Sample records for optic neuropathy aion

  1. Macular star formation in diabetic patients with non-arteritic anterior ischemic optic neuropathy (NA-AION)

    PubMed Central

    Galvez-Ruiz, Alberto

    2014-01-01

    Background NA-AION is a condition that exhibits a number of unique characteristics in diabetics compared with the rest of the population. In some diabetic patients with NA-AION, lipid deposits can be observed around the macula forming an incomplete macular star. Methods We describe 12 case studies of patients with NA-AION observing the development of lipid deposits around the macula forming an incomplete macular star. Results All our patients developed some level of lipid deposits around the macula in the form of a macular hemistar in the course of their illness. Conclusion Some authors have suggested that the macular star is formed by transudation from capillaries deep in the optic disk through the intermediary tissue of Kuhnt, which is located between the retina and the anterior portion of the lamina retinalis. However, the development of the macular star is currently understood not as a simple transudation but as a multifactorial process involving the presence of vascular damage around the optic disk, which is considered one of the most important factors leading to its occurrence. Although some studies mention the presence of a macular star in patients with NA-AION, we believe that this phenomenon may be significantly more common than the current literature suggests.

  2. Ischemic optic neuropathy

    Microsoft Academic Search

    Sohan Singh Hayreh

    1978-01-01

    Ischemic optic neuropathy (ION), based on vascular anatomy of the optic nerve, pathogenesis and clinical picture, consists of two distinct entities: anterior (AION) and posterior (PION) ischemic optic neuropathies. AION is due to interference with posterior ciliary artery supply to the optic nerve head and retrolaminar part of the optic nerve; it initially presents with visual loss and optic disc

  3. 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

  4. Ischemic Optic Neuropathies

    Microsoft Academic Search

    Anthony C. Arnold

    ? Ischemic optic neuropathy is classified by location as anterior or posterior and by etiology as arteritic or nonarteritic.\\u000a \\u000a \\u000a ? Anterior ischemic optic neuropathy (AION) presents with rapid, usually painless, monocular visual field loss in the presence\\u000a of optic disc edema. \\u000a \\u000a \\u000a \\u000a ? Arteritic AION is typically more severe and more frequently bilateral than nonarteritic AION, and is associated with severe

  5. Optic disc edema in non-arteritic anterior ischemic optic neuropathy

    Microsoft Academic Search

    Sohan Singh Hayreh; M. Bridget Zimmerman

    2007-01-01

    We investigated the clinical characteristics, time to resolution and the factors that influence it, and evolutionary pattern\\u000a of optic disc edema (ODE) in non-arteritic anterior ischemic optic neuropathy (NA-AION). Our study was conducted in 591 consecutive\\u000a patients (749 eyes) with NA-AION who fulfilled our inclusion criteria. On their first visit to our clinic, all patients had\\u000a a detailed ophthalmic and

  6. Hereditary optic neuropathies

    Microsoft Academic Search

    N J Newman; V Biousse

    2004-01-01

    Aims To provide a clinical update on the hereditary optic neuropathies.Methods Review of the literature.Results The hereditary optic neuropathies comprise a group of disorders in which the cause of optic nerve dysfunction appears to be hereditable, based on familial expression or genetic analysis. In some hereditary optic neuropathies, optic nerve dysfunction is typically the only manifestation of the disease. In

  7. Protein Z Plasma Levels are Not Elevated in Patients with Non-Arteritic Anterior Ischemic Optic Neuropathy

    PubMed Central

    Asproudis, Ioannis; Felekis, Taxiarchis L; Gorezis, Spiridon; Dova, Lefkothea; Dokou, Eleni; Vartholomatos, Georgios; Aspiotis, Miltiadis; Kolaitis, Nikolaos I

    2009-01-01

    Background: Protein Z is a glycoprotein that acts as a co-factor for the inhibition of activated coagulation factor X. Protein Z circulating in abnormal levels has been associated with increased risk for acute ischemic events. Non-arteritic Anterior Ischemic Optic Neuropathy (N-AION) is caused by acute ischemic infarction of the optic nerve head, supplied by the posterior ciliary arteries. Objectives: The aim was to investigate whether there is an association between N-AION and plasma protein Z levels. Patients and Methods: Twenty-six cases of confirmed N-AION and fifty-two controls were included in the study group. Protein Z was estimated in thawed citrate plasma on both N-AION cases and controls by an enzyme immunoassay. The imprecision of the estimation was satisfactory (CV = 4, 6%). Results: The controls’ protein Z values distributed within a range 340 to 4200 ng/ml (median = 1420, mean = 1673, SD = 1040 ng/ml). Patients’ protein Z values distributed within a range 420 to 3600 ng/ml (median = 1030, mean = 1520, SD = 939 ng/ml). There was no statistical difference between the two distributions (Independent t-test, p=0.529). Conclusion: In our study, protein Z levels are not implicated in the pathogenesis of non-arteritic anterior ischemic optic neuropathy (N-AION). PMID:19554219

  8. Light-chain amyloidosis mimicking giant cell arteritis in a bilateral anterior ischemic optic neuropathy case

    PubMed Central

    2013-01-01

    Background Herein we report a case of bilateral anterior ischemic optic neuropathy (AION) showing histopathologic evidence of AL-amyloidosis of the temporal arteries. It is known that light-chain (AL) amyloidosis may rarely affect the temporal arteries, mimicking giant cell arteritis, while, to our knowledge, the association between AL-amyloidosis and AION was not previously described. Case presentation A 64 year-old woman with AL-amyloidosis secondary to a monoclonal gammopathy of undetermined significance (MGUS) referred to our hospital for acute painless drop of vision due to bilateral AION. Age greater than 50 years, high erythrocyte sedimentation rate (ESR), and bilateral AION were suggestive of giant cell arteritis (GCA). However, a temporal artery biopsy excluded GCA, showing segmental stenosis of the lumen caused by amyloidosis of the artery wall. Conclusions The present case shows that AL-amyloidosis may present with AION, high ESR, and temporal artery involvement, mimicking GCA. In patients with monoclonal gammopathies, C-reactive protein may be a more specific index of GCA compared with the ESR. Patient medical history and pathology are crucial for a correct diagnosis. PMID:24359546

  9. Posterior Ischemic Optic Neuropathy

    Microsoft Academic Search

    Y. Isayama; T. Takahashi; M. Inoue; T. Jimura

    1983-01-01

    14 cases of posterior ischemic optic neuropathy (PION) were clinically analyzed, in whom we excluded known etiologies of optic nerve disturbances and confirmed the decreased blood supply to the posterior portion of the optic nerve. On the basis of our clinical findings, we have proposed the following criteria for the diagnosis of idiopathic PION: (1) sudden onset of unilateral visual

  10. 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

  11. Inherited Optic Neuropathies

    Microsoft Academic Search

    Marcela Votruba

    ? Inherited optic neuropathies are a diverse group of conditions presenting with mild to severe visual loss, colour vision\\u000a deficits, central\\/paracentral visual field defects, optic disc pallor and in many cases a positive family history. \\u000a \\u000a ? Modes of inheritance are dominant, recessive, X-linked and mitochondrial. \\u000a \\u000a \\u000a ? The absence of a family history does not exclude this diagnosis as there are

  12. [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

  13. Anterior ischemic optic neuropathy associated with Vogt–Koyanagi–Harada disease

    Microsoft Academic Search

    Kumiko Nakao; Yuka Mizushima; Noriko Abematsu; Nanako Goh; Taiji Sakamoto

    2009-01-01

    Background  Optic disc swelling is a common finding associated with Vogt–Koyanagi–Harada disease (VKH); however, visual field loss from\\u000a optic disc involvement is uncommon. This reports report presents recent findings regarding unusual patients with visual field\\u000a defects from optic disc involvement, thus suggesting the presence of anterior ischemic optic neuropathy (AION) in the acute\\u000a phase of VKH.\\u000a \\u000a \\u000a \\u000a Methods  Observational case series. A consecutive

  14. 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

  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 Nerve Inflammation and Demyelination in a Rodent Model of Nonarteritic Anterior Ischemic Optic Neuropathy

    PubMed Central

    Slater, Bernard J.; Vilson, Fernandino L.; Guo, Yan; Weinreich, Daniel; Hwang, Shelly; Bernstein, Steven L.

    2013-01-01

    Purpose. Optic nerve (ON) ischemia associated with nonarteric anterior ischemic optic neuropathy (NAION) results in axon and myelin damage. Myelin damage activates the intraneural Ras homolog A (RhoA), contributing to axonal regeneration failure. We hypothesized that increasing extrinsic macrophage activity after ON infarct would scavenge degenerate myelin and improve postischemic ON recovery. We used the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) to upregulate ON macrophage activity, and evaluated GM-CSF's effects after ON ischemia in the NAION rodent model (rAION). Methods. Following rAION induction, GM-CSF was administered via intraventricular injection. Retinal ganglion cell (RGC) stereologic analysis was performed 1 month postinduction. The retinae and optic nerve laminae of vehicle- and GM-CSF-treated animals were examined immunohistochemically and ultrastructurally using transmission electron microscopy (TEM). RhoA activity was analyzed using a rhotekin affinity immunoanalysis and densitometry. Isolated ONs were analyzed functionally ex vivo by compound action potential (CAP) analysis. Results. Rodent NAION produces ON postinfarct demyelination and myelin damage, functionally demonstrable by CAP analysis and ultrastructurally by TEM. Granulocyte-macrophage colony-stimulating factor increased intraneural inflammation, activating and recruiting endogenous microglia, with only a moderate amount of exogenous macrophage recruitment. Treatment with GM-CSF reduced postinfarct intraneural RhoA activity, but did not neuroprotect RGCs after rAION. Conclusions. Sudden ON ischemia results in previously unrecognized axonal demyelination, which may have a clinically important role in NAION-related functional defects and recovery. Granulocyte-macrophage colony-stimulating factor is not neuroprotective when administered directly to the optic nerve following ON ischemia, and does not improve axonal regeneration. It dramatically increases ON-microglial activation and recruitment. PMID:24065807

  17. Traumatic optic neuropathy: a review.

    PubMed

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

    2015-03-01

    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

  18. Genetics Home Reference: Leber hereditary optic neuropathy

    MedlinePLUS

    Leber hereditary optic neuropathy Mitochondrial DNA Related Gene(s) Related Condition(s) References Quick links to this topic MedlinePlus Health information Genetic and Rare Diseases Information Center Information about ...

  19. Progressive auditory neuropathy in patients with Leber's hereditary optic neuropathy

    PubMed Central

    Ceranic, B; Luxon, L

    2004-01-01

    Objective: To investigate auditory neural involvement in patients with Leber's hereditary optic neuropathy (LHON). Methods: Auditory assessment was undertaken in two patients with LHON. One was a 45 year old woman with Harding disease (multiple-sclerosis-like illness and positive 11778mtDNA mutation) and mild auditory symptoms, whose auditory function was monitored over five years. The other was a 59 year old man with positive 11778mtDNA mutation, who presented with a long standing progressive bilateral hearing loss, moderate on one side and severe to profound on the other. Standard pure tone audiometry, tympanometry, stapedial reflex threshold measurements, stapedial reflex decay, otoacoustic emissions with olivo-cochlear suppression, auditory brain stem responses, and vestibular function tests were undertaken. Results: Both patients had good cochlear function, as judged by otoacoustic emissions (intact outer hair cells) and normal stapedial reflexes (intact inner hair cells). A brain stem lesion was excluded by negative findings on imaging, recordable stapedial reflex thresholds, and, in one of the patients, olivocochlear suppression of otoacoustic emissions. The deterioration of auditory function implied a progressive course in both cases. Vestibular function was unaffected. Conclusions: The findings are consistent with auditory neuropathy—a lesion of the cochlear nerve presenting with abnormal auditory brain stem responses and with normal inner hair cells and the cochlear nucleus (lower brain stem). The association of auditory neuropathy, or any other auditory dysfunction, with LHON has not been recognised previously. Further studies are necessary to establish whether this is a consistent finding. PMID:15026512

  20. Magnetic resonance imaging of radiation optic neuropathy

    SciTech Connect

    Zimmerman, C.F.; Schatz, N.J.; Glaser, J.S. (Univ. of Miami, FL (USA))

    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. Systemic corticosteroids in nonarteritic ischemic optic neuropathy

    PubMed Central

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

    2014-01-01

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

  2. [An unusual cause of compressive optic neuropathy].

    PubMed

    Touitou, V; Boch, A-L; Lehoang, P

    2013-01-01

    Clinical manifestations of hydrocephalus vary according to the level of intracranial pressure, the speed of onset, and the etiological mechanism involved. We report the case of a 32-year-old patient with isolated compressive optic neuropathy associated with a dilated third ventricle, revealing congenital hydrocephalus. PMID:23159536

  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. Leber’s Hereditary Optic Neuropathy

    Microsoft Academic Search

    Alfredo A. Sadun; Chiara La Morgia; Valerio Carelli

    2011-01-01

    Opinion statement  Leber’s hereditary optic neuropathy (LHON) is a maternally inherited blinding disease with variable penetrance. Three primary\\u000a mitochondrial DNA mutations, affecting the respiratory complex I, are necessary but not sufficient to cause blindness. Reduced\\u000a efficiency of ATP synthesis and increased oxidative stress are believed to sensitize the retinal ganglion cells to apoptosis.\\u000a Different therapeutic strategies are considered to counteract this

  5. Drug-induced Optic Neuropathy—TB or Not TB

    Microsoft Academic Search

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

    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

  6. Reversal of dysthyroid optic neuropathy following orbital fat decompression

    PubMed Central

    Kazim, M.; Trokel, S.; Acaroglu, G.; Elliott, A.

    2000-01-01

    AIMS—To document the successful treatment of five patients with dysthyroid optic neuropathy by orbital fat decompression instead of orbital bone decompression after failed medical therapy.?METHODS—Eight orbits of five patients with dysthyroid optic neuropathy were selected for orbital fat decompression as an alternative to bone removal decompression. Treatment with systemic corticosteroids and/or orbital radiotherapy was either unsuccessful or contraindicated in each case. All patients satisfied clinical indications for orbital bone decompression to reverse the optic neuropathy. High resolution computerised tomographic (CT) scans were performed in all cases and in each case showed signs of enlargement of the orbital fat compartment. As an alternative to bone decompression, orbital fat decompression was performed on all eight orbits.?RESULTS—Orbital fat decompression was performed on five patients (eight orbits) with optic neuropathy. Optic neuropathy was reversed in all cases. There were no cases of postoperative diplopia, enophthalmos, globe ptosis, or anaesthesia. All patients were followed for a minimum of 1 year.?CONCLUSIONS—In a subset of patients with an enlarged orbital fat compartment and in whom extraocular muscle enlargement is not the solitary cause of optic neuropathy, fat decompression is a surgical alternative to bony decompression.?? PMID:10837384

  7. Toxic optic neuropathy: An unusual cause

    PubMed Central

    Ramkumar, Hema L; Savino, Peter J

    2014-01-01

    A 60-year-old woman with a history of chronic alcoholism and tobacco use presented with the complaint of a painless decrease in vision in both eyes. She lost vision first in the left eye then in the right eye. She admitted consuming at least one 16 ounce bottle of over the counter mouthwash daily and denied consumption of any other alcohols, methanol, or antifreeze. She stated that her vision had been continuing to deteriorate in both eyes. Her best-corrected visual acuity was 4/200 in each eye. Color vision was nil in each eye. Her pupils were sluggish bilaterally, and her optic discs were flat and hyperemic with peripapillary hemorrhages. Her visual fields revealed central scotomas bilaterally. The magnetic resonance imaging of the brain and lumbar puncture were within normal limits. Antinuclear antibody, human leukocyte antigen-B27 genotyping, and B12 were normal; serum thiamine was low. While continuing to ingest mouthwash, her vision decreased to count fingers at 2 feet, and maculopapillary bundle pallor developed. She was started on folate and thiamine supplementation. Once she discontinued mouthwash, her vision improved to 20/400 bilaterally, and her central scotomas improved. This case demonstrates an alcohol-induced toxic optic neuropathy from mouthwash ingestion with some visual recovery after discontinuation of the offending agent. PMID:25449946

  8. 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

  9. Ethmoidectomy decompression for the treatment of Graves' optic neuropathy.

    PubMed

    Hurwitz, J J; Freeman, J L; Eplett, C J; Fliss, D M; Avram, D R

    1992-10-01

    When orbital decompression becomes necessary in Graves' optic neuropathy, medial wall decompression is a necessary component of the decompression procedure. The ethmoidectomy approach allows more direct visualization of the posterior ethmoids and sphenoids to effect maximum decompression. This is particularly important in cases in which computed tomography shows the medial rectus muscle to be enlarged posteriorly in the orbit. The procedure provides excellent visualization of the medial rectus. As with any medial wall decompression procedure, postoperative restriction of horizontal motility is a frequent complication, often necessitating more than one subsequent operation. The authors describe their experience with the procedure in 25 patients with Graves' optic neuropathy. PMID:1451015

  10. Methylprednisolone pulse therapy in severe dysthyroid optic neuropathy

    SciTech Connect

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

    1989-07-01

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

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

    PubMed Central

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

    2014-01-01

    Optic nerve head drusen (ONHD) are incidental ophthalmologic finding in the optic nerve. Patients with ONHD are often asymptomatic, but sometimes present with transient visual obscuration's (TVO), the reported incidence of which is 8.6%. Optic nerve head drusen are of two types: Superficial; visible and deep. The deep-buried drusen mimic papilledema. Because of the varied presentation deep-buried drusen pose a diagnostic challenge to the ophthalmologists. In young patients, they are mistaken for papilledema as it is clinically difficult to detect a buried drusen in the optic nerve head, but are seen on the surface with aging as the retinal nerve fiber layer thins out. They are observed as pale yellow lesions more often located towards the poles. Clinical examination aided with diagnostic tests like computed tomography (CT) orbits and ultrasound B scan can help establish the diagnosis. Herein, we report a rare case of optic nerve head drusen in a young lady, who presented with loss of vision and clinical evaluation and investigations suggested ONHD with anterior ischemic optic neuropathy. PMID:25116784

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

    PubMed Central

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

    2014-01-01

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

  13. 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…

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

    PubMed Central

    2013-01-01

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

  15. Optic nerve degeneration and mitochondrial dysfunction: genetic and acquired optic neuropathies

    Microsoft Academic Search

    Valerio Carelli; Fred N. Ross-Cisneros; Alfredo A. Sadun

    2002-01-01

    Selective degeneration of the smallest fibers (papillo-macular bundle) of the human optic nerve occurs in a large number of optic neuropathies characterized primarily by loss of central vision. The pathophysiology that underlies this peculiar pattern of cell involvement probably reflects different forms of genetic and acquired mitochondrial dysfunction.Maternally inherited Leber’s hereditary optic neuropathy (LHON), dominant optic atrophy (Kjer disease), the

  16. 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

  17. [Optic neuropathies and peripheral oculomotor disorders in patients with AIDS].

    PubMed

    Torras-Sanvicens, J; Arruga-Ginebreda, J

    1996-12-01

    In patients with the acquired immunodeficiency syndrome (AIDS) there is an 8% incidence of neuro-ophthalmological changes. The commonest of these neuro-ophthalmological changes are: 1) Cranial nerve pareses 2) Optic neuropathy and 3) Pupil disorders. The cranial nerve pareses are usually combined, rather than single, and are due to intraparenchymatous lesions (toxoplasmosis or lymphoma) or to meningitis (tuberculous or lymphoma). The optic nerve changes tend to be papillitis due to CMV or optic neuropathy due to syphilis or to cryptococcal meningitis. Among the pupil changes, Bernard-Horner syndromes due to sympathetic involvement, Argyll-Robertson pupils due to mesencephalic tectal lesions and mydriasis associated with the common oculo-motor nerve have been described. PMID:9064185

  18. Optic neuropathy in methylmalonic acidemia: the role of neuroprotection

    Microsoft Academic Search

    Sergio Pinar-Sueiro; Ricardo Martínez-Fernández; Sergio Lage-Medina; Luis Aldamiz-Echevarria; Elena Vecino

    We report the case of a patient with an optic neuropathy induced by neurotoxicity in the setting of methylmalonic acidemia.\\u000a The patient responded with a significant and long-term improvement in visual acuity, perimetry, and chromatic function after\\u000a a neuroprotective treatment with vitamin E and coenzyme Q10 was started. Coenzyme Q10 levels had been proven to be normal\\u000a before starting treatment.

  19. Compressive Optic Neuropathy Caused by Orbital Non-Hodgkin's Lymphoma

    PubMed Central

    Ziaei, Mohammed M.; Ziaei, Hadi

    2012-01-01

    Purpose. To present a unique case of Non-Hodgkin's-Lymphoma- (NHL) associated compressive optic neuropathy. Method. An 89-year-old male presenting with acute unilateral visual loss and headache. Results. Patient was initially diagnosed with occult giant cell arteritis; however after visual acuity deteriorated despite normal inflammatory markers, an urgent MRI scan revealed an extensive paranasal sinus mass compressing the optic nerve. Conclusion. Paranasal sinus malignancies occasionally present to the ophthalmologist with signs of optic nerve compression and must be included in the differential diagnosis of acute visual loss. PMID:22606505

  20. 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.

  1. 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

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

    PubMed Central

    Abu-Amero, Khaled K.

    2011-01-01

    Our current understanding of Leber’s hereditary optic neuropathy (LHON)-mitochondrial connection falls short of comprehensive. Twenty years of intensive investigation have yielded a wealth of information about mitochondria, the mitochondrial genome, the metabolism of the optic nerve and other structures, and the phenotypic variability of classic LHON. However, we still cannot completely explain how primary LHON mutations injure the optic nerve or why the optic nerve is particularly at risk. We cannot explain the incomplete penetrance or the male predominance of LHON, the typical onset in young adult life without warning, or the synchronicity of visual loss. Moreover, primary LHON mutations clearly are not present in every family with the LHON phenotype (including multigenerational maternal inheritance), and they are present in only a minority of individuals who have the LHON optic neuropathy phenotype without a family history. All lines of evidence point to abnormalities of the mitochondria as the direct or indirect cause of LHON. Therefore, the mitochondria-LHON connection needs to be revisited and examined closely. This review will attempt to do that and provide an update on various aspects of LHON. PMID:21572729

  3. 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. (Univ. of Florida, Gainesville (USA))

    1991-03-01

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

  4. Optic neuropathy secondary to eosinophilic angiocentric fibrosis.

    PubMed

    Lloyd, Adam P; Benzimra, James D; Warfield, Adrian T; Prasad, Balaji T S; Matthews, Timothy D; Ahmed, Shahzada K

    2015-03-01

    : Eosinophilic angiocentric fibrosis (EAF) is a rare fibroinflammatory disorder with a predilection for upper respiratory tract submucosa. We report a 45-year-old man with progressive unilateral visual loss secondary to a retroorbital soft tissue mass with histological features consistent with EAF. The patient experienced marked improvement in vision after endoscopic optic nerve decompression through sphenoethmoidectomy. PMID:25232841

  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}, 1.36–1.64 ?m2/ms for incomplete recovery vs 1.75 ?m2/ms [95% CI, 1.67–1.83 ?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, 1.31–1.59 ?m2/ms] vs 1.19 ?m2/ms [95% CI, 1.10–1.28 ?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. 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.

  7. Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2

    Microsoft Academic Search

    S. Zuchner; Peter De Jonghe; Albena Jordanova; Kristl G. Claeys; Velina Guergueltcheva; Sylvia Cherninkova; Steven R. Hamilton; Greg Van Stavern; Karen M. Krajewski; Jeffery Stajich; Ivajlo Tournev; Kristien Verhoeven; Christine T. Langerhorst; Marianne de Visser; Frank Baas; Thomas Bird; Vincent Timmerman; Michael Shy; Jeffery M. Vance

    2006-01-01

    Objective: Charcot-Marie-Tooth (CMT) neuropathy with visual impairment due to optic atrophy has been designated as hereditary motor and sensory neuropathy type VI (HMSN VI). Reports of affected families have indicated autosomal dominant and recessive forms, but the genetic cause of this disease has remained elusive. Methods: Here, we describe six HMSN VI families with a subacute onset of optic atrophy

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

    SciTech Connect

    Lovato, A.A.; Char, D.H.; Quivey, J.M.; Castro, J.R. (Univ. of California, San Francisco (USA))

    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.

  9. 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

  10. 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

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

    PubMed

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

    2010-12-01

    Patients with Leber's hereditary optic neuropathy (LHON) have loss of central vision with severe damage of small-caliber fibers of the papillomacular bundle and optic nerve atrophy. The aim of this study was to define the presence and topographical distribution of brain grey matter (GM) and white matter (WM) injury in LHON patients using voxel-based morphometry (VBM). The correlation of such changes with neuro-ophthalmologic findings and measurements of peripapillary retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT) was also assessed. Dual-echo and fast-field echo scans were acquired from 12 LHON patients and 12 matched controls. VBM analysis was performed using SPM5 and an ANCOVA model. A complete neuro-ophthalmologic examination, including standardized automated Humphrey perimetry as well as average and temporal peripapillary RNFL thickness measurements were obtained in all the patients. Compared with controls, average peripapillary RNFL thickness was significantly decreased in LHON patients. LHON patients also had significant reduced GM volume in the bilateral primary visual cortex, and reduced WM volume in the optic chiasm, optic tract, and several areas located in the optic radiations (OR), bilaterally. Visual cortex and OR atrophy were significantly correlated with average and temporal peripapillary RNFL thickness (P < 0.001; r values ranging from 0.76 to 0.89). Brain damage in patients with LHON is not limited to the anterior visual pathways, but extends posteriorly to the OR and the primary visual cortex. Such a damage to the posterior parts of the visual pathways may be due either to trans-synaptic degeneration secondary to neuroaxonal damage in the retina and optic nerve or to local mitochondrial dysfunction. PMID:20827728

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

    PubMed

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

    2013-09-01

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

  13. Extensive investigation of a large Brazilian pedigree of 11778\\/haplogroup J Leber hereditary optic neuropathy

    Microsoft Academic Search

    Alfredo A Sadun; Valerio Carelli; Solange R Salomao; Adriana Berezovsky; Peter A Quiros; Federico Sadun; Anna-Maria DeNegri; Rafael Andrade; Milton Moraes; Angelo Passos; PatrÍcia Kjaer; Josenilson Pereira; Maria Lucia Valentino; Stan Schein; Rubens Belfort

    2003-01-01

    PurposeTo conduct systematic epidemiologic, neuro-ophthalmologic, psychophysical, and mitochondrial DNA (mtDNA) genetic examinations on a newly identified pedigree with Leber hereditary optic neuropathy (LHON).

  14. Ophthalmologic findings in a large pedigree of 11778\\/Haplogroup J Leber hereditary optic neuropathy

    Microsoft Academic Search

    Federico Sadun; Anna Maria De Negri; Valerio Carelli; Solange R. Salomao; Adriana Berezovsky; Rafael Andrade; Milton Moraes; Angelo Passos; Rubens Belfort; Arlon Bastos Da Rosa; Peter Quiros; Alfredo A. Sadun

    2004-01-01

    PurposeTo report the ophthalmologic characteristics of a newly identified seven-generation pedigree of 11778\\/Haplogroup J Leber hereditary optic neuropathy consisting of 328 living individuals, 111 of whom are maternally related.

  15. Cyclosporine-induced optic neuropathy, ophthalmoplegia, and nystagmus in a patient with Crohn disease

    Microsoft Academic Search

    Yair Porges; Sergiu Blumen; Zvi Fireman; Amos Sternberg; Doron Zamir

    1998-01-01

    PURPOSE: To report the cyclosporine-induced complications of optic neuropathy, partial external ophthalmoplegia, and other neurologic abnormalities.METHODS: Case report. A 22-year-old man with severe active Crohn disease developed bilateral optic neuropathy, nystagmus, external ophthalmoplegia, and ataxia on the fifth day of cyclosporine A (CyA) parenteral therapy.RESULTS: Cyclosporine therapy was discontinued as soon as toxic clinical manifestations appeared. Cyclosporine blood level detected

  16. Optical Coherence Tomography Study of Retinal Changes in Normal Aging and after Ischemia.

    PubMed

    Shariati, Mohammad Ali; Ho, Joyce K; Liao, Yaping Joyce

    2014-11-20

    Purpose. Age-related thinning of the retinal ganglion cell axons in the nerve fiber layer has been measured in humans using optical coherence tomography (OCT). In this study, we used OCT to measure inner retinal changes in 3-months-, one-year, and two-year-old mice and after experimental anterior ischemic optic neuropathy (AION). Methods. We used OCT to quantify retinal thickness in over 200 eyes at different ages before and after photochemical thrombosis model of AION. The scans were manually or automatically segmented. Results. In normal aging, there was 1.3 µm thinning of the ganglion cell complex (GCC) between 3-months and 1-year (P < 0.0001) and no further thinning at 2-years. In studying age-related inner retinal changes, measurement of the GCC (circular scan) was superior to the total retinal thickness (posterior pole scan) despite the need for manual segmentation because it was not contaminated by outer retinal changes. Three-weeks after AION, there was 8.9 µm thinning of the GCC (circular scan; P < 0.0001) and 50 µm thinning of the optic disc (posterior pole scan; P < 0.0001), and 17 µm thinning of the retinae (posterior pole scan; P < 0.0001) in the 3 months-old group. Changes in the older eyes were similar to that of the 3-month-old group. Conclusions. OCT imaging of a large number eyes showed that, like humans, mice exhibited small, age-related inner retinal thinning. GCC was superior to quantify age-related changes after AION, and both circular and posterior pole scans were useful to track short-term changes after AION. PMID:25414186

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

    PubMed

    Gallenmüller, C; Klopstock, T

    2014-03-01

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

  18. Bilateral optic neuropathy and permanent loss of vision after treatment with amiodarone.

    PubMed

    Kervinen, Marko; Falck, Aura; Hurskainen, Merja; Hautala, Nina

    2013-10-01

    Amiodarone is a commonly prescribed and one of the most effective anti-arrhythmic drugs available. However, its use is limited by serious toxic adverse effects including optic neuropathy. Previously, amiodarone-associated optic neuropathy has been reported at an incidence of 1.3%-1.8%. Nearly, one-third of patients with amiodarone-induced toxic optic neuropathy are asymptomatic and typically visual acuity improves after drug cessation. We describe the case of a 75-year-old woman who experienced severe optic neuropathy with bilateral optic disc edema and hemorrhages, irreversible loss of vision, and severe defects in visual fields after 1.5 months use of amiodarone. The optic disc edema resolved promptly after discontinuation of the drug, but the patient remained blind permanently. This is the first report of only 6.5 weeks of amiodarone treatment resulting in bilateral optic neuropathy with bilateral and irreversible loss of vision. To ideally establish a connection between amiodarone and optic neuropathy, re-exposure of the patient to the drug should reproduce the symptoms. As a limitation of the study, this was not done in the present case because it would have been unethical. The worldwide growth of the elderly population in number is expected to increase age-related conditions including cardiac diseases. The use of cardiovascular drugs, also anti-arrhythmic agents such as amiodarone, may increase. Thus, clinicians need to be aware of the possibility of drug-induced toxic optic neuropathy, especially if a patient receiving a regimen of amiodarone complains of visual problems. PMID:23921312

  19. Bilateral ischemic optic neuropathy after transurethral prostatic resection: a case report

    Microsoft Academic Search

    Luis M Sadaba; Alfredo Garcia-Layana; Miguel J Maldonado; Jose M Berian

    2006-01-01

    BACKGROUND: Nonarteritic ischemic optic neuropathy affects the anterior portion of the optic nerve and is characterized by sudden, painless visual loss. The affected eye has a relative afferent pupillary defect. The typical funduscopic appearance includes optic disc edema, with associated nerve fiber layer hemorrhage. Risk factors include advanced age, systemic hypertension, nocturnal hypotension, diabetes mellitus, and a small cup-to-disc ratio.

  20. Ischemic Optic Neuropathy Associated with Subarachnoid Hemorrhage after Rupture of Anterior Communicating Artery Aneurysm

    Microsoft Academic Search

    Naoto Hara; Kazuo Mukuno; Hironori Ohtaka; Kimiya Shimizu

    2003-01-01

    Two clinical cases in which ischemic optic neuropathy (ION) occurred after subarachnoid hemorrhage (SAH) are reported. Hemorrhage in the proximity of the optic chiasm was confirmed in 2 cases following rupture of an anterior communicating artery aneurysm. Optic disk atrophy with excavation and permanent visual field defect (altitudinal superior hemianopia) occurred in both cases. ION seems to occur in association

  1. Nonarteritic anterior ischemic optic neuropathy and ‘visual field defects’ following vitrectomy: could they be related?

    Microsoft Academic Search

    Mehran Taban; Hilel Lewis; Michael S. Lee

    2007-01-01

    Background  Visual field defects after uncomplicated vitrectomy have been reported but poorly explained. We describe two cases of nonarteritic\\u000a anterior ischemic optic neuropathy (NAION) observed following vitrectomy. We also reviewed the literature for cases of post-vitrectomy\\u000a visual field defects for evidence of optic nerve damage.\\u000a \\u000a \\u000a \\u000a Methods  Two patients developed optic disc edema and features of an optic neuropathy after uncomplicated vitrectomy for

  2. [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

  3. 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.

  4. Anterior ischemic optic neuropathy and stroke with use of PDE5 inhibitors for erectile dysfunction: Cause or coincidence?

    Microsoft Academic Search

    John E. Carter

    2007-01-01

    The PDE-5 inhibitors sildenafil (Viagra) vardenafil (Levitra) and tadalafil (Cialis) have been taken by millions of men for erectile dysfunction. Transient visual symptoms are common but there also have been fourteen cases of nonarteritic anterior ischemic optic neuropathy (NAION) described in patients using these drugs as well as a few other vascular events. NAION is a common optic neuropathy in

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

    Parsons, J.T.; Bova, F.J.; Million, R.R. [Univ. of Florida College of Medicine, Gainesville, FL (United States)] [and others

    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.

  8. Vision loss after maxillary artery embolization secondary to compressive optic neuropathy.

    PubMed

    Finnerty, Katie N; Mancini, Ronald

    2013-01-01

    The authors report a case of no light perception (NLP) vision in a patient with sinonasal melanoma after maxillary artery embolization secondary to presumptive compressive optic neuropathy. Two reports of NLP vision occurring after maxillary artery embolization are reported in the literature,, both occurring secondary to collateral blood flow to the ophthalmic artery resulting in central retinal artery occlusion. In the current case report, the presumed mechanism of vision loss is secondary to compressive optic neuropathy from local edema occurring after maxillary artery embolization. PMID:23503054

  9. An Abscess Causing a Delayed Optic Neuropathy After Decompression for Thyroid Eye Disease

    PubMed Central

    Patel, Rakesh M; Aakalu, Vinay K; Joe, Stephanie; Setabutr, Pete

    2014-01-01

    Thyroid orbitopathy is the most common cause of proptosis in adults. It often requires surgical decompression to relieve proptosis, keratopathy, and/or optic neuropathy (1). Complications including diplopia, sinusitis, infraorbital hypesthesia, and cerebrospinal fluid leak have been reported (2–4). Mucocele formation or orbital abscess after decompression surgery are rare (5–9). To our knowledge, there are no reports of an orbital abscess causing a compressive optic neuropathy after decompression. We describe such a patient with both orbital abscess and mucoceles that was treated with intravenous antibiotics, steroids, and surgery. PMID:24144317

  10. 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

  11. A VERY LARGE BRAZILIAN PEDIGREE WITH 11778 LEBER'S HEREDITARY OPTIC NEUROPATHY

    Microsoft Academic Search

    Alfredo A. Sadun; Valerio Carelli; Solange R. Salomao; Adriana Berezovsky; Peter Quiros; Federico Sadun; Anna-Maria DeNegri; Rafael Andrade; Stan Schein; Rubens Belfort

    Purpose: We conducted extensive epidemiological, neuro-ophthalmological, psychophysical, and blood examinations on a newly discovered, very large pedigree with molecular analysis showing mtDNA mutation for Leber's hereditary optic neuropathy (LHON). Methods: Four patients representing four index cases from a remote area of Brazil were sent to Sao Paulo, where complete ophthalmological examinations strongly suggested LHON. Molecular analysis of their blood demonstrated

  12. Clinical course of a cohort in the Cuban epidemic optic and peripheral neuropathy.

    PubMed

    Mojon, D S; Kaufmann, P; Odel, J G; Lincoff, N S; Márquez-Fernandez, M; Santiesteban, R; Fuentes-Pelier, D; Hirano, M

    1997-01-01

    Nearly 51,000 Cubans were afflicted during an outbreak of an optic neuropathy (ON) and peripheral neuropathy (PN) between 1991 and 1993. We re-examined 14 of 20 affected individuals 16 months after an initial evaluation. The optic features were painless symmetric vision loss with poor visual acuity, color vision loss, central or cecocentral scotoma, optic disc pallor, and nerve fiber layer drop-out. The neurologic symptoms included stocking-glove sensory changes, hearing loss, leg cramps, sensory ataxia, hyperactive or absent reflexes, and complaints of memory loss. Two of 11 ON probands tested harbored Leber's hereditary optic neuropathy (LHON)-associated mitochondrial DNA mutations. All patients had received multivitamin therapy. We performed comparisons using the paired two-tailed t test. On re-examination, 12 of 14 patients demonstrated improvement. One patient remained unchanged. One woman with the nt-3460 mtDNA mutation showed a decline in vision. In patients not harboring mtDNA mutations, overall visual acuity, color vision, and peripheral neuropathy manifestations improved significantly (p < 0.001 for each manifestation). Most of the patients with Cuban ON and PN improved on multivitamin therapy. The significance of the mtDNA mutations is unclear. In the 2 LHON patients, manifestation of the disease may have been precipitated by nutritional deficiency. Patients with poor recovery or further deterioration should be evaluated for other factors, including poor vitamin therapy compliance and alternative diagnoses. PMID:9008487

  13. Physiological significance of recombination-activating gene 1 in neuronal death, especially optic neuropathy.

    PubMed

    Hirano, Takao; Murata, Toshinori; Hayashi, Takuma

    2015-01-01

    Although the transcription factor nuclear factor-?B (NF-?B) is known to regulate cell death and survival, its precise role in cell death within the central nervous system remains unknown. We previously reported that mice with a homozygous deficiency for NF-?Bp50 spontaneously develop optic neuropathy. The aim of the present study was to demonstrate the expression and activation of the proapoptotic factor(s) that mediate optic neuropathy in p50-deficient mice. Recombination-activating gene (Rag) 1 is known to activate the recombination of immunoglobulin V(D)J. In this study, experiments with genetically engineered mice revealed the involvement of Rag1 expression in apoptosis of Brn3a-positive retinal ganglion cells, and also demonstrated the specific effect of p50 deficiency on the activation of Rag1 gene transcription. Furthermore, genetic analysis of murine neuronal stem-like cells clarified the biological significance of Rag1 in N-methyl-D-aspartate-induced neuronal apoptosis. We also detected the apoptosis-regulating factors Bax and cleaved caspase 3, 8 and 9 in HEK293 cells transfected-molecule of Rag1, and a human histological examination revealed the expression of Rag1 in retinal ganglion cells. The results of the present study indicate that Rag1 plays a role in optic neuropathy as a proapoptotic candidate in p50-deficient mice. This finding may lead to new therapeutic targets in optic neuropathy. PMID:25312244

  14. Non-arteritic anterior ischaemic optic neuropathy and the treatment of erectile dysfunction

    Microsoft Academic Search

    G McGwin Jr; M S Vaphiades; C Owsley

    2010-01-01

    Aim: To determine the association between Viagra (sildenafil) and Cialis (tadalafil) and non-arteritic anterior ischaemic optic neuropathy (NAION). Methods: A retrospective matched case-control study was conducted. 38 cases of NAION in males were identified from an academic ophthalmology practice in Birmingham, Alabama, and matched (on age) to 38 controls without a history of NAION. Self reported information regarding past and

  15. A Modified Surgical Procedure for Endoscopic Optic Nerve Decompression for the Treatment of Traumatic Optic Neuropathy

    PubMed Central

    Chen, Fenghong; Zuo, Kejun; Feng, Shaoyan; Guo, Jiebo; Fan, Yunping; Shi, Jianbo; Li, Huabin

    2014-01-01

    Background: Although the endoscopic anterior-to-posterior technique offers many advantages, the long-term effects of the iatrogenic trauma (removal of the uncinate process and anterior ethmoidal sinus) resulting from the complete ethmoidectomy procedure used to gain full access to the optic nerve canal is unknown, and sequelae such as nasal synechia and sinusitis should not be ignored. Aims: The aim of our study is to develop a less invasive procedure for endoscopic optic nerve decompression. Materials and Methods: We proposed a modified trans-sphenoidal surgical procedure for endoscopic optic nerve decompression in five patients with traumatic optic neuropathy (TON), all with high sphenoidal pneumatisation and without Onodi cellulae. Results: After performing a direct sphenoidotomy through the natural ostium of the sphenoid sinus rather than a complete ethmo-sphnoidectomy, we found that the modified approach provided adequate access to the optic nerve canal and the apex using a 45° angled endoscope. Successful decompression of the canal optic nerve was performed trans-sphenoidally in all five TON patients using an angled endoscope. No surgical complications occurred, and none of the patients suffered from anterior ethmoidal sinus or skull base damage. Conclusions: The modified trans-sphenoidal approach is a feasible, safe, effective, and minimally invasive approach for TON patients with high sphenoidal pneumatisation and without supersphenoid-ethmoid cellulae. PMID:25006562

  16. Bilateral optic neuropathy after bone marrow transplantation and cyclosporin A therapy

    Microsoft Academic Search

    Sebastian H. Walter; Hartmut Bertz; Jürgen Gerling

    2000-01-01

    Background: Cyclosporin A (CsA) is widely used as a prophylactic and therapeutic agent against graft-versus-host disease after bone marrow\\u000a transplantation. Under this condition optic neuropathy has been found and considered as a possible side effect of cyclosporin\\u000a A. Case report: A 52-year-old man presented with bilateral optic disc swelling and visual loss 6 months after bone marrow transplantation.\\u000a Cyclosporin A

  17. 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

  18. Non-arteritic anterior ischemic optic neuropathy secondary to acute primary-angle closure

    PubMed Central

    Kuriyan, Ajay E; Lam, Byron L

    2013-01-01

    Purpose To describe a case of non-arteritic ischemic optic neuropathy (NAION) secondary to acute primary-angle closure (APAC). Methods Case report. Results A 50-year-old woman with painful visual loss in the right eye was found to be in APAC with a right afferent pupillary defect. Laser peripheral iridotomy relieved pain but did not improve vision. Diffuse optic disc edema in the right eye and a small cup-to-disc ratio in the left eye were evident. Magnetic resonance imaging was normal. The patient was diagnosed with non-arteritic ischemic optic neuropathy (NAION) secondary to APAC, a rare clinical entity which can result in markedly decreased visual acuity. Conclusion NAION secondary to APAC is a rare clinical entity that can result in severe vision loss. PMID:23861575

  19. Optic neuropathy associated with the use of over-the-counter sexual enhancement supplements

    PubMed Central

    Karli, Sapir Z; Liao, Sophie D; Carey, Andrew R; Lam, Byron L; Wester, Sara T

    2014-01-01

    This case report details an association of the use of over-the-counter sexual enhancement supplements with atypical optic neuropathy. A 42-year-old man presented with right-sided headache and vision loss of the right eye, which deteriorated to a single quadrant of hand motion over 11 days. Serial orbital magnetic resonance imaging scans demonstrated progressive orbital optic nerve enhancement extending into the optic canal despite high-dose steroid treatment. The patient eventually admitted to using several over-the-counter sexual enhancement supplements prior to the onset of symptoms and throughout the course of his steroid treatment, which he subsequently discontinued. His vision improved to 20/200 with an expanded visual field. Anterior ischemic optic neuropathy has been reported in association with phosphodiesterase (PDE)-5 inhibitor use, but visual loss in association with unregulated sexual enhancement supplements has not been studied. While one case cannot establish association, our case is suggestive of potential dangers of over-the-counter sexual enhancement supplements, which may contain PDE-5 inhibitors, “male hormones,” and “substances that enhance blood production.” The case also underscores the importance of obtaining a careful history of supplements in patients with optic neuropathies. PMID:25378904

  20. Efficient mitochondrial biogenesis drives incomplete penetrance in Leber’s hereditary optic neuropathy

    PubMed Central

    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

    2014-01-01

    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

  1. Single Intravitreal Aflibercept Injection for Unilateral Acute Nonarteritic Ischemic Optic Neuropathy

    PubMed Central

    Ayhan, Ziya; Kocao?lu, Gamze; Bajin, Meltem Söylev; Saatci, A. Osman

    2015-01-01

    Acute nonarteritic ischemic optic neuropathy (ANAION) is the most common optic neuropathy in the elderly population without a well-established treatment. A 67-year-old man with a sudden painless visual loss in his left eye of one-day duration was diagnosed to have left ANAION. Next day, 2?mg aflibercept injection was injected intravitreally in OS. Visual acuity improved to 7/10 from 1/10 a week after the injection. Mean retinal nerve fiber layer thickness (RNFLT) was reduced to 159,7??m from 182,4??m at the first week. Visual fields improved dramatically during the follow-up of three months. The aim of this study is to present a case having ANAION treated with a single intravitreal aflibercept injection and discuss the place of intravitreal anti-VEGF injections in the treatment of armamentarium of ANAION. PMID:25632361

  2. Clinical Expression of Leber Hereditary Optic Neuropathy Is Affected by the Mitochondrial DNA–Haplogroup Background

    Microsoft Academic Search

    Gavin Hudson; Valerio Carelli; Liesbeth Spruijt; Mike Gerards; Catherine Mowbray; Alessandro Achilli; Angela Pyle; Joanna Elson; Neil Howell; Chiara La Morgia; Maria Lucia Valentino; Kirsi Huoponen; Marja-Liisa Savontaus; Eeva Nikoskelainen; Alfredo A. Sadun; Solange R. Salomao; Rubens Belfort; Philip Griffiths; Patrick Yu Wai Man; Rene F. M. de Coo; Rita Horvath; Massimo Zeviani; Hubert J. T. Smeets; Antonio Torroni; Patrick F. Chinnery

    2007-01-01

    Leber hereditary optic neuropathy (LHON) is due primarily to one of three common point mutations of mitochondrial DNA (mtDNA), but the incomplete penetrance implicates additional genetic or environmental factors in the pathophysiology of the disorder. Both the 11778G-->A and 14484T-->C LHON mutations are preferentially found on a specific mtDNA genetic background, but 3460G-->A is not. However, there is no clear

  3. 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

  4. 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

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

    PubMed Central

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

    2014-01-01

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

  6. [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

  7. When do optic disc edema and peripheral neuropathy constitute poetry?

    PubMed

    Brazis, P W; Liesegang, T J; Bolling, J P; Kashii, S; Trachtman, M; Burde, R M

    1990-01-01

    A patient with chronic, bilateral optic disc edema developed multiple systemic manifestations of POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes). A serum immunoelectrophoresis showed an abnormal serum IgG lambda protein, and urine immunoelectrophoresis revealed a monoclonal lambda protein plus an IgG lambda fragment. Bone survey and MRI scan revealed a sclerotic lesion of the first lumbar vertebra, and lymph node biopsy showed changes consistent with Castleman's disease. Thus, his optic disc edema was the presenting feature of the POEMS syndrome and osteosclerotic myeloma. PMID:2177227

  8. Mitochondrial dysfunction as a cause of optic neuropathies

    Microsoft Academic Search

    Valerio Carelli; Fred N. Ross-Cisneros; Alfredo A. Sadun

    2004-01-01

    Mitochondria are increasingly recognized as central players in the life and death of cells and especially of neurons. The energy-dependence of retinal ganglion cells (RGC) and their axons, which form the optic nerve, is singularly skewed. In fact, while mitochondria are very abundant in the initial, unmyelinated part of the axons anterior to the lamina cribrosa, their number suddenly decreases

  9. Characterization of macular thickness changes in Leber’s hereditary optic neuropathy by optical coherence tomography

    PubMed Central

    2014-01-01

    Background To characterize macular thickness (MT) changes in Leber’s hereditary optic neuropathy (LHON) patients by cirrus HD-optical coherence tomography (OCT), and to study the correlation between MT and best corrected visual acuity (BCVA). Methods Fifty-two eyes from 52 consecutive LHON patients and 14 eyes from 14 age- and sex-matched healthy controls were scanned by OCT. Affected eyes were classified into five groups according to disease duration (1st group: ?3 months; 2nd group: 3–6 months; 3rd group: 6–9 months; 4th group: 9–12 months; and 5th group: >12 months). MT was compared and analyzed. The correlation between BCVA and MT was calculated. Results Less than six months after LHON onset, the cube average thickness (CAT) and the MT in the superior, nasal, inferior, and temporal quadrants of the inner ring and the MT in the nasal quadrant of the outer ring were decreased (P?

  10. A Novel Rat Model to Study the Role of Intracranial Pressure Modulation on Optic Neuropathies

    PubMed Central

    Roy Chowdhury, Uttio; Holman, Bradley H.; Fautsch, Michael P.

    2013-01-01

    Reduced intracranial pressure is considered a risk factor for glaucomatous optic neuropathies. All current data supporting intracranial pressure as a glaucoma risk factor comes from retrospective and prospective studies. Unfortunately, there are no relevant animal models for investigating this link experimentally. Here we report a novel rat model that can be used to study the role of intracranial pressure modulation on optic neuropathies. Stainless steel cannulae were inserted into the cisterna magna or the lateral ventricle of Sprague-Dawley and Brown Norway rats. The cannula was attached to a pressure transducer connected to a computer that recorded intracranial pressure in real-time. Intracranial pressure was modulated manually by adjusting the height of a column filled with artificial cerebrospinal fluid in relation to the animal’s head. After data collection the morphological appearance of the brain tissue was analyzed. Based on ease of surgery and ability to retain the cannula, Brown Norway rats with the cannula implanted in the lateral ventricle were selected for further studies. Baseline intracranial pressure for rats was 5.5±1.5 cm water (n=5). Lowering of the artificial cerebrospinal fluid column by 2 cm and 4 cm below head level reduced ICP to 3.7±1.0 cm water (n=5) and 1.5±0.6 cm water (n=4), a reduction of 33.0% and 72.7% below baseline. Raising the cerebrospinal fluid column by 4 cm increased ICP to 7.5±1.4 cm water (n=2) corresponding to a 38.3% increase in intracranial pressure. Histological studies confirmed correct cannula placement and indicated minimal invasive damage to brain tissues. Our data suggests that the intraventricular cannula model is a unique and viable model that can be used to study the effect of altered intracranial pressure on glaucomatous optic neuropathies. PMID:24367501

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

    PubMed Central

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

    2014-01-01

    McCune-Albright syndrome (MAS) is characterized by a triad of poly/monostotic fibrous dysplasia, café-au-lait macules and hyperfunctioning endocrinopathies including human growth hormone excess. Acromegaly as a manifestation of endocrine hyperfunction with MAS is uncommon. Surgical excision may be challenging due to the associated severe fibrous dysplasia of the skull base. Through the endoscopic procedures, we treated a case of MAS presenting with compressive optic neuropathy due to fibrous dysplasia and acromegaly caused by growth hormone secreting pituitary adenoma. We reviewed the literature on GH excess in MAS to highlight its surgical and medical challenges. PMID:25368777

  12. Contrast Sensitivity of Thyroid Associated Ophthalmopathy Patients without Obvious Optic Neuropathy

    PubMed Central

    Beden, Ümit; Kaya, Sümeyra; Yeter, Volkan; Erkan, Dilek

    2013-01-01

    Purpose. To compare the contrast sensitivity levels of thyroid associated ophthalmopathy (TAO) patients without obvious optic neuropathy with those of healthy people. Methods. Forty eyes of 20 TAO patients without dysthyroid optic neuropathy and 40 eyes of 20 healthy subjects were evaluated in this prospective case-controlled study. The contrast sensitivity functions (CSFs) of all subjects were measured by the functional acuity contrast test (FACT) in five frequencies which were 1,5 cpd (A), 3 cpd (B), 6 cpd (C), 12 cpd (D), and 18 cpd (E). Results were compared for both groups, and a correlation of CSF with Hertel and clinical activity scores was assessed. Results. There was no statistically significant difference between TAO patients and control groups for age and sex. TAO patients had lower levels than the control group in all the frequencies of CSFs (P < 0.05) and the difference in contrast sensitivity functions between the groups seems to be more significant in higher frequencies (B, C, D, and E) (P < 0.001). Conclusions. TAO patients without DON can have contrast sensitivity loss and this would probably imply subtle optic nerve dysfunction in early disease phase. PMID:24453927

  13. [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 (IFN?) 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-? is used in the treatment of viral and neoplastic illnesses. Currently the drug is formulated as Interferon alfa pegilado (IFN?-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

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

    SciTech Connect

    Bhandare, Niranjan [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL (United States); Monroe, Alan T. [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL (United States); Morris, Christopher G. [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL (United States); Bhatti, M. Tariq [Department of Ophthalmology, Neurology, and Neurosurgery, University of Florida College of Medicine, Gainesville, FL (United States); Mendenhall, William M. [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL (United States)]. 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.

  15. Diabetic Neuropathy

    MedlinePLUS

    NINDS Diabetic Neuropathy Information Page Table of Contents (click to jump to sections) What is Diabetic Neuropathy? Is there any treatment? ... Organizations Additional resources from MedlinePlus What is Diabetic Neuropathy? Diabetic neuropathy is a peripheral nerve disorder caused ...

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

    PubMed Central

    Saxena, Rohit; Singh, Digvijay; Menon, Vimla

    2014-01-01

    Background: There is an increase in the incidence of traumatic optic neuropathy (TON) due to increasing urbanization and rapid spurt in the number of motor vehicles on the road. Despite early presentation and ease of diagnosis the visual outcomes in TON are still limited. There is also significant confusion about the timing, dose and efficacy of steroid treatment in its management. Purpose: To provide a clinical update of the pros and cons of steroid therapy for TON. Design: The paper is a retrospective review of the currently available literature in the English language indexed in PubMed. Methods: A PubMed search was conducted by the authors using the following terms: Traumatic optic neuropathy, megadose, steroids, methylprednisolone. Relevant original articles, review articles, and case reports related to the topic of discussion were evaluated and discussed in the paper. Results: There is no prospective randomized control trial evaluating the effect of steroids in TON. There are varying reports on the effect of steroid therapy from significant improvement to no difference compared to observation. Conclusion: The decision to give steroids to patients with TON has to be on an individual case to case basis and must involve informed consent from the patient. There are documented advantages and disadvantages of steroid therapy and a prospective, randomized, controlled trial is necessary comparing steroids, surgery and observation before definitive management can be evolved. PMID:25449942

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

    PubMed Central

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

    2015-01-01

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

  18. Intravitreal Transplantation of Human Umbilical Cord Blood Stem Cells Protects Rats from Traumatic Optic Neuropathy

    PubMed Central

    Jiang, Bing; Zhang, Pu; Zhou, Dan; Zhang, Jun; Xu, Xiang; Tang, Luosheng

    2013-01-01

    Objectives To treat traumatic optic neuropathy (TON) with transplantation of human umbilical cord blood stem cells (hUCBSC) and explore how transplanted stem cells participate in the neuron repairing process. Methods A total of 195 Sprague-Dawley rats were randomly assigned to three groups: sham-surgery, optic nerve injury, and stem cell transplant group. Optic nerve injury was established in rats by directly clamping the optic nerve for 30 seconds. hUCBSC was microinjected into the vitreous cavity of injured rats. Optic nerve function was evaluated by flash visual evoked potentials (F-VEP). Apoptosis in retina tissues was detected by TUNEL staining. GRP78 and CHOP gene expression was measured by RT-PCR. Results After injury, transplantation of hUCBSC significantly blunted a reduction in optic nerve function indicated by smaller decreases in amplitude and smaller increases in peak latency of F-VEP waveform compared to the injury alone group. Also, significant more in retinal ganglion cell (RGC) count and less in RGC apoptosis were detected after transplantation compared to injured rats. The protective effect correlated with upregulated GRP78 and downregulated CHOP mRNA expression. Conclusion Intravitreal transplantation of hUCBSCs significantly blunted a reduction in optic nerve function through increasing RGC survival and decreasing retinal cell apoptosis. The protective role of transplantation was associated with upregulation of GRP78 expression and downregulation of CHOP expression in retinal cells. PMID:23940534

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

    PubMed

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

    2015-01-12

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

  20. Vision recovery in human immunodeficiency virus-infected patients with optic neuropathy treated with highly active antiretroviral therapy: A case series

    PubMed Central

    Babu, Kalpana; Murthy, Krishna R; Rajagopalan, Nirmala; Satish, B

    2009-01-01

    We describe three patients with bilateral, presumed human immunodeficiency virus (HIV)-induced optic neuropathy. The above diagnosis was made by exclusion of infectious agents and neoplasms by detailed clinical and laboratory investigations. All patients had decreased visual acuity, pale optic discs and constriction of visual fields. Improvement was documented in all three patients for visual acuity and in one patient for visual fields following treatment with highly active antiretroviral therapy (HAART). Optic neuropathy in HIV-positive patients does not necessarily carry a poor prognosis even when a treatable cause is not found. This article emphasizes the effectiveness of HAART in presumed HIV-induced optic neuropathy. PMID:19574705

  1. A case series: Bilateral ischemic optic neuropathy secondary to large volume fluid resuscitation in critically ill burn patients.

    PubMed

    Medina, Miguel A; Moore, Danier A; Cairns, Bruce A

    2015-05-01

    Ischemic optic neuropathy (ION) in the trauma setting is a rare and devastating condition associated with systemic hypotension, massive volume resuscitation, and sepsis. The objective of this case series is to highlight a potential correlation between severe burn and ischemic optic neuropathy. We present three patients with total body surface area (TBSA) thermal injury burns ranging from 57 to 68% treated at the North Carolina Jaycee Burn Center that developed bilateral ischemic optic neuropathy during their hospital stay. Each patient required greater than 25L of crystalloid fluid within 24h after admission, suffered multiple bouts of sepsis, and required extended pressor support. We postulate that ischemic optic neuropathy develops as a result of the interplay between the patient's systemic pathophysiology, i.e. shock, sepsis and the continued need for large volume fluid resuscitation. Current treatments of ION have not proven to be effective, except for possibly limiting fluid resuscitation. In the few cases of refractory burn shock, the incidence of this condition is unlikely to be readily improved. However, it is important for clinicians to be aware of this devastating complication and consider early ophthalmology involvement in the care of severely burned patients. PMID:25406887

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

    Microsoft Academic Search

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

    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

  3. Intravitreal bevacizumab for the treatment of nonarteritic anterior ischemic optic neuropathy: a prospective trial

    PubMed Central

    Rootman, D B; Gill, H S; Margolin, E A

    2013-01-01

    Purpose There is currently no accepted treatment for Nonarteritic Anterior Ischemic Optic Neuropathy (NAION). One new therapeutic approach involves decreasing optic nerve edema with intravitreal bevacizumab in order to resolve a proposed compartment syndrome. Methods In this non-randomized controlled clinical trial, 1.25?mg intravitreal bevacizumab was compared with natural history. Patients were examined at baseline, 1, 3, and 6 months with a full neuro-ophthalmic exam, automated perimetry, and optic nerve optical coherence tomography (OCT) measurements. The primary outcome measure was change in mean deviation on Humphrey visual field testing. Secondary outcome measures were change in visual acuity and optic nerve OCT thickness. Incidence and type of complications were also recorded. Results Twenty-five patients were enrolled (17 treatment and 8 control). There was no significant effect of treatment on the primary outcome measure of mean deviation score (P=0.4). There was similarly no effect of group assignment on the secondary outcome measures of change in mean Early Treatment Diabetic Retinopathy Study letters (P=0.33) or nerve fiber layer thickness on OCT (P=0.11). In the bevacizumab group, there was one case of a corneal abrasion and two cases of recurrent NAION. No other complications were noted. Conclusions We found no difference between bevacizumab and natural history for change in visual field, visual acuity, or optic nerve OCT thickness. Based on the current evidence we would not recommend the use of intravitreal bevacizumab to treat patients with the new onset of NAION. PMID:23370417

  4. Axonal degeneration in peripheral nerves in a case of Leber’s Hereditary Optic Neuropathy

    PubMed Central

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

    2010-01-01

    Background Leber’s 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

  5. [Usefulness of extradural optic canal unroofing and decompression of the optic nerve for improvement of visual acuity in traumatic optic neuropathy].

    PubMed

    Nishida, Sho; Otani, Naoki; Inaka, Yasufumi; Morinaga, Yusuke; Kimura, Shohei; Tomura, Satoshi; Osada, Hideo; Harimoto, Kohzou; Takeuchi, Masaru; Wada, Kojiro; Mori, Kentaro

    2014-11-01

    An 81-year-old man presented with poor visual acuity of the left eye, swelling of the left eyelid, and elevation of the left intraocular pressure after contusion of the left palpebral portion. CT revealed left ocular proptosis and left intraorbital hematoma. Traumatic optic neuropathy was suspected, and emergent optic nerve decompression was performed through extradural anterior clinoidectomy followed by optic canal release. Postoperatively, his left visual acuity was markedly improved and the elevated intraocular pressure decreased. Postoperative CT demonstrated improvement of the left ocular proptosis and decompression of the optic nerve. Emergent optic canal release has been recommended in patients who have suffered visual dysfunction caused by optic canal fracture or intraorbital hematoma. The advantages of extradural anterior clinoidectomy followed by optic canal release include a shorter surgical route and easy identification of the optic nerve, resulting in fewer surgical complications. In addition, this procedure can achieve intraorbital decompression. We recommend extradural anterior clinoidectomy followed by optic canal release as a safe and reliable procedure for optic nerve decompression in patients with traumatic optic neuropathy. PMID:25351799

  6. 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.

  7. 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. [Inst. of Neurology, London (United Kingdom)

    1996-07-01

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

  8. 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

  9. 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 ...

  10. Neuropathy Association

    MedlinePLUS

    ... Neuropathy More Attention November 12: "Diabetic Peripheral Neuropathy" Facebook Chat November 6: "TTR-FAP--The Link Between ... Neuropathy Association Celebrates "20,000 Likes" Milestone on Facebook! NEW! The Latest Addition To Our Educational Toolkit -- ...

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

    SciTech Connect

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

    2012-02-01

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

  12. 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

  13. Neuroprotection against superoxide anion radical by metallocorroles in cellular and murine models of optic neuropathy

    PubMed Central

    Kanamori, Akiyasu; Catrinescu, Maria-Magdalena; Mahammed, Atif; Gross, Zeev; Levin, Leonard A.

    2010-01-01

    Corroles are tetrapyrrolic macrocycles that have come under increased attention because of their unique capabilities for oxidation catalysis, reduction catalysis, and biomedical applications. Corrole-metal complexes (metallocorroles) can decompose certain reactive oxygen species (ROS), similar to metalloporphyrins. We investigated whether Fe-, Mn- and Ga-corroles have neuroprotective effects on neurons and correlated this with superoxide scavenging activity in vitro and in vivo. Apoptosis was induced in RGC-5 neuronal precursor cells by serum deprivation. Cell death was measured with XTT and calcein-AM/propidium iodide assays. Fe- and Mn-corroles, but not the non redox-active Ga-corrole used as control, reduced RGC-5 cell death after serum deprivation. Serum deprivation caused increased levels of intracellular superoxide, detected by an increase in the fluorescence intensity of 2-hydroxyethidium, and this was blocked by Fe- and Mn-corroles, but not Ga-corrole. In vivo real-time confocal imaging of retinas after optic nerve transection assessed the superoxide production within individual rat retinal ganglion cells. Fe- and Mn-corroles but not Ga-corrole scavenged neuronal superoxide in vivo. Given that the neuroprotective activity of metallocorroles correlated with superoxide scavenging activity, Fe- and Mn-corroles could be candidate drugs for delaying neuronal death after axonal injury in optic neuropathies such as glaucoma. PMID:20456018

  14. Respiratory function in cybrid cell lines carrying European mtDNA haplogroups: implications for Leber's hereditary optic neuropathy

    Microsoft Academic Search

    Valerio Carelli; Lodovica Vergani; Barbara Bernazzi; Claudia Zampieron; Laura Bucchi; Maria Lucia Valentino; Chiara Rengo; Antonio Torroni; Andrea Martinuzzi

    2002-01-01

    The possibility that some combinations of mtDNA polymorphisms, previously associated with Leber's hereditary optic neuropathy (LHON), may affect mitochondrial respiratory function was tested in osteosarcoma-derived transmitochondrial cytoplasmic hybrids (cybrids). In this cellular system, in the presence of the same nuclear background, different exogenous mtDNAs are used to repopulate a parental cell line previously devoid of its original mtDNA. No detectable

  15. Gastric Helicobacter pylori infection as a cause of idiopathic Parkinson disease and non-arteric anterior optic ischemic neuropathy.

    PubMed

    Altschuler, E

    1996-11-01

    The mechanisms of pathogenesis for both idiopathic Parkinson disease and non-arteritic anterior optic ischemic neuropathy are unknown. A study has shown that, in both diseases, there is a higher prevalence of gastrointestinal ulcers than in age- and sex-matched controls or than in the reported rates for the general population. It is proposed that gastric Helicobacter pylori infection may be a cause of both these diseases. PMID:8951807

  16. Lack of Association between Leber’s Hereditary Optic Neuropathy Primary Point Mutations and Multiple Sclerosis in Iran

    Microsoft Academic Search

    M. Houshmand; M.-H. Sanati; I. Rashedi; F. Sharifpanah; E. Asghari; J. Lotfi

    2004-01-01

    The hypothesis that mitochondrial genes may implicate susceptibility to multiple sclerosis (MS) is supported by an increasing number of case reports on Leber’s hereditary optic neuropathy (LHON)-associated mitochondrial DNA (mtDNA) point mutations in patients with MS. A number of mtDNA mutations with primary pathogenic significance for LHON, a maternally inherited disease causing severe bilateral visual loss predominantly in young men,

  17. Visual Electrophysiologic Findings in Patients From an Extensive Brazilian Family with Leber's Hereditary Optic Neuropathy Visual electrophysiology in LHON

    Microsoft Academic Search

    Solange R. Salomão; Adriana Berezovsky; Rafael E. Andrade; Rubens Belfort Jr.; Valerio Carelli; Alfredo A. Sadun

    2004-01-01

    Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease, associated with mitochondrial DNA (mtDNA) point mutations and characterized by bilateral, usually sequential, rapid loss of central vision. The purpose of this study was to investigate electrophysiologically a small cohort of members from an extensive Brazilian family affected by LHON. Pattern-reversal visual evoked potentials (PVEP), and full-field electroretinograms (ERG) were

  18. 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

  19. 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

  20. Neuroprotective effects of near-infrared light in an in vivo model of mitochondrial optic neuropathy

    PubMed Central

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

    2008-01-01

    Near-infrared light (NIL) promotes a wide range of biological effects including enhancement of energy production, gene expression and prevention of cell death. This is the first report of the in vivo neuroprotective effects of NIL against optic neuropathy induced by mitochondrial complex I inhibition. Subjects were pigmented rats that received single bilateral intravitreal doses of rotenone, a mitochondrial complex I inhibitor, or rotenone plus one of three different doses of NIL. Treatment effects were evaluated at behavioral, structural and neurochemical levels. Rotenone induced a decrease in visual function, as determined by changes in the dark-adapted illuminance sensitivity threshold, escape latency and rate of successful trials in a two-choice visual task, compared to vehicle-treated controls. Behavioral impairment correlated with a decrease in retinal and visual pathway metabolic activity, retinal nerve fiber layer thickness and ganglion cell layer cell density. These changes were prevented by NIL treatments in a dose-dependent manner. Whole-brain cytochrome oxidase and superoxide dismutase activities were also increased in NIL-treated subjects in a dose-dependent manner, suggesting an in vivo transcranial effect of NIL. In whole-brain membrane isolates, NIL prevented the rotenone-induced decrease in cell respiration. The results show that NIL treatment can effectively prevent the neurotoxic effects of rotenone and that it might be used in the treatment of neurodegenerative disorders associated with mitochondrial dysfunction. PMID:19074024

  1. Spastic paraplegia, optic atrophy, and neuropathy: new observations, locus refinement, and exclusion of candidate genes.

    PubMed

    Macedo-Souza, Lúcia Inês; Kok, Fernando; Santos, Silvana; Licinio, Luciana; Lezirovitz, Karina; Cavaçana, Natale; Bueno, Clarissa; Amorim, Simone; Pessoa, André; Graciani, Zodja; Ferreira, Aurea; Prazeres, Abdísio; de Melo, Aurea Nogueira; Otto, Paulo Alberto; Zatz, Mayana

    2009-05-01

    SPOAN is an autosomal recessive neurodegenerative disorder which was recently characterized by our group in a large inbred Brazilian family with 25 affected individuals. This condition is clinically defined by: 1. congenital optic atrophy; 2. progressive spastic paraplegia with onset in infancy; and 3. progressive motor and sensory axonal neuropathy. Overall, we are now aware of 68 SPOAN patients (45 females and 23 males, with age ranging from 5 to 72 years), 44 of which are presented here for the first time. They were all born in the same geographic micro region. Those 68 patients belong to 43 sibships, 40 of which exhibit parental consanguinity. Sixty-one patients were fully clinically evaluated and 64 were included in the genetic investigation. All molecularly studied patients are homozygotes for D11S1889 at 11q13. This enabled us to reduce the critical region for the SPOAN gene from 4.8 to 2.3 Mb, with a maximum two point lod score of 33.2 (with marker D11S987) and of 27.0 (with marker D11S1889). Three genes located in this newly defined critical region were sequenced, but no pathogenic mutation was detected. The gene responsible for SPOAN remains elusive. PMID:19344448

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

    SciTech Connect

    Liang, Min [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China) [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Guan, Minqiang [Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China)] [Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Zhao, Fuxing; Zhou, Xiangtian [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China)] [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Yuan, Meixia [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China) [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Tong, Yi [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China) [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350005 (China); Yang, Li [Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 (United States)] [Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 (United States); Wei, Qi-Ping; Sun, Yan-Hong [Department of Ophthalmology, Dongfang Hospital, Beijing University of Chinese Medicine and Pharmacology, Beijing 100078 (China)] [Department of Ophthalmology, Dongfang Hospital, Beijing University of Chinese Medicine and Pharmacology, Beijing 100078 (China); Lu, Fan [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China)] [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Qu, Jia, E-mail: jqu@wzmc.net [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China) [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); and others

    2009-06-05

    We report here the clinical, genetic and molecular characterization of four Chinese families with Leber's hereditary optic neuropathy (LHON). There were variable severity and age-of-onset in visual impairment among these families. Strikingly, there were extremely low penetrances of visual impairment in these Chinese families. Sequence analysis of complete mitochondrial genomes in these pedigrees showed the homoplasmic T3394C (Y30H) mutation, which localized at a highly conserved tyrosine at position 30 of ND1, and distinct sets of mtDNA polymorphisms belonging to haplogroups D4b and M9a. The occurrence of T3394C mutation in these several genetically unrelated subjects affected by visual impairment strongly indicates that this mutation is involved in the pathogenesis of visual impairment. However, there was the absence of functionally significant mtDNA mutations in these four Chinese pedigrees carrying the T3394C mutation. Therefore, nuclear modifier gene(s) or environmental factor(s) may play a role in the phenotypic expression of the LHON-associated T3394C mutation.

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

    SciTech Connect

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

    1993-10-01

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

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

    PubMed

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

    2009-10-01

    Leber hereditary optic neuropathy and dystonia (LDYT) is a mitochondrial disorder associated with variable combinations of vision loss and progressive generalized dystonia. LDYT is a unique oxidative phosphorylation disorder caused by mutations in mitochondrial ND6 or ND4 gene. In this paper, we describe a Chinese family with 18 LDYT patients. The comprehensive nucleotide sequence analysis of the entire mitochondrial genome using resequencing microarray revealed a mutation (mtND3*10197A (m.10197G>A)) substituting a threonine for a highly conserved alanine at codon 47 of MTND3 on the background of haplogroup D4b. Quantitative analysis of the heteroplasmy of the mutation revealed a homoplasmy in the leukocytes of all the affected individuals on the maternal side. This is the first description of the ND3 mutation causing LDYT. The mtND3*10197A (m.10197G>A) mutation has recently been described in French and Korean patients with Leigh syndrome. These findings suggest that the clinical presentations associated with the mtND3*10197A (m.10197G>A) mutation (ND3) are much wider, encompassing those of LDYT and Leigh syndrome. PMID:19458970

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

    SciTech Connect

    Zhao, Fuxin [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China) [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Guan, Minqiang [Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China)] [Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Zhou, Xiangtian [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China)] [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Yuan, Meixia; Liang, Ming [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China) [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Liu, Qi [Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China)] [Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Liu, Yan; Zhang, Yongmei [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China) [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Yang, Li [Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229 (United States)] [Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229 (United States); Tong, Yi [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China) [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350005 (China); Wei, Qi-Ping; Sun, Yan-Hong [Department of Ophthalmology, Dongfang Hospital, Beijing University of Chinese Medicine and Pharmacology, Beijing 100078 (China)] [Department of Ophthalmology, Dongfang Hospital, Beijing University of Chinese Medicine and Pharmacology, Beijing 100078 (China); Qu, Jia, E-mail: jqu@wzmc.net [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China) [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); and others

    2009-11-20

    We report here the clinical, genetic, and molecular characterization of three Chinese families with Leber's hereditary optic neuropathy (LHON). There were variable severity and age of onset in visual impairment among these families. Strikingly, there were extremely low penetrances of visual impairment in these Chinese families. Sequence analysis of complete mitochondrial genomes in these pedigrees showed the homoplasmic T14502C (I58V) mutation, which localized at a highly conserved isoleucine at position 58 of ND6, and distinct sets of mtDNA polymorphisms belonging to haplogroups M10a, F1a1, and H2. The occurrence of T14502C mutation in these several genetically unrelated subjects affected by visual impairment strongly indicates that this mutation is involved in the pathogenesis of visual impairment. Here, mtDNA variants I187T in the ND1, A122V in CO1, S99A in the A6, and V254I in CO3 exhibited an evolutionary conservation, indicating a potential modifying role in the development of visual impairment associated with T14502C mutation in those families. Furthermore, nuclear modifier gene(s) or environmental factor(s) may play a role in the phenotypic manifestation of the LHON-associated T14502C mutation in these Chinese families.

  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. Orbital high resolution magnetic resonance imaging with fast spin echo in the acute stage of Leber’s hereditary optic neuropathy

    Microsoft Academic Search

    Yukihiko Mashima; Kazuhiro Oshitari; Yutaka Imamura; Suketaka Momoshima; Hayao Shiga; Yoshihisa Oguchi

    1998-01-01

    Some evidence suggests that the primary locus of the lesion in Leber’s hereditary optic neuropathy (LHON) may be intraocular rather than retrobulbar. To clarify this issue, the condition of the retrobulbar portion of the optic nerve was evaluated in patients with the acute stage of LHON. High resolution MRI with fast spin echo sequences of the optic nerve complex in

  8. Anterior ischemic optic neuropathy in a patient with Crohn's disease and aberrant MTHFR and GPIIIa gene variants.

    PubMed

    Felekis, T; Katsanos, K H; Zois, C D; Vartholomatos, G; Kolaitis, N; Asproudis, I; Tsianos, E V

    2010-10-01

    Large spectrums of ophthalmic manifestations from the anterior to the posterior segment have been so far reported in patients with inflammatory bowel disease. Anterior ischemic optic neuropathy is caused by acute ischemic infarction of the optic nerve head and is distinguished in two different types, non-arteritic anterior ischemic optic neuroparhy (NAION) which is the most frequent type and arteritic anterior ischemic optic neuropathy. Non-arteritic anterior ischemic optic neuroparhy may result in severe visual field loss. We present the case of a 69 year-old man with known history of Crohn's disease that was referred to the Department of Ophthalmology after noticing sudden blurred vision of his left eye. Ophthalmologic examination revealed a corrected visual acuity of 8/10 OS and 10/10 OD. Pupil examination showed a relative afferent pupillary defect of the left pupil and fluoroangiography revealed hyperfluorescence of the left optic disc, indicating edema and NAION attack on his left eye. Genetic analysis showed that the patient was homozygous for MTHFR C677T genetic polymorphism and A1/A2 heterozygous for GPIIIa polymorphism. PMID:21122545

  9. SUBCLINICAL CARRIERS AND CONVERSIONS IN LEBER HEREDITARY OPTIC NEUROPATHY: A PROSPECTIVE PSYCHOPHYSICAL STUDY

    PubMed Central

    Sadun, Alfredo A.; Salomao, Solange R.; Berezovsky, Adriana; Sadun, Federico; DeNegri, Anna Maria; Quiros, Peter A.; Chicani, Filipe; Ventura, Dora; Barboni, Piero; Sherman, Jerome; Sutter, Erich; Belfort, Rubens; Carelli, Valerio

    2006-01-01

    Purpose The authors previously presented the results of their 2001 field investigation to rural Brazil to investigate a 336-member pedigree of Leber hereditary optic neuropathy (LHON). The present work describes the yearly field investigations 2001 to 2005, utilizing a variety of highly sophisticated psychophysical and electrophysiologic procedures, in asymptomatic LHON carriers, some of whom converted to affected status. Methods Careful, repeated examinations of 75 carriers of homoplasmic 11778 LHON mtDNA J-haplogroup mutants were performed as part of the field investigation of this pedigree. All subjects underwent a detailed neuro-ophthalmologic investigation, including formal visual fields (Humphrey; HVF) and fundus photography. In addition, many subjects underwent rigorous psychophysical examination, including Cambridge Research Systems color vision and contrast sensitivity testing, OCT, GDx, and multifocal visual evoked response (mfVER) and multifocal electroretinogram (mfERG). Two patients followed as nonsymptomatic LHON carriers converted to affected status. Results Many LHON carriers did, in fact, show subclinical or occult abnormalities. Focal edema was often seen involving the arcuate nerve fiber bundles, and this corresponded with areas of relative paracentral or arcuate scotomas on HVF testing. Compared to controls, LHON carriers had significant losses in color vision affecting mostly the red-green system and reduction in spatial but not temporal contrast sensitivity. The mfVER and mfERG data showed that most carriers had depressed central responses and abnormal interocular asymmetries. Conclusions In this very large pedigree of 11778 LHON, the carriers frequently showed manifestations of optic nerve impairments. Their occult disease reflected low-grade compromise that waxed and waned. In two cases, these changes led to a crescendo of dramatic impairments that characterize conversion to affected status. PMID:17471325

  10. INTEGRINS IN THE OPTIC NERVE HEAD: POTENTIAL ROLES IN GLAUCOMATOUS OPTIC NEUROPATHY (AN AMERICAN OPHTHALMOLOGICAL SOCIETY THESIS)

    PubMed Central

    Morrison, John C.

    2006-01-01

    Purpose To demonstrate that specific distributions of integrin-based focal mechanoreceptors exist in primate optic nerve heads, suitable for translating stress and strain into the cellular responses of glaucomatous optic neuropathy. Methods Normal human (N = 20) and rhesus monkey (N = 14) optic nerve heads and 32 glaucomatous optic nerve heads were processed for immunohistochemistry to determine the structural distribution of integrin subunits ?1, ?2, ?3, ?4, ?5, ?6, ?v, ?1, ?2, ?3, and ?4. Labeling patterns in glaucoma specimens were compared with those of normal eyes. Results In all specimens, cells within collagenous laminar beams and sclera failed to label with any integrin antibodies. In normal eyes, ?2, ?3, ?6, ?1, and ?4 antibodies localized to astrocytes along the margins of laminar beams and within glial columns. ?3, ?5, ?6, ?v, ?1, and ?4 labeled vascular endothelial cells. In severely damaged glaucoma specimens, cells anterior to the compressed lamina cribrosa displayed persistent label for ?2, ?3, ?1, and ?4, whereas label for ?4 increased and ?6 was decreased. Conclusions Integrins ?2?1, ?3?1, ?6?1, and ?6?4 may provide attachment for astrocytes to basement membranes via laminin, providing opportunities to sense changes in stress and strain within and anterior to the lamina cribrosa. Vascular endothelial cell stress may be mediated by integrins ?3?1, ?6?1, and ?6?4, along with ?5?1 and ?v?1. In advanced damage, reduced ?6 label and variable label for ?? 4 anterior to the lamina cribrosa suggests astrocyte migration. Increased label for ?4 subunits suggests activation of microglia. PMID:17471356

  11. Diabetic neuropathy

    PubMed Central

    Bansal, V; Kalita, J; Misra, U K

    2006-01-01

    Diabetic neuropathy (DN) refers to symptoms and signs of neuropathy in a patient with diabetes in whom other causes of neuropathy have been excluded. Distal symmetrical neuropathy is the commonest accounting for 75% DN. Asymmetrical neuropathies may involve cranial nerves, thoracic or limb nerves; are of acute onset resulting from ischaemic infarction of vasa nervosa. Asymmetric neuropathies in diabetic patients should be investigated for entrapment neuropathy. Diabetic amyotrophy, initially considered to result from metabolic changes, and later ischaemia, is now attributed to immunological changes. For diagnosis of DN, symptoms, signs, quantitative sensory testing, nerve conduction study, and autonomic testing are used; and two of these five are recommended for clinical diagnosis. Management of DN includes control of hyperglycaemia, other cardiovascular risk factors; ? lipoic acid and L carnitine. For neuropathic pain, analgesics, non?steroidal anti?inflammatory drugs, antidepressants, and anticonvulsants are recommended. The treatment of autonomic neuropathy is symptomatic. PMID:16461471

  12. Pedigree analysis in Leber hereditary optic neuropathy families with a pathogenic mtDNA mutation.

    PubMed Central

    Harding, A E; Sweeney, M G; Govan, G G; Riordan-Eva, P

    1995-01-01

    Eighty-nine index patients from 85 families were defined as having Leber hereditary optic neuropathy (LHON) by the presence of one of the mtDNA mutations at positions 11778 (66 families), 3460 (8 families), or 14484 (11 families). There were 62 secondary cases. Overall, 64% of index cases had a history of similarly affected relatives. The ratios of affected males to affected females were 3.7:1 (11778), 4.3:1 (3460), and 7.7:1 (14484). The 95th centile for age at onset of symptoms was close to 50 years in index, secondary, male, and female patients. There were no differences in the distributions of age at onset between different mutation groups, between index and secondary cases, or between males and females, apart from this being slightly later in all female patients than in male 11778 patients. There was no significant correlation between age at onset in index cases and that in their affected siblings or cousins. Heteroplasmy (< 96% mutant mtDNA) was detected in 4% of affected subjects (67%-90% mutant mtDNA) and in 13.6% of 140 unaffected relatives (< 5%-90% mutant mtDNA). Analysis of all pedigrees, excluding sibships < 50 years of age and index cases, indicated recurrence risks of 30%, 8%, 46%, 10%, 31%, and 6%, respectively, to the brothers, sisters, nephews, nieces, and male and female matrilineal first cousins of index cases. Affected females were more likely to have affected children, particularly daughters, than were unaffected female carriers. The pedigree data were entirely compatible with the previously proposed X-linked susceptibility locus, with a gene frequency of .08, penetrance of .11 in heterozygous females, and 40% of affected females being homozygous, the remainder being explained by heterozygosity and disadvantageous X inactivation. PMID:7611298

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

    SciTech Connect

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

    2013-11-01

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

  14. 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

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

    PubMed

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

    2012-05-01

    The distinction between mild pathogenic mtDNA mutations and population polymorphisms can be ambiguous because both are homoplasmic, alter conserved functions, and correlate with disease. One possible explanation for this ambiguity is that the same variant may have different consequences in different contexts. The NADH dehydrogenase subunit 1 (ND1) nucleotide 3394 T > C (Y30H) variant is such a case. This variant has been associated with Leber hereditary optic neuropathy and it reduces complex I activity and cellular respiration between 7% and 28% on the Asian B4c and F1 haplogroup backgrounds. However, complex I activity between B4c and F1 mtDNAs, which harbor the common 3394T allele, can also differ by 30%. In Asia, the 3394C variant is most commonly associated with the M9 haplogroup, which is rare at low elevations but increases in frequency with elevation to an average of 25% of the Tibetan mtDNAs (odds ratio = 23.7). In high-altitude Tibetan and Indian populations, the 3394C variant occurs on five different macrohaplogroup M haplogroup backgrounds and is enriched on the M9 background in Tibet and the C4a4 background on the Indian Deccan Plateau (odds ratio = 21.9). When present on the M9 background, the 3394C variant is associated with a complex I activity that is equal to or higher than that of the 3394T variant on the B4c and F1 backgrounds. Hence, the 3394C variant can either be deleterious or beneficial depending on its haplogroup and environmental context. Thus, this mtDNA variant fulfills the criteria for a common variant that predisposes to a "complex" disease. PMID:22517755

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

    PubMed Central

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

    2012-01-01

    The distinction between mild pathogenic mtDNA mutations and population polymorphisms can be ambiguous because both are homoplasmic, alter conserved functions, and correlate with disease. One possible explanation for this ambiguity is that the same variant may have different consequences in different contexts. The NADH dehydrogenase subunit 1 (ND1) nucleotide 3394 T > C (Y30H) variant is such a case. This variant has been associated with Leber hereditary optic neuropathy and it reduces complex I activity and cellular respiration between 7% and 28% on the Asian B4c and F1 haplogroup backgrounds. However, complex I activity between B4c and F1 mtDNAs, which harbor the common 3394T allele, can also differ by 30%. In Asia, the 3394C variant is most commonly associated with the M9 haplogroup, which is rare at low elevations but increases in frequency with elevation to an average of 25% of the Tibetan mtDNAs (odds ratio = 23.7). In high-altitude Tibetan and Indian populations, the 3394C variant occurs on five different macrohaplogroup M haplogroup backgrounds and is enriched on the M9 background in Tibet and the C4a4 background on the Indian Deccan Plateau (odds ratio = 21.9). When present on the M9 background, the 3394C variant is associated with a complex I activity that is equal to or higher than that of the 3394T variant on the B4c and F1 backgrounds. Hence, the 3394C variant can either be deleterious or beneficial depending on its haplogroup and environmental context. Thus, this mtDNA variant fulfills the criteria for a common variant that predisposes to a “complex” disease. PMID:22517755

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

    PubMed Central

    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

  18. 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

  19. 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 (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

  20. Paraproteinemic neuropathies.

    PubMed

    Raheja, Divisha; Specht, Charles; Simmons, Zachary

    2015-01-01

    The paraproteinemias are a heterogeneous group of disorders in which monoclonal plasma cells cause the proliferation of monoclonal proteins. They are of importance to clinicians because they often occur in association with neuropathies. Neurologists play a particularly important role when the neuropathy is the presenting feature, in which case they may uncover clinical, laboratory, radiologic, electrodiagnostic, or biopsy findings that lead to identification of the underlying paraproteinemia. The frequency of neuropathies in these patients, and the extent to which such neuropathies dominate the clinical picture, varies significantly between the different paraproteinemias. Treatments may be aimed specifically at the neuropathy, or against the underlying hematologic disorder. In all patients with paraproteinemias, the neurologist can work collaboratively with the hematologist to formulate therapeutic plans and goals and can provide follow-up and monitoring to determine the response of the neuropathy to treatment. PMID:25288371

  1. Inherited Neuropathies

    Microsoft Academic Search

    Angelo Schenone; Lucilla Nobbio; Margherita Monti Bragadin; Giulia Ursino; Marina Grandis

    2011-01-01

    Opinion statement  Inherited peripheral neuropathies are among the most common hereditary diseases of the nervous system. Charcot-Marie-Tooth\\u000a (CMT) disease, also known from previous classifications as hereditary motor and sensory neuropathy (HMSN), is certainly the\\u000a most common inherited neuropathy. In the past several years, various treatments for CMT have been proposed, although specific\\u000a therapies are not yet available. In clinical practice, rehabilitative

  2. 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. [Univ. of Munich (Germany); Lorenz, B. [Univ. of Rogensburgh (Germany); Zerres, K. [Univ. of Bonn (Germany); Meire, F. [Univ. of Ghent (Belgium); Cochaux, P. [Univ. of Brussels (Belgium)] [and others

    1994-11-01

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

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

    PubMed

    Cwerman-Thibault, Hélène; Augustin, Sébastien; Ellouze, Sami; Sahel, José-Alain; Corral-Debrinski, Marisol

    2014-03-01

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

  4. 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

  5. X Chromosome-Linked and Mitochondrial Gene Control of Leber Hereditary Optic Neuropathy: Evidence from Segregation Analysis for Dependence on X Chromosome Inactivation

    Microsoft Academic Search

    Xiangdong Bu; Jerome I. Rotter

    1991-01-01

    Leber hereditary optic neuropathy (LHON) has been shown to involve mutation(s) of mitochondrial DNA, yet there remain several confusing aspects of its inheritance not explained by mitochondrial inheritance alone, including male predominance, reduced penetrance, and a later age of onset in females. By extending segregation analysis methods to disorders that involve both a mitochondrial and a nuclear gene locus, we

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

    PubMed Central

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

    1995-01-01

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

  7. Auditory Neuropathy

    MedlinePLUS

    ... the brain, where the impulses are interpreted as sound. Top Are there risk factors for auditory neuropathy? Several factors have been linked to auditory neuropathy in children. However, a clear cause and effect relationship has not been proven. Some children who ...

  8. [Sarcoid neuropathy].

    PubMed

    Koga, Michiaki

    2014-08-01

    Sarcoid neuropathy, a rare condition which is seen in 1% of patients with sarcoidosis, often emerges as one of the differential diagnoses of neuropathies with an unknown origin. Recent studies have revealed that sarcoid neuropathy shows a broader spectrum of clinical characteristics than previously expected, including a Guillain-Barré- or chronic inflammatory demyelinating polyneuropathy-like presentation, small fiber neuropathy, and typical subacute multiple mononeuropathy. This makes the diagnosis difficult in certain cases. Due to the lack of diagnostic markers for this condition, neurological, laboratory, neurophysiological, and image analyses are all necessary to evaluate the probability of sarcoid neuropathy during differential diagnosis. This review mentions several cues for guiding the diagnosis, and diagnostic criteria. PMID:25082319

  9. The fellow eye in naion: report from the ischemic optic neuropathy decompression trial follow-up study 1 1 InternetAdvance publication at ajo.com June 5, 2002

    Microsoft Academic Search

    Nancy J Newman; Roberta Scherer; Patricia Langenberg; Shalom Kelman; Steven Feldon; David Kaufman; Kay Dickersin

    2002-01-01

    PURPOSE: To examine the prevalence and incidence of second eye nonarteritic anterior ischemic optic neuropathy (NAION) and associated patient characteristics in patients enrolled in the Ischemic Optic Neuropathy Decompression Trial (IONDT) Follow-up Study.DESIGN: Randomized clinical trial with observational cohort.METHODS: Patients randomized to optic nerve sheath decompression surgery or careful follow-up had a diagnosis of acute unilateral NAION, visual acuity between

  10. Respiratory function in cybrid cell lines carrying European mtDNA haplogroups: implications for Leber's hereditary optic neuropathy.

    PubMed

    Carelli, Valerio; Vergani, Lodovica; Bernazzi, Barbara; Zampieron, Claudia; Bucchi, Laura; Valentino, Maria; Rengo, Chiara; Torroni, Antonio; Martinuzzi, Andrea

    2002-10-01

    The possibility that some combinations of mtDNA polymorphisms, previously associated with Leber's hereditary optic neuropathy (LHON), may affect mitochondrial respiratory function was tested in osteosarcoma-derived transmitochondrial cytoplasmic hybrids (cybrids). In this cellular system, in the presence of the same nuclear background, different exogenous mtDNAs are used to repopulate a parental cell line previously devoid of its original mtDNA. No detectable differences in multiple parameters exploring respiratory function were observed when mtDNAs belonging to European haplogroups X, H, T and J were used. Different possible explanations for the previously established association between haplogroup J and LHON 11778/ND4 and 14484/ND6 pathogenic mutations are discussed, including the unconventional proposal that mtDNA haplogroup J may exert a protective rather than detrimental effect. PMID:12379308

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

    SciTech Connect

    Mackey, D. (Royal Children's Hospital, Melbourne (Australia)); Howell, N. (Univ. of Texas, Galveston (United States))

    1992-12-01

    The Tas2 and Vic2 Australian families are affected with a variant of Leber hereditary optic neuropathy (LHON). The risk of developing the optic neuropathy shows strict maternal inheritance, and the opthalmological changes in affected family members are characteristic of LHON. However, in contrast to the common form of the disease, members of these two families show a high frequency of vision recovery. To ascertain the mitochondrial genetic etiology of the LHON in these families, both (a) the nucleotide sequences of the seven mitochondrial genes encoding subunits of respiratory-chain complex I and (b) the mitochondrial cytochrome b gene were determined for representatives of both families. Neither family carries any of the previously identified primary mitochondrial LHON mutations: ND4/11778, ND1/3460, or ND1/4160. Instead, both LHON families carry multiple nucleotide changes in the mitochondrial complex I genes, which produce conservative amino acid changes. From the available sequence data, it is inferred that the Vic2 and Tas2 LHON families are phylogenetically related to each other and to a cluster of LHON families in which mutations in the mitochondrial cytochrome b gene have been hypothesized to play a primary etiological role. However, sequencing analysis establishes that the Vic2 and Tas2 LHON families do not carry these cytochrome b mutations. There are two hypotheses to account for the unusual mitochondrial genetic etiology of the LHON in the Tas2 and Vic2 LHON families. One possibility is that there is a primary LHON mutation within the mitochondrial genome but that it is at a site that was not included in the sequencing analyses. Alternatively, the disease in these families may result from the cumulative effects of multiple secondary LHON mutations that have less severe phenotypic consequences. 29 refs., 3 figs., 3 tabs.

  12. Predictive Factors for Vision Recovery after Optic Nerve Decompression for Chronic Compressive Neuropathy: Systematic Review and Meta-Analysis

    PubMed Central

    Carlson, Andrew P.; Stippler, Martina; Myers, Orrin

    2012-01-01

    Objectives?Surgical optic nerve decompression for chronic compressive neuropathy results in variable success of vision improvement. We sought to determine the effects of various factors using meta-analysis of available literature. Design?Systematic review of MEDLINE databases for the period 1990 to 2010. Setting?Academic research center. Participants?Studies reporting patients with vision loss from chronic compressive neuropathy undergoing surgery. Main outcome measures?Vision outcome reported by each study. Odds ratios (ORs) and 95% confidence intervals (CIs) for predictor variables were calculated. Overall odds ratios were then calculated for each factor, adjusting for inter study heterogeneity. Results?Seventy-six studies were identified. Factors with a significant odds of improvement were: less severe vision loss (OR 2.31[95% CI?=?1.76 to 3.04]), no disc atrophy (OR 2.60 [95% CI?=?1.17 to 5.81]), smaller size (OR 1.82 [95% CI?=?1.22 to 2.73]), primary tumor resection (not recurrent) (OR 3.08 [95% CI?=?1.84 to 5.14]), no cavernous sinus extension (OR 1.88 [95% CI?=?1.03 to 3.43]), soft consistency (OR 4.91 [95% CI?=?2.27 to 10.63]), presence of arachnoid plane (OR 5.60 [95% CI?=?2.08 to 15.07]), and more extensive resection (OR 0.61 [95% CI?=?0.4 to 0.93]). Conclusions?Ophthalmologic factors and factors directly related to the lesion are most important in determining vision outcome. The decision to perform optic nerve decompression for vision loss should be made based on careful examination of the patient and realistic discussion regarding the probability of improvement. PMID:24436885

  13. 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.

  14. Hereditary Neuropathies

    MedlinePLUS

    ... appearance of an inverted champagne glass) or scoliosis (curvature of the spine). The symptoms of hereditary neuropathies ... Charcot-Marie-Tooth Disease Information Page Charcot-Marie-Tooth Disorder information page compiled by the National Institute of ...

  15. Peripheral Neuropathy

    MedlinePLUS

    ... to identify substances that will block the brain chemicals that generate pain signals, while others are investigating the pathways by which pain signals reach the brain. NIH Patient Recruitment for Peripheral Neuropathy ...

  16. Diabetic Neuropathy

    MedlinePLUS

    ... need to be treated at a hospital. In severe cases, you may need to have your foot amputated (removed). Because diabetes makes ... What can I do to avoid diabetic neuropathy? The most important thing is to keep ...

  17. 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

  18. Auditory neuropathy.

    PubMed

    Starr, Arnold; Rance, Gary

    2015-01-01

    Neural disorders of the auditory nerve are associated with particular disorders of auditory perceptions dependent on processing of acoustic temporal cues. These include: (1) speech perception; (2) localizing a sound's origin in space; and (3) identifying sounds in background noise. Auditory neuropathy (AN) is a consequence of: (1) presynaptic disorders affecting inner hair cell ribbon synapses; (2) postsynaptic disorders of auditory nerve dendrites; and (3) postsynaptic disorders of auditory nerve axons. The etiologies of these disorders are diverse, similar to other cranial or peripheral neuropathies. The pathologies cause attenuated and dyssynchronous auditory nerve discharges. Therapies and management of patients with AN are reviewed. PMID:25726287

  19. The Association between Diabetes Mellitus and Nonarteritic Anterior Ischemic Optic Neuropathy: A Systematic Review and Meta-Analysis

    PubMed Central

    Chen, Ting; Song, Delu; Shan, Guangliang; Wang, Ke; Wang, Yiwei; Ma, Jin; Zhong, Yong

    2013-01-01

    Background The association of diabetes mellitus (DM) with nonarteritic anterior ischemic optic neuropathy (NAION) has been inconclusive. Purpose To determine whether DM is associated with an increased risk of NAION. Methods A comprehensive literature search was performed for published studies reporting both DM and NAION based on PubMed and EMBASE. After reviewing characteristics of all the included studies systematically, meta-analytical method was employed to calculate the pooled odds ratio (OR) and associated 95% confidence interval (CI) from random-effects models. Heterogeneity was assessed by Q-statistic test. Funnel Plot, Begg's and Egger's linear regression test were applied to evaluate publication bias. A sensitivity analysis and meta-regression analysis were also performed to assess the robustness of results. Results 2,096 participants from 12 case-control studies were pooled for a meta-analysis. The result of meta-analysis of these studies indicated that DM is associated with increased risk of NAION (pooled OR?=?1.64, 95% CI?=?1.17–2.30; P?=?0.004). Sensitivity analysis indicated our findings are robust, and meta-regression analysis revealed no significant effect in terms of geographical area, gender, age of patients with NAION, the year of the publication, source of the controls, and sample size (all p>0.05). Evidence of publication bias was not observed in our study. Conclusion Meta-analysis suggests that DM might be associated with increased risk of NAION. PMID:24098798

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

    SciTech Connect

    Sun Yanhong [Department of Ophthalmology, Dongfang Hospital, Beijing University of Chinese Medicine and Pharmacology, Beijing 100078 (China); Wei Qiping [Department of Ophthalmology, Dongfang Hospital, Beijing University of Chinese Medicine and Pharmacology, Beijing 100078 (China); Zhou Xiangtian [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Qian Yaping [Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229 (United States); Zhou Jian [Department of Ophthalmology, Dongfang Hospital, Beijing University of Chinese Medicine and Pharmacology, Beijing 100078 (China); Lu Fan [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Qu Jia [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China)]. E-mail: jqu@wzmc.net; Guan Minxin [Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229 (United States) and Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China) and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229 (United States)]. 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.

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

    SciTech Connect

    Zhou Xiangtian [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China)]|[Zhejiang Provincial Key Lab. of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Wei Qiping [Dept. of Ophthalmology, Dongfang Hospital, Beijing Univ. of Chinese Medicine and Pharmacology, Beijing 100078 (China); Yang Li [Div. of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229 (United States); Tong Yi [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China)]|[First Affiliated Hospital, Fujian Medical Univ., Fuzhou, Fujian 350005 (China); Zhao Fuxin [Zhejiang Provincial Key Lab. of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Lu Chunjie [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Qian Yaping [Div. of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229 (United States); Sun Yanghong [Dept. of Ophthalmology, Dongfang Hospital, Beijing Univ. of Chinese Medicine and Pharmacology, Beijing 100078 (China); Lu Fan [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Qu Jia [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China)]|[Zhejiang Provincial Key Lab. of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China)]. E-mail: jqu@wzmc.net; Guan Minxin [Zhejiang Provincial Key Lab. of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China)]|[Div. of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229 (United States)]|[Dept. of Pediatrics, Univ. of Cincinnati College of Medicine, Cincinnati, OH 45229 (United States)]. 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.

  2. NEUROPATÍA ÓPTICA AUTOINMUNE RECIDIVANTE BILATERAL EN LA INFANCIA BILATERAL RECURRENT AUTOIMMUNE OPTICAL NEUROPATHY IN CHILDHOOD

    Microsoft Academic Search

    GARCÍA-GÓMEZ PJ; BELZUNCE A; SALINAS ALAMÁN

    Clinical case: A ten year-old girl, after a Yersinia gastroenteritis, developed an optic neuritis in the left eye. She was not treated and resulted ultimately in optic atrophy on the affected side. Six months later a similar episode occurred in the contralateral eye. On this occasion corticosteroid therapy was given. During this therapy the neuritis diminished; however the patient had

  3. 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 [Univ. Hospital Nijmegen (Netherlands); Went, L.N.; Bruyn, G.W. [Univ. of Leiden (Netherlands)] [and others

    1996-04-01

    A rare form of Leber hereditary optic neuropathy (LHON) that is associated with hereditary spastic dystonia has been studied in a large Dutch family. Neuropathy and ophthalmological lesions were present together in some family members, whereas only one type of abnormality was found in others. mtDNA mutations previously reported in LHON were not present. Sequence analysis of the protein-coding mitochondrial genes revealed two previously unreported mtDNA mutations. A heteroplasmic A{yields}G transition at nucleotide position 11696 in the ND4 gene resulted in the substitution of an isoleucine for valine at amino acid position 312. A second mutation, a homoplasmic T{yields}A transition at nucleotide position 14596 in the ND6 gene, resulted in the substitution of a methionine for the isoleucine at amino acid residue 26. Biochemical analysis of a muscle biopsy revealed a severe complex I deficiency, providing a link between these unique mtDNA mutations and this rare, complex phenotype including Leber optic neuropathy. 80 refs., 2 figs., 3 tabs.

  4. Peripheral Neuropathy

    MedlinePLUS

    ... or wrist. Diseases or disorders and their related processes (such as inflammation) can be associated with peripheral neuropathy. Metabolic and endocrine disorders impair the body’s ability to transform nutrients into energy and process waste products, and this can lead ...

  5. Autonomic neuropathy, II: Specific peripheral neuropathies.

    PubMed

    McDougall, A J; McLeod, J G

    1996-06-01

    Autonomic dysfunction is a common complication of peripheral neuropathies. It is often of little clinical importance, but some conditions may cause profound disturbance of autonomic function. These conditions include acute dysautonomia, diabetes, primary and familial amyloidosis, Guillain-Barré syndrome, porphyria, and some inherited neuropathies. A wide range of neuropathies are associated with lesser degrees of autonomic dysfunction. These include hereditary neuropathies, and neuropathies associated with metabolic disturbances, alcohol abuse, malignancy, medications, infections, and connective tissue disorders. PMID:8791232

  6. Diabetic Neuropathy

    PubMed Central

    Gibbons, Christopher H.; Freeman, Roy; Veves, Aristidis

    2010-01-01

    OBJECTIVE To determine the relationships among large, small, and autonomic fiber neurophysiological measures in a cross-sectional study of patients with diabetes. RESEARCH DESIGN AND METHODS We assessed 130 individuals: 25 healthy subjects and 105 subjects with diabetes. Subjects were classified by the presence or absence of neuropathy by physical examination. All subjects underwent autonomic testing, nerve conduction studies, quantitative sensory testing, and nerve-axon reflex vasodilation in addition to quantifiable neurological examination and symptom scores. Correlation and cluster analysis were used to determine relationships between and among different neurophysiological testing parameters. RESULTS Results of neurophysiological tests were abnormal in patients with clinical evidence of diabetic neuropathy compared with results in healthy control subjects and in those without neuropathy (P < 0.01, all tests). The correlations among individual tests varied widely, both within (r range <0.5–>0.9, NS to <0.001) and between test groups (r range <0.2–>0.5, NS to <0.01). A two-step hierarchical cluster analysis revealed that neurophysiological tests do not aggregate by typical “small,” “large,” or “autonomic” nerve fiber subtypes. CONCLUSIONS The modest correlation coefficients seen between the different testing modalities suggest that these techniques measure different neurophysiological parameters and are therefore not interchangeable. However, the data suggest that only a small number of neurophysiological tests are actually required to clinically differentiate individuals with neuropathy from those without. The natural clustering of both patients and healthy control subjects suggests that variations in the population will need to be considered in future studies of diabetic neuropathy. PMID:20805259

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

    PubMed Central

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

    2015-01-01

    Pathological examination of material from a nonextensive pars plana vitrectomy (PPV) in the right eye provided a diagnosis of nonfamilial amyloidosis in a 68-year-old woman, who presented with bilateral glass wool-like vitreous opacities. Genetic testing revealed a Tyr114Cys mutation in the transthyretin gene. Six months after PPV, perimetry showed intense constriction with a temporal island and central scotoma in the right eye. An extensive PPV was performed in the left eye. Spectral domain optical coherence tomography evidenced bilateral epimacular amyloid deposits and unreported reflective spots within the inner retina. One year later, visual acuity had decreased to 20/400 in the left eye, with mild vitreous opacity, pale cupped optic disc and inferior altitudinal field defect. Bilateral diurnal intraocular pressure, transiently increased after PPV, never exceeded 16 mmHg with medication. Our patient presented optic nerve blood supply impairment, due to amyloidosis, which caused optic atrophy. Epiretinal and intraretinal deposit detection could aid in diagnosing patients with suspected amyloidosis. PMID:25686071

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

    PubMed

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

    2015-01-01

    Pathological examination of material from a nonextensive pars plana vitrectomy (PPV) in the right eye provided a diagnosis of nonfamilial amyloidosis in a 68-year-old woman, who presented with bilateral glass wool-like vitreous opacities. Genetic testing revealed a Tyr114Cys mutation in the transthyretin gene. Six months after PPV, perimetry showed intense constriction with a temporal island and central scotoma in the right eye. An extensive PPV was performed in the left eye. Spectral domain optical coherence tomography evidenced bilateral epimacular amyloid deposits and unreported reflective spots within the inner retina. One year later, visual acuity had decreased to 20/400 in the left eye, with mild vitreous opacity, pale cupped optic disc and inferior altitudinal field defect. Bilateral diurnal intraocular pressure, transiently increased after PPV, never exceeded 16 mmHg with medication. Our patient presented optic nerve blood supply impairment, due to amyloidosis, which caused optic atrophy. Epiretinal and intraretinal deposit detection could aid in diagnosing patients with suspected amyloidosis. PMID:25686071

  9. 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

  10. 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 ...

  11. Diabetic Neuropathies

    Microsoft Academic Search

    Aaron I. Vinik

    Diabetic neuropathies (DN) are a heterogeneous group of disorders that include a wide range of abnormalities. They can be\\u000a focal or diffuse, proximal or distal, affecting both peripheral and autonomic nervous systems, causing morbidity with significant\\u000a impact on the quality of life of the person with diabetes, resulting in early mortality. Distal symmetric polyneuropathy,\\u000a the most common form of DN,

  12. 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. [Emory Univ. School of Medicine, Atlanta, GA (United States)

    1997-02-01

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

  13. 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. [Applied Genetics, San Diego, CA (United States); Bodis-Wollner, I. [State Univ. of New York College of Optometry, New York, NY (United States)] [and others

    1996-02-01

    Nucleotide-sequencing and multiplexed primer-extension assays have been used to quantitate the mutant-allele frequency in 14 maternal relatives, spanning three generations, from a family that is heteroplasmic for the primary Leber hereditary optic neuropathy (LHON) mutation at nucleotide 3460 of the mitochondrial genome. There was excellent agreement between the values that were obtained with the two different methods. The longitudinal study shows that the mutant-allele frequency was constant within individual family members over a sampling period of 3.5 years. Second, although there was an overall increase in the mutant-allele frequency in successive generations, segregation in the direction of the mutant allele was not invariant, and there was one instance in which there was a significant decrease in the frequency from parent to offspring. From these two sets of results, and from previous studies of heteroplasmic LHON families, we conclude that there is no evidence for a marked selective pressure that determines the replication, segregation, or transmission of primary LHON mutations to white blood cells and platelets. Instead, the mtDNA molecules are most likely to replicate and segregate under conditions of random drift at the cellular level. Finally, the pattern of transmission in this maternal lineage is compatible with a developmental bottleneck model in which the number of mitochondrial units of segregation in the female germ line is relatively small in relation to the number of mtDNA molecules within a cell. However, this is not an invariant pattern for humans, and simple models of mitochondrial gene transmission are inappropriate at the present time. 37 refs., 4 figs., 1 tab.

  14. Misonidazole neuropathy.

    PubMed

    Paulson, O B; Melgaard, B; Hansen, H S; Kamieniecka, Z; Køhler, O; Hansen, J M; Pedersen, A G; Tang, X; Trojaborg, W

    1984-01-01

    Neurotoxic side effects of misonidazole with peripheral neuropathy was investigated in two series of patients. The first series consisted of eight patients with carcinoma of the pharynx, larynx or lung who, during treatment with misonidazole, developed peripheral neuropathy dominated by severe sensory symptoms and signs localized mainly to the lower extremities. Misonidazole was given for three to seven weeks in a total dose of 9.6 - 12.6 g/m2 (11 g/m2 or more in four of the patients). The symptoms subsided partially within a few months after cessation of the therapy. Electrophysiological and histological findings indicated axonal neuropathy with loss of large fibres and secondary demyelination. The second series consisted of 70 patients with carcinoma of the pharynx or larynx who, in addition to radiotherapy, were given either placebo or misonidazole over four weeks in a total dose of 11 g/m2. Fourteen patients out of 36 receiving misonidazole (38%) developed peripheral polyneuropathy, mostly in the feet, while this occurred in only two of the 34 patient placebo group. PMID:6091392

  15. [Dysglobulinemic neuropathies].

    PubMed

    Gherardi, R; Zuber, M; Viard, J P

    1988-01-01

    Monoclonal gammopathies are frequently associated with peripheral neuropathies of which clinical, electrophysiological, pathological and possibly pathogenetical aspects are heterogeneous. Nevertheless some clinico-biological entities, which account for the majority of cases, have been recently recognized: 1) The IgM neuropathy is a chronic demyelinating sensori-motor polyneuropathy with tremor and ataxia as prominent features. It can be either associated with MGUS or Waldenstrom macroglobulinemia. The light chain of the gammopathy is kappa in a majority of cases. Numerous reports have demonstrated specific antibody activities supported by the M-protein and directed against various peripheral nerve antigens, usually myelin components such as the myelin associated glycoprotein (MAG). The ultrastructural evidence of widely spaced myelin is suggestive of the diagnosis but is not consistent. Treatment directed towards the gammopathy is occasionally associated with improvement of the symptoms. 2) The neuropathy of the osteosclerotic myelomas and solitary plasmacytomas present as a chronic sensori-motor polyradiculoneuropathy with conspicuous demyelination and may be associated with one or more of the systemic clinical features of the Crow-Fukase or POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, Skin changes). The POEMS syndrome may also be associated with "benign" monoclonal or even polyclonal dysproteinemias. The M-proteins are almost all IgG or IgA with lambda light chains. There are some relations between POEMS syndrome and Castleman's disease. The pathogenesis of both disorders remains obscure. Treatment is most favorable in case of solitary plasmacytomas, which may be completely removed. 3) The neuropathy observed in patients with primary AL amyloidosis or amylosis associated with malignant plasma-cell dyscrasias is rare. Sensory deficit and autonomic dysfunction are related to a prominent involvement of small myelinated and unmyelinated fibers. A clinical and/or electro-physiological carpal tunnel syndrome is frequent. In a majority of cases the light chain of the M-protein is lambda. Amyloid deposits are observed on nerve biopsy. Treatment is inefficient. 4) The neuropathy associated with cryoglobulinemias may be asymmetric, painful, cryosensitive and associated with cutaneous purpura and neuromuscular vasculitis. In fact, in a majority of cases the symptoms are less suggestive raising the problem of an incidental laboratory finding. 5) A motoneuron disease-like syndrome may develop in patients with various types of monoclonal gammopathies.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2847276

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

    PubMed Central

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

    2012-01-01

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

  17. 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

  18. Leber's Hereditary Optic Neuropathy with Olivocerebellar Degeneration due to G11778A and T3394C Mutations in the Mitochondrial DNA

    PubMed Central

    Adachi, Yoshiki; Fusayasu, Emi; Doi, Koji; Imamura, Keiko; Yasui, Kenichi; Nakashima, Kenji

    2012-01-01

    Background Leber's hereditary optic neuropathy (LHON) is a mitochondrial disorder with optic nerve atrophy. Although there are no other associated neurological abnormalities in most cases of LHON, cases of "LHON plus" have been reported. Case Report The proband was a 37-year-old man who had visual and gait disturbances that had first appeared at 10 years of age. He showed horizontal gaze palsy, gaze-evoked nystagmus, dysarthria, and cerebellar ataxia. Brain and orbit MRI disclosed atrophy of the optic nerve and cerebellum, and degenerative changes in the bilateral inferior olivary nucleus. Mutational analyses of mitochondrial DNA identified the coexistence of heteroplasmic G11778A and homoplasmic T3394C mutations. Conclusions These results suggest that the combination of G11778A and T3394C mutations leads to an atypical LHON phenotype. PMID:23091534

  19. Management of Diabetic Neuropathy

    PubMed Central

    Ali, Raymond Azman

    2003-01-01

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

  20. 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. [Ophthalmic Research Institute, Amsterdam (Netherlands)] [and others

    1995-10-01

    Three mtDNA point mutations at nucleotide position (np) 3460, at np 11778 and at np 14484, are thought to be of primary importance in the pathogenesis of Leber hereditary optic neuropathy (LHON), a maternally inherited disease characterized by subacute central vision loss. These mutations are present in genes coding for subunits of complex I (NADH dehydrogenase) of the respiratory chain, occur exclusively in LHON maternal pedigrees, and have never been reported to occur together. Johns and Neufeld postulated that an mtDNA mutation at np 9438, in the gene coding for one of the subunits (COX III) of complex IV (cytochrome c oxidase), was also of primary importance. Johns and Neufeld (1993) found this mutation, which changed a conserved glycine to a serine, in 5 unrelated LHON probands who did not carry one of the presently known primary mutations, but they did not find it in 400 controls. However, the role of this sequence variant has been questioned in the Journal when it has been found to occur in apparently healthy African and Cuban individuals. Subsequently, Johns et al. described this mutation in two Cuban individuals presenting with optic and peripheral neuropathy. 22 refs., 1 fig., 1 tab.

  1. A mitochondrial DNA mutation at nucleotide pair 14459 of the NADH dehydrogenase subunit 6 gene associated with maternally inherited Leber hereditary optic neuropathy and dystonia.

    PubMed Central

    Jun, A S; Brown, M D; Wallace, D C

    1994-01-01

    A five-generation Hispanic family expressing maternally transmitted Leber hereditary optic neuropathy and/or early-onset dystonia associated with bilateral basal ganglia lesions was studied. Buffy coat mitochondrial DNA (mtDNA) from a severely affected child was amplified by the polymerase chain reaction and greater than 90% sequenced. The mtDNA proved to be a Native American haplogroup D genotype and differed from the standard "Cambridge" sequence at 40 nucleotide positions. One of these variants, a G-to-A transition at nucleotide pair (np) 14459, changed a moderately conserved alanine to a valine at NADH dehydrogenase subunit 6 (ND6) residue 72. The np 14459 variant was not found in any of 38 Native American haplogroup D mtDNAs, nor was it detected in 108 Asian, 103 Caucasian, or 99 African mtDNAs. Six maternal relatives in three generations were tested and were found to harbor the mutation, with one female affected with Leber hereditary optic neuropathy being heteroplasmic. Thus, the np 14459 G-to-A missense mutation is specific to this family, alters a moderately conserved amino acid in a complex I gene, is a unique mtDNA variant in Native American haplogroup D, and is heteroplasmic, suggesting that it is the disease-causing mutation. Images PMID:8016139

  2. 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, E-mail: y_demizu@nifty.co [Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo (Japan); Murakami, Masao; Miyawaki, Daisuke; Niwa, Yasue [Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo (Japan); Akagi, Takashi [Department of Accelerator Managing, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo (Japan); Sasaki, Ryohei [Division of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Terashima, Kazuki [Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo (Japan); Suga, Daisaku [Department of Radiation Technology, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo (Japan); Kamae, Isao [Division of Medical Statistics, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Hishikawa, Yoshio [Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo (Japan)

    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.

  3. 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. ...

  4. Giant Axonal Neuropathy

    MedlinePLUS

    ... What is Giant Axonal Neuropathy? Giant axonal neuropathy (GAN) is a rare inherited genetic disorder that affects ... peripheral nervous systems. The majority of children with GAN will begin to show symptoms of the disease ...

  5. Neuropathy secondary to drugs

    MedlinePLUS

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

  6. 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. (Institute of Neurology, Queen Square, London (United Kingdom)); Toscano, A. (Clinica Neurologica, Messina (Italy))

    1992-10-01

    Leber hereditary optic neuropathy (LHON) is associated with mutations of mtDNA, but two features of LHON pedigrees are not explicable solely on the basis of mitochondrial inheritance. There is a large excess of affected males, and not all males at risk develop the disease. These observations could be explained by the existence of an X-linked visual loss susceptibility gene. This hypothesis was supported by linkage studies in Finland, placing the susceptibility locus at DXS7, with a maximum lod score of 2.48 at a recombination fraction of 0. Linkage studies in 1 Italian and 12 British families with LHON, analyzed either together or separately depending on the associated mtDNA mutation, have excluded the presence of such a locus from an interval of about 30 cM around DXS7 in these kindreds, with a total lod score of -26.51 at a recombination fraction of 0. 17 refs., 2 figs., 1 tab.

  7. 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. [Universita` di Roma (Italy)] [and others

    1996-07-01

    Leber hereditary optic neuropathy (LHON) is a maternally transmitted disease whose primary clinical manifestation is acute or subacute bilateral loss of central vision leading to central scotoma and blindness. To date, LHON has been associated with 18 mtDNA missense mutations, even though, for many of these mutations, it remains unclear whether they cause the disease, contribute to the pathology, or are nonpathogenic mtDNA polymorphisms. On the basis of numerous criteria, which include the specificity for LHON, the frequency in the general population, and the penetrance within affected pedigrees, the detection of associated defects in the respiratory chain, mutations at three nucleotide positions (nps), 11778 (G{r_arrow}A), 3460 (G{r_arrow}A), and 14484 (T{r_arrow}C) have been classified as high-risk and primary LHON mutations. Overall, these three mutations encompass {ge}90% of the LHON cases. 29 refs., 1 fig.

  8. Mitochondrial Gene Therapy Improves Respiration, Biogenesis, and Transcription in G11778A Leber's Hereditary Optic Neuropathy and T8993G Leigh's Syndrome Cells

    PubMed Central

    Bergquist, Kristen; Young, Kisha; Gnaiger, Erich; Rao, Raj R.

    2012-01-01

    Abstract Many incurable mitochondrial disorders result from mutant mitochondrial DNA (mtDNA) and impaired respiration. Leigh's syndrome (LS) is a fatal neurodegenerative disorder of infants, and Leber's hereditary optic neuropathy (LHON) causes blindness in young adults. Treatment of LHON and LS cells harboring G11778A and T8993G mutant mtDNA, respectively, by >90%, with healthy donor mtDNA complexed with recombinant human mitochondrial transcription factor A (rhTFAM), improved mitochondrial respiration by ?1.2-fold in LHON cells and restored >50% ATP synthase function in LS cells. Mitochondrial replication, transcription, and translation of key respiratory genes and proteins were increased in the short term. Increased NRF1, TFAMB1, and TFAMA expression alluded to the activation of mitochondrial biogenesis as a mechanism for improving mitochondrial respiration. These results represent the development of a therapeutic approach for LHON and LS patients in the near future. PMID:22390282

  9. Peripheral neuropathy in diabetes.

    PubMed

    Majumder, A; Chatterjee, S; Maji, D

    2013-06-01

    Peripheral neuropathy is common complication of diabetes. The prevalence of peripheral neuropathy among diabetic patients on the basis of loss of vibration sensation had been studied. Detailed clinical history of each patient including age, gender, duration of diabetes, foot ulcer and biothesiometry was recorded in 211 diabetic patients between 20 and 80 years of age. It was observed that all patients under 30 years age (n = 8) felt vibration below 15 volts (no risk zone); 77% (24 out of 31) of the patients in the age group of 30-39 years were in the no risk zone, and 23% (n = 7) had mild peripheral neuropathy. Sixty per cent of the patients between 40 and 50 years (n = 44) were in the no risk zone, while 32% (n = 24) had mild peripheral neuropathy, 5% (n = 4) had moderate neuropathy and 3% (n = 2) had severe peripheral neuropathy. Amongst patients above 50 years of age, 31% (n = 31) were in no risk zone, 34% (n = 34) had mild peripheral neuropathy, 22% (n = 20) had moderate peripheral neuropathy and 13% (n = 13) had severe peripheral neuropathy. Of the patients with diabetes for less than 5 years, 58% had no neuropathy, and only 3% had severe neuropathy. Of the patients with diabetes for 5 to 15 years, 50% had no neuropathy, 30% had mild, and 10% had severe peripheral neuropathy. When patients with diabetes for over 15 years were studied, only 6% had no neuropathy and 19% had severe peripheral neuropathy. The study re-establishes that the severity of peripheral neuropathy increases with age and vibration perception decreses progressively with increased duration of diabetes. Vibration perception threshold testing helps to identify the high risk subjects who require special counselling and education to protect their feet. PMID:24761495

  10. [Metabolic and nutritional neuropathy].

    PubMed

    Hattori, Naoki; Koike, Haruki; Sobue, Gen

    2008-11-01

    We assessed whether postgastrectomy polyneuropathy associated with thiamine deficiency is clinicopathologically identical to beriberi neuropathy, including a biochemical determination of thiamine status. The typical presentation for the two etiologies was as a symmetric sensorimotor polyneuropathy predominantly involving the lower limbs. In both groups, the main electrophysiologic findings were those of axonal neuropathy, most prominently in the lower limbs. Sural nerve biopsy specimens also indicated axonal degeneration in both groups. Subperineurial edema was commonly observed. Thiamine-deficiency neuropathies due to gastrectomy and dietary imbalance are identical despite variability in their clinicopathologic features and suggested that thiamine deficiency can be a major cause of postgastrectomy polyneuropathy. Characteristics of alcoholic neuropathy have been obscured by difficulty in isolating them from features of thiamine-deficiency neuropathy. We assessed 64 patients with alcoholic neuropathy including subgroups without and with coexisting thiamine deficiency. Thirty-two patients with nonalcoholic thiamine-deficiency neuropathy also were investigated for comparison. We concluded that pure-form of alcoholic neuropathy was distinct from pure-form of thiamine-deficiency neuropathy, supporting the view that alcoholic neuropathy can be caused by direct toxic effect of ethanol or its metabolites. However, features of alcoholic neuropathy is influenced by concomitant thiamine-deficiency state, having so far caused the obscure clinicopathological entity of alcoholic neuropathy. PMID:19198152

  11. Entrapment neuropathies III: lower limb.

    PubMed

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

    2010-11-01

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

  12. 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

  13. 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

  14. Inherited mitochondrial neuropathies.

    PubMed

    Finsterer, Josef

    2011-05-15

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

  15. Fast capillary electrophoresis-laser induced fluorescence analysis of ligase chain reaction products: human mitochondrial DNA point mutations causing Leber's hereditary optic neuropathy.

    PubMed

    Muth, J; Williams, P M; Williams, S J; Brown, M D; Wallace, D C; Karger, B L

    1996-12-01

    High speed capillary electrophoresis-laser-induced fluorescence (CE-LIF) has been used to separate and detect point mutations using the ligase chain reaction (LCR). The method utilizes short capillary columns (7.5 cm effective length) and fields of 400 V/cm to analyze DNA-ethidium bromide complexes using an He/Ne laser. The method was first demonstrated with a commercially available kit for LCR based on a lacI gene fragment inserted in a Bluescript II phagemid. LCR-CE-LIF was then applied to detect point mutations in human mitochondrial DNA, resulting in Leber's hereditary optic neuropathy (LHON). Three severe mutations were analyzed in which the original base is substituted by a thymidine base at positions 3460, 11778 and 14459. Appropriate primers were designed with polyT tails for length discrimination of pooled samples. Successful detection of mutated samples was achieved, with appropriate correction for small amounts of nonspecific ligated product. The method is rapid, easy to implement, and automatable. PMID:9034769

  16. 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. (Cedars-Sinai Medical Center, Los Angeles, CA (United States) Univ. of California, Los Angeles (United States))

    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.

  17. 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. [Univ. of Pittsburgh School of Medicine, PA (United States)] [Univ. of Pittsburgh School of Medicine, PA (United States); Carelli, V.; Cortelli, P. [Univ. of Bologna (Italy)] [and others] [Univ. of Bologna (Italy); and others

    1996-02-02

    Leber`s hereditary optic neuropathy (LHON) accounts for about 3% of the cases of blindness in young adult males. The underlying mitochondrial pathogenesis of LHON has been well studied, with specific mitochondrial DNA (mtDNA) mutations of structural genes described and well characterized. However, enigmatic aspects of the disease are not explained by mutation data, such as the higher proportion of affected males, the later onset of the disease in females, and the presence of unaffected individuals with a high proportion of mutant mtDNA. A hypothesis which has been put forward to explain the unusual disease expression is a dual model of mtDNA and X-linked nuclear gene inheritance. If a nuclear X-linked modifier gene influences the expression of the mitochondrial-linked mutant gene then the affected females should be either homozygous for the nuclear determinant, or if heterozygous, lyonization should favor the mutant X. In order to determine if an X-linked gene predisposes to LHON phenotype we studied X-inactivation patterns in 35 females with known mtDNA mutations from 10 LHON pedigrees. Our results do not support a strong X-linked determinant in LHON cause: 2 of the 10 (20%) manifesting carriers showed skewing of X-inactivation, as did 3 of the 25 (12%) nonmanifesting carriers. 39 refs., 2 figs., 1 tab.

  18. 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

  19. Controversial entrapment neuropathies.

    PubMed

    Campbell, William W; Landau, Mark E

    2008-10-01

    There is no significant disagreement about the major common entrapment neuropathies, such as carpal tunnel syndrome (CTS), ulnar neuropathy at the elbow, and peroneal neuropathy at the knee. In contrast, there is a group of entrapment syndromes about which there is major disagreement, including whether or not they even exist. There are other entrapment syndromes about which clinical questions arise on a regular basis, and which are the subject of this discussion. These include thoracic outlet syndrome, radial tunnel syndrome, ulnar nerve entrapment at the arcade of Struthers, piriformis syndrome, and tarsal tunnel syndrome. PMID:19010284

  20. [Developments in hereditary neuropathies].

    PubMed

    Dubourg, O

    2012-12-01

    Hereditary sensorimotor neuropathies, or Charcot-Marie-Tooth disease (CMT) comprise a group of diseases with heterogeneous clinical, electrophysiological and genetic expression. They are classified by the mode of inheritance (autosomal dominant, X-linked dominant, autosomal recessive) and their electrophysiological characteristics taking into account the speed of motor conduction of the median nerve (demyelinating, intermediary and axonal forms). Certain purely motor forms are called spinal CMT or hereditary distal motor neuropathy, or distal spinal amyotrophy. CMT involving an important sensorial component, trophic disorders, or signs of dysautonomia are included in the classification of hereditary sensory and autonomic neuropathies. PMID:23153686

  1. HIV Associated Sensory Neuropathy

    PubMed Central

    S, Praveen-kumar; B, Nataraju; BS, Nagaraja

    2014-01-01

    Background: In the era of highly active antiretroviral therapy, sensory neuropathies have increased in prevalence. We have documented the frequency and profile of the two most common forms of sensory neuropathies associated with Human Immunodeficiency Virus (HIV) infection and looked into clinicoelectrophysiological correlates to differentiate the two entities. Methods: The study population comprised of all consecutive patients detected to be HIV positive and attending the Neurology outpatient department (from March 2011 to March 2012) who were aged ? 18 years and were able to give informed consent. The data were collected from the patient records (including CD4 counts and treatment details) and questionnaire based interview with each patient. All patients underwent detailed clinical examination and nerve conduction studies (NCSs). Results: Among the total study population of 50 patients, there were 31 men and 19 women. Thirty two patients were in age range of 21 - 40 years and rest were above 40 years. 25 were on antiretroviral therapy (18 on regimen containing zidovudine; seven on regimen containing stavudine). The mean duration of antiretroviral therapy was 16.6±8.4 months. Low CD4 counts (<200) were noted in 24 patients (13 of these were on antiretroviral therapy). Clinically, the patients were classified as asymptomatic (n=34) and symptomatic (n=16). Among the symptomatic patients, nine were on antiretroviral therapy since less than one year (seven of these were on regimen containing stavudine). Ten patients aged more than 40-years had symptomatic neuropathy. No significant correlation was found between low CD4 counts and symptomatic neuropathy (p=0.21). Impaired vibration (100%) and absent ankle jerks (75%) were commoner than reduced pin sensitivity (46.6%). Twenty two patients had abnormal NCS results (18 of these were on antiretroviral therapy). Axonal distal symmetrical sensory neuropathy was the commonest pattern noted in 14 patients who were receiving antiretroviral therapy. Subclinical involvement as evidenced by abnormal NCSs was noted in 5 asymptomatic patients who were all on antiretroviral therapy. Conclusion: Symptomatic neuropathy was seen predominantly in HIV patients who were on antiretroviral therapy. All patients receiving stavudine containing regimen had severe symptomatic neuropathy within 1 year. There was an increase in the likelihood of symptomatic neuropathy among patients aged > 40 years. Subclinical neuropathy was common in those on antiretroviral therapy. Axonal neuropathy was the commonest pattern noted in patients who were receiving antiretroviral therapy and demyelinating neuropathy in patients not on antiretroviral therapy. Surprisingly no significant correlation was found between low CD4 counts and symptomatic neuropathy. PMID:25177587

  2. JOURNALDEPHYSIQUE CoiioqueC1, supplkment aunO 1, Tome41,janvier 1980,page Cl-393 A &SBAUER SnalY OF M E INTERACTION BETWEEN a-ION AND ALUMINOPHOSPHAE AND ALUMINO-CHROm)-PHOSPHATE

    E-print Network

    Paris-Sud XI, Université de

    Y OF M E INTERACTION BETWEEN a-ION AND ALUMINOPHOSPHAE AND ALUMINO-CHROm)-PHOSPHATE ADHESIVES R T.M. Peev, Hungary. The aluminophosphate and alumino-.chrmo- #2 -. 60 mg iron powder + 100 mg alumino-. phosphate + 50 mg Ti0 phosphate are frequently used as metal ado- 2' hesives. Ti02 is generally an additional

  3. Complete mitochondrial DNA genome sequence variation of Chinese families with mutation m.3635G>A and Leber hereditary optic neuropathy

    PubMed Central

    Bi, Rui; Zhang, A-Mei; Jia, Xiaoyun; Zhang, Qingjiong

    2012-01-01

    Purpose The majority of Leber hereditary optic neuropathy (LHON) cases are caused by one of three mitochondrial DNA (mtDNA) primary mutations (m.3460G>A, m.11778G>A, and m.14484T>C). In recent studies, we and others have shown that mutation m.3635G>A is a primary LHON mutation, particularly in Chinese. The purpose of this study was to perform a thorough analysis for the complete mtDNA genome sequence variation in Chinese patients with m.3635G>A and to identify potentially functional variants cosegregated with m.3635G>A. Methods The complete mtDNA genomes of five Chinese patients with LHON carrying m.3635G>A were determined. A phylogenetic tree was constructed to distinguish the private and ancestral mtDNA variants in each lineage. Previously unreported variants in each mtDNA were defined with a web-based and database search. mtDNA variants that changed the structure of the membrane-spanning region of the protein were also evaluated, together with evolutionary conservation analysis, to predict their potential pathogenicity. Results The five patients with LHON sequenced in this study belonged to haplogroups M7b4 (Le131), F1a (Le329 and Le337), B5b (Le569), and M7b6 (Le834), which suggested multiple origins of m.3635G>A. Private variants m.12811T>C, m.14063T>C, m.15237T>C, and m.9071C>T in these patients were predicted to change the structure of the membrane-spanning region of the respective proteins. Conclusions Mutation m.3635G>A had multiple origins in Chinese patients with LHON. We also identified several potentially functional variants cosegregated with m.3635G>A. PMID:23304069

  4. 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 Leber’s 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

  5. Congenital Hypomyelinating Neuropathy (CHN)

    MedlinePLUS

    ... Progress Search form Search Charcot-Marie-Tooth Disease (CMT) Congenital Hypomyelinating Neuropathy (CHN) What is Congenital Hypomyelinating ... is a subtype of Charcot-Marie-Tooth disease (CMT), a genetic, neurological disorder that causes damage to ...

  6. [Diabetes mellitus and autoimmune neuropathy].

    PubMed

    Deguchi, Takahisa; Nishio, Yoshihiko; Takashima, Hiroshi

    2014-02-01

    The term "diabetic neuropathy" refers to many varieties of neuropathies, including diabetic peripheral neuropathies (DPNs). DPNs are categorized into generalized and focal/multifocal varieties. Diabetic sensorimotor polyneuropathy (DSPN) and diabetic autonomic neuropathy (DAN) are typical DPNs, and their development is clearly linked to hyperglycemia and subsequent metabolic and ischemic change. On the other hand, other forms of neuropathy, including multifocal diabetic neuropathies (e.g., lumbosacral, thoracic, and cervical radiculoplexus neuropathies) are thought to be associated with inflammatory or immune processes. Diabetic patients can also develop chronic inflammatory demyelinating polyneuropathy (CIDP). CIDP in diabetic patients (DM-CIDP) should be ruled out, especially in patients with advanced DSPN. Recently, it was reported that diabetic radiculoplexus neuropathies as well as CIDP respond favorably to immunotherapy. Thus, these immune-mediated diabetic neuropathies are treatable, and should be differentiated from advanced DSPN. PMID:24523312

  7. Inherited mitochondrial neuropathies

    Microsoft Academic Search

    Josef Finsterer

    2011-01-01

    Mitochondrial disorders (MIDs) occasionally manifest as polyneuropathy either as the dominant feature or as one of many other manifestations (inherited mitochondrial neuropathy). MIDs in which polyneuropathy is the dominant feature, include NARP syndrome due to the transition m.8993T>, CMT2A due to MFN2 mutations, CMT2K and CMT4A due to GDAP1 mutations, and axonal\\/demyelinating neuropathy with external ophthalmoplegia due to POLG1 mutations.

  8. Chemotherapy-induced neuropathy

    Microsoft Academic Search

    Anjali Bhagra; Ravi D. Rao

    2007-01-01

    Peripheral neuropathy is a common dose-limiting toxicity of chemotherapy. Chemotherapy-induced peripheral neuropathy (CIPN)\\u000a causes numerous debilitating symptoms, impairs functional capacity, and results in dose reductions or possible cessation of\\u000a chemotherapy. Analgesic or neurotropic agents are only modestly effective in treating neuropathic symptoms. Animal and human\\u000a studies into the pathogenesis of CIPN have demonstrated heterogeneity in the mechanism(s) of nerve injury

  9. Treatments for diabetic neuropathy

    Microsoft Academic Search

    Andrew J. M. Boulton

    2001-01-01

    The management of symptomatic diabetic sensory neuropathy presents a therapeutic challenge to the practicing physician. Two\\u000a approaches are outlined in this article. First, symptomatic therapies, which will not influence the natural history of painful\\u000a neuropathy, are discussed. These include, in addition to the stable glycemic control, tricyclic drugs, a number of anticonvulsant\\u000a and antiarrhythmic agents, and opioid-like medications. Topical therapies

  10. 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

  11. 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

  12. [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

  13. Peripheral Neuropathy and Agent Orange

    MedlinePLUS

    ... Enter ZIP code here Peripheral Neuropathy and Agent Orange VA presumes Veterans' early-onset peripheral neuropathy is related to their exposure to Agent Orange or other herbicides during service when the disease ...

  14. Chemotherapy-induced peripheral neuropathy

    Microsoft Academic Search

    Stefan Quasthoff; Hans Peter Hartung

    2002-01-01

    The induction of peripheral neuropathy is a common factor in limiting therapy with chemotherapeutic drugs. Little is known\\u000a about the mechanisms responsible for the development of neuropathy. Depending on the substance used, a pure sensory and painful\\u000a neuropathy (with cisplatin, oxaliplatin, carboplatin) or a mixed sensorimotor neuropathy with or without involvement of the\\u000a autonomic nervous system (with vincristine, taxol, suramin)

  15. Diabetic autonomic neuropathy

    Microsoft Academic Search

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

    1979-01-01

    Summary  This review attempts to outline the present understanding of diabetic autonomic neuropathy. The clinical features have been increasingly recognised but knowledge of the localization and morphology of the lesions and their pathogenesis remains fragmentary. A metabolic causation as postulated in somatic nerves accords best with clinical observations. Most bodily systems, particularly the cardiovascular, gastrointestinal and urogenital, are involved with added

  16. Idiopathic neuropathy, prediabetes and the metabolic syndrome

    Microsoft Academic Search

    A. Gordon Smith; J. Robinson Singleton

    2006-01-01

    Peripheral neuropathy is a common problem encountered by neurologists and primary care physicians. While there are many causes for peripheral neuropathy, none can be identified in a large percentage of patients (“idiopathic neuropathy”). Despite its high prevalence, idiopathic neuropathy is poorly studied and understood. There is evolving evidence that impaired glucose tolerance (prediabetes) is associated with idiopathic neuropathy. Preliminary data

  17. Homeopathy in Cuban epidemic neuropathy: an open clinical trial

    Microsoft Academic Search

    BE Elliot; J Barnouin; P Fleites; A Araoz; M Morales; T Verdura; M Sanchez; C Serrano; JL Alvarez; J-J Veillard

    2001-01-01

    In an outbreak of epidemic neuropathy (EN) in Cuba (1992–1993), most patients were improved by vitamin therapy. In subjects with residual symptoms, alternative treatments including homeopathy were suggested to ameliorate optic and peripheral signs of the disease. An open clinical pilot trial was conducted on 31 patients with long standing symptoms of optic (OPTI group, n=15) or peripheral EN (PERI

  18. Genetics Home Reference: Giant axonal neuropathy

    MedlinePLUS

    ... PubMed Recent literature OMIM Genetic disorder catalog Conditions > Giant axonal neuropathy On this page: Description Genetic changes ... names Glossary definitions Reviewed October 2007 What is giant axonal neuropathy? Giant axonal neuropathy is an inherited ...

  19. Diabetic Neuropathy: Mechanisms to Management

    PubMed Central

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

    2014-01-01

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

  20. Experimental diabetic neuropathy: an update

    Microsoft Academic Search

    A. A. F. Sima; K. Sugimoto

    1999-01-01

    Diabetic neuropathy consists of several clinical syndromes affecting motor, sensory and autonomic nerves. Of these the most\\u000a common is distal symmetric sensory polyneuropathy usually referred to as diabetic neuropathy. Animal studies, mainly in diabetic\\u000a rodents, have contributed tremendously to our understanding of this disease. From these it is clear that the pathogenesis\\u000a of diabetic neuropathy is multifactorial involving sequentially occurring

  1. Lateral plantar neuropathy.

    PubMed

    Oh, S J; Kwon, K H; Hah, J S; Kim, D E; Demirci, M

    1999-09-01

    We report 8 cases of lateral plantar neuropathy (LPN). All had sensory impairment over the territory of the lateral plantar nerve. Near-nerve needle sensory nerve conduction study (NCS) of the plantar nerves showed abnormality confined to the lateral plantar nerve, confirming LPN. The most common cause for LPN was trauma and the most common site of injury was at the passage of the lateral plantar nerve through the abductor tunnel at the instep of the foot. PMID:10454719

  2. Canine inherited hypertrophic neuropathy

    Microsoft Academic Search

    J. F. Cummings; B. J. Cooper; A. Lahunta; T. J. Winkle

    1981-01-01

    A recessively inherited hypertrophic neuropathy was discovered in Tibetan Mastiff dogs. Affected pups developed a generalized weakness with hyporeflexia shortly after weaning. Diagnostic findings in 10–18-week-old pups included: moderate to severe reduction in nerve conduction velocities, infrequent denervation potentials, and inconstant elevation in CSF protein. Light- and electron-microscopic studies of peripheral nerves and roots revealed widespread demyelination and primitive onion

  3. [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

  4. Therapy for vasculitic neuropathies.

    PubMed

    Gorson, Kenneth C

    2006-03-01

    The term vasculitis refers to a pathologic condition defined by inflammatory cell infiltration and destruction of blood vessels. Systemic vasculitis is classified as primary (eg, polyarteritis nodosa, Churg-Strauss syndrome) or secondary, the latter associated with connective tissue disorders, infections, medications, and rarely, as a paraneoplastic phenomenon. Neuropathy is a common complication of systemic vasculitis and is related to ischemic nerve fiber damage with axon loss. Peripheral neuropathy may be the sole manifestation of vasculitis, a condition termed nonsystemic vasculitic neuropathy (NSVN). Treatment of vasculitic neuropathy requires long-term immunosuppressive therapies with potential side effects. The diagnosis of vasculitis should be established by tissue (preferably nerve) biopsy. High-dose prednisone is the standard platform therapy for patients with systemic and NSVN; for those with systemic vasculitis, at least 3 to 12 months of treatment with cyclophosphamide (monthly intravenous pulse or daily oral therapy) is also necessary to sustain remission and allow successful prednisone tapering. The use of cyclophosphamide in patients with NSVN is controversial, but recent retrospective data suggest that those treated with prednisone and cyclophosphamide from the outset fare better than those initially treated only with prednisone. If prednisone is administered as monotherapy, cyclophosphamide should be added after several months if there is no improvement or relapse occurs with tapering of prednisone. Intravenous pulse and daily oral cyclophosphamide probably offer similar efficacy, although the risk of complications is greater with oral therapy. Azathioprine can be safely substituted for cyclophosphamide after 3 months without an increased relapse rate. Azathioprine, methotrexate, intravenous immune globulin, mycophenolate mofetil, plasma exchange, and rituximab can be offered to patients who are intolerant or have a contraindication to cyclophosphamide. However, efficacy is unproven for any of these therapies. Interferon-alpha, sometimes combined with plasma exchange, is used to treat vasculitis associated with hepatitis B infection. Some patients also may improve with corticosteroids. The classification of diabetic lumbosacral radiculoplexus neuropathy as a vasculitic disorder remains controversial. However, there is compelling pathological evidence that this condition represents a T-cell-mediated microvasculitis. Some patients treated with intravenous corticosteroids may have greater recovery and improved pain control. PMID:16464407

  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. 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.

  7. Painful Peripheral Neuropathies

    PubMed Central

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

    2006-01-01

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

  8. Painful neuropathy: Mechanisms.

    PubMed

    Lee-Kubli, Corinne A; Calcutt, Nigel A

    2014-01-01

    Painful neuropathy, like the other complications of diabetes, is a growing healthcare concern. Unfortunately, current treatments are of variable efficacy and do not target underlying pathogenic mechanisms, in part because these mechanisms are not well defined. Rat and mouse models of type 1 diabetes are frequently used to study diabetic neuropathy, with rats in particular being consistently reported to show allodynia and hyperalgesia. Models of type 2 diabetes are being used with increasing frequency, but the current literature on the progression of indices of neuropathic pain is variable and relatively few therapeutics have yet been developed in these models. While evidence for spontaneous pain in rodent models is sparse, measures of evoked mechanical, thermal and chemical pain can provide insight into the pathogenesis of the condition. The stocking and glove distribution of pain tantalizingly suggests that the generator site of neuropathic pain is found within the peripheral nervous system. However, emerging evidence demonstrates that amplification in the spinal cord, via spinal disinhibition and neuroinflammation, and also in the brain, via enhanced thalamic activity or decreased cortical inhibition, likely contribute to the pathogenesis of painful diabetic neuropathy. Several potential therapeutic strategies have emerged from preclinical studies, including prophylactic treatments that intervene against underlying mechanisms of disease, treatments that prevent gains of nociceptive function, treatments that suppress enhancements of nociceptive function, and treatments that impede normal nociceptive mechanisms. Ongoing challenges include unraveling the complexity of underlying pathogenic mechanisms, addressing the potential disconnect between the perceived location of pain and the actual pain generator and amplifier sites, and finding ways to identify which mechanisms operate in specific patients to allow rational and individualized choice of targeted therapies. PMID:25410243

  9. Sciatic Injection Neuropathy

    PubMed Central

    Brown, Barton A.

    1972-01-01

    Prevention of sciatic injection neuropathy can best be accomplished by teaching that the injection should be made into the gluteal mass in the upper outer quadrant rather than the buttock, and that the needle should be introduced in a plane perpendicular to the surface of the bed when the patient is lying prone. Failing prevention, one must strive for early and correct diagnosis, especially in infants, and carry out exploration with internal and external neurolysis if there is no evidence of improvement within two to three months. PMID:4639840

  10. Neuropathy target esterase.

    PubMed Central

    Glynn, P

    1999-01-01

    Neuropathy target esterase (NTE) is an integral membrane protein present in all neurons and in some non-neural-cell types of vertebrates. Recent data indicate that NTE is involved in a cell-signalling pathway controlling interactions between neurons and accessory glial cells in the developing nervous system. NTE has serine esterase activity and efficiently catalyses the hydrolysis of phenyl valerate (PV) in vitro, but its physiological substrate is unknown. By sequence analysis NTE has been found to be related neither to the major serine esterase family, which includes acetylcholinesterase, nor to any other known serine hydrolases. NTE comprises at least two functional domains: an N-terminal putative regulatory domain and a C-terminal effector domain which contains the esterase activity and is, in part, conserved in proteins found in bacteria, yeast, nematodes and insects. NTE's effector domain contains three predicted transmembrane segments, and the active-site serine residue lies at the centre of one of these segments. The isolated recombinant domain shows PV hydrolase activity only when incorporated into phospholipid liposomes. NTE's esterase activity appears to be largely redundant in adult vertebrates, but organophosphates which react with NTE in vivo initiate unknown events which lead, after a delay of 1-3 weeks, to a neuropathy with degeneration of long axons. These neuropathic organophosphates leave a negatively charged group covalently attached to the active-site serine residue, and it is suggested that this may cause a toxic gain of function in NTE. PMID:10585848

  11. 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 ?-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, ?-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

  12. Mechanism of enterovirus involvement in epidemic neuropathy: hypothesis regarding pathophysiology

    Microsoft Academic Search

    P. Más Lago; M. Guadalupe Guzmán; L. Sarmiento; A. B. Pérez; M. Alvarez; V. Capó; I. Avalos; G. K. Flores

    2001-01-01

    During the epidemic of optic and peripheral neuropathy which occurred in Cuba in 1992–1993, viruses antigenically related to the Coxsackie viruses were isolated from cerebrospinal fluid of patients. Concurrently with the virologic studies, epidemiologic, toxicologic, nutritional, immunologic, and histopathologic investigations were also carried out. Although it was demonstrated that the illness was associated with toxic and nutritional risk factors, it

  13. [Occupational toxic neuropathies: morphology in peripheral nerve biopsies].

    PubMed

    Scelsi, Roberto; Candura, Stefano M

    2012-01-01

    Many peripheral neuropathies are caused by the (acute or chronic) toxic action of metals, solvents, pesticides, and other occupational and environmental contaminants. These agents often reproduce the anatomoclinical pictures of hereditary (e.g., Charcot-Marie-Tooth disease), autoimmune (Guillain-Barrè syndrome), or dysmetabolic (thiamine deficiency, diabetic neuropathy) forms. Toxic peripheral neuropathies can be classified on the basis of etiology, clinical features (sensitive, motor, sensitive-motor), or histopathology: neuronopathies (uncommon, mostly secondary to retrograde axonal degeneration; e.g., arsenic, thallium), axonopathies (acrylamide, esacarbons, CS2, organophosphate-induced delayed neuropathy), myelinopathies (trichloroethylene), mixed forms (axonal and demyelinating: lead). For many substances, experimental research has led to the identification of the molecular and cellular targets of neurotoxicity. Several compounds are active by biotransformation (e.g., the esacarbons n-hexane and MnBK are neurotoxic since they are metabolized to 2,5-hexanedione), Genetic, physiological and environmental factors determine the individual metabolic set-up, and they may give origin to differences in the workers' sensitivity. Cessation of exposure is often followed by (microscopically observable) regenerative phenomena and clinical improvement. The morphology of neuropathies can be studied through peripheral nerve biopsy. Samples of sural nerve (or other nervous trunks of the limbs), adequately fixed, sectioned, and stained, allow the observation of alterations in axonal fibres (e.g., giant-axonal neuropathy, dying back neuropathy), myelin (demyelination), Schwann cells, interstitium, and blood vessels; possible inflammatory infiltrates; fibre density; regenerative phenomena (growth cone, remyelination). In occupational medicine, biopsy is indicated when the anamnestic-clinical picture, laboratory tests, and instrumental exams leave doubts about the nature, type, and entity of the neurological damage. In such cases, current optical and electron microscopy techniques can be very useful for injury evaluation, prognosis, and follow-up. PMID:23477107

  14. Diabetic autonomic neuropathy.

    PubMed

    Vinik, Aaron I; Erbas, Tomris

    2013-01-01

    Autonomic neuropathy, once considered to be the Cinderella of diabetes complications, has come of age. The autonomic nervous system innervates the entire human body, and is involved in the regulation of every single organ in the body. Thus, perturbations in autonomic function account for everything from abnormalities in pupillary function to gastroparesis, intestinal dysmotility, diabetic diarrhea, genitourinary dysfunction, amongst others. "Know autonomic function and one knows the whole of medicine!" It is now becoming apparent that before the advent of severe pathological damage to the autonomic nervous system there may be an imbalance between the two major arms, namely the sympathetic and parasympathetic nerve fibers that innervate the heart and blood vessels, resulting in abnormalities in heart rate control and vascular dynamics. Cardiac autonomic neuropathy (CAN) has been linked to resting tachycardia, postural hypotension, orthostatic bradycardia and orthostatic tachycardia (POTTS), exercise intolerance, decreased hypoxia-induced respiratory drive, loss of baroreceptor sensitivity, enhanced intraoperative or perioperative cardiovascular lability, increased incidence of asymptomatic ischemia, myocardial infarction, and decreased rate of survival after myocardial infarction and congestive heart failure. Autonomic dysfunction can affect daily activities of individuals with diabetes and may invoke potentially life-threatening outcomes. Intensification of glycemic control in the presence of autonomic dysfunction (more so if combined with peripheral neuropathy) increases the likelihood of sudden death and is a caveat for aggressive glycemic control. Advances in technology, built on decades of research and clinical testing, now make it possible to objectively identify early stages of CAN with the use of careful measurement of time and frequency domain analyses of autonomic function. Fifteen studies using different end points report prevalence rates of 1% to 90%. CAN may be present at diagnosis, and prevalence increases with age, duration of diabetes, obesity, smoking, and poor glycemic control. CAN also cosegregates with distal symmetric polyneuropathy, microangiopathy, and macroangiopathy. It now appears that autonomic imbalance may precede the development of the inflammatory cascade in type 2 diabetes and there is a role for central loss of dopaminergic restraint on sympathetic overactivity. Restoration of dopaminergic tone suppresses the sympathetic dominance and reduces cardiovascular events and mortality by close to 50%. Cinderella's slipper can now be worn! PMID:24095132

  15. [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

  16. Compression and entrapment neuropathies.

    PubMed

    Bouche, P

    2013-01-01

    Peripheral nerve entrapments are frequent. They usually appear in anatomical tunnels such as the carpal tunnel. Nerve compressions may be due to external pressure such as the fibular nerve at the fibular head. Malignant or benign tumors may also damage the nerve. For each nerve from the upper and lower limbs, detailed clinical, electrophysiological, imaging, and therapeutic aspects are described. In the upper limbs, carpal tunnel syndrome and ulnar neuropathy at the elbow are the most frequent manifestations; the radial nerve is less frequently involved. Other nerves may occasionally be damaged and these are described also. In the lower limbs, the fibular nerve is most frequently involved, usually at the fibular head by external compression. Other nerves may also be involved and are therefore described. The clinical and electrophysiological examination are very important for the diagnosis, but imaging is also of great use. Treatments available for each nerve disease are discussed. PMID:23931789

  17. [Ulnar entrapment neuropathy].

    PubMed

    Blecher, Ronen; Loebenberg, Mark; Oron, Amir

    2010-02-01

    Ulnar nerve entrapment is one of the most common entrapment neuropathies in the upper limb. The most frequent location of this syndrome is behind the elbow. The clinical picture is associated with the localization of the entrapment but usually consists of an altered sensation at the fourth and fifth digits and a weakness of the intrinsic muscles of the palm. The most constructive tool in making the diagnosis and in assessing the treatment's efficacy is the physical examination. Treatment alternatives depend on entrapment location. Conservative treatment options such as rest, a change in the work environment and patterns as well as splints are all accepted modalities. A lack of improvement following conservative treatment or a deteriorating nerve function is an indication for surgical intervention. This includes procedures comprised of decompression of the ulnar nerve alone or those which combine its transposition. PMID:20549929

  18. Canine inherited hypertrophic neuropathy.

    PubMed

    Cummings, J F; Cooper, B J; de Lahunta, A; van Winkle, T J

    1981-01-01

    A recessively inherited hypertrophic neuropathy was discovered in Tibetan Mastiff dogs. Affected pups developed a generalized weakness with hyporeflexia shortly after weaning. Diagnostic findings in 10-18-week-old pups included: moderate to severe reduction in nerve conduction velocities, infrequent denervation potentials, and inconstant elevation in CSF protein. Light- and electron-microscopic studies of peripheral nerves and roots revealed widespread demyelination and primitive onion bulb formation with relatively little degeneration of axons. Myelin changes often were most striking in the cytoplasmic regions of the sheaths and consisted of separations at the major dense lines, anomalous incisure patterns, and marked filamentous accumulations in the inner spirals and adaxonal cytoplasm. The results of these initial studies suggest an inborn defect in the Schwann cell's ability to form or maintain a stable myelin sheath. PMID:6259873

  19. 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.

  20. Medication-induced peripheral neuropathy

    Microsoft Academic Search

    Louis H. Weimer

    2003-01-01

    Although not very common, medication-induced neuropathy is a treatable condition and, therefore, is important to identify.\\u000a Medications continue to grow in number and expand in usage; consequently, toxic neuropathy continues to be relevant to neurologists.\\u000a Many agents have toxicities that are tolerated because the treatments are necessary, such as therapies for HIV and malignancy.\\u000a Additional agents to prevent or ameliorate

  1. 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 [Department of Ophthalmology, Dongfang Hospital, Beijing University of Chinese Medicine and Pharmacology, Beijing 100078 (China); Zhou Xiangtian [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Yang Li [Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229 (United States); Sun Yanhong [Department of Ophthalmology, Dongfang Hospital, Beijing University of Chinese Medicine and Pharmacology, Beijing 100078 (China); Zhou Jian [Department of Ophthalmology, Dongfang Hospital, Beijing University of Chinese Medicine and Pharmacology, Beijing 100078 (China); Li Guang [Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229 (United States); Jiang, Robert [Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229 (United States); Lu Fan [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Qu Jia [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China)]. E-mail: jqu@wzmc.net; Guan Minxin [Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229 (United States) and Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China) and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229 (United States)]. 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.

  2. Other Optic Nerve Maladies in Cancer Patients

    Microsoft Academic Search

    Jade S. Schiffman; Anitha Raghunath; Rosa Ana Tang

    \\u000a Many optic neuropathies in cancer patients are related to the direct effect of cancer on the optic nerve (e.g., orbital and\\u000a parasellar skull base compressive lesions or infiltration of the optic nerve with leptomeningeal disease). However, a number\\u000a of optic neuropathies occur unrelated to those mechanisms. Other mechanisms of optic neuropathy in cancer patients include\\u000a those caused by raised intracranial

  3. Reversible Neuropathy in Chronic Renal Failure

    Microsoft Academic Search

    A. Roy; J. Kalita; N. Gayathri; S. K. Shankar; U. K. Misra

    1998-01-01

    Chronic renal failure is associated with distal symmetrical axonal neuropathy. We report a 50-year-old man who suffered from chronic renal failure due to benign enlargement of the prostate. He presented with fever and rapidly developing pure motor neuropathy. The nerve conduction velocity was slow and the F response delayed, suggestive of demyelinating neuropathy. A sural nerve biopsy specimen was also

  4. The spectrum of diabetic neuropathies.

    PubMed

    Tracy, Jennifer A; Dyck, P James B

    2008-02-01

    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 studied extensively, 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 caused directly by diabetes mellitus, whereas others are associated with it but not caused by hyperglycemia. This article discusses a number of the more common disorders of nerve found with diabetes mellitus. It discusses the symmetrical neuropathies, particularly generalized diabetic polyneuropathy, and then the focal or asymmetrical types of diabetes-associated neuropathy. PMID:18194747

  5. 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

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

    PubMed Central

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

    2014-01-01

    Leber’s Hereditary Optic Neuropathy (LHON) is one of the commonest mitochondrial diseases. It causes total blindness, and predominantly affects young males. For the disease to develop, it is necessary for an individual to carry one of the primary mtDNA mutations 11778G>A, 14484T>C or 3460G>A. However these mutations are not sufficient to cause disease, and they do not explain the characteristic features of LHON such as the higher prevalence in males, incomplete penetrance, and relatively later age of onset. In order to explore the roles of nuclear encoded mitochondrial proteins in development of LHON, we applied a proteomic approach to samples from affected and unaffected individuals from 3 pedigrees and from 5 unrelated controls. Two-dimensional electrophoresis followed by MS/MS analysis in the mitochondrial lysate identified 17 proteins which were differentially expressed between LHON cases and unrelated controls, and 24 proteins which were differentially expressed between unaffected relatives and unrelated controls. The proteomic data were successfully validated by western blot analysis of 3 selected proteins. All of the proteins identified in the study were mitochondrial proteins and most of them were down regulated in 11778G>A mutant fibroblasts. These proteins included: subunits of OXPHOS enzyme complexes, proteins involved in intermediary metabolic processes, nucleoid related proteins, chaperones, cristae remodelling proteins and an anti-oxidant enzyme. The protein profiles of both the affected and unaffected 11778G>A carriers shared many features which differed from those of unrelated control group, revealing similar proteomic responses to 11778G>A mutation in both affected and unaffected individuals. Differentially expressed proteins revealed two broad groups: a cluster of bioenergetic pathway proteins and a cluster involved in protein quality control system. Defects in these systems are likely to impede the function of retinal ganglion cells, and may lead to the development of LHON in synergy with the primary mtDNA mutation. PMID:25215595

  7. Use of transmitochondrial cybrids to assign a complex I defect to the mitochondrial DNA-encoded NADH dehydrogenase subunit 6 gene mutation at nucleotide pair 14459 that causes Leber hereditary optic neuropathy and dystonia.

    PubMed Central

    Jun, A S; Trounce, I A; Brown, M D; Shoffner, J M; Wallace, D C

    1996-01-01

    A heteroplasmic G-to-A transition at nucleotide pair (np) 14459 within the mitochondrial DNA (mtDNA)-encoded NADH dehydrogenase subunit 6 (ND6) gene has been identified as the cause of Leber hereditary optic neuropathy (LHON) and/or pediatric-onset dystonia in three unrelated families. This ND6 np 14459 mutation changes a moderately conserved alanine to a valine at amino acid position 72 of the ND6 protein. Enzymologic analysis of mitochondrial NADH dehydrogenase (complex I) with submitochondrial particles isolated from Epstein-Barr virus-transformed lymphoblasts revealed a 60% reduction (P < 0.005) of complex I-specific activity in patient cell lines compared with controls, with no differences in enzymatic activity for complexes II plus III, III and IV. This biochemical defect was assigned to the ND6 np 14459 mutation by using transmitochondrial cybrids in which patient Epstein-Barr virus-transformed lymphoblast cell lines were enucleated and the cytoplasts were fused to a mtDNA-deficient (p 0) lymphoblastoid recipient cell line. Cybrids harboring the np 14459 mutation exhibited a 39% reduction (p < 0.02) in complex I-specific activity relative to wild-type cybrid lines but normal activity for the other complexes. Kinetic analysis of the np 14459 mutant complex I revealed that the Vmax of the enzyme was reduced while the Km remained the same as that of wild type. Furthermore, specific activity was inhibited by increasing concentrations of the reduced coenzyme Q analog decylubiquinol. These observations suggest that the np 14459 mutation may alter the coenzyme Q-binding site of complex I. PMID:8622678

  8. 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

  9. Subdural Hemorrhage Mimicking Peripheral Neuropathy

    PubMed Central

    Kim, Hye Ihn; Oh, Yeo Jin; Cho, Yu Na

    2014-01-01

    Subdural hemorrhage (SDH) can manifest various neurologic symptoms. However, SDH presenting with only hand weakness has rarely been reported. We report two SDH cases with only hand weakness mimicking peripheral neuropathy. Since SDH can present with hand weakness only, we suggest the clinicians to do a careful history taking and recommend a CT scan in the elderly patients. PMID:25328658

  10. Early onset (childhood) monogenic neuropathies.

    PubMed

    Landrieu, Pierre; Baets, Jonathan

    2013-01-01

    Hereditary neuropathies (HN) with onset in childhood are categorized according to clinical presentation, pathogenic mechanism based on electrophysiology, genetic transmission and, in selected cases, pathological findings. Especially relevant to pediatrics are the items "secondary" versus "primary" neuropathy, "syndromic versus nonsyndromic," and "period of life." Different combinations of these parameters frequently point toward specific monogenic disorders. Ruling out a neuropathy secondary to a generalized metabolic disorder remains the first concern in pediatrics. As a rule, metabolic diseases include additional, orienting symptoms or signs, and their biochemical diagnosis is based on logical algorithms. Primary, motor sensory are the most frequent HN and are dominated by demyelinating autosomal dominant (AD) forms (CMT1). Other forms include demyelinating autosomal recessive (AR) forms, axonal AD/AR forms, and forms with "intermediate" electrophysiological phenotype. Peripheral motor neuron disorders are dominated by AR SMN-linked spinal muscular atrophies. (Distal) hereditary motor neuropathies represent <10% of HN but exhibit large clinical and genetic heterogeneity. Sensory/dysautonomic HN involves five classic subtypes, each one related to specific genes. However, genetic heterogeneity is larger than initially suspected. Syndromic HN distinguish "purely neurological syndromes", which are multisystemic, such as spinocerebellar atrophies +, spastic paraplegias +, etc. Peripheral neuropathy is possibly the presenting feature, including in childhood. Autosomal recessive forms, on average, start more frequently in childhood. "Multiorgan syndromes", on the other hand, are more specific to Pediatrics. AR forms, which are clearly degenerative, prompt the investigation of a large set of pleiotropic genes. Other syndromes expressed in the perinatal period are mainly developmental disorders, and can sometimes be related to specific transcription factors. Systematic malformative workup and ethical considerations are necessary. Altogether, >40 genes with various biological functions have been found to be responsible for primary HN. Many are responsible for various phenotypes, including some without the polyneuropathic trait, and some for various types of transmission. PMID:23931819

  11. Overview of Optic Nerve Disorders

    MedlinePLUS

    ... Resources for Help and Information The One-Page Merck Manual of Health Medical Terms Conversion Tables Manuals available ... Papilledema Optic Neuritis Ischemic Optic Neuropathy Toxic Amblyopia Merck Manual > Patients & Caregivers > Eye Disorders > Optic Nerve Disorders 4 ...

  12. ORIGINAL ARTICLE Peripheral Neuropathy in Military Aircraft Maintenance

    E-print Network

    Boggess, May M.

    ORIGINAL ARTICLE Peripheral Neuropathy in Military Aircraft Maintenance Workers in Australia Maya. Conclusion: This study highlights chronic persisting peripheral neuropathy in a population of aircraft maintainers. Peripheral neuropathies encompass a wide spectrum of clinical disorders associated with a large

  13. 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 ...

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

    MedlinePLUS

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

  15. [Chemotherapy-induced peripheral neuropathy].

    PubMed

    Noguchi, Emi; Maeda, Yoshiharu

    2011-11-01

    Chemotherapy-induced peripheral neuropathy(CIPN)is one of chemotherapy's common and disabling adverse effects. It may be caused by many chemotherapeutic agents including the taxanes(paclitaxel, docetaxel), the vinca alkaloids(vincristine, vinorelbine, vinblastine), the platinum analogues(cisplatin, carboplatin, oxaliplatin), bortezomib and thalidomide, among others. Once the symptoms have developed, they may lead to compromising patients' quality of life(QOL). For medical oncologists, the management of CIPN remains an important challenge. At the present time, no agent has shown enough solid beneficial evidence to be recommended for the treatment or/prophylaxis of CIPN. The standard of care for CIPN includes awareness and early detection of neuropathy, and dose reduction and/or discontinuation of the problematic agents. PMID:22083183

  16. Clinical features of taxane neuropathy.

    PubMed

    Kudlowitz, David; Muggia, Franco

    2014-05-01

    Sensory neuropathy is the dose-limiting toxicity of paclitaxel and also impacts on the use of docetaxel and other taxanes. The cause of this adverse effect has to do with their mechanism of action against microtubules and its interaction with neuronal cytoskeletal components. The variability of this toxicity is defined by several factors including disease type, taxane class, schedule and dose of the specific drug, patient demographics, and use of taxanes in combination regimens (especially with the platinums that are also neurotoxic). Prevention of life-long neuropathy is only produced if the causative drug is halted--treatments to reverse toxicity have shown only minimal improvement. This review investigates trials defining the clinical factors that determine the therapeutic window of taxanes and the enhanced susceptibility to this toxicity. In addition, case vignettes illustrate the range of clinical manifestations of this toxicity during taxane administration. PMID:24300917

  17. Animal Models of Autoimmune Neuropathy

    PubMed Central

    Soliven, Betty

    2014-01-01

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

  18. Neuromuscular ultrasound in common entrapment neuropathies.

    PubMed

    Cartwright, Michael S; Walker, Francis O

    2013-11-01

    Neuromuscular ultrasound involves the use of high-resolution ultrasound to image the peripheral nervous system of patients with suspected neuromuscular diseases. It complements electrodiagnostic studies well by providing anatomic information regarding nerves, muscles, vessels, tendons, ligaments, bones, and other structures that cannot be obtained with nerve conduction studies and electromyography. Neuromuscular ultrasound has been studied extensively over the past 10 years and has been used most often in the assessment of entrapment neuropathies. This review focuses on the use of neuromuscular ultrasound in 4 of the most common entrapment neuropathies: carpal tunnel syndrome, ulnar neuropathy at the elbow and wrist, and fibular neuropathy at the knee. PMID:23681885

  19. Gastric emptying in diabetic autonomic neuropathy

    Microsoft Academic Search

    I W Campbell; R C Heading; P Tothill; T A Buist; D J Ewing; B F Clarke

    1977-01-01

    Gastric emptying was studied in 12 diabetic patients, six with and six without objective evidence of autonomic neuropathy and in 20 non-diabetic controls, using a double isotope scinti-scanning technique which differentiated between solid and liquid emptying. Three patients with autonomic neuropathy exhibited gastric stasis, although this was detected by conventional radiology in only one. Neither the patients with stasis nor

  20. Entrapment neuropathies in chronic stroke patients.

    PubMed

    Hunkar, Remziye; Balci, Kemal

    2012-02-01

    Stroke is the third most common cause of mortality and is one of the most common causes of morbidity in the world. Entrapment neuropathies may cause morbidity after stroke. In this study, we aimed to evaluate the development of entrapment neuropathies in severe stroke patients within the chronic stages of the event. Thirty-two patients with first ever ischemic or hemorrhagic stroke were included in the study. The nerve conduction studies were performed at least 6 months after the event. Ten age- and sex-matched healthy subjects were evaluated as control subjects. Twelve patients (37.5%) had median nerve neuropathy at the wrist, and 12 patients (37.5%) had ulnar nerve neuropathy at the elbow in the symptomatic extremities. Eight patients (25%) had median nerve neuropathy at the wrist, and 6 patients (18.7%) had ulnar nerve neuropathy at the elbow in the asymptomatic extremities. Our results confirm that in chronic stroke patients, the entrapment neuropathies may be an important cause for morbidity, and these entrapment neuropathies could be seen bilaterally but more prominent in the paretic sides. PMID:22353993

  1. 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

  2. Cisplatin neuropathy in brain tumor chemotherapy

    Microsoft Academic Search

    A. Sghirlanzoni; A. Silvani; V. Scaioli; D. Pareyson; R. Marchesan; A. Boiardi

    1992-01-01

    38 patients with glial brain tumors received 135 mg\\/m2 cisplatin intravenously every month for 5 courses. Signs and symptoms of peripheral neuropathy were evaluated clinically and electrophysiologically. This approach differs from methods previously reported in that it offers two major advantages: primary brain tumors do not cause paraneoplastic neuropathy; no neurotoxic drugs other than cisplatin were employed. Our study confirmed

  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. 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

  5. Peripheral neuropathy incidence in inflammatory bowel disease

    PubMed Central

    Loftus, Edward V.; Harmsen, William S.; Dyck, P. James B.; Klein, Christopher J.

    2013-01-01

    Objective: Our aim was to determine the incidence of peripheral neuropathy in a population-based inflammatory bowel disease (IBD) cohort from Olmsted County, Minnesota. Methods: We retrospectively ascertained neuropathy incidence in a population-based cohort of adult persons newly diagnosed with IBD between 1940 and 2004 in Olmsted County, Minnesota, using the medical records linkage system of the Rochester Epidemiology Project. The Kaplan-Meier method was used to estimate the cumulative incidence of neuropathy. Results: A total of 772 Olmsted County residents aged 18 to 91 years were diagnosed with IBD. After 12,476 person-years, 9 patients developed neuropathy, providing an overall incidence rate of 72 (95% confidence interval [CI] 33–137) cases per 100,000 IBD person-years. The cumulative incidence rates after 10, 20, and 30 years were 0.7% (95% CI 0.0%–1.3%), 0.7% (95% CI 0.0%–1.5%), and 2.4% (95% CI 0.6%–4.6%), respectively. Neuropathy was diagnosed after 1 to 44 years from IBD onset. Only 2 patients had active bowel disease at the time of neuropathy onset. The clinical spectrum consisted of 1) monophasic immune radiculoplexus neuropathy (comorbid diabetes in 2 of 4 patients) and 2) chronic distal sensorimotor polyneuropathy (comorbid diabetes in 2 of 5 patients). Conclusions: Our population-based study suggests that neuropathy is uncommon in the patient population of IBD. Radiculoplexus neuropathy and sensorimotor polyneuropathy were both observed, commonly during periods of bowel disease inactivity. Clinicians should consider other etiologies of neuropathy in patients with IBD. PMID:23576624

  6. Persistence of tropical ataxic neuropathy in a Nigerian community

    PubMed Central

    Oluwole, O; Onabolu, A; Link, H.; Rosling, H.

    2000-01-01

    OBJECTIVES—The term tropical ataxic neuropathy (TAN) is currently used to describe several neurological syndromes attributed to toxiconutritional causes. However, TAN was initially proposed to describe a specific neurological syndrome seen predominantly among the Ijebu speaking Yorubas in south western Nigeria. In this study, the prevalence of TAN was determined in Ososa, a semiurban community in south western Nigeria described as endemic for TAN in 1969, and its neurological features were compared with Strachan's syndrome, prisoners of war neuropathy, the epidemic neuropathy in Cuba, and konzo.?METHODS—A census of Ososa was followed by door to door screening of all subjects aged 10 years and above with a newly designed screening instrument. Subjects who screened positive had a neurological examination, and the diagnosis of TAN was made if any two or more of bilateral optic atrophy, bilateral neurosensory deafness, sensory gait ataxia, or distal symmetric sensory polyneuropathy were present.?RESULTS—A total of 4583 inhabitants were registered in the census. Of these, 3428 subjects aged 10 years and above were screened. The diagnosis of TAN was made in 206 of 323 subjects who screened positive for TAN. The prevalence of TAN was 6.0%, 3.9% in males and 7.7% in females. The highest age specific prevalence was 24% in the 60-69 years age group in women.?CONCLUSION—The occurrence of TAN in Ososa continues at a higher prevalence than was reported 30 years ago. Its neurological features and natural history do not resemble those described for Strachan syndrome, epidemic neuropathy in Cuba, or konzo. The increasing consumption of cassava foods linked to its causation makes TAN of public health importance in Nigeria, the most populous African country.?? PMID:10864612

  7. Clinical features, molecular genetics, and pathophysiology of dominant optic atrophy

    Microsoft Academic Search

    M Votruba; A T Moore; S S Bhattacharya

    1998-01-01

    Inherited optic neuropathies are a significant cause of childhood and adult blindness and dominant optic atrophy (DOA) is the most common form of autosomally inherited (non-glaucomatous) optic neuropathy. Patients with DOA present with an insidious onset of bilateral visual loss and they characteristically have temporal optic nerve pallor, centrocaecal visual field scotoma, and a colour vision deficit, which is frequently

  8. PREVALENCE OF PERIPHERAL NEUROPATHY IN NEWLY DIAGNOSED TYPE 2 DIABETICS

    Microsoft Academic Search

    Arindam Dutta; Santa Naorem; Premchand Singh; Kunjabashi Wangjam

    Our objective was to determine the prevalence and risk factors of peripheral neuropathy in newly diagnosed type 2 diabetes mellitus. One hundred newly diagnosed type 2 diabetic patients attending Diabetes Clinic, Regional Institute of Medical Sciences, Imphal were randomly selected for clinical and electrophysiological studies for diagnosis of peripheral neuropathy. Peripheral neuropathy was evaluated by using Neuropathy Symptoms Score (NSS),

  9. Congenital Cataracts – Facial Dysmorphism – Neuropathy

    PubMed Central

    Kalaydjieva, Luba

    2006-01-01

    Congenital Cataracts Facial Dysmorphism Neuropathy (CCFDN) syndrome is a complex developmental disorder of autosomal recessive inheritance. To date, CCFDN has been found to occur exclusively in patients of Roma (Gypsy) ethnicity; over 100 patients have been diagnosed. Developmental abnormalities include congenital cataracts and microcorneae, primary hypomyelination of the peripheral nervous system, impaired physical growth, delayed early motor and intellectual development, mild facial dysmorphism and hypogonadism. Para-infectious rhabdomyolysis is a serious complication reported in an increasing number of patients. During general anaesthesia, patients with CCFDN require careful monitoring as they have an elevated risk of complications. CCFDN is a genetically homogeneous condition in which all patients are homozygous for the same ancestral mutation in the CTDP1 gene. Diagnosis is clinical and is supported by electrophysiological and brain imaging studies. The major differential diagnosis is Marinesco-Sjögren syndrome. The definitive diagnosis is molecular, based on homozygosity for the CTDP1 mutation. CTDP1 maps to 18qter and encodes a protein phosphatase whose only known substrate is the phosphorylated serine residues of the carboxy-terminal domain of the largest subunit of RNA polymerase II, indicating that CCFDN affects basic cellular processes of gene expression and developmental regulation. Families benefit from genetic counselling and predictive testing. Management includes surgical treatment of the cataracts, and rehabilitation and corrective orthopaedic surgery for the peripheral neuropathy. Thus, the most disabling manifestations, though not curable, are manageable, and allow an acceptable quality of life and everyday living. Current data indicate that patients survive well into adulthood. PMID:16939648

  10. 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

  11. Diabetic cervical radiculoplexus neuropathy: a distinct syndrome expanding the spectrum of diabetic radiculoplexus neuropathies.

    PubMed

    Massie, Rami; Mauermann, Michelle L; Staff, Nathan P; Amrami, Kimberly K; Mandrekar, Jayawant N; Dyck, Peter J; Klein, Christopher J; Dyck, P James B

    2012-10-01

    Diabetic lumbosacral radiculoplexus neuropathy is a subacute painful, asymmetrical lower limb neuropathy due to ischaemic injury and microvasculitis. The occurrence of a cervical diabetic radiculoplexus neuropathy has been postulated. Our objective was to characterize the clinical features and pathological alterations of diabetic cervical radiculoplexus neuropathy, to see if they are similar to diabetic lumbosacral radiculoplexus neuropathy and due to ischaemic injury and microvasculitis. We identified patients with diabetic cervical radiculoplexus neuropathy by review of the Mayo Clinic database from 1996 to 2008. We systematically reviewed the clinical features, laboratory studies, neurophysiological findings, neuroimaging and pathological features and compared the findings with a previously published diabetic lumbosacral radiculoplexus neuropathy cohort. Eighty-five patients (56 males, 67 with Type 2 diabetes mellitus) were identified. The median age was 62 years (range 32-83). The main presenting symptom was pain (53/85). At evaluation, weakness was the most common symptom (84/85), followed by pain (69/85) and numbness (56/85). Neuropathic deficits were moderate (median motor neuropathy impairment score 10.0 points) and improved at follow-up. Upper, middle and lower brachial plexus segments were involved equally and pan-plexopathy was not unusual (25/85). Over half of patients (44/85) had at least one additional body region affected (30 contralateral cervical, 20 lumbosacral and 16 thoracic) as is found in diabetic lumbosacral radiculoplexus neuropathy. Recurrent disease occurred in 18/85. Neurophysiology showed axonal neuropathy (80/80) with paraspinal denervation (21/65), and abnormal autonomic (23/24) and sensory testing (10/13). Cerebrospinal fluid protein was elevated (median 70 mg/dl). Magnetic resonance imaging showed brachial plexus abnormality in all (38/38). Nerve biopsies (11 upper and 11 lower limbs) showed ischaemic injury (axonal degeneration, multifocal fibre loss 15/22, focal perineurial thickening 16/22, injury neuroma 5/22) and increased inflammation (epineural perivascular inflammation 22/22, haemosiderin deposition 6/22, vessel wall inflammation 14/22 and microvasculitis 5/22). We therefore conclude that (i) diabetic cervical radiculoplexus neuropathy is a predominantly monophasic, upper limb diabetic neuropathy with pain followed by weakness and involves motor, sensory and autonomic fibres; (ii) the neuropathy begins focally and often evolves into a multifocal or bilateral condition; (iii) the pathology of diabetic cervical radiculoplexus neuropathy demonstrates ischaemic injury often from microvasculitis; and (iv) diabetic cervical radiculoplexus neuropathy shares many of the clinical and pathological features of diabetic lumbosacral radiculoplexus neuropathy, providing evidence that these conditions are best categorized together within the spectrum of diabetic radiculoplexus neuropathies. PMID:23065793

  12. Compressive neuropathy in the upper limb

    PubMed Central

    Thatte, Mukund R.; Mansukhani, Khushnuma A.

    2011-01-01

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

  13. Acute motor neuropathy with pure distal involvement--a case report of multifocal motor neuropathy.

    PubMed

    Ramdas, Sithara; Prasad, Manish; Spillane, Kate; Kirkpatrick, Martin

    2013-07-01

    Multifocal motor neuropathy is an acquired pure motor neuropathy seen principally in adults and usually responds to treatment with intravenous immunoglobulin. We report a 12 year old boy with marked distal weakness in both upper and lower limbs with no proximal involvement. These clinical features appear to be distinct from more common inflammatory childhood neuropathies and are in keeping with a diagnosis of Multifocal Motor Neuropathy. Confirming the diagnosis, serial nerve conduction studies showed a pattern of pure motor conduction block with normal sensory potentials. To our knowledge this is only the second case report of this condition occurring in childhood. PMID:23416060

  14. Coenzyme Q10 therapy in hereditary motor sensory neuropathy type VI with novel mitofusin 2 mutation.

    PubMed

    Takahashi, Ryoichi; Ikeda, Tokuhei; Hamaguchi, Ayumi; Iwasa, Kazuo; Yamada, Masahito

    2012-01-01

    Hereditary motor sensory neuropathy type VI (HMSN VI) is hereditary neuropathy accompanied by optic neuropathy. The feasibility of Coenzyme Q10 (CoQ10) as a treatment for subacute visual impairment of HMSN VI was examined. A 37-year-old patient with HMSN VI with a novel mitofusin 2 mutation was treated with high dose of CoQ10 (200 mg/day) for eight months. Visual impairment was partially resolved after CoQ10 therapy. High dose CoQ10 therapy may improve the prognosis of subacute visual impairment in HMSN VI. To confirm the effectiveness of CoQ10 on HMSN VI, further studies are needed. PMID:22466841

  15. Pathogenesis of Painful Diabetic Neuropathy

    PubMed Central

    Rajbhandari, Satyan

    2014-01-01

    The prevalence of diabetes is rising globally and, as a result, its associated complications are also rising. Painful diabetic neuropathy (PDN) is a well-known complication of diabetes and the most common cause of all neuropathic pain. About one-third of all diabetes patients suffer from PDN. It has a huge effect on a person's daily life, both physically and mentally. Despite huge advances in diabetes and neurology, the exact mechanism of pain causation in PDN is still not clear. The origin of pain could be in the peripheral nerves of the central nervous system. In this review, we discuss various possible mechanisms of the pathogenesis of pain in PDN. We discuss the role of hyperglycaemia in altering the physiology of peripheral nerves. We also describe central mechanisms of pain. PMID:24891949

  16. Diabetic neuropathies: components of etiology.

    PubMed

    Tomlinson, David R; Gardiner, Natalie J

    2008-06-01

    This review examines the putative role of glucose in the etiology of diabetic neuropathies. Excessive glucose generates several secondary metabolic anomalies - principally oxidative stress (via both the polyol pathway and glucoxidation) and non-enzymic glycation of macromolecules. The latter is also facilitated by glucoxidation. These metabolic deviations trigger cellular responses that are inappropriate to normal function. Principal among these are neurotrophic deficits and phosphorylation of mitogen-activated protein kinases (MAPK). Downstream of these events are aberrant ion channel function and disordered gene expression, leading to changes in cellular phenotype. This leads directly to disordered nerve conduction, a recognised early clinical sign, and indirectly, via as yet undisclosed links, to sensory loss and axonopathy. Recent work also links MAPK activation to the development of neuropathic pain. PMID:18601656

  17. 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

  18. Diabetic neuropathy: Clinical manifestations and current treatments

    PubMed Central

    Callaghan, Brian C.; Cheng, Hsinlin; Stables, Catherine L.; Smith, Andrea L.; Feldman, Eva L.

    2014-01-01

    Diabetic peripheral neuropathy is a prevalent, disabling condition. The most common manifestation is a distal symmetric polyneuropathy (DSP), but many patterns of nerve injury can occur. Currently, the only effective treatments are glucose control and pain management. While glucose control dramatically decreases the development of neuropathy in those with type 1 diabetes, the effect is likely much smaller in those with type 2 diabetes. High levels of evidence support the use of certain anticonvulsants and antidepressants for pain management in diabetic peripheral neuropathy. However, the lack of disease modifying therapies for diabetic DSP makes the identification of new modifiable risk factors essential. Intriguingly, growing evidence supports an association between metabolic syndrome components, including pre-diabetes, and neuropathy. Future studies are needed to further explore this relationship with implications for new treatments for this common disease. PMID:22608666

  19. Genetics Home Reference: Small fiber neuropathy

    MedlinePLUS

    ... disease or Sjogren syndrome, an inflammatory condition called sarcoidosis, and human immunodeficiency virus (HIV) infection. Read more ... palpitations ; peripheral ; peripheral nervous system ; peripheral neuropathy ; prevalence ; sarcoidosis ; sensitivity ; sodium ; sodium channel ; subunit ; syndrome ; virus You ...

  20. Auditory Neuropathy Spectrum Disorder (ANSD) (For Parents)

    MedlinePLUS

    ... ANSD Hearing loss is a common problem in newborns. Some cases are due to auditory neuropathy spectrum ... result, many questions remain about it. Not all newborn hearing screening programs can identify ANSD, so many ...

  1. Genetics Home Reference: Ataxia neuropathy spectrum

    MedlinePLUS

    ... contain a small amount of DNA, known as mitochondrial DNA (mtDNA), which is essential for the normal function ... dominant ; autosomal recessive ; cell ; deletion ; depletion ; depression ; DNA ; ... myoclonus ; neuropathy ; ophthalmoplegia ; oxygen ; prevalence ; protein ; ptosis ; ...

  2. Diagnosis of hereditary neuropathies in adult patients

    Microsoft Academic Search

    Davide Pareyson

    2003-01-01

    .   This paper reviews the clinical diagnostic approach to hereditary neuropathies in adults by analysing: elements that point\\u000a to a neuropathy of inherited origin, different modalities of presentation, laboratory and instrumental diagnostic tests, including\\u000a molecular tests, symptoms and signs of involvement of other organs. Different phenotypes may be identified according to: disease\\u000a course; involvement of motor, sensory, autonomic fibres; site

  3. Congenital cataracts, facial dysmorphism, and neuropathy syndrome.

    PubMed

    Tzifi, Flora; Pons, Roser; Athanassaki, Corina; Poulou, Myrto; Kanavakis, Emmanuel

    2011-09-01

    Congenital cataracts, facial dysmorphism, and neuropathy syndrome is a delineated genetic disease exclusively manifested in the Roma population. The pattern of inheritance is autosomal recessive, and a causative mutation is evident in the CTDP1 gene. Affected patients display congenital cataracts, microcornea, peripheral neuropathy, mild facial dysmorphism, hypogonadism, and psychomotor delay. We present the second case of this syndrome in a Greek Roma family, diagnosed in early infancy, along with the prenatal diagnosis in a subsequent pregnancy. PMID:21824574

  4. Sonography of entrapment neuropathies in the upper limb (wrist excluded).

    PubMed

    Martinoli, Carlo; Bianchi, Stefano; Pugliese, Francesca; Bacigalupo, Lorenzo; Gauglio, Cristina; Valle, Maura; Derchi, Lorenzo E

    2004-01-01

    The progressive refinement of broadband transducers with frequencies higher than 10 MHz and improved near-field resolution has enhanced the potential of sonography to evaluate a variety of nerve entrapment syndromes occurring in the upper limb, such as suprascapular neuropathy in the area of the spinoglenoid-supraspinous notch, the quadrilateral space syndrome (axillary neuropathy), radial neuropathy in the area of the spiral groove, the supinator syndrome (posterior interosseous neuropathy), the cubital tunnel syndrome (ulnar neuropathy), and the Kiloh-Nevin syndrome (anterior interosseous neuropathy). In these settings, high-resolution sonography can depict changes in the nerve's shape and echotexture and can depict many extrinsic causes of nerve entrapment. PMID:15558622

  5. MR Neurography in Ulnar Neuropathy as Surrogate Parameter for the Presence of Disseminated Neuropathy

    PubMed Central

    Bäumer, Philipp; Weiler, Markus; Ruetters, Maurice; Staub, Frank; Dombert, Thomas; Heiland, Sabine; Bendszus, Martin; Pham, Mirko

    2012-01-01

    Purpose Patients with ulnar neuropathy of unclear etiology occasionally present with lesion extension from elbow to upper arm level on MRI. This study investigated whether MRI thereby distinguishes multifocal neuropathy from focal-compressive neuropathy at the elbow. Methods This prospective study was approved by the institutional ethics committee and written informed consent was obtained from all participants. 122 patients with ulnar mononeuropathy of undetermined localization and etiology by clinical and electrophysiological examination were assessed by MRI at upper arm and elbow level using T2-weighted fat-saturated sequences at 3T. Twenty-one patients were identified with proximal ulnar nerve lesions and evaluated for findings suggestive of disseminated neuropathy (i) subclinical lesions in other nerves, (ii) unfavorable outcome after previous decompressive elbow surgery, and (iii) subsequent diagnosis of inflammatory or other disseminated neuropathy. Two groups served as controls for quantitative analysis of nerve-to-muscle signal intensity ratios: 20 subjects with typical focal ulnar neuropathy at the elbow and 20 healthy subjects. Results In the group of 21 patients with proximal ulnar nerve lesion extension, T2-w ulnar nerve signal was significantly (p<0.001) higher at upper arm level than in both control groups. A cut-off value of 1.92 for maximum nerve-to-muscle signal intensity ratio was found to be sensitive (86%) and specific (100%) to discriminate this group. Ten patients (48%) exhibited additional T2-w lesions in the median and/or radial nerve. Another ten (48%) had previously undergone elbow surgery without satisfying outcome. Clinical follow-up was available in 15 (71%) and revealed definitive diagnoses of multifocal neuropathy of various etiologies in four patients. In another eight, diagnoses could not yet be considered definitive but were consistent with multifocal neuropathy. Conclusion Proximal ulnar nerve T2 lesions at upper arm level are detected by MRI and indicate the presence of a non-focal disseminated neuropathy instead of a focal compressive neuropathy. PMID:23166762

  6. 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...

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

    MedlinePLUS

    ... to feel pain, heat, and cold. Deep pain perception, the feeling of pain from injuries to bones, ... gene ; growth factor ; hereditary ; inherited ; joint ; mutation ; neuropathy ; perception ; protein ; receptor ; recessive ; sensory nerve ; sensory neuropathy ; tissue ; ...

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

    MedlinePLUS

    ... nervous system ; autosomal ; autosomal recessive ; bud ; cell ; congenital ; digestion ; digestive ; esophagus ; gastroesophageal reflux ; gene ; hereditary ; inherited ; injury ; involuntary ; isoforms ; nervous system ; neuropathy ; prevalence ; protein ; recessive ; reflex ; sensory nerve ; sensory neuropathy ; sign ; spontaneous ; ...

  9. 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 ?-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

  10. 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

  11. Goiter and laryngeal sensory neuropathy.

    PubMed

    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?cm(3), with a range from 9.430 to 67.022?cm(3). 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

  12. 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

  13. 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

  14. [Original articles on axonal neuropathy in 2010].

    PubMed

    Attarian, S

    2011-12-01

    During 2010, 15 articles were published which focused on chronic sensorimotor axonal neuropathy; some will be discussed in this review. Clinical diagnosis from signs and symptoms seems to be excessively variable, often overestimating the incidence of diabetic sensorimotor polyneuropathy. Long-term use of Metformin is associated with malabsorption of vitamin B12. Metformin exposure may be a iatrogenic cause for exacerbation of peripheral neuropathy in patients with type 2 diabetes. The neuroprotective role of vitamin E against cisplatinperipheral neurotoxicity has been suggested by a phase III study. Metallosis after hip arthroplasty with a cobalt-chromium alloy prosthesis can cause progressive sensory disturbance, hearing loss and hypothyroidism. The effects of electrical stimulation on neuromuscular recovery after nerve crush injury in rats do not support a benefit of the tested protocol using electrical stimulation during the period of motor nerve recovery following injury. The rate of motor vehicle accidents in patients with neuropathy, based on surveys from 260 subjects, demonstrated that 40.6% were involved in traffic accidents. Accident frequency and discomfort with driving are higher in neuropathy patients compared to age-matched national statistics. Peripheral neuropathy in primary (AL) amyloidosis may be the cause of stepwise progressive, multiple upper limb mononeuropathies. PMID:22100324

  15. Nanostructured Biosensor for Measuring Neuropathy Target Esterase Activity

    E-print Network

    Lee, Ilsoon

    Nanostructured Biosensor for Measuring Neuropathy Target Esterase Activity Neeraj Kohli, Devesh, Ann Arbor, Michigan 48109-2029 Neuropathy target esterase (NTE) is a membrane protein found in human is believed to cause OP-induced delayed neuropathy (OPIDN), a type of paralysis for which

  16. The Center for Peripheral Neuropathy Department of Neurology

    E-print Network

    Sherman, S. Murray

    #12;The Center for Peripheral Neuropathy Department of Neurology The University of Chicago 5841 South Maryland Avenue, MC2030 Chicago, Illinois 60637 Director, Center for Peripheral Neuropathy Brian Popko, Ph.D. Phone: 773.702.4953 Fax: 773.702.5577 Appointments: 773-702-5659 Website: http://PeripheralNeuropathy

  17. Ulnar Neuropathy With Normal Electrodiagnosis and Abnormal Nerve Ultrasound

    Microsoft Academic Search

    Joon Shik Yoon; Francis O. Walker; Michael S. Cartwright

    2010-01-01

    Yoon JS, Walker FO, Cartwright MS. Ulnar neuropathy with normal electrodiagnosis and abnormal nerve ultrasound.Ulnar neuropathy at the elbow (UNE) is the second most common entrapment neuropathy. It is diagnosed with electrodiagnostic studies, but they can yield false-negative results. Ultrasound was used to examine 4 patients with UNE and negative electrodiagnostic findings, and it showed ulnar nerve enlargement near the

  18. Neuropathy of nitroimidazole radiosensitizers: clinical and pathological description

    Microsoft Academic Search

    Todd H. Wasserman; James S. Nelson; Debra Vongerichten

    1984-01-01

    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

  19. Microvasculitis in diabetic lumbosacral radiculoplexus neuropathy.

    PubMed

    Tracy, Jennifer A; Engelstad, JaNean K; Dyck, P James B

    2009-09-01

    We present a case of a 60-year-old man with mild type 2 diabetes mellitus and step-wise progression of bilateral lower limb weakness, numbness, and pain over a 1-year period. At the time of evaluation, he used a walker. He had elevated cerebrospinal fluid protein, abnormal cooling and heat-pain thresholds on quantitative sensory testing, and nerve conduction studies/electromyography consistent with bilateral lumbosacral radiculoplexus neuropathies. Because it was not clear whether the disease was still active, a right superficial peroneal nerve biopsy was performed and showed evidence of active axonal degeneration, ischemic injury, and microvasculitis. On the basis of these results, the patient was diagnosed with diabetic lumbosacral radiculoplexus neuropathy and was treated with weekly intravenous methylprednisolone with marked improvement of neurologic symptoms and signs. This case illustrates the typical clinical, electrophysiologic, and pathologic features of diabetic lumbosacral radiculoplexus neuropathy and the utility of nerve biopsy to judge ongoing disease activity. PMID:19730021

  20. Pupillary signs in diabetic autonomic neuropathy.

    PubMed Central

    Smith, S E; Smith, S A; Brown, P M; Fox, C; Sönksen, P H

    1978-01-01

    Pupillary function was investigated in 36 insulin-dependent diabetics and 36 controls matched for age and sex. About half of the diabetics had evidence of peripheral somatic or autonomic neuropathy, or both. The diabetic patients had abnormally small pupil diameters in the dark and less fluctuation in pupil size (hippus) during continuous illumination than the controls. They also had reduced reflex responses to light flashes of an intensity adjusted for individual retinal sensitivities. The pupillary findings were compared with results of five tests of cardiovascular function and five tests of peripheral sensory and motor nerve function. Almost all the patients with autonomic neuropathy had pupillary signs, which we therefore conclude are a common manifestation of diabetic autonomic neuropathy. PMID:709128

  1. [Diabetic neuropathies. IV. Autonomous neuropathy. Peripheral sympathetic innervation and the cardiovascular system].

    PubMed

    Gentile, S; Marmo, R; Costume, A; Persico, M; Bronzino, P; Contaldi, P; Stroffolini, T

    1984-04-28

    The clinical conditions due to damage to the peripheral sympathetic nervous system during diabetic neuropathy mainly involve alterations to subcutaneous vasomotility , temperature body regulation and exudation, which may take form of hyper or hypoactivity. Gustatory exudation and local anhydrosis are described in detail as well as the connection with aggravating factors like long duration, poor balance and early onset of diabetes mellitus . Change in the relevant cardiovascular reflexes, commonly used in diagnosing diabetic neuropathy, are also analysed with a discussion of their physiopathological background and clinical significance. Finally the painless infarct, sudden death and abnormal response to hypoglycaemia, that are the common features of diabetic neuropathy, are also described. PMID:6728256

  2. Early Electrophysiological Abnormalities and Clinical Neuropathy

    PubMed Central

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

    2013-01-01

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

  3. Retinitis pigmentosa, ataxia, and peripheral neuropathy.

    PubMed Central

    Tuck, R R; McLeod, J G

    1983-01-01

    The clinical features of four patients with retinitis pigmentosa, ataxia and peripheral neuropathy but with no increase in serum phytanic acid are reported. Three patients also had sensorineural deafness and radiological evidence of cerebellar atrophy. Nerve conduction studies revealed abnormalities of sensory conduction and normal or only mild slowing of motor conduction velocity. Sural nerve biopsy demonstrated a reduction in the density of myelinated fibres. There were no onion bulb formations. These cases clinically resemble Refsum's disease, but differ in having no detectable biochemical abnormality, and a peripheral neuropathy which is not hypertrophic in type. They may represent unusual cases of spinocerebellar degeneration. Images PMID:6302225

  4. 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

  5. Alpha-Lipoic Acid and Diabetic Neuropathy

    PubMed Central

    Vallianou, Natalia; Evangelopoulos, Angelos; Koutalas, Pavlos

    2009-01-01

    Diabetic neuropathy presents a major public health problem. It is defined by the symptoms and signs of peripheral nerve dysfunction in diabetic patients, in whom other causes of neuropathy have been excluded. Pathogenetic mechanisms that have been implicated in diabetic neuropathy are: a) increased flux through the polyol pathway, leading to accumulation of sorbitol, a reduction in myo-inositol, and an associated reduced Na+-K+-ATPase activity, and b) endoneurial microvascular damage and hypoxia due to nitric oxide inactivation by increased oxygen free radical activity. Alpha-lipoic acid seems to delay or reverse peripheral diabetic neuropathy through its multiple antioxidant properties. Treatment with alpha-lipoic acid increases reduced glutathione, an important endogenous antioxidant. In clinical trials, 600 mg alpha-lipoic acid has been shown to improve neuropathic deficits. This review focuses on the relationship of alpha-lipoic acid and auto-oxidative glycosylation. It discusses the impact of alpha-lipoic acid on hyperglycemia-induced oxidative stress, and examines the role of alpha-lipoic acid in preventing glycation process and nerve hypoxia. PMID:20043035

  6. 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…

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

    PubMed

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

    1990-01-01

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

  8. 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…

  9. Modulation of Nociception in Painful Diabetic Neuropathy

    E-print Network

    Katz, Natalie

    2014-05-31

    , suggesting that altered adenosine production and decreased activation of the antinociceptive A1 adenosine receptor (A1R) may contribute to the development of painful diabetic neuropathy. In the dorsal horn of the spinal cord, A1R is highly expressed where...

  10. [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

  11. Ozone partially prevents diabetic neuropathy in rats.

    PubMed

    Erken, H A; Genç, O; Erken, G; Ayada, C; Gündo?du, G; Do?an, H

    2015-02-01

    Neuropathy is one of the most common complications of diabetes mellitus. Although the beneficial effects of good blood glucose control on diabetic neuropathy are known, this control cannot completely prevent the occurrence and progression of diabetic neuropathy. The aim of this study was to investigate whether ozone prevents diabetic neuropathy. 36 adult female Sprague-Dawley rats were randomly divided into 6 groups (n=6): control (C), ozone (O), diabetic (D), ozone-treated diabetic (DO), insulin-treated diabetic (DI), and ozone- and insulin-treated diabetic (DOI). Diabetes was induced by a single injection of streptozotocin (60?mg/kg, intraperitoneal [i.p.]), after which insulin was administered (3 IU, i.p.) to the DI and DOI groups for 28 days, and 1.1?mg/kg (50?µg/ml) ozone was given to the O, DO, and DOI groups for 15 days. 4 weeks after the induction of diabetes, the nerve conduction velocity (NCV), amplitude of the compound action potential (CAP), total oxidant status (TOS), and total antioxidant status (TAS) were measured, and the oxidative stress index (OSI) was calculated. The NCV, amplitude of CAP, and TAS of the DI and DOI groups were higher than those of the D group; the amplitudes of CAP and TAS of the DO group were higher than those of the D group; and the TOS and OSI of the DO, DI, and DOI groups were lower than those of the D group. These findings indicate that ozone partially prevents diabetic neuropathy in rats. It appears that the preventive effects of ozone are mediated through oxidant/antioxidant mechanisms. PMID:25502578

  12. 77 FR 47795 - Disease Associated With Exposure to Certain Herbicide Agents: Peripheral Neuropathy

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-10

    ...Certain Herbicide Agents: Peripheral Neuropathy AGENCY: Department of Veterans Affairs...for acute and sub-acute peripheral neuropathy associated with exposure to certain...of service connection for peripheral neuropathy associated with exposure to...

  13. 77 FR 59930 - Clinical Development Programs for Disease-Modifying Agents for Peripheral Neuropathy; Public...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-01

    ...Disease-Modifying Agents for Peripheral Neuropathy; Public Workshop; Request for Comments...agents for the treatment of peripheral neuropathy. Discussion will focus on possible...agents, the types of painful peripheral neuropathies amenable to treatment with...

  14. Cerebellar learning distinguishes inflammatory neuropathy with and without tremor

    PubMed Central

    Schwingenschuh, Petra; Saifee, Tabish A.; Katschnig-Winter, Petra; Reilly, Mary M.; Lunn, Michael P.; Manji, Hadi; Aguirregomozcorta, Maria; Schmidt, Reinhold; Bhatia, Kailash P.; Rothwell, John C.

    2013-01-01

    Objectives: This study aims to investigate if patients with inflammatory neuropathies and tremor have evidence of dysfunction in the cerebellum and interactions in sensorimotor cortex compared to nontremulous patients and healthy controls. Methods: A prospective data collection study investigating patients with inflammatory neuropathy and tremor, patients with inflammatory neuropathy without tremor, and healthy controls on a test of cerebellar associative learning (eyeblink classical conditioning), a test of sensorimotor integration (short afferent inhibition), and a test of associative plasticity (paired associative stimulation). We also recorded tremor in the arms using accelerometry and surface EMG. Results: We found impaired responses to eyeblink classical conditioning and paired associative stimulation in patients with neuropathy and tremor compared with neuropathy patients without tremor and healthy controls. Short afferent inhibition was normal in all groups. Conclusions: Our data strongly suggest impairment of cerebellar function is linked to the production of tremor in patients with inflammatory neuropathy. PMID:23596070

  15. Dermatomyositis-associated sensory neuropathy: a unifying pathogenic hypothesis.

    PubMed

    Nguyen, Thy P; Bangert, Carolyn; Biliciler, Suur; Athar, Parveen; Sheikh, Kazim

    2014-09-01

    Neuropathy as extramuscular manifestation of dermatomyositis (DM) is controversial due to uncommon occurrence, heterogeneity of associated nerve pathology, and lack of unifying pathogenetic mechanism(s). We describe a patient with classic manifestations of DM and extramuscular manifestation of neuropathy. Nerve pathology showed deposits of terminal complement complex (C5b-9). Her examination showed mild proximal weakness, rash, and sensory impairment in fingertips, toes, and nose. EMG/NCS revealed irritable myopathy and mild sensory neuropathy. Muscle biopsy showed features suggestive of DM, including deposition of C5b-9. CK was elevated to 214 and ANA was positive at 1:160. Etiological work up for neuropathy, including diabetes, was negative. Sural nerve biopsy at light level revealed very mild large fiber sensory neuropathy. EM showed moderately severe involvement of small sensory fibers. Neuropathy may be an underrecognized manifestation of DM. Nerve pathology demonstrating complement-mediated damage could be a unifying mechanism of muscle and nerve injury. PMID:25137509

  16. Microvasculitis in Diabetic Lumbosacral Radiculoplexus Neuropathy

    PubMed Central

    Tracy, Jennifer A.; Engelstad, JaNean K.; Dyck, P. James B.

    2009-01-01

    We present a case of a 60-year-old man with mild type 2 diabetes mellitus and step-wise progression of bilateral lower limb weakness, numbness and pain over a one year period. At the time of evaluation, he used a walker. He had elevated CSF protein, abnormal cooling and heat-pain thresholds on quantitative sensory testing, and NCS/EMG consistent with bilateral lumbosacral radiculoplexus neuropathies. Because it was not clear if the disease was still active, a right superficial peroneal nerve biopsy was performed and showed evidence of active axonal degeneration, ischemic injury, and microvasculitis. Based on these results, the patient was diagnosed with diabetic lumbosacral radiculoplexus neuropathy (DLRPN) and was treated with weekly intravenous methylprednisolone with marked improvement of neurological symptoms and signs. This case illustrates the typical clinical, electrophysiologic and pathological features of DLRPN and the utility of nerve biopsy to judge ongoing disease activity. PMID:19730021

  17. [2013: what's new in inflammatory neuropathies].

    PubMed

    Kuntzer, T

    2014-12-01

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

  18. Diagnosis and Treatment of Pain in Small-fiber Neuropathy

    Microsoft Academic Search

    Alexandra Hovaguimian; Christopher H. Gibbons

    2011-01-01

    Small-fiber neuropathy manifests in a variety of different diseases and often results in symptoms of burning pain, shooting\\u000a pain, allodynia, and hyperesthesia. Diagnosis of small-fiber neuropathy is determined primarily by the history and physical\\u000a exam, but functional neurophysiologic testing and skin biopsy evaluation of intraepidermal nerve-fiber density can provide\\u000a diagnostic confirmation. Management of small-fiber neuropathy depends on the underlying etiology

  19. Cytoskeleton, Axonal Transport, and the Mechanisms of Axonal Neuropathy

    Microsoft Academic Search

    Hsinlin T. Cheng; Brian Callaghan; Jacqueline R. Dauch; Eva L. Feldman

    \\u000a Axonal neuropathy, or axonopathy, is a major category of neuropathy in the central and peripheral nervous systems. Axonopathy\\u000a is characterized by axonal degeneration and dysfunctional axonal transport. Peripheral axonopathies are more common than central\\u000a axonopathies due to their lack of protection from the blood–brain barrier and resultant vulnerability to metabolic challenges.\\u000a Although the pathogenic mechanisms of peripheral axonal neuropathy are

  20. Musculocutaneous Neuropathy: Case Report and Discussion

    Microsoft Academic Search

    Diana Besleaga; Vincenzo Castellano; Christopher Lutz; Joseph H. Feinberg

    2010-01-01

    The musculocutaneous nerve arises from the lateral cord of the brachial plexus and contains fibers from the C5, C6, and C7\\u000a spinal nerve roots. It innervates such muscles as the biceps brachii and brachialis as well as supply branches to the skin\\u000a over the lateral cubital and forearm regions via the lateral antebrachial cutaneous nerve. Musculocutaneous neuropathy can\\u000a arise from

  1. A case of an accelerated uremic neuropathy.

    PubMed

    Deger, Serpil Muge; Reis, Kadriye Altok; Guz, Galip; Bali, Musa; Erten, Yasemin

    2011-01-01

    We present a 62-year-old man, with a prior history of diabetes mellitus, atherosclerotic heart disease, and chronic renal failure requiring peritoneal dialysis, who developed accelerated uremic sensorimotor polyneuropathy. Our patient significantly improved after effective hemodialysis. Although renal transplantation is a curable therapy for uremic neuropathy, effective dialysis is still an important treatment for the group of patients who cannot undergo renal transplantation. PMID:21401366

  2. Intrapartum obturator neuropathy diagnosed after cesarean delivery.

    PubMed

    Hong, Bo Young; Ko, Young Jin; Kim, Hye Won; Lim, Seong Hoon; Cho, Ye Rim; Lee, Jong In

    2010-09-01

    Several postpartum neurologic injuries have been described in detail, while obturator nerve injuries are rarely reported. We report a woman who had weakness of the right leg and groin pain after cesarean delivery under general anesthesia. Obturator neuropathy was confirmed by electromyography and no compressive lesion of the nerve was seen on magnetic resonance imaging. The patient was treated conservatively and followed until she recovered fully. PMID:20306064

  3. Neurotrophic Factors and Diabetic Peripheral Neuropathy

    Microsoft Academic Search

    Stuart C. Apfel

    1999-01-01

    Recent evidence from animal models of diabetes and human diabetic subjects suggests that the reduced availability of neurotrophic factors may contribute to the pathogenesis of diabetic peripheral neuropathy (DPN). Of these proteins, nerve growth factor (NGF), brain-derived neurotrophic factor, neurotrophin (NT-3) and NT-4\\/5 appear to be important for the development and maintenance of peripheral neurons, but others, including insulin-like growth

  4. Nerve Growth Factor and Diabetic Neuropathy

    PubMed Central

    Vinik, Aaron

    2003-01-01

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

  5. Pathology and functional diagnosis of small-fiber painful neuropathy.

    PubMed

    Hsieh, Sung-Tsang

    2010-06-01

    Small-fiber sensory neuropathy with neuropathic pain had been a diagnostic challenge for neurologists. We and several groups have developed skin biopsy with quantitation of intraepidermal nerve fiber (IENF) density as a diagnostic approach. In the skin with small-fiber sensory neuropathy, there are pathological hallmarks: reduced IENF density with degeneration of subepidermal nerve plexuses and dermal nerves. Skin denervation is a major presentation of diabetic neuropathy and inflammatory neuropathies including Guillain-Barr syndrome and chronic inflammatory demyelinating polyneuropathy. The skin biopsy approach also provides an opportunity to examine dermal vasculature and inflammatory vasculopathy is demonstrated in vasculitic neuropathy, systemic lupus erythematosus, and eosinophilia-associated neuropathy. In addition to neuropahtologic evidence, the functional consequences of cutaneous nerve degeneration can be assessed with quantitative sensory testing (QST), contact heat evoked potential (CHEP), and functional magnetic resonance imaging (fMRI). One major etiology of small-fiber sensory neuropathy is familial amyloid polyneuropathy caused by mutations of transthyretin (TTR). We recently conducted studies on a large cohort of unique TTR mutation on Ala97Ser in Taiwan. These patients had significant skin denervation in addition to motor and autonomic neuropathy. Taken together, the skin biopsy with quantitation of IENF density provides diagnostic utility for small-fiber sensory neuropathy and the combination of psychophysical, physiological, and neuroimaging examinations offer comprehensive assessments for patients with neuropathic pain due o cutaneous nerve degeneration. PMID:20714957

  6. A Case of Auditory Neuropathy with Recovery of Normal Hearing

    PubMed Central

    Eom, Ji Hun; Min, Hyun Jung; Lee, Ho Ki

    2013-01-01

    Newborn hearing screening test is very important in the early diagnosis of childhood hearing loss because it affects language development. Auditory neuropathy is a spectrum disorder characterized by abnormal auditory brainstem response but preserved otoacoustic emission and cochlear microphonics. In general, auditory neuropathy patients have poor word discrimination and variable patterns of pure tone audiometry. We report on a patient with auditory neuropathy diagnosed at 16 months of age and started wearing hearing aids, but showed normal pure tone and speech audiometric findings 3 years later. Close follow-up for patients with auditory neuropathy is recommended. PMID:24653922

  7. Chemotherapy-induced neuropathy: A comprehensive survey.

    PubMed

    Miltenburg, N C; Boogerd, W

    2014-08-01

    Chemotherapy induced peripheral neuropathy (CIPN) is a potentially dose limiting side effect of commonly used chemotherapeutic agents like taxanes, vinca-alkaloids, platinum compounds, bortezomib and thalidomide. Supposed pathogenetic mechanisms of CIPN are axonopathy through dying back axon damage and neuronopathy in which the cell bodies of the dorsal root ganglia are involved. The exact pathophysiology however is not clear and different underlying mechanisms have been proposed for different classes of anti-cancer drugs. Sensory symptoms, like pain, numbness and tingling are most common, but motor weakness, autonomic dysfunction and even cranial nerve involvement may occur. CIPN can be painful and/or disabling, causing significant loss of functional abilities and decreasing quality of life. This can lead to dose reductions, discontinuation of treatment and may thus, ultimately, affect survival. Risk factors for CIPN include dose per cycle, cumulative dose, treatment schedule, duration of infusion, administration of other chemotherapeutics, comorbidity and pre-existing peripheral neuropathy. The exploration of polymorphisms in genes associated with incidence or severity of neuropathy might result in identifying individuals being at higher risk of neurotoxicity. An update on genes possibly associated with CIPN is given. CIPN may be reversible or be more or less permanent. Many preventive and treatment strategies have been explored, without significant efficacy up till now. In this review we describe the different drug-related characteristics of CIPN, pharmacogenomic studies, neurophysiological findings, treatment and outcome, and neuroprotective strategies. PMID:24830939

  8. Inherited peripheral neuropathies due to mitochondrial disorders.

    PubMed

    Cassereau, J; Codron, P; Funalot, B

    2014-05-01

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

  9. Focal peripheral neuropathies in instrumental musicians.

    PubMed

    Lederman, Richard J

    2006-11-01

    Instrumental musicians often seek medical consultation for symptoms suggestive of nerve entrapment. About 20% of those seen in the author's performing artists' clinic were diagnosed with a focal neuropathy. In general, neuropathies that are most common in the overall population tend also to be most common among musicians, although some expectations exist, including, for example, localized peri-oral sensory syndromes associated with playing a brass instrument, and, possibly, ulnar neuropathies related to the playing position of bowed string players. The diagnosis is made, as always, by careful clinical assessment, including observation of the instrumentalist playing, with ancillary procedures such as nerve conduction studies and needle electromyography adding to the accuracy of the diagnosis. Treatment is similar to that used in nonmusicians, but certain factors, including the musician's requirement for extraordinary neuromuscular dexterity, may influence the therapeutic decisions. Very limited long-term outcome results are available, and additional studies in musicians would be helpful in determining the most appropriate therapeutic approaches. Virtually no longitudinal studies have been performed to look at methods for preventing these disorders. PMID:17097478

  10. A reversible functional sensory neuropathy model.

    PubMed

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

    2014-06-13

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

  11. An unusual cause of peroneal neuropathy.

    PubMed

    Ananth, Amitha L; Yang, Yaping; Lalani, Seema R; Lotze, Timothy B

    2014-06-01

    We discuss the case of a teenage girl who presented with neurologic symptoms suggestive of a peripheral neuropathy, before the development of a central arteriovenous fistula. Electromyography and nerve conduction studies indicated peroneal motor neuropathy, but her comprehensive genetic study results were negative for common Charcot-Marie-Tooth mutations. After 2 years of stable symptoms, she presented with unilateral throbbing headache and tinnitus. Magnetic resonance angiography revealed a carotid cavernous fistula, which was confirmed with conventional angiography. A successful coil embolization of the fistula was performed. Whole exome sequencing demonstrated a de novo heterozygous c.3158G>A (p.G1056D) mutation in the COL31A gene, consistent with Ehlers-Danlos type IV. To our knowledge, this is the first reported case of isolated peroneal motor neuropathy in a patient with Ehlers-Danlos type IV. This case highlights the utility of whole exome sequencing in the diagnosis of patients with neurologic symptoms that do not fit a clear phenotype. PMID:25149929

  12. Aiding and Occluding the Contralateral Ear in Implanted Children with Auditory Neuropathy

    E-print Network

    Litovsky, Ruth

    Aiding and Occluding the Contralateral Ear in Implanted Children with Auditory Neuropathy Spectrum Sergey Tarima Abstract Background: The challenges associated with auditory neuropathy spectrum disorder

  13. 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.

  14. Comparison of Efficiencies of Michigan Neuropathy Screening Instrument, Neurothesiometer, and Electromyography for Diagnosis of Diabetic Neuropathy

    PubMed Central

    Mete, Turkan; Aydin, Yusuf; Saka, Mustafa; Cinar Yavuz, Halise; Bilen, Sule; Yalcin, Yavuz; Arli, Berna; Berker, Dilek; Guler, Serdar

    2013-01-01

    Aim. This study compares the effectiveness of Michigan Neuropathy Screening Instrument (MNSI), neurothesiometer, and electromyography (EMG) in detecting diabetic peripheral neuropathy in patients with diabetes type 2. Materials and Methods. 106 patients with diabetes type 2 treated at the outpatient clinic of Ankara Numune Education and Research Hospital Department of Endocrinology between September 2008 and May 2009 were included in this study. Patients were evaluated by glycemic regulation tests, MNSI (questionnaire and physical examination), EMG (for detecting sensorial and motor defects in right median, ulnar, posterior tibial, and bilateral sural nerves), and neurothesiometer (for detecting alterations in cold and warm sensations as well as vibratory sensations). Results. According to the MNSI score, there was diabetic peripheral neuropathy in 34 (32.1%) patients (score ?2.5). However, when the patients were evaluated by EMG and neurothesiometer, neurological impairments were detected in 49 (46.2%) and 79 (74.5%) patients, respectively. Conclusion. According to our findings, questionnaires and physical examination often present lower diabetic peripheral neuropathy prevalence. Hence, we recommend that in the evaluation of diabetic patients neurological tests should be used for more accurate results and thus early treatment options to prevent neuropathic complications. PMID:23818897

  15. Peripheral Insensate Neuropathy—A Tall Problem for US Adults?

    Microsoft Academic Search

    Yiling J. Cheng; Edward W. Gregg; Henry S. Kahn; Desmond E. Williams; Nathalie De Rekeneire; K. M. Venkat Narayan

    2006-01-01

    The relation between height and lower extremity peripheral insensate neuropathy among persons with and without diabetes was examined by use of the 1999-2002 US National Health and Nutrition Examination Survey with 5,229 subjects aged 40 or more years. A monofilament was used to determine whether any of three areas on each foot were insensate. Peripheral insensate neuropathy was defined as

  16. POEMS Syndrome Diagnosed 10?Years after Disabling Peripheral Neuropathy.

    PubMed

    Nguyen, Viet H

    2011-01-01

    Peripheral neuropathy is characterized as a generalized, relatively homogeneous process affecting many peripheral nerves and predominantly affecting distal nerves. The epidemiology of peripheral neuropathy is limited since the disease presents with varying etiology, pathology, and severity. Toxic, inflammatory, hereditary, and infectious factors can cause damage to the peripheral nerves resulting in peripheral neuropathy. Peripheral neuropathy is most commonly caused by diabetes, alcohol, HIV infection, and malignancy. We report a case of a 42-year-old female with 10-year history of progressively worsening peripheral neuropathy, hypothyroidism, and skin changes who presents with dyspnea secondary to recurrent pleural and pericardial effusions. Prior to her arrival, her peripheral neuropathy was believed to be secondary to chronic demyelinating inflammatory polyneuropathy (CDIP) given elevated protein in the cerebral spinal fluid (CSF) which was treated with intravenous immunoglobulin (IVIG) and corticosteroids. Unfortunately, her peripheral neuropathy did not have any improvement. Incidentally, patient was found to have splenomegaly and papilledema on physical exam. Serum protein electrophoresis showed a monoclonal pattern of IgA lambda. Patient met the diagnostic criteria for POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome. An underlying diagnosis of POEMS syndrome should be considered in patients with chronic debilitating neuropathy and an elevated protein in the CSF. PMID:22013451

  17. POEMS Syndrome Diagnosed 10?Years after Disabling Peripheral Neuropathy

    PubMed Central

    Nguyen, Viet H.

    2011-01-01

    Peripheral neuropathy is characterized as a generalized, relatively homogeneous process affecting many peripheral nerves and predominantly affecting distal nerves. The epidemiology of peripheral neuropathy is limited since the disease presents with varying etiology, pathology, and severity. Toxic, inflammatory, hereditary, and infectious factors can cause damage to the peripheral nerves resulting in peripheral neuropathy. Peripheral neuropathy is most commonly caused by diabetes, alcohol, HIV infection, and malignancy. We report a case of a 42-year-old female with 10-year history of progressively worsening peripheral neuropathy, hypothyroidism, and skin changes who presents with dyspnea secondary to recurrent pleural and pericardial effusions. Prior to her arrival, her peripheral neuropathy was believed to be secondary to chronic demyelinating inflammatory polyneuropathy (CDIP) given elevated protein in the cerebral spinal fluid (CSF) which was treated with intravenous immunoglobulin (IVIG) and corticosteroids. Unfortunately, her peripheral neuropathy did not have any improvement. Incidentally, patient was found to have splenomegaly and papilledema on physical exam. Serum protein electrophoresis showed a monoclonal pattern of IgA lambda. Patient met the diagnostic criteria for POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome. An underlying diagnosis of POEMS syndrome should be considered in patients with chronic debilitating neuropathy and an elevated protein in the CSF. PMID:22013451

  18. Peripheral Insensate Neuropathy-Is Height a Risk Factor?

    PubMed Central

    Kote, G S Sharath; Bhat, Ajay N; K, Thajuddeen; Ismail, Mohammed H; Gupta, Abhishek

    2013-01-01

    Introduction: Peripheral insensate neuropathy is one of the most commonest and the earliest forms of peripheral neuropathy. It is one of the leading causes of the disability in working population who are at risk. Methods: A study was conducted in Kasturba medical college (Manipal university) in the year 2009-12, which included examination of 818 people of more than 30yrs of age by random sampling method who were attending the outpatient clinic. A monofilament was used to determine the peripheral insensate neuropathy, which was defined by the presence of one or more insensate areas. Results: In our study , the prevalence of peripheral insensate neuropathy was 16.2 % ( p-0.0001), among which 9.7% were males and 7.5% were females. The males were 1.27 times significantly at a higher risk than the females , even after a height adjustment to the gender difference in height. As the height increased, the prevalence of peripheral insensate neuropathy increased, irrespective of the diabetic and hypertensive statuses. The risk of the peripheral insensate neuropathy increases at a height of >167 cm in males and at a height of >159 cm in females. Conclusion: The authors conclude that body height is an important and an independent risk factor for peripheral insensate neuropathy, irrespective of co morbidities. Height as a marker, helps the health care professionals in identifying the people who are at risk for peripheral insensate neuropathy. PMID:23542767

  19. Sympathetic skin response in acute sensory ataxic neuropathy

    Microsoft Academic Search

    G. R. Arunodaya; A. B. Taly; H. S. Swamy

    1995-01-01

    Sympathetic skin response (SSR) is a recently described objective method of studying sudomotor sympathetic nerve function and has been studied in a variety of peripheral neuropathies. We report SSR changes in nine patients with acute sensory ataxic neuropathy (ASAN). All had severe sensory and mild motor nerve conduction abnormalities; five had dysautonomia. SSR, elicited by electric shock and cough stimuli,

  20. Properties of human skin mechanoreceptors in peripheral neuropathy

    Microsoft Academic Search

    K Mizobuchi; S Kuwabara; S Toma; Y Nakajima; K Ogawara; T Hattori

    2002-01-01

    Objectives: To investigate the properties of mechanoreceptors in patients with peripheral neuropathy. The skin mechanoreceptor is a terminal organ of the primary sensory neuron, which is likely to be affected earlier and more severely than is the nerve trunk by peripheral neuropathies.Methods: Single sensory unit responses to air-puff and electric stimulation were recorded using the microneurographic technique in the glabrous

  1. Peripheral neuropathies of rheumatologic disease and gluten-related disorders.

    PubMed

    Reda, Haatem; Chin, Russell L

    2014-09-01

    Peripheral nervous system disease is a common and often debilitating feature of many systemic rheumatologic disorders. Such involvement takes many forms, reflecting the variety of underlying pathophysiology, though most patients present with painful multifocal neuropathy (usually vasculitic) or a distal sensory more than motor peripheral neuropathy (sometimes vasculitic and nearly always axonal). The presence of peripheral nervous system involvement is often an early signal of the generalization of inflammatory disease in blood vessels or extravascular tissues, though peripheral neuropathy is not itself an independent predictor of mortality. Nonetheless, progressive multifocal neuropathy, motor neuropathy, small fiber neuropathy, and sensory neuronopathy should be treated early and aggressively with immunosuppression (or the gluten-free diet in appropriate situations) to limit morbidity. Given the rapidly evolving therapeutic landscape, partnership with a rheumatologist is essential. Treatment is usually sustained for 1 to 2 years, and remission is possible in many cases within 6 to 12 months, with variable rates of relapse and treatment resistance. Patients should be meticulously monitored for relapse with serial laboratory testing, electrodiagnostic studies, and clinical examination. Functional rating scores, such as the neuropathy impairment scale and the total neuropathy score are useful for longitudinal assessment. PMID:25369437

  2. BAG3 mutations: another cause of giant axonal neuropathy.

    PubMed

    Jaffer, Fatima; Murphy, Sinéad M; Scoto, Mariacristina; Healy, Estelle; Rossor, Alexander M; Brandner, Sebastian; Phadke, Rahul; Selcen, Duygu; Jungbluth, Heinz; Muntoni, Francesco; Reilly, Mary M

    2012-06-01

    Mutations in Bcl-2 associated athanogene-3 (BAG3) are a rare cause of myofibrillar myopathy, characterised by rapidly progressive proximal and axial myopathy, cardiomyopathy and respiratory compromise. Neuropathy has been documented neurophysiologically in previously reported cases of BAG3-associated myofibrillar myopathy and in some cases giant axons were observed on nerve biopsies; however, neuropathy was not thought to be a dominant feature of the disease. In the context of inherited neuropathy, giant axons are typically associated with autosomal recessive giant axonal neuropathy caused by gigaxonin mutations but have also been reported in association with NEFL- and SH3TC2-associated Charcot-Marie-Tooth disease. Here, we describe four patients with heterozygous BAG3 mutations with clinical evidence of a sensorimotor neuropathy, with predominantly axonal features on neurophysiology. Three patients presented with a significant neuropathy. Muscle magnetic resonance imaging (MRI) in one patient revealed mild to moderate atrophy without prominent selectivity. Examination of sural nerve biopsies in two patients demonstrated giant axons. This report confirms the association of giant axonal neuropathy with BAG3-associated myofibrillar myopathy, and highlights that neuropathy may be a significant feature. PMID:22734908

  3. Evaluation Tools and Animal Models of Peripheral Neuropathies

    Microsoft Academic Search

    B. Fricker; A. Muller; F. René

    2008-01-01

    Peripheral neuropathies are common and frequently debilitating disorders linked to degeneration of peripheral nerves that supply mainly the distal muscles of the extremities. Due to the diverse origin of the pathology (genetic, systemic or environmental), peripheral neuropathies exhibit different clinical forms: acute or chronic, symmetrical or asymmetrical, demyelinating or axonal. In the last 30 years, to gain insight into cellular

  4. Comparison of different modalities for detection of small fiber neuropathy

    Microsoft Academic Search

    Karen Tobin; Michael J Giuliani; David Lacomis

    1999-01-01

    Objectives: In general, large fiber sensory function is easier to assess than small fiber function both clinically and electrophysiologically. Therefore, small fiber sensory neuropathies are more difficult to diagnose. The relative sensitivities of different electrodiagnostic tests for small fiber neuropathy are not known. We sought to determine and compare the sensitivities of quantitative thermal sensory testing (QST), quantitative sudomotor axon

  5. Small fiber neuropathy: a common and important clinical disorder

    Microsoft Academic Search

    E. Hoitsma; J. P. H. Reulen; M. de Baets; M. Drent; F. Spaans; C. G. Faber

    2004-01-01

    Small fiber neuropathy (SFN) is a neuropathy selectively involving small diameter myelinated and unmyelinated nerve fibers. Interest in this disorder has considerably increased during the past few years. It is often idiopathic and typically presents with peripheral pain and\\/or symptoms of autonomic dysfunction. Diagnosis is made on the basis of the clinical features, normal nerve conduction studies (NCS) and abnormal

  6. Gene therapy for optic nerve disease

    Microsoft Academic Search

    K R G Martin; H A Quigley

    2004-01-01

    Purpose There has been recent interest in the potential use of gene therapy techniques to treat ocular disease. In this article, we consider the optic nerve diseases that are potentially most amenable to gene therapy.Methods We discuss the recent success of gene transfer experiments in animal models of glaucoma, optic neuritis, Leber's hereditary optic neuropathy (LHON), and optic nerve transection,

  7. Surgical decompression in lower-extremity diabetic peripheral neuropathy.

    PubMed

    Rader, Andrew J

    2005-01-01

    Peripheral neuropathy can be a devastating complication of diabetes mellitus. This article describes surgical decompression as a means of restoring sensation and relieving painful neuropathy symptoms. A prospective study was performed involving patients diagnosed as having type 1 or type 2 diabetes with lower-extremity peripheral neuropathy. The neuropathy diagnosis was confirmed using quantitative sensory testing. Visual analog scales were used for subjective assessment before and after surgery. Treatment consisted of external and as-needed internal neurolysis of the common peroneal, deep peroneal, tibial, medial plantar, lateral plantar, and calcaneal nerves. Subjective pain perception and objective sensibility were significantly improved in most patients who underwent the described decompression. Surgical decompression of multiple peripheral nerves in the lower extremities is a valid and effective method of providing symptomatic relief of neuropathy pain and restoring sensation. PMID:16166461

  8. Purple pigments: the pathophysiology of acute porphyric neuropathy.

    PubMed

    Lin, Cindy S-Y; Lee, Ming-Jen; Park, Susanna B; Kiernan, Matthew C

    2011-12-01

    The porphyrias are inherited metabolic disorders arising from disturbance in the haem biosynthesis pathway. The neuropathy associated with acute intermittent porphyria (AIP) occurs due to mutation involving the enzyme porphobilinogen deaminase (PBGD) and is characterised by motor-predominant features. Definitive diagnosis often encompasses a combination of biochemical, enzyme analysis and genetic testing, with clinical neurophysiological findings of a predominantly motor axonal neuropathy. Symptomatic and supportive treatment are the mainstays during an acute attack. If administered early, intravenous haemin may prevent progression of neuropathy. While the pathophysiology of AIP neuropathy remains unclear, axonal dysfunction appears intrinsically linked to the effects of neural energy deficits acquired through haem deficiency coupled to the neurotoxic effects of porphyrin precursors. The present review will provide an overview of AIP neuropathy, including discussion of recent advances in understanding developed through neurophysiological approaches that have further delineated the pathophysiology of axonal degeneration. PMID:21855406

  9. 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

  10. [Paraneoplastic neuropathy with positive anti-Hu].

    PubMed

    Casas Parera, I; Fischman, D; Paz, L; Lehkuniec, E; Muchnik, S

    1998-01-01

    The case of a 72-year-old woman presenting sensory neuropathy and anti-Hu antibodies is reported. She was admitted in November 1995 with a one year history of sensory neuropathy. Her first symptoms were painful numbness and dysesthesias in both feet. She experienced progression of the sensory symptoms affecting upper limbs, and clumsiness of gait. One month before admission she complained of diminished strength in both hands. The neurologic examination showed anicocoric fixed pupils, with no reaction to light; convergence miosis was evident in the right eye (Argyll-Robertson pupil). In the lower limbs she had very mild distal weakness, and tendon reflexes were universally abolished. Pin and touch sensation, position sense and pallesthesia were absent in all four limbs. Romberg test was elicited, and a tabetic gait was patent. Pseudoathetotic movements were observed in hands and feet. An ulcer was present in the fifth finger of the right foot. Routine blood biochemistry and hematology showed a ESR of 105 and an increased IgG in the immune-electrophoretic run. Neurophysiologic evaluation disclosed a mild demyelinating neuropathy. Positive anti-Hu antibodies were found in the serum (Western blot - Athena Diagnostics); CSF was normal but not tested for anit-Hu. An abdominal CT scan disclosed multiple hypodense nodules in liver, right adrenal gland and peritoneum. A chest CT scan showed a hyperdense mass in the lower right pulmonary lobe and enlarged retrocava-pretracheal lymph nodes. A biopsy of the peritoneal nodule was performed, showing a metastatic small cell carcinoma. The patient died eight days after discharge. Although multiple organs were affected, she was independent until death, showing an indolent clinical course. PMID:9706256

  11. Clinical features and electrodiagnosis of ulnar neuropathies.

    PubMed

    Landau, Mark E; Campbell, William W

    2013-02-01

    In this review, we delineate clinical, electrodiagnostic, and radiographic features of ulnar mononeuropathies. Ulnar neuropathy at the elbow (UNE) is most commonly due to lesions at the level of the retroepicondylar groove (RTC), with approximately 25% at the humeroulnar arcade (HUA). The term 'cubital tunnel syndrome' should be reserved for the latter. The diagnostic accuracy of nerve conduction studies is limited by biological (e.g. low elbow temperature) and technical factors. Across-elbow distance measurements greater than 10 cm improve diagnostic specificity at the expense of decreased sensitivity. Short-segment incremental studies can differentiate lesions at the HUA from those at the RTC. PMID:23177030

  12. 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

  13. 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

  14. Acute Toxic Neuropathy Mimicking Guillain Barre Syndrome

    PubMed Central

    Jalal, Muhammed Jasim Abdul; Fernandez, Shirley Joan; Menon, Murali Krishna

    2015-01-01

    Case: A 30 year old male presented with numbness of palms and soles followed by weakness of upper limbs and lower limbs of 5 days duration, which was ascending and progressive. Three months back he was treated for oral and genital ulcers with oral steroids. His ulcers improved and shifted to indigenous medication. His clinical examination showed polyneuropathy. CSF study did not show albuminocytological dissociation. Nerve conduction study showed demyelinating polyneuropathy. His blood samples and the ayurvedic drug samples were sent for toxicological analysis. Inference: Acute toxic neuropathy - Arsenic

  15. Paclitaxel plus carboplatin–induced peripheral neuropathy

    Microsoft Academic Search

    Andreas A. Argyriou; Panagiotis Polychronopoulos; Gregoris Iconomou; Angelos Koutras; Haralabos P. Kalofonos; Elisabeth Chroni

    2005-01-01

    Objective  The current study intended to determine the incidence, severity and reversibility of paclitaxel plus carboplatin (CP)–induced\\u000a peripheral neuropathy (CPPN) and to describe its clinical and electrophysiological features.\\u000a \\u000a \\u000a \\u000a Patients and methods  We prospectively studied 21 adult patients scheduled to be treated with 6 courses of cumulative carboplatin plus paclitaxel\\u000a (CP) regimens for a non–myeloid malignancy. They were followed–up by neurological examination and

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

    Microsoft Academic Search

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

    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

  17. 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.

  18. [Peripheral neuropathies due to mitochondrial disorders].

    PubMed

    Funalot, B

    2009-12-01

    Involvement of peripheral nerves is frequent in mitochondrial disorders but with variable severity. Mitochondrial diseases causing peripheral neuropathies (PN) may be due to mutations of mitochondrial DNA (mtDNA), as is the case in MERRF and MELAS syndromes, or to mutations of nuclear genes. Secondary abnormalities of mtDNA (such as multiple deletions of muscle mtDNA) may result from mitochondrial disorders due to mutations in nuclear genes involved in mtDNA maintenance. This is the case in several syndromes caused by impaired mtDNA maintenance, such as Sensory Ataxic Neuropathy, Dysarthria and Ophthalmoplegia (SANDO) due to recessive mutations in the POLG gene, which encodes the catalytic subunit of mtDNA polymerase (DNA polymerase gamma), or Mitochondrial Neuro-Gastro-Intestinal Encephalomyopathy (MNGIE), due to recessive mutations in the TYMP gene, which encodes thymidine phosphorylase. Genetically-determined PN due to mutations of mitofusin 2, a GTPase involved in the fusion of external mitochondrial membranes, were identified during the last few years. Characteristic ultrastructural lesions (abnormalities of axonal mitochondria) are observed on longitudinal sections of nerve biopsies in patients with PN due to mitofusin 2 mutations. PMID:19942242

  19. Episodic neurological dysfunction in hereditary peripheral neuropathy

    PubMed Central

    Kulkarni, Girish Baburao; Mailankody, Pooja; Isnwara, Pawanraj Palu; Prasad, Chandrajit; Mustare, Veerendrakumar

    2015-01-01

    Episodic transient neurological symptoms are an important set of problems presenting to a neurologist in his routine practice. Occasionally, detailed clinical history including past and family history supplemented with focused examination can bring out a rare cause for such symptoms. We describe in this report in a young male presenting with episodic focal neurological dysfunction, with family history of similar episodes in mother and brother. Examination showed features of pes cavus and peripheral neuropathy for which patient was asymptomatic. Mother and brother were established cases of hereditary neuropathy. Imaging on multiple occasions showed reversible white matter abnormalities. Clinical suspicion of X-linked Charcot-Marie-Tooth disease type 1 (CMT1X) was confirmed with detection of mutation in Gap Junction B1 (GJB1) gene, which codes for connexin 32 protein (c.425G>A; p.R142Q hemizygous mutation). Though this mutation has been already reported in CMTX patients, it has not been associated with transient neurological dysfunctions. This is probably the first reported case of CMTX patient with transient neurological dysfunction from India, whose family members had similar episodes.

  20. 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

  1. 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.

  2. Surgical treatment of common entrapment neuropathies in the upper limbs.

    PubMed

    Arle, J E; Zager, E L

    2000-08-01

    Entrapment neuropathies of the upper extremity are common, debilitating conditions. Most patients with these neuropathies are readily diagnosed on purely clinical grounds and may be effectively managed with nonoperative measures. However, the broad differential diagnosis often necessitates electrodiagnostic testing and radiographic imaging to clarify the situation. This review focuses on three of the most common entrapment neuropathies in the upper limbs: carpal tunnel syndrome (median nerve entrapment at the wrist), cubital tunnel syndrome (ulnar nerve entrapment at the elbow), and radial tunnel syndrome (posterior interosseous nerve entrapment). Anatomical considerations, patient evaluation, indications for surgical intervention, options for surgical approaches, outcomes, and complications are discussed. PMID:10918251

  3. Entrapment neuropathies of the lower extremity.

    PubMed

    Craig, Anita

    2013-05-01

    Neuropathies that affect the lower limbs are often encountered after trauma or iatrogenic injury or by entrapment at areas of anatomic restriction. Symptoms may initially be masked by concomitant trauma or recovery from surgical procedures. The nerves that serve the lower extremities arise from the lumbosacral plexus, formed by the L2-S2 nerve roots. The major nerves that supply the lower extremities are the femoral, obturator, lateral femoral cutaneous, and the peroneal (fibular) and tibial, which arise from the sciatic nerve, and the superior and inferior gluteal nerves. An understanding of the motor and sensory functions of these nerves is critical in recognizing and localizing nerve injury. Electrodiagnostic studies are an important diagnostic tool. A well-designed electromyography study can help confirm and localize a nerve lesion, assess severity, and evaluate for other peripheral nerve lesions, such as plexopathy or radiculopathy. PMID:23542774

  4. Intravenous immunoglobulin therapy in proximal diabetic neuropathy

    PubMed Central

    Kawagashira, Yuichi; Watanabe, Hirohisa; Oki, Yumiko; Iijima, Masahiro; Koike, Haruki; Hattori, Naoki; Katsuno, Masahisa; Tanaka, Fumiaki; Sobue, Gen

    2009-01-01

    A 57-year-old man with type 2 diabetes mellitus for 10 years showed progressive loss of muscle strength in both legs, pain and muscle atrophy in the femoral region and significant weight loss. On admission, he could not stand alone and used a wheelchair. He also complained of severe pain in the lower extremities. He was diagnosed with proximal diabetic neuropathy (PDN) by characteristic clinical and electrophysiological features. Intravenous immunoglobulin therapy (IVIg 0.4 g/kg×5 days) markedly reduced the severe pain and muscle weakness in the legs. Eventually, pain assessed by the Visual Analogue Scale was relieved by 80% and muscle strength was also well recovered, thereby enabling the patient to walk with a cane. The present case suggests that IVIg therapy may be effective for the relief of pain in PDN. PMID:21686696

  5. Therapeutic strategies for the inherited neuropathies.

    PubMed

    Shy, Michael E

    2006-01-01

    More than 30 genetic causes have been identified for the inherited neuropathies collectively referred to as Charcot-Marie-Tooth (CMT) disease. Previous therapies for CMT were limited to traditional approaches such as rehabilitation medicine, ambulation aids, and pain management. Identification of the genes causing CMT has led to improved genetic counseling and assistance in family planning. Identification of these genes is beginning to delineate common molecular pathways in multiple forms of CMT that can be exploited in future molecular therapies. Scientifically based clinical trials for CMT are currently being implemented. Techniques of gene therapy are advancing to the point that they may become feasible options for patients with CMT and other neurodegenerative diseases. PMID:16775380

  6. Giant axonal neuropathy. Endocrinological and histological studies.

    PubMed

    Fois, A; Balestri, P; Farnetani, M A; Berardi, R; Mattei, R; Laurenzi, E; Alessandrini, C; Gerli, R; Ribuffo, A; Calvieri, S

    1985-09-01

    A case of giant axonal neuropathy (GAN) in a boy of 4 years and 6 months, is reported. Nerve conduction velocity (NCV), EEG and CT scan indicated both peripheral and central nervous system involvement. Intestinal absorption tests did not reveal vitamin B12 malabsorption; the endocrine situation was found to be substantially normal. The clinical picture was not modified by 18 months cyanocobalamine administration followed by 2 months therapy with prednisone. Electron microscopic (EM) examination revealed longitudinal and opposing grooves (pili canaliculi) in the hair and bundles of neuro-filaments in the myelinated and unmyelinated nerve fibre axons in sural nerve. EM of conjunctiva and skin revealed masses of intermediate-sized filaments within mast cells, fibroblasts, melanocytes, endothelial and Schwann cells. These findings confirm the hypothesis that GAN is a generalised abnormality of cytoplasmic microfilament formation, probably linked to an unknown disorder of protein metabolism. PMID:4054168

  7. 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

  8. Diagnosing Neuropathy: The Key to Understanding the Cause

    MedlinePLUS

    ... primarily involves the axons or the myelin sheaths. Electromyography (EMG): measures the electrical activity of muscles in response ... Biopsy Small fiber neuropathy cannot be diagnosed with EMG and nerve conduction studies that only measure the ...

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

    MedlinePLUS

    ... intolerance) and can lead to an unusual walking style (gait), frequent falls, and joint deformities (contractures) in ... Where can I find information about diagnosis or management of autosomal recessive axonal neuropathy with neuromyotonia? You ...

  10. Mechanisms of Disease: The Oxidative Stress Theory of Diabetic Neuropathy

    PubMed Central

    Figueroa-Romero, Claudia; Sadidi, Mahdieh; Feldman, Eva L.

    2014-01-01

    Diabetic neuropathy is the most common complication of diabetes, affecting 50% of diabetic patients. Currently, the only treatment for diabetic neuropathy is glucose control and careful foot care. In this review, we discuss the idea that excess glucose overloads the electron transport chain, leading to the production of superoxides and subsequent mitochondrial and cytosolic oxidative stress. Defects in metabolic and vascular pathways intersect with oxidative stress to produce the onset and progression of nerve injury present in diabetic neuropathy. These pathways include the production of advanced glycation end products, alterations in the sorbitol, hexosamine and protein kinase C pathways and activation of Poly-ADP ribose polymerase. New bioinformatics approaches can augment current research and lead to new discoveries to understand the pathogenesis of diabetic neuropathy and to identify more effective molecular therapeutic targets. PMID:18709457

  11. 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.

  12. EFFECT OF AEROBIC EXERCISE INTERVENTION ON PAINFUL DIABETIC NEUROPATHY

    E-print Network

    Yoo, Min

    2013-05-31

    Background: Painful diabetic peripheral neuropathy (DPN) is a common complication of diabetes. While the beneficial effect of exercise on diabetes has been well established, its effect specifically on painful DPN has not been thoroughly explored...

  13. African Mitochondrial DNA Subhaplogroups and Peripheral Neuropathy during Antiretroviral Therapy

    PubMed Central

    Canter, Jeffrey A.; Robbins, Gregory K.; Selph, Doug; Clifford, David B.; Kallianpur, Asha R.; Shafer, Robert; Levy, Shawn; Murdock, Deborah G.; Ritchie, Marylyn D.; Haas, David W.; Hulgan, Todd

    2010-01-01

    Susceptibility to peripheral neuropathy during antiretroviral therapy with nucleoside reverse transcriptase inhibitors (NRTIs) was previously associated with a European mitochondrial DNA (mtDNA) haplogroup among non-Hispanic white persons. To determine if NRTI-associated peripheral neuropathy was related to mtDNA variation in non-Hispanic black persons, we sequenced mtDNA of participants from AIDS Clinical Trials Group study 384. Of 156 non-Hispanic blacks with genomic data, 51 (33%) developed peripheral neuropathy. In a multivariate model, African mtDNA subhaplogroup L1c was an independent predictor of peripheral neuropathy (OR=3.7, 95% CI 1.1-12.0). An African mtDNA subhaplogroup is for the first time implicated in susceptibility to NRTI-associated toxicity. PMID:20402593

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

    MedlinePLUS

    ... to toxins, elevated temperature, injury, and disease. They block signals that lead to programmed cell death. In ... motor neuropathy, type II change single protein building blocks (amino acids) in the protein sequence. If either ...

  15. Peripheral neuropathy in HIV: an analysis of evidence-based approaches.

    PubMed

    Nicholas, Patrice K; Corless, Inge B; Evans, Linda A

    2014-01-01

    Peripheral neuropathy is a common and vexing symptom for people living with HIV infection (PLWH). Neuropathy occurs in several different syndromes and is identified in the literature as distal sensory polyneuropathy or distal sensory peripheral neuropathy. More recently, the HIV literature has focused on the syndrome as painful HIV-associated sensory neuropathy, addressing the symptom rather than the underlying pathophysiology. Assessment of neuropathy in PLWH is critical and must be incorporated into nursing practice for each visit. Neuropathy has been attributed to the direct effects of HIV, exposure to antiretroviral medications (particularly the nucleoside reverse transcriptase inhibitors), advanced immune suppression, and comorbid tuberculosis infection and exposure to antituberculosis medications. Evidence supports the importance of addressing neuropathy in PLWH with pharmacologic treatment regimens and complementary/alternative approaches. This paper examines the pathophysiology, evidence, and approaches to managing peripheral neuropathy. A case study has been included to illustrate a patient's experience with neuropathy symptoms. PMID:24698331

  16. Evaluation of thermal and vibration sensation in diabetic neuropathy

    Microsoft Academic Search

    R. J. C. Guy; C. A. Clark; P. N. Malcolm; P. J. Watkins

    1985-01-01

    Summary  Sensory evaluation of diabetic neuropathy was undertaken by a new technique for assessment of thermal sensitivity. The method is simple and reproducible, and the mean normal value of the lateral border of the foot was 6.0 °C (3.6–9.8 °C, 95% confidence limits). Four groups of patients with diabetic neuropathy were examined: 22 with neuropathic ulcers and\\/or Charcot joints (groups 1

  17. Mechanisms of disease: The oxidative stress theory of diabetic neuropathy

    Microsoft Academic Search

    Claudia Figueroa-Romero; Mahdieh Sadidi; Eva L. Feldman

    2008-01-01

    Diabetic neuropathy is the most common complication of diabetes, affecting 50% of diabetic patients. Currently, the only treatment\\u000a for diabetic neuropathy is glucose control and careful foot care. In this review, we discuss the idea that excess glucose\\u000a overloads the electron transport chain, leading to the production of superoxides and subsequent mitochondrial and cytosolic\\u000a oxidative stress. Defects in metabolic and

  18. Trigeminal sensory neuropathy with abnormal taste following acute sinusitis.

    PubMed

    Okuda, B; Tachibana, H; Sugita, M

    1994-02-01

    We report a case of isolated trigeminal sensory neuropathy associated with impairment of taste sensation following acute sinusitis. Sensory disturbance was distributed mainly in the ophthalmic division, and partly in the maxillary and mandibular divisions. No other cranial nerves were involved. An otological procedure resulted in complete recovery. The unique combination of trigeminal neuropathy and abnormal taste seemed to be caused by the infectious process involving the gasserian ganglion of the trigeminal nerve. PMID:8187388

  19. Misonidazole Neuropathy: a clinical, electrophysiological, and histological study.

    PubMed

    Melgaard, B; Hansen, H S; Kamieniecka, Z; Paulson, O B; Pedersen, A G; Tang, X; Trojaborg, W

    1982-07-01

    We studied eight patients with carcinoma of the pharynx and larynx (five cases) or lungs (three cases) who, during treatment with the radiosensitizing drug misonidazole, developed peripheral neuropathy dominated by severe sensory symptoms and signs mainly localized to the lower extremities. The symptoms partially subsided within months after cessation of therapy. Electrophysiological and histological findings indicated an axonal neuropathy with loss of large fibers and secondary demyelination. The neurotoxic property of misonidazole limits its therapeutic use. PMID:7114817

  20. Peripheral Neuropathy Associated With Nucleoside Reverse Transcriptase Inhibitor Therapy

    Microsoft Academic Search

    Bruce A. Cohen; Russell Bartt

    Peripheral neuropathies are the most common neurological syndromes associated with HIV infection. The spectrum of neuropathic\\u000a syndromes is broad (xi238-1|Table 1), and neuropathies may be encountered during any stage of the infection. Some disorders\\u000a of the peripheral nerves in patients with HIV infection are presumed to be caused by pathological factors resulting from the\\u000a virus itself, whereas others may result

  1. Peripheral neuropathy with essential mixed cryoglobulinemia: biopsies from 5 cases

    Microsoft Academic Search

    C. Vital; C. Deminière; A. Lagueny; F. X. Bergouignan; J. L. Pellegrin; M. S. Doutre; A. Clement; J. Beylot

    1988-01-01

    Essential mixed cryoglobulinemia, which can cause hypersensitivity vasculitis, was observed in five patients with peripheral neuropathy. Three cases presented with multifocal neuropathies and two cases with symmetrical polyneuropathy. One had cryoglobulinemia with IgM monoclonal gammopathy and IgG polyclonal gammopathy, and the other four had cryoglobulinemia with polyclonal gammopathy. Biopsies showed perivascular infiltration by mononuclaer cells around medium, and mainly small-sized

  2. 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

  3. The Association between Autoantibodies and Peripheral Neuropathy in Lupus Nephritis

    PubMed Central

    Su, Yu-Jih; Huang, Chi-Ren; Chang, Wen-Neng; Tsai, Nai-Wen; Kung, Chia-Te; Lin, Wei-Che; Huang, Chih-Cheng; Su, Chih-Min; Cheng, Ben-Chung; Chang, Ya-Ting; Lu, Cheng-Hsien

    2014-01-01

    Background and Aim. The sensitivity and specificity of biomarkers used for predicting peripheral neuropathy in patients with systemic lupus erythematosus (SLE) and nephritis (SLE-LN) remain unsatisfactory. This study aimed to determine the autoantibodies levels in SLE-LN patients with peripheral neuropathy. Methods. Data of 559 SLE-LN patients were collected retrospectively, including titers of autoantibodies, electrodiagnostic studies, and clinical manifestations. Results. The neurologic manifestations of the SLE-LN patients were diverse and nonspecific. The prevalence rate of peripheral polyneuropathy was 2.68%, of which about 73.33% was mixed sensory-motor polyneuropathy. Numbness and functional gastrointestinal problems were the most prevalent symptoms and these were noted in every subtype of peripheral neuropathy. Among all the serology markers, anti-Ro was significantly associated with neuropathy related to SLE (P = 0.009). Conclusion. Peripheral neuropathy among LN patients is rare and may be easily overlooked. This study demonstrated that positive anti-Ro antibody may imply neuropathy in LN patients. Thus, anti-Ro can be considered a biomarker that should be added to the panel of conventional autoantibodies in LN patients. PMID:24864250

  4. Treatment options for atypical optic neuritis

    PubMed Central

    Malik, Amina; Ahmed, Maryam; Golnik, Karl

    2014-01-01

    Context: Optic neuritis (ON) is defined as inflammation of the optic nerve and can have various etiologies. The most common presentation in the US is demyelinating, or “typical” ON, usually associated with multiple sclerosis. This is in contrast to “atypical” causes of ON, which differ in their clinical presentation, management, and prognosis. These atypical cases are characterized by lack of eye pain, exudates, and hemorrhages on exam, very severe, bilateral or progressive visual loss, or with failure to recover vision. Aims: The aim was to describe the clinical presentations of atypical ON and their treatments. Settings and Design: Review article. Materials and Methods: Literature review. Results: Types of atypical ON identified include neuromyelitis optica, autoimmune optic neuropathy, chronic relapsing inflammatory optic neuropathy, idiopathic recurrent neuroretinitis, and optic neuropathy associated with systemic diseases. Atypical ON usually requires corticosteroid treatment and often will require aggressive immunosuppression. Conclusions: Unlike demyelinating ON, atypical ON requires treatment to preserve vision. PMID:25449930

  5. Perineural invasion of sinonasal lymphoma: a rare cause of trigeminal neuropathy.

    PubMed

    Liang, Chih-Wei; Chen, Ying-Lin

    2007-02-01

    Trigeminal neuropathy is characterized by sensory disturbance of the division of trigeminal nerve, and sometimes is associated with pain. Trigeminal neuropathy secondary to perineural invasion of sinonasal lymphoma is extremely rare. Likewise, sinonasal lymphoma is infrequently demonstrated initially with cranial neuropathy. The present case served to broaden the differential diagnosis of secondary trigeminal neuropathy and to alert clinicians to cautiously assess perineural spread of occult neoplasm in sinonasal tract and larynx or pharynx for cases with evolving trigeminal neuropathy or even other cranial nerve neuropathy in which no definite cause is identified. PMID:17300375

  6. Giant axonal neuropathy: a rare inherited neuropathy with simple clinical clues.

    PubMed

    Kamate, Mahesh; Ramakrishna, Shashikala; Kambali, Shweta; Mahadevan, Anita

    2014-01-01

    Giant axonal neuropathy (GAN) is a rare hereditary neurodegenerative disorder characterised by accumulation of excess neurofilaments in the axons of peripheral and central nervous systems, which hampers signal transmission. It usually manifests in infancy and early childhood and is slowly progressive. Those affected with GAN have characteristic curly kinky hair, everted feet and a crouched gait, which suggest the diagnosis in most cases. We describe twin children who presented with difficulty in walking and an abnormal gait since they began walking; clinical clues such as hair changes led us to the final diagnosis. PMID:25216920

  7. Alcohol consumption enhances antiretroviral painful peripheral neuropathy by mitochondrial mechanisms.

    PubMed

    Ferrari, Luiz F; Levine, Jon D

    2010-09-01

    A major dose-limiting side effect of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) chemotherapies, such as the nucleoside reverse transcriptase inhibitors (NRTIs), is a small-fiber painful peripheral neuropathy, mediated by its mitochondrial toxicity. Co-morbid conditions may also contribute to this dose-limiting effect of HIV/AIDS treatment. Alcohol abuse, which alone also produces painful neuropathy, is one of the most important co-morbid risk factors for peripheral neuropathy in patients with HIV/AIDS. Despite the prevalence of this problem and its serious impact on the quality of life and continued therapy in HIV/AIDS patients, the mechanisms by which alcohol abuse exacerbates highly active antiretroviral therapy (HAART)-induced neuropathic pain has not been demonstrated. In this study, performed in rats, we investigated the cellular mechanism by which consumed alcohol impacts antiretroviral-induced neuropathic pain. NRTI 2',3'-dideoxycytidine (ddC; 50 mg/kg) neuropathy was mitochondrial-dependent and PKC?-independent, and alcohol-induced painful neuropathy was PKC?-dependent and mitochondrial-independent. At low doses, ddC (5 mg/kg) and alcohol (6.5% ethanol diet for 1 week), which alone do not affect nociception, together produce profound mechanical hyperalgesia. This hyperalgesia is mitochondrial-dependent but PKC?-independent. These experiments, which provide the first model for studying the impact of co-morbidity in painful neuropathy, support the clinical impression that alcohol consumption enhances HIV/AIDS therapy neuropathy, and provide evidence for a role of mitochondrial mechanisms underlying this interaction. PMID:20726883

  8. A High-Fat Diet Alters the Phenotype of Diabetic Neuropathy

    E-print Network

    Guilford, Brianne Lynn

    2013-05-31

    factor for diabetic neuropathy. The purpose of this body of work was to test the effects of diet and dyslipidemia on the development and progression of diabetic neuropathy and identify potential mechanisms underlying the pathogenesis of high-fat diet...

  9. 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...

  10. 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

  11. Slowly progressive ataxia, neuropathy, and oculomotor dysfunction.

    PubMed

    Jordan, Justin T; Samuel, Gincy; Vernino, Steven; Muppidi, Srikanth

    2012-10-01

    A 54-year-old white man presented with slowly progressive incoordination and weakness. He had normal motor development until, at 16 years of age, he noted difficulty walking and difficulty reading despite normal visual acuity. By the fourth decade of life, he developed poor coordination and balance, as well as inability to walk. In subsequent years, he developed progressive, painless sensory loss, weakness, and atrophy in his distal arms and legs. His vision problems progressed and he also developed dysarthria without dysphagia. Family history was negative except for an uncle who was described as "clumsy." Results of an oculomotor examination were notable for increased square-wave jerks, persistent bilateral gaze-evoked nystagmus with saccadic pursuit, intact vestibulo-ocular reflex, and saccadic dysmetria. He had a mixed dysarthria with flaccid and ataxic characteristics and severe weakness and atrophy in the distal limb muscles. Sensation was diminished to the midforearms and midthighs in all modalities. Deep tendon reflexes were absent throughout, with no response to plantar stimulation. He had marked appendicular ataxia with mild axial ataxia. Magnetic resonance imaging of the brain revealed severe cerebellar atrophy. Results of an electrodiagnostic study suggested a severe axonal sensorimotor polyneuropathy with active and chronic denervation. The differential diagnosis in a patient with ataxia, neuropathy, and oculomotor features is discussed; a methodical approach to the diagnostic workup is suggested; and the final diagnosis is revealed. PMID:23044593

  12. Median neuropathy at the wrist as an early manifestation of diabetic neuropathy

    PubMed Central

    Horinouchi, Shuji; Deguchi, Takahisa; Arimura, Kimiyoshi; Arimura, Aiko; Dochi, Yukari; Uto, Tadashi; Nakamura, Tomonori; Arimura, Yumiko; Nishio, Yoshihiko; Takashima, Hiroshi

    2014-01-01

    Aims/Introduction To elucidate the clinical significance of median neuropathy at the wrist (MN) in patients with diabetes. Materials and Methods In total, 340 patients with diabetes who were hospitalized for glycemic control were enrolled in the present study. The diagnoses of MN and diabetic polyneuropathy (DPN) were based on electrophysiological criteria. A total of 187 patients were divided into four subgroups: patients without MN or DPN; patients with MN without DPN; patients with MN and DPN; and patients with DPN without MN. Intergroup comparisons of clinical characteristics and results of nerve conduction studies were carried out. Results A total of 71 patients had neither MN nor DPN; 25 had MN, but no DPN; 55 had MN and DPN; and 36 had DPN, but no MN. In comparison with the MN and DPN group, the MN without DPN group included more patients in the early phase of diabetes (diagnosed within the past 5 years) and fewer patients with diabetic microangiopathy. Comparative median nerve conduction studies showed significantly lower motor and sensory nerve conduction velocities, longer F-wave latencies, and smaller sensory nerve action potentials in patients with MN and DPN than in those without DPN. Conclusions MN in patients with diabetes could be attributed to an impairment in axonal function at common entrapment sites, and could be used to identify an early manifestation of diabetic neuropathy. PMID:25422772

  13. Alcoholic neuropathy: possible mechanisms and future treatment possibilities

    PubMed Central

    Chopra, Kanwaljit; Tiwari, Vinod

    2012-01-01

    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

  14. 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.

  15. Assessment of sensory neuropathy in patients with diabetic foot problems

    PubMed Central

    Nather, Aziz; Keng Lin, Wong; Aziz, Zameer; HJ Ong, Christine; MC Feng, Bernard; B Lin, Clarabelle

    2011-01-01

    Our aim of this study was to compare the accuracy of three different modalities for testing sensory neuropathy in diabetic patients with and without diabetic foot problems. The three devices used included the pin-prick testing using the Neurotip® (PPT), the Semmes–Weinstein 5.07/10 g monofilament testing (SWMT), and the rapid-current perception threshold (R-CPT) measurements using the Neurometer® testing. Our study population consisted of 54 patients (108 feet) with diabetic foot problems treated at the National University Hospital in Singapore by our multi-disciplinary diabetic foot care team. Our results showed no difference in sensory neuropathy detected by PPT and 5.07/10 g SWMT in both the pathological and normal foot. In the pathological foot, there was significant increase in sensory neuropathy detected by the Neurometer® device at both the big toe and ankle sites as compared to PPT and 5.07/10 g SWMT. In the normal foot, there was a significant increase in sensory neuropathy detected by the Neurometer® device at the big toe site only as compared to PPT and 5.07/10 g SWMT. Finally, the Neurometer® measurements detected a statistically higher proportion of feet with sensory neuropathy as compared to detection by the PPT or 5.07/10 g SWMT. PMID:22396819

  16. Subclinical Ulnar Neuropathy at the Elbow in Diabetic Patients

    PubMed Central

    Jang, Ji Eun; Kim, Yun Tae; Park, Byung Kyu; Cheong, In Yae

    2014-01-01

    Objective To demonstrate the prevalence and characteristics of subclinical ulnar neuropathy at the elbow in diabetic patients. Methods One hundred and five patients with diabetes mellitus were recruited for the study of ulnar nerve conduction analysis. Clinical and demographic characteristics were assessed. Electrodiagnosis of ulnar neuropathy at the elbow was based on the criteria of the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM1 and AANEM2). The inching test of the ulnar motor nerve was additionally performed to localize the lesion. Results The duration of diabetes, the existence of diabetic polyneuropathy (DPN) symptoms, the duration of symptoms, and HbA1C showed significantly larger values in the DPN group (p<0.05). Ulnar neuropathy at the elbow was more common in the DPN group. There was a statistically significant difference in the number of cases that met the three diagnostic criteria between the no DPN group and the DPN group. The most common location for ulnar mononeuropathy at the elbow was the retrocondylar groove. Conclusion Ulnar neuropathy at the elbow is more common in patients with DPN. If the conduction velocities of both the elbow and forearm segments are decreased to less than 50 m/s, it may be useful to apply the AANEM2 criteria and inching test to diagnose ulnar neuropathy. PMID:24639928

  17. PGC-1? Regulation of Mitochondrial Degeneration in Experimental Diabetic Neuropathy

    PubMed Central

    Choi, Joungil; Chandrasekaran, Krish; Inoue, Tatsuya; Muragundla, Anjaneyulu; Russell, James W.

    2014-01-01

    Mitochondrial degeneration is considered to play an important role in the development of diabetic peripheral neuropathy in humans. Mitochondrial degeneration and the corresponding protein regulation associated with the degeneration were studied in an animal model of diabetic neuropathy. PGC-1? and its-regulated transcription factors including TFAM and NRF1, which are master regulators of mitochondrial biogenesis, are significantly downregulated in streptozotocin diabetic dorsal root ganglion (DRG) neurons. Diabetic mice develop peripheral neuropathy, loss of mitochondria, decreased mitochondrial DNA content and increased protein oxidation. Importantly, this phenotype is exacerbated in PGC-1? (?/?) diabetic mice, which develop a more severe neuropathy with reduced mitochondrial DNA and a further increase in protein oxidation. PGC-1? (?/?) diabetic mice develop an increase in total cholesterol and triglycerides, and a decrease in TFAM and NRF1 protein levels. Loss of PGC-1? causes severe mitochondrial degeneration with vacuolization in DRG neurons, coupled with reduced state 3 and 4 respiration, reduced expression of oxidative stress response genes and an increase in protein oxidation. In contrast, overexpression of PGC-1? in cultured adult mouse neurons prevents oxidative stress associated with increased glucose levels. The study provides new insights into the role of PGC-1? in mitochondrial regeneration in peripheral neurons and suggests that therapeutic modulation of PGC-1? function may be an attractive approach for treatment of diabetic neuropathy. PMID:24423644

  18. Clinical Approach to the Treatment of Painful Diabetic Neuropathy

    PubMed Central

    Hovaguimian, Alexandra; Gibbons, Christopher H.

    2011-01-01

    Painful neuropathy is a common and often progressive complication of diabetes. Patients frequently report symptoms of tingling, burning, lancinating pain, hyperesthesia, and allodynia. The natural history of the disease may vary from intermittent mild symptoms to severe chronic daily pain; the latter is often associated with diminished quality of life. There are a variety of pharmaceutical agents from different medicinal categories available for the symptomatic treatment of painful diabetic neuropathy, however selecting an agent is often challenging given the breadth of choices and lack of consistent guidelines. As a result, many patients remain untreated or undertreated. This article presents a practical clinical approach to the treatment of pain in diabetic neuropathy. Recommendations for first-, second-, and third-line medications are based on specific evidence for the treatment of painful diabetic neuropathy as well as safety, tolerability, drug interactions, and cost. Additional topics of discussion include breakthrough pain, opioid use, and topical therapies. This review does not comprehensively discuss all possible treatments for painful neuropathy, but provides a systematic approach designed to guide clinicians in tailoring therapies to the individual patient. PMID:21709806

  19. Tumor necrosis factor-alpha antagonists and neuropathy.

    PubMed

    Stübgen, Joerg-Patrick

    2008-03-01

    Tumor necrosis factor (TNF)-alpha plays an important role in many aspects of immune system development, immune-response regulation, and T-cell-mediated tissue injury. The evidence that TNF-alpha, released by autoreactive T cells and macrophages, may contribute to the pathogenesis of immune-mediated demyelinating neuropathies is reviewed. TNF-alpha antagonists (infliximab, etanercept, adalimumab) are indicated for the treatment of advanced inflammatory rheumatic and bowel disease, but these drugs can induce a range of autoimmune diseases that also attack the central and peripheral nervous systems. Case histories and series report on the association between anti-TNF-alpha treatment and various disorders of peripheral nerve such as Guillain-Barré syndrome, Miller Fisher syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy with conduction block, mononeuropathy multiplex, and axonal sensorimotor polyneuropathies. The proposed pathogeneses of TNF-alpha-associated neuropathies include both a T-cell and humoral immune attack against peripheral nerve myelin, vasculitis-induced nerve ischemia, and inhibition of signaling support for axons. Most neuropathies improve over a period of months by withdrawal of the TNF-alpha antagonist, with or without additional immune-modulating treatment. Preliminary observations suggest that TNF-alpha antagonists may be useful as an antigen-nonspecific treatment approach to immune-mediated neuropathies in patients with a poor response to, or intolerance of, standard therapies, but further studies are required. PMID:18041052

  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. Hereditary Neuropathy with Liability to Pressure Palsies: Case Report and Discussion

    Microsoft Academic Search

    Marc J. Grossman; Joseph Feinberg; Edward F. DiCarlo; Sherri B. Birchansky; Scott W. Wolfe

    2007-01-01

    Hereditary neuropathy with liability to pressure palsies (HNPP) is an uncommon diagnosis that should be considered in patients\\u000a with multiple compressive neuropathies. We present the case of a woman who presented with bilateral hand numbness and weakness.\\u000a Electrodiagnostic testing revealed bilateral carpal tunnel syndrome, bilateral ulnar neuropathy at the elbow, left peroneal\\u000a neuropathy at the fibular head, and a primarily

  2. Diabetic Neuropathies: Update on Definitions, Diagnostic Criteria, Estimation of Severity, and Treatments

    PubMed Central

    Tesfaye, Solomon; Boulton, Andrew J.M.; Dyck, Peter J.; Freeman, Roy; Horowitz, Michael; Kempler, Peter; Lauria, Giuseppe; Malik, Rayaz A.; Spallone, Vincenza; Vinik, Aaron; Bernardi, Luciano; Valensi, Paul

    2010-01-01

    Preceding the joint meeting of the 19th annual Diabetic Neuropathy Study Group of the European Association for the Study of Diabetes (NEURODIAB) and the 8th International Symposium on Diabetic Neuropathy in Toronto, Canada, 13–18 October 2009, expert panels were convened to provide updates on classification, definitions, diagnostic criteria, and treatments of diabetic peripheral neuropathies (DPNs), autonomic neuropathy, painful DPNs, and structural alterations in DPNs. PMID:20876709

  3. Noise-Enhanced Vibrotactile Sensitivity in Older Adults, Patients With Stroke, and Patients With Diabetic Neuropathy

    E-print Network

    Collins, James J.

    With Diabetic Neuropathy Wen Liu, PhD, Lewis A. Lipsitz, MD, Manuel Montero-Odasso, MD, Jonathan Bean, MD, D, and patients with diabetic neuropathy. Arch Phys Med Rehabil 2002;83: 171-6. Objective: To test the hypothesis that vibrotactile detection thresholds in older adults, patients with stroke, and patients with diabetic neuropathy

  4. QUANTITATIVE PREDICTION OF GRASP IMPAIRMENT FOLLOWING PERIPHERAL NEUROPATHIES OF THE HAND

    E-print Network

    Valero-Cuevas, Francisco

    QUANTITATIVE PREDICTION OF GRASP IMPAIRMENT FOLLOWING PERIPHERAL NEUROPATHIES OF THE HAND Joshua M peripheral neuropathies of the hand [1]. Using a novel computational framework for calculating grasp quality neuropathies: (i) carpal tunnel syndrome, (ii) low median nerve palsy, (iii) low ulnar nerve palsy, and (iv

  5. Neuropathy Target Esterase Biosensor Devesh Srivastava1, Neeraj Kohli1, Rudy J. Richardson2,

    E-print Network

    Lee, Ilsoon

    12 Neuropathy Target Esterase Biosensor Devesh Srivastava1, Neeraj Kohli1, Rudy J. Richardson2, University of Michigan United States of America 1. Introduction Neuropathy Target Esterase (NTE-induced delayed neuropathy (OPIDN) (Glynn, 1999). Signs of OPIDN include flaccid paralysis of the lower limbs

  6. Immediate heart-rate response to standing: simple test for autonomic neuropathy in diabetes

    Microsoft Academic Search

    D J Ewing; I W Campbell; A Murray; J M Neilson; B F Clarke

    1978-01-01

    The immediate heart-rate response to standing was measured in 22 normal controls and 25 patients with diabetes, 15 of whom had autonomic neuropathy. The response in the controls and patients without autonomic neuropathy was characteristic and consistent, with tachycardia maximal at around the 15th beat and relative bradycardia maximal at around the 30th beat. The diabetics with autonomic neuropathy, however,

  7. Soluble Epoxide Hydrolase Inhibition Is Antinociceptive in a Mouse Model of Diabetic Neuropathy

    E-print Network

    Hammock, Bruce D.

    Soluble Epoxide Hydrolase Inhibition Is Antinociceptive in a Mouse Model of Diabetic Neuropathy therapies without severe side effects to treat the uniquely persistent and tonic pain of neuropathy, the conditioned place preference assay has been used to evaluate the tonic nature of neuropathy in several animal

  8. A preventative foot care programme for people with diabetes with different stages of neuropathy

    Microsoft Academic Search

    Alfonso L Calle-Pascual; Alejandra Durán; Angeles Bened??; Maria I Calvo; Aniceto Charro; Jose A Diaz; Jose R Calle; Esther Gil; Juan P Marañes; Jose Cabezas-Cerrato

    2002-01-01

    The aim of this study was to assess the efficacy of a preventative foot care programme, applied in a normal outpatient setting to decrease the incidence of foot ulcers in people with diabetes diagnosed as having neuropathy by neuropathy disability score (NDS), in relation to the severity of neuropathy based on the vibration perception threshold (VPT). A structured continuous preventative

  9. Significance of immunoglobulin deposition in peripheral nerve in neuropathies associated with paraproteinaemia

    Microsoft Academic Search

    M Swash; J Perrin; M S Schwartz

    1979-01-01

    Direct and indirect immunofluorescent studies of sural nerves were carried out in two patients with paraproteinaemia and neuropathy, in four other patients with axonal or demyelinating neuropathies, and in one normal sural nerve. IgM was demonstrated directly in the two cases of paraproteinaemia and neuropathy, and indirectly, using the serum of one of these cases, in a case of axonal

  10. 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

  11. [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

  12. Auditory Neuropathy/Dys-synchrony and Its Perceptual Consequences

    PubMed Central

    Rance, Gary

    2005-01-01

    Auditory neuropathy/dys-synchrony is a form of hearing impairment in which cochlear outer hair cell function is spared but neural transmission in the auditory pathway is disordered. This condition, or group of conditions with a common physiologic profile, accounts for approximately 7% of permanent childhood hearing loss and a significant (but as yet undetermined) proportion of adult impairment. This paper presents an overview of the mechanisms underlying auditory neuropathy/dys-synchrony-type hearing loss and the clinical profile for affected patients. In particular it examines the perceptual consequences of auditory neuropathy/dys-synchrony, which are quite different from those associated with sensorineural hearing loss, and considers currently available, and future management options. PMID:15920648

  13. 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.

  14. Peripheral neuropathy in a cat with renal lymphoma.

    PubMed

    Cavana, Paola; Sammartano, Federica; Capucchio, Maria T; Catalano, Deborah; Valazza, Alberto; Farca, Anna M

    2009-10-01

    A 12-year-old male cat was referred for progressive limb weakness lasting 2 weeks. Physical examination detected muscle atrophy and bilateral renomegaly with distortion of the renal contours. The cat was ambulatory but tetraparetic. It showed a peculiar posture on forelimbs with bilateral flexion of the carpi and extrarotation of forearms. The cat was unable to go upstairs or jump. Neurological examination showed findings compatible with peripheral nervous system involvement. Histopathological findings revealed a high grade non-B, non-T cell renal lymphoma and peripheral neuropathy characterised by demyelination, axonal degeneration and muscle denervation. In the absence of congenital, metabolic and infectious diseases or exposure to toxins, a paraneoplastic peripheral neuropathy was hypothesised. In humans and dogs, paraneoplastic peripheral neuropathies have been documented with different neoplastic processes including lymphoproliferative disorders. To the authors' knowledge, this is the first report of suspected paraneoplastic polyneuropathy in a cat with malignant tumour. PMID:19464217

  15. Small-fiber neuropathy: answering the burning questions.

    PubMed

    Fink, Ezekiel; Oaklander, Anne Louise

    2006-03-01

    Small-fiber neuropathy is a peripheral nerve disease that most commonly presents in middle-aged and older people, who develop burning pain in their feet. Although it can be caused by disorders of metabolism such as diabetes, chronic infections (such as with human immunodeficiency virus), genetic abnormalities, toxicity from various drugs, and autoimmune diseases, the cause often remains a mystery because standard electrophysiologic tests for nerve injury do not detect small-fiber function. Inadequate ability to test for and diagnose small-fiber neuropathies has impeded patient care and research, but new tools offer promise. Infrequently, the underlying cause of small-fiber dysfunction is identified and disease-modifying therapy can be instituted. More commonly, the treatments for small-fiber neuropathy involve symptomatic treatment of neuropathic pain. PMID:16525192

  16. Epidermal Nerve Fiber Quantification in the Assessment of Diabetic Neuropathy

    PubMed Central

    Beiswenger, Kristina K.; Calcutt, Nigel A.; Mizisin, Andrew P.

    2008-01-01

    Summary Assessment of cutaneous innervation in skin biopsies is emerging as a valuable means of both diagnosing and staging diabetic neuropathy. Immunolabeling, using antibodies to neuronal proteins such as protein gene product 9.5, allows for the visualization and quantification of intraepidermal nerve fibers. Multiple studies have shown reductions in intraepidermal nerve fiber density in skin biopsies from patients with both type 1 and type 2 diabetes. More recent studies have focused on correlating these changes with other measures of diabetic neuropathy. A loss of epidermal innervation similar to that observed in diabetic patients has been observed in rodent models of both type 1 and type 2 diabetes and several therapeutics have been reported to prevent reductions in intraepidermal nerve fiber density in these models. This review discusses the current literature describing diabetes-induced changes in cutaneous innervation in both human and animal models of diabetic neuropathy. PMID:18384843

  17. Further studies of the central nervous system in canine giant axonal neuropathy.

    PubMed

    Griffiths, I R; Duncan, I D; McCulloch, M; Carmichael, S

    1980-01-01

    The CNS of three further cases of canine giant axonal neuropathy (GAN) were examined. The axonal swellings were present in the distal portions of the spinal long tracts and their terminations in the cerebellar vermis; in the distal optic pathways; the nuclei of the habenulo-interpeduncular tract; certain thalamic relay nuclei and the cerebral cortex. The swellings were present both paranodally and internodally with the myelin sheath being attenuated or even absent. Excessive numbers of disordered 10 nm neurofilaments were the main constituent although mitochondria, membranous bodies, glycogen bodies and amorphous electron dense material also accumulated, particularly in the fasciculus gracilis. The neurotubules tended to form small subaxolemmal or intra-axonal islands. Complex interdigitations of oligodendroglia and axolemma were found in the affected areas. A small number of fibres in the rostral fasciculus gracilis showed marked proliferation of the smooth endoplasmic reticulum which may represent abortive attempts at regeneration. A small proportion of astrocytic processes were markedly enlarged with excessive whorling of the glial filaments. The accumulation of these various organelles in the non-terminal axon in the absence of mechanical obstruction suggests a defect in axoplasmic transport which may result from an energy failure as suggested in toxic neuropathies. The significance and pathogenesis of the glial filamentous changes and those reported in other cells in human GAN is at present uncertain. PMID:7453946

  18. Painful neuropathies: the emerging role of sodium channelopathies.

    PubMed

    Brouwer, Brigitte A; Merkies, Ingemar S J; Gerrits, Monique M; Waxman, Stephen G; Hoeijmakers, Janneke G J; Faber, Catharina G

    2014-06-01

    Pain is a frequent debilitating feature reported in peripheral neuropathies with involvement of small nerve (A? and C) fibers. Voltage-gated sodium channels are responsible for the generation and conduction of action potentials in the peripheral nociceptive neuronal pathway where NaV 1.7, NaV 1.8, and NaV 1.9 sodium channels (encoded by SCN9A, SCN10A, and SCN11A) are preferentially expressed. The human genetic pain conditions inherited erythromelalgia and paroxysmal extreme pain disorder were the first to be linked to gain-of-function SCN9A mutations. Recent studies have expanded this spectrum with gain-of-function SCN9A mutations in patients with small fiber neuropathy and in a new syndrome of pain, dysautonomia, and small hands and small feet (acromesomelia). In addition, painful neuropathies have been recently linked to SCN10A mutations. Patch-clamp studies have shown that the effect of SCN9A mutations is dependent upon the cell-type background. The functional effects of a mutation in dorsal root ganglion (DRG) neurons and sympathetic neuron cells may differ per mutation, reflecting the pattern of expression of autonomic symptoms in patients with painful neuropathies who carry the mutation in question. Peripheral neuropathies may not always be length-dependent, as demonstrated in patients with initial facial and scalp pain symptoms with SCN9A mutations showing hyperexcitability in both trigeminal ganglion and DRG neurons. There is some evidence suggesting that gain-of-function SCN9A mutations can lead to degeneration of peripheral axons. This review will focus on the emerging role of sodium channelopathies in painful peripheral neuropathies, which could serve as a basis for novel therapeutic strategies. PMID:25250524

  19. Ulnar Neuropathy With Normal Electrodiagnosis and Abnormal Nerve Ultrasound

    PubMed Central

    Yoon, Joon Shik; Walker, Francis O.; Cartwright, Michael S.

    2010-01-01

    Ulnar neuropathy at the elbow (UNE) is the second most common entrapment neuropathy. It is diagnosed with electrodiagnostic studies, but they can yield false-negative results. Ultrasound was used to examine 4 patients with UNE and negative electrodiagnostic findings, and it showed ulnar nerve enlargement near the elbow in all cases, with a mean cross-sectional area of 20.1mm2. This indicates that ultrasound may be a useful tool for assessing those with UNE symptoms and normal electrodiagnostic findings. PMID:20159139

  20. Ulnar neuropathy at the elbow: an evidence-based algorithm.

    PubMed

    Chimenti, Peter C; Hammert, Warren C

    2013-08-01

    Ulnar neuropathy at the elbow is the second most common compression neuropathy of the upper extremity and poses a challenge for treating physicians. Lack of a standardized grading system, outcome measures, or surgical indications can make treatment decisions difficult to justify. Conclusions drawn from the available literature include similar rates of good to excellent outcomes for in situ decompression; transposition in the subcutaneous, submuscular, or intramuscular planes; and endoscopic decompression. Outcomes for revision surgery are generally less favorable. Development of standardized outcomes measures will be important in improving the quality and comparability of the literature on this subject. PMID:23895724

  1. Bortezomib-induced painful neuropathy in patients with multiple myeloma

    PubMed Central

    Usnarska-Zubkiewicz, Lidia; Pokryszko-Dragan, Anna

    2013-01-01

    Neurotoxicity towards the peripheral nervous system which appears clinically in the form of painful neuropathy is an essential dose-limiting factor during the treatment of multiple myeloma. In this review article different forms of this painful neuropathy are presented together with currently available diagnostic tools which are usually applied to confirm the diagnosis. Also, the most often used neurological scales estimating neurological deficit are presented. Special attention is paid to the management of the reversibility of bortezomib-induced neuropathic pain. PMID:24596530

  2. Ulnar neuropathy with normal electrodiagnosis and abnormal nerve ultrasound.

    PubMed

    Yoon, Joon Shik; Walker, Francis O; Cartwright, Michael S

    2010-02-01

    Ulnar neuropathy at the elbow (UNE) is the second most common entrapment neuropathy. It is diagnosed with electrodiagnostic studies, but they can yield false-negative results. Ultrasound was used to examine 4 patients with UNE and negative electrodiagnostic findings, and it showed ulnar nerve enlargement near the elbow in all cases, with a mean cross-sectional area of 20.1 mm. This indicates that ultrasound may be a useful tool for assessing those with UNE symptoms and normal electrodiagnostic findings. PMID:20159139

  3. Bilateral intraneural perineurioma presenting as ulnar neuropathy at the elbow.

    PubMed

    Beekman, Roy; Slooff, Willem-Bart M; Van Oosterhout, Matthijs F M; Lammens, Martin; Van Den Berg, Leonard H

    2004-08-01

    We describe a 36-year-old woman with progressive bilateral ulnar neuropathy. Sonographic and magnetic resonance imaging studies revealed extensive focal ulnar nerve enlargement at the elbow. Histological studies gave evidence of an intraneural perineurioma. Because intraneural perineurioma usually appears as a single mass lesion at sites other than typical entrapment sites, this mode of presentation is unusual. We discuss the nature of this benign tumor and the differential diagnosis of nerve enlargement. Knowledge of possible causes of nerve thickening is crucial when performing imaging in patients with neuropathies. PMID:15266642

  4. Autonomic Involvement in Subacute and Chronic Immune-Mediated Neuropathies

    PubMed Central

    Mazzeo, Anna; Stancanelli, Claudia; Vita, Giuseppe

    2013-01-01

    Autonomic function can be impaired in many disorders in which sympathetic, parasympathetic, and enteric arms of the autonomic nervous system are affected. Signs and symptoms of autonomic involvement are related to impairment of cardiovascular, gastrointestinal, urogenital, thermoregulatory, sudomotor, and pupillomotor autonomic functions. Availability of noninvasive, sensitive, and reproducible tests can help to recognize these disorders and to better understand specific mechanisms of some, potentially treatable, immune-mediated autonomic neuropathies. This paper describes autonomic involvement in immune-mediated neuropathies with a subacute or chronic course. PMID:23853716

  5. 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

  6. Generalized peripheral neuropathy in a dental technician exposed to methyl methacrylate monomer

    SciTech Connect

    Donaghy, M.; Rushworth, G.; Jacobs, J.M. (Department of Clinical Neurology, Radcliffe Infirmary, Oxford (England))

    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.

  7. Angiogenin gene polymorphism: A risk factor for diabetic peripheral neuropathy in the northern Chinese Han population

    PubMed Central

    Wang, Hongli; Fan, Dongsheng; Zhang, Yingshuang

    2013-01-01

    Angiogenin is associated with the pathogenesis of diabetic peripheral neuropathy. Here, we quenced the coding region of the angiogenin gene in genomic DNA from 207 patients with type 2 diabetes mellitus (129 diabetic peripheral neuropathy patients and 78 diabetic non-neuropathy patients) and 268 healthy controls. All subjects were from the Han population of northern China. No mutations were found. We then compared the genotype and allele frequencies of the angiogenin synonymous single nucleotide polymorphism rs11701 between the diabetic peripheral neuropathy patients and controls, and between the diabetic neuropathy and non-neuropathy patients, using a case-control design. We detected no statistically significant genetic associations. Angiogenin may not be associated with genetic susceptibility to diabetic peripheral neuropathy in the Han population of northern China. PMID:25206666

  8. Sciatic neuropathy secondary to total hip arthroplasty wear debris

    Microsoft Academic Search

    Steven R. Fischer; David J. Christ; Bernard A. Roehr

    1999-01-01

    Sciatic neuropathy after total hip arthroplasty can result from several causes. We present a case in which a large cystic mass developed around a failed total hip arthroplasty. The lesion extended through the greater sciatic notch and into the pelvis producing sciatic nerve compression. The diagnosis was delayed, and the patient underwent a laminectomy without relief of symptoms before an

  9. Rodent models of chemotherapy-induced peripheral neuropathy.

    PubMed

    Höke, Ahmet; Ray, Mitali

    2014-01-01

    Peripheral neuropathy is a common and dose-limiting side effect of many chemotherapeutic drugs. These include platinum compounds, taxanes, vinca alkaloids, proteasome inhibitors, and others such as thalidomide and suramin. Although many rodent models have been developed using either mice or rats, there is limited consistency in the dose or mode of delivery of the drug; the sex, age, and genetic background of the animal used in the study; and the outcome measures used in evaluation of the peripheral neuropathy. Behavioral assays are commonly used to evaluate evoked sensory responses but are unlikely to be a good representation of the spontaneous sensory paresthesias that the patients experience. Electrophysiologic tests evaluate the integrity of large myelinated populations and are useful in drugs that cause either demyelination or degeneration of large myelinated axons but are insensitive to degeneration of unmyelinated axons in early stages of neuropathy. Histopathologic tools offer an unbiased way to evaluate the degree of axonal degeneration or changes in neuronal cell body but are often time consuming and require processing of the tissue after the study is completed. Nevertheless, use of drug doses and mode of delivery that are relevant to the clinical protocols and use of outcome measures that are both sensitive and objective in evaluation of the length-dependent distal axonal degeneration seen in most chemotherapy-induced peripheral neuropathies may improve the translational utility of these rodent models. PMID:24615440

  10. Lacosamide has protective disease modifying properties in experimental vincristine neuropathy.

    PubMed

    Geis, Christian; Beyreuther, Bettina K; Stöhr, Thomas; Sommer, Claudia

    2011-09-01

    Pain and paresthesias are the most common symptoms of chemotherapy induced painful neuropathy (CIPN). Current treatment and preventive strategies of CIPN are ineffective, and the neuropathy may lead to discontinuation of anti-tumor therapy. Here we used experimental vincristine-induced neuropathy in rats to evaluate the disease modifying potential of lacosamide using a sustained release formulation and the acute treatment effects of a rapid release formulation. Pain behavior was assessed by withdrawal responses to von Frey hairs, acetone drops, the Randall-Selitto device, and to radiant heat. Neuropathy was assessed using electrophysiological recordings. Preventive lacosamide treatment (30 mg/kg subcutaneously b.i.d. for 17 days) was well tolerated, and pharmacokinetic analysis revealed a peak plasma concentration 2 h post-injection with a plasma half-life of approximately 3 h. Rats treated with lacosamide, in contrast to vehicle treated rats, did not develop vincristine-induced cold allodynia. Neurophysiology showed a delayed F-wave latency in vehicle treated rats, which was not present in lacosamide treated animals. We could thus demonstrate a protective disease modifying potency of lacosamide in an animal model of CIPN. Lacosamide may be a promising candidate for preventive treatment of CIPN in patients receiving chemotherapy with vinca alkaloids or platinum drugs. PMID:21586299

  11. Toxic peripheral neuropathy associated with commonly used chemotherapeutic agents.

    PubMed

    Argyriou, A A; Zolota, V; Kyriakopoulou, O; Kalofonos, H P

    2010-01-01

    Peripheral neuropathy ranks among the most common non-haematological adverse effects of a number of effective chemotherapeutic agents, including platinum compounds, taxanes and vinca alkaloids. Newer agents, such as bortezomib, thalidomide and lenalidomide, frequently exert similar neurotoxic effects on peripheral nerves. Chemotherapy-induced peripheral neuropathy (CIPN) may result from a variety of mechanisms and may be related to causal factors, such as single dose per course, cumulative dose and risk factors including treatment schedule, prior or concomitant administration of other neurotoxic agents, age and pre-existing peripheral neuropathy of other causes. The symptoms usually begin during chemotherapy and they may even worsen after cessation of treatment. In most of the cases, patients experience positive (pain, paresthesias) or negative (numbness) sensory symptoms in distal extremities in a stocking-and-glove distribution with less prominent motor and autonomic involvement. To date, several neuroprotective agents including thiols, neurotrophic factors, anticonvulsants and antioxidants have been tested in preclinical models and clinical open label or randomized controlled trials for their ability to prevent or treat symptoms of CIPN. Although several of these agents hold promise as possible neuroprotective factors, clinical data are still controversial and none have as yet robustly been proven effective against CIPN. This review critically looks at the pathogenesis, incidence, risk factors, diagnosis, characteristics and management of peripheral neuropathy associated with commonly used chemotherapeutic agents. We also highlight areas of future research to pursue. PMID:20941808

  12. Patient perceptions associated with chemotherapy-induced peripheral neuropathy.

    PubMed

    Tofthagen, Cindy

    2010-06-01

    Peripheral neuropathies are a common side effect of certain types of chemotherapy drugs, including taxanes, platinum-based drugs, vinca alkaloids, and thalidomide. Neuropathies may last for months or years following treatment and can impact functional performance and quality of life. The purpose of this study was to explore the effects of chemotherapy-induced peripheral neuropathy (CIPN) and neuropathic pain on the lives of patients with cancer. Participants were recruited from an urban outpatient medical oncology clinic in West Central Florida. Semistructured, private interviews with 14 participants were conducted and transcripts were reviewed for symptoms and effects. Participants often had difficulty describing neuropathic symptoms but reported simultaneous pain or discomfort and loss of sensation in the upper and lower extremities. Injuries secondary to numbness, muscle weakness, and loss of balance were reported. Neuropathic symptoms interfered with many aspects of daily life and participants voiced feelings of frustration, depression, and loss of purpose as a result of having to give up enjoyable activities. The results of this study emphasize the importance of ongoing assessment and communication with patients about their experiences with peripheral neuropathies. Knowledge of what patients with CIPN experience will guide nurses in suggesting interventions to promote safety and help alleviate symptoms. PMID:20529785

  13. 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 ...

  14. Giant axonal neuropathy: a conditional mutation affecting cytoskeletal organization

    Microsoft Academic Search

    MICHAEL W. KLYMKOWSKY; DOROTHY J. PLUMMER

    1985-01-01

    Giant axonal neuropathy (GAN) results from autosomal recessive mutations (gan-) that affect cytoskeletal organization; specifically, intermediate filaments (IFs) are found col- lapsed into massive bundles in a variety of different cell types. We studied the gan- fibroblast lines WG321 and WG139 derived from different GAN patients. Although previous studies implied that the gan- IF phenotype was constitutive, we find that

  15. Ménière’s Disease Is a Viral Neuropathy

    Microsoft Academic Search

    Richard R. Gacek

    2009-01-01

    Morphological and clinical evidence supports a viral neuropathy in Ménière’s disease (MD). Quantitative examination of 11 sectioned temporal bones (TBs) from 8 patients with a history of MD revealed a significant loss of vestibular ganglion cells in both the endolymph hydropic (EH) and non-EH ears. Transmission electron microscopy of vestibular ganglion cells excised from a patient with MD revealed viral

  16. Nerve biopsy and conduction studies in diabetic neuropathy

    Microsoft Academic Search

    F Behse; F Buchthal; F Carlsen

    1977-01-01

    Morphological findings in sural nerves were related to nerve conduction in 12 patients with diabetic neuropathy, five with mainly sensory involvement, four with severe, symmetrical sensory-motor polyneuropathy, and three with multiple mononeuropathy. All had loss of large and small myelinated and of unmyelinated fibres, even early in the disease; segmental remyelination was the most prominent myelin alteration in teased fibres,

  17. The natural history of acute painful neuropathy in diabetes mellitus

    Microsoft Academic Search

    A G Archer; P J Watkins; P K Thomas; A K Sharma; J Payan

    1983-01-01

    Observations have been made on nine cases of painful diabetic neuropathy of acute onset. All cases were male and all were associated with and preceded by precipitous and severe weight loss. The pain was of a continuous burning quality and experienced mainly in the legs, especially distally. Contact discomfort of the skin was often a troublesome feature, but sensory loss

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

    Microsoft Academic Search

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

    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

  19. Entrapment neuropathy of the wrist, forearm, and elbow.

    PubMed

    Xing, Shu Guo; Tang, Jin Bo

    2014-07-01

    This review discusses key diagnostic points and treatment guidelines for compression neuropathies of the wrist, forearm, and elbow. Recent treatment progress is reviewed, controversies are highlighted, and consensus is summarized. Limited or mini-open releases and endoscopic carpal tunnel releases are considered equally safe and efficient. Both methods are currently mainstays of surgical treatment. PMID:24996472

  20. Progress in the treatment of small fiber peripheral neuropathy.

    PubMed

    Chiang, Ming-Chang; Tseng, Ming-Tsung; Pan, Chun-Liang; Chao, Chi-Chao; Hsieh, Sung-Tsang

    2015-03-01

    Small fiber neuropathy is a syndrome of diverse disease etiology because of multiple pathophysiologic mechanisms with major presentations of neuropathic pain and autonomic symptoms. Over the past decade, there has been substantial progress in the treatments for neuropathic pain, dysautonomia and disease-modifying strategy. In particular, anticonvulsants and antidepressants alleviate neuropathic pain based on randomized clinical trials. PMID:25664678

  1. Management of treatment-emergent peripheral neuropathy in multiple myeloma

    Microsoft Academic Search

    P G Richardson; M Delforge; M Beksac; P Wen; J L Jongen; O Sezer; E Terpos; N Munshi; A Palumbo; S V Rajkumar; J L Harousseau; P Moreau; H Avet-Loiseau; J H Lee; M Cavo; G Merlini; P Voorhees; W J Chng; A Mazumder; S Usmani; H Einsele; R Comenzo; R Orlowski; D Vesole; J J Lahuerta; R Niesvizky; D Siegel; M-V Mateos; M Dimopoulos; S Lonial; S Jagannath; J Bladé; J San Miguel; G Morgan; K C Anderson; B G M Durie; P Sonneveld

    2012-01-01

    Peripheral neuropathy (PN) is one of the most important complications of multiple myeloma (MM) treatment. PN can be caused by MM itself, either by the effects of the monoclonal protein or in the form of radiculopathy from direct compression, and particularly by certain therapies, including bortezomib, thalidomide, vinca alkaloids and cisplatin. Clinical evaluation has shown that up to 20% of

  2. Experimental diabetes in neonatal mice induces early peripheral sensorimotor neuropathy.

    PubMed

    Ariza, L; Pagès, G; García-Lareu, B; Cobianchi, S; Otaegui, P J; Ruberte, J; Chillón, M; Navarro, X; Bosch, A

    2014-08-22

    Animal models of diabetes do not reach the severity of human diabetic neuropathy but relatively mild neurophysiological deficits and minor morphometric changes. The lack of degenerative neuropathy in diabetic rodent models seems to be a consequence of the shorter length of the axons or the shorter animal life span. Diabetes-induced demyelination needs many weeks or even months before it can be evident by morphometrical analysis. In mice myelination of the peripheral nervous system starts at the prenatal period and it is complete several days after birth. Here we induced experimental diabetes to neonatal mice and we evaluated its effect on the peripheral nerve 4 and 8 weeks after diabetes induction. Neurophysiological values showed a decline in sensory nerve conduction velocity at both time-points. Morphometrical analysis of the tibial nerve demonstrated a decrease in the number of myelinated fibers, fiber size and myelin thickness at both time-points studied. Moreover, aldose reductase and poly(ADP-ribose) polymerase activities were increased even if the amount of the enzyme was not affected. Thus, type 1 diabetes in newborn mice induces early peripheral neuropathy and may be a good model to assay pharmacological or gene therapy strategies to treat diabetic neuropathy. PMID:24846610

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

    MedlinePLUS

    ... and transport. This accumulation likely damages and kills motor neurons (specialized nerve cells in the brain and spinal cord that control muscle movement), leading to muscle weakness in the hands and ... to distal hereditary motor neuropathy, type V. The mutations probably reduce the ...

  4. Clinical research for neuropathies. | accrualnet.cancer.gov

    Cancer.gov

    The author discusses several ways in which participation in clinical research on neuropathies can be improved. Both patients and providers need to become better informed about the availability of trials. Patient advocacy groups and professional organizations should play a major role in informing their constituents about the value of clinical research and assist patients and providers in becoming involved.

  5. MR neurography in diagnosing nondiabetic lumbosacral radiculoplexus neuropathy.

    PubMed

    Filosto, Massimiliano; Pari, Elisa; Cotelli, Mariasofia; Todeschini, Alice; Vielmi, Valentina; Rinaldi, Fabrizio; Padovani, Alessandro; Gasparotti, Roberto

    2013-10-01

    Here we describe the imaging findings in a 73-year-old woman who had pain in the right inguinal region, followed by progressive weakness of muscles innervated by the right femoral and obturator nerves, diagnosed as nondiabetic lumbosacral radiculoplexus neuropathy. Magnetic resonance neurography showed thickening and increase in signal intensity of the right femoral and obturator nerves. PMID:23750469

  6. Chemotherapy-induced peripheral neuropathies in hematological malignancies.

    PubMed

    Jongen, Joost Louis Marie; Broijl, Annemiek; Sonneveld, Pieter

    2015-01-01

    Recent developments in the treatment of hematological malignancies, especially with the advent of proteasome inhibitors and immunomodulatory drugs in plasma cell dyscrasias, call for an increased collaboration between hematologists and neurologists. This collaboration involves differentiating chemotherapy-induced peripheral neuropathies (CiPN) from disease-related neurologic complications, early recognition of CiPN and treatment of neuropathic pain. Multiple myeloma, Waldenstrom's macroglobulinemia and light-chain amyloidosis frequently present with peripheral neuropathy. In addition, multiple myeloma, non-Hodgkin lymphomas and leukemia's may mimic peripheral neuropathy by compression or invasion of the extra/intradural space. Platinum compounds, vinca alkaloids, proteasome inhibitors and immunomodulatory drugs may all cause CiPN, each with different and often specific clinical characteristics. Early recognition, by identifying the distinct clinical phenotype of CiPN, is of crucial importance to prevent irreversible neurological damage. No recommendations can be given on the use of neuroprotective strategies because of a lack of convincing clinical evidence. Finally, CiPN caused by vinca-alkaloids, proteasome inhibitors and immunomodulatory drugs is often painful and neurologists are best equipped to treat this kind of painful neuropathy. PMID:25326770

  7. Neuropathological alterations in diabetic truncal neuropathy: evaluation by skin biopsy

    PubMed Central

    Lauria, G.; McArthur, J.; Hauer, P.; Griffin, J.; Cornblath, D.

    1998-01-01

    OBJECTIVES—To describe the neuropathological features in skin biopsies from patients with diabetic truncal neuropathy.?METHODS—Three patients with diabetic truncal neuropathy underwent skin biopsies from both symptomatic and asymptomatic regions of the chest and trunk. After local anaesthesia, biopsies were performed using a 3 mm diameter punch device (Acupunch). Intraepidermal nerve fibres (IENFs), the most distal processes of small myelinated and unmyelinated nerve fibres, were identified after staining with PGP 9.5 as previously described.?RESULTS—Diabetes was diagnosed at the time of the neurological presentation in two, and one was a known diabetic patient. All three had associated sensory-motor polyneuropathy. In all, skin biopsies showed a marked reduction of both epidermal and dermal nerve fibres in the symptomatic dermatomes, compared with skin from asymptomatic truncal areas. In one patient, a follow up skin biopsy when symptoms had improved showed a return of IENFs.?CONCLUSIONS—In diabetic truncal neuropathy, skin biopsies from symptomatic regions show a loss of IENFs. After clinical recovery, there is a return of the IENF population, suggesting that improvement occurs by nerve regeneration. These findings suggest that sensory nerve fibre injury in diabetic truncal neuropathy is distal to or within the sensory ganglia. Skin biopsy provides a possible tool for understanding the pathophysiology of the disease.?? PMID:9810952

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

    PubMed

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

    2012-11-01

    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. PMID:22889832

  9. Microneurographic evaluation of sympathetic activity in small fiber neuropathy

    Microsoft Academic Search

    Rocco Liguori; Maria Pia Giannoccaro; Vitantonio Di Stasi; Fabio Pizza; Pietro Cortelli; Agostino Baruzzi; Pasquale Montagna; Vincenzo Donadio

    2011-01-01

    ObjectiveSmall fiber neuropathy (SFN) may involve somatic and autonomic fibers. Assessment of somatic epidermal nerve fiber density (ENFs) is considered the gold standard test in the diagnosis of SFN. By contrast, autonomic involvement in SFN is more difficult to ascertain. Here we investigate peripheral sympathetic outflow by microneurography in patients with selective small nerve fiber involvement of different origin with

  10. Chronic inflammatory demyelinating polyneuropathy or hereditary motor and sensory neuropathy?

    Microsoft Academic Search

    A. A. W. M. Gabreëls-Festen; F. J. M. Gabreëls; J. E. Hoogendijk; P. A. Bolhuis; P. J. H. Jongen; H. M. Vingerhoets

    1993-01-01

    The pathological changes generally considered to distinguish chronic inflammatory demyelinating polyneuropathy (CIDP) from hereditary motor and sensory neuropathy (HMSN) are: mononuclear cell infiltrates, prominent endoneurial oedema, and marked fascicle-to-fascicle variability. We evaluated the diagnostic significance of these pathological features which are suggestive of CIDP. Nerve biopsies from 42 dominant HMSN type I cases with a normal disease course were investigated

  11. Fibered fluorescence microscopy (FFM) of intra epidermal nerve fibers--translational marker for peripheral neuropathies in preclinical research: processing and analysis of the data

    Microsoft Academic Search

    Frans Cornelissen; Steve De Backer; Jan Lemeire; Berf Torfs; Rony Nuydens; Theo Meert; Peter Schelkens; Paul Scheunders

    2008-01-01

    Peripheral neuropathy can be caused by diabetes or AIDS or be a side-effect of chemotherapy. Fibered Fluorescence Microscopy (FFM) is a recently developed imaging modality using a fiber optic probe connected to a laser scanning unit. It allows for in-vivo scanning of small animal subjects by moving the probe along the tissue surface. In preclinical research, FFM enables non-invasive, longitudinal

  12. Binaural speech processing in individuals with auditory neuropathy.

    PubMed

    Rance, G; Ryan, M M; Carew, P; Corben, L A; Yiu, E; Tan, J; Delatycki, M B

    2012-12-13

    Auditory neuropathy disrupts the neural representation of sound and may therefore impair processes contingent upon inter-aural integration. The aims of this study were to investigate binaural auditory processing in individuals with axonal (Friedreich ataxia) and demyelinating (Charcot-Marie-Tooth disease type 1A) auditory neuropathy and to evaluate the relationship between the degree of auditory deficit and overall clinical severity in patients with neuropathic disorders. Twenty-three subjects with genetically confirmed Friedreich ataxia and 12 subjects with Charcot-Marie-Tooth disease type 1A underwent psychophysical evaluation of basic auditory processing (intensity discrimination/temporal resolution) and binaural speech perception assessment using the Listening in Spatialized Noise test. Age, gender and hearing-level-matched controls were also tested. Speech perception in noise for individuals with auditory neuropathy was abnormal for each listening condition, but was particularly affected in circumstances where binaural processing might have improved perception through spatial segregation. Ability to use spatial cues was correlated with temporal resolution suggesting that the binaural-processing deficit was the result of disordered representation of timing cues in the left and right auditory nerves. Spatial processing was also related to overall disease severity (as measured by the Friedreich Ataxia Rating Scale and Charcot-Marie-Tooth Neuropathy Score) suggesting that the degree of neural dysfunction in the auditory system accurately reflects generalized neuropathic changes. Measures of binaural speech processing show promise for application in the neurology clinic. In individuals with auditory neuropathy due to both axonal and demyelinating mechanisms the assessment provides a measure of functional hearing ability, a biomarker capable of tracking the natural history of progressive disease and a potential means of evaluating the effectiveness of interventions. PMID:22982232

  13. Giant axonal neuropathy: clinical and genetic study in six cases

    PubMed Central

    Demir, E; Bomont, P; Erdem, S; Cavalier, L; Demirci, M; Kose, G; Muftuoglu, S; Cakar, A; Tan, E; Aysun, S; Topcu, M; Guicheney, P; Koenig, M; Topaloglu, H

    2005-01-01

    Background: Giant axonal neuropathy (GAN) is a severe recessive disorder characterised by variable combination of progressive sensory motor neuropathy, central nervous system (CNS) involvement, and "frizzly" hair. The disease is caused by GAN gene mutations on chromosome 16q24.1. Aims: To search for GAN gene mutations in Turkish patients with GAN and characterise the phenotype associated with them. Methods: Linkage and mutation analyses were performed in six affected patients from three consanguineous families. These patients were also investigated by cranial magnetic resonance imaging (MRI) and electroencephalography (EEG). Electromyography (EMG) was performed in heterozygous carriers from family 1 and family 3. Results: Linkage to 16q24.1 was confirmed by haplotype analysis. GAN mutations were identified in all families. Family 1 had the R293X mutation, previously reported in another Turkish family. Families 2 and 3, originating from close geographical areas, shared a novel mutation, 1502+1G>T, at the donor splice site of exon 9. All patients displayed a common phenotype, including peripheral neuropathy, cerebellar ataxia, and frizzly hair. Cranial MRI showed diffuse white matter abnormalities in two patients from family 1 and the patient from family 3, and minimal white matter involvement in the patient from family 2. EMG of a heterozygous R293X mutation carrier showed signs of mild axonal neuropathy, whereas a 1502+1G>T mutation carrier had normal EMG. EEG abnormalities were found in three patients. Conclusion: These findings highlight the association of CNS involvement, in particular white matter abnormalities, with peripheral neuropathy in GAN. The phenotypical consequences of both mutations (when homozygous) were similar. PMID:15897506

  14. [Review of the recent literature on hereditary neuropathies].

    PubMed

    Birouk, N

    2014-12-01

    The recent literature included interesting reports on the pathogenic mechanisms of hereditary neuropathies. The axonal traffic and its abnormalities in some forms of Charcot-Marie-Tooth (CMT) disease were particularly reviewed by Bucci et al. Many genes related to CMT disease code for proteins that are involved directly or not in intracellular traffic. KIF1B controls vesicle motility on microtubules. MTMR2, MTMR13 and FIG4 regulate the metabolism of phosphoinositide at the level of endosomes. The HSPs are involved in the proteasomal degradation. GDAP1 and MFN2 regulate the mitochondrial fission and fusion respectively and the mitochondial transport within the axon. Pareyson et al. reported a review on peripheral neuropathies in mitochondrial disorders. They used the term of "mitochondrial CMT" for the forms of CMT with abnormal mitochondrial dynamic or structure. Among the new entities, we can draw the attention to a proximal form of hereditary motor and sensory neuropathy with autosomal dominant inheritance, which is characterized by motor deficit with cramps and fasciculations predominating in proximal muscles. Distal sensory deficit can be present. The gene TFG on chromosome 3 has been recently identified to be responsible for this form. Another rare form of axonal autosomal recessive neuropathy due to HNT1 gene mutation is characterized by the presence of hands myotonia that appears later than neuropathy but constitute an interesting clinical hallmark to orientate the diagnosis of this form. In terms of differential diagnosis, CMT4J due to FIG4 mutation can present with a rapidly progressive and asymmetric weakness that resembles CIDP. Bouhy et al. made an interesting review on the therapeutic trials, animal models and the future therapeutic strategies to be developed in CMT disease. PMID:25459128

  15. Transforming Growth Factor-? Induces Cellular Injury in Experimental Diabetic Neuropathy

    PubMed Central

    Anjaneyulu, Muragundla; Berent-Spillson, Alison; Inoue, Tatsuya; Choi, Joungil; Cherian, Kay; Russell, James W.

    2008-01-01

    The mechanism/s leading to diabetic neuropathy are complex. Transforming growth factor-?1 (TGF-?1) has been associated with diabetic nephropathy and retinopathy but not neuropathy. In this study, changes in TGF-? isoforms were examined in-vivo and in-vitro. Two groups of animals, streptozotocin diabetic with neuropathy and non-diabetic controls were examined at 4 weeks (n=10/group) and 12 weeks (n=8/group). In diabetic DRG using quantitative real-time PCR (QRT-PCR), TGF-?1 and TGF-?2 mRNA, but not TGF-?3, was increased at 4 and 12 weeks. In sciatic nerve TGF-?3 mRNA was primarily increased. Immunohistochemistry (DRG) and immunoblotting (sciatic nerve) showed similar differential protein expression. In sciatic nerve TGF-? formed homo- and heterodimers, of which ?2/?3, ?1/?1, and ?1/?3 were significantly increased, while that of the TGF-?2/?2 homodimer was decreased, in diabetic compared to non-diabetic rats. In-vitro, pretreatment of embryonic DRG with TGF-? neutralizing antibody prevents the increase in total TGF-? protein observed with high glucose using immunoblotting. In high glucose conditions, combination with TGF-?2 > ?1 increases the percent of cleaved caspase-3 compared to high glucose alone and TGF-? neutralizing antibody inhibits this increase. Furthermore, consistent with the findings in diabetic DRG and nerve, TGF-? isoforms applied directly in vitro reduce neurite outgrowth, and this effect is partially reversed by TGF-? neutralizing antibody. These findings implicate upregulation of TGF-? in experimental diabetic peripheral neuropathy and indicate a novel mechanism of cellular injury related to elevated glucose levels. In combination, these findings indicate a potential new target for treatment of diabetic peripheral neuropathy. PMID:18406405

  16. Onion bulb neuropathy in the trembler mouse: A model of hypertrophic interstitial neuropathy (Dejerine-Sottas) in man

    Microsoft Academic Search

    Margaret M. Ayers; R. McD Anderson

    1973-01-01

    The trembler mouse is a spontaneous mutant showing dominant inheritance. Clinical symptoms become manifest from 10 to 14 days of age as an action tremor affecting the head, neck and limbs, convulsions which decrease with increasing age, and weakness and rigidity of the limbs. Histological examination revealed a normal central nervous system, and a peripheral onion bulb neuropathy similar to

  17. PKC/MEK inhibitors suppress oxaliplatin-induced neuropathy and potentiate the antitumor effects.

    PubMed

    Tsubaki, Masanobu; Takeda, Tomoya; Tani, Tadahumi; Shimaoka, Hirotaka; Suzuyama, Naohiro; Sakamoto, Kotaro; Fujita, Arisa; Ogawa, Naoki; Itoh, Tatsuki; Imano, Motohiro; Funakami, Yoshinori; Ichida, Seiji; Satou, Takao; Nishida, Shozo

    2015-07-01

    Oxaliplatin is a key drug commonly used in colorectal cancer treatment. Despite high clinical efficacy, its therapeutic application is limited by common, dose-limiting occurrence of neuropathy. As usual symptomatic neuropathy treatments fail to improve the patients' condition, there is an urgent need to advance our understanding of the pathogenesis of neuropathy to propose effective therapy and ensure adequate pain management. Oxaliplatin-induced neuropathy was recently reported to be associated with protein kinase C (PKC) activation. It is unclear, however, whether PKC inhibition can prevent neuropathy. In our current studies, we found that a PKC inhibitor, tamoxifen, inhibited oxaliplatin-induced neuropathy via the PKC/extracellular signal-regulated kinase (ERK)/c-Fos pathway in lumbar spinal cords (lumbar segments 4-6). Additionally, tamoxifen was shown to act in synergy with oxaliplatin to inhibit growth in tumor cells-implanted mice. Moreover, mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, PD0325901, suppressed oxaliplatin-induced neuropathy and enhanced oxaliplatin efficacy. Our results indicate that oxaliplatin-induced neuropathy is associated with PKC/ERK/c-Fos pathway in lumbar spinal cord. Additionally, we demonstrate that disruption of this pathway by PKC and MEK inhibitors suppresses oxaliplatin-induced neuropathy, thereby suggesting that PKC and MEK inhibitors may be therapeutically useful in preventing oxaliplatin-induced neuropathy and could aid in combination antitumor pharmacotherapy. PMID:25430564

  18. Assessment of Peripheral Neuropathy in Patients With Rheumatoid Arthritis Who Complain of Neurologic Symptoms

    PubMed Central

    Sim, Mi Kyung; Yoon, Jisun; Park, Dae Hwan; Kim, Yong-Gil

    2014-01-01

    Objective To assess the prevalence of peripheral neuropathy in patients with rheumatoid arthritis (RA) having neuropathic symptoms, and to investigate the relationship between electrophysiological findings of peripheral neuropathy and clinical findings of RA. Methods Patients with a clinical diagnosis of RA and who had tingling or burning sensation in any extremity were electrophysiologically examined for evidence of peripheral neuropathy. Study parameters, including age, gender, laboratory parameters, duration of RA, and medication, were recorded. The symptoms and signs of neuropathy were quantified with the neuropathy symptom score, and the functional statuses of these patients were assessed. Results Out of a total of 30 RA patients, 10 (33%) had peripheral neuropathy: 2 had bilateral carpal tunnel syndrome (CTS), 5 had unilateral CTS, 1 had sensory polyneuropathy, and 2 had motor-sensory polyneuropathy. The mean ages of the patients with and without peripheral neuropathy were 69.4 and 56.5 years, respectively (p<0.05). A significant relationship was found between peripheral neuropathy and anti-cyclic citrullinated peptide (anti-CCP) antibody. However, no relationship was found between peripheral neuropathy and the type of medication, RA duration, the patients' functional status, neuropathic symptoms, erythrocyte sedimentation rate, and C-reactive protein values. Conclusion Neuropathic symptoms are common in RA patients, and it is difficult to distinguish peripheral neuropathy symptoms from those of arthritis. Patients with RA, particularly elderly patients and anti-CCP antibody positive patients who complain of neuropathic symptoms should undergo electrophysiological examination. PMID:24855620

  19. Diabetic neuropathy after pancreas transplantation: determinants of recovery.

    PubMed

    Allen, R D; Al-Harbi, I S; Morris, J G; Clouston, P D; O'Connell, P J; Chapman, J R; Nankivell, B J

    1997-03-27

    Although simultaneous pancreas and kidney transplantation (SPK) achieves normoglycemia and correction of uremia in type I diabetic patients with renal failure, little data are available on long-term outcome and clinical determinants of recovery of peripheral neuropathy. In this prospective study, 219 electrophysiological studies using a standardized protocol were performed before and up to 8 years after SPK in 44 patients. Nine control diabetic recipients with functioning kidney but nonfunctioning pancreas transplants were studied on 35 occasions. Patients were 38.5+/-7.9 years old (mean+/-SD) with pretransplant diabetes present for 25.2+/-7.6 years. Significant polyneuropathy (total nerve conduction scores [NCS] <-1.0) was present in 89% before transplantation, which correlated with body weight (r=0.628, P<0.001). Two distinct patterns of neurological recovery were observed after SPK. Conduction velocity (CV) improved in a biphasic pattern, with a rapid initial recovery followed by subsequent stabilization. In contrast, the recovery of nerve amplitude was monophasic, and continued to improve for up to 8 years. Initial improvement in NCS was primarily due to an increase in CV (P=0.002 vs. baseline), and was best in shorter and younger patients. Recovery of total NCS at 6 months after SPK, assessed by multivariate analysis, was least in obese recipients and when performed in patients who had started dialysis before SPK, and was associated with lower transplant kidney isotopic glomerular filtration rate and HLA mismatch (P<0.05 to 0.001). Subsequent improvement was associated with less severe initial neuropathy, smaller body weight, and longer duration of diabetes (P<0.01 to 0.001). Fasting hyperinsulinemia was associated with impairment of initial recovery and subsequent NCS after SPK, but was worse in the control group. Recovery of nerve action potential amplitudes was predicted by better initial amplitudes and HLA mismatch, lower body weight, and the use of nifedipine (P<0.05 to 0.001). Nifedipine was used for hypertension in 33% of SPK and was associated with better CV and amplitudes, particularly in the upper limbs, where there was less neuropathy. The use of angiotensin-converting enzyme inhibitors also appeared beneficial, but this was confined to the lower limbs. SPK resulted in a gradual, sustained, and late improvement in nerve action potential amplitudes, consistent with axonal regeneration and partial reversal of diabetic neuropathy. These data suggest that early transplantation of uremic diabetic patients before onset of severe neuropathy, minimizing obesity and optimizing renal transplant function, maximizes neurological recovery after SPK. Furthermore, the preliminary data support randomized clinical trials for evaluation of nifedipine and angiotensin-converting enzyme inhibitors in diabetic neuropathy. PMID:9089222

  20. Nonsystemic vasculitic neuropathy: update on diagnosis, classification, pathogenesis, and treatment.

    PubMed

    Collins, Michael P; Periquet-Collins, Isabel

    2009-01-01

    The primary systemic vasculitides are autoimmune disorders characterized by chronic immune responses directed against vascular structures. They commonly affect small or medium-sized vessels in the peripheral nervous system (PNS), producing vasculitic neuropathies. Some patients develop vasculitis clinically restricted to the PNS, known as nonsystemic vasculitic neuropathy (NSVN), the most commonly encountered vasculitic neuropathy in pathologically based series. Diabetic and nondiabetic radiculoplexus neuropathies are clinical variants of NSVN. NSVN is clinically similar to systemic vasculitis-associated neuropathies except for reduced severity. Patients most commonly present with progressive, stepwise pain, weakness, and numbness over multiple months. Almost all exhibit a multifocal or asymmetric, distally accentuated pattern of involvement. The most commonly affected nerves are the common peroneal nerve in the leg and the ulnar nerve in the arm. Sedimentation rate is mildly to moderately elevated in 50%; other markers of systemic inflammation are generally normal. Electrodiagnostic studies reveal a predominantly axonal, asymmetric, sensorimotor polyneuropathy, but pseudo-conduction blocks may occur. Definite diagnosis requires biopsy evidence of vascular inflammation and signs of active or remote vascular damage. In biopsies lacking definite vasculitis, the diagnosis is suspected if axonal alterations are accompanied by perivascular inflammation and such supportive features as Wallerian-like degeneration, asymmetric fiber loss, hemosiderin, vascular immune deposits, neovascularization, myofiber necrosis/regeneration, focal perineurial damage, and endoneurial purpura. NSVN preferentially affects larger epineurial arterioles. Epineurial infiltrates are composed primarily of T cells and macrophages, suggesting that cellular cytotoxicity is the primary effector mechanism. Systemic vasculitides with progressive neuropathy are usually treated with cyclophosphamide and prednisone. No randomized controlled trial of therapy has been performed in NSVN, but data from retrospective cohorts suggest that combination therapy is more effective than steroid monotherapy. Once remission has been induced, cyclophosphamide should be replaced with azathioprine or methotrexate. Refractory patients can be treated with intravenous immunoglobulin, mycophenolate, rituximab, infliximab, or alemtuzumab. Although long-term outcome is reasonably good, more than one third of patients relapse, infrequent patients die from the disease or its treatment, and still others develop chronic pain. PMID:19349704

  1. Perceived Benefits of Group Exercise Among Individuals With Peripheral Neuropathy.

    PubMed

    Powell-Cope, Gail; Quigley, Patricia A; Besterman-Dahan, Karen; Lind, Jason D

    2014-03-12

    Exercise and training programs improve strength, functional balance, and prevent falls in a variety of populations. This article presents the qualitative findings related to the perceived benefits of participants in a randomized controlled trial that compared the effectiveness of group exercise on gait and balance in persons with peripheral neuropathy (PN). Participants with moderately severe PN were randomized into groups that received 10-week classes of Functional Balance Training (FBT) or Tai Chi or education alone. Perceptions of the intervention were overwhelmingly positive regardless of the study group. Perceived benefits reported by participants in the FBT and Tai Chi groups included awareness of how to deal with the effects of neuropathy by implementing balance strategies and a heightened sense of walking to prevent falls. This study offers a guide to design future exercise studies that promote simple balance exercises that can be performed in group settings. PMID:24622155

  2. Entrapment neuropathies I: upper limb (carpal tunnel excluded).

    PubMed

    Jacobson, Jon A; Fessell, David P; Lobo, Lucas Da Gama; Yang, Lynda J-S

    2010-11-01

    Several entrapment neuropathies of the upper extremity can cause hypoechoic swelling and nerve compression as seen at ultrasound. The ulnar nerve can be compressed at the cubital tunnel of the elbow and Guyon's canal at the wrist. The deep branch of the radial nerve can be compressed at the supinator muscle at the elbow, and the superficial radial nerve may be compressed at the dorsal wrist (Wartenberg's syndrome). In addition to compression at the carpal tunnel, the median nerve may be compressed at the elbow, related to a supracondylar process or by the pronator teres. Knowledge of these key anatomical sites of potential nerve compression is essential for accurate diagnosis of entrapment neuropathies. PMID:21072726

  3. [Visual analysis for an early detection of diabetic neuropathy].

    PubMed

    Röhlig, M; Luboschik, M; Kundt, G; Stachs, O; Peschel, S; Zhivov, A; Guthoff, R F; Winter, K; Schumann, H

    2014-12-01

    Diabetic neuropathy is the most common long-term complication of diabetes mellitus. It comes along with significant nerve dysfunction, which is not reversible. Hence, it is essential to detect nerve fibre abnormalities as early as possible. In this paper, we investigate markers describing degradation of corneal nerves. We apply statistical computations and visual analysis to identify those variables of two clinical studies that separate DN patients from a control group. In this way, the diagnosis of DN patients is supported. The visual analysis is based on different representations visualizing both the statistical results and the gathered multi-variate data. The user can interactively manipulate the views, or select data that will be shown by further displays. In this way, the understanding of the data and its classification is supported. Ambiguous categorisations can be identified and grouped into a so-called "fuzzy group". For this group, further investigations are needed to decide about diabetic neuropathy. PMID:25519502

  4. Solitary localised hypertrophic neuropathy of the cauda equina.

    PubMed

    Norris, Briony; Gonzales, Michael; Drummond, Katharine J

    2011-05-01

    Localised hypertrophic neuropathy (LHN) is an uncommon non-neoplastic lesion, which is rare in the central nervous system. We report a patient with LHN of the cauda equina. Pre-operatively these lesions cannot be differentiated from schwannoma or other benign tumours or expansions of the nerve roots. Treatment is generally surgical, largely to confirm the diagnosis, and examination of the surgical specimen reveals an expansion of the nerve by "onion bulb" whorls of Schwann cells (S-100 positive). Multiple lesions may be associated with the generalised diffuse hypertrophic neuropathies or chronic inflammatory demyelinating polyneuropathies. It should be differentiated from intraneural perineuroma, which has a similar appearance but comprises perineural cells (epithelial membrane antigen positive). Adjuvant therapy is not required. PMID:21345679

  5. Peripheral neuropathy related to misonidazole: incidence and pathology.

    PubMed Central

    Urtasun, R. C.; Chapman, J. D.; Feldstein, M. L.; Band, R. P.; Rabin, H. R.; Wilson, A. F.; Marynowski, B.; Starreveld, E.; Shnitka, T.

    1978-01-01

    The human tolerance to multiple dosages of misonidazole (Ro-07-0582) was studied in 28 patients with different types of malignant neoplasias. The mean total dose for this group of patients was 16.2 g. The main toxicity was peripheral neuropathy with an overall incidence of 35%. This neuropathy occurred more frequently and with greater severity when the drug was administered 3 times a week and when patients received total doses of over 18 g. The best tolerated schedule appears to be once or twice a week up to total dosages of 18 g or less (approximately 11 g/m2). Electron microscopy of a sural nerve biopsy from an affected patient revealed residual of previous distal axonal degeneration, with some segmental demyelination and remyelination, which affected both large and small myelinated nerve fibres. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:209809

  6. Peripheral neuropathy after hair dye exposure: a case report.

    PubMed

    Deeb, Wissam; Cachia, David; Quinn, Colin; Salameh, Johnny

    2014-06-01

    We present a case of length-dependent sensory axonal polyneuropathy due to lead exposure from a cosmetic product. Serial follow-ups showed a direct relationship between the lead level, clinical symptoms, and the polyneuropathy. Our patient had a relatively short-term exposure to lead after misusing a hair dye on his beard. Nerve conduction studies showed a predominantly axonal sensory neuropathy that correlated with lead blood levels and reached 3 times the upper limit of normal. The patient had an unexpected sensory predominant neuropathy. He had a full recovery after stopping the lead-containing product. Blood lead levels were noted to be below previously reported toxic levels. No other systemic signs of lead toxicity were noted. This could be related to the mucosal route of absorption inducing a reversible injury at lower than previously reported lead levels and after a shorter duration of exposure. PMID:24872215

  7. 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

  8. Role of nitrosative and oxidative stress in neuropathy in patients with type 2 diabetes mellitus

    PubMed Central

    Al-Nimer, Marwan S; Al-Ani, Fakhir S; Ali, Fatima S

    2012-01-01

    Objectives: Evidences of oxidative and/or nitrosative stress in type 2 diabetes mellitus were demonstrated in experimental and human studies. This study is aimed to assess the serum peroxynitrite and oxidized lipoproteins in patients with type 2 diabetes mellitus presented with clinical and laboratory evidences of peripheral neuropathy. Materials and Methods: Eighty four patients with type 2 diabetes mellitus (51 of them had neuropathy) and 31 apparent healthy subjects were studied in the unit of neurophysiology at the University Hospital of Medical College, Al-Nahrin University in Baghdad, Iraq. Neuropathy total symptom score (NTSS), neuropathy impairment score in the lower leg (NIS-LL), and nerve conduction velocity of sensory (ulnar and sural) and motor (ulnar and common peroneal) nerves were used to assess the neuropathy. Fasting venous blood was obtained from each participant for the determination of serum glucose and oxidized lipoproteins. Results: The electrophysiology study revealed significant decrease in conduction velocity of ulnar (sensory and motor components), sural, and common peroneal nerves in diabetic neuropathy compared to diabetics without neuropathy and healthy subjects. Significant high level of serum peroxynitrite was found in diabetic patients with or without neuropathy compared with non-diabetics. The changes in serum-oxidized lipoproteins in patients with diabetics with or without neuropathy were non-significantly differed from healthy subjects. Neither nitrosative stress nor oxidative stress indices correlated with the variables that are related to the neuropathy. Conclusion: It concludes that evidence of nitrosative and to less extent the oxidative stress is associated with neuropathy in type 2 diabetes mellitus and their indices not correlated with variables related to neuropathy. PMID:22346190

  9. Effectiveness of frequency-modulated electromagnetic neural stimulation in the treatment of painful diabetic neuropathy

    Microsoft Academic Search

    E. Bosi; M. Conti; C. Vermigli; G. Cazzetta; E. Peretti; M. C. Cordoni; G. Galimberti; L. Scionti

    2005-01-01

    Aims\\/hypothesis  The largely unsatisfactory results reported for the pharmacological treatment of diabetic neuropathy has spurred the search for alternative therapies. The aim of this study was to evaluate the efficacy of frequency-modulated electromagnetic neural stimulation (FREMS) as a novel treatment for painful diabetic neuropathy.Methods  Patients (n=31) with painful neuropathy associated with decreased nerve conduction velocity (25 V) were enrolled in a randomised, double-blind,

  10. Somatic and autonomic small fiber neuropathy induced by bortezomib therapy: an immunofluorescence study

    Microsoft Academic Search

    Maria Pia Giannoccaro; Vincenzo Donadio; Carolina Gomis Pèrez; Walter Borsini; Vitantonio Di Stasi; Rocco Liguori

    2011-01-01

    Bortezomib is a new chemotherapeutic agent approved for the treatment of relapsed\\/refractory and newly diagnosed multiple\\u000a myeloma. One of the major side effects of bortezomib is a peripheral length-dependent sensory axonal neuropathy and, less\\u000a frequently, a small fiber neuropathy. Autonomic symptoms like postural dizziness, syncope, diarrhoea, ileus, impotence and\\u000a urinary disturbances have been reported, nevertheless, autonomic neuropathy has never been

  11. Optics

    NSDL National Science Digital Library

    Wolfgang Christian

    This page allows users to simulate standard optic elements (lens, mirror, dielectrics, sources, apertures) and observe how light rays propagate through these elements. Element properties, such as position and focal length, can be adjusted using and a click and drag metaphor.

  12. Periaxin mutations cause a broad spectrum of demyelinating neuropathies

    Microsoft Academic Search

    Hiroshi Takashima; Cornelius F. Boerkoel; Peter De Jonghe; Chantal Ceuterick; Jean-Jacques Martin; Thomas Voit; Anna Williams; Peter J. Brophy; Vincent Timmerman; James R. Lupski

    2002-01-01

    Previous studies have demonstrated that apparent loss-of-function mutations in the periaxin gene cause autosomal re- cessive 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

  13. Dysfonctions mitochondriales à l’origine de neuropathies périphériques

    Microsoft Academic Search

    B. Funalot

    2009-01-01

    Involvement of peripheral nerves is frequent in mitochondrial disorders but with variable severity. Mitochondrial diseases causing peripheral neuropathies (PN) may be due to mutations of mitochondrial DNA (mtDNA), as is the case in MERRF and MELAS syndromes, or to mutations of nuclear genes. Secondary abnormalities of mtDNA (such as multiple deletions of muscle mtDNA) may result from mitochondrial disorders due

  14. Medial arterial calcification in diabetes and its relationship to neuropathy

    Microsoft Academic Search

    W. J. Jeffcoate; L. M. Rasmussen; L. C. Hofbauer

    2009-01-01

    Calcification of the media of arterial walls is common in diabetes and is particularly associated with distal symmetrical\\u000a neuropathy. Arterial calcification also complicates chronic kidney disease and is an independent risk factor for cardiovascular\\u000a and all-cause mortality. The term calcification is not strictly accurate because the morphological changes incorporate those\\u000a of new bone formation, i.e. ossification. The processes are complex,

  15. 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

  16. Pathophysiology of Diarrhea in Patients with Familial Amyloid Neuropathy

    Microsoft Academic Search

    G. E. Feurle

    1987-01-01

    Seven patients with familial amyloid neuropathy (AF amyloidosis) were studied to clarify the pathophysiology of the diarrhea associated with this disorder. Fecal weight and fat determinations, 14C-glycocholate breath tests, and a test of B12 absorption were performed before and after treatment with co-trimoxazole. Gastric emptying was assessed with conventional roentgen contrast medium and radio-opaque markers. Gastric emptying was delayed, fecal

  17. Diabetic Neuropathy: A Clinical and Neuropathological Study of 107 Patients

    PubMed Central

    Younger, David S.

    2010-01-01

    One hundred seven patients were retrospectively studied from 1992 to 2002 with diabetic neuropathy that underwent peripheral nerve biopsy. Nerve biopsy revealed the underlying histopathology, including cell and humoral-mediated immunological lesions in the majority of patients. When combined with clinical and laboratory studies, nerve biopsy has the potential to assist in the selection of patients who may benefit from immunomodulatory therapy. PMID:21152210

  18. Treatment of multifocal motor neuropathy with intravenous immunoglobulin.

    PubMed

    Koski, Carol Lee

    2014-07-01

    Multifocal motor neuropathy (MMN) is a rare inflammatory, chronically progressive, unremitting disorder affecting the peripheral nervous system. Although the etiology of this condition is not known, high titers of IgM Ab to GM1 may serve as a biomarker for this disease. Clinical findings of motor weakness are associated with focal conduction blocks and with time, axonal destruction. Evidence supporting an immune etiology as well as the use of intravenous immunoglobulin to limit the disease progression is reviewed. PMID:24699885

  19. Peripheral neuropathy as the presenting feature of multiple system atrophy

    Microsoft Academic Search

    Carmelo Rodolico; Antonio Toscano; Giovanni De Luca; Anna Mazzeo; Rita Di Leo; Sergio Baldari; Paolo Girlanda; Giuseppe Vita

    2001-01-01

    The authors report a case of multiple system atrophy (MSA) with an onset as a peripheral nerve involvement. Their patient,\\u000a a 55-year-old man, had a 3-year history of distal weakness and atrophy in upper limbs with dysesthesia in the feet. Other\\u000a identifiable causes of peripheral neuropathy were ruled out. The authors postulate that peripheral nervous system impairment\\u000a can anticipate the

  20. Prevalence of somatic small fiber neuropathy in obesity

    Microsoft Academic Search

    R M Herman; J B Brower; D G Stoddard; A R Casano; J H Targovnik; J H Herman; P Tearse

    2007-01-01

    Background:Somatic cutaneous small sensory fiber neuropathy (SSFN) can be an early manifestation of impaired glucose tolerance and diabetes mellitus and\\/or insulin resistance among obese subjects and is often associated with pain, wound occurrence and impaired wound healing. It is yet unclear as to whether SSFN is prevalent among obese individuals without glucose and\\/or insulin dysregulation despite abundant evidence of delayed

  1. Chemotherapy-Induced Peripheral Neuropathy: Prevention and Treatment

    Microsoft Academic Search

    D R Pachman; D L Barton; J C Watson; C L Loprinzi

    2011-01-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is a common, dose-limiting side effect of many chemotherapeutic agents. Although many therapies have been investigated for the prevention and\\/or treatment of CIPN, there is no well-accepted proven therapy. In addition, there is no universally accepted, well-validated measure for the assessment of CIPN. The agents for which there are the strongest preliminary data regarding their potential

  2. Other Therapeutic Agents for the Treatment of Diabetic Neuropathy

    Microsoft Academic Search

    Gary L. Pittenger; Henri Pharson; Jagdeesh Ullal; Aaron I. Vinik

    The pathogenesis of diabetic neuropathy is complex and it is important to understand the underlying pathology leading to the\\u000a complication in order to best tailor treatment for each individual patient. It is unlikely that reversing any single mechanism\\u000a will prove sufficient for reversing nerve damage. Several drugs, such as antioxidant, PKC inhibitors and nerve growth factors\\u000a can have effects on

  3. Evaluation of neuropathy during intensive vincristine chemotherapy for non-Hodgkin's lymphoma and Acute Lymphoblastic Leukemia

    PubMed Central

    Dorchin, M; Masoumi Dehshiri, R; Soleiman, S; Manashi, M

    2013-01-01

    Back ground: Vincristine (VCR), is a chemotherapy drug, useful in the treatment of leukemia, lymphoma and solid tumor and it is a potent neurotoxin and sensory neuropathy drug which a common behavioral toxicity of this drug. Neuropathy is common squeal of intensive chemotherapy protocols that contain vincristine and corticosteroids. Materials and Methods: This study was a retrospective and descriptive study of neuropathy during in chemotherapy program with vincristine for patients with non-Hodgkin's lymphoma (NHL) and Acute Lymphoblastic Leukemia (ALL). Data was analyzed by spss Version16 software. Results: From total of 51 cases, 23 patients had vincristine neuropathy (45%). Patients with visceral neuropathy have shown ileus, constipation in 13 patients (25%), occasionally severe diarrhea 11 (21%), mild diarrhea 7 (13.7%) and transient diarrhea in 16 patients (31%). Motor neuropathy were found in one patient with Bell, s palsy (1.9%) and one patient with Hoarseness. 12 patients (23.5%) had some type of complication together with sensory peripheral neuropathy. Conclusion: Almost half of patients with vincristin chemotherapy had neuropathy and the mean age of patients with neuropathy was 12.3 years. PMID:24575286

  4. Overview of neuropathy associated with taxanes for the treatment of metastatic breast cancer.

    PubMed

    Rivera, Edgardo; Cianfrocca, Mary

    2015-04-01

    Taxanes are an established option in the standard treatment paradigm for patients with metastatic breast cancer (MBC). Neuropathy is a common, dose-limiting side effect of taxane therapy that is often managed by dose reductions and delays. The severity, time to onset, and improvement in neuropathy are important considerations for patient management and vary among currently approved taxanes. The rate of grade ?3 neuropathy with taxanes has been shown to be dose and schedule dependent; however, time to improvement to grade ?1 is typically shorter for nab-paclitaxel than for other taxanes in patients with MBC. Many tools for assessing patient-reported neuropathy exist. Because MBC is incurable and patient quality of life must be critically considered when making treatment decisions, there is a need for more prospective trials to assess patient-reported neuropathy. Validated predictors of taxane-related neuropathy may play an important role in treatment decisions in the future. This review will focus on the toxicity profile (i.e., neuropathy) of each of the taxanes used in the treatment of MBC, will provide updates on tools used for the assessment of neuropathy, and will highlight newly discovered predictors of taxane-related neuropathy. PMID:25596818

  5. The natural history of acute painful neuropathy in diabetes mellitus.

    PubMed Central

    Archer, A G; Watkins, P J; Thomas, P K; Sharma, A K; Payan, J

    1983-01-01

    Observations have been made on nine cases of painful diabetic neuropathy of acute onset. All cases were male and all were associated with and preceded by precipitous and severe weight loss. The pain was of a continuous burning quality and experienced mainly in the legs, especially distally. Contact discomfort of the skin was often a troublesome feature, but sensory loss was mild or absent, and reflex loss or depression not invariable. There were no accompanying motor signs. Depression and impotence were constant features. The weight loss responded to adequate control of the diabetes with insulin and was followed by improvement in the neuropathy. The severe manifestations subsided in all cases within 10 months, and in most cases within 6 months, and later resolved completely in all except one. No recurrences were observed after follow-up periods of up to 6 years. Abnormalities of nerve conduction were mild or even lacking. Sural nerve biopsies from three cases taken in the acute stage showed evidence of active degeneration of myelinated nerve fibres of all diameters and also degeneration of unmyelinated axons. There was a mild degree of demyelination. It is concluded that acute painful diabetic neuropathy is a distinct syndrome, occurring in insulin or noninsulin dependent patients of any duration, and unrelated to other diabetic complications. It is separable from other types of painful diabetic sensory polyneuropathy that have been described. PMID:6875582

  6. Lowering plasma 1-deoxysphingolipids improves neuropathy in diabetic rats.

    PubMed

    Othman, Alaa; Bianchi, Roberto; Alecu, Irina; Wei, Yu; Porretta-Serapiglia, Carla; Lombardi, Raffaella; Chiorazzi, Alessia; Meregalli, Cristina; Oggioni, Norberto; Cavaletti, Guido; Lauria, Giuseppe; von Eckardstein, Arnold; Hornemann, Thorsten

    2015-03-01

    1-Deoxysphingolipids (1-deoxySLs) are atypical neurotoxic sphingolipids that are formed by the serine-palmitoyltransferase (SPT). Pathologically elevated 1-deoxySL concentrations cause hereditary sensory and autonomic neuropathy type 1 (HSAN1), an axonal neuropathy associated with several missense mutations in SPT. Oral L-serine supplementation suppressed the formation of 1-deoxySLs in patients with HSAN1 and preserved nerve function in an HSAN1 mouse model. Because 1-deoxySLs also are elevated in patients with type 2 diabetes mellitus, L-serine supplementation could also be a therapeutic option for diabetic neuropathy (DN). This was tested in diabetic STZ rats in a preventive and therapeutic treatment scheme. Diabetic rats showed significantly increased plasma 1-deoxySL concentrations, and L-serine supplementation lowered 1-deoxySL concentrations in both treatment schemes (P < 0.0001). L-serine had no significant effect on hyperglycemia, body weight, or food intake. Mechanical sensitivity was significantly improved in the preventive (P < 0.01) and therapeutic schemes (P < 0.001). Nerve conduction velocity (NCV) significantly improved in only the preventive group (P < 0.05). Overall NCV showed a highly significant (P = 5.2E-12) inverse correlation with plasma 1-deoxySL concentrations. In summary, our data support the hypothesis that 1-deoxySLs are involved in the pathology of DN and that an oral L-serine supplementation could be a novel therapeutic option for treating DN. PMID:25277395

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

    SciTech Connect

    Lebo, R.V.; Li, L.Y.; Flandermeyer, R.R. [Univ. of California, San Francisco, CA (United States)] [and others

    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.

  8. 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

  9. Sensory Neuropathy Due to Loss of Bcl-w

    PubMed Central

    Courchesne, Stephanie L.; Karch, Christoph; Pazyra-Murphy, Maria F.; Segal, Rosalind A.

    2010-01-01

    Small fiber sensory neuropathy is a common disorder in which progressive degeneration of small diameter nociceptors causes decreased sensitivity to thermal stimuli and painful sensations in the extremities. In the majority of patients, the cause of small fiber sensory neuropathy is unknown, and treatment options are limited. Here, we show that Bcl-w (Bcl-2l2) is required for the viability of small fiber nociceptive sensory neurons. Bcl-w ?/? mice demonstrate an adult-onset progressive decline in thermosensation and a decrease in nociceptor innervation of the epidermis. This denervation occurs without cell body loss, indicating that lack of Bcl-w results in a primary axonopathy. Consistent with this phenotype, we show that Bcl-w, in contrast to the closely related Bcl-2 and Bcl-xL, is enriched in axons of sensory neurons and that Bcl-w prevents the dying back of axons. Bcl-w ?/? sensory neurons exhibit mitochondrial abnormalities, including alterations in axonal mitochondrial size, axonal mitochondrial membrane potential, and cellular ATP levels. Collectively, these data establish bcl-w ?/? mice as an animal model of small fiber sensory neuropathy, and provide new insight regarding the role of bcl-w and of mitochondria in preventing axonal degeneration. PMID:21289171

  10. Pyridoxine-induced sensory ataxic neuronopathy and neuropathy: revisited.

    PubMed

    Kulkantrakorn, Kongkiat

    2014-11-01

    High dose pyridoxine is neurotoxic. Previous case reports were sparse and little is known about the clinical and electrodiagnostic findings. Three patients with pyridoxine-induced sensory ataxic neuropathy were studied and a review of the involved literature was performed. Three patients, aged 80, 83 and 83 years old, presented with sensory ataxia for 3-8 months. Examination showed signs of polyneuropathy and sensory ataxia. Six hundred milligrams of pyridoxine was consumed each day for 3-10 years, in the form of vitamin B1-6-12 combination tablet. Investigations for other causes of neuropathy were unremarkable. Blood levels of vitamin B6 were markedly elevated at 104.6, 81.4 and 66.9 times of upper normal limits. Electrodiagnostic tests showed symmetric axonal sensory polyneuropathy in two patients. Two years after vitamin discontinuation, all patients showed no significant improvement in the neuropathy and gait. In conclusion, consumption of high dose pyridoxine can cause sensory neuronopathy and axonal sensorimotor polyneuropathy, leading to sensory ataxia which may not be reversible. PMID:25056196

  11. Peripheral neuropathy associated with eosinophilia-myalgia syndrome.

    PubMed

    Heiman-Patterson, T D; Bird, S J; Parry, G J; Varga, J; Shy, M E; Culligan, N W; Edelsohn, L; Tatarian, G T; Heyes, M P; Garcia, C A

    1990-10-01

    In 1989, the Centers for Disease Control recognized the existence of an epidemic illness characterized by myalgia and eosinophilia in individuals taking preparations containing L-tryptophan. We evaluated 3 patients with eosinophilia-myalgia syndrome who presented with subacute progressive neuropathies. The neuropathies were predominantly motor and maximal in the lower extremities. Two patients were confined to a wheelchair and one was ventilator-dependent and bedridden. Sensory loss predominantly involved small fiber modalities. Electrophysiological studies showed multifocal marked conduction slowing and conduction block indicating segmental demyelination, with associated axonal degeneration that was accentuated distally. Examination of sural nerve biopsy specimens demonstrated axonal degeneration in all 3 patients and perivascular infiltrates in 2. Levels of quinolinic acid, a neurotoxic metabolite of L-tryptophan, were elevated in the cerebrospinal fluid in the 2 patients in whom it was measured. The cause of the neuropathy is unknown but may include immune mechanisms or toxicity of eosinophils, L-tryptophan, its metabolic products, or contaminants within L-tryptophan preparations. PMID:2174666

  12. The distributions of mitochondria and sodium channels reflect the specific energy requirements and conduction properties of the human optic nerve head

    Microsoft Academic Search

    M J Barron; P Griffiths; D M Turnbull; D Bates; P Nichols

    2004-01-01

    Aim: To study the normal distributions of mitochondria and voltage gated Na+ channels in the human optic nerve head in order to gain insight into the potential mechanisms of optic nerve dysfunction seen in the inherited optic neuropathies.Methods: Five fresh frozen human optic nerves were studied. Longitudinally orientated, serial cryosections of optic nerve head were cut for mitochondrial enzyme histochemistry

  13. 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

  14. Selected natural phenolic compounds - potential treatment for peripheral neuropathy?

    PubMed

    Smejkal, Karel

    2014-01-01

    Neuropathic pain is a syndrome comprising pain caused by a lesion or dysfunction of the nervous system, or resulting from lesions or diseases of the somatosensory system. Neuropathic pain is often connected with adverse effects of chemotherapy administered because of cancer, infiltration of the nervous tissue with cancer cells, neurodegeneration and diabetes mellitus. Disbalance in the production of various cytokines plays an important role in the pathogenesis of many of the diseases connected with neuropathies. These cytokines comprise in particular interleukins IL-1?, IL-15, and IL-6, tumour necrosis factors, and prostaglandins. The biochemistry of the production of cytokines is directed by nuclear factors, which affect the expression of the mRNA for the respective cytokines or enzymes metabolizing the cytokines. The main nuclear factor which regulates the expression of cytokines is NF-?B. Because of insufficient effectiveness or adverse effects of the pharmacological treatment of peripheral neuropathy, many patients seek supportive or adjuvant therapy. Natural compounds which modulate the production of inflammatory cytokines may reduce the symptoms of neuropathies. Many natural phenolic compounds belong to substances affecting the activity of NF-?B and consequently the activity of cytokines which are regulated by this substance. The aim of this mini-review is to present information about three natural phenols which are potentially usable for the treatment of neuropathies: curcumin, resveratrol and mangiferin, and bring attention to the practical usability thereof. Curcumin and mangiferin are active constituents of plants; they have been used for centuries in traditional medicine. Biological effects of resveratrol have been known for a relatively short time; since the discovery of the so-called French paradox, attention has been focused on resveratrol. This summary includes particularly the information related to the influence on the activity of NF-?B, expression of anti-inflammatory cytokines, and antiradical activity, because imbalance between the creation and degradation of free radicals plays an important role in the activation of NF-?B and in inflammatory processes. It also briefly summarizes basic information concerning bioavailability, metabolism and practical application of the aforementioned substances. Keywords: phenols curcumin mangiferin NF-?B peripheral neuropathy resveratrol. PMID:24870550

  15. mtDNA haplogroup J: a contributing factor of optic neuritis

    Microsoft Academic Search

    Pascal Reynier; Isabelle Penisson-Besnier; Corinne Moreau; Frédérique Savagner; Bruno Vielle; Jean Emile; Frédéric Dubas; Yves Malthièry

    1999-01-01

    Optic neuritis frequently occurs in multiple sclerosis (MS), and shares several similarities with the optic neuritis of Leber's hereditary optic neuropathy (LHON), which is mainly due to maternally transmitted mitochondrial DNA (mtDNA) mutations. Our report shows for the first time that a mitochondrial DNA background could influence the clinical expression of MS. One European mtDNA haplogroup was found only in

  16. Population Differences in Elastin Maturation in Optic Nerve Head Tissue and Astrocytes

    Microsoft Academic Search

    Zsolt Urban; Olga Agapova; Vishwanathan Hucthagowder; Ping Yang; Barry C. Starcher; M. Rosario Hernandez

    PURPOSE. Glaucomatous optic neuropathy is characterized by remodeling of the extracellular matrix with disorganization of elastic fibers in the optic nerve head (ONH). There are signif- icant differences in prevalence of glaucomatous optic neurop- athy between African Americans (AAs) and Caucasian Ameri- cans (CAs). The goal of this study was to evaluate differences in elastin synthesis and maturation in ONH

  17. Clinical Features: Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum (HMSN/ACC) [OMIM #218000

    E-print Network

    Ober, Carole

    1/13 Clinical Features: Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus sensorimotor neuropathy resulting in hypotonia, areflexia and amyotrophy, variable degrees of dysgenesis Neuropathy with Agenesis of the Corpus Callosum #12;1/13 Prenatal testing for a known mutation Sample

  18. Clinical Features: Charcot Marie Tooth Disease is a group of inherited neuropathies characterized by chronic motor and sensory

    E-print Network

    Ober, Carole

    6/11 Clinical Features: Charcot Marie Tooth Disease is a group of inherited neuropathies characterized by chronic motor and sensory neuropathy resulting in progressive distal muscle weakness.smeyers@ua.ac.be The Hereditary Neuropathy Foundation 1751 2nd Ave Suite 103 New York NY 10128 Phone: 877-463-1287; 212

  19. Clinical Features: Charcot Marie Tooth Disease is a group of inherited neuropathies characterized by chronic motor and sensory

    E-print Network

    Ober, Carole

    1/13 Clinical Features: Charcot Marie Tooth Disease is a group of inherited neuropathies characterized by chronic motor and sensory neuropathy resulting in progressive distal muscle weakness.smeyers@ua.ac.be The Hereditary Neuropathy Foundation 1751 2nd Ave Suite 103 New York NY 10128 Phone: 877-463-1287; 212

  20. Clinical Features: Charcot Marie Tooth Disease is a group of inherited neuropathies characterized by chronic motor and sensory

    E-print Network

    Gilad, Yoav

    10/08 Clinical Features: Charcot Marie Tooth Disease is a group of inherited neuropathies characterized by chronic motor and sensory neuropathy resulting in progressive distal muscle weakness.smeyers@ua.ac.be The Hereditary Neuropathy Foundation 1751 2nd Ave Suite 103 New York NY 10128 Phone: 877-463-1287; 212