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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. PMID:25859144

  2. 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

  3. [ORIGINAL PERFORMANCE INTEGRATED CIRCUITS NEUROPROTECTIVE LECHNIYA ANTERIOR ISCHEMIC OPTIC NEUROPATHY DEPENDING ON BLOOD PRESSURE].

    PubMed

    Bezdetko, P; Martynyuk, D

    2016-02-01

    Anterior ischemic optic neuropathy (AION) is one of the main reasons of vision disorders among middle-aged and elderly people. During the examination of patients with AION, we were interested by the fact of low efficiency of the standard treatment course. Moreover, over 60% of such patients underwent the development of AION on the other eye during 1 year after the beginning of the disease. The purpose of the given study is the development of efficient and original neuroprotection treatment scheme for AION, depending on the arterial pressure rate. We examined 58 patients (65 eyes) with AION, depending on the arterial pressure rate. The patients were divided into two clinical groups. For the first group of 38 patients (38 eyes), we used the original AION treatment scheme developed by us. The group was divided into 3 subgroups, depending on their arterial pressure rate: patients with normal ap., patients with hypertension of I-II stages and patients with hypotension. For the control group, the standard treatment scheme was used. The results received allow us to make a conclusion that the original treatment scheme, developed by us, is more efficient, and it can be recommended as a neuroprotection treatment scheme for AION among the patients with arterial hypertension of I-II stages. PMID:27001781

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    Maramattom, Boby Varkey

    2014-01-01

    Thrombotic microangiopathies (TMAs) are a group of disorders characterized by occurrence of thrombi of fibrin and/or platelets with microvascular occlusion and organ ischemia especially the kidney and brain. Hemolysis with a microangiopathic blood smear, elevated liver enzymes, and low platelet count (HELLP syndrome) is a type of TMA peculiar to pregnancy and may be associated with neurological complications. Visual complications in HELLP are usually related to cortical blindness. We present the first case of HELLP associated with bilateral anterior ischemic optic neuropathy (AION) and blindness which resolved with plasma exchange. PMID:25328716

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

    PubMed

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

    1988-01-01

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

  7. Giant Cell Arteritis Presenting as Unilateral Anterior Ischemic Optic Neuropathy Associated With Bilateral Optic Nerve Sheath Enhancement on Magnetic Resonance Imaging.

    PubMed

    Liu, Tin Yan A; Miller, Neil R

    2015-12-01

    A 67-year-old man developed jaw claudication followed by loss of vision in the left eye caused by anterior ischemic optic neuropathy (AION). An erythrocyte sedimentation rate was normal, but C-reactive protein was slightly elevated. Although the patient had no evidence of a right optic neuropathy, magnetic resonance imaging (MRI) revealed bilateral optic nerve sheath enhancement. A temporal artery biopsy was consistent with active giant cell arteritis (GCA). Our case demonstrates that bilateral optic nerve sheath enhancement on MRI can be seen in the setting of unilateral AION. This unique combination of clinical and imaging findings has not been reported previously and extends the clinical spectrum of presentation of GCA. PMID:26087368

  8. Infectious optic neuropathy.

    PubMed

    Golnik, Karl C

    2002-03-01

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

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

    PubMed

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

    2015-01-01

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

  10. Genetics Home Reference: Leber hereditary optic neuropathy

    MedlinePlus

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

  11. 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.

  12. 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

  13. Indirect traumatic optic neuropathy.

    PubMed

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

    2016-01-01

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

  14. Traumatic Optic Neuropathy: A Review

    PubMed Central

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

    2014-01-01

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

  15. Linezolid-induced optic neuropathy

    PubMed Central

    Karuppannasamy, Divya; Raghuram, Andavar; Sundar, Devisundaram

    2014-01-01

    Many systemic antimicrobials have been implicated to cause ocular adverse effects. This is especially relevant in multidrug therapy where more than one drug can cause a similar ocular adverse effect. We describe a case of progressive loss of vision associated with linezolid therapy. A 45-year-old male patient who was on treatment with multiple second-line anti-tuberculous drugs including linezolid and ethambutol for extensively drug-resistant tuberculosis (XDR-TB) presented to us with painless progressive loss of vision in both eyes. Color vision was defective and fundus examination revealed optic disc edema in both eyes. Ethambutol-induced toxic optic neuropathy was suspected and tablet ethambutol was withdrawn. Deterioration of vision occurred despite withdrawal of ethambutol. Discontinuation of linezolid resulted in marked improvement of vision. Our report emphasizes the need for monitoring of visual function in patients on long-term linezolid treatment. PMID:24088636

  16. Traumatic Optic Neuropathy - A Conundrum.

    PubMed

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

    2016-03-01

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

  17. Magnetic resonance imaging of radiation optic neuropathy

    SciTech Connect

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

    1990-10-15

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

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

    PubMed

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

    2007-12-01

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

  19. 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.

  20. Histopathologic studies of ischemic optic neuropathy.

    PubMed Central

    Knox, D L; Kerrison, J B; Green, W R

    2000-01-01

    PURPOSE: To define the histopathologic features of eyes in which a pathologic diagnosis of ischemic optic neuropathy had been made in the years 1951 through 1998. METHODS: The following data were documented: age of patient, race, sex, source of tissue, cause of death, clinical history, interval from loss of vision to death, enucleation, exenteration, and biopsy. The histopathologic criteria for diagnosis of ischemic optic neuropathy were the presence of localized ischemic edema, cavernous degeneration, or an area of atrophy located superior or inferior in the optic nerve. Cases with history of abrupt loss of vision were combined with reports from the literature to construct a time table of histopathologic features and associated conditions. RESULTS: Ischemic optic neuropathy was present in 193 eyes. There were 88 females and 65 males. The average age was 71.6 years. Ischemic edema without (early) and with (later) gitter macrophages was present in 26 (13.5%). Cavernous degeneration was present in 69 nerves (36%). Mucopolysaccharide (MPS) was present in 37 cavernous lesions 1 month or longer after loss of vision. Cavernous lesions were seen in 3 eyes in which peripapillary retinal nerve fiber layer hemorrhage had been observed prior to death. Atrophic lesions, the most common pattern, were observed in 133 optic nerves (66.8%). More than 1 ischemic lesion was seen in 38 optic nerves (19.7%). Bilateral ischemic lesions were seen in 50 (35.2%) of 142 paired eyes. CONCLUSIONS: Ischemic optic nerve lesions are initially acellular and later show macrophage infiltration. Cavernous lesions with MPS are present 4 weeks or longer after vision loss. The location of MPS posteriorly and along the internal margin suggests that MPS is produced at the edges of lesions. Progressive vision loss in ischemic optic neuropathy may be secondary to compression of intact nerve from ischemic edema and cavernous swelling, or a second ischemic lesion. Images FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 8 FIGURE 9 FIGURE 10 FIGURE 11 FIGURE 12 FIGURE 13 FIGURE 14 FIGURE 15 FIGURE 16 FIGURE 17 FIGURE 18 FIGURE 19 FIGURE 20 FIGURE 21 FIGURE 22 FIGURE 23 FIGURE 24 A FIGURE 24 B FIGURE 24 C FIGURE 24 D FIGURE 24 E FIGURE 24 F FIGURE 25 A FIGURE 25 B FIGURE 25 C FIGURE 25 D FIGURE 25 E FIGURE 25 F FIGURE 26 FIGURE 27 FIGURE 28 FIGURE 29 FIGURE 30 FIGURE 31 PMID:11190024

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

    PubMed

    Wilhelm, H; Beisse, F; Rüther, K

    2015-11-01

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

  2. Leber hereditary optic neuropathy in Australia.

    PubMed

    Mackey, D A; Buttery, R G

    1992-08-01

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

  3. Spheniodal mucocele causing bilateral optic neuropathy and ophthalmoplegia

    PubMed Central

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

    2014-01-01

    Sphenoid sinus mucocele comprises only 2% of all paranasal sinus mucoceles. In literature, there is a case report on sphenoidal mucocele causing bilateral optic neuropathy, with unilateral partial recovery and cranial nerve palsy, but we did not come across any literature with bilateral optic neuropathy and ophthalmoplegia together caused by spheno-ethmoidal mucocele. We present such a rare case of spheno-ethmoidal mucocele causing bilateral optic neuropathy and unilateral sixth nerve palsy who had postsurgery, unilateral good vision recovery, and complete resolution of sixth nerve palsy. PMID:23571243

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

    PubMed Central

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

    2004-01-01

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

  5. Optic neuropathy secondary to radiotherapy for nasal melanoma.

    PubMed

    Garrott, Helen; O'Day, Justin

    2004-06-01

    Optic neuropathy is a rare but important complication of radiotherapy used in the treatment of cancers of the head and neck, usually resulting in rapidly progressive blindness in one or both eyes. The case is presented of a 77-year-old woman with bilateral optic neuropathy resulting in blindness, secondary to radiotherapy for a melanoma of the nasal cavity. The onset of optic neuropathy occurred 9 months post-radiotherapy, at a cumulative dose of 6000 rad. The left eye was first involved, with the right eye becoming involved within 2 weeks. Despite treatment with oral anticoagulation and high dose intravenous methylprednisolone, there was progressive deterioration resulting in bilateral optic atrophy, with final visual acuities of perception of light in the right eye and no perception of light in the left eye. This case demonstrates that oral anticoagulation was ineffective in the treatment of progressive radiation-induced optic neuropathy. PMID:15180849

  6. 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

  7. Traumatic Optic Neuropathy – A Conundrum

    PubMed Central

    Selvaraj, Vinoth Kanna; Devanathan, Vasudevan

    2016-01-01

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

  8. Methylprednisolone pulse therapy in severe dysthyroid optic neuropathy

    SciTech Connect

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

    1989-07-01

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

  9. 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

  10. 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…

  11. 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

  12. Novel treatment for radiation optic neuropathy with intravenous bevacizumab.

    PubMed

    Farooq, Osman; Lincoff, Norah S; Saikali, Nicolas; Prasad, Dheerendra; Miletich, Robert S; Mechtler, Laszlo L

    2012-12-01

    Radiation optic neuropathy is a devastating form of vision loss that can occur months to years after radiation therapy for tumors and other lesions located in close proximity to the visual pathways. We present the case of a 24-year-old woman who underwent external beam radiation for treatment of a tectal pilocytic astrocytoma, and 5 years later she developed bilateral radiation optic neuropathy and radiation necrosis of the right temporal lobe. We opted to treat her with intravenous bevacizumab with 3 doses every 3 weeks, as well as dexamethasone and pentoxifylline. After the first infusion of bevacizumab, the patient noted improvement in vision and color vision, and a follow-up magnetic resonance imaging study showed that the previous enhancement of the optic nerves and chiasm was diminishing. Her vision improved dramatically and has remained stable over a 3-year period. PMID:22868640

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

    PubMed Central

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

    2014-01-01

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

  14. A Novel Rodent Model of Posterior Ischemic Optic Neuropathy

    PubMed Central

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

    2014-01-01

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

  15. 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.

  16. 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

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

    SciTech Connect

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

    1991-03-01

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

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

    PubMed

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

    2015-08-01

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

  19. 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.

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

    PubMed

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

    2016-01-01

    Leber hereditary optic neuropathy (LHON) was the first clinically characterized mitochondrial disorder. Since its first description in 1871, much has been discovered regarding the genetics and pathophysiology of the disease. This has enabled the development of in vitro cell and animal models that can be used to try to determine not only the effects of the genetic mutation upon the clinical phenotype but to also test potential novel therapies. Treatments for LHON have ranged from vitamins and minerals to immunosuppressants and, more recently, targeted gene therapy. This article reviews the pathophysiology and clinical features of LHON with a focus on translational research. PMID:26959136

  1. Biomechanical assessment in models of glaucomatous optic neuropathy.

    PubMed

    Nguyen, Thao D; Ethier, C Ross

    2015-12-01

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

  2. Bilateral Glaucomatous Optic Neuropathy Caused by Eye Rubbing.

    PubMed

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

    2015-01-01

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

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

    SciTech Connect

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

    1990-09-15

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

  4. 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

  5. Endoscopically assisted transconjunctival decompression of traumatic optic neuropathy.

    PubMed

    Chen, Chien-Tzung; Huang, Faye; Tsay, Pei-kwei; Tsai, Yueh-Ju; Lin, Chih-Hung; Chen, Yi-Chieh; Chen, Yu-Ray

    2007-01-01

    Traumatic optic neuropathy (TON) is a severe sequel after maxillofacial trauma. Recent clinical experience has suggested that optic canal decompression is beneficial in the treatment of TON. With the advent of endoscopy in orbital reconstruction, we extended this technique to decompress the optical canal and reported its outcome. This technique was applied to 30 patients with TON who did not improve after corticosteroids treatment. The average age of the patients at the time of injury was 26 years. Nine patients presented preoperative vision of light perception (LP) or better and 21 patients had no light perception (NLP). Surgery was performed within 1 week of injury in 10 patients, between 1 and 2 weeks in another 10 patients, and between 2 and 4 weeks in the last 10 patients. Thirteen patients were found to have optic canal fractures during surgery. The average follow-up time was 9.5 months. Vision improved in 12 patients including 6 patients (28.6%) with NLP and in 6 patients (66.7%) with LP or better. The improvement degree of visual acuity was 50% in average. Only patient age reflected differences in improvement of visual acuity when analyzing the effect of optic canal fracture, timing of surgery and initial visual acuity. Two patients experienced postoperative cerebrospinal fluid leakage due to associated skull base fractures. The endoscope-assisted transconjunctival technique successfully decompresses the optic canal and improves visual acuity with minimal morbidity. Younger patients had a significantly better visual outcome. PMID:17251830

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

    PubMed

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

    2012-03-01

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

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

    PubMed

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

    2016-03-01

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

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

    PubMed

    Rapoport, Yuna; Lavin, Patrick J M

    2016-06-01

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

  9. Autophagy in axonal degeneration in glaucomatous optic neuropathy.

    PubMed

    Munemasa, Yasunari; Kitaoka, Yasushi

    2015-07-01

    The role of autophagy in retinal ganglion cell (RGC) death is still controversial. Several studies focused on RGC body death, although the axonal degeneration pathway in the optic nerve has not been well documented in spite of evidence that the mechanisms of degeneration of neuronal cell bodies and their axons differ. Axonal degeneration of RGCs is a hallmark of glaucoma, and a pattern of localized retinal nerve fiber layer defects in glaucoma patients indicates that axonal degeneration may precede RGC body death in this condition. As models of preceding axonal degeneration, both the tumor necrosis factor (TNF) injection model and hypertensive glaucoma model may be useful in understanding the mechanism of axonal degeneration of RGCs, and the concept of axonal protection can be an attractive approach to the prevention of neurodegenerative optic nerve disease. Since mitochondria play crucial roles in glaucomatous optic neuropathy and can themselves serve as a part of the autophagosome, it seems that mitochondrial function may alter autophagy machinery. Like other neurodegenerative diseases, optic nerve degeneration may exhibit autophagic flux impairment resulting from elevated intraocular pressure, TNF, traumatic injury, ischemia, oxidative stress, and aging. As a model of aging, we used senescence-accelerated mice to provide new insights. In this review, we attempt to describe the relationship between autophagy and recently reported noteworthy factors including Nmnat, ROCK, and SIRT1 in the degeneration of RGCs and their axons and propose possible mechanisms of axonal protection via modulation of autophagy machinery. PMID:25816798

  10. 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

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

    PubMed

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

    2016-03-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  14. 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

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

    PubMed

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

    2015-11-01

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

  16. A new characterization for nonarteritic anterior ischemic optic neuropathy

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Lyseng-Williamson, Katherine A

    2016-05-01

    Idebenone (Raxone(®)), a short-chain benzoquinone, is the only disease-specific drug approved to treat visual impairment in adolescents and adults with Leber's hereditary optic neuropathy (LHON), a rare genetic mitochondrial disease that causes rapid and progressive bilateral vision loss. The mechanism of action of idebenone involves its antioxidant properties and ability to act as a mitochondrial electron carrier. Idebenone overcomes mitochondrial complex I respiratory chain deficiency in patients with LHON by transferring electrons directly to mitochondrial complex III (by-passing complex I), thereby restoring cellular energy (ATP) production and re-activating inactive-but-viable retinal ganglion cells, which ultimately prevents further vision loss and promotes vision recovery. The approval of idebenone in the treatment of LHON was based on the overall data from a randomized clinical trial, a follow-up study and real-world data. Taken together, these studies provide convincing evidence that oral idebenone 900 mg/day for 24 weeks has persistent beneficial effects in preventing further vision impairment and promoting vision recovery in patients with LHON relative to the natural course of the disease. Therefore, idebenone is a valuable agent to treat visual impairment in adolescents and adults with LHON. PMID:27071925

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

    Grillo, Stephanie L; Koulen, Peter

    2015-12-01

    Processing of visual information begins in the retina, with photoreceptors converting light stimuli into neural signals. Ultimately, signals are transmitted to the brain through signaling networks formed by interneurons, namely bipolar, horizontal and amacrine cells providing input to retinal ganglion cells (RGCs), which form the optic nerve with their axons. As part of the chronic nature of glaucomatous optic neuropathy, the increasing and irreversible damage and ultimately loss of neurons, RGCs in particular, occurs following progressive damage to the optic nerve head (ONH), eventually resulting in visual impairment and visual field loss. There are two behavioral assays that are typically used to assess visual deficits in glaucoma rodent models, the visual water task and the optokinetic drum. The visual water task can assess an animal's ability to distinguish grating patterns that are associated with an escape from water. The optokinetic drum relies on the optomotor response, a reflex turning of the head and neck in the direction of the visual stimuli, which usually consists of rotating black and white gratings. This reflex is a physiological response critical for keeping the image stable on the retina. Driven initially by the neuronal input from direction-selective RGCs, this reflex is comprised of a number of critical sensory and motor elements. In the presence of repeatable and defined stimuli, this reflex is extremely well suited to analyze subtle changes in the circuitry and performance of retinal neurons. Increasing the cycles of these alternating gratings per degree, or gradually reducing the contrast of the visual stimuli, threshold levels can be determined at which the animal is no longer tracking the stimuli, and thereby visual function of the animal can be determined non-invasively. Integrating these assays into an array of outcome measures that determine multiple aspects of visual function is a central goal in vision research and can be realized, for example, by the combination of measuring optomotor reflex function with electroretinograms (ERGs) and optical coherence tomography (OCT) of the retina. These structure-function correlations in vivo are urgently needed to identify disease mechanisms as potential new targets for drug development. Such a combination of the experimental assessment of the optokinetic reflex (OKR) or optomotor response (OMR) with other measures of retinal structure and function is especially valuable for research on GON. The chronic progression of the disease is characterized by a gradual decrease in function accompanied by a concomitant increase in structural damage to the retina, therefore the assessment of subtle changes is key to determining the success of novel intervention strategies. PMID:26144667

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

    PubMed

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

    2009-04-01

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

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

    PubMed Central

    Miller, Neil R.

    2015-01-01

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

  2. Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION): A Review and Update on Animal Models.

    PubMed

    Peeler, Crandall; Cestari, Dean M

    2016-01-01

    Non-arteritic anterior ischemic optic neuropathy (NAION) is a relatively common optic neuropathy in adults over the age of 50, typically causing sudden, painless, unilateral vision loss and always resulting in swelling of the optic nerve head. Though several anatomic and vascular risk factors have been identified, much remains unknown about its pathophysiology and there is no proven treatment. This article reviews the risk factors, clinical presentation, and therapies that have been investigated for NAION. In addition, we provide an update from recent rodent and primate models, which offer new insight into the pathophysiology of this disease and provide a platform for treatment trials. PMID:26959135

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

    PubMed

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

    2016-01-01

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

  4. Orbital Decompression for Compressive Optic Neuropathy in Patients with a Metastatic Orbital Tumor from Breast Carcinoma.

    PubMed

    Takahashi, Yasuhiro; Kakizaki, Hirohiko

    2015-06-01

    We report two patients who underwent orbital decompression for compressive optic neuropathy due to a metastatic orbital tumor from breast cancer. One patient was a 47-year-old woman with right compressive optic neuropathy. Balanced orbital decompression was performed 11 days after her first visit. At postoperative week 1, her right visual acuity and critical flicker frequency value had improved from 0.1 and 20 Hz to 1.0 and 35 Hz, respectively, and good vision was maintained at 6 months postoperatively. The other patient was a 61-year-old woman with right compressive optic neuropathy. Medial orbital wall decompression was performed 5 days after her first visit. Her right visual acuity and critical flicker frequency values improved until 38 days after the surgery, from 0.5 and 19 Hz to 1.2 and 31 Hz, respectively, with stable good vision for the following 6 months. PMID:25849137

  5. 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.

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

    SciTech Connect

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

    1994-11-15

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    1990-09-01

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

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

    PubMed

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

    2015-08-15

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

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

    PubMed Central

    La Morgia, Chiara; Ross-Cisneros, Fred N.; Hannibal, Jens; Munarini, Alessandra; Mantovani, Vilma; Barboni, Piero; Cantalupo, Gaetano; Tozer, Kevin R.; Sancisi, Elisa; Salomao, Solange R.; Moraes, Milton N.; Moraes-Filho, Milton N.; Heegaard, Steffen; Milea, Dan; Kjer, Poul; Montagna, Pasquale

    2010-01-01

    Mitochondrial optic neuropathies, that is, Leber hereditary optic neuropathy and dominant optic atrophy, selectively affect retinal ganglion cells, causing visual loss with relatively preserved pupillary light reflex. The mammalian eye contains a light detection system based on a subset of retinal ganglion cells containing the photopigment melanopsin. These cells give origin to the retinohypothalamic tract and support the non-image-forming visual functions of the eye, which include the photoentrainment of circadian rhythms, light-induced suppression of melatonin secretion and pupillary light reflex. We studied the integrity of the retinohypothalamic tract in five patients with Leber hereditary optic neuropathy, in four with dominant optic atrophy and in nine controls by testing the light-induced suppression of nocturnal melatonin secretion. This response was maintained in optic neuropathy subjects as in controls, indicating that the retinohypothalamic tract is sufficiently preserved to drive light information detected by melanopsin retinal ganglion cells. We then investigated the histology of post-mortem eyes from two patients with Leber hereditary optic neuropathy and one case with dominant optic atrophy, compared with three age-matched controls. On these retinas, melanopsin retinal ganglion cells were characterized by immunohistochemistry and their number and distribution evaluated by a new protocol. In control retinas, we show that melanopsin retinal ganglion cells are lost with age and are more represented in the parafoveal region. In patients, we demonstrate a relative sparing of these cells compared with the massive loss of total retinal ganglion cells, even in the most affected areas of the retina. Our results demonstrate that melanopsin retinal ganglion cells resist neurodegeneration due to mitochondrial dysfunction and maintain non-image-forming functions of the eye in these visually impaired patients. We also show that in normal human retinas, these cells are more concentrated around the fovea and are lost with ageing. The current results provide a plausible explanation for the preservation of pupillary light reaction despite profound visual loss in patients with mitochondrial optic neuropathy, revealing the robustness of melanopsin retinal ganglion cells to a metabolic insult and opening the question of mechanisms that might protect these cells. PMID:20659957

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

    PubMed

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

    2016-01-01

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

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

    PubMed

    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

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

    PubMed

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

    2015-03-01

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

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

    PubMed

    Igata, Akihiro

    2012-01-01

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

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

    PubMed

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

    2015-11-01

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

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

    PubMed Central

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

    2015-01-01

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

  17. The correlation between anterior ischemic optic neuropathy the non-arthritic form, and the treatment involving alpha-interferon.

    PubMed

    Costea, Claudia F; Petraru, D; Galan, B; Mareş, Laura Mihaela

    2013-01-01

    The anterior ischemic optic neuropathy is an uncommon complication of alpha-Interferon treatment, characterized by the either temporary or permanent diminishing in visual acuity. We are hereby presenting the clinical case of an anterior ischemic optic neuropathy (non-arteritic form) complicating interferon therapy for Chronic Hepatitis C. In such cases we recommend ophthalmological examinations and if severe ophthalmologic complications occur antiviral treatment should be stopped immediately. PMID:24502073

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-01-01

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

  20. Leber's hereditary optic neuropathy differentially affects smaller axons in the optic nerve.

    PubMed Central

    Sadun, A A; Win, P H; Ross-Cisneros, F N; Walker, S O; Carelli, V

    2000-01-01

    PURPOSE: Leber's hereditary optic neuropathy (LHON), though known to be due to 1 of 3 pathogenic mtDNA point mutations (nucleotide positions 11,778, 3460, and 14,484), usually manifests itself acutely in young adulthood with a stereotypical presentation of dyschromatopsia, loss of central vision, and loss of the papillomacular bundle nerve fiber layer. Histopathologic investigations have demonstrated devastating losses of axons with relative sparing of the most peripherally placed fibers in the optic nerves. This study was designed to morphometrically investigate the nerve fiber spectrum from ultrastructural studies of optic nerves obtained from 2 patients with LHON. METHODS: Two cases of LHON were molecularly characterized and the optic nerves from these cases studied by light microscopy and electron microscopy. Montages were made of electron micrographs cut orthogonal to fibers obtained from the periphery of each optic nerve, and these were then used for the measurement of each axon (short and long axis) and its myelin sheath. From this, a spectrum of nerve fiber layer was generated, yielding axon caliber profiles that could be compared between optic nerves. RESULTS: The total depletion of optic nerve fiber population in the 2 cases of LHON varied from 95% to 99%. Those fibers that were spared were limited to the peripheral optic nerve. The nerve fiber layer spectra of these remaining fibers showed a marked diminution of the first peak of axons of less than 1 micron in diameter, with relative emphasis of a second peak of axons of about 2 microns in diameter. In comparison to normal controls, this reflected a preferential loss of the smallest axons corresponding to the P-cell population. CONCLUSIONS: The clinical features of dyschromatopsia and central scotoma (with preservation of pupils) in LHON suggests the selective loss of the P-cell population known to subserve these (and not pupil) functions. This also correlates well with the fundus findings of early losses of the papillomacular bundle. The present study extends these findings to demonstrate a relative preservation of the M-cells in the optic nerve as reflected by the nerve fiber spectral profile. This selective loss of smaller fibers and their corresponding smaller retinal ganglion cells may, in addition to explaining the clinical features in LHON, provide valuable insights as to the exact pathophysiologic mechanisms by which mitochondrial impairment may induce apoptosis in vulnerable neurons. Images FIGURE 1A FIGURE 1B FIGURE 2A FIGURE 2B FIGURE 3A FIGURE 3B FIGURE 4 A FIGURE 4 B FIGURE 4 C FIGURE 4 D FIGURE 4 E FIGURE 4 F PMID:11190025

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  3. An unusual presentation of nonarteritic ischemic optic neuropathy with subretinal fluid treated with intravitreal bevacizumab

    PubMed Central

    Dave, Vivek Pravin; Pappuru, Rajeev R

    2016-01-01

    A 62-year-old hypertensive male presented with acute nonarteritic ischemic optic neuropathy (NAION) with contiguous macular edema and subretinal fluid in the right eye. Presenting vision was 20/1000. The patient was treated with intravitreal bevacizumab 1.25 mg/0.05 ml. At 1 month follow-up, the macular edema and the optic nerve head edema completely resolved with a good visual improvement up to 20/40. The visual improvement was maintained at the last follow-up 6 months postinjection. Intravitreal bevacizumab may be a good option for acute NAION especially in an unusual presentation with macular edema and subretinal fluid. PMID:26953030

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

    PubMed

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

    2016-06-01

    A 63-year-old female with history of a resected frontal lobe meningioma presented with bilaterally decreased vision after a bite from a brown recluse spider. The exam was significant for a left relative afferent pupillary defect, bilateral optic nerve pallor, decreased foveal sensitivity in the left eye and new bilateral visual field defects, despite stability of her meningioma. The findings remained stable at 1-year follow-up. To our knowledge, this is the first reported case of optic neuropathy secondary to a brown recluse spider bite. Visual field tests performed prior to the bite allowed us to compare and localize changes related to the bite. PMID:25869060

  5. An unusual presentation of nonarteritic ischemic optic neuropathy with subretinal fluid treated with intravitreal bevacizumab.

    PubMed

    Dave, Vivek Pravin; Pappuru, Rajeev R

    2016-01-01

    A 62-year-old hypertensive male presented with acute nonarteritic ischemic optic neuropathy (NAION) with contiguous macular edema and subretinal fluid in the right eye. Presenting vision was 20/1000. The patient was treated with intravitreal bevacizumab 1.25 mg/0.05 ml. At 1 month follow-up, the macular edema and the optic nerve head edema completely resolved with a good visual improvement up to 20/40. The visual improvement was maintained at the last follow-up 6 months postinjection. Intravitreal bevacizumab may be a good option for acute NAION especially in an unusual presentation with macular edema and subretinal fluid. PMID:26953030

  6. Early Diagnosis of Subclinical Interferon Alpha-Associated Optic Neuropathy Using Fluorescein Angiography.

    PubMed

    Cestari, Dean M; Lessell, Simmons; Mantopoulos, Dimosthenis

    2015-09-01

    We report a case of a 57-year-old man who presented with decreased visual acuity in the left eye secondary to nonarteritic anterior ischemic optic neuropathy (NAION) while on therapy with interferon-α for hepatitis C. Fundus fluorescein angiography revealed late leakage of both optic discs, consistent with bilateral disease. One week later, the patient developed clinical signs and symptoms consistent with NAION in the fellow eye. Fluorescein angiography may play an important role in identifying subclinical NAION in patients taking interferon-α. PMID:25793363

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

    PubMed

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

    2016-02-01

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

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

    PubMed Central

    Miller, N R; Arnold, A C

    2015-01-01

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

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

    PubMed Central

    MacDermot, K D; Walker, R W

    1987-01-01

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

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

    PubMed

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

    2016-03-01

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

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

    SciTech Connect

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

    2005-07-15

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

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

    PubMed

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

    2014-04-01

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

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

    PubMed

    Fortune, Brad

    2015-12-01

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

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

    PubMed

    van der Lugt, J J; Venter, I

    2007-01-01

    Toxicity of closantel, a halogenated salicylanilide anthelmintic, is described in 11 sheep and a goat, humanely killed 4-70 days after accidental overdosage. Status spongiosis of the cerebrum and cerebellum was present, its severity decreasing with time after treatment. Ultrastructurally, vacuoles in the cerebral white matter were seen to be intramyelinic due to splitting of myelin lamellae at the intraperiod lines, indicating myelin oedema. In the optic nerves, Wallerian degeneration and eventual fibrosis and atrophy of the nerves followed myelin vacuolation. Lesions in the optic nerves were particularly advanced in the intracanalicular portion, indicating a compressive neuropathy within the optic canal. Acute retinal lesions consisted of papilloedema, necrosis of the outer retinal layers (especially the photoreceptor layer), and retinal separation in tapetal and non-tapetal areas. In more chronic cases, the outer nuclear layer was diffusely attenuated and generally reduced to a single row of cells. PMID:17270202

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

    PubMed

    Arnold, Anthony C

    2016-06-01

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

  16. Acute ischemic optic neuropathy with extended prone position ventilation in a lung transplant recipient.

    PubMed

    Panchabhai, Tanmay S; Bandyopadhyay, Debabrata; Kapoor, Aanchal; Akindipe, Olufemi; Lane, Charles; Krishnan, Sudhir

    2016-01-01

    Prone position ventilation (PPV) improves mortality in severe acute respiratory distress syndrome (ARDS), but outcomes following its use in lung transplant recipients are not known. We report the case of a 42-year-old Caucasian man who presented with severe ARDS from Bordetella pertussis, 5 years after bilateral sequential lung transplant for cystic fibrosis. He was managed with PPV for 22 days and had a prolonged ICU stay complicated by hypoxic ischemic optic neuropathy leading to blindness. Since his discharge from the ICU 6 months ago, his FEV1 has recovered to 47% predicted compared to his pre-ICU peak FEV1 of 85% predicted, suggesting recovery of lung function. This is the first report of optic nerve damage and vision loss in patients undergoing PPV. Our report also suggests that, in appropriately selected lung transplant recipients, severe hypoxemia could potentially be managed with prone ventilation. PMID:27051622

  17. Acute ischemic optic neuropathy with extended prone position ventilation in a lung transplant recipient

    PubMed Central

    Panchabhai, Tanmay S; Bandyopadhyay, Debabrata; Kapoor, Aanchal; Akindipe, Olufemi; Lane, Charles; Krishnan, Sudhir

    2016-01-01

    Prone position ventilation (PPV) improves mortality in severe acute respiratory distress syndrome (ARDS), but outcomes following its use in lung transplant recipients are not known. We report the case of a 42-year-old Caucasian man who presented with severe ARDS from Bordetella pertussis, 5 years after bilateral sequential lung transplant for cystic fibrosis. He was managed with PPV for 22 days and had a prolonged ICU stay complicated by hypoxic ischemic optic neuropathy leading to blindness. Since his discharge from the ICU 6 months ago, his FEV1 has recovered to 47% predicted compared to his pre-ICU peak FEV1 of 85% predicted, suggesting recovery of lung function. This is the first report of optic nerve damage and vision loss in patients undergoing PPV. Our report also suggests that, in appropriately selected lung transplant recipients, severe hypoxemia could potentially be managed with prone ventilation.

  18. Hereditary Neuropathies

    MedlinePlus

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

  19. Peripheral Neuropathy

    MedlinePlus

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

  20. Auditory Neuropathy

    MedlinePlus

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2014-02-01

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

  4. 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.

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

    SciTech Connect

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

    1996-07-01

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

  6. Sildenafil citrate use and the incidence of nonarteritic anterior ischemic optic neuropathy

    PubMed Central

    Gorkin, L; Hvidsten, K; Sobel, RE; Siegel, R

    2006-01-01

    Summary Nonarteritic anterior ischemic optic neuropathy (NAION) has been reported rarely in men after taking sildenafil or other phosphodiesterase 5 inhibitors for erectile dysfunction (ED). The incidence of NAION in men receiving sildenafil treatment for ED was estimated using pooled safety data from global clinical trials and European observational studies. Based on clinical trial data in more than 13,000 men and on more than 35,000 patient-years of observation in epidemiologic studies, we estimated an incidence of 2.8 cases of NAION per 100,000 patient-years of sildenafil exposure. This is similar to estimates reported in general US population samples (2.52 and 11.8 cases per 100,000 men aged ≥50 years). The data cited herein do not suggest an increased incidence of NAION in men who took sildenafil for ED. PMID:16620369

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

    PubMed

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

    2014-12-15

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

  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-βb2. Microarray and qRT-PCR analyses verified the results at the mRNA level. IHC demonstrated that crystallins were expressed mainly in the ganglion cell layer. The data suggest that IOP and either topically applied antiglaucomatous drugs influence crystallin expression within the retina. Neuronal crystallins are thus suitable biomarkers for monitoring the progression of neuropathy and evaluating any neuroprotective effects. PMID:23468831

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

    PubMed

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

    2010-02-01

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

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

    SciTech Connect

    Finger, Paul T.; Chin, Kimberly J.

    2012-02-01

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

  11. Translamina Cribrosa Pressure Difference as Potential Element in the Pathogenesis of Glaucomatous Optic Neuropathy.

    PubMed

    Jonas, Jost B; Wang, Ningli; Yang, Diya

    2016-01-01

    The main proven risk factor for glaucomatous optic neuropathy (GON) is an intraocular pressure (IOP) higher than the pressure sensibility of the optic nerve head allows. Fulfilling Koch postulates, numerous studies have shown that the presence of high IOP leads to GON, that lowering IOP stops the progression of GON, and that a re-increase in IOP again causes the progression of GON. There are, however, many patients with glaucoma who have statistically normal or low IOP, and despite low IOP values, they develop progressing GON. These observations led to findings that IOP is only 1 of 2 determinants of the translamina cribrosa pressure difference (TLCPD), which is the main pressure-related parameter for the physiology and pathophysiology of the optic nerve head. The second parameter influencing TLCPD is orbital cerebrospinal fluid pressure (CSFP) as the counter pressure against IOP across the lamina cribrosa. Recent experimental and clinical studies have suggested that a low CSFP could be associated with GON in normal-pressure glaucoma. These investigations included studies with an experimental long-term reduction in CSFP in monkeys, population-based studies, and clinical retrospective and prospective investigations on patients with normal-pressure glaucoma. Besides TLCPD, other ocular parameters influenced by CSFP may be choroidal thickness, retinal vein pressure and diameter, occurrence of retinal vein occlusions, and occurrence and severity of diabetic retinopathy. PMID:26713405

  12. Leber hereditary optic neuropathy mtDNA mutations disrupt glutamate transport in cybrid cell lines.

    PubMed

    Beretta, Simone; Mattavelli, Laura; Sala, Gessica; Tremolizzo, Lucio; Schapira, Anthony H V; Martinuzzi, Andrea; Carelli, Valerio; Ferrarese, Carlo

    2004-10-01

    Leber hereditary optic neuropathy (LHON) is a maternally inherited form of retinal ganglion cell degeneration leading to optic atrophy which is caused by point mutations in the mitochondrial genome (mtDNA). Three pathogenic mutations (positions 11778/ND4, 3460/ND1 and 14484/ND6) account for the majority of LHON cases and they affect genes that encode for different subunits of mitochondrial complex I. Excitotoxic injury to retinal ganglion cells and the optic nerve has been previously hypothesized, especially given the high susceptibility of this neural cell type to glutamate toxicity. Osteosarcoma-derived cytoplasmic hybrids (cybrids) generated from six unrelated LHON patients, two cell lines for each pathogenic mutation, were compared with cybrids obtained from three healthy controls. Molecular and biochemical analyses showed that excitatory amino acid transporter 1 (EAAT1)/GLAST is the most active glutamate transporter in this cellular model. The glutamate uptake maximal velocity was significantly reduced in all LHON cybrids compared with control cybrids. This reduction was correlated in a mutation-specific fashion with the degree of mitochondrial production of reactive oxygen species, which is enhanced in LHON cybrids. Our findings support the hypothesis that the genetically determined mitochondrial dysfunction in LHON patients leads to impaired activity of the EAAT1 glutamate transporter. This observation is particularly relevant since EAAT1 is the major means of glutamate removal in the inner retina and this prevents retinal ganglion cells being damaged as a result of excitotoxicity. PMID:15342361

  13. [Diabetic neuropathy].

    PubMed

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

    2016-04-01

    These are the guidelines for diagnosis and treatment of diabetic neuropathy. This diabetic late complication comprises a number of mono- and polyneuropathies, plexopathies, radiculopathies and autonomic neuropathy. The position statement summarizes characteristic clinical symptoms and techniques for diagnostic assessment of diabetic neuropathy. Recommendations for the therapeutic management of diabetic neuropathy, especially for the control of pain in sensorimotor neuropathy, are provided. PMID:27052228

  14. 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

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

    PubMed Central

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

    2014-01-01

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

  16. Diabetic Neuropathy

    MedlinePlus

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

  17. 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 ...

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

    PubMed Central

    Kim, Tae-Woo; Hwang, Jeong-Min

    2016-01-01

    Purpose To compare the deep optic nerve head (ONH) structure between normal-tension glaucoma (NTG) and nonarteritic anterior ischemic optic neuropathy (NAION) and also in healthy subjects as a control using enhanced depth imaging (EDI) spectral-domain optical coherence tomography (SD-OCT). Methods This prospective cross-sectional study included 21 NAION patients who had been diagnosed as NAION at least 6 months prior to study entry, and 42 NTG patients and 42 healthy controls who were matched with NAION patients in terms of age, intraocular pressure (IOP), and optic disc area. The retinal nerve fiber layer (RNFL) thickness in the affected sector was also matched between NAION and NTG patients. The ONH was imaged using SD-OCT with the EDI technique. The anterior lamina cribrosa surface depth (LCD) and average prelaminar tissue (PT) thickness were measured in a sector of interest in each eye and compared among the three groups. Results In the sector-matched comparison, LCD was largest in NTG patients, followed by NAION patients, while PT was thinner in NTG patients than in NAION patients (all P < 0.001). NAION patients had a comparable LCD and a thinner PT relative to normal controls (P = 0.170 and < 0.001, respectively). Conclusion The deep ONH configuration is strikingly different between NTG and NAION. The differing features provide comparative insight into the pathophysiology of the two diseases, and may be useful for differential diagnosis. PMID:27035660

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

    PubMed

    Wan, Xing; Pei, Han; Zhao, Min-Jian; Yang, Shuo; Hu, Wei-Kun; He, Heng; Ma, Si-Qi; Zhang, Ge; Dong, Xiao-Yan; Chen, Chen; Wang, Dao-Wen; Li, Bin

    2016-01-01

    Leber's hereditary optic neuropathy (LHON) is a mitochondrially inherited disease leading to blindness. A mitochondrial DNA point mutation at the 11778 nucleotide site of the NADH dehydrogenase subunit 4 (ND4) gene is the most common cause. The aim of this study was to evaluate the efficacy and safety of a recombinant adeno-associated virus 2 (AAV2) carrying ND4 (rAAV2-ND4) in LHON patients carrying the G11778A mutation. Nine patients were administered rAAV2-ND4 by intravitreal injection to one eye and then followed for 9 months. Ophthalmologic examinations of visual acuity, visual field, and optical coherence tomography were performed. Physical examinations included routine blood and urine. The visual acuity of the injected eyes of six patients improved by at least 0.3 log MAR after 9 months of follow-up. In these six patients, the visual field was enlarged but the retinal nerve fibre layer remained relatively stable. No other outcome measure was significantly changed. None of the nine patients had local or systemic adverse events related to the vector during the 9-month follow-up period. These findings support the feasible use of gene therapy for LHON. PMID:26892229

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

    PubMed Central

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

    2015-01-01

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

  1. Peripheral neuropathy

    MedlinePlus

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

  2. 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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

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

    1993-10-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    SciTech Connect

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

    2009-06-05

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

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

    PubMed Central

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

    2003-01-01

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

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

    PubMed

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

    2008-12-10

    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 with 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

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

    SciTech Connect

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

    2009-11-20

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

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

    PubMed Central

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

    2015-01-01

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

  14. 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

  15. Glutathione-S-Transferase Deletions and Non-arteritic Anterior Ischemic Optic Neuropathy.

    PubMed

    Wan, Wencui; Peng, Tao; Jin, Xuemin; Li, Qiuming; Zhang, Fengyan; Zheng, Guangying; Lv, Yong; Wan, Guangming; Zhu, Yu

    2016-05-01

    In this study, we aimed at investigating the association between glutathione-S-transferase (GSTM1 and GSTT1) deletion genotypes and susceptibility to non-arteritic anterior ischemic optic neuropathy (NAION). We hope our findings may contribute to the understanding NAION pathogenesis and provide some clues for the prevention and treatment of optic diseases. The NAION group contains 113 subjects (33 males and 80 females, mean age 55.3 ± 9.8). And 98 subjects were enrolled in the control group (32 males and 66 females, mean age 56.7 ± 10.2). The individuals involved in the study were matched by gender and age to obtain two homogenous groups. GSTM1- and GSTT1- genotype and the combined genotype were investigated. The genotype distributions in NAION patients were compared with those in the controls. Significantly altered intraocular pressure (IOP) and cup-to-disc ratio (CDR) was detected between NAION patients and controls. An increased risk of NAION was observed among individuals with GSTM1- (P < 0.001). No significant difference was confirmed for GSTT1- (P = 0.290). Individuals with GSTM1-/GSTT1- have a higher susceptibility to NAION (P < 0.001); the GSTM1-/GSTT1+ genotype also had a significantly higher frequency in patients than in controls (P = 0.004). But the genotype of GSTM1+/GSTT1- seems to have no connection with NAION (P = 0.476). In conclusion, in this study, we confirmed the connection between NAION and GSTM1- genotype. But no significant association was observed between GSTT1- genotype and NAION susceptibility. In further analysis regarding combined genotype, a trend of protective effect was detected for GSTT1+ genotype. It is indicated by our result that oxidative compounds might play an important part in the pathogenesis of NAION. PMID:25990411

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  18. 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

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

    PubMed Central

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

    2009-01-01

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

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

    SciTech Connect

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

    2013-11-01

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

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

    PubMed Central

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

    1997-01-01

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

  2. Toxic neuropathies.

    PubMed

    Misra, Usha Kant; Kalita, Jayantee

    2009-01-01

    Toxic neuropathies generally result in length dependent axonal neuropathy with the exception of diphtheria and a few toxic neuropathies. In spite of occurrence of diphtheria in India there is paucity of published reports on diphtheritic neuropathy. Arsenic neuropathy commonly occurs in Bengal and Bangladesh because of ground water contamination whereas in Punjab it is due to contamination of opium. Lead neuropathy is rare and has been reported in battery workers and silver refining workers. It produces motor neuropathy resulting in foot drop and wrist drop. Organophosphates are used as pesticides, industrial chemicals and food adulterant. Certain organophosphates such as triorthocresyl phosphate used for or oil adulteration inhibit neurotoxic esterase and result in a delayed type of axonal neuropathy. Alcohol related neuropathy is a controversial issue whether it is due to alcohol related toxicity or due to nutritional deficiencies. Indian studies have revealed that neuropathy occurs both in alcoholic and nonalcoholic cirrhosis. Hexane neuropathy is reported in screen printers and these cases highlight the need for better preventive and occupational measures. Iatrogenic toxic neuropathies have been reported with cisplatin and vincristine. Because of geographical, occupational and health related conditions toxic neuropathies are likely to be more common than reported and greater awareness is needed. PMID:20139496

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

    PubMed

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

    2015-12-01

    Glaucoma is a disease characterized by progressive axonal pathology and death of retinal ganglion cells (RGCs), which causes structural changes in the optic nerve head and irreversible vision loss. Several experimental models of glaucomatous optic neuropathy (GON) have been developed, primarily in non-human primates and, more recently and commonly, in rodents. These models provide important research tools to study the mechanisms underlying glaucomatous damage. Moreover, experimental GON provides the ability to quantify and monitor risk factors leading to RGC loss such as the level of intraocular pressure, axonal health and the RGC population. Using these experimental models we are able to gain a better understanding of GON, which allows for the development of potential neuroprotective strategies. Here we review the advantages and disadvantages of the relevant and most often utilized methods for evaluating axonal degeneration and RGC loss in GON. Axonal pathology in GON includes functional disruption of axonal transport (AT) and structural degeneration. Horseradish peroxidase (HRP), rhodamine-B-isothiocyanate (RITC) and cholera toxin-B (CTB) fluorescent conjugates have proven to be effective reporters of AT. Also, immunohistochemistry (IHC) for endogenous AT-associated proteins is often used as an indicator of AT function. Similarly, structural degeneration of axons in GON can be investigated via changes in the activity and expression of key axonal enzymes and structural proteins. Assessment of axonal degeneration can be measured by direct quantification of axons, qualitative grading, or a combination of both methods. RGC loss is the most frequently quantified variable in studies of experimental GON. Retrograde tracers can be used to quantify RGC populations in rodents via application to the superior colliculus (SC). In addition, in situ IHC for RGC-specific proteins is a common method of RGC quantification used in many studies. Recently, transgenic mouse models that express fluorescent proteins under the Thy-1 promoter have been examined for their potential to provide specific and selective labeling of RGCs for the study of GON. While these methods represent important advances in assessing the structural and functional integrity of RGCs, each has its advantages and disadvantages; together they provide an extensive toolbox for the study of GON. PMID:26070986

  4. Peripheral Neuropathy

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS Peripheral Neuropathy Fact Sheet See a list of all NINDS ... can I get more information? What is peripheral neuropathy? An estimated 20 million people in the United ...

  5. Neuropathy Tests

    MedlinePlus

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

  6. 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

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

    PubMed

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

    2016-03-01

    To investigate the risk of nonarteritic anterior ischemic optic neuropathy (NAION) following end-stage renal disease (ESRD).A retrospective, nationwide, matched cohort study.ESRD patients identified by the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 585.The study cohort included 93,804 ESRD patients registered with the Taiwan National Health Insurance Research Database between January 2000 and December 2009. An age- and sex-matched control group comprised 93,804 patients (case:control = 1:1) selected from the Taiwan Longitudinal Health Insurance Database 2000. Information for each patient was collected from the index date until December 2011. The incidence and risk of NAION were compared between the ESRD and control groups. The adjusted hazard ratio (HR) for NAION after adjustment for potential confounders was obtained by a Cox proportional hazard regression analysis. A Kaplan-Meier analysis was used to calculate the cumulative incidence rate of NAION.The incidence of NAION following ESRD.In total, 133 ESRD patients (0.14%) and 51 controls (0.05%) had NAION (P < 0.001) during the follow-up period, leading to a significantly elevated risk of NAION in the ESRD patients compared with the controls (incidence rate ratio = 3.14, 95% confidence interval [CI] = 2.11-4.67). After adjustment for potential confounders including diabetes mellitus, hypertension, hypotension, hyperlipidemia, and 2-way interaction terms between any 2 factors, ESRD patients were 3.12 times more likely to develop NAION than non-ESRD patients in the full cohort (adjusted HR = 3.12, 95% CI = 2.10-4.64). Additionally, patients with hypertension and hyperlipidemia showed higher incidence rates of NAION in the ESRD group compared with the controls: 2.31 (95% CI = 1.40-3.82) for hypertension and 2.72 (95% CI = 1.14-6.50) for hyperlipidemia.ESRD increased the risk of NAION, which is an interdisciplinary emergency. Close collaboration between nephrologists and ophthalmologists is important in NAION management following ESRD to prevent fellow eye involvement. PMID:27015205

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

    SciTech Connect

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

    1994-11-01

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

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

    PubMed Central

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

    2015-01-01

    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 serves as a model for future investigators to design and implement reliable tests to assess the beneficial effects of therapeutic interventions for LHON disease. PMID:25481764

  10. 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

  11. 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

  12. 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

  13. [Diabetic neuropathy].

    PubMed

    Nakamura, Jiro; Kamiya, Hideki

    2015-12-01

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

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

    PubMed Central

    Santini, Paolo

    2016-01-01

    Here we have collected evidence suggesting that chronic changes in the NO homeostasis and the rise of reactive oxygen species bioavailability can contribute to cell dysfunction in Leber's hereditary optic neuropathy (LHON) patients. We report that peripheral blood mononuclear cells (PBMCs), derived from a female LHON patient with bilateral reduced vision and carrying the pathogenic mutation 11778/ND4, display increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS), as revealed by flow cytometry, fluorometric measurements of nitrite/nitrate, and 3-nitrotyrosine immunodetection. Moreover, viability assays with the tetrazolium dye MTT showed that lymphoblasts from the same patient are more sensitive to prolonged NO exposure, leading to cell death. Taken together these findings suggest that oxidative and nitrosative stress cooperatively play an important role in driving LHON pathology when excess NO remains available over time in the cell environment. PMID:26881022

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

    SciTech Connect

    Mackey, D. ); Howell, N. )

    1992-12-01

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

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

    PubMed Central

    Van Bergen, Nicole J; Crowston, Jonathan G.; Craig, Jamie E.; Burdon, Kathryn P.; Kearns, Lisa S.; Sharma, Shiwani; Hewitt, Alex W.; Mackey, David A.; Trounce, Ian A.

    2015-01-01

    Primary Open Angle Glaucoma (POAG) is a common neurodegenerative disease characterized by the selective and gradual loss of retinal ganglion cells (RGCs). Aging and increased intraocular pressure (IOP) are glaucoma risk factors; nevertheless patients deteriorate at all levels of IOP, implying other causative factors. Recent evidence presents mitochondrial oxidative phosphorylation (OXPHOS) complex-I impairments in POAG. Leber Hereditary Optic Neuropathy (LHON) patients suffer specific and rapid loss of RGCs, predominantly in young adult males, due to complex-I mutations in the mitochondrial genome. This study directly compares the degree of OXPHOS impairment in POAG and LHON patients, testing the hypothesis that the milder clinical disease in POAG is due to a milder complex-I impairment. To assess overall mitochondrial capacity, cells can be forced to produce ATP primarily from mitochondrial OXPHOS by switching the media carbon source to galactose. Under these conditions POAG lymphoblasts grew 1.47 times slower than controls, whilst LHON lymphoblasts demonstrated a greater degree of growth impairment (2.35 times slower). Complex-I enzyme specific activity was reduced by 18% in POAG lymphoblasts and by 29% in LHON lymphoblasts. We also assessed complex-I ATP synthesis, which was 19% decreased in POAG patients and 17% decreased in LHON patients. This study demonstrates both POAG and LHON lymphoblasts have impaired complex-I, and in the majority of aspects the functional defects in POAG were milder than LHON, which could reflect the milder disease development of POAG. This new evidence places POAG in the spectrum of mitochondrial optic neuropathies and raises the possibility for new therapeutic targets aimed at improving mitochondrial function. PMID:26496696

  17. Diabetic Neuropathies

    PubMed Central

    Russell, James W.; Zilliox, Lindsay A.

    2014-01-01

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

  18. 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.

  19. Peripheral Neuropathy

    MedlinePlus

    ... Listed in Reviewed February 4, 2014 Select a Language: Fact Sheet 555 Peripheral Neuropathy WHAT IS PERIPHERAL ... breakdown of the nerve endings (axons) that send sensations to the brain. Sometimes, PN is damage to ...

  20. Auditory Neuropathy

    MedlinePlus

    ... responding to the child. There are two main philosophies of how to teach infants and children with auditory neuropathy how to communicate. One philosophy favors using sign language as the child’s first ...

  1. Alcoholic neuropathy

    MedlinePlus

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2012-01-01

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

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

    PubMed Central

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

    2016-01-01

    Leber’s hereditary optic neuropathy (LHON) is a mitochondrially inherited disease leading to blindness. A mitochondrial DNA point mutation at the 11778 nucleotide site of the NADH dehydrogenase subunit 4 (ND4) gene is the most common cause. The aim of this study was to evaluate the efficacy and safety of a recombinant adeno-associated virus 2 (AAV2) carrying ND4 (rAAV2-ND4) in LHON patients carrying the G11778A mutation. Nine patients were administered rAAV2-ND4 by intravitreal injection to one eye and then followed for 9 months. Ophthalmologic examinations of visual acuity, visual field, and optical coherence tomography were performed. Physical examinations included routine blood and urine. The visual acuity of the injected eyes of six patients improved by at least 0.3 log MAR after 9 months of follow-up. In these six patients, the visual field was enlarged but the retinal nerve fibre layer remained relatively stable. No other outcome measure was significantly changed. None of the nine patients had local or systemic adverse events related to the vector during the 9-month follow-up period. These findings support the feasible use of gene therapy for LHON. PMID:26892229

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

    PubMed

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

    2016-04-01

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

  6. The Pupil Light Reflex in Leber's Hereditary Optic Neuropathy: Evidence for Preservation of Melanopsin-Expressing Retinal Ganglion Cells

    PubMed Central

    Moura, Ana Laura A.; Nagy, Balázs V.; La Morgia, Chiara; Barboni, Piero; Oliveira, André Gustavo Fernandes; Salomão, Solange R.; Berezovsky, Adriana; de Moraes-Filho, Milton Nunes; Chicani, Carlos Filipe; Belfort, Rubens; Carelli, Valerio; Sadun, Alfredo A.; Hood, Donald C.; Ventura, Dora Fix

    2013-01-01

    Purpose. To investigate the pupillary light reflex (PLR) of patients with severe loss of vision due to Leber's Hereditary Optic Neuropathy (LHON) in the context of a proposed preservation of melanopsin-expressing retinal ganglion cells (mRGCs). Methods. Ten LHON patients (7 males; 51.6 ± 14.1 years), with visual acuities ranging from 20/400 to hand motion perception and severe visual field losses, were tested and compared with 16 healthy subjects (7 males; 42.15 ± 15.4 years) tested as controls. PLR was measured with an eye tracker and the stimuli were controlled with a Ganzfeld system. Pupil responses were measured monocularly, to 1 second of blue (470 nm) and red (640 nm) flashes with 1, 10, 100, and 250 cd/m2 luminances. The normalized amplitude of peak of the transient PLR and the amplitude of the sustained PLR at 6 seconds after the flash offset were measured. In addition, optical coherence topography (OCT) scans of the peripapillary retinal nerve fiber layer were obtained. Results. The patient's peak PLR responses were on average 15% smaller than controls (P < 0.05), but 5 out of 10 patients had amplitudes within the range of controls. The patients' sustained PLRs were comparable with controls at lower flash intensities, but on average, 27% smaller to the 250 cd/m2 blue light, although there was considerable overlap with the PLR amplitudes of control. All patients had severe visual field losses and the retinal nerve fiber layer thickness was reduced to a minimum around the optic disc in 8 of the 10 patients. Conclusions. The PLR is maintained overall in LHON patients despite the severity of optic atrophy. These results are consistent with previous evidence of selective preservation of mRGCs. PMID:23737476

  7. Subacute myelo-optic neuropathy and clioquinol. An epidemiological case-history for diagnosis.

    PubMed Central

    Meade, T W

    1975-01-01

    Between about 1955 and 1970, some 100,000 Japanese were diagnosed as having subacute myelooptic neuropathy (SMON), a new disease characterized by abdominal and neurological manifestations, the former nearly always preceding the latter. Circumstantial evidence obtained in 1969-70 suggested that SMON might have been caused by clioquinol (CQL), a gastrointestinal disinfectant, and led to the suspension of further sales of CQL in Japan. However, several inconsistencies for the CQL theory of SMON have now emerged; first, CQL had been widely used in Japan for nearly 20 years before SMON occurred. Secondly, the SMON epidemic began to subside several months before CQL sales were suspended. Thirdly, a large proportion of SMON patients--probably about one-third and possibly more--had not taken CQL within six months of the onset of the disease (the modal interval between first taking CQL and the onset of SMON being about three weeks, and more than 100 days in only 4% of SMON patients); of the remaining two-thirds or so, many had taken CQL as part of the treatment of the first (that is, abdominal) symptoms of SMON itself. Fourthly, there was no dose-response relationship. Finally, SMON rarely, if ever, occurred outside Japan. CQL could, however, have been involved in the causation of SMON as an optional enhancer of some other necessary cause; the history of post-war environmental pollution in Japan is compatible with this hypothesis. Over-readiness to accept postulated toxic effects of medicines and chemicals as proven is likely to do at least as much harm as good to individual and community health. PMID:127638

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

    SciTech Connect

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

    2006-02-03

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

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

    SciTech Connect

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

    2006-08-18

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

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

    PubMed Central

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

    2006-01-01

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

  11. The ND1 gene of complex I is a mutational hot spot for Leber's hereditary optic neuropathy.

    PubMed

    Valentino, Maria Lucia; Barboni, Piero; Ghelli, Anna; Bucchi, Laura; Rengo, Chiara; Achilli, Alessandro; Torroni, Antonio; Lugaresi, Alessandra; Lodi, Raffaele; Barbiroli, Bruno; Dotti, Mariateresa; Federico, Antonio; Baruzzi, Agostino; Carelli, Valerio

    2004-11-01

    A novel mitochondrial DNA (mtDNA) transition (3733G-->A) inducing the E143 K amino acid change at a very conserved site of the NADH dehydrogenase subunit 1 (ND1) was identified in a family with six maternally related individuals with Leber's hereditary optic neuropathy (LHON) and in an unrelated sporadic case, all negative for known mutations and presenting with the canonical phenotype. The transition was not detected in 1,082 control mtDNAs and was heteroplasmic in several individuals from both pedigrees. In addition, the mtDNAs of the two families were found to belong to different haplogroups (H and X), thus confirming that the 3733G-->A mutation occurred twice independently. Phosphorus magnetic resonance spectroscopy disclosed an in vivo brain and skeletal muscle energy metabolism deficit in the four examined patients. Muscle biopsy from two patients showed slight mitochondrial proliferation with abnormal mitochondria. Biochemical investigations in platelets showed partially insensitive complex I to rotenone inhibition. We conclude that the 3733G-->A transition is a novel cause of LHON and, after those at positions 3460 and 4171, is the third ND1 mutation to be identified in multiple unrelated families. This finding shows that, in addition to ND6, the ND1 subunit gene is also a mutational hot spot for LHON. PMID:15505787

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Zhang, Xi; Yu, Shuaishuai; Tu, Yunhai; Huang, Wenjie

    2016-07-01

    Mutation in mitochondrial DNA (mtDNA) has been found to play an important role in the pathogenesis of Leber's Hereditary Optic Neuropathy (LHON). Three primary mutations, the ND4 G11778A, ND6 T14484C, and ND1 G3460A, have been found to account more than 90% of LHON patients in many families worldwide. In addition to the mutations in genes encoding the respiratory chain complex I, reports concerning the mt-tRNA gene mutations associated with LHON have increased, some pathogenic mutations caused the failure in mt-tRNA metabolism, thereby worsened the mitochondrial dysfunction that is responsible for LHON. Recently, the A15951G mutation in mt-tRNA(Thr) gene has been reported to be a "modified" factor in increasing the penetrance and expressivity of LHON-associated ND4 G11778A mutation in three Chinese families. However, evolutionary conservation analysis of this mutation suggested a poor conservation index and the pathogenicity scoring system showed that this mutation was a neutral polymorphism. PMID:26000946

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

    SciTech Connect

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

    1996-04-01

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

  15. 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

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

    PubMed

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

    1998-12-01

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

  17. Compression neuropathy caused by cancer metastasis to the optic nerve canal

    PubMed Central

    2013-01-01

    Background Cancerous cells are known to metastasize to different ocular structures. This happens especially to the choroid in males with lung cancer and females with breast cancer. However, we observed two cases of cancerous metastasis to the optic canal region. Both cases showed only a progressive decrease in vision without any other remarkable ophthalmological symptoms or abnormalities in the affected eye. Case presentation Two females, a 60-year-old and a 73-year-old, came to our hospital because of progressive loss of vision. These patients showed no remarkable symptoms or signs in their eyes except visual acuity loss. Several ophthalmoscopic examinations, such as slit lamp microscopy and fundoscopy, showed no abnormal changes in their affected eye but magnetic resonance imaging indicated a massive legion around the optic nerve. Conclusion It is possible for cancer to metastasize to the optic canal region and the existence of primary tumors should be considered. PMID:24359676

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

    PubMed

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

    2015-06-01

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

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

    PubMed Central

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

    2015-01-01

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

  20. Inherited neuropathies.

    PubMed

    Chance, P F; Reilly, M

    1994-10-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-06-01

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

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

    SciTech Connect

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

    1997-02-01

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

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

    SciTech Connect

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

    1996-02-01

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

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

    PubMed Central

    Giordano, L; Deceglie, S; d'Adamo, P; Valentino, M L; La Morgia, C; Fracasso, F; Roberti, M; Cappellari, M; Petrosillo, G; Ciaravolo, S; Parente, D; Giordano, C; Maresca, A; Iommarini, L; Del Dotto, V; Ghelli, A M; Salomao, S R; Berezovsky, A; Belfort, R; Sadun, A A; Carelli, V; Loguercio Polosa, P; Cantatore, P

    2015-01-01

    Leber's hereditary optic neuropathy (LHON), the most frequent mitochondrial disease, is associated with mitochondrial DNA (mtDNA) point mutations affecting Complex I subunits, usually homoplasmic. This blinding disorder is characterized by incomplete penetrance, possibly related to several genetic modifying factors. We recently reported that increased mitochondrial biogenesis in unaffected mutation carriers is a compensatory mechanism, which reduces penetrance. Also, environmental factors such as cigarette smoking have been implicated as disease triggers. To investigate this issue further, we first assessed the relationship between cigarette smoke and mtDNA copy number in blood cells from large cohorts of LHON families, finding that smoking was significantly associated with the lowest mtDNA content in affected individuals. To unwrap the mechanism of tobacco toxicity in LHON, we exposed fibroblasts from affected individuals, unaffected mutation carriers and controls to cigarette smoke condensate (CSC). CSC decreased mtDNA copy number in all cells; moreover, it caused significant reduction of ATP level only in mutated cells including carriers. This implies that the bioenergetic compensation in carriers is hampered by exposure to smoke derivatives. We also observed that in untreated cells the level of carbonylated proteins was highest in affected individuals, whereas the level of several detoxifying enzymes was highest in carriers. Thus, carriers are particularly successful in reactive oxygen species (ROS) scavenging capacity. After CSC exposure, the amount of detoxifying enzymes increased in all cells, but carbonylated proteins increased only in LHON mutant cells, mostly from affected individuals. All considered, it appears that exposure to smoke derivatives has a more deleterious effect in affected individuals, whereas carriers are the most efficient in mitigating ROS rather than recovering bioenergetics. Therefore, the identification of genetic modifiers that modulate LHON penetrance must take into account also the exposure to environmental triggers such as tobacco smoke. PMID:26673666

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

    PubMed Central

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

    2015-01-01

    We present the results from a patient with relapsing optic neuropathy treated within the Stem Cell Ophthalmology Treatment Study (SCOTS). SCOTS is an Institutional Review Board approved clinical trial and has become the largest ophthalmology stem cell study registered at the National Institutes of Health to date (www.clinicaltrials.gov Identifier NCT 01920867). SCOTS utilizes autologous bone marrow-derived stem cells (BMSCs) for treatment of retinal and optic nerve diseases. Pre-treatment and post-treatment comprehensive eye exams of a 54 year old female patient were performed both at the Florida Study Center, USA and at The Eye Center of Columbus, USA. As a consequence of a relapsing optic neuritis, the patient's previously normal visual acuity decreased to between 20/350 and 20/400 in the right eye and to 20/70 in the left eye. Significant visual field loss developed bilaterally. The patient underwent a right eye vitrectomy with injection of BMSCs into the optic nerve of the right eyeand retrobulbar, subtenon and intravitreal injection of BMSCs in the left eye. At 15 months after SCOTS treatment, the patient's visual acuity had improved to 20/150 in the right eye and 20/20 in the left eye. Bilateral visual fields improved markedly. Both macular thickness and fast retinal nerve fiber layer thickness were maximally improved at 3 and 6 months after SCOTS treatment. The patient also reduced her mycophenylate dose from 1,500 mg per day to 500 mg per day and required no steroid pulse therapy during the 15-month follow up. PMID:26604914

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

    PubMed

    Jacquet, Coralie; Garnier, Arnaud; Cheuret, Emmanuel

    2016-06-01

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

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

    PubMed

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

    2016-07-01

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

  9. 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

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

    PubMed

    Meng, Xiangjuan; Zhu, Jinping; Gao, Min; Zhang, Sai; Zhao, Fuxin; Zhang, Juanjuan; Liu, Xiaoling; Wei, Qiping; Tong, Yi; Zhang, Minglian; Qu, Jia; Guan, Minxin

    2014-04-01

    The m.14484T>C mutation in mitochondrial ND6 gene (MT-ND6) is a primary mutation underlying the development of Leber's hereditary optic neuropathy (LHON) , but by itself not enough to cause visual loss. To explore the role of mitochondrial haplogroups on the expression of LHON for the people carrying the m.14484T>C mutation, we performed systematic and extended mutational screening of MT-ND6 gene in a cohort of 1177 Han Chinese patients with LHON. A total of 67 affected subjects carried the homoplasmic m.14484T>C mutation, accounting for 5.7% of this LHON population. The penetrances of optic neuropathy among 51 pedigrees carrying the m.14484T>C mutation ranged from 5.6% to 100.0%, with the average of 21.5%. The sequence analysis of entire mitochondrial genomes of 51 probands exhibited distinct sets of polymorphisms belonging to 18 Eastern Asian haplogroups. The frequencies of haplogroup A and haplogroup F were sig-nificantly less in the LHON mtDNA samples than those in 106 Chinese controls. On the other hand, the haplogroup M10a accounted for 9.8% of the patient's mtDNA samples but was absent in 106 Chinese controls. Strikingly, the average pene-trance (46.13%) of optic neuropathy for the pedigrees carrying mitochondrial haplogroup M10a was higher than those car-rying other mtDNA haplogroups. These observations indicated that mitochondrial haplogroup M10a may increase the risk of visual loss. PMID:24846978

  11. Hereditary neuropathy.

    PubMed

    Heidenreich, Wayne F

    2010-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  13. [Amyloid neuropathy].

    PubMed

    Ikegawa, S

    1990-12-01

    Primary amyloidosis and myeloma associated amyloidosis causes neuropathy in 10% of the cases, and hemodialysis associated amyloidosis causes carpal tunnel syndrome. However, most severe amyloid neuropathy is observed in familial amyloidotic polyneuropathy (FAP). FAP type I is an autosomal dominant systemic amyloidosis characterized by sensory dominant systemic amyloidosis characterized by dissociated sensory disturbance and autonomic dysfunction. Amyloid deposition is noted universally in endoneurium of peripheral nerve, especially prominent in sural, sciatic nerve, dorsal root ganglia and sympathetic ganglia. Moderate deposition was also noted in dorsal spinal root. Amyloid was absent in CNS. The number of small myelinated fibers is decreased. Unmyelinated axons are severely depleted and amyloid fibrils are observed around the wall of small vessels. Amyloid fibril protein consists of variant transthyretin (TTR:prealbumin) with one amino acid substitution of methionine-for-valine at position 30. Other types of FAP show another one point mutation in TTR molecule. Transgenic mouse model of FAP was produced by microinjecting cloned human variant TTR gene into mice. Amyloid were demonstrated in thyroid, kidney and intestine and so on, but not in peripheral nerve in these mice. Pathogenesis of neuropathy of FAP is not known, but mechanical compression to the nerve, ischemia and metabolic abnormality may play some role combined to cause of nerve fiber damage. The effect of deposition on physiochemical functions of the neuron and mechanism to accumulate in nervous system of the TTR remain to be elucidated. PMID:1966018

  14. Biopsy-negative, varicella zoster virus (VZV)-positive giant cell arteritis, zoster, VZV encephalitis and ischemic optic neuropathy, all in one

    PubMed Central

    Teodoro, Tiago; Nagel, Maria A.; Geraldes, Ruth; White, Teresa; Mahalingam, Ravi; Batista, Paulo; Wellish, Mary; Pimentel, Jose; Khmeleva, Nelly; Heintzman, Anna; Albuquerque, Luísa; Boyer, Philip J.; Choe, Alexander; Peralta, Rita; Gilden, Don

    2014-01-01

    A 72-year-old man developed clinical features of giant cell arteritis (GCA) and ipsilateral ophthalmic-distribution zoster, followed within 2 weeks by VZV encephalitis and 2 months later by ischemic optic neuropathy. Temporal artery biopsy was histopathologically negative for GCA, but contained VZV antigen and VZV DNA in multiple non-contiguous (skip) areas. The collective clinical and laboratory findings revealed a remarkably close temporal association of zoster, multifocal VZV vasculopathy with temporal artery infection, biopsy-negative VZV-positive GCA and VZV encephalitis. PMID:24923742

  15. 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 ...

  16. Giant Axonal Neuropathy

    MedlinePlus

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

  17. Additional Types of Neuropathy

    MedlinePlus

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

  18. Optic Neuritis, its Differential Diagnosis and Management

    PubMed Central

    Hoorbakht, Hedieh; Bagherkashi, Farid

    2012-01-01

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

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

    PubMed Central

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

    2014-01-01

    Purpose The clinical impact of mDNA mutations on the development of Leber hereditary optic neuropathy (LHON) may be modulated by mitochondrial haplogroups, which vary across populations. The aim of this research was to determine the clinical spectrum and molecular characteristics, including the haplogroup, of 15 South American families with LHON. Methods This study was a prospective, observational study conducted between March 2006 and August 2012. All patients were referred to the Clinical Hospital of the University of Chile, where the clinical study was conducted. Molecular studies were conducted at the Biomedical Sciences Institute (ICBM) of the University of Chile. Fifteen index cases were identified with molecular analysis after initial neuroophthalmic examination at different centers throughout Chile. Clinical features of patients with LHON and maternal relatives of the 15 families (75 individuals: 26 affected and 49 healthy carriers) were evaluated. The primary mDNA mutations (m.3460G>A, m.11778G>A, or m.14484T>C) were determined with restriction fragment length polymorphism analysis in all individuals. Mitochondrial haplogroups were determined with direct sequencing of two hypervariable regions (HV1 and HV2) and compared with reference sequences. Results The m.11778G>A mutation was found in 59 subjects (78.7%), the m.14484T>C mutation was found in 12 subjects (16.0%), and the m.3460G>A mutation was found in four (5.3%) subjects. The average age of onset of symptoms in affected subjects was 22.2 years old (range 3 to 53 years); 21 (80.7%) were male, and five (19.3%) were female. Twelve families (80%) had Amerindian haplogroups: One family had the A2 haplogroup, four families had the B2i2 haplogroup, six families had the C1b haplogroup, and one family had the D1g haplogroup. Conclusions In this limited sample size, the Amerindian haplogroup A2 was associated with delayed onset of disease in this population. Patients with haplogroup C retained better vision than the patients with other haplogroups in this population. Disease in subjects with haplogroup D appeared to be underrepresented compared to the population at large. PMID:24672219

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

    SciTech Connect

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

    2009-12-01

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

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

    SciTech Connect

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

    1995-10-01

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

  2. 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

  3. Peripheral neuropathy associated with mitochondrial disease in children.

    PubMed

    Menezes, Manoj P; Ouvrier, Robert A

    2012-05-01

    Mitochondrial diseases in children are often associated with a peripheral neuropathy but the presence of the neuropathy is under-recognized because of the overwhelming involvement of the central nervous system (CNS). These mitochondrial neuropathies are heterogeneous in their clinical, neurophysiological, and histopathological characteristics. In this article, we provide a comprehensive review of childhood mitochondrial neuropathy. Early recognition of neuropathy may help with the identification of the mitochondrial syndrome. While it is not definite that the characteristics of the neuropathy would help in directing genetic testing without the requirement for invasive skin, muscle or liver biopsies, there appears to be some evidence for this hypothesis in Leigh syndrome, in which nuclear SURF1 mutations cause a demyelinating neuropathy and mitochondrial DNA MTATP6 mutations cause an axonal neuropathy. POLG1 mutations, especially when associated with late-onset phenotypes, appear to cause a predominantly sensory neuropathy with prominent ataxia. The identification of the peripheral neuropathy also helps to target genetic testing in the mitochondrial optic neuropathies. Although often subclinical, the peripheral neuropathy may occasionally be symptomatic and cause significant disability. Where it is symptomatic, recognition of the neuropathy will help the early institution of rehabilitative therapy. We therefore suggest that nerve conduction studies should be a part of the early evaluation of children with suspected mitochondrial disease. PMID:22435634

  4. Obturator neuropathy.

    PubMed

    Tipton, John Sison

    2008-12-01

    Obturator neuropathy is a difficult clinical problem to evaluate. One possible cause of pain is due to fascial entrapment of the nerve. Symptoms include medial thigh or groin pain, weakness with leg adduction, and sensory loss in the medial thigh of the affected side. Radiographic imaging provides limited diagnostic help. MRI may detect atrophy in the adductors of the leg. However, it is unable to detect any abnormality of the nerve or in the fibro-osseus tunnel. The best test for diagnosis is by electromyography (EMG) and can be confirmed by a local nerve block. Pharmacologic management of pain and physical therapy can be helpful in the acute phase of injury. Surgical decompression of the nerve should be considered for lesions documented by EMG or local nerve block, for those with predisposing risk factors (prior surgery, pelvic trauma, or hematoma) and with prolonged or severe lesions. PMID:19468309

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

    PubMed Central

    Feldon, Steven E

    2004-01-01

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

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

    PubMed

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

    2015-10-01

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

  7. 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. ...

  8. N-hexane neuropathy in offset printers.

    PubMed Central

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

    1993-01-01

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

  9. N-hexane neuropathy in offset printers.

    PubMed

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

    1993-05-01

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

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

    SciTech Connect

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

    1992-10-01

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

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

    SciTech Connect

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

    1996-07-01

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

  12. Partial mitochondrial complex I inhibition induces oxidative damage and perturbs glutamate transport in primary retinal cultures. Relevance to Leber Hereditary Optic Neuropathy (LHON).

    PubMed

    Beretta, Simone; Wood, John P M; Derham, Barry; Sala, Gessica; Tremolizzo, Lucio; Ferrarese, Carlo; Osborne, Neville N

    2006-11-01

    Leber Hereditary Optic Neuropathy (LHON) is a maternally inherited form of visual loss, due to selective degeneration of retinal ganglion cells. Despite the established aetiological association between LHON and mitochondrial DNA mutations affecting complex I of the electron transport chain, the pathophysiology of this disorder remains obscure. Primary rat retinal cultures were exposed to increasing concentrations of rotenone to titrate complex I inhibition. Neural cells were more sensitive than Müller glial cells to rotenone toxicity. Rotenone induced an increase in mitochondrial-derived free radicals and lipid peroxidation. Sodium-dependent glutamate uptake, which is mostly mediated by the glutamate transporter GLAST expressed by Müller glial cells, was reduced dose-dependently by rotenone with no changes in GLAST expression. Our findings suggest that complex I-derived free radicals and disruption of glutamate transport might represent key elements for explaining the selective retinal ganglion cell death in LHON. PMID:16959493

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

    PubMed

    Yang, Haixin; Liu, Rui; Wang, Chuan-Chao

    2016-09-01

    The co-occurrence of pathogenic or candidate mutations for Leber's hereditary optic neuropathy (LHON) and hearing loss has long been suggested to be a rare incident. The "rare" is probably caused by inadequate database searches. In this study, we created and released a comprehensive database with detailed information of haplogroup, variants, coding sites, and potential pathogenic mutations for more than 26,000 whole mitochondrial genomes. We found the co-occurrence in more than 200 individuals including not only LHON or hearing loss patients but also individuals sampled from general populations with various haplogroup backgrounds. The results highlighted the significant importance of adequate database searching in the genetic analysis of mitochondrial disorders. PMID:25714144

  14. Neuropathy secondary to drugs

    MedlinePlus

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

  15. Giant axonal neuropathy: visual and oculomotor deficits.

    PubMed

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

    1980-08-01

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

  16. Peripheral Neuropathy and Agent Orange

    MedlinePlus

    ... ZIP code here Enter ZIP code here Peripheral Neuropathy and Agent Orange VA presumes Veterans' early-onset ... percent disabling by VA's rating regulations. About peripheral neuropathy Peripheral neuropathy is a condition of the peripheral ...

  17. Peripheral Neuropathy: Symptoms and Signs

    MedlinePlus

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

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

    PubMed

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

    2015-08-01

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

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

    SciTech Connect

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

    1996-02-02

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

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

    SciTech Connect

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

    1991-09-15

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

  1. Inherited Peripheral Neuropathies

    PubMed Central

    Saporta, Mario A.; Shy, Michael E.

    2013-01-01

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

  2. 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

  3. Cardiac Involvement in Peripheral Neuropathies.

    PubMed

    Burakgazi, Ahmet Z; AlMahameed, Soufian

    2016-03-01

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

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

    PubMed Central

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

    2014-01-01

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

  5. 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

  6. Treatment of peripheral neuropathies.

    PubMed Central

    Hallett, M; Tandon, D; Berardelli, A

    1985-01-01

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

  7. [Metabolic and nutritional neuropathies].

    PubMed

    Lagueny, A

    2000-04-01

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

  8. Immunotherapy in Peripheral Neuropathies.

    PubMed

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

    2016-01-01

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

  9. [Chemotherapy induced peripheral neuropathy].

    PubMed

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

    2013-11-01

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

  10. HIV peripheral neuropathy.

    PubMed

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

    2013-01-01

    Peripheral neuropathies are the most common neurological manifestations occurring in HIV-infected individuals. Distal symmetrical sensory neuropathy is the most common form encountered today and is one of the few that are specific to HIV infection or its treatment. The wide variety of other neuropathies is akin to the neuropathies seen in the general population and should be managed accordingly. In the pre-ART era, neuropathies were categorized according to the CD4 count and HIV viral load. In the early stages of HIV infection when CD4 count is high, the inflammatory demyelinating neuropathies predominate and in the late stages with the decline of CD4 count opportunistic infection-related neuropathies prevail. That scenario has changed with the present almost universal use of ART (antiretroviral therapy). Hence, HIV-associated peripheral neuropathies are better classified according to their clinical presentations: distal symmetrical polyneuropathy, acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), mononeuropathies, mononeuropathies multiplex and cranial neuropathies, autonomic neuropathy, lumbosacral polyradiculomyelopathy, and amyotrophic lateral sclerosis (ALS)-like motor neuropathy. Treated with ART, HIV-infected individuals are living longer and are at a higher risk of metabolic and age-related complications; moreover they are also prone to the potentially neurotoxic effects of ART. There are no epidemiological data regarding the incidence and prevalence of the peripheral neuropathies. In the pre-ART era, most data were from case reports, series of patients, and pooled autopsy data. At that time the histopathological evidence of neuropathies in autopsy series was almost 100%. In large prospective cohorts presently being evaluated, it has been found that 57% of HIV-infected individuals have distal symmetrical sensory neuropathy and 38% have neuropathic pain. It is now clear that distal symmetrical sensory neuropathy is caused predominantly by the ART's neurotoxic effect but may also be caused by the HIV itself. With a sizeable morbidity, the neuropathic pain caused by distal symmetrical sensory neuropathy is very difficult to manage; it is often necessary to change the ART regimen before deciding upon the putative role of HIV infection itself. If the change does not improve the pain, there are few options available; the most common drugs used for neuropathic pain are usually not effective. One is left with cannabis, which cannot be recommended as routine therapy, recombinant human nerve growth factor, which is unavailable, and topical capsaicin with its side-effects. Much has been done to and learned from HIV infection in humans; HIV-infected individuals, treated with ART, are now dying mostly from cardiovascular disease and non-AIDS-related cancers. It hence behooves us to find new approaches to mitigate the residual neurological morbidity that still impacts the quality of life of that population. PMID:23931799

  11. Temperature sensitive auditory neuropathy.

    PubMed

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

    2016-05-01

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

  12. Permanent Peripheral Neuropathy

    PubMed Central

    Higgins, Elizabeth

    2014-01-01

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

  13. Multifocal motor neuropathy.

    PubMed

    Nowacek, Dustin G; Teener, James W

    2012-11-01

    Multifocal motor neuropathy is an acquired disorder in which demyelination of motor axons, presumably due to autoimmune attack, results in progressive painless weakness without sensory loss. Motor axonal damage also occurs. It is a frequent mimic of motor neuron disease. Recognition of multifocal motor neuropathy is critical because it tends to be very responsive to treatment. Infusion of intravenous immunoglobulin is the initial treatment of choice, but other immunosuppressive treatments may also be effective. It appears that corticosteroids produce minimal benefit. PMID:23677657

  14. 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

  15. [Ultrasonographic diagnosis of inflammatory neuropathies].

    PubMed

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

    2014-03-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-11-01

    The present study was designed to explore the antioxidative status and circulating biochemical markers having a potential role in the pathogenesis of ethambutol (EMB) induced toxic optic neuropathy (TON) among diabetic and non-diabetic patients. Fifty patients under complete therapy of EMB for tuberculosis were included in the present study. Inclusion criteria for patients were to receive EMB everyday during treatment, a dose of 25 mg/kg for initial 2 months and 15 mg/kg during the rest of therapy period. We conducted color vision and visual acuity test for all patients. Fifteen out of fifty EMB induced TON patients, were found to be diabetic. Color vision and visual acuity test results were evaluated for diabetic and non-diabetic as well as twenty age matched controls. The results demonstrated a significant pattern of circulating biochemical markers between the studied groups. Data regarding hematological (RBC, p value = 0.02; Hemoglobin, p value = 0.02), hepatic (total bilirubin, p value = 0.01), renal (urea, p value = 0.03; creatinine, p value = 0.007), lipid (total cholesterol, p value = 0.01; total triglycerides, p value = 0.03) and antioxidative (superoxide dismutase, p value = 0.005; glutathione, p value = 0.02; catalase, p value = 0.02) profile showed a highly significant difference among the studied groups specially patients with diabetes. Malondialdehyde (MDA) level had gone significantly up in diabetic TON patients (p value = 0.02), in comparison to other antioxidants and vitamins (Vit). Vit-A, E, B1, B12 and Zinc seem to be playing a major role in the pathogenesis of TON, specially Vit-E and B1 surpassed all the antioxidants as having highly significant inverse relationships with MDA (MDA vs Vit-E, r = -0.676(**) and MDA vs Vit-B1, r = -0.724(**) respectively). We conclude that during the ethambutol therapy the decreased levels of Vit-E and Vit-B1 possibly play a role in the development of TON and may be used as therapeutic agents to lessen the deleterious effects of ethambutol. PMID:26587002

  18. Peripheral neuropathies during biologic therapies.

    PubMed

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

    2016-03-01

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

  19. [Pathology of Vasculitic Neuropathies].

    PubMed

    Oka, Nobuyuki

    2016-03-01

    Prompt diagnosis of vasculitis is necessary because neuropathy may be the first symptom of vasculitic syndrome, and it is crucial for the management of patients. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, rheumatoid vasculitis, cryoglobulinemia, Sjogren's syndrome, and non-systemic vasculitic neuropathy are disorders frequently associated with vasculitic neuropathy. Pathological features such as the size of the involved vessels and the type of inflammatory cells, combined with general symptoms and laboratory data, may contribute to the specific diagnosis. ANCA may be involved in the pathogenesis of microscopic polyangiitis, and eosinophilic toxins may injure the nerve fibers in some patients with eosinophilic granulomatosis with polyangiitis. We detected B-cell follicle-like structures adjacent to the inflamed vessels in rheumatoid vasculitis, which may be associated with the pathogenesis. PMID:27001771

  20. Ultrasound of Focal Neuropathies.

    PubMed

    Hobson-Webb, Lisa D; Padua, Luca

    2016-04-01

    Focal neuropathies represent the most common indication for referral to electrodiagnostic laboratories. The etiologies range from chronic compression, as might be seen in carpal tunnel syndrome, to acute traumatic nerve injuries that require rapid intervention. The gold standard for diagnosis, electrodiagnostic testing, cannot provide the complementary anatomical information necessary to guide accurate diagnosis and treatment. An expanding body of literature supports the use of neuromuscular ultrasound as a standard component for evaluating focal neuropathies. In the current review, the role of ultrasound in both common and unusual compression neuropathies is reviewed, along with the use of ultrasound in traumatic nerve injury. The evidence demonstrates that nerve ultrasound has an essential, complementary role with electrodiagnostic testing. PMID:27035249

  1. Inherited peripheral neuropathy.

    PubMed

    Keller, M P; Chance, P F

    1999-01-01

    Hereditary disorders of the peripheral nerves constitute a group of frequently encountered neurological diseases. Charcot-Marie-Tooth neuropathy type 1 (CMT1) is genetically heterogeneous and characterized by demyelination with moderately to severely reduced nerve conduction velocities, absent muscle stretch reflexes and onion bulb formation. Genetic loci for CMT1 map to chromosome 17 (CMT1A), chromosome 1 (CMT1B), and another unknown autosome (CMT1C). CMT1A is most often associated with a tandem 1.5-megabase (Mb) duplication in chromosome 17p11.2-12, or in rare patients may result from a point mutation in the peripheral myelin protein-22 (PMP22) gene. CMT1 B result from point mutations in the myelin protein zero (Po or MPZ) gene. The molecular defect in CMT1 C is unknown. Mutations in the early growth response 2 gene (EGR2) are also associated with demyelinating neuropathy. Other rare forms of demyelinating peripheral neuropathies map to chromosome 8q, 10q, and 11q. X-linked Charcot-Marie-Tooth neuropathy (CMTX), which has clinical features similar to CMT1, is associated with mutations in the connexin32 gene. Charcot-Marie-Tooth neuropathy type 2 (CMT2) is characterized by normal or mildly reduced nerve conduction velocity with decreased amplitude and axonal loss without hypertrophic features. One form of CMT2 maps to chromosome 1 p36 (CMT2A), another to chromosome 3p (CMT2B) and another to 7p (CMT2D). Dejerine-Sottas disease (DSD), also called hereditary motor and sensory neuropathy type III (HMSNIII), is a severe, infantile-onset demyelinating polyneuropathy that may be associated with point mutations in either the PMP22 gene or the Po gene and shares considerable clinical and pathological features with CMT1. Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder that results in a recurrent, episodic demyelinating neuropathy. HNPP is associated with a 1.5-Mb deletion in chromosome 17p11.2-12 and results from reduced expression of the PMP22 gene. CMT1A and HNPP are reciprocal duplication/deletion syndromes originating from unequal crossover during germ cell meiosis. PMID:10716658

  2. Cardiac autonomic diabetic neuropathy.

    PubMed

    Schönauer, Martin; Thomas, Andreas; Morbach, Stephan; Niebauer, Josef; Schönauer, Ulrike; Thiele, Holger

    2008-11-01

    Cardiovascular autonomic diabetic neuropathy (CADN) is one of the most common diabetes-associated complications. Disturbed heart rate variability (HRV) is very often the earliest symptom, even in clinically asymptomatic patients. The following article offers a topical overview for those working or interested in the fields of diabetology and cardiology. PMID:18958844

  3. 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

  4. Autoimmune peripheral neuropathies.

    PubMed

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

    2015-09-20

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

  5. Diabetic Neuropathies: The Nerve Damage of Diabetes

    MedlinePlus

    ... PDF, 293 KB). Alternate Language URL Español Diabetic Neuropathies: The Nerve Damage of Diabetes Page Content On ... Points to Remember Clinical Trials What are diabetic neuropathies? Diabetic neuropathies are a family of nerve disorders ...

  6. Genetics Home Reference: giant axonal neuropathy

    MedlinePlus

    ... Home Health Conditions giant axonal neuropathy giant axonal neuropathy Enable Javascript to view the expand/collapse boxes. ... All Open All Close All Description Giant axonal neuropathy is an inherited condition involving dysfunction of a ...

  7. Genetics Home Reference: small fiber neuropathy

    MedlinePlus

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

  8. Management of painful neuropathies.

    PubMed

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

    2013-01-01

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

  9. Mimics and chameleons of optic neuritis.

    PubMed

    Weerasinghe, Dinushi; Lueck, Christian

    2016-04-01

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

  10. Peripheral neuropathy and solitary plasmacytoma.

    PubMed Central

    Read, D; Warlow, C

    1978-01-01

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

  11. 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

  12. 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.

  13. Cardiovascular autonomic neuropathy

    PubMed Central

    McCarty, Niamh

    2016-01-01

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

  14. [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

  15. Diabetic corneal neuropathy.

    PubMed Central

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

    1983-01-01

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

  16. Metabolic neuropathies and myopathies.

    PubMed

    D'Amico, Adele; Bertini, Enrico

    2013-01-01

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

  17. Pediatric sciatic neuropathies

    PubMed Central

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

    2011-01-01

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

  18. Diagnostic approach to peripheral neuropathy

    PubMed Central

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

    2008-01-01

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

  19. Auditory Neuropathy/Dyssynchrony in Biotinidase Deficiency.

    PubMed

    Talebi, Hossein; Yaghini, Omid

    2016-04-01

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

  20. Auditory Neuropathy/Dyssynchrony in Biotinidase Deficiency

    PubMed Central

    Yaghini, Omid

    2016-01-01

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

  1. [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

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

    SciTech Connect

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

    2007-06-15

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

  3. Diabetic autonomic neuropathy.

    PubMed

    Vinik, Aaron I; Maser, Raelene E; Mitchell, Braxton D; Freeman, Roy

    2003-05-01

    Diabetic autonomic neuropathy (DAN) is a serious and common complication of diabetes. Despite its relationship to an increased risk of cardiovascular mortality and its association with multiple symptoms and impairments, the significance of DAN has not been fully appreciated. The reported prevalence of DAN varies widely depending on the cohort studied and the methods of assessment. In randomly selected cohorts of asymptomatic individuals with diabetes, approximately 20% had abnormal cardiovascular autonomic function. DAN frequently coexists with other peripheral neuropathies and other diabetic complications, but DAN may be isolated, frequently preceding the detection of other complications. Major clinical manifestations of DAN include resting tachycardia, exercise intolerance, orthostatic hypotension, constipation, gastroparesis, erectile dysfunction, sudomotor dysfunction, impaired neurovascular function, "brittle diabetes," and hypoglycemic autonomic failure. DAN may affect many organ systems throughout the body (e.g., gastrointestinal [GI], genitourinary, and cardiovascular). GI disturbances (e.g., esophageal enteropathy, gastroparesis, constipation, diarrhea, and fecal incontinence) are common, and any section of the GI tract may be affected. Gastroparesis should be suspected in individuals with erratic glucose control. Upper-GI symptoms should lead to consideration of all possible causes, including autonomic dysfunction. Whereas a radiographic gastric emptying study can definitively establish the diagnosis of gastroparesis, a reasonable approach is to exclude autonomic dysfunction and other known causes of these upper-GI symptoms. Constipation is the most common lower-GI symptom but can alternate with episodes of diarrhea. Diagnostic approaches should rule out autonomic dysfunction and the well-known causes such as neoplasia. Occasionally, anorectal manometry and other specialized tests typically performed by the gastroenterologist may be helpful. DAN is also associated with genitourinary tract disturbances including bladder and/or sexual dysfunction. Evaluation of bladder dysfunction should be performed for individuals with diabetes who have recurrent urinary tract infections, pyelonephritis, incontinence, or a palpable bladder. Specialized assessment of bladder dysfunction will typically be performed by a urologist. In men, DAN may cause loss of penile erection and/or retrograde ejaculation. A complete workup for erectile dysfunction in men should include history (medical and sexual); psychological evaluation; hormone levels; measurement of nocturnal penile tumescence; tests to assess penile, pelvic, and spinal nerve function; cardiovascular autonomic function tests; and measurement of penile and brachial blood pressure. Neurovascular dysfunction resulting from DAN contributes to a wide spectrum of clinical disorders including erectile dysfunction, loss of skin integrity, and abnormal vascular reflexes. Disruption of microvascular skin blood flow and sudomotor function may be among the earliest manifestations of DAN and lead to dry skin, loss of sweating, and the development of fissures and cracks that allow microorganisms to enter. These changes ultimately contribute to the development of ulcers, gangrene, and limb loss. Various aspects of neurovascular function can be evaluated with specialized tests, but generally these have not been well standardized and have limited clinical utility. Cardiovascular autonomic neuropathy (CAN) is the most studied and clinically important form of DAN. Meta-analyses of published data demonstrate that reduced cardiovascular autonomic function as measured by heart rate variability (HRV) is strongly (i.e., relative risk is doubled) associated with an increased risk of silent myocardial ischemia and mortality. The determination of the presence of CAN is usually based on a battery of autonomic function tests rather than just on one test. Proceedings from a consensus conference in 1992 recommended that three tests (R-R variation, Valsalva maneuver, and postural blood pressure testing)or longitudinal testing of the cardiovascular autonomic system. Other forms of autonomic neuropathy can be evaluated with specialized tests, but these are less standardized and less available than commonly used tests of cardiovascular autonomic function, which quantify loss of HRV. Interpretability of serial HRV testing requires accurate, precise, and reproducible procedures that use established physiological maneuvers. The battery of three recommended tests for assessing CAN is readily performed in the average clinic, hospital, or diagnostic center with the use of available technology. Measurement of HRV at the time of diagnosis of type 2 diabetes and within 5 years after diagnosis of type 1 diabetes (unless an individual has symptoms suggestive of autonomic dysfunction earlier) serves to establish a baseline, with which 1-year interval tests can be compared. Regular HRV testing provides early detection and thereby promotes timely diagnostic and therapeutic interventions. HRV testing may also facilitate differential diagnosis and the attribution of symptoms (e.g., erectile dysfunction, dyspepsia, and dizziness) to autonomic dysfunction. Finally, knowledge of early autonomic dysfunction can encourage patient and physician to improve metabolic control and to use therapies such as ACE inhibitors and beta-blockers, proven to be effective for patients with CAN. PMID:12716821

  4. Crucifixion and median neuropathy

    PubMed Central

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

    2013-01-01

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

  5. Molecular basis of hereditary neuropathies.

    PubMed

    Chance, P F

    2001-05-01

    Inherited disorders of peripheral nerves represent a common group of neurologic diseases. Charcot-Marie-Tooth neuropathy type 1 (CMT1) is a genetically heterogeneous group of chronic demyelinating polyneuropathies with loci mapping to chromosome 17 (CMT1A), chromosome 1 (CMT1B) and to another unknown autosome (CMT1C). CMT1A is most often associated with a tandem 1.5-megabase (Mb) duplication in chromosome 17p11.2-12, or in rare patients may result from a point mutation in the peripheral myelin protein-22 (PMP22) gene. CMT1B is associated with point mutations in the myelin protein zero (P0 or MPZ) gene. The molecular defect in CMT1C is unknown. X-linked Charcot-Marie-Tooth neuropathy (CMTX), which has clinical features similar to CMT1, is associated with mutations in the connexin32 gene. Charcot-Marie-Tooth neuropathy type 2 (CMT2) is an axonal neuropathy, also of undetermined cause. Forms of CMT2 map to chromosome 1p36 (CMT2A), chromosome 3p (CMT2B), chromosome 7p (CMT2D), and to chromosome 8p21 (CMT2E). Dejerine-Sottas disease (DSD), also called hereditary motor and sensory neuropathy type III (HMSNIII), is a severe, infantile-onset, demyelinating polyneuropathy syndrome that may be associated with point mutations in either the PMP22 gene or the P0 gene and shares considerable clinical and pathologic features with CMT1. Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder that results in a recurrent, episodic demyelinating neuropathy. HNPP is associated with a 1.5-Mb deletion in chromosome 17p11.2-12 and results from reduced expression of the PMP22 gene. CMT1A and HNPP are reciprocal duplication/deletion syndromes originating from unequal crossover during germ cell meiosis. Other rare forms of demyelinating peripheral neuropathies map to chromosomes 8q, 10q, and 11q. Hereditary neuralgic amyotrophy (familial brachial plexus neuropathy) is an autosomal dominant disorder causing painful, recurrent brachial plexopathies and maps to chromosome 17q25. PMID:11345007

  6. Evaluation and prevention of diabetic neuropathy.

    PubMed

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

    2005-06-01

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

  7. 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

  8. Generalized pruritus preceding paraneoplastic neuropathy.

    PubMed

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

    2016-04-01

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

  9. Paraproteinemic neuropathy: a practical review.

    PubMed

    Rison, Richard A; Beydoun, Said R

    2016-01-01

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

  10. Entrapment neuropathy in laparoscopic herniorrhaphy.

    PubMed

    Seid, A S; Amos, E

    1994-09-01

    In laparoscopic hernia repairs, the staples used to affix prosthetic mesh have resulted in entrapment neuropathies. This paper describes the diagnosis and treatment of nine cases of entrapment neuropathy. Injuries to all the branches of the lumbar plexus, with the exception of the obdurator nerve, have been treated. Generally, the entrapments are self-limiting, but chronic disability requiring surgical intervention can occur. Staple removal and neurolysis controlled the severe, chronic pain of one femoral nerve entrapment. A thorough understanding of the anatomy of these nerves can prevent stapling in the areas of danger and thus greatly reduce the incidence of this complication. PMID:7992173

  11. 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

  12. Neuroactive steroids and peripheral neuropathy.

    PubMed

    Roglio, Ilaria; Giatti, Silvia; Pesaresi, Marzia; Bianchi, Roberto; Cavaletti, Guido; Lauria, Giuseppe; Garcia-Segura, Luis-Miguel; Melcangi, Roberto Cosimo

    2008-03-01

    Peripheral neuropathy, either inherited or acquired, represents a very common disorder for which effective clinical treatments are not available yet. Observations here summarized indicate that neuroactive steroids, such as progesterone, testosterone and their reduced metabolites, might represent a promising therapeutic option. Peripheral nerves are able to synthesize and metabolize neuroactive steroids and are a target for these molecules, since they express classical and non-classical steroid receptors. Neuroactive steroids modulate the expression of key transcription factors for Schwann cell function, regulate Schwann cell proliferation and promote the expression of myelin proteins involved in the maintenance of myelin multilamellar structure, such as myelin protein zero and peripheral myelin protein 22. These actions may result in the protection and regeneration of peripheral nerves affected by different forms of pathological alterations. Indeed, neuroactive steroids are able to counteract biochemical, morphological and functional alterations of peripheral nerves in different experimental models of neuropathy, including the alterations caused by aging, diabetic neuropathy and physical injury. Therefore, neuroactive steroids, pharmacological agents able to increase their local synthesis and synthetic ligands for their receptors have a promising potential for the treatment of different forms of peripheral neuropathy. PMID:17543391

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

    PubMed

    Takashima, Hiroshi

    2014-01-01

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

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

    PubMed

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

    2016-02-01

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

  15. A modified peripheral neuropathy scale: the Overall Neuropathy Limitations Scale.

    PubMed

    Graham, R C; Hughes, R A C

    2006-08-01

    A new peripheral neuropathy activities measure, the Overall Neuropathy Limitations Scale (ONLS), was derived by modifying the Overall Disability Sum Score (ODSS) slightly. Its inter-rater reliability was found to be high and its correlation with the ODSS (r = 0.97), 36-item Short Form Questionnaire Physical Component Summary Score, and participation and impairment measures was significant. Acceptable responsiveness (standardised response mean 0.76) was shown by the ONLS. The results obtained from the questionnaire agreed closely with those obtained from observation of the tasks on the ONLS, but were not equivalent. The simplicity of the ODSS is shared by the ONLS, but the ONLS has better content validity and less ceiling effect, which may make it more useful for clinical practice and research. PMID:16574730

  16. Guanethidine adrenergic neuropathy: an animal model of selective autonomic neuropathy.

    PubMed

    Zochodne, D W; Ward, K K; Low, P A

    1988-09-27

    Chronic administration of guanethidine to adult rats induces a selective autoimmune adrenergic neuropathy. Physiological and biochemical features of this disorder in the peripheral nervous system were explored in young adult Sprague-Dawley rats given daily intraperitoneal guanethidine monosulfate for 5 weeks. Control rats received daily saline injections. The guanethidine-treated animals gained less weight, had ptosis, and had a lower mean arterial blood pressure in the supine and upright tilted positions. Norepinephrine was depleted in the peroneal, sural, tibial, and vagal nerves, the nutrient artery to the tibial nerve and in the superior cervical sympathetic ganglion of the drug-treated animals. On light microscopy, there was an inflammatory cell infiltrate and neuron loss in the superior cervical ganglion. Caudal and sciatic-tibial nerve conduction values were well preserved in the guanethidine-treated animals as was the 'C' potential derived from unmyelinated vagal fibers recorded in an in vitro chamber. The 'C' potential recorded from the cervical sympathetic trunk, however, was reduced in amplitude correlating with the loss of norepinephrine content in the harvested contralateral superior cervical sympathetic ganglion. The findings further support the view that guanethidine produces a selective adrenergic neuropathy in the rat--providing a useful standard with which to gauge autonomic involvement in other models of neuropathy. In addition, loss of the cervical sympathetic 'C' potential suggests that this presumed preganglionic structure also contains postganglionic adrenergic fibers. PMID:3224270

  17. [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

  18. [Non-systemic Vasculitic Neuropathy].

    PubMed

    Koike, Haruki

    2016-03-01

    Non-systemic vasculitic neuropathy (NSVN) is a vasculitis confined to the peripheral nervous system. It is one of the most common causes of vasculitic neuropathy, along with microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome). It remains unclear whether this disease is truly an isolated nosological entity, or part of the spectrum of systemic vasculitides. Anti-neutrophil cytoplasmic antibodies (ANCA) are negative in NSVN even though the size of affected vessels in this disease is similar to that in ANCA-associated vasculitis. Although the concept of single organ vasculitis was added to the 2012 revised International Chapel Hill Consensus Conference (CHCC) nomenclature of vasculitides, a description of NSVN has not yet been incorporated. Further studies are needed to elucidate the pathogenesis of NSVN, particularly a search for causative antibodies or participation of complement pathways. These studies may help clarify the position of NSVN along the spectrum of vasculitides based on CHCC nomenclature. PMID:27001772

  19. Treatment of gastrointestinal autonomic neuropathy.

    PubMed

    Törnblom, Hans

    2016-03-01

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

  20. 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

  1. Drug-induced peripheral neuropathies.

    PubMed Central

    Argov, Z; Mastaglia, F L

    1979-01-01

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

  2. Painful diabetic neuropathy: clinical aspects.

    PubMed

    Didangelos, Triantafyllos; Doupis, John; Veves, Aristidis

    2014-01-01

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

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

    MedlinePlus

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

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

    MedlinePlus

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

  5. Genetics Home Reference: autosomal recessive axonal neuropathy with neuromyotonia

    MedlinePlus

    ... recessive axonal neuropathy with neuromyotonia autosomal recessive axonal neuropathy with neuromyotonia Enable Javascript to view the expand/ ... Open All Close All Description Autosomal recessive axonal neuropathy with neuromyotonia is a disorder that affects the ...

  6. Clinical and electrodiagnostic features of sciatic neuropathies.

    PubMed

    Distad, B Jane; Weiss, Michael D

    2013-02-01

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

  7. Imaging of neuropathies about the hip.

    PubMed

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

    2013-01-01

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

  8. 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

  9. A case of insulinoma with peripheral neuropathy.

    PubMed Central

    Jayasinghe, K. S.; Nimalasuriya, A.; Dharmadasa, K.

    1983-01-01

    A 25-year-old woman with chronic neuropsychiatric symptoms, peripheral neuropathy and hypoglycaemia was found to have an islet cell adenoma in the pancreas. Her neuropsychiatric symptoms disappeared following its removal and she partially recovered from her peripheral neuropathy. PMID:6302651

  10. Diabetic Cranio-Cervico-Radiculoplexus Neuropathy.

    PubMed

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

    2015-11-01

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

  11. 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

  12. 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

  13. Internal carotid artery pseudo occlusion with embolic cerebral ischemia and low flow in the central retinal artery: a diagnostic challenge

    PubMed Central

    Röhrer, Christoph; Ertl, Michael; Altmann, Mathias; Kasprzak, Piotr; Bogdahn, Ulrich; Schuierer, Gerhard; Schlachetzki, Felix

    2011-01-01

    We present a rare case of internal carotid artery pseudoocclusion (ICAPO) in a 60-year-old male Caucasian patient who experienced a reversible sudden loss of vision of the right eye for 10 min followed by recurrent blurring of vision as well as dysarthria and numbness in the left face. The referring ophthalmologist admitted the patient for suspicious occlusion of the internal carotid artery causing anterior ischemic optic neuropathy (AION). PMID:24765323

  14. Posterior interosseous neuropathy: electrodiagnostic evaluation.

    PubMed

    Bevelaqua, Anna-Christina; Hayter, Catherine L; Feinberg, Joseph H; Rodeo, Scott A

    2012-07-01

    Electrodiagnostic studies are used to anatomically localize nerve injuries. These tests help differentiate between cervical radiculopathies, brachial plexopathies, and peripheral nerve injuries. They also help to identify or rule out other underlying neurological diseases and disorders. In this case report, a 22-year-old male swimmer presented with left finger extensor weakness following pull-up exercises. Left wrist extension remained intact. Electrodiagnostic testing revealed a severe but incomplete posterior interosseous neuropathy. Magnetic resonance imaging confirmed inflammation of the nerve in the forearm. Posterior interosseous neuropathy is an uncommon but well-studied condition. Typically, this condition presents with weakness in finger and thumb extension with preserved wrist extension as the extensor carpi radialis longus is innervated proximal to the site of nerve compression in most cases. It is important to understand the anatomic course and distribution of the radial nerve in order to make an accurate diagnosis. Once the anatomy is understood, electrodiagnostic testing may be used to identify the location of nerve injury and exclude other disorders. PMID:23874261

  15. Peroneal neuropathy after weight loss.

    PubMed

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

    2000-06-01

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

  16. Chronic dysimmune neuropathies: Beyond chronic demyelinating polyradiculoneuropathy

    PubMed Central

    Khadilkar, Satish V.; Deshmukh, Shrikant S.; Dhonde, Pramod D.

    2011-01-01

    The spectrum of chronic dysimmune neuropathies has widened well beyond chronic demyelinating polyradiculoneuropathy (CIDP). Pure motor (multifocal motor neuropathy), sensorimotor with asymmetrical involvement (multifocal acquired demylinating sensory and motor neuropathy), exclusively distal sensory (distal acquired demyelinating sensory neuropathy) and very proximal sensory (chronic immune sensory polyradiculopathy) constitute the variants of CIDP. Correct diagnosis of these entities is of importance in terms of initiation of appropriate therapy as well as prognostication of these patients. The rates of detection of immune-mediated neuropathies with monoclonal cell proliferation (monoclonal gammopathy of unknown significance, multiple myeloma, etc.) have been facilitated as better diagnostic tools such as serum immunofixation electrophoresis are being used more often. Immune neuropathies associated with malignancies and systemic vasculitic disorders are being defined further and treated early with better understanding of the disease processes. As this field of dysimmune neuropathies will evolve in the future, some of the curious aspects of the clinical presentations and response patterns to different immunosuppressants or immunomodulators will be further elucidated. This review also discusses representative case studies. PMID:21808468

  17. [Disulfiram neuropathy. Report of 3 cases].

    PubMed

    Bevilacqua, Jorge A; Díaz, Mario; Díaz, Violeta; Silva, Carlos; Fruns, Manuel

    2002-09-01

    Disulfiram is widely used for aversive treatment of alcoholism. Although it is well tolerated in most patients, one in 15,000 patients will develop peripheral neuropathy every year, which is frequently misdiagnosed as alcoholic neuropathy. Disulfiram neuropathy can be mild or severe, depending on diverse factors such as time of exposure and the dosage. Most patients will present with a motor-sensory neuropathy of the lower limbs, which tends to improve as disulfiram administration ceases, however some cases may remain with permanent sequelae. We report the clinical, laboratory and electrophysiological features of three patients who developed disulfiram neuropathy during treatment of alcoholism. Recovery was incomplete at 8 weeks after treatment cessation in all of them. No other findings justified the clinical features described in these patients. Considering the incidence of alcoholism and the wide use of disulfiram treatment in Chile, we suggest that disulfiram neuropathy is being underdiagnosed. We also stress the fact that disulfiram neuropathy could be avoided by using lower doses. PMID:12434653

  18. Obstructive Sleep Apnea and Diabetic Neuropathy

    PubMed Central

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

    2012-01-01

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

  19. Novel MPZ mutations and congenital hypomyelinating neuropathy

    PubMed Central

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

    2010-01-01

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

  20. Chronic demyelinating peripheral neuropathy in cerebrotendinous xanthomatosis.

    PubMed

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

    1986-07-01

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

  1. Updates in diabetic peripheral neuropathy

    PubMed Central

    Juster-Switlyk, Kelsey; Smith, A. Gordon

    2016-01-01

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

  2. Hereditary Neuropathy with Liability to Pressure Palsies.

    PubMed

    Choi, Hyoung Won; Kuntz, Nancy L

    2015-11-01

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

  3. INHERITED NEUROPATHIES: CLINICAL OVERVIEW AND UPDATE

    PubMed Central

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

    2014-01-01

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

  4. Surgical treatment of a tomaculous neuropathy.

    PubMed

    Taggart, T F; Allen, T R

    2001-08-01

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

  5. Vitamin B supplementation for diabetic peripheral neuropathy

    PubMed Central

    Jayabalan, Bhavani; Low, Lian Leng

    2016-01-01

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

  6. Evidence for sensory neuropathy and pharmacologic management.

    PubMed

    Greene, Scott M; Simpson, C Blake

    2010-02-01

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

  7. Pattern Recognition Approach to Neuropathy and Neuronopathy

    PubMed Central

    Barohn, Richard J; Amato, Anthony A.

    2014-01-01

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

  8. Multiple cranial neuropathies following etanercept administration.

    PubMed

    Hunter, Jacob B; Rivas, Alejandro

    2016-01-01

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

  9. Autonomic neuropathy in patients with hepatic cirrhosis

    PubMed Central

    Bajaj, B; Agarwal, M; Ram, B

    2003-01-01

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

  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. Treatment of painful diabetic neuropathy

    PubMed Central

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

    2015-01-01

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

  12. Treatment of painful diabetic neuropathy.

    PubMed

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

    2015-01-01

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

  13. Small fiber neuropathy: Getting bigger!

    PubMed

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

    2016-05-01

    Etiological and clinical heterogeneity of small fiber neuropathy (SFN) precludes a unifying approach and necessitates reliance on recognizable clinical syndromes. Symptoms of SFN arise from dysfunction in nociception, temperature, and autonomic modalities. This review focuses on SFN involving nociception and temperature, examining epidemiology, etiology, clinical presentation, diagnosis, pathophysiology, and management. Prevalence of SFN is 52.95 per 100,000 population, and diabetes and idiopathic are the most common etiologies. Dysesthesia, allodynia, pain, burning, and coldness sensations frequently present in a length-dependent pattern. Additional autonomic features in gastrointestinal, urinary, or cardiovascular systems are frequent but poorly objectified. SFN is diagnosed by intraepidermal nerve fiber density and quantitative sensory and autonomic tests in combination with normal nerve conduction. Pathophysiological understanding centers on sodium channel dysfunction, and genetic forms are beginning to be understood. Treatment is directed at the underlying etiology supported by symptomatic treatment using antidepressants and anticonvulsants. Little is known about long-term outcomes, and systematic cohort studies are needed. Muscle Nerve 53: 671-682, 2016. PMID:26872938

  14. Inherited neuropathies: from gene to disease.

    PubMed

    Keller, M P; Chance, P F

    1999-04-01

    Inherited disorders of peripheral nerves represent a common group of neurologic diseases. Charcot-Marie-Tooth neuropathy type 1 (CMT1) is a genetically heterogeneous group of chronic demyelinating polyneuropathies with loci mapping to chromosome 17 (CMT1A), chromosome 1 (CMT1B) and to another unknown autosome (CMT1C). CMT1A is most often associated with a tandem 1.5-megabase (Mb) duplication in chromosome 17p11.2-12, or in rare patients may result from a point mutation in the peripheral myelin protein-22 (PMP22) gene. CMT1B is associated with point mutations in the myelin protein zero (P0 or MPZ) gene. The molecular defect in CMT1C is unknown. X-linked Charcot-Marie-Tooth neuropathy (CMTX), which has clinical features similar to CMT1, is associated with mutations in the connexin32 gene. Charcot-Marie-Tooth neuropathy type 2 (CMT2) is an axonal neuropathy, also of undetermined cause. One form of CMT2 maps to chromosome 1p36 (CMT2A), another to chromosome 3p (CMT2B) and another to 7p (CMT2D). Dejerine-Sottas disease (DSD), also called hereditary motor and sensory neuropathy type III (HMSNIII), is a severe, infantile-onset demyelinating polyneuropathy syndrome that may be associated with point mutations in either the PMP22 gene or the P0 gene and shares considerable clinical and pathological features with CMT1. Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder that results in a recurrent, episodic demyelinating neuropathy. HNPP is associated with a 1.5-Mb deletion in chromosome 17p11.2-12 and results from reduced expression of the PMP22 gene. CMT1A and HNPP are reciprocal duplication/deletion syndromes originating from unequal crossover during germ cell meiosis. Other rare forms of demyelinating peripheral neuropathies map to chromosome 8q, 10q and 11q. Hereditary neuralgic amyotrophy (familial brachial plexus neuropathy) is an autosomal dominant disorder causing painful, recurrent brachial plexopathies and maps to chromosome 17q25. PMID:10219749

  15. Pathogenesis of immune-mediated neuropathies.

    PubMed

    Dalakas, Marinos C

    2015-04-01

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

  16. Genetics Home Reference: hereditary sensory and autonomic neuropathy type V

    MedlinePlus

    ... Home Health Conditions HSAN5 hereditary sensory and autonomic neuropathy type V Enable Javascript to view the expand/ ... All Close All Description Hereditary sensory and autonomic neuropathy type V ( HSAN5 ) is a condition that primarily ...

  17. 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...

  18. Genetics Home Reference: hereditary sensory and autonomic neuropathy type II

    MedlinePlus

    ... Home Health Conditions HSAN2 hereditary sensory and autonomic neuropathy type II Enable Javascript to view the expand/ ... All Close All Description Hereditary sensory and autonomic neuropathy type II ( HSAN2 ) is a condition that primarily ...

  19. Genetics Home Reference: congenital cataracts, facial dysmorphism, and neuropathy

    MedlinePlus

    ... Health Conditions CCFDN congenital cataracts, facial dysmorphism, and neuropathy Enable Javascript to view the expand/collapse boxes. ... Close All Description Congenital cataracts, facial dysmorphism, and neuropathy ( CCFDN ) is a rare disorder that affects several ...

  20. Rheumatoid neuropathy: a histological and electrophysiological study

    PubMed Central

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

    1970-01-01

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

  1. PDE5 inhibitors in diabetic peripheral neuropathy.

    PubMed

    Hackett, G

    2006-09-01

    Peripheral neuropathy is the most common complication of diabetes. This paper reviews the case histories of five patients with diabetic peripheral neuropathy or severe peripheral vascular disease who reported improvement in their symptoms when treated with regular or daily dosing with phosphodiesterase type 5 inhibitors (PDE5Is). These patients had been previously treated with PDE5Is for erectile dysfunction (ED) and not responded to on-demand therapy with a PDE5I at maximal recommended dose. This improvement is likely to be due to the known benefit of these drugs on endothelial dysfunction via an improvement of blood supply to the vasa nervorum. These cases suggest that further research is indicated to evaluate the potential use of PDE5Is in the treatment and prevention of diabetic peripheral neuropathy, particularly as these drugs are already licensed to treat ED, which occurs in around 50% of male diabetics. PMID:16939556

  2. From ophthalmoplegic migraine to cranial neuropathy.

    PubMed

    Förderreuther, Stefanie; Ruscheweyh, Ruth

    2015-06-01

    Ophthalmoplegic migraine (OM)/recurrent painful ophthalmoplegic neuropathy (RPON) is a rare disease consisting of recurrent unilateral headache accompanied or followed by ipsilateral ophthalmoplegia. Because MRI findings suggest neuropathy and the relationship to typical migraine remains unclear, the disease has been renamed from "ophthalmoplegic migraine" to "recurrent painful oculomotor neuropathy" in the third edition of the International Classification of Headache Disorders (ICHD). However, it remains a fact that most cases of OM/RPON described in the literature have a history of migraine and that the headache during OM/RPON often has migrainous features. A more detailed clinical description of the headache during OM/RPON and additional results from imaging and possibly histology will be needed to better understand the pathophysiology of the disease and its relationship to typical migraine. PMID:26021754

  3. Focal posterior interosseous neuropathy in the presence of hereditary motor and sensory neuropathy, type I.

    PubMed

    Carter, G T; Kilmer, D D; Szabo, R M; McDonald, C M

    1996-05-01

    A 30-year-old male with hereditary motor and sensory neuropathy, type I (HMSN I), presented with asymmetric weakness of finger extension and radial deviation with left wrist extension, previously felt to be a manifestation of the peripheral neuropathy. Nerve conduction studies confirmed HMSN I; however, needle EMG revealed marked, ongoing axonal loss in muscles innervated by the left posterior interosseous nerve (PIN) only. At surgery there was focal fusiform swelling in the PIN at exit from the supinator muscle, compatible with localized hypertrophic neuropathy, which has not been reported before in HMSN I. A concomitant focal mononeuropathy should be considered in cases of hereditary neuropathy with marked asymmetry of weakness. PMID:8618563

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

    PubMed

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

    2014-01-01

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

  5. DIABETIC NEUROPATHY PART 2: PROXIMAL AND ASSYMMETRIC PHENOTYPES

    PubMed Central

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

    2014-01-01

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

  6. 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

  7. 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

  8. 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…

  9. 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…

  10. Painful peripheral neuropathy and sodium channel mutations.

    PubMed

    Hoeijmakers, Janneke G J; Faber, Catharina G; Merkies, Ingemar S J; Waxman, Stephen G

    2015-06-01

    Peripheral neuropathy can lead to neuropathic pain in a subset of patients. Painful peripheral neuropathy is a debilitating disorder, reflected by a reduced quality of life. Therapeutic strategies are limited and often disappointing, as in most cases targeted treatment is not available. Elucidating pathogenetic factors for pain might provide a target for optimal treatment. Voltage-gated sodium channels NaV1.7-NaV1.9 are expressed in the small-diameter dorsal root ganglion neurons and their axons. By a targeted gene approach, missense gain-of-function mutations of NaV1.7-NaV1.9 have been demonstrated in painful peripheral neuropathy. Functional analyses have shown that these mutations produce a spectrum of pro-excitatory changes in channel biophysics, with the shared outcome at the cellular level of dorsal root ganglion hyperexcitability. Reduced neurite outgrowth may be another consequence of sodium channel mutations, and possible therapeutic strategies include blockade of sodium channels or block of reverse operation of the sodium-calcium exchanger. Increased understanding of the pathophysiology of painful peripheral neuropathy offers new targets that may provide a basis for more effective treatment. PMID:25556685

  11. Hereditary neuropathy with liability to pressure palsy.

    PubMed

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

    2006-01-01

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

  12. Conduction block in acute motor axonal neuropathy.

    PubMed

    Kokubun, Norito; Nishibayashi, Momoka; Uncini, Antonino; Odaka, Masaaki; Hirata, Koichi; Yuki, Nobuhiro

    2010-10-01

    Guillain-Barré syndrome is divided into two major subtypes, acute inflammatory demyelinating polyneuropathy and acute motor axonal neuropathy. The characteristic electrophysiological features of acute motor axonal neuropathy are reduced amplitude or absence of distal compound muscle action potentials indicating axonal degeneration. In contrast, autopsy study results show early nodal changes in acute motor axonal neuropathy that may produce motor nerve conduction block. Because the presence of conduction block in acute motor axonal neuropathy has yet to be fully recognized, we reviewed how often conduction block occurred and how frequently it either reversed or was followed by axonal degeneration. Based on Ho's criteria, acute motor axonal neuropathy was electrodiagnosed in 18 patients, and repeated motor nerve conduction studies were carried out on their median and ulnar nerves. Forearm segments of these nerves and the across-elbow segments of the ulnar nerve were examined to evaluate conduction block based on the consensus criteria of the American Association of Electrodiagnostic Medicine. Twelve (67%) of the 18 patients with acute motor axonal neuropathy had definite (n=7) or probable (n=5) conduction blocks. Definite conduction block was detected for one patient (6%) in the forearm segments of both nerves and probable conduction block was detected for five patients (28%). Definite conduction block was present across the elbow segment of the ulnar nerve in seven patients (39%) and probable conduction block in two patients (11%). Conduction block was reversible in seven of 12 patients and was followed by axonal degeneration in six. All conduction blocks had disappeared or begun to resolve within three weeks with no electrophysiological evidence of remyelination. One patient showed both reversible conduction block and conduction block followed by axonal degeneration. Clinical features and anti-ganglioside antibody profiles were similar in the patients with (n=12) and without (n=6) conduction block as well as in those with (n=7) and without (n=5) reversible conduction block, indicating that both conditions form a continuum; a pathophysiological spectrum ranging from reversible conduction failure to axonal degeneration, possibly mediated by antibody attack on gangliosides at the axolemma of the nodes of Ranvier, indicating that reversible conduction block and conduction block followed by axonal degeneration and axonal degeneration without conduction block constitute continuous electrophysiological conditions in acute motor axonal neuropathy. PMID:20855419

  13. Hereditary Motor and Sensory Neuropathy Type VI with Bilateral Middle Cerebellar Peduncle Involvement

    PubMed Central

    Oh, Jung-Hwan; Lee, Han Sang; Cha, Dong Min

    2014-01-01

    Charcot-Marie-Tooth disease (CMT) 2A with optic atrophy is referred to as hereditary motor and sensory neuropathy type VI (HMSN VI) and is caused by mitofusin 2 gene (MFN2) mutation. In patients with MFN2 related CMT, central nervous system is known to be also involved and cerebral white matter is mostly involved. We report a patient confirmed as HMSN VI who had isolated bilateral middle cerebellar peduncular lesions in brain MRI. PMID:25258575

  14. The Rehabilitation of Oncological Patients Presenting Neuropathies

    PubMed Central

    MICU, ELENA CLAUDIA; IRSAY, LASZLO

    2014-01-01

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

  15. 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.

  16. [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

  17. Krabbe's disease presenting as a peripheral neuropathy.

    PubMed

    Marks, H G; Scavina, M T; Kolodny, E H; Palmieri, M; Childs, J

    1997-08-01

    A 13-year-old female initially presented with scoliosis and pes cavus. Initial examination revealed distal lower extremity weakness and sensory loss, as well as greater auricular nerve hypertrophy. There was a Babinski sign on the right. Nerve conduction velocities were consistent with a demyelinating neuropathy. Four years after initial presentation she developed lower extremity spasticity and bilateral Babinski signs. Magnetic resonance imaging of the brain showed diffuse white matter disease. Laboratory evaluation revealed an abnormally low galactocerebroside beta-galactosidase level. Nerve biopsy demonstrated inclusions consisting of globoid clusters and evidence of demyelination. DNA analysis was used to identify mutations consistent with Krabbe's disease. Patients presenting with an atypical peripheral neuropathy should be evaluated for Krabbe's disease. PMID:9236794

  18. Neuropathic pain in hereditary peripheral neuropathy

    PubMed Central

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

    2013-01-01

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

  19. Animal models for inherited peripheral neuropathies.

    PubMed

    Martini, R

    1997-10-01

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

  20. Animal models for inherited peripheral neuropathies

    PubMed Central

    MARTINI, RUDOLF

    1997-01-01

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

  1. 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

  2. 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

  3. Proximal median neuropathy secondary to humeral neck fracture.

    PubMed

    Veilleux, M; Richardson, P

    2000-03-01

    Median neuropathies proximal to the wrist are uncommon and usually result from penetrating injuries, fracture dislocation of the distal humerus, or compression by fibrous bands. A 66-year-old man suffered a comminuted fracture of the proximal humerus after a fall. Electrodiagnostic studies revealed a severe proximal median neuropathy and a mild distal radial mononeuropathy. Proximal median neuropathy rarely occurs in humeral neck fracture, mostly because the median nerve is not in close contact with the humerus proximally. PMID:10679720

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

    PubMed

    Ganu, Sneha; Mehta, Yesha

    2013-05-13

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

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

    PubMed

    Watson, James C; Dyck, P James B

    2015-07-01

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

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

    PubMed

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

    2016-06-01

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

  7. Obesity and hyperlipidemia are risk factors for early diabetic neuropathy.

    PubMed

    Smith, A Gordon; Singleton, J Robinson

    2013-01-01

    The Utah Diabetic Neuropathy Study (UDNS) examined 218 type 2 diabetic subjects without neuropathy symptoms, or with symptoms of<5 years, in order to evaluate risk factors for neuropathy development. Each subject completed symptom questionnaires, the Utah Early Neuropathy Scale (UENS), nerve conduction studies (NCS), quantitative sensory testing (QST) for vibration and cold detection, quantitative sudomotor axon reflex testing (QSART), and skin biopsy with measurement of intraepidermal nerve fiber density (IENFD). Those with abnormalities of≥3 were classified as having probable, and those with 1-2 as possible neuropathy. The relationship between glycemic control, lipid parameters (high density lipoprotein and triglyceride levels), blood pressure, and obesity, and neuropathy risk was examined. There was a significant relationship between the number of abnormalities among these features and neuropathy status (p<0.01). Hypertriglyceridemia, obesity and 3 or more abnormalities increased neuropathy risk (risk ratios 2.1 p<0.03, 2.9 p>0.02 and 3.0 p<0.004 respectively). Multivariate analysis found obesity and triglycerides were related to loss of small unmyelinated axons based on IENFD whereas elevated hemoglobin A1c was related to large myelinated fiber loss (motor conduction velocity). These findings indicate obesity and hypertriglyceridemia significantly increase risk for peripheral neuropathy, independent of glucose control. Obesity/hypertriglyceridemia and hyperglycemia may have differential effects on small versus large fibers. PMID:23731827

  8. Validity of the neurological examination in diagnosing diabetic peripheral neuropathy.

    PubMed

    Höliner, Isabella; Haslinger, Vera; Lütschg, Jürg; Müller, Guido; Barbarini, Daniela Seick; Fussenegger, Jörg; Zanier, Ulrike; Saely, Christoph H; Drexel, Heinz; Simma, Burkhard

    2013-09-01

    The aim of this study was to evaluate the prevalence of diabetic peripheral neuropathy in children and adolescents with type 1 diabetes mellitus and examine whether the neurological examination validly diagnoses diabetic peripheral neuropathy as compared with the gold standard of nerve conduction velocity in these patients. Nerve conduction velocity was measured in an unselected consecutive series of patients aged 8-18 years who had been suffering from type 1 diabetes mellitus for at least 1 year. For the neurological examination, neuropathy disability scores and neuropathy sign scores were used. Of the 39 patients, six (15%) had clinically evident diabetic peripheral neuropathy, whereas nerve conduction velocity testing revealed diabetic peripheral neuropathy in 15 (38%) patients. Sensitivity and specificity of the neurological examination for the diagnosis of diabetic peripheral neuropathy were 40% and 100%, respectively. The corresponding positive and negative predictive values were 100% and 72.7%, respectively. This conclusions from this study are that in children and adolescents with type 1 diabetes mellitus, diabetic peripheral neuropathy is highly prevalent, but in the majority of patients it is subclinical. Sensitivity and negative predictive values of the neurological examination are low. Therefore, routine nerve conduction velocity measurement for the assessment of diabetic peripheral neuropathy appears to be warranted in these patients. PMID:23831248

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

    PubMed

    Delval, Arnaud; Stojkovic, Tanya; Vermersch, Patrick

    2006-02-01

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

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

    PubMed Central

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

    1999-01-01

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

  11. Compressive femoral neuropathy: a rare complication of anticoagulation.

    PubMed

    Ong, H S

    2007-03-01

    The most common coagulation disorder associated with warfarin use is bleeding, but compressive femoral neuropathy is an unusual presentation. A 63-year-old man with compressive femoral neuropathy from an iliacus haematoma is reported. The diagnosis was confirmed on magnetic resonance imaging and treated conservatively with good clinical response and radiological evidence of resolution. PMID:17342281

  12. 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

  13. 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

  14. Recommendations to enable drug development for inherited neuropathies: Charcot-Marie-Tooth and Giant Axonal Neuropathy.

    PubMed

    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

  15. 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

  16. 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 PMID:25811007

  17. 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

  18. [Diabetic Retinopathy and Neuropathy: New in 2015].

    PubMed

    Henzen, Christoph

    2015-06-01

    In 2014 interesting new results were published in the field of diabetic microangiopathy: (1) In tensive treatment of type 1 diabetes for a mean of 6,5 years confers a lifelong reduction of the risk of diabetic retinopathy; (2) although the rates of diabetes-related complication have declined since 1990, the burden of disease persists because the prevalence of diabetes tripled during the same time; (3) subjects with diabetic neuropathy have structural brain changes, i.e. gray matter loss, findings with possible implications for the prognosis; (4) over 80% of type 2 diabetics who consider their feet to be normal have serious foot pathology. PMID:26098239

  19. 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

  20. 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

  1. Peripheral Neuropathy Due to Vitamin Deficiency, Toxins, and Medications

    PubMed Central

    Staff, Nathan P.; Windebank, Anthony J.

    2014-01-01

    Purpose of Review: Peripheral neuropathies secondary to vitamin deficiencies, medications, or toxins are frequently considered but can be difficult to definitively diagnose. Accurate diagnosis is important since these conditions are often treatable and preventable. This article reviews the key features of different types of neuropathies caused by these etiologies and provides a comprehensive list of specific agents that must be kept in mind. Recent Findings: While most agents that cause peripheral neuropathy have been known for years, newly developed medications that cause peripheral neuropathy are discussed. Summary: Peripheral nerves are susceptible to damage by a wide array of toxins, medications, and vitamin deficiencies. It is important to consider these etiologies when approaching patients with a variety of neuropathic presentations; additionally, etiologic clues may be provided by other systemic symptoms. While length-dependent sensorimotor axonal peripheral neuropathy is the most common presentation, several examples present in a subacute severe fashion, mimicking Guillain-Barré syndrome. PMID:25299283

  2. Investigation of Depression in Greek Patients with Diabetic Peripheral Neuropathy

    PubMed Central

    Rekleiti, Maria; Sarafis, Pavlos; Saridi, Maria; Toska, Aikaterini; Mellos, Chrysovaladis; Souliotis, Kyriakos; Tsironi, Maria

    2013-01-01

    Background: Considerable studies directly connect the complications in diabetic patients, and especially peripheral neuropathy, with the emergence of depression. Neuropathetic pain may deteriorate the general health status of the diabetic patient and glycaemic regulation. Purpose: The purpose of this study was to investigate the appearance and degree of diabetic peripheral neuropathy and its correlation with depression, with other parameters of the disease and also duration. Methods: 57 diabetic patients participated with diagnosed diabetic peripheral neuropathy (male n=27, female n= 30, mean of age 72.7±6.35 years). The first part of Michigan Neuropathy Screening Instrument and the Zung Depression Rating Scale were used as tools for our study. Data was analysed with the SPSS 18.0 statistic program. Results: 57.9% of the patients were overweight, 35.1% were obese and only 7% were within normal weight range. The BMI findings between the two genders indicate that male participants are more often obese than females. Women surpassed men in the category of overweight patients (p<0.05). The score based on MNSI was high and between 3 to 12 (mean average of 8.19±2.60 with 8 as intermediate rate). Almost 60% of patients had severe neuropathy, only 2 were found with mild symptoms and the rest had moderate neuropathtic symptoms, based on the score summary from the questionnaire. Investigating in detail the relation of diabetic neuropathy and depression, it derives that a high degree of diabetic neuropathy is related with high score of depression [F(3.160)=9.821, p=0.001]. Moderate and severe neuropathy was found with almost the same levels of depression. Conclusions: The correlation between diabetic neuropathy and depression is confirmed, while a very high depression rate was found in patients with severe neuropathy. The issue needs further study by using common instruments to obtain comparative results from the scientific community. PMID:23985112

  3. Progesterone Treatment in Two Rat Models of Ocular Ischemia

    PubMed Central

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

    2015-01-01

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

  4. Functional balance in elderly with diabetic neuropathy.

    PubMed

    Ghanavati, Tabassom; Shaterzadeh Yazdi, Mohammad Jafar; Goharpey, Shahin; Arastoo, Ali-Asghar

    2012-04-01

    Distal Sensorimotor Polyneuropathy (DPN) is one of the most common long-term complications of diabetes mellitus. Patients with DPN are at a high risk for falling and its life-threatening consequences. The objective of present study was the evaluation of functional balance in patients with diabetic neuropathy and normal older adults. Thus, present case-control study was designed to test the ability of two fourteen DPN patients and healthy people to control functional balance using Berg Balance Scale (BBS). Furthermore, the correlation between DNE and BBS scores were calculated using the Spearman's correlation coefficient. Comparison of two groups showed a significant decline in the overall score of BBS in DPN patients versus to the healthy control group (P<0.001). The most challenging tasks for DNP patients were single leg stance, tandem standing and forward reaching (P<0.001), followed by standing unsupported with feet together, sit to stand, stand to sit, transfers, standing unsupported with closed eyes, and placing the alternative foot on step or stool while standing unsupported tasks (P<0.05). There was a significant (P<0.001) strong negative (r=-0.77) correlation between DNE and BBS scores. In conclusion, DPN results in a remarkable functional imbalance that may expose these patients to danger of falling during daily activities and becomes more severe as the severity of neuropathy aggravates. PMID:22129655

  5. Early diabetic neuropathy: Triggers and mechanisms

    PubMed Central

    Dobretsov, Maxim; Romanovsky, Dmitry; Stimers, Joseph R

    2007-01-01

    Peripheral neuropathy, and specifically distal peripheral neuropathy (DPN), is one of the most frequent and troublesome complications of diabetes mellitus. It is the major reason for morbidity and mortality among diabetic patients. It is also frequently associated with debilitating pain. Unfortunately, our knowledge of the natural history and pathogenesis of this disease remains limited. For a long time hyperglycemia was viewed as a major, if not the sole factor, responsible for all symptomatic presentations of DPN. Multiple clinical observations and animal studies supported this view. The control of blood glucose as an obligatory step of therapy to delay or reverse DPN is no longer an arguable issue. However, while supporting evidence for the glycemic hypothesis has accumulated, multiple controversies accumulated as well. It is obvious now that DPN cannot be fully understood without considering factors besides hyperglycemia. Some symptoms of DPN may develop with little, if any, correlation with the glycemic status of a patient. It is also clear that identification of these putative non-glycemic mechanisms of DPN is of utmost importance for our understanding of failures with existing treatments and for the development of new approaches for diagnosis and therapy of DPN. In this work we will review the strengths and weaknesses of the glycemic hypothesis, focusing on clinical and animal data and on the pathogenesis of early stages and triggers of DPN other than hyperglycemia. PMID:17226897

  6. [Antiganglioside antibodies in neuropathies and motor neuronopathies].

    PubMed

    Gallardo, E; Serrano, C; Prat, C; Illa, I

    1996-12-01

    The presence of antiganglioside antibodies is associated with several neurologic disorders. These antibodies recognize several epitopes, generally saccharides present in these glucolipids. The presence of antiGM antibodies has been described in certain clinical syndromes, the main one being multifocal motor neuropathy with and without conduction blocks. The frequency of antiGM1 class IgM antibody falls between 20 and 80% in this disease. Axon predominant Guillain-Barré syndrome is also associated with high titers of antiGM1 antibodies, although in this case class IgG is implicated. The most important association to date has been established between Miller-Fisher syndrome and the presence of antiGQ1b antibodies. Several authors have reported molecular similarities among these gangliosides and bacterial lipopolysaccharides, mainly Campylobacter iejuni. The principal aims in the study of antiganglioside antibodies are to establish their pathogenic role as well as the clinical usefulness of analyzing for them, and to discover new specificities that aid in the diagnosis and classification of neuropathies, whether they are predominantly motor disorders or chronic sensory ones. PMID:9044577

  7. Mitotoxicity in distal symmetrical sensory peripheral neuropathies

    PubMed Central

    Bennett, Gary J.; Doyle, Timothy; Salvemini, Daniela

    2016-01-01

    Chronic distal symmetrical sensory peripheral neuropathy is a common neurological complication of cancer chemotherapy, HIV treatment and diabetes. Although aetiology-specific differences in presentation are evident, the clinical signs and symptoms of these neuropathies are clearly similar. Data from animal models of neuropathic pain suggest that the similarities have a common cause: mitochondrial dysfunction in primary afferent sensory neurons. Mitochondrial dysfunction is caused by mitotoxic effects of cancer chemotherapeutic drugs of several chemical classes, HIV-associated viral proteins, and nucleoside reverse transcriptase inhibitor treatment, as well as the (possibly both direct and indirect) effects of excess glucose. The mitochondrial injury results in a chronic neuronal energy deficit, which gives rise to spontaneous nerve impulses and a compartmental neuronal degeneration that is first apparent in the terminal receptor arbor—that is, intraepidermal nerve fibres—of cutaneous afferent neurons. Preliminary data suggest that drugs that prevent mitochondrial injury or improve mitochondrial function could be useful in the treatment of these conditions. PMID:24840972

  8. 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.

  9. Microsurgical Decompression for Peroneal Nerve Entrapment Neuropathy

    PubMed Central

    MORIMOTO, Daijiro; ISU, Toyohiko; KIM, Kyongsong; SUGAWARA, Atsushi; YAMAZAKI, Kazuyoshi; CHIBA, Yasuhiro; IWAMOTO, Naotaka; ISOBE, Masanori; MORITA, Akio

    2015-01-01

    Peroneal nerve entrapment neuropathy (PNEN) is one cause of numbness and pain in the lateral lower thigh and instep, and of motor weakness of the extensors of the toes and ankle. We report a less invasive surgical procedure performed under local anesthesia to treat PNEN and our preliminary outcomes. We treated 22 patients (33 legs), 7 men and 15 women, whose average age was 66 years. The mean postoperative follow-up period was 40 months. All patients complained of pain or paresthesia of the lateral aspect of affected lower thigh and instep; all manifested a Tinel-like sign at the entrapment point. As all had undergone unsuccessful conservative treatment, we performed microsurgical decompression under local anesthesia. Of 19 patients who had undergone lumbar spinal surgery (LSS), 9 suffered residual symptoms attributable to PNEN. While complete symptom abatement was obtained in the other 10 they later developed PNEN-induced new symptoms. Motor weakness of the extensors of the toes and ankle [manual muscle testing (MMT) 4/5] was observed preoperatively in 8 patients; it was relieved by microsurgical decompression. Based on self-assessments, all 22 patients were satisfied with the results of surgery. PNEN should be considered as a possible differential diagnosis in patients with L5 neuropathy due to lumbar degenerative disease, and as a causative factor of residual symptoms after LSS. PNEN can be successfully addressed by less-invasive surgery performed under local anesthesia. PMID:26227056

  10. Inherited focal, episodic neuropathies: hereditary neuropathy with liability to pressure palsies and hereditary neuralgic amyotrophy.

    PubMed

    Chance, Phillip F

    2006-01-01

    Hereditary neuropathy with liability to pressure palsies (HNPP; also called tomaculous neuropathy) is an autosomal-dominant disorder that produces a painless episodic, recurrent, focal demyelinating neuropathy. HNPP generally develops during adolescence, and may cause attacks of numbness, muscular weakness, and atrophy. Peroneal palsies, carpal tunnel syndrome, and other entrapment neuropathies may be frequent manifestations of HNPP. Motor and sensory nerve conduction velocities may be reduced in clinically affected patients, as well as in asymptomatic gene carriers. The histopathological changes observed in peripheral nerves of HNPP patients include segmental demyelination and tomaculous or "sausage-like" formations. Mild overlap of clinical features with Charcot-Marie-Tooth (CMT) disease type 1 (CMT1) may lead patients with HNPP to be misdiagnosed as having CMT1. HNPP and CMT1 are both demyelinating neuropathies, however, their clinical, pathological, and electrophysiological features are quite distinct. HNPP is most frequently associated with a 1.4-Mb pair deletion on chromosome 17p12. A duplication of the identical region leads to CMT1A. Both HNPP and CMT1A result from a dosage effect of the PMP22 gene, which is contained within the deleted/duplicated region. This is reflected in reduced mRNA and protein levels in sural nerve biopsy samples from HNPP patients. Treatment for HNPP consists of preventative and symptom-easing measures. Hereditary neuralgic amyotrophy (HNA; also called familial brachial plexus neuropathy) is an autosomal-dominant disorder causing episodes of paralysis and muscle weakness initiated by severe pain. Individuals with HNA may suffer repeated episodes of intense pain, paralysis, and sensory disturbances in an affected limb. The onset of HNA is at birth or later in childhood with prognosis for recovery usually favorable; however, persons with HNA may have permanent residual neurological dysfunction following attack(s). Episodes are often triggered by infections, immunizations, the puerperium, and stress. Electrophysiological studies show normal or mildly prolonged motor nerve conduction velocities distal to the affected brachial plexus. Pathological studies have found axonal degeneration in nerves examined distal to the plexus abnormality. In some HNA pedigrees there are characteristic facial features, including hypotelorism. The prognosis for recovery of normal function of affected limbs in HNA is good, although recurrent episodes may cause residual deficits. HNA is genetically linked to chromosome 17q25, where mutations in the septin-9 (SEPT9) gene have been found. PMID:16775374

  11. Identifying Common Genetic Risk Factors of Diabetic Neuropathies

    PubMed Central

    Witzel, Ini-Isabée; Jelinek, Herbert F.; Khalaf, Kinda; Lee, Sungmun; Khandoker, Ahsan H.; Alsafar, Habiba

    2015-01-01

    Type 2 diabetes mellitus (T2DM) is a global public health problem of epidemic proportions, with 60–70% of affected individuals suffering from associated neurovascular complications that act on multiple organ systems. The most common and clinically significant neuropathies of T2DM include uremic neuropathy, peripheral neuropathy, and cardiac autonomic neuropathy. These conditions seriously impact an individual’s quality of life and significantly increase the risk of morbidity and mortality. Although advances in gene sequencing technologies have identified several genetic variants that may regulate the development and progression of T2DM, little is known about whether or not the variants are involved in disease progression and how these genetic variants are associated with diabetic neuropathy specifically. Significant missing heritability data and complex disease etiologies remain to be explained. This article is the first to provide a review of the genetic risk variants implicated in the diabetic neuropathies and to highlight potential commonalities. We thereby aim to contribute to the creation of a genetic-metabolic model that will help to elucidate the cause of diabetic neuropathies, evaluate a patient’s risk profile, and ultimately facilitate preventative and targeted treatment for the individual. PMID:26074879

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

    PubMed Central

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

    2010-01-01

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

  13. 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

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

    PubMed

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

    2010-12-01

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

  15. Peripheral neuropathy in leprosy and its consequences.

    PubMed

    Van Brakel, W H

    2000-12-01

    Leprosy causes a 'mononeuritis multiplex' of immunological origin that results in autonomic, sensory and motor neuropathy. When detected and treated early, primary impairments may be reversible. However, 11-51% of patients do not recover. In addition, 33-56% of newly registered patients already have clinically detectable impairments, often no longer amenable to drug treatment. Among new patients, 6-27% present with secondary impairments, such as wounds, contractures and shortening of digits. All patients with impairments should be taught methods to prevent further impairment and subsequent disability (POID). As the result of impairments, many people experience limitation of activities of daily living, which can be partially overcome with the help of assistive devices, training, and surgery. As a result of these limitations, because of visible impairments, or simply because of the diagnosis 'leprosy', many people are restricted in their participation in society. Many overcome activity limitations and participation restrictions without assistance, despite residual impairments. However, some require intervention, such as physical or occupational therapy, reconstructive surgery or temporary socioeconomic assistance. Information on these issues is not collected routinely, and the few tools that exist to measure the severity or extent of impairment have not been widely used, nor have they been used to generate cohort-based statistics. There are no agreed indicators for monitoring POID activities or rehabilitation interventions. Work in the general field of rehabilitation has resulted in the ICIDH-2, which provides a conceptual framework for rehabilitation and the entire area of 'consequences of health conditions'. Although experience to date is very limited, the conceptual framework appears appropriate to leprosy. Data on the prevalence and incidence of primary and secondary impairments have been reported from several countries, the link between impairments and activity limitations has been investigated, and a few studies of the magnitude of the need for rehabilitation have been reported. Research priorities include studies of methods to improve detection of autonomic, sensory and motor neuropathy; trials of alternative drugs or regimens for treating neuropathy; studies of the use of various POID-monitoring systems that may be derived from these; studies of the design and use of instruments to assess limitations of activities and restrictions on participation; assessments of needs for rehabilitation and the development of methods to do these; studies of the efficacy of various types of rehabilitation interventions for particular conditions; and studies of the cost-effectiveness of such interventions. PMID:11201872

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

    PubMed

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

    1999-01-01

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

  17. 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.

  18. Clinimetric properties of a walking scale in peripheral neuropathy.

    PubMed

    Graham, R C; Hughes, R A C

    2006-08-01

    Difficulty in walking is seen in many people with peripheral neuropathies, but walking ability is not comprehensively measured by commonly used outcome measures. The clinimetric properties of the 12-Item Multiple Sclerosis Walking Scale (MSWS-12, renamed the Walk-12) were investigated in 65 patients with peripheral neuropathies. Owing to its excellent internal consistency and reliability, and strong correlation with measures of physical and social function (r>0.8), the Walk-12 is recommended for measuring walking ability in peripheral neuropathies. PMID:16574732

  19. Autophagy: The missing link in diabetic neuropathy?

    PubMed

    Yerra, Veera Ganesh; Gundu, Chayanika; Bachewal, Pragna; Kumar, Ashutosh

    2016-01-01

    Autophagy is a dynamic process which plays an important role in cellular homeostasis through recycling of damaged proteins and organelles. Chronic hyperglycemia associated with diabetes is known to impair the cellular autophagic pathways to a varied extent in some of the diabetic complications. But the role of autophagy driven quality control of proteins and the cellular organelles has been understudied in diabetic complications including neuropathy (DN). The present article hypothesizes that enhancing autophagy in neuronal cells may help them to get rid of bioenergetic crisis, necrosis, apoptosis associated with DN. Some forms of autophagic turnover also help to maintain integral, healthy mitochondria, malfunctioning of which produces cellular reactive oxygen species and may prevent accumulation of damaged protein aggregates. Involvement of various energy derived metabolic, cellular death pathways and oxidative stress in the pathogenesis of DN and how autophagy may halts the progression of DN has been discussed with supporting literature. PMID:26554509

  20. Isoniazid induced motor-dominant neuropathy.

    PubMed

    Arsalan, Rabeeya; Sabzwari, Saniya

    2015-10-01

    Isoniazid though a very effective treatment for tuberculosis can cause severe motor-dominant neuropathy which can be reversible with pyridoxine supplementation. A 45-year-old female diagnosed with psoas abscess, culture positive for mycobacterium tuberculosis, was started on anti- tuberculous treatment with four drugs, including isoniazid at a dose of 5 mg/kg/day. Three months later she developed severe motor weakness of lower limbs with loss of ankle and knee reflexes. She was treated with vitamin B6 injections and isoniazid treatment was continued. Her motor weakness gradually improved in a few months, but mild sensory impairment persisted even after two years. There is need for vigilance regarding neurological effects of isoniazid in seemingly low-risk individuals in whom development of symptoms should raise the suspicion about slow acetylator status. Timely therapeutic intervention with high-dose vitamin B6 can reduce the long-term morbidity associated with this easily reversible condition. PMID:26440850

  1. Multiple cranial neuropathy (a teaching case).

    PubMed

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

    2013-10-01

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

  2. Vasculitic neuropathy following exposure to minocycline

    PubMed Central

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

    2015-01-01

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

  3. Postpartum septic sacroiliitis misdiagnosed as sciatic neuropathy.

    PubMed

    Liu, Xiao-Qing; Li, Fang-Cai; Wang, Jia-Wei; Wang, Shuang

    2010-03-01

    Early diagnosis of septic sacroiliitis is difficult because symptoms are nonspecific, especially during pregnancy and the postpartum period. We describe a female patient with left buttock pain radiating down the thigh after an uncomplicated induction delivery. She was afebrile and had no apparent abnormality on pelvic x-ray or computed tomography scan. A sensory deficit in the lateral portion of her left lower limb was found, and electromyography showed neurogenic abnormalities in the left lower limb. She was initially misdiagnosed as sciatic neuropathy. As her symptoms worsened, septic sacroiliitis is considered. Bone scintigraphy showed increased Tc-methylene diphosphonate uptake in the left sacroiliac joint, and magnetic resonance imaging scan showed a signal abnormality in the left sacroiliac joint. The diagnosis of septic sacroiliitis was then confirmed by the rapid efficacy of antibiotic therapy. This report suggests that irritation and injury of spinal nerves can be the presenting signs in septic sacroiliitis. PMID:20090512

  4. Gut sensations in diabetic autonomic neuropathy.

    PubMed

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

    2007-10-01

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

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

    PubMed

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

    2007-09-01

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

  6. Sciatic neuropathy as first sign of metastasising prostate cancer

    PubMed Central

    Hansen, Jakob Møller; Rasti, Zoreh; Smith, Torben; Lassen, Lisbeth Hjorth

    2010-01-01

    Peripheral neuropathies are among the most common neurological diseases and have numerous causes, including diabetes, alcohol, hereditary, toxic, metabolic, infectious, inflammatory, ischaemic and paraneoplastic. Often, however, no definitive cause is identified and the condition is termed idiopathic neuropathy. Here we describe a patient who was initially diagnosed with idiopathic sciatic neuropathy but who was eventually diagnosed with prostate cancer. This is an uncommon manifestation of prostate cancer, and the diagnostic was difficult because prostate-specific antigen (PSA) was normal and the positron emission tomography scan negative. Changes in PSA should always raise the suspicion of prostate cancer, just as idiopathic progressive neuropathy should always raise the suspicion of an underlying malignancy, even when standard diagnostics fail to explain the patient's symptoms.

  7. Familial Idiopathic Cranial Neuropathy in a Chinese Family.

    PubMed

    Zhang, Li; Liang, Jianfeng; Yu, Yanbing

    2016-01-01

    Cranial neuropathy is usually idiopathic and familial cases are uncommon. We describe a family with 5 members with cranial neuropathy over 3 generations. All affected patients were women, indicating an X-linked dominant or an autosomal dominant mode of inheritance. Our cases and a review of the literature suggest that familial idiopathic cranial neuropathy is a rare condition which may be related to autosomal dominant vascular disorders (e.g. vascular tortuosity, sclerosis, elongation or extension), small posterior cranial fossas, anatomical variations of the posterior circulation, hypersensitivity of cranial nerves and other abnormalities. Moreover, microvascular decompression is the treatment of choice because vascular compression is the main factor in the pathogenesis. To the best of our knowledge, this is the first report of familial cranial neuropathy in China. PMID:27161475

  8. Antioxidant strategies in the management of diabetic neuropathy.

    PubMed

    Oyenihi, Ayodeji Babatunde; Ayeleso, Ademola Olabode; Mukwevho, Emmanuel; Masola, Bubuya

    2015-01-01

    Chronic hyperglycaemia (an abnormally high glucose concentration in the blood) resulting from defects in insulin secretion/action, or both, is the major hallmark of diabetes in which it is known to be involved in the progression of the condition to different complications that include diabetic neuropathy. Diabetic neuropathy (diabetes-induced nerve damage) is the most common diabetic complication and can be devastating because it can lead to disability. There is an increasing body of evidence associating diabetic neuropathy with oxidative stress. Oxidative stress results from the production of oxygen free radicals in the body in excess of its ability to eliminate them by antioxidant activity. Antioxidants have different mechanisms and sites of actions by which they exert their biochemical effects and ameliorate nerve dysfunction in diabetes by acting directly against oxidative damage. This review will examine different strategies for managing diabetic neuropathy which rely on exogenous antioxidants. PMID:25821809

  9. Genetics Home Reference: hereditary sensory neuropathy type IA

    MedlinePlus

    ... Ashby P, Wu L, de Jong P, Brown RH Jr. SPTLC1 is mutated in hereditary sensory neuropathy, ... V, Stoeckli ET, Nicholson G, Eichler F, Brown RH Jr, von Eckardstein A, Hornemann T. Hereditary sensory ...

  10. Antioxidant Strategies in the Management of Diabetic Neuropathy

    PubMed Central

    Oyenihi, Ayodeji Babatunde; Ayeleso, Ademola Olabode; Masola, Bubuya

    2015-01-01

    Chronic hyperglycaemia (an abnormally high glucose concentration in the blood) resulting from defects in insulin secretion/action, or both, is the major hallmark of diabetes in which it is known to be involved in the progression of the condition to different complications that include diabetic neuropathy. Diabetic neuropathy (diabetes-induced nerve damage) is the most common diabetic complication and can be devastating because it can lead to disability. There is an increasing body of evidence associating diabetic neuropathy with oxidative stress. Oxidative stress results from the production of oxygen free radicals in the body in excess of its ability to eliminate them by antioxidant activity. Antioxidants have different mechanisms and sites of actions by which they exert their biochemical effects and ameliorate nerve dysfunction in diabetes by acting directly against oxidative damage. This review will examine different strategies for managing diabetic neuropathy which rely on exogenous antioxidants. PMID:25821809

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

    PubMed

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

    1988-12-01

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

  12. Pathogenesis and treatment of immune-mediated neuropathies.

    PubMed

    Lehmann, Helmar C; Meyer Zu Horste, Gerd; Kieseier, Bernd C; Hartung, Hans-Peter

    2009-07-01

    Immune-mediated neuropathies represent a heterogeneous spectrum of peripheral nerve disorders that can be classified according to time course, predominant involvement of motor/sensory fibers, distribution of deficits and paraclinical parameters such as electrophysiology and serum antibodies. In the last few years, significant advances have been achieved in elucidating underlying pathomechanisms, which made it possible to identify potential therapeutic targets. In this review, we discuss the latest development in pathogenesis and treatment of immune-mediated neuropathies. PMID:21179533

  13. Peripheral neuropathy following intentional inhalation of naphtha fumes.

    PubMed Central

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

    1984-01-01

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

  14. Complications of Compressive Neuropathy: Prevention and Management Strategies

    PubMed Central

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

    2016-01-01

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

  15. Morphologic Changes in Autonomic Nerves in Diabetic Autonomic Neuropathy

    PubMed Central

    Jin, Heung Yong; Baek, Hong Sun

    2015-01-01

    Diabetic neuropathy is one of the major complications of diabetes, and it increases morbidity and mortality in patients with both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Because the autonomic nervous system, for example, parasympathetic axons, has a diffuse and wide distribution, we do not know the morphological changes that occur in autonomic neural control and their exact mechanisms in diabetic patients with diabetic autonomic neuropathy (DAN). Although the prevalence of sympathetic and parasympathetic neuropathy is similar in T1DM versus T2DM patients, sympathetic nerve function correlates with parasympathetic neuropathy only in T1DM patients. The explanation for these discrepancies might be that parasympathetic nerve function was more severely affected among T2DM patients. As parasympathetic nerve damage seems to be more advanced than sympathetic nerve damage, it might be that parasympathetic neuropathy precedes sympathetic neuropathy in T2DM, which was Ewing's concept. This could be explained by the intrinsic morphologic difference. Therefore, the morphological changes in the sympathetic and parasympathetic nerves of involved organs in T1DM and T2DM patients who have DAN should be evaluated. In this review, evaluation methods for morphological changes in the epidermal nerves of skin, and the intrinsic nerves of the stomach will be discussed. PMID:26706915

  16. Entrapment in anti myelin-associated glycoprotein neuropathy.

    PubMed

    Faber, Catharina G; Notermans, Nicolette C; Wokke, John H J; Franssen, Hessel

    2009-04-01

    Anti-myelin associated glycoprotein (MAG) neuropathy is a chronic disorder in which IgM antibodies react with Schwann cell glycoproteins, including MAG and peripheral myelin protein 22 (PMP22). Nerve conduction studies show features of axon loss and predominantly distal slowing consistent with demyelination. Because a genetic loss of PMP22 function yields hereditary neuropathy with liability to pressure palsies (HNPP), loss of PMP22 function due to anti- MAG antibodies may result in increased sensitivity to entrapment. We investigated this by performing standardized electrophysiological studies in 16 patients with anti-MAG neuropathy and 16 disease controls with genetically confirmed HNPP. Disproportionate slowing relative to adjacent segments occurred in similar proportions of patients with anti-MAG neuropathy and HNPP, and was of the same magnitude in each group. Affected were the elbow, carpal tunnel and the wrist-hand segments of the median and ulnar nerves. However, in anti-MAG neuropathy as compared to HNPP, absolute values of distal motor latencies and conduction velocities outside entrapment sites were slower and amplitudes were lower. In conclusion, increased sensitivity for entrapment may occur in anti-MAG neuropathy and contribute to part of the nerve damage. PMID:19306083

  17. Optical Coherence Tomography (OCT) in Optic Neuritis and Multiple Sclerosis

    PubMed Central

    Lamirel, Cédric; Newman, Nancy J.; Biousse, Valérie

    2010-01-01

    Optical coherence tomography (OCT) is a non-invasive imaging technique routinely used in ophthalmology to visualize and quantify the layers of the retina. It also provides information on optic nerve head topography, peripapillary retinal nerve fiber layer thickness, and macular volume which correlate with axonal loss. These measurements are of particular interest in optic neuropathies and in multiple sclerosis, and OCT parameters are now used as endpoints in neurologic clinical trials. PMID:20605617

  18. 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 PKCε-independent, and alcohol-induced painful neuropathy was PKCε-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 PKCε-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

  19. Spectrum of peripheral neuropathies associated with surgical interventions; A neurophysiological assessment

    PubMed Central

    2010-01-01

    Background We hypothesized that a wide range of surgical procedures may be complicated by neuropathies, not just in close proximity but also remote from procedural sites. The aim of this study was to classify post-operative neuropathies and the procedures associated with them. Methods We retrospectively identified 66 patients diagnosed with post-procedure neuropathies between January 2005 and June 2008. We reviewed their referral cards and medical records for patient demographics, information on procedures, symptoms, as well as clinical and neurophysiological findings. Results Thirty patients (45.4%) had neuropathies remote from procedural sites and 36 patients (54.5%) had neuropathies in close proximity to procedural sites. Half of the remote neuropathies (15/30) developed following relatively short procedures. In 27% of cases (8/30) remote neuropathies were bilateral. Seven patients developed neuropathies remote from operative sites following hip arthroplasties (7/30: 23.3%), making hip arthroplasty the most common procedure associated with remote neuropathies. Sciatic neuropathies due to hip arthroplasty (12/36, 33.3%) accounted for the majority of neuropathies occurring in close proximity to operative sites. Five medial cutaneous nerve of forearm neuropathies occurred following arterio-venous fistula (AVF) formation. Conclusions An array of surgical procedures may be complicated by neuropathy. Almost half of post-procedure neuropathies occur remote from the site of procedure, emphasizing the need to try to prevent not just local, but also remote neuropathies. Mechanical factors and patient positioning should be considered in the prevention of post-operative neuropathies. There is a possible association between AVF formation and medial cutaneous nerve of forearm neuropathy, which requires further study for validation. PMID:20398427

  20. Diabetic neuropathy: mechanisms, emerging treatments, and subtypes.

    PubMed

    Albers, James W; Pop-Busui, Rodica

    2014-08-01

    Diabetic neuropathies (DNs) differ in clinical course, distribution, fiber involvement (type and size), and pathophysiology, the most typical type being a length-dependent distal symmetric polyneuropathy (DSP) with differing degrees of autonomic involvement. The pathogenesis of diabetic DSP is multifactorial, including increased mitochondrial production of free radicals due to hyperglycemia-induced oxidative stress. Mechanisms that impact neuronal activity, mitochondrial function, membrane permeability, and endothelial function include formation of advanced glycosylation end products, activation of polyol aldose reductase signaling, activation of poly(ADP ribose) polymerase, and altered function of the Na(+)/K(+)-ATPase pump. Hyperglycemia-induced endoplasmic reticulum stress triggers several neuronal apoptotic processes. Additional mechanisms include impaired nerve perfusion, dyslipidemia, altered redox status, low-grade inflammation, and perturbation of calcium balance. Successful therapies require an integrated approach targeting these mechanisms. Intensive glycemic control is essential but is insufficient to prevent onset or progression of DSP, and disease-modifying treatments for DSP have been disappointing. Atypical forms of DN include subacute-onset sensory (symmetric) or motor (asymmetric) predominant conditions that are frequently painful but generally self-limited. DNs are a major cause of disability, associated with reduced quality of life and increased mortality. PMID:24954624

  1. Management of oxaliplatin-induced peripheral neuropathy

    PubMed Central

    Saif, M Wasif; Reardon, John

    2005-01-01

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

  2. 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

  3. Auditory neuropathy - neural and synaptic mechanisms.

    PubMed

    Moser, Tobias; Starr, Arnold

    2016-03-01

    Sensorineural hearing impairment is the most common form of hearing loss, and encompasses pathologies of the cochlea and the auditory nerve. Hearing impairment caused by abnormal neural encoding of sound stimuli despite preservation of sensory transduction and amplification by outer hair cells is known as 'auditory neuropathy'. This term was originally coined for a specific type of hearing impairment affecting speech comprehension beyond changes in audibility: patients with this condition report that they "can hear but cannot understand". This type of hearing impairment can be caused by damage to the sensory inner hair cells (IHCs), IHC ribbon synapses or spiral ganglion neurons. Human genetic and physiological studies, as well as research on animal models, have recently shown that disrupted IHC ribbon synapse function - resulting from genetic alterations that affect presynaptic glutamate loading of synaptic vesicles, Ca(2+) influx, or synaptic vesicle exocytosis - leads to hearing impairment termed 'auditory synaptopathy'. Moreover, animal studies have demonstrated that sound overexposure causes excitotoxic loss of IHC ribbon synapses. This mechanism probably contributes to hearing disorders caused by noise exposure or age-related hearing loss. This Review provides an update on recently elucidated sensory, synaptic and neural mechanisms of hearing impairment, their corresponding clinical findings, and discusses current rehabilitation strategies as well as future therapies. PMID:26891769

  4. Suprascapular Neuropathy in Collegiate Baseball Player

    PubMed Central

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

    2012-01-01

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

  5. 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

  6. Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice.

    PubMed

    Trammell, Samuel A J; Weidemann, Benjamin J; Chadda, Ankita; Yorek, Matthew S; Holmes, Amey; Coppey, Lawrence J; Obrosov, Alexander; Kardon, Randy H; Yorek, Mark A; Brenner, Charles

    2016-01-01

    Male C57BL/6J mice raised on high fat diet (HFD) become prediabetic and develop insulin resistance and sensory neuropathy. The same mice given low doses of streptozotocin are a model of type 2 diabetes (T2D), developing hyperglycemia, severe insulin resistance and diabetic peripheral neuropathy involving sensory and motor neurons. Because of suggestions that increased NAD(+) metabolism might address glycemic control and be neuroprotective, we treated prediabetic and T2D mice with nicotinamide riboside (NR) added to HFD. NR improved glucose tolerance, reduced weight gain, liver damage and the development of hepatic steatosis in prediabetic mice while protecting against sensory neuropathy. In T2D mice, NR greatly reduced non-fasting and fasting blood glucose, weight gain and hepatic steatosis while protecting against diabetic neuropathy. The neuroprotective effect of NR could not be explained by glycemic control alone. Corneal confocal microscopy was the most sensitive measure of neurodegeneration. This assay allowed detection of the protective effect of NR on small nerve structures in living mice. Quantitative metabolomics established that hepatic NADP(+) and NADPH levels were significantly degraded in prediabetes and T2D but were largely protected when mice were supplemented with NR. The data justify testing of NR in human models of obesity, T2D and associated neuropathies. PMID:27230286

  7. Contralateral ulnar neuropathy following total hip replacement and intraoperative positioning.

    PubMed

    O'Brien, S; Bennett, D; Spence, D J; Mawhinney, I; Beverland, D E

    2016-05-01

    Peripheral neuropathy is a rare but important complication of total hip arthroplasty (THA) and has previously been reported in the ipsilateral arm and associated with inflammatory arthritis. The results of 7004 primary hip arthroplasties performed between January 1993 and February 2009 were retrospectively reviewed to identify patients who reported ulnar neuropathy symptoms, with ten patients identified at mean follow-up of 57 months (range = 3-195 months). Eight patients experienced unilateral ulnar nerve symptoms in the contralateral upper limb post-surgery, one patient experienced symptoms in the ipsilateral upper limb and one patient experienced symptoms in both upper limbs. The incidence of post-THA ulnar neuropathy was 0.14%. All patients had a pre-operative diagnosis of osteoarthritis and none had diabetes, a previous history of neuropathy or inflammatory arthritis. All operations were primary arthroplasties and were performed under the care of a single surgeon in a single centre. Two of the ten patients (20%) had a general anaesthetic. The pattern of symptoms reported, i.e. mainly unilateral affecting the contralateral side with variable resolution, contrasts with previous studies and suggests that intraoperative patient positioning may be an important factor influencing ulnar neuropathy following THA. Attention to support and positioning of the contralateral arm may help reduce the incidence of this complication. PMID:26589446

  8. 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.

  9. 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

  10. Screening for peripheral neuropathy in chemical warfare victims.

    PubMed

    Holisaz, Mohammad Taghi; Rayegani, Seyyed Mansoor; Hafezy, Rahmatollah; Khedmat, Hossein; Motamedi, Mohammad Hosein K

    2007-03-01

    We aimed to assess the prevalence of peripheral neuropathy in chemical warfare victims. We speculated that peripheral neuropathy is a late complication of exposure to chemical warfare agents. Late complications of exposure to chemical warfare agents are not well known and are poorly discussed in the existing literature. Scientific data regarding delayed complications are sparse, but this warrants recognition, especially when the clinician has to treat chemical warfare victims. The hazards of organophosphate pesticides and several toxins, although recognized to some extent, are, however, different from the hazards of chemical warfare agents which are far more serious. In this study, 100 chemical warfare patients, with varying degrees of exposure and an average age of 37.2+/-9.0 years, were examined clinically and studied electrodiagnostically from January 2002 to January 2003. Five of these patients proved to be suffering from axonal neuropathy. This rate was significantly higher than that found in the normal population. Our data indicate that chemical warfare agents may cause peripheral neuropathy in chemical warfare victims. In conclusion, organophosphorous agents used against Iranian troops during the war on Iran correlate with delayed neuropathy in these victims. PMID:17293724

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

    PubMed

    Chopra, Kanwaljit; Tiwari, Vinod

    2012-03-01

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

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

    PubMed Central

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

    2015-01-01

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

  13. Peripheral neuropathy induced by combination chemotherapy of docetaxel and cisplatin.

    PubMed Central

    Hilkens, P. H.; Pronk, L. C.; Verweij, J.; Vecht, C. J.; van Putten, W. L.; van den Bent, M. J.

    1997-01-01

    Docetaxel, a new semisynthetic taxoid that has demonstrated promising activity as an antineoplastic agent, was administered in combination with cisplatin to 63 patients in a dose-escalating study. As both drugs were known to be potentially neurotoxic, peripheral neurotoxicity was prospectively assessed in detail. Neuropathy was evaluated by clinical sum-score for signs and symptoms and by measurement of the vibration perception threshold (VPT). The severity of neuropathy was graded according to the National Cancer Institute's 'Common Toxicity Criteria'. The docetaxel-cisplatin combination chemotherapy induced a predominantly sensory neuropathy in 29 (53%) out of 55 evaluable patients. At cumulative doses of both cisplatin and docetaxel above 200 mg m(-2), 26 (74%) out of 35 patients developed a neuropathy which was mild in 15, moderate in ten and severe in one patient. Significant correlations were present between both the cumulative dose of docetaxel and cisplatin and the post-treatment sum-score of neuropathy (P < 0.01) as well as the post-treatment VPT (P < 0.01). The neurotoxic effects of this combination were more severe than either cisplatin or docetaxel as single agent at similar doses. PMID:9020489

  14. NEUROPATHY TARGET ESTERASE INHIBITION BY ORGANOPHOSPHORUS ESTERS IN HUMAN NEUROBLASTOMA CELLS

    EPA Science Inventory

    Certain organophosphorus compounds (OPs) produce a delayed neuropathy (OPIDN) in man and some animal species. apability to cause OPIDN is generally predicted in animal models by early and irreversible inhibition of neuropathy target esterase (NTE, neurotoxic esterase) . In this s...

  15. Painless Ulcers and Fissures of Toes: Hereditary Sensory Neuropathy, Not Leprosy

    PubMed Central

    Rao, Angoori Gnaneshwar

    2016-01-01

    Hereditary sensory neuropathies (HSN) are rare genetically determined neuropathies. They often manifest as painless injuries in children. We present HSN in a 5-year-old boy who presented with recurrent fissuring and ulceration involving both great toes. PMID:26955138

  16. Vesiculobullous dermatomyositis with sensory motor neuropathy.

    PubMed

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

    2013-01-01

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

  17. 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.

  18. Clinical and pathological features of an autosomal recessive neuropathy.

    PubMed

    Bouldin, T W; Riley, E; Hall, C D; Swift, M

    1980-06-01

    Two siblings are described, ages 49 and 45 years, having a distinct hereditary motor and sensory neuropathy (HMSN) with severe peroneal nerve involvement. The neuropathic symptoms began in childhood. Both patients have sensorineural deafness. The proband was found to have a cardiac conduction abnormality in the absence of known ischemic heart disease. Electrodiagnostic studies were consistent with a demyelinating peripheral neuropathy. The presence of parental consanguinity and absence of affected individuals in succeeding or preceding generations suggested that the sensorimotor neuropathy in this family is inherited in an autosomal recessive manner. The sural nerve of the proband had significant loss of myelinated fibers and demyelination but few regenerating myelinated fibers and no onion-bulbs. The pathological findings, while nonspecific, are not characteristic of the hypertrophic, neuronal or intermediate types of HMSN. PMID:6247456

  19. Precise correlation between structural and electrophysiological disturbances in MADSAM neuropathy.

    PubMed

    Simon, Neil G; Kiernan, Matthew C

    2015-11-01

    Multifocal acquired demyelinating sensory and motor neuropathy is characterised by multifocal clinical deficits. Imaging studies have identified multifocal enlargements of nerve trunks, but a precise correlation between structural abnormalities and electrophysiological dysfunction has not been elucidated. Two patients diagnosed with multifocal acquired demyelinating sensory and motor neuropathy were evaluated with nerve conduction studies, including short segment nerve conduction studies to precisely localise motor conduction block, and ultrasound studies of corresponding nerve trunks. Motor conduction block was identified in each patient (upper limb nerves in two patients), superimposed on additional demyelinating neurophysiological features. Upper limb ultrasound studies demonstrated focal nerve enlargement that precisely correlated with neurophysiological conduction block. The results of this study suggest that factors contributing to focal structural abnormalities in multifocal acquired demyelinating sensory and motor neuropathy are also those that produce conduction block. PMID:26314279

  20. [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

  1. Is there a relationship between oral health and diabetic neuropathy?

    PubMed

    Borgnakke, Wenche S; Anderson, Patricia F; Shannon, Carol; Jivanescu, Anca

    2015-11-01

    Diabetic neuropathy is the most common microvascular complication of diabetes mellitus with high morbidity and mortality, and low quality of life. It has a broad spectrum of clinical forms, although distal symmetrical polyneuropathy is the most prevalent. Several oral complications including burning mouth syndrome, dry mouth, and impairment of the senses taste and smell are less-known manifestations of diabetic neuropathy and often overlooked. Periodontitis, tooth loss, and temporomandibular joint dysfunction may be also present in these patients and are equally debilitating. Periodontitis was declared the sixth complication of diabetes in 1993 and may contribute to poor glucose control. Hence, periodontitis and diabetes mutually and adversely affect each other. This review summarizes the available body of scientific literature that discusses oral manifestations in patients with diabetic neuropathy and identifies important areas where more research is needed. PMID:26374570

  2. [Acro-osteolysis with hereditary sensory ulcero-mutilating neuropathy. Apropos of an atypical case].

    PubMed

    Carabelli, A; Ruggeri, R; Pessina, R; Cerri, D; Bertani, E

    1989-01-01

    The authors report an acroosteolysis case with sensory radicular ulcero-mutilating neuropathy. The differential diagnosis are discussed and the case is presented as an intermediate form between the congenital sensory neuropathy, type II, according to Otha classification, and the non-progressive, sporadical sensory neuropathy. PMID:2638645

  3. 77 FR 59930 - Clinical Development Programs for Disease-Modifying Agents for Peripheral Neuropathy; Public...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-01

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

  4. Facial neuropathy with imaging enhancement of the facial nerve: a case report

    PubMed Central

    Mumtaz, Sehreen; Jensen, Matthew B

    2014-01-01

    A young women developed unilateral facial neuropathy 2 weeks after a motor vehicle collision involving fractures of the skull and mandible. MRI showed contrast enhancement of the facial nerve. We review the literature describing facial neuropathy after trauma and facial nerve enhancement patterns with different causes of facial neuropathy. PMID:25574155

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

    PubMed

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

    2014-06-01

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

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

    PubMed

    Ranoux, D

    2011-01-01

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

  7. Towards a Diagnosis of Cochlear Neuropathy with Envelope Following Responses.

    PubMed

    Shaheen, Luke A; Valero, Michelle D; Liberman, M Charles

    2015-12-01

    Listeners with normal audiometric thresholds can still have suprathreshold deficits, for example, in the ability to discriminate sounds in complex acoustic scenes. One likely source of these deficits is cochlear neuropathy, a loss of auditory nerve (AN) fibers without hair cell damage, which can occur due to both aging and moderate acoustic overexposure. Since neuropathy can affect up to 50 % of AN fibers, its impact on suprathreshold hearing is likely profound, but progress is hindered by lack of a robust non-invasive test of neuropathy in humans. Reduction of suprathreshold auditory brainstem responses (ABRs) can be used to quantify neuropathy in inbred mice. However, ABR amplitudes are highly variable in humans, and thus more challenging to use. Since noise-induced neuropathy is selective for AN fibers with high thresholds, and because phase locking to temporal envelopes is particularly strong in these fibers, the envelope following response (EFR) might be a more robust measure. We compared EFRs to sinusoidally amplitude-modulated tones and ABRs to tone-pips in mice following a neuropathic noise exposure. EFR amplitude, EFR phase-locking value, and ABR amplitude were all reduced in noise-exposed mice. However, the changes in EFRs were more robust: the variance was smaller, thus inter-group differences were clearer. Optimum detection of neuropathy was achieved with high modulation frequencies and moderate levels. Analysis of group delays was used to confirm that the AN population was dominating the responses at these high modulation frequencies. Application of these principles in clinical testing can improve the differential diagnosis of sensorineural hearing loss. PMID:26323349

  8. Progress in inflammatory neuropathy -the legacy of Dr Jack Griffin.

    PubMed

    Feldman, Eva L; Hughes, Richard A C; Willison, Hugh J

    2015-11-01

    The past quarter of a century has brought incredible advances in our understanding of inflammatory neuropathies, and the insights into Guillain-Barré syndrome (GBS) began in the 1990s with the seminal work of Dr Jack Griffin and his colleagues. In this essay, we provide a tribute to Jack, and review the recent progress in a field that he termed his personal favourite. In particular, we discuss the new developments in our understanding and diagnosis of inflammatory neuropathies, the recent emergence of the node of Ranvier and the paranode as sites of intensive investigation, and the mechanistic evidence that is providing a platform for therapeutic development studies. PMID:26458287

  9. The variable clinical manifestations of ulnar neuropathies at the elbow.

    PubMed Central

    Stewart, J D

    1987-01-01

    In twenty-five cases of ulnar neuropathy at the elbow, the involvement of the fibres from three sensory and to four motor branches were examined clinically and, where possible, electrophysiologically. Of the sensory fibres, those from the terminal digital nerves were most commonly involved. The fibres to the hand muscles were much more frequently involved than those to the forearm muscles. These findings suggest that in ulnar neuropathies at the elbow there is variable damage to the fascicles within the nerve. PMID:3031220

  10. Peripheral neuropathy in myotonic dystrophy: electrophysiological and clinical features.

    PubMed

    Logullo, F; Censori, B; Danni, M; Del Pesce, M; Di Bella, P; Provinciali, L

    1992-01-01

    Peripheral neuropathy was investigated in thirty-one patients with myotonic dystrophy (MyD) and sixteen relatives. Using standard electrophysiological criteria, a sensorimotor axonal peripheral neuropathy was found in 14 MyD cases (45%) and not in unaffected first-degree relatives. The whole group of the MyD patients showed significant impairment of mean motor and sensory conduction values, compared with controls. The presence of polyneuropathy was correlated with the patients' age and the severity and duration of the clinical manifestations of MyD. PMID:1332841

  11. Multiple Crush Concept Applied to Multiple Nerves in Leprous Neuropathy.

    PubMed

    Dellon, A Lee

    2016-04-01

    There is a large reservoir of leprosy patients, no longer contagious, due to multidrug therapy, who are considered cured and are becoming increasingly disabled due to progressive chronic nerve entrapment in the upper and lower extremities. After a review of the history of understanding leprous neuropathy, an approach is outlined based on the approach taken to relieve pain and restore sensation that prevents ulcers and amputations in diabetics with neuropathy and superimposed nerve compressions. The results of the first application of this approach in an indigenous area for leprosy, Guayaquil, Ecuador, is discussed with implications for international care of this neglected patient population. PMID:27013412

  12. Subacute multicranial neuropathy revealing an early case of meningeal syphilis.

    PubMed

    Casolla, Barbara; Ristori, Giovanni; Romano, Andrea; Bozzao, Alessandro; Orzi, Francesco

    2015-06-01

    We report a case of neurosyphilis presenting with meningitis and subacute multicranial neuropathy in a young immune-competent man. Signs of primary and secondary stages of syphilitic infection occurred almost contemporarily in our patient. MRI revealed the involvement of several cranial nerves. CSF examination proved to be diagnostic. Syphilitic meningitis should be considered among the differential diagnoses of subacute, multicranial neuropathy, or skull base meningitis. The clinical course of this patient shows that early diagnosis and treatment warrant a good neurological outcome. PMID:25739944

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

    PubMed

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

    2015-01-01

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

  14. 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

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

    TOXLINE Toxicology Bibliographic Information

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

    1997-12-01

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

  16. Targeted preventive measures and advanced approaches in personalised treatment of glaucoma neuropathy.

    PubMed

    Mozaffarieh, Maneli; Fraenkl, Stefan; Konieczka, Katarzyna; Flammer, Josef

    2010-06-01

    Glaucoma is a major cause of vision loss worldwide with nearly 8 million people bilaterally blind from the disease. This number is estimated to increase over the next 10 years. The key to preventing blindness from glaucoma is effective diagnosis and treatment. The classical glaucoma treatment focuses on intraocular pressure (IOP) reduction. Better knowledge of the pathogenesis has opened up additional therapeutical approaches often called non-IOP lowering treatment. Whilst most of these new avenues of treatment are still in the experimental phase, others are already used by some physicians. These new therapeutic approaches allow a more personalised patient treatment. Non-IOP lowering treatment includes improvements of ocular blood flow, particularly blood flow regulation. This can be achieved by improving the regulation of ocular blood flow (improving autoregulation) by drugs such as carbonic anhydrase inhibitors, magnesium or calcium channel blockers. It can also be improved by decreasing blood pressure over-dips. Blood pressure can be increased by an increase in salt intake or in rare cases by treatment with fludrocortisone. Experimentally, glaucomatous optic neuropathy can be prevented by inhibition of astrocyte activation, either by blockage of epidermal growth factor receptor or by counteracting Endothelin. Glaucomatous optic neuropathy can also be prevented by nitric oxide-2 synthase inhibition. Suppression of matrix metalloproteinase-9 inhibits apoptosis of retinal ganglion cells and tissue remodelling. Upregulation of heat shock proteins protects the retinal ganglion cells and the optic nerve head. Reduction of oxidative stress especially at the level of mitochondria also seems to be protective. This can be achieved by gingko, dark chocolate, polyphenolic flavonoids occurring in tea, coffee or red wine and anthocyanosides found in bilberries as well as by ubiquinone and melatonin. This review describes the individual mechanisms which may be targeted by non-IOP lowering treatment based on our pathogenic scheme. PMID:23199061

  17. Coincidental Optic Nerve Meningioma and Thyroid Eye Disease.

    PubMed

    Garg, Aakriti; Patel, Payal; Lignelli, Angela; Baron, Edward; Kazim, Michael

    2015-01-01

    A 57-year-old woman with diabetes mellitus, hypertension, obesity, and Graves disease presented with clinical evidence of thyroid eye disease (TED) and optic neuropathy. She was referred when a tapered dose of steroids prompted worsening of her TED. CT and MRI were consistent with TED and bilateral optic nerve meningioma. To the authors' knowledge, this is the first reported case of concurrent TED and unsuspected bilateral optic nerve meningioma. When investigating the etiology of TED-associated optic neuropathy, careful attention to orbital imaging is required because coexisting pathology may exist. PMID:24833445

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

    PubMed Central

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

    1988-01-01

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

  19. 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

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

    SciTech Connect

    Donaghy, M.; Rushworth, G.; Jacobs, J.M. )

    1991-07-01

    A 58-year-old dental prosthetic technician developed generalized sensorimotor peripheral neuropathy. Neurophysiologic studies showed a generalized sensorimotor neuropathy of axonal degeneration type. Examination of a sural nerve biopsy showed a moderately severe axonal neuropathy with loss of large myelinated fibers and unmyelinated axons. There was evidence of slow ongoing degeneration and considerable fiber regeneration. Electron microscopy showed increased numbers of filaments in a few fibers. These findings show resemblances to the nerve changes caused by another acrylic resin, acrylamide. They suggest that the neuropathy may have been caused by 30 years of occupational cutaneous and inhalational exposure to methyl methacrylate monomer since they excluded other recognized causes of neuropathy.

  1. Discordance of clinical symptoms and electrophysiologic findings in taxane plus platinum-induced neuropathy.

    PubMed

    Pan, Y; Kao, M-S

    2007-01-01

    Paclitaxel combined with carboplatin is currently accepted as the first-line treatment for ovarian carcinoma, frequently associated with neuropathy. Due to its frequent association with neuropathy, combination of docetaxel and carboplatin has been suggested as an alternative. A 47-year-old woman developed paresthesia after the first cycle of paclitaxel/carboplatin for ovarian cancer. Her nerve conduction study (NCS) showed only sural neuropathy after completion of six cycles, which returned to normal in 6 months. She had fewer neuropathy symptoms when treatment was changed to docetaxel/carboplatin for recurrent cancer. NCS revealed generalized sensory neuropathy following docetaxel/carboplatin treatment, which normalized after 12 months. Our observation indicated that there is a disparity between clinical symptoms and electrophysiologic examination in taxane-induced neuropathy. Although docetaxel was tolerated well by the patient, evidence of generalized sensory neuropathy was present in NCS. PMID:17362318

  2. Progression in idiopathic, diabetic, paraproteinemic, alcoholic, and B12 deficiency neuropathy.

    PubMed

    Sachedina, Shafina; Toth, Cory

    2013-09-01

    We determined prospectively the clinical and electrophysiological progression of idiopathic, diabetic, paraproteinemic, alcoholic, and B12 deficiency neuropathy in 606 subjects over 3 years. We hypothesized that idiopathic peripheral neuropathy would demonstrate slower progression when compared with other etiologies. Laboratory assessments were used to determine the etiology of peripheral neuropathy at baseline and after 3 years. When compared with peripheral neuropathy related to type 1 or type 2 diabetes mellitus, subjects with idiopathic peripheral neuropathy progressed much slower, but demonstrated similar rates of progression to that of the other groups. Overall, detectable progression was minimal over 3 years. After 3 years, only 3% of cases of idiopathic peripheral neuropathy had any potentially identifiable causes discovered. Clinical and electrophysiological detection of very slow progression for these five types of peripheral neuropathy is possible using currently established clinical scales and standard electrophysiological techniques. PMID:24028193

  3. 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

  4. 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

  5. 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

  6. 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

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

    MedlinePlus

    ... Web version Diabetic Neuropathy | What is a Total Contact Cast? What is a total contact cast? A total contact cast is a cast used to treat ulcers ( ... foot--that's why it is called a total contact cast. The cast helps to protect the skin ...

  8. Intrathecal gene therapy rescues a model of demyelinating peripheral neuropathy.

    PubMed

    Kagiava, Alexia; Sargiannidou, Irene; Theophilidis, George; Karaiskos, Christos; Richter, Jan; Bashiardes, Stavros; Schiza, Natasa; Nearchou, Marianna; Christodoulou, Christina; Scherer, Steven S; Kleopa, Kleopas A

    2016-04-26

    Inherited demyelinating peripheral neuropathies are progressive incurable diseases without effective treatment. To develop a gene therapy approach targeting myelinating Schwann cells that can be translatable, we delivered a lentiviral vector using a single lumbar intrathecal injection and a myelin-specific promoter. The human gene of interest, GJB1, which is mutated in X-linked Charcot-Marie-Tooth Disease (CMT1X), was delivered intrathecally into adult Gjb1-null mice, a genetically authentic model of CMT1X that develops a demyelinating peripheral neuropathy. We obtained widespread, stable, and cell-specific expression of connexin32 in up to 50% of Schwann cells in multiple lumbar spinal roots and peripheral nerves. Behavioral and electrophysiological analysis revealed significantly improved motor performance, quadriceps muscle contractility, and sciatic nerve conduction velocities. Furthermore, treated mice exhibited reduced numbers of demyelinated and remyelinated fibers and fewer inflammatory cells in lumbar motor roots, as well as in the femoral motor and sciatic nerves. This study demonstrates that a single intrathecal lentiviral gene delivery can lead to Schwann cell-specific expression in spinal roots extending to multiple peripheral nerves. This clinically relevant approach improves the phenotype of an inherited neuropathy mouse model and provides proof of principle for treating inherited demyelinating neuropathies. PMID:27035961

  9. Genetic determination of motor neuron disease and neuropathy.

    PubMed

    Vrebalov Cindro, Pavle; Vrebalov Cindro, Veselin

    2015-03-01

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

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

    PubMed

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

    2004-11-01

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

  11. Periaxin mutations cause a broad spectrum of demyelinating neuropathies.

    PubMed

    Takashima, Hiroshi; Boerkoel, Cornelius F; De Jonghe, Peter; Ceuterick, Chantal; Martin, Jean-Jacques; Voit, Thomas; Schröder, J-Michael; Williams, Anna; Brophy, Peter J; Timmerman, Vincent; Lupski, James R

    2002-06-01

    Previous studies have demonstrated that apparent loss-of-function mutations in the periaxin gene cause autosomal recessive Dejerine-Sottas neuropathy or severe demyelinating Charcot-Marie-Tooth disease. In this report, we extend the associated phenotypes with the identification of two additional families with novel periaxin gene mutations (C715X and R82fsX96) and provide detailed neuropathology. Each patient had marked sensory involvement; two siblings with a homozygous C715X mutation had much worse sensory impairment than motor impairment. Despite early disease onset, these siblings with the C715X mutation had relatively slow disease progression and adult motor impairment typical of classic demyelinating Charcot-Marie-Tooth neuropathy. In contrast, a patient with the homozygous R82fsX96 mutation had a disease course consistent with Dejerine-Sottas neuropathy. The neuropathology of patients in both families was remarkable for demyelination, onion bulb and occasional tomacula formation with focal myelin thickening, abnormalities of the paranodal myelin loops, and focal absence of paranodal septate-like junctions between the terminal loops and axon. Our study indicates a prominent sensory neuropathy resulting from periaxin gene mutations and suggests a role for the carboxyl terminal domain of the periaxin protein. PMID:12112076

  12. 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

  13. Exercise as Therapy for Diabetic and Prediabetic Neuropathy.

    PubMed

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

    2015-12-01

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

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

    PubMed

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

    2011-12-01

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

  15. Neurotrophic factors and their receptors in human sensory neuropathies.

    PubMed

    Anand, Praveen

    2004-01-01

    Neurotrophic factors may play key roles in pathophysiological mechanisms of human neuropathies. Nerve growth factor (NGF) is trophic to small-diameter sensory fibers and regulates nociception. This review focuses on sensory dysfunction and the potential of neurotrophic treatments. Genetic neuropathy. Mutations of the NGF high-affinity receptor tyrosine kinase A (Trk A) have been found in congenital insensitivity to pain and anhidrosis; these are likely to be partial loss-of-function mutations, as axon-reflex vasodilatation and sweating can be elicited albeit reduced, suggesting rhNGF could restore nociception in some patients. Leprous neuropathy. Decreased NGF in leprosy skin may explain cutaneous hypoalgesia even with inflammation and rhNGF may restore sensation, as spared nerve fibers show Trk A-staining. Diabetic neuropathy. NGF is depleted in early human diabetic neuropathy skin, in correlation with dysfunction of nociceptor fibers. We proposed rhNGF prophylaxis may prevent diabetic foot ulceration. Clinical trials have been disappointed, probably related to difficulty delivering adequate doses and need for multiple trophic factors. NGF and glial cell line-derived neurotrophic factor (GDNF) are both produced by basal keratinocytes and neurotrophin (NT-3) by suprabasal keratinocytes: relative mRNA expression was significantly lower in early diabetic neuropathy skin compared to controls, for NGF (P < 0.02), BDNF (P < 0.05), NT-3 (P < 0.05), GDNF (< 0.02), but not NT4/5, Trk A or p75 neurotrophin receptor (all P > 0.05). Posttranslational modifications of mature and pro-NGF may also affect bioactivity and immunoreactivity. A 53 kD band that could correspond to a prepro-NGF-like molecule was reduced in diabetic skin. Traumatic neuropathy and pain. While NGF levels are acutely reduced in injured nerve trunks, neuropathic patients with chronic skin hyperalgesia and allodynia show marked local increases of NGF levels; here anti-NGF agents may provide analgesia. Physiological combinations of NGF, NT-3 and GDNF, to mimic a 'surrogate target organ', may provide a novel 'homeostatic' approach to prevent the development and ameliorate intractable neuropathic pain (e.g., at painful amputation stumps). PMID:14699981

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

    PubMed

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

    2015-01-01

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

  17. [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

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

    PubMed

    Azpiroz, Fernando; Malagelada, Carolina

    2016-03-01

    The activity of the digestive tract is usually regulated to match its content: physiological stimuli in the gut induce modulatory reflexes that control digestive function so that digestion is normally not perceived. However, under certain circumstances, digestive stimuli may activate sensory afferents and give rise to conscious sensations. Both reflex and sensory signals are modulated by a balance of excitatory and inhibitory mechanisms. Patients with diabetes may develop a neuropathy affecting the control of gastric and/or intestinal motor function and the sensory innervation as well. During fasting the stomach is contracted and relaxes to accommodate a meal. After ingestion the stomach progressively recontracts and this contraction gently produces gastric emptying. Impairment of excitatory pathways affects the contraction of the stomach, which may result in delayed gastric emptying and vomiting of retained food. Conversely, alteration of the inhibitory neural pathways results in impaired relaxation of the stomach in response to a meal; in this case increased wall tension may produce early satiation, fullness and nausea. Diabetic neuropathy may distort the control of intestinal motility, which can lead to diverse symptoms such as diarrhoea, constipation, intestinal distension and abdominal pain. Neuropathy in diabetes may also affect the sensory nerves of the gut, and depending on which pathways are involved, perception may be increased or reduced. In summary, in patients with diabetic neuropathy, disorders of gut motor function are associated with sensory abnormalities, and the combination of impaired pathways determines the clinical consequences. This review summarises a presentation given at the 'Diagnosis and treatment of autonomic diabetic neuropathy in the gut' symposium at the 2015 annual meeting of the EASD. It is accompanied by another mini-review on a topic from this symposium (by Hans Törnblom, DOI: 10.1007/s00125-015-3829-9 ) and a commentary by the Session Chair, Péter Kempler (DOI: 10.1007/s00125-015-3826-y ). PMID:26643877

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

    PubMed Central

    Barohn, Richard J.; Katz, Jonathan

    2014-01-01

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

  20. 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

  1. Standard and emerging treatment options for diabetic neuropathy.

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2013-04-01

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

  3. Three-dimensional imaging of lower limb neuropathies.

    PubMed

    Ahlawat, Shivani; Carrino, John A

    2015-04-01

    Peripheral nerve pathology can be detected on high-resolution MRI on the basis of primary or secondary findings. Primary findings of nerve pathology include alterations in signal, course, and caliber; secondary findings include skeletal muscle denervation. Although two-dimensional (2D) MRI sequences comprised of a combination of fluid-sensitive and non-fat-suppressed anatomical sequences can detect changes in nerve size, signal, course, and architecture, three-dimensional (3D) imaging can play an important role in the detection and characterization of nerve pathology including caliber changes at typical compression sites, anomalous course, and nerve discontinuity. This article discusses the benefits of 3D MRI with respect to lower limb neuropathies. The article also reviews the normal anatomy of the nerves in the lower extremity from the hip joint to the foot, and it illustrates common causes and the imaging appearance of lower limb peripheral neuropathy. PMID:25764241

  4. 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 μg/kg body weight (BW), PO, q12h, which was reduced 3 days later to 600 μg/kg BW, q12h due to severe agitation and panting. Two weeks later the dosage of the levothyroxine-sodium (T4) was reduced to 400 μg/kg BW in the morning and 600 μg/kg BW in the evening. Eight weeks after the initial presentation, the dog had recovered with only mild convergent strabismus in the right eye. This is the first case report of suspected hypothyroid-associated neuropathy resulting in these symptoms. PMID:24082164

  5. Practical rules for electrodiagnosis in suspected multifocal motor neuropathy.

    PubMed

    Bromberg, Mark B; Franssen, Hessel

    2015-03-01

    Multifocal motor neuropathy (MMN) with conduction block (CB) is a rare chronic immune-mediated neuropathy, but important to diagnose as it is treatable. The key features in prototypic MMN are electrodiagnostic demonstration of focal CB away from common sites of entrapment and normal sensory conduction across these sites. However, there are challenges in distinguishing CB from the effects of abnormal temporal dispersion. Consensus electrodiagnostic criteria, reinforced by modeling studies, are available to support definite or probable CB. In addition, consideration of technical issues can guard against false-positive and false-negative conclusions. These include limb temperature, stimulus site, inadvertent stimulating electrode movement, and supramaximal and submaximal responses, as well as the possibility of Martin-Gruber anastamosis. Robust evidence supports the treatment of MMN with intravenous immunoglobulin, and guidelines have been developed. Application of practical and simple rules including a 4-step diagnostic algorithm can help practitioners correctly diagnose this treatable condition and improve patient outcomes. PMID:25695919

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

    PubMed Central

    Ko, Seung-Hyun

    2012-01-01

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

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

    PubMed

    López-Blanco, Roberto; Mejía-Jiménez, Inmaculada; de Fuenmayor-Fernández de la Hoz, Carlos Pablo; Ruiz-Morales, Juan

    2015-01-01

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

  8. [Chemotherapy-induced peripheral neuropathy; impact on quality of life].

    PubMed

    Scheel, Anne; Beijers, Antoinetta J M; Mols, Floortje; Faber, Catharina G; Vreugdenhil, Gerard

    2014-01-01

    Peripheral neuropathy is a frequently occurring side-effect of chemotherapy as a cancer treatment. The incidence of chemotherapy-induced peripheral neuropathy (CIPN) is increasing as a consequence of better treatment of cancer becoming available and increasing use of chemotherapy, and because CIPN occurs more frequently with use of new chemotherapeutics. The diagnosis 'CIPN' is made principally on clinical grounds, and it is characterized by predominantly sensory symptoms. The National Cancer Institute Common Toxicity Criteria (NCI-CTC) are commonly used to grade CIPN, but the reliability of these criteria is debated. If CIPN occurs, the only effective strategies are dose reduction or discontinuation of chemotherapy. CIPN impairs quality of life. It is important to evaluate the symptoms of CIPN, as well as the impact on daily living. PMID:25315326

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

    PubMed Central

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

    2010-01-01

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

  10. Hypertrophic neuropathy in Noonan syndrome with multiple lentigines.

    PubMed

    Maridet, Claire; Sole, Guilhem; Morice-Picard, Fanny; Taieb, Alain

    2016-06-01

    RASopathies comprise several genetic syndromes with mainly cardio-facial-cutaneous manifestations. We report a patient with Noonan syndrome with multiple lentigines (NSML) due to a PTPN11 (p.Thr468Met) mutation associated with hypertrophic neuropathy of lumbar plexus in an adult woman, initially referred for neuropathic pain. Differential diagnosis of neurofibromatosis type 1 (NF1) and other RASopathies is difficult without molecular testing. © 2016 Wiley Periodicals, Inc. PMID:26952712

  11. A new device to quantify tactile sensation in neuropathy

    PubMed Central

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

    2011-01-01

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

  12. Charcot-Marie-Tooth disease and related peripheral neuropathies.

    PubMed

    De Jonghe, P; Timmerman, V; Nelis, E; Martin, J J; Van Broeckhoven, C

    1997-01-01

    Soon after the description of Charcot-Marie-Tooth disease (CMT) in 1886, it became apparent that this syndrome is clinically and genetically heterogeneous. Neuropathological and electrophysiological studies have further dissected this syndrome into distinct categories that are now classified in a complex nosology of the inherited peripheral neuropathies. The recent advent of molecular genetics has dramatically increased our understanding of the underlying disease mechanisms. Genetic linkage studies have identified at least 17 genetic loci for different types of inherited neuropathies although most genes involved still remain to be found. The application of molecular genetics has already had an important impact on clinical practice and genetic counselling. Three genes responsible for hereditary motor and sensory neuropathy type I (HMSNI) or CMT1 have been identified: peripheral myelin protein 22 (PMP22) and myelin protein zero (MPZ) for the autosomal dominant form and connexin 32 (Cx32) for the X-linked dominant variant. The PMP22 gene is also involved in the majority of families with hereditary neuropathy with liability to pressure palsies (HNPP). The observation of a 1.5 Mb tandem duplication in chromosome 17p11.2, containing the PMP22 gene, in CMT1 and the reciprocal deletion in the same region in HNPP has provided a novel disease paradigm for autosomal dominant disorders, i.e. the gene dosage mechanism. The study of phenotype-genotype correlations in transgenic animal models for PMP22, MPZ and Cx32 mutations will help elucidate the underlying disease mechanisms and will provide a basis for gene therapy and/or other therapeutic approaches such as treatment with neurotrophic growth factors. PMID:10975746

  13. Postural sway in diabetic peripheral neuropathy among Indian elderly

    PubMed Central

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

    2015-01-01

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

  14. Entrapment neuropathy about the foot and ankle: an update.

    PubMed

    Pomeroy, Gregory; Wilton, James; Anthony, Steven

    2015-01-01

    Occurrences of entrapment neuropathies of the lower extremity are relatively infrequent; therefore, these conditions may be underappreciated and difficult to diagnose. Understanding the anatomy of the peripheral nerves and their potential entrapment sites is essential. A detailed physical examination and judicious use of imaging modalities are also vital when establishing a diagnosis. Once an accurate diagnosis is obtained, treatment is aimed at reducing external pressure, minimizing inflammation, correcting any causative foot and ankle deformities, and ultimately releasing any constrictive tissues. PMID:25538131

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

    PubMed Central

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

    2015-01-01

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

  16. 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

  17. Auditory nerve disease and auditory neuropathy spectrum disorders.

    PubMed

    Kaga, Kimitaka

    2016-02-01

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

  18. Sharpening the Tandem Walking Test for Screening Peripheral Neuropathy

    PubMed Central

    Cohen, Helen S.; Mulavara, Ajitkumar P.; Peters, Brian T.; Sangi-Haghpeykar, Haleh; Kung, Doris H.; Mosier, Dennis R.; Bloomberg, Jacob J.

    2013-01-01

    Objective Few tests of functional motor behavior are useful for rapidly screening people for lower extremity peripheral neuropathy. The goal of this study was to improve the widely used Tandem Walking test (TW). Methods We tested adult normals and ambulatory peripheral neuropathy patients (PN) with eyes open and eyes closed, while they performed TW on industrial carpeting, in sock-covered feet. Each subject wore a torso-mounted inertial motion unit to measure kinematic data. PN subjects’ data were also compared to historical data on patients with vestibular impairments (VI). Results The normal and PN groups differed significantly on TW on the number of steps completed. PN and VI data also differed significantly on both visual conditions. Kinematic data showed that PN patients were more unstable than normals. For the number of steps taken during the eyes open condition receiver operating characteristic (ROC) values were only 0.81. For the number of steps taken during the eyes closed condition, however, ROC=0.88. Although not optimal, this ROC value is better. Sensitivity and specificity at a cut-off of 2 steps were 0.81 and 0.92, respectively, and at a cut-off of 3 steps was 0.86 and 0.75, respectively. ROC values for kinematic data were all < 0.8 and, when combined with the ROC value for the number of steps, the total ROC value did not improve appreciably. Conclusions Although not ideal for screening patients who may have peripheral neuropathy, counting the number of steps during TW is a quick and useful clinical test. TW is most sensitive to peripheral neuropathy patients when they are tested with eyes closed. PMID:24096950

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

    PubMed Central

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

    1970-01-01

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

  20. Induction of p75NGFR in human diabetic neuropathy.

    PubMed

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

    1996-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    SciTech Connect

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

    1994-09-01

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

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

    PubMed

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

    2016-03-01

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

  4. DADS neuropathy associated with anti-TNF-α therapy.

    PubMed

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

    2015-01-01

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

  5. Suramin-induced neuropathy in an animal model.

    PubMed

    Russell, J W; Gill, J S; Sorenson, E J; Schultz, D A; Windebank, A J

    2001-11-15

    Suramin is being used either alone, or in combination with other chemotherapeutic agents, in the treatment of hormone-refractory or metastatic prostate cancer. Use of this potentially valuable chemotherapy is limited by a dose-dependent polyneuropathy. It has been difficult in human studies to characterize peripheral suramin toxicity separately from cancer-related neuropathy. To characterize suramin-induced neuropathy in a rat model, adult rats were given either a single dose of 500 mg/kg (high dose) or 50 mg/kg (low dose) weekly suramin for 2 months. Electrophysiology and peroneal/sural nerve morphometry were performed. In high dose animals, neuropathy developed within 2 weeks, most severe in the digital sensory responses (DSR) (p<0.05) and tail and hind limb compound muscle action potential (p<0.001). Histologically, there was evidence of axonal degeneration and axon atrophy. With low dose suramin, the DSR (p<0.05) and tail distal sensory and motor responses (p<0.01) were most severely affected at 2 months. Axonal degeneration was seen in teased fibers from most animals. With TEM, there were abundant characteristic lysosomal inclusion bodies in DRG and Schwann cells. Electrophysiological and histological evidence of peripheral demyelination was rare, being observed in only one animal. Suramin induced a length, dose and time-dependent axonal sensorimotor polyneuropathy associated with axonal degeneration, atrophy, and accumulation of glycolipid lysosomal inclusions. PMID:11701155

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2013-11-01

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

  9. Pathogenesis of diabetic neuropathy: focus on neurovascular mechanisms.

    PubMed

    Sytze Van Dam, P; Cotter, Mary A; Bravenboer, Bert; Cameron, Norman E

    2013-11-01

    Neuropathies of the peripheral and autonomic nervous systems affect up to half of all people with diabetes, and are major risk factors for foot ulceration and amputation. The aetiology is multifactorial: metabolic changes in diabetes may directly affect neural tissue, but importantly, neurodegenerative changes are precipitated by compromised nerve vascular supply. Experiments in animal models of diabetic neuropathy suggest that similar metabolic sequelae affect neurons and vasa nervorum endothelium. These include elevated polyol pathway activity, oxidative stress, the formation of advanced glycation and lipoxidation end products, and various pro-inflammatory changes such as elevated protein kinase C, nuclear factor κB and p38 mitogen activated protein kinase signalling. These mechanisms do not work in isolation but strongly interact in a mutually facilitatory fashion. Nitrosative stress and the induction of the enzyme poly (ADP-ribose) polymerase form one important link between physiological stressors such as reactive oxygen species and the pro-inflammatory mechanisms. Recently, evidence points to endoplasmic stress and the unfolded protein response as forming another crucial link. This review focuses on the aetiopathogenesis of neurovascular changes in diabetic neuropathy, elucidated in animal studies, and on putative therapeutic targets the majority of which have yet to be tested for efficacy in clinical trials. PMID:23872412

  10. Inflammatory Neuropathy of the Lumbosacral Plexus following Periacetabular Osteotomy

    PubMed Central

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

    2016-01-01

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

  11. Recovery features in ulnar neuropathy at the elbow

    PubMed Central

    Yıldırım, Pelin; Yildirim, Apdullah; Misirlioglu, Tugce Ozekli; Evcili, Gokhan; Karahan, Ali Yavuz; Gunduz, Osman Hakan

    2015-01-01

    [Purpose] This study evaluated the effect of age, sex, and entrapment localization on recovery time in patients treated conservatively for ulnar neuropathy at the elbow. [Subjects] Thirty-five patients (16 women and 15 men) who were diagnosed with ulnar neuropathy at the elbow using short segment conduction studies were evaluated retrospectively. [Methods] Definition of recovey was made based on patient satisfaction. The absence of symptoms was considered as the marker of recovery. Patients who recovered within 0–4 weeks were in Group 1, and patients who recovered within 4 weeks to 6 months were in Group 2. The differences between Group 1 and Group 2 in terms of age, sex and entrapment localization were investigated. [Results] Entrapment was most frequent in the retroepicondylar groove (54.3%). No significant difference was found in terms of age and entrapment localizations between Groups 1 and 2. There was a statistically significant difference between the groups for the male sex. [Conclusion] In ulnar neuropathy at the elbow, age and entrapment localization do not affect recovery time. However, male sex appears to be associated with longer recovery time. PMID:26157226

  12. Mechanisms of distal axonal degeneration in peripheral neuropathies.

    PubMed

    Cashman, Christopher R; Höke, Ahmet

    2015-06-01

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

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

    PubMed

    Koehler, Peter J

    2003-04-01

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

  14. Sciatic Neuropathy: Case Report and Discussion of the Literature on Postoperative Sciatic Neuropathy and Sciatic Nerve Tumors

    PubMed Central

    Sethi, Shikha

    2006-01-01

    Sciatic nerve injury and dysfunction is not an uncommon cause of lower extremity symptoms in a musculoskeletal practice. We present the case of a man who presented with lower extremity weakness, pain, and cramps, and was initially diagnosed at an outside institution with bilateral S1 radiculopathies and recommended for spine surgery. He came to us for a second opinion. Electrodiagnostic testing revealed an isolated sciatic neuropathy and the patient was referred for imaging, which showed a sciatic nerve sheath tumor. Review of the literature on sciatic neuropathies shows that there can be many possible etiologies of sciatic nerve dysfunction, but that hip arthroplasty continues to be the leading risk factor. Sciatic nerve tumors are not commonly described in the literature and their definitive management remains unclear. PMID:18751834

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

    ClinicalTrials.gov

    2015-04-28

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

  16. [Segmental testicular infarction. Unusual complication of intravenous immunoglobulin therapy for multifocal motor neuropathy].

    PubMed

    Rüb, J; Rehmann, R; von Landenberg, N; Roghmann, F; Stude, P; Tegenthoff, M; Noldus, J; Pastor, J

    2015-10-01

    We describe the previously unknown case of segmental testicular infarction as an iatrogenic complication of intravenous immunoglobulin administration in a patient with multifocal motor neuropathy. PMID:26303740

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

    PubMed

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

    2014-01-01

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

  18. 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

  19. Genetic evaluation of inherited motor/sensory neuropathy.

    PubMed

    Chance, Phillip F

    2004-01-01

    Inherited disorders of peripheral nerves represent a common group of neurologic diseases. Charcot-Marie-Tooth neuropathy type 1 (CMT1) is a genetically heterogeneous group of chronic demyelinating polyneuropathies with loci mapping to chromosome 17 (CMT1A), chromosome 1 (CMT1B), chromosome 16 (CMT1C) and chromosome 10 (CMT1D). CMT1A is most often associated with a tandem 1.5-megabase (Mb) duplication in chromosome 17p11.2-p12. In rare patients it may result from a point mutation in the peripheral myelin protein-22 (PMP22) gene. CMT1B is associated with point mutations in the myelin protein zero (Po or MPZ) gene. Mutations in the SIMPLE gene cause CMT1C, and CMT1D is the result of mutations in the early response 2 (ERG2 or Krox-20) gene. An X-linked form of CMT1 (CMT1X) maps to Xq13 and is associated with mutations in the connexin32 (Cx32) gene. Charcot-Marie-Tooth neuropathy type 2 (CMT2) is an axonal neuropathy that maps to chromosome 1p35-p36 (CMT2A), chromosome 3q13-q22 (CMT2B), chromosome 7p14 (CMT2D), chromosome 8p21 (CMT2E), chromosome 1q22-q23 (CMT2F) or chromosome 3q13 (CMT2G). Two X-linked forms of CMT2 have been reported (CMT2XA and CMT2XB), but the genes remain unidentified. An area that has recently expanded is the identification of autosomal recessive forms of CMT type 1 and 2. Of the eight recessive forms of CMT1 that have been identified to date, only two have been fully characterized at the molecular level (CMT1 AR B 1 and CMT1 AR D). Point mutations were found in the myotubularin-related protein-2 (MTM2) gene for CMT1 AR B1. CMT1 AR D is the result of point mutations in the N-myc downstream-regulated gene 1 (NDRG1). Dejerine-Sottas disease (DSD), also called hereditary motor and sensory neuropathy type III (HMSNIII), is a severe, infantile-onset demyelinating polyneuropathy syndrome that may be associated with point mutations in either the PMP22 gene, PO gene, EGR2 gene or the PRX gene (for the recessive form). It shares considerable clinical and pathological features with CMT1. Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder that results in a recurrent, episodic demyelinating neuropathy. HNPP is associated with a 1.5-Mb deletion in chromosome 17p11.2-p12 that results in reduced expression of the PMP22 gene. CMT1A and HNPP are reciprocal duplication/deletion syndromes that originate from unequal crossover during germ cell meiosis. Other rare forms of demyelinating peripheral neuropathies map to chromosome 8q, 10q and 11q. PMID:16106622

  20. The identification of gene expression profiles associated with progression of human diabetic neuropathy

    PubMed Central

    Hur, Junguk; Sullivan, Kelli A.; Pande, Manjusha; Hong, Yu; Sima, Anders A. F.; Jagadish, Hosagrahar V.; Kretzler, Matthias

    2011-01-01

    Diabetic neuropathy is a common complication of diabetes. While multiple pathways are implicated in the pathophysiology of diabetic neuropathy, there are no specific treatments and no means to predict diabetic neuropathy onset or progression. Here, we identify gene expression signatures related to diabetic neuropathy and develop computational classification models of diabetic neuropathy progression. Microarray experiments were performed on 50 samples of human sural nerves collected during a 52-week clinical trial. A series of bioinformatics analyses identified differentially expressed genes and their networks and biological pathways potentially responsible for the progression of diabetic neuropathy. We identified 532 differentially expressed genes between patient samples with progressing or non-progressing diabetic neuropathy, and found these were functionally enriched in pathways involving inflammatory responses and lipid metabolism. A literature-derived co-citation network of the differentially expressed genes revealed gene subnetworks centred on apolipoprotein E, jun, leptin, serpin peptidase inhibitor E type 1 and peroxisome proliferator-activated receptor gamma. The differentially expressed genes were used to classify a test set of patients with regard to diabetic neuropathy progression. Ridge regression models containing 14 differentially expressed genes correctly classified the progression status of 92% of patients (P < 0.001). To our knowledge, this is the first study to identify transcriptional changes associated with diabetic neuropathy progression in human sural nerve biopsies and describe their potential utility in classifying diabetic neuropathy. Our results identifying the unique gene signature of patients with progressive diabetic neuropathy will facilitate the development of new mechanism-based diagnostics and therapies. PMID:21926103