation and MRI of the nerve roots, plexus, and sciatic nerve did not indicate the underlying aetiology. When extended electrophysiological tests revealed multiple subclinical compression neuropathies in the upper limbs, HNPP was contemplated and eventually confirmed by genetic testing. PMID:25326571

  10. [Colonic Crohn's disease complicated with peripheral neuropathy].

    PubMed

    Chaoui, F; Hellal, H; Balamane, M; Boudhane, M; Mikol, J; Masmoudi, A

    1990-01-01

    The association of Crohn's disease and peripheral neuropathy is a rare event and the pathogenic factors often implicated are vitamin B12 deficiency or metronidazole treatment. We report a case of severe axonal polyneuropathy associated with Crohn's disease and unrelated to vitamin deficiency or metronidazole treatment. This represents a very rare extra-digestive manifestation of Crohn's disease. PMID:2125951

  11. Diabetic Neuropathies: The Nerve Damage of Diabetes

    MedlinePlus

    ... falling in response to normal body functions and physical activity. Digestive System Nerve damage to the digestive system most commonly ... neuropathy on the basis of symptoms and a physical exam. During the exam, the doctor ... temperature, or light touch. Foot Exams Experts recommend ...

  12. Auditory Neuropathy Spectrum Disorder: A Review

    ERIC Educational Resources Information Center

    Norrix, Linda W.; Velenovsky, David S.

    2014-01-01

    Purpose: Auditory neuropathy spectrum disorder, or ANSD, can be a confusing diagnosis to physicians, clinicians, those diagnosed, and parents of children diagnosed with the condition. The purpose of this review is to provide the reader with an understanding of the disorder, the limitations in current tools to determine site(s) of lesion, and…

  13. Speech Perception in Individuals with Auditory Neuropathy

    ERIC Educational Resources Information Center

    Zeng, Fan-Gang; Liu, Sheng

    2006-01-01

    Purpose: Speech perception in participants with auditory neuropathy (AN) was systematically studied to answer the following 2 questions: Does noise present a particular problem for people with AN: Can clear speech and cochlear implants alleviate this problem? Method: The researchers evaluated the advantage in intelligibility of clear speech over…

  14. The Rehabilitation of Oncological Patients Presenting Neuropathies

    PubMed Central

    MICU, ELENA CLAUDIA; IRSAY, LASZLO

    2014-01-01

    The International Association for the Study of Pain (IASP 2011) defines neuropathic pain as “the pain caused by an injury or disease of the somatosensory portion of the nervous system”. The central neuropathic pain is defined as “the pain caused by an injury or disease of the central somatosensory central nervous system”, whereas the peripheral neuropathic pain is defined as “the pain caused by an injury or disease of the peripheral somatosensory nervous system” [1]. The peripheral neuropathy describes any affection of the peripheral nervous system. The etiology is vast, there being a number of over 100 possible causes, which causes the global morbidity rate to reach approximately 2.4%. The chronic nature of the pain superposes the everyday routine and leads to the high intake of medication for pain alleviation. The number of cases of neuroplasia has always increased today. This disturbing diagnosis which can potentiate the signs and symptoms of peripheral neuropathy as well as reduce and limit the treatment options associated with neuropathies. The treatment presupposes a multidisciplinary approach, while the solution to prevent complications involves the control of risk factors and pathophysiological treatment. Chemotherapy-induced peripheral neuropathy (CPIN) is a significant disabling symptom that is tightly connected to the administration of neurotoxic cytostatic agents used for the treatment of neoplasia. CPIN compromises the quality of life and produces pain or discomfort [2]. I have sought to produce a presentation of the medicated and physical-kinetic treatment options that have proved their effectiveness during clinical studies or random trials and can be applied to cancer patients presenting with symptoms associated with peripheral neuropathy, namely with neuropathic pain, and support it with arguments. PMID:26528000

  15. Central recruitment in individual with auditory neuropathy.

    PubMed

    Sahu, Preeti; Mishra, Rajkishor; Mahallik, Debadatta; Ansari, Imran; Mungutwar, Varsha

    2014-12-01

    Auditory neuropathy (AN) describes patients with dysfunction of the auditory nerve in the presence of preserved cochlear outer hair-cell receptor functions in presence of normal otoacoustic emissions and/or cochlear microphonics. In individuals with auditory neuropathy speech are disproportionate to their hearing sensitivity and reported to be dependent on cortical evoked potentials. In individuals with AN, who have normal cortical potentials have better speech identification scores when compared to those with abnormal cortical potentials reflect relation between the cortical potentials and the speech identification scores. One group comparison research design was used for present study. The purpose of the study was to compare shift in latency of LLR peaks at different sensation level in subjects with auditory neuropathy and age matched normal individuals. 6 subjects (11 ears) diagnosed as having auditory neuropathy and 6 subjects (12 ears) with normal hearing Sensitivity participated for the study. Pure tone audiometry, immittance, reflexometry and otoacoustic emissions were administered. ABR was recorded for all the subjects at a repetition rate of 11.1 at an intensity of 90 dB nHL. LLR was carried out at different intensity levels for/da/speech stimulus at an intensity of 90 dB nHL. Latency of N1 and P2 of LLR was calculated at different sensation levels for both the groups. Descriptive analysis was carried out to find out the mean and standard deviation for latency of N1 and P2 for both, AN and normal hearing group. There was delay in latency of N1 and P2 for individuals with auditory neuropathy. PMID:26396961

  16. 10 CFR 9.56 - Accompanying persons.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... for Information, Access Or Amendment of Records Maintained About Them § 9.56 Accompanying persons. An individual requesting access to records about himself may be accompanied by another individual of his own choosing. Both the individual requesting access and the individual accompanying him shall sign the...

  17. 19 CFR 148.4 - Accompanying articles.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 2 2012-04-01 2012-04-01 false Accompanying articles. 148.4 Section 148.4 Customs... (CONTINUED) PERSONAL DECLARATIONS AND EXEMPTIONS General Provisions § 148.4 Accompanying articles. (a) Generally. Articles shall be considered as accompanying a passenger or brought in by him if the...

  18. 19 CFR 148.4 - Accompanying articles.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 2 2014-04-01 2014-04-01 false Accompanying articles. 148.4 Section 148.4 Customs... (CONTINUED) PERSONAL DECLARATIONS AND EXEMPTIONS General Provisions § 148.4 Accompanying articles. (a) Generally. Articles shall be considered as accompanying a passenger or brought in by him if the...

  19. 19 CFR 148.4 - Accompanying articles.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 2 2013-04-01 2013-04-01 false Accompanying articles. 148.4 Section 148.4 Customs... (CONTINUED) PERSONAL DECLARATIONS AND EXEMPTIONS General Provisions § 148.4 Accompanying articles. (a) Generally. Articles shall be considered as accompanying a passenger or brought in by him if the...

  20. 19 CFR 148.4 - Accompanying articles.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 2 2011-04-01 2011-04-01 false Accompanying articles. 148.4 Section 148.4 Customs... (CONTINUED) PERSONAL DECLARATIONS AND EXEMPTIONS General Provisions § 148.4 Accompanying articles. (a) Generally. Articles shall be considered as accompanying a passenger or brought in by him if the...

  1. 19 CFR 148.4 - Accompanying articles.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Accompanying articles. 148.4 Section 148.4 Customs... (CONTINUED) PERSONAL DECLARATIONS AND EXEMPTIONS General Provisions § 148.4 Accompanying articles. (a) Generally. Articles shall be considered as accompanying a passenger or brought in by him if the...

  2. Optical Coherence Tomography in Glaucoma

    NASA Astrophysics Data System (ADS)

    Berisha, Fatmire; Hoffmann, Esther M.; Pfeiffer, Norbert

    Retinal nerve fiber layer (RNFL) thinning and optic nerve head cupping are key diagnostic features of glaucomatous optic neuropathy. The higher resolution of the recently introduced SD-OCT offers enhanced visualization and improved segmentation of the retinal layers, providing a higher accuracy in identification of subtle changes of the optic disc and RNFL thinning associated with glaucoma.

  3. Erythromycin induces supranormal gall bladder contraction in diabetic autonomic neuropathy.

    PubMed Central

    Catnach, S M; Ballinger, A B; Stevens, M; Fairclough, P D; Trembath, R C; Drury, P L; Watkins, P J

    1993-01-01

    Gall bladder motor function is impaired in some patients with diabetes. It has been suggested that the abnormalities of gall bladder motility are confined to those patients with autonomic neuropathy. Erythromycin, a motilin receptor agonist, causes gall bladder contraction in both normal subjects and patients with gall stones with impaired gall bladder emptying. The effect of erythromycin on gall bladder motility in seven patients with diabetes with an autonomic neuropathy, six patients with diabetes without autonomic neuropathy, and 17 normal subjects was studied using ultrasound. There was no significant difference in gall bladder fasting volume between the three groups, but the patients with diabetes with autonomic neuropathy had impaired postprandial gall bladder emptying compared with normal subjects (percentage emptied (SEM) 40 (10.3)% v 64 (2.8)%, p < 0.01) and those with autonomic neuropathy (48 (7.7)%, NS). Erythromycin produced a dramatic reduction in gall bladder fasting volume in patients with diabetes with an autonomic neuropathy, compared with either normal subjects or patients with diabetes without autonomic neuropathy (percentage reduction 62 (4.6)% in patients with autonomic neuropathy, v 37 (17.6)% in those without autonomic neuropathy, and 26 (7.3)% in the normal subjects, (p < 0.02) and returned gall bladder emptying to normal in all patients with impaired emptying. The pronounced effect of erythromycin in diabetic autonomic neuropathy suggests denervation supersensitivity and that the action of erythromycin on the gall bladder is neurally modulated. PMID:8174966

  4. Optical energy storage and reemission based weak localization of light and accompanying random lasing action in disordered Nd{sup 3+} doped (Pb, La)(Zr, Ti)O{sub 3} ceramics

    SciTech Connect

    Xu, Long; Zhao, Hua; Xu, Caixia; Zhang, Siqi; Zhang, Jingwen

    2014-08-14

    Multi-mode random lasing action and weak localization of light were evidenced and studied in normally transparent but disordered Nd{sup 3+} doped (Pb,La)(Zr,Ti)O{sub 3} ceramics. Noticeable localized zone and multi-photon process were observed under strong pumping power. A tentative phenomenological physical picture was proposed by taking account of diffusive process, photo-induced scattering, and optical energy storage process as dominant factors in elucidating the weak localization of light observed. Both the decreased transmittance (increased reflectivity) of light and the observed long lasting fading-off phenomenon supported the physical picture proposed by us.

  5. Novel insights on diagnosis, cause and treatment of diabetic neuropathy: focus on painful diabetic neuropathy

    PubMed Central

    Tavakoli, Mitra; Asghar, Omar; Alam, Uazman; Petropoulos, Ioannis N.; Fadavi, Hassan; Malik, Rayaz A.

    2010-01-01

    Diabetic neuropathy is common, under or misdiagnosed, and causes substantial morbidity with increased mortality. Defining and developing sensitive diagnostic tests for diabetic neuropathy is not only key to implementing earlier interventions but also to ensure that the most appropriate endpoints are employed in clinical intervention trials. This is critical as many potentially effective therapies may never progress to the clinic, not due to a lack of therapeutic effect, but because the endpoints were not sufficiently sensitive or robust to identify benefit. Apart from improving glycaemic control, there is no licensed treatment for diabetic neuropathy, however, a number of pathogenetic pathways remain under active study. Painful diabetic neuropathy is a cause of considerable morbidity and whilst many pharmacological and nonpharmacological interventions are currently used, only two are approved by the US Food and Drug Administration. We address the important issue of the ‘placebo effect’ and also consider potential new pharmacological therapies as well as nonpharmacological interventions in the treatment of painful diabetic neuropathy. PMID:23148152

  6. [2013: what's new in inflammatory neuropathies].

    PubMed

    Kuntzer, T

    2014-12-01

    Several high-quality publications were published in 2013 and some major trials studies were started. In Guillain-Barré syndrome, events included the launch of IGOS and a better understanding of diagnostic limits, the effect of influenza vaccination, and better care, but uncertainty remains about analgesics. A new mouse model was also described. In chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), diagnostic pitfalls can be recalled. Our knowledge of underlying pathophysiological processes has improved, and the value of monitoring with function and deficit scores has been demonstrated. IVIG can sometimes be effective longer than expected, but CIDP remains sensitive to corticosteroids, particularly with the long-term beneficial effects of megadose dexamethasone. The impact of fingolimod remains to be demonstrated in an ongoing trial. Advances concerning multifocal motor neuropathy, inflammatory plexopathy, and neuropathy with anti -MAG activity are discussed but treatments already recognized as effective should not be changed. Imaging of peripheral nerve progresses. PMID:25459118

  7. 77 FR 47795 - Disease Associated With Exposure to Certain Herbicide Agents: Peripheral Neuropathy

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-10

    ... herbicide exposure and the occurrence of ``acute and subacute transient peripheral neuropathy.'' In... established a regulatory presumption of service connection for ``acute and subacute peripheral neuropathy...'s current regulation presumes service connection for ``acute and subacute peripheral...

  8. Animal models for inherited peripheral neuropathies

    PubMed Central

    MARTINI, RUDOLF

    1997-01-01

    Recent progress in human genetics and neurobiology has led to the identification of various mutations in particular myelin genes as the cause for many of the known inherited demyelinating peripheral neuropathies. Mutations in 3 distinct myelin genes, PMP22, P0, and connexin 32 cause the 3 major demyelinating subtypes of Charcot-Marie-Tooth (CMT) disease, CMT1A, CMT1B and CMTX, respectively. In addition, a reduction in the gene dosage of PMP22 causes hereditary neuropathy with liability to pressure palsies (HNPP), while particular point mutations in PMP22 and P0 cause the severe Dejerine-Sottas (DS) neuropathy. A series of spontaneous and genetically engineered rodent mutants for genes for the above-mentioned myelin constituents are now available and their suitability to serve as models for these still untreatable diseases is an issue of particular interest. The spontaneous mutants Trembler-J and Trembler, with point mutations in PMP22, reflect some of the pathological alterations seen in CMT1A and DS patients, respectively. Furthermore, engineered mutants that either over or underexpress particular myelin genes are suitable models for patients who are similarly compromised in the gene dosage of the corresponding genes. In addition, engineered mutants heterozygously or homozygously deficient in the myelin component P0 show the pathology of distinct CMT1B and DS patients, respectively, while Cx32 deficient mice develop pathological abnormalities similar to those of CMTX patients. Mutants that mimic human peripheral neuropathies might allow the development of strategies to alleviate the symptoms of the diseases, and help to define environmental risk factors for aggravation of the disease. In addition, such mutants might be instrumental in the development of strategies to cure the diseases by gene therapy. PMID:9418989

  9. Animal models for inherited peripheral neuropathies.

    PubMed

    Martini, R

    1997-10-01

    Recent progress in human genetics and neurobiology has led to the identification of various mutations in particular myelin genes as the cause for many of the known inherited demyelinating peripheral neuropathies. Mutations in 3 distinct myelin genes, PMP22, P0, and connexin 32 cause the 3 major demyelinating subtypes of Charcot-Marie-Tooth (CMT) disease, CMT1A, CMT1B and CMTX, respectively. In addition, a reduction in the gene dosage of PMP22 causes hereditary neuropathy with liability to pressure palsies (HNPP), while particular point mutations in PMP22 and P0 cause the severe Dejerine-Sottas (DS) neuropathy. A series of spontaneous and genetically engineered rodent mutants for genes for the above-mentioned myelin constituents are now available and their suitability to serve as models for these still untreatable diseases is an issue of particular interest. The spontaneous mutants Trembler-J and Trembler, with point mutations in PMP22, reflect some of the pathological alterations seen in CMT1A and DS patients, respectively. Furthermore, engineered mutants that either over or underexpress particular myelin genes are suitable models for patients who are similarly compromised in the gene dosage of the corresponding genes. In addition, engineered mutants heterozygously or homozygously deficient in the myelin component P0 show the pathology of distinct CMT1B and DS patients, respectively, while Cx32 deficient mice develop pathological abnormalities similar to those of CMTX patients. Mutants that mimic human peripheral neuropathies might allow the development of strategies to alleviate the symptoms of the diseases, and help to define environmental risk factors for aggravation of the disease. In addition, such mutants might be instrumental in the development of strategies to cure the diseases by gene therapy. PMID:9418989

  10. Nerve Growth Factor and Diabetic Neuropathy

    PubMed Central

    Vinik, Aaron

    2003-01-01

    Neuropathy is one of the most debilitating complications of both type 1 and type 2 diabetes, with estimates of prevalence between 50–90% depending on the means of detection. Diabetic neuropathies are heterogeneous and there is variable involvement of large myelinated fibers and small, thinly myelinated fibers. Many of the neuronal abnormalities in diabetes can be duplicated by experimental depletion of specific neurotrophic factors, their receptors or their binding proteins. In experimental models of diabetes there is a reduction in the availability of these growth factors, which may be a consequence of metabolic abnormalities, or may be independent of glycemic control. These neurotrophic factors are required for the maintenance of the neurons, the ability to resist apoptosis and regenerative capacity. The best studied of the neurotrophic factors is nerve growth factor (NGF) and the related members of the neurotrophin family of peptides. There is increasing evidence that there is a deficiency of NGF in diabetes, as well as the dependent neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) that may also contribute to the clinical symptoms resulting from small fiber dysfunction. Similarly, NT3 appears to be important for large fiber and IGFs for autonomic neuropathy. Whether the observed growth factor deficiencies are due to decreased synthesis, or functional, e.g. an inability to bind to their receptor, and/or abnormalities in nerve transport and processing, remains to be established. Although early studies in humans on the role of neurotrophic factors as a therapy for diabetic neuropathy have been unsuccessful, newer agents and the possibilities uncovered by further studies should fuel clinical trials for several generations. It seems reasonable to anticipate that neurotrophic factor therapy, specifically targeted at different nerve fiber populations, might enter the therapeutic armamentarium. PMID:14668049

  11. Inherited peripheral neuropathies due to mitochondrial disorders.

    PubMed

    Cassereau, J; Codron, P; Funalot, B

    2014-05-01

    Mitochondrial disorders (MIDs) are frequently responsible for neuropathies with variable severity. Mitochondrial diseases causing peripheral neuropathies (PNP) may be due to mutations of mitochondrial DNA (mtDNA), as is the case in MERRF and MELAS syndromes, or to mutations of nuclear genes. Secondary abnormalities of mtDNA (such as multiple deletions of muscle mtDNA) may result from mitochondrial disorders due to mutations in nuclear genes involved in mtDNA maintenance. This is the case in several syndromes caused by impaired mtDNA maintenance, such as Sensory Ataxic Neuropathy, Dysarthria and Ophthalmoplegia (SANDO) due to recessive mutations in the POLG gene, which encodes the catalytic subunit of mtDNA polymerase (DNA polymerase gamma), or Mitochondrial Neuro-Gastro-Intestinal Encephalomyopathy (MNGIE), due to recessive mutations in the TYMP gene, which encodes thymidine phosphorylase. The last years have seen a growing list of evidence demonstrating that mitochondrial bioenergetics and dynamics might be dysfunctional in axonal Charcot-Marie-Tooth disease (CMT2), and these mechanisms might present a common link between dissimilar CMT2-causing genes. PMID:24768438

  12. A reversible functional sensory neuropathy model.

    PubMed

    Danigo, Aurore; Magy, Laurent; Richard, Laurence; Sturtz, Franck; Funalot, Benoît; Demiot, Claire

    2014-06-13

    Small-fiber neuropathy was induced in young adult mice by intraperitoneal injection of resiniferatoxin (RTX), a TRPV1 agonist. At day 7, RTX induced significant thermal and mechanical hypoalgesia. At day 28, mechanical and thermal nociception were restored. No nerve degeneration in skin was observed and unmyelinated nerve fiber morphology and density in sciatic nerve were unchanged. At day 7, substance P (SP) was largely depleted in dorsal root ganglia (DRG) neurons, although calcitonin gene-related peptide (CGRP) was only moderately depleted. Three weeks after, SP and CGRP expression was restored in DRG neurons. At the same time, CGRP expression remained low in intraepidermal nerve fibers (IENFs) whereas SP expression had improved. In summary, RTX induced in our model a transient neuropeptide depletion in sensory neurons without nerve degeneration. We think this model is valuable as it brings the opportunity to study functional nerve changes in the very early phase of small fiber neuropathy. Moreover, it may represent a useful tool to study the mechanisms of action of therapeutic strategies to prevent sensory neuropathy of various origins. PMID:24792390

  13. [Vasculitic Peripheral Neuropathies: Clinical Features and Diagnostic Laboratory Tests].

    PubMed

    Ogata, Katsuhisa

    2016-03-01

    Vasculitic peripheral neuropathy (VPN) occurs due to ischemic changes of peripheral nerves, resulting from a deficit of vascular blood supply due to damaged vasa nervorum leading to vasculitis. VPN usually manifests as sensorimotor or sensory disturbances accompanied by pain, presenting as a type of multiple mononeuropathy, with a scattered distribution in distal limbs. VPN may also present as a mononeuropathy, distal symmetric polyneuropathy, plexopathy, or radiculopathy. The rapidity of VPN is variable, ranging from days to months, with symptoms occasionally changing with the appearance of new lesions. Careful history taking and neurological examination provides an exact diagnosis. The most common cause of VPN is primary vasculitis predominantly affecting small vessels, including vasa nervorum, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and polyarteritis nodosa. Similar vasculitic processes can also result from a systemic collagen disorder or secondary vasculitis. Electrophysiological studies and pathological investigation of biopsied peripheral nerves and muscles are important for diagnosis of vasculitis. Serological tests, including ANCA, are useful for diagnosis of vasculitis. Accurate neurological examinations are essential for diagnosis and evaluation of clinical course. PMID:27001769

  14. Relapsing sensorimotor neuropathy with ophthalmoplegia, antidisialosyl antibodies, and extramembranous glomerulonephritis.

    PubMed

    Delval, Arnaud; Stojkovic, Tanya; Vermersch, Patrick

    2006-02-01

    A 72-year-old man presented with oculomotor dysfunction, subacute relapsing sensorimotor neuropathy, elevated erythrocyte sedimentation rate, IgM monoclonal paraprotein, cold agglutinins, and antidisialosyl IgM antibodies, features previously described by the acronym CANOMAD (chronic ataxic neuropathy with ophthalmoplegia, M protein, agglutination, and disialosyl antibodies). The patient also had extramembranous glomerulopathy associated with this syndrome. Treatment with corticosteroids improved both the neuropathy and glomerulopathy. This case suggests that the spectrum of neuropathy associated with monoclonal gammopathy may be broader than originally believed. PMID:16258949

  15. Abnormal Nutritional Factors in Patients Evaluated at a Neuropathy Center.

    PubMed

    Latov, Norman; Vo, Mary L; Chin, Russell L; Carey, Bridget T; Langsdorf, Jennifer A; Feuer, Naomi T

    2016-06-01

    Abnormal concentrations of nutritional factors were found in 24.1% of 187 patients with neuropathy who were newly seen at our academic neuropathy referral center over a 1-year period. All patients presented with sensory axonal or small fiber neuropathy. In 7.3%, they were present in association with at least one other identifiable cause for neuropathy. Elevated levels of pyridoxal phosphate or mercury occurred more frequently than deficiencies in vitamins B1, B12, or B6. The nutritional abnormalities are amenable to correction by dietary intervention. PMID:27224436

  16. Motor neuropathy in porphobilinogen deaminase–deficient mice imitates the peripheral neuropathy of human acute porphyria

    PubMed Central

    Lindberg, Raija L.P.; Martini, Rudolf; Baumgartner, Matthias; Erne, Beat; Borg, Jacques; Zielasek, Jürgen; Ricker, Kenneth; Steck, Andreas; Toyka, Klaus V.; Meyer, Urs A.

    1999-01-01

    Acute porphyrias are inherited disorders caused by partial deficiency of specific heme biosynthesis enzymes. Clinically, porphyrias are manifested by a neuropsychiatric syndrome that includes peripheral neuropathy. Although much is known about the porphyrias’ enzyme defects and their biochemical consequences, the cause of the neurological manifestations remains unresolved. We have studied porphyric neuropathy in mice with a partial deficiency of porphobilinogen deaminase (PBGD). PBGD-deficient mice (PBGD–/–) imitate acute porphyria through massive induction of hepatic δ-aminolevulinic acid synthase by drugs such as phenobarbital. Here we show that PBGD–/– mice develop impairment of motor coordination and muscle weakness. Histologically femoral nerves of PBGD–/– mice exhibit a marked decrease in large-caliber (>8 μm) axons and ultrastructural changes consistent with primary motor axon degeneration, secondary Schwann cell reactions, and axonal regeneration. These findings resemble those found in studies of affected nerves of patients with acute porphyria and thus provide strong evidence that PBGD deficiency causes degeneration of motor axons without signs of primary demyelination, thereby resolving a long-standing controversy. Interestingly, the neuropathy in PBGD–/– mice developed chronically and progressively and in the presence of normal or only slightly (twofold) increased plasma and urinary levels of the putative neurotoxic heme precursor δ-aminolevulinic acid. These data suggest that heme deficiency and consequent dysfunction of hemeproteins can cause porphyric neuropathy. PMID:10207164

  17. MNGIE neuropathy: five cases mimicking chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Bedlack, Richard S; Vu, Tuan; Hammans, Simon; Sparr, Steven A; Myers, Bennett; Morgenlander, Joel; Hirano, Michio

    2004-03-01

    We report five patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) who had demyelinating peripheral neuropathy. The MNGIE neuropathy had clinical and electrodiagnostic features typical of acquired, rather than inherited, etiologies. In fact, three patients were actually treated for chronic inflammatory demyelinating polyneuropathy (CIDP). We discuss findings that may help distinguish patients with MNGIE from those with CIDP. PMID:14981734

  18. Lithium-Induced Motor Neuropathy: An Unusual Presentation

    PubMed Central

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

    2016-01-01

    Peripheral neuropathy secondary to lithium is under-recognized. Most cases of polyneuropathy were reported with lithium intoxication. However, very few cases were reported without lithium toxicity. We present a case of motor neuropathy due to the use of lithium in a 26-year-old male with a therapeutic lithium level. PMID:27335523

  19. Peripheral neuropathies of rheumatologic disease and gluten-related disorders.

    PubMed

    Reda, Haatem; Chin, Russell L

    2014-09-01

    Peripheral nervous system disease is a common and often debilitating feature of many systemic rheumatologic disorders. Such involvement takes many forms, reflecting the variety of underlying pathophysiology, though most patients present with painful multifocal neuropathy (usually vasculitic) or a distal sensory more than motor peripheral neuropathy (sometimes vasculitic and nearly always axonal). The presence of peripheral nervous system involvement is often an early signal of the generalization of inflammatory disease in blood vessels or extravascular tissues, though peripheral neuropathy is not itself an independent predictor of mortality. Nonetheless, progressive multifocal neuropathy, motor neuropathy, small fiber neuropathy, and sensory neuronopathy should be treated early and aggressively with immunosuppression (or the gluten-free diet in appropriate situations) to limit morbidity. Given the rapidly evolving therapeutic landscape, partnership with a rheumatologist is essential. Treatment is usually sustained for 1 to 2 years, and remission is possible in many cases within 6 to 12 months, with variable rates of relapse and treatment resistance. Patients should be meticulously monitored for relapse with serial laboratory testing, electrodiagnostic studies, and clinical examination. Functional rating scores, such as the neuropathy impairment scale and the total neuropathy score are useful for longitudinal assessment. PMID:25369437

  20. Recommendations to enable drug development for inherited neuropathies: Charcot-Marie-Tooth and Giant Axonal Neuropathy

    PubMed Central

    Sames, Lori; Moore, Allison; Arnold, Renee; Ekins, Sean

    2014-01-01

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

  1. Purple pigments: the pathophysiology of acute porphyric neuropathy.

    PubMed

    Lin, Cindy S-Y; Lee, Ming-Jen; Park, Susanna B; Kiernan, Matthew C

    2011-12-01

    The porphyrias are inherited metabolic disorders arising from disturbance in the haem biosynthesis pathway. The neuropathy associated with acute intermittent porphyria (AIP) occurs due to mutation involving the enzyme porphobilinogen deaminase (PBGD) and is characterised by motor-predominant features. Definitive diagnosis often encompasses a combination of biochemical, enzyme analysis and genetic testing, with clinical neurophysiological findings of a predominantly motor axonal neuropathy. Symptomatic and supportive treatment are the mainstays during an acute attack. If administered early, intravenous haemin may prevent progression of neuropathy. While the pathophysiology of AIP neuropathy remains unclear, axonal dysfunction appears intrinsically linked to the effects of neural energy deficits acquired through haem deficiency coupled to the neurotoxic effects of porphyrin precursors. The present review will provide an overview of AIP neuropathy, including discussion of recent advances in understanding developed through neurophysiological approaches that have further delineated the pathophysiology of axonal degeneration. PMID:21855406

  2. Diagnosis and Treatment of Pain in Small Fiber Neuropathy

    PubMed Central

    Hovaguimian, Alexandra

    2011-01-01

    Small fiber neuropathy manifests in a variety of different diseases and often results in symptoms of burning pain, shooting pain, allodynia, and hyperesthesia. Diagnosis of small fiber neuropathy is determined primarily by the history and physical exam, but functional neurophysiologic testing and skin biopsy evaluation of intraepidermal nerve fiber density can provide diagnostic confirmation. Management of small fiber neuropathy depends on the underlying etiology with concurrent treatment of associated neuropathic pain. A variety of recent guidelines propose the use of antidepressants, anticonvulsants, opioids, topical therapies, and nonpharmacologic treatments as part of the overall management of neuropathic pain. Unfortunately, little data about the treatment of pain specifically in small fiber neuropathy exist because most studies combine mixed neuropathic pain syndromes in the analysis. Additional studies targeting the treatment of pain in small fiber neuropathy are needed to guide decision making. PMID:21286866

  3. Surgical decompression in lower-extremity diabetic peripheral neuropathy.

    PubMed

    Rader, Andrew J

    2005-01-01

    Peripheral neuropathy can be a devastating complication of diabetes mellitus. This article describes surgical decompression as a means of restoring sensation and relieving painful neuropathy symptoms. A prospective study was performed involving patients diagnosed as having type 1 or type 2 diabetes with lower-extremity peripheral neuropathy. The neuropathy diagnosis was confirmed using quantitative sensory testing. Visual analog scales were used for subjective assessment before and after surgery. Treatment consisted of external and as-needed internal neurolysis of the common peroneal, deep peroneal, tibial, medial plantar, lateral plantar, and calcaneal nerves. Subjective pain perception and objective sensibility were significantly improved in most patients who underwent the described decompression. Surgical decompression of multiple peripheral nerves in the lower extremities is a valid and effective method of providing symptomatic relief of neuropathy pain and restoring sensation. PMID:16166461

  4. Peripheral Neuropathy Due to Vitamin Deficiency, Toxins, and Medications

    PubMed Central

    Staff, Nathan P.; Windebank, Anthony J.

    2014-01-01

    Purpose of Review: Peripheral neuropathies secondary to vitamin deficiencies, medications, or toxins are frequently considered but can be difficult to definitively diagnose. Accurate diagnosis is important since these conditions are often treatable and preventable. This article reviews the key features of different types of neuropathies caused by these etiologies and provides a comprehensive list of specific agents that must be kept in mind. Recent Findings: While most agents that cause peripheral neuropathy have been known for years, newly developed medications that cause peripheral neuropathy are discussed. Summary: Peripheral nerves are susceptible to damage by a wide array of toxins, medications, and vitamin deficiencies. It is important to consider these etiologies when approaching patients with a variety of neuropathic presentations; additionally, etiologic clues may be provided by other systemic symptoms. While length-dependent sensorimotor axonal peripheral neuropathy is the most common presentation, several examples present in a subacute severe fashion, mimicking Guillain-Barré syndrome. PMID:25299283

  5. Sciatic neuropathy developed after injection during curettage.

    PubMed

    Altıntaş, Ayşe; Gündüz, Ayşegül; Kantarcı, Fatih; Gözübatık Çelik, Gökçen; Koçer, Naci; Kızıltan, Meral E

    2016-01-01

    Intramuscular injections are likely the most common cause of sciatic nerve injury in developing countries. Less common causes include piriformis syndrome, primary tumors of the sciatic nerve, metastatic tumors invading or compressing the nerve, endometriosis, vascular malformations, and prolonged immobilization or positioning. While the most reliable diagnostic and prognostic methods include nerve conduction studies and electromyography, magnetic resonance imaging has been suggested as an alternative method of determining type of lesion, establishing location, and investigating level of nerve involvement. A case of sciatic neuropathy that developed after intramuscular injection, with patient in prolonged lithotomy position and under sedation, is described. PMID:27225613

  6. Molecular Mechanisms of Inherited Demyelinating Neuropathies

    PubMed Central

    SCHERER, STEVEN S.; WRABETZ, LAWRENCE

    2008-01-01

    The past 15 years have witnessed the identification of more than 25 genes responsible for inherited neuropathies in humans, many associated with primary alterations of the myelin sheath. A remarkable body of work in patients, as well as animal and cellular models, has defined the clinical and molecular genetics of these illnesses and shed light on how mutations in associated genes produce the heterogeneity of dysmyelinating and demyelinating phenotypes. Here, we review selected recent developments from work on the molecular mechanisms of these disorders and their implications for treatment strategies. PMID:18803325

  7. [Diabetic Retinopathy and Neuropathy: New in 2015].

    PubMed

    Henzen, Christoph

    2015-06-01

    In 2014 interesting new results were published in the field of diabetic microangiopathy: (1) In tensive treatment of type 1 diabetes for a mean of 6,5 years confers a lifelong reduction of the risk of diabetic retinopathy; (2) although the rates of diabetes-related complication have declined since 1990, the burden of disease persists because the prevalence of diabetes tripled during the same time; (3) subjects with diabetic neuropathy have structural brain changes, i.e. gray matter loss, findings with possible implications for the prognosis; (4) over 80% of type 2 diabetics who consider their feet to be normal have serious foot pathology. PMID:26098239

  8. [Peripheral neuropathies due to mitochondrial disorders].

    PubMed

    Funalot, B

    2009-12-01

    Involvement of peripheral nerves is frequent in mitochondrial disorders but with variable severity. Mitochondrial diseases causing peripheral neuropathies (PN) may be due to mutations of mitochondrial DNA (mtDNA), as is the case in MERRF and MELAS syndromes, or to mutations of nuclear genes. Secondary abnormalities of mtDNA (such as multiple deletions of muscle mtDNA) may result from mitochondrial disorders due to mutations in nuclear genes involved in mtDNA maintenance. This is the case in several syndromes caused by impaired mtDNA maintenance, such as Sensory Ataxic Neuropathy, Dysarthria and Ophthalmoplegia (SANDO) due to recessive mutations in the POLG gene, which encodes the catalytic subunit of mtDNA polymerase (DNA polymerase gamma), or Mitochondrial Neuro-Gastro-Intestinal Encephalomyopathy (MNGIE), due to recessive mutations in the TYMP gene, which encodes thymidine phosphorylase. Genetically-determined PN due to mutations of mitofusin 2, a GTPase involved in the fusion of external mitochondrial membranes, were identified during the last few years. Characteristic ultrastructural lesions (abnormalities of axonal mitochondria) are observed on longitudinal sections of nerve biopsies in patients with PN due to mitofusin 2 mutations. PMID:19942242

  9. Treating Painful Diabetic Peripheral Neuropathy: An Update.

    PubMed

    Snyder, Matthew J; Gibbs, Lawrence M; Lindsay, Tammy J

    2016-08-01

    Painful diabetic peripheral neuropathy occurs in approximately 25% of patients with diabetes mellitus who are treated in the office setting and significantly affects quality of life. It typically causes burning pain, paresthesias, and numbness in a stocking-glove pattern that progresses proximally from the feet and hands. Clinicians should carefully consider the patient's goals and functional status and potential adverse effects of medication when choosing a treatment for painful diabetic peripheral neuropathy. Pregabalin and duloxetine are the only medications approved by the U.S. Food and Drug Administration for treating this disorder. Based on current practice guidelines, these medications, with gabapentin and amitriptyline, should be considered for the initial treatment. Second-line therapy includes opioid-like medications (tramadol and tapentadol), venlafaxine, desvenlafaxine, and topical agents (lidocaine patches and capsaicin cream). Isosorbide dinitrate spray and transcutaneous electrical nerve stimulation may provide relief in some patients and can be considered at any point during therapy. Opioids and selective serotonin reuptake inhibitors are optional third-line medications. Acupuncture, traditional Chinese medicine, alpha lipoic acid, acetyl-l-carnitine, primrose oil, and electromagnetic field application lack high-quality evidence to support their use. PMID:27479625

  10. Microsurgical Decompression for Peroneal Nerve Entrapment Neuropathy

    PubMed Central

    MORIMOTO, Daijiro; ISU, Toyohiko; KIM, Kyongsong; SUGAWARA, Atsushi; YAMAZAKI, Kazuyoshi; CHIBA, Yasuhiro; IWAMOTO, Naotaka; ISOBE, Masanori; MORITA, Akio

    2015-01-01

    Peroneal nerve entrapment neuropathy (PNEN) is one cause of numbness and pain in the lateral lower thigh and instep, and of motor weakness of the extensors of the toes and ankle. We report a less invasive surgical procedure performed under local anesthesia to treat PNEN and our preliminary outcomes. We treated 22 patients (33 legs), 7 men and 15 women, whose average age was 66 years. The mean postoperative follow-up period was 40 months. All patients complained of pain or paresthesia of the lateral aspect of affected lower thigh and instep; all manifested a Tinel-like sign at the entrapment point. As all had undergone unsuccessful conservative treatment, we performed microsurgical decompression under local anesthesia. Of 19 patients who had undergone lumbar spinal surgery (LSS), 9 suffered residual symptoms attributable to PNEN. While complete symptom abatement was obtained in the other 10 they later developed PNEN-induced new symptoms. Motor weakness of the extensors of the toes and ankle [manual muscle testing (MMT) 4/5] was observed preoperatively in 8 patients; it was relieved by microsurgical decompression. Based on self-assessments, all 22 patients were satisfied with the results of surgery. PNEN should be considered as a possible differential diagnosis in patients with L5 neuropathy due to lumbar degenerative disease, and as a causative factor of residual symptoms after LSS. PNEN can be successfully addressed by less-invasive surgery performed under local anesthesia. PMID:26227056

  11. Microsurgical Decompression for Peroneal Nerve Entrapment Neuropathy.

    PubMed

    Morimoto, Daijiro; Isu, Toyohiko; Kim, Kyongsong; Sugawara, Atsushi; Yamazaki, Kazuyoshi; Chiba, Yasuhiro; Iwamoto, Naotaka; Isobe, Masanori; Morita, Akio

    2015-01-01

    Peroneal nerve entrapment neuropathy (PNEN) is one cause of numbness and pain in the lateral lower thigh and instep, and of motor weakness of the extensors of the toes and ankle. We report a less invasive surgical procedure performed under local anesthesia to treat PNEN and our preliminary outcomes. We treated 22 patients (33 legs), 7 men and 15 women, whose average age was 66 years. The mean postoperative follow-up period was 40 months. All patients complained of pain or paresthesia of the lateral aspect of affected lower thigh and instep; all manifested a Tinel-like sign at the entrapment point. As all had undergone unsuccessful conservative treatment, we performed microsurgical decompression under local anesthesia. Of 19 patients who had undergone lumbar spinal surgery (LSS), 9 suffered residual symptoms attributable to PNEN. While complete symptom abatement was obtained in the other 10 they later developed PNEN-induced new symptoms. Motor weakness of the extensors of the toes and ankle [manual muscle testing (MMT) 4/5] was observed preoperatively in 8 patients; it was relieved by microsurgical decompression. Based on self-assessments, all 22 patients were satisfied with the results of surgery. PNEN should be considered as a possible differential diagnosis in patients with L5 neuropathy due to lumbar degenerative disease, and as a causative factor of residual symptoms after LSS. PNEN can be successfully addressed by less-invasive surgery performed under local anesthesia. PMID:26227056

  12. Mitotoxicity in distal symmetrical sensory peripheral neuropathies

    PubMed Central

    Bennett, Gary J.; Doyle, Timothy; Salvemini, Daniela

    2016-01-01

    Chronic distal symmetrical sensory peripheral neuropathy is a common neurological complication of cancer chemotherapy, HIV treatment and diabetes. Although aetiology-specific differences in presentation are evident, the clinical signs and symptoms of these neuropathies are clearly similar. Data from animal models of neuropathic pain suggest that the similarities have a common cause: mitochondrial dysfunction in primary afferent sensory neurons. Mitochondrial dysfunction is caused by mitotoxic effects of cancer chemotherapeutic drugs of several chemical classes, HIV-associated viral proteins, and nucleoside reverse transcriptase inhibitor treatment, as well as the (possibly both direct and indirect) effects of excess glucose. The mitochondrial injury results in a chronic neuronal energy deficit, which gives rise to spontaneous nerve impulses and a compartmental neuronal degeneration that is first apparent in the terminal receptor arbor—that is, intraepidermal nerve fibres—of cutaneous afferent neurons. Preliminary data suggest that drugs that prevent mitochondrial injury or improve mitochondrial function could be useful in the treatment of these conditions. PMID:24840972

  13. Early diabetic neuropathy: Triggers and mechanisms

    PubMed Central

    Dobretsov, Maxim; Romanovsky, Dmitry; Stimers, Joseph R

    2007-01-01

    Peripheral neuropathy, and specifically distal peripheral neuropathy (DPN), is one of the most frequent and troublesome complications of diabetes mellitus. It is the major reason for morbidity and mortality among diabetic patients. It is also frequently associated with debilitating pain. Unfortunately, our knowledge of the natural history and pathogenesis of this disease remains limited. For a long time hyperglycemia was viewed as a major, if not the sole factor, responsible for all symptomatic presentations of DPN. Multiple clinical observations and animal studies supported this view. The control of blood glucose as an obligatory step of therapy to delay or reverse DPN is no longer an arguable issue. However, while supporting evidence for the glycemic hypothesis has accumulated, multiple controversies accumulated as well. It is obvious now that DPN cannot be fully understood without considering factors besides hyperglycemia. Some symptoms of DPN may develop with little, if any, correlation with the glycemic status of a patient. It is also clear that identification of these putative non-glycemic mechanisms of DPN is of utmost importance for our understanding of failures with existing treatments and for the development of new approaches for diagnosis and therapy of DPN. In this work we will review the strengths and weaknesses of the glycemic hypothesis, focusing on clinical and animal data and on the pathogenesis of early stages and triggers of DPN other than hyperglycemia. PMID:17226897

  14. [Antalgic radiotherapy in lumbosacral carcinomatous neuropathies].

    PubMed

    Russi, E G; Gaeta, M; Pergolizzi, S; Settineri, N; Frosina, P; De Renzis, C

    1994-06-01

    Lumbosacral carcinomatous neuropathy (LCN) may be caused by infiltration or compression of the lumbosacral plexi and nerves from intrapelvic or paraaortic neoplasms. The authors submitted 23 patients complaining of LCN with CT documented intrapelvic or paraaortic tumors to palliative radiotherapy. Megavoltage external beam irradiation was administered using a 6-MV linear accelerator. Treatment field sizes ranged from 56 cm2 to 235 cm2 (mean: 150.54 cm2) and encompassed only the site where the disease involved the lumbosacral plexus or its branches. > or = 3 Gy/day fractions were used. Twenty-one of 22 assessable patients (95.4%) obtained LCN pain relief; 19 (86.3%) obtained complete LCN pain relief. The median time to pain progression (TPP) was 150 days (range: 39-510 days). The median survival was 165 days. Seven patients were LCN pain-free at death. Two patients are alive and LCN pain-free. The remaining 12 patients had recurrent LCN pain: four of them were reirradiated at the site of previous neuropathy and only two had partial relief again. The authors conclude that it is advisable to submit to palliative radiotherapy the inoperable disseminated and/or recurrent cancer patients complaining of LCN, to use large fractions not to occupy the extant time of their already short life-expectancy, and to design small fields to avoid acute side-effects. PMID:7518934

  15. Episodic neurological dysfunction in hereditary peripheral neuropathy

    PubMed Central

    Kulkarni, Girish Baburao; Mailankody, Pooja; Isnwara, Pawanraj Palu; Prasad, Chandrajit; Mustare, Veerendrakumar

    2015-01-01

    Episodic transient neurological symptoms are an important set of problems presenting to a neurologist in his routine practice. Occasionally, detailed clinical history including past and family history supplemented with focused examination can bring out a rare cause for such symptoms. We describe in this report in a young male presenting with episodic focal neurological dysfunction, with family history of similar episodes in mother and brother. Examination showed features of pes cavus and peripheral neuropathy for which patient was asymptomatic. Mother and brother were established cases of hereditary neuropathy. Imaging on multiple occasions showed reversible white matter abnormalities. Clinical suspicion of X-linked Charcot-Marie-Tooth disease type 1 (CMT1X) was confirmed with detection of mutation in Gap Junction B1 (GJB1) gene, which codes for connexin 32 protein (c.425G>A; p.R142Q hemizygous mutation). Though this mutation has been already reported in CMTX patients, it has not been associated with transient neurological dysfunctions. This is probably the first reported case of CMTX patient with transient neurological dysfunction from India, whose family members had similar episodes. PMID:25745327

  16. Computer aided diagnosis of diabetic peripheral neuropathy

    NASA Astrophysics Data System (ADS)

    Chekh, Viktor; Soliz, Peter; McGrew, Elizabeth; Barriga, Simon; Burge, Mark; Luan, Shuang

    2014-03-01

    Diabetic peripheral neuropathy (DPN) refers to the nerve damage that can occur in diabetes patients. It most often affects the extremities, such as the feet, and can lead to peripheral vascular disease, deformity, infection, ulceration, and even amputation. The key to managing diabetic foot is prevention and early detection. Unfortunately, current existing diagnostic techniques are mostly based on patient sensations and exhibit significant inter- and intra-observer differences. We have developed a computer aided diagnostic (CAD) system for diabetic peripheral neuropathy. The thermal response of the feet of diabetic patients following cold stimulus is captured using an infrared camera. The plantar foot in the images from a thermal video are segmented and registered for tracking points or specific regions. The temperature recovery of each point on the plantar foot is extracted using our bio-thermal model and analyzed. The regions that exhibit abnormal ability to recover are automatically identified to aid the physicians to recognize problematic areas. The key to our CAD system is the segmentation of infrared video. The main challenges for segmenting infrared video compared to normal digital video are (1) as the foot warms up, it also warms up the surrounding, creating an ever changing contrast; and (2) there may be significant motion during imaging. To overcome this, a hybrid segmentation algorithm was developed based on a number of techniques such as continuous max-flow, model based segmentation, shape preservation, convex hull, and temperature normalization. Verifications of the automatic segmentation and registration using manual segmentation and markers show good agreement.

  17. Inherited focal, episodic neuropathies: hereditary neuropathy with liability to pressure palsies and hereditary neuralgic amyotrophy.

    PubMed

    Chance, Phillip F

    2006-01-01

    Hereditary neuropathy with liability to pressure palsies (HNPP; also called tomaculous neuropathy) is an autosomal-dominant disorder that produces a painless episodic, recurrent, focal demyelinating neuropathy. HNPP generally develops during adolescence, and may cause attacks of numbness, muscular weakness, and atrophy. Peroneal palsies, carpal tunnel syndrome, and other entrapment neuropathies may be frequent manifestations of HNPP. Motor and sensory nerve conduction velocities may be reduced in clinically affected patients, as well as in asymptomatic gene carriers. The histopathological changes observed in peripheral nerves of HNPP patients include segmental demyelination and tomaculous or "sausage-like" formations. Mild overlap of clinical features with Charcot-Marie-Tooth (CMT) disease type 1 (CMT1) may lead patients with HNPP to be misdiagnosed as having CMT1. HNPP and CMT1 are both demyelinating neuropathies, however, their clinical, pathological, and electrophysiological features are quite distinct. HNPP is most frequently associated with a 1.4-Mb pair deletion on chromosome 17p12. A duplication of the identical region leads to CMT1A. Both HNPP and CMT1A result from a dosage effect of the PMP22 gene, which is contained within the deleted/duplicated region. This is reflected in reduced mRNA and protein levels in sural nerve biopsy samples from HNPP patients. Treatment for HNPP consists of preventative and symptom-easing measures. Hereditary neuralgic amyotrophy (HNA; also called familial brachial plexus neuropathy) is an autosomal-dominant disorder causing episodes of paralysis and muscle weakness initiated by severe pain. Individuals with HNA may suffer repeated episodes of intense pain, paralysis, and sensory disturbances in an affected limb. The onset of HNA is at birth or later in childhood with prognosis for recovery usually favorable; however, persons with HNA may have permanent residual neurological dysfunction following attack(s). Episodes are often

  18. Identifying Common Genetic Risk Factors of Diabetic Neuropathies

    PubMed Central

    Witzel, Ini-Isabée; Jelinek, Herbert F.; Khalaf, Kinda; Lee, Sungmun; Khandoker, Ahsan H.; Alsafar, Habiba

    2015-01-01

    Type 2 diabetes mellitus (T2DM) is a global public health problem of epidemic proportions, with 60–70% of affected individuals suffering from associated neurovascular complications that act on multiple organ systems. The most common and clinically significant neuropathies of T2DM include uremic neuropathy, peripheral neuropathy, and cardiac autonomic neuropathy. These conditions seriously impact an individual’s quality of life and significantly increase the risk of morbidity and mortality. Although advances in gene sequencing technologies have identified several genetic variants that may regulate the development and progression of T2DM, little is known about whether or not the variants are involved in disease progression and how these genetic variants are associated with diabetic neuropathy specifically. Significant missing heritability data and complex disease etiologies remain to be explained. This article is the first to provide a review of the genetic risk variants implicated in the diabetic neuropathies and to highlight potential commonalities. We thereby aim to contribute to the creation of a genetic-metabolic model that will help to elucidate the cause of diabetic neuropathies, evaluate a patient’s risk profile, and ultimately facilitate preventative and targeted treatment for the individual. PMID:26074879

  19. Oxidative stress in the development, maintenance and resolution of paclitaxel-induced painful neuropathy.

    PubMed

    Duggett, Natalie A; Griffiths, Lisa A; McKenna, Olivia E; de Santis, Vittorio; Yongsanguanchai, Nutcha; Mokori, Esther B; Flatters, Sarah J L

    2016-10-01

    Paclitaxel is a first-line chemotherapeutic with the major dose-limiting side effect of painful neuropathy. Previous preclinical studies indicate mitochondrial dysfunction and oxidative stress are associated with this disorder; however no direct assessment of reactive oxygen species (ROS) levels and antioxidant enzyme activity in sensory neurons following paclitaxel has been undertaken. As expected, repeated low doses of systemic paclitaxel in rats induced long-lasting pain behaviour with a delayed onset, akin to the clinical scenario. To elucidate the role of ROSinthe development and maintenance ofpaclitaxel-inducedpainful neuropathy, we have assessed ROS and antioxidant enzyme activity levels in the nociceptive system in vivo at three key behavioural time-points; prior to pain onset (day 7), peak pain severity and pain resolution. In isolated dorsal root ganglia (DRG) neurons, ROS levels were unchanged following paclitaxel-exposure in vitro or in vivo. ROS levels were further assessed in DRG and spinal cord in vivo following intrathecal MitoTracker®RedCM-H2XRos administration in paclitaxel-/vehicle-treated rats. ROS levels were increased at day 7, specifically in non-peptidergic DRG neurons. In the spinal cord, neuronally-derived ROS was increased at day 7, yet ROS levels in microglia and astrocytes were unaltered. In DRG, CuZnSOD and glutathione peroxidase (GPx) activity were increased at day 7 and peak pain time-points, respectively. In peripheral sensory nerves, CuZnSOD activity was increased at day 7, and at peak pain, MnSOD, CuZnSOD and GPx activity were increased. Catalase activity was unaltered in DRG and saphenous nerves. These data suggest that neuronally-derived mitochondrial ROS, accompanied with an inadequate endogenous antioxidant enzyme response, are contributory factors in paclitaxel-induced painful neuropathy. PMID:27393249

  20. Neuropathy of nitroimidazole radiosensitizers: clinical and pathological description

    SciTech Connect

    Wasserman, T.H.; Nelson, J.S.; VonGerichten, D.

    1984-09-01

    The dose limiting toxicity of the nitroimidazole radiosensitizers is peripherial neuropathy. Improved pharmacology of newer drugs has eliminated the encephalopathy. Peripheral neuropathies are predominently mild to moderate paresthesias of both hands and feet. Subjective changes occur with or without minimal objective changes on neurologic exam. All of the neuropathies occurred within 30 days of the last drug dose and are of varible duration. Sural nerve biopsies from patients indicate progressive axonal degeneration affecting both large and small caliber myelinated fibers. Axonal damage appears to be more severe in the distal portion of the nerves. More data are needed for correlation of clinical and pathological changes.

  1. Neuroactive steroid treatment modulates myelin lipid profile in diabetic peripheral neuropathy.

    PubMed

    Mitro, Nico; Cermenati, Gaia; Brioschi, Elisabetta; Abbiati, Federico; Audano, Matteo; Giatti, Silvia; Crestani, Maurizio; De Fabiani, Emma; Azcoitia, Inigo; Garcia-Segura, Luis Miguel; Caruso, Donatella; Melcangi, Roberto Cosimo

    2014-09-01

    Diabetic peripheral neuropathy causes a decrease in the levels of dihydroprogesterone and 5α-androstane-3α,17β-diol (3α-diol) in the peripheral nerves. These two neuroactive steroids exert protective effects, by mechanisms that still remain elusive. We have previously shown that the activation of Liver X Receptors improves the peripheral neuropathic phenotype in diabetic rats. This protective effect is accompanied by the restoration to control values of the levels of dihydroprogesterone and 3α-diol in peripheral nerves. In addition, activation of these receptors decreases peripheral myelin abnormalities by improving the lipid desaturation capacity, which is strongly blunted by diabetes, and ultimately restores the myelin lipid profile to non-diabetic values. On this basis, we here investigate whether dihydroprogesterone or 3α-diol may exert their protective effects by modulating the myelin lipid profile. We report that both neuroactive steroids act on the lipogenic gene expression profile in the sciatic nerve of diabetic rats, reducing the accumulation of myelin saturated fatty acids and promoting desaturation. These changes were associated with a reduction in myelin structural alterations. These findings provide evidence that dihydroprogesterone and 3α-diol are protective agents against diabetic peripheral neuropathy by regulating the de novo lipogenesis pathway, which positively influences myelin lipid profile. PMID:24607810

  2. Postpartum septic sacroiliitis misdiagnosed as sciatic neuropathy.

    PubMed

    Liu, Xiao-Qing; Li, Fang-Cai; Wang, Jia-Wei; Wang, Shuang

    2010-03-01

    Early diagnosis of septic sacroiliitis is difficult because symptoms are nonspecific, especially during pregnancy and the postpartum period. We describe a female patient with left buttock pain radiating down the thigh after an uncomplicated induction delivery. She was afebrile and had no apparent abnormality on pelvic x-ray or computed tomography scan. A sensory deficit in the lateral portion of her left lower limb was found, and electromyography showed neurogenic abnormalities in the left lower limb. She was initially misdiagnosed as sciatic neuropathy. As her symptoms worsened, septic sacroiliitis is considered. Bone scintigraphy showed increased Tc-methylene diphosphonate uptake in the left sacroiliac joint, and magnetic resonance imaging scan showed a signal abnormality in the left sacroiliac joint. The diagnosis of septic sacroiliitis was then confirmed by the rapid efficacy of antibiotic therapy. This report suggests that irritation and injury of spinal nerves can be the presenting signs in septic sacroiliitis. PMID:20090512

  3. Isoniazid induced motor-dominant neuropathy.

    PubMed

    Arsalan, Rabeeya; Sabzwari, Saniya

    2015-10-01

    Isoniazid though a very effective treatment for tuberculosis can cause severe motor-dominant neuropathy which can be reversible with pyridoxine supplementation. A 45-year-old female diagnosed with psoas abscess, culture positive for mycobacterium tuberculosis, was started on anti- tuberculous treatment with four drugs, including isoniazid at a dose of 5 mg/kg/day. Three months later she developed severe motor weakness of lower limbs with loss of ankle and knee reflexes. She was treated with vitamin B6 injections and isoniazid treatment was continued. Her motor weakness gradually improved in a few months, but mild sensory impairment persisted even after two years. There is need for vigilance regarding neurological effects of isoniazid in seemingly low-risk individuals in whom development of symptoms should raise the suspicion about slow acetylator status. Timely therapeutic intervention with high-dose vitamin B6 can reduce the long-term morbidity associated with this easily reversible condition. PMID:26440850

  4. Endoneurial Microvascular Pathology in Feline Diabetic Neuropathy

    PubMed Central

    Estrella, Jeannelyn S.; Nelson, Richard N.; Sturges, B.K.; Vernau, Karen M.; Williams, D. Collette; LeCouteur, Richard A.; Shelton, G. Diane; Mizisin, Andrew P.

    2008-01-01

    Endoneurial capillaries in nerve biopsies from 12 adult diabetic cats with varying degrees of neurological dysfunction were examined for evidence of microvascular pathology and compared to nerves obtained at autopsy from 7 adult non-diabetic cats without clinical evidence of neurological dysfunction. As reported previously (Mizisin et al., 2007), the diabetic cats had elevated glycosylated hemoglobin and serum fructosamine levels, decreased motor nerve conduction velocity and compound muscle action potentials (CMAP), and markedly decreased myelinated nerve fiber densities. Compared to non-diabetic cats, there was a non-significant 26% increase in capillary density and a significant (P<0.009) 45% increase in capillary size in diabetic cats. Capillary luminal size was also significantly (P<0.001) increased, while an index of vasoconstriction was significantly decreased (P<0.001) in diabetic cats compared to non-diabetic controls. No differences in endothelial cell size, endothelial cell number or pericyte size were detected between non-diabetic and diabetic cats. In diabetic cats, basement membrane thickening, seen as a reduplication of the basal lamina, was significantly (P<0.0002) increased by 73% compared to non-diabetic controls. Regression analysis of either myelinated nerve fiber density or CMAP amplitude against basement membrane size demonstrated a negative correlation with significant slopes (P<0.03 and P<0.04, respectively). These data demonstrate that myelinated nerve fiber injury in feline diabetic neuropathy is associated with microvascular pathology and that some of these changes parallel those documented in experimental rodent and human diabetic neuropathy. PMID:18207200

  5. Optic Neuropathy in Thyroid Eye Disease: A Case Series

    PubMed Central

    Seng, Wong Hon; Isa, Hazlita Dato' Mohd

    2016-01-01

    In patients with thyroid disease, ocular involvement or thyroid ophthalmopathy is common, irrespective of their thyroid status. A common feature of thyroid eye disease is eyelid retraction, which leads to a classical starry gaze (Kocher sign). Treatment with radioactive iodine (RAI) is a known therapy for hyperthyroidism. However, this treatment may lead to or worsen thyroid ophthalmopathy. We report a case series of two patients with thyrotoxicosis, who presented with an atypical and subtle occurrence of thyroid eye disease (TED) soon after RAI therapy. One of the patients was initially diagnosed and treated for dry eyes; however, over a period of time, the patient's vision progressively deteriorated. Clinical and radiological investigations confirmed thyroid ophthalmopathy with low serum thyroid hormone levels. Both patients recovered well after immediate intensive intravenous steroid treatment. These cases highlight the importance of recognizing partial ptosis as one of the presenting signs of active TED among general practitioners and physicians. PMID:27274392

  6. Antioxidant Strategies in the Management of Diabetic Neuropathy

    PubMed Central

    Oyenihi, Ayodeji Babatunde; Ayeleso, Ademola Olabode; Masola, Bubuya

    2015-01-01

    Chronic hyperglycaemia (an abnormally high glucose concentration in the blood) resulting from defects in insulin secretion/action, or both, is the major hallmark of diabetes in which it is known to be involved in the progression of the condition to different complications that include diabetic neuropathy. Diabetic neuropathy (diabetes-induced nerve damage) is the most common diabetic complication and can be devastating because it can lead to disability. There is an increasing body of evidence associating diabetic neuropathy with oxidative stress. Oxidative stress results from the production of oxygen free radicals in the body in excess of its ability to eliminate them by antioxidant activity. Antioxidants have different mechanisms and sites of actions by which they exert their biochemical effects and ameliorate nerve dysfunction in diabetes by acting directly against oxidative damage. This review will examine different strategies for managing diabetic neuropathy which rely on exogenous antioxidants. PMID:25821809

  7. Familial Idiopathic Cranial Neuropathy in a Chinese Family.

    PubMed

    Zhang, Li; Liang, Jianfeng; Yu, Yanbing

    2016-01-01

    Cranial neuropathy is usually idiopathic and familial cases are uncommon. We describe a family with 5 members with cranial neuropathy over 3 generations. All affected patients were women, indicating an X-linked dominant or an autosomal dominant mode of inheritance. Our cases and a review of the literature suggest that familial idiopathic cranial neuropathy is a rare condition which may be related to autosomal dominant vascular disorders (e.g. vascular tortuosity, sclerosis, elongation or extension), small posterior cranial fossas, anatomical variations of the posterior circulation, hypersensitivity of cranial nerves and other abnormalities. Moreover, microvascular decompression is the treatment of choice because vascular compression is the main factor in the pathogenesis. To the best of our knowledge, this is the first report of familial cranial neuropathy in China. PMID:27161475

  8. Transcriptomic analyses of genes and tissues in inherited sensory neuropathies.

    PubMed

    Sapio, Matthew R; Goswami, Samridhi C; Gross, Jacklyn R; Mannes, Andrew J; Iadarola, Michael J

    2016-09-01

    Inherited sensory neuropathies are caused by mutations in genes affecting either primary afferent neurons, or the Schwann cells that myelinate them. Using RNA-Seq, we analyzed the transcriptome of human and rat DRG and peripheral nerve, which contain sensory neurons and Schwann cells, respectively. We subdivide inherited sensory neuropathies based on expression of the mutated gene in these tissues, as well as in mouse TRPV1 lineage DRG nociceptive neurons, and across 32 human tissues from the Human Protein Atlas. We propose that this comprehensive approach to neuropathy gene expression leads to better understanding of the involved cell types in patients with these disorders. We also characterize the genetic "fingerprint" of both tissues, and present the highly tissue-specific genes in DRG and sciatic nerve that may aid in the development of gene panels to improve diagnostics for genetic neuropathies, and may represent specific drug targets for diseases of these tissues. PMID:27343803

  9. Optical Coherence Tomography (OCT) in Optic Neuritis and Multiple Sclerosis

    PubMed Central

    Lamirel, Cédric; Newman, Nancy J.; Biousse, Valérie

    2010-01-01

    Optical coherence tomography (OCT) is a non-invasive imaging technique routinely used in ophthalmology to visualize and quantify the layers of the retina. It also provides information on optic nerve head topography, peripapillary retinal nerve fiber layer thickness, and macular volume which correlate with axonal loss. These measurements are of particular interest in optic neuropathies and in multiple sclerosis, and OCT parameters are now used as endpoints in neurologic clinical trials. PMID:20605617

  10. Pathogenesis and treatment of immune-mediated neuropathies.

    PubMed

    Lehmann, Helmar C; Meyer Zu Horste, Gerd; Kieseier, Bernd C; Hartung, Hans-Peter

    2009-07-01

    Immune-mediated neuropathies represent a heterogeneous spectrum of peripheral nerve disorders that can be classified according to time course, predominant involvement of motor/sensory fibers, distribution of deficits and paraclinical parameters such as electrophysiology and serum antibodies. In the last few years, significant advances have been achieved in elucidating underlying pathomechanisms, which made it possible to identify potential therapeutic targets. In this review, we discuss the latest development in pathogenesis and treatment of immune-mediated neuropathies. PMID:21179533

  11. An unusual demyelinating neuropathy in a patient with Waardenburg's syndrome.

    PubMed

    Jacobs, J M; Wilson, J

    1992-01-01

    We present clinical and laboratory data from a patient with Waardenburg's syndrome type II comprising iris heterochromia and deafness, complicated by Hirschsprung's disease--a known association--and an unusual demyelinating peripheral neuropathy--a unique association. The neuropathy is characterised by excessive focal folding of myelin sheaths. It is our view that, although both disorders could represent the consequences of neural crest embryopathy, it is more likely that they are associated by chance. PMID:1636383

  12. Peripheral neuropathy in HIV: an analysis of evidence-based approaches.

    PubMed

    Nicholas, Patrice K; Corless, Inge B; Evans, Linda A

    2014-01-01

    Peripheral neuropathy is a common and vexing symptom for people living with HIV infection (PLWH). Neuropathy occurs in several different syndromes and is identified in the literature as distal sensory polyneuropathy or distal sensory peripheral neuropathy. More recently, the HIV literature has focused on the syndrome as painful HIV-associated sensory neuropathy, addressing the symptom rather than the underlying pathophysiology. Assessment of neuropathy in PLWH is critical and must be incorporated into nursing practice for each visit. Neuropathy has been attributed to the direct effects of HIV, exposure to antiretroviral medications (particularly the nucleoside reverse transcriptase inhibitors), advanced immune suppression, and comorbid tuberculosis infection and exposure to antituberculosis medications. Evidence supports the importance of addressing neuropathy in PLWH with pharmacologic treatment regimens and complementary/alternative approaches. This paper examines the pathophysiology, evidence, and approaches to managing peripheral neuropathy. A case study has been included to illustrate a patient's experience with neuropathy symptoms. PMID:24698331

  13. Entrapment in anti myelin-associated glycoprotein neuropathy.

    PubMed

    Faber, Catharina G; Notermans, Nicolette C; Wokke, John H J; Franssen, Hessel

    2009-04-01

    Anti-myelin associated glycoprotein (MAG) neuropathy is a chronic disorder in which IgM antibodies react with Schwann cell glycoproteins, including MAG and peripheral myelin protein 22 (PMP22). Nerve conduction studies show features of axon loss and predominantly distal slowing consistent with demyelination. Because a genetic loss of PMP22 function yields hereditary neuropathy with liability to pressure palsies (HNPP), loss of PMP22 function due to anti- MAG antibodies may result in increased sensitivity to entrapment. We investigated this by performing standardized electrophysiological studies in 16 patients with anti-MAG neuropathy and 16 disease controls with genetically confirmed HNPP. Disproportionate slowing relative to adjacent segments occurred in similar proportions of patients with anti-MAG neuropathy and HNPP, and was of the same magnitude in each group. Affected were the elbow, carpal tunnel and the wrist-hand segments of the median and ulnar nerves. However, in anti-MAG neuropathy as compared to HNPP, absolute values of distal motor latencies and conduction velocities outside entrapment sites were slower and amplitudes were lower. In conclusion, increased sensitivity for entrapment may occur in anti-MAG neuropathy and contribute to part of the nerve damage. PMID:19306083

  14. Morphologic Changes in Autonomic Nerves in Diabetic Autonomic Neuropathy.

    PubMed

    Jin, Heung Yong; Baek, Hong Sun; Park, Tae Sun

    2015-12-01

    Diabetic neuropathy is one of the major complications of diabetes, and it increases morbidity and mortality in patients with both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Because the autonomic nervous system, for example, parasympathetic axons, has a diffuse and wide distribution, we do not know the morphological changes that occur in autonomic neural control and their exact mechanisms in diabetic patients with diabetic autonomic neuropathy (DAN). Although the prevalence of sympathetic and parasympathetic neuropathy is similar in T1DM versus T2DM patients, sympathetic nerve function correlates with parasympathetic neuropathy only in T1DM patients. The explanation for these discrepancies might be that parasympathetic nerve function was more severely affected among T2DM patients. As parasympathetic nerve damage seems to be more advanced than sympathetic nerve damage, it might be that parasympathetic neuropathy precedes sympathetic neuropathy in T2DM, which was Ewing's concept. This could be explained by the intrinsic morphologic difference. Therefore, the morphological changes in the sympathetic and parasympathetic nerves of involved organs in T1DM and T2DM patients who have DAN should be evaluated. In this review, evaluation methods for morphological changes in the epidermal nerves of skin, and the intrinsic nerves of the stomach will be discussed. PMID:26706915

  15. Animal models of peripheral neuropathy due to environmental toxicants.

    PubMed

    Rao, Deepa B; Jortner, Bernard S; Sills, Robert C

    2014-01-01

    Despite the progress in our understanding of pathogeneses and the identification of etiologies of peripheral neuropathy, idiopathic neuropathy remains common. Typically, attention to peripheral neuropathies resulting from exposure to environmental agents is limited relative to more commonly diagnosed causes of peripheral neuropathy (diabetes and chemotherapeutic agents). Given that there are more than 80,000 chemicals in commerce registered with the Environmental Protection Agency and that at least 1000 chemicals are known to have neurotoxic potential, very few chemicals have been established to affect the peripheral nervous system (mainly after occupational exposures). A wide spectrum of exposures, including pesticides, metals, solvents, nutritional sources, and pharmaceutical agents, has been related, both historically and recently, to environmental toxicant-induced peripheral neuropathy. A review of the literature shows that the toxicity and pathogeneses of chemicals adversely affecting the peripheral nervous system have been studied using animal models. This article includes an overview of five prototypical environmental agents known to cause peripheral neuropathy--namely, organophosphates, carbon disulfide, pyridoxine (Vitamin B6), acrylamide, and hexacarbons (mainly n-hexane, 2,5-hexanedione, methyl n-butyl ketone). Also included is a brief introduction to the structural components of the peripheral nervous system and pointers on common methodologies for histopathologic evaluation of the peripheral nerves. PMID:24615445

  16. Mechanical surface waves accompany action potential propagation.

    PubMed

    El Hady, Ahmed; Machta, Benjamin B

    2015-01-01

    Many diverse studies have shown that a mechanical displacement of the axonal membrane accompanies the electrical pulse defining the action potential (AP). We present a model for these mechanical displacements as arising from the driving of surface wave modes in which potential energy is stored in elastic properties of the neuronal membrane and cytoskeleton while kinetic energy is carried by the axoplasmic fluid. In our model, these surface waves are driven by the travelling wave of electrical depolarization characterizing the AP, altering compressive electrostatic forces across the membrane. This driving leads to co-propagating mechanical displacements, which we term Action Waves (AWs). Our model allows us to estimate the shape of the AW that accompanies any travelling wave of voltage, making predictions that are in agreement with results from several experimental systems. Our model can serve as a framework for understanding the physical origins and possible functional roles of these AWs. PMID:25819404

  17. Ocular myasthenia gravis accompanied by anosmia.

    PubMed

    Chen, Ying; Wang, Li; Zhou, Li; Gao, Ying

    2016-02-01

    We report a case of ocular myasthenia gravis (MG) accompanied by anosmia. A 76-year-old man had idiopathic anosmia of 2-year duration. Four months before consultation, he began to have drooping in the right upper eyelid along with muscle soreness, distension, and pain in the nape. His tongue was dark-red with a thin and white coating; his pulse was wiry and slippery. According to Traditional Chinese Medicine, eyelid drooping and anosmia are the main signs of liver constraint and spleen deficiency. In Western Medicine, the diagnosis was ocular MG and idiopathic anosmia. Our patient, along with the literature, suggests that anosmia may be an early symptom before MG. MG accompanied by anosmia could be a special subtype of MG according to antibody production and symptoms. PMID:26946629

  18. Mechanical surface waves accompany action potential propagation

    NASA Astrophysics Data System (ADS)

    El Hady, Ahmed; Machta, Benjamin B.

    2015-03-01

    Many diverse studies have shown that a mechanical displacement of the axonal membrane accompanies the electrical pulse defining the action potential (AP). We present a model for these mechanical displacements as arising from the driving of surface wave modes in which potential energy is stored in elastic properties of the neuronal membrane and cytoskeleton while kinetic energy is carried by the axoplasmic fluid. In our model, these surface waves are driven by the travelling wave of electrical depolarization characterizing the AP, altering compressive electrostatic forces across the membrane. This driving leads to co-propagating mechanical displacements, which we term Action Waves (AWs). Our model allows us to estimate the shape of the AW that accompanies any travelling wave of voltage, making predictions that are in agreement with results from several experimental systems. Our model can serve as a framework for understanding the physical origins and possible functional roles of these AWs.

  19. Epidemic neuropathy in Cuba: a plea to end the United States economic embargo on a humanitarian basis.

    PubMed

    Román, G C

    1994-10-01

    During 1992-1993, an epidemic of neurologic disease in Cuba affected 50,862 patients with optic neuropathy, sensorineural deafness, predominantly sensory peripheral neuropathy, and dorsolateral myelopathy. The clinical syndromes were identical to those of prisoners of war subjected to nutritional restriction in tropical prison camps during World War II (Strachan's disease). A dietary deficiency of group B vitamins and sulfur-containing amino acids appears to have been the primary cause of the epidemic. This was a consequence of economic and political events in Cuba linked to the collapse of the Soviet Union and socialist countries. The recently toughened 30-year-old US economic embargo on Cuba contributed to these problems and hampered the investigation, treatment, and prevention of the epidemic. A plea is made to the neurologic community to request the lifting of the trade blockade on a humanitarian basis. PMID:7936221

  20. Metastatic Basal Cell Carcinoma Accompanying Gorlin Syndrome

    PubMed Central

    Bilir, Yeliz; Gokce, Erkan; Ozturk, Banu; Deresoy, Faik Alev; Yuksekkaya, Ruken; Yaman, Emel

    2014-01-01

    Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity and mortality. A 66-year-old male patient with a history of recurrent basal cell carcinoma was presented with exophthalmus in the left eye and the lesions localized in the left lateral orbita and left zygomatic area. His physical examination revealed hearing loss, gapped teeth, highly arched palate, and frontal prominence. Left orbital mass, cystic masses at frontal and ethmoidal sinuses, and multiple pulmonary nodules were detected at CT scans. Basal cell carcinoma was diagnosed from biopsy of ethmoid sinus. Based on the clinical and typical radiological characteristics (falx cerebri calcification, bifid costa, and odontogenic cysts), the patient was diagnosed with metastatic skin basal cell carcinoma accompanied by Gorlin syndrome. Our case is a basal cell carcinoma with aggressive course accompanying a rarely seen syndrome. PMID:25506011

  1. Giant axonal neuropathy: a rare inherited neuropathy with simple clinical clues

    PubMed Central

    Kamate, Mahesh; Ramakrishna, Shashikala; Kambali, Shweta; Mahadevan, Anita

    2014-01-01

    Giant axonal neuropathy (GAN) is a rare hereditary neurodegenerative disorder characterised by accumulation of excess neurofilaments in the axons of peripheral and central nervous systems, which hampers signal transmission. It usually manifests in infancy and early childhood and is slowly progressive. Those affected with GAN have characteristic curly kinky hair, everted feet and a crouched gait, which suggest the diagnosis in most cases. We describe twin children who presented with difficulty in walking and an abnormal gait since they began walking; clinical clues such as hair changes led us to the final diagnosis. PMID:25216920

  2. [Auditory neuropathy (auditory neuropathy spectrum disorders): the approaches to diagnostics and rehabilitation].

    PubMed

    Tavartkiladze, G A

    2014-01-01

    Auditory neuropathies (auditory neuropathy spectrum disorders, ANSD) may be a consequence of dysfunction of inner hair cells and/or of synapses between these cells and auditory nerve fibers. Another cause of these disorders is supposed to be pathological changes in the auditory nerve itself. The outcome of the rehabilitative treatment of the patients presenting with this disorder depends on the quality of diagnosis and precise location of the pathological process. The present study involved 82 patients with auditory neuropathies. The audiological data obtained in the course of this work were compared with the results of other authors published during the recent years. The objective audiological examination included electrocochleography, registration of auditory brainstem response (ABR) and otoacoustic emission of short-latency and long-latency evoked auditory nerve action potentials. High-amplitude cochlear microphonic and transient evoked otoacoustic emission (TEOAE) potentials were recorded in 82 patients. In 17 (20.7%) patients, otoacoustic emission disappeared in the course of time even though the microphonic potential remained stable. It was shown that the results of electrical acoustic correction in the patients exhibiting long-latency evoked auditory action potentials and positive ABR to electrical stimulation (positive promontory test) were better than in the remaining cases. The outcome of cochlear implantation to a large extent depended on the localization of the pathological process. Specifically, the results of the treatment of the patients with high-amplitude summation potentials, prolonged latency, and positive auditory action potentials in response to electrical stimulation (typical of pre-synaptic localization of the pathological process) were better than in the patients with normal summation potentials, pathological auditory nerve action potentials, TEOAE, and negative ABR to electrical stimulation (indicative of post-synaptic localization of the

  3. Spectrum of peripheral neuropathies associated with surgical interventions; A neurophysiological assessment

    PubMed Central

    2010-01-01

    Background We hypothesized that a wide range of surgical procedures may be complicated by neuropathies, not just in close proximity but also remote from procedural sites. The aim of this study was to classify post-operative neuropathies and the procedures associated with them. Methods We retrospectively identified 66 patients diagnosed with post-procedure neuropathies between January 2005 and June 2008. We reviewed their referral cards and medical records for patient demographics, information on procedures, symptoms, as well as clinical and neurophysiological findings. Results Thirty patients (45.4%) had neuropathies remote from procedural sites and 36 patients (54.5%) had neuropathies in close proximity to procedural sites. Half of the remote neuropathies (15/30) developed following relatively short procedures. In 27% of cases (8/30) remote neuropathies were bilateral. Seven patients developed neuropathies remote from operative sites following hip arthroplasties (7/30: 23.3%), making hip arthroplasty the most common procedure associated with remote neuropathies. Sciatic neuropathies due to hip arthroplasty (12/36, 33.3%) accounted for the majority of neuropathies occurring in close proximity to operative sites. Five medial cutaneous nerve of forearm neuropathies occurred following arterio-venous fistula (AVF) formation. Conclusions An array of surgical procedures may be complicated by neuropathy. Almost half of post-procedure neuropathies occur remote from the site of procedure, emphasizing the need to try to prevent not just local, but also remote neuropathies. Mechanical factors and patient positioning should be considered in the prevention of post-operative neuropathies. There is a possible association between AVF formation and medial cutaneous nerve of forearm neuropathy, which requires further study for validation. PMID:20398427

  4. Painful Diabetic Neuropathy: Prevention or Suppression?

    PubMed

    Todorovic, S M

    2016-01-01

    Pain-sensing sensory neurons (nociceptors) of the dorsal root ganglia (DRG) and dorsal horn (DH) can become sensitized (hyperexcitable) in response to pathological conditions such as diabetes, which in turn may lead to the development of painful peripheral diabetic neuropathy (PDN). Because of incomplete knowledge about the mechanisms underlying painful PDN, current treatment for painful PDN has been limited to somewhat nonspecific systemic drugs that have significant side effects or potential for abuse. Recent studies have established that several ion channels in DRG and DH neurons are dysregulated and make a previously unrecognized contribution to sensitization of pain responses by enhancing excitability of nociceptors in animal models of type 1 and type 2 PDN. Furthermore, it has been reported that targeting posttranslational modification of nociceptive ion channels such as glycosylation and methylglyoxal metabolism can completely reverse mechanical and thermal hyperalgesia in diabetic animals with PDN in vivo. Understanding details of posttranslational regulation of nociceptive channel activity may facilitate development of novel therapies for treatment of painful PDN. We argue that pharmacological targeting of the specific pathogenic mechanism rather than of the channel per se may cause fewer side effects and reduce the potential for drug abuse in patients with diabetes. PMID:27133151

  5. Auditory neuropathy--neural and synaptic mechanisms.

    PubMed

    Moser, Tobias; Starr, Arnold

    2016-03-01

    Sensorineural hearing impairment is the most common form of hearing loss, and encompasses pathologies of the cochlea and the auditory nerve. Hearing impairment caused by abnormal neural encoding of sound stimuli despite preservation of sensory transduction and amplification by outer hair cells is known as 'auditory neuropathy'. This term was originally coined for a specific type of hearing impairment affecting speech comprehension beyond changes in audibility: patients with this condition report that they "can hear but cannot understand". This type of hearing impairment can be caused by damage to the sensory inner hair cells (IHCs), IHC ribbon synapses or spiral ganglion neurons. Human genetic and physiological studies, as well as research on animal models, have recently shown that disrupted IHC ribbon synapse function--resulting from genetic alterations that affect presynaptic glutamate loading of synaptic vesicles, Ca(2+) influx, or synaptic vesicle exocytosis--leads to hearing impairment termed 'auditory synaptopathy'. Moreover, animal studies have demonstrated that sound overexposure causes excitotoxic loss of IHC ribbon synapses. This mechanism probably contributes to hearing disorders caused by noise exposure or age-related hearing loss. This Review provides an update on recently elucidated sensory, synaptic and neural mechanisms of hearing impairment, their corresponding clinical findings, and discusses current rehabilitation strategies as well as future therapies. PMID:26891769

  6. Phenotypic variability of TRPV4 related neuropathies.

    PubMed

    Evangelista, Teresinha; Bansagi, Boglarka; Pyle, Angela; Griffin, Helen; Douroudis, Konstantinos; Polvikoski, Tuomo; Antoniadi, Thalia; Bushby, Kate; Straub, Volker; Chinnery, Patrick F; Lochmüller, Hanns; Horvath, Rita

    2015-06-01

    Mutations in the transient receptor potential vanilloid 4 (TRPV4) gene have been associated with autosomal dominant skeletal dysplasias and peripheral nervous system syndromes (PNSS). PNSS include Charcot-Marie-Tooth disease (CMT) type 2C, congenital spinal muscular atrophy and arthrogryposis and scapuloperoneal spinal muscular atrophy. We report the clinical, electrophysiological and muscle biopsy findings in two unrelated patients with two novel heterozygous missense mutations in the TRPV4 gene. Whole exome sequencing was carried out on genomic DNA using Illumina Truseq(TM) 62Mb exome capture. Patient 1 harbours a de novo c.805C > T (p.Arg269Cys) mutation. Clinically, this patient shows signs of both scapuloperoneal spinal muscular atrophy and skeletal dysplasia. Patient 2 harbours a novel c.184G > A (p.Asp62Asn) mutation. While the clinical phenotype is compatible with CMT type 2C with the patient's muscle harbours basophilic inclusions. Mutations in the TRPV4 gene have a broad phenotypic variability and disease severity and may share a similar pathogenic mechanism with Heat Shock Protein related neuropathies. PMID:25900305

  7. Diabetic neuropathy: mechanisms, emerging treatments, and subtypes.

    PubMed

    Albers, James W; Pop-Busui, Rodica

    2014-08-01

    Diabetic neuropathies (DNs) differ in clinical course, distribution, fiber involvement (type and size), and pathophysiology, the most typical type being a length-dependent distal symmetric polyneuropathy (DSP) with differing degrees of autonomic involvement. The pathogenesis of diabetic DSP is multifactorial, including increased mitochondrial production of free radicals due to hyperglycemia-induced oxidative stress. Mechanisms that impact neuronal activity, mitochondrial function, membrane permeability, and endothelial function include formation of advanced glycosylation end products, activation of polyol aldose reductase signaling, activation of poly(ADP ribose) polymerase, and altered function of the Na(+)/K(+)-ATPase pump. Hyperglycemia-induced endoplasmic reticulum stress triggers several neuronal apoptotic processes. Additional mechanisms include impaired nerve perfusion, dyslipidemia, altered redox status, low-grade inflammation, and perturbation of calcium balance. Successful therapies require an integrated approach targeting these mechanisms. Intensive glycemic control is essential but is insufficient to prevent onset or progression of DSP, and disease-modifying treatments for DSP have been disappointing. Atypical forms of DN include subacute-onset sensory (symmetric) or motor (asymmetric) predominant conditions that are frequently painful but generally self-limited. DNs are a major cause of disability, associated with reduced quality of life and increased mortality. PMID:24954624

  8. Diabetic neuropathy and plasma glucose control.

    PubMed

    Porte, D; Graf, R J; Halter, J B; Pfeifer, M A; Halar, E

    1981-01-01

    Diabetic neuropathy is defined, and theories of its pathogenesis are reviewed. Recent studies designed to investigate the influence of plasma glucose on nerve function in noninsulin-dependent diabetic patients are summarized. Motor nerve conduction velocities in the median and peroneal nerves were measured using a double-stimulus technique, and sensory conduction velocity was measured by conventional methods before and after therapy with oral agents or insulin. The degree of hyperglycemia was assessed by measurement of fasting plasma glucose and glycosylated hemoglobin concentrations. The degree of slowing in motor nerve conduction velocity in untreated patients was found to correlate with the fasting plasma glucose and glycosylated hemoglobin concentrations, but sensory nerve function, although abnormal, did not show such correlation. Reduction of hyperglycemia was associated with improvement in motor nerve conduction velocity in the peroneal and median motor nerves of these patients, but sensory nerve conduction velocity showed no such improvement. Improvement in median motor nerve conduction velocity was directly related to the degree of reduction in fasting plasma glucose concentration. These findings suggest that metabolic factors related to hyperglycemia are important in the impaired motor nerve function seen in noninsulin-dependent patients with maturity-onset diabetes. PMID:7457487

  9. Diabetic Neuropathy and Oxidative Stress: Therapeutic Perspectives

    PubMed Central

    Hosseini, Asieh; Abdollahi, Mohammad

    2013-01-01

    Diabetic neuropathy (DN) is a widespread disabling disorder comprising peripheral nerves' damage. DN develops on a background of hyperglycemia and an entangled metabolic imbalance, mainly oxidative stress. The majority of related pathways like polyol, advanced glycation end products, poly-ADP-ribose polymerase, hexosamine, and protein kinase c all originated from initial oxidative stress. To date, no absolute cure for DN has been defined; although some drugs are conventionally used, much more can be found if all pathophysiological links with oxidative stress would be taken into account. In this paper, although current therapies for DN have been reviewed, we have mainly focused on the links between DN and oxidative stress and therapies on the horizon, such as inhibitors of protein kinase C, aldose reductase, and advanced glycation. With reference to oxidative stress and the related pathways, the following new drugs are under study such as taurine, acetyl-L-carnitine, alpha lipoic acid, protein kinase C inhibitor (ruboxistaurin), aldose reductase inhibitors (fidarestat, epalrestat, ranirestat), advanced glycation end product inhibitors (benfotiamine, aspirin, aminoguanidine), the hexosamine pathway inhibitor (benfotiamine), inhibitor of poly ADP-ribose polymerase (nicotinamide), and angiotensin-converting enzyme inhibitor (trandolapril). The development of modern drugs to treat DN is a real challenge and needs intensive long-term comparative trials. PMID:23738033

  10. Phenotypic variability of TRPV4 related neuropathies

    PubMed Central

    Evangelista, Teresinha; Bansagi, Boglarka; Pyle, Angela; Griffin, Helen; Douroudis, Konstantinos; Polvikoski, Tuomo; Antoniadi, Thalia; Bushby, Kate; Straub, Volker; Chinnery, Patrick F.; Lochmüller, Hanns; Horvath, Rita

    2015-01-01

    Mutations in the transient receptor potential vanilloid 4 (TRPV4) gene have been associated with autosomal dominant skeletal dysplasias and peripheral nervous system syndromes (PNSS). PNSS include Charcot–Marie–Tooth disease (CMT) type 2C, congenital spinal muscular atrophy and arthrogryposis and scapuloperoneal spinal muscular atrophy. We report the clinical, electrophysiological and muscle biopsy findings in two unrelated patients with two novel heterozygous missense mutations in the TRPV4 gene. Whole exome sequencing was carried out on genomic DNA using Illumina TruseqTM 62Mb exome capture. Patient 1 harbours a de novo c.805C > T (p.Arg269Cys) mutation. Clinically, this patient shows signs of both scapuloperoneal spinal muscular atrophy and skeletal dysplasia. Patient 2 harbours a novel c.184G > A (p.Asp62Asn) mutation. While the clinical phenotype is compatible with CMT type 2C with the patient's muscle harbours basophilic inclusions. Mutations in the TRPV4 gene have a broad phenotypic variability and disease severity and may share a similar pathogenic mechanism with Heat Shock Protein related neuropathies. PMID:25900305

  11. Prevalence of peripheral neuropathy and painful peripheral neuropathy in Turkish diabetic patients.

    PubMed

    Erbas, Tomris; Ertas, Mustafa; Yucel, Aysen; Keskinaslan, Abdulkadir; Senocak, Mustafa

    2011-02-01

    The aim of this study was to determine the prevalence of diabetic peripheral neuropathy (DPN) and neuropathic pain in diabetic patients attending university outpatient clinics in Turkey. In this multicenter cross-sectional study, neurologic examinations and nerve conduction studies along with clinical diabetic neuropathy score, and Leeds Assessment of Neuropathic Symptoms and Signs pain scale were performed on 1,113 patients (46.2% male) from 14 centers. Prevalence of DPN determined only by clinical examination was 40.4% and increased to 62.2%, by combining nerve conduction studies with clinical examination. According to Leeds Assessment of Neuropathic Symptoms and Signs scores, neuropathic pain prevalence was 16.0% in those who reported pain. Poor glycemic control, retinopathy, microalbuminuria, hyperlipidemia, diabetic foot, and foot amputation were more commonly observed in patients with DPN. Clinical DPN affected 40.4% of diabetic patients, and neuropathic pain prevalence in diabetic patient population was 14.0%. Clinical examinations and nerve conduction studies are important components for early detection and accurate diagnosis of DPN and painful DPN. PMID:21221008

  12. Myanmarese Neuropathy: Clinical Description of Acute Peripheral Neuropathy Detected among Myanmarese Refugees in Malaysia.

    PubMed

    Fu Liong, Hiew; Santhi, Datuk Puvanarajah; Shanthi, Viswanathan; Mohd Hanip, Rafia

    2014-01-01

    Background. Since 2008, we have observed an increasing number of Myanmarese refugees in Malaysia being admitted for acute/subacute onset peripheral neuropathy. Most of them had a preceding history of starvation. Methods. We retrospectively studied the clinical features of all Myanmarese patients admitted with peripheral neuropathy from September 2008 to January 2014. Results. A total of 24 patients from the Chin, Rohingya, and Rakhine ethnicities (mean age, 23.8 years; male, 96%) had symmetrical, ascending areflexic weakness with at least one additional presenting symptom of fever, lower limb swelling, vomiting, abdominal pain, or difficulty in breathing. Twenty (83.3%) had sensory symptoms. Ten (41.6%) had cranial nerve involvement. Nineteen patients had cerebrospinal fluid examinations but none with evidence of albuminocytological dissociation. Neurophysiological assessment revealed axonal polyneuropathy, predominantly a motor-sensory subtype. Folate and vitamin B12 deficiencies were detected in 31.5% of them. These findings suggested the presence of a polyneuropathy related to nutrition against a backdrop of other possible environmental factors such as infections, metabolic disorders, or exposure to unknown toxin. Supportive treatment with appropriate vitamins supplementation improved functional outcome in most patients. Conclusion. We report a spectrum of acquired reversible neurological manifestations among Myanmarese refugees likely to be multifactorial with micronutrient deficiencies playing an important role in the pathogenesis. PMID:27350989

  13. Myanmarese Neuropathy: Clinical Description of Acute Peripheral Neuropathy Detected among Myanmarese Refugees in Malaysia

    PubMed Central

    Santhi, Datuk Puvanarajah; Mohd Hanip, Rafia

    2014-01-01

    Background. Since 2008, we have observed an increasing number of Myanmarese refugees in Malaysia being admitted for acute/subacute onset peripheral neuropathy. Most of them had a preceding history of starvation. Methods. We retrospectively studied the clinical features of all Myanmarese patients admitted with peripheral neuropathy from September 2008 to January 2014. Results. A total of 24 patients from the Chin, Rohingya, and Rakhine ethnicities (mean age, 23.8 years; male, 96%) had symmetrical, ascending areflexic weakness with at least one additional presenting symptom of fever, lower limb swelling, vomiting, abdominal pain, or difficulty in breathing. Twenty (83.3%) had sensory symptoms. Ten (41.6%) had cranial nerve involvement. Nineteen patients had cerebrospinal fluid examinations but none with evidence of albuminocytological dissociation. Neurophysiological assessment revealed axonal polyneuropathy, predominantly a motor-sensory subtype. Folate and vitamin B12 deficiencies were detected in 31.5% of them. These findings suggested the presence of a polyneuropathy related to nutrition against a backdrop of other possible environmental factors such as infections, metabolic disorders, or exposure to unknown toxin. Supportive treatment with appropriate vitamins supplementation improved functional outcome in most patients. Conclusion. We report a spectrum of acquired reversible neurological manifestations among Myanmarese refugees likely to be multifactorial with micronutrient deficiencies playing an important role in the pathogenesis. PMID:27350989

  14. NEUROPATHY TARGET ESTERASE INHIBITION BY ORGANOPHOSPHORUS ESTERS IN HUMAN NEUROBLASTOMA CELLS

    EPA Science Inventory

    Certain organophosphorus compounds (OPs) produce a delayed neuropathy (OPIDN) in man and some animal species. apability to cause OPIDN is generally predicted in animal models by early and irreversible inhibition of neuropathy target esterase (NTE, neurotoxic esterase) . In this s...

  15. Painless Ulcers and Fissures of Toes: Hereditary Sensory Neuropathy, Not Leprosy

    PubMed Central

    Rao, Angoori Gnaneshwar

    2016-01-01

    Hereditary sensory neuropathies (HSN) are rare genetically determined neuropathies. They often manifest as painless injuries in children. We present HSN in a 5-year-old boy who presented with recurrent fissuring and ulceration involving both great toes. PMID:26955138

  16. Tumor necrosis factor-alpha antagonists and neuropathy.

    PubMed

    Stübgen, Joerg-Patrick

    2008-03-01

    Tumor necrosis factor (TNF)-alpha plays an important role in many aspects of immune system development, immune-response regulation, and T-cell-mediated tissue injury. The evidence that TNF-alpha, released by autoreactive T cells and macrophages, may contribute to the pathogenesis of immune-mediated demyelinating neuropathies is reviewed. TNF-alpha antagonists (infliximab, etanercept, adalimumab) are indicated for the treatment of advanced inflammatory rheumatic and bowel disease, but these drugs can induce a range of autoimmune diseases that also attack the central and peripheral nervous systems. Case histories and series report on the association between anti-TNF-alpha treatment and various disorders of peripheral nerve such as Guillain-Barré syndrome, Miller Fisher syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy with conduction block, mononeuropathy multiplex, and axonal sensorimotor polyneuropathies. The proposed pathogeneses of TNF-alpha-associated neuropathies include both a T-cell and humoral immune attack against peripheral nerve myelin, vasculitis-induced nerve ischemia, and inhibition of signaling support for axons. Most neuropathies improve over a period of months by withdrawal of the TNF-alpha antagonist, with or without additional immune-modulating treatment. Preliminary observations suggest that TNF-alpha antagonists may be useful as an antigen-nonspecific treatment approach to immune-mediated neuropathies in patients with a poor response to, or intolerance of, standard therapies, but further studies are required. PMID:18041052

  17. Clinical Approach to the Treatment of Painful Diabetic Neuropathy

    PubMed Central

    Hovaguimian, Alexandra; Gibbons, Christopher H.

    2011-01-01

    Painful neuropathy is a common and often progressive complication of diabetes. Patients frequently report symptoms of tingling, burning, lancinating pain, hyperesthesia, and allodynia. The natural history of the disease may vary from intermittent mild symptoms to severe chronic daily pain; the latter is often associated with diminished quality of life. There are a variety of pharmaceutical agents from different medicinal categories available for the symptomatic treatment of painful diabetic neuropathy, however selecting an agent is often challenging given the breadth of choices and lack of consistent guidelines. As a result, many patients remain untreated or undertreated. This article presents a practical clinical approach to the treatment of pain in diabetic neuropathy. Recommendations for first-, second-, and third-line medications are based on specific evidence for the treatment of painful diabetic neuropathy as well as safety, tolerability, drug interactions, and cost. Additional topics of discussion include breakthrough pain, opioid use, and topical therapies. This review does not comprehensively discuss all possible treatments for painful neuropathy, but provides a systematic approach designed to guide clinicians in tailoring therapies to the individual patient. PMID:21709806

  18. Decreased gastric secretory functions in diabetic patients with autonomic neuropathy.

    PubMed

    Nakamura, T; Takebe, K; Imamura, K; Miyazawa, T; Ishii, M; Kudoh, K; Terada, A; Machida, K; Kikuchi, H; Kasai, F

    1994-06-01

    A total of 37 subjects consisted of 10 healthy subjects (Group III), 15 diabetic patients without autonomic neuropathy (Group II), and 12 diabetic patients with autonomic neuropathy including gastroparesis in 6 cases (Group I). All three groups were comparable in age. In order to clarify the gastric function in diabetic patients with autonomic neuropathy, secretion of serum gastrin, gastric secretory function, endoscopic Congo red test of fundic glands, and coefficiency of variance of electrocardiographic beat-to-beat intervals (C.V. R-R) were examined. In Group I, 5 patients had hypergastrinemia, but its elevation was inhibited when an acid solution was injected into the stomach. Gastric secretion and C.V. R-R were markedly lower in Group I, compared with Groups II and III. In Group I, the area of fundic glands (parietal cells) was reduced considerably. The C.V. R-R was significantly correlated with fasting serum gastrin concentration and with maximal acid output. From these results, in diabetic patients with autonomic neuropathy (vagal neuropathy), gastric acid secretion in response to tetragastrin stimulation was lowered with a reduction in area of fundic gland distribution. Hypergastrinemia may reflect a negative feedback mechanism responding to decreased acidity of gastric content in the antrum. PMID:7817384

  19. Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice.

    PubMed

    Trammell, Samuel A J; Weidemann, Benjamin J; Chadda, Ankita; Yorek, Matthew S; Holmes, Amey; Coppey, Lawrence J; Obrosov, Alexander; Kardon, Randy H; Yorek, Mark A; Brenner, Charles

    2016-01-01

    Male C57BL/6J mice raised on high fat diet (HFD) become prediabetic and develop insulin resistance and sensory neuropathy. The same mice given low doses of streptozotocin are a model of type 2 diabetes (T2D), developing hyperglycemia, severe insulin resistance and diabetic peripheral neuropathy involving sensory and motor neurons. Because of suggestions that increased NAD(+) metabolism might address glycemic control and be neuroprotective, we treated prediabetic and T2D mice with nicotinamide riboside (NR) added to HFD. NR improved glucose tolerance, reduced weight gain, liver damage and the development of hepatic steatosis in prediabetic mice while protecting against sensory neuropathy. In T2D mice, NR greatly reduced non-fasting and fasting blood glucose, weight gain and hepatic steatosis while protecting against diabetic neuropathy. The neuroprotective effect of NR could not be explained by glycemic control alone. Corneal confocal microscopy was the most sensitive measure of neurodegeneration. This assay allowed detection of the protective effect of NR on small nerve structures in living mice. Quantitative metabolomics established that hepatic NADP(+) and NADPH levels were significantly degraded in prediabetes and T2D but were largely protected when mice were supplemented with NR. The data justify testing of NR in human models of obesity, T2D and associated neuropathies. PMID:27230286

  20. Animal Models of Peripheral Neuropathy Due to Environmental Toxicants

    PubMed Central

    Rao, Deepa B.; Jortner, Bernard S.; Sills, Robert C.

    2014-01-01

    Despite the progress in our understanding of pathogeneses and the identification of etiologies of peripheral neuropathy, idiopathic neuropathy remains common. Typically, attention to peripheral neuropathies resulting from exposure to environmental agents is limited relative to more commonly diagnosed causes of peripheral neuropathy (diabetes and chemotherapeutic agents). Given that there are more than 80,000 chemicals in commerce registered with the Environmental Protection Agency and that at least 1000 chemicals are known to have neurotoxic potential, very few chemicals have been established to affect the peripheral nervous system (mainly after occupational exposures). A wide spectrum of exposures, including pesticides, metals, solvents, nutritional sources, and pharmaceutical agents, has been related, both historically and recently, to environmental toxicant-induced peripheral neuropathy. A review of the literature shows that the toxicity and pathogeneses of chemicals adversely affecting the peripheral nervous system have been studied using animal models. This article includes an overview of five prototypical environmental agents known to cause peripheral neuropathy—namely, organophosphates, carbon disulfide, pyridoxine (Vitamin B6), acrylamide, and hexacarbons (mainly n-hexane, 2,5-hexanedione, methyl n-butyl ketone). Also included is a brief introduction to the structural components of the peripheral nervous system and pointers on common methodologies for histopathologic evaluation of the peripheral nerves. PMID:24615445

  1. Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice

    PubMed Central

    Trammell, Samuel A.J.; Weidemann, Benjamin J.; Chadda, Ankita; Yorek, Matthew S.; Holmes, Amey; Coppey, Lawrence J.; Obrosov, Alexander; Kardon, Randy H.; Yorek, Mark A.; Brenner, Charles

    2016-01-01

    Male C57BL/6J mice raised on high fat diet (HFD) become prediabetic and develop insulin resistance and sensory neuropathy. The same mice given low doses of streptozotocin are a model of type 2 diabetes (T2D), developing hyperglycemia, severe insulin resistance and diabetic peripheral neuropathy involving sensory and motor neurons. Because of suggestions that increased NAD+ metabolism might address glycemic control and be neuroprotective, we treated prediabetic and T2D mice with nicotinamide riboside (NR) added to HFD. NR improved glucose tolerance, reduced weight gain, liver damage and the development of hepatic steatosis in prediabetic mice while protecting against sensory neuropathy. In T2D mice, NR greatly reduced non-fasting and fasting blood glucose, weight gain and hepatic steatosis while protecting against diabetic neuropathy. The neuroprotective effect of NR could not be explained by glycemic control alone. Corneal confocal microscopy was the most sensitive measure of neurodegeneration. This assay allowed detection of the protective effect of NR on small nerve structures in living mice. Quantitative metabolomics established that hepatic NADP+ and NADPH levels were significantly degraded in prediabetes and T2D but were largely protected when mice were supplemented with NR. The data justify testing of NR in human models of obesity, T2D and associated neuropathies. PMID:27230286

  2. Cisplatin neuropathy. Risk factors, prognosis, and protection by WR-2721

    SciTech Connect

    Mollman, J.E.; Glover, D.J.; Hogan, W.M.; Furman, R.E.

    1988-06-01

    A prospective study of patients receiving cis-diaminedichloroplatin II (DDP) was carried out to determine if risk factors could be identified related to the patient's living habits or past medical history that would predict in which patients DDP neuropathy might develop. Sixty-nine patients receiving six different combinations of chemotherapeutic agents, including DDP were examined. Twenty-eight of these patients received DDP in combination with the radioprotective agent S-2-(3-aminopropylamino)-ethylphosporothioic acid (WR 2721). No risk factors were identified relating to personal habits or past medical history of the patients. However, patients receiving DDP (40 mg/m2) on 5 consecutive days had a significantly higher incidence of neuropathy. Patients receiving DDP in combination with WR 2721 had a significantly lower incidence of neuropathy, and the mean dose at onset was significantly higher than the mean dose at onset of neuropathy for all other groups. In addition, five of six patients who were available for long-term follow-up demonstrated nearly complete reversal of the signs and symptoms of neuropathy.

  3. Contralateral ulnar neuropathy following total hip replacement and intraoperative positioning.

    PubMed

    O'Brien, S; Bennett, D; Spence, D J; Mawhinney, I; Beverland, D E

    2016-05-01

    Peripheral neuropathy is a rare but important complication of total hip arthroplasty (THA) and has previously been reported in the ipsilateral arm and associated with inflammatory arthritis. The results of 7004 primary hip arthroplasties performed between January 1993 and February 2009 were retrospectively reviewed to identify patients who reported ulnar neuropathy symptoms, with ten patients identified at mean follow-up of 57 months (range = 3-195 months). Eight patients experienced unilateral ulnar nerve symptoms in the contralateral upper limb post-surgery, one patient experienced symptoms in the ipsilateral upper limb and one patient experienced symptoms in both upper limbs. The incidence of post-THA ulnar neuropathy was 0.14%. All patients had a pre-operative diagnosis of osteoarthritis and none had diabetes, a previous history of neuropathy or inflammatory arthritis. All operations were primary arthroplasties and were performed under the care of a single surgeon in a single centre. Two of the ten patients (20%) had a general anaesthetic. The pattern of symptoms reported, i.e. mainly unilateral affecting the contralateral side with variable resolution, contrasts with previous studies and suggests that intraoperative patient positioning may be an important factor influencing ulnar neuropathy following THA. Attention to support and positioning of the contralateral arm may help reduce the incidence of this complication. PMID:26589446

  4. Peripheral neuropathy induced by combination chemotherapy of docetaxel and cisplatin.

    PubMed Central

    Hilkens, P. H.; Pronk, L. C.; Verweij, J.; Vecht, C. J.; van Putten, W. L.; van den Bent, M. J.

    1997-01-01

    Docetaxel, a new semisynthetic taxoid that has demonstrated promising activity as an antineoplastic agent, was administered in combination with cisplatin to 63 patients in a dose-escalating study. As both drugs were known to be potentially neurotoxic, peripheral neurotoxicity was prospectively assessed in detail. Neuropathy was evaluated by clinical sum-score for signs and symptoms and by measurement of the vibration perception threshold (VPT). The severity of neuropathy was graded according to the National Cancer Institute's 'Common Toxicity Criteria'. The docetaxel-cisplatin combination chemotherapy induced a predominantly sensory neuropathy in 29 (53%) out of 55 evaluable patients. At cumulative doses of both cisplatin and docetaxel above 200 mg m(-2), 26 (74%) out of 35 patients developed a neuropathy which was mild in 15, moderate in ten and severe in one patient. Significant correlations were present between both the cumulative dose of docetaxel and cisplatin and the post-treatment sum-score of neuropathy (P < 0.01) as well as the post-treatment VPT (P < 0.01). The neurotoxic effects of this combination were more severe than either cisplatin or docetaxel as single agent at similar doses. PMID:9020489

  5. Facial neuropathy with imaging enhancement of the facial nerve: a case report

    PubMed Central

    Mumtaz, Sehreen; Jensen, Matthew B

    2014-01-01

    A young women developed unilateral facial neuropathy 2 weeks after a motor vehicle collision involving fractures of the skull and mandible. MRI showed contrast enhancement of the facial nerve. We review the literature describing facial neuropathy after trauma and facial nerve enhancement patterns with different causes of facial neuropathy. PMID:25574155

  6. [Acro-osteolysis with hereditary sensory ulcero-mutilating neuropathy. Apropos of an atypical case].

    PubMed

    Carabelli, A; Ruggeri, R; Pessina, R; Cerri, D; Bertani, E

    1989-01-01

    The authors report an acroosteolysis case with sensory radicular ulcero-mutilating neuropathy. The differential diagnosis are discussed and the case is presented as an intermediate form between the congenital sensory neuropathy, type II, according to Otha classification, and the non-progressive, sporadical sensory neuropathy. PMID:2638645

  7. Image analysis software for following progression of peripheral neuropathy

    NASA Astrophysics Data System (ADS)

    Epplin-Zapf, Thomas; Miller, Clayton; Larkin, Sean; Hermesmeyer, Eduardo; Macy, Jenny; Pellegrini, Marco; Luccarelli, Saverio; Staurenghi, Giovanni; Holmes, Timothy

    2009-02-01

    A relationship has been reported by several research groups [1 - 4] between the density and shapes of nerve fibers in the cornea and the existence and severity of peripheral neuropathy. Peripheral neuropathy is a complication of several prevalent diseases or conditions, which include diabetes, HIV, prolonged alcohol overconsumption and aging. A common clinical technique for confirming the condition is intramuscular electromyography (EMG), which is invasive, so a noninvasive technique like the one proposed here carries important potential advantages for the physician and patient. A software program that automatically detects the nerve fibers, counts them and measures their shapes is being developed and tested. Tests were carried out with a database of subjects with levels of severity of diabetic neuropathy as determined by EMG testing. Results from this testing, that include a linear regression analysis are shown.

  8. Epidermal Nerve Fiber Quantification in the Assessment of Diabetic Neuropathy

    PubMed Central

    Beiswenger, Kristina K.; Calcutt, Nigel A.; Mizisin, Andrew P.

    2008-01-01

    Summary Assessment of cutaneous innervation in skin biopsies is emerging as a valuable means of both diagnosing and staging diabetic neuropathy. Immunolabeling, using antibodies to neuronal proteins such as protein gene product 9.5, allows for the visualization and quantification of intraepidermal nerve fibers. Multiple studies have shown reductions in intraepidermal nerve fiber density in skin biopsies from patients with both type 1 and type 2 diabetes. More recent studies have focused on correlating these changes with other measures of diabetic neuropathy. A loss of epidermal innervation similar to that observed in diabetic patients has been observed in rodent models of both type 1 and type 2 diabetes and several therapeutics have been reported to prevent reductions in intraepidermal nerve fiber density in these models. This review discusses the current literature describing diabetes-induced changes in cutaneous innervation in both human and animal models of diabetic neuropathy. PMID:18384843

  9. Clinical and pathological features of an autosomal recessive neuropathy.

    PubMed

    Bouldin, T W; Riley, E; Hall, C D; Swift, M

    1980-06-01

    Two siblings are described, ages 49 and 45 years, having a distinct hereditary motor and sensory neuropathy (HMSN) with severe peroneal nerve involvement. The neuropathic symptoms began in childhood. Both patients have sensorineural deafness. The proband was found to have a cardiac conduction abnormality in the absence of known ischemic heart disease. Electrodiagnostic studies were consistent with a demyelinating peripheral neuropathy. The presence of parental consanguinity and absence of affected individuals in succeeding or preceding generations suggested that the sensorimotor neuropathy in this family is inherited in an autosomal recessive manner. The sural nerve of the proband had significant loss of myelinated fibers and demyelination but few regenerating myelinated fibers and no onion-bulbs. The pathological findings, while nonspecific, are not characteristic of the hypertrophic, neuronal or intermediate types of HMSN. PMID:6247456

  10. Precise correlation between structural and electrophysiological disturbances in MADSAM neuropathy.

    PubMed

    Simon, Neil G; Kiernan, Matthew C

    2015-11-01

    Multifocal acquired demyelinating sensory and motor neuropathy is characterised by multifocal clinical deficits. Imaging studies have identified multifocal enlargements of nerve trunks, but a precise correlation between structural abnormalities and electrophysiological dysfunction has not been elucidated. Two patients diagnosed with multifocal acquired demyelinating sensory and motor neuropathy were evaluated with nerve conduction studies, including short segment nerve conduction studies to precisely localise motor conduction block, and ultrasound studies of corresponding nerve trunks. Motor conduction block was identified in each patient (upper limb nerves in two patients), superimposed on additional demyelinating neurophysiological features. Upper limb ultrasound studies demonstrated focal nerve enlargement that precisely correlated with neurophysiological conduction block. The results of this study suggest that factors contributing to focal structural abnormalities in multifocal acquired demyelinating sensory and motor neuropathy are also those that produce conduction block. PMID:26314279

  11. Auditory Neuropathy/Dys-synchrony and Its Perceptual Consequences

    PubMed Central

    Rance, Gary

    2005-01-01

    Auditory neuropathy/dys-synchrony is a form of hearing impairment in which cochlear outer hair cell function is spared but neural transmission in the auditory pathway is disordered. This condition, or group of conditions with a common physiologic profile, accounts for approximately 7% of permanent childhood hearing loss and a significant (but as yet undetermined) proportion of adult impairment. This paper presents an overview of the mechanisms underlying auditory neuropathy/dys-synchrony-type hearing loss and the clinical profile for affected patients. In particular it examines the perceptual consequences of auditory neuropathy/dys-synchrony, which are quite different from those associated with sensorineural hearing loss, and considers currently available, and future management options. PMID:15920648

  12. [Electron microscopy as a tool for the diagnosis of neuropathies].

    PubMed

    Vallat, Jean-Michel; Richard, Laurence; Sindou, Philippe; Magy, Laurent

    2008-12-01

    Ultrastructural examination of a peripheral nerve biopsy may be particularly useful and sometimes indispensable for identification of the type of nerve lesion and of the aetiologies of peripheral neuropathies. The ultrastructural findings have, anyway, to be correlated with the clinical findings, the electrophysiological examination and the laboratory investigations. In this presentation, the various causes of peripheral neuropathies for which nerve biopsy study by electron microscope can provide diagnostic information are discussed. The principal aetiologies that will benefit from such an ultrastructural study are toxic, infectious, haemopathic and storage disorders. Chiefly for Charcot-Marie-Tooth sporadic cases, there are still indications for nerve biopsy to orientate diagnostic research in molecular biology. Sometimes, the electron microscopic examination will help to determine not only the cause of the peripheral neuropathy, but also the mechanism of nerve lesions which may induce specific and efficient treatments. PMID:19084717

  13. Retinal Failure in Diabetes: a Feature of Retinal Sensory Neuropathy.

    PubMed

    Gray, Ellyn J; Gardner, Thomas W

    2015-12-01

    Physiologic adaptations mediate normal responses to short-term and long-term stresses to ensure organ function. Organ failure results if adaptive responses fail to resolve persistent stresses or maladaptive reactions develop. The retinal neurovascular unit likewise undergoes adaptive responses to diabetes resulting in a retinal sensory neuropathy analogous to other sensory neuropathies. Vision-threatening diabetic retinal neuropathy results from unremitting metabolic and inflammatory stresses, leading to macular edema and proliferative diabetic retinopathy, states of "retinal failure." Current regulatory strategies focus primarily on the retinal failure stages, but new diagnostic modalities and understanding of the pathophysiology of diabetic retinopathy may facilitate earlier treatment to maintain vision in persons with diabetes. PMID:26458378

  14. Is there a relationship between oral health and diabetic neuropathy?

    PubMed

    Borgnakke, Wenche S; Anderson, Patricia F; Shannon, Carol; Jivanescu, Anca

    2015-11-01

    Diabetic neuropathy is the most common microvascular complication of diabetes mellitus with high morbidity and mortality, and low quality of life. It has a broad spectrum of clinical forms, although distal symmetrical polyneuropathy is the most prevalent. Several oral complications including burning mouth syndrome, dry mouth, and impairment of the senses taste and smell are less-known manifestations of diabetic neuropathy and often overlooked. Periodontitis, tooth loss, and temporomandibular joint dysfunction may be also present in these patients and are equally debilitating. Periodontitis was declared the sixth complication of diabetes in 1993 and may contribute to poor glucose control. Hence, periodontitis and diabetes mutually and adversely affect each other. This review summarizes the available body of scientific literature that discusses oral manifestations in patients with diabetic neuropathy and identifies important areas where more research is needed. PMID:26374570

  15. Role of A3 adenosine receptor in diabetic neuropathy.

    PubMed

    Yan, Heng; Zhang, Enshui; Feng, Chang; Zhao, Xin

    2016-10-01

    Neuropathy is the most common diabetic complication. Although the A1 and A2A adenosine receptors are important pharmacological targets in alleviating diabetic neuropathy, the role of the A3 adenosine receptor remains unknown. Because the A3 adenosine receptor regulates pain induced by chronic constriction injury or chemotherapy, its stimulation might also attenuate diabetic neuropathy. This study examines the effects of systemic treatment with the A3 adenosine receptor agonist 1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-N-methyl-β-d-ribofuranuronamide (IB-MECA) on diabetic neuropathy and explores the putative mechanisms underlying its pharmacological effects. We show that IB-MECA alleviated mechanical hyperalgesia and thermal hypoalgesia in mice 2 weeks but not 4 weeks after streptozocin (STZ) treatment. Furthermore, IB-MECA prevented the reduction in sciatic motor nerve conduction velocity and sensory nerve conduction velocity in diabetic mice 2 weeks but not 4 weeks after STZ treatment. Similarly, IB-MECA inhibited the activation of nuclear factor-κB and decreased the generation of tumor necrosis factor-α in the spinal cord of mice 2 weeks but not 4 weeks after STZ treatment. These phenomena were associated with reduction of A3 adenosine receptor expression in the spinal cord after long-term diabetes. Our results suggest that the A3 adenosine receptor plays a critical role in regulating diabetic neuropathy and that reduction in A3 adenosine receptor expression/function might contribute to the progression of diabetic neuropathy. © 2016 Wiley Periodicals, Inc. PMID:27319979

  16. Towards a Diagnosis of Cochlear Neuropathy with Envelope Following Responses.

    PubMed

    Shaheen, Luke A; Valero, Michelle D; Liberman, M Charles

    2015-12-01

    Listeners with normal audiometric thresholds can still have suprathreshold deficits, for example, in the ability to discriminate sounds in complex acoustic scenes. One likely source of these deficits is cochlear neuropathy, a loss of auditory nerve (AN) fibers without hair cell damage, which can occur due to both aging and moderate acoustic overexposure. Since neuropathy can affect up to 50 % of AN fibers, its impact on suprathreshold hearing is likely profound, but progress is hindered by lack of a robust non-invasive test of neuropathy in humans. Reduction of suprathreshold auditory brainstem responses (ABRs) can be used to quantify neuropathy in inbred mice. However, ABR amplitudes are highly variable in humans, and thus more challenging to use. Since noise-induced neuropathy is selective for AN fibers with high thresholds, and because phase locking to temporal envelopes is particularly strong in these fibers, the envelope following response (EFR) might be a more robust measure. We compared EFRs to sinusoidally amplitude-modulated tones and ABRs to tone-pips in mice following a neuropathic noise exposure. EFR amplitude, EFR phase-locking value, and ABR amplitude were all reduced in noise-exposed mice. However, the changes in EFRs were more robust: the variance was smaller, thus inter-group differences were clearer. Optimum detection of neuropathy was achieved with high modulation frequencies and moderate levels. Analysis of group delays was used to confirm that the AN population was dominating the responses at these high modulation frequencies. Application of these principles in clinical testing can improve the differential diagnosis of sensorineural hearing loss. PMID:26323349

  17. Painful neuropathies: the emerging role of sodium channelopathies.

    PubMed

    Brouwer, Brigitte A; Merkies, Ingemar S J; Gerrits, Monique M; Waxman, Stephen G; Hoeijmakers, Janneke G J; Faber, Catharina G

    2014-06-01

    Pain is a frequent debilitating feature reported in peripheral neuropathies with involvement of small nerve (Aδ and C) fibers. Voltage-gated sodium channels are responsible for the generation and conduction of action potentials in the peripheral nociceptive neuronal pathway where NaV 1.7, NaV 1.8, and NaV 1.9 sodium channels (encoded by SCN9A, SCN10A, and SCN11A) are preferentially expressed. The human genetic pain conditions inherited erythromelalgia and paroxysmal extreme pain disorder were the first to be linked to gain-of-function SCN9A mutations. Recent studies have expanded this spectrum with gain-of-function SCN9A mutations in patients with small fiber neuropathy and in a new syndrome of pain, dysautonomia, and small hands and small feet (acromesomelia). In addition, painful neuropathies have been recently linked to SCN10A mutations. Patch-clamp studies have shown that the effect of SCN9A mutations is dependent upon the cell-type background. The functional effects of a mutation in dorsal root ganglion (DRG) neurons and sympathetic neuron cells may differ per mutation, reflecting the pattern of expression of autonomic symptoms in patients with painful neuropathies who carry the mutation in question. Peripheral neuropathies may not always be length-dependent, as demonstrated in patients with initial facial and scalp pain symptoms with SCN9A mutations showing hyperexcitability in both trigeminal ganglion and DRG neurons. There is some evidence suggesting that gain-of-function SCN9A mutations can lead to degeneration of peripheral axons. This review will focus on the emerging role of sodium channelopathies in painful peripheral neuropathies, which could serve as a basis for novel therapeutic strategies. PMID:25250524

  18. Multiple Crush Concept Applied to Multiple Nerves in Leprous Neuropathy.

    PubMed

    Dellon, A Lee

    2016-04-01

    There is a large reservoir of leprosy patients, no longer contagious, due to multidrug therapy, who are considered cured and are becoming increasingly disabled due to progressive chronic nerve entrapment in the upper and lower extremities. After a review of the history of understanding leprous neuropathy, an approach is outlined based on the approach taken to relieve pain and restore sensation that prevents ulcers and amputations in diabetics with neuropathy and superimposed nerve compressions. The results of the first application of this approach in an indigenous area for leprosy, Guayaquil, Ecuador, is discussed with implications for international care of this neglected patient population. PMID:27013412

  19. [Diagnosis and therapy of auditory synaptopathy/neuropathy].

    PubMed

    Moser, T; Strenzke, N; Meyer, A; Lesinski-Schiedat, A; Lenarz, T; Beutner, D; Foerst, A; Lang-Roth, R; von Wedel, H; Walger, M; Gross, M; Keilmann, A; Limberger, A; Steffens, T; Strutz, J

    2006-11-01

    Pathological auditory brainstem responses (lack of responses, elevated thresholds and perturbed waveforms) in combination with present otoacoustic emissions are typical audiometric findings in patients with a hearing impairment that particularly affects speech comprehension or complete deafness. This heterogenous group of disorders first described as "auditory neuropathy" includes dysfunction of peripheral synaptic coding of sound by inner hair cells (synaptopathy) and/or of the generation and propagation of action potentials in the auditory nerve (neuropathy). This joint statement provides prevailing background information as well as recommendations on diagnosis and treatment. The statement focuses on the handling in the german language area but also refers to current international statements. PMID:17041780

  20. The variable clinical manifestations of ulnar neuropathies at the elbow.

    PubMed Central

    Stewart, J D

    1987-01-01

    In twenty-five cases of ulnar neuropathy at the elbow, the involvement of the fibres from three sensory and to four motor branches were examined clinically and, where possible, electrophysiologically. Of the sensory fibres, those from the terminal digital nerves were most commonly involved. The fibres to the hand muscles were much more frequently involved than those to the forearm muscles. These findings suggest that in ulnar neuropathies at the elbow there is variable damage to the fascicles within the nerve. PMID:3031220

  1. Progress in inflammatory neuropathy -the legacy of Dr Jack Griffin.

    PubMed

    Feldman, Eva L; Hughes, Richard A C; Willison, Hugh J

    2015-11-01

    The past quarter of a century has brought incredible advances in our understanding of inflammatory neuropathies, and the insights into Guillain-Barré syndrome (GBS) began in the 1990s with the seminal work of Dr Jack Griffin and his colleagues. In this essay, we provide a tribute to Jack, and review the recent progress in a field that he termed his personal favourite. In particular, we discuss the new developments in our understanding and diagnosis of inflammatory neuropathies, the recent emergence of the node of Ranvier and the paranode as sites of intensive investigation, and the mechanistic evidence that is providing a platform for therapeutic development studies. PMID:26458287

  2. The ACOSTA accompanying measure A2106.

    PubMed

    Thayer, C; De Moor, G; Van Goor, J

    1994-10-01

    At a time when the informatics and telecommunications industries are looking for new markets to exploit in relation, for example, to the emerging ISDN and broadband communications networks, there is a need to create a broad consensus in Europe by bringing together systematically the relevant industries including telecom service providers, health care providers, insurance organisations, standardisation experts and policy makers. The aim of the ACOSTA (Consensus Formation and Standardisation Promotion) Accompanying Measure is the creation of more general awareness of the relevant environment among all the parties, better specification of common requirements and options taking better account of the real needs of the users, and enlargement of the common market in health care telematics. PMID:7889758

  3. Sacral Perineural Cyst Accompanying Disc Herniation

    PubMed Central

    Ju, Chang Il; Shin, Ho; Kim, Hyeun Sung

    2009-01-01

    Although most of sacral perineural cysts are asymptomatic, some may produce symptoms. Specific radicular pain may be due to distortion, compression, or stretching of nerve root by a space occupying cyst. We report a rare case of S1 radiculopathy caused by sacral perineural cyst accompanying disc herniation. The patient underwent a microscopic discectomy at L5-S1 level. However, the patient's symptoms did not improved. The hypesthesia persisted, as did the right leg pain. Cyst-subarachnoid shunt was set to decompress nerve root and to equalize the cerebrospinal fluid pressure between the cephalad thecal sac and cyst. Immediately after surgery, the patient had no leg pain. After 6 months, the patient still remained free of leg pain. PMID:19352483

  4. Sacral perineural cyst accompanying disc herniation.

    PubMed

    Ju, Chang Il; Shin, Ho; Kim, Seok Won; Kim, Hyeun Sung

    2009-03-01

    Although most of sacral perineural cysts are asymptomatic, some may produce symptoms. Specific radicular pain may be due to distortion, compression, or stretching of nerve root by a space occupying cyst. We report a rare case of S1 radiculopathy caused by sacral perineural cyst accompanying disc herniation. The patient underwent a microscopic discectomy at L5-S1 level. However, the patient's symptoms did not improved. The hypesthesia persisted, as did the right leg pain. Cyst-subarachnoid shunt was set to decompress nerve root and to equalize the cerebrospinal fluid pressure between the cephalad thecal sac and cyst. Immediately after surgery, the patient had no leg pain. After 6 months, the patient still remained free of leg pain. PMID:19352483

  5. The Mechanism of Atomization Accompanying Solid Injection

    NASA Technical Reports Server (NTRS)

    Castleman, R A , Jr

    1933-01-01

    A brief historical and descriptive account of solid injection is followed by a detailed review of the available theoretical and experimental data that seem to throw light on the mechanism of this form of atomization. It is concluded that this evidence indicates that (1) the atomization accompanying solid injection occurs at the surface of the liquid after it issues as a solid stream from the orifice; and (2) that such atomization has a mechanism physically identical with the atomization which takes place in an air stream, both being due merely to the formation, at the gas-liquid interface, of fine ligaments under the influence of the relative motion of gas and liquid, and to their collapse, under the influence of surface tension, to form the drops in the spray.

  6. [How to accompany a suicidal patient].

    PubMed

    Dorfman Lerner, B

    1986-06-01

    In this paper the author offers the prospective T.C. an orientation for the treatment of patients who have intended suicide. After examining general questions such as who and when people commit suicide, she presents an "Assessment of self-destructive potentiality" by Tabachnik & Farberow as a guide to the best prevention of the suicidal act. The metapsychological view of Freud as regards the repressed homicidal motivation in suicide is complemented by the views of Garma and Abadi. In respect to the process of accompaniment in these cases, the author suggests the appearance of four phases (simultaneous or in succession) that are: 1. the presence and the regard in which what is important for the patient is that the T.C. is there and affectionately regards him; 2. the listening, in which the T.C. provides facilities for the patient to speak; 3. the key word, in which "I comprehend" is the privileged T.C. expression; and 4. the dialogue. Within phase 3. discrimination can be made between different psycholinguistic aspects of the key expression, such as: a) its constituting aspects; b) its catarctic or economic aspect; c) its meaning a recognition of the patient's identity; and d) the emergence of hope. Also, as suicide is the end point of different psychopathologies, a brief indication of possible T.C. responses is given. In all these, the principal aim is to help the patient to elaborate a new life project. A clinical successful example shows how three T.C. were included in the treatment of a suicidal patient to accompany her in the recognition and tolerance of her own and others' aggressive feelings. Some philosophical considerations are added. PMID:3788628

  7. Cystic lesions accompanying extra-axial tumours.

    PubMed

    Lohle, P N; Wurzer, H A; Seelen, P J; Kingma, L M; Go, K G

    1999-01-01

    We examined the mechanism of cyst formation in extra-axial tumours in the central nervous system (CNS). Cyst fluid, cerebrospinal fluid (CSF) and blood plasma were analysed in eight patients with nine peritumoral cysts: four with meningiomas, two with intracranial and two spinal intradural schwannomas. Measuring concentrations of various proteins [albumin, immunoglobulin G (IgG), IgA, alpha 2-macroglobulin and IgM] in cyst fluid, CSF and blood plasma provides insight into the state of the semipermeability of the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier. Peritumoral cysts accompanying intra-axial brain tumours are the end result of disruption of the BBB and oedema formation. Unlike intra-axial tumours which lie embedded within nervous tissue, extra-axial tumours tend to be separated from nervous tissue by arachnoid and pia mater. High concentrations of proteins were measured in the cyst fluid, approaching blood plasma levels, suggesting a local barrier disruption, and passage across the arachnoid, pia mater and cortical/medullary layer into the CNS parenchyma, leaving the protein concentrations of CSF practically unchanged. We confirmed that very high concentrations of protein are to be found in tumour cysts, plasma proteins forming almost 90% of the total protein in the cyst. We review current hypotheses on the pathogenesis of cysts accompanying neoplasms, particularly meningiomas and schwannomas, and conclude that the majority of proteins in cyst fluid in extra-axial, intradural meningiomas and schwannomas are plasma proteins. This provides a strong argument for pathogenesis of extra-axial intradural tumour cysts in favour of leakage of plasma proteins out of the tumour vessels into the nervous tissue. PMID:9987761

  8. Treatment of patients with multifocal motor neuropathy with immunoglobulins in clinical practice: the SIGNS registry

    PubMed Central

    Stangel, Martin; Gold, Ralf; Pittrow, David; Baumann, Ulrich; Borte, Michael; Fasshauer, Maria; Hensel, Manfred; Huscher, Dörte; Reiser, Marcel; Sommer, Claudia

    2016-01-01

    Objectives: The management of patients with multifocal motor neuropathy (MMN) under everyday clinical conditions has been insufficiently studied. We therefore collected comprehensive observational data on patients with MMN who received intravenous (IV) or subcutaneous (SC) immunoglobulins (IGs) as maintenance therapy. Methods: This was a prospective, noninterventional study (registry) in neurological centres (hospitals and offices) throughout Germany. Results: As of 1 December 2015, 80 patients with MMN were included (mean age 55.4 ± 9.8 years, 67% males, mean disease duration 10.7 ± 10.2 years). The affected limb regions were predominantly distal muscle groups of the upper extremities. On the inflammatory neuropathy cause and treatment (INCAT) scale, 94% of the patients had some disability in the arms and 61% in the legs. At inclusion, 98.8% received IVIG and 1.3% SCIG. Substantial variation was observed between IVIG treatment intervals (every 0.7 to 17.3 weeks) and dosage (0.2–2.1 g/kg body weight received during a single administration; mean monthly dosage, 0.9 g/kg body weight). However, the mean monthly dosage was steady over time. At 1-year follow up, improvement was seen in muscle strength, INCAT and quality of life (QoL) scores (SF-36 questionnaire). Conclusions: The management of patients with MMN in everyday clinical practice demonstrates a wide range of absolute dosages and treatment intervals of IG, supporting the recommended practice of determining treatment dose on an individual patient basis. The improvements in muscle strength and reduction in disability, accompanied by increased QoL, strengthen the case for use of IG as a maintenance treatment for MMN. PMID:27134672

  9. Hereditary neuropathy with liability to pressure palsies: case report and discussion.

    PubMed

    Grossman, Marc J; Feinberg, Joseph; DiCarlo, Edward F; Birchansky, Sherri B; Wolfe, Scott W

    2007-09-01

    Hereditary neuropathy with liability to pressure palsies (HNPP) is an uncommon diagnosis that should be considered in patients with multiple compressive neuropathies. We present the case of a woman who presented with bilateral hand numbness and weakness. Electrodiagnostic testing revealed bilateral carpal tunnel syndrome, bilateral ulnar neuropathy at the elbow, left peroneal neuropathy at the fibular head, and a primarily demyelinating generalized sensorimotor neuropathy. Subsequent genetic testing identified a deletion at chromosome 17p11.2 to confirm the diagnosis of HNPP. Treatment of this largely self-limiting disease is controversial, and this patient suffered minimal disability with treatment including splinting and surgical releases. PMID:18751796

  10. Generalized peripheral neuropathy in a dental technician exposed to methyl methacrylate monomer

    SciTech Connect

    Donaghy, M.; Rushworth, G.; Jacobs, J.M. )

    1991-07-01

    A 58-year-old dental prosthetic technician developed generalized sensorimotor peripheral neuropathy. Neurophysiologic studies showed a generalized sensorimotor neuropathy of axonal degeneration type. Examination of a sural nerve biopsy showed a moderately severe axonal neuropathy with loss of large myelinated fibers and unmyelinated axons. There was evidence of slow ongoing degeneration and considerable fiber regeneration. Electron microscopy showed increased numbers of filaments in a few fibers. These findings show resemblances to the nerve changes caused by another acrylic resin, acrylamide. They suggest that the neuropathy may have been caused by 30 years of occupational cutaneous and inhalational exposure to methyl methacrylate monomer since they excluded other recognized causes of neuropathy.

  11. Progression in idiopathic, diabetic, paraproteinemic, alcoholic, and B12 deficiency neuropathy.

    PubMed

    Sachedina, Shafina; Toth, Cory

    2013-09-01

    We determined prospectively the clinical and electrophysiological progression of idiopathic, diabetic, paraproteinemic, alcoholic, and B12 deficiency neuropathy in 606 subjects over 3 years. We hypothesized that idiopathic peripheral neuropathy would demonstrate slower progression when compared with other etiologies. Laboratory assessments were used to determine the etiology of peripheral neuropathy at baseline and after 3 years. When compared with peripheral neuropathy related to type 1 or type 2 diabetes mellitus, subjects with idiopathic peripheral neuropathy progressed much slower, but demonstrated similar rates of progression to that of the other groups. Overall, detectable progression was minimal over 3 years. After 3 years, only 3% of cases of idiopathic peripheral neuropathy had any potentially identifiable causes discovered. Clinical and electrophysiological detection of very slow progression for these five types of peripheral neuropathy is possible using currently established clinical scales and standard electrophysiological techniques. PMID:24028193

  12. Blocking mitochondrial calcium release in Schwann cells prevents demyelinating neuropathies

    PubMed Central

    Berthelot, Jade; Jiner, Jennifer; Perrin-Tricaud, Claire; Fernando, Ruani; Chrast, Roman; Lenaers, Guy

    2016-01-01

    Schwann cells produce myelin sheath around peripheral nerve axons. Myelination is critical for rapid propagation of action potentials, as illustrated by the large number of acquired and hereditary peripheral neuropathies, such as diabetic neuropathy or Charcot-Marie-Tooth diseases, that are commonly associated with a process of demyelination. However, the early molecular events that trigger the demyelination program in these diseases remain unknown. Here, we used virally delivered fluorescent probes and in vivo time-lapse imaging in a mouse model of demyelination to investigate the underlying mechanisms of the demyelination process. We demonstrated that mitochondrial calcium released by voltage-dependent anion channel 1 (VDAC1) after sciatic nerve injury triggers Schwann cell demyelination via ERK1/2, p38, JNK, and c-JUN activation. In diabetic mice, VDAC1 activity was altered, resulting in a mitochondrial calcium leak in Schwann cell cytoplasm, thereby priming the cell for demyelination. Moreover, reduction of mitochondrial calcium release, either by shRNA-mediated VDAC1 silencing or pharmacological inhibition, prevented demyelination, leading to nerve conduction and neuromuscular performance recovery in rodent models of diabetic neuropathy and Charcot-Marie-Tooth diseases. Therefore, this study identifies mitochondria as the early key factor in the molecular mechanism of peripheral demyelination and opens a potential opportunity for the treatment of demyelinating peripheral neuropathies. PMID:26878172

  13. Post-traumatic trigeminal neuropathy. A study of 63 cases

    PubMed Central

    Peñarrocha, David; Bagán, José V.; Peñarrocha, Miguel

    2012-01-01

    Introduction. Trigeminal neuropathy is most often secondary to trauma. The present study explores the underlying causes and the factors that influence recovery. Material and methods. A retrospective case study was made involving 63 patients with trigeminal neuropathy of traumatologic origin, subjected to follow-up for at least 12 months. Results. Fifty-four percent of all cases were diagnosed after mandibular third molar surgery. In 37 and 19 patients the sensory defect was located in the territory innervated by the mental and lingual nerve, respectively. Pain was reported in 57% of the cases, and particularly among the older patients. Regarding patient disability, quality of life was not affected in three cases, while mild alterations were recorded in 25 subjects and severe alterations in 8. Partial or complete recovery was observed in 25 cases after 6 months, and in 32 after one year. There were few recoveries after this period of time. Recovery proved faster in the youngest patients, who moreover were the individuals with the least pain. Conclusion. Our patients with trigeminal neuropathy recovered particularly in the first 6 months and up to one year after injury. The older patients more often suffered pain associated to the sensory defect. On the other hand, their discomfort was more intense, and the patients with most pain and the poorest clinical scores also showed a comparatively poorer course. Key words:Post-traumatic trigeminal neuropathy. PMID:22143689

  14. Intrathecal gene therapy rescues a model of demyelinating peripheral neuropathy.

    PubMed

    Kagiava, Alexia; Sargiannidou, Irene; Theophilidis, George; Karaiskos, Christos; Richter, Jan; Bashiardes, Stavros; Schiza, Natasa; Nearchou, Marianna; Christodoulou, Christina; Scherer, Steven S; Kleopa, Kleopas A

    2016-04-26

    Inherited demyelinating peripheral neuropathies are progressive incurable diseases without effective treatment. To develop a gene therapy approach targeting myelinating Schwann cells that can be translatable, we delivered a lentiviral vector using a single lumbar intrathecal injection and a myelin-specific promoter. The human gene of interest, GJB1, which is mutated in X-linked Charcot-Marie-Tooth Disease (CMT1X), was delivered intrathecally into adult Gjb1-null mice, a genetically authentic model of CMT1X that develops a demyelinating peripheral neuropathy. We obtained widespread, stable, and cell-specific expression of connexin32 in up to 50% of Schwann cells in multiple lumbar spinal roots and peripheral nerves. Behavioral and electrophysiological analysis revealed significantly improved motor performance, quadriceps muscle contractility, and sciatic nerve conduction velocities. Furthermore, treated mice exhibited reduced numbers of demyelinated and remyelinated fibers and fewer inflammatory cells in lumbar motor roots, as well as in the femoral motor and sciatic nerves. This study demonstrates that a single intrathecal lentiviral gene delivery can lead to Schwann cell-specific expression in spinal roots extending to multiple peripheral nerves. This clinically relevant approach improves the phenotype of an inherited neuropathy mouse model and provides proof of principle for treating inherited demyelinating neuropathies. PMID:27035961

  15. Periaxin mutations cause a broad spectrum of demyelinating neuropathies.

    PubMed

    Takashima, Hiroshi; Boerkoel, Cornelius F; De Jonghe, Peter; Ceuterick, Chantal; Martin, Jean-Jacques; Voit, Thomas; Schröder, J-Michael; Williams, Anna; Brophy, Peter J; Timmerman, Vincent; Lupski, James R

    2002-06-01

    Previous studies have demonstrated that apparent loss-of-function mutations in the periaxin gene cause autosomal recessive Dejerine-Sottas neuropathy or severe demyelinating Charcot-Marie-Tooth disease. In this report, we extend the associated phenotypes with the identification of two additional families with novel periaxin gene mutations (C715X and R82fsX96) and provide detailed neuropathology. Each patient had marked sensory involvement; two siblings with a homozygous C715X mutation had much worse sensory impairment than motor impairment. Despite early disease onset, these siblings with the C715X mutation had relatively slow disease progression and adult motor impairment typical of classic demyelinating Charcot-Marie-Tooth neuropathy. In contrast, a patient with the homozygous R82fsX96 mutation had a disease course consistent with Dejerine-Sottas neuropathy. The neuropathology of patients in both families was remarkable for demyelination, onion bulb and occasional tomacula formation with focal myelin thickening, abnormalities of the paranodal myelin loops, and focal absence of paranodal septate-like junctions between the terminal loops and axon. Our study indicates a prominent sensory neuropathy resulting from periaxin gene mutations and suggests a role for the carboxyl terminal domain of the periaxin protein. PMID:12112076

  16. Diabetic Neuropathy: What is a Total Contact Cast?

    MedlinePlus

    ... Web version Diabetic Neuropathy | What is a Total Contact Cast? What is a total contact cast? A total contact cast is a cast used to treat ulcers ( ... foot--that's why it is called a total contact cast. The cast helps to protect the skin ...

  17. Chemotherapy-induced peripheral neuropathies in hematological malignancies.

    PubMed

    Jongen, Joost Louis Marie; Broijl, Annemiek; Sonneveld, Pieter

    2015-01-01

    Recent developments in the treatment of hematological malignancies, especially with the advent of proteasome inhibitors and immunomodulatory drugs in plasma cell dyscrasias, call for an increased collaboration between hematologists and neurologists. This collaboration involves differentiating chemotherapy-induced peripheral neuropathies (CiPN) from disease-related neurologic complications, early recognition of CiPN and treatment of neuropathic pain. Multiple myeloma, Waldenstrom's macroglobulinemia and light-chain amyloidosis frequently present with peripheral neuropathy. In addition, multiple myeloma, non-Hodgkin lymphomas and leukemia's may mimic peripheral neuropathy by compression or invasion of the extra/intradural space. Platinum compounds, vinca alkaloids, proteasome inhibitors and immunomodulatory drugs may all cause CiPN, each with different and often specific clinical characteristics. Early recognition, by identifying the distinct clinical phenotype of CiPN, is of crucial importance to prevent irreversible neurological damage. No recommendations can be given on the use of neuroprotective strategies because of a lack of convincing clinical evidence. Finally, CiPN caused by vinca-alkaloids, proteasome inhibitors and immunomodulatory drugs is often painful and neurologists are best equipped to treat this kind of painful neuropathy. PMID:25326770

  18. Experimental diabetes in neonatal mice induces early peripheral sensorimotor neuropathy.

    PubMed

    Ariza, L; Pagès, G; García-Lareu, B; Cobianchi, S; Otaegui, P J; Ruberte, J; Chillón, M; Navarro, X; Bosch, A

    2014-08-22

    Animal models of diabetes do not reach the severity of human diabetic neuropathy but relatively mild neurophysiological deficits and minor morphometric changes. The lack of degenerative neuropathy in diabetic rodent models seems to be a consequence of the shorter length of the axons or the shorter animal life span. Diabetes-induced demyelination needs many weeks or even months before it can be evident by morphometrical analysis. In mice myelination of the peripheral nervous system starts at the prenatal period and it is complete several days after birth. Here we induced experimental diabetes to neonatal mice and we evaluated its effect on the peripheral nerve 4 and 8 weeks after diabetes induction. Neurophysiological values showed a decline in sensory nerve conduction velocity at both time-points. Morphometrical analysis of the tibial nerve demonstrated a decrease in the number of myelinated fibers, fiber size and myelin thickness at both time-points studied. Moreover, aldose reductase and poly(ADP-ribose) polymerase activities were increased even if the amount of the enzyme was not affected. Thus, type 1 diabetes in newborn mice induces early peripheral neuropathy and may be a good model to assay pharmacological or gene therapy strategies to treat diabetic neuropathy. PMID:24846610

  19. Reappraising entrapment neuropathies--mechanisms, diagnosis and management.

    PubMed

    Schmid, Annina B; Nee, Robert J; Coppieters, Michel W

    2013-12-01

    The diagnosis of entrapment neuropathies can be difficult because symptoms and signs often do not follow textbook descriptions and vary significantly between patients with the same diagnosis. Signs and symptoms which spread outside of the innervation territory of the affected nerve or nerve root are common. This Masterclass provides insight into relevant mechanisms that may account for this extraterritorial spread in patients with entrapment neuropathies, with an emphasis on neuroinflammation at the level of the dorsal root ganglia and spinal cord, as well as changes in subcortical and cortical regions. Furthermore, we describe how clinical tests and technical investigations may identify these mechanisms if interpreted in the context of gain or loss of function. The management of neuropathies also remains challenging. Common treatment strategies such as joint mobilisation, neurodynamic exercises, education, and medications are discussed in terms of their potential to influence certain mechanisms at the site of nerve injury or in the central nervous system. The mechanism-oriented approach for this Masterclass seems warranted given the limitations in the current evidence for the diagnosis and management of entrapment neuropathies. PMID:24008054

  20. Effects of vibrating insoles on standing balance in diabetic neuropathy.

    PubMed

    Hijmans, Juha M; Geertzen, Jan H B; Zijlstra, Wiebren; Hof, At L; Postema, Klaas

    2008-01-01

    This study investigated the effects on standing balance of random vibrations applied to the plantar side of the feet by vibrating insoles in subjects with neuropathy and nondisabled subjects. In four different conditions (eyes open or closed and with or without an attention-demanding task [ATD]), subjects with neuropathy secondary to diabetes mellitus (n = 17) and nondisabled subjects (n = 15) stood for 60 s on vibrating insoles placed on a force plate. During each condition, the insoles were turned on for 30 s and off for 30 s (random order). The calculated balance measures were mean velocity of the center of pressure displacements and root-mean-square of the velocity of these displacements in the anteroposterior and mediolateral directions. In subjects with neuropathy, an interaction effect between vibration and an ADT was found for balance. No effects of vibration on balance were found in nondisabled subjects. Vibrating insoles improved standing balance in subjects with neuropathy only when attention was distracted. Improvement of the insoles and their activation is needed to make their implementation in daily living possible and effective. PMID:19319766