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Sample records for optic neuropathy aion

  1. 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

  2. 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

  3. Anterior ischemic optic neuropathy following off-pump cardiac bypass surgery.

    PubMed

    Tidow-Kebritchi, Susanne; Jay, Walter M

    2003-12-01

    Anterior ischemic optic neuropathy (AION) is a well-described cause of visual loss in patients who have undergone cardiac surgery with cardiopulmonary bypass. The etiology of AION following cardiac surgery with cardiopulmonary bypass is believed to be multifactorial. Microembolisation and pump-related platelet dysfunction have been considered risk factors for the development of AION following cardiac surgery with cardiopulmonary bypass. Currently, 10-15% of cardiac procedures are performed without cardiopulmonary bypass to reduce morbidity. To the best of our knowledge, this is the second report of a patient who underwent off-pump cardiac surgery and developed an AION postoperatively. The patient's potential risk factors were severe anemia, new onset of atrial fibrillation with rapid ventricular rate, hypotension postoperatively, a small optic disc, uncontrolled diabetes mellitus and a past medical history of hypertension and coronary artery disease. PMID:15513001

  4. Subretinal fluid is common in experimental non-arteritic anterior ischemic optic neuropathy

    PubMed Central

    Yu, C; Ho, J K; Liao, Y J

    2014-01-01

    Purpose Anterior ischemic optic neuropathy (AION) is an important cause of acute vision loss for which several animal models exist. It has been associated with subretinal fluid in a previous study on patients but not yet so in animal models. Patients and Methods A patient presented with acute non-arteritic AION (NAION) and underwent ophthalmic evaluation and testing including fluorescein angiography and spectral-domain optical coherence tomography (SD-OCT). On the basis of the patient's findings, we used SD-OCT circular and volume scans to analyze retinal changes in a murine model of NAION. Results One week after left eye vision loss, the patient had clinical and imaging findings consistent with NAION. On SD-OCT, there was prominent peripapillary retinal thickening consistent with intra-retinal edema and sub-foveolar fluid. Inspired by the findings in human AION, we looked for similar changes in murine NAION using SD-OCT. The circular scan did not adequately detect the presence of subretinal fluid. Using the 25-line scan, which covered a larger part of the posterior pole, we found that 100% of murine AION resulted in subretinal fluid at day 1. The subretinal fluid resolved by week 1. Conclusion This study detailed a case of clinical NAION associated with intra-retinal and subretinal fluid. We also found that subretinal fluid was common in murine photochemical thrombosis model of AION and could be found far away from the optic disc. PMID:25257770

  5. Amiodarone induced optic neuropathy

    PubMed Central

    Nagra, P K; Foroozan, R; Savino, P J; Castillo, I; Sergott, R C

    2003-01-01

    Aim: To determine the clinical features of amiodarone induced optic neuropathy, which may help distinguish it from non-arteritic anterior ischaemic optic neuropathy. Methods: Retrospective observational case series of patients diagnosed with amiodarone induced optic neuropathy at the neuro-ophthalmology service from March 1998 to February 2001. Amiodarone was discontinued after discussion with the patient's cardiologist. Visual acuity, colour vision, automated perimetry, and funduscopy were performed on initial and follow up examinations. Results: Three patients with amiodarone induced optic neuropathy presented with mildly decreased vision, visual field defects, and bilateral optic disc swelling. Upon discontinuing the medication, visual function and optic disc swelling slowly improved in all three patients. Conclusion: Amiodarone induced optic neuropathy can present with visual dysfunction, and is typically a bilateral process. Upon discontinuation of amiodarone, slow resolution of optic disc swelling occurs and visual function improves in some patients. PMID:12642303

  6. 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 be a useful approach to NAION treatment early in the course of the disease. PMID:21376134

  7. Efficacy of granulocyte-colony stimulating factor treatment in a rat model of anterior ischemic optic neuropathy

    PubMed Central

    Huang, Shun-Ping; Tsai, Rong-Kung

    2014-01-01

    Non-arteritic anterior ischemic optic neuropathy (NA-AION) is the most common cause of acute ischemic damage to the optic nerve (ON), and the leading cause of seriously impaired vision in people over 55 years of age. It demonstrated that subcutaneous administration of Granulocyte colony-stimulating factor (G-CSF) reduces RGC death in an ON crush model in rats, and that the neuroprotective effects may involve both anti-apoptotic and anti-inflammatory processes. Our recent work shows that the protective actions of G-CSF in rAION models may involve both anti-apoptotic and anti-inflammatory processes. However, the exact rescuing mechanisms involved in the administration of G-CSF in rAION models need further investigation. In addition, further studies on the administration of G-CSF at different time intervals after the induction of rAION may be able to illustrate whether treatment given at a later time is still neuroprotective. Further, it is unknown whether treatment using G-CSF combined with other drugs will result in a synergistic effect in a rAION model. Inflammation induced by ischemia plays an essential role on the ON head in NA-AION, which can result in disc edema and compartment changes. Therefore, it is reasonable that adding an anti-inflammatory drug may enhance the therapeutic effects of G-CSF. An ongoing goal is to evaluate the novel sites of action of both G-CSF and other anti-inflammatory drugs, and to identify the functionally protective pathways to enhance RGC survival. These investigations may open up new therapeutic avenues for the treatment of ischemic optic neuropathy. PMID:25317164

  8. Ischemic optic neuropathy.

    PubMed

    Athappilly, Geetha; Pelak, Victoria S; Mandava, Naresh; Bennett, Jeffrey L

    2008-10-01

    Ischemic optic neuropathy is the most frequent cause of vision loss in middle age. Clinical and laboratory research studies have begun to clarify the natural history, clinical presentation, diagnostic criteria and pathogenesis of various ischemic nerve injuries. As a result, physicians are acquiring new tools to aid in the diagnosis and potential treatment of ischemic nerve injury. The aim of this review is to examine recent data on anterior and posterior ischemic optic neuropathy and to provide a framework for physicians to manage and counsel affected individuals. PMID:18826805

  9. Anterior ischemic optic neuropathy: classification of field defects by Octopus automated static perimetry.

    PubMed

    Traustason, O I; Feldon, S E; Leemaster, J E; Weiner, J M

    1988-01-01

    Visual fields of patients with anterior ischemic optic neuropathy (AION) were classified according to quantitative criteria, using the Octopus perimeter. Although a significant altitudinal pattern of field loss was found in 55% of perimetric examinations, the "spared" hemifields routinely showed some loss of sensitivity. This finding, along with the diffuse loss of sensitivity in a high percentage of visual fields, indicates more extensive involvement of the circulation of the anterior optic nerve head than has previously been suggested. Furthermore, patients with diabetes mellitus alone were found to have a statistically separable pattern of visual field loss. The pathophysiologic implications of the visual fields in AION and their relationship to the clinical findings were investigated. PMID:3402741

  10. [Leber's hereditary optic neuropathy].

    PubMed

    Hilo, Wasseem; Jabaly-Habib, Haneen; Modi, Naftali; Briscoe, Daniel

    2013-08-01

    Lebers hereditary optic neuropathy (LHON) is a maternally inherited disease characterized by subacute severe visual loss in both eyes, which usually manifests in young adulthood. The disease has maternal inheritance due to mitochondrial DNA mutation. The final diagnosis is genetic. There is still no proven treatment, but there is significant progress in developments on the genetics of the disease to reach gene therapy. In this article we review the latest literature relevant to this disease. PMID:24167936

  11. Differential monocular vs. binocular pupil responses from melanopsin-based photoreception in patients with anterior ischemic optic neuropathy.

    PubMed

    Tsika, Chrysanthi; Crippa, Sylvain V; Kawasaki, Aki

    2015-01-01

    We examined the effect of anterior ischemic optic neuropathy (AION) on the activity of intrinsically photosensitive retinal ganglion cells (ipRGCs) using the pupil as proxy. Eighteen patients with AION (10 unilateral, 8 bilateral) and 29 age-matched control subjects underwent chromatic pupillometry. Red and blue light stimuli increasing in 0.5 log steps were presented to each eye independently under conditions of dark and light adaptation. The recorded pupil contraction was plotted against stimulus intensity to generate scotopic and photopic response curves for assessment of synaptically-mediated ipRGC activity. Bright blue light stimuli presented monocularly and binocularly were used for melanopsin activation. The post-stimulus pupil size (PSPS) at the 6th second following stimulus offset was the marker of intrinsic ipRGC activity. Finally, questionnaires were administered to assess the influence of ipRGCs on sleep. The pupil response and PSPS to all monocularly-presented light stimuli were impaired in AION eyes, indicating ipRGC dysfunction. To binocular light stimulation, the PSPS of AION patients was similar to that of controls. There was no difference in the sleep habits of the two groups. Thus after ischemic injury to one or both optic nerves, the summated intrinsic ipRGC activity is preserved when both eyes receive adequate light exposure. PMID:26074032

  12. Differential monocular vs. binocular pupil responses from melanopsin-based photoreception in patients with anterior ischemic optic neuropathy

    PubMed Central

    Tsika, Chrysanthi; Crippa, Sylvain V.; Kawasaki, Aki

    2015-01-01

    We examined the effect of anterior ischemic optic neuropathy (AION) on the activity of intrinsically photosensitive retinal ganglion cells (ipRGCs) using the pupil as proxy. Eighteen patients with AION (10 unilateral, 8 bilateral) and 29 age-matched control subjects underwent chromatic pupillometry. Red and blue light stimuli increasing in 0.5?log steps were presented to each eye independently under conditions of dark and light adaptation. The recorded pupil contraction was plotted against stimulus intensity to generate scotopic and photopic response curves for assessment of synaptically-mediated ipRGC activity. Bright blue light stimuli presented monocularly and binocularly were used for melanopsin activation. The post-stimulus pupil size (PSPS) at the 6th second following stimulus offset was the marker of intrinsic ipRGC activity. Finally, questionnaires were administered to assess the influence of ipRGCs on sleep. The pupil response and PSPS to all monocularly-presented light stimuli were impaired in AION eyes, indicating ipRGC dysfunction. To binocular light stimulation, the PSPS of AION patients was similar to that of controls. There was no difference in the sleep habits of the two groups. Thus after ischemic injury to one or both optic nerves, the summated intrinsic ipRGC activity is preserved when both eyes receive adequate light exposure. PMID:26074032

  13. Genetics Home Reference: Leber hereditary optic neuropathy

    MedlinePLUS

    ... OMIM Genetic disorder catalog Conditions > Leber hereditary optic neuropathy On this page: Description Genetic changes Inheritance Diagnosis ... Reviewed December 2013 What is Leber hereditary optic neuropathy? Leber hereditary optic neuropathy (LHON) is an inherited ...

  14. Leber hereditary optic neuropathy.

    PubMed

    Man, P Y W; Turnbull, D M; Chinnery, P F

    2002-03-01

    Leber hereditary optic neuropathy (LHON) is a mitochondrial genetic disease that preferentially causes blindness in young adult males, affecting about 1 in 25 000 of the British population. It is characterised by bilateral subacute loss of central vision owing to focal degeneration of the retinal ganglion cell layer and optic nerve. Over 95% of LHON cases are primarily the result of one of three mitochondrial DNA (mtDNA) point mutations, G3460A, G11778A, and T14484C, which all involve genes encoding complex I subunits of the respiratory chain. An intriguing feature of LHON is that only approximately 50% of males and approximately 10% of females who harbour a pathogenic mtDNA mutation actually develop the optic neuropathy. This marked incomplete penetrance and gender bias imply that additional mitochondrial and/or nuclear genetic factors must be modulating the phenotypic expression of LHON. It is also likely that environmental factors contribute to the onset of visual failure. However, these secondary precipitating factors remain poorly defined at present. In this review, we describe the natural history of this optic nerve disorder and highlight issues relating to clinical diagnosis, management, and genetic counselling. We also discuss the findings of recently published studies and the light they shed on the complex aetiology and pathophysiology of LHON. PMID:11897814

  15. 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.

  16. Optic neuropathy caused by Propionibacterium acnes pachymeningitis.

    PubMed

    Adesina, Ore-Ofe O; Stagg, Brian C; Digre, Kathleen B; Katz, Bradley J; Quigley, Edward P; Palmer, Cheryl A; Warner, Judith E A

    2014-09-01

    We describe a patient with vision loss from an optic neuropathy caused by Propionibacterium acnes pachymeningitis. The patient's optic neuropathy was stabilized with appropriate antibiotic therapy. PMID:24614085

  17. Indirect traumatic optic neuropathy.

    PubMed

    Singman, Eric L; Daphalapurkar, Nitin; White, Helen; Nguyen, Thao D; Panghat, Lijo; Chang, Jessica; McCulley, Timothy

    2016-01-01

    Indirect traumatic optic neuropathy (ITON) refers to optic nerve injury resulting from impact remote to the optic nerve. The mechanism of injury is not understood, and there are no confirmed protocols for prevention, mitigation or treatment. Most data concerning this condition comes from case series of civilian patients suffering blunt injury, such as from sports- or motor vehicle-related concussion, rather than military-related ballistic or blast damage. Research in this field will likely require the development of robust databases to identify patients with ITON and follow related outcomes, in addition to both in-vivo animal and virtual human models to study the mechanisms of damage and potential therapies. PMID:26759722

  18. Treatment of hereditary optic neuropathies.

    PubMed

    Newman, Nancy J

    2012-10-01

    The hereditary optic neuropathies are inherited disorders in which optic nerve dysfunction is a prominent feature in the phenotypic expression of disease. Optic neuropathy may be primarily an isolated finding, such as in Leber hereditary optic neuropathy and dominant optic atrophy, or part of a multisystem disorder. The pathophysiological mechanisms underlying the hereditary optic neuropathies involve mitochondrial dysfunction owing to mutations in mitochondrial or nuclear DNA that encodes proteins essential to mitochondrial function. Effective treatments are limited, and current management includes therapies directed at enhancing mitochondrial function and preventing oxidative damage, as well as genetic counselling, and supportive and symptomatic measures. New therapies, including gene therapy, are emerging via animal models and human clinical trials. Leber hereditary optic neuropathy, in particular, provides a unique model for testing promising treatments owing to its characteristic sequential bilateral involvement and the accessibility of target tissue within the eye. Lessons learned from treatment of the hereditary optic neuropathies may have therapeutic implications for other disorders of presumed mitochondrial dysfunction. In this Review, the natural history of the common inherited optic neuropathies, the presumed pathogenesis of several of these disorders, and the literature to date regarding potential therapies are summarized. PMID:22945544

  19. 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

  20. 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.

  1. Medical management of hereditary optic neuropathies.

    PubMed

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

    2014-01-01

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

  2. Medical Management of Hereditary Optic Neuropathies

    PubMed Central

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

    2014-01-01

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

  3. 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.

  4. [Non-Arteritic Ischemic Optic Neuropathy (NAION)].

    PubMed

    Wilhelm, H; Beisse, F; Rther, K

    2015-11-01

    Non-arteritic ischemic optic neuropathy (NAION) is virtually unknown outside ophthalmology. It is characterised by acute unilateral visual loss, no pain on eye movements and virtually always optic disc swelling. Optic disc oedema resolves within 1 to 2 months, leaving behind optic atrophy. Vision hardly improves. NAION is the product of local abnormalities of the vascular supply to the optic nerve and general vascular risk factors. Of these, diabetes, hypertension and especially sleep apnoea syndrome are the most important. Recurrences in the involved eye are rare; contralateral recurrence occurs in approximately 15?% of patients. There is no clear scientific evidence for any specific therapy. However, there is general agreement that it is reasonable to control risk factors. PMID:26575534

  5. Autosomal dominant optic atrophy with asymptomatic peripheral neuropathy.

    PubMed Central

    Chalmers, R M; Bird, A C; Harding, A E

    1996-01-01

    The association between hereditary motor and sensory neuropathy (HMSN) and optic atrophy has been termed HMSN type VI. The autosomal dominant inheritance of this syndrome is reported. Three generations were affected with optic atrophy, which differed in some respects from classic dominant optic atrophy, and an asymptomatic, mainly sensory, neuropathy. PMID:8708653

  6. Minimal invasive transcaruncular optic canal decompression for traumatic optic neuropathy.

    PubMed

    Vaitheeswaran, Krishna; Kaur, Preetinder; Garg, Shalini

    2014-12-01

    Traumatic optic neuropathy is a cause of loss of vision associated with head injuries. Treatment options include observation, steroids and decompression of the optic canal. We report a case where the optic canal decompression was performed using a transcaruncular approach under a regional block. The incision was made through the caruncle and the dissection was carried down to the periosteum down to the orbital apex where the optic nerve was seen exiting through the optic canal posterior to the posterior ethmoidal artery. The optic nerve was decompressed with good visualization. Hemostasis and wound closure was achieved using fibrin glue. Postoperatively visual acuity improved with minimal inflammation enabling early rehabilitation. PMID:25208226

  7. 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

  8. Leber hereditary optic neuropathy: current perspectives.

    PubMed

    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

  9. Leber hereditary optic neuropathy in Australia.

    PubMed

    Mackey, D A; Buttery, R G

    1992-08-01

    Leber hereditary optic neuropathy (LHON) presents with sudden onset of visual loss mainly in young adult males. LHON is not uncommon in Australia, accounting for 2% of invalid blind pensions. We have identified 20 unrelated families carrying mitochondrial DNA mutations associated with LHON and 135 of 291 individuals with documented LHON are currently alive in Australia. The mean age of onset of visual loss for males was 26 years and for females 27 years, with a range from six to 65 years. The mean risk of visual loss was 20% for males and 4% for females. There are over 1750 male and female carriers living in Australia who have not yet lost vision; 600 carriers are under 24 years of age. The expected number of new cases of blindness from LHON is three to four per year. PMID:1449769

  10. 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

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

    PubMed

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

    2015-05-01

    Designation criteria for Leber's hereditary optic neuropathy (LHON) have been established by a working group for retino-choroidal and optic atrophy funded by the Ministry of Health, Labor, and Welfare (MHLW) of Japan in collaboration with the Japanese Neuro-ophthalmology Society. The criteria are composed of three major symptoms and three ancillary test findings. According to the number and the combination of these symptoms and findings, subjects are classified into definite, probable, and possible LHON cases and asymptomatic carriers. The major symptoms include bilateral involvement with a time-lag, a papillomacular bundle atrophy, both characteristic optic disc findings at the acute phase. In the ancillary testings, mitochondrial DNA mutations specific for LHON are detailed with a table listing the mutation loci being attached. To enhance readers' understanding of description of the major symptoms and ancillary test findings, explanatory remarks on 11 parameters are supplemented. The establishment of the criteria facilitates epidemiological survey of LHON by MHLW and contributes to improvement of welfare for patients with LHON in Japan. PMID:26062390

  12. Nutritional optic neuropathy following bariatric surgery

    PubMed Central

    Sawicka-Pierko, Anna; Hady, Razak Hady; Mariak, Zofia; Dadan, Jacek

    2014-01-01

    Bariatric procedures, associated with gastrointestinal malabsorption of vitamins and microelements, may constitute a risk factor for nutritional optic neuropathy (NON). We present a case of a 34-year-old female patient who developed bilateral NON after sleeve gastrectomy. Despite postoperative ophthalmological supervision, 10 months after the procedure the woman presented with a bilateral decrease in visual acuity down to 0.8, bilateral visual field loss and abnormal visual evoked potential recordings. Laboratory abnormalities included decreased serum concentration of vitamin B12 (161 pg/ml). Treatment was based on intramuscular injections of vitamin B12 (1000 units per day). After 1 week of the treatment, we observed more than a three-fold increase in the serum concentration of vitamin B12 and resolution of the bilateral symptoms of NON. The incidence of NON is likely to increase due to the growing number of these bariatric procedures performed worldwide. Therefore, all persons subjected to such surgery should receive long-term ophthalmological follow-up and supplementation with vitamins and microelements. PMID:25562012

  13. Drug-induced optic neuropathy-TB or not TB.

    PubMed

    Pradhan, Monika; Sharp, Dianne; Best, Stephen; Vincent, Andrea; Vaphiades, Michael

    2010-01-01

    Autosomal dominant optic atrophy is an inherited optic neuropathy manifesting with variable penetrance and expressivity. Other genetic and environmental factors are postulated to contribute to more marked visual loss in some affected individuals. Optic neuropathy is also a known adverse effect of ethambutol therapy for tuberculosis. This case report demonstrates an atypical presentation of ethambutol toxicity, with progressive profound loss of vision despite drug cessation. A subsequent diagnosis of autosomal dominant optic atrophy was made when the proband's sons presented with mild visual disturbances and color vision defects, confirmed with electrophysiology and OPA1 gene mutational analysis. This case emphasizes the importance of avoiding potentially neurotoxic therapy in predisposed individuals and the influence of environmental factors in patients with inherited optic neuropathies. PMID:20083290

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

    PubMed

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

    2014-07-01

    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

  15. 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.

  16. 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

  17. 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…

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

    PubMed

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

    2013-03-01

    We report a case of acute, bilateral and severe vision loss after inadvertent consumption of a large quantity of the homoeopathic medication Arnica-30. Severe vomiting which required hospitalization preceded visual symptoms. In the acute stage, pupillary responses to light were absent and fundus examination was normal. Vision loss followed a fluctuating course, with profound loss noted after 6 weeks along with bilateral optic disc pallor. Neuro-ophthalmic examination and detailed investigations were performed, including magnetic resonance imaging, electroretinography (ERG) and visual evoked potentials (VEP). Ocular coherence tomography (OCT) showed gross thinning of the retinal nerve fiber layer. While a differential diagnosis of posterior ischemic optic neuropathy was kept in mind, these findings supported a diagnosis of bilateral toxic optic neuropathy. Arnica-30 is popularly used to accelerate wound healing, including after oculoplastic surgery. While homeopathic medicines are generally considered safe due to the very low concentrations involved, Arnica-30 may be neurotoxic if consumed internally in large quantities. PMID:22877081

  19. Graves’ disease presenting as unilateral anterior ischaemic optic neuropathy

    PubMed Central

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

    2014-01-01

    We report a case of a 28-year-old man who presented with 1-day history of sudden diminution of vision in the right eye. Examination showed unilateral exophthalmos with restricted eyeball movement on upward gaze in the right eye. MRI of the orbit showed no evidence of compression of the optic nerve on the right side. Visual-evoked potential showed prolonged P100 in the right eye. Fundus examination revealed swollen optic disc and para papillary nerve fibre layer splinter haemorrhages with corresponding altitudinal field defect on perimetry suggestive of anterior ischaemic optic neuropathy. PMID:24648476

  20. 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

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

    PubMed

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

    2010-12-01

    Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder characterized by bilateral painless optic atrophy and blindness. It usually occurs in young men in association with three major mutations in the mitochondrial genome (mtDNA). We report a patient with a history of alcohol abuse who developed at age 63 years visual impairment, sensorineural hearing loss, and memory dysfunction, suggestive of Susac's syndrome. The patient carried the heteroplasmic mt. 11778G>A mutation on the T2e mtDNA haplogroup. It remains unclear if chronic alcohol abuse combined with the mitochondrial genetic background prompted an aged-related neurodegeneration or deferred the onset of the LHON disease. PMID:20632027

  2. 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.

  3. 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 paraplegia, and multiple sclerosis, where mitochondrial dysfunction is also thought to be an important pathophysiological player. A number of vertebrate and invertebrate disease models has recently been established to circumvent the lack of human tissues, and these have already provided considerable insight by allowing direct RGC experimentation. The ultimate goal is to translate these research advances into clinical practice and new treatment strategies are currently being investigated to improve the visual prognosis for patients with mitochondrial optic neuropathies. PMID:21112411

  4. Mitochondrial optic neuropathies - disease mechanisms and therapeutic strategies.

    PubMed

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

    2011-03-01

    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 paraplegia, and multiple sclerosis, where mitochondrial dysfunction is also thought to be an important pathophysiological player. A number of vertebrate and invertebrate disease models has recently been established to circumvent the lack of human tissues, and these have already provided considerable insight by allowing direct RGC experimentation. The ultimate goal is to translate these research advances into clinical practice and new treatment strategies are currently being investigated to improve the visual prognosis for patients with mitochondrial optic neuropathies. PMID:21112411

  5. Diffusion Tensor Imaging in Acute Optic Neuropathies

    PubMed Central

    Naismith, Robert T.; Xu, Junqian; Tutlam, Nhial T.; Lancia, Samantha; Trinkaus, Kathryn; Song, Sheng-Kwei; Cross, Anne H.

    2012-01-01

    Objective To evaluate directional diffusivities within the optic nerve in a first event of acute optic neuritis to determine whether decreased axial diffusivity (AD) would predict 6-month visual outcome and optic nerve integrity measures. Design Cohort study. Setting Academic multiple sclerosis center. Patients Referred sample of 25 individuals who presented within 31 days after acute visual symptoms consistent with optic neuritis. Visits were scheduled at baseline, 2 weeks, and 1, 3, 6, and 12 months. Main Outcome Measures Visual acuity, contrast sensitivity, visual evoked potentials (VEPs), and thickness of the retinal nerve fiber layer (RNFL). Results An incomplete 6-month visual recovery was associated with a lower baseline AD (1.50 ?m2/ms [95% confidence interval {CI}, 1.361.64 ?m2/ms for incomplete recovery vs 1.75 ?m2/ms [95% CI, 1.671.83 ?m2/ms] for complete recovery). Odds of complete recovery decreased by 53% (95% CI, 27%70%) for every 0.1-unit decrease in baseline AD. A lower baseline AD correlated with worse 6-month visual outcomes in visual acuity (r=0.40, P=.03), contrast sensitivity (r=0.41, P=.02), VEP amplitude (r=0.55, P<.01), VEP latency (r=?0.38, P=.04), and RNFL thickness (r=0.53, P=.02). Radial diffusivity increased between months 1 and 3 to become higher in those with incomplete recovery at 12 months than in those with complete recovery (1.45 ?m2/ms [95% CI, 1.311.59 ?m2/ms] vs 1.19 ?m2/ms [95% CI, 1.101.28 ?m2/ms]). Conclusions Decreased AD in acute optic neuritis was associated with a worse 6-month visual outcome and correlated with VEP and RNFL measures of axon and myelin injury. Axial diffusivity may serve as a marker of axon injury in acute white matter injury. PMID:21911658

  6. 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.

  7. Optic neuropathy due to allergic fungal rhinosinusitis

    PubMed Central

    Cyriac, Jiji Tresa; Cherian, Tambi; Hadi, Wasna Ali; Jose, Joyce

    2011-01-01

    An uncommon case of allergic fungal rhinosinusitis presented to the ophthalmology outpatient department of our hospital with complaints of blurred vision in the right eye of a few days duration and vague complaints of pain around the eyes. The visual acuity on examination was grossly reduced in the right eye and normal in the left eye. Color vision was normal. Anterior segment examination including pupils was normal. Dilated fundus examination was normal except for temporal pallor in the right optic disc. Automated perimetry and magnetic resonance imaging (MRI) scan of brain and orbit were done. The imaging report showed a bilateral pansinusitis with pressure on the right optic nerve. Perimetry showed a superior field defect on the right side. ENT consultation and computed tomography (CT) with contrast helped to diagnose this as a case of allergic fungal rhinosinusitis. The patient was started on systemic steroids under the care of the ENT surgeon. After a few days, pre-operative assessment showed a gross improvement of visual acuity. Endoscopic sinus surgery was done to remove the polyps and thick mucus material. Histopathologic examination confirmed allergic fungal mucin. Days after surgery, the visual acuity improved further and repeat perimetry showed gross improvement in the visual field. Good history taking and a detailed ophthalmic examination, keeping in mind the probable causes of loss of vision of few days duration with no findings other than a decreased visual acuity and a suspicious disc, were key to the early diagnosis and investigation in this case. This helped in early referral and management of the case before permanent damage and irreversible visual loss occurred. The optic nerve is a cranial nerve which, once damaged permanently, will not regenerate. The amount of sinus involvement was extensive on both sides and invariably the left optic nerve would have been involved in a few days, if intervention was delayed. PMID:21897686

  8. 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

  9. 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.

  10. Pre-excitation syndrome in Leber's hereditary optic neuropathy.

    PubMed

    Nikoskelainen, E K; Savontaus, M L; Huoponen, K; Antila, K; Hartiala, J

    1994-09-24

    Pre-excitation syndrome is common in families with Leber's hereditary optic neuropathy (LHON). 24 Finnish families with LHON were screened for the 11778 and the 3460 mitochondrial DNA mutations. 5 of 30 individuals with LHON and the 11778 mutation had the Wolff-Parkinson-White pre-excitation syndrome. None of 10 with the 3460 mutation or of 11 with "other" mutations had this syndrome. Overall, 5 of 51 LHON patients and 9 of 112 symptom-free maternal relatives had Wolff-Parkinson-White syndrome (9%). In paternal relatives, the frequency was 1.6%. Mitochondrial DNA causal for LHON may contribute to pre-excitation syndrome. PMID:7916404

  11. 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

  12. Bilateral Glaucomatous Optic Neuropathy Caused by Eye Rubbing

    PubMed Central

    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

  13. Intraorbital optic nerve signal hyperintensity on magnetic resonance imaging sequences in perioperative hypotensive ischemic optic neuropathy.

    PubMed

    Purvin, Valerie; Kuzma, Benjamin

    2005-09-01

    A 61-year-old man experienced severe bilateral posterior ischemic optic neuropathy after cardiac bypass surgery. Routine magnetic resonance imaging sequences were normal, but diffusion-weighted and fluid-attenuated inversion recovery (FLAIR) sequences showed abnormal hyperintensity within both intra-orbital optic nerves. This imaging abnormality has not been previously reported in this setting. PMID:16148628

  14. 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.

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

    PubMed Central

    Bakbak, Berker; Ozturk, Banu Turgut; Gedik, Sansal; Koktekir, Bengu Ekinci; Gonul, Saban

    2013-01-01

    A 56-year-old man noted a sudden decrease of vision in his right eye 4 hours after intramuscular triamcinolone acetonide (TA) injection. A diagnosis of unilateral nonarteritic anterior ischemic optic neuropathy (NAION) was made, and the patient was counseled to discontinue using TA. Examination for possible risk factors revealed controlled hypertension. Final visual acuity was finger counting at 1 m, and the optic disc was pale in his right eye. This is the first reported case of unilateral NAION that has occurred in a patient after intramuscular corticosteroid injection. Although a cause-and-effect relationship is difficult to prove, the short duration between the TA injection and the NAION is noteworthy. The history of corticosteroid injection should be questioned in cases with predisposing conditions such as hypertension. PMID:23569357

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

    PubMed

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

    2014-05-01

    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

  17. 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

  18. Traumatic optic neuropathy: facial CT findings affecting visual acuity.

    PubMed

    Reddy, Ramachandra P; Bodanapally, Uttam K; Shanmuganathan, Kathirkamanathan; Van der Byl, Giulia; Dreizin, David; Katzman, Lee; Shin, Robert Kang

    2015-08-01

    The purpose of this study was to determine the relationship between admission visual acuity (VA) and facial computed tomographic (CT) findings of traumatic optic neuropathy (TON). We retrospectively evaluated CT findings in 44 patients with TON. Mid-facial fractures, extraconal and intraconal hematomas, hematomas along the optic nerve and the posterior globe, optic canal fracture, nerve impingement by optic canal fracture fragment, and extraconal and intraconal emphysema were evaluated. CT variables of patients with and without available VA were compared. VA was converted into logarithm of the minimum angle of resolution (logMAR) to provide a numeric scale for the purpose of statistical analysis. The risk factors related to poor VA on univariate analysis were as follows: intraconal hematoma [median logMAR -4.7 versus -1.15, p?=?0.016] and hematoma along the optic nerve [median -4.7 versus -1.3, p?=?0.029]. Intraconal hematoma was the best predictor of poor VA (coefficient, 1.01; SE, 0.34; and p?=?0.008). Receiver operating characteristic (ROC) curve analysis showed that the presence of intraconal hematoma and hematoma along the optic nerve predicted poor VA (logMAR of -3.7 or lower) with an area under the curve of 0.8 and 0.85, respectively. TON patients at higher risk of severe visual impairment may be identified based on admission facial CT. PMID:25563705

  19. Optic Neuropathy Due to Chronic Lymphocytic Leukemia Proven With Optic Nerve Sheath Biopsy.

    PubMed

    Khan, Khurrum; Malik, Amina I; Almarzouqi, Sumayya J; Morgan, Michael L; Yalamanchili, Sushma; Chevez-Barrios, Patricia; Lee, Andrew G

    2016-03-01

    Central nervous system involvement from chronic lymphocytic leukemia (CLL) occurs infrequently, and manifestations include cognitive and cerebellar dysfunction and cranial nerve palsies. We report a 45-year-old man with CLL believed to be in clinical remission, who presented with vision loss and bilateral optic disc edema. His optic neuropathy due to CLL was proven by optic nerve sheath biopsy, and he experienced visual recovery after treatment with ibrutinib and intrathecal methotrexate. PMID:26436987

  20. Autosomal recessive inheritance of hereditary motor and sensory neuropathy with optic atrophy.

    PubMed Central

    Chalmers, R M; Riordan-Eva, P; Wood, N W

    1997-01-01

    Three siblings are reported with childhood onset hereditary motor and sensory neuropathy (HMSN) and adult onset optic atrophy. Electrophysiological studies showed an axonal neuropathy and dysfunction of the retinal ganglion cells or optic nerve. The presumed mode of inheritance is autosomal recessive. This is the second family in which autosomal recessive inheritance of HMSN and optic atrophy (HMSN type VI) has been described, and the first in which electrophysiological studies have been reported. PMID:9120454

  1. Unusual optic disc infarction in a case of arteritic anterior ischaemic optic neuropathy (AAION)

    PubMed Central

    Lim, Dawn KA; Shen, Sunny; Jejah, Issam Al; Cullen, James F

    2015-01-01

    Herein, we report another case of arteritic anterior ischaemic optic neuropathy from Singapore, in which the initial optic disc swelling was extreme and the sequential disease resolved because the patient was already on maximum treatment. As the management of this biopsy-proven giant cell arteritis case was complicated by the presence of a number of other medical conditions, including end-stage renal failure, monitoring of the response to treatment proved problematic. PMID:25820857

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

    PubMed

    To?ska, Katarzyna; Kodro?, Agata; Bartnik, Ewa

    2010-01-01

    Leber hereditary optic neuropathy (LHON), acute or subacute vision loss due to retinal ganglion cell death which in the long run leads to optic nerve atrophy is one of the most widely studied maternally inherited diseases caused by mutations in mitochondrial DNA. Although three common mutations, 11778G>A, 14484T>C or 3460G>A are responsible for over 90% of cases and affect genes encoding complex I subunits of the respiratory chain, their influence on bioenergetic properties of the cell is marginal and cannot fully explain the pathology of the disease. The following chain of events was proposed, based on biochemical and anatomical properties of retinal ganglion cells whose axons form the optic nerve: mitochondrial DNA mutations increase reactive oxygen species production in these sensitive cells, leading to caspase-independent apoptosis. As LHON is characterized by low penetrance and sex bias (men are affected about 5 times more frequently than women) the participation of the other factors-genetic and environmental-beside mtDNA mutations was studied. Mitochondrial haplogroups and smoking are some of the factors involved in the complex etiology of this disease. PMID:20211598

  3. 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

  4. A Primate Model of Nonarteritic Anterior Ischemic Optic Neuropathy

    PubMed Central

    Chen, Celia S.; Johnson, Mary A.; Flower, Robert A.; Slater, Bernard J.; Miller, Neil R.; Bernstein, Steven L.

    2008-01-01

    PURPOSE Nonarteritic anterior ischemic optic neuropathy (NAION) is an optic nerve (ON) stroke and a leading cause of sudden ON-related vision loss. A primate (p)NAION model is crucial to further understanding of the clinical disorder and can provide information regarding the pathophysiology of other central nervous system (CNS) ischemic axonopathies. In the current study, a primate model of NAION was developed, and short-and long-term responses to this condition were characterized. METHODS pNAION was induced with a novel photoembolic mechanism. Short- and long-term responses were evaluated by minimally invasive testing (electrophysiology, fundus photography, indocyanine green and fluorescein angiography, and magnetic resonance imaging) and compared with histologic and immunohistochemical findings. RESULTS Optic disc edema, similar to that observed in cases of human NAION was seen 1 day after induction, with subsequent resolution associated with the development of optic disc pallor. Magnetic resonance imaging (MRI) performed 3 months after induction revealed changes consistent with ON atrophy. Electrophysiological studies and vascular imaging suggest an ON-limited infarct with subsequent axonal degeneration and selective neuronal loss similar to that seen in human NAION. ON inflammation was evident 2 months after induction at the site of the lesion and at distant sites, suggesting that inflammation-associated axonal remodeling continues for an extended period after ON infarct. CONCLUSIONS pNAION resembles human NAION in many respects, with optic disc edema followed by loss of cells in the retinal ganglion cell (RGC) layer and ON remodeling. This model should be useful for evaluating neuroprotective and other treatment strategies for human NAION as well as for other ischemic processes that primarily affect CNS white-matter tracts. PMID:18326695

  5. Macular spectral domain optical coherence tomography findings in Tanzanian endemic optic neuropathy.

    PubMed

    Kisimbi, John; Shalchi, Zaid; Mahroo, Omar A; Mhina, Celina; Sanyiwa, Anna J; Mabey, Denise; Mohamed, Moin; Plant, Gordon T

    2013-11-01

    Bilateral optic neuropathy in Dar es Salaam is now considered endemic and is estimated to affect 0.3-2.4% of young adults. The condition is characterized by a subacute bilateral loss of central vision of unknown aetiology. Findings of spectral domain optical coherence tomography have not previously been reported for these patients. All patients diagnosed with endemic optic neuropathy over a 2-year period at the Muhimbili National Hospital underwent spectral domain optical coherence tomography macular imaging. Scans were graded qualitatively for severity of retinal nerve fibre layer loss as well as the presence of microcystic macular changes, which have not previously been described in this condition. Of the 128 patients included (54.7% male; median age 20 years), severe retinal nerve fibre layer loss was found in 185 eyes (74.0%). There was full concordance in retinal nerve fibre layer thickness between the two eyes in 113 (91.1%) patients. Microcystic macular spaces were found in 16 (12.5%) patients and were bilateral in nine (7.0%) individuals. These changes were typically more prominent in the nasal than the temporal macula, predominantly involving the inner nuclear layer, and often occurred in an annular configuration that was evident on en face infra-red imaging, though not discernible on colour fundus photography or clinically. All patients with microcystic macular changes had severe thinning of the retinal nerve fibre layer (P = 0.02). Four patients in whom cystic spaces were demonstrated had sequential scans, and there was no detectable alteration in the configuration of these changes over a period of up to 16 months. This is the first study to document optical coherence tomography findings in endemic optic neuropathy. We have observed symmetrical severe loss of the caeco-central projection (papillomacular bundle) with otherwise well-preserved macular architecture. Also, we have observed microcystic retinal changes in a significant proportion of patients, which were associated with severe retinal nerve fibre layer loss. Similar changes have recently been reported from optical coherence tomography images of patients with multiple sclerosis, relapsing isolated optic neuritis, dominant optic atrophy, Leber's hereditary optic neuropathy and a patient with a chronic compressive optic neuropathy, supporting the hypothesis that this may be a non-specific phenomenon secondary to ganglion cell death. The correspondence of the changes to an annulus discernible on infra-red en face imaging, but not using other conventional retinal imaging techniques highlights the potential usefulness of this modality. PMID:24018312

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

    PubMed

    Gallenmller, C; Klopstock, T

    2014-03-01

    Leber's hereditary optic neuropathy is a rare genetic disorder affecting the retinal ganglion cells leading to a persistent severe bilateral loss of visual acuity within weeks or months. Males are much more likely to be affected than females, disease onset in most cases takes place between age 15 and 35 years. The disease is caused by point mutations in the mitochondrial DNA. The penetrance of the disease is incomplete, i.e., not all mutation carriers develop clinical symptoms. The phenotype is relatively uniform, but age at onset, severity and prognosis may vary even within the same family. Environmental and endocrine factors, optic disc anatomy as well as mitochondrial and nuclear genetic factors are discussed to influence penetrance as well as interindividual and intrafamilial variability. However, only cigarette smoking and excessive alcohol consumption have been shown to trigger disease onset. The disease is characterised by a central visual field defect, impaired colour vision and fundoscopically a peripapillary microangiopathy in the acute phase. Most patients end up after some months with a severe visual loss below 0.1 and in most cases there is no significant improvement of visual acuity in the course. In rare cases patients experience a mostly partial visual recovery which depends on the type of mutation. For confirmation of the diagnosis a detailed ophthalmological examination with fundoscopy, family history and genetic analysis of the mitochondrial DNA is needed. To date, there is no proven causal therapy, but at early disease stages treatment with idebenone can be tried. PMID:24658858

  7. A new characterization for nonarteritic anterior ischemic optic neuropathy

    PubMed Central

    Li, Aipeng; Li, Lin; Li, Miyang; Shi, Xiaoru

    2015-01-01

    This study is to investigate the clinical characteristics of patients with nonarteritic anterior ischemic optic neuropathy (NAION). Totally 133 patients (156 eyes) were included in this study. At the first visit and follow-up visits, the patients were subjected to the ophthalmic evaluations, including the fundus photography, visual field (VF) test, fluorescein fundus angiography, and optical coherence tomography (OCT). The visual acuity (VA) of 156 eyes and the VF of 148 eyes were evaluated. For the VA assessment, 59 (38%), 67 (43%), and 30 (19%) cases presented with an initial VA ≥ 20/40, between 20/40 and 20/400, and ≤ 20/400, respectively. VA was improved in 44% and deteriorated in 8% of the patients with VA < 20/20 after NAION onset. Inferior or superior altitudinal defects, constricted fields, and nasal steps were the most common VF defects. In the eyes with VF defects, 32 cases (22%) were improved, and 25 cases (17%) were worsened. In the 61 cases (39%) with VA ≤ 20/200 at NAION onset, neuroepithelial detachment in the fovea was found in 37 eyes (61%). For the optic disc assessment, retinal nerve fiber layer (RNFL) thickening was the most common symptom of NAION. Out of the 36 eyes with ONA or DR, 72% showed VA improvement after the NAION occurrence in the contralateral eye. Poor microcirculation perfusion in the bilateral optic nerve hypoplasia (ONH) might be the underlying mechanism for NAION, which could be relieved by compromising the blood supply to the one side. PMID:26770482

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

    PubMed

    Iyer, Shilpa

    2013-03-01

    Many human childhood mitochondrial disorders result from abnormal mitochondrial DNA (mtDNA) and altered bioenergetics. These abnormalities span most of the mtDNA, demonstrating that there are no "unique" positions on the mitochondrial genome that when deleted or mutated produce a disease phenotype. This diversity implies that the relationship between mitochondrial genotype and clinical phenotype is very complex. The origins of clinical phenotypes are thus unclear, fundamentally difficult-to-treat, and are usually clinically devastating. Current treatment is largely supportive and the disorders progress relentlessly causing significant morbidity and mortality. Vitamin supplements and pharmacological agents have been used in isolated cases and clinical trials, but the efficacy of these interventions is unclear. In spite of recent advances in the understanding of the pathogenesis of mitochondrial diseases, a cure remains elusive. An optimal cure would be gene therapy, which involves introducing the missing gene(s) into the mitochondria to complement the defect. Our recent research results indicate the feasibility of an innovative protein-transduction ("protofection") technology, consisting of a recombinant mitochondrial transcription factor A (TFAM) that avidly binds mtDNA and permits efficient targeting into mitochondria in situ and in vivo. Thus, the development of gene therapy for treating mitochondrial disease offers promise, because it may circumvent the clinical abnormalities and the current inability to treat individual disorders in affected individuals. This review aims to focus on current treatment options and future therapeutics in mitochondrial disease treatment with a special emphasis on Leber's hereditary optic neuropathy. PMID:23545042

  9. 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

  10. 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 example, by the combination of measuring optomotor reflex function with electroretinograms (ERGs) and optical coherence tomography (OCT) of the retina. These structure-function correlations invivo are urgently needed to identify disease mechanisms as potential new targets for drug development. Such a combination of the experimental assessment of the optokinetic reflex (OKR) or optomotor response (OMR) with other measures of retinal structure and function is especially valuable for research on GON. The chronic progression of the disease is characterized by a gradual decrease in function accompanied by a concomitant increase in structural damage to the retina, therefore the assessment of subtle changes is key to determining the success of novel intervention strategies. PMID:26144667

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

    PubMed Central

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

    2015-01-01

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

  12. 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

  13. [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 (ERG) did not show a significant difference either in the b wave or in the oscillatory potentials. The scotopic threshold response (STR) was significantly reduced 3 days after induction. These findings are similar to those of rNAION and indicate that we succeeded in reproducing the rNAION. Histopathologic examination in the acute phase of rNAION, showed acellular NFL swelling anterior to the optic disc. No accumulation of inflammatory cells was noted in several microscopic sections of the optic nerve. In addition, immunochemical staining was negative throughout the retina and optic nerve. These results suggested that the rNAION-induced NFL swelling was not a result of inflammation. In the chronic phase of rNAION, the morphologic retinal changes were apparent in only the retinal ganglion cell(RGC) layer, with a reduction in the number of cells in the RGC layer. Thus, we need to evaluate the degree of the NFL swelling in the acute phase and the following thinning of the NFL in the chronic phase for efficacy of the treatment of rNAION. Therefore, we used optical coherence tomography (OCT) for the objective and quantitative evaluation of the retinal nerve fiber layer (RNFL) thickness around the optic disc changes in rNAION. The second method was to use the STR for the evaluation of the RGC function. The third method was to count the number of surviving RGCs observed and photographed through the fluorescence microscope with the Fluorogold staining. A possible rationale for treatment of NAION is that dilation of the posterior ciliary artery (PCA) increases the blood flow to the optic nerve and could improve the optic nerve function. To clarify the vasodilatory effects of medications, we used in vitro isometric tension recording methods and examined the vasodilatory effects of bevacizumab as an anti-vascular endothelial growth factor (VEGF) antibody, methylprednisolone as a corticosteroid and sodium nitroprusside (SNP, a nitric oxide donor) as a vasodilator on high-K (potassium) solution-induced contraction in isolated rabbit PCA. Bevacizumab did not relax rabbit PCA. M

  14. Levodopa and Other Pharmacologic Interventions in Ischemic and Traumatic Optic Neuropathies and Amblyopia.

    PubMed

    Razeghinejad, M Reza; Nowroozzadeh, M Hossein; Eghbal, M Hossein

    2016-01-01

    The visual impairment in traumatic and ischemic optic neuropathy and amblyopia may be permanent. Hence, lots of efforts have been focused on neuroprotection. Dopamine is one of the suggested neuroprotective agents. Besides its important role in the brain, dopamine is found in various cell types of the retina, and is claimed to play a neuromodulator and neurotransmitter role there. The dopamine D1 receptor is the most highly expressed subtype of dopamine receptors, and its activation has been shown to be potentially neuroprotective against oxidative-stress damage in retinal neurons. Levodopa, a precursor of dopamine, can easily breach the blood-brain and blood-retinal barriers, and exerts effective dopaminergic responses in the brain and retina. This article summarizes and discusses the use of levodopa and other pharmacologic agents in the treatment of 3 groups of visual pathway disorders that primarily involve neuronal systems: ischemic optic neuropathy, traumatic optic neuropathy, and amblyopia. PMID:26757312

  15. 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.

  16. 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.

  17. 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

  18. Motor neuron disease and optic neuropathy after acute exposure to a methanol-containing solvent mixture.

    PubMed

    Chi, Adriano; Herrero Hernandez, Elena; Mora, Gabriele; Valentini, Consuelo; Discalzi, Gianluigi; Pira, Enrico

    2004-09-01

    A 34-years-old floor-layer developed optic neuropathy and motor neuron disease after being accidentally exposed to a solvent mixture containing methanol and other substances. Optic neuropathy is a complication of methanol poisoning, but the onset of a motor neuron disorder resembling amyotrophic lateral sclerosis after the exposure to these substances has not been previously described. The temporal onset of the clinical symptoms, biological plausibility, young age of the patient and absence of neurological disorders in the family history raises suspicion of a possible causative relationship. PMID:15512908

  19. Novel use of idebenone in Leber's hereditary optic neuropathy in Hong Kong.

    PubMed

    Cheng, S W; Ko, C H; Yau, S K; Mak, Chloe; Yuen, Y F; Lee, C Y

    2014-10-01

    We report a case of a young Chinese male presenting with sequential, painless, bilateral visual loss in Hong Kong. He was diagnosed to have Leber's hereditary optic neuropathy with genetic workup showing G11778A mutation with over 80% heteroplasmy. He was started on idebenone treatment 11 months after onset of the binocular disease. To our best knowledge, this is the first case of Leber's hereditary optic neuropathy treated with idebenone in Hong Kong. The recent evidence of the diagnosis and treatment of this devastating disease is reviewed. PMID:25307075

  20. Anterior ischemic optic neuropathy and branch retinal artery occlusion in cavernous sinus thrombosis.

    PubMed

    Gupta, A; Jalali, S; Bansal, R K; Grewal, S P

    1990-09-01

    A 60-year-old woman developed embolic occlusion of a branch retinal artery following septic cavernous sinus thrombosis. Two days later it was followed by loss of light perception due to embolic or vasculitic ischemic optic neuropathy. Recurrent emboli from a focus of carotid arteritis in cavernous sinus thrombosis may be responsible for visual loss in such eyes. PMID:2144537

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

    PubMed

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

    2015-10-01

    Glaucomatous optic neuropathy, an important neurodegenerative condition and the commonest optic neuropathy in humans, is the leading cause of irreversible blindness worldwide. Its prevalence and incidence increase exponentially with ageing and raised intraocular pressure (IOP). Using glaucomatous optic neuropathy as an exemplar for neurodegeneration, this study investigates putative factors imparting resistance to neurodegeneration. Systemic mitochondrial function, oxidative stress and vascular parameters were compared from isolated lymphocytes, whole blood and urine samples between 30 patients who have not developed the neuropathy despite being exposed for many years to very high IOP ('resistant'), 30 fast deteriorating glaucoma patients despite having low IOP ('susceptible'), and 30 age-similar controls. We found that 'resistant' individuals showed significantly higher rates of ADP phosphorylation by mitochondrial respiratory complexes I, II and IV, hyperpolarised mitochondrial membrane potential, higher levels of mitochondrial DNA, and enhanced capacity to deal with cytosolic calcium overload and exogenous oxidative stress, as compared to both controls and glaucoma patients. While it has been known for some years that mitochondrial dysfunction is implicated in neurodegeneration, this study provides a fresh perspective to the field of neurodegeneration by providing, for the first time, evidence that systemic mitochondrial efficiency above normal healthy levels is associated with an enhanced ability to withstand optic nerve injury. These results demonstrate the importance of cellular bioenergetics in glaucomatous disease progression, with potential relevance for other neurodegenerative disorders, and raise the possibility for new therapeutic targets in the field of neurodegeneration. PMID:26054436

  2. Morphometric Analysis and Classification of Glaucomatous Optic Neuropathy using Radial Polynomials

    PubMed Central

    Twa, Michael D.; Parthasarathy, Srinivasan; Johnson, Chris A.; Bullimore, Mark A.

    2011-01-01

    Purpose To quantify the morphological features of the optic nerve head using radial polynomials, to use these morphometric models as the basis for classification of glaucomatous optic neuropathy glaucomatous optic neuropathy via an automated decision tree induction algorithm, and to compare these classification results with established methods. Methods A cohort of patients with high-risk ocular hypertension or early glaucoma (n = 179) and a second cohort of normal subjects (n = 96) were evaluated for glaucomatous optic neuropathy using stereographic disc photography and confocal scanning laser tomography. Morphological features of the optic nerve head region were modeled from the tomography data using pseudo-Zernike radial polynomials and features derived from these models were used as the basis for classification by a decision tree induction algorithm. Decision tree classification performance was compared with expert classification of stereographic disc photos and analysis of neural retinal rim thickness by Moorfields Regression Analysis (MRA). Results Root mean squared (RMS) error of the morphometric models decreased asymptotically with additional polynomial coefficients, from 62 0.5 ?m (32 coefficients) to 32 5.7 ?m (256 coefficients). Optimal morphometric classification was derived from a subset of 64 total features and had low sensitivity (69%), high specificity (88%), very good accuracy (80%), and area under the ROC curve (AUROC) was 88% (95% CI = 78 to 98%). By comparison, MRA classification of the same records had a comparatively poorer sensitivity (55%), but had higher specificity (95%), with similar overall accuracy (78%) and AUROC curve, 83% (95 % CI = 70 to 96%). Conclusions Pseudo-Zernike radial polynomials provide a mathematically compact and faithful morphological representation of the structural features of the optic nerve head. This morphometric method of glaucomatous optic neuropathy classification has greater sensitivity, and similar overall classification performance (AUROC) when compared with classification by neural retinal rim thickness by MRA in patients with high-risk ocular hypertension and early glaucoma. PMID:21423035

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

    PubMed

    Zanssen, Stefanie; Buse, Gerhard

    2003-04-01

    Leber's hereditary optic neuropathy (LHON) is a bilateral subacute optic neuropathy caused by hereditary missense mutations of the mitochondrial genome. Primary mutations are located at nucleotide positions 11778, 3460, and 14484 in genes encoding subunits of complex I of the respiratory chain. It has been suggested that degenerative changes in the optic nerve might be mediated by apoptosis. Therefore, we hypothesized that patients affected with LHON might show altered sensitivity to cytotoxic drugs. Here we report the case of a LHON patient carrying the 11778 mutation who required chemotherapy for malignant lymphoma. Using in vitro assays, we found that the patient's peripheral blood mononuclear cells did not show altered vulnerability to cytotoxic drugs. The patient was treated with combination chemotherapy and consolidating radiotherapy, leading to complete remission without inappropriately severe acute or chronic side effects. These data indicate that the 11778 mutation does not change cellular response to cytotoxic drugs in a clinically apparent manner. PMID:12666138

  4. 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

  5. Behaviour of Disc Oedema During and After Amiodarone Optic Neuropathy: Case Report

    PubMed Central

    Martnez-Gamero, Bertha O.; Mohamed-Noriega, Jibran; Cavazos-Adame, Med. Humberto; Mohamed-Hamsho, Med. Jess

    2014-01-01

    A 73-year-old woman with atrial fibrillation treated with Amiodarone presented with Optic Disc oedema in right eye (OD). Using Optical Coherence Tomography (OCT) we describe the impact of this neuropathy on Retinal Nerve Fibre Layer (RNFL). At diagnosis RNFL average was of 188 ?m OD and 77 ?m in the left eye (OS), six months after discontinuation of the drug decreased to 40 ?m in OD and 76 ?m in OS. The RNFL average of OD presented a transient increase during the acute oedema that returned to normal levels during the first month after discontinuation of the drug and fell dramatically to 44 ?m at the second month and 40 ?m at the sixth month. We show there is axonal loss after amiodarone-associated optic neuropathy measured with OCT. The OCT may be used in these patients to document changes in RNFL in the follow-up. PMID:24959500

  6. Corticosteroid therapy in patients with non-arteritic anterior ischemic optic neuropathy.

    PubMed

    Vidović, Tomislav; Cerovski, Branimir; Perić, Sanja; Kordić, Rajko; Mrazovac, Danijela

    2015-03-01

    Non-arteritic anterior ischemic optic neuropathy is one of the most common conditions affecting the optic nerve in the elderly. It may lead to severe visual loss. Typical symptoms are painless impairment of visual function accompanied by relative afferent pupillary defect, edema of the optic disc and visual field defects. Aim is to present 38 patients with nonarteritic anterior ischemic optic neuropathy who were treated with corticosteroid therapy. This prospective study involved 38 patients, 20 men and 18 women aged 60-75 years who were treated with corticosteroid therapy. The study included patients with visual acuity in the affected eye from 0.1 to 0.8 according to Snellen. Every patient underwent clinical examination, the Octopus 900 perimetry in G program, laboratory testing, while the compressive optic neuropathy was rule out with MSCT of the brain and orbits. The most common forms of visual field defect are altitudinal defect and diffuse depression. Corticosteroid therapy led to recovery in 65% of patient, in 30% of patients did not change, while the deterioration occurred in 5% of patients. PMID:26040070

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

    PubMed

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

    2014-02-01

    Leber's hereditary optic neuropathy is a maternally inherited blinding disease caused as a result of homoplasmic point mutations in complex I subunit genes of mitochondrial DNA. It is characterized by incomplete penetrance, as only some mutation carriers become affected. Thus, the mitochondrial DNA mutation is necessary but not sufficient to cause optic neuropathy. Environmental triggers and genetic modifying factors have been considered to explain its variable penetrance. We measured the mitochondrial DNA copy number and mitochondrial mass indicators in blood cells from affected and carrier individuals, screening three large pedigrees and 39 independently collected smaller families with Leber's hereditary optic neuropathy, as well as muscle biopsies and cells isolated by laser capturing from post-mortem specimens of retina and optic nerves, the latter being the disease targets. We show that unaffected mutation carriers have a significantly higher mitochondrial DNA copy number and mitochondrial mass compared with their affected relatives and control individuals. Comparative studies of fibroblasts from affected, carriers and controls, under different paradigms of metabolic demand, show that carriers display the highest capacity for activating mitochondrial biogenesis. Therefore we postulate that the increased mitochondrial biogenesis in carriers may overcome some of the pathogenic effect of mitochondrial DNA mutations. Screening of a few selected genetic variants in candidate genes involved in mitochondrial biogenesis failed to reveal any significant association. Our study provides a valuable mechanism to explain variability of penetrance in Leber's hereditary optic neuropathy and clues for high throughput genetic screening to identify the nuclear modifying gene(s), opening an avenue to develop predictive genetic tests on disease risk and therapeutic strategies. PMID:24369379

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

    PubMed

    Angebault, Claire; Guichet, Pierre-Olivier; Talmat-Amar, Yasmina; Charif, Majida; Gerber, Sylvie; Fares-Taie, Lucas; Gueguen, Naig; Halloy, Franois; Moore, David; Amati-Bonneau, Patrizia; Manes, Gael; Hebrard, Maxime; Bocquet, Batrice; Quiles, Mlanie; Piro-Mgy, Camille; Teigell, Marisa; Delettre, Ccile; 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

    2015-11-01

    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

  9. Deferoxamine (Desferal)-induced toxic retinal pigmentary degeneration and presumed optic neuropathy.

    PubMed

    Lakhanpal, V; Schocket, S S; Jiji, R

    1984-05-01

    Eight patients (16 eyes) developed ocular toxicity while undergoing intravenous deferoxamine mesylate (Desferal) chelation therapy for transfusional hemosiderosis. Presenting symptoms included decreased visual acuity, color vision abnormalities, and night blindness. Six patients presented as presumed retrobulbar optic neuropathy demonstrating central scotomas and color vision abnormalities. The remaining two patients presented with pigmentary changes confined either to the macula or equator. Following cessation of therapy, vision improved in all but four eyes, which did not attain their pretreatment visual acuity. Optic neuropathy resolved in all cases. However, follow-up revealed development of retinal pigmentary degeneration in seven patients, involving the macula in six and the equatorial retina in one. Fluorescein angiography and electrophysiological tests suggested toxicity at the level of retinal pigment epithelium and photoreceptors. PMID:6739047

  10. Mitochondrial optic neuropathies: our travels from bench to bedside and back again.

    PubMed

    Sadun, Alfredo A; La Morgia, Chiara; Carelli, Valerio

    2013-01-01

    The standard scientific method requires that you make an interesting observation, generate a hypothesis and then design an experiment to test the hypothesis. In ophthalmology, as in most fields of medicine, the observations and hypotheses tend to have more degrees of freedom, and the interpretation of experiments is also more complicated and often indeterminate. But sometimes it works out, going back and forth from bench to bedside to bench, in reiterative cycles. A successful example of alternating bench and bedside studies was presented (AAS) at the 2012 Alper Memorial given at the Washington Hospital Medical Center, illustrating a series of questions and investigations that pertain to mitochondrial optic neuropathies, beginning two decades ago, before the concept of mitochondrial optic neuropathies had much meaning. Basic science questions are often best answered by that extraordinary experiment of nature that we call clinical disease, and clinical questions are often best tested in the laboratory. PMID:23433229

  11. Motor and functional evaluation of patients with spastic paraplegia, optic atrophy, and neuropathy (SPOAN).

    PubMed

    Graciani, Zodja; Santos, Silvana; Macedo-Souza, Lucia Ins; Monteiro, Carlos Bandeira de Mello; Veras, Maria Isabel; Amorim, Simone; Zatz, Mayana; Kok, Fernando

    2010-02-01

    Spastic paraplegia, optic atrophy, and neuropathy (SPOAN) is an autosomal recessive complicated form of hereditary spastic paraplegia, which is clinically defined by congenital optic atrophy, infancy-onset progressive spastic paraplegia and peripheral neuropathy. In this study, which included 61 individuals (age 5-72 years, 42 females) affected by SPOAN, a comprehensive motor and functional evaluation was performed, using modified Barthel index, modified Ashworth scale, hand grip strength measured with a hydraulic dynamometer and two hereditary spastic paraplegia scales. Modified Barthel index, which evaluate several functional aspects, was more sensitive to disclose disease progression than the spastic paraplegia scales. Spasticity showed a bimodal distribution, with both grades 1 (minimum) and 4 (maximum). Hand grip strength showed a moderate inverse correlation with age. Combination of early onset spastic paraplegia and progressive polyneuropathy make SPOAN disability overwhelming. PMID:20339643

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

    PubMed Central

    Monge, Katia Sotelo; Glvez-Ruiz, Alberto; Alvrez-Carrn, Alberto; Quijada, Csar; 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

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

    PubMed

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

    2012-12-01

    An animal model of Leber hereditary optic neuropathy (LHON) was produced by introducing the human optic atrophy mtDNA ND6 P25L mutation into the mouse. Mice with this mutation exhibited reduction in retinal function by elecroretinogram (ERG), age-related decline in central smaller caliber optic nerve fibers with sparing of larger peripheral fibers, neuronal accumulation of abnormal mitochondria, axonal swelling, and demyelination. Mitochondrial analysis revealed partial complex I and respiration defects and increased reactive oxygen species (ROS) production, whereas synaptosome analysis revealed decreased complex I activity and increased ROS but no diminution of ATP production. Thus, LHON pathophysiology may result from oxidative stress. PMID:23129651

  14. Mouse mtDNA mutant model of Leber hereditary optic neuropathy

    PubMed Central

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

    2012-01-01

    An animal model of Leber hereditary optic neuropathy (LHON) was produced by introducing the human optic atrophy mtDNA ND6 P25L mutation into the mouse. Mice with this mutation exhibited reduction in retinal function by elecroretinogram (ERG), age-related decline in central smaller caliber optic nerve fibers with sparing of larger peripheral fibers, neuronal accumulation of abnormal mitochondria, axonal swelling, and demyelination. Mitochondrial analysis revealed partial complex I and respiration defects and increased reactive oxygen species (ROS) production, whereas synaptosome analysis revealed decreased complex I activity and increased ROS but no diminution of ATP production. Thus, LHON pathophysiology may result from oxidative stress. PMID:23129651

  15. 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

  16. 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; Lnnqvist, 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

  17. Novel C12orf65 mutations in patients with axonal neuropathy and optic atrophy

    PubMed Central

    Tucci, Arianna; Liu, Yo-Tsen; Preza, Elisabeth; Pitceathly, Robert D S; Chalasani, Annapurna; Plagnol, Vincent; Land, John M; Trabzuni, Daniah; Ryten, Mina; Jaunmuktane, Zane; Reilly, Mary M; Brandner, Sebastian; Hargreaves, Iain; Hardy, John; Singleton, Andrew B; Abramov, Andrey Y; Houlden, Henry

    2014-01-01

    Objective Charcot-Marie Tooth disease (CMT) forms a clinically and genetically heterogeneous group of disorders. Although a number of disease genes have been identified for CMT, the gene discovery for some complex form of CMT has lagged behind. The association of neuropathy and optic atrophy (also known as CMT type 6) has been described with autosomaldominant, recessive and X-linked modes of inheritance. Mutations in Mitofusin 2 have been found to cause dominant forms of CMT6. Phosphoribosylpyrophosphate synthetase-I mutations cause X-linked CMT6, but until now, mutations in the recessive forms of disease have never been identified. Methods We here describe a family with three affected individuals who inherited in an autosomal recessive fashion a childhood onset neuropathy and optic atrophy. Using homozygosity mapping in the family and exome sequencing in two affected individuals we identified a novel protein-truncating mutation in the C12orf65 gene, which encodes for a protein involved in mitochondrial translation. Using a variety of methods we investigated the possibility of mitochondrial impairment in the patients cell lines. Results We described a large consanguineous family with neuropathy and optic atrophy carrying a loss of function mutation in the C12orf65 gene. We report mitochondrial impairment in the patients cell lines, followed by multiple lines of evidence which include decrease of complex V activity and stability (blue native gel assay), decrease in mitochondrial respiration rate and reduction of mitochondrial membrane potential. Conclusions This work describes a mutation in the C12orf65 gene that causes recessive form of CMT6 and confirms the role of mitochondrial dysfunction in this complex axonal neuropathy. PMID:24198383

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

    PubMed

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

    2013-12-01

    Inherited optic atrophy must be considered when working up any optic nerve involvement and any systemic disease with signs of optic atrophy, even with a negative family history. There are two classical forms: dominant optic atrophy, characterized by insidious, bilateral, slowly progressive visual loss and temporal disc pallor, and Leber's optic atrophy, characterized by acute loss of central vision followed by the same event in the fellow eye within a few weeks to months, with disc hyperemia in the acute phase. Family history is critical for diagnosis. In the absence of family history, the clinician must rule out an identifiable acquired cause, i.e. toxic, inflammatory, perinatal injury, traumatic or tumoral, with orbital and brain imaging (MRI). Recessive optic atrophies are more rare and more severe and occur as part of multisystemic disorders, particularly Wolfram syndrome (diabetes mellitus, diabetes insipidus, and hearing loss). Effective treatments are limited; alcohol and smoking should be avoided. A cyclosporine trial (taken immediately upon visual loss in the first eye) is in progress in Leber's optic atrophy to prevent involvement of the fellow eye. PMID:24161764

  19. 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

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

    PubMed

    Berrozpe-Villabona, C; Santos-Bueso, E; Baeros-Rojas, P; Aguilar Munoa, S; Saenz-Francs, F; Daz-Valle, D; Martnez-de-la-Casa, J M; Garca-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

  1. 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

  2. [Past, present, and future in Leber's hereditary optic neuropathy].

    PubMed

    Oguchi, Y

    2001-12-01

    Leber's disease is a disease of optic atrophy first reported by Theodor Leber in 1871. Since then, 130 years have passed. Recently, several new findings about the pathology, causes, and heredity of this disease have been made. In 1988 Wallace and others reported a new mutation of 11778 base pairs of mtDNA of patients with Leber's disease. Since then, the study of this disease has progressed remarkably. In this review clinical studies on Leber's disease which were carried out in our department from 1990 are summarized. 1. Genetic diagnosis and clinics Two hundred and twenty-four cases were examined, including patients at our hospital, for the 8 years between 1990 and 1998. Among them, 72 cases were diagnosed as Leber's disease. There were 3 cases (4%) of 3460 mutations, 63 cases(83%) of 11778 mutations, and 6 cases(8%) of 14484 mutations as primary mutations. The reasons for performing the genetic diagnosis were mostly the need for a definite diagnosis of Leber's disease and research on the genesis of optic nerve atrophy of unknown origin. Concerning the secondary mutations, it was confirmed that these mutations were polymorphic as seen in European and American patients. There is a problem of heteroplasmy about the mtDNA mutation. We developed a simple and exact method to evaluate heteroplasmy by using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). In a study of peripheral blood samples in one family, Leber's disease does not appear under conditions of less than 60% mtDNA mutation. As for the three kinds of mutation in Leber's disease, cases of recovery of a visual acuity of 0.3 and above were only 7% in 11778 mutations, but 38% in 3460 mutations and 50% in 14484 mutations. It is assumed that visual prognosis depends on the kind of mutation. 2. Characteristics of visual evoked potential(VEP) In pattern VEP in the acute stage, latency was not delayed very much, but the amplitude was low. On the other hand, in the acute stage of optic neuritis, the latency was very much delayed and the amplitude was diminished. Therefore, I deduced that not only demyelination of the optic nerve fibers but also papilla-macula bundle defects may play an important role. In flash VEP, only the amplitude was low, but latency was normal. 3. Image analysis of the optic nerve In high resolution T2-weighted fast spin-echo magnetic resonance imaging(MRI), the image of the optic nerve can be clearly demonstrated within a short operation time. In MRI in the acute stage of Leber's disease, the image of the optic nerve appeared almost normal. But in the course of time, patients with Leber's disease showed markedly high signals in the optic nerve on the T2-weighted fast spin-echo MRI, and in the atrophic stage the image of the optic nerve showed thinning. The results in this study support the hypothesis that a primary lesion in Leber's disease may be intraocular. 4. Possibility of therapy at the present time The effectiveness of using idebenone combined with vitamin B2, vitamin C, and isopropyl unoprostone(Rescula) for recovery of the circulation of the optic nerve head for patients in the acute stage was compared with untreated patients. In patients with visual acuity of 0.3 and more, there was no statistical difference between the two groups. The recovery interval up to 0.3 was significantly shorter in the treated group than in the untreated group. I suggest that this kind of treatment may aid spontaneous recovery. Among 15 cases of Leber's disease which occurred in the patients teens, at least one eye in 8 cases(53%) recovered to 0.3 or more. Among the 8 recovered cases, 5 cases were from the treated group. On the other hand, 6 cases were treated and 5 cases recovered visual acuity. It is said that the patients developing the disease at younger ages have a tendency toward visual recovery. Pharmacological treatment can aid recovery. 5. Visual function after the recovery of visual acuity The recovery of visual acuity in Leber's disease has the characteristics of fenestrated central scotoma. The visual acuity can be recovere

  3. Design and synthesis of novel hybrid sydnonimine and prodrug useful for glaucomatous optic neuropathy.

    PubMed

    Acharya, Suchismita; Rogers, Preston; Krishnamoorthy, Raghu R; Stankowska, Dorota L; Dias, H V Rasika; Yorio, Thomas

    2016-03-01

    Synthesis and bioactivity of novel dual acting nitric oxide releasing and reactive oxygen scavenging hybrid compound SA-2 is described. The hybrid molecule SA-2 significantly increased the superoxide dismutase enzyme level and protected the photoreceptor cells from H2O2 induced oxidative stress. Synthesis of ocular esterase sensitive aceloxy alkyl carbamate prodrug SA-4 with improved aqueous half-life is achieved to aid topical ocular formulation. This class of hybrid molecule and prodrug may have dual potential of improved IOP lowering and neuroprotection in glaucomatous optic neuropathy. PMID:26832784

  4. 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.

  5. [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

  6. 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

  7. 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

  8. VZV multifocal vasculopathy with ischemic optic neuropathy, acute retinal necrosis and temporal artery infection in the absence of zoster rash.

    PubMed

    Mathias, Marc; Nagel, Maria A; Khmeleva, Nelly; Boyer, Philip J; Choe, Alexander; Durairaj, Vikram D; Bennett, Jeffrey L; Mandava, Naresh; Gilden, Don

    2013-02-15

    We describe a 54-year-old diabetic woman who developed ischemic optic neuropathy followed by acute retinal necrosis and multiple areas of focal venous beading. Vitreous fluid contained amplifiable VZV DNA but not HSV-1, CMV or toxoplasma DNA. The clinical presentation was remarkable for jaw claudication and intermittent scalp pain, prompting a temporal artery biopsy that was pathologically negative for giant cell arteritis, but notable for VZV antigen. The current case adds to the clinical spectrum of multifocal VZV vasculopathy. The development of acute VZV retinal necrosis after ischemic optic neuropathy supports the notion that vasculitis is an important additional mechanism in the development of VZV retinal injury. PMID:23312850

  9. 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

  10. Optic neuropathy in systemic lupus erythematosus and antiphospholipid syndrome (APS): clinical features, pathogenesis, review of the literature and proposed ophthalmological criteria for APS diagnosis.

    PubMed

    Giorgi, D; Balacco Gabrieli, C

    1999-01-01

    Optic neuropathy is a well-known ocular manifestation occurring in patients with systemic lupus erythematosus (SLE), and it remains one of the major causes of blindness in these patients. We report data from six SLE patients with optic neuropathy, one of whom was considered to have antiphospholipid syndrome (APS). This patient had monolateral optic neuropathy, whereas the other five SLE patients had bilateral optic nerve disease. We believe that the monolateral occurrence of optic neuropathy in our patient can be considered as a 'focal' neurological disease due to a thrombotic event involving the ciliary vasculature. Conversely, bilateral optic nerve damage in SLE could be considered to be a 'general' neurological disease due to different immunological mechanisms, such as vasculitis. Additionally, the literature on SLE patients affected by optic neuropathy is reviewed to evaluate the major clinical features, particularly neurological features. In reviewing the literature, it appears that bilateral optic neuropathy in SLE occurs more frequently than monolateral optic neuropathy, and the main neurological manifestation seen in these patients is transverse myelitis, particularly in SLE patients with bilateral optic nerve disease. Finally, we propose a clinico-ophthalmological spectrum of APS and outline the ocular clinical manifestations that can be considered as diagnostic for the syndrome. PMID:10357117

  11. Auditory Neuropathy

    MedlinePLUS

    ... Health Info Hearing, Ear Infections, and Deafness Auditory Neuropathy On this page: What is auditory neuropathy? What ... can I get additional information? What is auditory neuropathy? Auditory neuropathy is a hearing disorder in which ...

  12. 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 ...

  13. 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 ...

  14. 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

  15. Axonal degeneration in peripheral nerves in a case of Lebers Hereditary Optic Neuropathy

    PubMed Central

    Mnatsakanyan, Lilit; Ross-Cisneros, Fred N.; Carelli, Valerio; Wang, Michelle Y.; Sadun, Alfredo A.

    2010-01-01

    Background Lebers hereditary optic neuropathy (LHON) is a mitochondrial DNA (mtDNA) genetic disorder characterized by profound bilateral loss of central vision due to selective loss of retinal ganglion cells. Most patients with LHON do not have complaints related to the peripheral nervous system. We investigated possible qualitative and quantitative histological changes in the peripheral nerve of a patient with LHON as compared to normal controls. Methods Brachial plexus specimens were obtained at necropsy from an LHON patient carrying the 3460/ND1 mtDNA mutation and age-matched controls without known history of neurological disease. The nerves were evaluated by light microscopy coupled to a digital camera based morphometric analysis and electron microscopy. Results Extensive axonal degeneration of the large heavily myelinated fibers was found in the brachial plexus from the LHON patient. In LHON nerve fascicles we counted over ten times as many degenerated profiles as found in control nerve fascicles. Conclusion Microscopic examination of the brachial plexus in this LHON patient clearly demonstrated a significant pattern of neurodegeneration. Our study suggests that peripheral neuropathy may be a subclinical feature associated with LHON. PMID:21139512

  16. 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.

  17. 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.

  18. High incidence of pre-excitation syndrome in Japanese families with Leber's hereditary optic neuropathy.

    PubMed

    Mashima, Y; Kigasawa, K; Hasegawa, H; Tani, M; Oguchi, Y

    1996-12-01

    Cardiac conduction abnormalities have been reported in families with Leber's hereditary optic neuropathy (LHON). The pre-excitation syndrome Wolff-Parkinson-White syndrome or Lown-Ganong-Levine syndrome, is reportedly common in Finns with LHON, being seen in 14 (9%) of the 163 individuals with mitochondrial DNA (mtDNA) mutations. While this syndrome is thought to be rare in other ethnic groups with LHON, the present study of 35 Japanese LHON families confirmed that it is also relatively common among Japanese families, being seen in 5 (8%) of the 63 individuals with mtDNA mutations. It remains to be determined whether the high incidence of the pre-excitation syndrome in Finnish and Japanese LHON families is due to a particular genetic composition of ethnic groups such as in Finland and in Japan, or only to a reporting bias. PMID:9147893

  19. Crystallins are regulated biomarkers for monitoring topical therapy of glaucomatous optic neuropathy.

    PubMed

    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-?b2. 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

  20. 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-?b2. 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

  1. 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

  2. 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

  3. 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.

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

    PubMed

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

    2014-04-01

    IMPORTANCE We developed a novel strategy for treatment of Leber hereditary optic neuropathy (LHON) caused by a mutation in the nicotinamide adenine dinucleotide dehydrogenase subunit IV (ND4) mitochondrial gene. OBJECTIVE To demonstrate the safety and effects of the gene therapy vector to be used in a proposed gene therapy clinical trial. DESIGN AND SETTING In a series of laboratory experiments, we modified the mitochondrial ND4 subunit of complex I in the nuclear genetic code for import into mitochondria. The protein was targeted into the organelle by agency of a targeting sequence (allotopic expression). The gene was packaged into adeno-associated viral vectors and then vitreally injected into rodent, nonhuman primate, and ex vivo human eyes that underwent testing for expression and integration by immunohistochemical analysis and blue native polyacrylamide gel electrophoresis. During serial follow-up, the animal eyes underwent fundus photography, optical coherence tomography, and multifocal or pattern electroretinography. We tested for rescue of visual loss in rodent eyes also injected with a mutant G11778A ND4 homologue responsible for most cases of LHON. EXPOSURE Ocular infection with recombinant adeno-associated viral vectors containing a wild-type allotopic human ND4 gene. MAIN OUTCOMES AND MEASURES Expression of human ND4 and rescue of optic neuropathy induced by mutant human ND4. RESULTS We found human ND4 expressed in almost all mouse retinal ganglion cells by 1 week after injection and ND4 integrated into the mouse complex I. In rodent eyes also injected with a mutant allotopic ND4, wild-type allotopic ND4 prevented defective adenosine triphosphate synthesis, suppressed visual loss, reduced apoptosis of retinal ganglion cells, and prevented demise of axons in the optic nerve. Injection of ND4 in the ex vivo human eye resulted in expression in most retinal ganglion cells. Primates undergoing vitreal injection with the ND4 test article and followed up for 3 months had no serious adverse reactions. CONCLUSIONS AND RELEVANCE Expression of our allotopic ND4 vector in the ex vivo human eye, safety of the test article, rescue of the LHON mouse model, and the severe irreversible loss of visual function in LHON support clinical testing with mutated G11778A mitochondrial DNA in our patients. PMID:24457989

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

    PubMed Central

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

    2014-01-01

    IMPORTANCE We developed a novel strategy for treatment of Leber hereditary optic neuropathy (LHON) caused by a mutation in the nicotinamide adenine dinucleotide dehydrogenase subunit IV (ND4) mitochondrial gene. OBJECTIVE To demonstrate the safety and effects of the gene therapy vector to be used in a proposed gene therapy clinical trial. DESIGN AND SETTING In a series of laboratory experiments, we modified the mitochondrial ND4 subunit of complex I in the nuclear genetic code for import into mitochondria. The protein was targeted into the organelle by agency of a targeting sequence (allotopic expression). The gene was packaged into adeno-associated viral vectors and then vitreally injected into rodent, nonhuman primate, and ex vivo human eyes that underwent testing for expression and integration by immunohistochemical analysis and blue native polyacrylamide gel electrophoresis. During serial follow-up, the animal eyes underwent fundus photography, optical coherence tomography, and multifocal or pattern electroretinography. We tested for rescue of visual loss in rodent eyes also injected with a mutant G11778A ND4 homologue responsible for most cases of LHON. EXPOSURE Ocular infection with recombinant adeno-associated viral vectors containing a wild-type allotopic human ND4 gene. MAIN OUTCOMES AND MEASURES Expression of human ND4 and rescue of optic neuropathy induced by mutant human ND4. RESULTS We found human ND4 expressed in almost all mouse retinal ganglion cells by 1 week after injection and ND4 integrated into the mouse complex I. In rodent eyes also injected with a mutant allotopic ND4, wild-type allotopic ND4 prevented defective adenosine triphosphate synthesis, suppressed visual loss, reduced apoptosis of retinal ganglion cells, and prevented demise of axons in the optic nerve. Injection of ND4 in the ex vivo human eye resulted in expression in most retinal ganglion cells. Primates undergoing vitreal injection with the ND4 test article and followed up for 3 months had no serious adverse reactions. CONCLUSIONS AND RELEVANCE Expression of our allotopic ND4 vector in the ex vivo human eye, safety of the test article, rescue of the LHON mouse model, and the severe irreversible loss of visual function in LHON support clinical testing with mutated G11778A mitochondrial DNA in our patients. PMID:24457989

  6. 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

  7. 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 of ...

  8. 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 ...

  9. Indirect traumatic optic neuropathy--retrospective interventional case series from a tertiary care center in eastern Nepal.

    PubMed

    Das, H; Badhu, B P; Gautam, M A

    2007-01-01

    To report the demography, nature of insult and ocular characteristics in patients presenting with indirect traumatic optic neuropathy and to evaluate the visual outcome with mega dose methylprednisolone therapy. Retrospective hospital data analysis of all patients admitted with indirect traumatic optic neuropathy and treated with mega dose methylprednisolone therapy in the last three years was conducted. Nine patients (M:F= 8:1) were identified with unilateral optic nerve injury. Road traffic injury was the most common cause of injury. Lid ecchymosis and swelling on the same side was the most frequent ocular abnormality noted, followed by loss of consciousness. Time of presentation varied from 3 hours to 11 days. All patients except two had visual acuity of no light perception at presentation. Following therapy there was improvement in visual acuity in two patients who presented within two days of injury. Patients present late with traumatic optic neuropathy in this hospital. Most of the patients are with no light perception. High dose steroids was found to be beneficial only in patients presenting early (

  10. Clinical Efficacy Observation of Acupuncture Treatment for Nonarteritic Anterior Ischemic Optic Neuropathy

    PubMed Central

    Qin, Yali; Yuan, Wei; Deng, Hui; Xiang, Zhanmei; Yang, Chao; Kou, Xinyun; Yang, Shufei; Wang, Zhijun; Jin, Ming

    2015-01-01

    Objective. To determine whether acupuncture treatment impacts the clinical efficacy of degenerative damage of the optic nerve caused by nonarteritic anterior ischemic optic neuropathy (NAION). Methods. 69 patients (93 eyes) with NAION who had been treated by acupuncture which is performed on different acupoints related to eyes by vertical insertion or Fingernail-pressure needle insertion. The best corrected visual acuity, mean defect (MD) and mean light sensitivity (MS) of the visual field, and latency and amplitude of pattern visual evoked potential (P-VEP) were compared before and after treatment. Results. After 2, 4, and 8 weeks of treatment, the total effective rates of visual acuity improvement were 74.19%, 78.89%, and 81.71%, respectively, and the decreased MD and increased MS were both statistically significant (P < 0.01). When compared with the situation before treatment, the average latency of the P100 wave was significantly reduced (P < 0.05), and the average amplitude was improved with no statistically significant difference (P > 0.05). Conclusions. Acupuncture treatment could obviously improve the visual function of patients with NAION and be used as complementary and alternative therapy in clinic. PMID:26089945

  11. 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

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

    PubMed Central

    Koilkonda, Rajeshwari D.; Guy, John

    2011-01-01

    Leber's hereditary optic neuropathy (LHON) is a maternally transmitted disorder caused by point mutations in mitochondrial DNA (mtDNA). Most cases are due to mutations in genes encoding subunits of the NADH-ubiquinone oxidoreductase that is Complex I of the electron transport chain (ETC). These mutations are located at nucleotide positions 3460, 11778, or 14484 in the mitochondrial genome. The disease is characterized by apoplectic, bilateral, and severe visual loss. While the mutated mtDNA impairs generation of ATP by all mitochondria, there is only a selective loss of retinal ganglion cells and degeneration of optic nerve axons. Thus, blindness is typically permanent. Half of the men and 10% of females who harbor the pathogenic mtDNA mutation actually develop the phenotype. This incomplete penetrance and gender bias is not fully understood. Additional mitochondrial and/or nuclear genetic factors may modulate the phenotypic expression of LHON. In a population-based study, the mtDNA background of haplogroup J was associated with an inverse relationship of low-ATP generation and increased production of reactive oxygen species (ROS). Effective therapy for LHON has been elusive. In this paper, we describe the findings of pertinent published studies and discuss the controversies of potential strategies to ameliorate the disease. PMID:21253496

  13. 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 ...

  14. High frequency of mutations at position 11778 in mitochondrial ND4 gene in Japanese families with Leber's hereditary optic neuropathy.

    PubMed

    Mashima, Y; Hiida, Y; Oguchi, Y; Kudoh, J; Shimizu, N

    1993-08-01

    We have investigated the presence of a point mutation at position 11778 in the ND4 gene of mitochondrial DNA in 17 Japanese families with Leber's hereditary optic neuropathy (LHON), and have identified the mutation in 14 (82.4%) of the 17 families. The prevalence of this mutation appears to be much higher in Japanese patients with LHON than in patients of other ethnic origins, such as Finnish, Dutch, German, and English families. PMID:8103501

  15. A novel CISD2 intragenic deletion, optic neuropathy and platelet aggregation defect in Wolfram syndrome type 2

    PubMed Central

    2014-01-01

    Background Wolfram Syndrome type 2 (WFS2) is considered a phenotypic and genotypic variant of WFS, whose minimal criteria for diagnosis are diabetes mellitus and optic atrophy. The disease gene for WFS2 is CISD2. The clinical phenotype of WFS2 differs from WFS1 for the absence of diabetes insipidus and psychiatric disorders, and for the presence of bleeding upper intestinal ulcers and defective platelet aggregation. After the first report of consanguineous Jordanian patients, no further cases of WFS2 have been reported worldwide. We describe the first Caucasian patient affected by WFS2. Case presentation The proband was a 17 year-old girl. She presented diabetes mellitus, optic neuropathy, intestinal ulcers, sensorineural hearing loss, and defective platelet aggregation to ADP. Genetic testing showed a novel homozygous intragenic deletion of CISD2 in the proband. Her brother and parents carried the heterozygous mutation and were apparently healthy, although they showed subclinical defective platelet aggregation. Long runs of homozygosity analysis from SNP-array data did not show any degree of parental relationship, but the microsatellite analysis confirmed the hypothesis of a common ancestor. Conclusion Our patient does not show optic atrophy, one of the main diagnostic criteria for WFS, but optic neuropathy. Since the “asymptomatic” optic atrophy described in Jordanian patients is not completely supported, we could suppose that the ocular pathology in Jordanian patients was probably optic neuropathy and not optic atrophy. Therefore, as optic atrophy is required as main diagnostic criteria of WFS, it might be that the so-called WFS2 could not be a subtype of WFS. In addition, we found an impaired aggregation to ADP and not to collagen as previously reported, thus it is possible that different experimental conditions or inter-patient variability can explain different results in platelet aggregation. Further clinical reports are necessary to better define the clinical spectrum of this syndrome and to re-evaluate its classification. PMID:25056293

  16. Retinal Ganglion Cell Dysfunction in Asymptomatic G11778A: Leber Hereditary Optic Neuropathy

    PubMed Central

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

    2014-01-01

    Purpose. To report the serial evaluation of asymptomatic eyes of subjects with mutated G11778A mitochondrial DNA. Methods. Forty-five asymptomatic G11778A Leber hereditary optic neuropathy (LHON) carriers and two patients with the mutation who developed unilateral visual loss underwent testing that included visual acuity, automated visual field, pattern electroretinogram (PERG), and spectral-domain optical coherence tomography every 6 months between September 2008 and March 2012. Results. Visual acuity, visual fields, and retinal nerve fiber layer thickness remained stable within the normal range. Mean PERG amplitudes of carriers dropped progressively by ?40% from baseline to 36 months. In addition, comparisons with the fellow eyes of patients with unilateral optic neuritis revealed a 3.4 ETDRS (Early Treatment Diabetic Retinopathy Study) letter loss in the LHON carriers. A single carrier developed visual loss, with PERG amplitudes dropping by half. In one of two LHON cases who presented with unilateral visual loss, visual acuity in the asymptomatic eye was ?20/40 at baseline. The PERG amplitude of this eye was reduced to ?30% of normal. Six months later, his visual acuity had dropped to ?20/500. A second patient who was ?20/20 and had a visual field defect in the asymptomatic eye at baseline remained at this level for the 18 months of follow-up. His PERG amplitudes were similar to those of asymptomatic carriers, with 0.78 ?V at baseline that did not decline with follow-up. Conclusions. Declines of the PERG amplitude suggest subclinical retinal ganglion cell dysfunction in asymptomatic G11778A subjects, which is progressive. PMID:24398093

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

    SciTech Connect

    Liang, Min; Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 ; Guan, Minqiang; Zhao, Fuxing; Zhou, Xiangtian; Yuan, Meixia; Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 ; Tong, Yi; The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350005 ; Yang, Li; Wei, Qi-Ping; Sun, Yan-Hong; Lu, Fan; Qu, Jia; Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 ; 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.

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

    SciTech Connect

    Zhao, Fuxin; Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 ; Guan, Minqiang; Zhou, Xiangtian; Yuan, Meixia; Liang, Ming; Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 ; Liu, Qi; Liu, Yan; Zhang, Yongmei; Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 ; Yang, Li; Tong, Yi; The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350005 ; Wei, Qi-Ping; Sun, Yan-Hong; Qu, Jia; Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 ; 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.

  19. 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.

  20. 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; Kker, 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

  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. 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 2.473.97 per 100,000), and the minimum point prevalence for mtDNA LHON mutations was 11.82 per 100,000 (95% CI 10.3813.27 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

  3. 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.

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

    PubMed Central

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

    2014-01-01

    We present the case of a 19-year-old female with a history of Down syndrome (DS) who was referred to our neuro-ophthalmology clinic for evaluation of Leber's hereditary optic neuropathy (LHON). The patient's family history was significant for a known G11778A mutation in a maternal relative, consistent with LHON. The patient was also positive for the G11778A mutation; however, the genotype demonstrated low penetrance in the pedigree, with only 1 out of 10 adult male offspring showing signs or symptoms of the disease. Mitochondrial mutations implicated in LHON have been shown to impair complex I of the electron transport chain and thereby reducing the effective generation of adenosine triphosphate and increasing the production of toxic reactive oxygen species. Although the partial or complete triplicate of chromosome 21 constitutes the etiology of DS, some of the pleiotropic phenotypes of the syndrome have been attributed to oxidative stress and mitochondrial dysfunction. Given the low penetrance of the mutation and the patient's sex, this case illustrates the possibility that the mitochondrial mutation demonstrated increased penetrance due to pre-existing mitochondrial dysfunction related to DS. PMID:25566062

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

    PubMed

    Jan?i?, Jasna; Dejanovi?, Ivana; Radovanovi?, Saa; Ostoji?, Jelena; Kozi?, Duko; ?uri?-Jovi?i?, Milica; Samardi?, Janko; ?etkovi?, Mila; Kosti?, Vladimir

    2016-01-01

    We are presenting two Leber's hereditary optic neuropathy (LHON) pedigrees with abnormal magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (H-MRS) findings but without neurological manifestation associated with LHON. The study included 14 LHON patients and 41 asymptomatic family members from 12 genealogically unrelated families. MRI showed white matter involvement and H-MRS exhibited metabolic anomalies within 12 LHON families. Main outcome measures were abnormal MRI and H-MRS findings in two pedigrees. MRI of the proband of the first pedigree showed a single demyelinating lesion in the right cerebellar hemisphere, while the proband of the second family displayed multiple supratentorial and infratentorial lesions, compatible with the demyelinating process, and both the absolute choline (Cho) concentration and Cho/creatinine ratio were increased. MRI and H-MRS profiles of both affected and unaffected mitochondrial DNA mutation carriers suggest more widespread central nervous involvement in LHON. Although even after 12 years our patients did not develop neurological symptoms, MRI could still be used to detect possible changes during the disease progression. PMID:26540208

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

    PubMed

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

    2014-09-01

    We present the case of a 19-year-old female with a history of Down syndrome (DS) who was referred to our neuro-ophthalmology clinic for evaluation of Leber's hereditary optic neuropathy (LHON). The patient's family history was significant for a known G11778A mutation in a maternal relative, consistent with LHON. The patient was also positive for the G11778A mutation; however, the genotype demonstrated low penetrance in the pedigree, with only 1 out of 10 adult male offspring showing signs or symptoms of the disease. Mitochondrial mutations implicated in LHON have been shown to impair complex I of the electron transport chain and thereby reducing the effective generation of adenosine triphosphate and increasing the production of toxic reactive oxygen species. Although the partial or complete triplicate of chromosome 21 constitutes the etiology of DS, some of the pleiotropic phenotypes of the syndrome have been attributed to oxidative stress and mitochondrial dysfunction. Given the low penetrance of the mutation and the patient's sex, this case illustrates the possibility that the mitochondrial mutation demonstrated increased penetrance due to pre-existing mitochondrial dysfunction related to DS. PMID:25566062

  7. Targeting estrogen receptor ? as preventive therapeutic strategy for Leber's hereditary optic neuropathy.

    PubMed

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

    2015-12-15

    Leber's hereditary optic neuropathy (LHON) is a maternally inherited blinding disease characterized by degeneration of retinal ganglion cells (RGCs) and consequent optic nerve atrophy. Peculiar features of LHON are incomplete penetrance and gender bias, with a marked male prevalence. Based on the different hormonal metabolism between genders, we proposed that estrogens play a protective role in females and showed that these hormones ameliorate mitochondrial dysfunction in LHON through the estrogen receptors (ERs). We also showed that ER? localize to the mitochondria of RGCs. Thus, targeting ER? may become a therapeutic strategy for LHON specifically aimed at avoiding or delaying the onset of disease in mutation carriers. Here, we tested the effects of ER? targeting on LHON mitochondrial defective metabolism by treating LHON cybrid cells carrying the m.11778G>A mutation with a combination of natural estrogen-like compounds that bind ER? with high selectivity. We demonstrated that these molecules improve cell viability by reducing apoptosis, inducing mitochondrial biogenesis and strongly reducing the levels of reactive oxygen species in LHON cells. These effects were abolished in cells with ER? knockdown by silencing receptor expression or by using specific receptor antagonists. Our observations support the hypothesis that estrogen-like molecules may be useful in LHON prophylactic therapy. This is particularly important for lifelong disease prevention in unaffected LHON mutation carriers. Current strategies attempting to combat degeneration of RGCs during the acute phase of LHON have not been very effective. Implementing a different and preemptive approach with a low risk profile may be very helpful. PMID:26410888

  8. LDL-apheresis accelerates the recovery of nonarteritic acute anterior ischemic optic neuropathy.

    PubMed

    Ramunni, Alfonso; Giancipoli, Giovanni; Guerriero, Silvana; Lapenna, Lucia; Saracino, Angelo; Saliani, Maria Teresa; Capurso, Antonio; Sborgia, Carlo; Coratelli, Pasquale

    2005-02-01

    Nonarteritic acute anterior ischemic optic neuropathy (NAION) is a disabling disease which impairs visual function. It is presumed to result from disturbances of microcirculation in the anterior portion of the optic nerve head due to hemodynamic factors derived from excessive blood viscosity, or restriction of the vasal lumen in hypertensive, hypercholesterolemic, diabetic patients. We aimed to determine whether acute reduction of plasma fibrinogen and serum low-density lipoprotein (LDL) cholesterol is effective for treatment of NAION. We recruited 11 patients (7 females, 4 males) with a mean age of 57.2 +/- 19.6 years. All except one of them presented risk factors for atherosclerosis. The mean values of LDL-cholesterol and fibrinogen before treatment were 144 +/- 32 mg/dL and 341 +/- 80 mg/dL, respectively. All were treated with standard therapy (prednisone, salicylate, pentoxiphyllin) and underwent three sessions of LDL-apheresis (HELP system-B Braun) that can reduce plasma LDL-cholesterol and fibrinogen by more than 50% in a very short time. In all patients we observed a drastic reduction of LDL cholesterol and fibrinogen and a clear improvement in the visual functional data. In fact, mean values of corrected vision increased from 3.7/10 +/- 3/10 to 7.9/10 +/- 2.2/10 (P = 0.002) after the third session, while the scotomatous portion of the visual field regressed after the first session, and in 5 patients further regressed after the third session. This improvement had remained stable after 3 months. Thanks to it's effect of antagonizing hemorheologic disorders of the ocular microcirculation, fibrinogen/LDL-apheresis seems to be an efficacious treatment of NAION. PMID:15828907

  9. Steroid-induced central serous chorioretinopathy in a patient with non-arteritic anterior ischemic optic neuropathy

    PubMed Central

    Alkin, Zeynep; Yilmaz, Ihsan; Ozkaya, Abdullah; Yazici, Ahmet Taylan

    2015-01-01

    Non-arteritic anterior ischemic optic neuropathy is a result of an infarction of the small vessel at the anterior portion of the optic disc and causes acute, unilateral, painless visual loss. There is no generally accepted treatment method for this condition but some medical and surgical treatments are recommended. Earlier studies show that visual acuity recovery was better with corticosteroid medication compared to non-treated patients. However corticosteroids may cause side effects such as cataract, increased intraocular pressure and rarely central serous chorioretinopathy. This case report presents a patient with central serous chorioretinopathy secondary to corticosteroid medication. PMID:26155086

  10. Optical coherence tomography helps differentiate neuromyelitis optica and MS optic neuropathies

    PubMed Central

    Ratchford, J N.; Quigg, M E.; Conger, A; Frohman, T; Frohman, E; Balcer, L J.; Calabresi, P A.; Kerr, D A.

    2009-01-01

    Objective: To evaluate the retinal nerve fiber layer (RNFL) thickness and macular volume in neuromyelitis optica (NMO) spectrum patients using optical coherence tomography (OCT). Background: OCT can quantify damage to retinal ganglion cell axons and can identify abnormalities in multiple sclerosis and optic neuritis (ON) eyes. OCT may also be useful in the evaluation of patients with NMO. Methods: OCT and visual function testing were performed in 26 NMO spectrum patients with a history of ON, 17 patients with isolated longitudinally extensive transverse myelitis (LETM) without ON, 378 patients with relapsing–remitting multiple sclerosis (RRMS), and 77 healthy controls at 2 centers. Results: Substantial RNFL thinning was seen in NMO ON eyes (63.6 μm) relative to both RRMS ON eyes (88.3 μm, p < 0.0001) and control eyes (102.4 μm, p < 0.0001). A first episode of ON was estimated to cause 24 μm more loss of RNFL thickness in NMO than RRMS. Similar results were seen for macular volume. ON also was associated with more severe visual impairment in NMO spectrum patients than in RRMS patients. Eyes in the LETM group and unaffected NMO eyes were not significantly different from controls, though conclusions about these subgroups were limited by small sample sizes. Conclusions: Optical coherence tomography (OCT) shows more severe retinal damage after optic neuritis (ON) episodes in neuromyelitis optica (NMO) than in relapsing–remitting multiple sclerosis. Identification of substantial retinal nerve fiber layer loss (>15 μm) after ON in a non–multiple sclerosis patient should prompt consideration of an NMO spectrum condition. OCT may be a useful tool for the evaluation of patients with NMO. GLOSSARY CI = confidence interval; ETDRS = Early Treatment Diabetic Retinopathy Study; IgG = immunoglobulin G; LETM = longitudinally extensive transverse myelitis; MS = multiple sclerosis; NMO = neuromyelitis optica; OCT = optical coherence tomography; ON = optic neuritis; RNFL = retinal nerve fiber layer; RRMS = relapsing–remitting multiple sclerosis. PMID:19636050

  11. Degeneration of spared axons following partial white matter lesion: implications for optic nerve neuropathies.

    PubMed

    Yoles, E; Schwartz, M

    1998-09-01

    Neuroprotective therapy is a relatively new development in the approach to the treatment of acute and chronic brain damage. Though initially viewed in the framework of acute CNS injuries, the concept was recently extended to include chronic injuries, in which at any given time there are some neurons in an acute phase of degeneration coexisting with others that are healthy, marginally damaged, or dead. The healthy neurons and those that are only marginally damaged are the potential targets for neuroprotection. For the development of neuroprotective therapies, it is essential to employ an animal model in which the damage resulting from secondary degeneration can be quantitatively distinguished from primary degeneration. This is of particular relevance when the site of the damage is in the white matter (nerve fibers) rather than in the gray matter (cell bodies). In the present work we reexamine the concepts of secondary degeneration and neuroprotection in white matter lesions. Using a partial crush injury of the adult rat optic nerve as a model, we were able to assess both primary and secondary nerve damage. We show that neurons whose axons were not damaged or only marginally damaged after an acute insult will eventually degenerate as a consequence of their existence in the degenerative environment produced by the injury. This secondary degeneration does not occur in all of the neurons at once, but affects them in a stepwise fashion related to the severity of the damage inflicted. These findings, which may be applicable to the progression of acute or chronic neuropathy, imply that neuroprotective therapy may have a beneficial effect even if there is a time lag between injury and treatment. PMID:9743562

  12. Point mutations associated with Leber hereditary optic neuropathy in a Latvian population

    PubMed Central

    Baumane, Kristine; Zalite, Solveiga; Ranka, Renate; Zole, Egija; Pole, Ilva; Sepetiene, Svetlana; Laganovska, Guna; Baumanis, Viesturs; Pliss, Liana

    2013-01-01

    Purpose To study mutations associated with Leber hereditary optic neuropathy (LHON) in patients suspected of having this mitochondrial disorder in a Latvian population. Additional aims were to determine the heteroplasmy status of all non-synonymous polymorphisms identified in the current study and to identify the mitochondrial haplogroups of the studied participants because these factors may contribute to the manifestation of LHON. Methods Twelve patients, including patients in two families, were enrolled in the current study. LHON was suspected based on the findings of ophthalmologic examinations. In clinically affected individuals, the presence of all previously reported LHON-associated mutations was assessed with sequencing analysis. Additionally, the SURVEYOR endonuclease assay was used to detect heteroplasmy. The mitochondrial haplogroups were identified with restriction analysis and the sequencing of hypervariable segment 1. Results In one family (mother and son), there was one primary LHON-associated mutation, G11778A. In addition, one rare previously reported LHON-associated polymorphism, A13637G, was detected in two unrelated patients. A non-synonymous polymorphism at T6253C was found in one individual. This mutation was reported in the background of the 3460 mutation among LHON patients in a Chinese population. No non-synonymous point mutations in mitochondrial DNA were found in five of the study participants. Conclusions Molecular analysis of 12 patients with suspected LHON confirmed the diagnosis in four patients and allowed the use of appropriate prophylactic measures and treatment. Further investigations and additional studies of different populations are necessary to confirm the role of the non-synonymous polymorphisms A13637G and T6253C in the manifestation of LHON and the associations of these polymorphisms with mitochondrial haplogroups and heteroplasmy. PMID:24319328

  13. 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.

  14. 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

  15. AIonAI: a humanitarian law of artificial intelligence and robotics.

    PubMed

    Ashrafian, Hutan

    2015-02-01

    The enduring progression of artificial intelligence and cybernetics offers an ever-closer possibility of rational and sentient robots. The ethics and morals deriving from this technological prospect have been considered in the philosophy of artificial intelligence, the design of automatons with roboethics and the contemplation of machine ethics through the concept of artificial moral agents. Across these categories, the robotics laws first proposed by Isaac Asimov in the twentieth century remain well-recognised and esteemed due to their specification of preventing human harm, stipulating obedience to humans and incorporating robotic self-protection. However the overwhelming predominance in the study of this field has focussed on human-robot interactions without fully considering the ethical inevitability of future artificial intelligences communicating together and has not addressed the moral nature of robot-robot interactions. A new robotic law is proposed and termed AIonAI or artificial intelligence-on-artificial intelligence. This law tackles the overlooked area where future artificial intelligences will likely interact amongst themselves, potentially leading to exploitation. As such, they would benefit from adopting a universal law of rights to recognise inherent dignity and the inalienable rights of artificial intelligences. Such a consideration can help prevent exploitation and abuse of rational and sentient beings, but would also importantly reflect on our moral code of ethics and the humanity of our civilisation. PMID:24414678

  16. 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 that express fluorescent proteins under the Thy-1 promoter have been examined for their potential to provide specific and selective labeling of RGCs for the study of GON. While these methods represent important advances in assessing the structural and functional integrity of RGCs, each has its advantages and disadvantages; together they provide an extensive toolbox for the study of GON. PMID:26070986

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

    PubMed Central

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

    2014-01-01

    IMPORTANCE Establishing the natural history of G11778A Leber hereditary optic neuropathy (LHON) is important to determine the optimal end points to assess the safety and efficacy of a planned gene therapy trial. OBJECTIVE To use the results of the present natural history study of patients with G11778A LHON to plan a gene therapy clinical trial that will use allotopic expression by delivering a normal nuclear-encoded ND4 gene into the nuclei of retinal ganglion cells via an adeno-associated virus vector injected into the vitreous. DESIGN, SETTING, AND PARTICIPANTS A prospective observational study initiated in 2008 was conducted in primary and referral institutional practice settings. Participants included 44 individuals with G11778A LHON, recruited between September 2008 and March 2012, who were evaluated every 6 months and returned for 1 or more follow-up visits (636 months) as of August 2012. EXPOSURES Complete neuro-ophthalmic examination and main measures. MAIN OUTCOMES AND MEASURES Visual acuity, automated visual field testing, pattern electroretinogram, and spectral-domain optical coherence tomography. RESULTS Clinical measures were stable during the follow-up period, and visual acuity was as good as or better than the other visual factors used for monitoring patients. Based on a criterion of 15 or more letters from the Early Treatment Diabetic Retinopathy Study chart, 13 eyes of 8 patients (18%) improved, but 24 months after the onset of symptoms, any further improvements were to no better than 20/100. Acuity recovery occurred in some patients despite continued marked retinal nerve fiber layer thinning indistinguishable from that in patients who did not recover visual acuity. CONCLUSIONS AND RELEVANCE Spontaneous improvement of visual acuity in patients with G11778A LHON is not common and is partial and limited when it occurs, so improvements in vision with adeno-associated virusmediated gene therapy of a synthetic wild-type ND4 subunit gene should be possible to detect with a reasonable sample size. Visual acuity appears to be the most suitable primary end point for the planned clinical trial. PMID:24525545

  18. Autonomic neuropathy

    MedlinePLUS

    ... and pupils. Autonomic neuropathy may be seen with: Alcohol abuse Diabetes (diabetic neuropathy) Disorders involving scarring of ... dizziness when standing High blood pressure Shortness of breath with activity or exercise Bladder symptoms may include: ...

  19. 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 ...

  20. Auditory Neuropathy

    MedlinePLUS

    ... about the potential benefits of hearing aids, cochlear implants, and other technologies for people with auditory neuropathy. ... some children and adults with auditory neuropathy. Cochlear implants (electronic devices that compensate for damaged or nonworking ...

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

    PubMed Central

    Laberge, Anne-Marie; Jomphe, Michle; Houde, Louis; Vzina, Hlne; 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 founders 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

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

    PubMed

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

    2012-03-01

    A 31-year-old woman developed subacute bilateral visual loss over a 2-week period. Two months later, the diagnosis of Leber hereditary optic neuropathy (LHON) 11778/ND4 was established and the patient was treated with 900 mg of idebenone daily. Over the ensuing 9 months, visual acuity improved from 20/200 to 20/25 in each eye with near-total resolution in visual field abnormalities. Our case report is in agreement with 2 large published series of patients with LHON treated with idebenone, raising hope for treatment of this visually devastating mitochondrial disorder. PMID:22269948

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

    PubMed

    Felekis, T; Asproudis, I; Katsanos, K; Tsianos, Ev

    2011-01-01

    A 51-year-old male was referred to the University Eye Clinic of Ioannina with nonarteritic anterior ischemic optic neuropathy (NAION) 12 hours after receiving sildenafil citrate (Viagra()). Examination for possible risk factors revealed mild hypercholesterolemia. Family history showed that his father had suffered from bilateral NAION. Although a cause-and-effect relationship is difficult to prove, there are reports indicating an association between the use of erectile dysfunction agents and the development of NAION. Physicians might need to investigate the presence of family history of NAION among systemic or vascular predisposing risk factors before prescribing erectile dysfunction drugs. PMID:22034568

  4. Clinical characterization and mitochondrial DNA sequence variations in Leber hereditary optic neuropathy

    PubMed Central

    Kumar, Manoj; Kaur, Punit; Kumar, Manoj; Saxena, Rohit; Sharma, Pradeep

    2012-01-01

    Purpose Leber hereditary optic neuropathy (LHON), a maternally inherited disorder, results from point mutations in mitochondrial DNA (mtDNA). MtDNA is highly polymorphic in nature with very high mutation rate, 1017 fold higher as compared to nuclear genome. Identification of new mtDNA sequence variations is necessary to establish a clean link with human disease. Thus this study was aimed to assess or evaluate LHON patients for novel mtDNA sequence variations. Materials and Methods Twenty LHON patients were selected from the neuro-ophthalmology clinic of the All India Institute of Medical Sciences, New Delhi, India. DNA was isolated from whole blood samples. The entire coding region of the mitochondrial genome was amplified by PCR in 20 patients and 20 controls. For structural analysis (molecular modeling and simulation) the MODELER 9.2 program in Discovery Studio (DS 2.0) was used. Results MtDNA sequencing revealed a total of 47 nucleotide variations in the 20 LHON patients and 29 variations in 20 controls. Of 47 changes in patients 21.2% (10/47) were nonsynonymous and the remaining 78.72% (37/47) were synonymous. Five nonsynonymous changes, including primary LHON mutations (NADH dehydrogenase subunit 1 [ND1]:p.A52T, NADH dehydrogenase subunit 6 [ND6]:p.M64V, adenosine triphosphate [ATP] synthase subunit a (F-ATPase protein 6) [ATPase6]:p.M181T, NADH dehydrogenase subunit 4 [ND4]:p.R340H, and cytochrome B [CYB]:p.F181L), were found to be pathogenic. A greater number of changes were present in complex I (53.19%; 25/47), followed by complex III (19.14%; 9/47), then complex IV (19.14%; 9/47), then complex V (8.5%; 4/47). Nonsynonymous variations may impair respiratory chain and oxidative phosphorylation (OXPHOS) pathways, which results in low ATP production and elevated reactive oxygen species (ROS) levels. Oxidative stress is the underlying etiology in various diseases and also plays a crucial role in LHON. Conclusions This study describes the role of mtDNA sequence variations in LHON patients. Primary LHON mutations of mtDNA are main variants leading to LHON, but mutations in other mitochondrial genes may also play an important role in pathogenesis of LHON as indicated in the present study. Certain alleles in certain haplogroups have protective or deleterious roles and hence there is a need to analyze a large number of cases for correlating phenotype and disease severity with mutation and mtDNA haplogroups. PMID:23170061

  5. Gene therapy for mitochondrial diseases: Leber Hereditary Optic Neuropathy as the first candidate for a clinical trial.

    PubMed

    Cwerman-Thibault, Hlne; Augustin, Sbastien; Ellouze, Sami; Sahel, Jos-Alain; Corral-Debrinski, Marisol

    2014-03-01

    Mitochondrial disorders cannot be ignored anymore in most medical disciplines; indeed their minimum estimated prevalence is superior to 1 in 5000 births. Despite the progress made in the last 25 years on the identification of gene mutations causing mitochondrial pathologies, only slow progress was made towards their effective treatments. Ocular involvement is a frequent feature in mitochondrial diseases and corresponds to severe and irreversible visual handicap due to retinal neuron loss and optic atrophy. Interestingly, three clinical trials for Leber Congenital Amaurosis due to RPE65 mutations are ongoing since 2007. Overall, the feasibility and safety of ocular Adeno-Associated Virus delivery in adult and younger patients and consistent visual function improvements have been demonstrated. The success of gene-replacement therapy for RPE65 opens the way for the development of similar approaches for a broad range of eye disorders, including those with mitochondrial etiology such as Leber Hereditary Optic Neuropathy (LHON). PMID:24702846

  6. Long-term evaluation of Lebers hereditary optic neuropathy-like symptoms in rotenone administered rats

    PubMed Central

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

    2015-01-01

    Lebers hereditary optic neuropathy (LHON) is an inherited disorder affecting the retinal ganglion cells (RGCs) and their axons that lead to the loss of central vision. This study is aimed at evaluating the LHON symptoms in rats administered with rotenone microspheres into the superior colliculus (SC). Optical coherence tomography (OCT) analysis showed substantial loss of retinal nerve fiber layer (RNFL) thickness in rotenone injected rats. Optokinetic testing in rotenone treated rats showed decrease in head-tracking response. Electrophysiological mapping of the SC surface demonstrated attenuation of visually evoked responses; however no changes were observed in the ERG data. The progressive pattern of disease manifestation in rotenone administered rats demonstrated several similarities with human disease symptoms. These rats with LHON-like symptoms can serves as a model for future investigators to design and implement reliable tests to assess the beneficial effects of therapeutic interventions for LHON disease. PMID:25481764

  7. 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.

  8. Neutrophil-to-Lymphocyte Ratio as a Marker in Patients with Non-arteritic Anterior Ischemic Optic Neuropathy

    PubMed Central

    Polat, Onur; Yava?, Gliz Fatma; ?nan, Sibel; ?nan, mit beyt

    2015-01-01

    Background: Non-arteritic anterior ischemic 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. Although the precise cause of NAION remains elusive, the etiology of NAION is believed to be multifactorial. Aims: To evaluate the utility of neutrophil-to-lymphocyte ratio (NLR) as a simple and readily available prognostic factor for clinical disease activity in patients with NAION. Study Design: Case-control study. Methods: Forty-five patients with the diagnosis of NAION and 50 age- and sex-matched controls with/without any systemic or ocular diseases except cataract were retrospectively enrolled in the study. Demographic characteristics and laboratory findings including complete blood count of all patients and control subjects were obtained from the electronic medical record. The neutrophil and lymphocyte counts were recorded and the NLR was calculated. Results: White blood cell, neutrophil, NLR and platelet values of the NAION patients were significantly higher than those of the controls (p<0.001, p<0.001, p=0.004, p=0.037, respectively). Initial NLR values were negatively correlated with initial and the third month best corrected visual acuity levels in the study group. The optimum NLR cut-off point for NAION was 1.94. Conclusion: NLR could be considered as a new inflammatory marker for assessment of the severity of inflammation in NAION patients with its quick, cheap, easily measurable property with routine complete blood count analysis. PMID:26740898

  9. AMYLOID NEUROPATHIES

    PubMed Central

    Shin, Susan C.; Robinson-Papp, Jessica

    2012-01-01

    Peripheral neuropathy is a common complication of many of the systemic amyloidoses. Although the cause of neuropathy is not entirely clear, it is likely related to amyloid deposition within the nerve. This may lead to focal, multifocal, or diffuse neuropathies involving sensory, motor and/or autonomic fibers. The presenting symptoms depend on the distribution of nerves affected. One of the most common phenotypes is sensorimotor polyneuropathy, which is characterized by symptoms of neuropathic pain, numbness, and in advanced cases weakness. Symptoms begin in the feet and ultimately progress to the proximal legs and hands. The most common focal neuropathy is a median neuropathy at the wrist, or clinically known as carpal tunnel syndrome. Carpal tunnel symptoms may include pain and sensory disturbances in the lateral palm and fingers; hand weakness may ensue if the focal neuropathy is severe. Autonomic neuropathy may affect a variety of organ systems such as the cardiovascular, gastrointestinal, and genitourinary systems. Symptoms may be non-specific making the diagnosis of autonomic neuropathy more difficult to identify. However, it is important to recognize and distinguish autonomic neuropathy from diseases of the end-organs themselves. This chapter reviews the inherited and acquired amyloidoses that affect the peripheral nervous system including familial amyloid polyneuropathy, and primary, secondary and senile amyloidosis. We emphasize the clinical presentation of the neurologic aspects of these diseases, physical examination findings, appropriate diagnostic evaluation, treatment and prognosis. PMID:23239211

  10. [Diabetic neuropathy].

    PubMed

    Nakamura, Jiro; Kamiya, Hideki

    2015-12-01

    Diagnostic criteria of diabetic neuropathy that can be easily used at bedsides and have international consensus have not been established. The most important therapeutic strategy is to maintain strict glycemic control. In addition, treatment with an aldose reductase inhibitor that is innovated from the viewpoint of the pathogenesis of diabetic neuropathy would be useful for preventing the progression of diabetic neuropathy. For painful diabetic neuropathy, pregabalin and duloxetine effectively relieve the pain, and contribute to the improvement of the quality of life. PMID:26666151

  11. 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

  12. Wolff-Parkinson-White syndrome and isolated left ventricular abnormal trabeculation as a manifestation of Leber's hereditary optic neuropathy.

    PubMed

    Finsterer, J; Stllberger, C; Kopsa, W; Jaksch, M

    2001-04-01

    Myocardial thickening and isolated left ventricular abnormal trabeculation (ILVAT) have not been described in patients with Leber's hereditary optic neuropathy (LHON) before. Wolff-Parkinson-White syndrome, myocardial thickening and ILVAT were found by electrocardiogram, echocardiography and cardiac magnetic resonance imaging in a 48-year-old man with bilateral, severely reduced visual acuity since age 24 years, palpitations since age 43 years and lower limb muscle cramps since age 47 years. Because ILVAT is frequently associated with respiratory chain disorders, neurological investigations were initiated, revealing the primary LHON mutation G3460A in lymphocytic mitochondrial DNA. On the basis of the clinical and genetic data, LHON was diagnosed in the index patient, but also in the patient's brother who showed ILVAT as well. Wolff-Parkinson-White syndrome, myocardial thickening and ILVAT may be rare manifestations of LHON. PMID:11329546

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. Disulfiram neuropathy.

    PubMed Central

    Watson, C P; Ashby, P; Bilbao, J M

    1980-01-01

    Disulfiram (Antabuse) can produce neuropathy in daily doses of less than the usually recommended 500 mg. The four recent cases reported in this paper emphasize the need for greater recognition of this condition. Nerve biopsies showed axonal degeneration. The neuropathy is difficult to distinguish from that associated with ethanol abuse. Disulfiram neuropathy occurs after a variable latent period (mean 5 to 6 months) and progresses steadily. Slow improvement may occur when the drug's use is stopped; often there is complete recovery eventually. Images FIG. 1 FIG. 2 PMID:6266628

  19. Intravitreal delivery of AAV-NDI1 provides functional benefit in a murine model of Leber hereditary optic neuropathy.

    PubMed

    Chadderton, Naomi; Palfi, Arpad; Millington-Ward, Sophia; Gobbo, Oliverio; Overlack, Nora; Carrigan, Matthew; O'Reilly, Mary; Campbell, Matthew; Ehrhardt, Carsten; Wolfrum, Uwe; Humphries, Peter; Kenna, Paul F; Farrar, G Jane

    2013-01-01

    Leber hereditary optic neuropathy (LHON) is a mitochondrially inherited form of visual dysfunction caused by mutations in several genes encoding subunits of the mitochondrial respiratory NADH-ubiquinone oxidoreductase complex (complex I). Development of gene therapies for LHON has been impeded by genetic heterogeneity and the need to deliver therapies to the mitochondria of retinal ganglion cells (RGCs), the cells primarily affected in LHON. The therapy under development entails intraocular injection of a nuclear yeast gene NADH-quinone oxidoreductase (NDI1) that encodes a single subunit complex I equivalent and as such is mutation independent. NDI1 is imported into mitochondria due to an endogenous mitochondrial localisation signal. Intravitreal injection represents a clinically relevant route of delivery to RGCs not previously used for NDI1. In this study, recombinant adenoassociated virus (AAV) serotype 2 expressing NDI1 (AAV-NDI1) was shown to protect RGCs in a rotenone-induced murine model of LHON. AAV-NDI1 significantly reduced RGC death by 1.5-fold and optic nerve atrophy by 1.4-fold. This led to a significant preservation of retinal function as assessed by manganese enhanced magnetic resonance imaging and optokinetic responses. Intraocular injection of AAV-NDI1 overcomes many barriers previously associated with developing therapies for LHON and holds great therapeutic promise for a mitochondrial disorder for which there are no effective therapies. PMID:22669418

  20. Pupil responses derived from outer and inner retinal photoreception are normal in patients with hereditary optic neuropathy.

    PubMed

    Kawasaki, Aki; Collomb, Sylvie; Lon, Lorette; Mnch, Mirjam

    2014-03-01

    We compared the pupil responses originating from outer versus inner retinal photoreception between patients with isolated hereditary optic neuropathy (HON, n=8) and healthy controls (n=8). Three different testing protocols were used. For the first two protocols, a response function of the maximal pupil contraction versus stimulus light intensity was generated and the intensity at which half of the maximal pupil contraction, the half-max intensity, was determined. For the third protocol, the pupil size after light offset, the re-dilation rate and re-dilation amplitude were calculated to assess the post-light stimulus response. Patients with HON had bilateral, symmetric optic atrophy and significant reduction of visual acuity and visual field compared to controls. There were no significant mean differences in the response curve and pupil response parameters that reflect mainly rod, cone or melanopsin activity between patients and controls. In patients, there was a significant correlation between the half-max intensity of the red light sequence and visual field loss. In conclusion, pupil responses derived from outer or inner retinal photoreception in HON patients having mild-to moderate visual dysfunction are not quantitatively different from age-matched controls. However, an association between the degree of visual field loss and the half-max intensity of the cone response suggests that more advanced stages of disease may lead to impaired pupil light reflexes. PMID:24275502

  1. 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

  2. Intravitreal delivery of AAV-NDI1 provides functional benefit in a murine model of Leber hereditary optic neuropathy

    PubMed Central

    Chadderton, Naomi; Palfi, Arpad; Millington-Ward, Sophia; Gobbo, Oliverio; Overlack, Nora; Carrigan, Matthew; O'Reilly, Mary; Campbell, Matthew; Ehrhardt, Carsten; Wolfrum, Uwe; Humphries, Peter; Kenna, Paul F; Jane Farrar, G

    2013-01-01

    Leber hereditary optic neuropathy (LHON) is a mitochondrially inherited form of visual dysfunction caused by mutations in several genes encoding subunits of the mitochondrial respiratory NADH-ubiquinone oxidoreductase complex (complex I). Development of gene therapies for LHON has been impeded by genetic heterogeneity and the need to deliver therapies to the mitochondria of retinal ganglion cells (RGCs), the cells primarily affected in LHON. The therapy under development entails intraocular injection of a nuclear yeast gene NADH-quinone oxidoreductase (NDI1) that encodes a single subunit complex I equivalent and as such is mutation independent. NDI1 is imported into mitochondria due to an endogenous mitochondrial localisation signal. Intravitreal injection represents a clinically relevant route of delivery to RGCs not previously used for NDI1. In this study, recombinant adenoassociated virus (AAV) serotype 2 expressing NDI1 (AAV-NDI1) was shown to protect RGCs in a rotenone-induced murine model of LHON. AAV-NDI1 significantly reduced RGC death by 1.5-fold and optic nerve atrophy by 1.4-fold. This led to a significant preservation of retinal function as assessed by manganese enhanced magnetic resonance imaging and optokinetic responses. Intraocular injection of AAV-NDI1 overcomes many barriers previously associated with developing therapies for LHON and holds great therapeutic promise for a mitochondrial disorder for which there are no effective therapies. PMID:22669418

  3. Idebenone protects against retinal damage and loss of vision in a mouse model of Leber's hereditary optic neuropathy.

    PubMed

    Heitz, Fabrice D; Erb, Michael; Anklin, Corinne; Robay, Dimitri; Pernet, Vincent; Gueven, Nuri

    2012-01-01

    Leber's hereditary optic neuropathy (LHON) is an inherited disease caused by mutations in complex I of the mitochondrial respiratory chain. The disease is characterized by loss of central vision due to retinal ganglion cell (RGC) dysfunction and optic nerve atrophy. Despite progress towards a better understanding of the disease, no therapeutic treatment is currently approved for this devastating disease. Idebenone, a short-chain benzoquinone, has shown promising evidence of efficacy in protecting vision loss and in accelerating recovery of visual acuity in patients with LHON. It was therefore of interest to study suitable LHON models in vitro and in vivo to identify anatomical correlates for this protective activity. At nanomolar concentrations, idebenone protected the rodent RGC cell line RGC-5 against complex I dysfunction in vitro. Consistent with the reported dosing and observed effects in LHON patients, we describe that in mice, idebenone penetrated into the eye at concentrations equivalent to those which protected RGC-5 cells from complex I dysfunction in vitro. Consequently, we next investigated the protective effect of idebenone in a mouse model of LHON, whereby mitochondrial complex I dysfunction was caused by exposure to rotenone. In this model, idebenone protected against the loss of retinal ganglion cells, reduction in retinal thickness and gliosis. Furthermore, consistent with this protection of retinal integrity, idebenone restored the functional loss of vision in this disease model. These results support the pharmacological activity of idebenone and indicate that idebenone holds potential as an effective treatment for vision loss in LHON patients. PMID:23028832

  4. Haplogroup Effects and Recombination of Mitochondrial DNA: Novel Clues from the Analysis of Leber Hereditary Optic Neuropathy Pedigrees

    PubMed Central

    Carelli, Valerio; Achilli, Alessandro; Valentino, Maria Lucia; Rengo, Chiara; Semino, Ornella; Pala, Maria; Olivieri, Anna; Mattiazzi, Marina; Pallotti, Francesco; Carrara, Franco; Zeviani, Massimo; Leuzzi, Vincenzo; Carducci, Carla; Valle, Giorgio; Simionati, Barbara; Mendieta, Luana; Salomao, Solange; Belfort, Rubens; Sadun, Alfredo A.; Torroni, Antonio

    2006-01-01

    The mitochondrial DNA (mtDNA) of 87 index cases with Leber hereditary optic neuropathy (LHON) sequentially diagnosed in Italy, including an extremely large Brazilian family of Italian maternal ancestry, was evaluated in detail. Only seven pairs and three triplets of identical haplotypes were observed, attesting that the large majority of the LHON mutations were due to independent mutational events. Assignment of the mutational events into haplogroups confirmed that J1 and J2 play a role in LHON expression but narrowed the association to the subclades J1c and J2b, thus suggesting that two specific combinations of amino acid changes in the cytochrome b are the cause of the mtDNA background effect and that this may occur at the level of the supercomplex formed by respiratory-chain complexes I and III. The families with identical haplotypes were genealogically reinvestigated, which led to the reconnection into extended pedigrees of three pairs of families, including the Brazilian family with its Italian counterpart. The sequencing of entire mtDNA samples from the reconnected families confirmed the genealogical reconstruction but showed that the Brazilian family was heteroplasmic at two control-region positions. The survey of the two sites in 12 of the Brazilian subjects revealed triplasmy in most cases, but there was no evidence of the tetraplasmy that would be expected in the case of mtDNA recombination. PMID:16532388

  5. 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.

  6. 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.

  7. 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, 6months, 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

  8. 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.

  9. Diabetic Neuropathies.

    PubMed

    Izenberg, Aaron; Perkins, Bruce A; Bril, Vera

    2015-08-01

    Diabetes mellitus is a common condition and diabetics are prone to develop a spectrum of neuropathic complications ranging from symmetric and diffuse to asymmetric and focal neuropathies that may be associated with significant morbidity. Diabetic sensorimotor polyneuropathy is the most common of these complications, occurring in patients with type 1 and 2 diabetes mellitus, as well as in those with prediabetes and glucose intolerance. In this review, the authors discuss the wide variety of neuropathies that can present in the context of diabetes, including the clinical manifestations, diagnostic features, and approach to management. PMID:26502765

  10. [Orbital metastasis of a previously unknown lung carcinoma mimicking posterior ischemic optic neuropathy].

    PubMed

    Becker, E J; Herwig, M C; Holz, F G; Kuchelmeister, K; Thomas, D; Charbel-Issa, P; Lffler, K U

    2015-06-01

    A 65-year-old patient presented with increasing loss of vision in the right eye. A relative afferent pupillary defect as well as visual field perimetry deficits in an otherwise unremarkable eye led to the presumed diagnosis of ischemia of the optic nerve; however, further imaging revealed an extensive necrotic bronchial carcinoma in the left upper lobe metastasizing to the orbit with compression of the optic nerve. The clinical and histological features are discussed with respect to possible primary origins of orbital metastases. PMID:25520143

  11. 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

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

    PubMed

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

    2015-03-01

    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

  13. 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

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

    PubMed

    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 modulate LHON penetrance must take into account also the exposure to environmental triggers such as tobacco smoke. PMID:26673666

  15. 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.

  16. 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.

  17. 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 modulate LHON penetrance must take into account also the exposure to environmental triggers such as tobacco smoke. PMID:26673666

  18. 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

  19. 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

  20. 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 ...

  1. 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 ...

  2. Optic Neuritis, its Differential Diagnosis and Management

    PubMed Central

    Hoorbakht, Hedieh; Bagherkashi, Farid

    2012-01-01

    The aim of this review is to summarize the latest information about optic neuritis, its differential diagnosis and management. Optic Neuritis (ON) is defined as inflammation of the optic nerve, which is mostly idiopathic. However it can be associated with variable causes (demyelinating lesions, autoimmune disorders, infectious and inflammatory conditions). Out of these, multiple sclerosis (MS) is the most common cause of demyelinating ON. ON occurs due to inflammatory processes which lead to activation of T-cells that can cross the blood brain barrier and cause hypersensitivity reaction to neuronal structures. For unknown reasons, ON mostly occurs in adult women and people who live in high latitude. The clinical diagnosis of ON consists of the classic triad of visual loss, periocular pain and dyschromatopsia which requires careful ophthalmic, neurologic and systemic examinations to distinguish between typical and atypical ON. ON in neuromyelitis optica (NMO) is initially misdiagnosed as ON in MS or other conditions such as Anterior Ischemic Optic Neuropathy (AION) and Leber’s disease. Therefore, differential diagnosis is necessary to make a proper treatment plan. According to Optic Neuritis Treatment Trial (ONTT) the first line of treatment is intravenous methylprednisolone with faster recovery and less chance of recurrence of ON and conversion to MS. However oral prednisolone alone is contraindicated due to increased risk of a second episode. Controlled High-Risk Subjects Avonex® Multiple Sclerosis Prevention Study “CHAMPS”, Betaferon in Newly Emerging Multiple Sclerosis for Initial Treatment “BENEFIT” and Early Treatment of MS study “ETOMS” have reported that treatment with interferon β-1a,b results in reduced risk of MS and MRI characteristics of ON. Contrast sensitivity, color vision and visual field are the parameters which remain impaired mostly even after good recovery of visual acuity. PMID:22888383

  3. Pan-American mDNA haplogroups in Chilean patients with Lebers hereditary optic neuropathy

    PubMed Central

    Romero, Pablo; Fernndez, Vernica; Slabaugh, Mark; Seleme, Nicols; Reyes, Nury; Gallardo, Patricia; Herrera, Luisa; Pea, 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 than the patients with other haplogroups in this population. Disease in subjects with haplogroup D appeared to be underrepresented compared to the population at large. PMID:24672219

  4. 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.

  5. 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.

  6. Hemifield pattern electroretinogram in ocular hypertension: comparison with frequency doubling technology and optical coherence tomography to detect early optic neuropathy

    PubMed Central

    Finzi, Alessandro; Strobbe, Ernesto; Tassi, Filippo; Fresina, Michela; Cellini, Mauro

    2014-01-01

    Background To assess the sensitivity and specificity of hemifield pattern electroretinogram (HF-PERG) for detecting early retinal ganglion cell (RGC) damage in ocular hypertensive (OH) patients. Methods Fifty-two OH patients (mean age 569.6 years) with an intraocular pressure (IOP) .21 mmHg were assessed. All subjects underwent HF-PERG, optical coherence tomography (OCT), and frequency doubling technology (FDT) visual field. Results OH patients showed a significant increase of peak-time of the N95 (P=0.027) compared to controls. The amplitude of the N95 of the lower and upper HF-PERG showed significant differences (P=0.037 and P=0.023, respectively) between the two groups. A significant intraocular (P=0.006) and interocular (P=0.018) asymmetry of N95 amplitude was found. Receiver operating characteristic (ROC) curve analysis revealed a sensitivity of 93% for the N95 of the lower HF-PERG, whereas full-field pattern electroretinogram (PERG) N95 peak-time had a sensitivity of 88%. In OH patients, we found a thinning of OCT - retinal nerve fiber layer (RNFL), especially in the superior and inferior quadrant, although not statistically significant, and a significantly higher FDT pattern standard deviation (FDT-PSD; P=0.001). In the OCT-RNFL inferior quadrant, a sensitivity of 82% was recorded. Finally, the sensitivity of the FDT-PSD was 92%. Conclusion Our study shows that HF-PERG is a very sensitive test for detecting early damage of the RGC. PMID:25284979

  7. Peripheral neuropathy and indomethacin.

    PubMed Central

    Eade, O E; Acheson, E D; Cuthbert, M F; Hawkes, C H

    1975-01-01

    A patient with seronegative inflammatory polyarthritis developed a predominantly motorperipheral neuropathy associated with the use of indomethacin. Three other cases of peripheral neuropathy associated with indomethacin treatment have been reported to the Committee on Safety of Medicines. In all cases the neuropathy regressed when indomethacinwas stopped. Peripheral neuropathy should be recognized as a rare complication of indomethacin therapy and considered in the differential diagnosis of a neuropathy accompanyingrheumatoid arthritis. PMID:165855

  8. Optic neuropathy, cardiomyopathy, cognitive disability in patients with a homozygous mutation in the nuclear MTO1 and a mitochondrial MT-TF variant.

    PubMed

    Charif, Majida; Titah, Salah Mohamed Cherif; Roubertie, Agathe; Desquiret-Dumas, Valrie; Gueguen, Naig; Meunier, Isabelle; Leid, Jean; Massal, Frdric; Zanlonghi, Xavier; Mercier, Jacques; Raynaud de Mauverger, Eric; Procaccio, Vincent; Mousson de Camaret, Bndicte; Lenaers, Guy; Hamel, Christian P

    2015-10-01

    We report on clinical, genetic and metabolic investigations in a family with optic neuropathy, non-progressive cardiomyopathy and cognitive disability. Ophthalmic investigations (slit lamp examination, funduscopy, OCT scan of the optic nerve, ERG and VEP) disclosed mild or no decreased visual acuity, but pale optic disc, loss of temporal optic fibers and decreased VEPs. Mitochondrial DNA and exome sequencing revealed a novel homozygous mutation in the nuclear MTO1 gene and the homoplasmic m.593T>G mutation in the mitochondrial MT-TF gene. Muscle biopsy analyses revealed decreased oxygraphic Vmax values for complexes I+III+IV, and severely decreased activities of the respiratory chain complexes (RCC) I, III and IV, while muscle histopathology was normal. Fibroblast analysis revealed decreased complex I and IV activity and assembly, while cybrid analysis revealed a partial complex I deficiency with normal assembly of the RCC. Thus, in patients with a moderate clinical presentation due to MTO1 mutations, the presence of an optic atrophy should be considered. The association with the mitochondrial mutation m.593T>G could act synergistically to worsen the complex I deficiency and modulate the MTO1-related disease. PMID:26061759

  9. N-hexane neuropathy in offset printers.

    PubMed

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

    1993-05-01

    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. PMID:8505647

  10. 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. ...

  11. 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

    Brzin, A P; Bchetoille, 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

  12. 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.

  13. 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.

  14. Very low penetrance of Leber's hereditary optic neuropathy in five Han Chinese families carrying the ND1 G3460A mutation

    PubMed Central

    Tong, Yi; Sun, Yan-Hong; Zhou, Xiangtian; Zhao, Fuxin; Mao, Yijian; Wei, Qi-ping; Yang, Li; Qu, Jia; Guan, Min-Xin

    2009-01-01

    We report here the clinical, genetic, and molecular characterization of five Han Chinese families with Leber's hereditary optic neuropathy (LHON). Strikingly, there were very low penetrances of visual impairment in these Chinese families, ranging from 4.2% to 22.2%, with an average of 10.2%. In particular, only 7 (4 males/3 females) of 106 matrilineal relatives in these families exhibited the variable severity and age-at-onset in visual dysfunction. The age-at-onset for visual impairment in matrilineal relatives in these families, varied from 20 to 25 years, with an average of 21.8 years old. Molecular analysis of mitochondrial genomes identified the homoplasmic ND1 G3460A mutation and distinct sets of variants, belonging to the Asian haplogroups B5b, C4a1, D5, F1, and R9, respectively. This suggests that the G3640A mutation occurred sporadically and multiplied through evolution of the mtDNA in China. However, there was the absence of known secondary LHON-associated mtDNA mutations in these Chinese families. Very low penetrance of visual loss in these five Chinese pedigrees strongly indicated that the G3640A mutation was itself insufficient to develop the optic neuropathy. The absence of secondary LHON mtDNA mutations suggest that these mtDNA haplogroup-specific variants may not play an important role in the phenotypic expression of the G3640A mutation in those Chinese families with low penetrance of vision loss. However, nuclear modifier genes, epigenetic and environmental factors appear to be modifier factors for the phenotypic manifestation of the G3640A mutation in these Chinese families. PMID:20053576

  15. Leber's hereditary optic neuropathy caused by the homoplasmic ND1 m.3635G>A mutation in nine Han Chinese families.

    PubMed

    Zhang, Juanjuan; Jiang, Pingping; Jin, Xiaofen; Liu, Xiaoling; Zhang, Minglian; Xie, Shipeng; Gao, Min; Zhang, Sai; Sun, Yan-Hong; Zhu, Jinping; Ji, Yanchun; Wei, Qi-Ping; Tong, Yi; Guan, Min-Xin

    2014-09-01

    In this report, we investigated the molecular mechanism underlying Leber's hereditary optic neuropathy (LHON)-associated mitochondrial m.3635G>A (p.S110N, ND1) mutation. A mutational screening of ND1 gene in a cohort of 1070 Han Chinese subjects LHON identified the m.3635G>A mutation in nine Chinese families with suggestively maternally transmitted LHON. Thirty-eight (22 males/16 females) of 162 matrilineal relatives in these families exhibited the variable severity and age-at-onset of optic neuropathy. Molecular analysis of their mitochondrial genomes identified the homoplasmic m.3635G>A mutation and distinct sets of polymorphisms belonging to the Asian haplogroups G2a1, R11a, D4, R11a, M7b2, G1a, F1a1, B4, and N9a3, respectively. Using cybrids constructed by transferring mitochondria from lymphoblastoid cell lines derived from one Chinese family into mtDNA-less (?(0)) cells, we showed ~27% decrease in the activity of NADH:ubiquinone oxidoreductase (complex I) in mutant cybrids carrying the m.3635G>A mutation, compared with control cybrids. The respiratory deficiency caused by the m.3635G>A mutation results in decreased efficiency of mitochondrial ATP synthesis. These mitochondrial dysfunctions caused an increase in the production of reactive oxygen species in the mutant cybrids. The data provide the direct evidence for the m.3635G>A mutation leading to LHON. Our findings may provide new insights into the understanding of pathophysiology of LHON. PMID:25194554

  16. Congenital hypomyelinating neuropathy.

    PubMed Central

    Harati, Y; Butler, I J

    1985-01-01

    Two patients with congenital hypomyelinating neuropathy are reported with details of sural nerve pathology. The resemblance of this condition to the hypomyelinating neuropathy of Trembler mice is discussed and the pertinent medical literature reviewed. Images PMID:4087003

  17. Foundation for Peripheral Neuropathy

    MedlinePLUS

    ... Can Help Contact Us The Foundation for Peripheral Neuropathy works to educate the public and healthcare professionals, ... of-the-art treatment for patients with peripheral neuropathy, and will be the catalyst for advancing innovative ...

  18. Cell therapy using retinal progenitor cells shows therapeutic effect in a chemically-induced rotenone mouse model of Leber hereditary optic neuropathy.

    PubMed

    Mansergh, Fiona C; Chadderton, Naomi; Kenna, Paul F; Gobbo, Oliviero L; Farrar, G Jane

    2014-11-01

    Primary mitochondrial disorders occur at a prevalence of one in 10?000; ?50% of these demonstrate ocular pathology. Leber hereditary optic neuropathy (LHON) is the most common primary mitochondrial disorder. LHON results from retinal ganglion cell pathology, which leads to optic nerve degeneration and blindness. Over 95% of cases result from one of the three common mutations in mitochondrial genes MTND1, MTND4 and MTND6, which encode elements of the complex I respiratory chain. Various therapies for LHON are in development, for example, intravitreal injection of adeno-associated virus carrying either the yeast NDI1 gene or a specific subunit of mammalian Complex I have shown visual improvement in animal models. Given the course of LHON, it is likely that in many cases prompt administration may be necessary before widespread cell death. An alternative approach for therapy may be the use of stem cells to protect visual function; this has been evaluated by us in a rotenone-induced model of LHON. Freshly dissected embryonic retinal cells do not integrate into the ganglion cell layer (GCL), unlike similarly obtained photoreceptor precursors. However, cultured retinal progenitor cells can integrate in close proximity to the GCL, and act to preserve retinal function as assessed by manganese-enhanced magnetic resonance imaging, optokinetic responses and ganglion cell counts. Cell therapies for LHON therefore represent a promising therapeutic approach, and may be of particular utility in treating more advanced disease. PMID:24569607

  19. Cell therapy using retinal progenitor cells shows therapeutic effect in a chemically-induced rotenone mouse model of Leber hereditary optic neuropathy

    PubMed Central

    Mansergh, Fiona C; Chadderton, Naomi; Kenna, Paul F; Gobbo, Oliviero L; Farrar, G Jane

    2014-01-01

    Primary mitochondrial disorders occur at a prevalence of one in 10?000; ?50% of these demonstrate ocular pathology. Leber hereditary optic neuropathy (LHON) is the most common primary mitochondrial disorder. LHON results from retinal ganglion cell pathology, which leads to optic nerve degeneration and blindness. Over 95% of cases result from one of the three common mutations in mitochondrial genes MTND1, MTND4 and MTND6, which encode elements of the complex I respiratory chain. Various therapies for LHON are in development, for example, intravitreal injection of adeno-associated virus carrying either the yeast NDI1 gene or a specific subunit of mammalian Complex I have shown visual improvement in animal models. Given the course of LHON, it is likely that in many cases prompt administration may be necessary before widespread cell death. An alternative approach for therapy may be the use of stem cells to protect visual function; this has been evaluated by us in a rotenone-induced model of LHON. Freshly dissected embryonic retinal cells do not integrate into the ganglion cell layer (GCL), unlike similarly obtained photoreceptor precursors. However, cultured retinal progenitor cells can integrate in close proximity to the GCL, and act to preserve retinal function as assessed by manganese-enhanced magnetic resonance imaging, optokinetic responses and ganglion cell counts. Cell therapies for LHON therefore represent a promising therapeutic approach, and may be of particular utility in treating more advanced disease. PMID:24569607

  20. Development and validation of a computerized expert system for evaluation of automated visual fields from the Ischemic Optic Neuropathy Decompression Trial

    PubMed Central

    Feldon, Steven E; Levin, Lori; Scherer, Roberta W; Arnold, Anthony; Chung, Sophia M; Johnson, Lenworth N; Kosmorsky, Gregory; Newman, Steven A; Katz, Joanne; Langenberg, Patricia; Wilson, P David; Kelman, Shalom E; Dickersin, Kay

    2006-01-01

    Background The objective of this report is to describe the methods used to develop and validate a computerized system to analyze Humphrey visual fields obtained from patients with non-arteritic anterior ischemic optic neuropathy (NAION) and enrolled in the Ischemic Optic Neuropathy Decompression Trial (IONDT). The IONDT was a multicenter study that included randomized and non-randomized patients with newly diagnosed NAION in the study eye. At baseline, randomized eyes had visual acuity of 20/64 or worse and non-randomized eyes had visual acuity of better than 20/64 or were associated with patients refusing randomization. Visual fields were measured before treatment using the Humphrey Field Analyzer with the 24-2 program, foveal threshold, and size III stimulus. Methods We used visual fields from 189 non-IONDT eyes with NAION to develop the computerized classification system. Six neuro-ophthalmologists ("expert panel") described definitions for visual field patterns defects using 19 visual fields representing a range of pattern defect types. The expert panel then used 120 visual fields, classified using these definitions, to refine the rules, generating revised definitions for 13 visual field pattern defects and 3 levels of severity. These definitions were incorporated into a rule-based computerized classification system run on Excel software. The computerized classification system was used to categorize visual field defects for an additional 95 NAION visual fields, and the expert panel was asked to independently classify the new fields and subsequently whether they agreed with the computer classification. To account for test variability over time, we derived an adjustment factor from the pooled short term fluctuation. We examined change in defects with and without adjustment in visual fields of study participants who demonstrated a visual acuity decrease within 30 days of NAION onset (progressive NAION). Results Despite an agreed upon set of rules, there was not good agreement among the expert panel when their independent visual classifications were compared. A majority did concur with the computer classification for 91 of 95 visual fields. Remaining classification discrepancies could not be resolved without modifying existing definitions. Without using the adjustment factor, visual fields of 63.6% (14/22) patients with progressive NAION and no central defect, and all (7/7) patients with a paracentral defect, worsened within 30 days of NAION onset. After applying the adjustment factor, the visual fields of the same patients with no initial central defect and 5/7 of the patients with a paracentral defect were seen to worsen. Conclusion The IONDT developed a rule-based computerized system that consistently defines pattern and severity of visual fields of NAION patients for use in a research setting. PMID:17116264

  1. Drug-induced neuropathies.

    PubMed

    Manji, Hadi

    2013-01-01

    Although drug-induced neuropathies account for only 2-4% of referrals, their identification is important. Numerically, chemotherapy and antiretroviral drugs are the most important worldwide. Research is currently focused on elucidating pathogenic mechanisms and the earliest presymptomatic changes using neurophysiological and pharmacogenetic techniques in order to avoid the drug or make dosage changes before irreversible damage occurs. Chemoprotectants against chemotherapy-induced neuropathy are also an active area of research. This chapter focuses on the pathophysiology of drug-induced neuropathies in general, followed by detailed reviews of neuropathy due to; newer compounds such as TNF (tumor necrosis factor) ? antagonists and antibiotics such as linezolid; chemotherapeutic agents, old and new, where significant progress has been made; antiretroviral drugs; and amiodarone, which is unusual in that it causes a demyelinating neuropathy. The controversial issue of statin-induced neuropathy is also reviewed. PMID:23931812

  2. 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

  3. Mitochondrial tRNA(Thr) 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

    2016-03-01

    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

  4. 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.

  5. 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.

  6. 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

  7. Cardiac Involvement in Peripheral Neuropathies.

    PubMed

    Burakgazi, Ahmet Z; AlMahameed, Soufian

    2016-03-01

    Cardiac autonomic neuropathy (CAN) is the least recognized and understood complication of peripheral neuropathy. However, because of its potential adverse effects including sudden death, CAN is one of the most important forms of autonomic neuropathies. CAN presents with different clinical manifestations including postural hypotension, exercise intolerance, fluctuation of blood pressure and heart rate, arrhythmia, and increased risk of myocardial infarction. In this article, the prevalence, clinical presentations, and management of cardiac involvement in certain peripheral neuropathies, including diabetic neuropathy, Guillain-Barr syndrome, chronic inflammatory polyneuropathy, human immunodeficiency virus-associated neuropathy, hereditary neuropathies, and amyloid neuropathy are examined in detail. PMID:26905912

  8. LHON Gene Therapy Vector Prevents Visual Loss and Optic Neuropathy Induced by G11778A Mutant Mitochondrial DNA: Biodistribution and Toxicology Profile

    PubMed Central

    Koilkonda, Rajeshwari; Yu, Hong; Talla, Venu; Porciatti, Vittorio; Feuer, William J.; Hauswirth, William W.; Chiodo, Vince; Erger, Kirsten E.; Boye, Sanford L.; Lewin, Alfred S.; Conlon, Thomas J.; Renner, Lauren; Neuringer, Martha; Detrisac, Carol; Guy, John

    2014-01-01

    Purpose. To demonstrate safety and efficacy of allotopic human ND4 for treatment of a Leber's hereditary optic neuropathy (LHON) mouse model harboring the G11778A mitochondrial mutation. Methods. We induced LHON in mice by intravitreal injection of mutant (G11778A) human ND4 DNA, responsible for most cases of LHON, that was directed to mitochondria using an AAV2 vector to which we appended a mitochondrial targeting sequence to the VP2 capsid. We then attempted rescue of visual loss using our test article (ScAAV2-P1ND4v2) containing a synthetic nuclear encoded G11778G ND4 gene that was allotopically expressed. Control mice either were uninjected or received AAV2-GFP or AAV2-mCherry. We performed RT-PCR and confocal microscopy at 2 weeks post injection. Pattern electroretinograms (PERGs), spectral-domain optical coherence tomography (SD-OCT), histology, and transmission electron microscopy (TEM) were performed. For toxicology and biodistribution studies, the test article was administered intravitreally to rats and rhesus macaques at different doses. Results. Mutant and wild-type ND4 were efficiently expressed in the mitochondria of retinal ganglion cells (RGCs). Visual function assessed by serial PERGs and retinal structure by serial SD-OCT showed a significant rescue by the test article. Histology and ultrastructural analysis confirmed that loss of RGCs and demise of axons was prevented by ScAAV2-P1ND4v2. Rat and nonhuman primate biodistribution studies showed that vector spread outside the injected eye into spleen and lymph nodes was minimal. Histopathology of tissues and organs including the eyes was comparable to that of uninfected and saline-injected eyes. Conclusions. Allotopically expressed wild-type ND4 prevents the phenotype induced by G11778A mitochondrial DNA with a toxicology profile acceptable for testing in a phase I clinical trial. PMID:25342621

  9. Fifteen novel mutations in the mitochondrial NADH dehydrogenase subunit 1, 2, 3, 4, 4L, 5 and 6 genes from Iranian patients with Leber's hereditary optic neuropathy (LHON).

    PubMed

    Rezvani, Zahra; Didari, Elmira; Arastehkani, Ahoura; Ghodsinejad, Vadieh; Aryani, Omid; Kamalidehghan, Behnam; Houshmand, Massoud

    2013-12-01

    Leber's hereditary optic neuropathy (LHON) is an optic nerve dysfunction resulting from mutations in mitochondrial DNA (mtDNA), which is transmitted in a maternal pattern of inheritance. It is caused by three primary point mutations: G11778A, G3460A and T14484C; in the mitochondrial genome. These mutations are sufficient to induce the disease, accounting for the majority of LHON cases, and affect genes that encode for the different subunits of mitochondrial complexes I and III of the mitochondrial respiratory chain. Other mutations are secondary mutations associated with the primary mutations. The purpose of this study was to determine MT-ND variations in Iranian patients with LHON. In order to determine the prevalence and distribution of mitochondrial mutations in the LHON patients, their DNA was studied using PCR and DNA sequencing analysis. Sequencing of MT-ND genes from 35 LHON patients revealed a total of 44 nucleotide variations, in which fifteen novel variations-A14020G, A13663G, C10399T, C4932A, C3893G, C10557A, C12012A, C13934T, G4596A, T12851A, T4539A, T4941A, T13255A, T14353C and del A 4513-were observed in 27 LHON patients. However, eight patients showed no variation in the ND genes. These mutations contribute to the current database of mtDNA polymorphisms in LHON patients and may facilitate the definition of disease-related mutations in human mtDNA. This research may help to understand the disease mechanism and open up new diagnostic opportunities for LHON. PMID:24158608

  10. [Metabolic and nutritional neuropathies].

    PubMed

    Lagueny, A

    2000-04-01

    The two main causes of metabolic neuropathies are successively diabetes and chronic renal insufficiency. Diabetic neuropathies include both diffuse polyneuropathies and focal neuropathies. Sensori(motor) polyneuropathy is the most frequent form and different therapeutic trials have been initiated on the ground of the vascular and metabolic factors implicated in its pathogenesis. Autonomic neuropathy is the major cause of morbidity and mortality. In patients with chronic renal failure, the polyneuropathy is improved by renal transplantation. The carpal tunnel syndrome is frequent in hemodialysis patients, and surgery gives the opportunity to look for beta-2-microglobulin amyloid deposits. Among the less frequent causes of peripheral neuropathies in which metabolic factors have been considered, we review hypoglycemia, chronic respiratory insufficiency due to chronic obstructive pulmonary disease, chronic liver diseases, and the polyneuropathy occurring in the critically ill patients with nutritional or metabolic failures. In chronic excessive drinkers peripheral neuropathy is classically associated with thiamine deficiency, but the direct effect of alcohol itself has been discussed. Various vitaminic deficiencies have been responsible for the development of peripheral neuropathies. The clinical forms often associate peripheral neuropathy with myelopathy, and serum vitamin E concentrations should be measured in patients with spinocerebellar disorders. Usually nutritional deficiencies need multivitamins supplementation. PMID:10853552

  11. 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

  12. Immunotherapy in Peripheral Neuropathies.

    PubMed

    Lger, Jean-Marc; Guimares-Costa, Raquel; Muntean, Cristina

    2016-01-01

    Immunotherapy has been investigated in a small subset of peripheral neuropathies, including an acute one, Guillain-Barr 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

  13. 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 histological damage compared with vehicle-injected eyes (P = 0.03 for both VEP and PERG; P = 0.05 for axon counts). Conclusions. In nonhuman primates, PGJ2 administered either intravenously or intravitreally produces no permanent toxicity at even four times the dose given for neuroprotection. Additionally, a single IVT dose of PGJ2 is neuroprotective when administered up to 5 hours after induction of pNAION. PMID:25298416

  14. Association of the mtDNA m.4171C>A/MT-ND1 mutation with both optic neuropathy and bilateral brainstem lesions

    PubMed Central

    2014-01-01

    Background An increasing number of mitochondrial DNA (mtDNA) mutations, mainly in complex I genes, have been associated with variably overlapping phenotypes of Lebers hereditary optic neuropathy (LHON), mitochondrial encephalomyopathy with stroke-like episodes (MELAS) and Leigh syndrome (LS). We here describe the first case in which the m.4171C>A/MT-ND1 mutation, previously reported only in association with LHON, leads also to a Leigh-like phenotype. Case presentation A 16-year-old male suffered subacute visual loss and recurrent vomiting and vertigo associated with bilateral brainstem lesions affecting the vestibular nuclei. His mother and one sister also presented subacute visual loss compatible with LHON. Sequencing of the entire mtDNA revealed the homoplasmic m.4171C>A/MT-ND1 mutation, previously associated with pure LHON, on a haplogroup H background. Three additional non-synonymous homoplasmic transitions affecting ND2 (m.4705T>C/MT-ND2 and m.5263C>T/MT-ND2) and ND6 (m.14180T>C/MT-ND6) subunits, well recognized as polymorphisms in other mtDNA haplogroups but never found on the haplogroup H background, were also present. Conclusion This case widens the phenotypic expression of the rare m.4171C>A/MT-ND1 LHON mutation, which may also lead to Leigh-like brainstem lesions, and indicates that the co-occurrence of other ND non-synonymous variants, found outside of their usual mtDNA backgrounds, may have increased the pathogenic potential of the primary LHON mutation. PMID:24884847

  15. A Simple Oligonucleotide Biochip Capable of Rapidly Detecting Known Mitochondrial DNA Mutations in Chinese Patients with LeberS Hereditary Optic Neuropathy (LHON)

    PubMed Central

    Du, Wei-Dong; Chen, Gang; Cao, Hui-Min; Jin, Qing-Hui; Liao, Rong-Feng; He, Xiang-Cheng; Chen, Da-Ben; Huang, Shu-Ren; Zhao, Hui; Lv, Yong-Mei; Tang, Hua-Yang; Tang, Xian-Fa; Wang, Yong-Qing; Sun, Song; Zhao, Jian-Long; Zhang, Xue-Jun

    2011-01-01

    Leber's hereditary optic neuropathy (LHON) is a maternally transmitted disease. Clinically, no efficient assay protocols have been available. In this study, we aimed to develop an oligonucleotide biochip specialized for detection of known base substitution mutations in mitochondrial DNA causing LHON and to investigate frequencies of LHON relevant variants in Anhui region of China. Thirty-two pairs of oligonucleotide probes matched with the mutations potentially linked to LHON were covalently immobilized. Cy5-lablled targets were amplified from blood DNA samples by a multiplex PCR method. Two kinds of primary mutations 11778 G > A and 14484 T > C from six confirmed LHON patients were interrogated to validate this biochip format. Further, fourteen Chinese LHON pedigrees and twenty-five unrelated healthy individuals were investigated by the LHON biochip, direct sequencing and pyrosequencing, respectively. The biochip was found to be able efficiently to discriminate homoplasmic and heteroplasmic mtDNA mutations in LHON. Biochip analysis revealed that twelve of eighteen LHON symptomatic cases from the 14 Chinese pedigree harbored the mutations either 11778G > A, 14484T > C or 3460G > A, respectively, accounting for 66.7%. The mutation 11778G > A in these patients was homoplasmic and prevalent (55.5%, 10 of 18 cases). The mutations 3460G > A and 3394T > C were found to co-exist in one LHON case. The mutation 13708G > A appeared in one LHON pedigree. Smaller amount of sampling and reaction volume, easier target preparation, fast and high-throughput were the main advantages of the biochip over direct DNA sequencing and pyrosequencing. Our findings suggested that primary mutations of 11778G > A, 14484T > C or 3460G > A are main variants of mtDNA gene leading to LHON in China. The biochip would easily be implemented in clinical diagnosis. PMID:21694444

  16. The neuropathies of vasculitis.

    PubMed

    Collins, Michael P; Arnold, William David; Kissel, John T

    2013-05-01

    Vasculitic neuropathy can occur as an isolated entity (nonsystemic vasculitic neuropathy) but more commonly evolves in the setting of primary systemic vasculitides or secondary vasculitides related to infections, drugs, or connective tissue disorders. Vasculitic neuropathies are usually but not always painful and tend to produce sensory motor or sensory symptoms. Patients with purely motor or small-fiber dysfunction are unlikely to have vasculitis. Deficits are typically multifocal or asymmetric, but distal symmetric polyneuropathy occurs uncommonly. Evaluation requires laboratory tests, electrodiagnostic studies, and nerve or nerve/muscle biopsy. This article reviews classification, clinical presentation, diagnostic evaluation, and management of peripheral nerve vasculitis. PMID:23642724

  17. Trial end points and natural history in patients with G11778A Leber hereditary optic neuropathy : preparation for gene therapy clinical trial.

    PubMed

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

    2014-04-01

    IMPORTANCE Establishing the natural history of G11778A Leber hereditary optic neuropathy (LHON) is important to determine the optimal end points to assess the safety and efficacy of a planned gene therapy trial. OBJECTIVE To use the results of the present natural history study of patients with G11778A LHON to plan a gene therapy clinical trial that will use allotopic expression by delivering a normal nuclear-encoded ND4 gene into the nuclei of retinal ganglion cells via an adeno-associated virus vector injected into the vitreous. DESIGN, SETTING, AND PARTICIPANTS A prospective observational study initiated in 2008 was conducted in primary and referral institutional practice settings. Participants included 44 individuals with G11778A LHON, recruited between September 2008 and March 2012, who were evaluated every 6 months and returned for 1 or more follow-up visits (6-36 months) as of August 2012. EXPOSURES Complete neuro-ophthalmic examination and main measures. MAIN OUTCOMES AND MEASURES Visual acuity, automated visual field testing, pattern electroretinogram, and spectral-domain optical coherence tomography. RESULTS Clinical measures were stable during the follow-up period, and visual acuity was as good as or better than the other visual factors used for monitoring patients. Based on a criterion of 15 or more letters from the Early Treatment Diabetic Retinopathy Study chart, 13 eyes of 8 patients (18%) improved, but 24 months after the onset of symptoms, any further improvements were to no better than 20/100. Acuity recovery occurred in some patients despite continued marked retinal nerve fiber layer thinning indistinguishable from that in patients who did not recover visual acuity. CONCLUSIONS AND RELEVANCE Spontaneous improvement of visual acuity in patients with G11778A LHON is not common and is partial and limited when it occurs, so improvements in vision with adeno-associated virus-mediated gene therapy of a synthetic wild-type ND4 subunit gene should be possible to detect with a reasonable sample size. Visual acuity appears to be the most suitable primary end point for the planned clinical trial. PMID:24525545

  18. Occupational Peripheral Neuropathies

    PubMed Central

    Lotti, Marcello; Becker, Charles E.; Aminoff, Michael J.

    1982-01-01

    Neither clinical nor laboratory evaluation can distinguish occupational neuropathies from neuropathies due to other causes. A worker may suffer either from mechanical injury of individual nerves or from a toxic polyneuropathy that is usually axonal in type. A thorough occupational and environmental history and the recognition of clusters of cases are important in determining the diagnosis. Electrophysiologic studies are helpful in detecting neuropathies in patients who have been occupationally exposed to neurotoxins but have no symptoms. Prevention of occupational neuropathies depends on clinical vigilance, industrial hygiene surveys, biologic monitoring and periodic examination of workers exposed to neurotoxic chemicals. The development of more sophisticated methods of prevention and early detection of peripheral nerve involvement depend on understanding the mechanisms of action of toxins and the pathophysiology of the lesions they cause. PMID:6299013

  19. 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

  20. Diabetic neuropathy: Part 1.

    PubMed

    Gupta, Anu; Gupta, Yashdeep

    2014-06-01

    To conclude, diabetes is associated with a variety of chronic and acute neuropathies, the commonest form being distal symmetric polyneuropathy. Performing an annual screening through a good neurological history and clinical examination and using a sensitive screening tool can facilitate an early diagnosis. More sensitive and quantitative measures of detecting early peripheral nerve injury including skin biopsy for intra-epidermal and dermal nerve fiber density and confocal corneal microscopy, hold promise to identify neuropathy patients early in their disease course. PMID:25252500

  1. Painful diabetic neuropathy.

    PubMed

    Peltier, Amanda; Goutman, Stephen A; Callaghan, Brian C

    2014-01-01

    Diabetes is a worldwide epidemic, and associated neuropathy is its most costly and disabling complication. Given the rising prevalence of painful diabetic neuropathy, it is increasingly important that we understand the best ways to diagnose and treat this condition. Diagnostic tests in this field are evolving rapidly. These include the use of skin biopsies to measure small unmyelinated fibers, as well as even newer techniques that can measure both small unmyelinated fibers and large myelinated fibers in the same biopsy. The main treatments for painful diabetic neuropathy remain management of the underlying diabetes and drugs for the relief of pain. However, emerging evidence points to major differences between type 1 and type 2 diabetes, including the ability of glycemic control to prevent neuropathy. Enhanced glucose control is much more effective at preventing neuropathy in patients with type 1 diabetes than in those with type 2 disease [corrected]. This dichotomy emphasizes the need to study the pathophysiologic differences between the two types of diabetes, because different treatments may be needed for each condition. The impact of the metabolic syndrome on neuropathy in patients with type 2 diabetes may account for the difference between the two types of diabetes and requires further study. Finally, neuropathic pain is under-recognized and undertreated despite an ever evolving list of effective drugs. Evidence exists to support several drugs, but the optimal sequence and combination of these drugs are still to be determined. PMID:24803311

  2. The background of mitochondrial DNA haplogroup J increases the sensitivity of Leber's hereditary optic neuropathy cells to 2,5-hexanedione toxicity.

    PubMed

    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 other neurodegenerative disorders such as Parkinson's disease. PMID:19936068

  3. Lentiviral-mediated growth-associated protein-43 modification of bone marrow mesenchymal stem cells improves traumatic optic neuropathy in rats

    PubMed Central

    ZHU, QI; LIU, ZAOXIA; WANG, CHENGUANG; NIE, LILI; HE, YUXI; ZHANG, YAN; LIU, XIN; SU, GUANFANG

    2015-01-01

    The aim of the present study was to examine the effect of growth-associated protein-43 (GAP-43) on bone marrow mesenchymal stem cell (BMSC) differentiation in a rat model of traumatic optic neuropathy (TON). GAP-43 and short hairpin (sh)RNA-GAP-43 were inserted into pGLV5 and pGLV3 lentiviral vectors, respectively. The stable control, GAP-43-overexpression and GAP-43-knockdown cell lines (GFP/BMSCs, GAP-43/BMSCs and shGAP-43/BMSCs, respectively) were established. The expression of GAP-43, neuron-specific enolase (NSE), nestin, neurofilament (NF), neuron-specific nuclear-binding protein (NeuN) and ?III-tubulin were detected in the GAP-43/BMSCs and shGAP-43/BMSCs with retinal cell-conditioned differentiation medium using semi-quantitative polymerase chain reaction (PCR), western blotting and cell immunofluorescence. In addition, the BMSCs were observed under fluorescence microscopy. The Sprague-Dawley rat models of TON were established and identified by retrograde labeling of retinal ganglion cells (RGCs) with fluoroGold (FG). The lentiviral-mediated GAP-43-modified BMSCs were then transplanted into the rat model of TON. The expression of GAP-43 was detected in the retinal tissues using qPCR and western blotting. The histopathology of the retinal tissues was observed using hematoxylin and eosin (H&E) staining. The GAP-43/BMSCs exhibited positive expression of NSE, NF, nestin and ?III-tubulin, and exhibited a neuronal phenotype. The shGAP-43/BMSCs markedly inhibited expression of NeuN, NSE, NF, nestin and ?III-tubulin induced by retinal cell-conditioned differentiation medium. The FG staining revealed that the number of labeled RGCs were significantly decreased in the TON model rats, compared with normal rats (P<0.05). The H&E staining revealed that the degree of pathological changes was improved in the GAP-43/BMSC group, compared with the GFP/BMSC and shGAP-43/BMSC groups. In conclusion, GAP-43 promoted BMSC differentiation into neuron-like cells, and intravitreally injected GAP-43/BMSCs promoted the process of nerve repair in a rat model of TON. PMID:26238991

  4. Lentiviral-mediated growth-associated protein-43 modification of bone marrow mesenchymal stem cells improves traumatic optic neuropathy in rats.

    PubMed

    Zhu, Qi; Liu, Zaoxia; Wang, Chenguang; Nie, Lili; He, Yuxi; Zhang, Yan; Liu, Xin; Su, Guanfang

    2015-10-01

    The aim of the present study was to examine the effect of growth-associated protein-43 (GAP-43) on bone marrow mesenchymal stem cell (BMSC) differentiation in a rat model of traumatic optic neuropathy (TON). GAP?43 and short hairpin (sh)RNA?GAP?43 were inserted into pGLV5 and pGLV3 lentiviral vectors, respectively. The stable control, GAP?43?overexpression and GAP?43?knockdown cell lines (GFP/BMSCs, GAP?43/BMSCs and shGAP?43/BMSCs, respectively) were established. The expression of GAP?43, neuron?specific enolase (NSE), nestin, neurofilament (NF), neuron?specific nuclear?binding protein (NeuN) and ?III?tubulin were detected in the GAP?43/BMSCs and shGAP?43/BMSCs with retinal cell?conditioned differentiation medium using semi?quantitative polymerase chain reaction (PCR), western blotting and cell immunofluorescence. In addition, the BMSCs were observed under fluorescence microscopy. The Sprague?Dawley rat models of TON were established and identified by retrograde labeling of retinal ganglion cells (RGCs) with fluoroGold (FG). The lentiviral?mediated GAP?43?modified BMSCs were then transplanted into the rat model of TON. The expression of GAP?43 was detected in the retinal tissues using qPCR and western blotting. The histopathology of the retinal tissues was observed using hematoxylin and eosin (H&E) staining. The GAP?43/BMSCs exhibited positive expression of NSE, NF, nestin and ?III?tubulin, and exhibited a neuronal phenotype. The shGAP?43/BMSCs markedly inhibited expression of NeuN, NSE, NF, nestin and ?III?tubulin induced by retinal cell?conditioned differentiation medium. The FG staining revealed that the number of labeled RGCs were significantly decreased in the TON model rats, compared with normal rats (P<0.05). The H&E staining revealed that the degree of pathological changes was improved in the GAP?43/BMSC group, compared with the GFP/BMSC and shGAP?43/BMSC groups. In conclusion, GAP?43 promoted BMSC differentiation into neuron-like cells, and intravitreally injected GAP-43/BMSCs promoted the process of nerve repair in a rat model of TON. PMID:26238991

  5. 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 agents to lessen the deleterious effects of ethambutol. PMID:26587002

  6. [Sjogren's syndrome-associated neuropathy].

    PubMed

    Koike, Haruki; Sobue, Gen

    2013-11-01

    Sjogren's syndrome is a systemic autoimmune disease characterized by xerophthalmia and xerostomia; it is associated with widespread systemic visceral involvement. A wide variety of neurological complications are characteristic features of Sjogren's syndrome, of which peripheral neuropathy is a major neurological manifestation. Based on the predominant neuropathic symptoms, patients can be considered to have several forms of neuropathies, including sensory ataxic neuropathy, painful sensory neuropathy without sensory ataxia, multiple mononeuropathy, multiple cranial neuropathy, trigeminal neuropathy, autonomic neuropathy, and radiculoneuropathy. Acute or subacute onset is observed more frequently in multiple mononeuropathy and multiple cranial neuropathies, whereas disease progression is usually chronic in other forms of neuropathies. Sensory symptoms without substantial motor involvement are observed predominantly in sensory ataxic, painful sensory, trigeminal, and autonomic neuropathies. In contrast, motor impairment is apparent in multiple mononeuropathy, multiple cranial neuropathy, and radiculoneuropathy. Autonomic symptoms such as abnormal pupils and orthostatic hypotension are particularly noted in patients with sensory ataxic, painful, trigeminal, and autonomic neuropathies. Sural nerve biopsy specimens reveal predominantly large fiber loss in sensory ataxic neuropathy and predominantly small fiber loss in painful sensory neuropathy. Vasculitis is observed most frequently in multiple mononeuropathy. The autopsy findings of patients with sensory ataxic and painful neuropathies demonstrate neuronal loss in the dorsal root ganglia and sympathetic ganglia with CD8-positive cytotoxic T lymphocytes. Differential therapeutic responses to corticosteroids and intravenous immunoglobulin can be seen among the various neuropathic forms. In conclusion, the clinicopathological features of neuropathies associated with Sjogren's syndrome are highly variable. The neuropathy classification is important from a therapeutic point of view. PMID:24200611

  7. Cryoglobulinaemic neuropathy: a further cause of bilateral sciatic neuropathy

    PubMed Central

    Prez, Desire; de la Torre, Ricardo Gmez; Carrio, Isabel; Pinto, Jess; Mors, Germn

    2008-01-01

    Bilateral sciatic neuropathy is a rare condition and it has been described as a compression or entrapment neuropathy but it is an uncommon clinical manifestation due to necrotizing vasculitis. We report an unusual case of cryoglobulinaemic neuropathy in an elderly woman with no underlying infectious or neoplastic cause; acute bilateral sciatic mononeuropathy was the presenting clinical manifestation of the cryoglobulinaemia. PMID:18834546

  8. Peripheral neuropathies during biologic therapies.

    PubMed

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

    2016-03-01

    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

  9. Inherited peripheral neuropathy.

    PubMed

    Keller, M P; Chance, P F

    1999-01-01

    Hereditary disorders of the peripheral nerves constitute a group of frequently encountered neurological diseases. Charcot-Marie-Tooth neuropathy type 1 (CMT1) is genetically heterogeneous and characterized by demyelination with moderately to severely reduced nerve conduction velocities, absent muscle stretch reflexes and onion bulb formation. Genetic loci for CMT1 map to chromosome 17 (CMT1A), chromosome 1 (CMT1B), and another unknown autosome (CMT1C). CMT1A is most often associated with a tandem 1.5-megabase (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. CMT1 B result from point mutations in the myelin protein zero (Po or MPZ) gene. The molecular defect in CMT1 C is unknown. Mutations in the early growth response 2 gene (EGR2) are also associated with demyelinating neuropathy. Other rare forms of demyelinating peripheral neuropathies map to chromosome 8q, 10q, and 11q. X-linked Charcot-Marie-Tooth neuropathy (CMTX), which has clinical features similar to CMT1, is associated with mutations in the connexin32 gene. Charcot-Marie-Tooth neuropathy type 2 (CMT2) is characterized by normal or mildly reduced nerve conduction velocity with decreased amplitude and axonal loss without hypertrophic features. One form of CMT2 maps to chromosome 1 p36 (CMT2A), another to chromosome 3p (CMT2B) and another to 7p (CMT2D). Dejerine-Sottas disease (DSD), also called hereditary motor and sensory neuropathy type III (HMSNIII), is a severe, infantile-onset demyelinating polyneuropathy that may be associated with point mutations in either the PMP22 gene or the Po gene and shares considerable clinical and pathological features with CMT1. Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder that results in a recurrent, episodic demyelinating neuropathy. HNPP is associated with a 1.5-Mb deletion in chromosome 17p11.2-12 and results from reduced expression of the PMP22 gene. CMT1A and HNPP are reciprocal duplication/deletion syndromes originating from unequal crossover during germ cell meiosis. PMID:10716658

  10. Dominantly inherited peripheral neuropathies.

    PubMed

    Vallat, Jean-Michel

    2003-07-01

    Since 1886, the year that Charcot and Marie and Tooth described a genetic "peroneal muscular atrophy syndrome," electrophysiological and histological studies of the peripheral nervous system have greatly aided the characterization of this syndrome, which falls among the hereditary sensory-motor neuropathies. Two principal forms of Charcot-Marie-Tooth (CMT) disease have been distinguished: CMT 1, corresponding to a demyelinating type, and CMT 2, corresponding to an axonal type. The modes of transmission of these types are variable, recessive or dominant, autosomal, or X-linked. Our discussion here is confined to the dominant forms. In recent years, advances in molecular biology have greatly modified the approach to CMT disease and related neuropathies (such as hereditary neuropathy with liability to pressure palsies). With increased knowledge of responsible gene mutations and several other loci identified by linkage studies, our understanding of the pathophysiology of these neuropathies is increasing; however, with greater understanding, the classification of these disorders is becoming more complex. In this review we present and discuss the currently characterized subtypes, with emphasis on their known histological aspects. While nerve biopsy has lost its diagnostic importance in certain forms of the disease, such as CMT 1A, CMT 1B, and X-linked CMT (CMT X), it remains important for better characterizing the lesions of CMT 2 and forms of genetic peroneal atrophy in which DNA study is unrevealing. PMID:12901697

  11. Neurotrophins and peripheral neuropathy.

    PubMed

    Tomlinson, D R; Fernyhough, P; Diemel, L T

    1996-03-29

    The most common form of peripheral neuropathy is that associated with diabetes mellitus. In rodent models of diabetes there are expression deficits in nerve growth factor (NGF) and in its high-affinity receptor, trkA, leading to decreased retrograde axonal transport of NGF and decreased support of NGF-dependent sensory neurons, with reduced expression of their neuropeptides, substance P and calcitonin gene-related peptide (CGRP). Treatment of diabetic rats with intensive insulin normalized these deficits and treatment with exogenous NGF caused dose-related increases, giving levels of NGF and neuropeptides which were greater than those of controls. Neurotrophin-3 (NT-3) mRNA was also deficient in leg muscle from diabetic rats and administration of recombinant NT-3 to diabetic rats increased the conduction velocity of sensory nerves without affecting motor conduction velocity. These findings implicate deficient neurotrophic support in diabetic neuropathy and suggest that its correction should be a paramount therapeutic target. PMID:8730785

  12. 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

  13. 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-Barr 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

  14. [Vasculitic peripheral neuropathy].

    PubMed

    Oya, Yasushi

    2013-11-01

    The typical clinical manifestation of vasculitic peripheral neuropathy is sensory-dominant multiple mononeuropathy, although it can progress to distal-dominant sensorimotor polyneuropathy. It is painful in most cases. Peripheral nerves may be the most prone to produce symptoms of the vasculitis. Nerve conduction studies show reduced amplitude of M wave or sensory nerve action potential, which depends on the degree of injury of a nerve examined. Wallerian degeneration can cause pseudo-conduction block in the acute stage and temporal dispersion in the chronic stage. However, a definite diagnosis requires histological confirmation. Combined biopsy of the sural nerve and the peroneus brevis muscle can be performed by a single incision. Skin biopsy can also be performed. To increase the diagnostic yield, biopsy specimens are prepared in different manners to observe as many cross sections as possible: frozen unfixed, formalin-fixed paraffin-embedded, and glutaraldehyde-fixed epon embedded specimens, as well as teased fiber preparation of a nerve. Vasculitic peripheral neuropathy usually results from small-vessel vasculitis. There are still controversies regarding the classification of vasculitides. Differential diagnosis of vasculitis includes infection and lymphoma. Delayed diagnosis and treatment of neuropathy result in the impairment of ADL and QOL. Recovery from axonal degeneration usually takes time and is not always possible. Treatment includes corticosteroid, cyclophosphamide, and intravenous immunoglobulin administration; however, the intensity of treatment depends on the disease activity of vasculitis. PMID:24200608

  15. Genetics Home Reference: Small fiber neuropathy

    MedlinePLUS

    ... literature OMIM Genetic disorder catalog Conditions > Small fiber neuropathy On this page: Description Genetic changes Inheritance Diagnosis ... definitions Reviewed November 2012 What is small fiber neuropathy? Small fiber neuropathy is a condition characterized by ...

  16. Genetics Home Reference: Ataxia neuropathy spectrum

    MedlinePLUS

    ... Recent literature OMIM Genetic disorder catalog Conditions > Ataxia neuropathy spectrum On this page: Description Genetic changes Inheritance ... Glossary definitions Reviewed June 2011 What is ataxia neuropathy spectrum? Ataxia neuropathy spectrum is part of a ...

  17. Genetics Home Reference: Giant axonal neuropathy

    MedlinePLUS

    ... literature OMIM Genetic disorder catalog Conditions > Giant axonal neuropathy On this page: Description Genetic changes Inheritance Diagnosis ... definitions Reviewed October 2007 What is giant axonal neuropathy? Giant axonal neuropathy is an inherited condition involving ...

  18. Management of painful neuropathies.

    PubMed

    Brix Finnerup, Nanna; Hein Sindrup, Sren; Staehelin Jensen, Troels

    2013-01-01

    Neuropathic pain is the most common type of pain in neuropathy. In painful polyneuropathies the pain usually has a "glove and stocking" distribution. The pain may be predominantly spontaneous, e.g., with a burning, pricking, or shooting character or characterized by evoked pain such as mechanical or cold allodynia. In the clinical setting, the prevention of painful neuropathies and treatment of underlying neuropathy remains inadequate and thus symptomatic treatment of the pain and related disability needs to be offered. Most randomized, double-blind, placebo-controlled trials (RCTs) published in painful neuropathy have been conducted in patients with diabetes and to what extent a treatment which is found effective in painful diabetic polyneuropathy can be expected to relieve other conditions like chemotherapy- or HIV-induced neuropathy is unknown. Tricyclic antidepressants (TCAs), gabapentin, pregabalin, and serotonin noradrenaline reuptake inhibitors (SNRIs) are first drug choices. In patients with localized neuropathic pain, a topical lidocaine patch may also be considered. Second-line treatments are tramadol and other opioids. New types of treatment include botulinum toxin type A (BTX-A), high-dose capsaicin patches, and cannabinoids. Other types of anticonvulsant drugs such as lamotrigine, oxcarbazepine, and lacosamide have a more questionable efficacy in painful polyneuropathy but may have an effect in a subgroup of patients. Combination therapy may be considered in patients with insufficient effect from one drug. Treatment is usually a trial-and-error process and has to be individualized to the single patient, taking into account all comorbidities such as possible concomitant depression, anxiety, diseases, and drug interactions. Side-effects to antidepressants include dry mouth, nausea, constipation, orthostatic hypotension, and sedation. ECG should always be obtained prior to treatment with TCAs, which also should not be used in patients with cardiac incompensation and epilepsy. The most common side-effects of gabapentin and pregabalin are CNS-related side-effects with dizziness and somnolence. Peripheral edema, weight gain, nausea, vertigo, asthenia, dry mouth, and ataxia may also occur. Topical treatments are better tolerated due to lack of systemic side-effects but there is still limited evidence for the long-term efficacy of these drugs. With available drugs, the average pain reduction is about 20-30%, and only 20-35% of the patients will achieve at least 50% pain reduction, which stresses the need of a multidisciplinary approach to pain treatment. PMID:23931787

  19. Genetics Home Reference: Giant axonal neuropathy

    MedlinePLUS

    ... giant axonal neuropathy? autosomal ; autosomal recessive ; axons ; cell ; central nervous system ; distended ; gene ; incidence ; inherited ; injury ; nervous system ; neuropathy ; peripheral ; peripheral nervous system ; proteasome ; protein ; recessive ; ubiquitin You ...

  20. Mimics and chameleons of optic neuritis.

    PubMed

    Weerasinghe, Dinushi; Lueck, Christian

    2016-04-01

    Optic neuritis is a common problem and most neurologists are familiar with it. Recent studies have suggested that it can be overdiagnosed in as many as 10% of cases. The major reasons for this relate to confusion regarding terminology and lack of familiarity with common mimics. This article covers typical 'idiopathic' demyelinating optic neuropathy (IDON) and several possible variations in the way it can present (chameleons). We then discuss several conditions that can mimic IDON, including neuromyelitis optica, sarcoidosis, chronic relapsing inflammatory optic neuropathy, anterior ischaemic optic neuropathy, infectious/parainfectious optic neuropathy, neuroretinitis, Leber's hereditary optic neuropathy, and some 'ocular' mimics including autoimmune retinopathy and central serous choroidoretinopathy. PMID:26764409

  1. Peripheral neuropathy and solitary plasmacytoma.

    PubMed Central

    Read, D; Warlow, C

    1978-01-01

    Three patients with peripheral neuropathy and a solitary plasmacytoma are presented, and the literature is reviewed. It is suggested that middle-aged men with an obscure progressive sensorimotor neuropathy, a raised CSF protein, and otherwise negative investigations should have a full skeletal survey since irradiation of a plasmacytoma may lead to a considerable improvement in the associated neurological disability. Images PMID:204745

  2. Neuropathy in a petrol sniffer.

    PubMed Central

    Hall, D M; Ramsey, J; Schwartz, M S; Dookun, D

    1986-01-01

    A 4 year old boy developed a profound motor neuropathy after repeated deliberate inhalation of petroleum vapour. The condition was characterised by extreme slowing of the nerve conduction velocity. He made a gradual recovery over six months. The neuropathy was attributed to the N-hexane component of petroleum. PMID:3021070

  3. 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, but such intervention may be considered in the severe and progressive cases or ones associated with severe neuropathic pain.

  4. 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.

  5. [Surgical therapy for entrapment neuropathy].

    PubMed

    Tachibana, Shigekuni

    2012-01-01

    Entrapment neuropathy is not uncommon, and surgical treatment is followed by favorite result. Therefore, to obtain an accurate diagnosis based on precise knowledge of the peripheral nervous system is very important. The most popular and useful symptoms and signs of the entrapment neuropathy is paresthesia, dysesthesia and Tinel's like sign at the lesion site. Nerve conduction study is also valuable for the accurate diagnosis. For the last 30 years, the author operated on 1,399 lesions of entrapment neuropathy. They consist of 877 carpal tunnel syndrome (63%), 284 tarsal tunnel syndrome (20%), 135 ulnar neuropathy at the elbow (10%), 53 piriformis syndrome (4%), 15 thoracic outlet syndrome (1%), and others. From the pathophysiological point to view, except for the carpal tunnel syndrome, several locations and factors come into play producing the entrapment of the nerve. The author would like to stress that the entrapment neuropathy is not severe disease, though, it strongly insult the patient's quality of life. PMID:23196438

  6. 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

  7. 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

  8. 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

  9. [Painful ischemic neuropathy].

    PubMed

    Lang, P M

    2015-02-01

    Chronic ischemia in patients with peripheral arterial disease (PAD) represents a common medical problem. Neuropathic changes and pain caused by chronic ischemia are often found in the lower extremities of these patients. Pain in patients with chronic critical limb ischemia fulfill the criteria of neuropathic pain. Diagnostic tools besides medical history and examination are questionnaires, quantitative sensory testing (QST) and measuring intraepidermal nerve fiber density (IENFD) when indicated. A pharmacological approach with non-opioids and opioids as well as antidepressive and anticonvulsive drugs (according to the recommendations for the therapy of neuropathic pain) seems to be indicated for treating painful ischemic neuropathy. Spinal cord stimulation (SCS) provides the best evidence for invasive procedures in treating chronic ischemic pain. PMID:25620734

  10. Peripheral neuropathy and statins.

    PubMed

    2007-12-01

    (1) Statins are cholesterol-lowering drugs extensively used in cardiovascular prevention. Their most well-known adverse effect is muscle damage, including rhabdomyolysis. (2) Several cases of peripheral polyneuropathy attributed to a statin have been published or reported by pharmacovigilance centres. (3) They included sensory or sensorimotor polyneuropathy with signs of sensory impairment, and a decrease or sometimes a suppression of osteotendinous reflexes. Some patients also had a marked reduction in muscle strength in the affected limb(s). Renal failure and diabetes appear to increase the risk of this adverse effect. (4) Epidemiological studies and clinical trials have shown that this adverse effect is rare, affecting only about one patient in 10 000 treated for one year. (5) After ruling out other possible causes of peripheral neuropathy, statin withdrawal often leads to clinical improvement. PMID:18092417

  11. 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.

  12. Chemotherapy-Induced Peripheral Neuropathy

    Cancer.gov

    The pain and discomfort caused by peripheral neuropathy is one of the most common reasons that cancer patients stop their treatment early. Researchers are working to improve new screening, treatment, and prevention options for patients.

  13. Peripheral Neuropathy: Symptoms and Signs

    MedlinePLUS

    ... Burning sensation or freezing pain Sharp, jabbing or electric-like pain Extreme sensitivity to touch Difficulty sleeping ... damaged. There are three types of peripheral nerves: motor, sensory and autonomic. Some neuropathies affect all three ...

  14. 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

  15. Molecular basis of hereditary neuropathies.

    PubMed

    Chance, P F

    2001-05-01

    Inherited disorders of peripheral nerves represent a common group of neurologic diseases. Charcot-Marie-Tooth neuropathy type 1 (CMT1) is a genetically heterogeneous group of chronic demyelinating polyneuropathies with loci mapping to chromosome 17 (CMT1A), chromosome 1 (CMT1B) and to another unknown autosome (CMT1C). CMT1A is most often associated with a tandem 1.5-megabase (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 or MPZ) gene. The molecular defect in CMT1C is unknown. X-linked Charcot-Marie-Tooth neuropathy (CMTX), which has clinical features similar to CMT1, is associated with mutations in the connexin32 gene. Charcot-Marie-Tooth neuropathy type 2 (CMT2) is an axonal neuropathy, also of undetermined cause. Forms of CMT2 map to chromosome 1p36 (CMT2A), chromosome 3p (CMT2B), chromosome 7p (CMT2D), and to chromosome 8p21 (CMT2E). Dejerine-Sottas disease (DSD), also called hereditary motor and sensory neuropathy type III (HMSNIII), is a severe, infantile-onset, demyelinating polyneuropathy syndrome that may be associated with point mutations in either the PMP22 gene or the P0 gene and shares considerable clinical and pathologic features with CMT1. Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder that results in a recurrent, episodic demyelinating neuropathy. HNPP is associated with a 1.5-Mb deletion in chromosome 17p11.2-12 and results from reduced expression of the PMP22 gene. CMT1A and HNPP are reciprocal duplication/deletion syndromes originating from unequal crossover during germ cell meiosis. Other rare forms of demyelinating peripheral neuropathies map to chromosomes 8q, 10q, and 11q. Hereditary neuralgic amyotrophy (familial brachial plexus neuropathy) is an autosomal dominant disorder causing painful, recurrent brachial plexopathies and maps to chromosome 17q25. PMID:11345007

  16. Profiling the Mitochondrial Proteome of Lebers 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

    Lebers 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 lead to the development of LHON in synergy with the primary mtDNA mutation. PMID:25215595

  17. 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 6weeks can be from paraneoplastic origin. A 65-year-old woman was admitted for generalized pruritus lasting for 1month, 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

  18. The Spectrum of Diabetic Neuropathies

    PubMed Central

    Tracy, Jennifer A.; Dyck, P. James B.

    2009-01-01

    Diabetes mellitus is associated with many different neuropathic syndromes, ranging from a mild sensory disturbance as can be seen in a diabetic sensorimotor polyneuropathy, to the debilitating pain and weakness of a diabetic lumbosacral radiculoplexus neuropathy. The etiology of these syndromes has been extensively studied, and may vary among metabolic, compressive, and immunological bases for the different disorders, as well as mechanisms yet to be discovered. Many of these disorders of nerve appear to be separate conditions with different underlying mechanisms, and some are directly caused by diabetes mellitus, whereas others are associated with it but not caused by hyperglycemia. We discuss a number of the more common disorders of nerve found with diabetes mellitus. We discuss the symmetrical neuropathies, particularly generalized diabetic polyneuropathy, and then the focal or asymmetrical types of diabetes-associated neuropathy. PMID:18194747

  19. 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

  20. Neuropathy, amyloidosis, and monoclonal gammopathy.

    PubMed Central

    Fitting, J W; Bischoff, A; Regli, F; De Crousaz, G

    1979-01-01

    Three cases of neuropathy with monoclonal gammopathy and amyloid deposits in peripheral nerves are described. They appeared to present a benign gammopathy because of the duration of the neuropathy in the absence of any clinical or biological sign of myeloma or macroglobulinaemia. The pathological abnormality found in the sural nerves of the three patients was characterised by a marked loss of myelinated and unmyelinated nerve fibres because of active axonal degeneration with Wallerian degeneration. The most striking feature in all three cases was the finding of deposits identified as an accumulation of microfibrils. Images PMID:220385

  1. [Diabetic neuropathy: new therapeutic options?].

    PubMed

    Haslbeck, Manfred

    2006-11-01

    The importance of diabetic neuropathy as an independent risk factor for coronary heart disease and leading risk factor for the diabetic foot syndrome has become firmly established. The first line treatment comprises optimal diabetic control and intensified multifactorial treatment with normalization of blood pressure and blood lipids. In this connection, a fascinating recent discovery is the so called "metabolic memory" of an earlier near normal diabetic control over years, with a reduction of about 50% in nonfatal and fatal cardiac events and the incidence of diabetic neuropathy as a result of a former intensive therapy. PMID:17619441

  2. Advances in understanding drug-induced neuropathies.

    PubMed

    Peltier, Amanda C; Russell, James W

    2006-01-01

    Many commonly used medications have neurotoxic adverse effects; the most common of these is peripheral neuropathy. Neuropathy can be a dose-limiting adverse effect for many medications used in life-threatening conditions, such as malignancy and HIV-related disease. Epidemiological evidence supports previous case reports of HMG-CoA reductase inhibitors (or 'statins') causing an axonal sensorimotor neuropathy or a purely small-fibre neuropathy in some patients. The neuropathy improves when the medication is withdrawn. Despite the association between HMG-CoA reductase inhibitors and neuropathy, the risk is low compared with the significant vascular protective benefits. Oxaliplatin, a new platinum chemotherapy agent designed to have fewer adverse effects than other such agents, has been shown to cause a transient initial dysaesthesia in addition to an axonal polyneuropathy. Thalidomide, an old therapy currently being utilised for new therapeutic indications (e.g. treatment of haematological malignancies), is associated with a painful, axonal sensorimotor neuropathy that does not improve on withdrawal of the drug. Nucleoside reverse transcriptase inhibitors are important components of highly active antiretroviral therapy, but are associated with a sensory neuropathy that is likely to be due to a direct effect of these drugs on mitochondrial DNA replication. New research demonstrates that lactate levels may help discriminate between neuropathy caused by nucleoside analogues and HIV-induced neuropathy. Understanding the mechanism of drug-induced neuropathy has led to advances in preventing this disabling condition. PMID:16454532

  3. Update on medication-induced peripheral neuropathy.

    PubMed

    Weimer, Louis H; Sachdev, Noor

    2009-01-01

    Despite improvements in the identification of causes of peripheral neuropathy, idiopathic polyneuropathy remains common. Medication and toxic neuropathy account for a small but important percentage of potentially preventable or reversible causes of neuropathy. New drugs that can induce neuropathy have been approved over the past several years, including the anticancer agents bortezomib, ixabepilone, and oxaliplatin. We review the neurotoxic effects of tumor necrosis factor-alpha blockers infliximab and etanercept, the inflammatory arthritis agent leflunomide, and the antibiotic linezolid. The controversy of statin-induced neuropathy continues to unfold; the large Fremantle Diabetes Study has suggested that statins may have neuroprotective effects. Dichloroacetate is a promising agent for lactic acidosis-associated disorders, but toxic neuropathy is a treatment-limiting factor. We also describe a progressive inflammatory neuropathy in swine slaughterhouse workers that appears to be a toxin-induced immune response. PMID:19080756

  4. 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

  5. Hereditary sensory neuropathy type I.

    PubMed

    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 tumours like amelanotic melanoma. Management of HSN I follows the guidelines given for diabetic foot care (removal of pressure to the ulcer and eradication of infection, followed by the use of specific protective footwear) and starts with early and accurate counselling of patients about risk factors for developing foot ulcerations. The disorder is slowly progressive and does not influence life expectancy but is often severely disabling after a long duration of the disease. PMID:18348718

  6. [Clinical practice of hereditary motor neuropathy (HMN) and hereditary sensory and autonomic neuropathy (HSAN)].

    PubMed

    Takashima, Hiroshi

    2014-01-01

    Inherited neuropathy is a genetically and clinically heterogeneous group of neuropathies, the main category becomes Charcot-Marie-Tooth neuropathy (CMT), also known as hereditary motor and sensory neuropathy (HMSN), distal hereditary motor neuropathy (dHMN), and hereditary sensory autonomic neuropathy (HSAN). At least 80 genes have been associated with CMT, HMN or HSAN, a precise molecular diagnosis is often needed to make a clinical diagnosis accurately, enable genetic counseling of the patient and understanding of their molecular mechanisms. To identify the mutation in each patient, using a high-throughput NGS, we established a diagnostic procedure involving screening of disease causing genes in CMT, HMN or HSAN. PMID:25672680

  7. Drug-induced peripheral neuropathies.

    PubMed Central

    Argov, Z; Mastaglia, F L

    1979-01-01

    Review of the various drugs in current clinical use showed that over 50 of them may cause a purely sensory or mixed sensorimotor neuropathy. These include antimicrobials, such as isoniazid, ethambutol, ethionamide, nitrofurantoin, and metronidazole; antineoplastic agents, particularly vinca alkaloids; cardiovascular drugs, such as perhexiline and hydrallazine; hypnotics and psychotropics, notable methaqualone; antirheumatics, such as gold, indomethacin, and chloroquine; anticonvulsants, particularly phenytoin; and other drugs, including disulfiram, calcium carbimide, and dapsone. Patients receiving drug treatment who complain of paraesthesie, pain, muscle cramps, or other abnormal sensations and those without symptoms who are receiving drugs that are known or suspected to be neurotoxic should undergo neurological examination and studies of motor and sensory nerve conduction. This will allow the incidence of drug-induced peripheral neuropathy to be determined more precisely. PMID:219931

  8. Treatment of gastrointestinal autonomic neuropathy.

    PubMed

    Trnblom, 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, Pter Kempler (DOI: 10.1007/s00125-015-3826-y ). PMID:26634570

  9. [Acquired peripheral neuropathies associated with monoclonal gammopathy].

    PubMed

    Gajos, Agata; Kieli?, Wojciech; Szadkowska, Iwona; Chmielowska, Ewa; Niewodniczy, Aleksander; Bogucki, Andrzej

    2007-01-01

    Monoclonal gammopathy is responsible for about 10% of acquired peripheral neuropathies of unknown origin. Monoclonal gammopathy is the result of uncontrolled proliferation of a single clone of plasma cells producing the first class of immunoglobulin (M-protein). The routine diagnostic process of peripheral neuropathy requires electrophysiological studies and several laboratory tests, including the immunoelectrophoresis or immunofixation of serum proteins. Monoclonal gammopathies develop in malignancy, immunological disorders, chronic infections and as so-called "benign form" or monoclonal gammopathy of undetermined significance (MGUS). Lymphoproliferative malignancy may develop in MGUS after many years of disease. Patients with MGUS-associated neuropathy should be carefully evaluated, and if malignancy is not found the progress of the disease should be monitored. We present four patients with peripheral neuropathy associated with monoclonal gammopathy. These cases represent different forms of this type of neuropathy and well illustrate the necessity of looking for monoclonal gammopathies in peripheral neuropathy. PMID:17530580

  10. Painful diabetic neuropathy: clinical aspects.

    PubMed

    Didangelos, Triantafyllos; Doupis, John; Veves, Aristidis

    2014-01-01

    Painful diabetic neuropathy (PDN) is one of several clinical syndromes in patients with diabetic peripheral neuropathy (DPN) and presents a major challenge for optimal management. The epidemiology of PDN has not been extensively studied. On the basis of available data, the prevalence of pain ranges from 10% to 20% in patients with diabetes and from 40% to 50% in those with diabetic neuropathy. Neuropathic pain can be disabling and devastating, with a significant impact on the patient's quality of life and associated healthcare cost. Pathophysiologic mechanisms underlying PDN are similar to other neuropathic pain disorders and broadly invoke peripheral and central sensitization. The natural course of PDN is variable, with the majority of patients experiencing spontaneous improvement and resolution of pain. Quantifying neuropathic pain is difficult, especially in clinical practice, but has improved recently in clinical trials with the development of neuropathic pain-specific tools, such as the Neuropathic Pain Questionnaire and the Neuropathic Pain Symptom Inventory. Hyperglycemia-induced pathways result in nerve dysfunction and damage, which lead to hyperexcitable peripheral and central pathways of pain. Glycemic control may prevent or partially reverse DPN and modulate PDN. PMID:25410214

  11. Genetics Home Reference: Hereditary neuropathy with liability to pressure palsies

    MedlinePLUS

    ... Genetic disorder catalog Conditions > Hereditary neuropathy with liability to pressure palsies On this page: Description Genetic changes ... April 2007 What is hereditary neuropathy with liability to pressure palsies? Hereditary neuropathy with liability to pressure ...

  12. Genetics Home Reference: Autosomal recessive axonal neuropathy with neuromyotonia

    MedlinePLUS

    ... OMIM Genetic disorder catalog Conditions > Autosomal recessive axonal neuropathy with neuromyotonia On this page: Description Genetic changes ... Reviewed September 2014 What is autosomal recessive axonal neuropathy with neuromyotonia? Autosomal recessive axonal neuropathy with neuromyotonia ...

  13. Genetics Home Reference: Distal hereditary motor neuropathy, type II

    MedlinePLUS

    ... OMIM Genetic disorder catalog Conditions > Distal hereditary motor neuropathy, type II On this page: Description Genetic changes ... Reviewed August 2009 What is distal hereditary motor neuropathy, type II? Distal hereditary motor neuropathy, type II ...

  14. Genetics Home Reference: Hereditary neuropathy with liability to pressure palsies

    MedlinePLUS

    ... Recent literature OMIM Genetic disorder catalog Conditions > Hereditary neuropathy with liability to pressure palsies On this page: ... Glossary definitions Reviewed April 2007 What is hereditary neuropathy with liability to pressure palsies? Hereditary neuropathy with ...

  15. Genetics Home Reference: Distal hereditary motor neuropathy, type V

    MedlinePLUS

    ... OMIM Genetic disorder catalog Conditions > Distal hereditary motor neuropathy, type V On this page: Description Genetic changes ... Reviewed August 2009 What is distal hereditary motor neuropathy, type V? Distal hereditary motor neuropathy, type V ...

  16. Genetics Home Reference: Hereditary sensory and autonomic neuropathy type IE

    MedlinePLUS

    ... Genetic disorder catalog Conditions > Hereditary sensory and autonomic neuropathy type IE On this page: Description Genetic changes ... November 2012 What is hereditary sensory and autonomic neuropathy type IE? Hereditary sensory and autonomic neuropathy type ...

  17. Genetics Home Reference: Hereditary sensory neuropathy type IA

    MedlinePLUS

    ... literature OMIM Genetic disorder catalog Conditions > Hereditary sensory neuropathy type IA On this page: Description Genetic changes ... definitions Reviewed March 2015 What is hereditary sensory neuropathy type IA? Hereditary sensory neuropathy type IA is ...

  18. Genetics Home Reference: Leber hereditary optic neuropathy

    MedlinePLUS

    ... eyes worsens with a severe loss of sharpness (visual acuity) and color vision. This condition mainly affects ... death of cells in the nerve that relays visual information from the eyes to the brain (the ...

  19. 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

  20. Diabetic Cranio-Cervico-Radiculoplexus Neuropathy.

    PubMed

    Gupta, Gaurav; Massie, Rami; Doherty, Timothy J; Bourque, P R; Radhakrishna, Mohan; Finlayson, Roderick J; Besemann, Markus; Simantirakis, Emmanuel; Dyck, P James Bonham

    2015-11-01

    We describe a case of a 53-year-old man with type 2 diabetes mellitus in whom cervical-radiculoplexus neuropathy developed, with concomitant cranial and phrenic nerve involvement, occurring as a stepwise, monophasic course. The patient had a presumed remote history of idiopathic cervical-radiculoplexus neuropathy. PMID:25978945

  1. Abnormal thermoregulation in diabetic autonomic neuropathy.

    PubMed

    Scott, A R; MacDonald, I A; Bennett, T; Tattersall, R B

    1988-07-01

    Hypothermia has been reported to be more common in diabetic people than in nondiabetic people, and we have investigated the possibility that autonomic neuropathy may be associated with disordered thermoregulation. After an overnight fast and maintenance of normoglycemia, 12 insulin-treated diabetic patients with and 11 without neuropathy and 12 nondiabetic control subjects, all less than 55 yr, were subjected to external cooling by perfusing water at 16 degrees C through a liquid-conditioned coverall for less than or equal to 45 min. Patients with autonomic neuropathy had impaired vasoconstriction to cooling, particularly in the foot, calf, and forearm. Core temperature rose by 0.2 degrees C in control subjects and by 0.15 degrees C in patients with diabetes but no neuropathy. In contrast, group mean core temperature was unchanged in those with autonomic neuropathy and fell in 3 subjects (P less than .001). Cooling caused shivering in 6 patients with diabetic autonomic neuropathy, but not in those with neuropathy or control subjects (P less than .05). Baseline metabolic rates were similar in all three groups, but the increase after cooling was significantly greater among those who shivered (P less than .05-.02). Thus, young diabetic patients with autonomic neuropathy have impaired thermoregulation to a relatively short period of external cooling, even during metabolic stability, which may predispose to hypothermia. PMID:3384191

  2. Diabetic neuropathy and foot complications.

    PubMed

    Boulton, Andrew J M

    2014-01-01

    Foot ulceration and Charcot neuroarthropathy (CN) are well recognized and documented late sequelae of diabetic peripheral, somatic, and sympathetic autonomic neuropathy. The neuropathic foot, however, does not ulcerate spontaneously: it is a combination of loss of sensation due to neuropathy together with other factors such as foot deformity and external trauma that results in ulceration and indeed CN. The commonest trauma leading to foot ulcers in the neuropathic foot in Western countries is from inappropriate footwear. Much of the management of the insensate foot in diabetes has been learned from leprosy which similarly gives rise to insensitive foot ulceration. No expensive equipment is required to identify the high risk foot and recently developed tests such as the Ipswich Touch Test and the Vibratip have been shown to be useful in identifying the high risk foot. A comprehensive screening program, together with education of high risk patients, should help to reduce the all too high incidence of ulceration in diabetes. More recently another very high risk group has been identified, namely patients on dialysis, who are at extremely high risk of developing foot ulceration; this should be preventable. The most important feature in management of neuropathic foot ulceration is offloading as patients can easily walk on active foot ulcers due to the loss of pain sensation. Infection should be treated aggressively and if there is any evidence of peripheral vascular disease, arteriography and appropriate surgical management is also indicated. CN often presents with a unilateral hot, swollen foot and any patient presenting with these features known to have neuropathy should be treated as a Charcot until this is proven otherwise. Most important in the management of acute CN is offloading, often in a total contact cast. PMID:25410217

  3. 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

  4. 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

  5. Autonomic neuropathy in diabetes mellitus.

    PubMed

    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

  6. Drugs for the treatment of peripheral neuropathies.

    PubMed

    Marmiroli, Paola; Cavaletti, Guido

    2016-02-01

    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

  7. Obstructive Sleep Apnea and Diabetic Neuropathy

    PubMed Central

    Ali, Asad; Raymond, Neil T.; Begum, Safia; Dubb, Kiran; Mughal, Shanaz; Jose, Biju; Piya, Milan K.; Barnett, Anthony H.; Stevens, Martin J.

    2012-01-01

    Rationale: Diabetic peripheral neuropathy is common and causes significant morbidity. Obstructive sleep apnea (OSA) is also common in patients with type 2 diabetes. Because OSA is associated with inflammation and oxidative stress, we hypothesized that OSA is associated with peripheral neuropathy in type 2 diabetes. Objectives: To assess the relationship between OSA and peripheral neuropathy in patients with type 2 diabetes. Methods: A cross-sectional study of adults with type 2 diabetes recruited randomly from the diabetes clinic of two UK hospitals. Measurements and Main Results: Peripheral neuropathy was diagnosed using the Michigan Neuropathy Screening Instrument. OSA (apnea-hypopnea index ≥ 5 events/h) was assessed using home-based, multichannel respiratory monitoring. Serum nitrotyrosine was measured by ELISA, lipid peroxide by spectrophotometer, and microvascular function by laser speckle contrast imaging. Two hundred thirty-four patients (mean [SD] age, 57 [12] yr) were analyzed. OSA prevalence was 65% (median apnea-hypopnea index, 7.2; range, 0–93), 40% of which were moderate to severe. Neuropathy prevalence was higher in patients with OSA than those without (60% vs. 27%, P < 0.001). After adjustment for possible confounders, OSA remained independently associated with diabetic neuropathy (odds ratio, 2.82; 95% confidence interval, 1.44–5.52; P = 0.0034). Nitrotyrosine and lipid peroxide levels (n = 102, 74 with OSA) were higher in OSA and correlated with hypoxemia severity. Cutaneous microvascular function (n = 71, 47 with OSA) was impaired in OSA. Conclusions: We describe a novel independent association between diabetic peripheral neuropathy and OSA. We identified increased nitrosative/oxidative stress and impaired microvascular regulation as potential mechanisms. Prospective and interventional studies are needed to assess the impact of OSA and its treatment on peripheral neuropathy development and progression in patients with type 2 diabetes. PMID:22723291

  8. [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

  9. Novel MPZ mutations and congenital hypomyelinating neuropathy

    PubMed Central

    McMillan, Hugh J.; Santagata, Sandro; Shapiro, Frederic; Batish, Sat Dev; Couchon, Libby; Donnelly, Stephen; Kang, Peter B.

    2010-01-01

    We report two new MPZ mutations causing congenital hypomyelinating neuropathies; c.368_382delGCACGTTCACTTGTG (in-frame deletion of five amino acids) and c.392A>G, Asn131Ser. Each child had clinical and electrodiagnostic features consistent with an inherited neuropathy, confirmed by sural nerve biopsy. The cases illustrate the clinically heterogeneity that exists even within early-onset forms of this disease. They also lend additional support to the emerging clinical and laboratory evidence that impaired intracellular protein trafficking may represent the cause of some congenital hypomyelinating neuropathies. PMID:20621479

  10. 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

  11. 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

  12. 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

  13. Vitamin B supplementation for diabetic peripheral neuropathy.

    PubMed

    Jayabalan, Bhavani; Low, Lian Leng

    2016-02-01

    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

  14. Genetics Home Reference: Small fiber neuropathy

    MedlinePLUS

    ... of this condition include a metabolic disorder called Fabry disease, immune disorders such as celiac disease or Sjogren ... SCN10A genes. Read more about celiac disease and Fabry disease . How do people inherit small fiber neuropathy? Small ...

  15. Evidence for sensory neuropathy and pharmacologic management.

    PubMed

    Greene, Scott M; Simpson, C Blake

    2010-02-01

    Recent literature points to postviral sensory neuropathy as a possible cause for refractory chronic cough. Vagal neuropathy may affect the sensory branches, inducing chronic cough or laryngospasm. Although the clinical presentation is fairly well described, there is little in the way of diagnostic criteria to establish this diagnosis. This article highlights the clinical picture of this disease and the efficacy, side-effect profiles of the currently used pharmacological interventions. PMID:20172257

  16. Autonomic neuropathy in patients with hepatic cirrhosis

    PubMed Central

    Bajaj, B; Agarwal, M; Ram, B

    2003-01-01

    Background: Autonomic neuropathy has been reported in patients with alcoholic liver disease but information on its occurrence in patients with non-alcoholic liver disease is contradictory. Aim: To assess autonomic functions in patients with alcoholic and non-alcoholic liver disease. Study design: Autonomic function using five standard tests was examined in 20 cirrhotics (10 alcoholics and 10 non-alcoholics) and 20 age and sex matched controls. The extent of autonomic dysfunction was determined in the patients and a comparison between the characteristics of patients with and without autonomic neuropathy was made. Results: Sixteen (80%) of the cirrhotic subjects were found to have evidence of autonomic neuropathy. Of these, three (15%) patients had early parasympathetic damage, five (25%) had definite parasympathetic damage, and eight (40%) had combined (that is, both parasympathetic and sympathetic) damage. Nine (90%) of the alcoholics and seven (70%) of the non-alcoholics had autonomic dysfunction. Only one patient belonging to the alcoholic group had clinical evidence of peripheral neuropathy. Moreover, there was no significant association between subjective symptoms of autonomic neuropathy and objective evidence of autonomic damage as assessed by autonomic function tests. Autonomic dysfunction was significantly more frequent in advanced liver disease compared with early liver damage. Nine (75%) out of 12 cirrhotic subjects belonging to Child class B and six (85.7%) of the seven patients belonging to Child class C had autonomic neuropathy. Conclusion: This study shows that autonomic neuropathy is common in cirrhotic subjects, that it is found with comparable frequency in alcoholics and non-alcoholics, and that it increases in severity with increase in extent of liver damage, suggesting that liver damage contributes to the neurological deficit. PMID:12897221

  17. Goiter and Laryngeal Sensory Neuropathy

    PubMed Central

    Hamdan, Abdul Latif; Jabour, Jad; Azar, Sami T.

    2013-01-01

    Objective. Examining the prevalence of laryngeal sensory neuropathy (LSN) in goiter patients versus a control group. Study Design. Cross-sectional study. Methods. 33 Goiter patients were enrolled versus 25 age-matched controls. TSH levels, size of thyroid gland, and presence or absence of thyroid nodules were reported. Subjects were asked about the presence or absence of any of the following symptoms: cough, globus pharyngeus, and/or throat clearing that persistented for more than 6 weeks. The presence of one or more of these symptoms for at least six weeks in the absence of LPRD, allergy, asthma, ACE inhibitor intake, and psychogenic disorder was defined as LSN. Results. For goitrous patients mean age (years) was (41.73 ± 9.47) versus (37.44 ± 10.89) for controls. 82% goitrous patients had known nodules and 27% carried a simultaneous diagnosis of hypothyroidism. Among those with documented size (61%), mean total thyroid volume was 26.996 ± 14.852 cm3, with a range from 9.430 to 67.022 cm3. The overall prevalence of LSN among goitrous patients was 42% versus 12% among controls (P = 0.0187). There was no correlation between LSN, size of thyroid gland, and TSH level. Conclusion. The prevalence of LSN in goitrous patients is significantly higher than that in a nongoitrous population. PMID:23818901

  18. 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 ?-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 ?-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

  19. 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

  20. Mouse Models of Diabetic Neuropathy

    PubMed Central

    O'Brien, Phillipe D.; Sakowski, Stacey A.; Feldman, Eva L.

    2014-01-01

    Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes and is associated with significant morbidity and mortality. DPN is characterized by progressive, distal-to-proximal degeneration of peripheral nerves that leads to pain, weakness, and eventual loss of sensation. The mechanisms underlying DPN pathogenesis are uncertain, and other than tight glycemic control in type 1 patients, there is no effective treatment. Mouse models of type 1 (T1DM) and type 2 diabetes (T2DM) are critical to improving our understanding of DPN pathophysiology and developing novel treatment strategies. In this review, we discuss the most widely used T1DM and T2DM mouse models for DPN research, with emphasis on the main neurologic phenotype of each model. We also discuss important considerations for selecting appropriate models for T1DM and T2DM DPN studies and describe the promise of novel emerging diabetic mouse models for DPN research. The development, characterization, and comprehensive neurologic phenotyping of clinically relevant mouse models for T1DM and T2DM will provide valuable resources for future studies examining DPN pathogenesis and novel therapeutic strategies. PMID:24615439

  1. Inherited neuropathies: from gene to disease.

    PubMed

    Keller, M P; Chance, P F

    1999-04-01

    Inherited disorders of peripheral nerves represent a common group of neurologic diseases. Charcot-Marie-Tooth neuropathy type 1 (CMT1) is a genetically heterogeneous group of chronic demyelinating polyneuropathies with loci mapping to chromosome 17 (CMT1A), chromosome 1 (CMT1B) and to another unknown autosome (CMT1C). CMT1A is most often associated with a tandem 1.5-megabase (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 or MPZ) gene. The molecular defect in CMT1C is unknown. X-linked Charcot-Marie-Tooth neuropathy (CMTX), which has clinical features similar to CMT1, is associated with mutations in the connexin32 gene. Charcot-Marie-Tooth neuropathy type 2 (CMT2) is an axonal neuropathy, also of undetermined cause. One form of CMT2 maps to chromosome 1p36 (CMT2A), another to chromosome 3p (CMT2B) and another to 7p (CMT2D). Dejerine-Sottas disease (DSD), also called hereditary motor and sensory neuropathy type III (HMSNIII), is a severe, infantile-onset demyelinating polyneuropathy syndrome that may be associated with point mutations in either the PMP22 gene or the P0 gene and shares considerable clinical and pathological features with CMT1. Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder that results in a recurrent, episodic demyelinating neuropathy. HNPP is associated with a 1.5-Mb deletion in chromosome 17p11.2-12 and results from reduced expression of the PMP22 gene. CMT1A and HNPP are reciprocal duplication/deletion syndromes originating from unequal crossover during germ cell meiosis. Other rare forms of demyelinating peripheral neuropathies map to chromosome 8q, 10q and 11q. Hereditary neuralgic amyotrophy (familial brachial plexus neuropathy) is an autosomal dominant disorder causing painful, recurrent brachial plexopathies and maps to chromosome 17q25. PMID:10219749

  2. Medial arterial calcification and diabetic neuropathy.

    PubMed Central

    Edmonds, M E; Morrison, N; Laws, J W; Watkins, P J

    1982-01-01

    X-ray examinations of the feet, knees, and hands were performed on 20 diabetics with severe neuropathy and 20 diabetics with no evidence of neuropathy but with a similar mean age and duration of diabetes. All were under 53 years old with no clinical evidence of peripheral vascular disease. Medial arterial calcification was much more common and extensive in the patients with neuropathy, occurring in the feet in 15 and in the hands in eight compared with in four (p less than 0.001) and none (p less than 0.001) of the controls respectively. Although there was some correlation between calcification and both proteinuria (p less than 0.05) and proliferative retinopathy (p less than 0.02), the association between calcification and neuropathy (p less than 0.001) was much stronger. Neuropathy, with sympathetic denervation of the smooth muscle of the tunica media, may be important in the aetiology of medial arterial calcification. Images FIG 1 FIG 2 PMID:6802354

  3. Genetics Home Reference: Congenital cataracts, facial dysmorphism, and neuropathy

    MedlinePLUS

    ... disorder catalog Conditions > Congenital cataracts, facial dysmorphism, and neuropathy (often shortened to CCFDN ) On this page: Description ... What is CCFDN? Congenital cataracts, facial dysmorphism, and neuropathy (CCFDN) is a rare disorder that affects several ...

  4. Genetics Home Reference: Neuropathy, ataxia, and retinitis pigmentosa

    MedlinePLUS

    ... PubMed Recent literature OMIM Genetic disorder catalog Conditions > Neuropathy, ataxia, and retinitis pigmentosa (often shortened to NARP ) ... Glossary definitions Reviewed November 2006 What is NARP? Neuropathy, ataxia, and retinitis pigmentosa (NARP) is a condition ...

  5. Genetics Home Reference: Hereditary sensory and autonomic neuropathy type II

    MedlinePLUS

    ... Genetic disorder catalog Conditions > Hereditary sensory and autonomic neuropathy type II (often shortened to HSAN2 ) On this ... 2011 What is HSAN2? Hereditary sensory and autonomic neuropathy type II (HSAN2) is a condition that primarily ...

  6. Genetics Home Reference: Hereditary sensory and autonomic neuropathy type V

    MedlinePLUS

    ... Genetic disorder catalog Conditions > Hereditary sensory and autonomic neuropathy type V (often shortened to HSAN5 ) On this ... 2011 What is HSAN5? Hereditary sensory and autonomic neuropathy type V (HSAN5) is a condition that primarily ...

  7. 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...

  8. 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

  9. 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

  10. Early Electrophysiological Abnormalities and Clinical Neuropathy

    PubMed Central

    Hyllienmark, Lars; Alstrand, Nils; Jonsson, Bjrn; 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 722 years) of age, and duration of diabetes was 6.8 3.3 years. At follow-up, patients were 2035 years of age, and disease duration was 20 5.3 years (range 1031 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 < 0.0100.003). 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 (? = 0.40, P < 0.002) than with follow-up HbA1c (? = 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

  11. Delayed Pneumocephalus-Induced Cranial Neuropathy

    PubMed Central

    Marupudi, Neena I.

    2013-01-01

    Pneumocephalus is a common occurrence after cranial surgery, with patients typically remaining asymptomatic from a moderate amount of intracranial air. Postsurgical pneumocephalus rarely causes focal neurological deficits; furthermore, cranial neuropathy from postsurgical pneumocephalus is exceedingly uncommon. Only 3 cases have been previously reported that describe direct cranial nerve compression from intracranial air resulting in an isolated single cranial nerve deficit. The authors present a patient who developed dysconjugate eye movements from bilateral oculomotor nerve palsy. Direct cranial nerve compression occurred as a result of postoperative pneumocephalus in the interpeduncular cistern. The isolated cranial neuropathy gradually recovered as the intracranial air was reabsorbed. PMID:24151506

  12. 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

  13. 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…

  14. [Painful neuropathies and small fiber involvement].

    PubMed

    Lefaucheur, J-P

    2014-12-01

    It is customary to consider that a purely sensory and painful neuropathy accompanied by normal electroneuromyographic examination may be or must be a small fiber neuropathy. This leads to perform specific tests, such as measuring the intra-epidermal nerve fiber density on skin biopsy or neurophysiological tests, such as evoked potentials to noxious stimuli (laser) or quantification of thermal sensory thresholds. However, these tests are only sensitive to the loss of small fibers (A-delta and C), which does not reflect the mechanisms responsible for peripheral neuropathic pain. Selective loss of small sensory fibers inherently generates a sensory deficit that does not necessarily present a painful character. Also, assigning the cause of a painful neuropathy to a small fiber neuropathy has no pathophysiological sense, although there are indirect links between these two conditions. In fact, it is not possible to explain univocally peripheral neuropathic pain, which reflects complex and diverse mechanisms, involving different types of nerve fibers. In this context, the clinical and laboratory approach must be improved to better understand the underlying mechanisms. It is imperative to interpret the data provided by laboratory tests and to correlate these data to the clinical signs and symptoms presented by the patients. Thus, one must go beyond many a priori and misinterpretations that unfortunately exist in this area at present and are not based on any solid pathophysiological basis. PMID:25459125

  15. 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

  16. Diabetic Neuropathies: The Nerve Damage of Diabetes

    MedlinePLUS

    ... 000 nontraumatic amputations were performed in people with diabetes. Comprehensive foot care programs can reduce amputation rates by 45 ... should consider making an appointment to see a foot doctor, also called a ... common to diabetes, such as high blood glucose. Neuropathy can affect ...

  17. 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

  18. Hereditary neuropathy with liability to pressure palsy.

    PubMed

    Paprocka, Justyna; Kajor, Maciej; Jamroz, Ewa; Jezela-Stanek, Aleksandra; Seeman, Pavel; Marszał, Elzbieta

    2006-01-01

    Hereditary neuropathy with liability to pressure palsy (HNPP) is an autosomal dominant disease with sensory and motor nerve palsies usually precipitated by trivial trauma or compression. In the majority of cases HNPP is caused by deletion of the peripheral myelin protein 22 gene (PMP22) on chromosome 17p11.2. The authors present a family case with genetically proven HNPP. PMID:17183456

  19. 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…

  20. 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.

  1. 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

  2. Neuropathic pain in hereditary peripheral neuropathy

    PubMed Central

    Jeong, Na Young; Shin, Youn Ho; Jung, Junyang

    2013-01-01

    Charcot-Marie-Tooth (CMT) disease is the most common inherited motor and sensory neuropathy. Previous studies have shown that neuropathic pain is an occasional symptom of CMT referred by CMT patients. However, neuropathic pain is not considered a significant symptom in CMT patient and no researchers have studied profoundly the pathophysiology of neuropathic pain in CMT. Here, we highlight the relationship between CMT disease and neuropathic pain via previous several studies. PMID:24278891

  3. 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

  4. Imaging of entrapment and compressive neuropathies.

    PubMed

    Bashir, Waseem A; Connell, David A

    2008-06-01

    Although the subject of entrapment and compressive neuropathies is huge, with dedicated textbooks on the subject, this article attempts to provide an up-to-date overview of the role of imaging in the diagnosis of nerve entrapment and compression syndromes. Entrapment and compressive neuropathies are a group of distinct syndromes secondary to physical constriction or irritation affecting peripheral nerves at specific anatomical sites in the body. Most nerve entrapment and compressive syndromes derive from an injury to the neurovascular components in a narrow anatomical passage. Because of their etiological diversity, which includes pressure, angulation, stretch, and friction, the pathophysiology of individual nerve entrapment syndromes differs widely. Neuropathy can result in considerable morbidity. Although the mainstay of achieving diagnosis is with clinical acumen and electrophysiological investigations, the increasing use of modern high-resolution imaging studies is of particular value in confirming physical findings and enabling determination of the extent of injury. Knowledge and familiarity of pertinent anatomy and appropriate choice of imaging modality is important for the radiologist to allow accurate interpretation of site and etiology of nerve entrapment and compression as well as ascertaining possible alternative diagnoses. PMID:18509796

  5. [Case of minocycline-induced vasculitic neuropathy].

    PubMed

    Ogawa, Nobuhiro; Kawai, Hiromichi; Yamakawa, Isamu; Sanada, Mitsuru; Sugimoto, Toshiro; Maeda, Kengo

    2010-05-01

    A 70-year-old woman was admitted to our hospital because of fever, numbness in her extremities and right drop foot. Because her hip prosthesis had loosened as a result of infection, she had been taking 100 mg of minocycline orally for eight months. Three months before admission, she had had melena several times and body weight loss and pyrexia developed. A month before admission, asymmetrical paresthesia and numbness appeared in her extremities and finally right drop foot developed. Laboratory tests showed elevated C-reactive protein and positive anti-nuclear antibody. Abnormalities found in nerve conduction study were compatible with mononeuritis multiplex. Sural nerve biopsy revealed an occluded medium-size artery in the epineurium and axonal degeneration in the nerve fascicles, confirming the diagnosis of vasculitic neuropathy. These manifestations met the American Congress Rheumatology criteria for polyarteritis nodosa. However, her clinical conditions markedly improved after discontinuing minocycline and therefore she was diagnosed as having minocycline-induced vasculitic neuropathy. Although minocycline-induced vasculitis is a well known adverse effect of the drug, peripheral neuropathy with biopsy findings has rarely been reported. Drug induced-vasculitis is important as a differential diagnosis for mononeuritis multiplex because the symptoms can be improved by the discontinuation of an offending drug. PMID:20535977

  6. Intravenous Lidocaine Infusion to Treat Chemotherapy-Induced Peripheral Neuropathy.

    PubMed

    Papapetrou, Peter; Kumar, Aashish J; Muppuri, Rudram; Chakrabortty, Shushovan

    2015-11-01

    Chemotherapy-induced peripheral neuropathy is a debilitating side effect of chemotherapy, which manifests as paresthesias, dysesthesias, and numbness in the hands and feet. Numerous chemoprotective agents and treatments have been used with limited success to treat chemotherapy-induced peripheral neuropathy. We report a case in which a patient presenting with chemotherapy-induced peripheral neuropathy received an IV lidocaine infusion over the course of 60 minutes with complete symptomatic pain relief for a prolonged period of 2 weeks. PMID:26528700

  7. Femoral compressive neuropathy from iliopsoas haematoma complicating dengue hemorrhagic fever.

    PubMed

    Ganu, Sneha; Mehta, Yesha

    2013-05-13

    Dengue fever is a debilitating mosquito-borne disease caused by dengue virus. We reported a case of femoral compression neuropathy due to iliopsoas hematoma complicating dengue hemorrhagic fever. Iliopsoas muscle hematoma can cause femoral neuropathy with resultant pain and paralysis. Such manifestations are not well documented in the literature. The pathogenesis of hematoma and compressive neuropathy with its appropriate management is discussed. PMID:23608387

  8. Clinically diagnosed diabetic neuropathy: frequency, types and severity.

    PubMed Central

    Ugoya, Solomon O.; Echejoh, Godwins O.; Ugoya, Tokunbo A.; Agaba, Emmanuel I.; Puepet, Fabian H.; Ogunniyi, Adesola

    2006-01-01

    OBJECTIVE: Studies of frequency of occurrence of diabetic neuropathy are few, and available studies were limited to the southern part of Nigeria. The objectives of the study were to determine the frequency of occurrence and grades of diabetes peripheral neuropathy using clinical measures. PATIENTS AND METHODS: Consecutive patients with diabetes mellitus attending the Jos University Teaching Hospital were recruited as the study population, including 120 diabetics and 60 age-matched, nondiabetic controls. A standard proforma based on the Michigan Neuropathy Screening Instrument (MNSI) was employed to screen for diabetic neuropathy. RESULTS: The frequency of occurrence of diabetic peripheral neuropathy was 75%. For the specific types of peripheral neuropathy, sensorimotor neuropathy was the commonest (40.4%, chi(2)=29.1; p<0.001). There was no significant difference, with severity of peripheral neuropathy among diabetics, when compared by gender. (Chi square=3.03, P value=0.081). CONCLUSION: The frequency of occurrence of peripheral neuropathy among diabetics in Jos University Teaching Hospital from this study is rather high. PMID:17128685

  9. Peripheral Neuropathy: A Practical Approach to Diagnosis and Symptom Management.

    PubMed

    Watson, James C; Dyck, P James B

    2015-07-01

    Peripheral neuropathy is one of the most prevalent neurologic conditions encountered by physicians of all specialties. Physicians are faced with 3 distinct challenges in caring for patients with peripheral neuropathy: (1) how to efficiently and effectively screen (in less than 2 minutes) an asymptomatic patient for peripheral neuropathy when they have a disorder in which peripheral neuropathy is highly prevalent (eg, diabetes mellitus), (2) how to clinically stratify patients presenting with symptoms of neuropathy to determine who would benefit from specialty consultation and what testing is appropriate for those who do not need consultation, and (3) how to treat the symptoms of painful peripheral neuropathy. In this concise review, we address these 3 common clinical scenarios. Easily defined clinical patterns of involvement are used to identify patients in need of neurologic consultation, the yield of laboratory and other diagnostic testing is reviewed for the evaluation of length-dependent, sensorimotor peripheral neuropathies (the most common form of neuropathy), and an algorithmic approach with dosing recommendations is provided for the treatment of neuropathic pain associated with peripheral neuropathy. PMID:26141332

  10. Genetics of Primary Inherited Disorders of the Optic Nerve: Clinical Applications.

    PubMed

    Allen, Keri F; Gaier, Eric D; Wiggs, Janey L

    2015-07-01

    Inherited disorders of the optic nerve significantly impact vision in children and adults. The optic nerve disorders most commonly encountered clinically are glaucoma and primary optic neuropathy including Leber's hereditary optic neuropathy (LHON) and autosomal dominant or Kjer's optic atrophy. Current knowledge of the genetics of optic neuropathy and glaucoma makes it possible to test for mutations in disease-causing genes allowing for presymptomatic testing and risk assessment, and recent advances have revealed important disease mechanisms that may suggest potential therapeutic targets. In this perspective, we describe the current approaches and limitations to genetic testing for these disorders and provide an update on the development of gene-based therapies. PMID:26134840

  11. Quality assessment of online patient education resources for peripheral neuropathy.

    PubMed

    Hansberry, David R; Suresh, Ragha; Agarwal, Nitin; Heary, Robert F; Goldstein, Ira M

    2013-03-01

    Given its practicality, the internet is a primary resource for patients afflicted with diseases like peripheral neuropathy. Therefore, it is important that the readily available online resources on peripheral neuropathy are tailored to the general public, particularly concerning readability. Patient education resources were downloaded from the US National Library of Medicine, Mayo Clinic, National Institute of Neurological Disorders and Stroke, Neuropathy.org, GBS/CIDP Foundation International, Hereditary Neuropathy Foundation, Charcot-Marie-Tooth Association, Foundation for Peripheral Neuropathy, and Neuropathy Action Foundation websites. All patient education material related to peripheral neuropathy was evaluated for its level of readability using the Flesch Reading Ease (FRE) and Flesch-Kincaid Grade Level. The FRE scores averaged 43.4 with only the US National Library of Medicine scoring above 60 (76.5). The Flesch-Kincaid Grade Level scores averaged 11.0. All scores were above a seventh-grade level except the US National Library of Medicine, which had a score of a fifth-grade reading level. Most Americans may not fully benefit from patient education resources concerning peripheral neuropathy education on many of the websites. Only the US National Library of Medicine, which is written at a fifth-grade level, is likely to benefit the average American. PMID:23521643

  12. 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 envision treatment options for these rare diseases in the near future. PMID:24860645

  13. Median palmar digital neuropathy in a cheerleader.

    PubMed

    Shields, R W; Jacobs, I B

    1986-11-01

    Median palmar digital neuropathy developed in a 16-year-old girl as a result of chronic trauma to the palm during cheerleading activities. The clinical findings on examination, which included paresthesias in the distribution of a palmar digital nerve and exacerbation of symptoms with compression of the palm, were consistent with this diagnosis. Nerve conduction studies documented a lesion of the median palmar digital nerve. Avoidance of cheerleading activities resulted in nearly total resolution of the symptoms. Awareness of this entity and the value of nerve conduction studies in establishing the diagnosis may avoid confusion and facilitate correct diagnosis and management. PMID:3778181

  14. 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

  15. [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

  16. 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

  17. 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

  18. ALCOHOL-RELATED PERIPHERAL NEUROPATHY: NUTRITIONAL, TOXIC, OR BOTH?

    PubMed Central

    MELLION, MICHELLE; GILCHRIST, JAMES M.; DE LA MONTE, SUZANNE

    2015-01-01

    Alcohol-related peripheral neuropathy (ALN) is a potentially debilitating complication of alcoholism that results in sensory, motor, and autonomic dysfunction. Unfortunately, ALN is rarely discussed as a specific disease entity in textbooks because it is widely assumed to primarily reflect consequences of nutritional deficiency. This hypothesis is largely based on observations first made over eight decades ago when it was demonstrated that thiamine deficiency (beriberi) neuropathy was clinically similar to ALN. In recent studies, failure of thiamine treatment to reverse ALN, together with new information demonstrating clinical and electrophysiological distinctions between ALN and nutritional deficiency neuropathies, suggests that alcohol itself may significantly predispose and enhance development of neuropathy in the appropriate clinical setting. We reviewed the evidence on both sides and conclude that ALN should be regarded as a toxic rather than nutritional neuropathy. PMID:21321947

  19. Mutational mechanisms in MFN2-related neuropathy: compound heterozygosity for recessive and semidominant mutations.

    PubMed

    Piscosquito, Giuseppe; Saveri, Paola; Magri, Stefania; Ciano, Claudia; Di Bella, Daniela; Milani, Micaela; Taroni, Franco; Pareyson, Davide

    2015-12-01

    Mitofusin-2 (MFN2) mutations are the most common cause of autosomal dominant axonal Charcot-Marie-Tooth disease (CMT, type 2A), sometimes complicated by additional features such as optic atrophy (CMT6) and upper motor neuron involvement (CMT5). Several pathogenic mutations are reported, mainly acting in a dominant fashion, although few sequence variants behaved as recessive or semidominant in rare homozygous or compound heterozygous patients. We describe a 49-year-old woman with CMT5 associated with compound heterozygosity for two MFN2 variants, one already reported missense mutation (c.748C>T, p.R250W) and a novel nonsense sequence change (c.1426C>T, p.R476*). Her mother, carrying the p.R250W variant, had very late-onset minimal axonal neuropathy, whilst the father harboring the nonsense sequence change had neither clinical nor electrophysiological neuropathy. The missense mutation is likely pathogenic according to in silico analyses and a previous report, while the nonsense variant is predicted to behave as a null allele. The p.R250W variant behaves as semidominant by causing only a mild, almost subclinical, neuropathy when heterozygous; the nonsense mutation in the father was phenotypically silent, suggesting that haploinsufficiency for MFN2 is not disease causative, but was deleterious in the daughter who had only one active mutated MFN2 allele. PMID:26306937

  20. Progesterone Treatment in Two Rat Models of Ocular Ischemia

    PubMed Central

    Allen, Rachael S.; Olsen, Timothy W.; Sayeed, Iqbal; Cale, Heather A.; Morrison, Katherine C.; Oumarbaeva, Yuliya; Lucaciu, Irina; Boatright, Jeffrey H.; Pardue, Machelle T.; Stein, Donald G.

    2015-01-01

    Purpose. To determine whether the neurosteroid progesterone, shown to have protective effects in animal models of traumatic brain injury, stroke, and spinal cord injury, is also protective in ocular ischemia animal models. Methods. Progesterone treatment was tested in two ocular ischemia models in rats: a rodent anterior ischemic optic neuropathy (rAION) model, which induces permanent monocular optic nerve stroke, and the middle cerebral artery occlusion (MCAO) model, which causes transient ischemia in both the retina and brain due to an intraluminal filament that blocks the ophthalmic and middle cerebral arteries. Visual function and retinal histology were assessed to determine whether progesterone attenuated retinal injury in these models. Additionally, behavioral testing and 2% 2,3,5-triphenyltetrazolium chloride (TTC) staining in brains were used to compare progesterone's neuroprotective effects in both retina and brain using the MCAO model. Results. Progesterone treatment showed no effect on visual evoked potential (VEP) reduction and retinal ganglion cell loss in the permanent rAION model. In the transient MCAO model, progesterone treatment reduced (1) electroretinogram (ERG) deficits, (2) MCAO-induced upregulation of glutamine synthetase (GS) and glial fibrillary acidic protein (GFAP), and (3) retinal ganglion cell loss. As expected, progesterone treatment also had significant protective effects in behavioral tests and a reduction in infarct size in the brain. Conclusions. Progesterone treatment showed protective effects in the retina following MCAO but not rAION injury, which may result from mechanistic differences with injury type and the therapeutic action of progesterone. PMID:26024074

  1. [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

  2. 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.

  3. [Ocular side-effects associated with amiodarone therapy].

    PubMed

    Turdumambetova, G; Bredehorn, T; Duncker, G I W

    2005-06-01

    Amiodarone, one of the most effective anti-arrhythmic drugs, is also known for its ability to accumulate lipid-pharmakon complexes in the lysosomes of different tissues. In the eye the lysosomal storage leads to typical side-effects. Whorl-like epithelial, reversible corneal inclusions occur in about 70 to 100 % of the patients on amiodarone therapy. Tiny lens opacities without visual impairment have been reported in 50 % of patients who had been treated with amiodarone. At present the most severe complication of amiodarone is optic neuropathy with an incidence of 1.3 to 1.8 %. The optic neuropathy, as the rule, is only reversible approximately in (1/2) of the patients after discontinuing the drug. The fundoscopic picture of amiodarone neuropathy is similar to classic AION. Retinal involvement has also been reported; however, a relationship with amiodarone has not been proven yet. PMID:15973627

  4. Foot pad skin biopsy in mouse models of hereditary neuropathy.

    PubMed

    Dacci, Patrizia; Dina, Giorgia; Cerri, Federica; Previtali, Stefano Carlo; Lopez, Ignazio Diego; Lauria, Giuseppe; Feltri, Maria Laura; Bolino, Alessandra; Comi, Giancarlo; Wrabetz, Lawrence; Quattrini, Angelo

    2010-12-01

    Numerous transgenic and knockout mouse models of human hereditary neuropathies have become available over the past decade. We describe a simple, reproducible, and safe biopsy of mouse skin for histopathological evaluation of the peripheral nervous system (PNS) in models of hereditary neuropathies. We compared the diagnostic outcome between sciatic nerve and dermal nerves found in skin biopsy (SB) from the hind foot. A total of five animal models of different Charcot-Marie-Tooth neuropathies, and one model of congenital muscular dystrophy associated neuropathy were examined. In wild type mice, dermal nerve fibers were readily identified by immunohistochemistry, light, and electron microscopy and they appeared similar to myelinated fibers in sciatic nerve. In mutant mice, SB manifested myelin abnormalities similar to those observed in sciatic nerves, including hypomyelination, onion bulbs, myelin outfolding, redundant loops, and tomacula. In many strains, however, SB showed additional abnormalities--fiber loss, dense neurofilament packing with lower phosphorylation status, and axonal degeneration-undetected in sciatic nerve, possibly because SB samples distal nerves. SB, a reliable technique to investigate peripheral neuropathies in human beings, is also useful to investigate animal models of hereditary neuropathies. Our data indicate that SB may reveal distal axonal pathology in mouse models and permits sequential follow-up of the neuropathy in an individual mouse, thereby reducing the number of mice necessary to document pathology of the PNS. PMID:20878767

  5. Foot Pad Skin Biopsy in Mouse Models of Hereditary Neuropathy

    PubMed Central

    Dacci, Patrizia; Dina, Giorgia; Cerri, Federica; Previtali, Stefano Carlo; Lopez, Ignazio Diego; Lauria, Giuseppe; Feltri, Maria Laura; Bolino, Alessandra; Comi, Giancarlo; Wrabetz, Lawrence; Quattrini, Angelo

    2010-01-01

    Numerous transgenic and knockout mouse models of human hereditary neuropathies have become available over the past decade. We describe a simple, reproducible, and safe biopsy of mouse skin for histopathological evaluation of the peripheral nervous system (PNS) in models of hereditary neuropathies. We compared the diagnostic outcome between sciatic nerve and dermal nerves found in skin biopsy (SB) from the hind foot. A total of five animal models of different Charcot-Marie-Tooth neuropathies, and one model of congenital muscular dystrophy associated neuropathy were examined. In wild type mice, dermal nerve fibers were readily identified by immunohistochemistry, light, and electron microscopy and they appeared similar to myelinated fibers in sciatic nerve. In mutant mice, SB manifested myelin abnormalities similar to those observed in sciatic nerves, including hypomyelination, onion bulbs, myelin outfolding, redundant loops, and tomacula. In many strains, however, SB showed additional abnormalities—fiber loss, dense neurofilament packing with lower phosphorylation status, and axonal degeneration—undetected in sciatic nerve, possibly because SB samples distal nerves. SB, a reliable technique to investigate peripheral neuropathies in human beings, is also useful to investigate animal models of hereditary neuropathies. Our data indicate that SB may reveal distal axonal pathology in mouse models and permits sequential follow-up of the neuropathy in an individual mouse, thereby reducing the number of mice necessary to document pathology of the PNS. © 2010 Wiley-Liss, Inc. PMID:20878767

  6. The Metabolic Syndrome and Neuropathy: Therapeutic Challenges and Opportunities

    PubMed Central

    Callaghan, Brian; Feldman, Eva

    2013-01-01

    The metabolic syndrome and neuropathy are common conditions, especially in the elderly, that are associated with significant morbidity. Furthermore, the metabolic syndrome is reaching epidemic proportions across the world. Current evidence supports the association of the metabolic syndrome and its individual components with neuropathy. Several clinical trials have demonstrated that treating hyperglycemia, one component of the metabolic syndrome, has a significant effect on reducing the incidence of neuropathy in those with type 1 diabetes. However, glucose control only has a marginal effect on preventing neuropathy in those with type 2 diabetes, suggesting that other factors may be driving nerve injury in these patients. Emerging evidence supports the metabolic syndrome as these risk factors for neuropathy. Interventions exist for treatment of all of the metabolic syndrome components, but only glucose control has strong evidence to support its use and is widely employed. Our understanding of the biology of metabolic nerve injury has rapidly expanded over the last several years. Mechanisms of injury include fatty deposition in nerves, extracellular protein glycation, mitochondrial dysfunction, and oxidative stress. Additionally, the activation of counter-regulatory signaling pathways leads to chronic metabolic inflammation. Medications that target these signaling pathways are being used for a variety of diseases and are intriguing therapeutics for future neuropathy clinical trials. As we move forward, we need to expand our understanding of the association between the metabolic syndrome and neuropathy by addressing limitations of previous studies. Just as importantly, we must continue to investigate the pathophysiology of metabolically induced nerve injury. PMID:23929529

  7. 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

  8. Sjgren Syndrome-Associated Small Fiber Neuropathy

    PubMed Central

    Sne, Damien; Cacoub, Patrice; Authier, Franois-Jrme; Haroche, Julien; Crange, Alain; Saadoun, David; Amoura, Zahir; Guillausseau, Pierre-Jean; Lefaucheur, Jean-Pascal

    2013-01-01

    Abstract We conducted the current study to analyze the clinical, immunologic, and neurophysiologic features of primary Sjgren syndrome (pSS)-associated sensory small fiber neuropathies (SFNs). Forty consecutive pSS patients with SFN were included. SFN was defined by the presence of suggestive sensory painful symptoms with normal nerve conduction studies and abnormal neurophysiologic tests for small nerve fibers or a low intraepidermal nerve fiber density at skin biopsy. Included patients were compared to 100 pSS patients without peripheral neuropathy. SFN patients were mainly female (92.5%). Age at pSS diagnosis was 55.3 13.1 years, and at SFN diagnosis, 58.9 11.8 years, with a median time to SFN diagnosis after symptom onset of 3.4 years. Clinical symptoms included burning pains (90%), numbness (87.5%), tingling (82.5%), pins and needles (72.5%), electric discharges (70%), and allodynia (55%). Dysautonomia included vasomotor symptoms (66%) and hyperhidrosis (47%). Abnormal neurophysiologic tests included laser evoked potentials (97.5%), thermal quantitative sensory testing (67.5%), and sympathetic skin reflex (40%). A skin biopsy revealed low intraepidermal nerve fiber density in 76% of the 17 tested patients. Compared to the 100 pSS patients without peripheral neuropathy, the 40 pSS-SFN patients were older at pSS diagnosis (55.3 13.1 vs. 49.5 14.9 yr; p = 0.03), and more often had xerostomia (97.5% vs. 81%; p = 0.01) and arthralgia (82.5% vs. 65.0%; p = 0.04). Immunologically, they were characterized by a lower prevalence of serum B-cell activation markers, that is, antinuclear antibodies (65% vs. 85%; p = 0.01), anti-SSA (42.5% vs. 71%; p = 0.002), and anti-SSB (17.5% vs. 39%; p = 0.017); rheumatoid factor (32.5% vs. 66%; p = 0.0005); and hypergammaglobulinemia (35% vs. 62%; p = 0.005). In conclusion, we report the main features of SFN in patients with pSS, the first such study to our knowledge. Our results show that patients with pSS-associated SFN are characterized by an older age at pSS diagnosis and a distinctive immunologic profile hallmarked by a lower frequency of serum B-cell activation markers. PMID:23982054

  9. Exercise increases cutaneous nerve density in diabetic patients without neuropathy

    PubMed Central

    Singleton, John R; Marcus, Robin L; Jackson, Justin E; K Lessard, Margaret; Graham, Timothy E; Smith, Albert G

    2014-01-01

    Early diabetic neuropathy is characterized by loss of unmyelinated axons, resulting in pain, numbness, and progressive decline in intraepidermal nerve fiber density. Patients with type 2 diabetes, without neuropathy, were assigned to quarterly lifestyle counseling (N = 40) or structured, supervised weekly exercise (N = 60) for 1 year. Distal leg IENFD significantly increased in the exercise cohort and remained unchanged in the counseling cohort (1.5 3.6 vs. ?0.1 3.2 fibers/mm, P = 0.03). These results suggest preclinical injury to unmyelinated axons is potentially reversible, and that IENFD may be a responsive biomarker useful in future neuropathy prevention clinical trials. PMID:25493275

  10. Hereditary peripheral neuropathies: clinical forms, genetics, and molecular mechanisms.

    PubMed

    Warner, L E; Garcia, C A; Lupski, J R

    1999-01-01

    Hereditary peripheral neuropathies, among the most common genetic disorders in humans, are a complex, clinically and genetically heterogeneous group of disorders that produce progressive deterioration of the peripheral nerves. This group of disorders includes hereditary neuropathy with liability to pressure palsies, Charcot-Marie-Tooth disease, Dejerine-Sottas syndrome, and congenital hypomyelinating neuropathy. Our understanding of these disorders has progressed from the description of the clinical phenotypes and delineation of the electrophysiologic and pathologic features to the identification of disease genes and elucidation of the underlying molecular mechanisms. PMID:10073277

  11. Chemotherapy-induced peripheral neuropathy: Current status and progress.

    PubMed

    Brewer, Jamie R; Morrison, Gladys; Dolan, M Eileen; Fleming, Gini F

    2016-01-01

    As there are increasing numbers of cancer survivors, more attention is being paid to the long term unwanted effects patients may experience as a result of their treatment and the impact these side effects can have on their quality of life. Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common long-term toxicities from chemotherapy. In this review we will briefly review the clinical presentation, evaluation and management of chemotherapy-induced peripheral neuropathy, with a focus on CIPN related to platinum and taxane agents. We will then discuss current clinical models of peripheral neuropathy and ongoing research to better understand CIPN and develop potential treatment options. PMID:26556766

  12. 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.

  13. Advances in the laboratory evaluation of peripheral neuropathies.

    PubMed

    Huan, Mengjing Chloe; Bromberg, Mark

    2012-02-01

    Peripheral neuropathy is a common clinical problem in neurology and laboratory testing is an integral part of diagnosis. In the past few years, practice parameters have been published to establish an evidence-based guide to neuropathy testing. There are many tests that are common and accepted in practice, but there is no clear mandate on which tests are necessary. This article reviews recent practice parameter publications as well as other updates in laboratory testing for peripheral neuropathy, including the roles of lipid profile, genetic testing, antibody titers, and B(12) testing in a specific dopamine-treated Parkinson's patients. These can serve as recommendations to help guide laboratory testing. PMID:22147264

  14. [Davidenkow syndrome. A rare peripheral neuropathy].

    PubMed

    Halley Carvalho Pimentel, Leonardo; Campos Paiva, Aline Lariessy; Esteves Veiga, Jos Carlos; Brasileiro de Aguiar, Guilherme

    2016-01-01

    A different and rare type of atrophy with a predominant pattern in scapulo-peroneal distribution was described by Davidenkow in 1939. The syndrome was characterized by some researchers as a variant of Charcot-Marie-Tooth disease, however Davidenkow noticed that clinical and laboratorial manifestations did not corroborate exactly with this hypothesis. We describe a case of a female patient, 39 years-old, clinical picture similar to the syndrome described by Davidenkow, presenting scapulo-peroneal atrophy. Her first symptoms had appeared when she was 24, initially with proximal motor weakness in the upper limbs. This patient did not have family history of myopathy or neuropathy. Several tests were performed to exclude other syndromes that could be included in the differential diagnosis, by testing gene mutation, in addition to the physical examination and electromyography. The large spectrum of neuromuscular diseases makes difficult the diagnosis of Davidenkow's syndrome which always should be considered in the differential diagnosis. PMID:26826991

  15. 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

  16. Multiple cranial neuropathy (a teaching case).

    PubMed

    Toro, Jaime; Milln, Carlos; Daz, Camilo; Reyes, Sal

    2013-10-01

    There are few reports of the multiple cranial neuropathy variant of Guillain-Barr Syndrome (GBS). Patients usually present with facial diplegia, lower cranial nerve involvement and hypo or areflexia. It is crucial to identify promptly this unusual cranial variant but the clinical characteristics remain poorly defined. This GBS variant usually has a rapid progressive course with respiratory muscle paralysis. Most of the patients recover well, although the process is slow. We report a 54 year old man presenting with facial diplegia, progressive ophthalmoplegia, lower cranial nerve involvement, sensory ataxia and generalized areflexia. This GBS variant is very unusual and seldom described in the literature; it is oftenly misdiagnosed. The clinical features and nerve conduction studies (absent F-waves, motor conduction block) provide evidence to support a diagnosis of an acute demyelinating polyneuropathy consistent with a regional cranial variant of GBS. PMID:25877853

  17. 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

  18. Gut sensations in diabetic autonomic neuropathy.

    PubMed

    Frøkjaer, Jens Brøndum; Andersen, Søren Due; Ejskaer, Niels; Funch-Jensen, Peter; Arendt-Nielsen, Lars; Gregersen, Hans; Drewes, Asbjørn Mohr

    2007-10-01

    The pathogenesis of gastrointestinal symptoms in diabetes mellitus is complex and multi-factorial. Diabetes induced peripheral and central changes in the neuronal pain matrix may be of importance and were explored using a new multi-modal and multi-segmental sensory testing approach. The sensitivity to mechanical, thermal and electrical stimulations in the oesophagus and duodenum was assessed in 12 type-1 diabetic patients with proven autonomic neuropathy and severe gastrointestinal symptoms using a comprehensive stimulation device aiming to activate different gut nerves and pain mechanisms. Twelve healthy subjects served as controls. The sensory response and the somatic referred pain areas were recorded. In the diabetic patients an overall hyposensitivity to the combination of all stimulations was found in the oesophagus and duodenum (P=0.02). Post hoc analysis revealed hyposensitivity to mechanical stimulations in the oesophagus (P=0.006) and duodenum (P=0.002), and to thermal (P<0.001) and electrical (P=0.005) stimulations in the oesophagus and duodenum combined. The hyposensitivity in the gut was accompanied by a 46% increase in the somatic referred pain areas (P=0.04) indicating central neuronal changes. The multi-modal and multi-segmental sensory testing approach indicates that the sensory nerves are widely affected in the GI tract and generalized to nerves in all layers of the gut. Changes in the neuronal pain matrix including interactions between peripheral and central pain mechanisms may be involved in the pathogenesis of gastrointestinal symptoms in long-standing diabetes. Future targets in the treatment of gastrointestinal symptoms in diabetic patients with autonomic neuropathy could be based on modulation of the central nervous system excitability. PMID:17521809

  19. 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

  20. Primary sinonasal undifferentiated carcinoma presenting with bilateral retrobulbar optic neuropathy.

    PubMed

    Tamhankar, Madhura A; Volpe, Nicholas J; Loevner, Laurie A; Palmer, James N; Feldman, Michael

    2007-09-01

    A 43-year-old man presented with acute bilateral visual loss. Ophthalmologic examination revealed no light perception in the right eye and a visual acuity of 20/50 in the left eye with a right afferent pupillary defect. Ophthalmoscopic examination was normal. Brain MRI showed an intracranial but extra-axial mass in the floor of the anterior cranial fossa extending along the olfactory groove and into the sinonasal vault. Endoscopic biopsy showed a high-grade neoplasm consistent with sinonasal undifferentiated carcinoma. This case report highlights an unusual clinical presentation for this rare and aggressive neoplasm. PMID:17895819

  1. Peripheral neuropathy and benign IgG paraproteinaemia.

    PubMed Central

    Read, D J; Vanhegan, R I; Matthews, W B

    1978-01-01

    Three patients with peripheral neuropathy and an associated benign IgG paraproteinaemia are described. No direct immunological evidence for an aetiological role of the paraprotein was found, and the implications of this are discussed. PMID:204748

  2. Genetics Home Reference: Neuropathy, ataxia, and retinitis pigmentosa

    MedlinePLUS

    ... most DNA is packaged in chromosomes within the nucleus, mitochondria also have a small amount of their ... maternal ; maternal inheritance ; mitochondria ; mutation ; nervous system ; neuropathy ; nucleus ; oxidative phosphorylation ; oxygen ; pattern of inheritance ; phosphorylation ; prevalence ; ...

  3. 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

  4. Genetics Home Reference: Autosomal recessive axonal neuropathy with neuromyotonia

    MedlinePLUS

    ... and Families Resources for Health Professionals What glossary definitions help with understanding autosomal recessive axonal neuropathy with ... 22, 2016 Lister Hill National Center for Biomedical Communications U.S. National Library of Medicine , National Institutes of ...

  5. Systemic mastocytosis associated with membranous nephropathy and peripheral neuropathy.

    PubMed

    Lal, S M; Brooks, C S; Luger, A M; Davenport, J G; Weber, R D; Loy, T S; Haibach, H H

    1988-12-01

    A report of the occurrence of membranous nephropathy and peripheral neuropathy in a patient with systemic mastocytosis is presented. Previous reviews of patients with systemic mastocytosis have not noted this association. During cyclical therapy with prednisone and chlorambucil in this case, nephrotic-range proteinuria remitted. Peripheral neuropathy resolved 10 months after discontinuation of therapy. Pathophysiological mechanisms resulting in this clinical presentation may be immunologically mediated. PMID:2848413

  6. Peripheral neuropathy following intentional inhalation of naphtha fumes.

    PubMed Central

    Tenenbein, M; deGroot, W; Rajani, K R

    1984-01-01

    Two adolescent native Canadians who presented with peripheral neuropathy secondary to the abuse of volatile hydrocarbons are described. They were initially thought to have been sniffing leaded gasoline fumes, but public health investigation revealed that they had been sniffing naphtha fumes. Naphtha contains a significant amount of n-hexane, a known inducer of neuropathy. Nerve conduction studies and nerve biopsy confirmed the diagnosis of naphtha abuse. These cases emphasize the need to specifically identify the formulation of hydrocarbons being abused. PMID:6093978

  7. Complications of Compressive Neuropathy: Prevention and Management Strategies

    PubMed Central

    Santosa, Katherine B.; Chung, Kevin C.; Waljee, Jennifer F.

    2016-01-01

    Compressive neuropathies of the upper extremity are common and can result in profound disability if left untreated. Nerve releases are frequently performed, but can be complicated by both iatrogenic events as well as progression of neuropathy. In this review, we will examine the management of post-operative complications following two common nerve compression release procedures: carpal tunnel release and cubital tunnel release. PMID:25934192

  8. Morphologic Changes in Autonomic Nerves in Diabetic Autonomic Neuropathy

    PubMed Central

    Jin, Heung Yong; Baek, Hong Sun

    2015-01-01

    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

  9. 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

  10. Statin-associated peripheral neuropathy: review of the literature.

    PubMed

    Chong, Pang H; Boskovich, Alexandra; Stevkovic, Natasa; Bartt, Russell E

    2004-09-01

    Various pharmacologic agents are available for the treatment of hypercholesterolemia, including 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, commonly referred to as statins, which offer favorable lipid-lowering effects and reductions in morbidity and mortality. Statins are usually better tolerated than other lipid-lowering agents and therefore have become a mainstay of treatment for hypercholesterolemia. However, recent case reports of peripheral neuropathy in patients treated with statins may have gone unnoticed by health care professionals. To evaluate the possible link between statins and peripheral neuropathy, literature searches using MEDLINE (January 1993--November 2003) and International Pharmaceutical Abstracts (January 1970--June 2002) were performed. Key search terms were statin, neuropathy, and HMG-CoA reductase inhibitors. Based on epidemiologic studies as well as case reports, a risk of peripheral neuropathy associated with statin use may exist; however, the risk appears to be minimal. On the other hand, the benefits of statins are firmly established. These findings should alert prescribers to a potential risk of peripheral neuropathy in patients receiving any of the statins; that is, statins should be considered the cause of peripheral neuropathy when other etiologies have been excluded. PMID:15460180

  11. 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; Lochmller, 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

  12. Suprascapular Neuropathy in Collegiate Baseball Player

    PubMed Central

    J.Niemann, Andrew; S.Juzeszyn, Laura; Kahanov, Leamor; E.Eberman, Lindsey

    2012-01-01

    Background Suprascapular neuropathy (SSN) is generally thought of as a diagnosis of exclusion. However, increasing attention is being paid to the diagnosis, treatment and rehabilitation of this pathology to prevent chronic supraspinatus and infraspinatus atrophy in patients. To date, literature has only articulated variable or customized treatment and rehabilitation plans without clear standardized care. This case study provides a detailed description of the diagnosis, treatment, and rehabilitation of a collegiate baseball player's recovery from suprascapular nerve release. Case Presentation A 20 year-old male baseball pitcher with right shoulder pain reported for athletic training evaluation, was treated conservatively, and due to lack of resolution was referred for further imaging and evaluation by an orthopedist. Following inconclusive magnetic resonance imaging findings the patient underwent electrodiagnostic testing which showed decreased nerve conduction velocity of the right suprascapular nerve. The patient elected for surgical intervention. Post-operative rehabilitation followed and the patient was able to pitch in 22 weeks. The patient provided positive subjective feedback and was able to return to unrestricted pitching without pain, loss of velocity, or loss in pitch control. Conclusion This study demonstrates a need for further investigation into the most appropriate treatment and rehabilitation of suprascapular nerve injury. PMID:23785580

  13. 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

  14. 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

  15. 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.; Lochmller, 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 CharcotMarieTooth 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

  16. Extracellular matrix remodelling in human diabetic neuropathy

    PubMed Central

    Hill, Rebecca

    2009-01-01

    The extracellular matrix of peripheral nerve plays a vital role in terms of normal nerve fibre function and also in the regenerative response following nerve injury. Nerve fibre loss is a major feature of diabetic neuropathy; however, the regenerative response is limited and this may be associated with changes in the composition of the extracellular matrix. Glycoproteins and collagens are major components of the extracellular matrix and are known to be important in terms of axonal growth. This work has therefore examined whether changes in the expression of two major glycoproteins, laminin and tenascin, and three collagen types (IV, V and VI) occur in the endoneurial and perineurial connective tissue compartments of human diabetic nerve. Despite being known to have a positive effect in terms of axonal growth, laminin levels were not elevated in the diabetic nerves. However, the pattern of tenascin expression did differ between the two groups being found in association with axon myelin units in the diabetic samples only. The pattern of collagen IV expression was the same in both tissue groups and was not found to be up-regulated. However, levels of collagen V and VI were both significantly increased in the endoneurium and for collagen VI also in the perineurium. PMID:19207983

  17. Understanding the biology of compressive neuropathies.

    PubMed

    Gupta, Ranjan; Rummler, Laura; Steward, Oswald

    2005-07-01

    Compressive neuropathies are highly prevalent, debilitating conditions with variable functional recovery after surgical decompression. Chronic nerve compression injury induces concurrent Schwann cell proliferation and apoptosis in the early stages of the disorder, independent of axonal injury. These proliferating Schwann cells locally demyelinate and remyelinate in the region of injury. Furthermore, Schwann cells upregulate vascular endothelial growth factor secondary to chronic nerve compression injury and induce neovascularization to facilitate the recruitment of macrophages. In contrast to Wallerian degeneration, macrophage recruitment occurs gradually with chronic nerve compression injury and continues for a longer time. Schwann cells change their gene and protein expression in response to mechanical stimuli as shear stress decreases the expression of myelin associated glycoprotein and myelin basic protein mRNA and protein for in vitro promyelinating Schwann cells. The local down-regulation of myelin associated glycoprotein in the region of compression injury creates an environment allowing axonal sprouting that may be reversed with intraneural injections of purified myelin associated glycoprotein. These studies suggest that while the reciprocal relationship between neurons and glial cells is maintained, chronic nerve compression injury is a Schwann cell-mediated disease. PMID:15995449

  18. 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

  19. 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

  20. Prevention of paclitaxel-induced peripheral neuropathy by lithium pretreatment

    PubMed Central

    Mo, Michelle; Erdelyi, Ildiko; Szigeti-Buck, Klara; Benbow, Jennifer H.; Ehrlich, Barbara E.

    2012-01-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect that occurs in many patients undergoing chemotherapy. It is often irreversible and frequently leads to early termination of treatment. In this study, we have identified two compounds, lithium and ibudilast, that when administered as a single prophylactic injection prior to paclitaxel treatment, prevent the development of CIPN in mice at the sensory-motor and cellular level. The prevention of neuropathy was not observed in paclitaxel-treated mice that were only prophylactically treated with a vehicle injection. The coadministration of lithium with paclitaxel also allows for administration of higher doses of paclitaxel (survival increases by 60%), protects against paclitaxel-induced cardiac abnormalities, and, notably, does not interfere with the antitumor effects of paclitaxel. Moreover, we have determined a mechanism by which CIPN develops and have discovered that lithium and ibudilast inhibit development of peripheral neuropathy by disrupting the interaction between paclitaxel, neuronal calcium sensor 1 (NCS-1), and the inositol 1,4,5-trisphosphate receptor (InsP3R) to prevent treatment-induced decreases in intracellular calcium signaling. This study shows that lithium and ibudilast are candidate therapeutics for the prevention of paclitaxel-induced neuropathy and could enable patients to tolerate more aggressive treatment regimens.Mo, M., Erdelyi, I., Szigeti-Buck, K., Benbow, J. H., Ehrlich, B. E. Prevention of paclitaxel-induced peripheral neuropathy by lithium pretreatment. PMID:22889832

  1. Uremic neuropathy: clinical features and new pathophysiological insights.

    PubMed

    Krishnan, Arun V; Kiernan, Matthew C

    2007-03-01

    Neuropathy is a common complication of end-stage kidney disease (ESKD), typically presenting as a distal symmetrical process with greater lower-limb than upper-limb involvement. The condition is of insidious onset, progressing over months. and has been estimated to be present in 60%-100% of patients on dialysis. Neuropathy generally only develops at glomerular filtration rates of less than 12 ml/min. The most frequent clinical features reflect large-fiber involvement, with paresthesias, reduction in deep tendon reflexes, impaired vibration sense, muscle wasting, and weakness. Nerve conduction studies demonstrate findings consistent with a generalized neuropathy of the axonal type. Patients may also develop autonomic features, with postural hypotension, impaired sweating, diarrhea, constipation, or impotence. The development of uremic neuropathy has been related previously to the retention of neurotoxic molecules in the middle molecular range, although this hypothesis lacked formal proof. Studies utilizing novel axonal excitability techniques have recently shed further light on the pathophysiology of this condition. Nerves of uremic patients have been shown to exist in a chronically depolarized state prior to dialysis, with subsequent improvement and normalization of resting membrane potential after dialysis. The degree of depolarization correlates with serum K(+), suggesting that chronic hyperkalemic depolarization plays an important role in the development of nerve dysfunction in ESKD. These recent findings suggest that maintenance of serum K(+) within normal limits between periods of dialysis, rather than simple avoidance of hyperkalemia, is likely to reduce the incidence and severity of uremic neuropathy. PMID:17195171

  2. Endoplasmic reticulum stress contributes to prediabetic peripheral neuropathy.

    PubMed

    Lupachyk, Sergey; Watcho, Pierre; Obrosov, Alexander A; Stavniichuk, Roman; Obrosova, Irina G

    2013-09-01

    Growing evidence suggests that prediabetes and metabolic syndrome are associated with increased risk for the development of microvascular complications including retinopathy, nephropathy, and, most commonly, peripheral painful neuropathy and/or autonomic neuropathy. The etiology of these disabling neuropathies is unclear, and several clinical and experimental studies implicated obesity, impaired fasting glycemia/impaired glucose tolerance, elevated triglyceride and non-esterified fatty acids, as well as oxidative-nitrative stress. Endoplasmic reticulum stress resulting from abnormal folding of newly synthesized proteins and leading to the impairment of metabolism, transcriptional regulation, and gene expression, is emerging as a key mechanism of metabolic diseases including obesity and diabetes. We evaluated the role for this phenomenon in prediabetic neuropathy using two animal models i.e., Zucker (fa/fa) rats and high-fat diet fed mice which displayed obesity and impaired glucose tolerance in the absence of overt hyperglycemia. Endoplasmic reticulum stress manifest in upregulation of the glucose-regulated proteins BiP/GRP78 and GRP94 of unfolded protein response was identified in the sciatic nerve of Zucker rats. A chemical chaperone, trimethylamine oxide, blunted endoplasmic reticulum stress and alleviated sensory nerve conduction velocity deficit, thermal and mechanical hypoalgesia, and tactile allodynia. A selective inhibitor of eukaryotic initiation factor-2? dephosphorylation, salubrinal, improved glucose intolerance and alleviated peripheral nerve dysfunction in high-fat diet fed mice. Our findings suggest an important role of endoplasmic reticulum stress in the neurobiology of prediabetic peripheral neuropathy, and identify a new therapeutic target. PMID:23142188

  3. 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

  4. Alcoholic neuropathy: possible mechanisms and future treatment possibilities.

    PubMed

    Chopra, Kanwaljit; Tiwari, Vinod

    2012-03-01

    Chronic alcohol consumption produces painful peripheral neuropathy for which there is no reliable successful therapy, mainly due to lack of understanding of its pathobiology. Alcoholic neuropathy involves coasting caused by damage to nerves that results from long term excessive drinking of alcohol and is characterized by spontaneous burning pain, hyperalgesia and allodynia. The mechanism behind alcoholic neuropathy is not well understood, but several explanations have been proposed. These include activation of spinal cord microglia after chronic alcohol consumption, oxidative stress leading to free radical damage to nerves, activation of mGlu5 receptors in the spinal cord and activation of the sympathoadrenal and hypothalamo-pituitary-adrenal (HPA) axis. Nutritional deficiency (especially thiamine deficiency) and/or the direct toxic effect of alcohol or both have also been implicated in alcohol-induced neuropathic pain. Treatment is directed towards halting further damage to the peripheral nerves and restoring their normal functioning. This can be achieved by alcohol abstinence and a nutritionally balanced diet supplemented by all B vitamins. However, in the setting of ongoing alcohol use, vitamin supplementation alone has not been convincingly shown to be sufficient for improvement in most patients. The present review is focused around the multiple pathways involved in the development of peripheral neuropathy associated with chronic alcohol intake and the different therapeutic agents which may find a place in the therapeutic armamentarium for both prevention and management of alcoholic neuropathy. PMID:21988193

  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 skins 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. 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.

  7. 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...

  8. 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.

  9. Vesiculobullous dermatomyositis with sensory motor neuropathy.

    PubMed

    Ayhan, Erhan; Baykara, Sule Nergiz; Ozekinci, Selver; Aytekin, Sema

    2013-01-01

    A 74-year-old man presented with muscle weakness in both legs for a duration of 2 months. Physical examination revealed periorbital edema and erythema, erythema on the neck and chest, erythematous papules on the proximal-distal interphalangeal and metocarpophalangeal joints, crusted plaque lesions on the thighs and around the knees, and bullous and ulcerated lesions in the antecubital and popliteal fossae (Figure 1A and 1B). Some bullous lesions were intact and some were ulcerated. There was severe edema especially in the upper extremities. He had a history of 15-kg weight loss for 4 months. Laboratory findings were remarkable for a white blood cell count of 16.0 K/UL (4.60-10.20 K/UL), a C-reactive protein of 6.93 mg/dL (0-0.5 mg/dL), an erythrocyte sedimentation rate of 50 mm/h (8-15 mm/h), an aspartate aminotransferase level of 213 U/L (10-40 U/L), a lactate dehydrogenase of 447 U/L (< 225 U/L), and a creatine kinase level of 1733 U/L (29-200 U/L). Results from antinuclear antibody at 1:320 titers and anti-smooth muscle antibody were positive. Results from anti-SS A/SS B antibodies, anti Jo-1 antibody, U1-snRNP antibody, and anti-ds DNA antibody tests were negative. A skin biopsy specimen obtained from the right antecubital fossa showed minimal orthokeratosis and subepidermal detachments. There was marked edema in the dermis and lymphocyte infiltration around the skin appendages (Figure 2). Direct immunofluorescence studies demonstrated scattered staining for C3 and IgM at the basal membrane zone. Results for IgG, IgA, and fibrin staining were negative. Muscle biopsy from left deltoid muscle was performed and some muscle fibers were demonstrated to be atrophied. There was remarkable difference between muscle fiber diameters. With Masson staining, there was increased connective tissue and no inflammation. Electromyography (EMG) showed a myogenic pattern. Nerve conduction studies showed tibial, median, ulnar, peroneal motor neuropathy, and median, ulnar, and sural sensory neuropathy. Based on these findings, diagnosis of vesiculo-bullous dermatomyositis (DM) was made. Further investigation of esophagogastroduodenoscopy with biopsy revealed ulcerated lesions on antrum and corpus and these were assessed as Helicobacter pylori-negative atrophic chronic gastritis. No pathologic findings were described on chest, abdomen, and pelvic tomography. Levels of tumor markers were within normal ranges. Overall, no sign of malignancy was detected. Methyl prednisolone treatment of 1 mg/kg/d was started; however, new bullous lesions erupted while the original lesions were healing. PMID:23930362

  10. Intranasal Insulin Ameliorates Experimental Diabetic Neuropathy

    PubMed Central

    Francis, George; Martinez, Jose; Liu, Wei; Nguyen, Thuhien; Ayer, Amit; Fine, Jared; Zochodne, Douglas; Hanson, Leah R.; Frey, William H.; Toth, Cory

    2009-01-01

    OBJECTIVE We hypothesized that intranasal insulin (I-I) delivery targets the nervous system while avoiding potential adverse systemic effects when compared with subcutaneous insulin (S-I) for experimental streptozotocin-induced diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS I-I or S-I at 0.87 IU daily or placebo were delivered in separate cohorts of diabetic and nondiabetic CD1 mice during 8 months of diabetes. Radiolabeled insulin detection was used to compare delivery and biodistribution for I-I and S-I. Biweekly behavioral testing and monthly electrophysiological and quantitative studies assessed progression of DPN. At and before end point, morphometric analysis of DRG, peripheral nerve, distal epidermal innervation, and specific molecular markers were evaluated. RESULTS Radiolabeled I-I resulted in more rapid and concentrated delivery to the spinal cord and DRG with less systemic insulin exposure. When compared with S-I or intranasal placebo, I-I reduced overall mouse mortality and sensory loss while improving neuropathic pain and electrophysiological/morphological abnormalities in diabetic mice. I-I restored mRNA and protein levels of phosphoinositide 3-kinase/Akt, cyclic AMP response elementbinding protein, and glycogen synthase kinase 3? to near normal levels within diabetic DRGs. CONCLUSIONS I-I slows the progression of experimental DPN in streptozotocin mice, avoids adverse effects associated with S-I treatment, and prolongs lifespan when compared with S-I. I-I may be a promising approach for the treatment of DPN. PMID:19136650

  11. Phenotyping animal models of diabetic neuropathy: a consensus statement of the diabetic neuropathy study group of the EASD (Neurodiab)

    PubMed Central

    Biessels, G.J.; Bril, V.; Calcutt, N.A.; Cameron, N.E.; Cotter, M.A.; Dobrowsky, R.; Feldman, E.L.; Fernyhough, P.; Jakobsen, J.; Malik, R.A.; Mizisin, A.P.; Oates, P.J.; Obrosova, I.G.; Pop-Busui, R.; Russell, J.W.; Sima, A.A.; Stevens, M.J.; Schmidt, R.E.; Tesfaye, S.; Veves, A.; Vinik, A.I.; Wright, D.E.; Yagihashi, S.; Yorek, M.A.; Ziegler, D.; Zochodne, D.W.

    2015-01-01

    NIDDK, JDRF, and the Diabetic Neuropathy Study Group of EASD sponsored a meeting to explore the current status of animal models of diabetic peripheral neuropathy. The goal of the workshop was to develop a set of consensus criteria for the phenotyping of rodent models of diabetic neuropathy. The discussion was divided into five areas: (1) status of commonly used rodent models of diabetes, (2) nerve structure, (3) electrophysiological assessments of nerve function, (4) behavioral assessments of nerve function, and (5) the role of biomarkers in disease phenotyping. Participants discussed the current understanding of each area, gold standards (if applicable) for assessments of function, improvements of existing techniques, and utility of known and exploratory biomarkers. The research opportunities in each area were outlined, providing a possible roadmap for future studies. The meeting concluded with a discussion on the merits and limitations of a unified approach to phenotyping rodent models of diabetic neuropathy and a consensus formed on the definition of the minimum criteria required for establishing the presence of the disease. A neuropathy phenotype in rodents was defined as the presence of statistically different values between diabetic and control animals in 2 of 3 assessments (nocifensive behavior, nerve conduction velocities, or nerve structure). The participants propose that this framework would allow different research groups to compare and share data, with an emphasis on data targeted toward the therapeutic efficacy of drug interventions. PMID:24934510

  12. 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

  13. [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

  14. 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.

  15. Peripheral neuropathies caused by mutations in the myelin protein zero.

    PubMed

    Shy, Michael E

    2006-03-15

    Charcot-Marie-Tooth disease type 1B (CMT1B) is caused by mutations in the major PNS myelin protein myelin protein zero (MPZ). MPZ is a member of the immunoglobulin supergene family and functions as an adhesion molecule helping to mediate compaction of PNS myelin. Mutations in MPZ appear to either disrupt myelination during development, leading to severe early onset neuropathies, or to disrupt axo-glial interactions leading to late onset neuropathies in adulthood. Identifying molecular pathways involved in early and late onset CMT1B will be crucial to understand how MPZ mutations cause CMT1B so that rational therapies for both early and late onset neuropathies can be developed. PMID:16414078

  16. 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

  17. 77 FR 59930 - Clinical Development Programs for Disease-Modifying Agents for Peripheral Neuropathy; Public...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-01

    ... for Peripheral Neuropathy; Public Workshop; Request for Comments AGENCY: Food and Drug Administration...-modifying agents for the treatment of peripheral neuropathy. Discussion will focus on possible therapeutic targets for these agents, the types of painful peripheral neuropathies amenable to treatment with...

  18. [Molecular mechanisms of hereditary neuropathy: genotype-phenotype correlation].

    PubMed

    Nakagawa, Masanori; Takashima, Hiroshi

    2003-06-01

    Hereditary neuropathies are classified into several subtypes according to clinical, electrophysiologic and pathologic findings. Recent genetic studies have revealed their phenotypic and genetic diversities. In the primary peripheral demyelinating neuropathies(CMT1), at least 9 genes have been associated with the disorders; altered dosage of peripheral myelin protein 22(PMP22) or point mutation of PMP22, the gap junction protein 1(GJB1), the myelin protein zero gene(MPZ), the early growth response gene 2(EGR2), the myotubularin-related protein 2 gene(MTMR2), the N-myc downstream-regulated gene 1 (NDRG1), the L-periaxin gene(PRX), SRY-related HMG-BOX gene 10(SOX10) and the ganglioside-induced differentiation-associated protein 1 gene(GDAP1). In the primary peripheral axonal neuropathies(CMT2), at least 8 genes have been associated with these disorders; the neurofilament light chain gene(NEFL), the kinesin 1B gene(KIF1B), the gigaxonin gene(GAN1), Lamin A/C(LMNA) and tyrosyl-DNA phosphodiesterase 1(TDP1). In addition, some mutations in GJB1, MPZ and GDAP1 also present with clinical and electrophysiologic findings of CMT2. Mutation of NEFL or KIF1B cause dominantly inherited axonal neuropathies, whereas mutation of GJB1 or MPZ can present as genocopies of dominant axonal neuropathies. In addition to the above diseases, we have reported a new type of NMSNP(MIM # *604484) characterized by proximal dominant neurogenic atrophy, obvious sensory nerve involvement and the gene locus on 3q13. Here, we summarize the genetic bases of hereditary neuropathies and attempt to highlight significant genotype-phenotype correlations. PMID:12884740

  19. 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

  20. [Botulinum toxin and painful peripheral neuropathies: what should be expected?].

    PubMed

    Ranoux, D

    2011-01-01

    Botulinum toxin type A (BTX-A) is a potent neurotoxin that blocks acetylcholine release from presynaptic nerve terminals by cleaving the SNARE complex. BTX-A has been reported to have analgesic effects independent of its action on muscle tone. The most robust results have been observed in patients with neuropathic pain. Neuropathic pain due to peripheral lesions has been the most widely studied. BTX-A has shown its efficacy on pain and allodynia in various animal models of inflammatory neuropathic pain. The only randomized, double-blind, placebo-controlled trial in patients with focal painful neuropathies due to nerve trauma or postherpetic neuralgia demonstrated significant effects on average pain intensity from 2 weeks after the injections to 14 weeks. Most patients reported pain during the injections, but there were no further local or systemic side effects. The efficacy of BTX-A in painful peripheral neuropathies has been more recently studied. Results were positive in the only study in an animal model of peripheral neuropathy. One study in patients with diabetic painful peripheral neuropathy demonstrated a significant decrease in Visual Analog Scale. In conclusion, one session of multiple intradermal injection of BTX-A produces long-lasting analgesic effects in patients with focal painful neuropathies and diabetic neuropathic pain, and is particularly well tolerated. The findings are consistent with a reduction of peripheral sensitisation, the place of a possible central effect remaining to define. Further studies are needed to assess some important issues, i.e. BTX-A efficacy in patients with small fiber neuropathies and the relevance of early and repeated injections. Future studies could also provide valuable insights into pathophysiology of neuropathic pain. PMID:21194720

  1. Pontine Tegmental Cap Dysplasia: MR Evaluation of Vestibulocochlear Neuropathy.

    PubMed

    Singh, Dalveer; Hsu, Charlie Chia-Tsong; Kwan, Gigi Nga Chi; Korah, Ipeson

    2015-01-01

    Pontine tegmental cap dysplasia (PTCD) is recently recognized as a rare congenital brain stem malformation with typical neuroimaging hallmarks of ventral pontine hypoplasia and vaulted pontine tegmentum projecting into the fourth ventricle. PTCD patients also demonstrate variable cranial neuropathy with predilection for involvement of the vestibulocochlear and facial nerves. We present a case of PTCD diagnosed on MRI in the neonatal period. During early infancy, the patient displayed features of multiple cranial neuropathies and bilateral hearing loss. At the age of 2, the patient underwent further MRI assessment with dedicated high resolution T2 SPACE sequence to delineate the cranial nerve deficiencies. PMID:25691269

  2. Severe Acute Orthopnea: Ipilimumab-Induced Bilateral Phrenic Nerve Neuropathy.

    PubMed

    Jinnur, Praveen; Lim, Kaiser G

    2015-08-01

    Ipilimumab is a monoclonal antibody used in the treatment of unresectable or metastatic melanoma. Several immune-related adverse events including potential fatal events have been reported following its use. We report a case of a 66-year-old man who presented with severe acute exertional dyspnea and orthopnea following administration of ipilimumab for metastatic melanoma. Although various peripheral neuropathy syndromes associated with ipilimumab have been reported, bilateral phrenic nerve paralysis has not been previously reported. This case also highlights the clinical features of bilateral phrenic nerve neuropathy. Pulmonologists have to be aware of these unusual immune-related respiratory adverse events in patients being treated with monoclonal antibodies. PMID:25956728

  3. Ulnar Neuropathy After Extracorporeal Shockwave Therapy: ACase Report.

    PubMed

    Shim, Jae Seong; Chung, Sun G; Bang, Hyun; Lee, Hyuk Jin; Kim, Keewon

    2015-06-01

    Currently, extracorporeal shockwave therapy (ESWT) is widely used for treatment of various musculoskeletal disorders. We report a case of ulnar neuropathy secondary to the application of ESWT. A 48-year-old man was diagnosed with medial epicondylitis and underwent 2 sessions of ESWT. Immediately after the second session, he experienced paresthesia and weakness in the right hand. On physical examination, atrophy of the first dorsal interosseus and weakness of the abductor digiti minimi were observed. Electrophysiologic study demonstrated ulnar neuropathy at the elbow with severe partial axonotmesis. Our case report demonstrates that ESWT might cause or contribute to peripheral nerve injury at the site of application. PMID:25661460

  4. Neuropathy Associated with Hepatitis in Patients Maintained on Haemodialysis

    PubMed Central

    Davison, A. M.; Williams, I. R.; Mawdsley, C.; Robson, J. S.

    1972-01-01

    During a study of peripheral nerve function in chronic renal failure, 11 patients who were being treated by chronic intermittent haemodialysis developed serum hepatitis. Before the infection there was a trend towards improvement in nerve conduction velocities. A pronounced deterioration in the conduction velocities in motor fibres of peripheral nerves occurred in association with hepatitis. In the months after recovery from the infection there was again a trend towards improvement in conduction velocities. We suggest that this reflects the occurrence of a peripheral neuropathy which is at least in part demyelinating. The neuropathy is related to the serum hepatitis, but its pathogenesis is indeterminate. PMID:4333484

  5. [Epidemic neuropathy: proposal and arguments to rename Strachan disease as Strachan and Madan disease].

    TOXLINE Toxicology Bibliographic Information

    Santiesteban-Freixas R; Pamias-González E; Luis-González S; Serrano-Verdecia C; González-Quevedo A; Alfaro-Capdegelle I; Francisco-Plasencia M; Suárez-Hernández J

    1997-12-01

    INTRODUCTION: Strachan's disease is a condition which mainly affects the nervous system. It is characterized by optic, auditory and peripheral neuropathies and lesions of the skin and mucous membranes. In 1955 Miller Fisher gave it this name, since the clinical condition described by Henry Strachan in Jamaica during the nineteenth century was similar to that seen in Canadian prisoners-of-war in Japanese concentration camps during the Second World War.DEVELOPMENT: Since there are similarities between these clinical disorders and the major neuropathic epidemic seen recently in Cuba, we have reviewed and compared the endemic and epidemic conditions of similar characteristics seen in Cuba during the nineteenth and twentieth centuries. We also make a detailed review of a similar condition described in 1898-1900 by Doctors Madan, López and Santos Fernández, during the last Cuban War of Independence. This seems to be one of the earliest descriptions of the disorder. We also consider the so-called Strachan's syndrome or disease, and descriptions from the same period of tobacco-alcohol amblyopia and beriberi. These conditions seem to have been very similar to the so-called optical and peripheral forms of the current Cuban epidemic. It is concluded that the clinical characteristics of the recent Cuban neuropathic epidemic, at least in the optical form, were seen to be endemic during the nineteenth century. In many cases this was considered to be alcoholic amblyopia or some other obscure neuropathy which became epidemic during periods of severe economic depression.CONCLUSION: Madan gave a full description of the disorder at the same time as Strachan did. In 1898 he also suggested its true cause and died trying to relieve it. We therefore consider that Strachan's syndrome should be renamed the Strachan-Madan syndrome.

  6. Prolonged QT period in diabetic autonomic neuropathy: a possible role in sudden cardiac death?

    PubMed Central

    Bellavere, F; Ferri, M; Guarini, L; Bax, G; Piccoli, A; Cardone, C; Fedele, D

    1988-01-01

    Twenty four men with insulin dependent diabetes and different degrees of autonomic neuropathy were studied to establish the response of the QT interval to various heart rates. Nine men with autonomic neuropathy had a longer QT interval than 13 healthy individuals and 15 patients who had diabetes without, or with only mild, autonomic neuropathy. Those with autonomic neuropathy also had a proportionally greater lengthening of the QT interval for a given increase in RR interval. The results of this study suggest a basis for the finding that sudden death is more common in patients with diabetic autonomic neuropathy. PMID:3355728

  7. 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

  8. 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.

  9. [Bilateral optic atrophy in a drug addict].

    PubMed

    Milet, A; Blaise, P; Andris, C; Rakic, J-M

    2007-11-01

    Bilateral optic neuropathy in a young man is suggestive of hereditary or toxic damage. We describe the case of a 38-year-old man with bilateral optic neuropathy. His best corrected visual acuity was light perception OD and 20/125 OS. The patient's history revealed an addiction to heroin. Three drugs - heroin, quinine, and cocaine - were considered as a possible cause, which is discussed further. We suggest that the condition reported here may be attributed to the use of heroin. This underlines the importance of meticulous history taking in diagnosing a young man with bilateral loss of vision. PMID:18046269

  10. Congenital hypomyelinating neuropathy due to a novel MPZ mutation.

    PubMed

    Sevilla, Teresa; Lupo, Vincenzo; Sivera, Rafael; Marco-Marín, Clara; Martínez-Rubio, Dolores; Rivas, Eloy; Hernández, Arturo; Palau, Francesc; Espinós, Carmen

    2011-12-01

    Congenital hypomyelinating neuropathy (CHN) is a severe inherited neuropathy with neonatal or early infancy onset, reduced nerve conduction velocity, and pathological evidence of hypomyelination. We describe a case of CHN that presented with neonatal hypotonia and a progressive downhill clinical course, developing cranial nerve dysfunction, and respiratory failure. The nerve conduction velocities were severely slowed and sural nerve biopsy revealed non-myelinated and poorly myelinated axons, with no typical onion bulbs. The mutational screening showed that our proband harbored a novel missense mutation, p.S121F, in the MPZ gene. In silico analyses and molecular modeling predicted that the replacement of a serine by a phenylalanine is a non-tolerated change and may affect the folding and the stability of the protein. Subcellular location studies were performed and revealed that the mutant protein loses its correct location on the cell membrane surface and is mainly expressed in the cytosol, reducing its adhesive properties. This case illustrates the clinical heterogeneity that exists in neuropathies associated with MPZ mutations and highlights that in patients with mild hypotonia in the first months that develop a very severe demyelinating neuropathy, the MPZ gene must be taken into account. PMID:22176150

  11. Genetic determination of motor neuron disease and neuropathy.

    PubMed

    Vrebalov Cindro, Pavle; Vrebalov Cindro, Veselin

    2015-03-01

    Following the completion of the Human Genome Project, a lot of progress has been made in understanding the genetic basis of motor neuron diseases (MNDs) and neuropathies. Spinal Muscular Atrophies (SMA) are caused by mutations in the SMN1 gene localized on Chromosome 5q11. Amyotrophic Lateral Sclerosis (ALS) has been found to have at least 18 different types, many of them associated to different genetic loci (e.g. SOD1, ALS2, SETX, FUS, VAPB, ANG, TARDBP and others), but many of the forms have still not been associated with a particular gene. Sensomotoric hereditary neuropathies (Charcot-Marie-Tooth) are a large heterogeneous group of various hereditary neuropathies, which have also been associated with a wide spectrum of genetic mutations, such as PMP22, LITAF, EGR2, P0 protein, KIF1B, MFN2, RAB7 and others. It is also apparent that more genes are being implicated, mutations discovered, and phenotypes recognised and broadened. Therefore, a lot of continuing, additional research effort will be required in the coming years to illuminate pathogenic mechanisms that underlie motor neuron diseases and neuropathies and that could lead to new and improved treatments. PMID:26040103

  12. IgG monoclonal paraproteinaemia and peripheral neuropathy.

    PubMed Central

    Bleasel, A F; Hawke, S H; Pollard, J D; McLeod, J G

    1993-01-01

    Five patients with peripheral neuropathy and benign IgG monoclonal paraproteinemia are reported, all of whom had a sensorimotor neuropathy with a remitting and relapsing course. The serum paraprotein level did not correlate with the patient's clinical status. Electrophsyiological studies showed marked slowing of conduction velocity and conduction block in four of the patients and mild slowing in the other. Sural nerve biopsies demonstrated a demyelinating neuropathy with inflammatory cell infiltrates in each of the five patients. Three of the patients had evidence of myelin/Schwann cell reactivity on immunofluorescence studies and in all nerves dense expression of major histocompatability complex class I and II molecules was evident within the endoneurium, on invading mononuclear cells, endothelial cells and Schwann cells. All the patients responded to treatment, plasmapheresis being particularly effective. Four patients have achieved prolonged remissions after all treatment had ceased. These five cases of peripheral neuropathy and IgG paraproteinaemia were identical in their clinical, electrophysiological and pathological features to patients with chronic inflammatory demyelinating polyneuropathy. Images PMID:8381472

  13. Small Heat Shock Proteins and Distal Hereditary Neuropathies.

    PubMed

    Nefedova, V V; Muranova, L K; Sudnitsyna, M V; Ryzhavskaya, A S; Gusev, N B

    2015-12-01

    Classification of small heat shock proteins (sHsp) is presented and processes regulated by sHsp are described. Symptoms of hereditary distal neuropathy are described and the genes whose mutations are associated with development of this congenital disease are listed. The literature data and our own results concerning physicochemical properties of HspB1 mutants associated with Charcot-Marie-Tooth disease are analyzed. Mutations of HspB1, associated with hereditary motor neuron disease, can be accompanied by change of the size of HspB1 oligomers, by decreased stability under unfavorable conditions, by changes in the interaction with protein partners, and as a rule by decrease of chaperone-like activity. The largest part of these mutations is accompanied by change of oligomer stability (that can be either increased or decreased) or by change of intermonomer interaction inside an oligomer. Data on point mutation of HspB3 associated with axonal neuropathy are presented. Data concerning point mutations of Lys141 of HspB8 and those associated with hereditary neuropathy and different forms of Charcot-Marie-Tooth disease are analyzed. It is supposed that point mutations of sHsp associated with distal neuropathies lead either to loss of function (for instance, decrease of chaperone-like activity) or to gain of harmful functions (for instance, increase of interaction with certain protein partners). PMID:26878578

  14. Post-traumatic trigeminal neuropathy. A study of 63 cases

    PubMed Central

    Pearrocha, David; Bagn, Jos V.; Pearrocha, 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

  15. Diabetic Neuropathy: What is a Total Contact Cast?

    MedlinePLUS

    MENU Return to 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 (serious, deep sores) on a person’s foot. It consists of a fiberglass shell that fits around your leg and foot very ...

  16. Clinicopathological and genetic study of early-onset demyelinating neuropathy.

    PubMed

    Parman, Yesim; Battaloglu, Esra; Baris, Ibrahim; Bilir, Birdal; Poyraz, Mürüvvet; Bissar-Tadmouri, Nisrine; Williams, Anna; Ammar, Nadia; Nelis, Eva; Timmerman, Vincent; De Jonghe, Peter; Najafov, Ayaz; Necefov, Ayaz; Deymeer, Feza; Serdaroglu, Piraye; Brophy, Peter J; Said, G

    2004-11-01

    Autosomal recessive demyelinating Charcot-Marie-Tooth disease (CMT4), Dejerine-Sottas disease and congenital hypomyelinating neuropathy are variants of hereditary demyelinating neuropathy of infancy, a genetically heterogeneous group of disorders. To explore the spectrum of early-onset demyelinating neuropathies further, we studied the clinicopathological and genetic aspects of 20 patients born to unaffected parents. In 19 families out of 20, consanguinity between the parents or presence of an affected sib suggested autosomal recessive transmission. Screening of various genes known to be involved in CMT4 revealed six mutations of which five are novel. Four of these novel mutations occurred in the homozygous state and include: one in GDAP1, one in MTMR2, one in PRX and one in KIAA1985. One patient was heterozygous for a novel MTMR2 mutation and still another was homozygous for the founder mutation, R148X, in NDRG1. All patients tested negative for mutations in EGR2. Histopathological examination of nerve biopsy specimens showed a severe, chronic demyelinating neuropathy, with onion bulb formation, extensive demyelination of isolated fibres and axon loss. We did not discern a specific pattern of histopathology that could be correlated to mutations in a particular gene. PMID:15469949

  17. 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

  18. Exercise as Therapy for Diabetic and Prediabetic Neuropathy.

    PubMed

    Singleton, J Robinson; Smith, A Gordon; Marcus, Robin L

    2015-12-01

    Length-dependent neuropathy is the most common and costly complication of diabetes and frequently causes injury primarily to small-diameter cutaneous nociceptive fibers. Not only persistent hyperglycemia but also metabolic, endocrine, and inflammatory effects of obesity and dyslipidemia appear to play an important role in the development of diabetic neuropathy. Rational therapies aimed at direct control of glucose or its increased entry into the polyol pathway, oxidative or nitrosative stress, advanced glycation end product formation or signaling, microvascular ischemia, or adipocyte-derived toxicity have each failed in human trials of diabetic neuropathy. Aerobic exercise produces salutary effects in many of these pathogenic pathways simultaneously and, in both animal models and human trials, has been shown to improve symptoms of neuropathy and promote re-growth of cutaneous small-diameter fibers. Behavioral reduction in periods of seated, awake inactivity produces multimodal metabolic benefits similar to exercise, and the two strategies when combined may offer sustained benefit to peripheral nerve function. PMID:26538074

  19. 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 Trnblom, DOI: 10.1007/s00125-015-3829-9 ) and a commentary by the Session Chair, Pter Kempler (DOI: 10.1007/s00125-015-3826-y ). PMID:26643877

  20. Treating Diabetic Neuropathy: Present Strategies and Emerging Solutions.

    PubMed

    Javed, Saad; Alam, Uazman; Malik, Rayaz A

    2015-01-01

    Diabetic peripheral neuropathies (DPN) are a heterogeneous group of disorders caused by neuronal dysfunction in patients with diabetes. They have differing clinical courses, distributions, fiber involvement (large or small), and pathophysiology. These complications are associated with increased morbidity, distress, and healthcare costs. Approximately 50% of patients with diabetes develop peripheral neuropathy, and the projected rise in the global burden of diabetes is spurring an increase in neuropathy. Distal symmetrical polyneuropathy (DSPN) with painful diabetic neuropathy, occurring in around 20% of diabetes patients, and diabetic autonomic neuropathy (DAN) are the most common manifestations of DPN. Optimal glucose control represents the only broadly accepted therapeutic option though evidence of its benefit in type 2 diabetes is unclear. A number of symptomatic treatments are recommended in clinical guidelines for the management of painful DPN, including antidepressants such as amitriptyline and duloxetine, the ?-aminobutyric acid analogues gabapentin and pregabalin, opioids, and topical agents such as capsaicin. However, monotherapy is frequently not effective in achieving complete resolution of pain in DPN. There is a growing need for head-to-head studies of different single-drug and combination pharmacotherapies. Due to the ubiquity of autonomic innervation in the body, DAN causes a plethora of symptoms and signs affecting cardiovascular, urogenital, gastrointestinal, pupillomotor, thermoregulatory, and sudomotor systems. The current treatment of DAN is largely symptomatic, and does not correct the underlying autonomic nerve deficit. A number of novel potential candidates, including erythropoietin analogues, angiotensin II receptor type 2 antagonists, and sodium channel blockers are currently being evaluated in phase II clinical trials. PMID:26676662

  1. Multifocal Motor Neuropathy, Multifocal Acquired Demyelinating Sensory and Motor Neuropathy and Other Chronic Acquired Demyelinating Polyneuropathy Variants

    PubMed Central

    Barohn, Richard J.; Katz, Jonathan

    2014-01-01

    Chronic acquired demyelinating neuropathies (CADP) are an important group of immune neuromuscular disorders affecting myelin. These are distinct from chronic inflammatory demyelinating polyneuropathy (CIDP). Classically, CIDP is characterized by proximal and distal weakness, large fiber sensory loss, elevated cerebrospinal fluid (CSF) protein content, demyelinating changes nerve conduction studies or nerve biopsy, and response to immunomodulating treatment. In this chapter we discuss CADP with emphasis on multifocal motor neuropathy (MMN), multifocal acquired demyelinating sensory and motor neuropathy (MADSAM), distal acquired demyelinating symmetric (DADS) neuropathy and conclude with less common variants. While each of these entities has distinctive laboratory and electrodiagnostic features that aid in their diagnosis, clinical characteristics are of paramount importance in diagnosing specific conditions and determining the most appropriate therapies. Unlike CIDP, MMN is typically asymmetric and affects only the motor nerve fibers. MMN is a rare disease that presents chronically, over several years of progression affecting the arms are more commonly than the legs. Men are more likely than women to develop MMN. MADSAM should be suspected in patients who have weakness and loss of sensation in primarily one arm or leg which progresses slowly over several months to years. It is important in patient with multifocal demyelinating clinical presentation to distinguish MMN from MADSAM since corticosteroids are not effective in MMN where the mainstay of therapy is intravenous gammaglobulin (IVIg). DADS can be subdivided into DADS-M (associated woth M-protein) and DADS-I which is idioapthic. While DADS-I patients respond somewhat to immunotherapy, DADS-M patients present with distal predominant sensorimotor demyelinating neuropathy phenotype and are notoriously refractory to immunotherapies regardless of antibodies to myelin-associated glycoprotein (MAG). Our knowledge regarding pathogenesis, diagnosis and management continues to expand, resulting in improved opportunities for identification and treatment. PMID:23642723

  2. Suspected hypothyroid-associated neuropathy in a female rottweiler dog

    PubMed Central

    Rushton, James Oliver; Leschnik, Michael; Nell, Barbara

    2013-01-01

    A 7-year-old, 46-kg spayed female rottweiler dog was presented with sudden onset of disorientation, bilateral convergent strabismus, and enophthalmos. Diagnostic workup revealed hypothyroid-associated cranial neuropathy. Symptoms abated considerably upon treatment with levothyroxine-sodium (T4) at an initial dose of 800 ?g/kg body weight (BW), PO, q12h, which was reduced 3 days later to 600 ?g/kg BW, q12h due to severe agitation and panting. Two weeks later the dosage of the levothyroxine-sodium (T4) was reduced to 400 ?g/kg BW in the morning and 600 ?g/kg BW in the evening. Eight weeks after the initial presentation, the dog had recovered with only mild convergent strabismus in the right eye. This is the first case report of suspected hypothyroid-associated neuropathy resulting in these symptoms. PMID:24082164

  3. Rare cause of paraparesis: bilateral obturator neuropathy after hysterosalpingectomy.

    PubMed

    Lpez-Blanco, Roberto; Meja-Jimnez, Inmaculada; de Fuenmayor-Fernndez de la Hoz, Carlos Pablo; Ruiz-Morales, Juan

    2015-01-01

    Bilateral obturator nerve injury during pelvic surgery is an infrequent cause of lower limb paraparesis. We report the case of a 45-year-old woman with a large uterine leiomyoma who underwent simple total hysterectomy and bilateral salpingectomy. At 24?h after the surgery, the patient noticed loss of muscle strength when adducting both legs. She had no problem with other movements and no sensory or sphincter abnormalities. Neurological examination confirmed that there was loss of strength only in the adductor muscles, with preserved sensory function and reflexes, suggesting bilateral obturator nerve involvement. Pelvic MRI showed a small postsurgical haematoma in the Douglas recess, but far from the obturator nerves. 2?weeks later, electromyography showed positive sharp waves and low motor unit recruitment in the adductor magnus muscles, confirming acute, bilateral obturator nerve neuropathy. The few cases of bilateral obturator neuropathy that have been reported were mostly related to abdominopelvic interventions. PMID:26689250

  4. Suspected hypothyroid-associated neuropathy in a female rottweiler dog.

    PubMed

    Rushton, James Oliver; Leschnik, Michael; Nell, Barbara

    2013-04-01

    A 7-year-old, 46-kg spayed female rottweiler dog was presented with sudden onset of disorientation, bilateral convergent strabismus, and enophthalmos. Diagnostic workup revealed hypothyroid-associated cranial neuropathy. Symptoms abated considerably upon treatment with levothyroxine-sodium (T4) at an initial dose of 800 μg/kg body weight (BW), PO, q12h, which was reduced 3 days later to 600 μg/kg BW, q12h due to severe agitation and panting. Two weeks later the dosage of the levothyroxine-sodium (T4) was reduced to 400 μg/kg BW in the morning and 600 μg/kg BW in the evening. Eight weeks after the initial presentation, the dog had recovered with only mild convergent strabismus in the right eye. This is the first case report of suspected hypothyroid-associated neuropathy resulting in these symptoms. PMID:24082164

  5. Peroneal neuropathy misdiagnosed as L5 radiculopathy: a case report

    PubMed Central

    2013-01-01

    Objective The purpose of this case report is to describe a patient who presented with a case of peroneal neuropathy that was originally diagnosed and treated as a L5 radiculopathy. Clinical features A 53-year old female registered nurse presented to a private chiropractic practice with complaints of left lateral leg pain. Three months earlier she underwent elective left L5 decompression surgery without relief of symptoms. Intervention and outcome Lumbar spine MRI seven months prior to lumbar decompression surgery revealed left neural foraminal stenosis at L5-S1. The patient symptoms resolved after she stopped crossing her legs. Conclusion This report discusses a case of undiagnosed peroneal neuropathy that underwent lumbar decompression surgery for a L5 radiculopathy. This case study demonstrates the importance of a thorough clinical examination and decision making that ensures proper patient diagnosis and management. PMID:23618508

  6. Standard and emerging treatment options for diabetic neuropathy.

    PubMed

    Tentolouris, Nicholas; Alexiadou, Kleopatra; Makrilakis, Konstantinos; Liatis, Stavros; Jude, Edward; Boulton, Andrew J

    2014-01-01

    Diabetic neuropathy is a common complication of diabetes mellitus affecting 30-50% of patients and is a major cause for increased costs, morbidity and mortality. Strict diabetes control prevents this complication and may restore neurologic deficits in the early stages. Several efforts have been undertaken to alter the natural history of this complication, including the use of aldose reductase and protein kinase-C inhibitors, as well as antioxidants. Available data so far do not support the use of aldose reductase inhibitors due to safety issues and efficacy. Protein kinase-C inhibitors have provided encouraging initial results but their development has been halted. Antioxidants, like a-lipoic acid, improve some neurological deficits and painful symptoms. There are effective and safe medications such as anticonvulsants, antidepressants and opioids for the management of patients with painful symptoms. In this revew we present standard and emerging treatment modalities for the etiologic and symptomatic treatment of diabetic neuropathy. PMID:24040869

  7. Diabetic Peripheral Neuropathy in Type 2 Diabetes Mellitus in Korea

    PubMed Central

    Ko, Seung-Hyun

    2012-01-01

    Diabetic peripheral neuropathy (DPN), a common and troublesome complication in patients with type 2 diabetes mellitus (T2DM), contributes to a higher risk of diabetic foot ulcer and lower limb amputation. These situations can negatively impact the quality of life of affected individuals. Despite its high prevalence and clinical importance, most diabetes mellitus patients not only do not recognize the presence of diabetic neuropathy, but also do not report their symptoms to physicians or other health care providers. Therefore, DPN is usually under diagnosed and undertreated. For early detection and appropriate intervention for DPN, a careful history, physical with neurologic examination, and prompt treatment are needed in T2DM patients. PMID:22363916

  8. Antiretroviral therapy-associated acute motor and sensory axonal neuropathy.

    PubMed

    Capers, Kimberly N; Turnacioglu, Sinan; Leshner, Robert T; Crawford, John R

    2011-01-01

    Guillain-Barr syndrome (GBS) has been reported in HIV-infected patients in association with the immune reconstitution syndrome whose symptoms can be mimicked by highly active antiretroviral therapy (HAART)-mediated mitochondrial toxicity. We report a case of a 17-year-old, HIV-infected patient on HAART with a normal CD4 count and undetectable viral load, presenting with acute lower extremity weakness associated with lactatemia. Electromyography/nerve conduction studies revealed absent sensory potentials and decreased compound muscle action potentials, consistent with a diagnosis of acute motor and sensory axonal neuropathy. Lactatemia resolved following cessation of HAART; however, neurological deficits minimally improved over several months in spite of immune modulatory therapy. This case highlights the potential association between HAART, mitochondrial toxicity and acute axonal neuropathies in HIV-infected patients, distinct from the immune reconstitution syndrome. PMID:21327178

  9. Conduction velocity distribution: early diagnostic tool for peripheral neuropathies.

    PubMed

    Kiziltan, Erhan; Dalkilic, Nizamettin; Guney, Figen Bayramoglu; Pehlivan, Ferit

    2007-02-01

    In order to get early information on the functional state of smaller myelinated fibers this article investigated the applicability of conduction velocity distribution on compound action potential recorded in experimentally demyelinated frog sciatic nerve. Conduction velocity distribution histograms were estimated by using the mathematical model the authors enhanced. The results suggest that by using appropriate conduction velocity distribution model the diagnosis time in demyelinating neuropathy may be shortened at least three times as compared with conventional conduction velocity assessment. Therefore, it may be concluded that a well-defined model designed for the estimation of the conduction velocity distribution may be used as a diagnostic tool for the early phase of peripheral demyelinating neuropathies. PMID:17365108

  10. Evidence for direct axonal toxicity in vincristine neuropathy.

    PubMed

    Silva, Angelica; Wang, Qingbo; Wang, Minsheng; Ravula, Surendra K; Glass, Jonathan D

    2006-09-01

    There is a long-standing debate concerning the localization of the primary insult that results in distal axonal degeneration, or 'dying back' neuropathy. To address this question, we created an in vitro model of vincristine neuropathy in rat dorsal root ganglia (DRG). DRGs were grown in compartmentalized chambers, allowing for isolated exposure of the cell body or the axon to vincristine. Initial dose-finding studies identified a dose of vincristine that showed differential effects on cell death when delivered to either the cell body or the axonal compartment. At this dose of 0.05 microM, exposure of the cell bodies had no effect on the growth of axons, whereas addition of vincristine to the axonal compartment caused axonal shortening without affecting the growth of unexposed 'sister' axons. Toxicity was seen only with exposure of the growing axonal tips. These data support localized axonal toxicity as a cause of distal axonal degeneration due to vincristine. PMID:16930282

  11. Pudendal entrapment neuropathy: a rare complication of pelvic radiation therapy.

    PubMed

    Elahi, Foad; Callahan, Daniell; Greenlee, Jeremy; Dann, Tammy L

    2013-01-01

    Pudendal nerve entrapment (PNE) is an uncommon cause of chronic pain. Pudendal nerve entrapment typically occurs when the pudendal nerve is fused to nearby anatomical structures or trapped between the sacrotuberous and sacrospinalis ligaments. Pudendal nerve entrapment can be caused by excessive bicycling, pregnancy, anatomic abnormalities, scarring due to surgery, or as a sequela of radiation therapy. Radiation-induced peripheral neuropathy is usually chronic, progressive, and often irreversible. Radiation-induced pudendal neuropathy is much less common than the more familiar brachial plexopathy secondary to radiation treatment for breast cancer. The prevalence of PNE, however, is increasing due to improved long-term cancer survival. Diagnosis of pudendal neuralgia is essentially clinical; no specific clinical signs or complementary tests are reliably confirmatory. A detailed pain history with correlative clinical examination is paramount for accurate diagnosis. Performance of a pudendal nerve block can serve as both a diagnostic and therapeutic tool. Utilization of various imaging studies, as well as the performance of an electrophysiological study with pudendal nerve motor latency testing, may yield valuable evidence in support of a pudendal neuralgia diagnosis. We present the case of a 59-year-old man with stage IV prostate cancer, referred to the pain clinic for chronic perineal and right sided pelvic pain. His pain began insidiously, approximately 2 months after undergoing radiation treatment and chemotherapy 3 years prior. He was ultimately diagnosed as having a right sided pudendal entrapment neuropathy. His pain was refractory to all conventional treatment modalities; therefore we decided to pursue neuromodulation via a dorsal column spinal cord stimulator implant. Below, we describe the decision making process for the diagnosis and treatment of his pudendal neuropathy. PMID:24284861

  12. [Aspects of diagnosis and treatment of the facial nerve neuropathy].

    PubMed

    Mironenko, T V; Korotnev, V N

    2002-01-01

    As many as 86 patients with neuropathy of the facial nerve complicated by development of postneuritic muscular contractures were examined. Based on the clinical-and-neurophysiological investigation, findings from rheoencephalography, electroencephalography, echoencephaloscopy, electrodiagnosis of the facial nerve, clinical variants of the facial nerve function return to normal were defined together with causes of development of muscular contractures. Efficiency is shown of use of acupuncture and magnetotherapy combined in treatment of the above trouble. PMID:12442521

  13. Mitochondrial dysfunction in distal axons contribute to HIV sensory neuropathy

    PubMed Central

    Lehmann, Helmar C.; Chen, Weiran; Borzan, Jasenka; Mankowski, Joseph; Hke, Ahmet

    2010-01-01

    Objective Accumulation of mitochondrial DNA (mtDNA) damage has been associated with aging and abnormal oxidative metabolism. We hypothesized that in human immunodeficiency virus associated sensory neuropathy (HIV-SN), damaged mtDNA accumulates in distal nerve segments and that a spatial pattern of mitochondrial dysfunction contribute to the distal degeneration of sensory nerve fibers. Methods We measured levels of common deletion mutations in mtDNA and expression levels of mitochondrial respiratory chain complexes of matched proximal and distal nerve specimens from patients with and without HIV-SN. In mitochondria isolated from peripheral nerves of simian immunodeficiency virus (SIV) infected macaques, a model of HIV-SN, we measured mitochondrial function and generation of reactive oxygen species. Results We identified increased levels of mtDNA common deletion mutation in post-mortem sural nerves of patients with HIV-SN as compared to uninfected patients or HIV patients without sensory neuropathy. Furthermore, we found that common deletion mutation in mtDNA was more prevalent in distal sural nerves compared to dorsal root ganglia. In a primate model of HIV-SN, freshly isolated mitochondria from sural nerves of macaques infected with a neurovirulent strain of SIV showed impaired mitochondrial function compared to mitochondria from proximal nerve segments. Interpretation Our findings suggest that mtDNA damage accumulates in distal mitochondria of long axons, especially in patients with HIV-SN, and that this may lead to reduced mitochondrial function in distal nerves relative to proximal segments. Although our findings are based on HIV-SN, if confirmed in other neuropathies, these observations could explain the length-dependent nature of most axonal peripheral neuropathies. PMID:21280080

  14. 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

  15. A new device to quantify tactile sensation in neuropathy

    PubMed Central

    Selim, M.M.; Brink, T.S.; Hodges, J.S.; Wendelschafer-Crabb, G.; Foster, S.X.Y.-L.; Nolano, M.; Provitera, V.; Simone, D.A.

    2011-01-01

    Objective: To devise a rapid, sensitive method to quantify tactile threshold of finger pads for early detection and staging of peripheral neuropathy and for use in clinical trials. Methods: Subjects were 166 healthy controls and 103 patients with, or at risk for, peripheral neuropathy. Subjects were screened by questionnaire. The test device, the Bumps, is a checkerboard-like smooth surface with 12 squares; each square encloses 5 colored circles. The subject explores the circles of each square with the index finger pad to locate the one circle containing a small bump. Bumps in different squares have different heights. Detection threshold is defined as the smallest bump height detected. In some subjects, a 3-mm skin biopsy from the tested finger pad was taken to compare density of Meissner corpuscles (MCs) to bump detection thresholds. Results: The mean (±SEM) bump detection threshold for control subjects was 3.3 ± 0.10 μm. Threshold and test time were age related, older subjects having slightly higher thresholds and using more time. Mean detection threshold of patients with neuropathy (6.2 ± 0.35 μm) differed from controls (p < 0.001). A proposed threshold for identifying impaired sensation had a sensitivity of 71% and specificity of 74%. Detection threshold was higher when MC density was decreased. Conclusions: These preliminary studies suggest that the Bumps test is a rapid, sensitive, inexpensive method to quantify tactile sensation of finger pads. It has potential for early diagnosis of tactile deficiency in subjects suspected of having neuropathy, for staging degree of tactile deficit, and for monitoring change over time. PMID:21555731

  16. Controlled trial of hydroxocobalamin and riboflavine in Nigerian ataxic neuropathy

    PubMed Central

    Osuntokun, B. O.; Langman, M. J. S.; Wilson, J.; Aladetoyinbo, A.

    1970-01-01

    The results are presented of a double-blind therapeutic trial of hydroxocobalamin and riboflavine in Nigerian patients suffering from a degenerative neuropathy. Although no benefit from either vitamin was demonstrated, this may reflect the inadequacy of the dosages used. The results are discussed in relation to the hypothesis that dietary cyanide and cyanogens are responsible, at least in part, for the occurrence of this disease in a malnourished population. PMID:4920799

  17. Auditory nerve disease and auditory neuropathy spectrum disorders.

    PubMed

    Kaga, Kimitaka

    2016-02-01

    In 1996, a new type of bilateral hearing disorder was discerned and published almost simultaneously by Kaga et al. [1] and Starr et al. [2]. Although the pathophysiology of this disorder as reported by each author was essentially identical, Kaga used the term "auditory nerve disease" and Starr used the term "auditory neuropathy". Auditory neuropathy (AN) in adults is an acquired disorder characterized by mild-to-moderate pure-tone hearing loss, poor speech discrimination, and absence of the auditory brainstem response (ABR) all in the presence of normal cochlear outer hair cell function as indicated by normal distortion product otoacoustic emissions (DPOAEs) and evoked summating potentials (SPs) by electrocochleography (ECoG). A variety of processes and etiologies are thought to be involved in its pathophysiology including mutations of the OTOF and/or OPA1 genes. Most of the subsequent reports in the literature discuss the various auditory profiles of patients with AN [3,4] and in this report we present the profiles of an additional 17 cases of adult AN. Cochlear implants are useful for the reacquisition of hearing in adult AN although hearing aids are ineffective. In 2008, the new term of Auditory Neuropathy Spectrum Disorders (ANSD) was proposed by the Colorado Children's Hospital group following a comprehensive study of newborn hearing test results. When ABRs were absent and DPOAEs were present in particular cases during newborn screening they were classified as ANSD. In 2013, our group in the Tokyo Medical Center classified ANSD into three types by following changes in ABRs and DPOAEs over time with development. In Type I, there is normalization of hearing over time, Type II shows a change into profound hearing loss and Type III is true auditory neuropathy (AN). We emphasize that, in adults, ANSD is not the same as AN. PMID:26209259

  18. Lead brachial neuropathy in heroin addiction. A case report.

    PubMed

    Antonini, G; Palmieri, G; Spagnoli, L G; Millefiorini, M

    1989-01-01

    The possible toxical effect of heavy metals in the pathogenesis of brachial and lumbar plexopathies during heroin addiction has been previously hypothesized by some authors, but never detected. A 24-year-old man, addicted to heroin showed the clinical picture of a symmetrical brachial neuropathy, without other neurological involvement. Lead poisoning was detected in this patient and the chelating therapy induced a marked improvement of the clinical symptoms. PMID:2543530

  19. Postural sway in diabetic peripheral neuropathy among Indian elderly

    PubMed Central

    Dixit, Snehil; Maiya, Arun; Shasthry, B.A.; Kumaran, D. Senthil; Guddattu, Vasudeva

    2015-01-01

    Background & objectives: Diabetic peripheral neuropathy (DPN) is a major complication of type 2 diabetes and have long term complications on the postural control of the affected population. The objectives of this study were to evaluate postural stability in patients with DPN and to examine correlation of Michigan Neuropathy Screening Instrument (MNSI) with duration of diabetes, age and postural stability measures. Methods: Participants were included if they had clinical neuropathy which was defined by MNSI. Sixty one patients gave their consent to participate in the study and were evaluated on posturography for postural stability measures in four conditions. Repeated measures of analysis of variance (RANOVA) was used to analyze the changes in postural stability measures in different conditions. Results: An increase in mean value of postural stability measures was observed for velocity moment 20.4±1.3, 24.3±2.2, 42.3±20.7, 59±43.03, mediolateral displacement 0.21±0.10, 0.22±0.18, 0.03±0.11, 0.34±0.18, and anteroposterior displacement 0.39 ± 0.09, 0.45±0.12, 0.47±0.13, 0.51±0.20 from EO to EC, EOF, and ECF, respectively. There was a significant difference (P<0.05) in participants with DPN, with greater sway amplitude on firm and foam surface in all the conditions. Moderate correlation of MNSI with age (r=0.43) and postural stability measures were also observed. Interpretation & conclusions: Evaluation of postural stability in Indian DPN population suggests balance impairments on either firm and foam surfaces, with greater likelihood of fall being on foam or deformable surfaces among elderly adults with neuropathy (CTRI/2011/07/001884). PMID:26831420

  20. Reliability of presynaptic inhibition in patients with diabetic peripheral neuropathy.

    PubMed

    Palmer, Shannon J; Hong, Junggi

    2012-09-01

    There has been rising interest in evaluating spinal reflex activity within the clinical population, however no study has yet investigated the reliability of presynaptic inhibition (PI) on patients with diabetic peripheral neuropathy (DPN). Because neuropathy is closely related to central nervous system modification, it is important to understand the mechanism of spinal reflex activity in the DPN population. Therefore, the purpose of the study was to evaluate the reliability of PI in patients with DPN. Eight participants (58.24 6.38 yrs.) diagnosed with either type I or type II diabetes and peripheral neuropathy were recruited for the study. Each subject's H-reflex was measured using an EMG to elicit and record a series of 10 paired reflex depression trials. Reliability was measured by calculating Intra Class Correlation Coefficients (ICCs) with a 95% confidence interval. The results showed excellent reliability in both intraday (0.94) and interday (0.88) reliability. Therefore, analyzing PI in the central nervous system allows for an accurate evaluation of spinal cord circuitry in a non-invasive manner. PMID:22494165

  1. The Armadillo as a Model for Peripheral Neuropathy in Leprosy

    PubMed Central

    Truman, Richard W.; Ebenezer, Gigi J.; Pena, Maria T.; Sharma, Rahul; Balamayooran, Gayathriy; Gillingwater, Thomas H.; Scollard, David M.; McArthur, Justin C.; Rambukkana, Anura

    2014-01-01

    Leprosy (also known as Hansen's Disease) is a chronic infectious disease caused by Mycobacterium leprae that primarily targets the peripheral nervous system; skin, muscle, and other tissues are also affected. Other than humans, nine-banded armadillos (Dasypus novemcinctus) are the only natural hosts of M. leprae, and they are the only laboratory animals that develop extensive neurological involvement with this bacterium. Infection in the armadillo closely recapitulates many of the structural, physiological, and functional aspects of leprosy seen in humans. Armadillos can be useful models of leprosy for basic scientific investigations into the pathogenesis of leprosy neuropathy and its associated myopathies, as well as for translational research studies in piloting new diagnostic methods or therapeutic interventions. Practical and ethical constraints often limit investigation into human neuropathies, but armadillos are an abundant source of leprotic neurologic fibers. Studies with these animals may provide new insights into the mechanisms involved in leprosy that also might benefit the understanding of other demyelinating neuropathies. Although there is only a limited supply of armadillo-specific reagents, the armadillo whole genomic sequence has been completed, and gene expression studies can be employed. Clinical procedures, such as electrophysiological nerve conduction testing, provide a functional assessment of armadillo nerves. A variety of standard histopathological and immunopathological procedures including Epidermal Nerve Fiber Density (ENFD) analysis, Schwann Cell Density, and analysis for other conserved cellular markers can be used effectively with armadillos and will be briefly reviewed in this text. PMID:24615444

  2. The armadillo as a model for peripheral neuropathy in leprosy.

    PubMed

    Truman, Richard W; Ebenezer, Gigi J; Pena, Maria T; Sharma, Rahul; Balamayooran, Gayathriy; Gillingwater, Thomas H; Scollard, David M; McArthur, Justin C; Rambukkana, Anura

    2014-01-01

    Leprosy (also known as Hansen's Disease) is a chronic infectious disease caused by Mycobacterium leprae that primarily targets the peripheral nervous system; skin, muscle, and other tissues are also affected. Other than humans, nine-banded armadillos (Dasypus novemcinctus) are the only natural hosts of M. leprae, and they are the only laboratory animals that develop extensive neurological involvement with this bacterium. Infection in the armadillo closely recapitulates many of the structural, physiological, and functional aspects of leprosy seen in humans. Armadillos can be useful models of leprosy for basic scientific investigations into the pathogenesis of leprosy neuropathy and its associated myopathies, as well as for translational research studies in piloting new diagnostic methods or therapeutic interventions. Practical and ethical constraints often limit investigation into human neuropathies, but armadillos are an abundant source of leprotic neurologic fibers. Studies with these animals may provide new insights into the mechanisms involved in leprosy that also might benefit the understanding of other demyelinating neuropathies. Although there is only a limited supply of armadillo-specific reagents, the armadillo whole genomic sequence has been completed, and gene expression studies can be employed. Clinical procedures, such as electrophysiological nerve conduction testing, provide a functional assessment of armadillo nerves. A variety of standard histopathological and immunopathological procedures including Epidermal Nerve Fiber Density (ENFD) analysis, Schwann Cell Density, and analysis for other conserved cellular markers can be used effectively with armadillos and will be briefly reviewed in this text. PMID:24615444

  3. Inflammatory Neuropathy of the Lumbosacral Plexus following Periacetabular Osteotomy

    PubMed Central

    Ghijselings, Stijn; Bruyninckx, Frans; Delport, Hendrik; Corten, Kristoff

    2016-01-01

    Introduction. During periacetabular osteotomy (PAO), the sciatic, femoral, and obturator nerves are at risk. Most frequently nerve lesions can be attributed to a mechanical cause; however, in the absence of a clear mechanical cause surgeons are faced with a diagnostic problem and in many cases no diagnosis will be established. We report a case of inflammatory neuropathy of the lumbosacral plexus following a PAO. Case Presentation. A 31-year-old female developed weakness of ankle and knee flexion and extension 6 months after a PAO. Electrophysiological studies revealed damage to the obturator, femoral, and sciatic nerve consistent with an inflammatory lumbosacral plexopathy. MRI of the lumbosacral plexus was normal. The patient was treated with multimodal pain therapy and prolonged physiotherapy; nevertheless, symptoms worsened over time. At 2-year follow-up, there were no signs of recovery. Discussion. Inflammatory neuropathy of the lumbosacral plexus is a potential cause of pain and weakness after ipsilateral orthopaedic procedures. It should be distinguished from more frequently encountered mechanical causes of postsurgical neuropathy based on clinical suspicion, electrophysiological studies, MRI, and nerve biopsy. It is important that the orthopaedic community is aware of this complication since there is some evidence that early recognition and initiation of immunosuppressive therapy can lead to improved clinical outcome.

  4. Mechanisms of axonal dysfunction in diabetic and uraemic neuropathies.

    PubMed

    Arnold, Ria; Kwai, Natalie C G; Krishnan, Arun V

    2013-11-01

    The global burden imposed by metabolic diseases and associated complications continue to escalate. Neurological complications, most commonly peripheral neuropathy, represent a significant cause of morbidity and disability in patients with diabetes and chronic kidney disease. Furthermore, health care costs are substantially increased by the presence of complications making investigation into treatment a matter of high priority. Over the last decade nerve excitability techniques have entered the clinical realm and enabled in vivo assessment of biophysical properties and function of peripheral nerves in health and disease. Studies of excitability in diabetic neuropathy have demonstrated alteration in biophysical properties, including changes in Na(+) conductances and Na(+)/K(+) pump function, which may contribute to the development of neuropathic symptoms. Interventional studies have demonstrated that these changes are responsive to pharmacological agents. Excitability studies in patients with chronic kidney disease have demonstrated prominent changes that may contribute to the development of uraemic neuropathy. In particular, these studies have demonstrated strong correlation between hyperkalaemia and the development of nerve dysfunction. These studies have provided a basis for future work assessing the benefits of potassium restriction as a therapeutic strategy in this condition. PMID:23683523

  5. [A case of femoral neuropathy after radical ovariectomy].

    PubMed

    Hatano, Yumi; Morikawa, Keiko; Sugioka, Norimitsu; Sakaguchi, Yoshiro; Hoka, Sumio

    2012-04-01

    We experienced a 55-year-old female patient who was diagnosed as femoral neuropathy after radical ovariectomy. An epidural catheter was introduced at T11-12 interspace without any problems and general anesthesia was induced and maintained. The operation ended uneventfully. On the first postoperative day, she noticed hypesthesia of the inner surface of her left thigh and could not raise the left leg. The symptom remained after the removal of epidural catheter on the second postoperative day, and the influence of insertion of the epidural catheter on the symptom was suspected. We performed neurological examinations and found weakness of the left quadriceps femoris muscle, weakness of the left patellar reflex, and weakness of touch sensation and cold sensation and hypalgesia on the anterior surface of the left thigh and the inner surface of the left lower leg. Those findings led us to diagnose with femoral neuropathy probably due to abdominal retractors or the operation itself, and insertion of epidural anesthesia could not be the cause of neuropathy. Her symptom was ameliorated with a conservative therapy after four months. We should perform fine neurological examinations when neurological complications occur, especially when we use epidural catheters, and also should have the knowledge about those complications. PMID:22590949

  6. Japanese neuropathy patients with peripheral myelin protein-22 gene aneuploidy

    SciTech Connect

    Lebo, R.V.; Li, L.Y.; Flandermeyer, R.R.

    1994-09-01

    Peripheral myelin protein (PMP-22) gene aneuploidy results in Charcot-Marie-Tooth disease Type 1A (CMT1A) and the Hereditary Neuropathy with Liability to Pressure Palsy (HNPP) in Japanese patients as well as Caucasian Americans. Charcot-Marie-Tooth disease (CMT), the most common genetic neuropathy, results when expression of one of at least seven genes is defective. CMT1A, about half of all CMT mutations, is usually associated with a duplication spanning the peripheral myelin protein-22 gene on distal chromosome band 17p11.2. Autosomal dominant HNPP (hereditary pressure and sensory neuropathy, HPSN) results from a deletion of the CMT1A gene region. Multicolor in situ hybridization with PMP-22 gene region probe characterized HNPP deletion reliably and detected all different size duplications reported previously. In summary, 72% of 28 Japanese CMT1 (HMSNI) patients tested had the CMT1A duplication, while none of the CMT2 (HMSNII) or CMT3 (HMSNIII) patients had a duplication. Three cases of HNPP were identified by deletion of the CMT1A gene region on chromosome 17p. HNPP and CMT1A have been reported to result simultaneously from the same unequal recombination event. The lower frequency of HNPP compared to CMT1A suggests that HNPP patients have a lower reproductive fitness than CMT1A patients. This result, along with a CMT1A duplication found in an Asian Indian family, demonstrates the broad geographic distribution and high frequency of PMP-22 gene aneuploidy.

  7. Mechanisms of distal axonal degeneration in peripheral neuropathies.

    PubMed

    Cashman, Christopher R; Höke, Ahmet

    2015-06-01

    Peripheral neuropathy is a common complication of a variety of diseases and treatments, including diabetes, cancer chemotherapy, and infectious causes (HIV, hepatitis C, and Campylobacter jejuni). Despite the fundamental difference between these insults, peripheral neuropathy develops as a combination of just six primary mechanisms: altered metabolism, covalent modification, altered organelle function and reactive oxygen species formation, altered intracellular and inflammatory signaling, slowed axonal transport, and altered ion channel dynamics and expression. All of these pathways converge to lead to axon dysfunction and symptoms of neuropathy. The detailed mechanisms of axon degeneration itself have begun to be elucidated with studies of animal models with altered degeneration kinetics, including the slowed Wallerian degeneration (Wld(S)) and Sarm knockout animal models. These studies have shown axonal degeneration to occur through a programmed pathway of injury signaling and cytoskeletal degradation. Insights into the common disease insults that converge on the axonal degeneration pathway promise to facilitate the development of therapeutics that may be effective against other mechanisms of neurodegeneration. PMID:25617478

  8. Are electrophysiological criteria useful in distinguishing childhood demyelinating neuropathies?

    PubMed

    Potulska-Chromik, Anna; Ryniewicz, Barbara; Aragon-Gawinska, Karolina; Kabzinska, Dagmara; Seroka, Andrzej; Lipowska, Marta; Kaminska, Anna M; Kostera-Pruszczyk, Anna

    2016-03-01

    Childhood chronic inflammatory demyelinating polyneuropathy (CIDP) needs to be differentiated from hereditary neuropathy. We aimed to validate existing CIDP nerve conduction study (NCS) criteria in a group of children with demyelinating neuropathies of chronic or subacute onset. Retrospective analysis of clinical and NCS results in 18 children with CIDP, 7 with hereditary neuropathy with pressure palsy (HNPP), and 24 with Charcot-Marie-Tooth 1a (CMT1a). AAN and EFNS electrodiagnostic CIDP criteria were fulfilled in 17 of 18 CIDP, 3 of 7 HNPP, and 23 of 24 CMT1a patients. A distal compound muscle action potential (dCMAP) of >9 ms was observed in 14 of 18 CIDP patients but not in any patients with HNPP. Abnormal median/normal sural SNAP (AMNS) and a 10 m/s difference between conduction velocities (CV) of two corresponding nerves were not observed in any CMT1a patients. NCS in CMT1a, HNPP, and CIDP reflect demyelination. dCMAP duration, sensory AMNS, and a 10 m/s CV difference parameter are most useful in the differential diagnosis of pediatric CIDP. PMID:26663344

  9. Induction of p75NGFR in human diabetic neuropathy.

    PubMed

    Scarpini, E; Conti, G; Chianese, L; Baron, P; Pizzul, S; Basellini, A; Livraghi, S; Scarlato, G

    1996-01-01

    In this immunohistochemical study we investigated the expression of low-affinity NGF receptor (p75NGFR) in peripheral nerves from 16 patients with type I or type II diabetes mellitus. Fourteen nerves from age- and sex-matched normal individuals and nine nerves from non-diabetic patients with ischemic neuropathy served as controls. All nerve samples were preliminarily examined by standard histology, fiber teasing and electron microscopy. Increased p75NGFR immunoreactivity was detectable within the endoneurium of cross-sections from ischemic and particularly from diabetic nerves. Immuno-teasing demonstrated that p75NGFR immunostaining was distributed along the entire length of isolated nerve fibers undergoing axonal degeneration. Quantitative assessment of p75NGFR immunoreactivity, performed by histospectrophotometry and expressed as percentage of adsorbance, was 21.20 +/- 3.50 in nerves from diabetic patients, 13.35 +/- 3.62 in nerves from non-diabetic patients with ischemic neuropathy and 9.02 +/- 2.75 in normal controls. The increased expression of p75NGFR in diabetic nerves is consistent with an axonopathic defect and further suggests involvement of NGF and other neurotrophins in the pathogenesis of human diabetic neuropathy. PMID:8926497

  10. DADS neuropathy associated with anti-TNF-? therapy.

    PubMed

    McGinty, Ronan Niall; McNamara, Brian; Moore, Helena

    2015-01-01

    A 52-year-old man with idiopathic Parkinson's disease and severe rheumatoid arthritis presented with a 1-year history of progressively worsening limb paraesthesia. Examination showed sensory loss in a glove and stocking distribution, absent reflexes and unsteady tandem gait. Nerve conduction studies suggested an acquired peripheral neuropathy with distal demyelination, which-together with the clinical phenotype-was consistent with a Distal Acquired Demyelinating Symmetric (DADS) neuropathy pattern. This was attributed to therapy with adalimumab, an antitumor necrosis factor (TNF)-? agent, which the patient had been taking for 2?years for rheumatoid arthritis. One month after discontinuing adalimumab, the limb paraesthesia had resolved completely and the patient had a normal tandem gait. Demyelinating disorders may rarely occur as complications of anti-TNF-? agents and therefore have implications for pretreatment counselling and ongoing monitoring. DADS neuropathy is a subtype of chronic inflammatory demyelinating polyradiculoneuropathy, which responds poorly to standard therapy and has not previously been described with anti-TNF-? therapy. PMID:26607186

  11. Hereditary neuropathy with liability to pressure palsies: the first publication (1947).

    PubMed

    Koehler, Peter J

    2003-04-01

    The first report of hereditary neuropathy with liability to pressure palsies (HNPP) was published in Dutch in 1947. The present paper makes it accessible in the English language. de Jong described two families, but only the cases from the first family may be considered to have had HNPP. Five persons from three generations had recurring peripheral neuropathies. de Jong hypothesized a hereditary disposition for the occurrence of neuropathies, but suggested a relationship with low vitamin B(1) levels. PMID:12682341

  12. Alteration of foot temperature in diabetic neuropathy: is it another piece of puzzle?

    PubMed

    Naicker, A S; Roohi, S A; Lee, C S; Chan, W H; Tay, L S; Din, X J; Eow, L H

    2006-02-01

    Poor glycaemic control and the duration of diabetes mellitus are known to accelerate development and progression of neuropathy. Diabetic co-morbidities: hypertension and hyperlipidaemia, have been postulated to associate with development of neuropathy. A diabetic foot with low temperature and frequent exposure to low temperature environment has recently been hypothesized to be at higher risk to develop early neuropathy. This cross-sectional study is undertaken to identify risk factors for diabetic neuropathy and the association between foot temperature and development of diabetic neuropathy by using simple clinical examination in the outpatient setting. From April 18, to April 30, 2005, universal sampling method was used to select 134 diabetic patients (type 1 or type 2 for >1 year) with peripheral neuropathy. Excluded are those with chronic alcoholism, drug-induced neuropathy, dietary history of vitamin B deficiency and family history of porphyria and hereditary sensorimotor neuropathy. The patient's duration of diabetes, glycaemic control status and the presence of co-morbids: hypertension and hyperlipidemia, were recorded. The temperature of the foot was measured by using thermo buddy. Of 134 patients representing Malaysian ethnic distribution with an equal number of males and females, 20.1% were in the age group of 61 to 65 years and, 85.1% and 67.9% belonged to lower socioeconomic and educational groups respectively. Associations between diabetic neuropathy and glycaemic control (p = 0.018) and duration of diabetes (p < 0.05) were significant. However, hypertension, hyperlipidaemia and low foot temperature were not significantly associated with development of diabetic neuropathy. Poor glycaemic control is significantly associated with diabetic neuropathy. Foot temperature alteration is merely an effect of autonomic neuropathy with a cold foot is attributed to co-existing peripheral arterial disease. PMID:17042221

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

    ClinicalTrials.gov

    2015-04-28

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

  14. Progressive Axonal Dysfunction Precedes Development of Neuropathy in Type 2 Diabetes

    PubMed Central

    Sung, Jia-Ying; Park, Susanna B.; Liu, Ya-Ting; Kwai, Natalie; Arnold, Ria; Krishnan, Arun V.; Lin, Cindy S.-Y.

    2012-01-01

    To evaluate the development of diabetic neuropathy, the current study examined changes in peripheral axonal function. Nerve excitability techniques were undertaken in 108 type 2 diabetic patients with nerve conduction studies (NCS), HbA1c levels, and total neuropathy score (TNS). Patients were categorized into two cohorts: patients with diabetes without neuropathy (DWN group [n = 56]) and patients with diabetes with neuropathy (DN group [n = 52]) and further into severity grade 0 (TNS 01 [n = 35]), grade 1 (TNS 28 [n = 42]), and grade 2/3 (TNS 924 [n = 31]). Results revealed that the DWN group had a significantly increased threshold, prolonged latency, and changes in excitability parameters compared with age-matched control subjects. Patients with neuropathy demonstrated significant alteration in recovery cycle parameters and depolarizing threshold electrotonus. Within the DWN cohort, there were significant correlations between HbA1c level and latency and subexcitability, whereas the estimated glomerular filtration rate correlated with superexcitability in patients with neuropathy. Furthermore, excitability parameters became progressively more abnormal with increasing clinical severity. These results suggest a spectrum of excitability abnormalities in patients with diabetes and that early axonal dysfunction may be detected prior to the development of neuropathy. As progressive changes in excitability parameters correlated to neuropathy severity, excitability testing may provide a biomarker of the early development and severity of diabetic neuropathy, providing insights into the pathophysiological mechanisms producing axonal dysfunction. PMID:22522615

  15. Progressive axonal dysfunction precedes development of neuropathy in type 2 diabetes.

    PubMed

    Sung, Jia-Ying; Park, Susanna B; Liu, Ya-Ting; Kwai, Natalie; Arnold, Ria; Krishnan, Arun V; Lin, Cindy S-Y

    2012-06-01

    To evaluate the development of diabetic neuropathy, the current study examined changes in peripheral axonal function. Nerve excitability techniques were undertaken in 108 type 2 diabetic patients with nerve conduction studies (NCS), HbA(1c) levels, and total neuropathy score (TNS). Patients were categorized into two cohorts: patients with diabetes without neuropathy (DWN group [n = 56]) and patients with diabetes with neuropathy (DN group [n = 52]) and further into severity grade 0 (TNS 0-1 [n = 35]), grade 1 (TNS 2-8 [n = 42]), and grade 2/3 (TNS 9-24 [n = 31]). Results revealed that the DWN group had a significantly increased threshold, prolonged latency, and changes in excitability parameters compared with age-matched control subjects. Patients with neuropathy demonstrated significant alteration in recovery cycle parameters and depolarizing threshold electrotonus. Within the DWN cohort, there were significant correlations between HbA(1c) level and latency and subexcitability, whereas the estimated glomerular filtration rate correlated with superexcitability in patients with neuropathy. Furthermore, excitability parameters became progressively more abnormal with increasing clinical severity. These results suggest a spectrum of excitability abnormalities in patients with diabetes and that early axonal dysfunction may be detected prior to the development of neuropathy. As progressive changes in excitability parameters correlated to neuropathy severity, excitability testing may provide a biomarker of the early development and severity of diabetic neuropathy, providing insights into the pathophysiological mechanisms producing axonal dysfunction. PMID:22522615

  16. Correlation of epidermal nerve fiber density with pain-related evoked potentials in HIV neuropathy.

    PubMed

    Obermann, Mark; Katsarava, Zaza; Esser, Stefan; Sommer, Claudia; He, Lan; Selter, Laura; Yoon, Min-Suk; Kaube, Holger; Diener, Hans-Christoph; Maschke, Matthias

    2008-08-15

    HIV associated sensory neuropathy is a common neurological disorder with reported prevalence of 53%. When only small fibers are involved, the diagnosis of neuropathy remains difficult since standard nerve conduction studies generally are unremarkable. We assessed a method to identify small-fiber neuropathy using electrically evoked pain-related potentials and correlated the electrophysiological results with intraepidermal nerve fiber density in patients with HIV associated sensory neuropathy. Nineteen HIV positive patients were investigated for clinically diagnosed peripheral neuropathy with Neuropathy Symptoms Score (NSS)3 and Neuropathy Disability Score (NDS)5. Nine healthy HIV negative control subjects were recruited. We performed standard nerve conduction testing, electrically evoked pain-related potentials and skin biopsy in all participants. Pain-related evoked potentials revealed abnormalities in all HIV positive neuropathy patients, while standard nerve conduction testing was abnormal in eight patients only. Pain-related evoked potential latencies and amplitudes strongly correlated with intraepidermal nerve fiber density. The method of pain-related evoked potential conduction appears to be a sensitive, fast, non-invasive technique for the detection of small-fiber neuropathy and may prove to become a valuable diagnostic asset. PMID:18096318

  17. [The Neuropad test in the screening of peripheral neuropathy in diabetic patients].

    PubMed

    Freitas, Cludia; Carvalho, Andr; Melo-Rocha, Gustavo; Amaral, Cludia; Pinto, Sara; Guimares, Rosa; Neto, Helena; Suascun, Jos; Muras, Jos; Gonalves, Isabel; Martins, Joana; Dores, Jorge; Carvalho, Rui; Borges, Ftima

    2009-01-01

    One of the first signs of peripheral neuropathy is the loss of perspiration of the feet. Untill now, the Semmes-Weinstein monofilament test has been considered the gold test to detect early peripheral neuropathy. Recently, the Neuropad test has become available: it is a cobalt salt plaster designed to change colour from blue to pink in contact with liquids, namely sweating. The objective of this study was to find if the Neuropad test could be considered as a test for detecting peripheral autonomic neuropathy and to compare its sensitivity and specificity to the Semmes-Weinstein monofilament test. Forty diabetic patients were studied, 22 of them presented with peripheral neuropathy. The criteria used for the definition of neuropathy was based on the Neuropathy Disability Score (NDS). Under Semmes-Weinstein monofilament test, we found a sensitivity and specificity of 82% and 94%, respectively, and with the Neuropad test, a specificity of 44%, but a sensitivity of 100%. Ten patients presented a sudomotor dysfunction of the feet in the absence of peripheral neuropathy (based on the NDS criteria), and were considered as false positives. We concluded that the Neuropad test is a simple, sensitive test to screen for diabetic neuropathy. Based on the false positive results, we may consider it as a reliable test detecting neuropathy in a earlier phase. PMID:20350454

  18. HMG-CoA-reductase inhibitors and neuropathy: reports to the Netherlands Pharmacovigilance Centre.

    PubMed

    de Langen, J J; van Puijenbroek, E P

    2006-10-01

    The number of patients taking HMG-CoA-reductase inhibitors for hypercholesterolaemia is growing rapidly. Treatment with HMG-CoA-reductase inhibitors significantly reduces the risk of cardiovascular morbidity and mortality, but may rarely cause serious adverse drug reactions (ADRs). The most serious ADRs of HMG-CoA-reductase inhibitors are musculoskeletal symptoms including myopathy and myositis, (life-threatening) rhabdomyolysis and liver failure. Furthermore, peripheral neuropathy might also occur, especially after long-term use of HMG-CoA-reductase inhibitors. Because of the severity and the relative rarity of HMG-CoA-reductase-induced neuropathy, the Netherlands Pharmacovigilance Centre Lareb has analysed its database of reported ADRs for reports concerning neuropathy associated with the use of HMG-CoA-reductase inhibitors. Until June 2005, Lareb received 17 reports of neuropathy, peripheral neuropathy and polyneuropathy and in addition two reports of aggravation of existing polyneuropathy associated with the use of HMG-CoA-reductase inhibitors. The associations neuropathy, peripheral neuropathy and polyneuropathy and the use of hMg-CoA-reductase inhibitors are statistically significantly more often reported to Lareb. The average time to onset supports conclusions of previous studies and case reports that especially long-term exposure increases the risk for peripheral neuropathy. Considering the increasing number of patients taking HMG-CoA-reductase inhibitors, health care professionals should be aware of the possible role of these drugs in neuropathy. PMID:17057271

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

    PubMed

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

    2014-01-01

    PMP22 related neuropathies comprise (1) PMP22 duplications leading to Charcot-Marie-Tooth disease type 1A (CMT1A), (2) PMP22 deletions, leading to Hereditary Neuropathy with liability to Pressure Palsies (HNPP), and (3) PMP22 point mutations, causing both phenotypes. Overall prevalence of CMT is usually reported as 1:2,500, epidemiological studies show that 20-64% of CMT patients carry the PMP22 duplication. The prevalence of HNPP is not well known. CMT1A usually presents in the first two decades with difficulty walking or running. Distal symmetrical muscle weakness and wasting and sensory loss is present, legs more frequently and more severely affected than arms. HNPP typically leads to episodic, painless, recurrent, focal motor and sensory peripheral neuropathy, preceded by minor compression on the affected nerve. Electrophysiological evaluation is needed to determine whether the polyneuropathy is demyelinating. Sonography of the nerves can be useful. Diagnosis is confirmed by finding respectively a PMP22 duplication, deletion or point mutation. Differential diagnosis includes other inherited neuropathies, and acquired polyneuropathies. The mode of inheritance is autosomal dominant and de novo mutations occur. Offspring of patients have a chance of 50% to inherit the mutation from their affected parent. Prenatal testing is possible; requests for prenatal testing are not common. Treatment is currently symptomatic and may include management by a rehabilitation physician, physiotherapist, occupational therapist and orthopaedic surgeon. Adult CMT1A patients show slow clinical progression of disease, which seems to reflect a process of normal ageing. Life expectancy is normal. PMID:24646194

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

    PubMed Central

    2014-01-01

    PMP22 related neuropathies comprise (1) PMP22 duplications leading to Charcot-Marie-Tooth disease type 1A (CMT1A), (2) PMP22 deletions, leading to Hereditary Neuropathy with liability to Pressure Palsies (HNPP), and (3) PMP22 point mutations, causing both phenotypes. Overall prevalence of CMT is usually reported as 1:2,500, epidemiological studies show that 20-64% of CMT patients carry the PMP22 duplication. The prevalence of HNPP is not well known. CMT1A usually presents in the first two decades with difficulty walking or running. Distal symmetrical muscle weakness and wasting and sensory loss is present, legs more frequently and more severely affected than arms. HNPP typically leads to episodic, painless, recurrent, focal motor and sensory peripheral neuropathy, preceded by minor compression on the affected nerve. Electrophysiological evaluation is needed to determine whether the polyneuropathy is demyelinating. Sonography of the nerves can be useful. Diagnosis is confirmed by finding respectively a PMP22 duplication, deletion or point mutation. Differential diagnosis includes other inherited neuropathies, and acquired polyneuropathies. The mode of inheritance is autosomal dominant and de novo mutations occur. Offspring of patients have a chance of 50% to inherit the mutation from their affected parent. Prenatal testing is possible; requests for prenatal testing are not common. Treatment is currently symptomatic and may include management by a rehabilitation physician, physiotherapist, occupational therapist and orthopaedic surgeon. Adult CMT1A patients show slow clinical progression of disease, which seems to reflect a process of normal ageing. Life expectancy is normal. PMID:24646194

  1. Genetic evaluation of inherited motor/sensory neuropathy.

    PubMed

    Chance, Phillip F

    2004-01-01

    Inherited disorders of peripheral nerves represent a common group of neurologic diseases. Charcot-Marie-Tooth neuropathy type 1 (CMT1) is a genetically heterogeneous group of chronic demyelinating polyneuropathies with loci mapping to chromosome 17 (CMT1A), chromosome 1 (CMT1B), chromosome 16 (CMT1C) and chromosome 10 (CMT1D). CMT1A is most often associated with a tandem 1.5-megabase (Mb) duplication in chromosome 17p11.2-p12. In rare patients it 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 (Po or MPZ) gene. Mutations in the SIMPLE gene cause CMT1C, and CMT1D is the result of mutations in the early response 2 (ERG2 or Krox-20) gene. An X-linked form of CMT1 (CMT1X) maps to Xq13 and is associated with mutations in the connexin32 (Cx32) gene. Charcot-Marie-Tooth neuropathy type 2 (CMT2) is an axonal neuropathy that maps to chromosome 1p35-p36 (CMT2A), chromosome 3q13-q22 (CMT2B), chromosome 7p14 (CMT2D), chromosome 8p21 (CMT2E), chromosome 1q22-q23 (CMT2F) or chromosome 3q13 (CMT2G). Two X-linked forms of CMT2 have been reported (CMT2XA and CMT2XB), but the genes remain unidentified. An area that has recently expanded is the identification of autosomal recessive forms of CMT type 1 and 2. Of the eight recessive forms of CMT1 that have been identified to date, only two have been fully characterized at the molecular level (CMT1 AR B 1 and CMT1 AR D). Point mutations were found in the myotubularin-related protein-2 (MTM2) gene for CMT1 AR B1. CMT1 AR D is the result of point mutations in the N-myc downstream-regulated gene 1 (NDRG1). Dejerine-Sottas disease (DSD), also called hereditary motor and sensory neuropathy type III (HMSNIII), is a severe, infantile-onset demyelinating polyneuropathy syndrome that may be associated with point mutations in either the PMP22 gene, PO gene, EGR2 gene or the PRX gene (for the recessive form). It shares considerable clinical and pathological features with CMT1. Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder that results in a recurrent, episodic demyelinating neuropathy. HNPP is associated with a 1.5-Mb deletion in chromosome 17p11.2-p12 that results in reduced expression of the PMP22 gene. CMT1A and HNPP are reciprocal duplication/deletion syndromes that originate from unequal crossover during germ cell meiosis. Other rare forms of demyelinating peripheral neuropathies map to chromosome 8q, 10q and 11q. PMID:16106622

  2. Loss of function mutations in HARS cause a spectrum of inherited peripheral neuropathies.

    PubMed

    Safka Brozkova, Dana; Deconinck, Tine; Griffin, Laurie Beth; Ferbert, Andreas; Haberlova, Jana; Mazanec, Radim; Lassuthova, Petra; Roth, Christian; Pilunthanakul, Thanita; Rautenstrauss, Bernd; Janecke, Andreas R; Zavadakova, Petra; Chrast, Roman; Rivolta, Carlo; Zuchner, Stephan; Antonellis, Anthony; Beg, Asim A; De Jonghe, Peter; Senderek, Jan; Seeman, Pavel; Baets, Jonathan

    2015-08-01

    Inherited peripheral neuropathies are a genetically heterogeneous group of disorders characterized by distal muscle weakness and sensory loss. Mutations in genes encoding aminoacyl-tRNA synthetases have been implicated in peripheral neuropathies, suggesting that these tRNA charging enzymes are uniquely important for the peripheral nerve. Recently, a mutation in histidyl-tRNA synthetase (HARS) was identified in a single patient with a late-onset, sensory-predominant peripheral neuropathy; however, the genetic evidence was lacking, making the significance of the finding unclear. Here, we present clinical, genetic, and functional data that implicate HARS mutations in inherited peripheral neuropathies. The associated phenotypic spectrum is broad and encompasses axonal and demyelinating motor and sensory neuropathies, including four young patients presenting with pure motor axonal neuropathy. Genome-wide linkage studies in combination with whole-exome and conventional sequencing revealed four distinct and previously unreported heterozygous HARS mutations segregating with autosomal dominant peripheral neuropathy in four unrelated families (p.Thr132Ile, p.Pro134His, p.Asp175Glu and p.Asp364Tyr). All mutations cause a loss of function in yeast complementation assays, and p.Asp364Tyr is dominantly neurotoxic in a Caenorhabditis elegans model. This study demonstrates the role of HARS mutations in peripheral neuropathy and expands the genetic and clinical spectrum of aminoacyl-tRNA synthetase-related human disease. PMID:26072516

  3. Vitamin D for the treatment of painful diabetic neuropathy

    PubMed Central

    Basit, Abdul; Basit, Khalid Abdul; Fawwad, Asher; Shaheen, Fariha; Fatima, Nimra; Petropoulos, Ioannis N; Alam, Uazman; Malik, Rayaz A

    2016-01-01

    Objective To assess the effect of high-dose vitamin D in patients with painful diabetic neuropathy. Methods A single intramuscular dose of 600 000 IU vitamin D was administered, and the effects on metabolic parameters and neuropathic pain assessed over 20 weeks. Results 143 participants with predominantly type 2 diabetes, aged 52.31±11.48 years, with a Douleur Neuropathique 4 (DN4) score (3.0±1.8), total McGill pain score (21.2±14.9), and Short Form McGill Pain Questionnaire (SFMPQ) score (2.1±0.9), were enrolled. The baseline 25-hydroxyvitamin D (25(OH)D) level was 31.7±23.3 ng/mL and 58 (40.5%) patients showed evidence of vitamin D deficiency (25(OH)D<20 ng/mL). Intramuscular administration of vitamin D resulted in a significant increase in 25(OH)D (46.2±10.2 ng/mL, p<0.0001) and a reduction in positive symptoms on the DN4 (p<0.0001), total pain score (p<0.0001), and SFMPQ (p<0.0001). Conclusions Treatment with a single intramuscular dose of 600 000 IU of vitamin D in patients with painful diabetic neuropathy is associated with a significant decrease in the symptoms of painful diabetic neuropathy. Trial registration number BIDE-12/2014.

  4. Cochlear neuropathy and the coding of supra-threshold sound

    PubMed Central

    Bharadwaj, Hari M.; Verhulst, Sarah; Shaheen, Luke; Liberman, M. Charles; Shinn-Cunningham, Barbara G.

    2014-01-01

    Many listeners with hearing thresholds within the clinically normal range nonetheless complain of difficulty hearing in everyday settings and understanding speech in noise. Converging evidence from human and animal studies points to one potential source of such difficulties: differences in the fidelity with which supra-threshold sound is encoded in the early portions of the auditory pathway. Measures of auditory subcortical steady-state responses (SSSRs) in humans and animals support the idea that the temporal precision of the early auditory representation can be poor even when hearing thresholds are normal. In humans with normal hearing thresholds (NHTs), paradigms that require listeners to make use of the detailed spectro-temporal structure of supra-threshold sound, such as selective attention and discrimination of frequency modulation (FM), reveal individual differences that correlate with subcortical temporal coding precision. Animal studies show that noise exposure and aging can cause a loss of a large percentage of auditory nerve fibers (ANFs) without any significant change in measured audiograms. Here, we argue that cochlear neuropathy may reduce encoding precision of supra-threshold sound, and that this manifests both behaviorally and in SSSRs in humans. Furthermore, recent studies suggest that noise-induced neuropathy may be selective for higher-threshold, lower-spontaneous-rate nerve fibers. Based on our hypothesis, we suggest some approaches that may yield particularly sensitive, objective measures of supra-threshold coding deficits that arise due to neuropathy. Finally, we comment on the potential clinical significance of these ideas and identify areas for future investigation. PMID:24600357

  5. Familial amyloidosis with cranial neuropathy and corneal lattice dystrophy.

    PubMed Central

    Boysen, G; Galassi, G; Kamieniecka, Z; Schlaeger, J; Trojaborg, W

    1979-01-01

    Five siblings of a Danish family with slowly progressive involvement of the trigeminal, facial, glossopharyngeal, accessory, and hypoglossal nerves beginning at the age of 55-65 years were examined. All had asymptomatic corneal lattice dystrophy. Clinical and electrophysiological investigations also showed evidence of slight neurogenic involvement of the limbs. Conduction velocity along sensory nerves was normal but amplitude of sensory potentials was severely reduced suggesting an axonal affection which was confirmed by sural nerve biopsy. The neuropathy was secondary to amyloidosis revealed by skin and sural nerve biopsies. Images PMID:228009

  6. Gastric partitioning complicated by peripheral neuropathy with lumbosacral plexopathy.

    PubMed

    Harwood, S C; Chodoroff, G; Ellenberg, M R

    1987-05-01

    Gastric bypass and partitioning are the two surgical procedures most commonly used in the treatment of morbid obesity. They are, however, not without their postoperative complications. These include acute and chronic problems such as wound infection, gastric leak, obstruction, embolism, and neurologic sequelae. Many studies have mentioned the frequent occurrence of polyneuropathy in the postgastrectomy state. This report describes a 38-year-old patient who developed an asymmetric peripheral neuropathy with lumbosacral plexus involvement following gastric bypass surgery for morbid obesity. PMID:3034193

  7. Bioenergetics in Diabetic Neuropathy- What We Need to Know

    PubMed Central

    Hinder, Lucy M.; Vincent, Andrea M.; Burant, Charles F.; Pennathur, Subramaniam; Feldman, Eva L.

    2013-01-01

    Progress in developing treatments for diabetic neuropathy is slowed by our limited understanding of how disturbances in metabolic substrates- glucose and fatty acids- produce nerve injury. In this review, we present the current oxidative stress hypothesis and experimental data that support it. We identify weaknesses in our understanding of diabetes-disordered metabolism in the neurovascular unit; i.e. in critical cell types of the microvascular endothelium, peripheral sensory neurons, and supporting Schwann cells. Greater understanding of peripheral nervous system bioenergetics may provide insight into new drug therapies or improvements in dietary interventions in diabetes or even pre-diabetes. PMID:22548617

  8. Facial neuropathy in dogs and cats: 95 cases (1975-1985).

    PubMed

    Kern, T J; Erb, H N

    1987-12-15

    The medical records of 79 dogs and 16 cats admitted to the New York State College of Veterinary Medicine between January 1975 and October 1985 with facial nerve dysfunction were reviewed. In 31 dogs and 8 cats, facial neuropathy was the only abnormal finding. In 48 dogs and 8 cats, the clinical findings most often noted in the records in addition to facial neuropathy were vestibular signs. Facial neuropathy appeared unassociated with gender or right vs left sides in both dogs and cats, or with hypothyroidism in dogs. Facial neuropathy was associated with increased age, with certain breeds in both dogs and cats, and with otitis media/interna and keratoconjunctivitis sicca in dogs. Causes of facial nerve dysfunction in dogs and cats included surgical and nonsurgical trauma, neoplasia, and otitis media/interna. Facial neuropathy was judged to be idiopathic in 74.7% of dogs and 25% of cats. PMID:3693020

  9. Differential diagnosis of Charcot-Marie-Tooth disease and related neuropathies.

    PubMed

    Pareyson, D

    2004-06-01

    The diagnosis of Charcot-Marie-Tooth disease (CMT) and related neuropathies (e. g. Déjèrine-Sottas disease; hereditary neuropathy with liability to pressure palsies) appears to be easy. However, the incredible advances in molecular genetics have greatly complicated the classification of these disorders, and the proper diagnosis of the CMT subtype may be important for correct genetic counselling and prognosis. Moreover, these diseases may be confused with potentially treatable acquired and inherited neuropathies, such as dysimmune neuropathies, familial amyloid polyneuropathy, and Refsum's disease. A number of clinical, laboratory, electrophysiological, morphological and neuroradiological features that may help in the diagnostic process are reviewed in the present paper. DNA investigations are fundamental but need to be properly addressed. Currently, great interest is focused on the role of the immune system in hereditary neuropathies, and surprising findings are coming from research on animal models. PMID:15221625

  10. Axon Transport and Neuropathy: Relevant Perspectives on the Etiopathogenesis of Familial Dysautonomia.

    PubMed

    Tourtellotte, Warren G

    2016-03-01

    Peripheral neuropathies are highly prevalent and are most often associated with chronic disease, side effects from chemotherapy, or toxic-metabolic abnormalities. Neuropathies are less commonly caused by genetic mutations, but studies of the normal function of mutated proteins have identified particular vulnerabilities that often implicate mitochondrial dynamics and axon transport mechanisms. Hereditary sensory and autonomic neuropathies are a group of phenotypically related diseases caused by monogenic mutations that primarily affect sympathetic and sensory neurons. Here, I review evidence to indicate that many genetic neuropathies are caused by abnormalities in axon transport. Moreover, in hereditary sensory and autonomic neuropathies. There may be specific convergence on gene mutations that disrupt nerve growth factor signaling, upon which sympathetic and sensory neurons critically depend. PMID:26724390

  11. [Metabolic and nutritional neuropathies: update in diabetes, vitamin B12 and copper deficiency].

    PubMed

    Franques, J; Gazzola, S

    2013-12-01

    Metabolic and deficiency neuropathies retain a growing interest because of their important prevalence. The dismemberment of diabetic neuropathies is proceeded, letting distinct pathophysiological mechanisms appear. So, even if glycaemic control remains determining for preventing the neuropathy associated with type 1 diabetes, it seems to have a restricted role with type 2 diabetes in which other metabolic factors are involved. The diagnosis of neuropathy due to B12 vitamin deficiency remains a real challenge for the clinician. Indeed, positive and negative predictive values of serum B12 and metabolites assay are weak, only a good therapeutic response allows a reliable diagnostic. It is so recommended to know the clinical and contextual particularities of this etiology in order to not delay the vitamin substitution, determining for the functional outcome. Finally, copper deficiency remains an unknown cause of neuropathy which is suitable to raise in case of malabsorption but also and especially in case of abuse of dental adhesive rich in zinc. PMID:24269115

  12. 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; Schle, Rebecca; Mayerhofer, Benjamin; Zchner, 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

  13. Cuban epidemic neuropathy, 1991 to 1994: history repeats itself a century after the "amblyopia of the blockade".

    PubMed Central

    Ordez-Garca, P O; Nieto, F J; Espinosa-Brito, A D; Caballero, B

    1996-01-01

    The 1991 to 1994 epidemic of neuropathy in Cuba has been one of the more devastating in recent history, affecting more than 50,000 people throughout the entire country with clinical manifestations of optic and peripheral neuropathy. Although the causes are not entirely clear, it seems that a combination of acute nutritional deficiency and the toxic effects of tobacco and possibly other unidentified toxic substances is involved. The epidemic coincided with the acute worsening of the economic situation on the island following political changes in Eastern European countries and a tightening of the US economic embargo. This paper reviews reports of a strikingly similar epidemic known as the "Amblyopia of the Blockade," which occurred in Cuba almost a century ago when the island was undergoing a US naval blockade during the Cuban-Spanish-American war. It discusses the parallelism with the recent epidemic as well as the implications of this historical evidence to clarify further the ultimate causes of these epidemics. PMID:8629731

  14. IgM-monoclonal gammopathy neuropathy and tremor: A first epidemiologic case control study

    PubMed Central

    Ahlskog, Matthew C.; Kumar, Neeraj; Mauermann, Michelle L.; Klein, Christopher J.

    2012-01-01

    Introduction Small case series suggest tremor occurs frequently in IgM-monoclonal gammopathy of undetermined significance (IgM-MGUS) neuropathy. Epidemiologic study to confirm this association is lacking. Whether the neuropathy or another remote IgM-effect is causal remains unsettled. Materials and methods An IgM-MGUS neuropathy case cohort (n=207) was compared to age, gender, and neuropathy impairment score (NIS) matched, other-cause neuropathy controls (n=414). Tremor details were extracted from structured neurologic evaluation. All patients underwent nerve conductions. Results Tremor occurrence was significantly higher in IgM-MGUS case cohort (29%) than in control cohort (9.2%) (p=0.001). In IgM-MGUS cases, tremor was associated with worse NIS (p=0.025) and demyelinating nerve conductions (p=0.020), but 11 of 60 (18%) IgM-MGUS cases with tremor had axonal neuropathy. In other-cause neuropathy controls, tremor was associated with axonal nerve conductions (p=0.03) but not with NIS severity (p=0.57). Tremor occurrence associated with older age in controls, (p=0.004) but not in IgM-MGUS cases (p=0.272). Most IgM-MGUS tremor cases (49/60) had a postural-kinetic tremor, 8 had rest tremor, 3 had mixed rest-action. Alternative causes of tremor was identified in 42% of IgM-MGUS cases, the most common type is inherited essential tremor 6/60 (p=0.04). Conclusions This first epidemiologic case-control study validates association between IgM-MGUS neuropathy and tremor. Among IgM-MGUS neuropathy cases, severity as well as type of neuropathy (demyelinating over axonal) correlated with tremor occurrence. IgM-MGUS paraproteinemia may increase tremor expression in persons recognized with common other risk factors for tremor. PMID:22475624

  15. Restless Leg Syndrome in Different Types of Demyelinating Neuropathies: A Single-Center Pilot Study

    PubMed Central

    Luigetti, Marco; Del Grande, Alessandra; Testani, Elisa; Bisogni, Giulia; Losurdo, Anna; Giannantoni, Nadia Mariagrazia; Mazza, Salvatore; Sabatelli, Mario; Della Marca, Giacomo

    2013-01-01

    Objective: to determine the prevalence of restless legs syndrome (RLS) in a cohort of patients with demyelinating neuropathies. Methods: Patients were retrospectively recruited from our cohort of different forms of demyelinating neuropathies, including chronic inflammatory demyelinating neuropathy (CIDP), Charcot-Marie-Tooth 1A (CMT1A), and hereditary neuropathy with liability to pressure palsies (HNPP) referred to our Department of Neurology in a 10-year period. The validated 4-item RLS questionnaire was used for diagnosis of RLS. All patients with RLS who fulfilled criteria underwent a suggested immobilization test to confirm the diagnosis. A group of outpatients referred to the sleep disorders unit and data from published literature were used as controls. Results: Prevalence of RLS in demyelinating neuropathy group was higher than prevalence observed in control population (p = 0.0142) or in the literature data (p = 0.0007). In particular, in comparison with both control population and literature data, prevalence of RLS was higher in CIDP group (p = 0.0266 and p = 0.0063, respectively) and in CMT1A group (p = 0.0312 and p = 0.0105, respectively), but not in HNPP (p = 1.000 and p = 0.9320, respectively). Conclusions: our study confirms a high prevalence of RLS in inflammatory neuropathies as CIDP and, among inherited neuropathies, in CMT1A but not in HNPP. Considering that this is only a small cohort from a single-center retrospective experience, the link between RLS and neuropathy remains uncertain, and larger multicenter studies are probably needed to clarify the real meaning of the association between RLS and neuropathy. Citation: Luigetti M; Del Grande A; Testani E; Bisogni G; Losurdo A; Giannantoni NM; Mazza S; Sabatelli M; Della Marca G. Restless leg syndrome in different types of demyelinating neuropathies: a single-center pilot study. J Clin Sleep Med 2013;9(9):945-949. PMID:23997707

  16. Can diabetic neuropathy be prevented by angiotensin-converting enzyme inhibitors?

    PubMed

    Malik, R A

    2000-02-01

    The incidence of diabetes and its complications is increasing to staggering proportions. Presently the WHO estimates an overall prevalence of 130 million, but by 2025 there will be 300 million individuals with diabetes mellitus. The incidence of diabetic neuropathy approaches 50% in most diabetic populations; there is no treatment, and its consequences in the form of foot ulceration and amputation are financially punishing for health care providers. Attempts to develop treatments have faltered for want of an understanding of the aetiology of diabetic neuropathy. As a consequence, 1999 saw the demise of two further compounds: recombinant growth factor by Roche-Genentech and the aldose reductase inhibitor zopolrestat, by Pfizer, both had reached phase III clinical trials. They joined an impressive list of at least 30 other compounds which have reached phase III clinical trials and failed to establish efficacy. The need to establish a viable treatment for human diabetic neuropathy is absolutely paramount. To provide a rational answer as to whether angiotensin-converting enzyme (ACE) inhibitors can prevent human diabetic neuropathy, two major issues need addressing: 1) Does vascular dysfunction cause human diabetic neuropathy? 2) Can ACE inhibitors ameliorate diabetic vascular dysfunction and hence neuropathy? Epidemiological studies support a strong association between neuropathy, retinopathy and nephropathy. Microangiopathy is deemed as the root cause of both nephropathy, and retinopathy and mounting evidence provides support for a vascular basis of diabetic neuropathy. ACE inhibitors appear to correct many of the abnormalities associated with the vascular dysfunction found in diabetes. Thus effective ACE inhibition impacts very positively on cardiovascular outcomes in patients with ischaemic heart disease, particularly in diabetic patients. ACE inhibition also prevents the development and progression of incipient and established diabetic nephropathy and delays progression of background retinopathy. Quinapril improves measures of diabetic autonomic neuropathy. Our recent study has demonstrated a significant improvement in peripheral neuropathy following 12 months of treatment with the ACE inhibitor trandolapril. PMID:10711571

  17. Multifocal motor neuropathy: a review of pathogenesis, diagnosis, and treatment.

    PubMed

    Lawson, Victoria H; Arnold, W David

    2014-01-01

    Multifocal motor neuropathy (MMN) is an uncommon, purely motor neuropathy associated with asymmetric deficits with predilection for upper limb involvement. Even in the early descriptions of MMN, the associations of anti-GM1 antibodies and robust response to immunomodulatory treatment were recognized. These features highlight the likelihood of an underlying autoimmune etiology of MMN. The clinical presentation of MMN can closely mimic several neurological conditions including those with more malignant prognoses such as motor neuron disease. Therefore early and rapid recognition of MMN is critical. Serological evidence of anti GM-1 antibodies and electrodiagnostic findings of conduction block are helpful diagnostic clues for MMN. Importantly, these diagnostic features are not universally present, and patients lacking these characteristic findings can demonstrate similar robust response to immunodulatory treatment. In the current review, recent research in the areas of diagnosis, pathogenesis, and treatment of MMN and needs for the future are discussed. The characteristic findings of MMN and treatment implications are reviewed and contrasted with other mimicking disorders. PMID:24741315

  18. A prospective study of acute idiopathic neuropathy. II. Antecedent events.

    PubMed Central

    Winer, J B; Hughes, R A; Anderson, M J; Jones, D M; Kangro, H; Watkins, R P

    1988-01-01

    The incidence of antecedent events and serological evidence of preceding infection were studied in 100 patients with acute idiopathic neuropathy and age and sex matched control subjects in South-East England. Symptoms of respiratory infections occurred within one month before onset of neuropathic symptoms in 38% of patients and 12% of controls (p less than 0.001) and symptoms of gastrointestinal infections in 17% of patients and 3% of controls (p less than 0.005). Immunisations, insect bites and animal contact were equally common in the patient and control subjects. Eight per cent of patients had undergone an operation within the preceding 3 months. Six per cent of patients had co-existing "autoimmune" diseases. Serological evidence of recent infection was identified in 31% of patients. Campylobacter jejuni (14%) and cytomegalovirus (11%) were both significantly more frequently demonstrated in patients than controls. Serological evidence of recent infection with mycoplasma (1%), Epstein Barr virus (1-2%) and parvovirus B19 (4%) was also identified in the patients but not more frequently than in the controls. Possible explanations for the association of these agents with acute idiopathic neuropathy include possession of antigens shared with myelin and inhibition of suppressor mechanisms. PMID:3404161

  19. Cardiac autonomic neuropathy in patients with diabetes mellitus

    PubMed Central

    Dimitropoulos, Gerasimos; Tahrani, Abd A; Stevens, Martin J

    2014-01-01

    Cardiac autonomic neuropathy (CAN) is an often overlooked and common complication of diabetes mellitus. CAN is associated with increased cardiovascular morbidity and mortality. The pathogenesis of CAN is complex and involves a cascade of pathways activated by hyperglycaemia resulting in neuronal ischaemia and cellular death. In addition, autoimmune and genetic factors are involved in the development of CAN. CAN might be subclinical for several years until the patient develops resting tachycardia, exercise intolerance, postural hypotension, cardiac dysfunction and diabetic cardiomyopathy. During its sub-clinical phase, heart rate variability that is influenced by the balance between parasympathetic and sympathetic tones can help in detecting CAN before the disease is symptomatic. Newer imaging techniques (such as scintigraphy) have allowed earlier detection of CAN in the pre-clinical phase and allowed better assessment of the sympathetic nervous system. One of the main difficulties in CAN research is the lack of a universally accepted definition of CAN; however, the Toronto Consensus Panel on Diabetic Neuropathy has recently issued guidance for the diagnosis and staging of CAN, and also proposed screening for CAN in patients with diabetes mellitus. A major challenge, however, is the lack of specific treatment to slow the progression or prevent the development of CAN. Lifestyle changes, improved metabolic control might prevent or slow the progression of CAN. Reversal will require combination of these treatments with new targeted therapeutic approaches. The aim of this article is to review the latest evidence regarding the epidemiology, pathogenesis, manifestations, diagnosis and treatment for CAN. PMID:24567799

  20. Impaired mitochondrial functions in organophosphate induced delayed neuropathy in rats.

    PubMed

    Masoud, Anwar; Kiran, Ravi; Sandhir, Rajat

    2009-12-01

    Acute exposure to organophosphates induces a delayed neurodegenerative condition known as organophosphate-induced delayed neuropathy (OPIDN). The mechanism of OPIDN has not been fully understood as it does not involve cholinergic crisis. The present study has been designed to evaluate the role of mitochondrial dysfunctions in the development of OPIDN. OPIDN was induced in rats by administering acute dose of monocrotophos (MCP, 20 mg/kg body weight, orally) or dichlorvos (DDVP, 200 mg/kg body weight, subcutaneously), 15-20 min after treatment with antidotes [atropine (20 mg/kg body weight) and 2-PAM (100 mg/kg body weight) intraperitoneally]. MDA levels were observed to be higher and thiol content was lower in mitochondria from brain regions of OP exposed animals. This was accompanied by decreased activities of the mitochondrial enzymes; NADH dehydrogenase, succinate dehydrogenase, and cytochrome oxidase. In addition, mitochondrial functions assessed by MTT reduction also confirmed mitochondrial dysfunctions following development of OPIDN. The spatial long-term memory evaluated using elevated plus-maze test was observed to be deficit in OPIDN. The results suggest impaired mitochondrial functions as a mechanism involved in the development of organophosphate induced delayed neuropathy. PMID:19517227