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Toxic optic neuropathy  

PubMed Central

Toxic optic neuropathy (TON) is a disease entity which is not only underdiagnosed, but also often diagnosed at a stage when recovery of vision is not possible. This article gives an overview of common causes, clinical features, and management of TON.

Sharma, Pradeep; Sharma, Reena



Inherited Optic Neuropathies  

Microsoft Academic Search

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

Marcela Votruba


Radiation optic neuropathy  

SciTech Connect

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.

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



Radiation-induced optic neuropathy  

Microsoft Academic Search

Radiation-induced optic neuropathy (RION) is a devastating late complication of radiotherapy to the anterior visual pathway resulting in acute, profound, irreversible visual loss. It is thought to be a result of radiation necrosis of the anterior visual pathway. Visual loss may be unilateral or bilateral; simultaneous or sequential. RION occurs commonly between 10-20 months, with an average of 18 months

Helen V. Danesh-Meyer



Calciphylaxis and bilateral optic neuropathy.  


A 51-year-old woman on hemodialysis for chronic renal failure complained of visual loss in her right eye. Right optic disc edema was observed on fundus examination. An arteritic optic neuropathy was suspected. However, a first biopsy did not reveal any inflammatory cells. Two months later, the patient experienced sudden visual loss in her left eye and presented with necrotic cutaneous lesions at the distal phalanges of several fingers of the right hand. Necrotic lesions also appeared on the inner aspect of the thighs. Biopsy of the cutaneous lesions revealed calcification in the wall of a small artery. A new biopsy of the temporal artery showed large calcium deposits in the artery's tunica media. The diagnosis of optic neuropathy secondary to calciphylaxis was made. A temporal artery biopsy should be repeated if the first one is inconclusive. An early diagnosis leading to appropriate treatment may help to prevent an irreversible loss of vision in these patients. PMID:21680055

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



Management of ischemic optic neuropathies  

PubMed Central

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

Hayreh, Sohan Singh



Leber's hereditary optic neuropathy mutations in ethambutol-induced optic neuropathy.  


Primary mitochondrial DNA (mtDNA) mutation at the nt 11778 site in Leber's hereditary optic neuropathy (LHON) has been reported to be present in patients with ethambutol-induced optic neuropathy. To study further this association between LHON and ethambutol-induced optic neuropathy, we tested ethambutol-induced optic neuropathy patients for the presence of the mtDNA mutations at nucleotides (nt)-11778, nt-14484, nt-3460, nt-15257, nt-9438, nt-9804, nt-13730, and nt-14459 in 24, 15, 8, 6, 5, 5, 5, and 5 patients respectively. However, none of the ethambutol-induced optic neuropathy patients was found to exhibit any pathogenic LHON mtDNA mutation. In conclusion, we found no evidence of any association between ethambutol-induced optic neuropathy and the LHON mutations. PMID:12527998

Hwang, Jeong-Min; Kim, Jiyeon; Park, Sung Sup



Mitochondrial optic neuropathies: additional facts and concepts.  


I feel it necessary to make some comment in relation to the excellent article by Sadun and collaborators [doi: 10.1111/ceo.12086] published recently in Clinical and Experimental Ophthalmology(1) and related to a lecture given by Professor Sadun in 2012. It should be said that these authors are considered to be leading experts in the field of mitochondrial optic neuropathies but nevertheless would like to make certain points. It is stated that "tobacco-alcohol amblyopia" and general nutritional deficiencies, constitute a mixed version of an acquired Mitochondrial Optic Neuropathy. However, Carroll(2) demonstrated many years ago that the ocular symptoms of tobacco-alcohol optic neuropathy were attenuated with vitamin B treatment. A partial or full restoration of vision occurred even when tobacco and alcohol intake still occurred.(2) Also, similar ocular manifestations as associated with tobacco-alcohol amblyopia occurred in undernourished individuals during and immediately after World War I and II. Alcohol optic neuropathy is therefore a nutritional optic neuropathy. It might be that it is exacerbated through the toxic influences of alcohol and tobacco constituents to optic nerve function but present evidence strongly suggests that "alcohol-tobacco amblyopia" is not a specific type of optic neuropathy.(3.) PMID:23777247

Grzybowski, Andrzej



Chlamydia in Anterior Ischemic Optic Neuropathy  

Microsoft Academic Search

There is an increasing body of evidence linking the common respiratory human pathogen Chlamydia pneumoniae with atherosclerosis and other vascular disorders. Our research was designed to investigate the association of this organism with anterior ischemic optic neuropathy (AION), representing an acute ischemic disorder of the optic nerve head. Sera were examined of 14 consecutive patients with AION and of 14

Pia V. Vécsei; Karl Kircher; Andreas Reitner; Gelas Khanakha; Gerold Stanek



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

PubMed Central

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

Farmer, Kevin L.; Li, Chengyuan



Pegylated Interferon Alpha-Associated Optic Neuropathy  

PubMed Central

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

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



MRI findings in chronic relapsing inflammatory optic neuropathy.  


Chronic relapsing inflammatory optic neuropathy is a steroid responsive recurrent optic neuropathy. We describe a patient who presented with recurrent episodes of painful visual loss over a period of 19 years and atypical findings on cranial MRI. PMID:23417378

Sharma, Ankush; Khurana, Dheeraj; Kesav, Praveen



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

PubMed Central

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

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



Postirradiation optic neuropathy in antral carcinoma  

SciTech Connect

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.

Singh, J.; Vashist, S.



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

PubMed Central

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

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



Mitochondrial Abnormalities in Patients with LHON-like Optic Neuropathies  

Microsoft Academic Search

PURPOSE. To investigate certain biochemical and molecular characteristics of mitochondria in patients with Leber heredi- tary optic neuropathy (LHON)-like optic neuropathies. METHODS. Patients who had LHON-like optic neuropathies in both eyes were selected from neuro-ophthalmology clinics. Evaluation included clinical examination, neuroimaging, and assessment of several mitochondrial parameters in the blood, including sequencing the entire mitochondrial (mt)DNA cod- ing region, measuring

Khaled K. Abu-Amero; Thomas M. Bosley



Histopathologic studies of ischemic optic neuropathy.  

PubMed Central

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

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



Anterior Ischemic Optic Neuropathy Associated with Udenafil  

PubMed Central

We report a case of anterior ischemic optic neuropathy associated with udenafil. A 54-year-old male presented with an acute onset visual field defect of the right eye after udenafil use. Examination revealed a relative afferent pupillary defect and a swollen disc. Automated visual fields revealed an enlarged blind spot and a narrowed visual field. Fluorescein angiography revealed both an inferior choroidal filling delay and an inferior sector filling delay of the optic disc in the arteriovenous phase as well as diffuse leakage of the optic disc in the late phase. Optical coherent tomography revealed increased thickness of the retinal nerve fiber layer, especially in the area of the inferior disc. The patient was counseled to discontinue the use of udenafil and to monitor his blood pressure regularly. The disc swelling was resolved with residual optic atrophy one month after discontinuing the use of udenafil.

Kim, In-Gun



A review of primary hereditary optic neuropathies.  


The primary inherited optic neuropathies are a heterogeneous group of disorders that result in loss of retinal ganglion cells, leading to the clinical appearance of optic atrophy. They affect between 1:10,000 to 1:50,000 people. The main clinical features are a reduction in visual acuity, colour vision abnormalities, centro-caecal visual field defects and pallor of the optic nerve head. Electrophysiological testing shows a normal flash electroretinogram, absent or delayed pattern visually evoked potentials suggestive of a conduction deficit and N95 waveform reduction on the pattern electroretinogram, consistent with a primary ganglion cell pathology. The primary inherited optic neuropathies may be sporadic or familial. The mode of inheritance may be autosomal dominant, autosomal recessive, X-linked recessive or mitochondrial. Within each of these groups, the phenotypic characteristics vary in such features as the mode and age of onset, the severity of the visual loss, the colour deficit and the overall prognosis. A number of different genes (most as yet unidentified) in both nuclear and mitochondrial genomes, underlie these disorders. The elucidation of the role of the encoded proteins will improve our understanding of basic mechanisms of ganglion cell development, physiology and metabolism and further our understanding of the pathophysiology of optic nerve disease. It will also improve diagnosis, counselling and management of patients, and eventually lead to the development of new therapeutic modalities. PMID:12889662

Votruba, M; Aijaz, S; Moore, A T



Treatment of Nonarteritic Anterior Ischemic Optic Neuropathy  

PubMed Central

Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common clinical presentation of acute ischemic damage to the optic nerve. Most treatments proposed for NAION are empirical and include a wide range of agents presumed to act on thrombosis, on the blood vessels, or on the disc edema itself. Others are presumed to have a neuroprotective effect. Although there have been multiple therapies attempted, most have not been adequately studied, and animal models of NAION have only recently emerged. The Ischemic Optic Neuropathy Decompression Trial (IONDT), the only class I large multicenter prospective treatment trial for NAION, found no benefit from surgical intervention. One recent large, nonrandomized controlled study suggested that oral steroids might be helpful for acute NAION. Others recently proposed interventions are intravitreal injections of steroids or anti-vascular endothelial growth factor (anti-VEGF) agents. There are no class I studies showing benefit from either medical or surgical treatments. Most of the literature on the treatment of NAION consists of retrospective or prospective case series and anecdotal case reports. Similarly, therapies aimed at secondary prevention of fellow eye involvement in NAION remain of unproven benefit.

Atkins, Edward J.; Bruce, Beau B.; Newman, Nancy J.; Biousse, Valerie



A biotinidase Km variant causing late onset bilateral optic neuropathy  

Microsoft Academic Search

A patient with a newly recognised variant of biotinidase deficiency presented with acute loss of vision at the age of 10 years. Progressive bilateral optic neuropathy, spastic paraparesis, and a predominantly motor type neuropathy developed over the next five years. Metabolic investigations revealed biotin depletion causing multiple carboxylase deficiency. The basic defect was a biotin recycling disorder due to a

V T Ramaekers; T M Suormala; M Brab; R Duran; G Heimann; E R Baumgartner



Spheniodal mucocele causing bilateral optic neuropathy and ophthalmoplegia.  


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

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



[Current concepts in the pathogenesis of glaucomatous optic neuropathy].  


On the basis of review of available literature, the concept of vascular dysregulation, excitotoxicity in the pathogenesis of glaucoma, and influence of intraocular pressure and immunology system on mechanism of glaucomatous optic neuropathy was described. PMID:14552189

Chmielewska, Katarzyna



Chlamydia in anterior ischemic optic neuropathy.  


There is an increasing body of evidence linking the common respiratory human pathogen Chlamydia pneumoniae with atherosclerosis and other vascular disorders. Our research was designed to investigate the association of this organism with anterior ischemic optic neuropathy (AION), representing an acute ischemic disorder of the optic nerve head. Sera were examined of 14 consecutive patients with AION and of 14 age- and sex-matched control subjects with noncardiovascular, nonpulmonary disorders. Antibodies against chlamydial lipopolysaccharide (LPS) and outer membrane proteins of C. pneumoniae were determined by ELISA. Further, nucleic acid amplification tests were done in order to detect C. pneumoniae-specific nucleotide sequences. Four patients (29%) were IgA positive, 11 (79%) were IgG positive and 1 (7%) was IgM positive for chlamydial LPS antibodies. In the control group, 36, 79 and 7% were IgA, IgG and IgM positive and showed no significant difference. IgA, IgG and IgM antibodies to C. pneumoniae were found in 43, 79 and 0% and did not differ from matched controls. By the nucleic acid amplification test, specific C. pneumo niae sequences were neither detected in the AION patients nor in the control group. These data do not support the association of AION with previous C. pneumoniae infection. However, it remains unclear whether Chlamydia actually initiates atherosclerotic injury, facilitates its progression or plays another role in other vascular disorders. PMID:12065860

Vécsei, Pia V; Kircher, Karl; Reitner, Andreas; Khanakha, Gelas; Stanek, Gerold


Reversal of dysthyroid optic neuropathy following orbital fat decompression  

PubMed Central

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

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



Multifocal visual-evoked potential in unilateral compressive optic neuropathy  

PubMed Central

Aim To evaluate the effects of unilateral compressive optic neuropathy on amplitude and latency of multifocal visual evoked potentials (mfVEPs). Methods Static automated perimetry and mfVEP recordings were obtained from six patients with presumed meningiomas affecting one optic nerve. Monocular and interocular amplitude and latency analyses were performed and compared with normal control subjects. Results The change in the mfVEP amplitude agreed with visual field findings with regard to topography and severity of deviation from normal. The delay in recordable responses from affected eyes ranged from 7.6 to 20.7?ms (interocular analysis) and 7.9 to 13.9?ms (monocular analysis). Conclusions Compressive optic neuropathy decreases the amplitude and increases the latency of the mfVEP. The changes in latency were similar to those seen in optic neuritis but larger than those in ischaemic optic neuropathy and glaucoma.

Semela, Linda; Yang, E Bo; Hedges, Thomas R; Vuong, Laurel; Odel, Jeffery G; Hood, Donald C



Visual field defects in optic neuritis and anterior ischemic optic neuropathy: distinctive features  

Microsoft Academic Search

•   Background: We analyzed the value of visual field defects in the differential diagnosis of optic neuritis (ON) and non-arteritic\\u000a anterior ischemic optic neuropathy (AION).?• Methods: Ninety-nine consecutive patients with acute-onset optic neuropathy formed\\u000a the basis for this study. Compressive and vasculitic neuropathies were excluded. Eighty-six patients fulfilled the criteria\\u000a for either ON (50 patients): ? 35 years, normal disk,

J. Gerling; Jörg Heinrich Meyer; Guntram Kommerell



Nutritional optic and peripheral neuropathy: a case report  

PubMed Central

Introduction The link between nutritional status and either optic or peripheral neuropathies is well established with tobacco, ethanol, deficiencies in thiamine, vitamin A, B12, B3 and B6 and protein-energy malnutrition all being causative. Case presentation We describe the case of a 32-year-old Afro-Caribbean of Jamaican origin presenting with blurred vision and a painful burning sensation in his feet. The clinical features were consistent with optic and peripheral neuropathy. Conclusions The patient followed a strict vegan diet and consumed no animal products. A review of the literature highlights similarities between this case and Strachan's syndrome, a combination of optic and peripheral neuropathy and cutaneous excoriation, providing further evidence for the association between this clinical presentation, dietary deficiency and, as recently postulated, previous residence in a tropical or sub-tropical climate.

Paviour, Dominic C



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

PubMed Central

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

Poole, C J; Kind, P R



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

PubMed Central

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.



Oestrogens ameliorate mitochondrial dysfunction in Leber's hereditary optic neuropathy  

PubMed Central

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

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



The role of transcranial Doppler in nonarteritic ischemic optic neuropathy  

Microsoft Academic Search

PURPOSE: To investigate through the use of cerebral Doppler technology whether emboli are a more common cause of nonarteritic anterior ischemic optic neuropathy (NAION) than previously recognized.METHODS: Eleven patients with a recent (121 days) were examined using a Nicolet Pioneer 2020 transcranial Doppler (TCD) unit with a 2-MHz bilateral continuous monitoring capability. The right and left middle cerebral arteries were

G. Kosmorsky; J. Straga; C. Knight; A. Dagirmanjian; D. A. Davis



Crohn's Disease Initially Accompanied by Deep Vein Thrombosis and Ulnar Neuropathy without Metronidazole Exposure  

PubMed Central

Extraintestinal manifestations are not uncommon in Crohn's disease, and a thromboembolic event is a disastrous potential complication. Deep vein thrombosis is the most common manifestation of a thromboembolic event and typically occurs in association with active inflammatory disease. Peripheral neuropathy in Crohn's disease has rarely been reported and is considered an adverse effect of metronidazole therapy. Here, we describe a patient who was initially diagnosed with Crohn's disease complicated with deep vein thrombosis and ulnar neuropathy without metronidazole exposure. The simultaneous occurrence of these complications in the early stage of Crohn's disease has never been reported in the English literature.

Kim, Woohyeon; Kang, Borami; Kim, Joon Sung; Lee, Hae-Mi; Lim, Eun-Joo; Kim, Jong In; Kang, Bong-Koo; Ji, Jeong-Seon; Lee, Bo-In; Choi, Hwang



Amiodarone-Associated Optic Neuropathy: A Critical Review  

PubMed Central

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

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



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

PubMed Central

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

Ziaei, Mohammed M.; Ziaei, Hadi



Optic neuropathy in patient with Wegener's granulomatosis.  


A 32-year-old white male presented to the Jones Eye Institute at the University of Arkansas for Medical Sciences with blurred vision of the right eye (OD) and severe bilateral retrobulbar pain. He had an eight-year history of Wegener's granulomatosis. On examination there was optic disc edema OD and extensive bilateral orbital involvement with compression of the right optic nerve by neuroimaging studies. Optic nerve compression is rare in Wegener's granulomatosis. The ophthalmic manifestations are reviewed. PMID:15200283

Lovelace, Kirn; Cannon, Thomas C; Flynn, Steven; Davis, Pomona; Schmucker, Tracey; Westfall, Christopher T



Nutritional optic and peripheral neuropathy: a case report  

Microsoft Academic Search

INTRODUCTION: The link between nutritional status and either optic or peripheral neuropathies is well established with tobacco, ethanol, deficiencies in thiamine, vitamin A, B12, B3 and B6 and protein-energy malnutrition all being causative. CASE PRESENTATION: We describe the case of a 32-year-old Afro-Caribbean of Jamaican origin presenting with blurred vision and a painful burning sensation in his feet. The clinical

Laura M Nightingale; Dominic C Paviour



Leber’s hereditary optic neuropathy and vitamin B12 deficiency  

Microsoft Academic Search

Background  Leber’s hereditary optic neuropathy (LHON) is a maternally inherited optic neuropathy caused by mutations in mitochondrial DNA (mtDNA). It is also believed that several epigenetic factors have an influence on the development of LHON.Methods  A case series was observed.Results  Three patients who developed bilateral optic neuropathy are presented. All patients had a primary LHON mutation in their mtDNA, but also a subnormal

Jan Willem R. Pott; Kwok H. Wong



Mitochondrial DNA Mutation Associated with Leber's Hereditary Optic Neuropathy  

NASA Astrophysics Data System (ADS)

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.

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



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


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

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



Bilateral Ischemic Optic Neuropathy Developed under Interferon Therapy.  


Introduction. Interferon is a glycoprotein produced by assigned cells of immune system. It has been used in many different diseases. Although flu-like syndrome, myalgia, rash, hypotension, thrombocytopenia and peripheral neuropathy due to interferon use are encountered frequently, ocular side effects are rare, generally mild and transient. Case Report. 47-year-old female patient, presented with a mass lesion in right renal pelvis. Right radical nephrectomy was applied and the histopathological examination was consistent with papillary renal cell carcinoma. Interferon alpha treatment was started subcutaneously at the dose of 5?MIU/3 times in a week. Four weeks after the interferon therapy, suddenly bilateral visual loss developed. We discussed the diagnosis, followup, and treatment of the patient who developed irreversible ischemic optic neuropathy and had no previous known primary systemic disease to cause this condition. Conclusion. We suggest that patients should be screened for risk factors causing optic ischemic neuropathy, before interferon therapy. Although there was no adequate information in the literature for the followup, patients should be monitorized before, 1 month after, and 2 months after the treatment. And if there is no complication, we suggest that they should be followed up at 3-month intervals. PMID:23119208

Selcukbiricik, Fatih; Tural, Deniz; Senel, Tuba Elif; Sar?ca, Ahmet; Soyluk, Ozlem; Serdengecti, Suheyla



Bilateral Ischemic Optic Neuropathy Developed under Interferon Therapy  

PubMed Central

Introduction. Interferon is a glycoprotein produced by assigned cells of immune system. It has been used in many different diseases. Although flu-like syndrome, myalgia, rash, hypotension, thrombocytopenia and peripheral neuropathy due to interferon use are encountered frequently, ocular side effects are rare, generally mild and transient. Case Report. 47-year-old female patient, presented with a mass lesion in right renal pelvis. Right radical nephrectomy was applied and the histopathological examination was consistent with papillary renal cell carcinoma. Interferon alpha treatment was started subcutaneously at the dose of 5?MIU/3 times in a week. Four weeks after the interferon therapy, suddenly bilateral visual loss developed. We discussed the diagnosis, followup, and treatment of the patient who developed irreversible ischemic optic neuropathy and had no previous known primary systemic disease to cause this condition. Conclusion. We suggest that patients should be screened for risk factors causing optic ischemic neuropathy, before interferon therapy. Although there was no adequate information in the literature for the followup, patients should be monitorized before, 1 month after, and 2 months after the treatment. And if there is no complication, we suggest that they should be followed up at 3-month intervals.

Selcukbiricik, Fatih; Tural, Deniz; Senel, Tuba Elif; Sar?ca, Ahmet; Soyluk, Ozlem; Serdengecti, Suheyla



Radiation-induced optic neuropathy: A magnetic resonance imaging study  

SciTech Connect

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.

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



Mitochondrial optic neuropathies - Disease mechanisms and therapeutic strategies  

PubMed Central

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.

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



Diffusion Tensor Imaging in Acute Optic Neuropathies  

PubMed Central

Objective To evaluate directional diffusivities within the optic nerve in a first event of acute optic neuritis to determine whether decreased axial diffusivity (AD) would predict 6-month visual outcome and optic nerve integrity measures. Design Cohort study. Setting Academic multiple sclerosis center. Patients Referred sample of 25 individuals who presented within 31 days after acute visual symptoms consistent with optic neuritis. Visits were scheduled at baseline, 2 weeks, and 1, 3, 6, and 12 months. Main Outcome Measures Visual acuity, contrast sensitivity, visual evoked potentials (VEPs), and thickness of the retinal nerve fiber layer (RNFL). Results An incomplete 6-month visual recovery was associated with a lower baseline AD (1.50 ?m2/ms [95% confidence interval {CI}, 1.36–1.64 ?m2/ms for incomplete recovery vs 1.75 ?m2/ms [95% CI, 1.67–1.83 ?m2/ms] for complete recovery). Odds of complete recovery decreased by 53% (95% CI, 27%–70%) for every 0.1-unit decrease in baseline AD. A lower baseline AD correlated with worse 6-month visual outcomes in visual acuity (r=0.40, P=.03), contrast sensitivity (r=0.41, P=.02), VEP amplitude (r=0.55, P<.01), VEP latency (r=?0.38, P=.04), and RNFL thickness (r=0.53, P=.02). Radial diffusivity increased between months 1 and 3 to become higher in those with incomplete recovery at 12 months than in those with complete recovery (1.45 ?m2/ms [95% CI, 1.31–1.59 ?m2/ms] vs 1.19 ?m2/ms [95% CI, 1.10–1.28 ?m2/ms]). Conclusions Decreased AD in acute optic neuritis was associated with a worse 6-month visual outcome and correlated with VEP and RNFL measures of axon and myelin injury. Axial diffusivity may serve as a marker of axon injury in acute white matter injury.

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



A retrospective review of 26 cases of dysthyroid optic neuropathy  

SciTech Connect

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.

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




PubMed Central

We present a case of acute traumatic optic neuropathy in 54 year old male patient. The patient presented with acute loss of vision in the right eye due to a blunt trauma to the eye. Lid haematoma and subconjunctival hemorrhage were present. Fluorescein staining was negative, anterior chamber and lens was clear. Intraocular pressure was normal. Retina and optic nerve head appeared normal on fundoscopy. The vision was “counting fingers at 1 meter” in the right eye. Color test indicated color perception dysfunction of the right eye. Relative afferent pupillary defect (RAPD) was positive. Ocular ultrasound, orbital X ray and CT scan was normal, but visual evoked potentials test was pathologic. The consideration was made whether to treat a patient or not since there are no consensus on the treatment of traumatic optic neuropathy. We decided to treat the patient immediately with the megadoses of steroids following the protocol suggested by Cerovski. The patient responded well to the treatment and recovered vision to normal.

Samardzic, Kristian; Samardzic, Josip; Janjetovic, Zeljka; Samardzic, Ivan; Sekelj, Sandra; Latic-Hodzic, Leila



The role of copper on ethambutol's antimicrobial action and implications for ethambutol-induced optic neuropathy.  


The principal side effect of the antimycobacterial agent ethambutol (EMB) is an optic neuropathy with clinical features very similar to a mitochondrial hereditary optic neuropathy (Leber's). The mechanism of EMB-induced optic neuropathy may be EMB's chelation of copper, thereby precluding normal cytochrome c oxidase activity and mitochondrial metabolism in the optic nerve. Before attempting to use therapeutic copper to replenish endogenous stores in an attempt to preclude EMB-induced optic neuropathy, we wished to determine whether EMB is still effective against mycobacteria in the presence of copper. EMB and copper, alone and in combination, were tested against six strains of Mycobacterium tuberculosis and five strains of Mycobacterium avium using a radiometric broth macrodilution assay. Copper did not effect EMB's antimicrobial actions against either species of mycobacteria. This in vitro study suggests that if copper were given to patients to prevent EMB-induced optic neuropathy, it would not compromise EMB's bacteriostatic properties. PMID:9554173

Kozak, S F; Inderlied, C B; Hsu, H Y; Heller, K B; Sadun, A A



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


Optic neuropathy refers to dysfunction and/or degeneration of axons of the optic nerve with subsequent optic nerve atrophy. A common feature of different optic neuropathies is retinal ganglion cell (RGC) apoptosis and axonal damage. Glaucoma and optic neuritis are the two major degenerative causes of optic nerve damage. Here, we review the anatomy and pathology of the optic nerve, and etiological categories of optic neuropathies, and discuss rodent models that can mimic these conditions. Electrophysiology can reveal signature features of RGC damage using the pattern electroretinogram (PERG), scotopic threshold response (STR) and photopic negative response (PhNR). The amplitude of the visual evoked potential (VEP) also reflects RGC axonal damage. The neurotrophin-mediated survival pathways, as well as the extrinsic and intrinsic cell apoptotic pathways, play a critical role in the pathogenesis of RGC loss. Finally, promising neuroprotective approaches based on the molecular signaling are analyzed for the treatment of optic neuropathies. PMID:23612594

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



Evaluation of acute radiation optic neuropathy by B-scan ultrasonography  

SciTech Connect

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.

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



Bilateral consecutive optic neuropathy in a patient with thrombophilia.  


A 39-year-old man was admitted with a sudden visual loss in the left eye. Visual acuities were 10/10 on the right and 1/10 on the left. Fundus examination did not show any abnormalities. Visual acuity improved to 10/10 and visual field defect regressed in the following 2 weeks. Three years later, the patient returned with acute visual loss in the right eye. Visual acuities were 2/10 on the right and 10/10 on the left. Right optic disc had blurred margins with mild oedema. The tests revealed methylenetetrahydrofolate reductase A1298C mutation with positive lupus anticoagulant and hyperhomocysteinaemia. Enoxaparin was initialised with vitamin B12 supplementation. Complete visual recovery occurred in the following 3 weeks in both eyes. Thrombophilic screening seems to be important in the treatment and prevention of an attack in the second eye of patients with non-arteritic anterior ischaemic optic neuropathy. PMID:23771968

Ornek, Nurgül; Onaran, Zafer; Ornek, Kemal; Büyüktortop, Nesrin



Can intramuscular corticosteroid injection cause nonarteritic anterior ischemic optic neuropathy?  

PubMed Central

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

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



Imaging studies for diagnosing Graves' orbitopathy and dysthyroid optic neuropathy  

PubMed Central

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

Goncalves, Allan C. Pieroni; Gebrim, Eloisa M. M. S.; Monteiro, Mario L. R.



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


DNA samples of 50 patients with optic neuropathy (ON) associated with congenital cataract were studied to find 3 major mt-DNA mutations (m.11778G>A, m.3460G>A, m.14484T>C), mutations in "hot" regions of OPA 1 gene (exons 8, 14, 15, 16, 18, 27, 28) and in the entire coding sequence of OPA3 gene for molecular genetic confirmation of diagnosis of hereditary Leber and autosomal dominant ON. Primary mutations of mtDNA responsible for hereditary Leber ON were found in 16 patients (32%). Pathogenic mutations of OPAl gene (c.869G>A and c. 2850delT) were identified in 2 patients (4%), these mutations were not found in the literature. OPA3 gene mutations were not revealed. PMID:23808173

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


Optic disc edema in non-arteritic anterior ischemic optic neuropathy  

Microsoft Academic Search

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

Sohan Singh Hayreh; M. Bridget Zimmerman



A case of anterior ischemic optic neuropathy associated with uveitis  

PubMed Central

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

Sugahara, Michitaka; Fujimoto, Takayuki; Shidara, Kyoko; Inoue, Kenji; Wakakura, Masato



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


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

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



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


Leber's hereditary optic neuropathy (LHON) is characterized by retinal ganglion cell (RGC) degeneration with the preferential involvement of those forming the papillomacular bundle. The optic nerve is considered the main pathological target for LHON. Our aim was to investigate the possible involvement of the post-geniculate visual pathway in LHON patients. We used diffusion-weighted imaging for in vivo evaluation. Mean diffusivity maps from 22 LHON visually impaired, 11 unaffected LHON mutation carriers and 22 healthy subjects were generated and compared at level of optic radiation (OR). Prefrontal and cerebellar white matter were also analyzed as internal controls. Furthermore, we studied the optic nerve and the lateral geniculate nucleus (LGN) in post-mortem specimens obtained from a severe case of LHON compared to an age-matched control. Mean diffusivity values of affected patients were higher than unaffected mutation carriers (P<0.05) and healthy subjects (P<0.01) in OR and not in the other brain regions. Increased OR diffusivity was associated with both disease duration (B?=?0.002; P<0.05) and lack of recovery of visual acuity (B?=?0.060; P<0.01). Post-mortem investigation detected atrophy (41.9% decrease of neuron soma size in the magnocellular layers and 44.7% decrease in the parvocellular layers) and, to a lesser extent, degeneration (28.5% decrease of neuron density in the magnocellular layers and 28.7% decrease in the parvocellular layers) in the LHON LGN associated with extremely severe axonal loss (99%) in the optic nerve. The post-geniculate involvement in LHON patients is a downstream post-synaptic secondary phenomenon, reflecting de-afferentation rather than a primary neurodegeneration due to mitochondrial dysfunction of LGN neurons. PMID:23209682

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



Secondary Post-Geniculate Involvement in Leber's Hereditary Optic Neuropathy  

PubMed Central

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

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



Role of Adenosine Receptor A2A in Traumatic Optic Neuropathies.  

National Technical Information Service (NTIS)

Our goal is to develop an early therapeutic intervention before the progression of traumatic optic neuropathy (TON), a vision-threatening complication in head injury, becomes irreversible. Under the stress of TON, extracellular levels of adenosine increas...

G. I. Liou M. Naime N. Fatteh S. Ahmad S. Khan



Leber hereditary optic neuropathy, progressive visual loss, and multiple-sclerosis-like symptoms  

Microsoft Academic Search

PURPOSE: To report a case of Leber hereditary optic neuropathy with multiple-sclerosis-like symptoms.METHODS: Observational case report. A 34-year-old man was found to have Leber hereditary optic neuropathy and a mutation at position 11778 of the mitochondrial genome. The progression of vision loss and onset of weakness in the right leg warranted neuroimaging.RESULTS: Magnetic resonance imaging documented multiple lesions in the

Mai Tran; Ravi Bhargava; Ian M MacDonald



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

PubMed Central

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

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



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

Microsoft Academic Search

For diagnosing radiation optic neuropathy (RON) ophthalmological and imaging data were evaluated from 63 acromegalic patients, irradiated between 1967 and 1998. Two patients developed RON: one patient in one optic nerve 10 years and another patient in both optic nerves 5 months after radiation therapy. RON is a rare complication after external beam radiation therapy for acromegaly, which can occur

Alfons C. M van den Bergh; Marjanke A Hoving; Thera P Links; Robin P. F Dullaart; Adelita V Ranchor; Cees A ter Weeme; Alof A Canrinus; Ben G Szabó; Jan-Willem R Pott



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

PubMed Central

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.

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



Photopic ERGs in Patients with Optic Neuropathies: Comparison with Primate ERGs after Pharmacologic Blockade of Inner Retina  

Microsoft Academic Search

PURPOSE. To determine whether anterior ischemic optic neu- ropathy and compressive optic neuropathy in humans alter the photopic flash ERG and to investigate the cellular origins of the waves that are affected by pharmacologic agents in primates. METHODS. Photopic flash ERGs were recorded differentially, with DTL electrodes, between the two eyes of 22 patients with diagnosed optic neuropathy (n 17,

Nalini V. Rangaswamy; Laura J. Frishman; E. Ulysses Dorotheo; Jade S. Schiffman; Hasan M. Bahrani; Rosa A. Tang



Traumatic optic neuropathy: a review of 61 patients.  


The outcome of traumatic optic neuropathy was evaluated following penetrating and blunt injuries to assess the effect of treatment options, including high-dose steroids, surgical intervention, and observation alone. Factors that affected improvement in visual acuity were identified and quantified. Sixty-one consecutive, nonrandomized patients presenting with visual loss after facial trauma between 1984 and 1996 were assessed for outcome. Pretreatment and posttreatment visual acuities were compared using a standard ophthalmologic conversion from the values of no light perception, light perception, hand motion, finger counting, and 20/800 down to 20/15 to a logarithm of the minimum angle of resolution (log MAR). The percentage of patients showing visual improvement and the degree of improvement were calculated for each patient group and treatment method. Measurements of visual acuity are in log MAR units +/- standard error of the mean. Patients who sustained penetrating facial trauma (n = 21) had worse outcomes than patients with blunt trauma (n = 40). Improvement in visual acuity after treatment was seen in 19 percent of patients with penetrating trauma compared with 45 percent of patients with blunt trauma (p < 0.05). Furthermore, patients with penetrating trauma improved less than those with blunt trauma, with a mean improvement of 0.4 +/- 0.23 log MAR compared with 1.1 +/- 0.24 in blunt-trauma patients (p = 0.03). The patients with blunt trauma underwent further study. There was no significant difference in improvement of visual acuity in patients treated with surgical versus nonsurgical methods; however, 83 percent of patients without orbital fractures had improvement compared with 38 percent of patients with orbital fractures (p < 0.05). The mean improvement in patients without orbital fractures was 1.8 +/- 0.65 log MAR compared with 0.95 +/- 0.26 in patients with orbital fractures (p = 0.1). Twenty-seven percent of patients who had no light perception on presentation experienced improvement in visual acuity after treatment compared with 100 percent of patients who had light perception on admission (p < 0.05). The mean improvement in patients who were initially without light perception was 0.85 +/- 0.29 log MAR compared with 1.77 +/- 0.35 in patients who had light perception (p < 0.05). There were no significant differences in improvement of visual acuity when analyzing the effect of patient age and timing of surgery. Patients who sustain penetrating trauma have a worse prognosis than those with blunt trauma. The presence of no light perception and an orbital fracture are poor prognostic factors in visual loss following blunt facial trauma. It seems that clinical judgment on indication and timing of surgery, and not absolute criteria, should be used in the management of traumatic optic neuropathy. PMID:11391181

Wang, B H; Robertson, B C; Girotto, J A; Liem, A; Miller, N R; Iliff, N; Manson, P N



Clinical Profile of Patients with Nonarteritic Anterior Ischemic Optic Neuropathy Presented to a Referral Center from 2003 to 2008  

Microsoft Academic Search

Background: We conducted this study to report the demographics and clinical profile of patients with nonarteritic anterior ischemic optic neuropathy referred to a referral neuro- ophthalmology center in Iran. Methods: During a five-year period, 107 patients with nonarteritic anterior ischemic optic neuropathy were studied. A detailed history of previous or current systemic diseases was obtained and a complete ophthalmic evaluation

Khalil Ghasemi Falavarjani; Mostafa Soltan Sanjari; Mehdi Modarres; Farzaneh Aghamohammadi


A diagnostic challenge: chronic myelomonocytic leukaemia and recurrent anterior ischaemic optic neuropathy.  


We report the first case of ischaemic optic neuropathy (ION) linked to chronic myelomonocytic leukaemia (CMML) and its associated vasculitis. We discuss the link between CMML and vasculitis and the evidence suggesting it can cause anterior ischaemic optic neuropathy through a vasculitic process. We highlight the difficulty and delay in diagnosis as the use of steroids masked an underlying systemic process. Recurrent ION and raised inflammatory markers should raise suspicion of vasculitis. Together with an elevated monocyte but low platelet count, CMML should be considered. PMID:23179230

De Smit, Elisabeth; O'Sullivan, Eoin



Progressive optic neuropathy in congenital glaucoma associated with the Sirsasana yoga posture.  


The authors describe a case of progressive optic neuropathy in a patient with congenital glaucoma who had routinely practiced the Sirsasana (headstand) yoga posture for several years. Ophthalmic examination included best-corrected visual acuity, anterior segment examination, indirect ophthalmoscopy, ultrasound pachymetry for central corneal thickness, and intraocular pressure before, during, and after maintaining the Sirsasana posture for 5 minutes. Intraocular pressure increased significantly during the Sirsasana posture. Transient elevation in intraocular pressure during yoga exercises may lead to progressive glaucomatous optic neuropathy, especially in susceptible patients with congenital glaucoma. PMID:18717444

de Barros, Daniela S Monteiro; Bazzaz, Sheila; Gheith, Moataz E; Siam, Ghada A; Moster, Marlene R


Irreversible Anterior Ischemic Optic Neuropathy Complicating Interferon Alpha and Ribaverin Therapy  

PubMed Central

Ophthalmologic complications with interferon therapy are rare and usually reversible. The anterior ischemic optic neuropathy is an uncommon complication of interferon treatment. A case of irreversible anterior ischemic optic neuropathy complicating interferon therapy for chronic hepatitis C is reported. We suggest that periodic ophthalmological examinations, including visual acuity and fundus examinations, should be performed to patients with high risk of ocular complications after starting and during treatment. We also suggest that an ophthalmologist would be able to detect these complications. Antiviral treatment should be stopped immediately if severe ophthalmologic complications occur.

Seddik, Hassan; Tamzaourte, Mouna; Rouibaa, Fadoua; Fadlouallah, Maha; Benkirane, Ahmed



Irreversible anterior ischemic optic neuropathy complicating interferon alpha and ribaverin therapy.  


Ophthalmologic complications with interferon therapy are rare and usually reversible. The anterior ischemic optic neuropathy is an uncommon complication of interferon treatment. A case of irreversible anterior ischemic optic neuropathy complicating interferon therapy for chronic hepatitis C is reported. We suggest that periodic ophthalmological examinations, including visual acuity and fundus examinations, should be performed to patients with high risk of ocular complications after starting and during treatment. We also suggest that an ophthalmologist would be able to detect these complications. Antiviral treatment should be stopped immediately if severe ophthalmologic complications occur. PMID:21994872

Seddik, Hassan; Tamzaourte, Mouna; Rouibaa, Fadoua; Fadlouallah, Maha; Benkirane, Ahmed



Nonarteritic Anterior Ischemic Optic Neuropathy: Natural History of Visual Outcome  

PubMed Central

Objective To investigate systematically the natural history of visual outcome in nonarteritic anterior ischemic optic neuropathy (NAION). Design Cohort study. Participants Three hundred forty consecutive untreated patients (386 eyes) with NAION, first seen in our clinic from 1973 to 2000. Methods At first visit, all patients gave a detailed ophthalmic and medical history and underwent a comprehensive ophthalmic evaluation. Visual evaluation was done by recording visual acuity, using the Snellen visual acuity chart, and visual fields with a Goldmann perimeter. The same ophthalmic evaluation was performed at each follow-up visit. Main Outcome Measures Natural history of visual acuity and visual field outcome in NAION. Results Of the 386 eyes, 332 had 8 weeks or more of follow-up from the initial visit. At the initial visit, in eyes seen ?2 weeks from onset of symptoms, 49% had visual acuity of ?20/30 and 23% had ?20/200; in these eyes, 38% had minimal to mild visual field defect and 43% marked to severe defect. In those who were first seen ?2 weeks after onset with visual acuity ?20/70, there was improvement in 41% at 6 months and in 42% at 1 year after the initial visit. Two years after the initial visit, there was deterioration in 9% of eyes with initial visual acuity of ?20/60, and in 18% of those with initial visual acuity of ?20/70. In those who were first seen ?2 weeks of onset with moderate to severe visual field defect, there was improvement in 26% at 6 months and 27% at 1 year after the initial visit. Two years after the initial visit, 27% of eyes with initial minimal to mild field defects showed worsening, as did 19% of those with moderate to severe defects. Conclusions About half of the eyes with NAION presented with almost normal visual acuity (20/15 to 20/30) at the initial visit. Thus, the presence of normal visual acuity does not rule out NAION. Visual acuity and visual fields showed improvement or further deterioration mainly up to 6 months, with no significant change after that.

Hayreh, Sohan Singh; Zimmerman, M. Bridget



Optic disc excavation in the atrophic stage of Leber's hereditary optic neuropathy: comparison with normal tension glaucoma  

Microsoft Academic Search

Background. Abnormal optic disc excavations are reportedly seen in patients with Leber's hereditary optic neuropathy (LHON), a mitochondrial dysfunction disease. We examined the disc morphology in the eyes of patients with LHON at the atrophic stage and compared it to that in eyes with normal-tension glaucoma (NTG). Methods. We studied 15 LHON patients with the 11778 mutation, 15 patients with

Yukihiko Mashima; Itaru Kimura; Yusuke Yamamoto; Hisao Ohde; Yuichirou Ohtake; Tomihiko Tanino; Goji Tomita; Yoshihisa Oguchi



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

PubMed Central

Mutations in the spastic paraplegia 7 (SPG7) gene encoding paraplegin are responsible for autosomal recessive hereditary spasticity. We screened 135 unrelated index cases, selected in five different settings: SPG7-positive patients detected during SPG31 analysis using SPG31/SPG7 multiplex ligation-dependent probe amplification (n = 7); previously reported ambiguous SPG7 cases (n = 5); patients carefully selected on the basis of their phenotype (spasticity of the lower limbs with cerebellar signs and/or cerebellar atrophy on magnetic resonance imaging/computer tomography scan and/or optic neuropathy and without other signs) (n = 24); patients with hereditary spastic paraparesis referred consecutively from attending neurologists and the national reference centre in a diagnostic setting (n = 98); and the index case of a four-generation family with autosomal dominant optic neuropathy but no spasticity linked to the SPG7 locus. We identified two SPG7 mutations in 23/134 spastic patients, 21% of the patients selected according to phenotype but only 8% of those referred directly. Our results confirm the pathogenicity of Ala510Val, which was the most frequent mutation in our series (65%) and segregated at the homozygous state with spastic paraparesis in a large family with autosomal recessive inheritance. All SPG7-positive patients tested had optic neuropathy or abnormalities revealed by optical coherence tomography, indicating that abnormalities in optical coherence tomography could be a clinical biomarker for SPG7 testing. In addition, the presence of late-onset very slowly progressive spastic gait (median age 39 years, range 18–52 years) associated with cerebellar ataxia (39%) or cerebellar atrophy (47%) constitute, with abnormal optical coherence tomography, key features pointing towards SPG7-testing. Interestingly, three relatives of patients with heterozygote SPG7 mutations had cerebellar signs and atrophy, or peripheral neuropathy, but no spasticity of the lower limbs, suggesting that SPG7 mutations at the heterozygous state might predispose to late-onset neurodegenerative disorders, mimicking autosomal dominant inheritance. Finally, a novel missense SPG7 mutation at the heterozygous state (Asp411Ala) was identified as the cause of autosomal dominant optic neuropathy in a large family, indicating that some SPG7 mutations can occasionally be dominantly inherited and be an uncommon cause of isolated optic neuropathy. Altogether, these results emphasize the clinical variability associated with SPG7 mutations, ranging from optic neuropathy to spastic paraplegia, and support the view that SPG7 screening should be carried out in both conditions.

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



Optic Disc Morphology in Open-Angle Glaucoma Compared with Anterior Ischemic Optic Neuropathies  

PubMed Central

Purpose. To compare optic disc topography performed by confocal laser ophthalmoscopy in eyes with nonarteritic anterior ischemic optic neuropathy (NAION), arteritic anterior ischemic optic neuropathy (AAION), and open-angle glaucoma (OAG), adjusting for the amount of retinal ganglion cell (RGC) loss, as measured by nerve fiber layer (NFL) thickness and average visual field loss. Methods. At four referral centers, patients who met specific diagnostic criteria for OAG (103 persons, 152 eyes), NAION (53 persons, 57 eyes), or AAION (18 persons, 20 eyes) underwent Heidelberg Retinal Tomography (HRT; Heidelberg Engineering, Heidelberg, Germany), Stratus Optical Coherence Tomography (OCT; Carl Zeiss Meditec, Inc., Dublin, CA), and Humphrey visual field testing (HFA; Carl Zeiss Meditec, Inc.). HRT parameters were compared in univariate and multivariate models, accounting for degree of RGC loss by either OCT NFL thickness or visual field mean deviation (MD). Acute AION occurred at least 6 weeks before testing. Results. After adjustment for degree of injury according to either MD or mean NFL thickness, all HRT parameters were significantly different between OAG and both NAION and AAION. With similar damage, OAG eyes had larger, deeper cups; smaller rims; more cup volume; and less rim volume (all P ? 0.001). There were differences in disc topography between NAION and AAION, but they were not consistent for both measures of damage. Disc area and MD were also significantly associated with many HRT parameters. NFL thickness was greater at the same MD for both AAION and NAION compared with OAG. Conclusions. NAION and AAION cause loss of RGCs, but have significantly different disc topography compared with OAG at a given level of RGC loss.

Boland, Michael V.; Savino, Peter J.; Miller, Neil R.; Subramanian, Prem S.; Girkin, Christopher A.; Quigley, Harry A.



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

PubMed Central

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

Chai, Samantha J; Foroozan, Rod



Sudden visual loss due to posterior ischemic optic neuropathy following craniotomy for a ruptured intracranial aneurysm.  


The authors report a rare case of acute ipsilateral blindness that occurred after a standard fronto-temporal craniotomy for aneurysm in supine position. Posterior ischemic optic neuropathy caused by external pressure on the ipsilateral eye, its differentials and subsequent medico-legal implications are discussed. PMID:17558125

Choudhari, Kishor A; Pherwani, Anupama A


[Non-arteritic anterior ischemic optic neuropathy associated with erectile dysfunction medications].  


Erectile dysfunction medications such as sildenafil citrate (Viagra) or tadalafil (Cialis) are commonly prescribed worldwide. They are selective phosphodiesterase-5 inhibitor and partial phosphodiesterase-6 inhibitors causing smooth muscle relaxation in the corpus cavernosum, allowing penile vasodilatation and erection in response to sexual stimuli. Over the years, there have been an increasing number of case reports concerning patients who developed ischemic optic neuropathy soon after the ingestion of these drugs. Although a cause and effect relationship between usage of the drugs and the development of ischemic optic neuropathy is difficult to prove, it is common nowadays to advise patients, especially those suffering from diabetes, hypertension, and ischemic heart disease, regarding the potential risk of visual loss due to ischemic optic neuropathy and treatment with erectile dysfunction drugs. Patients who were diagnosed with ischemic optic neuropathy soon after the ingestion of these erectile dysfunction drugs should be warned about a similar event in their fellow eye and should be advised regarding drug discontinuation. PMID:23513498

Krashin-Bichler, Iris; Dotan, Gad



A Case of Bickerstaff's Brainstem Encephalitis with Guillain-Barré Syndrome Presenting Optic Neuropathy and Seizure  

Microsoft Academic Search

Bickerstaff's brainstem encephalitis (BBE), characterized by acute ophthalmoplegia and ataxia, often causes impaired consciousness and hyperreflexia. A 17-year-old man was admitted with an acute meningitic condition including high and neck stiffness. His condition rapidly deteriorated over 2 weeks, and he showed ophthal- moplegia, ataxia, seizure, tetraplegia, comatose mentality, and optic neuropathy. Electroencephalography showed diffuse slow waves. Visual evoked potentials showed

Ji Eun Kim; Jae Hyuk Kwak; O Dae Kwon; Jin Kuk Do; Dong Kuck Lee


[Peripheral neuropathy, myelopathy, cerebellar ataxia, and subclinical optic neuropathy associated with copper deficiency occurring 23 years after total gastrectomy].  


We report a 61-year-old man with slowly progressive gait disturbance and paresthesia in the lower extremities following a total gastrectomy for gastric cancer 23 years previously. The patient presented with hyperreflexia, peripheral sensory neuropathy, and cerebellar ataxia. Magnetic resonance imaging showed atrophy of the cerebellum, and electrophysiological findings suggested the presence of disorder in both sides of the pyramidal tract, dorsal column, peripheral nerves, and optic nerve. Laboratory findings revealed anemia, neutropenia, and a remarkably low serum copper level (10 microg/dl; normal: 68-128). His serum vitamin E was slightly low and his serum vitamin B12 was within the normal limits. After administering an oral copper supplement, his symptoms improved with normalization of the serum copper level. We need to pay attention to myeloneuropathy caused by copper deficiency if the patient has a past history of total gastrectomy. PMID:21735733

Inaba, Meiko; Torii, Takako; Shinoda, Koji; Yamasaki, Ryo; Ohyagi, Yasumasa; Kira, Jun-ichi



Accompanying optical interferometry worldwide: the JMMC tools and services  

NASA Astrophysics Data System (ADS)

This poster advertizes the Jean-Marie Mariotti Center software tools, databases and services aimed at facilitating the use of optical interferometry worldwide such as preparation of observations, data reduction and data analysis. Its mission and organization are presented before listing the current software suite. Finally some facts and perspectives are mentioned.

Mella, G.; Lafrasse, S.; Bourgès, L.; Chelli, A.; Duvert, G.; Chesneau, O.; Malbet, F.; Tallon-Bosc, I.; Vannier, M.; Absil, O.; Benisty, M.; Berger, J.-P.; Beust, H.; Bonneau, D.; Cruzalebes, P.; Delfosse, X.; Domiciano de Souza, A.; Kervella, P.; Kluska, J.; Le Bouquin, J.-B.; Meimon, S.; Merand, A.; Millour, F.; Monin, J.-L.; Mourard, D.; Mugnier, L.; Nardetto, N.; Perraut, K.; Tallon, M.



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


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

La Morgia, Chiara; Ross-Cisneros, Fred N; Sadun, Alfredo A; 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; Carelli, Valerio



Radiation-induced bilateral optic neuropathy in cancer of the nasopharynx  

Microsoft Academic Search

Case Report  A case history of unanticipated radiation-induced bilateral optic neuropathy, 18 months after induction chemotherapy and radiation\\u000a therapy for a locally advanced nasopharyngeal carcinoma, is presented. Retrospective reanalysis of the radiation therapy technique,\\u000a with emphasis on the doses received by the optic pathway structures, was performed. These re-calculations revealed unexpectedly\\u000a high doses in the range 79 to 82 Gy (cumulative

Oda B. Wijers; Peter C. Levendag; Gre P. M. Luyten; Bert A. Bakker; Nicole J. M. Freling; Julie Klesman-Bradley; Evert Woudstra



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

Microsoft Academic Search

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

Niranjan Bhandare; Alan T. Monroe; Christopher G. Morris; M. Tariq Bhatti; William M.. Mendenhall



Receptor for advanced glycation end products is upregulated in optic neuropathy of Alzheimer’s disease  

Microsoft Academic Search

Although Alzheimer’s disease (AD) has been shown to be associated with a true primary optic neuropathy, the underlying pathophysiology\\u000a of this disease and in particular the optic nerve disorder is still poorly understood. The receptor for advanced glycation\\u000a end products (RAGE) has been implicated in the pathogenesis of AD by mediating the transport of plasma amyloid-? into the\\u000a brain. Once

Michelle Y. Wang; Fred N. Ross-Cisneros; Divya Aggarwal; Chiao-Ying Liang; Alfredo A. Sadun



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


We describe a 43-year-old patient who experienced visual loss 4 years after beginning antiepileptic therapy with topiramate. Ophthalmological and neurological examinations led to a preliminary diagnosis of bilateral toxic optic neuritis. Mitochondrial genome sequence analysis detected a Leber hereditary optic neuropathy 11778G>A mutation. The possibility that topiramate might favor a conversion disease, alerts physicians to seek a history of blindness in patients undergoing chronic antiepileptic therapy. PMID:21898092

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



[Retrobulbar optic neuropathy secondary to an undifferentiated carcinoma of the sphenoid sinus].  


Undifferentiated carcinoma of the paranasal sinuses is a rare malignant tumor, characterized by rapid growth, local/regional invasion, metastatic potential and poor prognosis despite aggressive treatment. Clinically, this tumor may manifest as episodes of epistaxis, headache or ophthalmic signs, particularly oculomotor nerve palsies, optic atrophy or even proptosis in the case of orbital extension. We report the case of a patient admitted with a left retrobulbar optic neuropathy, which led to a diagnosis of undifferentiated carcinoma of the sphenoid sinus. PMID:23141167

Soufi, G; Hajji, Z; Imdary, I; Slassi, N; Essakalli Housseini, L; Maher, M; Benchekroun, N; Boulanouar, A; Berraho, A



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

PubMed Central

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

Petzold, Axel; Plant, Gordon T.



Mode conversion accompanying forward SBS in optical fibers  

NASA Astrophysics Data System (ADS)

The interaction of symmetric modes with transverse acoustic waves in stimulated Brillouin scattering (SBS) is analyzed. It is shown that forward as well as backward SBS can occur in multimode fibers because the modes are no longer phase-velocity-degenerate. The SBS efficiency under these conditions is sensitive to the amplitude of the scattering acoustic wave injected externally into the fiber. It is concluded that efficient mode conversion in optical fibers of relativistic lengths can be achieved by exciting a sufficiently intense acoustic wave.

Burlak, G. N.; Grimalskii, V. V.; Kotsarenko, N. Ia.



Morphometric Analysis and Classification of Glaucomatous Optic Neuropathy using Radial Polynomials  

PubMed Central

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

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



Non-arteritic anterior ischaemic optic neuropathy associated with neovascular glaucoma.  


We report a case of non-arteritic anterior ischaemic optic neuropathy (NAION) associated with neovascular glaucoma (NVG). A 63-year-old man who had undergone cataract surgery 3 months previously presented with sudden visual loss in his right eye. Ocular examination revealed a relative afferent pupillary defect, intraocular pressure (IOP) of 27 mm Hg, and 360° neovascularisation. Fundus examination revealed a pale and swollen optic disc with diabetic retinopathy. NAION associated with NVG was diagnosed. NVG, leading to reduced optic nerve perfusion pressure, concurrent with ischaemic processes of diabetic retinopathy, resulted in NAION. PMID:21686787

Wanichwecharungruang, Boonsong; Chantra, Somporn



Non-arteritic anterior ischaemic optic neuropathy associated with neovascular glaucoma  

PubMed Central

We report a case of non-arteritic anterior ischaemic optic neuropathy (NAION) associated with neovascular glaucoma (NVG). A 63-year-old man who had undergone cataract surgery 3 months previously presented with sudden visual loss in his right eye. Ocular examination revealed a relative afferent pupillary defect, intraocular pressure (IOP) of 27 mm Hg, and 360° neovascularisation. Fundus examination revealed a pale and swollen optic disc with diabetic retinopathy. NAION associated with NVG was diagnosed. NVG, leading to reduced optic nerve perfusion pressure, concurrent with ischaemic processes of diabetic retinopathy, resulted in NAION.

Wanichwecharungruang, Boonsong; Chantra, Somporn



Mouse mtDNA mutant model of Leber hereditary optic neuropathy.  


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

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



Anterior ischemic optic neuropathy after a trans-Atlantic airplane journey  

Microsoft Academic Search

PURPOSE: To report a case of anterior ischemic optic neuropathy after a trans-Atlantic airplane journey.DESIGN: An observational case report.METHODS: A 48-year-old healthy man presented with severe visual loss in his left eye within 12 hours after a 15-hour-long trans-Atlantic airplane flight. The patient underwent slit-lamp examination, funduscopy, fluorescein angiography, automated perimetry, and various blood examinations.RESULTS: Visual acuity was LE: 20\\/30,

Igor Kaiserman; Joseph Frucht-Pery



Extra-Visual Functional and Structural Connection Abnormalities in Leber's Hereditary Optic Neuropathy  

Microsoft Academic Search

We assessed abnormalities within the principal brain resting state networks (RSNs) in patients with Leber's hereditary optic neuropathy (LHON) to define whether functional abnormalities in this disease are limited to the visual system or, conversely, tend to be more diffuse. We also defined the structural substrates of fMRI changes using a connectivity-based analysis of diffusion tensor (DT) MRI data. Neuro-ophthalmologic

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



Outer retinal abnormalities associated with inner retinal pathology in nonglaucomatous and glaucomatous optic neuropathies  

PubMed Central

Inner and outer retinal morphology were quantified in vivo for 6 nonglaucomatous and 10 glaucomatous optic neuropathy patients. Custom, ultrahigh-resolution imaging modalities were used to evaluate segmented retinal layer thickness in 3D volumes (Fourier-domain optical coherence tomography), cone photoreceptor density (adaptive optics fundus camera), and the length of inner and outer segments of cone photoreceptors (adaptive optics–optical coherence tomography). Quantitative comparisons were made with age-matched controls, or by comparing affected and nonaffected retinal areas defined by changes in visual fields. The integrity of outer retinal layers on optical coherence tomography B-scans and density of cone photoreceptors were correlated with visual field sensitivity at corresponding retinal locations following reductions in inner retinal thickness. The photoreceptor outer segments were shorter and exhibited greater variability in retinal areas associated with visual field losses compared with normal or less affected areas of the same patient's visual field. These results demonstrate that nonglaucomatous and glaucomatous optic neuropathies are associated with outer retinal changes following long-term inner retinal pathology.

Werner, J S; Keltner, J L; Zawadzki, R J; Choi, S S



Changes in Cellular Structures Revealed by Ultra-high Resolution Retinal Imaging in Optic Neuropathies  

PubMed Central

PURPOSE To study the integrity of inner and outer retinal layers in patients with various types of optic neuropathy by using high-resolution imaging modalities. METHODS Three high-resolution imaging systems constructed at the University of California Davis were used to acquire retinal images from patients with optic neuropathy: (1) adaptive optics (AO)-flood–illuminated fundus camera, (2) high-resolution Fourier domain optical coherence tomography (FDOCT), and (3) adaptive optics-Fourier domain optical coherence tomography (AO-FDOCT). The AO fundus camera provides en face images of photoreceptors whereas cross-sectional images (B-scans) of the retina are obtained with both FDOCT and AO-FDOCT. From the volumetric FDOCT data sets, detailed thickness maps of a three-layer complex consisting of the nerve fiber (NF), ganglion cell (GC), and inner plexiform (IP) layers were created. The number of visible cones in the en face images of photoreceptors was then compared with visual sensitivity maps from Humphrey visual field (HVF; Carl Zeiss Meditec, Inc., Dublin, CA) testing, as well as FDOCT and AO-FDOCT images, including the thickness maps of the NF–GC–IP layer complex. Five types of optic neuropathy were studied: (1) optic neuritis with multiple sclerosis (MS), (2) idiopathic intracranial hypertension (pseudotumor cerebri), (3) nonarteritic anterior ischemic optic neuropathy (NAION), (4) optic nerve head drusen with NAION, and (5) systemic lupus erythematosus with MS and arthritis. RESULTS With permanent visual field loss and thinning of the NF–GC–IP layer complex, cone photoreceptors showed structural changes, making them less reflective, which caused the appearance of dark spaces in the en face images (hence, reduced number of visible cones) and indistinct outer retinal layers in OCT images. However, when the visual field loss was only transient, with a normal NF–GC–IP layer complex, there were no detectable abnormalities in cone photoreceptors (i.e., they were densely packed and had distinct photoreceptor layering in the OCT images). CONCLUSIONS Cone photoreceptors show structural changes when there is permanent damage to overlying inner retinal layers. There was a positive relation between the thickness of the three-layer inner retinal complex, visual sensitivity, and integrity of the cone mosaic.

Choi, Stacey S.; Zawadzki, Robert J.; Keltner, John L.; Werner, John S.



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


Ethambutol (EMB), widely used in the treatment of tuberculosis, has been reported to cause Leber's hereditary optic neuropathy in patients carrying mitochondrial DNA mutations. We study the effect of EMB on mitochondrial metabolism in fibroblasts from controls and from a man carrying an OPA1 mutation, in whom the drug induced the development of autosomal dominant optic atrophy (ADOA). EMB produced a mitochondrial coupling defect together with a 25% reduction in complex IV activity. EMB induced the formation of vacuoles associated with decreased mitochondrial membrane potential and increased fragmentation of the mitochondrial network. Mitochondrial genetic variations may therefore be predisposing factors in EMB-induced ocular injury. PMID:19900585

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



Accuracy of the RTVue-100 Fourier-domain optical coherence tomograph in an optic neuropathy screening trial.  


The aim of this study was to evaluate the usefulness of the RTVue-100 Fourier-domain optical coherence tomograph (RTVue-100 OCT) in screening for glaucoma and non-arteritic anterior ischemic optic neuropathy (NA-AION). In a non-population-based pre-publicised trial, self-recruited Caucasian participants were screened for glaucoma and NA-AION using the RTVue-100 OCT, and also by independent clinical examination. For the RTVue-100 OCT measurements, the optic nerve head (ONH) scan and the macular ganglion cell complex (GCC) scan were applied. Subjects with possible optic neuropathy (as indicated by any of the scans and/or by the clinical examination) underwent a detailed clinical investigation to verify or exclude the disease. Of the 146 attendees, 133 participants (256 eyes) successfully underwent the RTVue-100 OCT measurements. Of these, six eyes (2.3%) had glaucoma and three eyes (1.2%) had partial optic atrophy due to earlier NA-AION. The retinal nerve fibre layer (RNFL) parameters (provided by the instrument software) had 99.2-99.6% specificity, 96.5-96.9% accuracy, and positive likelihood ratio (PLR) of 27.3-54.7, but only 11.1-22.2% sensitivity. Accuracy and PLR for the ONH parameters were <95% and <8.3, respectively. The GCC scan of the macula provided up to 95.9% specificity, 94.0% accuracy, 10.7 PLR and 44.4% sensitivity. During the screening of this Caucasian population with 3.5% prevalence of optic neuropathy due to glaucoma and NA-AION, the RTVue-100 OCT was found to be useful for screening, with both RNFL and GCC parameters providing high accuracy and PLR values >10. PMID:21424554

Garas, Anita; Kóthy, Péter; Holló, Gábor



Accuracy of the RTVue-100 Fourier-domain optical coherence tomograph in an optic neuropathy screening trial  

Microsoft Academic Search

The aim of this study was to evaluate the usefulness of the RTVue-100 Fourier-domain optical coherence tomograph (RTVue-100\\u000a OCT) in screening for glaucoma and non-arteritic anterior ischemic optic neuropathy (NA-AION). In a non-population-based pre-publicised\\u000a trial, self-recruited Caucasian participants were screened for glaucoma and NA-AION using the RTVue-100 OCT, and also by independent\\u000a clinical examination. For the RTVue-100 OCT measurements, the

Anita Garas; Péter Kóthy; Gábor Holló



Central retinal artery and vein collapse pressure in giant cell arteritis versus nonarteritic anterior ischaemic optic neuropathy.  


Arteritic anterior ischaemic optic neuropathy and nonarteritic anterior ischaemic optic neuropathy are acute optic neuropathies, which have to be differentiated from each other. It was the purpose of this study to assess whether ophthalmodynamometry with an assessment of the collapse pressure of the central retinal artery (CRA) and vein (CRV) is helpful for that. Using a Goldmann contact lens-associated ophthalmodynamometer, the diastolic collapse pressure of the CRA and CRV were measured in six patients (eight eyes) with giant cell arteritis-induced anterior ischaemic optic neuropathy (GC-AION) and in 10 patients (12 eyes) with acute non-arteritic anterior ischaemic optic neuropathy (NAION). CRA collapse pressure was significantly (P=0.001; 95% confidence interval (CI): -68.7, -20.0) lower in the GC-AION group (52.7+/-24.6 arbitrary units) than in the NAION group (97.0+/-25.8 arbitrary units). CRV collapse pressure did not vary significantly (P=0.47). As measured by ophthalmodynamometry, CRA pressure is significantly lower in GC-AION than in NAION. CRV pressure does not vary markedly. These finding may be helpful for the clinical differentiation between GC-AION and NAION, and may give hints for the pathogenesis. PMID:17384573

Jonas, J B; Harder, B



No evidence for ‘skewed’ inactivation of the X-chromosome as cause of Leber's hereditary optic neuropathy in female carriers  

Microsoft Academic Search

Leber's hereditary optic neuropathy (LHON) is a maternally inherited disorder of the optic nerves. It has been proposed that the specific mutations in the mitochondrial DNA (mtDNA) that are associated with LHON require and X-chromosomally encoded permissive factor in order to become expressed. This would explain both the preponderance of male patients and the fact that most carriers of specific

Roelof-Jan Oostra; Stephan Kemp; Pieter A. Bolhuis; Elisabeth M. Sleeker-Wagemakers



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

PubMed Central

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

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



Magnetic resonance imaging, magnetisation transfer imaging, and diffusion weighted imaging correlates of optic nerve, brain, and cervical cord damage in Leber's hereditary optic neuropathy  

Microsoft Academic Search

OBJECTIVESLeber's hereditary optic neuropathy (LHON) is a mitochondrial disease leading to bilateral loss of central vision and severe optic nerve atrophy. A subtype of LHON presents additional clinical and MRI aspects indistinguishable from those of multiple sclerosis (MS) (LHON-MS). In patients with LHON or LHON-MS, an assessment was made of (a) the severity of optic nerve damage, using MRI and

M Inglese; M Rovaris; S Bianchi; L La Mantia; G L Mancardi; A Ghezzi; P Montagna; F Salvi; M Filippi



Non-arteritic anterior ischemic optic neuropathy: role of systemic corticosteroid therapy  

Microsoft Academic Search

Objective  To investigate systematically the role of systemic corticosteroid therapy in non-arteritic anterior ischemic optic neuropathy\\u000a (NA-AION).\\u000a \\u000a \\u000a \\u000a Methods  The study consists of a cohort of 613 consecutive patients (696 eyes), first seen in our clinic from 1973 to 2000. Of this\\u000a cohort, 312 patients (364 eyes) voluntarily opted for systemic steroid therapy, and 301 (332 eyes) for no treatment. At first\\u000a visit,

Sohan Singh Hayreh; M. Bridget Zimmerman



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

PubMed Central

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

MacDermot, K D; Walker, R W



Anterior Ischemic Optic Neuropathy in a Patient with Churg-Strauss Syndrome  

PubMed Central

We describe a patient with Churg-Strauss syndrome who developed unilateral anterior ischemic optic neuropathy. A 54-year-old man with a history of bronchial asthma, allergic rhinitis, and sinusitis presented with sudden decreased visual acuity in his right eye that had begun 2 weeks previously. The visual acuity of his right eye was 20 / 50. Ophthalmoscopic examination revealed a diffusely swollen right optic disc and splinter hemorrhages at its margin. Goldmann perimetry showed central scotomas in the right eye and fluorescein angiography showed remarkable hyperfluorescence of the right optic nerve head. Marked peripheral eosinphilia, extravascular eosinophils in a bronchial biopsy specimen, and an increased sedimentation rate supported the diagnosis of Churg-Strauss syndrome. Therapy with methylprednisolone corrected the laboratory abnormalities, improved clinical features, and preserved vision, except for the right central visual field defect. Early recognition of this systemic disease by ophthalmologists may help in preventing severe ocular complications.

Lee, Ji Eun; Lee, Seung Uk; Kim, Soo Young; Jang, Tae Won



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

PubMed Central

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

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



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


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

Gunn, David J; O'Hagan, Stephen


Anterior ischemic optic neuropathy in patient with hereditary spherocytosis and coexisting angioid streaks.  


Purpose. To describe a rare case of hereditary spherocytosis (HE) with angioid streaks that developed anterior ischemic optic neuropathy (AION).?Method. Case report.?Results. A 53-year-old woman with HE had a 3-day history of blurred vision in the lower hemifield in the left eye. At presentation, her visual acuity was 20/20 OD and 20/200 OS. Perimetric testing showed a relative scotoma in the superior parafoveal region in the right eye and an inferior altitudinal field defect in the left eye. Fundus examination demonstrated angioid streaks in both eyes with swelling of the optic disc in the left eye. Both parvovirus B19 immunoglobulin M and immunoglobulin G were identified in her serum. ?Conclusions. This is the first report of AION in HE and coexisting angioid streaks. The infection by parvovirus itself might be involved in the development of AION. PMID:23112036

Sawada, Akira; Oie, Shinya; Mochizuki, Kiyofumi; Yamamoto, Tetsuya



Bilateral posterior ischaemic optic neuropathy after severe diabetic ketoacidosis, cardiopulmonary resuscitation and respiratory failure.  


A 44-year-old male European with type I diabetes mellitus fell into diabetic ketoacidosis. In the emergency room, he developed an episode of asystole and respiratory failure requiring one cycle of cardiopulmonary resuscitation and extracorporeal membrane oxygenation (ECMO). Waking up 7 days later, he presented a bilateral complete loss of vision. Ophthalmological examination including funduscopy on days 1 and 10, after extubation, showed bilateral large round pupils non-reactive to light and a normal fundus. Neuroimaging studies, including MRI and MRA of the brain, were all within normal limits. A lumbar puncture and comprehensive serological testing excluded an infectious or rheumatic cause. An empirical high-dose intravenous steroid treatment administered for 5 days had no effect on his vision. His eye examination at 1.5 months follow-up showed a normal fundus except for progressive bilateral optic nerve disc pallor, which pointed towards the diagnosis of a posterior ischaemic optic neuropathy. PMID:23417383

Wirth, Christina Doris; Leitner, Christoph; Perrig, Martin



Teaching NeuroImages: Chiasmal enlargement and enhancement in Leber hereditary optic neuropathy.  


A 19-year-old man was admitted for subacute severe painless bilateral loss of vision. The patient was known to be a healthy carrier of the mitochondrial G11778A mutation, with a family history of Leber hereditary optic neuropathy. Funduscopy revealed bilateral optic disk elevation and hyperemia (figure). Goldmann visual fields demonstrated large central scotomas in both eyes. CSF disclosed normal opening pressure and cytochemical examination. Unexpectedly, brain MRI revealed an asymmetrical chiasmal enlargement and enhancement (figure). Similar cases have rarely been reported.(1,2) These findings would suggest disruption of the blood-brain barrier at the early stage of the disease,(2) likely due to an inflammatory-like mechanism. PMID:24145886

Ong, Elodie; Biotti, Damien; Abouaf, Lucie; Louis-Tisserand, Guy; Tilikete, Caroline; Vighetto, Alain



Simultaneous optic and vestibulocochlear syphilitic neuropathy in a patient with HIV infection  

PubMed Central

Background The purpose of this report is to present a case of optic and vestibulocochlear neuropathy as a manifestation of concurrent HIV and syphilis coinfection. This is an interventional case report of a 37-year-old man who complained of blurry central vision in his left eye and hearing loss in his left ear over the past 2?weeks. Findings Visual acuity was 20/20 in both eyes, and the anterior segment was normal in both eyes without relative afferent pupillary defect. Fundoscopy revealed swelling of the left optic disc. Optic coherence tomography and the Heidelberg retina tomograph confirmed and quantified the oedema of the left optic disc. An audiometry showed a left sensorineural deafness. Serological examinations disclosed confirmed HIV and syphilis infection. Magnetic resonance imaging of the brain showed no abnormalities. Properly treated with intravenous penicillin, the lesions resolved. Conclusions Simultaneous optic and auditive involvement can be the first manifestation of syphilitic and HIV coinfection. To our knowledge, this report is the first to describe the rare occurrence of syphilitic optic neuritis and ipsilateral affectation of the vestibulocochlear nerve.



Diabetic Peripheral Neuropathy  

Microsoft Academic Search

Diabetic peripheral neuropathy is the most prevalent peripheral neuropathy in the Western world. It has been reported to affect\\u000a nearly 50% of people with diabetes (1,2). It is responsible for a significant proportion of the mortality and morbidity that accompany diabetes and ranks third in\\u000a lifetime expenditures associated with diabetic complications (3). Diabetic peripheral neuropathy was until recently thought to

Rachel Nardin; Roy Freeman


Nonsense mutation in TMEM126A causing autosomal recessive optic atrophy and auditory neuropathy  

PubMed Central

Purpose To define the phenotype and elucidate the molecular basis for an autosomal recessively inherited optic atrophy and auditory neuropathy in a consanguineous family with two affected children. Methods Family members underwent detailed ophthalmologic, electrophysiological, and audiological assessments. An autozygosity mapping strategy using high-density single nucleotide polymorphism microarrays and microsatellite markers was used to detect regions of genome homozygosity that might contain the disease gene. Candidate genes were then screened for mutations by direct sequencing. Results Both affected subjects had poor vision from birth and complained of progressive visual loss over time. Current visual acuity ranged from 6/60 to 6/120. Fundus examination revealed bilateral temporal optic nerve pallor in both patients with otherwise normal retinal findings. International-standard full-field electroretinograms were normal in both individuals, with no evidence of generalized retinal dysfunction. Pattern cortical visual evoked potentials were grossly abnormal bilaterally in both cases. The pattern electroretinogram N95:P50 ratio was subnormal, and the P50 was of shortened peak time bilaterally in both patients. The electrophysiological findings were consistent with bilateral retinal ganglion cell/optic nerve dysfunction. Audiological investigation in both siblings revealed abnormalities falling within the auditory neuropathy/dysynchrony spectrum. There were no auditory symptoms and good outer hair cell function (as demonstrated by transient evoked otoacoustic emissions) but impaired inner hair cell/neural function with abnormal stapedial reflex thresholds and abnormal or absent auditory brainstem-evoked responses. The single nucleotide polymorphism microarray data demonstrated a 24.17 Mb region of homozygosity at 11q14.1–11q22.3, which was confirmed by microsatellite marker analysis. The candidate target region contained the transmembrane protein 126A (TMEM126A) gene, and direct sequencing identified a previously described nonsense mutation (c.163C>T; p.Arg55X). Conclusions We describe the first detailed phenotyping of patients with autosomal recessive TMEM126A-associated optic atrophy and auditory neuropathy. These findings will facilitate the identification of individuals with this recently described disorder.

Meyer, Esther; Michaelides, Michel; Tee, Louise J.; Robson, Anthony G.; Rahman, Fatimah; Pasha, Shanaz; Luxon, Linda M.; Moore, Anthony T.



Cellular Inflammation in Nonarteritic Anterior Ischemic Optic Neuropathy and Its Primate Model  

PubMed Central

Objective To correlate potential inflammatory responses in nonarteritic anterior ischemic optic neuropathy (NAION) with a lesion possessing many physiologic and histologic similarities from a model of nonhuman primate NAION (pNAION). Methods Using immunohistochemistry and confocal microscopic analysis, we evaluated the relative numbers of inflammatory cell types in the single available clinical specimen of early NAION (21 days after event). We correlated this with the temporal inflammatory response occurring in optic nerve tissue at different times following pNAION induction. Results In pNAION, there is a previously unsuspected infiltration of polymorphonuclear leukocytes occurring almost immediately after infarct induction, followed by invasion of ED1+ extrinsic macrophages, which peaks 5 weeks after infarct. Intrinsic microglia accumulate up to 70 days after induction in the area of primary axonal loss. The analyzed human NAION specimen was similar to 21-day pNAION tissue, with extrinsic macrophages and intrinsic microglial cells in the region of focal axon loss. Conclusions Cellular inflammation plays a major early role following white-matter (optic nerve) infarct, with both polymorphonuclear leukocyte and macrophage function involved in debris elimination and tissue remodeling. The optic nerve in NAION and its primate model are associated with early cellular inflammation, previously unsuspected, that may contribute to postinfarct optic nerve damage.

Salgado, Cristian; Vilson, Fernandino; Miller, Neil R.; Bernstein, Steven L.



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

Microsoft Academic Search

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

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



Shape Analysis of the Peripapillary RPE Layer in Papilledema and Ischemic Optic Neuropathy  

PubMed Central

Purpose. Geometric morphometrics (GM) was used to analyze the shape of the peripapillary retinal pigment epithelium–Bruch's membrane (RPE/BM) layer imaged on the SD-OCT 5-line raster in normal subjects and in patients with papilledema and ischemic optic neuropathy. Methods. Three groups of subjects were compared: 30 normals, 20 with anterior ischemic optic neuropathy (AION), and 25 with papilledema and intracranial hypertension. Twenty equidistant semilandmarks were digitized on OCT images of the RPE/BM layer spanning 2500 ?m on each side of the neural canal opening (NCO). The data were analyzed using standard GM techniques, including a generalized least-squares Procrustes superimposition, principal component analysis, thin-plate spline (to visualize deformations), and permutation statistical analysis to evaluate differences in shape variables. Results. The RPE/BM layer in normals and AION have a characteristic V shape pointing away from the vitreous; the RPE/BM layer in papilledema has an inverted U shape, skewed nasally inward toward the vitreous. The differences were statistically significant. There was no significant difference in shapes between normals and AION. Pre- and posttreatment OCTs, in select cases of papilledema, showed that the inverted U-shaped RPE/BM moved posteriorly into a normal V shape as the papilledema resolved with weight loss or shunting. Conclusions. The shape difference in papilledema, absent in AION, cannot be explained by disc edema alone. The difference is a consequence of both the translaminar pressure gradient and the material properties of the peripapillary sclera. GM offers a novel way of statistically assessing shape differences of the peripapillary optic nerve head.

Kupersmith, Mark J.; Rohlf, F. James



Long-term retinal nerve fiber layer changes following nonarteritic anterior ischemic optic neuropathy  

PubMed Central

Background In cases of nonarteritic anterior ischemic optic neuropathy (NAION), retinal nerve fiber layer (RNFL) thickness changes have been described during the first 12 months following the acute event. The purpose of this study was to report on the long-term RNFL changes in these eyes beyond the first year following onset of NAION. Methods Fourteen eyes of 13 patients with NAION were analyzed in this retrospective observational case series study. Uninvolved eyes served as controls. All patients underwent a complete neuro-ophthalmological examination and repeat measurements of peripapillary RNFL thickness using Stratus optical coherence tomography. Results On optical coherence tomography scan performed on average 6 months following onset of NAION, the mean global RNFL thickness (59.8 ± 11.8 ?m) was significantly thinner (P < 0.001) compared with uninvolved eyes (95.1 ± 13.9 ?m). In a second optical coherence tomography scan performed on average 13 (range 12–23) months later, the mean global RNFL thickness (58.9 ± 6.5 ?m) was not significantly different (P = 0.702) from the first scan. Conclusion There appears to be no further RNFL loss beyond the first 6 months following an acute event of NAION.

Dotan, Gad; Goldstein, Michaella; Kesler, Anat; Skarf, Barry



Neuroprotective effects of brimonidine treatment in a rodent model of ischemic optic neuropathy.  


Ischemic optic neuropathy (ION) is a common disorder caused by disruption of the arterial blood supply to the optic nerve. It can result in significant loss of visual acuity and/or visual field. An ischemic optic nerve injury was produced in rats by intravenous injection of Rose Bengal dye followed by argon green laser application to the retinal arteries overlying the optic nerve, causing a coagulopathy within the blood vessels and disruption of optic nerve and retinal perfusion. The effect of brimonidine tartrate eye drops on survival of retinal ganglion cell axons in this experimental paradigm was studied. One eye was treated and the contralateral eye served as a control. Four groups of animals were used for this study. Group 1 received 7 days of treatment with 0.15% brimonidine tartrate eye drops twice a day prior to the ischemic injury. Group 2 animals received 0.15% brimonidine tartrate eye drops twice a day for 14 days after photocoagulation injury. Animal groups 3 and 4 received eye drops of 0.9% NaCl twice a day either daily for 7 days before injury or daily for 14 days, respectively. All rats were sacrificed 5 months after the injury to ascertain long-term optic axon survival. Coagulopathy-induced optic nerve ischemia resulted in a 71% loss of optic axons. Treatment with brimonidine daily for the 7 days prior to the injury resulted in a greater survival of optic axons, with only a 56.1% loss compared to control. Brimonidine treatment every day for 14 days after the ischemic injury did not result in a significant rescue of optic axons compared to injury alone. In summary, the application of brimonidine eye drops for one week prior to an ischemic injury resulted in a statistically significant increase in survival of optic axons within the injured optic nerves. Brimonidine treatment of the eye after the ischemic injury did not result in axon rescue, and axon loss was similar to the injured optic nerves treated with saline only. These results suggest that brimonidine may have potential use for prevention of ION in at-risk patients. PMID:17113077

Danylkova, Nataliya O; Alcala, Sandra R; Pomeranz, Howard D; McLoon, Linda K



Bilateral simultaneous nonarteritic anterior ischemic optic neuropathy after ingestion of sildenafil for erectile dysfunction.  


Purpose. To describe a patient who developed bilateral, simultaneous nonarteritic anterior ischemic optic neuropathy (NAION) after ingestion of Sildenafil citrate (Viagra) for erectile dysfunction. Methods. Observational case report. Results. A 60-year-old diabetic man noted sudden decrease of vision in both eyes 16 hours after his third consecutive 50?mg daily Sildenafil ingestion. A diagnosis of bilateral NAION was made and he was treated for three days with methylprednisolone 1 g/d intravenously, followed by oral prednisone 75?mg/d. Final visual acuity was 20/50 right eye (OD) and 20/20 left eye (OS). He had preexisting diabetes. Conclusion. This is the first reported case of simultaneous bilateral NAION occurred in a diabetic patient early after Sildenafil intake. Patients with predisposing conditions such as diabetes have to be warned against the use of PDE inhibitors. PMID:22481954

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



Raised Intraocular Pressure as a Potential Risk Factor for Visual Loss in Leber Hereditary Optic Neuropathy  

PubMed Central

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

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



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


Chronic relapsing inflammatory optic neuropathy (CRION) is an entity that was described in 2003. Early recognition of patients suffering from CRION is relevant because of the associated risk for blindness if treated inappropriately. It seems timely to have a clinical review on this recently defined entity. A systematic literature review, irrespective of language, retrieved 22 case series and single reports describing 122 patients with CRION between 2003 and 2013. We review the epidemiology, diagnostic workup, differential diagnosis, and treatment (acute, intermediate, and long term) in view of the collective data. These data suggest that CRION is a distinct nosological entity, which is seronegative for anti-aquaporin four auto-antibodies and recognized by and managed through its dependency on immuno-suppression. Revised diagnostic criteria are proposed in light of the data compromising a critical discussion of relevant limitations. PMID:23700317

Petzold, Axel; Plant, Gordon T



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


To report a case of clinical and electrophysiological recovery in Leber hereditary optic neuropathy (LHON) with G3460A Mutation. A 10-year-old boy with a three-month history of painless bilateral sequential visual loss upon presentation underwent visual acuity (diminished), anterior and posterior segment examination (normal), fluorescein angiography (normal), Goldman kinetic perimetry (bilateral central scotomata), genetic (a point G3460A mutation) and electrophysiological investigation (undetectable pattern visual evoked potentials (VEP); low amplitude, broadened and reduced flash VEPs and loss of the N95 component in the pattern electroretinograms). Diagnosis of LHON was made. Eighteen months later vision and electrophysiological tests results began spontaneously improving. Kinetic perimetry revealed reduced density and size of scotomata. Two years later, there had been further electrophysiological improvement. This report describes both clinical and electrophysiological improvement in LHON with G3460A mutation. PMID:22684678

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



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

SciTech Connect

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.

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



Hereditary Neuropathies  


... neuropathy, hereditary motor neuropathy, and hereditary sensory and autonomic neuropathy. The most common type is Charcot-Marie- ... Certain types of hereditary neuropathies can affect the autonomic nerves, resulting in impaired sweating, postural hypotension, or ...


Diabetic Neuropathy  


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


Diabetic neuropathy  

Microsoft Academic Search

Diabetic neuropathy (DN) refers to symptoms and signs of neuropathy in a patient with diabetes in whom other causes of neuropathy have been excluded. Distal symmetrical neuropathy is the commonest accounting for 75% DN. Asymmetrical neuropathies may involve cranial nerves, thoracic or limb nerves; are of acute onset resulting from ischaemic infarction of vasa nervosa. Asymmetric neuropathies in diabetic patients

V Bansal; J Kalita; U K Misra



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


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

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



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

PubMed Central

Some evidence suggests that the primary locus of the lesion in Leber's hereditary optic neuropathy (LHON) may be intraocular rather than retrobulbar. To clarify this issue, the condition of the retrobulbar portion of the optic nerve was evaluated in patients with the acute stage of LHON. High resolution MRI with fast spin echo sequences of the optic nerve complex in the orbit was carried out. Five patients with acute stage LHON were compared with seven patients with acute stage optic neuritis. On T2 weighted fast spin echo MRI, signal changes did not appear in the retrobulbar optic nerve complex in acute stage LHON. By comparison, patients with optic neuritis showed pronounced high signals in the optic nerve. Subsequent orbital MRI in the atrophic stages of the same patients with LHON showed an increase in signal intensity in the optic nerve toward the orbital apex in both eyes. The present results support the hypothesis that a primary lesion in LHON may be intraocular.??

Mashima, Y.; Oshitari, K.; Imamura, Y.; Momoshima, S.; Shiga, H.; Oguchi, Y.



The Effect of an Intravitreal Triamcinolone Acetonide Injection for Acute Nonarteritic Anterior Ischemic Optic Neuropathy  

PubMed Central

The purpose of this case report is to evaluate the visual outcome of an intravitreal triamcinolone acetonide injection (IVTA) as a treatment for a patient with acute nonarteritic anterior ischemic optic neuropathy (NAION). A 65-year-old male patient with severe visual loss due to acute NAION was treated with 4 mg/0.1mL IVTA. Fundus examination and measurements of the patient's best-corrected visual acuity and visual field were performed before and after the injection at 2 weeks, 1 month, 3 months, and 6 months. The best-corrected visual acuity changed from 0.05 before the injection to 0.16 at 2 weeks, 0.3 at 1 month, and 0.4 at 3 months and at the final visit. Optic disc swelling had markedly decreased at 1 week postoperatively and disappeared at 2 weeks after the injection. The clinical course of this patient suggests that an IVTA may be effective in increasing visual acuity following an acute NAION. A large randomized controlled trial is needed to assess the efficacy of IVTA as a treatment for NAION.

Sohn, Byung Jae; Kwon, Jung Yoon



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

PubMed Central

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

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



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

PubMed Central

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

Koilkonda, Rajeshwari D.; Guy, John



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

PubMed Central

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

Aleyasin, A; Ghazanfari, M; Houshmand, M



Combined optic neuropathy and central retinal artery occlusion in presumed ocular tuberculosis without detectable systemic infection.  


Purpose: To report a rare case of combined optic neuropathy and central retinal artery occlusion in presumed ocular tuberculosis without systemic infection. Case Report: A young man presented with sudden onset of decreased vision in his left eye with combined optic disc swelling and central retinal artery occlusion in a background of vasculitic changes of the same eye. There were no signs or symptoms of active systemic tuberculosis infection. Chest X-ray and computed tomography thorax findings were normal and sputum cultures for tuberculosis were negative. The Mantoux and QuantiFERON-TB Gold tests were strongly positive. No tuberculosis polymerase chain reaction testing was done. Anti-tuberculosis therapy was initiated, based on the strong clinical evidence. Conclusion: The ocular findings improved remarkably with the anti-tuberculosis treatment, although the left eye vision remained poor. A high index of suspicion is required to diagnose ocular tuberculosis when all other systemic investigations are negative, especially in this part of the world where tuberculosis is endemic. PMID:21834697

Ooi, Y L; Tai, L Y; Subrayan, V; Tajunisah, I



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

PubMed Central

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

Papageorgiou, Eleni; Karamagkiolis, Spyridon; Dimera, Vasiliki



The Role of Copper on Ethambutol’s Antimicrobial Action and Implications for Ethambutol-induced Optic Neuropathy 1 1 Grant support for this research: NIH (R01EY 11396-01A1 and AI25140)  

Microsoft Academic Search

The principal side effect of the antimycobacterial agent ethambutol (EMB) is an optic neuropathy with clinical features very similar to a mitochondrial hereditary optic neuropathy (Leber’s). The mechanism of EMB-induced optic neuropathy may be EMB’s chelation of copper, thereby precluding normal cytochrome c oxidase activity and mitochondrial metabolism in the optic nerve. Before attempting to use therapeutic copper to replenish

Scott F Kozak; Clark B Inderlied; Hugo Y Hsu; Keith B Heller; Alfredo A Sadun



mtDNA haplogroup distribution in Chinese patients with Leber’s hereditary optic neuropathy and G11778A mutation  

Microsoft Academic Search

Mitochondrial DNA background has been shown to be involved in the penetrance of Leber’s hereditary optic neuropathy (LHON) in western Eurasian populations. To analyze mtDNA haplogroup distribution pattern in Han Chinese patients with LHON and G11778A mutation, we analyzed the mtDNA haplogroups of 41 probands with LHON known to harbor G11778A mutation by sequencing the mtDNA control region hypervariable segments

Yanli Ji; Xiaoyun Jia; Qingjiong Zhang; Yong-Gang Yao



Molecular characterization of six Chinese families with m.3460G>A and Leber hereditary optic neuropathy  

Microsoft Academic Search

The primary mutation m.3460G>A occurs with a very low frequency (?1%) in Chinese patients with Leber hereditary optic neuropathy\\u000a (LHON). Up to now, there is no comprehensive study of Chinese patients harboring this mutation. We characterized six unrelated\\u000a probands with m.3460G>A in this study, which were identified from 1,626 patients with LHON or suspected with LHON. The overall\\u000a penetrance of

Dandan Yu; Xiaoyun Jia; A-Mei Zhang; Xiangming Guo; Ya-Ping Zhang; Qingjiong Zhang; Yong-Gang Yao



Thiamine-deficient optic neuropathy associated with Wernicke's encephalopathy in patients with chronic diarrhea.  


The deficiency of thiamine manifesting as Wernicke's encephalopathy (WE) and concurrent optic neuropathy is rare. Herein, we report the case of a 29-year-old patient who suffered from bilateral sudden blindness and a disturbance of consciousness after 2 months of chronic diarrhea and minimal food intake. In addition, bilateral abducens nerve palsy with multidirectional nystagmus and no light perception in both eyes were noted. An ophthalmoscopic examination revealed bilateral disc edema with peripapillary flame-shaped hemorrhages. Although the results of analyzing the composition of cerebrospinal fluid showed that they are within normal limits, magnetic resonance imaging (MRI) revealed bilateral hyperintensity over the mammillary body, dorsal medial thalamus, and periaqueductal gray matter. As we suspected thiamine deficiency-induced WE, a high dose of intravenous thiamine was prescribed. After the administration of thiamine, both visual acuity and visual field rapidly improved with the simultaneous recovery of consciousness. This case indicates that, although rare, thiamine deficiency with WE may still occur in patients with chronic diarrhea in Taiwan. Thiamine deficiency should be considered in the differential diagnosis for patients who encounter sudden visual loss after prolonged periods of poor food intake and poor vitamin supplementation. PMID:23473530

Yeh, Wei-Yi; Lian, Li-Ming; Chang, Anna; Cheng, Cheng-Kuo



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

PubMed Central

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 isoleusine 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 in the A6 and V254L 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.

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



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

PubMed Central

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.

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



Genetic polymorphisms associated with endothelial function in nonarteritic anterior ischemic optic neuropathy  

PubMed Central

Purpose To examine the relationship between nonarteritic anterior ischemic optic neuropathy (NAION) and genetic polymorphisms of enzymes influencing endothelial function. Methods The subjects were 34 patients with NAION (mean age, 62.4 years old; 59% male) and 102 controls (mean age, 63.8 years old; 66% male). Genetic polymorphisms were investigated in three candidate genes associated with endothelial function: endothelin-1 (ET-1), angiotensin-converting enzyme (ACE), and methylenetetrahydrofolate reductase (MTHFR). The genotype distributions in the patients with NAION were compared with those in the controls. Results There were no significant differences in the genotype distributions of the ACE I/D and MTHFR C677T polymorphisms between the NAION and control groups (p=0.261 and p=0.354, respectively), whereas the genotype distribution of the G/T (Lys198Asn) polymorphism of the ET-1 gene varied significantly between the groups (p=0.009). After adjusting for covariates, individuals with the TT genotype of the Lys198Asn polymorphism were more likely to develop NAION compared with those with the GG genotype (odds ratio=4.43, 95% confidence interval 1.33–14.73, p=0.015). Conclusions We found an increased prevalence of a G/T polymorphism of the ET-1 gene in patients with NAION. Our data suggest that this polymorphism may be an important risk factor in developing NAION in the Japanese population.

Shikishima, Keigo; Matsushima, Masato; Tsuneoka, Hiroshi



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


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

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



Clinical Profile and Visual Outcomes after Treatment in Patients with Dysthyroid Optic Neuropathy  

PubMed Central

Purpose To report the clinical data and visual outcomes after treatment of patients with dysthyroid optic neuropathy (DON). Methods We retrospectively reviewed the medical records and orbital images of 40 patients (65 eyes) with DON and analyzed the visual outcomes after treatment with intravenous steroids pulse therapy, radiotherapy and orbital decompression. Results The study included 21 men and 19 women, with 10 (25%) being diabetic patients. Visual field test results revealed defects in 88.7% of DON eyes; afferent pupillary defects in 63.2%; reduced color vision in 78.5%; and abnormal visual evoked potentials in 84%. Orbital imaging showed moderate to severe apical crowding in 95% of the orbits and intracranial fat prolapse in 24.2%. Median best corrected visual acuity improved from 0.4 to 1.0 after one year of treatment (p < 0.001). We noted more improvement in vision with the use of decompressive surgery than with non-surgical methods (p < 0.05). Recurrences occurred in 7 patients who had not received orbital radiotherapy. Conclusions Visual field defects and apical crowding seen on orbital imaging were the most sensitive indicators for the detection of DON. Treatment with intravenous steroids pulse therapy, radiotherapy and orbital decompression effectively improved visual outcomes in cases of DON.

Jeon, Chan; Shin, Jae Ho; Woo, Kyung In



Erectile dysfunction drugs and risk of anterior ischaemic optic neuropathy: casual or causal association?  

PubMed Central

Phosphodiesterase type 5 (PDE5) inhibitor drugs for erectile dysfunction have revolutionised the treatment of male sexual dysfunction and are among the best selling drugs worldwide. Several cases of non?arteritic anterior ischaemic optic neuropathy (NAION) have been reported since 2005 in users of these agents. NAION is a sudden irreversible cause of visual loss with a poorly understood aetiology that affects up to 10 adults per 100?000 each year. Following a series of such case reports, WHO and FDA have labelled the association between use of PDE5 inhibitors and risk of NAION as “possibly” causal. There have been several recent studies of this association, including a rechallenge case report and a large managed care database study. However, the inability to confirm or refute claims of an association between NAION and EDD is generating clinical and regulatory uncertainty. Questions surrounding use of PDE5 inhibitors and risk of NAION highlight weaknesses in current systems used to identify and evaluate uncommon adverse effects of medication use. This paper reviews all the recent evidence on PDE5 inhibitors and the risk of NAION.

Danesh-Meyer, Helen V; Levin, Leonard A



Toxic optic neuropathy after concomitant use of melatonin, zoloft, and a high-protein diet.  


Melatonin is a neuromodulating hormone found in the pineal gland and retina. It is involved in light-dark circadian rhythms and mediates retinal processes in a manner antagonistic to that of dopamine. Zoloft (sertraline) is an antidepressant drug that blocks the reuptake of serotonin at the neural synapse. Serotonin is the natural precursor of melatonin. A 42-year-old woman sought treatment for visual acuity loss, dyschromatopsia, and altered light adaptation. Neuro-ophthalmologic examination was otherwise normal except for evolving bilateral cecocentral scotomas. She had taken Zoloft for 4 years and began a high-protein diet with melatonin supplementation 2 weeks before onset of visual symptoms. Visual acuity and color vision improved within 2 months after melatonin and the high-protein diet were discontinued. Combined use of melatonin, Zoloft, and a high-protein diet may have resulted in melatonin/dopamine imbalance in the retina, manifesting as a toxic optic neuropathy. Physicians and patients should be alerted to this potential drug interaction. PMID:10608673

Lehman, N L; Johnson, L N



Optic Nerve Head Change in Non-Arteritic Anterior Ischemic Optic Neuropathy and Its Influence on Visual Outcome  

PubMed Central

Purpose To evaluate changes in cup/disc (C/D) diameter ratios and parapapillary atrophy in patients with non-arteritic anterior ischemic optic neuropathy (NA-AION), using morphometric methods. Methods The clinical non-interventional study included 157 patients with unilateral or bilateral NA-AION. Optic disc photographs taken from both eyes at the end of follow-up were morphometrically examined. Results Follow-up was 86.3±70.3 months. Horizontal and vertical disc diameters (P?=?0.30;P?=?0.61, respectively), horizontal and vertical C/D ratios (P?=?0.47;P?=?0.19,resp.), and size of alpha zone and beta zone of parapapillary atrophy (P?=?0.27;P?=?0.32,resp.) did not differ significantly between affected eyes and contralateral normal eyes in patients with unilateral NA-AION. Similarly, horizontal and vertical disc diameters, horizontal and vertical C/D ratios, and size of alpha zone and beta zone did not vary significantly (all P>0.05) between the unaffected eyes of patients with unilateral NA-AION and the eyes of patients with bilateral NA-AION. Optic disc diameters, C/D ratios, size of alpha zone or beta zone of parapapillary atrophy were not significantly associated with final visual outcome in the eyes affected with NA-AION (all P>0.20) nor with the difference in final visual acuity between affected eyes and unaffected eyes in patients with unilateral NA-AION (all P>0.25). Conclusions NA-AION did not affect C/D ratios nor alpha zone and beta zone of parapapillary atrophy. Optic disc size was not related to the final visual acuity outcome in NA-AION.

Jonas, Jost B.; Hayreh, Sohan Singh; Tao, Yong; Papastathopoulos, Konstantinos I.; Rensch, Florian



Diabetic neuropathy  


Nerve damage - diabetic; Diabetes - neuropathy ... the heart, bladder, stomach, and intestines (called autonomic neuropathy) ... develop: Bladder or kidney infection Diabetes foot ulcers Neuropathy that may hide the symptoms of angina, chest ...


Exploiting mTOR Signaling: A Novel Translatable Treatment Strategy for Traumatic Optic Neuropathy?  


Retinal ganglion cell (RGC) death and a failure of axon regeneration contribute to the profound visual loss experienced by patients after traumatic optic neuropathy (TON), for which there are no effective treatments. Experimental manipulations of cellular signaling pathways in animal models have demonstrated that neuronal survival and axon regeneration in the mature central nervous system (CNS) are possible, and increased understanding of the molecular basis of prosurvival and regenerative signals has led to the identification of candidate targets for novel therapeutic strategies. The axogenic pathway is activated sequentially, after growth factor/receptor binding, through phosphoinositide-3-kinase (PI3K) and the downstream serine/threonine kinase Akt. Akt is a nodal point for the regulation of growth cone dynamics by glycogen synthase kinase (GSK3?) and axon protein synthesis/RGC survival by the mammalian target of rapamycin (mTOR). The mTOR signaling pathway has a pivotal role in numerous cellular processes. It is active during development, but downregulated in the mature CNS and further suppressed by axonal injury, and experimental upregulation of mTOR signaling promotes RGC survival and axon regeneration after optic nerve crush injury. However, several translational challenges remain, including understanding the regulatory mechanisms of axotomy-induced mTOR and GSK3? signaling, and the disparity between the RGC survival and axon regenerative effects. In this review, we explore the molecular basis of RGC regenerative failure and assess the potential for manipulations of mTOR signaling as a novel translatable treatment for TON. PMID:24154996

Morgan-Warren, Peter J; Berry, Martin; Ahmed, Zubair; Scott, Robert A H; Logan, Ann




PubMed Central

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

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



Changes in Cholinergic Amacrine Cells after Rodent Anterior Ischemic Optic Neuropathy (rAION)  

PubMed Central

Purpose. Displaced cholinergic amacrine cell neurons comprise a significant fraction of the retinal ganglion cell (RGC) layer. Rodent anterior ischemic optic neuropathy (rAION) is an optic nerve infarct, which results in RGC loss in mice. The goal was to determine whether rAION produces changes in amacrine cell neurons. Methods. rAION was generated in transgenic mice carrying a cyan fluorescent reporter protein (CFP) gene linked to the Thy-1 promoter, which expresses CFP in RGCs. rAION was induced with standard parameters. Retinas were examined pre-and post-induction by retinal fundus microscopy. rAION induction severity was scored by changes in retinal transparency and RGC loss. Cholinergic amacrine cells were identified via choline acetyltransferase (ChAT) immunohistochemistry. ChAT and CFP expression was evaluated in flat-mounted retinas examined by confocal microscopy and western analysis. Results. Moderate rAION induction levels (defined as early retention of retinal transparency and <70% RGC loss) did not alter amacrine cell numbers in the RGC layer, but changed the relative levels of ChAT expression by immunohistochemistry. No changes in total ChAT protein were seen. Severe rAION induction (defined as loss of retinal transparency and >70% RGC loss) resulted in a trend toward amacrine cell loss and decreased ChAT protein levels. Conclusions. There is wide disparity in mouse rAION induction levels using standardized parameters. Moderate rAION induction levels without direct retinal compromise produces isolated RGC loss, with displaced amacrine cell changes likely due to changes in RGC-amacrine communication. Severe rAION induction results in both RGC and amacrine cell loss, possibly due to intra-retinal ischemic changes.

Guo, Yan



Variation in OPA1 does not explain the incomplete penetrance of Leber hereditary optic neuropathy  

PubMed Central

Purpose Leber hereditary optic neuropathy (LHON) is a common cause of inherited blindness, primarily due to one of three mitochondrial DNA (mtDNA) mutations. These mtDNA pathogenic mutations have variable clinical penetrance. Recent linkage evidence raised the possibility that the nuclear gene optic atrophy 1 (OPA1) determines whether mtDNA mutation carriers develop blindness. To validate these findings we studied OPA1 in three independent LHON cohorts: sequencing the gene in discordant male sib pairs, carrying out a family-based association study of common functional genetic variants, and carrying out a population-based association study of the same genetic variants. Methods We tested 3 hypothesis in three separate study groups. Study group 1: Direct sequencing of OPA1 coding regions was performed using sequencing methodologies (Applied Biosystems, Foster City, CA). Chromatograms were compared with the GenBank reference sequence NM_015560.1. Splice-site prediction was performed using GeneSplicer. Study group 2: Genotyping for rs166850 and rs10451941 was performed by restriction fragment length polymorphism (RFLP) analysis with specific primers for both genotypes, using The restriction enzymes RsaI and FspBI to discriminate genotypes. Study group 3: Genotyping for rs166850 and rs10451941 was performed by primer extension of allele-specific extensions products by matrix-associated laser desorption/ionisation time-of-flight (MALDI-TOF, Seqeunom, San Diego, CA) mass spectrometry. Allele and genotype frequencies were compared using Pearson’s chi-square test. Multiple logistic regression was performed to look for interactions between the variables. All analyses were performed using SPSS software version 17.0 (SPSS Inc.). Results In all three groups we were unable to find an association between OPA1 genetic variation and visual failure in LHON mtDNA mutation carriers. Conclusions Our findings suggest that genetic variation in OPA1 is unlikely to make a major contribution to the risk of blindness in LHON mutation carriers.

Hudson, Gavin; Yu-Wai-Man, Patrick; Griffiths, Phillip G.; Caporali, Leonardo; Salomao, Solange S.; Berezovsky, Adriana; Carelli, Valerio; Zeviani, Massimo



Optic nerve infarction and post-ischemic inflammation in the rodent model of anterior ischemic optic neuropathy (rAION)  

PubMed Central

Nonarteritic anterior ischemic optic neuropathy (NAION) results from isolated anterior optic nerve (ON)-axonal ischemia near the retina–optic nerve junction. We utilized a rodent model of NAION (rAION) to study the in vivo inflammatory response after pure axonal ischemic infarct. ON ischemia was generated using laser-coupled rose Bengal dye photoactivation, and the infarct localized using tetrazolium red and histology. ON inflammation was evaluated following infarct using extrinsic macrophage (ED1) and microglial (isolated Iba1) cell markers. In naive ONs, some ED1(+)/Iba1(+) cells, representing extrinsic macrophages, were present in intraretinal ON region, but not in the retroscleral (isolated ON) region. Numerous ED1(?)/Iba1(+) cells, likely representing intrinsic microglia, were present throughout the entire ON. One day post-stroke, slight increases in both ED1(+) and Iba1(+) cells were apparent in the eye region immediately surrounding the anterior ON. Three days post-stroke, there was marked infiltration and aggregates of ED1(+)/Iba1(+) cells, with axon structural disruption in the region of the ischemic infarct. ED1(+) and Iba1(+) cells were present in the portion of the ON surrounding the infarct, possibly representing a penumbral region similar to that seen in ischemic brain infarcts. Although ED1(+) cells decreased by 7–14 days post-stroke, large numbers of Iba1(+) cells persisted in the anterior ON. Similar to other CNS ischemic strokes, pure axonal ischemia results in the early recruitment of extrinsic macrophages to the ischemic region. Manipulation of the inflammatory response may be an important variable that could potentially improve visual outcome.

Zhang, Cheng; Guo, Yan; Miller, Neil R.; Bernstein, Steven L.



Optic nerve infarction and post-ischemic inflammation in the rodent model of anterior ischemic optic neuropathy (rAION).  


Nonarteritic anterior ischemic optic neuropathy (NAION) results from isolated anterior optic nerve (ON)-axonal ischemia near the retina-optic nerve junction. We utilized a rodent model of NAION (rAION) to study the in vivo inflammatory response after pure axonal ischemic infarct. ON ischemia was generated using laser-coupled rose Bengal dye photoactivation, and the infarct localized using tetrazolium red and histology. ON inflammation was evaluated following infarct using extrinsic macrophage (ED1) and microglial (isolated Iba1) cell markers. In naive ONs, some ED1(+)/Iba1(+) cells, representing extrinsic macrophages, were present in intraretinal ON region, but not in the retroscleral (isolated ON) region. Numerous ED1(-)/Iba1(+) cells, likely representing intrinsic microglia, were present throughout the entire ON. One day post-stroke, slight increases in both ED1(+) and Iba1(+) cells were apparent in the eye region immediately surrounding the anterior ON. Three days post-stroke, there was marked infiltration and aggregates of ED1(+)/Iba1(+) cells, with axon structural disruption in the region of the ischemic infarct. ED1(+) and Iba1(+) cells were present in the portion of the ON surrounding the infarct, possibly representing a penumbral region similar to that seen in ischemic brain infarcts. Although ED1(+) cells decreased by 7-14 days post-stroke, large numbers of Iba1(+) cells persisted in the anterior ON. Similar to other CNS ischemic strokes, pure axonal ischemia results in the early recruitment of extrinsic macrophages to the ischemic region. Manipulation of the inflammatory response may be an important variable that could potentially improve visual outcome. PMID:19401181

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



Renin-angiotensin-aldosterone system genes and nonarteritic anterior ischemic optic neuropathy  

PubMed Central

Purpose Recent literature suggests a genetic component for non-arteritic anterior ischemic optic neuropathy (NAION). We examined the association of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme gene, of the M235T polymorphism of the angiotensinogen gene, and of the A1166C polymorphism of the angiotensin II type 1 receptor gene with NAION. Methods Forty-seven patients with NAION and 76 controls, age- and gender-matched, were recruited and genotyped for renin-angiotensin-aldosterone system (RAAS) genes. Genotypes were determined by polymerase chain reaction and restriction enzyme analysis. NAION and control groups were compared in regard to the prevalence of renin-angiotensin-aldosterone system polymorphisms, and further stratified by age and gender. Results NAION occurrence was not associated with the M235T polymorphism of the angiotensinogen gene and the A1166C polymorphism of the angiotensin II, type 1 receptor gene. Regarding the angiotensin-converting enzyme insertion/deletion polymorphism, our findings suggest that the II genotype could be a risk factor for NAION in younger male patients when compared to all cases and controls (p=0.033, odds ratio=5.71, confidence interval=1.152¨C28.35 and p=0.03, odds ratio=5.33, confidence interval=1.17¨C24.31 respectively). Furthermore I allele was present in all male patients younger than 55 years, making this allele a likely predisposing factor for NAION in young males. Conclusions Since NAION may occur when compromised watershed microcirculation is combined with insufficient autoregulation of systematic circulation, polymorphisms of genes involved in systematic circulation, such as the RAAS genes, may be associated with NAION occurrence. Large-scale, multicentered, controlled prospective studies are needed to further explore the effects of RAAS polymorphisms or other genetic factors on NAION susceptibility.

Markoula, Sofia; Asproudis, Ioannis; Kostoulas, Charilaos; Nikas, Alexios; Bagli, Eleni; Kyritsis, Athanassios P.; Georgiou, Ioannis



Extra-Visual Functional and Structural Connection Abnormalities in Leber's Hereditary Optic Neuropathy  

PubMed Central

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

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



[Spectrum of pathogenic mtDNA mutations in Leber hereditary optic neuropathy families from Siberia].  


The results of clinical, genealogical and molecular investigation of eighteen families with Leber hereditary optic neuropathy (LHON), identified on the territory of Siberia during the period from 1997 to 2005, are presented. Comprehensive analysis of mitochondrial genome variations in probands and their matrilineal relatives revealed the presence of relatively frequent (G11778A, G3460A, and T14484C), as well as rare and new mutations with the established or presumptive pathological effect (T10663C, G363A, C4640T, and A14619G). The G11778A mutation was detected in nine pedigrees (50%), mostly in the families of ethnic Russians. In eight of these families G11778A was found in preferred association with the coding-region substitutions, typical of western Eurasian mtDNA lineage (haplogroup) TJ. On the contrary, the G3460A mutation was detected in the three families belonging to the indigenous Siberian populations (Tuvinians, Altaians, and Buryats). It was associated with clearly different haplotypes of eastern Eurasian haplogroups, C3, D5, and D8. Unexpectedly, the G3460A de novo mutation was found in a large Tuvinian pedigree. At the same time, in eleven out of fourteen families of Caucasoid origin pathogenic mutations in the ND genes were associated with the T4216C and C1542A coding-region mutations, marking the root motif of haplogoup TJ. It is suggested that phylogenetically ancient mutations could have provided their carriers with the adaptive advantages upon the development of Central and Northern Europe at the end of the last glaciation (10 000 to 9 000 years ago), thereby, contributing to the preservation of weekly pathogenic LHON mutations, appearing at specific genetic background. PMID:16523671

Volod'ko, N V; L'vova, M A; Starikovskaia, E B; Derbeneva, O A; Bychkov, I Iu; Mikha?lovskaia, I E; Pogozheva, I V; Fedotov, F F; Soyan, G V; Procaccio, V; Wallace, D C; Sukernik, R I



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

PubMed Central

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

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



Neuroprotective Effect of Hyperbaric Oxygen Therapy on Anterior Ischemic Optic Neuropathy  

PubMed Central

The study investigated the therapeutic effect of hyperbaric oxygen (HBO) on anterior ischemic optic neuropathy in a rodent model (rAION). rAION was laser-induced in one eye of 63 mice. The fellow (uninjured) eye served as an internal control. Thirty-three mice underwent two 90-min sessions of 100% oxygen (2?atm) treatment immediately following injury and one session daily thereafter for up to 14?days. The remaining mice were untreated. Retinas were harvested at different time points, and mRNA levels of various genes were analyzed by real-time polymerase chain reaction and histologic study. Untreated mice: day 1 post-rAION – SOD-1 (oxidative-stress-related) decreased to 82% of control (uninjured eye) levels (P?

Avraham-Lubin, Bat-Chen R.; Dratviman-Storobinsky, Olga; El, Shimrit Dadon-Bar; Hasanreisoglu, Murat; Goldenberg-Cohen, Nitza



All-optical XOR logic gate accompanied with OOK\\/PSK format conversion by the use of cross phase modulation in optical fiber  

Microsoft Academic Search

We propose and demonstrate an all-optical XOR logic gate accompanied with modulation format conversion from non-return-to-zero on-off-keying to return-to-zero binary phase-shift-keying by the use of cross-phase modulation in optical fiber.

Akihiro Maruta; Satoru Kitagawa



High-dose intravenous methylprednisolone in recent traumatic optic neuropathy; a randomized double-masked placebo-controlled clinical trial  

Microsoft Academic Search

Background  To compare the effect of high-dose intravenous corticosteroid therapy with placebo in the treatment of recent traumatic optic\\u000a neuropathy (TON).\\u000a \\u000a \\u000a \\u000a Methods  In a double-masked placebo-controlled clinical trial, 31 eyes of 31 patients were randomly assigned to two groups. Patients\\u000a with history of trauma ?7 days were included. Unconscious patients, eyes with penetrating trauma and candidates for decompression\\u000a surgery were excluded. The treatment

Morteza Entezari; Zhaleh Rajavi; Neda Sedighi; Narssis Daftarian; Masoumeh Sanagoo



Non-arteritic anterior ischemic optic neuropathy: role of systemic corticosteroid therapy  

PubMed Central

Objective To investigate systematically the role of systemic corticosteroid therapy in non-arteritic anterior ischemic optic neuropathy (NA-AION). Methods The study consists of a cohort of 613 consecutive patients (696 eyes), first seen in our clinic from 1973 to 2000. Of this cohort, 312 patients (364 eyes) voluntarily opted for systemic steroid therapy, and 301 (332 eyes) for no treatment. At first visit, all patients in both groups had a detailed ophthalmic and medical history, and comprehensive ophthalmic evaluation. Visual evaluation was done by recording Snellen visual acuity, and visual fields with a Goldmann perimeter. The same ophthalmic evaluation was performed at each follow-up visit. Patients in the steroid-treated group were initially given 80 mg Prednisone daily for 2 weeks, and then tapered down to 70 mg for 5 days, 60 mg for 5 days, and then cutting down by 5 mg every 5 days. Visual outcome in the two groups was compared Results Median follow-up was 3.8 years. At 6 months from onset of NA-AION, of the eyes with initial visual acuity 20/70 or worse and seen within 2 weeks of onset, there was visual acuity improvement in 69.8% (95% confidence interval (CI): 57.3%, 79.9%) in the treated group, compared to 40.5% (95% CI: 29.2%, 52.9%) in the untreated group (odds ratio of improvement: 3.39; 95% CI:1.62, 7.11; p=0.001). Comparison of visual field defect at 6 months from onset of NA-AION, among those seen within 2 weeks of NA-AION onset with moderate to severe initial visual field defect, there was improvement in 40.1% (95% CI: 33.1%, 47.5%) of the treated group, and 24.5% (95% CI: 17.7%, 32.9%) of the untreated group (odds ratio: 2.06, 95% CI: 1.24, 3.40; p= 0.005). In both treated and untreated groups, the visual acuity and visual fields kept improving up to about 6 months from onset of NA-AION, and very little thereafter. Conclusion This study suggested that NA-AION eyes treated during the acute phase with systemic corticosteroids resulted in a significantly higher probability of improvement in visual acuity (p=0.001) and visual field (p=0.005) than in the untreated group. Both visual acuity and visual fields improved up to 6 months after onset of NA-AION.

Hayreh, Sohan Singh; Zimmerman, M. Bridget



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

PubMed Central

Purpose Leber hereditary optic neuropathy (LHON), a maternally inherited disorder, results from point mutations in mitochondrial DNA (mtDNA). MtDNA is highly polymorphic in nature with very high mutation rate, 10–17 fold higher as compared to nuclear genome. Identification of new mtDNA sequence variations is necessary to establish a clean link with human disease. Thus this study was aimed to assess or evaluate LHON patients for novel mtDNA sequence variations. Materials and Methods Twenty LHON patients were selected from the neuro-ophthalmology clinic of the All India Institute of Medical Sciences, New Delhi, India. DNA was isolated from whole blood samples. The entire coding region of the mitochondrial genome was amplified by PCR in 20 patients and 20 controls. For structural analysis (molecular modeling and simulation) the MODELER 9.2 program in Discovery Studio (DS 2.0) was used. Results MtDNA sequencing revealed a total of 47 nucleotide variations in the 20 LHON patients and 29 variations in 20 controls. Of 47 changes in patients 21.2% (10/47) were nonsynonymous and the remaining 78.72% (37/47) were synonymous. Five nonsynonymous changes, including primary LHON mutations (NADH dehydrogenase subunit 1 [ND1]:p.A52T, NADH dehydrogenase subunit 6 [ND6]:p.M64V, adenosine triphosphate [ATP] synthase subunit a (F-ATPase protein 6) [ATPase6]:p.M181T, NADH dehydrogenase subunit 4 [ND4]:p.R340H, and cytochrome B [CYB]:p.F181L), were found to be pathogenic. A greater number of changes were present in complex I (53.19%; 25/47), followed by complex III (19.14%; 9/47), then complex IV (19.14%; 9/47), then complex V (8.5%; 4/47). Nonsynonymous variations may impair respiratory chain and oxidative phosphorylation (OXPHOS) pathways, which results in low ATP production and elevated reactive oxygen species (ROS) levels. Oxidative stress is the underlying etiology in various diseases and also plays a crucial role in LHON. Conclusions This study describes the role of mtDNA sequence variations in LHON patients. Primary LHON mutations of mtDNA are main variants leading to LHON, but mutations in other mitochondrial genes may also play an important role in pathogenesis of LHON as indicated in the present study. Certain alleles in certain haplogroups have protective or deleterious roles and hence there is a need to analyze a large number of cases for correlating phenotype and disease severity with mutation and mtDNA haplogroups.

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



Diabetic neuropathy.  


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

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



Diabetic neuropathy  

PubMed Central

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

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



Successful Amelioration of Mitochondrial Optic Neuropathy Using the Yeast NDI1 Gene in a Rat Animal Model  

PubMed Central

Background Leber's hereditary optic neuropathy (LHON) is a maternally inherited disorder with point mutations in mitochondrial DNA which result in loss of vision in young adults. The majority of mutations reported to date are within the genes encoding the subunits of the mitochondrial NADH-quinone oxidoreductase, complex I. Establishment of animal models of LHON should help elucidate mechanism of the disease and could be utilized for possible development of therapeutic strategies. Methodology/Principal Findings We established a rat model which involves injection of rotenone-loaded microspheres into the optic layer of the rat superior colliculus. The animals exhibited the most common features of LHON. Visual loss was observed within 2 weeks of rotenone administration with no apparent effect on retinal ganglion cells. Death of retinal ganglion cells occurred at a later stage. Using our rat model, we investigated the effect of the yeast alternative NADH dehydrogenase, Ndi1. We were able to achieve efficient expression of the Ndi1 protein in the mitochondria of all regions of retinal ganglion cells and axons by delivering the NDI1 gene into the optical layer of the superior colliculus. Remarkably, even after the vision of the rats was severely impaired, treatment of the animals with the NDI1 gene led to a complete restoration of the vision to the normal level. Control groups that received either empty vector or the GFP gene had no effects. Conclusions/Significance The present study reports successful manifestation of LHON-like symptoms in rats and demonstrates the potential of the NDI1 gene therapy on mitochondrial optic neuropathies. Our results indicate a window of opportunity for the gene therapy to be applied successfully after the onset of the disease symptoms.

Marella, Mathieu; Seo, Byoung Boo; Thomas, Biju B.; Matsuno-Yagi, Akemi; Yagi, Takao



Very high penetrance and occurrence of Leber's hereditary optic neuropathy in a large Han Chinese pedigree carrying the ND4 G11778A mutation  

PubMed Central

We report here the clinical, genetics and molecular characterization of a five-generation Han Chinese family with Leber’s hereditary optic neuropathy (LHON). Strikingly, this family exhibits very high penetrance and occurrence of optic neuropathy. In particular, twenty-five (10 males/15 females) of 30 matrilineal relatives exhibited the variable severity, ranging from profound to mild of visual impairment. This penetrance of optic neuropathy in this Chinese family is much higher than those in many families with LHON worldwide. The age-at-onset for visual impairment in matrilineal relatives in this Chinese family varied from 7 to 24 years old, with the average of 15 years old. Furthermore, the ratio between affected male and female matrilineal relatives is 1:1.5 in the Chinese family. This observation is in contrast with the typical features in LHON pedigrees that there was predominance of affected males in LHON in many families from different ethnic origins. Molecular analysis of mitochondrial genome identified the known ND4 G11778A mutation and 51 variants, belonging to Asian haplogroup C4a1. The absence of other known secondary LHON-associated and functionally significant mtDNA mutations in this Chinese family suggested that mitochondrial variants may not play an important role in the phenotypic manifestation of the G11778A mutation in this Chinese family. Therefore, nuclear modifier gene(s) may be responsible for very high penetrance and occurrence of optic neuropathy in this Chinese pedigree.

Zhou, Xiangtian; Zhang, Hongxing; Zhao, Fuxin; Ji, Yanchun; Tong, Yi; Zhang, Juanjuan; Zhang, Yu; Yang, Li; Qian, Yaping; Lu, Fan; Qu, Jia; Guan, Min-Xin



RhoA activity and post-ischemic inflammation in an experimental model of adult rodent anterior ischemic optic neuropathy.  


Activation of inflammatory cells and the RhoA signaling pathway may contribute to optic nerve damage following non-arteritic anterior ischemic optic neuropathy (NAION). We induced an optic nerve infarct with a photothrombotic mechanism in a rat model of AION (rAION). Immunohistochemistry and Western blot were performed to detect activation of RhoA signaling and inflammation. The extent of Rho activity, inflammation, retinal ganglion cell (RGC) loss and extent of axon regeneration were determined at 8 and 14 days after infarct. Eight days after stroke, we observed significant inflammation and RhoA activity at the site of infarction as well as loss of cells in the RGC layer. RhoA activity had decreased and inflammation had decreased at day 14 compared with day 8; however, loss of RGCs was greater at 14 days than at 8 days. Stroked eyes showed minor axon regeneration around the optic nerve lesion site at both 8 and 14 days. These results demonstrate that inflammation and RhoA activation occur in rAION at the site of infarction. PMID:23973747

Fard, Masoud Aghsaei; Ebrahimi, Katayoon Baradaran; Miller, Neil R



Acoustic effects at interaction of laser radiation with a liquid accompanied by optical breakdown  

SciTech Connect

The experimental researches of acoustic emission from optical breakdown in liquids are presented. Spectral characteristics and power of the acoustic waves generated in a liquid by optical breakdown at interaction of laser radiation with the wavelength of 532 nanometers were studied. It is shown, that two spectral maxima characterizing acoustic emission are observed. The shift of low-frequency maximum depending on the laser energy pulse is observed. As a whole, the linear dependence of acoustic pressure on the energy of laser pulse is observed. It is shown, that using acoustic data it is possible to reproduce function R(t) which will be in accord with characteristic dependences R(t), obtained from optical data. The last is especially important for breakdown studying in opaque environments.

Bulanov, A. V.; Nagorny, I. G. [V.I. Il'ichev Pacific Oceanologic Institute Far Eastern Branch of Russian Academy of Sciences, 43, Baltic Str., Vladivostok, 690041 (Russian Federation); Far Eastern Federal University, 8, Sukhanova Str., Vladivostok, 690950 (Russian Federation)



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


Glaucomatous optic neuropathy is a primary pathological condition responsible for visual dysfunction due to glaucoma. However, how intraocular pressure and other risk factors lead to glaucomatous optic neuropathy is not fully understood. Given that static or kinetic visual field tests for evaluating visual dysfunction in glaucomatous optic neuropathy are a subjective assessments based on a psychophysical principle, the development of a tool for objective assessment of the visual field is needed. In this study, we attempt to elucidate the pathophysiology of glaucomatous optic neuropathy and to refine a modality for the objective assessment of the visual dysfunction due to it. Aquaporin (AQP) water channels are located primarily in the plasma membrane. These proteins form either a homo- or hetero-tetramer and allow water to cross the plasma membrane bi-directionally. The transmembrane water movement through AQPs is critically involved in the maintenance of normal neuronal activity. Among the 13 isoforms indentified so far, AQP-4 is known to be expressed in the retrobulbar portion of the optic nerve. However, the optic nerve head, the primary pathological site of glaucomatous optic neuropathy, reportedly does not express AQP-4. We found that in control rats, astrocytes throughout the optic nerve express AQP-9. The chronic elevation of intraocular pressure due to cauterization of three episcleral veins substantially reduced both gene expression and immunoreactivity of AQP-9, whereas it did not change the AQP-4 gene or protein expression in the retrobulbar portion of the optic nerve. These findings are implicated in the chronic elevation of intraocular pressure in astrocytes. Similar findings were also observed in the eyes of a monkey with angle-laser-induced ocular hypertension and of a human with primary open-angle glaucoma. AQP-9 was also expressed in the cell bodies of retinal ganglion cells in control rats and its expression was significantly reduced in the eyes of rats with ocular hypertension. Recently, the astrocyte-to-neuron lactate shuttle hypothesis has been proposed. This hypothesis suggests that lactate generated by glucose during glycolysis in astrocytes is used by neurons as an energy substrate. Given that AQP-9 belongs to an aquaglyceroporin subfamily and allows solutes other than water (e.g., lactate) to cross the plasma membrane, chronic ocular hypertension may perturb this physiological passage of lactate. Thus, lactate as the energy substrate may be unable to be transported from astrocytes to retinal ganglion cells at the cell bodies and axons due to the reduction of AQP-9 expression by astrocytes at the optic nerve head and retinal ganglion cells. The multifocal visual evoked potential (mfVEP) is an objective visual field test, which enables the recording of cortical potential corresponding to 60 local retinal areas simultaneously. Evidence is accumulating that the signal-to-noise ratio (SNR) has been enhanced by recording mfVEPs from multiple channels at the same time. However, previous studies evaluated the mfVEPs mostly in Caucasians. It has not yet been proven whether this strategy is applicable to Japanese people who have a skull frame that may be different from that of Caucasians. We calculated the relative position of the calcarine landmark for electrode placement during the mfVEP recording, from brain MRI images of 200 individuals, which were found to be 1 cm lower than those reported in Caucasians with a statistical significance. Then, we recorded mfVEPs from 110 normal controls using three channels and conducted receiver-operating characteristic (ROC) curve analysis of the overlap of SNR distribution at signal and noise windows. We found that a combination of one horizontal channel straddling the inion with either one of the two perpendicular vertical channels yielded the largest area under the ROC curve (AUC). Next, we showed that the SNR-AUC exhibited a similar diagnostic performance to, and a significant correlation with, a total deviation of the Humphrey visual field in 56 eyes with mild to

Nakamura, Makoto



Inflammatory neuropathies.  


Inflammatory neuropathies are acquired disorders of peripheral nerves and occasionally of the central nervous system that can affect individuals at any age. The course can be monophasic, relapsing, or progressive. Inflammatory neuropathies are classified as acute or chronic. The acute form reaches a nadir by 4 weeks and the chronic form over 8 weeks or greater. The most common example of an acute inflammatory neuropathy is acute inflammatory demyelinating polyradiculoneuropathy (AIDP), which is part of the Guillain-Barré syndrome (GBS). The most common chronic inflammatory neuropathy is chronic inflammatory demyelinating polyradiculopathy (CIDP). Other chronic inflammatory neuropathies are multifocal motor neuropathy (MMN) and the Lewis-Sumner syndrome. The Fisher syndrome and Bickerstaff brainstem encephalitis occur acutely and have clinical overlap with AIDP. PMID:20941668

Whitesell, Jackie



Acquired neuropathies.  


Acquired neuropathies represent most of the neuropathies encountered in clinical practice. Hundreds of causes have been identified even though up to 41 % of patients are still classified as idiopathic (Rajabally and Shah in J Neurol 258:1431-1436, 1). Routine evaluation relies on comprehensive medical history taking, clinical examination, nerve conduction studies and laboratory tests. Other investigations such as nerve biopsy or nerve or muscle imaging are performed in specific settings. This review focuses on recent advances in acquired neuropathies. PMID:23771508

Lozeron, Pierre; Trocello, Jean-Marc; Kubis, Nathalie



Diabetic Neuropathy  

Microsoft Academic Search

Polyneuropathy is one of the commonest complications of the diabetes and the commonest form of neuropathy in the developed\\u000a world. Diabetic polyneuropathy encompasses several neuropathic syndromes, the most common of which is distal symmetrical neuropathy,\\u000a the main initiating factor for foot ulceration. The epidemiology of diabetic neuropathy has recently been reviewed in reasonable\\u000a detail (1). Several clinic- (2,3) and populationbased

Solomon Tesfaye


Peripheral Neuropathy  


... diet, correcting vitamin deficiencies, and limiting or avoiding alcohol consumption -- can reduce the physical and emotional effects of peripheral neuropathy. Systemic diseases frequently require more complex ...


Cytotoxicity and vitreous stability of chemically modified connexin43 mimetic peptides for the treatment of optic neuropathy.  


Optic neuropathy is associated with retinal ganglion cell (RGC) loss leading to optic nerve damage and visual impairment. Unregulated connexin (Cx) hemichannel opening plays a role in RGC loss. Thus, inhibition via Cx43-specific mimetic peptides (MP) may prevent further cell death. However, the highly hydrophilic character and poor stability of native peptides prevent their efficient delivery across biological membranes. The present study aimed to improve the stability of Cx43 MP by conjugation to C12-lipoamino acid (C12-Laa) or sugar groups. Unmodified and modified Cx43 MP were synthesized using solid-phase peptide synthesis. Their functionality was assessed by propidium iodide (PI) uptake into NT2 cells, a human testicular carcinoma progenitor cell line able to differentiate into astrocytes, whereas the stability in ocular vitreous was measured by reversed-phase high-performance liquid chromatography. PI uptake studies showed inhibition of hemichannel opening for unmodified and modified Cx43 MP. Stability measurements revealed improved stability of modified Cx43 MP, with two Laa groups increasing the peptide half-life in bovine vitreous more than twofold. Conjugation to C12 -Laa or sugar did not affect the functionality of Cx43 MP, but addition of two C12-Laa groups significantly improved peptide stability. Laa-modifications may therefore offer improved stability and retinal delivery of peptides in vivo. PMID:23696181

Chen, Ying-Shan; Toth, Istvan; Danesh-Meyer, Helen V; Green, Colin R; Rupenthal, Ilva D



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

PubMed Central

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.

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



Role of aspirin in reducing the frequency of second eye involvement in patients with non-arteritic anterior ischaemic optic neuropathy  

Microsoft Academic Search

Purpose To retrospectively evaluate in patients with non-arteritic ischaemic optic neuropathy (NAION) whether aspirin reduces the frequency of second eye involvement.Methods In 52 patients who presented with NAION between 1984 and 1997 adequate information was available regarding use of aspirin, presence of risk factors and second eye involvement.Results Second eye involvement was noted in 8 of 16 patients (50%) who

Ophira Salomon; Ruth Huna-Baron; David M Steinberg; Shimon Kurtz; Uri Seligsohn



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

Microsoft Academic Search

Leber's hereditary optic neuropathy (LHON) is a maternally inherited blinding disease due to mitochondrial DNA (mtDNA) point mutations in complex I subunit genes, whose incomplete penetrance has been attributed to both genetic and environmental factors. Indeed, the mtDNA background defined as haplogroup J is known to increase the penetrance of the 11778\\/ND4 and 14484\\/ND6 mutations. Recently it was also documented

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



A Mitochondrial DNA Mutation at Nucleotide Pair 14459 of the NADH Dehydrogenase Subunit 6 Gene Associated with Maternally Inherited Leber Hereditary Optic Neuropathy and Dystonia  

Microsoft Academic Search

A five-generation Hispanic family expressing maternally transmitted Leber hereditary optic neuropathy and\\/or early-onset dystonia associated with bilateral basal ganglia lesions was studied. Buffy coat mitochondrial DNA (mtDNA) from a severely affected child was amplified by the polymerase chain reaction and greater than 90% sequenced. The mtDNA proved to be a Native American haplogroup D genotype and differed from the standard

Albert S. Jun; Michael D. Brown; Douglas C. Wallace



Correlations Between Retinal Nerve Fiber Layer and Visual Field in Eyes with Non-Arteritic Anterior Ischemic Optic Neuropathy  

PubMed Central

Purpose To evaluate correlations between Retinal Nerve Fiber Layer (RNFL) thickness with visual field (VF) sensitivities in eyes with Non-artertic Anterior Ischemic Optic Neuropathy (NAION). Design case-control study. Methods This study was conducted in an academic, institutional setting. One eye from 21 NAION patients and 32 healthy participants were included in this prospective study. Humphrey Visual Field (HVF) sensitivities were obtained from standard achromatic HVF test (24-2 SITA). RNFL was measured with scanning laser polarimetry (GDx-VCC) and optical coherence tomographer (StratusOCT). Correlations were evaluated between RNFL and sensitivities from global, hemifields and regional locations of the VF pertinent to the RNFL distribution. 15 NAION eyes had an inferior altitudinal HVF defects and their global and regional RNFL was compared to that of control eyes. The main outcome measure was correlation between HVF sensitivities and RNFL. Results Correlations of global, hemifield and sectorial HVF sensitivities with RNFL were greater when RNFL was measured with StratusOCT than with GDx-VCC, except for nasal and infero-nasal sectors. RNFL thickness was significantly lower in the hemiretinas corresponding to the relative unaffected hemifield in eyes with altitudinal visual field defect compared to controls. Conclusions In patients with NAION, RNFL measured by StratusOCT provided better correlation to HVF changes than GDx-VCC did. Both instruments showed decreased RNFL in NAION eyes with altitudinal visual field defects compared to control eyes, demonstrating loss of RNFL even in sectors of the optic disc that corresponded to relatively unaffected hemifield, suggesting greater damaged beyond the extent estimated by visual field methods.

DeLeon-Ortega, Julio; Carroll, Kristin E.; Arthur, Stella N.; Girkin, Christopher A.



Low penetrance of Leber's hereditary optic neuropathy in ten Han Chinese families carrying the ND6 T11484C mutation  

PubMed Central

We report there the clinical, genetic and molecular characterization of 10 Han Chinese families with Leber’s hereditary optic neuropathy. Clinical evaluation revealed that ten families exhibited extremely low penetrance of visual impairment, with the average of 10%. In particular, ten (8 males/2 females) of 114 matrilineal relatives in these families exhibited the variable severity and age-at-onset in visual dysfunction. The average age-of-onset of vision loss was 19 years old. Molecular analysis of mitochondrial DNA (mtDNA) identified the homoplasmic ND6 T14484C mutation and distinct sets of variants, belonging to the Asian haplogroups B5b, D4, D4g1b, G3a2, R11, R11a and Z3, respectively. However, there was the absence of secondary LHON-associated mtDNA mutations in these ten Chinese families: The low penetrance of vision loss in these Chinese pedigrees strongly indicated that the T14484C mutation was itself insufficient to produce a clinical phenotype. The absence of secondary LHON mtDNA mutations suggest that these mtDNA haplogroup-specific variants may not play an important role in the phenotypic expression of the T14484C mutation in those Chinese families with low penentrace of vision loss. However, nuclear modifier genes and environmental factors appear to be modifier factors for the phenotypic manifestation of the T14484C mutation in these Chinese families.

Qu, Jia; Zhou, Xiangtian; Zhao, Fuxin; Liu, Xiaoling; Zhang, Minglian; Sun, Yan-Hong; Liang, Min; Yuan, Meixia; Liu, Qi; Tong, Yi; Wei, Qi-Ping; Yang, Li; Guan, Min-Xin



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

PubMed Central

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

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



mtDNA haplogroup distribution in Chinese patients with Leber's hereditary optic neuropathy and G11778A mutation.  


Mitochondrial DNA background has been shown to be involved in the penetrance of Leber's hereditary optic neuropathy (LHON) in western Eurasian populations. To analyze mtDNA haplogroup distribution pattern in Han Chinese patients with LHON and G11778A mutation, we analyzed the mtDNA haplogroups of 41 probands with LHON known to harbor G11778A mutation by sequencing the mtDNA control region hypervariable segments and some coding region polymorphisms. Each mtDNA was classified according to the available East Asian haplogroup system. The haplogroup distribution pattern of LHON sample was then compared to the reported Han Chinese samples. Haplogroups M7, D, B, and A were detected in 11 (26.8%), 10 (24.4%), 8 (19.5%), and 5 (12.2%) LHON families, respectively, and accounted for 82.9% of the total samples examined. For the remaining seven mtDNAs, six belonged to M8a, M10a, C, N9a, F1a, and R11, respectively, and one could only be assigned into macro-haplogroup M. The LHON sample was distinguished from other Han Chinese samples in the principal component map based on haplogroup distribution frequency. Our results show that matrilineal genetic components of Chinese LHON patients with G11778A are diverse and differ from related Han Chinese regional samples. mtDNA background might affect the expression of LHON and the G11778A mutation in Chinese population. PMID:17942074

Ji, Yanli; Jia, Xiaoyun; Zhang, Qingjiong; Yao, Yong-Gang



Peripheral Neuropathy  


... long fiber that extends out from the main nerve cell body). Some neuropathies are caused by inflammation resulting ... the ability to regenerate, as long as the nerve cell itself has not been killed. Symptoms often can ...


Alcoholic neuropathy  


... and the effect of poor nutrition associated with alcoholism. Up to half of all long-term heavy ... alcoholic neuropathy include: Long-term, heavy alcohol use Alcoholism that is present for 10 years or more


Progressive optic neuropathy and sensorineural hearing loss due to chronic glue sniffing  

Microsoft Academic Search

A 27-year-old male developed cerebral and cerebellar atrophy over a period of five years of extensive glue sniffing. He also developed bilateral optic atrophy with blindness and severe sensorineural hearing loss. Investigation failed to show any other cause for the visual or hearing loss. Peripheral polyneuropathy and central nervous system damage may follow chronic toluene toxicity, but these auditory and

A Ehyai; F R Freemon



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


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

Hexdall, Eric J; Butler, Frank K


T cell immunity to copolymer 1 confers neuroprotection on the damaged optic nerve: Possible therapy for optic neuropathies  

Microsoft Academic Search

We recently reported that the posttraumatic spread of degeneration in the damaged optic nerve can be attenuated by the adoptive transfer of autoimmune T cells specific to myelin basic protein. However, it would be desirable to obtain immune neuroprotection free of any possible autoimmune disease. In an attempt to obtain disease-free immune neuroprotection, we used the synthetic four-amino acid polymer

Jonathan Kipnis; Eti Yoles; Ziv Porat; Avi Cohen; Felix Mor; Michael Sela; Irun R. Cohen; Michal Schwartz



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

PubMed Central

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

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



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

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.

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



Efficacy of Intravitreal Ranibizumab Injection in Acute Nonarteritic Ischemic Optic Neuropathy: A Long-Term Follow Up§  

PubMed Central

Background: To evaluate the effect of a single intravitreal ranibizumab injection in eyes with acute nonarteritic ischemic optic neuropathy (NAION). Subjects and Methods: In this retrospective clinical data analysis, 17 eyes of sixteen patients who experienced a visual loss with duration of 15 days or less comprised the study group. In addition to standard ophthalmic examination, retinal nerve fiber layer thickness (RNFLT) analysis with spectral domain OCT was also performed prior to 0.5 mg Ranibizumab injection, one week, one, three, six months and one year after the injection. Results: The mean time between visual loss and intravitreal injection was 7.5 days (Range, 2-15 days). Mean age of patients was 59 years (Range, 41-90 years). Male to female ratio was 6:10. After a single dose of ranibizumab injection, visual gain was noted in 14 of 17 study eyes. In two eyes, visual acuity was minimally reduced and no change was noted in the remaining eye with an initial visual acuity of hand motions. While pre-injection mean best-corrected visual acuity (BCVA) was 1.45 ±0.88 log Mar unit, post-injection mean BCVA was 1.00±0.68, 0.86 ±0.70, 0.80 ±0.71, 0.77 ±0.70, 0.77 ±0.70 log Mar unit respectively at the first week, first month, third month, sixth month and first year. In all patients, the mean RNFLT dramatically decreased after the injection during the follow- up. While pre-injection mean RNFLT was 210 ±38 µm, post-injection mean RNFLT was 162.11±40.2, 94±27, 71.23±22.5, 63 ±19 and 57 ±18 µm respectively at the first week, first month, third month, sixth month and first year. No injection related complication was noted during the follow-up period. Conclusion: Intravitreal ranibizumab injection can be a treatment modality in eyes with acute NAION.

Saatci, Ali Osman; Taskin, Okan; Selver, Ozlem Barut; Yaman, Aylin; Bajin, Meltem Soylev



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

PubMed Central

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

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



Diabetic Neuropathies  

Microsoft Academic Search

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

Aaron I. Vinik


The mitochondrial tRNA Glu A14693G mutation may influence the phenotypic manifestation of ND1 G3460A mutation in a Chinese family with Leber’s hereditary optic neuropathy  

Microsoft Academic Search

We report here the clinical, genetic, and molecular characterization of one Han Chinese family with maternally transmitted Leber’s hereditary optic neuropathy (LHON). Three of seven matrilineal relatives in this family exhibited the variable degree of central vision loss at the age of 12, 14, and 16 years old, respectively. Sequence analysis of the complete mitochondrial DNA in this pedigree revealed

Yi Tong; Yijian Mao; Xiangtian Zhou; Li Yang; Juanjuan Zhang; Wanshi Cai; Fuxing Zhao; Xinjian Wang; Fan Lu; Jia Qu; Min-Xin Guan



Neuropathies of the optic nerve and visual evoked potentials with special reference to color vision and differential light threshold measured with the computer perimeter OCTOPUS.  


The contrast evoked potentials (VEPs) to different check sizes were recorded in about 200 cases of discrete optic neuropathies (ON) of different origin. Differential light threshold (DLT) was tested with the computer perimeter OCTOPUS. Saturated and desaturated tests were applied to evaluate the degree of acquired color vision deficiency. Delayed VEP responses are not confined to optic neuritis (RBN) alone and the different latency times obtained from other ON are confluent. The delay may be due to demyelination, to an increasing dominance of paramacular VEP subcomponents or to an increasing dominance of the upper half-field responses. Recording with smaller check sizes has the advantage that discrete dysfunctions in the visual field (VF) center are more easily detected: a correlation between amplitudes and visual acuity is best in strabismic amblyopias, is less expressed in maculopathies of the retina and weak in ON. The absence or reduction of amplitudes to smaller check sizes, however, is an important indication of a disorder in the VF center of ON in an early or recovered stage. Acquired color vision defects of the tritan-like type are more confined to discrete ON, whereas the red/green type is reserved to more severe ON. The DLT of the VF center is reduced in a different, significant and non significant extent in discrete optic neuropathies and the correlation between DLT and visual acuity is weak. A careful numerical analysis is needed in types of discrete ON where the central DLT lies within normal statistical limits: a side difference of the DLT between the affected and the normal fellow eye is always present. Evaluation of visual fatigue effects and of the relative sensitivity loss of VF center and VF periphery may provide further diagnostic information. PMID:6510191

Wildberger, H



Uremic neuropathy.  


Polyneuropathy is a common complication of end-stage renal failure especially when treatment with periodic hemodialysis is started too late. Large myelinated fibers bear the brunt of the many biological changes associated with renal failure. Nerve conduction slowing is common in this setting. Compression of the median nerve in the carpal tunnel commonly occurs in these patients, as a result of amyloid deposits at this site. End-stage renal failure in diabetic patients is often associated with severe distal motor and sensory deficits. Improved quality of periodic hemodialysis and renal transplantation have dramatically reduced the prevalence and severity of peripheral neuropathy in these patients. PMID:23931805

Said, Gérard



Mitochondrial gene therapy improves respiration, biogenesis, and transcription in G11778A Leber's hereditary optic neuropathy and T8993G Leigh's syndrome cells.  


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

Iyer, Shilpa; Bergquist, Kristen; Young, Kisha; Gnaiger, Erich; Rao, Raj R; Bennett, James P



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

PubMed Central

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

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



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

SciTech Connect

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.

Torroni, A.; Petrozzi, M.; Terracina, M. [Universita` di Roma (Italy)] [and others



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

PubMed Central

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

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



Leprous neuropathy.  


Leprous neuropathy, which is due to infection of nerve cells by Mycobacterium leprae, still affects millions of people in many developing countries. The clinical and pathological manifestations are determined by the natural resistance of the host to invasion of M. Leprae. Failure of early detection of leprosy often leads to severe disability in spite of eradication of mycobacterium at a later date. In the lepromatous type, bacilli are easily found in the skin and in nerve cells including Schwann cells, endothelial cells, and macrophages. In the tuberculoid type, a strong cell-mediated immune reaction leads to formation of granulomas and destruction of cells harboring bacilli and neighboring nerve fibers. In many cases, treatment of patients with the multibacillary leprosy is complicated by reversal reaction and further nerve damage. Nerve lesions lead to a symmetrical, pseudo-polyneuritic pattern in most cases of lepromatous leprosy, which is usually associated with typical skin lesions, but pure neuritic forms occur in up to 10% of patients with lepromatous leprosy. In the pure neuropathic cases, only nerve biopsy permits diagnosis. The multifocal pattern is more common in tuberculoid leprosy. Treatment is currently based on multidrug therapy with dapsone, rifampicin, and clofazimine. The use of corticosteroids can reduce or prevent nerve damage in reversal reactions. It is important to remember that sequelae, especially sensory loss, are extremely common, which can lead to secondary trophic changes due to repeated trauma in painless areas. PMID:23931798

de Freitas, Marcos R G; Said, Gérard



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

PubMed Central

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

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



An Optical-Near-infrared Outburst with no Accompanying ?-Rays in the Blazar PKS 0208-512  

NASA Astrophysics Data System (ADS)

We report the discovery of an anomalous flare in a bright blazar, namely, PKS 0208-512, one of the targets of the Yale/SMARTS optical-near-IR (OIR) monitoring program of Fermi blazars. We identify three intervals during which PKS 0208-512 undergoes outbursts at OIR wavelengths lasting for gsim3 months. Its brightness increases and then decreases again by at least 1 mag in these intervals. In contrast, the source undergoes bright phases in GeV energies lasting gsim1 month during intervals 1 and 3 only. The OIR outburst during interval 2 is comparable in brightness and temporal extent to the OIR flares during intervals 1 and 3, which do have ?-ray counterparts. By analyzing the ?-ray, OIR, and supporting multi-wavelength variability data in details, we speculate that the OIR outburst during interval 2 was caused by a change in the magnetic field without any change in the total number of emitting electrons or Doppler factor of the emitting region. Alternatively, it is possible that the location of the outburst in the jet during interval 2 was closer to the black hole where the jet is more compact and the bulk Lorentz factor of the material in the jet is smaller. We also discuss the complex OIR spectral behavior during these three intervals.

Chatterjee, Ritaban; Fossati, G.; Urry, C. M.; Bailyn, C. D.; Maraschi, L.; Buxton, M.; Bonning, E. W.; Isler, J.; Coppi, P.



Primary cell culture of meningothelial cells—a new model to study the arachnoid in glaucomatous optic neuropathy  

Microsoft Academic Search

Background  In a previous report, we found that the occurrence and amount of meningothelial cell nests in the subarachnoid space are significantly\\u000a increased in glaucomatous optic nerves compared to normals. In order to allow research into the role of meningothelial cells\\u000a during diseases of the optic nerve, an in vitro model is necessary. For this purpose, we developed a culture method

Xiaorong Xin; Bin Fan; Hanspeter E. Killer; Albert Neutzner; Josef Flammer; Peter Meyer



Risk of non-arteritic anterior ischaemic optic neuropathy (NAION) after cataract extraction in the fellow eye of patients with prior unilateral NAION  

PubMed Central

Aim To determine the risk of non?arteritic anterior ischaemic optic neuropathy (NAION) after cataract extraction (CE) in the fellow eye of patients with prior unilateral NAION. Design Retrospective, cohort study. Methods Medical records of patients with NAION evaluated in our institution between 1 January 1986 and 31 December 2001 were reviewed to determine the onset of NAION and the time of CE. Patients were excluded if the date of NAION and CE was unreliable, or if CE in the fellow eye was performed before the unilateral NAION. Statistical analysis was performed by including fellow eye CE as a time?dependent covariate in a Cox proportional hazards regression model of NAION incidence in the fellow eye. Results Of the 325 eligible patients, 9 (53%) of 17 patients with NAION who underwent CE in the fellow eye developed fellow eye NAION, and 59 (19%) of 308 patients with NAION who did not undergo CE in the fellow eye developed fellow eye NAION. Cataract extraction in the fellow eye increased the risk of NAION occurrence in the fellow eye by 3.6?fold (Cox regression, p?=?0.001). Conclusions Patients with unilateral NAION are at a significantly higher risk of developing NAION in the fellow eye after CE.

Lam, Byron L; Jabaly-Habib, Haneen; Al-Sheikh, Nabih; Pezda, Matthew; Guirgis, Medhat F; Feuer, William J; McCulley, Timothy J



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

SciTech Connect

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.

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



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

SciTech Connect

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.

Xiangdong Bu; Rotter, J.I. (Cedars-Sinai Medical Center, Los Angeles, CA (United States) Univ. of California, Los Angeles (United States))



Development of spontaneous optic neuropathy in NF-kappaBetap50-deficient mice: requirement for NF-kappaBetap50 in ganglion cell survival.  


Although the transcription factor NF-kappaBeta is known to regulate cell death and survival, its precise role in cell death within the central nervous system remains unknown. The purpose of this study was to investigate the role of NF-kappaBetap50 in the age-related survival of retinal ganglion cells (RGCs). Eyes of mice with a deleted NF-kappaBetap50 gene and its wild-type mice at each of age were studied by histopathological studies. The number of RGCs was counted using retrograde labelling methods. Mice were subjected to intravitreous injection of N-methyl-D aspartate (NMDA) to induce RGC death. In p50-deficient mice, the number of RGCs significantly decreased with age in total independence of intraocular pressure measurement. Optic nerves of p50-deficient mice showed hypertrophy astrocytes and enlargement of the axons, together with a decreased number of axons. Immunohistochemistry showed a strong expression of glial fibrillary acidic protein. The histological results show obvious excavation of the optic nerve head in p50-deficient mice at 10 months of age. Intravitreal injection of NMDA in young p50-deficient mice damaged RGCs more intensively than in control animals. We further noticed that autoantibodies against RGCs were produced in p50-deficient mice. Our results show that p50 deficiency induced age-related RGC death, indicating a new insight into the role of p50 in the pathophysiology of neuropathy, and further experiments with p50-deficient mice may provide new targets for therapeutic intervention for human glaucoma. PMID:17931357

Takahashi, Y; Katai, N; Murata, T; Taniguchi, S-I; Hayashi, T



Disease mechanisms in inherited neuropathies  

Microsoft Academic Search

Inherited neuropathies are caused by dominant or recessive mutations in genes that are expressed by neurons and\\/or Schwann cells. In demyelinating neuropathies, the deleterious effects originate primarily in myelinating Schwann cells. In axonal neuropathies, neurons (axons) are initially affected. In demyelinating neuropathies, the axonal cytoskeleton is altered and axonal transport is disrupted. In some axonal neuropathies, genes that are directly

Steven S. Scherer; Ueli Suter



Brachial plexus neuropathy  

PubMed Central

Branchial plexus neuropathy is characterized by acute onset of intense pain in the shoulder or arm followed shortly by focal muscle weakness. This presentation may mislead the clinician into diagnosing shoulder or cervical spine pathology. Although brachial plexus neuropathy is not common, it should be considered in the differential diagnosis of pain and weakness of the arm. We present a patient with brachial plexus neuropathy who was originally misdiagnosed as having a cervical disc herniation. ImagesFigure 1Figure 2Figure 3

Hubka, Michael J; King, Laurie; Cassidy, J David; Donat, JR



Complete mitochondrial DNA sequence analysis in two southern Chinese pedigrees with Leber hereditary optic neuropathy revealed secondary mutations along with the primary mutation  

PubMed Central

AIM To investigate mitochondrial factors associated with Leber hereditary optic neuropathy (LHON) through complete sequencing and analysis of the mitochondrial genome of Chinese patients with this disease. METHODS Two unrelated southern Chinese families with LHON and 10 matched healthy controls were recruited, and their entire mitochondrial DNA (mtDNA) was amplified and sequenced with the universal M13 primer. Then DNA sequence analysis and variation identification were perfomed by DNAssist and Chromas 2 software and compared with authoritative databases such as Mitomap. RESULTS Mutational analysis of mtDNA in these two Chinese pedigrees revealed one common LHON-associated mutation, G11778A (Arg?His), in the MT-ND4 gene. In addition, there were two secondary mutations in Pedigree 1: C3497T (Ala?Val), and C3571T (Leu?Phe) in the MT-ND1 gene, which have not been reported; and two secondary mutations occurred in Pedigree 2: A10398G (Thr?Ala) in the MT-ND3 gene, and T14502C (Ile?Val) in the MT-ND6 gene. Three polymorphisms, A73G, G94A and A263G in the mtDNA control region, were also found. CONCLUSION Our study confirmed that the known MT-ND4*G11778A mutation is the most significant cause of LHON. The C3497T and C3571T mutations in Pedigree 1 were also both at hot-spots of MT-ND1; they may affect the respiratory chain in coordination with the primary mutation G11778A. In Pedigree 2, the two secondary mutations A10398G of MT-ND3 and T14502C of MT-ND6 may influence mitochondrial respiratory complex I, leading to the mitochondrial respiratory chain dysfunction which results in optic atrophy together with G11778A. Therefore, not only the common primary LHON mutation is responsible for the visual atrophy, but other secondary mtDNA mutations should also be considered when giving genetic counseling.

Shu, Lei; Zhang, Yong-Ming; Huang, Xiao-Xiao; Chen, Chun-Yue; Zhang, Xian-Ning



Voriconazole-Induced Neuropathy  

Microsoft Academic Search

Background: Fungal infections are common and life threatening among immunosupressive patients. Rare side effects may occur related to the use of voriconazole, which is the drug of choice in invasive aspergillosis. Patients and Methods: Neuropathy was determined through clinical and electromyographic findings during the course of voriconazole therapy in 2 patients developing invasive aspergillosis. Results: Since examinations revealed no neuropathy

Firdevs Aksoy; Elif Akdogan; Kemalettin Aydin; Mustafa Yilmaz; Vildan Altunayoglu; Ebru Emel Sozen; Serdar Bedii Omay; Iftihar Koksal



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

NASA Astrophysics Data System (ADS)

Porous poly(4-acetoxystyrene) swellable microspheres with diameters approximately 1~2 ?m were prepared by seeded emulsion polymerization. Toluene was used as the porogenic solvent and divinylbenzene was used as the crosslinker. The seed particles with diameters approximately 0.5~1 ?m were prepared by dispersion polymerization without adding porogenic solvent and crosslinker. Functionality was introduced by two derivatization reactions, hydrolysis and nitration, to form nitrated poly(4-hydroxystyrene). These polymer microspheres swell at high pH due to the deprotonation of the hydroxyl group on the polymer backbone. Swelling is accompanied by an increase in water content which causes the polymer refractive index to decrease. These microspheres, were embedded in a hydrogel for pH sensing. When either dibenzo-18-crown-6 or valinomycin was co- immobilized on the polymer, they were then used to sense potassium ion. Poly(2-hydroxyethylmethacrylate) or poly(vinylalcohol) hydrogel membranes with embedded nitrated poly(4- hydroxystyrene) microspheres were prepared by photopolymerization. These membranes possess desirable optical properties for pH sensing. The refractive index of the hydrated hydrogel is constant and not affected by pH, but the refractive index of the microspheres does vary with pH. When the membrane is in contact with a buffer at high pH, the membrane turbidity decreases because the refractive index difference between the microspheres and the hydrogel decreases. The apparent pKa values can be adjusted by varying the nitrogen percentage of the microspheres, by controlling the conditions of the nitration reaction. The observed pK a value can be as low as 5.6 or as high as 10.2. The response time of the membrane with microspheres prepared by seeded emulsion polymerization utilizing PVA as the membrane matrix was 10~15 seconds. Response times were longer for the poly(HEMA) matrix with embedded microspheres synthesized by dispersion polymerization. A very small amount of particles, 0.1 wt%, in a 127 ?m thickness membrane was needed to obtain significant changes in turbidity. Stability tests showed that the poly(HEMA) hydrogel membranes were mechanically stable when they were stored in pH 4, pH 10, deionized water, and dry under room temperature, 80°C, or in sunlight for about a month. Membranes consisting of ionophore modified nitrated poly(4-hydroxystyrene) microspheres in a hydrogel were prepared for potassium ion sensing. The sensing concept can be modeled as a cation-exchange system. When the membrane is immersed in a solution of potassium ions, the neutral ionophore, DB18C6 or valinomycin, in the polymer will selectively bind the potassium ion to form the cation complex. The ion binding is accompanied by release of a proton to maintain electroneutrality. This introduces charged sites into the polymer causing it to swell. The observed detection limit was as low as 10-4 M potassium ion. The response time of the PVA membrane with microspheres prepared by seeded emulsion polymerization was ~2 minutes.

Wang, Hongming



Neuropathy secondary to drugs  


... weakness. Many medications may affect the development of neuropathy, including: Heart or blood pressure medications Amiodarone Hydralazine Perhexiline Drugs used to fight cancer Cisplatin Docetaxel Paclitaxel Suramin Vincristine Drugs used to fight infections ...


Additional Types of Neuropathy  


Complications Heart Disease Ketoacidosis (DKA) Men's Health Women's Health Eye Complications Foot Complications Hearing Loss Neuropathy Skin Complications High Blood Pressure (Hypertension) Stroke Hyperosmolar Hyperglycemic Nonketotic Syndrome (HHNS) Gastroparesis ...


Occupational Peripheral Neuropathies  

PubMed Central

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

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



Leprosy neuropathy: clinical presentations.  


Leprosy is a chronic infectious peripheral neuropathy caused by Mycobacterium leprae. The different clinical presentations of the disease are determined by the quality of the host immune response. Early detection of leprosy and treatment by multidrug therapy are the most important steps in preventing deformity and disability. Thus the early recognition of the clinical leprosy presentation is essential. Mononeuritis, mononeuritis multiplex (MM), polyneuritis (MM summation) are the most frequent. The frequent anesthetic skin lesions are absent in the pure neuritic leprosy presentation form. Isolated peripheral nerve involvement is common, including the cranial ones. Arthritic presentation is occasionally seen, usually misdiagnosed as rheumatoid arthritis. Attention should be given to autonomic dysfunctions in leprosy. There are clinical presentations with severe neuropathic pain - painful small-fiber neuropathy. Leprous late-onset neuropathy (LLON) clinical presentation should be considered facing a patient who develop an inflammatory neuropathy many years after a previous skin leprosy treatment. PMID:24141500

Nascimento, Osvaldo J M



Chemotherapy-induced neuropathy  

Microsoft Academic Search

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

Anjali Bhagra; Ravi D. Rao



Herpes zoster laryngitis accompanied by ramsay hunt syndrome.  


The most common presentation of herpes zoster in the head and neck region is called Ramsay Hunt syndrome (RHS), which rarely accompanies multiple cranial neuropathy. Herpes zoster also involves the mucous membrane of the tongue, palate, pharynx, and larynx. Herpes zoster infection of the larynx accompanied by Ramsay Hunt syndrome with cranial polyneuropathy is extremely rare, with only few reported cases in the literature. At the time of this report, a review of the medical literature disclosed 4 reported cases of herpes zoster laryngitis accompanied by Ramsay Hunt syndrome. Herein, we present 2 additional cases and report the clinical outcome of cranial polyneuropathy with a review of the literature. PMID:24036828

Lee, Dong Hoon; Yoon, Tae Mi; Lee, Joon Kyoo; Joo, Young Eun; Lim, Sang Chul



Neuropathy and monoclonal gammopathy.  


The association of neuropathy with monoclonal gammopathy has been known for several years, even if the clinical and pathogenetic relevance of this association is not completely defined. This is not a marginal problem since monoclonal gammopathy is present in 1-3% of the population above 50 years in whom it is often asymptomatic, and in at least 8% of patients is associated with a symptomatic neuropathy, representing one of the leading causes of neuropathy in aged people. Monoclonal gammopathy may result from malignant lymphoproliferative diseases including multiple myeloma or solitary plasmocytoma, Waldenström's macroglobulinemia (WM), other IgM-secreting lymphoma or chronic lymphocytic leukemia, and primary systemic amyloidosis (AL). In most instances it is not associated with any of these disorders and is defined monoclonal gammopathy of undetermined significance (MGUS) for its possible, though infrequent, evolution into malignant forms. Several data support the pathogenetic role of the monoclonal gammopathy in the neuropathy particularly when of IgM isotype where IgM reactivity to several neural antigens has been reported. Increased levels of VEGF have been implicated in POEMS syndrome. However, there are as yet no defined therapies for these neuropathies, as their efficacy has not been confirmed in randomized trials. PMID:23931795

Nobile-Orazio, Eduardo



Chemotherapy-induced peripheral neuropathy  

Microsoft Academic Search

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

Stefan Quasthoff; Hans Peter Hartung



Clinical research for neuropathies.  


The National Institutes of Health (NIH) has a long-standing commitment to neuropathy research. From 2005-2009, the NIH has committed US $115 million each year. A collaborative effort between researchers and patients can accelerate the translation of pre-clinical discoveries into better treatments for neuropathy patients. Clinical trials are needed to test these new treatments, but they can only be implemented in a timely fashion if patients with neuropathies are willing to participate. This perspective focuses on the value of having various outlets for informing both the patients and the physicians about existing clinical research opportunities and on the potential benefit of establishing patient registries to help with trial recruitment. Once data have been collected, there is a need to broadly share the data in order to inform future trials, and a first step would be to harmonize data collection by using Common Data Elements (CDEs). PMID:22548622

Kaufmann, Petra



Multifocal motor neuropathy.  


Multifocal motor neuropathy (MMN) is a chronic immune-mediated neuropathy that is particular for its asymmetric, multifocal, purely motor clinical presentation, often related to the distribution of individual nerves. Upper limbs are usually primarily and more severely affected, but lower limbs may be involved during the course of the disease. The hallmark of the disease is the presence, in electrophysiological studies, of persistent conduction blocks in the affected motor nerves, located outside the usual sites of nerve compression, contrasting with normal sensory nerve conduction velocities. The most typical laboratory finding is the presence of high levels of serum IgM antibodies to the ganglioside GM1, and less frequently to asialo-GM1, GD1a or GM2. These striking features may help distinguishing this neuropathy from both motor neuron disease and other chronic immune-mediated neuropathies. Several randomized controlled trials (RCT) have established the efficacy of high-dose intravenous immunoglobulin (IVIg), as well as subcutaneous immunoglobulin (SCIg). However, this therapy has a short-lasting effect, and need to be maintained with periodic infusions. This disappointing status has led to the search of other immune therapies whose efficacy has not been so far confirmed in RCT. This review intends to summarize current contents in the diagnosis and the treatment of MMN. PMID:23623583

Guimarães-Costa, Raquel; Bombelli, Francesco; Léger, Jean-Marc



Painful diabetic neuropathy management.  


Diabetic neuropathy is the most common complication of diabetes as it affects a significant number of patients. The management of patients with diabetic neuropathy is complicated by several factors including the varied symptoms and response to the various treatments available. Strict blood glucose control remains the key to the management thus far nonetheless; it is associated with complications such as hypoglycaemia. In order to provide the most up-to-date evidence-based clinical recommendations pertinent to the management of diabetic neuropathy, several databases and clinical practice guidelines were searched for this evidence-based report. The main outcome measures are reduction in pain associated with diabetic neuropathy and the number of withdrawal rates due to adverse effects of the medications both of which are discussed in this report. Various pharmacological and non-pharmacological treatments are available with varying degrees of success in pain relief. The current evidence suggests that use of tricyclics antidepressants and conventional anticonvulsants for the short term of pain relief is beneficial. Combination therapy of opioids and anticonvulsants has also been found to be superior to monotherapy. Other treatment modalities such as the use of alpha-lipoic acid as an antioxidant and evening primrose oil through increased PGE1 synthesis have also been trialled with evidence of improvement in neuropathic pain. Evidence also supports non-pharmacological treatment such as the use of percutaneous electrical nerve stimulation. There is a scope for further improvement of the reporting of rating pain scales and including various outcomes measures such as quality of life and physical function when trialling new therapies for better evaluation of future treatments. PMID:23448333

Khalil, Hanan



Folate responsive neuropathy.  


The literature on folate related neuropathy has been reviewed. Twenty patients fulfilled the following criteria (a) they presented with neurological findings for which no other cause could be found (b) the serum or red cell and/or the CSF folate was low (c) the serum vitamin B12 or vitamin B12 absorption was normal and (d) they showed a significant response to folic acid. Ten presented with a peripheral neuropathy, eight with subacute combined degeneration of the cord and two with a myelopathy. In two patients the neuropathy occurred when treatment for congenital malabsorption of folate--an isolated lesion affecting folate alone--lapsed. Two patients with subacute combined degeneration died and posterio-lateral sclerosis of the cord was confirmed at autopsy. Three patients were mentally retarded and nine showed mental changes which also responded to folate in addition to the neurological disorder. A single biochemical reaction, the methionine synthetase reaction, is suggested as the basis for the neurological as well as the haematological consequences of both vitamin B12 and folate deficiency. The pitfalls in diagnosis are discussed and a greater awareness of the condition urged. PMID:8177846

Parry, T E



Docetaxel neuropathy: a distal axonopathy  

Microsoft Academic Search

Docetaxel has been implicated as a causative agent in peripheral neuropathy, but pathological changes in peripheral nerve\\u000a have not been described. During docetaxel treatment a 54-year-old man developed a sensorimotor polyneuropathy when the overall\\u000a docetaxel dosage was 540 mg\\/m2. Neurophysiological investigation revealed a sensorimotor axonal neuropathy. Fascicular sural nerve biopsy showed an axonal\\u000a neuropathy with a preferentially loss of large

Raffaella Fazio; Angelo Quattrini; Angelo Bolognesi; Gianni Bordogna; Eugenio Villa; Stefano Previtali; Nicola Canal; Raffaello Nemni



Experimental diabetic neuropathy: an update  

Microsoft Academic Search

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

A. A. F. Sima; K. Sugimoto



MBK neuropathy among spray painters.  


It has been suggested that the solvent methyl N-butyl ketone (MBK) may cause peripheral neuropathy in humans. An investigation was undertaken after two cases of peripheral neuropathy among spray painters at one work site were reported to the National Institute for Occupational Safety and Health. Twenty-six painters were interviewed and examined. Two were found to have definite peripheral neuropathy and one had a probable case. Although one of these men had been exposed to lead in the past, there are strong reasons to believe that MBK was responsible for his neuropathy. There was nothing to suggest excessive lead absorption in the other two men. PMID:176479

Mallov, J S



Hypertrophic changes in diabetic neuropathy  

Microsoft Academic Search

Observations have been made on 10 consecutive nerve biopsies from patients with diabetic neuropathy. 1 patient showed the typical appearances of hypertrophic neuropathy on light and electron microscopy. 5 displayed typical hypertrophic changes visible only on electron microscopy and minor abnormalities of a similar nature were seen in 2 others. It was considered that they were likely to have resulted

R. H. M. Ballin; P. K. Thomas



Painful Peripheral Neuropathies  

PubMed Central

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.

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



Multicluster accompanied fission  

SciTech Connect

In this process a heavy or superheavy nucleus spontaneously breaks into four, five, or six nuclei of which two are asymmetric or symmetric heavy fragments and the others are light clusters, e.g., {alpha} particles, {sup 10}Be, {sup 14}C, {sup 20}O, or combinations of them. Examples are presented for the two-, three-, and four-cluster accompanied cold fission of {sup 252}Cf and {sup 262}Rf, in which the emitted clusters are 2{alpha}, {alpha}+{sup 6}He, {alpha}+{sup 10}Be, {alpha}+{sup 14}C, 3{alpha}, {alpha}+{sup 6}He+{sup 10}Be, 2{alpha}+{sup 6}He, 2{alpha}+{sup 8}Be, 2{alpha}+{sup 14}C, and 4{alpha}. A comparison is made with the recently observed {sup 252}Cf cold binary fission, and cold ternary (accompanied by {alpha} particle or by {sup 10}Be cluster). The strong shell effect corresponding to the doubly magic heavy fragment {sup 132}Sn is emphasized. The most favorable mechanism of such a decay mode should be the emission from an elongated neck formed between the two heavy fragments. {copyright} {ital 1999} {ital The American Physical Society}

Poenaru, D.N.; Gherghescu, R.A. [National Institute of Physics and Nuclear Engineering, P.O. Box MG-6, RO-76900 Bucharest (Romania); Poenaru, D.N.; Greiner, W.; Gherghescu, R.A. [Institut fuer Theoretische Physik der Universitaet, Postfach 111932, D-60054 Frankfurt am Main (Germany); Poenaru, D.N.; Greiner, W.; Hamilton, J.H.; Ramayya, A.V. [Department of Physics and Astronomy, Vanderbilt University, Nashville, Tennessee 37235 (United States); Poenaru, D.N.; Hourany, E. [Institut de Physique Nucleaire, F-91406 Orsay Cedex (France)



Co-occurrence of m.1555A>G and m.11778G>A mitochondrial DNA mutations in two Indian families with strikingly different clinical penetrance of Leber hereditary optic neuropathy  

PubMed Central

Background Mitochondrial DNA (mtDNA) mutations are known to cause Leber hereditary optic neuropathy (LHON). However, the co-occurrence of double pathogenic mutations with different pathological significance in pedigrees is a rare event. Methods Detailed clinical investigation and complete mtDNA sequencing analysis was performed for two Indian families with LHON. The haplogroup was constructed based on evolutionarily important mtDNA variants. Results We observed the existence of double pathogenic mutations (m.11778G>A and m.1555A>G) in two Indian LHON families, who are from different haplogroup backgrounds (M5a and U2e1), with different clinical penetrance of the disease (visual impairment). The m.11778G>A mutation in the MT-ND4 gene is associated primarily with LHON; whereas, m.1555A>G in the 12S rRNA gene has been reported with aminoglycoside-induced non-syndromic hearing loss. Conclusions The absence of hearing abnormality and widely varying clinical expression of LHON suggest additional nuclear modifier genes, environmental factors, and population heterogeneity might play an important role in the expression of visual impairment in these families.

Khan, Nahid Akhtar; Govindaraj, Periyasamy; Jyothi, Vuskamalla; Meena, Angamuthu K



Haplotype and phylogenetic analyses suggest that one European-specific mtDNA background plays a role in the expression of Leber hereditary optic neuropathy by increasing the penetrance of the primary mutations 11778 and 14484.  

PubMed Central

mtDNAs from 37 Italian subjects affected by Leber hereditary optic neuropathy (LHON) (28 were 11778 positive, 7 were 3460 positive, and 2 were 14484 positive) and from 99 Italian controls were screened for most of the mutations that currently are associated with LHON. High-resolution restriction-endonuclease analysis also was performed on all subjects, in order to define the phylogenetic relationships between the mtDNA haplotypes and the LHON mutations observed in patients and in controls. This analysis shows that the putative secondary/intermediate LHON mutations 4216, 4917, 13708, 15257, and 15812 are ancient polymorphisms, are associated in specific combinations, and define two common Caucasoid-specific haplotype groupings (haplogroups J and T). On the contrary, the same analysis shows that the primary mutations 11778, 3460, and 14484 are recent and are due to multiple mutational events. However, phylogenetic analysis also reveals a different evolutionary pattern for the three primary mutations. The 3460 mutations are distributed randomly along the phylogenetic trees, without any preferential association with the nine haplogroups (H, I, J, K, T, U, V, W, and X) that characterize European populations, whereas the 11778 and 14484 mutations show a strong preferential association with haplogroup J. This finding suggests that one ancient combination of haplogroup J-specific mutations increases both the penetrance of the two primary mutations 11778 and 14484 and the risk of disease expression.

Torroni, A; Petrozzi, M; D'Urbano, L; Sellitto, D; Zeviani, M; Carrara, F; Carducci, C; Leuzzi, V; Carelli, V; Barboni, P; De Negri, A; Scozzari, R



Metabolic neuropathies and myopathies.  


Inborn errors of metabolism may impact on muscle and peripheral nerve. Abnormalities involve mitochondria and other subcellular organelles such as peroxisomes and lysosomes related to the turnover and recycling of cellular compartments. Treatable causes are ?-oxidation defects producing progressive neuropathy; pyruvate dehydrogenase deficiency, porphyria, or vitamin B12 deficiency causing recurrent episodes of neuropathy or acute motor deficit mimicking Guillain-Barré syndrome. On the other hand, lysosomal (mucopolysaccharidosis, Gaucher and Fabry diseases), mitochondriopathic (mitochondrial or nuclear mutations or mDNA depletion), peroxisomal (adrenomyeloneuropathy, Refsum disease, sterol carrier protein-2 deficiency, cerebrotendinous xanthomatosis, ?-methylacyl racemase deficiency) diseases are multisystemic disorders involving also the heart, liver, brain, retina, and kidney. Pathophysiology of most metabolic myopathies is related to the impairment of energy production or to abnormal production of reactive oxygen species (ROS). Main symptoms are excercise 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

D'amico, Adele; Bertini, Enrico



Multiple myeloma, painful neuropathy, acupuncture?  


Thalidomide and bortezomib are remarkably efficacious in the treatment of multiple myeloma. Unfortunately, their use can cause sensory neuropathy, a common and serious adverse event that frequently limits dose and duration of treatment. Although the relationship between peripheral neuropathy and therapeutic dose is controversial, many authors have demonstrated a positive correlation between neuropathy and cumulative dose, dose intensity, and length of therapy. Peripheral neuropathic pain is the most troublesome symptom of neuropathy. Spontaneous pain, allodynia, hyperalgesia, and hyperpathia are often associated with decreased physical activity, increased fatigue, mood, and sleep problems. Symptoms are often difficult to manage, and available treatment options rarely provide total relief. Moreover, the adverse effects of these treatments often limit their use. Several studies have demonstrated the efficacy of acupuncture, with fewer adverse effects than analgesic drugs, in the treatment of painful diabetic and human immunodeficiency virus-related neuropathy. However, the effectiveness of acupuncture in treating toxic neuropathy has not been assessed. Although its putative mechanisms remain elusive, acupuncture has strong potential as an adjunctive therapy in thalidomide- or bortezomib-induced painful neuropathy, and a better understanding might guide its use in the management of chemotherapy-induced neuropathic pain. Well-designed clinical trials with adequate sample size and power are warranted. PMID:19887992

Zhou, Yuhong; Garcia, M Kay; Chang, David Z; Chiang, Joseph; Lu, Jin; Yi, Qing; Romaguera, Jorge; Delasalle, Kay; Guo, Ying; Forman, Arthur; Fang, Wenjing; Wang, Michael



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


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

Scelsi, Roberto; Candura, Stefano M


Compression and entrapment neuropathies.  


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

Bouche, P



Early Treatment of Diabetic Neuropathy.  

National Technical Information Service (NTIS)

Treatment of diabetic neuropathy is a difficult clinical problem. In this paper, clinical experience on managing 120 newly discovered, untreated, noninsulin dependent cases is presented. Besides strict control of diabetes, the therapeutic effect of differ...

X. Zhong B. Zheng G. Hu X. Zhu Z. Hu



Posttraumatic childhood lumbosacral plexus neuropathy.  


A 13-month-old male received crush injury to the abdomen resulting in paraparesis due to lumbosacral plexus neuropathy. The child was monitored with serial clinical examinations and electromyography/nerve conduction studies. He had complete clinical recovery. Lumbosacral plexus neuropathy is unusual in childhood and has not been previously reported as a result of abdominal trauma. This patient is presented with details of the clinical course, electrodiagnostic studies, discussion, and literature review. PMID:7748364

Egel, R T; Cueva, J P; Adair, R L



Crucifixion and median neuropathy  

PubMed Central

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.

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



Functional deficits in peripheral nerve mitochondria in rats with paclitaxel- and oxaliplatin-evoked painful peripheral neuropathy.  


Cancer chemotherapeutics like paclitaxel and oxaliplatin produce a dose-limiting chronic sensory peripheral neuropathy that is often accompanied by neuropathic pain. The cause of the neuropathy and pain is unknown. In animal models, paclitaxel-evoked and oxaliplatin-evoked painful peripheral neuropathies are accompanied by an increase in the incidence of swollen and vacuolated mitochondria in peripheral nerve axons. It has been proposed that mitochondrial swelling and vacuolation are indicative of a functional impairment and that this results in a chronic axonal energy deficiency that is the cause of the neuropathy's symptoms. However, the significance of mitochondrial swelling and vacuolation is ambiguous and a test of the hypothesis requires a direct assessment of the effects of chemotherapy on mitochondrial function. The results of such an assessment are reported here. Mitochondrial respiration and ATP production were measured in rat sciatic nerve samples taken 1-2 days after and 3-4 weeks after induction of painful peripheral neuropathy with paclitaxel and oxaliplatin. Significant deficits in Complex I-mediated and Complex II-mediated respiration and significant deficits in ATP production were found for both drugs at both time points. In addition, prophylactic treatment with acetyl-l-carnitine, which inhibited the development of paclitaxel-evoked and oxaliplatin-evoked neuropathy, prevented the deficits in mitochondrial function. These results implicate mitotoxicity as a possible cause of chemotherapy-evoked chronic sensory peripheral neuropathy. PMID:21907196

Zheng, Huaien; Xiao, Wen Hua; Bennett, Gary J



Update on medication-induced peripheral neuropathy  

Microsoft Academic Search

Despite improvements in the identification of causes of peripheral neuropathy, idiopathic polyneuropathy remains common. Medication\\u000a and toxic neuropathy account for a small but important percentage of potentially preventable or reversible causes of neuropathy.\\u000a New drugs that can induce neuropathy have been approved over the past several years, including the anticancer agents bortezomib,\\u000a ixabepilone, and oxaliplatin. We review the neurotoxic effects

Louis H. Weimer; Noor Sachdev



Peripheral neuropathy in mitochondrial disorders.  


Why is peripheral neuropathy common but mild in many mitochondrial disorders, and why is it, in some cases, the predominant or only manifestation? Although this question remains largely unanswered, recent advances in cellular and molecular biology have begun to clarify the importance of mitochondrial functioning and distribution in the peripheral nerve. Mutations in proteins involved in mitochondrial dynamics (ie, fusion and fission) frequently result in a Charcot-Marie-Tooth phenotype. Peripheral neuropathies with different phenotypic presentations occur in mitochondrial diseases associated with abnormalities in mitochondrial DNA replication and maintenance, or associated with defects in mitochondrial respiratory chain complex V. Our knowledge of mitochondrial disorders is rapidly growing as new nuclear genes are identified and new phenotypes described. Early diagnosis of mitochondrial disorders, essential to provide appropriate genetic counselling, has become crucial in a few treatable conditions. Recognising and diagnosing an underlying mitochondrial defect in patients presenting with peripheral neuropathy is therefore of paramount importance. PMID:24050734

Pareyson, Davide; Piscosquito, Giuseppe; Moroni, Isabella; Salsano, Ettore; Zeviani, Massimo



The Spectrum of Diabetic Neuropathies  

PubMed Central

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

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



Reversible Neuropathy in Chronic Renal Failure  

Microsoft Academic Search

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

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



Diagnosis and new treatments in genetic neuropathies  

Microsoft Academic Search

The genetic neuropathies are a clinically and genetically heterogeneous group of diseases of which the most common types are Charcot–Marie–Tooth disease (CMT), the hereditary sensory and autonomic neuropathies and the distal hereditary motor neuropathies. More than 30 causative genes have been described, making an accurate genetic diagnosis increasingly possible. Although no specific therapies are yet available, research into their pathogenesis

M M Reilly; M E Shy



Electrophysiological studies in diabetic neuropathy  

PubMed Central

In 30 patients with diabetic neuropathy sensory potentials in the median nerve, motor conduction in the lateral popliteal and median nerves, and electromyographic findings in distal and proximal muscles were compared with the severity of symptoms and signs. All patients had abnormalities in at least one of the electrophysiological parameters. The sensory potentials were the most sensitive indicator of subclinical involvement; abnormalities were found in 24 patients, 12 of whom had no sensory symptoms or signs and five of whom had no other clinical or electrophysiological evidence of neuropathy in the upper extremities. This indicates that sensory nerve fibres may be affected before motor. The next most sensitive parameter was the presence of fibrillation potentials, found in more than half the distal muscles examined. Slowing in motor conduction in the lateral popliteal nerve was the only electrophysiological change correlated to the severity of the neuropathy, and no other electrophysiological parameter was correlated to the duration or the severity of the neuropathy or the diabetes. An onset of neuropathy before or simultaneously with the manifestations of the diabetes, as well as the frequent occurrence of asymptomatic changes in sensory conduction, support the evidence at hand that the neuropathy develops concomitantly with and as an integral part of the metabolic disturbance rather than as a consequence of the vascular complications of diabetes. Of three patients with clinical signs or symptoms of a diabetic amyotrophy, two had asymptomatic electrophysiological abnormalities in distal nerves and muscles, consistent with widespread involvement of the peripheral nerves. The third patient had electromyographic changes in the medial vastus muscles suggestive of a myopathy. Motor and sensory conduction in distal and proximal nerves were normal. Images

Lamontagne, Albert; Buchthal, Fritz



Emerging toxic neuropathies and myopathies.  


There is a daunting list of toxins that can affect the peripheral nervous system, with new drugs and chemicals added to this list every year. This article focuses on some of the more recent toxic neuropathies and myopathies that have emerged from the medical literature. Among these are toxic myopathies caused by statins, daptomycin, imatinib, hydroxychloroquine, and highly active antiretroviral therapy; neuromuscular junction toxicity caused by tandutinib; toxic peripheral neuropathies caused by bortezomib, angel's trumpet, cisplatin, oxaliplatin, tumor necrosis factor ? antagonists, cobalt-chromium, and ixabepilone; and a unique syndrome reported in workers exposed to aerosolized porcine neural tissue. PMID:21803218

Kushlaf, Hani A



[Metabolic neuropathies: overview in 2011].  


Metabolic diseases constitute a frequent etiologic group of axonal and small-fiber neuropathies. Recent works in this field are dominated by diabetic neuropathy (clinical presentation, prognostic factors) because of its prevalence. Vitamin B12 deficiency aroused several studies in 2011. This renewed interest for this well known entity ensues from the lack of sensibility of its biological markers underestimating its prevalence, its clinical spectrum and therefore, access to its therapy. Finally, 2011 highlighted the growing interest of the measure of the intra-epidermic nerve fibers density by skin biopsy for some metabolic disorders such as infra-clinical hypothyroïdism, chronic renal failure or Fabry disease. PMID:23107883

Franques, J; Verschueren, A



[Neuropathy pain: tactic of treatment].  


Diagnostics of neuropathy pain is presented in the article, where most essential are methods of clinical estimation with the use of questionnaires and scales for verification and quantitative estimation of pain. The neurological inspection of patients with suspicion on neuropathy pain must plug in itself of the motive, sensory and vegetative phenomena with the purpose of authentication of all signs of neurological dysfunction. If on a background immunotherapy it is not succeeded fully a pain syndrome preparations of the first row, setting of combined pharmacotherapy allows to promote efficiency of treatment at the less dosages of preparations and reduce the risk of development of by-effects. PMID:23373387

Murashko, N K



Congenital Cataracts – Facial Dysmorphism – Neuropathy  

Microsoft Academic Search

Congenital Cataracts Facial Dysmorphism Neuropathy (CCFDN) syndrome is a complex developmental disorder of autosomal recessive inheritance. To date, CCFDN has been found to occur exclusively in patients of Roma (Gypsy) ethnicity; over 100 patients have been diagnosed. Developmental abnormalities include congenital cataracts and microcorneae, primary hypomyelination of the peripheral nervous system, impaired physical growth, delayed early motor and intellectual development,

Luba Kalaydjieva



Peripheral Neuropathy in Cockayne's Syndrome  

Microsoft Academic Search

A detailed study has been made of a typical case of Cockayne's syndrome. An associated peripheral neuropathy has been demonstrated by slow nerve conduction velocities and by evidence of segmental demyelination on sural nerve biopsy. Cockayne's syndrome is probably a leucodystrophy.

A. Moosa; V. Dubowitz



Bladder dysfunction in peripheral neuropathies.  


Normal bladder function depends on the complex interaction of sensory and motor pathways. Bladder dysfunction can develop as a result of several neurological conditions. It can happen in a number of ways, including diabetic cystopathy, detrusor overactivity, bladder outlet obstruction, and urge and stress urinary incontinence. Diabetic neuropathy is the most common cause of peripheral neuropathy-associated bladder dysfunction. Guillain-Barré syndrome (GBS), human immunodeficiency virus (HIV)-associated neuropathy, chronic inflammatory demyelinating polyneuropathy (CIDP), and amyloid neuropathy are other major causes. The diagnosis of bladder dysfunction should be established by the history of neurological symptoms, neurological examination, and urological evaluation. Functional evaluation of the lower urinary tract includes cystometry, sphincter electromyography, uroflowmetry, and urethral pressure profilometry. Management of urinary symptoms in patients with bladder dysfunction is usually supportive. In some cases, alpha-blocker and/or anti-muscarinic agents are needed to help improve urinary dysfunction. Intermittent self-catheterization is needed occasionally for patients with slow and/or poor recovery. PMID:22190298

Burakgazi, Ahmet Z; Alsowaity, Bander; Burakgazi, Zeynep Aydin; Unal, Dogan; Kelly, John J



[Hereditary neuropathy with pressure hypersensitivity or tomaculous neuropathy].  


Hereditary neuropathy liability to pressure palsies is characterized by recurring accesses of painless paralysis at the level of various nerves likely to be compressed. This affection remains underdiagnosed because of its usually benign course, sometimes without any symptom. The diagnosis is supported by clinical and electrophysiological data associated with, in the majority of patients, a deletion of one of the alleles coding for protein PMP 22 on the level of the locus 17p11.2. PMID:12481468

Tinant, F; Zeevaert, B; Benkirane, H; Laurent, L; Wang, F



Pachydermoperiostosis Accompanied by Heart Failure  

PubMed Central

Pachydermoperiostosis or primary hypertrophic osteoarthropathy is an uncommon disease of acromegaloid facial feature, but characterized by unique phenotype (digital clubbing and pachydermia) and distinctive radiographic appearances like periostosis. We experienced a case with complete form of pachydermoperiostosis accompanied by heart failure. He presented with typical features consisting of clubbing with enlargement of the hand, thickening of facial skin and periosteal new bone formation involving lower leg. Echocardiography revealed severely decreased left ventricular systolic function. Treatment with medications resulted in an improvement of cardiac function and symptom. There is no previous report documenting pachydermoperiostosis accompanied by heart failure. We report that case for the first time.

Shin, Kwen-Chul; Lee, Ki Young; Shin, Mi-Seung; Kim, Sei-Hyun; Jo, Yun Jeong; Park, Yae Min; Ahn, Tae Hoon; Choi, In Suk; Shin, Eak Kyun



[Molecular genetics of inherited neuropathies].  


Inherited neuropathies are clinically and genetically heterogeneous. At least 28 genes and 12 loci have been associated with Charcot-Marie-Tooth disease (CMT) and related inherited neuropathies. Most causes of inherited neuropathy have been discovered by positional cloning technique and in the past two years, the pace of CMT gene discovery has accelerated. Genetic studies have revealed the following gene mutations as the causes of inherited neuropathies; PMP22, MPZ, EGR2, SOX10, SIMPLE/LITAF, ARHGEF10 for CMT1 (autosomal dominant demyelinating form); GDAP1, MTMR2, SBF2/MTMR13, KIAA1985, NDRG1 PRX for CMT4 (autosomal recessive demyelinating form), MFN2, KIF1B, RAB7, GARS, NEFL, HSPB1, HSPB8 for CMT2 (autosomal dominant axonal form); LMNA, GAN1, KCC3, TDP1, APTX, SETX for AR-CMT2 (autosomal recessive axonal form); GIB1 for CMTX (X-linked CMT); DNM2 for CMT-DI (autosomal dominant CMT with intermediate nerve conduction velocities); and DHH for minifascicular neuropathy. These discovered CMT causing genes/proteins include those which show unpredictable correlations with the peripheral nervous system. However, these genes/proteins are definitely important for the peripheral nerve, and their discovery should pave the way for dramatic progress in the understanding of peripheral nerve biology. On the other hand, genotype-phenotype correlations of these genes are also important in order to understand the pathomechanisms of inherited neuropathy. Because, based on mutation studies, a large number of genes associated with both the CMT1/4 and CMT2 forms have been identified, it is usually difficult to predict the causative gene based on clinical information from patients without specific complications. To clarify the specific features and molecular mechanisms of five diseases that we previously reported, we reviewed recent progress in HMSN-P linked to chromosome 3, CMT4F caused by PRX, CMT4A caused by GDAP1, CMT4B2 caused by SBF2/MTMR13, and SCAN1 caused by TDP1. HMSN-P is characterized by late onset, proximal dominant severe muscle weakness, fasciculations, muscle cramp and sensory involvement. HMSN-P is a primary neuronopathy. Mutations in periaxin are associated with a broad spectrum of demyelinating neuropathies including DSS, a sensory dominant form and early onset slowly progressive CMT. Pathologically, loss of myelinated fibers, demyelination, small onion bulb formations, tomacula formation and myelin foldings were seen in sural nerves. Absence of septate like junction in the paranodal loop suggests that periaxin could be required for the adhesion complex. GDAP1 is a relatively common cause of CMT4. Half of reported patients showed the demyelinating form, while the rest showed the axonal form. The typical feature of CMT4A is paresis of the vocal cords and diaphragm. CMT4B2 is characterized by autosomal recessive, juvenile onset glaucoma and focally folded myelin in sural nerves. SBF2/MTMR13 mutations cause CMT4B2. Early onset glaucoma was seen in patients with nonsense mutations. SBF2/MTMR13 and MTMR2, which is the cause of CMT4B1, could be acting on the same 3-phosphoinositide signaling pathway. Clinical phenotypes of patients with TDP1, APTX, or SETX mutations share common clinical findings, namely cerebellar ataxia and axonal neuropathy. TDP1 and aprataxin both act on the single strand break repair pathway, with TDP1 working specifically on topoisomerase I related SSBR. Senataxin is a RNA helicase acting on RNA maturation and termination in yeast. Since these three proteins share a common pathway, disruption in any of them could induce a delay in the transcription process. The low rate of protein supply could lead to deaths of large neuronal cells. PMID:16541790

Takashima, Hiroshi



Congenital Cataracts - Facial Dysmorphism - Neuropathy  

Microsoft Academic Search

Key words Disease name\\/synonyms Definition\\/diagnostic criteria Epidemiology Abstract Congenital Cataracts Facial Dysmorphism Neuropathy (CCFDN) syndrome is a complex developmental disorder of autosomal recessive inheritance. CCFDN is a genetically homogeneous condition in which all patients are homozygous for the same ancestral mutation in the CTDP1 gene. To date, it has been found to occur exclusively in patients of Roma (Gypsy) ethnicity;

Marianne de Visser


Pathogenesis of Human Diabetic Neuropathy  

Microsoft Academic Search

Experimental studies have provided multiple mechanisms for the development of diabetic neuropathy, yet very few findings have\\u000a been replicated in patients. Hyperglycemia mediated nerve damage may begin very early even prior to overt diabetes as evidenced\\u000a by several recent studies in patients with impaired glucose tolerance. Polyol pathway abnormalities have been exhaustively\\u000a explored in animals, but studies in man are

Rayaz Ahmed Malik; Aristides Veves


Treatment of Painful Diabetic Neuropathy  

Microsoft Academic Search

Up to 50% of patients with chronic sensorimotor diabetic neuropathy will experience painful or uncomfortable symptoms, and\\u000a of these a significant minority may require pharmacological therapy. As painful symptomatology may be worsened by a sudden\\u000a change in glycaemic control, the first step in management should be the quest for stable, near normal glycaemic control avoiding\\u000a glycaemic flux. Of all the

Andrew J. M. Boulton


[Compression neuropathy of upper limbs in miners].  


The authors analyzed prevalence of individual types of upper limb compression neuropathy in miners of coal and iron-ore mines. Medical examination covered main mining occupations exposed to suchhazards as local vibration, cooling microclimate, functional overstrain. Some types of compression neuropathies appeared to depend on duration of exposure to the hazards and on the occupation hands disease stage. PMID:16898248

Rodin, S I; Matveeva, O V



Peripheral neuropathy associated with the sicca syndrome  

Microsoft Academic Search

Three patients with the sicca syndrome and chronic sensory neuropathy are described; in two of them neuropathy was the presenting feature of the disease. The sicca syndrome can give rise to a characteristic neurological syndrome comprising areflexia and asymmetrical sensory loss, particularly of proprioception, in the limbs. This is often associated with tonic pupils and trigeminal anaesthesia.

R P Kennett; A E Harding



Bortezomib-induced severe autonomic neuropathy.  


Peripheral neuropathy is a known side effect of bortezomib therapy. Acute autonomic neuropathy may also follow treatment with this cytotoxic agent used for treatment of multiple myeloma. Here, we report clinical characteristics and patterns of autonomic involvement in a 75-year-old patient who presented with recurring syncopes. PMID:22532274

Stratogianni, A; Tosch, M; Schlemmer, H; Weis, J; Katona, I; Isenmann, S; Haensch, C A



Alcoholic vagal neuropathy: recovery following prolonged abstinence  

Microsoft Academic Search

Cardiac vagal reflexes were studied in 11 alcoholic subjects, 1 to 6 weeks after withdrawal and again after up to 27 months of continued abstinence. On initial investigation six subjects had vagal neuropathy. On the second occasion only two subjects had vagal neuropathy and significant improvement was seen in the total patient group with regard to heart rate responses to

E T Tan; R H Johnson; D G Lambie; E A Whiteside



Problems of etiology in femoral neuropathies  

Microsoft Academic Search

29 cases of femoral mononeuropathy are reported. While the clinical features of the femoral neuropathy are easily identified, the etiology is often hard to establish. The cases reported tend to fall into three general categories: 1) cases without major diagnostic difficulties (e.g. diabetic neuropathy); 2) those in which the definite diagnosis results from combined evidence of laboratory and instrumental data

L. Compagnoni; A. Lanzetti; A. Laterza; A. Nappo



Sensory neuropathy in two Border collie puppies.  


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

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



Diagnosis and treatment in inflammatory neuropathies  

Microsoft Academic Search

The inflammatory neuropathies are a large diverse group of immune-mediated neuropathies that are amenable to treatment and may be reversible. Their accurate diagnosis is essential for informing the patient of the likely course and prognosis of the disease, informing the treating physician of the appropriate therapy and informing the scientific community of the results of well-targeted, designed and performed clinical

M P T Lunn; H J Willison



Persistence of tropical ataxic neuropathy in a Nigerian community  

PubMed Central

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

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



Posterior interosseous neuropathy: electrodiagnostic evaluation.  


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

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



Treatment of painful peripheral neuropathy.  


Treatment of neuropathic pain is the primary focus of management for many patients with painful peripheral neuropathies. Antidepressants and anticonvulsants are the two medication classes most widely studied and represent first-line agents in the management of neuropathic pain. The number of pharmacologic agents and interventional procedures that have shown effectiveness in the treatment of neuropathic pain continues to expand. Pain management should begin with a concerted effort to identify the etiology of the neuropathy, because directed therapy can help alleviate the symptoms. When initiating pharmacotherapy for neuropathic pain, one must individualize treatment and choose an agent that is likely to be tolerated, because adverse events are common for many of these agents. Neuropathic pain management remains challenging because of heterogeneous responses between individuals and the fact that pain relief is rarely complete. However, monotherapy with a well-chosen agent or rational polypharmacy that combines medications with different mechanisms of action will benefit a majority of patients with neuropathic pain. PMID:19078690

Wolfe, Gil I; Hotz, Susan E; Barohn, Richard J



Suprascapular neuropathy: diagnosis and management.  


Although historically considered a diagnosis of exclusion, suprascapular neuropathy may be more common than once believed, as more recent reports are describing the condition as a cause of substantial pain and weakness in patients with and without concomitant shoulder pathology. The etiology is traction or compression of the suprascapular nerve. This can result from a space-occupying lesion, such as a ganglion cyst, or a traction injury as a result of repetitive overhead activities. More recent studies have cited cases of traction injuries occurring with retraction of a large rotator cuff tear. Atrophy of the infraspinatus and/or supraspinatus rotator cuff muscles with resultant weakness in forward flexion and/or external rotation of the shoulder on physical examination may be demonstrated. Magnetic resonance imaging (MRI) is the preferred modality to assess atrophy of the rotator cuff muscles as well as assess potential causes of suprascapular nerve compression. Electromyography and nerve conduction velocity studies remain the gold standard for confirmation of the diagnosis of suprascapular neuropathy; however, nerve pain may occur even in the setting of a negative electromyography. Initial management is usually nonoperative, consisting of activity modification, physical therapy, and nonsteroidal anti-inflammatory drugs. Surgical intervention is considered for patients with nerve compression by an external source or for symptoms refractory to conservative measures. Decompression of the suprascapular nerve may be accomplished through an open approach, although arthroscopic surgical approaches have become more common in the past several years. PMID:22508253

Freehill, Michael T; Shi, Lewis L; Tompson, Jeffrey D; Warner, Jon J P



Pinealitis accompanying equine recurrent uveitis.  


There is no direct verification of pineal gland involvement in human uveitis. Specimens of pineal tissue are not available during active uveitis in human patients. Naturally occurring uveitis in horses gives us an opportunity to examine tissues during active ocular inflammation. We examined the pineal gland of a horse that was killed because it had become blind during an episode of uveitis. The clinical history and histopathology of the eyes were consistent with post-leptospiral equine recurrent uveitis. The pineal gland of this horse had significant inflammatory infiltration consisting mainly of lymphocytes with some eosinophils. This observation of pinealitis accompanying equine uveitis supports the animal models of experimental autoimmune uveoretinitis with associated pinealitis and suggests that the pineal gland may be involved in some human uveitides. PMID:8435400

Kalsow, C M; Dwyer, A E; Smith, A W; Nifong, T P



Pinealitis accompanying equine recurrent uveitis.  

PubMed Central

There is no direct verification of pineal gland involvement in human uveitis. Specimens of pineal tissue are not available during active uveitis in human patients. Naturally occurring uveitis in horses gives us an opportunity to examine tissues during active ocular inflammation. We examined the pineal gland of a horse that was killed because it had become blind during an episode of uveitis. The clinical history and histopathology of the eyes were consistent with post-leptospiral equine recurrent uveitis. The pineal gland of this horse had significant inflammatory infiltration consisting mainly of lymphocytes with some eosinophils. This observation of pinealitis accompanying equine uveitis supports the animal models of experimental autoimmune uveoretinitis with associated pinealitis and suggests that the pineal gland may be involved in some human uveitides. Images

Kalsow, C M; Dwyer, A E; Smith, A W; Nifong, T P



Characterization of oxaliplatin-induced chronic painful peripheral neuropathy in the rat and comparison with the neuropathy induced by paclitaxel.  


Anti-neoplastic agents in the platinum-complex, taxane, vinca alkaloid, and proteasome-inhibitor classes induce a dose-limiting, chronic, distal, symmetrical, sensory peripheral neuropathy that is often accompanied by neuropathic pain. Clinical descriptions suggest that these conditions are very similar, but clinical data are insufficient to determine the degree of similarity and to determine if they share common pathophysiological mechanisms. Animal models do not have the limitations of clinical studies and so we have characterized a rat model of chronic painful peripheral neuropathy induced by a platinum-complex agent, oxaliplatin, in order to compare it with a previously characterized model of chronic painful peripheral neuropathy induced by a taxane agent, paclitaxel. The oxaliplatin model evokes mechano-allodynia, mechano-hyperalgesia, and cold-allodynia that have a delayed onset, gradually increasing severity, a distinct delay to peak severity, and duration of about 2.5 months. There is no effect on heat sensitivity. Electron microscopy (EM) analyses found no evidence for axonal degeneration in peripheral nerve, and there is no upregulation of activating transcription factor-3 in the lumbar dorsal root ganglia. There is a statistically significant loss of intraepidermal nerve fibers in the plantar hind paw skin. Oxaliplatin treatment causes a significant increase in the incidence of swollen and vacuolated mitochondria in peripheral nerve axons, but not in their Schwann cells. Nerve conduction studies found significant slowing of sensory axons, but no change in motor axons. Single fiber recordings found an abnormal incidence of A- and C-fibers with irregular, low-frequency spontaneous discharge. Prophylactic dosing with two drugs that are known to protect mitochondria, acetyl-l-carnitine and olesoxime, significantly reduced the development of pain hypersensitivity. Our results are very similar to those obtained previously with paclitaxel, and support the hypothesis that these two agents, and perhaps other chemotherapeutics, produce very similar conditions because they have a mitotoxic effect on primary afferent neurons. PMID:22200546

Xiao, W H; Zheng, H; Bennett, G J



Compressive neuropathy in the upper limb  

PubMed Central

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

Thatte, Mukund R.; Mansukhani, Khushnuma A.



?-Lipoic acid, diabetic neuropathy, and Nathan's prophecy.  


Both oral and intravenous administration of alpha-lipoic acid (ALA) has been investigated as add-on treatment for diabetic peripheral neuropathy. The recent Neurological Assessment of Thioctic Acid in Diabetic Neuropathy (NATHAN) 1 trial has shown that 4-year oral ALA administration is of some value in achieving a clinically meaningful improvement and a slight delay in the progression of neuropathic deficits among patients with mild/moderate diabetic peripheral neuropathy. Despite these promising results, important questions remain to be answered, mainly appropriate patient selection and optimal treatment duration. Moreover, a cost-benefit analysis would be useful. PMID:22253286

Papanas, N; Maltezos, E



[Neuropathies associated with paraproteinemia (monoclonal gammopathy)].  


Coexistence of neuropathy and paraproteinemia (monoclonal gammopathy) is a common and complex problem seen in clinical practice and requires the distinction of specific syndromes. The clinical courses of these neuropathies are typically chronic and progressive. A precise distinction of the type of haematologic disorder associated (benign or malignant), investigation of other organs manifestations, and assessment of specific markers are mandatory. These steps are important to initiate an appropriate therapy that may include chemotherapy and/or immunosuppressive treatment targeting the neuropathy and the haematological dysfunction. PMID:23717902

Lalive, P H; Kuntzer, T; Dietrich, P-Y



Chemotherapy-induced peripheral neuropathy.  


Recent advances in the development and administration of chemotherapy for malignant diseases have led to prolonged survival of patients and the promise of a return to normal lives. The cost of progress comes with a price, however, and the nervous system is frequently the target of therapy-induced toxicity. Unlike more immediate toxicities that affect the gastrointestinal tract and bone marrow, chemotherapy-induced neurotoxicity is frequently delayed in onset and may progress over time. In the peripheral nervous system, the major brunt of the toxic attack is directed against the peripheral nerve, targeting the neuronal cell body, the axonal transport system, the myelin sheath, and glial support structures, resulting in chemotherapy-induced peripheral neuropathy. PMID:18367040

Malik, Bushra; Stillman, Mark



Lifestyle risk factors for ulnar neuropathy and ulnar neuropathy-like symptoms.  


Introduction: We examined whether lifestyle factors differ between patients with ulnar neuropathy confirmed by electroneurography (ENG) and those with ulnar neuropathy-like symptoms with normal ulnar nerve ENG. Methods: Among patients examined by ENG for suspected ulnar neuropathy, we identified 546 patients with ulnar neuropathy and 633 patients with ulnar neuropathy-like symptoms. These groups were compared with 2 separate groups of matched community referents and to each other. Questionnaire information on lifestyle was obtained. The electrophysiological severity of neuropathy was also graded. We used conditional and unconditional logistic regression. Results: Responses were obtained from 59%. Ulnar neuropathy was related to smoking, adjusted odds ratio (OR) 4.31 (95% confidence interval [CI] 2.43-7.64) for >24 pack-years. Ulnar neuropathy-like symptoms were related to body mass index ?30 kg/m(2) , OR 1.99 (95% CI 1.25-3.19). Smoking was associated with increased severity of ulnar neuropathy. Conclusions: Findings suggest that smoking specifically affects the ulnar nerve. Muscle Nerve 48: 507-515, 2013. PMID:23424094

Frost, Poul; Johnsen, Birger; Fuglsang-Frederiksen, Anders; Svendsen, Susanne W



Neuromuscular ultrasound in common entrapment neuropathies.  


Neuromuscular ultrasound involves the use of high-resolution ultrasound to image the peripheral nervous system of patients with suspected neuromuscular diseases. It complements electrodiagnostic studies well by providing anatomic information regarding nerves, muscles, vessels, tendons, ligaments, bones, and other structures that cannot be obtained with nerve conduction studies and electromyography. Neuromuscular ultrasound has been studied extensively over the past 10 years and has been used most often in the assessment of entrapment neuropathies. This review focuses on the use of neuromuscular ultrasound in 4 of the most common entrapment neuropathies: carpal tunnel syndrome, ulnar neuropathy at the elbow and wrist, and fibular neuropathy at the knee. Muscle Nerve 48:696-704, 2013. PMID:23681885

Cartwright, Michael S; Walker, Francis O



APOE gene polymorphisms and diabetic peripheral neuropathy  

PubMed Central

Genetic factors may influence the natural course of diabetic peripheral neuropathy and explain some of its variability. The aim of this review was to examine the association between apolipoprotein E (apoE) gene polymorphisms and diabetic peripheral neuropathy. Four relevant studies were identified. The two earlier works provided evidence that the ?4 allele is a risk factor for this complication, while the two more recent studies were negative. Important differences in the methodology used and in the populations included are obvious, rendering difficult the comparison between studies. In conclusion, the association between APOE gene polymorphisms and diabetic peripheral neuropathy is still unclear. Available evidence is rather limited and results have so far been contradictory. Future studies should employ more robust methodology, adjusting for potential confounders and for the prevalence of neuropathy in the general population with diabetes.

Papanas, Nikolaos; Veletza, Stavroula; Maltezos, Efstratios



Inherited neuropathies: Clinical overview and update.  


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. Muscle Nerve 48: 604-622, 2013. PMID:23801417

Klein, Christopher J; Duan, Xiaohui; Shy, Michael E



Diagnosis of hereditary neuropathies in adult patients  

Microsoft Academic Search

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

Davide Pareyson



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


A 47-year-old man, who suffered from acute lymphocytic leukemia at 45 years old and was treated with hematopoietic stem cell transplantation at 46 years old after the induction of complete remission by the standard chemotherapy, developed the symptoms of chronic graft-versus-host disease (cGVHD) such as dry eyes, dry mouth, skin thickening, skin scaling, skin pigmentation and impaired liver function. He was admitted to our hospital because of the acute development of diplopia and weakness of his left upper extremity accompanying with the exacerbation of other symptoms of cGVHD. Neurological examinations revealed the right abducens nerve palsy and asymmetric muscular weakness of the extremities; the proximal part of the left upper extremity and the distal part of the right upper extremity were markedly involved. Neurophysiological studies including magnetic motor root stimulation revealed demyelinating neuropathy specifically involving the motor nerves. On the basis of these findings, a diagnosis of peripheral neuropathy associated with cGVHD was made. Nighteen reports are available on peripheral neuropathy in cGVHD patients, but to date little is known about the pathophysiology of this condition. Most of those patients have been diagnosed as having symmetric demyelinating polyneuropathy, such as Guillain-Barré syndrome or chronic inflammatory demyelinating polyneuropathy. In this study, contrary to previous reports, the asymmetric involvement of motor nerves is noteworthy. Accumulation and further analyses of the cases like the present case are necessary to elucidate the pathogenesis of peripheral neuropathy in cGVHD. PMID:16318371

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



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

PubMed Central

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

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



Photolysis Accompanying Peptide Absorption in Proteins  

PubMed Central

Exposure of proteins and polypeptides to ultraviolet radiation below 240 nm produces peptide cleavage which may or may not be accompanied by observable changes in conformation and optical rotary dispersion (ORD) properties, depending on the stability of the secondary and tertiary structure of the macromolecule under the experimental conditions. Helical and coiled forms of poly-L-glutamic acid undergo degradation at similar rates but only the helical form shows a significant change in rotatory properties. The helical form of poly-L-lysine, but neither the coiled nor ? forms, shows a change in [?]233 on irradiation at 233 nm. ?-Lactoglobulin shows essentially no change in [?]233 on irradiation in either dilute salt solution or 4 M urea at room temperature; however, in 4 M urea at 56°C a large change occurs. A model is developed which shows that studies of the effect of radiation on ORD properties may be useful in providing information on possible intermediate steps in protein denaturation. The method is illustrated with results on bovine plasma albumin. A quantum yield, 4.3 × 10-3 moles/einstein, was obtained for peptide cleavage in this protein at 225 nm. These studies, based on gel electrophoresis, also showed that the fragments produced are essentially random, suggesting that transfer of energy from aromatic residues is not an important contributor to the peptide photolysis. Possible errors which could arise in ORD and other studies involving intense ultraviolet radiation are considered.

Wilson, W. David; Foster, Joseph F.



Diabetic neuropathy--choices of treatment.  


Diabetic neuropathy represents a heterogeneous pathology taking place during diabetes mellitus (DM) evolution, hiding possibilities for rapid evolution which threaten even the life of the diabetic person. As a result, the recognition as precocious as possible of the neuropathy-induced alterations and the ways of treating this complication are essential. Diabetic neuropathy is classified in peripheral and vegetative, each of them with numerous clinical forms. Nevertheless, its etiopathogeny remains not totally understood, many theories existing for explaining it, its development being probably the result of a mixture of pathogenic mechanisms. Although there are difficulties in appreciation of the neuropathy prevalence in diabetic people, it is generally known that this alteration is one of the most frequent and invalidant major complication that affects this population, treatment as precocious as possible being essential. alpha-lipoic acid, substance with antioxidant properties, plays a central role in the energetic metabolism, principally functioning as a coenzyme in multienzymatic mitochondrial complexes alpha-lipoic acid has complex actions on different levels of the human organism, having many indications in different diseases, including DM. The results of numerous clinical studies have confirmed its efficacy in treating diabetic neuropathy. The present study has proposed itself to investigate the long-term effect of the short-term i.v. treatment with Thiogamma 600 (alpha-lipoic acid) in patients having type I or 2 DM, proving neuropathy symptoms and signs reduction evaluated in 3 months time, without metabolic control of the disease. If this amelioration proves to be persistent in time, with or without continuing the medication, this treatment will represent the most evident and efficient present solution in neuropathy. PMID:15526540

Bruckner, Ioana; Bustan, Catrinel; Adamescu, E; Dobjanschi, Carmen



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

PubMed Central

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

Vasilescu, C; Alexianu, M; Dan, A



Peripheral Neuropathy in Rats Exposed to Dichloroacetate  

PubMed Central

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

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



[Original articles on axonal neuropathy in 2010].  


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

Attarian, S



Phenylmethylsulfonyl Fluoride Protects Rats from Mipafox-Induced Delayed Neuropathy.  

National Technical Information Service (NTIS)

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 wh...

B. Veronesi S. Padilla




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...


Lacosamide has protective disease modifying properties in experimental vincristine neuropathy  

Microsoft Academic Search

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

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



Nonsystemic Vasculitic Neuropathy: Update on Diagnosis, Classification, Pathogenesis, and Treatment  

Microsoft Academic Search

The primary systemic vasculitides are autoimmune disorders characterized by chronic immune responses directed against vascular structures. They commonly affect small or medium-sized vessels in the peripheral nervous system (PNS), producing vasculitic neuropathies. Some patients develop vasculitis clinically restricted to the PNS, known as nonsystemic vasculitic neuropathy (NSVN), the most commonly encountered vasculitic neuropathy in pathologically based series. Diabetic and nondiabetic

Michael P. Collins; Isabel Periquet-Collins



Retinitis pigmentosa, ataxia, and peripheral neuropathy.  

PubMed Central

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

Tuck, R R; McLeod, J G



Delayed Pneumocephalus-Induced Cranial Neuropathy  

PubMed Central

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

Marupudi, Neena I.



Ischemic Neuropathy Associated with Livedoid Vasculitis  

PubMed Central

Background Livedoid vasculitis is a chronic dermatological problem with an unclear etiology. Clinical findings are petechiae with painful ulcers in both lower extremities, which heal to become hyperpigmented and porcelain-white satellite lesions. There are only a few reported cases of livedoid vasculitis presenting in combination with peripheral neuropathy. Case Report We report the first case of a Korean patient presenting with mononeuritis multiplex combined with livedoid vasculitis, which was confirmed by electrophysiological and pathological studies. Conclusions Our report supports the possible vaso-occlusive etiology of livedoid vasculitis in multifocal ischemic neuropathy.

Kim, Jee-Eun; Park, Su-Yeon; Sinn, Dong In; Kim, Sung-Min; Hong, Yoon-Ho; Park, Kyung Seok; Lee, Kwang-Woo



Curcumin Treatment Abrogates Endoplasmic Reticulum Retention and Aggregation-Induced Apoptosis Associated with Neuropathy-Causing Myelin Protein Zero-Truncating Mutants  

PubMed Central

Mutations in MPZ, the gene encoding myelin protein zero (MPZ), the major protein constituent of peripheral myelin, can cause the adult-onset, inherited neuropathy Charcot-Marie-Tooth disease, as well as the more severe, childhood-onset Dejerine-Sottas neuropathy and congenital hypomyelinating neuropathy. Most MPZ-truncating mutations associated with severe forms of peripheral neuropathy result in premature termination codons within the terminal or penultimate exons that are not subject to nonsense-mediated decay and are stably translated into mutant proteins with potential dominant-negative activity. However, some truncating mutations at the 3? end of MPZ escape the nonsense-mediated decay pathway and cause a mild peripheral neuropathy phenotype. We examined the functional properties of MPZ-truncating proteins that escaped nonsense-mediated decay, and we found that frameshift mutations associated with severe disease cause an intracellular accumulation of mutant proteins, primarily within the endoplasmic reticulum (ER), which induces apoptosis. Curcumin, a chemical compound derived from the curry spice tumeric, releases the ER-retained MPZ mutants into the cytoplasm accompanied by a lower number of apoptotic cells. Our findings suggest that curcumin treatment is sufficient to relieve the toxic effect of mutant aggregation-induced apoptosis and may potentially have a therapeutic role in treating selected forms of inherited peripheral neuropathies.

Khajavi, Mehrdad; Inoue, Ken; Wiszniewski, Wojciech; Ohyama, Tomoko; Snipes, G. Jackson; Lupski, James R.



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


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

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



Light chain deposition disease neuropathy resembling amyloid neuropathy in a multiple myeloma patient  

Microsoft Academic Search

A 65-year-old man with IgG lambda multiple myeloma developed severe polyneuropathy with prominent thermal-pain sensory impairment\\u000a and autonomic failure. Although the clinical presentation suggested amyloid neuropathy, nerve biopsy showed the immunohistochemical\\u000a and ultrastructural features typical of light chain deposition disease (LCDD). A precise morphologic and clinical description\\u000a of LCDD neuropathy is given for the first time in the present report.

M. P. Grassi; F. Clerici; C. Perin; M. Borella; A. Mangoni; A. Gendarini; A. Quattrini; R. Nemni



Microangiopathy in human diabetic neuropathy: relationship between capillary abnormalities and the severity of neuropathy  

Microsoft Academic Search

Summary  Clinical, electrophysiological and ultrastractural morphometric observations were made in 5 diabetic non-neuropathic patients, 5 diabetic patients with mild neuropathy and 11 diabetic patients with severe neuropathy. Capillary abnormalities were assessed in simultaneous nerve, muscle and skin biopsies and compared with results from 6 age-matched, non-diabetic control subjects.Nerve capillaries demonstrated markedly greater pathology than skin and muscle capillaries. Endoneurial capillary density

R. A. Malik; P. G. Newrick; A. K. Sharma; A. Jennings; A. K. Ah-See; T. M. Mayhew; J. Jakubowski; A. J. M. Boulton; J. D. Ward



A novel mitochondrial mutation m.8989G>C associated with neuropathy, ataxia, retinitis pigmentosa - the NARP syndrome.  


The archetypal NARP syndrome is almost exclusively associated with the m.8993T>C/G mutation in the sixth subunit of the mitochondrial ATP synthase, whereas other mutations in the MT-ATP6 gene primarily associate with Leigh syndrome or Leber's hereditary optic neuropathy (LHON). We report a novel mitochondrial point mutation, m.8989G>C, in a patient presenting with neuropathy, ataxia and retinitis pigmentosa constituting the classical NARP phenotype. This mutation alters the amino acid right next to canonical NARP mutation. We suggest that classic NARP syndrome relates to a defined dysfunction of p.MT-ATP6. PMID:23266623

Duno, Morten; Wibrand, Flemming; Baggesen, Kirsten; Rosenberg, Thomas; Kjaer, Niels; Frederiksen, Anja L



Optic neuritis: differential diagnosis.  


Optic neuritis can be mimicked by other optic neuropathies and by anterior segment, choroidal or retinal diseases. Retinal diseases may cause central visual loss when they involve the macular or peripapillary area. Central serous retinopathy, hereditary retinal diseases, white dots syndromes and autoimmune retinopathies may present a clinical picture similar to that of optic neuritis. Complete neuro-ophthalmological examination must be performed to differentiate optic nerve damage from other ocular structures involvement. As in optic neuritis, optic disc and macula appearance may be completely normal in several retinal diseases. Fluorescein angiography and electrophysiological testing are relevant for the differential diagnosis in many challenging cases. PMID:11794478

Bianchi Marzoli, S; Martinelli, V



The epidemiology of diabetic neuropathy. Diabetic Cardiovascular Autonomic Neuropathy Multicenter Study Group.  


Although neuropathy has long been recognized as a complication of diabetes, the impact of this condition has not been adequately established. The prevalence of diabetic neuropathy is virtually unknown because the published studies differ considerably with regard to definition, method of assessment, and patient selection. Furthermore, the determination of prevalence has been hampered by the fact that there is no generally accepted classification of the variety of manifestations of diabetic neuropathy. The introduction of new sensitive diagnostic methods aids in the detection of less severe stages of neuropathy, as compared with clinically based assessment, and renders the disease more prevalent. The prevalence of diabetic neuropathy in the few reported population-based studies was approximately 30%. We have evaluated the prevalence of cardiovascular autonomic neuropathy in a group of approximately 1000 diabetic patients randomly included from 21 hospitals in Germany, Austria, and Switzerland. The results of this study and those of a prospective study on the natural history of neural dysfunction during the first 5 years after diagnosis of type 1 diabetes will be presented. PMID:1562759

Ziegler, D; Gries, F A; Spüler, M; Lessmann, F


Myasthenia gravis with autoimmune autonomic neuropathy  

Microsoft Academic Search

The autoantibodies that impair neuromuscular junction transmission in myasthenia gravis are specific for the nicotinic acetylcholine receptor (AChR) of muscle. Antibodies specific for AChRs in ganglionic neurons are found in a majority of patients with subacute autonomic neuropathy. Dysautonomia is not a recognized feature of myasthenia gravis, but there have been rare reports of myasthenia gravis coexisting with autonomic failure,

Steven Vernino; William P. Cheshire; Vanda A. Lennon



Speech Perception in Individuals With Auditory Neuropathy  

Microsoft Academic Search

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 conversational speech in 13 participants with AN. Of these participants, 7

Fan-Gang Zeng; Sheng Liu



Hemimasticatory spasm --a peripheral paroxysmal cranial neuropathy?  

PubMed Central

The clinical and electrophysiological features of a case of hemimasticatory spasm are presented. The findings are in many respects similar to those described in hemifacial spasm. A peripheral cranial neuropathy as proposed in hemifacial spasm also may be responsible for hemimasticatory spasm. Images

Thompson, PD; Carroll, WM



Tactile stimulation and mechanoreceptors in sensory neuropathies  

Microsoft Academic Search

Meissner corpuscles are supposed to play a primary role in generating tactile responses. To verity this hypothesis, we combined electrophysiological and morphological methods. In a group of twelve patients affected by congenital or acquired neuropathies, electrical and tactile evoked potentials were near-nerve recorded along the median nerve. The density of Meissner corpuslces was calculated in the fingertip, exactly in the

M. Nolano; V. Provitera; F. Lullo; A. M. Saltalamacchia; C. Crisci; B. Lanzillo; L. Santoro



Alpha-lipoic Acid and diabetic neuropathy.  


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

Vallianou, Natalia; Evangelopoulos, Angelos; Koutalas, Pavlos



[Autonomic neuropathy in diabetics, treatment possibilities].  


Diabetic neuropathy is a chronic complication of diabetes. It involves non-inflammatory damage of the function and structure of peripheral nerves by metabolic vascular pathogenic processes. In case of affection of vegetative nerves (small non-myelinated C fibres) autonomic neuropathy develops. It is a relatively frequent form of neuropathy which remains for a long time without clinical symptoms and therefore is rarely diagnosed and treated. Manifestations of the affection are encountered in all organs which are supplied by vegetative nerves. The presence of this complication of diabetes is signalized by tachycardia at rest, deterioration of gastric evacuation, diabetic diarrhoea or constipation, erectile dysfunction, impaired function of the sweat glans or impaired pupillary reaction. The advanced form involves the danger of latent myocardial ischaemia, serious postural hypotension and sudden death. It increases significantly the mortality of the affected patients. Similarly as the treatment of other complication of diabetes, treatment of autonomic neuropathy is difficult. The objective of the present paper is to review contemporary therapeutic possibilities. An essential prerequisite remain efforts to achieve optimal compensation. The authors draw attention to the effect of alpha-lipoic acid which exerts a positive effect not only on subjective symptoms but also on the objective finding. The other mentioned drugs are used either only experimentally or for purely symptomatic treatment. PMID:12132356

Lacigová, S; Rusavý, Z; Cechurová, D; Jankovec, Z; Zourek, M



Autonomic neuropathy: a marker of cardiovascular risk  

Microsoft Academic Search

C ardiac autonomic neuropathy (CAN) represents a serious complication as it carries an approximately five-fold risk of mortality in patients with diabetes just as in those with chronic liver diseases. The high mortality rate may be related to silent myocardial infarction, cardiac arrhythmias, cardiovascular and cardiorespiratory instability and to other causes not yet explained. Resting tachycardia due to parasympathetic damage




Diagnosis and Management of Diabetic Peripheral Neuropathy  

Microsoft Academic Search

Diabetic peripheral neuropathy (DPN) is one of the most commonly occurring major complications of diabetes. The disease may manifest in several clinical patterns: most frequently as distal symmetrical sensory polyneuropathy. Guidelines are available for the diagnosis of DPN by the primary care physician. These recommend that a review of diabetic patients, including a questionnaire and inspection and neurological examination of

Isabel Illa



[Spontaneous acquired localized neuropathies in childhood].  


Acquired non-surgical, non-traumatic localized neuropathies, excluding cranial nerve disorders, are rare in infancy. We review the clinical histories of six children, studied for this disorders amongst a total of 2,105 children seen in the Neuropediatric Department of the Hospital Miguel Servet in Zaragoza. Two were diagnosed as familial neuropathy with pressure sensitive paralysis. Two plexopathies were considered to be familial brachial plexopathy with minor dysmorphic features. One case was diagnosed as idiopathic radial neuropathy and a further case as idiopathic lumbosacral plexopathy. We emphasize that although rare in pediatrics, spontaneous localized neuropathies often show constitutional pathology, frequently hereditary. Idiophatic cases may also be hereditary, and it may be difficult to confirm the diagnosis if there is no family history or phenotypic characteristics. Diagnosis depends on the personal and family history, physical examination, neurophysiological study, absence of abnormal neuroimaging findings and awareness of the possibility of this diagnosis. These disorders probably occur more often than is generally believed. PMID:9244623

Peña, J L; Marco, M; Gros, L; López Pisón, J



Inherited Neuropathy Can Cause Postpartum Foot Drop  

Microsoft Academic Search

Postpartum neurological complications occur in up to 1% of deliveries. Often prior anesthetic procedures are blamed, with medicolegal implications. We de- scribe a young woman who presented with postpar- tum foot drop diagnosed as an iatrogenic L5 root le- sion after uncomplicated epidural anesthesia. After neurological assessment some 5 mo later she tested positive for the common hereditary neuropathy with



Optic nerve ultrastructure following amiodarone therapy.  


Amiodarone has been implicated in the pathogenesis of optic neuropathy in several cases. However, that relationship is unclear, as subjects placed on amiodarone represent a high-risk group for various vasoocclusive accidents. In order to investigate the effect of amiodarone on the optic nerve, we examined histopathologically sections of the retrobulbar optic nerve obtained from an asymptomatic subject taking amiodarone. Lamellar inclusions were selectively found in the large axons. Amiodarone may have a chronic neurotoxic effect on the optic nerve via a drug-induced lipidosis. This neurotoxicity may be related to some of the acute forms of optic neuropathy described in the literature. PMID:2977138

Mansour, A M; Puklin, J E; O'Grady, R



Perineural optic nerve enhancement on magnetic resonance imaging in giant cell arteritis.  


Giant cell arteritis (GCA) may cause visually devastating optic neuropathy. In atypical cases, diagnosis of optic neuropathy can be delayed. We present 2 such atypical cases and demonstrate that contrast-enhanced orbital magnetic resonance imaging may be a valuable tool in patient evaluation and aid in the diagnosis of GCA. PMID:23845995

Liu, Katy C; Chesnutt, David A



Melatonin, a Promising Role in Taxane-Related Neuropathy  

PubMed Central

Purpose: Melatonin has neuroprotective effects in animal studies and has been suggested to decrease adverse reactions of chemotherapy including neuropathy. This pilot trial aimed at assessing whether melatonin, given during taxane chemotherapy for breast cancer, will decrease the incidence and/or severity of neuropathy. Methods: Twenty two consecutive patients beginning chemotherapy for breast cancer with paclitaxel, or docetaxel were enrolled. Patients received melatonin 21 mg daily at bedtime. Incidence and severity of neuropathy were assessed using neurological examinations, toxicity assessment per NCI-CTC 3.0 scale and FACT-Taxane quality of life questionnaire. Results: Neuropathy was seen in 45% (n = 10) of patients, 23% (n = 6) grade 1 and 22% (n = 5) Grade 2 neuropathy. No grade 3 neuropathies were reported. The majority (55%) of all patients reported no neuropathy. Compliance with melatonin (>60% of dose) was seen in most patients (86%) No patient reported daytime sedation. The median FACT-Taxane quality of life end of study score was 137, with only a 0.5 median decline from baseline. Conclusion: Patients receiving melatonin during taxane chemotherapy had a reduced incidence of neuropathy. Melatonin may be useful in the prevention or reduction of taxane-induced neuropathy and in maintaining quality of life. Larger trials are warranted to further explore the role of melatonin in neuropathy treatment and prevention.

Nahleh, Z.; Pruemer, J.; Lafollette, J.; Sweany, S.



Erythromycin induces supranormal gall bladder contraction in diabetic autonomic neuropathy.  

PubMed Central

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

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



The prevalence of diabetic peripheral neuropathy in an outpatient setting.  


This study was undertaken to clinically estimate the prevalence of diabetic peripheral neuropathy amongst patients attending an outpatient clinic and to evaluate their risk factors for developing peripheral neuropathy. It was a cross-sectional study of 134 diabetes mellitus patients who attended the Primary Care Clinic, University Hospital, Kuala Lumpur. The patients were interviewed for their demographic data, past and present medical/surgical history, social history, personal habits and symptoms of peripheral neuropathy. Foot examination and clinical neurological tests were conducted and the presence of peripheral neuropathy was assessed. The main outcome measures were the Neuropathy Symptom Score and the Neuropathy Disability Score. The prevalence of diabetic peripheral neuropathy was found to be 50.7%. Peripheral neuropathy was related to the age of the patient and the duration of diabetes but did not seem to be significantly related to diabetic control. To conclude, there was a high prevalence of peripheral neuropathy amongst the diabetics in this study. These patients developed peripheral neuropathy at a younger age and shorter duration of diabetes compared to a similar study that was done in the UK. PMID:15190629

Mimi, O; Teng, C L; Chia, Y C



Clinicopathological features of neuropathy associated with lymphoma.  


Lymphoma causes various neurological manifestations that might affect any part of the nervous system and occur at any stage of the disease. The peripheral nervous system is one of the major constituents of the neurological involvement of lymphoma. In this study we characterized the clinical, electrophysiological and histopathological features of 32 patients with neuropathy associated with non-Hodgkin's lymphoma that were unrelated to complications resulting from treatment for lymphoma. Nine patients had pathologically-proven neurolymphomatosis with direct invasion of lymphoma cells into the peripheral nervous system. These patients showed lymphomatous cell invasion that was more prominent in the proximal portions of the nerve trunk and that induced demyelination without macrophage invasion and subsequent axonal degeneration in the portion distal from the demyelination site. Six other patients were also considered to have neurolymphomatosis because these patients showed positive signals along the peripheral nerve on fluorodeoxyglucose positron emission tomography imaging. Spontaneous pain can significantly disrupt daily activities, as frequently reported in patients diagnosed with neurolymphomatosis. In contrast, five patients were considered to have paraneoplastic neuropathy because primary peripheral nerve lesions were observed without the invasion of lymphomatous cells, with three patients showing features compatible with chronic inflammatory demyelinating polyneuropathy, one patient showing sensory ganglionopathy, and one patient showing vasculitic neuropathy. Of the other 12 patients, 10 presented with multiple mononeuropathies. These patients showed clinical and electrophysiological features similar to those of neurolymphomatosis rather than paraneoplastic neuropathy. Electrophysiological findings suggestive of demyelination were frequently observed, even in patients with neurolymphomatosis. Eleven of the 32 patients, including five patients with neurolymphomatosis, fulfilled the European Federation of Neurological Societies/Peripheral Nerve Society electrodiagnostic criteria of definite chronic inflammatory demyelinating polyneuropathy. Some of these patients, even those with neurolymphomatosis, responded initially to immunomodulatory treatments, including the administration of intravenous immunoglobulin and steroids. Patients with lymphoma exhibit various neuropathic patterns, but neurolymphomatosis is the major cause of neuropathy. Misdiagnoses of neurolymphomatosis as chronic inflammatory demyelinating polyneuropathy are frequent due to a presence of a demyelinating pattern and the initial response to immunomodulatory treatments. The possibility of the concomitance of lymphoma should be considered in various types of neuropathy, even if the diagnostic criteria of chronic inflammatory demyelinating polyneuropathy are met, particularly in patients complaining of pain. PMID:23884813

Tomita, Minoru; Koike, Haruki; Kawagashira, Yuichi; Iijima, Masahiro; Adachi, Hiroaki; Taguchi, Jun; Abe, Takenori; Sako, Kazuya; Tsuji, Yukiko; Nakagawa, Masanori; Kanda, Fumio; Takeda, Fusako; Sugawara, Masashiro; Toyoshima, Itaru; Asano, Naoko; Sobue, Gen



Therapy of chemotherapy-induced peripheral neuropathy.  


Chemotherapy-induced peripheral neuropathy (CIPN) is still a common and disabling side effect of many chemotherapy agents in use today. Unfortunately, neither prophylactic strategies nor symptomatic treatments have proven useful yet. This review will discuss the diagnosis and evaluation of neuropathy in cancer patients, as well as reviewing the various prophylactic and symptomatic treatments that have been proposed or tried. However, sufficient evidence is lacking to recommend any of these treatments to patients suffering with CIPN. Therefore, the best approach is to treat symptomatically, and to start with broad-spectrum analgesic medications such as non-steroidal anti-inflammatory drugs (NSAIDs). If NSAIDs fail, a reasonable second-line agent in properly selected patients may be an opioid. Unfortunately, even when effective in other types of neuropathic pain, anti-depressants and anticonvulsants have not yet proven effective for treating the symptoms of CIPN. PMID:19170681

Kaley, Thomas J; Deangelis, Lisa M



Diabetic neuropathy: new strategies for treatment.  


Current therapeutic possibilities can be divided into two groups: the pathogenetically oriented and the symptomatic therapy. One of the most important component of etiology-based treatment is the stabilization of glycemic control. Based on efficacy and safety data benfotiamine and alpha-lipoic acid should be considered as first choices among pathogenetically oriented treatments of diabetic neuropathy. Promising data were published about the aldose reductase inhibitor ranirestat. The symptomatic effect of antiepileptic drugs in diabetic painful neuropathy (DPN) is originated from several possible pharmacological properties. Pregabalin and gabapentin have the highest efficacy and the lowest frequency of adverse events among these drugs. Antidepressants also extensively used for symptomatic treatment in DPN. In the last years several studies were published about the benefial effect of duloxetine. Most likely combination therapy will be frequently applied in the future for the treatment of DPN, the optimal choice could be to combine pathogenetically oriented and symptomatic treatment. PMID:17593238

Várkonyi, Tamás; Kempler, Peter



Ulnar neuropathy associated with subdermal contraceptive implant.  


Side effects are a common occurrence in the use of subdermal contraceptive implants (Norplant); approximately 70% to 80% of women using the device report abnormal uterine bleeding, headaches, acne, mastalgia, nervousness, appetite changes, and weight gain. Local implant site reactions range from 0.4% to 4.7%, with pain being the most common. Other insertion site complications include infection and implant expulsion. Only three cases have been described in the literature concerning implant site-related neuropathy, involving the sensory branch of the musculocutaneous nerve (lateral cutaneous nerve) in two cases and the antebrachial cutaneous nerve in the third case. We believe our report is the first case of an axonal loosing motor and sensory ulnar neuropathy associated with the removal of a subdermal contraceptive implant (Norplant). We review insertion site complications and their most likely causes. Also, we discuss alternative removal techniques for difficult-to-remove implants. PMID:9743065

Marin, R; McMillian, D



Suprascapular Neuropathy in a Collegiate Pitcher  

PubMed Central

A healthy, 20-year-old, highly competitive collegiate baseball pitcher developed vague pain and soreness in the dominant posterior shoulder with live pitching. The symptoms intensified, and, after a particularly poor starting performance, the athlete presented for physical examination. Examination revealed visible atrophy of the infraspinatus muscle and decreased strength in external rotation and abduction. Magnetic Resonance Imaging was inconclusive. Electromyographic examination revealed decreased suprascapular nerve conduction to the infraspinatus muscle. Our diagnosis was entrapment neuropathy from traction on the suprascapular nerve at the spinoglenoid notch, causing delayed conduction to the infraspinatus muscle. We took a conservative approach of shoulder rehabilitation and activity modification, which resulted in the athlete returning to a highly competitive level without further problems, despite the remaining atrophy and muscle weakness. Examination of injuries to the shoulder complex, especially in athletes involved in repetitive overhead motions, should take suprascapular neuropathy into consideration.

Smith, Andrew N.



Oxaliplatin-Induced Neuropathy in Colorectal Cancer  

PubMed Central

Oxaliplatin use in palliative and adjuvant treatment of colon cancer is frequently limited by cumulative neurotoxicity, leading to reduced quality of life and decreased dose. The mechanism of this neurotoxicity is unclear, but may relate to neuronal voltage-gated sodium channels involving calcium chelation by a metabolite of the drug. Various preventative measures have been tested to reduce the incidence of neurotoxicity, including calcium and magnesium infusions, dose interruption of the drug, and prophylactic neuromodulatory agents. Despite the promising efficacy of these measures, they are not universally accepted. Less is known about the best way to treat established neurotoxicity, which is permanent in some patients, although venlafaxine has shown promise in small clinical trials. This paper analyzes the extent, cause and risk factors for neuropathy, and the potential preventative and therapeutic treatments for oxaliplatin-induced neuropathy.

Weickhardt, Andrew; Wells, Keith; Messersmith, Wells



Musculocutaneous Neuropathy: Case Report and Discussion  

Microsoft Academic Search

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

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



Punch Skin Biopsy in Diabetic Neuropathy  

Microsoft Academic Search

Measurement of unmyelinated C and A delta nociceptors through punch skin biopsy has been an important development in diabetic\\u000a peripheral neuropathy over the past decade. The technique provides an objective pathological window into a population of fibers\\u000a that is invisible to standard electrophysiological techniques and as a result has been difficult to investigate. Clinically,\\u000a the punch biopsy technique is most

Michael Polydefkis


Intrapartum obturator neuropathy diagnosed after cesarean delivery  

Microsoft Academic Search

Several postpartum neurologic injuries have been described in detail, while obturator nerve injuries are rarely reported.\\u000a We report a woman who had weakness of the right leg and groin pain after cesarean delivery under general anesthesia. Obturator\\u000a neuropathy was confirmed by electromyography and no compressive lesion of the nerve was seen on magnetic resonance imaging.\\u000a The patient was treated conservatively

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



Chemotherapy-induced peripheral neuropathy: pathogenesis and emerging therapies  

Microsoft Academic Search

Peripheral neuropathy is a major dose-limiting side effect of many chemotherapeutic agents. The type and degree of neuropathy depend on the chemotherapy drug, dose-intensity, and cumulative dose. Disabling peripheral neuropathy has a significant negative impact on quality of life. Accordingly, a reliable assessment of chemotherapy-induced peripheral neurotoxicity is necessary, especially if potential neuroprotective agents are to be investigated. Chemoprotectants are

Allyson J. Ocean; Linda T. Vahdat



Common Peroneal Neuropathy Secondary to Squatting during Childbirth  

Microsoft Academic Search

Background: Common peroneal neuropathy occurs fairly frequently in the adult population; however, very few cases of peroneal neuropathy after prolonged squatting have been reported.Case: A 29-year-old woman noted right foot numbness and weakness immediately after childbirth, which involved 15–30 minutes of pushing in a squatting position. Physical examination and an electrodiagnostic study confirmed a common peroneal neuropathy. The patient was

Marietta Babayev; Mark P Bodack; Chris Creatura



Clinically diagnosed diabetic neuropathy: frequency, types and severity.  

PubMed Central

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

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



Excessive uterine activity accompanying induced labor  

Microsoft Academic Search

Objective: To estimate the incidence and timing of excessive uterine activity accompanying induction of labor with misoprostol using different routes (oral or vaginal) and forms (intact tablet or crushed) and to compare these with dinoprostone gel, oxytocin, and spontaneous labor.Methods: This retrospective cohort study included 519 women at term who had labor induced and 86 women at term in spontaneous

Joan M. G Crane; David C Young; Kimberly D Butt; Kelly A Bennett; Donna Hutchens



Hard Metal Alveolitis Accompanied by Rheumatoid Arthritis  

Microsoft Academic Search

Hard metal lung diseases (HML) are rare, and complex to diagnose. We describe the case of a patient with allergic alveolitis accompanied by rheumatoid arthritis. A sharpener of hard metal by trade, our patient was a 45-year-old, nonsmoking Caucasian female who experienced symptoms of cough and phlegm, and dyspnea on exertion. Preliminary lung findings were inspiratory rales in both basal

Paula A. Hahtola; Ritva E. Järvenpää; Kari Lounatmaa; Jorma J. Mattila; Immo Rantala; Jukka A. Uitti; Seppo Sutinen



Comparison of efficiencies of michigan neuropathy screening instrument, neurothesiometer, and electromyography for diagnosis of diabetic neuropathy.  


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

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



Information from cochlear potentials and genetic mutations helps localize the lesion site in auditory neuropathy  

PubMed Central

Auditory neuropathy (AN) is a disorder characterized by disruption of auditory nerve activity resulting from lesions involving the auditory nerve (postsynaptic AN), inner hair cells and/or the synapses with auditory nerve terminals (presynaptic AN). Affected subjects show impairment of speech perception beyond that expected for the hearing loss, abnormality of auditory brainstem potentials and preserved outer hair-cell activities. Furthermore, AN can be identified either as an isolated disorder or as an associated disorder with multisystem involvement including peripheral and optic neuropathies (non-isolated AN). Mutations in several nuclear and mitochondrial genes have been identified as underlying these forms of AN. Recently, new genes have been identified as involved in both isolated (DIAPH3, OTOF) and non-isolated AN (OPA1). Moreover, abnormal cochlear potentials have been recorded from patients with specific gene mutations by using acoustic stimuli or electrical stimulation through cochlear implant. In this review, different types of genetically based auditory neuropathies are discussed and the proposed molecular mechanisms underlying AN are reviewed.



Evaluation Tools and Animal Models of Peripheral Neuropathies  

Microsoft Academic Search

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

B. Fricker; A. Muller; F. René



The role of autonomic neuropathy in diabetic foot ulceration  

Microsoft Academic Search

Five standard, non-invasive tests of cardiovascular, autonomic function were performed in each of four groups of 30 subjects: controls, group 1, diabetics without clinical evidence of neuropathy; group 2, diabetics with neuropathy, but without foot ulceration; group 3, diabetics with neuropathic ulceration of the foot. The results showed a significant impairment of autonomic function in diabetics without clinically demonstrable somatic

M E Ahmed; L Delbridge; L P Le Quesne



Surrogate markers of small fiber damage in human diabetic neuropathy.  


Surrogate markers of diabetic neuropathy are being actively sought to facilitate the diagnosis, measure the progression, and assess the benefits of therapeutic intervention in patients with diabetic neuropathy. We have quantified small nerve fiber pathological changes using the technique of intraepidermal nerve fiber (IENF) assessment and the novel in vivo technique of corneal confocal microscopy (CCM). Fifty-four diabetic patients stratified for neuropathy, using neurological evaluation, neurophysiology, and quantitative sensory testing, and 15 control subjects were studied. They underwent a punch skin biopsy to quantify IENFs and CCM to quantify corneal nerve fibers. IENF density (IENFD), branch density, and branch length showed a progressive reduction with increasing severity of neuropathy, which was significant in patients with mild, moderate, and severe neuropathy. CCM also showed a progressive reduction in corneal nerve fiber density (CNFD) and branch density, but the latter was significantly reduced even in diabetic patients without neuropathy. Both IENFD and CNFD correlated significantly with cold detection and heat as pain thresholds. Intraepidermal and corneal nerve fiber lengths were reduced in patients with painful compared with painless diabetic neuropathy. Both IENF and CCM assessment accurately quantify small nerve fiber damage in diabetic patients. However, CCM quantifies small fiber damage rapidly and noninvasively and detects earlier stages of nerve damage compared with IENF pathology. This may make it an ideal technique to accurately diagnose and assess progression of human diabetic neuropathy. PMID:17513704

Quattrini, Cristian; Tavakoli, Mitra; Jeziorska, Maria; Kallinikos, Panagiotis; Tesfaye, Solomon; Finnigan, Joanne; Marshall, Andrew; Boulton, Andrew J M; Efron, Nathan; Malik, Rayaz A



Vibrotactile perception threshold measurements for diagnosis of sensory neuropathy  

Microsoft Academic Search

Summary Recognition of the fact that impairment of the tactile sense may occur independently of other disturbances in the vibration syndrome has rekindled an interest in developing a diagnostic method for early detection of vibration-induced neuropathy. There is also evidence suggesting that vibrotactile measurements represent a valuable diagnostic tool in compressive neuropathies, such as the carpal tunnel syndrome. The method

R. Lundström; T. Strömberg; G. Lundborg



Diabetic neuropathy in Mauritius: prevalence and risk factors  

Microsoft Academic Search

The study of diabetic neuropathy has been primarily in Europids, despite the high prevalence of diabetes in other populations. We set out to ascertain the prevalence of diabetic neuropathy and its risk factors in the island nation of Mauritius. Population surveys were carried out in 1987 and 1992 in Mauritius to establish the prevalence of Type 2 diabetes. In the

Jonathan E Shaw; Allison M Hodge; Maximilian de Courten; Gary K Dowse; Hassam Gareeboo; Jaakko Tuomilehto; K. George M. M Alberti; Paul Z Zimmet



Neuropathological alterations in diabetic truncal neuropathy: evaluation by skin biopsy  

Microsoft Academic Search

OBJECTIVESTo describe the neuropathological features in skin biopsies from patients with diabetic truncal neuropathy.METHODSThree patients with diabetic truncal neuropathy underwent skin biopsies from both symptomatic and asymptomatic regions of the chest and trunk. After local anaesthesia, biopsies were performed using a 3 mm diameter punch device (Acupunch). Intraepidermal nerve fibres (IENFs), the most distal processes of small myelinated and unmyelinated

Giuseppe Lauria; Justin C McArthur; Peter E Hauer; John W Griffin; David R Cornblath



[Paraneoplastic neuropathy with positive anti-Hu].  


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

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



Alpha Accompanied Ternary Fission of Superheavy Nuclei  

NASA Astrophysics Data System (ADS)

Potential energy surfaces corresponding to the alpha accompanied ternary fragmentation in superheavy mass region have been investigated. The lowest value of potential energy is found for the configuration having alpha particle in between other two fragments. The position of deepest valleys in the potential energy surface indicates the most probable tri-partition of a given nucleus. The isotopic effect on the variation of the deepest valley has also been investigated. For the isotopic chain of Z = 114, the minimum is found at 140Ce + 4He + 136Xe, suggesting this to be the most probable tri-partition. Similar possible configurations have been studied for Z = 116, 118 and 120 and the presence of proton/neutron magic number has been found in all the most probable combinations for alpha accompanied ternary fission.

Thakur, Shagun; Kumar, Rajesh; Vijayaraghavan, K. R.; Balasubramaniam, M.



Paclitaxel plus carboplatin–induced peripheral neuropathy  

Microsoft Academic Search

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

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



Median palmar digital neuropathy in a cheerleader.  


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

Shields, R W; Jacobs, I B



Odontodysplasia, gingival manifestations, and accompanying abnormalities.  


Regional odontodysplasia is an uncommon developmental dental disorder that may occasionally be accompanied by other abnormalities. A case is described in which the chief report was of a gingival enlargement arising in a female patient who also had dolichocephaly, thin calvarium, clinodactyly and transverse grooving of her fingernails, and a history of abnormal hair. Previously suggested etiologic factors and cases reported in association with other abnormalities are reviewed. PMID:8850490

Fanibunda, K B; Soames, J V



Diagnosis and treatment of pain in small-fiber neuropathy.  


Small-fiber neuropathy manifests in a variety of different diseases and often results in symptoms of burning pain, shooting pain, allodynia, and hyperesthesia. Diagnosis of small-fiber neuropathy is determined primarily by the history and physical exam, but functional neurophysiologic testing and skin biopsy evaluation of intraepidermal nerve-fiber density can provide diagnostic confirmation. Management of small-fiber neuropathy depends on the underlying etiology with concurrent treatment of associated neuropathic pain. A variety of recent guidelines proposes the use of antidepressants, anticonvulsants, opioids, topical therapies, and nonpharmacologic treatments as part of the overall management of neuropathic pain. Unfortunately, little data about the treatment of pain specifically in small-fiber neuropathy exist because most studies combine mixed neuropathic pain syndromes in the analysis. Additional studies targeting the treatment of pain in small-fiber neuropathy are needed to guide decision making. PMID:21286866

Hovaguimian, Alexandra; Gibbons, Christopher H



Diagnosis and Treatment of Pain in Small Fiber Neuropathy  

PubMed Central

Small fiber neuropathy manifests in a variety of different diseases and often results in symptoms of burning pain, shooting pain, allodynia, and hyperesthesia. Diagnosis of small fiber neuropathy is determined primarily by the history and physical exam, but functional neurophysiologic testing and skin biopsy evaluation of intraepidermal nerve fiber density can provide diagnostic confirmation. Management of small fiber neuropathy depends on the underlying etiology with concurrent treatment of associated neuropathic pain. A variety of recent guidelines propose the use of antidepressants, anticonvulsants, opioids, topical therapies, and nonpharmacologic treatments as part of the overall management of neuropathic pain. Unfortunately, little data about the treatment of pain specifically in small fiber neuropathy exist because most studies combine mixed neuropathic pain syndromes in the analysis. Additional studies targeting the treatment of pain in small fiber neuropathy are needed to guide decision making.

Hovaguimian, Alexandra



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

Microsoft Academic Search

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

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



Methylene Blue Provides Behavioral and Metabolic Neuroprotection Against Optic Neuropathy  

Microsoft Academic Search

Methylene blue (MB) is a diaminophenothiazine with potent antioxidant and unique redox properties that prevent morphologic\\u000a degenerative changes in the mouse retina induced by rotenone, a specific mitochondrial complex I inhibitor. This study evaluated\\u000a pigmented rats to determine whether MB’s neuroprotective effects against rotenone-mediated retinal neurotoxicity have functional\\u000a relevance and whether these effects are mediated by an improvement in neuronal

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



Auditory neuropathy: unexpectedly common in a screened newborn population.  


Auditory neuropathy, or dyssynchrony, is defined by an abnormal or absent auditory brainstem response but intact otoacoustic emissions or cochlear microphonics. It is associated with impaired hearing on behavioural pure-tone audiometry, absent acoustic reflexes, and poor speech perception, particularly in noisy environments. These results suggest a disorder of inner hair-cell and or eighth-nerve function. We describe a case-note survey of patients with and without auditory neuropathy, using data from the local newborn hearing screening programme collected prospectively from 2002 to 2007. During this period, 45 050 infants were screened with otoacoustic emissions, 30 patients were diagnosed with suspected severe to profound hearing loss (16 males, 14 females), and 12 of those 30 had auditory neuropathy (six males, six females). Mean gestational age was 33 weeks 1 day in the auditory neuropathy group and 35 weeks in the non-auditory neuropathy group. The most significant risk factors for auditory neuropathy were hyperbilirubinaemia (p=0.018), sepsis (p=0.024), and gentamicin exposure (p=0.024). Children with auditory neuropathy comprise a subgroup of patients with hearing impairment involving different pathologies most commonly associated with the risk factors related to admission to neonatal intensive care units. Improvement is possible with maturity, at least in a minority. PMID:19416324

Dowley, Andrew C; Whitehouse, William P; Mason, Steve M; Cope, Yvonne; Grant, Judith; Gibbin, Kevin P



Neuropathy associated with microtubule inhibitors: diagnosis, incidence, and management.  


Microtubule inhibitor (MTI)-based chemotherapies used in the treatment of breast cancer--including vinca alkaloids, taxanes, and epothilones--are known to be associated with peripheral neuropathy. The incidence and severity of neuropathy, most frequently sensory in nature, depend on the agent used, absolute and cumulative drug dose, administration schedule, and presence of comorbidities. Although some first-generation vinca alkaloids, such as vincristine, were associated with severe mixed sensory/motor neuropathy, the deficits associated with newer agents in this class (eg, vinflunine) are generally milder and limited to distal sensory signs and symptoms. Among the taxanes, sensory neuropathy is reported more often with administration of paclitaxel and albumin-bound paclitaxel and less frequently with docetaxel. Epothilones, a new class of MTI, may be associated with grade 3/4 peripheral neuropathy; however, the neuropathy associated with ixabepilone, a novel epothilone B analog, is generally mild to moderate and reversible to baseline or grade 1 levels. The neuropathy induced by MTI therapy is best managed with dose adjustments and/or treatment delay. This article provides an overview of the incidence, characteristics, and management of MTI-associated neurotoxicities for known vinca alkaloids and taxanes, as well as newer agents, such as vinflunine and ixabepilone. PMID:18567992

Swain, Sandra M; Arezzo, Joseph C



Endoneurial Microvascular Pathology in Feline Diabetic Neuropathy  

PubMed Central

Endoneurial capillaries in nerve biopsies from 12 adult diabetic cats with varying degrees of neurological dysfunction were examined for evidence of microvascular pathology and compared to nerves obtained at autopsy from 7 adult non-diabetic cats without clinical evidence of neurological dysfunction. As reported previously (Mizisin et al., 2007), the diabetic cats had elevated glycosylated hemoglobin and serum fructosamine levels, decreased motor nerve conduction velocity and compound muscle action potentials (CMAP), and markedly decreased myelinated nerve fiber densities. Compared to non-diabetic cats, there was a non-significant 26% increase in capillary density and a significant (P<0.009) 45% increase in capillary size in diabetic cats. Capillary luminal size was also significantly (P<0.001) increased, while an index of vasoconstriction was significantly decreased (P<0.001) in diabetic cats compared to non-diabetic controls. No differences in endothelial cell size, endothelial cell number or pericyte size were detected between non-diabetic and diabetic cats. In diabetic cats, basement membrane thickening, seen as a reduplication of the basal lamina, was significantly (P<0.0002) increased by 73% compared to non-diabetic controls. Regression analysis of either myelinated nerve fiber density or CMAP amplitude against basement membrane size demonstrated a negative correlation with significant slopes (P<0.03 and P<0.04, respectively). These data demonstrate that myelinated nerve fiber injury in feline diabetic neuropathy is associated with microvascular pathology and that some of these changes parallel those documented in experimental rodent and human diabetic neuropathy.

Estrella, Jeannelyn S.; Nelson, Richard N.; Sturges, B.K.; Vernau, Karen M.; Williams, D. Collette; LeCouteur, Richard A.; Shelton, G. Diane; Mizisin, Andrew P.



Sacral Perineural Cyst Accompanying Disc Herniation  

PubMed Central

Although most of sacral perineural cysts are asymptomatic, some may produce symptoms. Specific radicular pain may be due to distortion, compression, or stretching of nerve root by a space occupying cyst. We report a rare case of S1 radiculopathy caused by sacral perineural cyst accompanying disc herniation. The patient underwent a microscopic discectomy at L5-S1 level. However, the patient's symptoms did not improved. The hypesthesia persisted, as did the right leg pain. Cyst-subarachnoid shunt was set to decompress nerve root and to equalize the cerebrospinal fluid pressure between the cephalad thecal sac and cyst. Immediately after surgery, the patient had no leg pain. After 6 months, the patient still remained free of leg pain.

Ju, Chang Il; Shin, Ho; Kim, Hyeun Sung



Bremsstrahlung Accompanied ? Decay of 210Po  

NASA Astrophysics Data System (ADS)

We report on a high-statistics measurement of bremsstrahlung emitted in the ? decay of 210Po. The measured differential emission probabilities, which we could follow up to ?-energies of ~ 500 keV, allow for the first time for a serious test of various model calculations of bremsstrahlung accompanied a decay.1 Taking into account the interference between the electric dipole and quadrupole amplitudes, which we calculated within the framework of a refined quasi-classical approximation2 and which modifies the angular correlation between the ? particle and the emitted photon, we find good agreement of the measured ?-emission probabilities with those calculated in our quasi-classical model as well as with the fully quantum mechanical prediction of Ref. 3.

Boie, H.; Scheit, H.; Jentschura, U. D.; Köck, F.; Lauer, M.; Milstein, A. I.; Terekhov, I. S.; Schwalm, D.



Peripheral neuropathy: evidence-based treatment of a complex disorder.  


Peripheral neuropathy (PN) is a common and often progressive condition frequently seen in primary care. The chronic pain associated with PN, or neuropathic pain, can significantly diminish patients' quality of life and be challenging to treat. PMID:22460540

Hammersla, Margaret; Kapustin, Jane Faith



Unusual association of multiple sclerosis and tomaculous neuropathy.  


We describe two cases in which multiple sclerosis (MS) occurred in association with tomaculous neuropathy, presenting as chronic, distal sensorimotor polyneuropathy. In Case 1, monoclonal gammopathy of undetermined significance with monoclonal IgG lambda reactive against GM1 ganglioside, was also detected. The diagnosis of tomaculous neuropathy was established after sural nerve biopsy. Teased fibers examination revealed focal 'sausage-like' thickenings of the myelin sheaths in intact fibers and in fibers with segmental demyelination. Electron microscopy showed them to be due, mostly, to multiple windings of redundant myelin and concentric apposition of numerous lamellae, in contact with an intact myelin sheath. These are the first reported cases of tomaculous neuropathy in patients with MS. Whether the combination of the two conditions is purely coincidental or suggests the possible causal relation between MS and tomaculous neuropathy, is not certain. PMID:9619649

Drulovi?, J; Dozi?, S; Levi?, Z; Stojsavljevi?, N; Triki?, R; Cvetkovi?, D; Apostolski, S



African Mitochondrial DNA Subhaplogroups and Peripheral Neuropathy during Antiretroviral Therapy  

PubMed Central

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

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



Sciatic neuropathy as first sign of metastasising prostate cancer  

PubMed Central

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.

Hansen, Jakob M?ller; Rasti, Zoreh; Smith, Torben; Lassen, Lisbeth Hjorth



Treating Pain from Chemotherapy-Induced Peripheral Neuropathy

In this trial, patients with painful peripheral neuropathy caused by prior treatment with paclitaxel or oxaliplatin will be randomly assigned to receive either duloxetine or placebo pills for 6 weeks.


Evaluation of thermal and vibration sensation in diabetic neuropathy  

Microsoft Academic Search

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

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



Animal models of chemotherapy-evoked painful peripheral neuropathies  

Microsoft Academic Search

Summary  This review examines recent preclinical research on toxic peripheral neuropathy and potential therapeutic developments. Chemotherapy-induced\\u000a peripheral neurotoxicity is a major clinical problem because it represents the dose-limiting side effects of a significant\\u000a number of antineoplastic drugs. Patients are unable to complete full or optimal treatment schedules. The incidence of chemotherapy-induced\\u000a peripheral neuropathy varies depending on the drugs and schedules used,

Nicolas Authier; David Balayssac; Fabien Marchand; Bing Ling; Aude Zangarelli; Juliette Descoeur; François Coudore; Emmanuel Bourinet; Alain Eschalier



Suramin-induced neuropathy in an animal model  

Microsoft Academic Search

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

James W Russell; Jagjit S Gill; Eric J Sorenson; Debra A Schultz; Anthony J Windebank



Unilateral Pudendal Neuropathy is Common in Patients with Fecal Incontinence  

Microsoft Academic Search

\\u000a Purpose  Pudendal neuropathy and fecal incontinence frequently coexist; however, the contribution of neuropathy is unknown. The pudendal\\u000a nerve innervates the external anal sphincter muscle, anal canal skin, and coordinates reflex pathways. Lateral dominance or\\u000a a dominantly innervating nerve and its subsequent damage may have major implications in the etiology and treatment of fecal\\u000a incontinence. This study was designed to establish the

Mayoni L. Gooneratne; S. Mark Scott; Peter J. Lunniss



Chronic demyelinating neuropathy and intra-axonal polyglucosan bodies  

Microsoft Academic Search

In this study we evaluated the relationship between polyglucosan bodies and peripheral nerve lesions. The biopsied sural nerve from a patient with late-onset chronic sensori-motor neuropathy showed many intra-axonal polyglucosan bodies and segmental demyelination\\/remyelination. The formation of Schwann cell hyperplasia around the demyelinated axons was found at the sites of polyglucosan bodies. These findings suggest that demyelinating neuropathy is a

K. Matsumuro; S. Izumo; Y. Minauchi; M. Inose; I. Higuchi; M. Osame



[Multiple entrapments neuropathy in adult polyglucosan body disease].  


Adult polyglucosan body disease (APBD) is a rare condition characterized by neuropathy, dementia, upper motor neuron dysfunction and neurogenic bladder. For diagnosis, the presence of polyglucosan bodies (PB), or PAS (+) glucose polymers, must be demonstrated. In this description of a woman with APBD and multiple entrapment neuropathy, we discuss a possible role for morphological changes induced by PB in increasing susceptibility to pressure palsies. PMID:7786544

Gil-Néciga, E; Pareja, J A; Chincón, I; Jarrín, S; Chaparro, P



Ischemic neuropathy and rhabdomyolysis as presenting symptoms of postpartum cardiomyopathy  

Microsoft Academic Search

Rhabdomyolysis and peripheral neuropathy are two distinct disease entities which are rarely encountered in combination. We\\u000a present a woman with rhabdomyolysis and peripheral neuropathy 3 weeks postpartum. Her symptoms were caused by bilateral femoral\\u000a artery thrombosis due to postpartum cardiomyopathy (PPCM). This demonstrates that PPCM may present with predominantly non-cardial\\u000a symptoms and underscores the importance of rapidly recognizing this disorder.

Rick C. G. Helmich; Hanneke W. M. van Laarhoven; Hennie C. Schoonderwaldt; Mirian C. H. Janssen



Cisplatin induced neuropathy: Central, peripheral and autonomic nerve involvement  

Microsoft Academic Search

Summary  A prospective study was performed in patients treated with cisplatin to evaluate the occurrence and degree of central, peripheral\\u000a and autonomic neuropathy and to determine the most accurate method to study this neuropathy. Twelve patients were examined\\u000a before, during and after treatment. Evaluation included neurologic examination, conventional nerve conduction studies of the\\u000a median and peroneal nerves and short latency somatosensory

Willem Boogerd; Wim W. ten Bokkel Huinink; Otilia Dalesio; Walter J. J. F. Hoppenbrouwers; J. Jacob van der Sande



?-Lipoic Acid, Diabetic Neuropathy, and Nathan’s Prophecy  

Microsoft Academic Search

Both oral and intravenous administration of alpha-lipoic acid (ALA) has been investigated as add-on treatment for diabetic peripheral neuropathy. The recent Neurological Assessment of Thioctic Acid in Diabetic Neuropathy (NATHAN) 1 trial has shown that 4-year oral ALA administration is of some value in achieving a clinically meaningful improvement and a slight delay in the progression of neuropathic deficits among

N. Papanas; E. Maltezos



Pediatric sciatic neuropathies due to unusual vascular causes.  


Four cases of pediatric sciatic neuropathies due to unusual vascular mechanisms are reported. Pediatric sciatic neuropathies were seen after umbilical artery catheterization, embolization of arteriovenous malformation, meningococcemia, and hypereosinophilic vasculitis. Electrophysiologic studies demonstrated abnormalities in motor studies of peroneal and tibial nerves. Sensory studies demonstrated abnormalities of sural and superficial peroneal nerves. Results of needle electromyography were abnormal in sciatic-innervated muscles. Prognosis was variable and depended on the severity of the initial nerve injury. PMID:18658074

Srinivasan, Jayashri; Escolar, Diane; Ryan, Monique; Darras, Basil; Jones, H Royden



Pulsed radiofrequency for the treatment of chronic ilioinguinal neuropathy  

Microsoft Academic Search

Background  Ilioinguinal neuropathy is a rare but disabling condition. The condition may arise spontaneously or in the setting of pelvic\\u000a surgery. To date, most therapeutic options have been limited to neuropathic pain medications, anti-inflammatory medications,\\u000a nerve blocks with local anesthetics, or neurectomy. Long-term results of non-surgical interventions are fair at best. We present\\u000a a case of chronic ilioinguinal neuropathy treated with

Raj Mitra; Afshin Zeighami; Sean Mackey



Coexistent entrapment neuropathies in patients with amyotrophic lateral sclerosis  

Microsoft Academic Search

Objective: To determine the incidence of entrapment neuropathy in patients with amyotrophic lateral sclerosis (ALS). Although it is well known that patients with motor neuron disease may have coexisting focal neuropathies, their prevalence has not been previously determined.Methods: Electrophysiologic studies (EMG\\/NCS) were reviewed from 126 patients with ALS seen at a university-affiliated hospital from 1991 to 1994. Every patient had

Milind J. Kothari; Seward B. Rutkove; Eric L. Logigian; Jeremy M. Shefner



Mechanisms of disease: The oxidative stress theory of diabetic neuropathy  

Microsoft Academic Search

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

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



Motor and sensory neuropathy due to myelin infolding and paranodal damage in a transgenic mouse model of Charcot-Marie-Tooth disease type 1C.  


Charcot-Marie-Tooth disease type 1C (CMT1C) is a dominantly inherited motor and sensory neuropathy. Despite human genetic evidence linking missense mutations in SIMPLE to CMT1C, the in vivo role of CMT1C-linked SIMPLE mutations remains undetermined. To investigate the molecular mechanism underlying CMT1C pathogenesis, we generated transgenic mice expressing either wild-type or CMT1C-linked W116G human SIMPLE. Mice expressing mutant, but not wild type, SIMPLE develop a late-onset motor and sensory neuropathy that recapitulates key clinical features of CMT1C disease. SIMPLE mutant mice exhibit motor and sensory behavioral impairments accompanied by decreased motor and sensory nerve conduction velocity and reduced compound muscle action potential amplitude. This neuropathy phenotype is associated with focally infolded myelin loops that protrude into the axons at paranodal regions and near Schmidt-Lanterman incisures of peripheral nerves. We find that myelin infolding is often linked to constricted axons with signs of impaired axonal transport and to paranodal defects and abnormal organization of the node of Ranvier. Our findings support that SIMPLE mutation disrupts myelin homeostasis and causes peripheral neuropathy via a combination of toxic gain-of-function and dominant-negative mechanisms. The results from this study suggest that myelin infolding and paranodal damage may represent pathogenic precursors preceding demyelination and axonal degeneration in CMT1C patients. PMID:23359569

Lee, Samuel M; Sha, Di; Mohammed, Anum A; Asress, Seneshaw; Glass, Jonathan D; Chin, Lih-Shen; Li, Lian



Mitotoxicity and bortezomib-induced chronic painful peripheral neuropathy.  


Many of the most effective anti-cancer drugs induce a dose-limiting peripheral neuropathy that compromises therapy. Evidence from animal models of chemotherapy-induced painful peripheral neuropathy produced by the taxane agent, paclitaxel, and the platinum-complex agent, oxaliplatin, indicate that they produce neuropathy via a common mechanism-a toxic effect on the mitochondria in primary afferent sensory neurons. Bortezomib is from the proteasome-inhibitor class of chemotherapeutics. It also produces a dose-limiting peripheral neuropathy, but its effects on neuronal mitochondria are unknown. To investigate this, we developed a model of bortezomib-induced painful peripheral neuropathy in the rat and assessed mitochondrial function (respiration and ATP production) in sciatic nerve samples harvested at two time points: day 7, which is three days after treatment and before pain appears, and day 35, which is one month post-treatment and the time of peak pain severity. We found significant deficits in Complex I-mediated and Complex II-mediated respiration, and in ATP production at both time points. Prophylactic treatment with acetyl-L-carnitine, which has previously been shown to prevent paclitaxel- and oxaliplatin-induced mitochondrial dysfunction and pain, completely blocked bortezomib's effects on mitochondria and pain. These results suggest that mitotoxicity may be the core pathology for all chemotherapy-induced peripheral neuropathy and that drugs that protect mitochondrial function may be useful chemotherapy adjuncts. PMID:22947198

Zheng, H; Xiao, W H; Bennett, G J



Dyslipidemia as a contributory factor in etiopathogenesis of diabetic neuropathy  

PubMed Central

Objectives: The pathogenesis of neuropathy in type 2 diabetes mellitus is multifactorial.Dyslipidemia may contribute to the development of diabetic neuropathy. This study aimed to assess the atherogenic lipid indices in type 2 diabetic patients with neuropathy. Material and Methods: Fifty-one patients with type 2 diabetes mellitus and 31 healthy subjects were studied in the Unit of Neurophysiology at the University Hospital of Medical College, Al-Nahrin University in Baghdad, Iraq, from January 2002 to January 2003. Neuropathy total symptom score (NTSS), neuropathy impairment score in the lower leg (NIS-LL), and electrophysiological study of sensory (ulnar and sural) and motor (ulnar and common peroneal) nerves were used to assess nerve function. Fasting venous blood was obtained from each participant for determination of lipid profile and atherogenic lipid ratios. Results: The frequency of high blood pressure was significantly higher in neuropathic patients. The electrophysiology study revealed significant decrease in conduction velocity of ulnar (sensory and motor components), sural, and common peroneal nerves. The minimum F-wave latency of motor nerve was significantly prolonged. Among the lipid fractions, only high-density lipoprotein–cholesterol was significantly reduced by 14% of healthy participant's value. Atherogenic lipid ratios were significantly higher in diabetic patients than corresponding healthy ratios. Conclusion: Metabolic lipid disturbances in terms of atherogenicity co-existwith neuropathy in type 2 diabetes mellitus, irrespective of duration of disease.

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



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

PubMed Central

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

Ordunez-Garcia, P O; Nieto, F J; Espinosa-Brito, A D; Caballero, B



Challenges in developing novel therapies for peripheral neuropathies: a summary of The Foundation for Peripheral Neuropathy Scientific Symposium 2012.  


On March 14-16, 2012, The Foundation for Peripheral Neuropathy organized a scientific meeting that brought together basic and clinical scientists studying peripheral neuropathies and mechanisms of axonal degeneration and representatives from the drug industry, National Institutes of Health, and Federal Drug Administration. This meeting summary covers the main discussion points laid out by the participants that hamper development of novel therapies for peripheral neuropathies and neuropathic pain. In each section of the meeting, the discussion was led by a keynote talk and was followed by a panel of discussants that were asked to bring two key questions in their areas of research. With audience participation, this format led to a lively discussion that pointed out the deficiencies in both animal modeling of human diseases and issues in clinical trial design unique to the peripheral neuropathies and neuropathic pain. PMID:23521637

Höke, Ahmet; Simpson, David M; Freeman, Roy



Spinal subarachnoid hemorrhage accompanied with intraventricular hemorrhage  

PubMed Central

Spinal hematoma is a rare and usually severe neurological disorder that, without adequate treatment, often leads to death or permanent neurological deficit. Epidural as well as subdural and subarachnoid hematomas have been investigated in some studies. A 66-year-old man referred to our hospital because of acute onset paraplegia and incontinency started 3 h before admission. With impression of spinal hemorrhage, emergent cervicothoracic spinal MRI performed. On magnetic resonance imagination (MRI) mixed hyper/iso intense lesion in anterior subarachnoid space from C7 to T5 was seen. On brain A computerised tomography (CT) scan, subarachnoid hemorrhage and intraventricular hemorrhage in posterior parts of brain was seen. Unfortunately, the patient died 10 days later. About our patient, severe back pain accompanying by immediate paraplegia, sphincter disturbances, sensory level, and prominent meningeal signs guided us clinically to spinal subarachnoid hemorrhage. Further brain CT scan revealed diffusion of blood to brain subarachnoid space and ventricles. An outstanding finding on brain CT was the presence of blood only in posterior horn of lateral ventricles and dorsal fissures of brain supporting our theory that blood has diffused from spinal subarachnoid space to dorsal subarachnoid space of brain because of supine position of patient. In this patient anticoagulation may be the only sinister factor for developing complications.

Fatehi, Farzad; Basiri, Keivan; Ghorbani, Askar



Gastroesophageal reflux disease accompanying urticaria pigmentosa.  


A few case reports have only been published to date, which show the possible link between mastocytosis and gastroesophageal reflux disease (GERD). Here, we present a 17-month-old boy with urticaria pigmentosa who also suffered from GERD. First skin lesions accompanied by gastrointestinal symptoms (regurgitations, appetite worsening) were noticed at the age of four months. At that time, they were misdiagnosed as symptoms of cow's milk allergy. Despite the cow's milk-free diet, the skin and gastrointestinal symptoms slowly worsened and the patient was referred to us for further diagnostics several months later. Based on the clinical presentation of skin lesions, presence of pruritus and positive Darier's sign, cutaneous mastocytosis was diagnosed; 24-hour pH-metry revealed an increased number of acidic refluxes and biopsy of duodenal mucosa showed numerous mast cells. Taking into account these findings, the gastrointestinal symptoms were supposed to be a manifestation of mastocytosis. Treatment with sodium cromoglycate, cetirizine, ranitidine and probiotics resulted in pruritus alleviation, improvement of appetite and sleeping as well as increase of body weight. PMID:22185927

Reich, Magdalena; Reich, Adam; Rzeszutko, Marta; Iwa?czak, Barbara



Atmospheric Optics  

NSDL National Science Digital Library

This collection, created and maintained by Harald Edens, contains photographs of many different atmospheric optical phenomena. Those phenomena include ice crystal halos, light scattering, and atmospheric refraction, among others. The pictures of each phenomenon are accompanied by a brief explanation of what causes it. Prints of the pictures can be purchased from the web site.

Edens, Harald



9 CFR 93.314 - Horses, certification, and accompanying equipment.  

Code of Federal Regulations, 2010 CFR

...Products 1 2010-01-01 2010-01-01 false Horses, certification, and accompanying equipment. ...FOR MEANS OF CONVEYANCE AND SHIPPING CONTAINERS Horses § 93.314 Horses, certification, and accompanying equipment....



9 CFR 93.314 - Horses, certification, and accompanying equipment.  

Code of Federal Regulations, 2010 CFR

...Products 1 2009-01-01 2009-01-01 false Horses, certification, and accompanying equipment. ...FOR MEANS OF CONVEYANCE AND SHIPPING CONTAINERS Horses § 93.314 Horses, certification, and accompanying equipment....



Perimetrist's Guide for Optic Disc Visual Field Screening: The Armaly-Drance Method.  

National Technical Information Service (NTIS)

Disc-related defects constitute over 90% of field defects found in typical outpatient clinical population--e.g., ischemic neuropathy, optic neuritis, glaucoma. This handout is designed for anyone who uses a Goldman Visual Field Perimeter. It describes an ...

D. W. Carlson L. Tychsen



Cytomegalovirus multifocal neuropathy in AIDS: analysis of 15 consecutive cases.  


A severe multifocal neuropathy caused by cytomegalovirus (CMV-MN) can occur in the late stage of human immunodeficiency virus (HIV) infection. In a retrospective study, we identified 15 consecutive HIV-positive patients with a diagnosis of CMV-MN based on (1) markedly asymmetric neuropathy, (2) fewer than 100 CD4+ cells per mm3, (3) exclusion of other causes of neuropathy, and (4) characteristic CMV cytopathic changes on neuromuscular biopsy (2 patients), positive CSF culture for CMV (2 patients), or clinical improvement on anti-CMV therapy given for concurrent extraneurologic CMV disease (8 patients) or neuropathy (3 patients). All patients were men and had severe immunosuppression (mean CD4+ cell count, 18 per mm3). The initial symptoms were numbness and painful paresthesias showing a patchy, multifocal distribution. After a mean of 11 weeks (range, 1 to 10 months), the patients developed moderate or severe sensorimotor asymmetric neuropathy. Extraneurologic CMV infection occurred in 10 patients before diagnosis. Electrophysiologic studies showed axonal neuropathy and CMV DNA was present in CSF by the polymerase chain reaction (PCR) technique in 90% of patients tested. Fourteen patients showed a marked improvement 1 to 4 weeks after starting ganciclovir or foscarnet therapy. During follow-up on maintenance therapy (13 patients), the neuropathy relapsed in three patients and probable or confirmed CMV encephalitis occurred in five. Twelve patients died during follow-up, at a mean interval of 9.5 months after their first symptoms. These results extend the clinical spectrum of CMV-MN and show that PCR detection of CMV DNA in CSF may be a useful diagnostic marker. PMID:7969979

Roullet, E; Assuerus, V; Gozlan, J; Ropert, A; Saïd, G; Baudrimont, M; el Amrani, M; Jacomet, C; Duvivier, C; Gonzales-Canali, G



Neuropathy and paraproteins: review of a complex association.  


Coexistence of neuropathy and monoclonal gammopathy represents a common but complex problem in clinical practice. This association is here reviewed considering latest available literature. The association is not infrequent, and various possible syndromes need to be distinguished. However, coincidental co-occurrence also needs to be recognized. The monoclonal gammopathy may be a 'monoclonal gammopathy of uncertain significance' (MGUS) or occur in a context of malignancy such as multiple myeloma or Waldenström's macroglobulinaemia. IgM paraproteins can bind to myelin-associated glycoprotein (MAG) in peripheral nerve. In this case, the paraprotein is directly linked to the neuropathy, causing a specific phenotype. One randomized controlled trial of this ('Anti-MAG') neuropathy showed possible moderate effect of rituximab on disability. Results of another trial are awaited. IgM/G/A paraproteins can be associated with a polyneuropathy indistinguishable from chronic inflammatory demyelinating polyneuropathy. Axonal neuropathies may coexist with IgM/G/A MGUS. There is insufficient evidence about causality or effective treatment in such cases. Pain/dysautonomia with an axonal neuropathy and serum paraprotein raises the possibility of amyloidosis. Specific haematological treatment is required for malignant disorders, although caution is required with neurotoxic agents. Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome and chronic ataxic neuropathy with ophthalmoplegia, M-protein, cold agglutinins and disialosyl antibodies represent rare separate entities for which evidence-based treatment options are still lacking. The association of monoclonal gammopathy and neuropathy requires the appropriate neurological/haematological investigations for a precise diagnosis. Causality is only established in few cases. Adequate management ideally requires joint neurological/haematological input for diagnosis, monitoring and treatment. PMID:21418441

Rajabally, Y A



Suprascapular Neuropathy in Collegiate Baseball Player  

PubMed Central

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.

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



Diabetic cardiovascular autonomic neuropathy: clinical implications.  


Diabetic cardiovascular autonomic neuropathy (DCAN), the impairment of the autonomic balance of the cardiovascular system in the setting of diabetes mellitus (DM), is frequently observed in both Type 1 and 2 DM, has detrimental effects on the quality of life and portends increased mortality. Clinical manifestations include: resting heart rate disorders, exercise intolerance, intraoperative cardiovascular lability, orthostatic alterations in heart rate and blood pressure, QT-interval prolongation, abnormal diurnal and nocturnal blood pressure variation, silent myocardial ischemia and diabetic cardiomyopathy. Clinical tests for autonomic nervous system evaluation, heart rate variability analysis, autonomic innervation imaging techniques, microneurography and baroreflex analysis are the main diagnostic tools for DCAN detection. Aldose reductase inhibitors and antioxidants may be helpful in DCAN therapy, but a regular, more generalized and multifactorial approach should be adopted with inclusion of lifestyle modifications, strict glycemic control and treatment of concomitant traditional cardiovascular risk factors, in order to achieve the best therapeutic results. In the present review, the authors provide aspects of DCAN pathophysiology, clinical presentation, diagnosis and an algorithm regarding the evaluation and management of DCAN in DM patients. PMID:22894631

Karayannis, Georgios; Giamouzis, Gregory; Cokkinos, Dennis V; Skoularigis, John; Triposkiadis, Filippos



Radiation-induced neuropathy in cancer survivors.  


Radiation-induced peripheral neuropathy is a chronic handicap, frightening because progressive and usually irreversible, usually appearing several years after radiotherapy. Its occurrence is rare but increasing with improved long-term cancer survival. The pathophysiological mechanisms are not yet fully understood. Nerve compression by indirect extensive radiation-induced fibrosis plays a central role, in addition to direct injury to nerves through axonal damage and demyelination and injury to blood vessels by ischaemia following capillary network failure. There is great clinical heterogeneity in neurological presentation since various anatomic sites are irradiated. The well-known frequent form is radiation-induced brachial plexopathy (RIBP) following breast cancer irradiation, while tumour recurrence is easier to discount today with the help of magnetic resonance imaging and positron emission tomography. RIBP incidence is in accordance with the irradiation technique, and ranges from 66% RIBP with 60Gy in 5Gy fractions in the 1960s to less than 1% with 50Gy in 2Gy fractions today. Whereas a link with previous radiotherapy is forgotten or difficult to establish, this has recently been facilitated by a posteriori conformal radiotherapy with 3D-dosimetric reconstitution: lumbosacral radiculo-plexopathy following testicular seminoma or Hodgkin's disease misdiagnosed as amyotrophic lateral sclerosis. Promising treatments via the antioxidant pathway for radiation-induced fibrosis suggest a way to improve the everyday quality of life of these long-term cancer survivors. PMID:23245644

Delanian, Sylvie; Lefaix, Jean-Louis; Pradat, Pierre-François



Painful diabetic neuropathy: treatment and future aspects.  


Around one of three diabetic patients is affected by distal symmetric polyneuropathy (DSP) which represents a major health problem, as it may present with partly excruciating neuropathic pain and is responsible for substantial morbidity and increased mortality. Treatment is based on four cornerstones: (1) multifactorial intervention aimed at (near)-normoglycaemia and reduction in cardiovascular risk factors, (2) treatment based on pathogenetic mechanisms, (3) symptomatic treatment, and (4) avoidance of risk factors and complications. Among the pathogenetic treatments only alpha-lipoic acid and epalrestat are available for treatment in several countries. Neuropathic pain, which is present in 8-26% of diabetic patients, exerts a substantial impact on the quality of life, particularly by causing considerable interference in sleep and enjoyment of life. Non-pharmacologic options such as nerve or muscle stimulation should always be given consideration. Among the centrally acting analgesic drugs for many years mainly the tricyclic antidepressants (TCA), carbamazepine, gabapentin, and opioids have been used to treat neuropathic pain. More recently, significant pain relief has been reported in clinical trials of painful diabetic neuropathy using agents such as the dual selective serotonin noradrenaline reuptake inhibitor (SNRI), duloxetine and the anticonvulsant pregabalin, a specific modulator of the alpha(2)delta subunit of the voltage-dependent calcium channels. A promising new anticonvulsant is lacosamide. In future, drug combinations might also include those aimed at symptomatic pain relief and quality of life on one hand and improvement or slowing the progression of the underlying neuropathic process on the other hand. PMID:18395890

Ziegler, Dan


Diabetic Neuropathy and Oxidative Stress: Therapeutic Perspectives  

PubMed Central

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.

Hosseini, Asieh; Abdollahi, Mohammad



Diabetic neuropathy and oxidative stress: therapeutic perspectives.  


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

Hosseini, Asieh; Abdollahi, Mohammad



Prevalence of peripheral neuropathy and painful peripheral neuropathy in Turkish diabetic patients.  


The aim of this study was to determine the prevalence of diabetic peripheral neuropathy (DPN) and neuropathic pain in diabetic patients attending university outpatient clinics in Turkey. In this multicenter cross-sectional study, neurologic examinations and nerve conduction studies along with clinical diabetic neuropathy score, and Leeds Assessment of Neuropathic Symptoms and Signs pain scale were performed on 1,113 patients (46.2% male) from 14 centers. Prevalence of DPN determined only by clinical examination was 40.4% and increased to 62.2%, by combining nerve conduction studies with clinical examination. According to Leeds Assessment of Neuropathic Symptoms and Signs scores, neuropathic pain prevalence was 16.0% in those who reported pain. Poor glycemic control, retinopathy, microalbuminuria, hyperlipidemia, diabetic foot, and foot amputation were more commonly observed in patients with DPN. Clinical DPN affected 40.4% of diabetic patients, and neuropathic pain prevalence in diabetic patient population was 14.0%. Clinical examinations and nerve conduction studies are important components for early detection and accurate diagnosis of DPN and painful DPN. PMID:21221008

Erbas, Tomris; Ertas, Mustafa; Yucel, Aysen; Keskinaslan, Abdulkadir; Senocak, Mustafa



Demographic characteristics of individuals with diabetes mellitus and peripheral neuropathy.  


Background: Studies have established a positive association between peripheral neuropathy and diabetes mellitus. The purpose of the present investigation is to determine the predictor variables for demographic characteristics of individuals with diabetes mellitus and peripheral neuropathy. Methods: Frequency and ?(2) statistic analyses were conducted on the data to determine significance of predictor variables. Results: Among individuals with and without diabetes mellitus, men are more at risk to develop complications related to peripheral neuropathy, such as foot insensate areas and numbness in extremities. Diabetic individuals older than 61 years are at higher risk than other age groups. Among diabetic patients with peripheral neuropathy, women are more likely to have emotional disorders such as panic, anxiety disorder, and depression than men of the same age or younger. Conclusions: Predictor variables will assist clinicians in better diagnosing peripheral neuropathy, contributing to more effective treatments and shortening of healing time. Diagnostic measures to be taken into consideration include race, age, education, marital status, duration of diabetes mellitus, numbness in hands or feet, participation in moderate physical activity, and use of tobacco. PMID:24072362

Tata, Sharada; Morewitz, Stephen; Tan, Kea Hong; Clark, Joel


Current and future strategies for the management of diabetic neuropathy.  


Diabetic neuropathy is common, related to increased morbidity and mortality, and has no effective treatment at present. Interventions based on putative pathways thought to contribute to damage and repair of nerve fibres have yielded little success to date. Pain is a potentially debilitating manifestation of diabetic neuropathy and has many potential sites of origin and, hence, modulation. Its cause is unclear and it does not respond well to traditional pain therapies, proposed to mediate their benefits via multiple peripheral and central mechanisms. A better understanding of the mechanisms leading to nerve fibre degeneration and regeneration as well as pain has recently resulted in the development of a more targeted approach to the treatment of diabetic neuropathy. Thus, specific NMDA receptor antagonists and more specific neuronal serotonin and norepinephrine (noradrenaline) uptake inhibitors offer promise in the treatment of painful diabetic neuropathy. A number of treatments which include the aldose reductase inhibitors and neurotrophins have failed to reach the clinical arena. However, the antioxidant alpha-lipoic acid, as well as compounds which correct vascular dysfunction and hence neuropathy, such as ACE inhibitors and protein kinase C-beta inhibitors, have demonstrated more success. PMID:15981943

Malik, Rayaz A



Assessment of sensory neuropathy in patients with diabetic foot problems.  


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

Nather, Aziz; Keng Lin, Wong; Aziz, Zameer; Hj Ong, Christine; Mc Feng, Bernard; B Lin, Clarabelle



Diabetic neuropathies: clinical manifestations and current treatment options.  


Diabetic neuropathies are a heterogeneous group of disorders that include a wide range of abnormalities. They can be focal or diffuse, proximal or distal, affecting both peripheral and autonomic nervous systems, causing morbidity with significant impact on the quality of life of the person with diabetes, and can result in early death. Distal symmetric polyneuropathy, the most common form of diabetic neuropathy, usually involves small and large nerve fibers. Small-nerve-fiber neuropathy often presents with pain but without objective signs or electrophysiologic evidence of nerve damage, and is recognized as a component of the impaired glucose tolerance and metabolic syndromes. The greatest risk resulting from small-fiber neuropathy is foot ulceration and subsequent gangrene and amputation. Large-nerve-fiber neuropathies produce numbness, ataxia and uncoordination, impairing activities of daily living and causing falls and fractures. A careful history and detailed physical examination are essential for the diagnosis. Symptomatic therapy has become available and newer and better treatment modalities, based on etiologic factors, are being explored with potential for significant impact on morbidity and mortality. Preventive strategies and patient education still remain key factors in reducing complication rates and mortality. PMID:16932298

Vinik, Aaron; Ullal, Jagdeesh; Parson, Henri K; Casellini, Carolina M



Clinical Approach to the Treatment of Painful Diabetic Neuropathy  

PubMed Central

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

Hovaguimian, Alexandra; Gibbons, Christopher H.



Endoplasmic reticulum stress contributes to prediabetic peripheral neuropathy.  


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

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



An HST Search for Supernovae Accompanying X-Ray Flashes  

NASA Astrophysics Data System (ADS)

We present the results from a Hubble Space Telescope ACS search for supernovae associated with X-ray flashes 020903, 040701, 040812, and 040916. We find strong evidence that XRF 020903 (z=0.25) was associated with a SN 1998bw-like supernova and confirm this using optical spectroscopy at t~25 days. We find no evidence, however, for SN 1998bw-like supernovae associated with the other three events. In the case of XRF 040701 (z=0.21), we rule out even a faint supernova similar to SN 2002ap, using template light curves for several local Type Ic supernovae. For the two cases in which the redshift is not known, XRFs 040812 and 040916, we derive robust redshift limits, assuming that they were accompanied by supernovae similar to SN 1998bw, and compare these limits with photometric redshift constraints provided by their host galaxies. We supplement this analysis with results for three additional events (XRFs 011030, 020427, and 030723) and discuss the observed diversity of supernovae associated with X-ray flashes and gamma-ray bursts. We conclude that XRF-SNe exist but can be significantly fainter than SN 1998bw, possibly consistent with the observed spread in local Type Ibc supernovae.

Soderberg, A. M.; Kulkarni, S. R.; Fox, D. B.; Berger, E.; Price, P. A.; Cenko, S. B.; Howell, D. A.; Gal-Yam, A.; Leonard, D. C.; Frail, D. A.; Moon, D.; Chevalier, R. A.; Hamuy, M.; Hurley, K. C.; Kelson, D.; Koviak, K.; Krzeminski, W.; Kumar, P.; MacFadyen, A.; McCarthy, P. J.; Park, H. S.; Peterson, B. A.; Phillips, M. M.; Rauch, M.; Roth, M.; Schmidt, B. P.; Shectman, S.



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


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

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



Peripheral neuropathy in metachromatic leucodystrophy. A study of 40 cases from south India  

PubMed Central

Background: There is a paucity of literature from India on metachromatic leucodystrophy (MLD), a rare metabolic disorder of childhood resulting from aryl sulfatase A (ASA) deficiency. Patients/Methods: Case records of histopathologically verified cases of MLD, evaluated over a period of 12 years at the National Institute of Mental Health and Neurosciences, Bangalore, India, were reviewed. Results: The late infantile group (36) manifested with regression of milestones (all), delayed mile stones (14), gait abnormalities (14), and seizures (11). Despite spasticity (29), there was hypo/areflexia in 25 patients. Optic atrophy (six) was rare. Consanguinity was noted in 25 children and four had a history of similar illness in siblings. Behavioural problems dominated in the juvenile group (four), but associated cognitive decline and hyporeflexia provided a clue to the diagnosis. Low serum ASA (seven of 20), raised cerebrospinal fluid protein (five of 12), and urinary metachromatic granules (two of 32) were infrequent. Electrophysiological evidence of severe demyelinating and length dependent sensory motor neuropathy was observed in all, even in the presence of hyper-reflexia. In addition to metachromatic dysmyelinating neuropathy in all patients, sural nerve biopsy in 20 patients revealed orthochromatic deposits within perivascular macrophages, particularly among those patients with normal ASA values (11 of 14), suggesting the accumulation of other glycosphingolipids. Conclusions: This study produced some noteworthy observations: the high degree of consanguinity associated with MLD in India, the existence of MLD with normal serum concentrations of ASA, the deposition of orthochromatic lipids, and electrophysiological evidence of a partial conduction block.

Bindu, P; Mahadevan, A; Taly, A; Christopher, R; Gayathri, N; Shankar, S



An unusual cause for an optic disc haemorrhage  

PubMed Central

A 51-year-old male on chemotherapy for myeloma presented initially with a unilateral optic disc haemorrhage and signs of optic neuropathy. This rapidly progressed to affect both eyes and within a few days he developed retinal features suggestive of progressive outer retinal necrosis. He was treated with intravenous acyclovir that was subsequently changed to ganciclovir when serological tests for cytomegalovirus were found to be positive for immunoglobulin M antibodies. His visual loss continued to deteriorate despite treatment, and he subsequently developed a retinal detachment in one eye. The causes of optic neuropathy in immunocompromised patients and the importance of eliminating an infective cause are discussed.

Baxter, Julia; Kailasanathan, Anusha; Chen, Hean



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

Microsoft Academic Search

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

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



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

PubMed Central

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

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



Carcinomatous versus radiation-induced brachial plexus neuropathy in breast cancer  

Microsoft Academic Search

A retrospective study was performed of 18 women in whom ipsilateral brachial plexus neuropathy developed after treatment for carcinoma of the breast. In the absence of metastatic tumor elsewhere, the only distinguishing feature between carcinomatous neuropathy and radiation-induced neuropathy was the symptom-free interval after mastectomy and radiation therapy. Women with an interval of less than a year have radiation-induced neuropathy.

Frederick H. Bagley; John W. Walsh; Blake Cady; Ferdinand A. Salzman; Richard A. Oberfield; Artemis G. Pazianos



Electrolyte imbalance triggering relapse of inflammatory neuropathy.  


Electrolyte imbalance is a well-known cause of acute neurological deterioration in the central and peripheral nervous systems. Rapid correction of hyponatraemia1 can cause central pontine myelinolysis, and in muscle tetany may result from hypocalcaemia. However the role of electrolyte imbalance in peripheral neuropathy although well-described is encountered less frequently. We describe a case of a 71 year old female with a fourteen year history of chronic inflammatory demyelinating polyneuropathy (CIDP) and stable monoclonal gammopathy, normally maintained on three-weekly intravenous immunoglobulin (IVIG) therapy. At her best baseline, she has a normal motor examination and reduced vibration sense only to the ankles. She presented with a four week history of progressive numbness and paresthesiae in all four limbs, reduced balance, a decline in mobility with frequent falls and reduced hand function. The deterioration developed after a week of non-bloody diarrhoea with night sweats but continued to progress through two courses of her regular IVIG. She also had a past history of breast cancer, hypertension and a duodenal ulcer. On examination she had a profound sensory ataxia and pseudo-athetosis of the upper limbs. Power was preserved. Pinprick was reduced to the forearm and thighs. Vibration sense was present only at the sternum. Proprioception was reduced to the shoulders and hips. She was areflexic. General examination was normal. Blood investigations showed hypomagnesaemia of 0.1 (range 0.6-1.0), hypocalcaemia of 1.75 (range 2.15-2.55), mild hypokalaemia of 3.2 (range 3.5-5.1) but stable renal function. Nerve conduction studies showed a length-dependent demyelinating sensorimotor neuropathy with significant deterioration from previous studies. Her paraprotein level was stably low. Thus we considered the metabolic disturbance as a potential cause of her acute severe relapse of her CIDP. The diarrhoea resolved spontaneously and potassium and calcium levels normalised after oral treatment. However the hypomagnesaemia required high-dose oral and intravenous supplementation. Investigations for a malabsorption syndrome were negative. She was taking two medications known to be associated with hypomagnesaemia. After stopping indapamide, a thiazide-like diuretic, her urine magnesium output was low, so a renal cause was unlikely. Omeprazole, which had been doubled in the last year after the diagnosis of her duodenal ulcer, is known in multiple case series to be associated with severe symptomatic hypomagnesaemia that is thought to be a class effect of proton pump inhibitors (PPIs).(2) This prompted us to halve the dose of omeprazole. Her serum magnesium level stabilised in the low-to-normal range and she was treated with two further courses of 2 g/kg IVIG. She had a marked improvement in sensory examination and functional ability. Her proprioceptive loss and sensory ataxia resolved. A logical approach to investigating for reversible causes for her deterioration pointed to drug-induced hypomagnesaemia as a potentially important cause of acute decompensation in CIDP. Her severe relapse remained refractory to treatment until her metabolic disturbance was normalised, after which she showed an excellent response. PMID:24108985

Keshavan, A; Gandhi, S; Lunn, Mp; Reilly, Mm



Alcohol-induced stress in painful alcoholic neuropathy.  


Chronic alcohol consumption induces a painful small-fiber peripheral neuropathy, the severity of which increases during alcohol withdrawal. Chronic alcohol consumption also produces a sustained increase in stress hormones, epinephrine and corticosterone, that is exacerbated during alcohol withdrawal. We report that adrenal medullectomy and administration of a glucocorticoid receptor antagonist, mifepristone (RU 38486), both prevented and reversed a model of painful peripheral neuropathy in alcohol binge-drinking rats. Chronic administration of stress levels of epinephrine to rats that had undergone adrenal medullectomy and were being fed the alcohol diet reconstituted this phenotype. Intrathecal administration of oligodeoxynucleotides antisense to the beta(2)-adrenergic- or glucocorticoid-receptor also prevented and reversed the pro-nociceptive effects of ethanol. Our results suggest a convergence of the effects of mediators of the hypothalamic-pituitary- and sympathoadrenal-stress axes on sensory neurons in the induction and maintenance of alcohol-induced painful peripheral neuropathy. PMID:18093169

Dina, Olayinka A; Khasar, Sachia G; Alessandri-Haber, Nicole; Green, Paul G; Messing, Robert O; Levine, Jon D



Sulfonyl fluorides and the promotion of diisopropyl fluorophosphate neuropathy.  


Phenylmethanesulfonyl fluoride (PMSF) enhances the neuropathic response when given to hens after organophosphates causing delayed polyneuropathy. This study was undertaken to ascertain whether other sulfonyl fluorides promote diisopropyl fluorophosphate (DFP) neuropathy in hens and if they inhibit neuropathy target esterase (NTE), the target for organophosphate-induced delayed polyneuropathy. Among seven sulfonyl fluoride analogs of PMSF (alkyl-, and phenylsulfonyl fluorides), only n-butanesulfonyl fluoride was found to be an NTE inhibitor in vitro at a concentration (I50 = 60 microM) similar to that of PMSF, n-Butanesulfonyl fluoride (0.2 sc to hens) caused both NTE inhibition in nervous tissues (> 80%) and promotion of neuropathy after DFP (0.003 sc) similar to those observed after the same molar dose of PMSF. These results confirm that, so far, all known promoters of organophosphate polyneuropathy are also NTE inhibitors. PMID:8921348

Osman, K A; Moretto, A; Lotti, M



Peripheral neuropathy in a cat with renal lymphoma.  


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

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



Diagnosis and Treatment of Chronic Immune-mediated Neuropathies.  


The chronic autoimmune neuropathies are a diverse group of disorders, whose diagnosis and classification is based on the clinical presentations and results of ancillary tests. In chronic inflammatory demyelinating polyneuropathy, controlled therapeutic trials demonstrated efficacy for intravenous gamma-globulins, corticosteroids, and plasmaphereis. In multifocal motor neuropathy, intravenous gamma-globulins have been shown to be effective. In the other immune-mediated neuropathies, there are no reported controlled therapeutic trials, but efficacy has been reported for some treatments in non-controlled trials on case studies. Choice of therapy in individual cases is based on reported efficacy, as well as severity, progression, coexisting illness, predisposition to developing complications, and potential drug interactions. PMID:19078800

Latov, Norman; Gorson, Kenneth C; Brannagan, Thomas H; Freeman, Roy L; Apostolski, Slobodan; Berger, Alan R; Bradley, Walter G; Briani, Chiara; Bril, Vera; Busis, Neil A; Cros, Didier P; Dalakas, Marinos C; Donofrio, Peter D; Dyck, P James B; England, John D; Fisher, Morris A; Herrmann, David N; Menkes, Daniel L; Sahenk, Zarife; Sander, Howard W; Triggs, William J; Vallat, Jean Michel



Peripheral neuropathy induced by amiodarone chlorhydrate. A clinicopathological study.  


Four cases of amiodarone neuropathy are reported. Patients presented a sensorimotor neuropathy with distal predominance. Improvement occurred after drug discontinuation. Nerve conduction velocities were significantly decreased. Other secondary effects of amiodarone were noted in two cases. In one case serum levels of amiodarone and N-monodesethylamiodarone were evaluated during and after treatment. Pathological study of nerve with morphometric evaluation was performed. Axonal degeneration changes were predominant in 3 cases. Aspects of segmental demyelination and remyelination were noted in one case and related to secondary demyelination. Numerous lysosomal inclusions were present in Schwann cells, fibroblasts, capillary endothelial and perithelial cells and in perineural cells. Similar inclusions have been observed in other drug-induced lipidosis. The factors responsible for this neuropathy are unknown. In one case, amiodarone-induced hepatic failure might explain the persisting high serum levels of the drug. PMID:6323638

Pellissier, J F; Pouget, J; Cros, D; De Victor, B; Serratrice, G; Toga, M



Oxidative stress and diabetic neuropathy: pathophysiological mechanisms and treatment perspectives.  


Increased oxidative stress is a mechanism that probably plays a major role in the development of diabetic complications, including peripheral neuropathy. This review summarises recent data from in vitro and in vivo studies that have been performed both to understand this aspect of the pathophysiology of diabetic neuropathy and to develop therapeutic modalities for its prevention or treatment. Extensive animal studies have demonstrated that oxidative stress may be a final common pathway in the development of diabetic neuropathy, and that antioxidants can prevent or reverse hyperglycaemia-induced nerve dysfunction. Most probably, the effects of antioxidants are mediated by correction of nutritive blood flow, although direct effects on endoneurial oxidative state are not excluded. In a limited number of clinical studies, antioxidant drugs including alpha-lipoic acid and vitamin E were found to reduce neuropathic symptoms or to correct nerve conduction velocity. These data are promising, and additional larger studies with alpha-lipoic acid are currently being performed. PMID:12112935

van Dam, P Sytze


Femoral Neuropathy and Meralgia Paresthetica Secondary to an Iliacus Hematoma  

PubMed Central

Compressive femoral and lateral femoral cutaneous neuropathies from an iliacus hematoma are unusual presentation. We report a case of a 16-year-old boy who developed right femoral and lateral femoral cutaneous neuropathies as a complication of traumatic ipsilateral iliacus hematoma formation. The patient complained of numbness in the right thigh and calf as well as right leg weakness, and pain in the right inguinal area. Nerve conduction study and needle electromyography identified the neuropathies. After the electrodiagnostic studies, the pelvic bone MRI revealed a large, 9×5×4.5 cm right iliacus hematoma. As a result, diagnosis of a right iliacus hematoma compress