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1

Traumatic Optic Neuropathy Accompanying Orbital Grease Gun Injury  

PubMed Central

We report a case of traumatic optic neuropathy accompanying a grease gun injury to the orbit. A 48-year-old man with a grease gun injury visited our clinic with decreased visual acuity, proptosis and limited extraocular movement (EOM). Orbital CT revealed a crescent mass of fat in the medial intraconal space. The grease was exuded from a lacerated conjunctival wound. The visual evoked potential (VEP) test demonstrated a decreased response in the left eye. Proptosis and EOM were improved after surgical removal of the grease. Systemic high-dose corticosteroid therapy was administered for suspected traumatic optic neuropathy, after which VEP nearly recovered, while visual acuity was slightly improved. A second surgery for traumatic cataract did not further improve visual acuity.

Park, Ji Hyun; Jang, Jae Woo; Kim, Sung Joo

2010-01-01

2

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

2011-01-01

3

[Leber's hereditary optic neuropathy].  

PubMed

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

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

2013-08-01

4

[Leber's hereditary optic neuropathy].  

PubMed

Leber's hereditary optic neuropathy (LHON) is a rare disease primarily affecting the retinal ganglion cells. In most cases patients with LHON develop permanent visual loss with a large central scotoma in the visual field of both eyes. The optic disc becomes partially or completely pale. At the onset of the disease many patients are considered to suffer from an optic neuritis and are treated under the diagnostic and therapeutic regimen of optic neuritis. LHON is mostly only considered when high dose cortisone therapy fails to be effective or the second eye is affected. Thereafter, molecular genetic analysis will prove LHON in these cases. Detailed anamnesis including pedigree analysis in combination with observance of the peripapillary microangiopathic alterations at the fundus will help to speed up the diagnosis of LHON, but even after exact clinical and molecular genetic diagnosis of LHON some aspects of the disease still remain a mystery today. PMID:22130685

Leo-Kottler, B; Wissinger, B

2011-12-01

5

Optic neuropathy in Paget's disease.  

PubMed

Of 22 patients (18 men and four women ranging in age from 50 to 89 years) with radiographic and clinical evidence of Paget's disease, nine had visual field defects. All nine had arcuate scotomas and five of the nine had generalized constriction. The visual field changes were asymptomatic in six of nine patients and progressive in two patients. Only two patients had radiographic evidence of optic canal constriction by bony impingement. There was no objective improvement in the optic neuropathy in the three patients treated with synthetic salmon calcitonin. Our data suggested that the optic neuropathy of Paget's disease cannot be explained solely on the basis of bony compression and the cause of optic neuropathy in patients with normal optic canals remains unknown. PMID:6720822

Eretto, P; Krohel, G B; Shihab, Z M; Wallach, S; Hay, P

1984-04-01

6

Diagnostic approach in optic neuropathy.  

PubMed

The diagnostic of optic neuropathy (ON) is a clinical diagnostic, relying on a detailed medical history, and a thorough clinical examination. In some cases, the attribution of the vision loss to a lesion of the optic nerve can be challenging, and further work-up is required to confirm the optic neuropathy. Once the diagnostic of optic neuropathy is stated, the pathophysiological mechanism of the ON has to be determined so that the appropriate therapeutic strategy can be initiated as promptly as possible. The diagnostic work-up must be as targeted as possible, oriented by the clinical examination. The different steps leading to the positive diagnostic of ON, and the etiologic work-up are detailed hereafter in order to achieve the most targeted work-up as possible. Differentials and current pitfalls are being reviewed. PMID:22999102

Touitou, V; LeHoang, P

2012-10-01

7

Optic Disc Cupping in Arteritic Anterior Ischemic Optic Neuropathy  

Microsoft Academic Search

Patients with anterior ischemic optic neuropathy due to giant cell arteritis are thought to develop optic disc cupping, resembling that seen in glaucomatous eyes, while such cupping does not seem to occur in nonarteritic anterior ischemic optic neuropathy. However, this remains controversial. We describe a patient with arteritic anterior ischemic optic neuropathy (the clinical diagnosis was confirmed with a biopsy

S. Orgül; A. Gass; J. Flammer

1994-01-01

8

[Hereditary optic neuropathies: clinical and molecular genetic characteristics].  

PubMed

The article presents a review of literature on hereditary optic neuropathies: Leber mitochondrial hereditary optic neuropathy, autosomal dominant and autosomal recessive optic neuropathies, X-linked optic atrophy. Clinical and molecular genetic characteristics are covered. Isolated optic neuropathies, as well as hereditary optic disorders, being a part of a complex syndromic disease are described. PMID:24624809

Khanakova, N A; Sheremet, N L; Loginova, A N; Chukhrova, A L; Poliakov, A V

2013-01-01

9

Linezolid-induced optic neuropathy.  

PubMed

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

Karuppannasamy, Divya; Raghuram, Andavar; Sundar, Devisundaram

2014-04-01

10

Linezolid-induced optic neuropathy  

PubMed Central

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

Karuppannasamy, Divya; Raghuram, Andavar; Sundar, Devisundaram

2014-01-01

11

An epidemic of optic neuropathy and painful sensory neuropathy in Cuba: Clinical aspects  

Microsoft Academic Search

An epidemic of bilateral optic neuropathy and painful sensory neuropathy occurred in Cuba in 1991–1993. Over 45 000 individuals were stated to have been affected. We report a clinical study on 25 patients seen in Cuba in 1993–1994. Affected patients showed either bilateral optic neuropathy with caecocentral scotomata or a distal predominantly sensory neuropathy sometimes associated with deafness, or a

P. K. Thomas; G. T. Plant; P. Baxter; C. Bates; R. Santiago Luis

1995-01-01

12

Genetics Home Reference: Leber hereditary optic neuropathy  

MedlinePLUS

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

13

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

2012-01-01

14

Multifocal visual evoked potential in optic neuritis, ischemic optic neuropathy and compressive optic neuropathy  

PubMed Central

Purpose: To investigate the effect of optic neuritis (ON), ischemic optic neuropathy (ION) and compressive optic neuropathy (CON) on multifocal visual evoked potential (mfVEP) amplitudes and latencies, and to compare the parameters among three optic nerve disorders. Materials and Methods: mfVEP was recorded for 71 eyes of controls and 48 eyes of optic nerve disorders with subgroups of optic neuritis (ON, n = 21 eyes), ischemic optic neuropathy (ION, n = 14 eyes), and compressive optic neuropathy (CON, n = 13 eyes). The size of defect in mfVEP amplitude probability plots and relative latency plots were analyzed. The pattern of the defect in amplitude probability plot was classified according to the visual field profile of optic neuritis treatment trail (ONTT). Results: Median of mfVEP amplitude (log SNR) averaged across 60 sectors were reduced in ON (0.17 (0.13-0.33)), ION (0.14 (0.12-0.21)) and CON (0.21 (0.14-0.30)) when compared to controls. The median mfVEP relative latencies compared to controls were significantly prolonged in ON and CON group of 10.53 (2.62-15.50) ms and 5.73 (2.67-14.14) ms respectively compared to ION group (2.06 (-4.09-13.02)). The common mfVEP amplitude defects observed in probability plots were diffuse pattern in ON, inferior altitudinal defect in ION and temporal hemianopia in CON eyes. Conclusions: Optic nerve disorders cause reduction in mfVEP amplitudes. The extent of delayed latency noted in ischemic optic neuropathy was significantly lesser compared to subjects with optic neuritis and compressive optic neuropathy. mfVEP amplitudes can be used to objectively assess the topography of the visual field defect.

Jayaraman, Manju; Gandhi, Rashmin Anilkumar; Ravi, Priya; Sen, Parveen

2014-01-01

15

Atypical anterior optic neuropathy caused by toxoplasmosis  

Microsoft Academic Search

PURPOSE: To report atypical anterior optic neuropathy due to toxoplasmosis.METHODS: Interventional case report. A 33-year-old male presented with sudden painless loss of vision and floaters in the right eye. Examination demonstrated a best-corrected visual acuity of 20\\/200, optic nerve head edema, retinal hemorrhages, and vitreous opacities.RESULTS: Nine days later, a granuloma at the optic nerve head was apparent, and the

Alice Song; Ingrid U. Scott; Janet L. Davis; Byron L. Lam

2002-01-01

16

A case of eosinophilic chronic rhinosinusitis associated with optic neuropathy.  

PubMed

We report a case of eosinophilic chronic rhinosinusitis (ECRS) associated with optic neuropathy. The visual acuity in the right eye was suddenly reduced to no light perception on awakening in the morning. Fundus examination of both eyes on the same day showed no remarkable changes. Emergency computed tomography showed pan-sinusitis bilaterally and a partial defect of the sphenoid bone on the right side. From the clinical findings, the case was diagnosed as optic neuropathy associated with chronic sinusitis. Endoscopic sinus surgery (ESS) was performed on the same day, and all of the major sinuses were found to be filled with highly viscous fluid. Part of the optic canal had a defect probably due to inflammatory invasion from the adjacent sphenoid bone. Steroid therapy was started immediately postoperatively. Histopathological examination of excised polyps showed that numerous eosinophils had invaded the polyps but no hyphae were present. The patient reported that he had bronchial asthma and had had nasal polypectomy. Six months after the ESS and steroid therapy, the patient had a recurrence of the sinusitis. At that time, laboratory examination showed an elevation of total IgE and eosinophil numbers. From the clinical findings and course, this case was diagnosed as ECRS accompanied by optic neuropathy. Although ECRS rarely has ocular complications, the inflammation can spread and the optic nerve can be affected. PMID:21760710

Kurimoto, Takuji; Tonari, Masahiro; Ishizaki, Norihiko; Matsuo, Junko; Oku, Hidehiro; Sugasawa, Jun; Ikeda, Tsunehiko

2011-01-01

17

[Sudden blindness: consider Leber's hereditary optic neuropathy  

Microsoft Academic Search

In 3 young male patients, aged 10, 19 and 21 years respectively, sequential, severe, painless bilateral visual loss occurred. Ophthalmological examination revealed no other abnormalities and this delayed the diagnosis Leber's hereditary optic neuropathy (LHON). LHON is a mitochondrial genetic disease characterised by bilateral acute or subacute painless loss of central vision. LHON causes blindness, predominantly in young adult males

J. H. Schieving; L. B. A. de Vries; F. A. Hol; H. Stroink

2008-01-01

18

[An unusual cause of compressive optic neuropathy].  

PubMed

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

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

2013-01-01

19

Subclinical optic neuropathy in Graves' orbitopathy  

Microsoft Academic Search

Purpose: The aims of the study were to detect early changes in the optic nerve function of patients with Graves' orbitopathy (GrO) who do not have any signs and symptoms of optic neuropathy, using pattern visual evoked potentials (P-VEP), and investigate any possible relation between the disease activity and P-VEP P100 latencies of the patient group.Methods: The study was conducted

Gölge Acaro?lu; Tülay ?im?ek; Solmaz Özalp; Ay?e Mutluay

2003-01-01

20

Clinical spectrum of posterior ischemic optic neuropathy  

Microsoft Academic Search

PURPOSE : To describe the systemic and visual characteristics and prognosis in patients with posterior ischemic optic neuropathy (PION).DESIGN : Observational case series.METHODS : Retrospective chart review in a multicenter setting. Seventy-two patients (98 eyes) with a clinical diagnosis of PION. Co-morbid systemic diseases and visual function were recorded at both initial presentation and after mean visual follow-up of 4.1

Srinivas R. Sadda; Michelle Nee; Neil R. Miller; Valerie Biousse; Nancy J. Newman; Anthony Kouzis

2001-01-01

21

Diagnosis and classification of autoimmune optic neuropathy.  

PubMed

The spectrum of autoimmune optic neuropathies (ON) is extending. The phenotypic spectrum includes single isolated optic neuritis (SION), relapsing isolated optic neuritis (RION), chronic relapsing inflammatory optic neuropathy (CRION), the neuromyelitis optica (NMO) spectrum disorder, multiple sclerosis associated optic neuritis (MSON) and unclassified optic neuritis (UCON) forms. Epidemiological data suggests a slight female predominance. The ethnic heritage is relevant as Caucasian patients are more likely to suffer from MSON, whilst SION, RION, CRION and NMO are more frequent in non-Caucasian patients. Importantly, prognosis for recovery of visual function is good in MSON, but poorer in NMO and CRION which also have a high chance for recurrent episodes. Testing for serum anti-AQP4 autoantibodies is advised in all patients with severe, atypical or recurrent ON because of the high diagnostic specificity. The diagnostic specificity may be aided by testing for glial biomarkers in the CSF and prognostic accuracy by testing for biomarkers for neuroaxonal degeneration. Optical coherence tomography is a highly accurate tool to document the final outcome. The current clinical classification criteria rely on the phenotype, response to treatment and presence of anti-AQP4 autoantibodies. PMID:24424177

Petzold, Axel; Plant, Gordon T

2014-01-01

22

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

2006-01-01

23

Reversal of dysthyroid optic neuropathy following orbital fat decompression  

Microsoft Academic Search

AIMSTo document the successful treatment of five patients with dysthyroid optic neuropathy by orbital fat decompression instead of orbital bone decompression after failed medical therapy.METHODSEight 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

Michael Kazim; Stephen L Trokel; Golge Acaroglu; Alexandra Elliott

2000-01-01

24

Optic neuropathy following an altitude exposure.  

PubMed

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

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

2003-09-01

25

A Venous Etiology for Nonarteritic Anterior Ischemic Optic Neuropathy  

Microsoft Academic Search

isual information travels from the eye to the brain via the optic nerve, a 3.5-mm-thick central nervous system structure approximately the same diameter as the cable con- nectingavideocameratoacomputer.Asmightbeexpected,damagetotheopticnerve deprives the brain of visual input and causes visual loss. Nonarteritic anterior ische- mic optic neuropathy (NAION) is the most common acute optic neuropathy of middle and late life, with an annual

Leonard A. Levin; Helen V. Danesh-Meyer

2008-01-01

26

Optic neuropathy associated with CANOMAD: description of 2 cases.  

PubMed

CANOMAD is a chronic ataxic neuropathy associated with IgM paraproteinemia and reactivity against disialosyl gangliosides. Ophthalmoplegia is a typical feature, but optic pathway involvement has not been reported previously. We describe 2 cases of CANOMAD associated with optic neuropathy. Severe visual loss was present in 1 case. We postulate that optic nerve damage may be related to antibody reactivity against gangliosides. Our report broadens the spectrum of cranial nerve involvement in this rare entity. PMID:21996808

Sanvito, Lara; Rajabally, Yusuf A

2011-09-01

27

Combined optic neuropathy and myelopathy secondary to copper deficiency.  

PubMed

We report two patients, both with a history of gastric surgery, who presented with progressive optic neuropathy and myelopathy. The patients' symptoms were initially attributed to vitamin B12 deficiency and/or neuromyelitis optica; however, after the neurologic deficits continued to progress with the use of conventional treatments, further evaluation was initiated, and a severe copper deficiency was revealed. Copper deficiency is a rare cause of progressive optic neuropathy and myelopathy and should be considered in the differential diagnosis. It is crucial to elicit a history of gastric surgery or other risk factors for hypocupremia in those patients undergoing an evaluation for subacute or chronically progressive optic neuropathy or myelopathy. PMID:20451943

Pineles, Stacy L; Wilson, Christina A; Balcer, Laura J; Slater, Robert; Galetta, Steven L

2010-01-01

28

Spheniodal mucocele causing bilateral optic neuropathy and ophthalmoplegia.  

PubMed

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

2014-04-01

29

Spheniodal mucocele causing bilateral optic neuropathy and ophthalmoplegia  

PubMed Central

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.

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

2014-01-01

30

[Research progress of Leber hereditary optic neuropathy].  

PubMed

Leber hereditary optic neuropathy (LHON; MIM 535000) is one of the most common mitochondrial diseases, with a clinical manifestation of painless, acute or sub-acute bilateral visual loss in young adults leading to blindness and central scotoma. Over 95% of LHON patients were caused by one of three primary mtDNA mutations (m.11778G>A, m.3460G>A and m.14484T>C). Incomplete penetrance and gender bias are two riddles of this disease. Here we summarized recent research progress of LHON, with a focus on the molecular pathogenic mechanisms, clinical features, in vitro experiments and animal models, and prevention and treatment of LHON. In particular, we presented the main findings and challenges in our recent efforts to decipher genetic susceptibility and mechanism of LHON in Chinese patients. PMID:23448924

Zhang, A-Mei; Yao, Yong-Gang

2013-02-01

31

Sildenafil-associated nonarteritic anterior ischemic optic neuropathy  

Microsoft Academic Search

PurposeTo describe the clinical features of five patients who developed nonarteritic anterior ischemic optic neuropathy (NAION) after ingestion of sildenafil citrate (Viagra; Pfizer Pharmaceuticals, New York, NY).

Howard D Pomeranz; Kyle H Smith; William M Hart; Robert A Egan

2002-01-01

32

Nonarteritic ischemic optic neuropathy developed after capsular block syndrome  

PubMed Central

A 65-year-old man developed capsular block syndrome in the early postoperative period, following phacoemulsification surgery. After neodymium-doped yttrium aluminum garnet (Nd:YAG) laser anterior capsulotomy, the intraocular pressure remained elevated for 4 days despite antiglaucomatous medication. On the postoperative fifth day, nonarteritic ischemic optic neuropathy was diagnosed. To the best of our knowledge, this is the first report of a case with nonarteritic ischemic optic neuropathy associated with early postoperative capsular block syndrome after phacoemulsification surgery.

Hurmeric, Volkan; Bayer, Atilla; Durukan, Ali H; Mutlu, Fatih M

2014-01-01

33

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.

2000-01-01

34

Drug-induced optic neuropathy-TB or not TB.  

PubMed

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

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

2010-01-01

35

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

2007-01-01

36

Obstructive sleep apnea and optic neuropathy: is there a link?  

PubMed

Over the last decade, there has been an emerging interest in the link between obstructive sleep apnea (OSA) and ocular health. Though the evidence for OSA playing a role in cerebrovascular disease risk seems clear, the same cannot be said for optic neuropathies. The association between OSA and glaucoma or non-arteritic anterior ischemic optic neuropathy (NAION) has been postulated to be secondary to direct hypoxia or mechanisms of optic nerve head vascular dysregulation. Papilledema and increased intracranial pressure have also been reported in OSA and are thought to be due to increased cerebral perfusion pressure and cerebral venous dilation secondary to hypoxia and hypercapnia. This article reviews the evidence for possible pathophysiological links between OSA and optic nerve pathology. The epidemiologic and clinical evidence for an association, direct or indirect, between OSA and glaucoma, non-arteritic anterior ischemic optic neuropathy (NAION), and papilledema or idiopathic intracranial hypertension is presented. PMID:24942500

L Fraser, Clare

2014-08-01

37

[Optic neuritis and optic ischemic neuropathy: the problem of differential diagnosis].  

PubMed

Based on a numerous data (220 patients, 285 eyes) clinical criteria of differential diagnosis of optic neuritis and nonarteritic ischemic optic neuropathy are studied. Neuronal network method was used for multivariate analysis of studied parameters, that allowed to estimate linear and nonlinear correlations of different factors, significance of every diagnostic criteria for the identification of etiology of optic neuropathies. PMID:23120916

Sheremet, N L; Ronzina, I A; Smirnova, T V; Razumova, I Iu; Sheludchenko, V M

2012-01-01

38

Sticky platelet syndrome and anterior ischaemic optic neuropathy.  

PubMed

We report a young patient who presented with nonarteritic anterior ischaemic optic neuropathy associated with the sticky platelet syndrome (SPS, a congenital prothrombotic disorder). A 15-year-old boy presented with a sudden, painless onset of a right inferior altitudinal visual field defect and marked optic disc oedema. Cranial magnetic resonance imaging (including orbits), orbital ultrasound and haematological investigations including a routine hypercoagulability work-up were negative. Further evaluation showed a positive assay for SPS which was confirmed on repeat testing. The SPS (characterized by platelet hyperaggregability and vascular occlusion) may be a potential thrombophilic risk factor for nonarteritic anterior ischaemic optic neuropathy. PMID:17997790

Randhawa, Sandeep; Van Stavern, Gregory P

2007-11-01

39

Use of magnetic resonance imaging to differentiate optic neuritis and nonarteritic anterior ischemic optic neuropathy  

Microsoft Academic Search

ObjectiveTo determine if magnetic resonance imaging (MRI) of the optic nerves obtained during the acute phase can distinguish patients with optic neuritis (ON) from those with nonarteritic anterior ischemic optic neuropathy (NAION).

Joseph F Rizzo; Christopher M Andreoli; James D Rabinov

2002-01-01

40

Diabetes mellitus as a Risk Factor for Glaucomatous Optic Neuropathy  

Microsoft Academic Search

Open-angle glaucoma (OAG) is an optic neuropathy characterized by progressive retinal ganglion cell (RGC) death and optic disk excavation. Evidence is accumulating that RGC apoptosis is the fundamental pathology of OAG. Among several risk factors for development and progression of OAG, inclusion of comorbid diabetes has been controversial. Some large population-based prevalence and incidence studies found a positive association between

Makoto Nakamura; Akiyasu Kanamori; Akira Negi

2005-01-01

41

[Cavernous hemangioma in the orbital apex revealed by optic neuropathy].  

PubMed

Cavernous hemangioma is the most common primary vascular neoplasm. It typically occurs in middle-aged women, causing a progressive painless proptosis as the principal symptom. It exceptionally compresses the optic nerve. We report the case of a cavernous hemangioma revealed by optic neuropathy in a 33-year-old female. PMID:20347181

Baklouti, K; Ayachi, M; Chaker, N; Ahmed, N Ben; Mrabet, A; Kammoun, S; Kilani, W; Khanoussi, S; Matri, L El

2010-04-01

42

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

2013-01-01

43

Traumatic optic neuropathy and second optic nerve injuries.  

PubMed

IMPORTANCE Current controversy about the primary treatment of traumatic optic neuropathy (TON) has anchored on final vision following injury, but, to our knowledge, no study has examined the effect of different treatments on regaining and protecting optic nerve reserve or on the outcome of second optic nerve injuries. OBJECTIVE To assess vision improvement in patients treated by various methods who have a second incidence of TON. DESIGN, SETTING, AND PARTICIPANTS Retrospective medical record review of 12 patients with a second TON seen in an 18-year period (mean follow-up, 11.3 months) at a single tertiary care oculoplastic practice. INTERVENTIONS Observation, high-dose corticosteroids, optic nerve decompression, or high-dose corticosteroids plus optic nerve decompression. MAIN OUTCOMES AND MEASURES Change in vision on the Snellen eye chart. RESULTS All second TON events involved the same-side optic nerve as initially injured, and with observation alone, corticosteroids, or corticosteroids and partial optic canal decompression, all patients had vision improvement after their initial injury (P?=?.004). However, following the second optic nerve injury, most patients' vision fell to the pretreatment level of the first injury, and subsequent management of the second injury with corticosteroids and/or optic canal decompression provided little or no vision return (P?=?.05). In contrast, optic canal decompressions performed for 91 primary TON injuries resulted in 82.4% having some degree of vision improvement. CONCLUSIONS AND RELEVANCE Patients with TON may have a second optic nerve insult, and vision recovery from the second event may be limited regardless of primary treatment choice. PMID:24744023

Guy, William Marshall; Soparkar, Charles N S; Alford, Eugene L; Patrinely, James R; Sami, Mirwat S; Parke, Robert B

2014-05-01

44

Bilateral posterior ischemic optic neuropathy after spinal surgery  

Microsoft Academic Search

PURPOSE: To report the association between bilateral posterior ischemic optic neuropathy and spinal surgery.METHOD: Case report.RESULTS: After prone-position spinal surgery of 8 hours’ duration, a 68-year-old woman was completely blind in both eyes. Moderate periorbital edema and temporal conjunctival chemosis were present bilaterally. Ophthalmic examination disclosed normal-appearing optic nerve heads, except for bilateral nasal fullness related to bilateral optic nerve

George Alexandrakis; Byron L. Lam

1999-01-01

45

Sight-threatening optic neuropathy is associated with paranasal lymphoma  

PubMed Central

Malignant lymphoma around the orbit is very rare. We present a rare case of optic neuropathy caused by lymphoma. A 61-year-old Japanese woman was referred to our hospital for evaluation of idiopathic optic neuropathy affecting her right eye. The patient was treated with steroid pulse therapy (methyl-predonisolone 1 g daily for 3 days) with a presumed diagnosis of idiopathic optic neuritis. After she had been switched to oral steroid therapy, endoscopic sinus surgery had been performed, which revealed diffuse large B cell lymphoma of the ethmoidal sinus. Although R-CHOP therapy was immediately started, prolonged optic nerve compression resulted in irreversible blindness. Accordingly, patients with suspected idiopathic optic neuritis should be carefully assessed when they show a poor response, and imaging of the orbits and brain should always be done for initial diagnosis because they may have compression by a tumor.

Hayashi, Takahiko; Watanabe, Ken; Tsuura, Yukio; Tsuji, Gengo; Koyama, Shingo; Yoshigi, Jun; Hirata, Naoko; Yamane, Shin; Iizima, Yasuhito; Toyota, Shigeo; Takeuchi, Satoshi

2010-01-01

46

Hyperbaric Oxygen Therapy for Radiation-induced Optic Neuropathy  

Microsoft Academic Search

Introduction: Radiation-induced optic neuropathy (RON) is an infrequent but devastating consequence of radiation exposure to the visual pathways, usually following months to years after the treatment of paranasal or intracranial tumours. Hyperbaric oxygen (HBO) therapy is one of several therapies that have been tried for this condition. The purpose of this review is to describe the clinical characteristics of RON,

Richard L Levy; Neil R Miller

47

Glaucomatous Optic Neuropathy Management: the Role of Neuroprotective Agents  

PubMed Central

Glaucoma is a major cause of worldwide irreversible blindness. The central role of raised intraocular pressure (IOP) is being questioned as many patients continue to demonstrate a clinically downhill course despite initial control of IOP. The latest concept of recognizing glaucoma as a multifactorial, progressive, neurodegenerative disease of retinal ganglion cells (RGCSs) associated with characteristic axon degeneration in the optic nerve emphasizes that several pressure-independent mechanisms are responsible for the development and progression of glaucomatous optic neuropathy. Neuroprotection as a pharmacological strategy to mitigate retinal ganglion cell death has been a popular current approach. The aim of this review is to evaluate the neuroprotective potential of calcium channel blockers in glaucomatous optic neuropathy.

L. Shahsuvaryan, Marianne

2013-01-01

48

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.

2011-01-01

49

[Leber's hereditary optic neuropathy after head trauma: a case report].  

PubMed

A previously healthy 34-year-old man sustained multiple skull fractures in a traffic accident. Radiological findings and visual field examination did not detect any abnormality. Shortly after the accident, he noticed blurred vision in both eyes. Six months after the accident, he gradually developed disturbance of visual acuity in the right eye. His best corrected visual acuity (BCVA) was 0.8 OD and 1.2 OS and brain MRI did not show any abnormality, while Humphrey visual field analysis demonstrated right homonymous hemianopsia. Two months after the initial presentation, his BCVA showed 0.1 OD and 0.08 OS. Visual field examination suggested that both right homonymous hemianopsia and left blind spot had become enlarged. Mitochondrial DNA analysis demonstrated G11,778A mutation and a diagnosis of Leber's hereditary optic neuropathy (LHON) was made. A few reports have documented mild acute insult to the head or blunt optic trauma as triggers of optic neuropathy in subjects with LHON. Although, the precise mechanism of LHON following trauma remains unknown, it appears that an acute insult may be sufficient to precipitate neuropathy in the optic nerve already compromised by mitochondrial dysfunction. Asymptomatic carriers should be advised to avoid possible precipitating factors such as head trauma. PMID:22019873

Hayashi, Shintaro; Okamoto, Koichi

2011-10-01

50

Visual Recovery Patterns in Children with Leber's Hereditary Optic Neuropathy  

Microsoft Academic Search

Three patients with Leber’s hereditary optic neuropathy (LHON) showed spontaneous improvement in visual acuities after months\\u000a of legal blindness. Two male patients with bilateral subacute visual loss were 14 years of age at presentation. The first\\u000a male patient had a mitochondrial DNA mutation at nucleotide position 11778. The second male patient was found to be negative\\u000a for the designated primary

Gölge Acaro?lu; Tülay Kansu; Çi?dem F. Do?ulu

2001-01-01

51

Sequential episodes of perioperative ischemic optic neuropathy after hip surgery.  

PubMed

Perioperative ischemic optic neuropathy (ION) after nonocular surgery is a rare complication leading to permanent and often severe vision loss. Due in part to the low prevalence of this complication, there remains no reliable way to predict which patients will develop ION. We present a patient with sequential episodes of unilateral perioperative ION, both occurring after otherwise uncomplicated hip operations. Patients and physicians should be aware that perioperative ION after one surgery may increase the risk of ION after subsequent surgeries. PMID:24621863

Marshall, Brigid K; Goel, Manik; Pitha, Ian F; Van Stavern, Gregory P; McClelland, Collin M

2014-06-01

52

Posterior ischemic optic neuropathy in the setting of posterior reversible encephalopathy syndrome and hypertensive emergency.  

PubMed

We present the magnetic resonance imaging findings of posterior ischemic optic neuropathy in a patient with posterior reversible encephalopathy syndrome secondary to hypertensive emergency. PMID:24647142

Joos, Zachary P; Adesina, Ore-Ofe O; Katz, Bradley J

2014-06-01

53

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

PubMed

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

2010-12-01

54

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.

2011-01-01

55

Optic neuropathy due to allergic fungal rhinosinusitis  

PubMed Central

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

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

2011-01-01

56

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

PubMed

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

2013-01-01

57

Visual recovery patterns in children with Leber's hereditary optic neuropathy.  

PubMed

Three patients with Leber's hereditary optic neuropathy (LHON) showed spontaneous improvement in visual acuities after months of legal blindness. Two male patients with bilateral subacute visual loss were 14 years of age at presentation. The first male patient had a mitochondrial DNA mutation at nucleotide position 11778. The second male patient was found to be negative for the designated primary mutations (11778, 14484, 3460) and two of the secondary mutations (15257, 9804). The third patient was a 20-year-old female who presented with bilateral optic atrophy. She had been diagnosed as LHON and was found positive for the 3460 mutation when she was 15. These patients' pattern of visual recovery by developing small islands of normal vision within a central scotoma is characteristic in such rare cases of LHON. PMID:14750573

Acaro?lu, G; Kansu, T; Do?ulu, C F

2001-01-01

58

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

PubMed Central

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

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

2014-01-01

59

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

PubMed

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

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

2014-05-01

60

Nonarteritic anterior ischemic optic neuropathy in a child with optic disk drusen.  

PubMed

Optic disk drusen are calcific deposits that form in the optic nerve head secondary to abnormalities in axonal metabolism and degeneration. The clinical course is variable, ranging from stable vision to acute or progressive visual loss. We evaluated a healthy 12-year-old boy with a history of asymptomatic bilateral disk drusen who presented with acute painless unilateral visual loss after hiking to an altitude of 11,000 feet. Findings were consistent with nonarteritic anterior ischemic optic neuropathy. PMID:22525184

Nanji, Afshan A; Klein, Kathryn S; Pelak, Victoria S; Repka, Michael X

2012-04-01

61

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

PubMed

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

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

2012-03-01

62

Visual recovery from optic atrophy following acute optic neuropathy in the fellow eye  

PubMed Central

The left eye of a 65-year-old male was blind due to optic atrophy and only seeing eye had also dry type age-related macular degeneration. An anterior ischemic optic neuropathy developed in the better seeing eye. Vision recovered in the blind eye in a short time after losing the better eye. Gaining some vision in a blind eye may be an adaptation of visual pathway in such patients.

Ornek, Kemal; Ornek, Nurgul

2012-01-01

63

Disulfiram-induced combined irreversible anterior ischemic optic neuropathy and reversible peripheral neuropathy: a prospective case report and review of the literature.  

PubMed

Disulfiram is an alcohol-deterring agent with few rare serious adverse effects, usually dose-related, reversible, and more frequent with comorbid alcohol and nicotine dependence. We report a prospective follow-up of such a case with reversible peripheral neuropathy and irreversible optic neuropathy. PMID:24247861

Kulkarni, Ranganath R; Pradeep, A V; Bairy, Bhavya K

2013-01-01

64

Cell response to oxidative stress induced apoptosis in patients with Leber’s hereditary optic neuropathy  

Microsoft Academic Search

Objectives: Leber’s hereditary optic neuropathy (LHON) is a maternally inherited disease in which acute or subacute bilateral visual loss occurs preferentially in young men. Over 95% of LHON cases are associated with one of three mitochondrial DNA (mtDNA) point mutations, but only 50% of men and 10% of women who harbour a pathogenetic mtDNA mutation develop optic neuropathy. This incomplete

C Battisti; P Formichi; E Cardaioli; S Bianchi; P Mangiavacchi; S A Tripodi; P Tosi; A Federico

2004-01-01

65

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

2001-01-01

66

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

2012-01-01

67

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

PubMed

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

2012-01-01

68

A Primate Model of Nonarteritic Anterior Ischemic Optic Neuropathy  

PubMed Central

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

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

2008-01-01

69

Neural network differentiation of optic neuritis and anterior ischaemic optic neuropathy.  

PubMed Central

AIMS: The efficacy of an artificial intelligence technique, neural network analysis, was examined in differentiating two optic neuropathies with overlapping clinical profiles-idiopathic optic neuritis (ON) and non-arteritic anterior ischaemic optic neuropathy (AION). METHODS: A neural network was trained with data from 116 patients with 'gold standard' diagnoses of ON or AION. It was then tested with data from 128 patients with presumed ON or AION, and the correlation of the network's diagnosis with that of expert clinicians tabulated. RESULTS: The network agreed with the clinicians on 97.8% (88 of 90) of the patients with presumed ON and 94.7% (36 of 38) of the patients with presumed AION. Youth, female sex, better initial acuity, a central scotoma, subsequent improvement in acuity, or progressive disease biased the network towards a diagnosis of ON, while advanced age, male sex, presence of hypertension, poor initial acuity, an altitudinal field defect, disc oedema, or less improvement in acuity biased the network towards a diagnosis of AION. CONCLUSION: Neural network analysis is a useful technique for classification of optic neuropathies, particularly where there is overlap of clinical findings.

Levin, L A; Rizzo, J F; Lessell, S

1996-01-01

70

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

Microsoft Academic Search

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

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

2006-01-01

71

[Hemodilution therapy in patients with acute anterior ischemic optic neuropathy].  

PubMed

A prospective study was performed in 22 patients with an anterior ischaemic optic neuropathy (AION). All patients underwent iso- (Hct > or = 42%) or hypervolemic (Hct < 42%) haemodilution for 10 days with daily infusion of 250 ml hydroxyethyl starch (MW 200,000/0.5, 10% HAES-sterile) in combination with pentoxifylline (p.o.: 1200 mg/day; i.v.: 300 mg/day; Trental). Only patients with recent AION (less than 2 weeks' duration of symptoms) were considered for the prospective trial. Clinical, haemodynamic (arterio-venous passage time) and rheological (haematocrit, plasma viscosity, erythrocyte aggregation) data of all patients were recorded before therapy and after 10 days. An improvement of central vision by 2 or more lines was seen in 7 patients after 10 days. Initially the arterio-venous passage time was significantly prolonged in patients (2.42 +/- 0.7 s) with AION compared with healthy volunteers (1.45 +/- 0.4 s). After the 10-day trial arterio-venous passage time was significantly shorter than baseline values. In addition, the initially elevated plasma viscosity (1.33 +/- 0.1 mPa) was significantly lowered by haemodilution therapy. PMID:7680252

Wolf, S; Schulte-Strake, U; Bertram, B; Schulte, K; Arend, O; Reim, M

1993-02-01

72

Novel therapeutic approaches for Leber's hereditary optic neuropathy.  

PubMed

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

Iyer, Shilpa

2013-03-01

73

Leber's hereditary optic neuropathy masquerading as optic neuritis with spontaneous visual recovery.  

PubMed

We report a case of Leber's hereditary optic neuropathy (LHON) masquerading as optic neuritis with late visual recovery. A 28-year-old man had gradual visual loss in both eyes for two weeks. Visual acuity was 0.4 in the right eye and 0.7 in the left. Fundus examination revealed hyperaemic discs in each eye. Fluorescein angiography revealed dye leakage at both optic discs in the late phase. Static perimetry (Humphrey 30-2) revealed bilateral relative central scotomata. Magnetic resonance imaging of the optic nerves was normal and his lumbar puncture showed normal opening pressure. He received steroid pulse therapy for three days. Nevertheless, vision in his right eye deteriorated to 0.1 one month later and left vision worsened to 0.05 six months later. Fifteen months after onset, his vision began to improve. At 21 months, his vision recovered to 0.9?R and 1.0?L. Peripheral blood DNA sequencing revealed 14484 mutation of mitochondrial DNA (mtDNA). Visual recovery can occur in patients with Leber's hereditary optic neuropathy with mtDNA 14484 mutation. LHON could be misdiagnosed as optic neuritis in some cases. Molecular examination of mtDNA mutation can confirm the diagnosis of LHON in clinically controversial patients. We should keep in mind the diagnosis of LHON when optic neuritis shows poor response to pulse therapy. PMID:23905692

Hsu, Tsui-Kang; Wang, An-Guor; Yen, May-Yung; Liu, Jorn-Hon

2014-01-01

74

Leber Hereditary Optic Neuropathy Gene Therapy Clinical Trial Recruitment  

PubMed Central

Objective To describe the patient profiles of the Leber hereditary optic neuropathy (LHON) Gene Therapy Clinical Trial, year 1. This study aims to identify and characterize affected patients and carriers with the G11778A mutation in mitochondrial DNA for planned gene therapy that will use “allotopic expression” by delivering a normal nuclear-encoded ND4 gene into the nuclei of retinal ganglion cells via an adeno-associated virus vector injected into the vitreous. Methods Patients with LHON with visual loss as well as asymptomatic maternally related family members were molecularly screened for ND1, ND4, and ND6 mutations in mitochondrial DNA commonly associated with LHON. All patients and maternal relatives also underwent complete neuro-ophthalmic examination, automated visual field testing, pattern electroretinogram (PERG), and OCT3. Results Twenty-five subjects with LHON and 21 carriers positive for the G11778A mitochondrial DNA mutation were recruited. Three additional mutations in the ND4 gene, G11719A, G11947A, or G11914A, were detected. Mean retinal nerve fiber layer (RNFL) thickness was 78.3 ?m up to 32 months after visual loss. It was 63.5 ?m for all affected patients and 100.7 ?m for carriers (P<.01). Mean PERG amplitude was lower in affected patients (40% of normal) than in carriers (94% of normal) (P<.01). Four carriers with PERG amplitudes less than 75% of normal had Early Treatment Diabetic Retinopathy Study acuity more than 20/25, mean defect more than ?2 dB, and average RNFL thickness more than 80 ?m. Conclusions Potential candidates for future gene therapy may include affected patients, as late as 32 months after loss of vision, with mildly reduced RNFL thickness or carriers with low PERG amplitudes and normal RNFL thickness, if the PERG amplitude is a predictor of conversion to LHON in these carriers.

Lam, Byron L.; Feuer, William J.; Abukhalil, Fawzi; Porciatti, Vittorio; Hauswirth, William W.; Guy, John

2011-01-01

75

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

PubMed

Nonarteritic ischemic optic neuropathy (NAION) is one of the most common acute unilaterally onset optic nerve diseases. One management problem in terms of NAION is the difficulty of differential diagnosis between NAION and anterior optic neuritis (ON). A second problem is that there is no established treatment for the acute stage of NAION. A third problem is that there is no preventive treatment for a subsequent attack on the fellow eye, estimated to occur in 15 to 25% of patients with NAION. For differentiation of acute NAION from anterior optic neuritis, we investigated the usefulness of laser speckle flowgraphy (LSFG). In the normal control group, the tissue blood flow did not significantly differ between the right and left eyes. In the NAION group, all 6 patients had 29.5% decreased mean blur rate (MBR), which correlates to optic disc blood flow, of the NAION eye compared with the unaffected eye. In the anterior ON group, all 6 cases had 15.9% increased MBR of the anterior ON eye compared with the unaffected eye. Thus, LSFG showed a difference of the underlying pathophysiology between NAION and anterior ON despite showing disc swelling in both groups and could be useful for differentiating both groups. For the treatment of acute stage of NAION, we tried to reproduce the rodent model of NAION (rNAION) developed by Bernstein and colleagues. To induce rNAION, after the administration of rose bengal(RB) (2.5 mM) into the tail vein of SD rats, the small vessels of the left optic nerve were photoactivated using a 514 nm argon green laser (RB-laser-induction). In the RB-laser-induction eyes, the capillaries within the optic disc were reduced markedly, the optic disc became swollen, and fluorescein angiography showed filling defect in the choroid and the optic disc at an early stage, followed by hyperfluorescence at a late stage. Electrophysiological evaluation revealed that visual evoked potential (VEP) amplitude was significantly decreased but an electroretinogram (ERG) did not show a significant difference either in the b wave or in the oscillatory potentials. The scotopic threshold response (STR) was significantly reduced 3 days after induction. These findings are similar to those of rNAION and indicate that we succeeded in reproducing the rNAION. Histopathologic examination in the acute phase of rNAION, showed acellular NFL swelling anterior to the optic disc. No accumulation of inflammatory cells was noted in several microscopic sections of the optic nerve. In addition, immunochemical staining was negative throughout the retina and optic nerve. These results suggested that the rNAION-induced NFL swelling was not a result of inflammation. In the chronic phase of rNAION, the morphologic retinal changes were apparent in only the retinal ganglion cell(RGC) layer, with a reduction in the number of cells in the RGC layer. Thus, we need to evaluate the degree of the NFL swelling in the acute phase and the following thinning of the NFL in the chronic phase for efficacy of the treatment of rNAION. Therefore, we used optical coherence tomography (OCT) for the objective and quantitative evaluation of the retinal nerve fiber layer (RNFL) thickness around the optic disc changes in rNAION. The second method was to use the STR for the evaluation of the RGC function. The third method was to count the number of surviving RGCs observed and photographed through the fluorescence microscope with the Fluorogold staining. A possible rationale for treatment of NAION is that dilation of the posterior ciliary artery (PCA) increases the blood flow to the optic nerve and could improve the optic nerve function. To clarify the vasodilatory effects of medications, we used in vitro isometric tension recording methods and examined the vasodilatory effects of bevacizumab as an anti-vascular endothelial growth factor (VEGF) antibody, methylprednisolone as a corticosteroid and sodium nitroprusside (SNP, a nitric oxide donor) as a vasodilator on high-K (potassium) solution-induced contraction in isolated rabbit PCA. Bevacizumab did not relax rabbit PCA. M

Chuman, Hideki

2014-04-01

76

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

77

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

PubMed

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

2013-08-01

78

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

2012-01-01

79

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

PubMed Central

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

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

2014-01-01

80

Late-onset Leber hereditary optic neuropathy mimicking Susac’s syndrome  

Microsoft Academic Search

Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder characterized by bilateral painless optic atrophy and\\u000a blindness. It usually occurs in young men in association with three major mutations in the mitochondrial genome (mtDNA). We\\u000a report a patient with a history of alcohol abuse who developed at age 63 years visual impairment, sensorineural hearing loss,\\u000a and memory dysfunction, suggestive of Susac’s

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

2010-01-01

81

Optic atrophy differentially diagnosed as spinocerebellar ataxia from Leber hereditary optic neuropathy by gene mutation analysis.  

PubMed

Optic atrophy describes a group of diseases of retinal ganglion cells and axons that eventually lead to loss of vision. Optic atrophy has both congenital and acquired causes, and its diagnosis (or differential diagnosis) is complicated. This case report describes a 20-year-old man who presented with a 1-year history of progressive vision loss in both eyes and no obvious systemic symptoms. Fundus examination revealed bilateral optic atrophy. Based on clinical characteristics, visual field analysis and pattern visual evoked potential examination, the presumptive diagnosis was Leber hereditary optic neuropathy (LHON). Analysis of mitochondrial DNA indicated the absence of all of three common mutations associated with LHON (m.3460G>A, m.11778G>A, m.14484T>C). Detailed questioning of the patient revealed a history of prolonged language development and poor balance. Neurological examination indicated abnormal co-ordination, suggesting the presence of inherited spinocerebellar ataxia (SCA). Analysis of the SCA7 gene revealed a high number of trinucleotide repeats [(CAG)(n), n > 64], confirming the diagnosis of SCA. The aetiology of optic atrophies is complicated and the molecular genetic detection approach provides the best information for diagnosing these diseases. PMID:23206485

Song, Y P; Chen, Z S; Mo, G Y; Ding, Q; Zhu, L; Yan, M

2012-01-01

82

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.

2012-01-01

83

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.

2011-01-01

84

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

PubMed Central

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

Martinez-Gamero, Bertha O.; Mohamed-Noriega, Jibran; Cavazos-Adame, Med. Humberto; Mohamed-Hamsho, Med. Jesus

2014-01-01

85

Myopia and diabetes mellitus as modificatory factors of glaucomatous optic neuropathy.  

PubMed

Myopic deformation of the eye and metabolic alterations of the nerve tissue of patients with diabetes may modify glaucomatous optic neuropathy (GON). Blockage of axonal transport of neurotrophic factors (NTFs) is the event crucial to understanding the factors that affect GON. The primary, but not sole, blockage site is at the lamina cribrosa (LC). Other than this primary site of damage at the LC, 7 other factors may explain atypical nerve fiber layer (NFL) defects and the vulnerability of the nerve fibers in eyes with high myopia and glaucoma: a second point of blockage at the edge of the posterior scleral foramen; ectatic strain on the NFL; ectasia and distortion of the LC; association of a hypoplastic optic disc; thin and weak collagen fibers; peripapillary chorioretinal atrophy; and myopic neuropathy. Among diabetic patients, diabetic neuropathy in the retinal NFL is present initially, and increased resistance to aqueous outflow leads to ocular hypertension. Superimposition of GON on diabetic neuropathy and ocular hypertension in patients with diabetes may enhance their susceptibility to nerve damage. Results of a meta-analysis study suggested a positive association between diabetes mellitus and glaucoma whereas other reports suggested that leakage of vascular endothelial growth factor, a survival mechanism of ischemic neural tissue, and enhanced stiffness of the LC as a result of diabetic glycation may protect neurons from apoptosis. Thus, modification of GON as a result of diabetes remains controversial. PMID:23942995

Chihara, Etsuo

2014-01-01

86

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

PubMed Central

Although Alzheimer's disease (AD) has been shown to be associated with a true primary optic neuropathy, the underlying pathophysiology of this disease and in particular the optic nerve disorder is still poorly understood. The receptor for advanced glycation end products (RAGE) has been implicated in the pathogenesis of AD by mediating the transport of plasma amyloid-? into the brain. Once ligated, RAGE can play a role in signal transduction, leading to amplification and perpetuation of inflammatory processes. As a key player in the reaction to CNS injury, astrocytes have been shown to associate with RAGE in a number of diseases, including AD. To investigate the role of RAGE and astrocytes in the pathogenesis of AD optic neuropathy, we conducted immunohistochemical studies to examine the presence of RAGE in donor eyes from patients with AD (n = 10) and controls (n = 3). Both qualitative observation and quantitative analyses using imaging software were used to document the extent of RAGE in the neural tissues. The intensity and extent of RAGE expression was more prominent in AD nerves compared to controls (P < 0.05). The RAGE immunoreactivity was observed in the microvasculature and in close proximity to astrocytic processes. While RAGE immunoreactivity increased with age, the increase was more precipitous in the AD group compared to the controls. The up-regulation of RAGE in the AD optic nerves indicates that RAGE may play a role in the pathophysiology of AD optic neuropathy.

Wang, Michelle Y.; Ross-Cisneros, Fred N.; Aggarwal, Divya; Liang, Chiao-Ying

2010-01-01

87

Mutation survey of the optic atrophy 1 gene in 193 Chinese families with suspected hereditary optic neuropathy  

PubMed Central

Purpose Dominant optic atrophy (DOA) is the most common form of autosomal inherited optic neuropathy, mainly caused by mutations in the optic atrophy 1 (OPA1) gene. The purpose of this study was to detect OPA1 gene mutations and associated phenotypes in Chinese patients with suspected hereditary optic neuropathy. Methods A cohort of 193 Chinese families with suspected hereditary optic neuropathy was collected, which had been excluded from the three common primary mitochondrial DNA mutations associated with Leber hereditary optic neuropathy in our prior screening. Sanger sequencing was used to analyze variants in the coding and adjacent regions of OPA1. Results In this study, 11 heterozygous OPA1 mutations, among which eight were novel and three were known, were identified in 12 of the 193 families (6.2%) but in none of the 192 control individuals. These novel mutations consisted of two nonsense mutations (p.E707* and p.K797*), two missense mutations (p.T330S and p.V377I), two deletions (p.S64fs and p.L331fs), one small insertion (p.L17fs), and one splice site mutation (c.2614–2A>G). Of the 12 families, three had a family history of optic neuropathy while nine were sporadic cases. Analysis of the family members in the two sporadic cases demonstrated that one parent in each of the two families had the OPA1 mutation and mild phenotype of optic atrophy. A 4-year-old boy with severe ocular phenotype was found to be compound heterozygous for two OPA1 mutations, a p.S64fs frameshift deletion and a p.V377I missense mutation, possibly implying an additive effect. Conclusions This study implies that the frequency of DOA is much lower than that of Leber hereditary optic neuropathy in Chinese compared with other ethnic groups. Lack of awareness of the mild phenotype of DOA may contribute to the low frequency of OPA1-related DOA in Chinese. The phenotype associated with compound heterozygous OPA1 mutations may suggest a possible addictive effect.

Chen, Yabin; Jia, Xiaoyun; Wang, Panfeng; Xiao, Xueshan; Li, Shiqiang; Guo, Xiangming

2013-01-01

88

Optical Coherence Tomography Study of Experimental Anterior Ischemic Optic Neuropathy and Histologic Confirmation  

PubMed Central

Purpose. The optic nerve is part of the central nervous system, and interruption of this pathway due to ischemia typically results in optic atrophy and loss of retinal ganglion cells. In this study, we assessed in vivo retinal changes following murine anterior ischemic optic neuropathy (AION) by using spectral-domain optical coherence tomography (SD-OCT) and compared these anatomic measurements to that of histology. Methods. We induced ischemia at the optic disc via laser-activated photochemical thrombosis, performed serial SD-OCT and manual segmentation of the retinal layers to measure the ganglion cell complex (GCC) and total retinal thickness, and correlated these measurements with that of histology. Results. There was impaired perfusion and leakage at the optic disc on fluorescein angiography immediately after AION and severe swelling and distortion of the peripapillary retina on day-1. We used SD-OCT to quantify the changes in retinal thickness following experimental AION, which revealed significant thickening of the GCC on day-1 after ischemia followed by gradual thinning that plateaued by week-3. Thickness of the peripapillary sensory retina was also increased on day-1 and thinned chronically. This pattern of acute retinal swelling and chronic thinning on SD-OCT correlated well with changes seen in histology and corresponded to loss of retinal ganglion layer cells after ischemia. Conclusions. This was a serial SD-OCT quantification of acute and chronic changes following experimental AION, which revealed changes in the GCC similar to that of human AION, but over a time frame of weeks rather than months.

Ho, Joyce K.; Stanford, Madison P.; Shariati, Mohammad A.; Dalal, Roopa; Liao, Yaping Joyce

2013-01-01

89

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

PubMed Central

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

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

2014-01-01

90

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

PubMed

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

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

2014-02-01

91

Acute Posterior Ischemic Optic Neuropathy Mimicking Posterior Cerebral Artery Stroke Visualized by 3-Tesla MRI  

PubMed Central

Acute ischemic lesions of the posterior optic nerve and optic tract can produce a variety of visual field defects. A 71-year-old woman presented with acute hemianopia, which led to rt-PA thrombolysis for suspected posterior cerebral artery ischemia. 3-Tesla cMRI, however, revealed the cause to be an acute posterior ischemic optic neuropathy. Cases like this may be more common than thought and quite regularly overlooked in clinical practice, especially when there is no high-resolution MRI available. This case strengthens the importance of repeat MR imaging in patients with persistent visual field defects.

Menzel, Tilman; Kern, Rolf; Griebe, Martin; Hennerici, Michael; Fatar, Marc

2012-01-01

92

Mouse mtDNA mutant model of Leber hereditary optic neuropathy.  

PubMed

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

2012-12-01

93

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

2009-01-01

94

A randomized placebo-controlled trial of idebenone in Leber's hereditary optic neuropathy  

PubMed Central

Major advances in understanding the pathogenesis of inherited metabolic disease caused by mitochondrial DNA mutations have yet to translate into treatments of proven efficacy. Leber’s hereditary optic neuropathy is the most common mitochondrial DNA disorder causing irreversible blindness in young adult life. Anecdotal reports support the use of idebenone in Leber’s hereditary optic neuropathy, but this has not been evaluated in a randomized controlled trial. We conducted a 24-week multi-centre double-blind, randomized, placebo-controlled trial in 85 patients with Leber’s hereditary optic neuropathy due to m.3460G>A, m.11778G>A, and m.14484T>C or mitochondrial DNA mutations. The active drug was idebenone 900 mg/day. The primary end-point was the best recovery in visual acuity. The main secondary end-point was the change in best visual acuity. Other secondary end-points were changes in visual acuity of the best eye at baseline and changes in visual acuity for both eyes in each patient. Colour-contrast sensitivity and retinal nerve fibre layer thickness were measured in subgroups. Idebenone was safe and well tolerated. The primary end-point did not reach statistical significance in the intention to treat population. However, post hoc interaction analysis showed a different response to idebenone in patients with discordant visual acuities at baseline; in these patients, all secondary end-points were significantly different between the idebenone and placebo groups. This first randomized controlled trial in the mitochondrial disorder, Leber’s hereditary optic neuropathy, provides evidence that patients with discordant visual acuities are the most likely to benefit from idebenone treatment, which is safe and well tolerated.

Klopstock, Thomas; Yu-Wai-Man, Patrick; Dimitriadis, Konstantinos; Rouleau, Jacinthe; Heck, Suzette; Bailie, Maura; Atawan, Alaa; Chattopadhyay, Sandip; Schubert, Marion; Garip, Aylin; Kernt, Marcus; Petraki, Diana; Rummey, Christian; Leinonen, Mika; Metz, Gunther; Griffiths, Philip G.; Meier, Thomas

2011-01-01

95

Evidence for a novel x-linked modifier locus for leber hereditary optic neuropathy.  

PubMed

Leber Hereditary Optic Neuropathy (LHON) is a maternally inherited blinding disease caused by missense mutations in the mitochondrial DNA (mtDNA). However, incomplete penetrance and a predominance of male patients presenting with vision loss suggest that modifying factors play an important role in the development of the disease. Evidence from several studies suggests that both nuclear modifier genes and environmental factors may be necessary to trigger the optic neuropathy in individuals harboring an LHON-causing mtDNA mutation. Recently, an optic neuropathy susceptibility locus at Xp21-Xq21 has been reported. In this study, we performed X-chromosomal linkage analysis in a large Brazilian family harboring a homoplasmic G11778A mtDNA mutation on a haplogroup J background. We report the identification of a novel LHON susceptibility locus on chromosome Xq25-27.2, with multipoint non-parametric linkage scores of > 5.00 (P = 0.005) and a maximum two-point non-parametric linkage score of 10.12, (P = 0.003) for marker DXS984 (Xq27.1). These results suggest genetic heterogeneity for X-linked modifiers of LHON. PMID:18363168

Shankar, Suma P; Fingert, John H; Carelli, Valerio; Valentino, Maria L; King, Terri M; Daiger, Stephen P; Salomao, Solange R; Berezovsky, Adriana; Belfort, Rubens; Braun, Terri A; Sheffield, Val C; Sadun, Alfredo A; Stone, Edwin M

2008-03-01

96

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

PubMed Central

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

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

2013-01-01

97

Is the Efficacy of LDL Apheresis in Ischemic Optic Neuropathy Linked to a Reduction in Endothelial Activation Markers?  

Microsoft Academic Search

Endothelial dysfunction of the optic microcirculation is considered to be the main pathogenetic mechanism in nonarteritic ischemic optic neuropathy. The aim of the present work was to assess whether a clinical improvement is correlated with a reduction in the endothelial activation markers by means of LDL apheresis (LDLA). Three weekly sessions of LDLA were administered in 23 patients affected by

A. Ramunni; G. Ranieri; G. Giancipoli; S. Guerriero; R. Ria; M. T. Saliani; L. Sborgia; P. Ranieri; P. Coratelli

2006-01-01

98

Leber’s Hereditary Optic Neuropathy Mitochondrial DNA Mutations at Nucleotides 11778 and 3460 in Multiple Sclerosis  

Microsoft Academic Search

Objectives: Leber’s hereditary optic neuropathy (LHON) can be difficult to distinguish from optic neuritis seen in multiple sclerosis (MS). About half of the LHON patients harbor a mutation at nucleotide (nt) 11778 in the mitochondrial (mt) DNA. In addition, mutations at nt-3460 and nt-14484 have been associated with LHON. An association of LHON and MS has been suspected for decades,

Daniel S. Mojon; Joseph Herbert; Saud A. Sadiq; James R. Miller; Michelle Madonna; Michio Hirano

1999-01-01

99

A novel all-optical AND gate using frequency shift accompanied by cross-phase modulation in semiconductor optical amplifier  

NASA Astrophysics Data System (ADS)

In this paper, we propose a novel all-optical AND gate using frequency shift accompanied by cross-phase modulation in semiconductor optical amplifier. Theoretical model is built to analyze the performance of the proposed gate. Through numerical simulations, we find the bandwidth of the optical band filter can be optimized to improve the quality of the output signals. The AND gate with short pulse-width and high energy of the control signals is adaptive to high-speed optical packet-switched and label-switched network.

Wang, Ling; Zhang, Min; Zhao, Yongpeng; Ye, Peida

2005-02-01

100

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

2010-01-01

101

A novel rat model to study the role of intracranial pressure modulation on optic neuropathies.  

PubMed

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

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

2013-01-01

102

Leber's hereditary optic neuropathy associated with a multiple-sclerosis-like picture in a man.  

PubMed

A 35-year-old young man displayed Leber's optic neuropathy (LHON) due to T14484C and multiple sclerosis (MS) phenotype that was dominated by symptoms and signs of spinal cord impairment. Magnetic resonance imaging (MRI) revealed demyelinating lesions extending from D6 to D11 in the spinal cord with gadolinium enhancement, while only three linear demyelinating lesions were seen on brain MRI. In the literature, a major involvement of the spinal cord was already reported in three of four male patients with the 14484 LHON mutation who developed MS, but the reasons of this peculiar association remain unknown, and further research in this area is needed. PMID:21685233

La Russa, Antonella; Cittadella, Rita; Andreoli, Virginia; Valentino, Paola; Trecroci, Francesca; Caracciolo, Manuela; Gallo, Olivier; Gambardella, Antonio; Quattrone, Aldo

2011-06-01

103

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

PubMed

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

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

2014-04-01

104

Contrast Sensitivity of Thyroid Associated Ophthalmopathy Patients without Obvious Optic Neuropathy  

PubMed Central

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

Beden, Umit; Kaya, Sumeyra; Yeter, Volkan; Erkan, Dilek

2013-01-01

105

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

PubMed Central

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

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

1995-01-01

106

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

2001-01-01

107

Electrophysiological changes in optic neuropathy of streptozotocin induced diabetic rats  

PubMed Central

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

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

2013-01-01

108

Cell response to oxidative stress induced apoptosis in patients with Leber's hereditary optic neuropathy  

PubMed Central

Objectives: Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease in which acute or subacute bilateral visual loss occurs preferentially in young men. Over 95% of LHON cases are associated with one of three mitochondrial DNA (mtDNA) point mutations, but only 50% of men and 10% of women who harbour a pathogenetic mtDNA mutation develop optic neuropathy. This incomplete penetrance and preference for men suggests that additional genetic (nuclear or mitochondrial) and/or environmental factors must modulate phenotype expression in LHON. A role for reactive oxygen species (ROS) in mitochondrial diseases, secondary to mtDNA mutations, or as a result of the direct effect of ROS cytotoxicity, has been implicated in many mitochondrial disorders, including LHON. The purpose of this study was to investigate the role of oxidative stress induced apoptosis in LHON. Methods: The 2-deoxy-D-ribose induced apoptotic response of peripheral blood lymphocytes from six patients with LHON and six healthy subjects was investigated using light microscopy, flow cytometry, agarose gel electrophoresis, and the measurement of mitochondrial membrane potential. Results: Cells of patients with LHON had a higher rate of apoptosis than those of controls and there was evidence of mitochondrial involvement in the activation of the apoptotic cascade. Conclusions: These differences in oxidative stress induced apoptosis are in line with the hypothesis that redox homeostasis could play a role in the expression of genetic mutations in different individuals and could represent a potential target in the development of new therapeutic strategies.

Battisti, C; Formichi, P; Cardaioli, E; Bianchi, S; Mangiavacchi, P; Tripodi, S; Tosi, P; Federico, A

2004-01-01

109

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

2013-01-01

110

Bilateral optic neuropathy associated with cryptococcal meningitis in an immunocompetent patient.  

PubMed

Cryptococcal meningitis is associated with significant morbidity and is rare among immunocompetent patients. Clinical presentation as well as the course of disease is usually indolent which may delay the diagnosis. We present the case of a 52-year-old woman admitted with headaches, vomiting and fatigue for 3?weeks. She was diagnosed with cryptococcal meningitis and treated with antifungal therapy. She was referred for ophthalmological examination presenting with decreased vision in the left eye (OS; count fingers), left relative afferent pupillary defect and bilateral sixth nerve palsy. Funduscopy revealed florid bilateral papilloedema. Cranial MRI showed indirect signs of intracranial hypertension as well as multiple parenchymal lesions and optic nerve sheath enhancement after contrast administration. A ventriculoperitoneal shunt was placed. In spite of the control of intracranial pressure there was a decrease in vision in the right eye (OD) and deterioration of visual fields. Intravenous methylprednisolone was used to reverse optic neuropathy and to prevent OD visual loss. PMID:24920512

Portelinha, Joana; Passarinho, Maria Picoto; Almeida, Ana Catarina; Costa, João Marques

2014-01-01

111

Papillitis as an onset sign of Leber's hereditary optic neuropathy: a case report.  

PubMed

Leber's hereditary optic neuropathy is a maternally transmitted disease resulting from a point mutation in mitochondrial (mt) DNA. In this report we describe a case of Leber's disease with typical clinical findings but atypical ophthalmoscopic presentation. A 14-year-old boy developed severe loss of vision acuity in the left eye, with only partial recovery, followed 4 months later by the same symptoms in the right eye. Fundoscopic examination showed hyperemic papilla on the right eye and optic disc pallor on the left eye. Polymerase chain reaction analysis of lymphocytic mt-DNA revealed a point mutation at 11778. Leber's disease should be considered in young patients (not always male) with sudden visual loss and simple papillary involvement at fundoscopic examination but without the typical telangiectatic microangiopathy. PMID:11248462

Pantaleoni, C; D'Arrigo, S; Bagnasco, I; Piozzi, E; Carrara, F; Scaioli, V; Riva, D

2001-03-01

112

Retinal Ganglion Cell Functional Plasticity and Optic Neuropathy: A Comprehensive Model  

PubMed Central

The clinical management of glaucoma and optic neuropathies has traditionally focused on stages of the diseases at which there are congruent losses of visual function and optic nerve tissue. Increasing clinical and experimental evidence suggests that the electrical activity of retinal ganglion cells, as measured by pattern electroretinogram (PERG), may be altered long before measurable changes in the thickness of the retinal nerve fiber layer. In addition, PERG alterations in early glaucoma may be either reversed by lowering the intraocular pressure or induced with head-down body posture. Here we apply the well-known concept of neural plasticity to model the reversible/inducible changes of retinal ganglion cell electrical activity during a critical period of dysfunction preceding death. Identification and characterization of this stage of modifiable retinal ganglion cell function represents both a rationale and a target for treatment to change the natural history of the disease.

Porciatti, Vittorio; Ventura, Lori M.

2013-01-01

113

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

PubMed Central

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

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

2013-01-01

114

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

2006-01-01

115

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

2011-01-01

116

Clinical features of dysthyroid optic neuropathy: a European Group on Graves' Orbitopathy (EUGOGO) survey  

PubMed Central

Background This study was performed to determine clinical features of dysthyroid optic neuropathy (DON) across Europe. Methods Forty seven patients with DON presented to seven European centres during one year. Local protocols for thyroid status, ophthalmic examination and further investigation were used. Each eye was classified as having definite, equivocal, or no DON. Results Graves' hyperthyroidism occurred in the majority; 20% had received radioiodine. Of 94 eyes, 55 had definite and 17 equivocal DON. Median Clinical Activity Score was 4/7 but 25% scored 3 or less, indicating severe inflammation was not essential. Best corrected visual acuity was 6/9 (Snellen) or worse in 75% of DON eyes. Colour vision was reduced in 33 eyes, of which all but one had DON. Half of the DON eyes had normal optic disc appearance. In DON eyes proptosis was > 21?mm (significant) in 66% and visual fields abnormal in 71%. Orbital imaging showed apical muscle crowding in 88% of DON patients. Optic nerve stretch and fat prolapse were infrequently reported. Conclusion Patients with DON may not have severe proptosis and orbital inflammation. Optic disc swelling, impaired colour vision and radiological evidence of apical optic nerve compression are the most useful clinical features in this series.

McKeag, David; Lane, Carol; Lazarus, John H; Baldeschi, Lelio; Boboridis, Kostas; Dickinson, A Jane; Hullo, A Iain; Kahaly, George; Krassas, Gerry; Marcocci, Claudio; Marino, Michele; Mourits, Maarten P; Nardi, Marco; Neoh, Christopher; Orgiazzi, Jacques; Perros, Petros; Pinchera, Aldo; Pitz, Susanne; Prummel, Mark F; Sartini, Maria S; Wiersinga, Wilmar M

2007-01-01

117

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

PubMed

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

2014-01-01

118

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

PubMed Central

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

Tugcu, Betul; Acar, Nur; Coskun, Cigdem Tanr?verdi; Celik, Selda; Yigit, Fadime Ulviye

2014-01-01

119

Haemorheological parameters in patients with retinal artery occlusion and anterior ischaemic optic neuropathy.  

PubMed Central

The haemorheological parameters haematocrit (Hct), plasma viscosity (PV), red cell aggregation (RCA), red cell filterability (RCF), apparent whole blood viscosity (WBV), and fibrinogen were measured in 31 patients with retinal artery occlusion (RAO), 25 patients with anterior ischaemic optic neuropathy (AION), and 19 patients with giant cell arteritis (GCA). The patient groups were compared with controls of same age and similar prevalence of cardiovascular risk factors. Patients with RAO and AION have a significantly decreased RCF in comparison with controls. All other parameters showed no differences. Patients with GCA had significantly decreased Hct and RCF and increased PV and fibrinogen. After 2 weeks of systemic treatment with high dose steroids in patients with GCA the plasma viscosity had returned to normal and was even lower than in controls, and the Hct and fibrinogen had reached normal levels.

Wiek, J; Krause, M; Schade, M; Wiederholt, M; Hansen, L L

1992-01-01

120

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

PubMed

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

2012-08-01

121

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

2013-01-01

122

Raised intraocular pressure as a potential risk factor for visual loss in Leber Hereditary Optic Neuropathy.  

PubMed

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. PMID:23667621

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

2013-01-01

123

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

PubMed

Leber hereditary optic neuropathy (LHON) is caused by point mutations in mitochondrial DNA (mtDNA), and is characterized by bilateral, painless sub-acute visual loss that develops during the second decade of life. Here we report the case of a five year old girl who presented with clinical and neuroradiological findings reminiscent of Leigh syndrome but carried a mtDNA mutation m.11778G>A (p.R340H) in the MTND4 gene usually observed in patients with LHON. This case is unusual for age of onset, gender, associated neurological findings and evolution, further expanding the clinical spectrum associated with primary LHON mtDNA mutations. PMID:21414825

Fruhman, Gary; Landsverk, Megan L; Lotze, Timothy E; Hunter, Jill V; Wangler, Michael F; Adesina, Adekunle M; Wong, Lee-Jun C; Scaglia, Fernando

2011-06-01

124

Mathematically Modeling the Involvement of Axons in Leber's Hereditary Optic Neuropathy  

PubMed Central

Purpose. Leber's hereditary optic neuropathy (LHON), a mitochondrial disease, has clinical manifestations that reflect the initial preferential involvement of the papillomacular bundle (PMB). The present study seeks to predict the order of axonal loss in LHON optic nerves using the Nerve Fiber Layer Stress Index (NFL-SI), which is a novel mathematical model. Methods. Optic nerves were obtained postmortem from four molecularly characterized LHON patients with varying degrees of neurodegenerative changes and three age-matched controls. Tissues were cut in cross-section and stained with p-phenylenediamine to visualize myelin. Light microscopic images were captured in 32 regions of each optic nerve. Control and LHON tissues were evaluated by measuring axonal dimensions to generate an axonal diameter distribution map. LHON tissues were further evaluated by determining regions of total axonal depletion. Results. A size gradient was evident in the control optic nerves, with average axonal diameter increasing progressively from the temporal to nasal borders. LHON optic nerves showed an orderly loss of axons, starting inferotemporally, progressing centrally, and sparing the superonasal region until the end. Values generated from the NFL-SI equation fit a linear regression curve (R2 = 0.97; P < 0.001). Conclusions. The quantitative histopathologic data from this study revealed that the PMB is most susceptible in LHON, supporting clinical findings seen early in the course of disease onset. The present study also showed that the subsequent progression of axonal loss within the optic nerve can be predicted precisely with the NFL-SI equation. The results presented provided further insight into the pathophysiology of LHON.

Pan, Billy X.; Ross-Cisneros, Fred N.; Carelli, Valerio; Rue, Kelly S.; Salomao, Solange R.; Moraes-Filho, Milton N.; Moraes, Milton N.; Berezovsky, Adriana; Belfort, Rubens; Sadun, Alfredo A.

2012-01-01

125

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

PubMed

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

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

2014-04-01

126

The role of angiotensin converting enzyme and angiotensin ii type 1 receptor gene polymorphisms in patients with nonarteritic anterior ischemic optic neuropathy  

Microsoft Academic Search

ObjectiveTo determine the role of angiotensin converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R) polymorphisms in the pathogenesis of nonartertic anterior ischemic optic neuropathy (NAION).

Ophira Salomon; Rima Dardik; David M Steinberg; Shimon Kurtz; Nurit Rosenberg; Joseph Moisseiev; Ruth Huna-Baron

2000-01-01

127

Hyperhomocystinemia in patients with nonarteritic anterior ischemic optic neuropathy, central retinal artery occlusion, and central retinal vein occlusion 1 1 Received October 23, 1999. Accepted March 28, 2000  

Microsoft Academic Search

ObjectiveThis study aimed to determine the prevalence of hyperhomocystinemia among patients with nonarteritic anterior ischemic optic neuropathy (NAION), central retinal artery occlusion (CRAO), or central retinal vein occlusion (CRVO).

Pazit Pianka; Yehoshua Almog; Oran Man; Michaela Goldstein; Ben-Ami Sela; Anat Loewenstein

2000-01-01

128

Central corneal thickness measurements in nonarteritic anterior ischemic optic neuropathy patients: a controlled study.  

PubMed

Purpose. To measure central corneal thickness (CCT) in patients with history of nonarteritic anterior ischemic optic neuropathy (NAION). Patients and Methods. Patients older than 40 years with a history of NAION (group 1) were prospectively evaluated including full eye examination and central corneal thickness (CCT) pachymetry. Patients with a history of intraocular surgery, corneal disease, glaucoma, and contact lens wear were excluded. Measurements were also performed in a gender and age matched control group (group 2). Results. Thirty-one eyes of 31 NAION patients in group 1 were included and 30 eyes of 30 participants in group 2. There were 15 men in group 1 and 9 in group 2 (P = 0.141), and mean age of the patients was 59 ± 10 years in group 1 versus 61 ± 11 years in group 2 (P = 0.708). Mean CCT was 539 ± 30 microns in group 1 and 550 ± 33 microns in group 2 (P = 0.155). Conclusion. Patients with NAION have no special characteristic of CCT in contrast to the crowded optic disc known to be a significant anatomic risk factor for NAION. More studies should be carried out to investigate CCT and other structure related elements in NAION patients. PMID:24804080

Jabaly-Habib, Haneen; Naftali, Modi; Habib, George

2014-01-01

129

A mutation of mitochondrial DNA in Japanese families with Leber's hereditary optic neuropathy.  

PubMed

Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease characterized by optic nerve degeneration associated with severe bilateral visual loss in young men and occasionally in women. A mitochondrial DNA (mtDNA) replacement mutation in LHON patient, G to A transition at nucleotide position (nt) 11778 converting the 340th arginine to histidine in the NADH dehydrogenase subunit 4, was detected as SfaNI site polymorphism (Wallace et al., Science, 242: 1427-1430, 1988). To evaluate if the SfaNI site loss can be used to diagnose LHON patients, mtDNAs from peripheral blood of six affected males including five probands from five unrelated Japanese families with LHON, a pair of parents and a normal sister of one of the probands and 4 control persons were analyzed using PCR amplification method. The mutation of leukocyte mtDNA at nt 11778 was identified in all of the affected patients, the normal mother and the sister examined, while the father who is normal and 4 control persons did not show the change. These findings support that the mutation at nt 11778 is also associated with LHON in the Japanese and the test of the SfaNI site loss described here is useful for confirming the clinical diagnosis of LHON patients with the mutation at nt 11778. PMID:1681125

Fujiki, K; Hotta, Y; Hayakawa, M; Saito, K; Ara, F; Ueda, S; Goto, T; Ishida, M; Yanashima, K; Shiono, T

1991-06-01

130

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

2011-01-01

131

Central Corneal Thickness Measurements in Nonarteritic Anterior Ischemic Optic Neuropathy Patients: A Controlled Study  

PubMed Central

Purpose. To measure central corneal thickness (CCT) in patients with history of nonarteritic anterior ischemic optic neuropathy (NAION). Patients and Methods. Patients older than 40 years with a history of NAION (group 1) were prospectively evaluated including full eye examination and central corneal thickness (CCT) pachymetry. Patients with a history of intraocular surgery, corneal disease, glaucoma, and contact lens wear were excluded. Measurements were also performed in a gender and age matched control group (group 2). Results. Thirty-one eyes of 31 NAION patients in group 1 were included and 30 eyes of 30 participants in group 2. There were 15 men in group 1 and 9 in group 2 (P = 0.141), and mean age of the patients was 59 ± 10 years in group 1 versus 61 ± 11 years in group 2 (P = 0.708). Mean CCT was 539 ± 30 microns in group 1 and 550 ± 33 microns in group 2 (P = 0.155). Conclusion. Patients with NAION have no special characteristic of CCT in contrast to the crowded optic disc known to be a significant anatomic risk factor for NAION. More studies should be carried out to investigate CCT and other structure related elements in NAION patients.

Jabaly-Habib, Haneen; Naftali, Modi; Habib, George

2014-01-01

132

Posterior reversible encephalopathy syndrome in a leber hereditary optic neuropathy patient with mitochondrial DNA 11778G>A point mutation.  

PubMed

Leber hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disorder that primarily affects the optic nerve. We report a case of reduced visual acuity secondary to optic atrophy in a 13-year-old boy. Transient seizures developed subsequently. Serial magnetic resonance imaging of the brain showed posterior reversible encephalopathy syndrome. Ragged red fibers were not detected on skeletal muscle biopsy. A 11778G>A mitochondrial DNA point mutation was identified in the lymphocytes isolated from peripheral blood. His younger brother was a carrier with the same mutation. The presentation of this case is unusual documenting LHON in association with PRES. PMID:23782927

Da, Yuwei; Zhang, Xuxiang; Li, Fang; Yang, Xiaoping; Zhang, Xinqing; Jia, Jianping

2013-09-01

133

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

2007-01-01

134

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

Microsoft Academic Search

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

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

2002-01-01

135

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

PubMed Central

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

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

2011-01-01

136

Grand Rounds: Could Occupational Exposure to n-Hexane and Other Solvents Precipitate Visual Failure in Leber Hereditary Optic Neuropathy?  

PubMed Central

Context Leber hereditary optic neuropathy (LHON) is a maternally inherited loss of central vision related to pathogenic mutations in the mitochondrial genome, which are a necessary but not sufficient condition to develop the disease. Investigation of precipitating environmental/occupational (and additional genetic) factors could be relevant for prevention. Case presentation After a 6-month period of occupational exposure to n-hexane and other organic solvents, a 27-year-old man (a moderate smoker) developed an optic neuropathy. The patient had a full ophthalmologic and neurologic investigation, including standardized cycloergometer test for serum lactic acid levels and a skeletal muscle biopsy. His exposure history was also detailed, and he underwent genetic testing for LHON mitochondrial DNA mutations. The patient suffered a sequential optic neuropathy with the hallmarks of LHON and tested positive for the homoplasmic 11778G ? A/ND4 mutation. Routine laboratory monitoring revealed increased concentrations of urinary 2.5 hexandione (n-hexane metabolite) and hippuric acid (toluene metabolite) in the period immediately preceding the visual loss. Discussion In a subject carrying an LHON mutation, the strict temporal sequence of prolonged appreciable occupational exposure followed by sudden onset of visual loss must raise a suspicion of causality (with a possible further interaction with tobacco smoke). Relevance In this article, we add to the candidate occupational/environmental triggers of LHON and highlight the need for appropriate case–control (and laboratory) studies to validate the causal effect of mixed toxic exposures.

Carelli, Valerio; Franceschini, Flavia; Venturi, Silvia; Barboni, Piero; Savini, Giacomo; Barbieri, Giuseppe; Pirro, Ettore; La Morgia, Chiara; Valentino, Maria L.; Zanardi, Francesca; Violante, Francesco S.; Mattioli, Stefano

2007-01-01

137

Leber's hereditary optic neuropathy with 14484 mutation in Central Java, Indonesia.  

PubMed

Leber's hereditary optic neuropathy (LHON) is a maternally inherited late-onset form of blindness characterized by acute or subacute bilateral retinal degradation resulting in a permanent loss of central vision. G11778A, C3460A, and T14484C mutations on mitochondrial DNA (mtDNA) are specific for LHON and account for most, but not all, worldwide LHON cases. A six-generation Indonesian LHON family with the T14484C mutation was analyzed. Polymerase chain reaction/restriction fragment length polymorphism analysis showed that all of the maternal lineages had the T14484C mutation in a homoplasmic form. Penetrance of the disease (33.3%) and male predominance (3:1) was similar to other worldwide LHON with the T14484C mutation. The incidence of offspring born to affected mothers was no different from that of unaffected mothers, and the age distribution of cases was no higher than that of asymptomatic carriers. Eight secondary mutations were sought but not detected. The patients of this family belonged to haplogroup M. These findings support the idea that the mtDNA backgrounds involved in the expression of LHON mutations in southeast Asians are different from those of Europeans. PMID:12827453

Nishioka, Tomoki; Tasaki, Mamoru; Soemantri, Augustinus; Dyat, Marbaniati; Susanto, J C; Tamam, Moedrik; Sudarmanto, Bambang; Ishida, Takafumi

2003-01-01

138

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

PubMed Central

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

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

2008-01-01

139

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

PubMed

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

2008-12-10

140

The NDUFB11 gene is not a modifier in Leber hereditary optic neuropathy.  

PubMed

Over 95% of Leber hereditary optic neuropathy (LHON) cases are due to mutations in mitochondrial DNA-encoded subunits of NADH:ubiquinone oxidoreductase (E.C.1.6.5.3., complex I). A recessive X-linked susceptibility gene that acts synergistically with the primary mtDNA mutation to produce visual loss is suggested by the high male-to-female ratio among LHON patients. The ESSS protein is a recently isolated subunit of bovine heart mitochondrial complex I. We revisited the genomic sequence of NDUFB11, the human homolog mapping to chromosome Xp11.23, and identified two mRNA isoforms showing different expression profiles in human tissues. Cultured skin fibroblasts from four LHON patients showed a pattern of expression similar to normal controls. Moreover, NDUFB11 did not seem to influence risk and age at onset of visual loss in a total of 65 individuals from 35 Italian LHON families. Also, the gene was not affected in 11 children with a severe encephalopathy associated with decreased complex I activity in skeletal muscle. PMID:17292333

Petruzzella, Vittoria; Tessa, Alessandra; Torraco, Alessandra; Fattori, Fabiana; Dotti, Maria Teresa; Bruno, Claudio; Cardaioli, Elena; Papa, Sergio; Federico, Antonio; Santorelli, Filippo M

2007-03-30

141

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

PubMed Central

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

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

2003-01-01

142

Pseudo-Foster Kennedy syndrome in a patient with anterior ischemic optic neuropathy and a nonbasal glioma.  

PubMed

A 49-year-old woman with a 6-year history of headaches was found to have a pale right optic disc with narrowed retinal arterioles and a congested left optic disc. Her visual acuity was 20/20 in each eye with normal visual fields in May 1983. These findings were attributed to a previous attack of non-arteritic anterior ischemic optic neuropathy (AION). She had a normal neurologic examination and a normal head computed tomographic (CT) scan performed 2 years prior to her initial ophthalmologic evaluation. She was followed over the next 2 years without change in her fundus examination. In December 1987, after a generalized tonic-clonic seizure, she was found to have a large right frontoparietal mass without direct impingement on the optic nerves, or chiasm on neuroradiological studies. At this time she developed marked papilledema in the left eye with a pale optic disc in the right eye remaining unchanged. Histopathological diagnosis of malignant glioma was made. Two diseases, ischemic optic neuropathy and glioma, in one patient represents a bizarre example of the pseudo-Foster Kennedy syndrome. PMID:2144536

Limaye, S R; Adler, J

1990-09-01

143

Glaucomatous optic neuropathy evaluation project: factors associated with underestimation of glaucoma likelihood.  

PubMed

IMPORTANCE Glaucoma is a significant health problem for which diagnosis remains suboptimal. Optic disc evaluation, which is fundamental to the diagnosis, is a difficult skill to acquire. OBJECTIVES To determine the optic disc characteristics that most influence decision making in the assessment of glaucoma likelihood and to ascertain the optic disc features associated with overestimation and underestimation of glaucoma likelihood. DESIGN, SETTING, AND PARTICIPANTS This prospective, observational, Internet-based study with multinational participation included 197 ophthalmic clinicians (37 glaucoma subspecialists, 51 comprehensive ophthalmologists, and 109 ophthalmology trainees) from 22 countries who self-registered for the Glaucomatous Optic Neuropathy Evaluation (GONE) Project from December 1, 2008 through June 30, 2010. INTERVENTIONS A series of 42 monoscopic optic disc photographs of healthy and glaucomatous eyes were presented to clinicians using the GONE Project Program. Participants were asked to assess each disc according to 9 conventional topographic features and assign a presumptive grade for glaucoma likelihood. MAIN OUTCOMES AND MEASURES Agreement (? and weighted ?) among participants for disc signs and glaucoma likelihood and contributions of disc-related factors to overestimation and underestimation of glaucoma likelihood. RESULTS Ophthalmology trainees and comprehensive ophthalmologists underestimated glaucoma likelihood in a mean (SD) of 22.1%?(1.6%) and 23.8%?(1.8%) of discs, respectively. Underestimation of vertical cup-disc ratio and failure to identify retinal nerve fiber layer loss, disc hemorrhage, or rim loss were most likely to lead to underestimation of glaucoma. When all 4 features were inaccurately assessed, underestimation of glaucoma likelihood increased to 43.0%. Ophthalmology trainees and comprehensive ophthalmologists overestimated glaucoma likelihood in a mean (SD) of 13.0%?(1.2%) and 8.9%?(1.3%) of discs, respectively. Overestimation of glaucoma likelihood was associated with overestimation of retinal nerve fiber layer loss, rim loss, vertical cup-disc ratio, disc hemorrhage, and incorrect assessment of disc tilt and was more likely in large discs. CONCLUSIONS AND RELEVANCE Ophthalmology trainees and comprehensive ophthalmologists underestimated glaucoma likelihood in approximately 1 in 5 disc photographs and were twice as likely to underestimate as overestimate glaucoma likelihood. Underestimating the vertical cup-disc ratio and cup shape and missing retinal nerve fiber layer defects and disc hemorrhage were the key errors that led to underestimation. When all 4 parameters were incorrectly assessed, underestimation increased to almost 1 in 2. PMID:24699817

O'Neill, Evelyn C; Gurria, Lulu U; Pandav, Surinder S; Kong, Yu Xiang G; Brennan, Jessica F; Xie, Jing; Coote, Michael A; Crowston, Jonathan G

2014-05-01

144

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

PubMed Central

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

Morrison, John C.

2006-01-01

145

Clinical features of MS associated with Leber hereditary optic neuropathy mtDNA mutations  

PubMed Central

Objective: To determine whether the association between multiple sclerosis (MS) and Leber hereditary optic neuropathy (LHON) (known as “Harding disease”) is a chance finding, or the 2 disorders are mechanistically linked. Methods: We performed a United Kingdom–wide prospective cohort study of prevalent cases of MS with LHON mitochondrial DNA (mtDNA) mutations. The new cases were compared with published cases, enabling a comprehensive clinical description. We also performed a meta-analysis of studies screening patients with MS for LHON mtDNA mutations to find evidence of a genetic association. Results: Twelve new patients were identified from 11 pedigrees, and 44 cases were identified in the literature. The combined cohort had the following characteristics: multiple episodes of visual loss, predominance for women, and lengthy time interval before the fellow eye is affected (average 1.66 years), which is very atypical of LHON; conversely, most patients presented without eye pain and had a poor visual prognosis, which is unusual for optic neuritis associated with MS. The number of UK cases of LHON-MS fell well within the range predicted by the chance occurrence of MS and the mtDNA mutations known to cause LHON. There was no association between LHON mtDNA mutations and MS in a meta-analysis of the published data. Conclusions: Although the co-occurrence of MS and LHON mtDNA mutations is likely to be due to chance, the resulting disorder has a distinct phenotype, implicating a mechanistic interaction. Patients with LHON-MS have a more aggressive course, and prognostication and treatment should be guarded.

Pfeffer, Gerald; Burke, Ailbhe; Yu-Wai-Man, Patrick; Compston, D. Alastair S.

2013-01-01

146

Genetic variation in the methylenetetrahydrofolate reductase gene, MTHFR, does not alter the risk of visual failure in Leber's hereditary optic neuropathy  

PubMed Central

Purpose Focal neurodegeneration of the optic nerve in Leber hereditary optic neuropathy (LHON) is primarily due to a maternally inherited mitochondrial DNA mutation. However, the markedly reduced penetrance of LHON and segregation pattern of visual failure within families implicates an interacting nuclear genetic locus modulating the phenotype. Folate deficiency is known to cause bilateral optic neuropathy, and defects of folate metabolism have been associated with nonarteritic ischemic optic neuropathy. Methods Methylenetetrahydrofolate reductase (MTHFR) catalyzes a critical step in folate metabolism, and genetic variation in MTHFR has been associated with several late-onset neurodegenerative diseases. Results We therefore determined whether functional genetic variants in MTHFR could account for the reduced penetrance in LHON by studying 414 LHON mtDNA mutation carriers. We found no evidence of association between visual failure in LHON and MTHFR polymorphisms or the MTHFR haplotype. Conclusions Genetic variation in MTHFR does not provide an explanation for the variable phenotype in LHON.

Hudson, Gavin; Yu-Wai-Man, Patrick; Zeviani, Massimo

2009-01-01

147

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

2011-01-01

148

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.

2012-01-01

149

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

PubMed Central

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

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

2013-01-01

150

Effects of Idebenone on Color Vision in Patients With Leber Hereditary Optic Neuropathy  

PubMed Central

Background: The authors investigated the correlation of protan and tritan color vision with disease characteristics in Leber hereditary optic neuropathy (LHON). The authors also characterized the therapeutic potential of idebenone in protecting patients from developing dyschromatopsia in LHON. Methods: Color contrast data of 39 LHON patients participating in a randomized, double-blind placebo-controlled intervention study were evaluated. Patients reported disease onset <5 years before enrolment and were genetically confirmed. Protan and tritan color contrast sensitivity was measured using a computer graphics method in patients receiving idebenone (Catena; 900 mg/d; N = 28) or placebo (N = 11) for 6 months. Results: Mean age of patients was 28.1 years, 87.2% were men, 76.9% carried the m11778G>A mutation, and mean duration since onset was 2 years. Assessing protan and tritan color vision at baseline revealed a high degree of color confusion even in young patients (<25 years) and with a short history of disease (<1 year). Treatment with idebenone improved tritan color vision compared with placebo (P = 0.008 at week 24); a similar trend was seen for protan. The effect of idebenone was most prominent in patients with discordant visual acuity (interocular difference of logMAR >0.2). In this subgroup, the treatment effect at week 24 was 20.4% (P = 0.005) in favor of idebenone for the tritan color domain and 13.5% (P = 0.067) for the protan domain. Conclusion: This study confirms that protan and tritan color confusion is an early symptom in LHON. Treatment with idebenone can protect from loss of color vision, particularly in patients who are at imminent risk of further vision loss.

Rudolph, Guenther; Dimitriadis, Konstantinos; Buchner, Boriana; Heck, Suzette; Al-Tamami, Jasmina; Seidensticker, Florian; Rummey, Christian; Leinonen, Mika; Meier, Thomas

2013-01-01

151

ANTERIORNA ISHEMI?NA OPTI?NA NEVROPATIJA KOT POSLEDICA ZDRAVLJENJA Z INTERFERONOM ALFA ANTERIOR ISCHEMIC OPTIC NEUROPATHY SECONDARY TO INTERFERON ALPHA  

Microsoft Academic Search

Background. Anterior ischemic optic neuropathy rarely occurs with interferon alpha therapy. The mechanism by which interferon induces anterior ischemic optic neuro- pathy is unknown. Methods. A 62-year-old man presented with complaints of sudden severe loss of vision in the left eye. He has been re- ceiving interferon alpha and ribavirin for chronic infection with hepatitis C virus. Vision loss occurred

Stanka Godina-Kariž; Nives Avancini

152

Characterization of retinal nerve fiber layer thickness changes associated with Leber's hereditary optic neuropathy by optical coherence tomography  

PubMed Central

In the present study, the changes in the retinal nerve fiber layer (RNFL) thickness associated with Leber’s hereditary optic neuropathy (LHON) were examined by Cirrus high definition-optical coherence tomography (OCT), and the correlation between the RNFL thickness and the best corrected visual acuity (BCVA) was evaluated. A cross-sectional study was performed. Sixty-eight eyes from patients with LHON and 30 eyes from healthy individuals were scanned. Affected eyes were divided into 5 groups according to disease duration: Group 1, ?3 months; group 2, 4–6 months; group 3, 7–9 months; group 4, 10–12 months; and group 5, >12 months. The RNFL thickness of the temporal, superior, nasal and inferior quadrants and the 360° average were compared between the LHON groups and the control group. The eyes in groups 1 and 2 were observed to have a thicker RNFL in the superior, nasal and inferior quadrants and a higher 360°-average RNFL thickness compared with those of the control group (P<0.05), the RNFL was observed to be thinner in the temporal quadrant in groups 1 and 2. The eyes in groups 3 and 4 showed a thinner RNFL in the temporal (P=0.001), superior and inferior (both P<0.05) quadrants, and a lower 360°-average RNFL thickness as compared with controls (P=0.001). No significant correlation was identified between BCVA and RNFL thickness. RNFL thickness was observed to undergo a unique process from thickening to thinning in the patients with LHON. Changes in different quadrants occurred at different time periods and the BCVA was not found to be correlated with RNFL thickness.

ZHANG, YIXIN; HUANG, HOUBIN; WEI, SHIHUI; QIU, HUAIYU; GONG, YAN; LI, HONGYANG; DAI, YANLI; JIANG, ZHAOCAI; LIU, ZIHAO

2014-01-01

153

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

PubMed

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

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

2012-03-01

154

Peripheral Neuropathy  

MedlinePLUS

... central part of the body. Many people with diabetic neuropathy experience this pattern of ascending nerve damage. ... to reduce neuropathic symptoms and help people with diabetic neuropathy avoid further nerve damage. Inflammatory and autoimmune ...

155

Rare Primary Mitochondrial DNA Mutations and Probable Synergistic Variants in Leber's Hereditary Optic Neuropathy  

PubMed Central

Background Leber’s hereditary optic neuropathy (LHON) is a maternally inherited blinding disorder, which in over 90% of cases is due to one of three primary mitochondrial DNA (mtDNA) point mutations (m.11778G>A, m.3460G>A and m.14484T>C, respectively in MT-ND4, MT-ND1 and MT-ND6 genes). However, the spectrum of mtDNA mutations causing the remaining 10% of cases is only partially and often poorly defined. Methodology/Principal Findings In order to improve such a list of pathological variants, we completely sequenced the mitochondrial genomes of suspected LHON patients from Italy, France and Germany, lacking the three primary common mutations. Phylogenetic and conservation analyses were performed. Sixteen mitochondrial genomes were found to harbor at least one of the following nine rare LHON pathogenic mutations in genes MT-ND1 (m.3700G>A/p.A132T, m.3733G>A-C/p.E143K-Q, m.4171C>A/p.L289M), MT-ND4L (m.10663T>C/p.V65A) and MT-ND6 (m.14459G>A/p.A72V, m.14495A>G/p.M64I, m.14482C>A/p.L60S, and m.14568C>T/p.G36S). Phylogenetic analyses revealed that these substitutions were due to independent events on different haplogroups, whereas interspecies comparisons showed that they affected conserved amino acid residues or domains in the ND subunit genes of complex I. Conclusions/Significance Our findings indicate that these nine substitutions are all primary LHON mutations. Therefore, despite their relative low frequency, they should be routinely tested for in all LHON patients lacking the three common mutations. Moreover, our sequence analysis confirms the major role of haplogroups J1c and J2b (over 35% in our probands versus 6% in the general population of Western Europe) and other putative synergistic mtDNA variants in LHON expression.

Olivieri, Anna; Pala, Maria; Hooshiar Kashani, Baharak; Reynier, Pascal; La Morgia, Chiara; Valentino, Maria Lucia; Liguori, Rocco; Pizza, Fabio; Barboni, Piero; Sadun, Federico; De Negri, Anna Maria; Zeviani, Massimo; Dollfus, Helene; Moulignier, Antoine; Ducos, Ghislaine; Orssaud, Christophe; Bonneau, Dominique; Procaccio, Vincent; Leo-Kottler, Beate; Fauser, Sascha; Wissinger, Bernd; Amati-Bonneau, Patrizia; Torroni, Antonio; Carelli, Valerio

2012-01-01

156

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

PubMed

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

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

2014-03-01

157

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

2010-01-01

158

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

159

Deep sequencing unearths nuclear mitochondrial sequences under Leber's hereditary optic neuropathy-associated false heteroplasmic mitochondrial DNA variants.  

PubMed

Leber's hereditary optic neuropathy (LHON) is associated with mitochondrial DNA (mtDNA) ND mutations that are mostly homoplasmic. However, these mutations are not sufficient to explain the peculiar features of penetrance and the tissue-specific expression of the disease and are believed to be causative in association with unknown environmental or other genetic factors. Discerning between clear-cut pathogenetic variants, such as those that appear to be heteroplasmic, and less penetrant variants, such as the homoplasmic, remains a challenging issue that we have addressed here using next-generation sequencing approach. We set up a protocol to quantify MTND5 heteroplasmy levels in a family in which the proband manifests a LHON phenotype. Furthermore, to study this mtDNA haplotype, we applied the cybridization protocol. The results demonstrate that the mutations are mostly homoplasmic, whereas the suspected heteroplasmic feature of the observed mutations is due to the co-amplification of Nuclear mitochondrial Sequences. PMID:22589247

Petruzzella, Vittoria; Carrozzo, Rosalba; Calabrese, Claudia; Dell'Aglio, Rosa; Trentadue, Raffaella; Piredda, Roberta; Artuso, Lucia; Rizza, Teresa; Bianchi, Marzia; Porcelli, Anna Maria; Guerriero, Silvana; Gasparre, Giuseppe; Attimonelli, Marcella

2012-09-01

160

[Optic nerve swelling and gadolinium contrast enhancement on magnetic resonance imaging in the subacute stage of Leber's hereditary optic neuropathy: a case report].  

PubMed

We report the case of a 50-year-old man with subacute onset of bilateral visual field loss and visual acuity loss. His visual acuity was 0.07 OD/0.09 OS and Goldmann perimetry showed central scotomas. The optic fundi were normal bilaterally. Magnetic resonance imaging (MRI) showed hyperintensity in the right optic nerve on T(2) weighted imaging and swelling of the optic chiasm with slight enhancement of the bilateral optic nerves and the optic chiasm on gadolinium-enhanced imaging. Since sensory disturbance in the left hand and leg was noted in addition to the visual problem, multiple sclerosis (MS) was suspected initially. The patient was treated with intravenous methylprednisolone (1,000 mg/day), plasma exchange therapy, and immunosuppressant therapy. However, his visual disturbance did not improve. He had a history of deafness and family history of visual disturbance, because of which we performed an analysis of mitochondrial DNA. G11778A point mutation was found, and a diagnosis of Leber's hereditary optic neuropathy (LHON) was made. Although gadolinium contrast enhancement and swelling of the optic nerve are rare, this case shows that these findings are not in conflict with LHON. The present case also suggests that mitochondrial dysfunction may trigger the onset of MS-like extraocular symptoms in patients with LHON. PMID:22354234

Furuki, Misako; Ohkubo, Takuya; Ota, Kiyobumi; Ishikawa, Kinya; Yokota, Takanori; Mizusawa, Hidehiro

2012-01-01

161

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

SciTech Connect

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

Krylov, P. N., E-mail: ftt@uni.udm.ru; Zakirova, R. M.; Fedotova, I. V. [Udmurt State University (Russian Federation)] [Udmurt State University (Russian Federation)

2013-10-15

162

[Sarcoid neuropathy].  

PubMed

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

Koga, Michiaki

2014-08-01

163

Patterns of white matter diffusivity abnormalities in Leber's hereditary optic neuropathy: a tract-based spatial statistics study.  

PubMed

Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease characterized by retinal ganglion cell degeneration and optic nerve atrophy, leading to a loss of central vision. The aim of this study was to explore the topographical pattern of damage to the brain white matter (WM) tracts from patients with chronic LHON using diffusion tensor (DT) MRI and tract-based spatial statistics (TBSS). Brain dual-echo and DT MRI scans were acquired from 13 patients with chronic LHON and 25 matched controls using a 3.0 T scanner. TBSS analysis was performed using the FMRIB's Diffusion Toolbox. A complete neuro-ophthalmologic examination, including standardized automated Humphrey perimetry as well as average and temporal peripapillary retinal nerve fiber layer thickness (PRNFL) measurements, was obtained in all patients. Mean average and temporal PRNFL thicknesses were decreased significantly in LHON patients. Compared to controls, TBSS analysis revealed significant diffusivity abnormalities in these patients, which were characterized by a decreased fractional anisotropy (FA) and an increased mean diffusivity and radial diffusivity, affecting exclusively the optic tracts and optic radiations (OR). In patients, a significant correlation was found between optic tract average FA and mean visual acuity (r = 0.57, p = 0.04). In LHON patients, DT MRI reveals a microstructural alteration of the WM along the entire visual pathways, with a sparing of the other main WM tracts of the brain. Damage to the OR may be secondary either to trans-synaptic degeneration, which in turn is due to neuroaxonal loss in the retina and optic nerve, or to local mitochondrial dysfunction. PMID:22249289

Milesi, Jacopo; Rocca, Maria A; Bianchi-Marzoli, Stefania; Petrolini, Melissa; Pagani, Elisabetta; Falini, Andrea; Comi, Giancarlo; Filippi, Massimo

2012-09-01

164

Sustained Neuroprotection From a Single Intravitreal Injection of PGJ2 in a Rodent Model of Anterior Ischemic Optic Neuropathy  

PubMed Central

Purpose. Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common cause of sudden optic nerve–related vision loss in persons older than 50 in the United States. There currently is no treatment for this disorder. We previously showed that systemic administration of 15-deoxy, delta (12, 14) prostaglandin J2 (PGJ2) is neuroprotective in our rodent model of AION (rAION). In this study, we determined if a single intravitreal (IVT) injection of PGJ2 is neuroprotective after rAION, and if this method of administration is toxic to the retina, optic nerve, or both. Methods. Toxicity was assessed after a single IVT injection of PGJ2 in one eye and PBS in the contralateral eye of normal, adult Long-Evans rats. Efficacy was assessed by inducing rAION in one eye and injecting either PGJ2 or vehicle immediately following induction, with the fellow eye serving as naïve control. Visual evoked potentials (VEPs) and ERGs were performed before induction and at specific intervals thereafter. Animals were euthanized 30 days after induction, after which immunohistochemistry, transmission electron microscopy, and quantitative stereology of retinal ganglion cell (RGC) numbers were performed. Results. Toxicity: IVT PGJ2 did not alter the VEP or ERG compared with PBS-injected control eyes, and neither IVT PGJ2 nor PBS reduced overall RGC numbers. Efficacy: IVT PGJ2 preserved VEP amplitude, reduced optic nerve edema, and resulted in significant preservation of RGCs and axons in eyes with rAION. Conclusions. A single IVT injection of PGJ2 is nontoxic to the retina and optic nerve and neuroprotective when given immediately after rAION induction.

Touitou, Valerie; Johnson, Mary A.; Guo, Yan; Miller, Neil R.; Bernstein, Steven L.

2013-01-01

165

Entrapment neuropathies.  

PubMed

Compression neuropathy includes a heterogeneous group of focal neuropathy syndromes related to peripheral nerve compression. Although acute or chronic compression-related injury may occur in essentially any peripheral nerve, certain anatomic considerations may predispose certain nerves to intrinsic or extrinsic compression-related injury. The clinical presentations of specific compression or entrapment syndromes depend on factors such as chronicity, location, severity, and mechanism of involvement of a particular nerve. In this article the diagnosis and management strategies of the more common and well-established entrapment and compression-related neuropathy syndromes are addressed. PMID:23642716

Arnold, William David; Elsheikh, Bakri H

2013-05-01

166

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

PubMed

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

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

2013-01-01

167

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

2013-01-01

168

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

PubMed

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

Kawasaki, Aki; Collomb, Sylvie; Léon, Lorette; Münch, Mirjam

2014-03-01

169

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

PubMed

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

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

2012-01-01

170

?-Tocopherol\\/lipid ratio in blood is decreased in patients with Leber's hereditary optic neuropathy and asymptomatic carriers of the 11778 mtDNA mutation  

Microsoft Academic Search

OBJECTIVESLeber's hereditary optic neuropathy (LHON) is a maternally inherited disease characterised by acute or subacute bilateral visual loss in young patients. The primary aetiological event is a mutation in the mitochondrial genome (mtDNA) affecting in most cases mtDNA-encoded subunits of the respiratory chain NADH: coenzyme Q oxidoreductase (complex I). The impaired function of complex I leads to a decline in

P Klivenyi; E Karg; C Rozsa; R Horvath; S Komoly; I Nemeth; S Turi; L Vecsei

2001-01-01

171

Peripheral Neuropathy  

MedlinePLUS

... vitamins. Several B vitamins are useful in treating diabetic neuropathy. These include biotin, choline, inositol, and thiamine. ... primrose oil, has reversed nerve damage in some diabetics. Magnets: A recent study found that socks containing ...

172

Central retinal vein occlusion and nonarteritic ischemic optic neuropathy in 2 patients with mild iron deficiency anemia.  

PubMed

We report on 2 patients with ophthalmologic complications associated with mild iron deficiency anemia. Case 1, a 37-year-old female patient, presented after 4 days of blurred vision in her left eye. Ophthalmoscopic and angiographic findings were consistent with the diagnosis of central retinal vein occlusion (CRVO). Further hematologic investigation into possible causes disclosed mild iron deficiency anemia (Hb 9.4 g/dl, hematocrit 30.5%). After the patient's visual acuity had worsened progressively to 20/50, an initial thrombolytic treatment and continuous intravenous heparinization was started on day 8, followed by oral substitution therapy with ferrous sulfate. On day 14, her visual acuity recovered to 20/20 OS and remained stable during follow-up. Case 2, a 50-year-old female patient, presented with a 1-week-history of blurred vision and metamorphopsia. Her visual acuity was 20/200. Further examination revealed a nonarteritic ischemic optic neuropathy and an iron deficiency anemia as the underlying disease (Hb 7.3 g/dl, hematocrit 25%). Despite intravenous heparinization and systemic treatment with steroids, there was no improvement in visual acuity. Clinicians involved in the management of chronic iron deficiency anemia should be aware of possible ophthalmic manifestations in this disease. PMID:11244344

Kacer, B; Hattenbach, L O; Hörle, S; Scharrer, I; Kroll, P; Koch, F

2001-01-01

173

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

2009-01-01

174

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

PubMed Central

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

2014-01-01

175

A case of polyarteritis nodosa complicated by left central retinal artery occlusion, ischemic optic neuropathy, and retinal vasculitis.  

PubMed

A 23-year-old single female patient developed constitutional manifestations in the form of fever, weight loss, anorexia, malaise, fatigue, and generalized aches in January 1995, 2 weeks after an attack of German measles. This was followed by painful, reddish, macular skin lesions over both legs which healed by dark pigmentation (leucocytoclastic vasculitis), mononeuritis multiplex, and Raynaud's phenomena of both hands and feet. Angiography of lower limbs was done to visualize the arterial tree of both lower limbs and revealed typical beading of distal arterial branches, a diagnosis compatible with polyarteritis nodosa (PAN). At that time, the patient received prednisone (45 mg/day) and azatioprin (100 mg/day) and responded well to treatment. In a second presentation in June 2005, the patient developed sudden attack of loss of vision in her left eye. Ophthalmological examination of the patient revealed evidence of left central retinal artery occlusion, ischemic optic neuropathy. The patient received methyl prednisolone, 1 g IV infusion, daily infusion for three consecutive days followed by oral prednisolone, 30 mg/day. The patient received pulse cyclophosphamide IV infusion (0.6 g/m2) on the fourth day. One week after receiving therapy, the patient progressed from having light perception to counting of fingers from a distance of 1 m. PMID:16575492

Emad, Y; Basaffar, S; Ragab, Y; Zeinhom, F; Gheita, T

2007-05-01

176

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

PubMed Central

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

De Vries, D. D.; Went, L. N.; Bruyn, G. W.; Scholte, H. R.; Hofstra, R. M.; Bolhuis, P. A.; van Oost, B. A.

1996-01-01

177

Classification of Orbital Fractures Using the AO/ASIF System in a Population Surveillance Cohort of Traumatic Optic Neuropathy.  

PubMed

Abstract Purpose: In our prospective nationwide surveillance study of traumatic optic neuropathy (TON) in the United Kingdom, the prevalence of orbital fractures was found to be 39% (47/121). The prevalence of skull fractures was 7.4% (9/121). This study aims to identify the association of craniofacial-orbital fractures with the severity of visual loss. Methods: TON patients who sustained orbital fractures were identified prospectively by population-based active surveillance through the British Ophthalmic Surveillance Unit over a 2-year period. Available CT scans were classified by a head and neck radiologist according to the Arbeitsgemeinschaft für Osteosynthesefragen/Association for the Study of Internal Fixation (AO/ASIF) scheme: the face was divided into 4 units; fractures in each unit were graded according to displacement (A-C) and severity (1.1-3.3). Correlation between severity of craniofacial orbital fractures and visual acuity as well as number of fractured units and visual acuity were evaluated. Results: Twelve of the 25 patients (48%) with imaging available had adequate high resolution craniofacial CT imaging for review and classification using the AO/ASIF system (i.e. 48 classifiable units). Three of 48 (6%) units were undisplaced (grade A), 18 of 48 (29%) units were minimally displaced (grade B), and 4 of 48 (8%) units had largely displaced (grade C) fractures. Twenty-three units (47.9%) had no fractures; 5 patients had radiological evidence of optic canal fractures. Poor visual acuities positively correlated with severity of fractures graded using the AO/ASIF classification (Spearman's rho?=?0.95, p?=?0.05) and number of fractured units (Spearman's rho?=?1.0, p?

Ong, Hon Shing; Qatarneh, Dania; Ford, Rebecca L; Lingam, Ravi Kumar; Lee, Vickie

2014-08-01

178

A case of paraneoplastic optic neuropathy and outer retinitis positive for autoantibodies against collapsin response mediator protein-5, recoverin, and ?-enolase  

PubMed Central

Background Specific cross-reacting autoimmunity against recoverin or collapsin response mediator protein (CRMP)-5 is known to cause cancer-associated retinopathy or paraneoplastic optic neuropathy, respectively. We report a rare case with small cell lung carcinoma developing bilateral neuroretinitis and unilateral focal outer retinitis positive for these antibodies. Case presentation A 67-year-old man developed bilateral neuroretinitis and foveal exudation in the right eye. Optical coherence tomography showed a dome-shaped hyperreflective lesion extending from inner nuclear layer to the photoreceptor layer at the fovea in the right eye. Single-flash electroretinography showed normal a-waves in both eyes and slightly reduced b-wave in the left eye. Results of serological screening tests for infection were within normal limits. The patient’s optic disc swelling and macular exudation rapidly improved after oral administration of prednisolone. Systemic screening detected lung small cell carcinoma and systemic chemotherapy was initiated. Immunoblot analyses using the patient’s serum detected autoantibodies against recoverin, CRMP-5, and ?-enolase, but not carbonic anhydrase II. Neuroretinitis once resolved after almost remission of carcinoma on imaging but it recurred following the recurrence of carcinoma. Conclusions The development of neuroretinitis in this cancer patient with anti-retinal and anti-optic nerve antibodies depended largely on the cancer activity, suggesting the possible involvement of paraneoplastic mechanisms. Patients with paraneoplastic optic neuropathy and retinopathy are likely to develop autoimmune responses against several antigens, thus leading to various ophthalmic involvements.

2014-01-01

179

Compression neuropathy caused by cancer metastasis to the optic nerve canal  

PubMed Central

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

2013-01-01

180

Porphyric neuropathy.  

PubMed

Porphyric neuropathy often poses a diagnostic dilemma; it is typically associated with the hepatic porphyrias, characterized by acute life-threatening attacks of neurovisceral symptoms that mimic a range of acute medical and psychiatric conditions. The development of acute neurovisceral attacks is responsive to environmental factors, including drugs, hormones, and diet. This chapter reviews the clinical manifestations, genetics, pathophysiology, and mechanisms of neurotoxicity of the acute hepatic porphyrias. While the etiology of the neurological manifestations in the acute porphyrias remains undefined, the main hypotheses include toxicity of porphyrin precursors and deficiency of heme synthesis. These hypotheses will be discussed with reference to novel experimental models of porphyric neuropathy. PMID:23931806

Lin, Cindy Shin-Yi; Park, Susanna B; Krishnan, Arun V

2013-01-01

181

Mitochondrial DNA mutation m.10680G > A is associated with Leber hereditary optic neuropathy in Chinese patients  

PubMed Central

Background Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder with gender biased and incomplete penetrance. The majority of LHON patients are caused by one of the three primary mutations (m.3460G > A, m.11778G > A and m.14484T > C). Rare pathogenic mutations have been occasionally reported in LHON patients. Methods We screened mutation m.10680G > A in the MT-ND4L gene in 774 Chinese patients with clinical features of LHON but lacked the three primary mutations by using allele specific PCR (AS-PCR). Patients with m.10680G > A were further determined entire mtDNA genome sequence. Results The optimal AS-PCR could detect as low as 10% heteroplasmy of mutation m.10680G > A. Two patients (Le1263 and Le1330) were identified to harbor m.10680G > A. Analysis of the complete mtDNA sequences of the probands suggested that they belonged to haplogroups B4a1 and D6a1. There was no other potentially pathogenic mutation, except for a few private yet reported variants in the MT-ND1 and MT-ND5 genes, in the two lineages. A search in reported mtDNA genome data set (n = 9277; excluding Chinese LHON patients) identified no individual with m.10680G > A. Frequency of m.10680G > A in Chinese LHON patients analyzed in this study and our previous studies (3/784) was significantly higher than that of the general populations (0/9277) (P = 0.0005). Conclusion Taken together, we speculated that m.10680G > A may be a rare pathogenic mutation for LHON in Chinese. This mutation should be included in future clinical diagnosis.

2012-01-01

182

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

PubMed

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

2012-01-01

183

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

PubMed

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

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

2014-04-01

184

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

PubMed

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

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

2014-08-15

185

A case of neuromyelitis optica harboring both anti-aquaporin-4 antibodies and a pathogenic mitochondrial DNA mutation for Leber's hereditary optic neuropathy.  

PubMed

We report the first case of definite neuromyelitis optica (NMO) with a pathogenic mitochondrial DNA (mtDNA) mutation for Leber's hereditary optic neuropathy (LHON) (G11778A point mutation). A 36-year-old Japanese woman had experienced recurrent neurological symptoms originating from involvements of the optic nerves and spinal cord. She finally lost her bilateral vision, and spastic paraparesis and sensory disturbances below the T6 level remained despite intensive immunotherapies. Brain and spinal magnetic resonance imaging (MRI) revealed T2-high-intensity lesions in the optic nerves and thoracic spinal cord, but no lesions in the brain. A blood examination revealed positivity for both anti-aquaproin-4 antibodies and an LHON mtDNA mutation. PMID:24263387

Shiraishi, Wataru; Hayashi, Shintaro; Kamada, Takashi; Isobe, Noriko; Yamasaki, Ryo; Murai, Hiroyuki; Ohyagi, Yasumasa; Kira, Jun-ichi

2014-02-01

186

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

187

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

2009-12-01

188

Inflammatory neuropathies.  

PubMed

Although not quite as well protected as in the CNS, nerve fibres in peripheral nerves are relatively protected from systemic immune responses and inflammatory reactions by the specialized endoneurial endothelial and perineurial barriers. Expression of MHC class II molecules is restricted to a few macrophage-like cells. Compared with peripheral nerve trunks, there are more of these cells and more permeable blood vessels in the dorsal root ganglia and spinal roots. These are sites of predilection for the inflammatory response in experimental allergic neuritis. This experimental disease can be induced by immunization with either of two myelin proteins, P0 and P2, and a similar but less inflammatory, more chronic demyelinating neuropathy can be induced in rabbits with the glycolipid galactocerebroside. In myelin protein induced EAN CD4+ T helper cell responses are sufficient to transfer full-blown disease but antibodies, of undefined specificity, may also play a part. In rabbit galactocerebroside neuritis, antibodies are probably more important and are directed predominantly against a haptenic group including galactose. Experimental allergic neuritis provides an accurate histological model of GBS and CIDP. A small proportion of patients with GBS and CIDP show T-cell responses to P0 and/or P2 which may mark important pathogenetic reactions. Also some patients with GBS and CIDP have antibodies to gangliosides, including for instance the most abundant peripheral nerve ganglioside LM1, which may also be important. In particular, patients with acute severe GBS and marked axonal degeneration often have IgG antibodies to GM1 and GD1b, while patients with Miller Fisher syndrome are characterized by antibodies to GQ1b. IgM antibodies to ganglioside GM1 are often found in multifocal motor neuropathy with conduction block, but are not a sensitive or specific test for that condition. Antibodies to sulphatide have recently been found in some patients with distal predominantly sensory axonal neuropathy. High titres of antibody to MAG which also react with SGPG are specific for IgM paraproteinaemic demyelinating neuropathy. Antibodies to an approximately 37kDa protein present in neuronal nuclei (Hu) are specific for paraneoplastic sensory neuronopathy usually associated with SCLC. Autoimmune responses to neural antigens have become useful diagnostically in some diseases and probably indicate important pathogenetic mechanisms. In inflammatory demyelinating neuropathy, macrophage-mediated demyelination is probably targetted by both antibody and T-cell mediated autoimmune responses. The nature of the autoantigen and the relative importance of T- versus B-cell responses are likely to vary depending on the nature of any initiating immunization and the host immunogenetic background.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:7921591

Hughes, R A

1994-04-01

189

Ultrafast all-optical switching based on frequency shift accompanied by the semiconductor band-filling effect  

Microsoft Academic Search

Ultrafast all-optical switches are quite attractive for future optical communications and processing. For practical application, important issues are switching speed, repetition rate, and switching energy. We recently proposed a transient cross-phase modulation (T-XPM) all-optical switch. This switch utilizes a frequency shift induced by a transient nonlinear phase shift. The mechanism of the T-XPM all-optical switch not only provides ultrafast and

S. Nakamura; Y. Ueno; K. Tajima

1998-01-01

190

Severe manifestation of Leber's hereditary optic neuropathy due to 11778G>A mtDNA mutation in a female with hypoestrogenism due to Perrault syndrome.  

PubMed

Perrault syndrome (PS) is a rare autosomal recessive condition with ovarian dysgenesis, hearing deficit and neurological abnormalities in female patients. The molecular basis of the syndrome is heterogeneous, mutations in the HSD17B4 gene have been identified in one family and mutations in the HARS2 gene have been found in another one. We have excluded pathogenic changes in the HSD17B4 gene and in the HARS2 gene by a direct sequencing of all coding exons in a female with clinical hallmarks of PS, ataxia and mild mental retardation. In addition, the patient suffers from severe Leber's hereditary optic neuropathy (LHON) due to 11778G>A mtDNA mutation. This case is the first reported patient with PS and LHON. Possible influence of hypoestrogenism on the manifestation of optic neuropathy in this patient is discussed in the context of recent findings concerning the crucial role of estrogens in supporting the vision capacity in LHON-related mtDNA mutation carriers. PMID:23748049

Badura-Stronka, Magdalena; Wawrocka, Anna; Zawieja, Krzysztof; Silska, Sylwia; Krawczy?ski, Maciej Robert

2013-11-01

191

Peripheral neuropathy associated with mitochondrial disease in children.  

PubMed

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

Menezes, Manoj P; Ouvrier, Robert A

2012-05-01

192

Uremic neuropathy.  

PubMed

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

2013-01-01

193

Sudden blindness caused by anterior ischemic optic neuropathy in 5 children on continuous peritoneal dialysis 1 1 Published partially (case 3) in abstract form in Arch Ped 7:437, 2000, and in Pediatr Nephrol 16:C4, 2001  

Microsoft Academic Search

The authors report the occurrence of sudden blindness in 5 children (mean age, 32 months; range, 11 to 60) during continuous peritoneal dialysis regimen. All children presented with loss of light perception, visual fixation and ocular pursuit, and bilateral mydriasis unreactive to bright light. Fundoscopic examination found signs of anterior ischemic optic neuropathy with disc swelling, edema, and hemorrhages. Whereas

Anne-Laure Lapeyraque; Elie Haddad; Jean-Luc André; Dominique Brémond-Gignac; C. Mark Taylor; Pornpimol Rianthavorn; Isidro B Salusky; Chantal Loirat

2003-01-01

194

Subacute diabetic proximal neuropathy  

NASA Technical Reports Server (NTRS)

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

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

1997-01-01

195

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.

2012-01-01

196

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

PubMed Central

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

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

1997-01-01

197

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

PubMed

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

2012-06-01

198

Efficacy of levodopa and carbidopa on visual function in patients with non-arteritic anterior ischaemic optic neuropathy.  

PubMed

The benefit of levodopa and carbidopa therapy in improving visual function in patients with non-arteritic anterior ischaemic neuropathy (NAION) was evaluated. Twenty-four subjects with NAION were randomly selected to receive either levodopa-carbidopa or a placebo. Visual functions of neither the study nor the placebo groups showed improvement. Side effects of levodopa such as dizziness, orthostatic hypotension, vomiting and cardiac arrhythmia were seen. Levodopa and carbidopa had no therapeutic effect on visual recovery in our patients with NAION. PMID:15857324

Simsek, T; Eryilmaz, T; Acaroglu, G

2005-03-01

199

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

2006-01-01

200

Bilateral paraneoplastic optic neuropathy and unilateral retinal compromise in association with prostate cancer: a differential diagnostic challenge in a patient with unexplained visual loss.  

PubMed

We report a 77-year-old Caucasian man with a 1-year complaint of unexplained visual loss and a 4-year history of prostate cancer. A complete ophthalmologic exam, Goldmann visual fields (GVFs), intravenous fluorescein angiography (IVFA), macular and disc optical coherence tomography (OCT), pattern-reversal visual evoked potentials (PVEPs), and flash electroretinograms (ERGs) were performed. On examination, visual acuity was reduced bilaterally. Fundus exam showed juxtapapillary changes (OS > OD) and, in OS, disc pallor, peripheral RPE dropout and whitish retinal discoloration along the arcades. OCTs were normal OU. Cancer-associated retinopathy (CAR) was suspected. A flash ERG was normal OD and markedly reduced and electronegative OS. An IVFA showed bilateral juxtapapillary staining and changes highly suggestive of sequelae of central retinal artery occlusion (CRAO) OS , in which a cilioretinal artery existed along the papillomacular bundle. GVFs showed bilateral blind spot enlargement and centrocecal scotomas, and PVEPs were delayed. These findings suggested cancer-associated optic neuropathy (CAON), confirmed by presence of anti-optic nerve autoantibodies (auto-Abs). No anti-retinal auto-Abs were found. CAON is a less common paraneoplastic manifestation than CAR and it is rarely observed in association with prostate cancer. A combination of visual function testing methods permitted the recognition, in this highly unusual case, of the concurrent presence of unilateral ERG changes most likely attributable to CRAO complications in OS, in all likelihood unrelated to CAON, and not to be confused with unilateral CAR. Auto-Ab testing in combination with visual function tests helps achieve a better understanding of the pathophysiology of vision loss in paraneoplastic visual syndromes. PMID:22569848

Carboni, Giovannella; Forma, Gina; Bond, April D; Adamus, Grazyna; Iannaccone, Alessandro

2012-08-01

201

ND4L gene concurrent 10609T>C and 10663T>C mutations are associated with Leber's hereditary optic neuropathy in a large pedigree from Kuwait  

PubMed Central

Background Leber's hereditary optic neuropathy (LHON) is a condition characterised by a rapid bilateral central vision loss due to death of the retinal ganglion cells, leading to visual impairment commonly occurring during young adulthood. The disease manifests itself more in male patients than female patients. The mtDNA mutations m.11778G>A, m.3460G>A and m.14484T>C are by far more frequent in LHON than any other mutation. In this report, a multi-generational Arab family from Kuwait with 14 male members with LHON was investigated. Methods Complete mtDNA mutational analysis by direct Sanger's sequencing was carried out to detect pathogenic mutations, polymorphisms and haplogrouping. Results All maternally related subjects from this study who were examined expressed the L3 haplotype background, with two concurrent mtDNA mutations, 10609T>C and 10663T>C, that led to non-conservative amino acid changes of Ile47Thr and Val65Ala, respectively. The two variations were absent in 144 normal and ethnicity-matched controls. Conclusions The two identified mutations associated with LHON in this family may exert their pathogenicity through a cumulative or haplogroup effect. This is the first report of the presence of two concurrent mutations in the ND4L gene in individuals with LHON who carry the L3 haplogroup.

Behbehani, Raed; Melhem, Motasem; Alghanim, Ghazi; Behbehani, Kazem; Alsmadi, Osama

2014-01-01

202

Anterior ischaemic optic neuropathy in eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome): a case report and review of the literature.  

PubMed

We report a 62-year-old man with mild fever, headache and acute visual loss in his right eye due to anterior ischaemic optic neuropathy (AION), followed a few days later by pain in the legs and left arm associated with numbness and weakness. Giant cell arteritis complicated by AION was suspected at the beginning and high-dose oral glucocorticoids were started. However, on the basis of the past medical history of nasal polyposis, asthma, and hypereosynophilia as well as of further investigations (biopsy of the nasal mucosa showing granulomatous inflammation with a rich eosinophilic infiltrate, electromyography demonstrating, mononeuritis multiplex and positive p-ANCA), eosinophilic granulomatosis with polyangiitis (EGPA), previously known as Churg-Strauss syndrome, was diagnosed. Because visual acuity in the right eye deteriorated despite glucocorticoid therapy, pulse intravenous cyclophosphamide was started, subsequently replaced by oral azathioprine, while prednisone was slowly tapered. This treatment led to gradual improvement of the neurological symptoms, whereas the right visual impairment remained unchanged. EGPA-related AION is an uncommon lesion that is probably due to vasculitic involvement of posterior ciliary and/or chorioretinal arteries. The prognosis of established AION is poor for the affected eye, even when glucocorticoid treatment is started immediately. However, early recognition of AION and prompt aggressive treatment with high-dose glucocorticoids plus cyclophosphamide can prevent visual loss in the unaffected eye. PMID:24144341

Padovano, Ilaria; Pazzola, Giulia; Pipitone, Nicolò; Cimino, Luca; Salvarani, Carlo

2014-01-01

203

Anti-sulphatide antibodies in peripheral neuropathy.  

PubMed Central

A study was carried out on 135 patients with chronic idiopathic neuropathy (63), neuropathy associated with monoclonal gammopathy (51, including eight with anti-MAG antibody activity) and the Guillain-Barré syndrome (GBS) (21). Serum IgM, IgG and IgA anti-sulphatide antibody titres were compared with titres in 304 patients with other neurological or immunological diseases and in 50 normal subjects. Titres were presented a) as the highest serum dilution at which reactivity could be detected, and b) in the linear region of the optical density curve. A substantial number of patients with neurological or immunological diseases had higher titres than normal subjects. Compared with normal and disease controls, five patients with neuropathy associated with IgMk monoclonal gammopathy had raised titres of IgM anti-sulphatide antibodies and one patient with GBS had raised IgM, IgG and IgA anti-sulphatide antibodies in the acute phase of the disease. Two patients had a predominantly axonal sensory neuropathy with presenting symptoms of painful paresthesiae and minimal neurological deficit. Three patients had a predominantly demyelinating sensorimotor neuropathy associated with anti-MAG antibody activity. The patient with GBS had extensive sensory loss and antibody titres returned to normal within three weeks. Raised titres of anti-sulphatide antibodies occurred in several types of neuropathy, but all had some degree of sensory impairment and associated immunological abnormality.

van den Berg, L H; Lankamp, C L; de Jager, A E; Notermans, N C; Sodaar, P; Marrink, J; de Jong, H J; Bar, P R; Wokke, J H

1993-01-01

204

Inherited peripheral neuropathies.  

PubMed

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

Saporta, Mario A; Shy, Michael E

2013-05-01

205

Inherited mitochondrial neuropathies.  

PubMed

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

Finsterer, Josef

2011-05-15

206

Inherited Peripheral Neuropathies  

PubMed Central

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

Saporta, Mario A.; Shy, Michael E.

2013-01-01

207

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

PubMed

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

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

2013-12-01

208

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

2008-01-01

209

Treatment of peripheral neuropathies.  

PubMed Central

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

Hallett, M; Tandon, D; Berardelli, A

1985-01-01

210

Unilateral pudendal neuropathy  

Microsoft Academic Search

PURPOSE: Obstetric trauma and excessive defecatory straining with perineal descent may lead to pudendal neuropathy with bilateral increase in pudendal nerve terminal motor latencies (PNTML). We have frequently observed unilateral prolongation of PNTML. Diagnostic and therapeutic implications of unilateral pudendal neuropathy are discussed. METHODS: Records of 174 patients referred to pelvic floor laboratory for anorectal manometry and PNTML testing were

Yash P. Sangwan; John A. Coller; Richard C. Barrett; John J. Murray; Patricia L. Roberts; David J. Schoetz

1996-01-01

211

Inducible nitric oxide synthase, Nos2, does not mediate optic neuropathy and retinopathy in the DBA/2J glaucoma model  

PubMed Central

Background Nitric oxide synthase 2 (NOS2) contributes to neural death in some settings, but its role in glaucoma remains controversial. NOS2 is implicated in retinal ganglion cell degeneration in a rat glaucoma model in which intraocular pressure (IOP) is experimentally elevated by blood vessel cauterization, but not in a rat glaucoma model where IOP was elevated by injection of hypertonic saline. To test the importance of NOS2 for an inherited glaucoma, in this study we both genetically and pharmacologically decreased NOS2 activity in the DBA/2J mouse glaucoma model. Methods The expression of Nos2 in the optic nerve head was analyzed at both the RNA and protein levels at different stages of disease pathogenesis. To test the involvement of Nos2 in glaucomatous neurodegeneration, a null allele of Nos2 was backcrossed into DBA/2J mice and the incidence and severity of glaucoma was assessed in mice of each Nos2 genotype. Additionally, DBA/2J mice were treated with the NOS2 inhibitor aminoguanidine and the disease compared to untreated mice. Results Optic nerve head Nos2 RNA levels varied and increased during moderate but decreased at early and severe stages of disease. Despite the presence of a few NOS2 positive cells in the optic nerve head, NOS2 protein was not substantially increased during the glaucoma. Genetic deficiency of Nos2 or aminoguanidine treatment did not alter the IOP profile of DBA/2J mice. Additionally, neither Nos2 deficiency nor aminoguanidine had any detectable affect on the glaucomatous optic nerve damage. Conclusion Glaucomatous neurodegeneration in DBA/2J mice does not require NOS2 activity. Further experiments involving various models are needed to assess the general importance of Nos2 in glaucoma.

Libby, Richard T; Howell, Gareth R; Pang, Iok-Hou; Savinova, Olga V; Mehalow, Adrienne K; Barter, Joseph W; Smith, Richard S; Clark, Abbot F; John, Simon WM

2007-01-01

212

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

PubMed Central

Background An increasing number of mitochondrial DNA (mtDNA) mutations, mainly in complex I genes, have been associated with variably overlapping phenotypes of Leber’s hereditary optic neuropathy (LHON), mitochondrial encephalomyopathy with stroke-like episodes (MELAS) and Leigh syndrome (LS). We here describe the first case in which the m.4171C>A/MT-ND1 mutation, previously reported only in association with LHON, leads also to a Leigh-like phenotype. Case presentation A 16-year-old male suffered subacute visual loss and recurrent vomiting and vertigo associated with bilateral brainstem lesions affecting the vestibular nuclei. His mother and one sister also presented subacute visual loss compatible with LHON. Sequencing of the entire mtDNA revealed the homoplasmic m.4171C>A/MT-ND1 mutation, previously associated with pure LHON, on a haplogroup H background. Three additional non-synonymous homoplasmic transitions affecting ND2 (m.4705T>C/MT-ND2 and m.5263C>T/MT-ND2) and ND6 (m.14180T>C/MT-ND6) subunits, well recognized as polymorphisms in other mtDNA haplogroups but never found on the haplogroup H background, were also present. Conclusion This case widens the phenotypic expression of the rare m.4171C>A/MT-ND1 LHON mutation, which may also lead to Leigh-like brainstem lesions, and indicates that the co-occurrence of other ND non-synonymous variants, found outside of their usual mtDNA backgrounds, may have increased the pathogenic potential of the primary LHON mutation.

2014-01-01

213

Hyperhomocyst(e)inaemia, but not MTHFR C677T mutation, as a risk factor for non-arteritic ischaemic optic neuropathy  

PubMed Central

BACKGROUND/AIMS—Hyperhomocyst(e)inaemia has been identified as a strong risk factor for stroke, myocardial infarction, and deep vein thrombosis. A point mutation of methylene tetrahydrofolate reductase (MTHFR C677T) has been associated with increased plasma homocyst(e)ine levels. To investigate whether hyperhomocyst(e)inaemia and/or MTHFR C677T mutation are associated with non-arteritic ischaemic optic neuropathy (NAION), a case-control study including 59 consecutive patients with NAION and 59 controls matched for age and sex was performed.?METHODS—Fasting plasma homocyst(e)ine levels, MTHFR C677T genotypes, and plasma levels of folate and vitamin B-12 were determined.?RESULTS—Mean plasma homocyst(e)ine levels were significantly higher in patients than in controls (11.8 (SD 5.7) µmol/l v 9.8 (2.5) µmol/l, p = 0.02). The odds ratio for patients with homocyst(e)ine levels exceeding the 95th percentile of control homocyst(e)ine levels was 5.8 (95% CI 1.5-21.4). Mean plasma folate levels were significantly lower in patients than in controls (4.3 (1.7) ng/ml v 5.5 (1.9) ng/ml, p = 0.001), whereas plasma vitamin B-12 levels did not differ significantly. Prevalence of the MTHFR C677T mutation was not significantly increased in patients with NAION compared with controls.?CONCLUSION—These results suggest that hyperhomocyst(e)inaemia, but not MTHFR C677T mutation is associated with NAION. Determination of plasma homocyst(e)ine levels might be of diagnostic value in patients with NAION.??

Weger, M.; Stanger, O.; Deutschmann, H.; Simon, M.; Renner, W.; Schmut, O.; Semmelrock, J.; Haas, A.

2001-01-01

214

Leber hereditary optic neuropathy mutations in the ND6 subunit of mitochondrial complex I affect ubiquinone reduction kinetics in a bacterial model of the enzyme.  

PubMed

LHON (Leber hereditary optic neuropathy) is a maternally inherited disease that leads to sudden loss of central vision at a young age. There are three common primary LHON mutations, occurring at positions 3460, 11778 and 14484 in the human mtDNA (mitochondrial DNA), leading to amino acid substitutions in mitochondrial complex I subunits ND1, ND4 and ND6 respectively. We have now examined the effects of ND6 mutations on the function of complex I using the homologous NuoJ subunit of Escherichia coli NDH-1 (NADH:quinone oxidoreductase) as a model system. The assembly level of the NDH-1 mutants was assessed using electron transfer from deamino-NADH to the 'shortcut' electron acceptor HAR (hexammine ruthenium), whereas ubiquinone reductase activity was determined using DB (decylubiquinone) as a substrate. Mutant growth in minimal medium with malate as the main carbon source was used for initial screening of the efficiency of energy conservation by NDH-1. The results indicated that NuoJ-M64V, the equivalent of the common LHON mutation in ND6, had a mild effect on E. coli NDH-1 activity, while nearby mutations, particularly NuoJ-Y59F, NuoJ-V65G and NuoJ-M72V, severely impaired the DB reduction rate and cell growth on malate. NuoJ-Met64 and NuoJ-Met72 position mutants lowered the affinity of NDH-1 for DB and explicit C-type inhibitors, whereas NuoJ-Y59C displayed substrate inhibition by oxidized DB. The results are compatible with the notion that the ND6 subunit delineates the binding cavity of ubiquinone substrate, but does not directly take part in the catalytic reaction. How these changes in the enzyme's catalytic properties contribute to LHON pathogenesis is discussed. PMID:17894548

Pätsi, Jukka; Kervinen, Marko; Finel, Moshe; Hassinen, Ilmo E

2008-01-01

215

[The analysis of Leber's hereditary optic neuropathy associated with mitochondrial tRNAAla C5601T mutation in seven Han Chinese families].  

PubMed

We reported here the clinical, genetic, and molecular characterization of Leber's hereditary optic neuropathy (LHON) with C5601T mutation in seven Chinese families. The ophthalmologic examinations of seven Chinese families who were clinically diagnosed LHON were conducted. Strikingly, these families exhibited very low penetrance of visual impairment, and the penetrance was 9.5%, 14.3%, 4.5%, 8.3%, 10.0%, 22.2% and 25.0%. Meanwhile, entire mitochondrial genome of seven probands was amplified by PCR using 24 pairs of oligonucleotide primers with overlapping fragments. Molecular analysis of mitochondrial DNA (mtDNA) in these pedigrees revealed the absence of three common LHON associated G11778A, G3460A and T14484C mutations but the presence of homoplastic LHON associated tRNAAla C5601T mutation in probands and other matrilineal relatives. These mtDNA polymorphism sites belongs to the Asian haplogroups G2, G2a1, G2a1, G2, G2b, G2a1 and G2. By analyzing mitochondrial genome, seven LHON families all carry the C5601T mutation. The C5601T mutation occurs at the highly conserved nucleotide (conventional position 59) of tRNAAla, thereby contributing to the structural formation and stabilization of functional tRNAs and leading to mitochondrial dysfunction involved in visual impairment. The incomplete penetrance of visual loss in these seven Chinese pedigrees strongly indicates that the tRNAAla C5601T mutation was itself insufficient to produce a clinical phenotype. The lack of functional mtDNA variants in these pedigrees ruled out the role of mitochondrial background in the phenotypic expression of visual loss. Therefore, nuclear backgrounds and environmental factors seem to be modifying factors for the phenotypic manifestation of the tRNAAla C5601T mutation in the seven Chinese families. PMID:22917908

Zhou, Hui-Hui; Dai, Xian-Ning; Lin, Bei; Mi, Hui; Liu, Xiao-Ling; Zhao, Fu-Xin; Zhang, Juan-Juan; Zhou, Xiang-Tian; Sun, Yan-Hong; Wei, Qi-Ping; Qu, Jia; Guan, Min-Xin

2012-08-01

216

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

PubMed

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

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

2014-04-01

217

A comparison of dose-response characteristics of four NTCP models using outcomes of radiation-induced optic neuropathy and retinopathy  

PubMed Central

Background Biological models are used to relate the outcome of radiation therapy to dose distribution. As use of biological models in treatment planning expands, uncertainties associated with the use of specific models for predicting outcomes should be understood and quantified. In particular, the question to what extent model predictions are data-driven or dependent on the choice of the model has to be explored. Methods Four dose-response models--logistic, log-logistic, Poisson-based and probit--were tested for their ability and consistency in describing dose-response data for radiation-induced optic neuropathy (RION) and retinopathy (RIRP). Dose to the optic nerves was specified as the minimum dose, Dmin, received by any segment of the organ to which the damage was diagnosed by ophthalmologic evaluation. For retinopathy, the dose to the retina was specified as the highest isodose covering at least 1/3 of the retinal surface (D33%) that geometrically covered the observed retinal damage. Data on both complications were modeled separately for patients treated once daily and twice daily. Model parameters D50 and ? and corresponding confidence intervals were obtained using maximum-likelihood method. Results Model parameters were reasonably consistent for RION data for patients treated once daily, D50 ranging from 94.2 to 104.7 Gy and ? from 0.88 to 1.41. Similar consistency was seen for RIRP data which span a broad range of complication incidence, with D50 from 72.2 to 75.0 Gy and ? from 1.51 to 2.16 for patients treated twice daily; 72.2-74.0 Gy and 0.84-1.20 for patients treated once daily. However, large variations were observed for RION in patients treated twice daily, D50 from 96.3 to 125.2 Gy and ? from 0.80 to 1.56. Complication incidence in this dataset in any dose group did not exceed 20%. Conclusions For the considered data sets, the log-logistic model tends to lead to larger D50 and lower ? compared to other models for all datasets. Statements regarding normal tissue radiosensitivity and steepness of dose-response, based on model parameters, should be made with caution as the latter are not only model-dependent but also sensitive to the range of complication incidence exhibited by clinical data.

2011-01-01

218

[Chemotherapy induced peripheral neuropathy].  

PubMed

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

Kolak, Agnieszka; Staros?awska, Elzbieta; Kubiatowski, Tomasz; Kieszko, Dariusz; Cisek, Pawe?; Patyra, Krzysztof Ireneusz; Surdyka, Dariusz; Mocarska, Agnieszka; Burdan, Franciszek

2013-11-01

219

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

2000-10-01

220

HIV peripheral neuropathy.  

PubMed

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

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

2013-01-01

221

Treatments for diabetic neuropathy  

Microsoft Academic Search

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

Andrew J. M. Boulton

2001-01-01

222

Facial expression accompanying pain  

Microsoft Academic Search

The study of facial expression accompanying pain is of both practical and theoretical importance. It has been suggested that nonverbal behavior may provide accurate information on pain states to supplement self-report and that perhaps facial expressions could even serve as accurate measures of pain in the absence of verbal report. Recent studies of specific facial expressions accompanying pain have benefited

Linda LeResche; Samuel F. Dworkin

1984-01-01

223

The altered activity of complex III may contribute to the high penetrance of Leber's hereditary optic neuropathy in a Chinese family carrying the ND4 G11778A mutation.  

PubMed

The ND4 G11778A mutation is the most common mitochondrial DNA mutation leading to Leber's hereditary optic neuropathy (LHON). Despite considerable clinical evidences, the modifier role of nuclear background and mitochondrial haplotypes in phenotypic manifestation of LHON remains poorly understood. We investigated the effect of these modifiers on bioenergetics in lymphoblastoid cell lines derived from five affected subjects of one Chinese family carrying the G11778A mutation and five Chinese controls. Significant reductions in the activities of complexes I and III were observed in mutant cell lines from the Chinese family, whereas the mutant cell lines from other families carrying the same mutation exhibited only reduced activity of complex I. The reduced activities of complexes I and III caused remarkably higher reductions of ATP synthesis in mutant cell lines from the Chinese family than those from other families. The deficient respiration increased generation of reactive oxygen species. The defect in complex III activity, likely resulting from the mitochondrial haplotype or nuclear gene alteration, worsens mitochondrial dysfunction caused by the G11778A mutation, thereby causing extremely high penetrance and expressivity of optic neuropathy in this Chinese family. Our data provide the first experimental evidence that altered activity of complex III modulates the phenotypic manifestation of LHON-associated G11778A mutation. Thus, our findings may provide new insights into the pathophysiology of LHON. PMID:21742061

Qian, Yaping; Zhou, Xiangtian; Liang, Min; Qu, Jia; Guan, Min-Xin

2011-11-01

224

Optic nerve degeneration in the DBA\\/2NNia mouse: is the lamina cribrosa important in the development of glaucomatous optic neuropathy?  

Microsoft Academic Search

To study optic nerve (ON) degeneration in the DBA\\/2NNia (DBA) mouse, a species lacking a lamina cribrosa and a model for secondary\\u000a angle-closure glaucoma, serial semi- and ultra-thin sectioning of the myelinated ON and of the ON head was performed and sections\\u000a evaluated qualitatively and quantitatively by light and electron microscopy. Immunohistochemistry was performed using antibodies\\u000a against collagen type I,

Christian Albrecht May; Thom Mittag

2006-01-01

225

Brachial and lumbar neuropathies.  

PubMed

Sporadic acute brachial plexus neuropathy occurs in approximately 1.64/100,000 population, but may present in epidemic form. Sporadic lumbosacral plexus neuropathy is far less common and has to be distinguished from more common disorders affecting the plexus and roots such as diabetes. Early this century, when serum therapy became popular to treat or prevent prevalent infectious diseases, it became apparent that a plexopathy could follow treatment. It has thus been assumed that many of the cases are due to an autoimmune or inflammatory lesion of the plexus. A wide variety of vaccines, infections and medications seem able to precipitate the disorder. Recent work has shown that cultured lymphocytes from affected patients, but not controls, are able to mount a blastogenic response to components of cadaver brachial plexus. This response seems to be selective not only to the brachial plexus, but also to discrete components of the plexus. The recovery rate in brachial plexus neuropathy is good, being almost 90% at 3 years. Recovery with lumbosacral disease is less satisfactory. Histological material and descriptions of acute brachial plexus neuropathy are rare. There is some evidence that an inflammatory process is present, but the role of demyelination and axonal atrophy in producing the observed clinical signs, is still uncertain. Virtually nothing is known about the histological changes in lumbosacral plexus neuropathy. Treatment is mainly supportive, but important in limiting disability. Steroids may help relieve pain in the acute stages, but do not seem to alter the prognosis. PMID:7921588

Russell, J W; Windebank, A J

1994-04-01

226

Diseases accompanying congenital hypothyroidism.  

PubMed

Abstract Introduction: Extrathyroidal abnormality incidence and especially the incidence of congenital cardiac disease are increased with congenital hypothyroidism. In this present study, it is aimed to evaluate patients who were being followed up for congenital hypothyroidism for accompanying diseases, and to compare impacts of accompanying diseases on prognosis under the light of published articles in the literature. Material and methods: A total of 400 cases which were diagnosed with, treated and followed up for congenital hypothyroidism in our clinic were retrospectively evaluated. Cases with complaining symptoms and without any complaints, but were diagnosed with hypothyroidism as the result of screening tests were enrolled in the study. Results: Of 400 subjects included due to congenital hypothyroidism, 186 (46.5%) were girls and 214 (53.5%) were boys. Accompanying diseases were diagnosed in 113 cases (28.2%). Accompanying diseases according to the frequency order were congenital cardiac disease (n=32, 8.0%), Down syndrome (n=25, 6.3%), inguinal hernia (n=21, 5.30%), undescended testicles (n=8, 2.0%), GH deficiency (n=4, 1.0%), and some other systemic diseases (n=23, 5.8%). In cases accompanied by congenital cardiac diseases, ventricular septal defect (n=10), atrial septal defect (n=9), pulmonary stenosis (n=7), patent ductus arteriosis (n=7), and aortic coarctation (n=3) were detected. Conclusion: In this present study, it was defined that approximately one third of patients with congenital hypothyroidism had an accompanying disease, and cardiac diseases were the most common problem. It is concluded that evaluation of congenital hypothyroidism cases for accompanying diseases, detailed cardiological examination being in the first order, is important for prognosis. PMID:24353135

Ba?, Veysel Nijat; Ozgelen, Sebnem; Cetinkaya, Semra; Aycan, Zehra

2014-05-01

227

Mitochondria and peripheral neuropathies.  

PubMed

There has been considerable progress during the past 24 years in the molecular genetics of mitochondrial DNA and related nuclear DNA mutations, and more than 100 nerve biopsies from hereditary neuropathies related to mitochondrial cytopathy have been accurately examined. Neuropathies were first reported in diseases related to point mutations of mitochondrial DNA, but they proved to be a prominent feature of the phenotype in mitochondrial disorders caused by defects in nuclear DNA, particularly in 3 genes: polymerase gamma 1 (POLG1), mitofusin 2 (MFN2), and ganglioside-induced differentiation-associated protein 1 (GDAP1). Most patients have sensory-motor neuropathy, sometimes associated with ophthalmoplegia, ataxia, seizures, parkinsonism, myopathy, or visceral disorders. Some cases are caused by consanguinity, but most are sporadic with various phenotypes mimicking a wide range of other etiologies. Histochemistry on muscle biopsy, as well as identification of crystalloid inclusions at electron microscopy, may provide a diagnostic clue to mitochondriopathy, but nerve biopsy is often less informative. Nevertheless, enlarged mitochondria containing distorted or amputated cristae are highly suggestive, particularly when located in the Schwann cell cytoplasm. Also noticeable are clusters of regenerating myelinated fibers surrounded by concentric Schwann cell processes, and such onion bulb-like formations are frequently observed in neuropathies caused by GDAP1 mutations. PMID:23147504

Vital, Anne; Vital, Claude

2012-12-01

228

Painful diabetic neuropathy  

Microsoft Academic Search

Chronic painful diabetic neuropathy can cause a variety of challenges, particularly in successful treatment. The pain, which can last for years, can severely impair quality of life. Management is difficult, although the careful use of drugs can be significantly beneficial. Tricyclic and anticonvulsant drugs may be effective, with a variety of drugs available as second line agents. Newer non-drug systems

S. J. Benbow; I. A. MacFarlane

1999-01-01

229

Co-doped TiO{sub 2} films grown on glass: Room-temperature ferromagnetism accompanied with anomalous Hall effect and magneto-optical effect  

SciTech Connect

Room-temperature ferromagnetic oxide semiconductor Co-doped TiO{sub 2} films are grown on glass substrates by sputtering method. Conducting films are ferromagnetic at room temperature that is consistent with the carrier-mediated nature of the ferromagnetism. Nearly full-polarized magnetization, large magneto-optical effect, and anomalous Hall effect are observed at room temperature. The magneto-optical effect shows nearly fourfold enhancement in a one-dimensional magnetophotonic crystal structure with a standard dielectric multilayer (SiO{sub 2}/TiO{sub 2})

Yamasaki, T.; Yamada, Y.; Nakano, M. [Institute for Materials Research, Tohoku University, Sendai 980-8577 (Japan); Fukumura, T. [Institute for Materials Research, Tohoku University, Sendai 980-8577 (Japan); PRESTO, Japan Science and Technology Agency, Saitama 332-0012 (Japan); Ueno, K.; Makino, T. [WPI Advanced Institute for Materials Research, Tohoku University, Sendai 980-8577 (Japan); Kawasaki, M. [WPI Advanced Institute for Materials Research, Tohoku University, Sendai 980-8577 (Japan); Institute for Materials Research, Tohoku University, Sendai 980-8577 (Japan); CREST, Japan Science and Technology Agency, Tokyo 102-0075 (Japan)

2009-03-09

230

Diabetic Neuropathy: Mechanisms to Management  

PubMed Central

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

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

2014-01-01

231

Megaoesophagus due to acrylamide neuropathy.  

PubMed Central

Greyhound dogs exposed to oral acrylamide for a period of eight weeks developed a sensorimotor peripheral neuropathy that had many features in common with acrylamide neuropathy seen in other species. Most of the animals also developed the clinical and radiological features of megaoesophagus. The association of neuropathy and megaoesophagus suggests that an axonopathy of the vagus may be an aetiological factor in this disorder. Images

Satchell, P M; McLeod, J G

1981-01-01

232

The Epidemiology of Diabetic Neuropathy  

Microsoft Academic Search

Peripheral neuropathy is a devastating complication of diabetes mellitus because of the debilitating symptoms it causes or\\u000a associated higher risk of other complications, in particular those involving the lower extremity. This chapter will review\\u000a the prevalence, incidence, and risk factors for different types of diabetic neuropathy. There are seven major types of diabetic\\u000a neuropathy: (1) distal symmetric polyneuropathy, (2) autonomic

Stephanie Wheeler; Nalini Singh; Edward J. Boyko

233

Triphenylphosphite neuropathy in hens  

Microsoft Academic Search

Single doses of triphenyl phosphite (TPP), a triester of trivalent phosphorus, cause ataxia and paralysis in hens. Characteristics\\u000a of neurotoxicity were described as somewhat different from organophosphate induced delayed polyneuropathy (OPIDP), which is\\u000a caused by triesters of pentavalent phosphorus. The onset of TPP neuropathy was reported to occur earlier than that of OPIDP\\u000a (5–10 versus 7–14 days after dosing, respectively),

F. Fioroni; A. Moretto; M. Lotti

1995-01-01

234

Canine inherited hypertrophic neuropathy  

Microsoft Academic Search

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

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

1981-01-01

235

[Radiation-induced neuropathy].  

PubMed

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

Kolak, Agnieszka; Staros?awska, Elzbieta; Kieszko, Dariusz; Cisek, Pawe?; Patyra, Krzysztof Ireneusz; Surdyka, Dariusz; Dobrzy?ska-Rutkowska, Aneta; ?opacka-Szatan, Karolina; Burdan, Franciszek

2013-12-01

236

[Vasculitic peripheral neuropathy].  

PubMed

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

Oya, Yasushi

2013-11-01

237

Peripheral neuropathy and solitary plasmacytoma.  

PubMed Central

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

Read, D; Warlow, C

1978-01-01

238

Neuropathy in a petrol sniffer.  

PubMed

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

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

1986-09-01

239

Neuropathy in a petrol sniffer  

Microsoft Academic Search

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

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

1986-01-01

240

Early asymmetric neuropathy in primary Sjögren’s syndrome  

Microsoft Academic Search

We report three female patients, 43, 47, and 50 years old, with a rare asymmetric form of clinically pure sensory neuropathy\\u000a associated with primary Sjögren’s syndrome. In all three patients glandular involvement was accompanied by peripheral nerve\\u000a disease. Sensory conduction studies showed completely normal results in two of three patients. Yet assessment of thermal-specific\\u000a thresholds and thermal pain thresholds, combined

Miro Denišli?; Duška Meh

1997-01-01

241

Investigation of the Elementary Physical Processes in Plasma of Filamentation and Optical Breakdown Regions Accompanying the Propagation of the Femtosecond Laser Pulse with Wavelength of 950 nm in Air at Atmospheric Pressure  

NASA Astrophysics Data System (ADS)

For the first time comparative investigations are performed of the emission spectra of pure air breakdown plasma initiated by a high-voltage pulse nanosecond discharge and nanosecond and femtosecond optical pulses. The plasma initiated in air by femtosecond laser pulses differs significantly from the plasma initiated by the nanosecond high-voltage discharge and optical breakdown. The propagation of femtosecond laser radiation in pure nitrogen in the filamentation region is accompanied by stimulated emission on transitions of the molecular nitrogen ion at a wavelength of 427.8 nm. The energy of the laser electromagnetic field is accumulated in the field of charged particles and is mainly dissipated in the processes of dissipative recombination. It is demonstrated that the emission spectra of air in the range 0.6-1 ?m coincide almost completely for all excitation types, and in the range 0.2-0.6 ?m, these spectra have the characteristic features caused by the parameters of high-voltage and optical breakdown plasma.

Prokopyev, V. E.; Ivanov, N. G.; Krivonosenko, D. A.; Losev, V. F.

2014-03-01

242

Neuropathy target esterase.  

PubMed Central

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

Glynn, P

1999-01-01

243

Pediatric sciatic neuropathies  

PubMed Central

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

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

2011-01-01

244

Diabetic corneal neuropathy.  

PubMed Central

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

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

1983-01-01

245

Diagnostic approach to peripheral neuropathy  

PubMed Central

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

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

2008-01-01

246

Antibody testing in peripheral neuropathies.  

PubMed

Many autoantibodies have been described in association with peripheral neuropathy, but the use of antibody testing in clinical practice remains a matter of some debate. Serum autoantibodies to gangliosides or glycoproteins are implicated in a variety of sensory and motor neuropathy syndromes. Paraneoplastic antibodies help identify patients who have a neuropathy related to an underlying malignancy. Detection of an autoantibody in the right clinical setting provides some evidence that the peripheral nerve disturbance is immune mediated and that immunomodulatory therapy may be of benefit. PMID:17324719

Vernino, Steven; Wolfe, Gil I

2007-02-01

247

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

2013-01-01

248

Alcoholism, peripheral neuropathy (PNP) and cardiovascular autonomic neuropathy (CAN)  

Microsoft Academic Search

In contrast to diabetic autonomic neuropathy, cardiovascular autonomic neuropathy (CAN) in long-term alcoholics has been studied rarely. Using both standardized bedside tests and computer-assisted analysis of heart rate variability (HRV), we prospectively compared autonomic neurocardial function between 35 strictly selected, detoxified alcoholics (DSM-III-R), and 80 well matched healthy controls. Evidence for a potential CAN was found in 25.7% of all

M. W Agelink; R Malessa; U Weisser; W Lemmer; T Zeit; T Majewski; E Klieser

1998-01-01

249

Canine inherited hypertrophic neuropathy.  

PubMed

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

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

1981-01-01

250

Compression and entrapment neuropathies.  

PubMed

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

2013-01-01

251

Immune-mediated autonomic neuropathies  

Microsoft Academic Search

Improved recognition and availability of noninvasive testing of autonomic disorders has prompted a better understanding of\\u000a disease mechanisms of some disease forms, especially potentially treatable immune-mediated autonomic neuropathies. Development\\u000a is acute, subacute, or less commonly chronic. Autonomic involvement is common and an important cause of morbidity and mortality\\u000a in Guillain-Barré syndrome. Acute autonomic neuropathy can affect parasympathetic, sympathetic, and enteric

Mill Etienne; Louis H. Weimer

2006-01-01

252

Medication-induced peripheral neuropathy  

Microsoft Academic Search

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

Louis H. Weimer

2003-01-01

253

Physical examination of upper extremity compressive neuropathies.  

PubMed

A thorough history and physical examination are vital to the assessment of upper extremity compressive neuropathies. This article summarizes relevant anatomy and physical examination findings associated with upper extremity compressive neuropathies. PMID:23026457

Popinchalk, Samuel P; Schaffer, Alyssa A

2012-10-01

254

Crucifixion and median neuropathy.  

PubMed

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

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

2013-05-01

255

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

PubMed Central

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

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

1996-01-01

256

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

2009-01-01

257

Gold toxicity presenting as peripheral neuropathy  

Microsoft Academic Search

Summary A patient with rheumatoid arthritis developed gold induced peripheral neuropathy after 255 mgms of aurothioglucose. This neuropathy is characterized by weakness and numbness of the hands and feet in association with hyperalgesia of the palmar surface of the hands. The absence of vasculitis permits differentiation of gold neuropathy from the neuritis associates with rheumatoid arthritis or systemic lupus erythematosus.

J. J. Weiss; G. R. Thompson; R. Lazaro

1982-01-01

258

[Neuropathy pain: tactic of treatment].  

PubMed

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

2012-01-01

259

Mitochondrial dynamics in peripheral neuropathies.  

PubMed

Abstract Significance: Mitochondrial dynamics describes the continuous change in the position, size, and shape of mitochondria within cells. The morphological and functional complexity of neurons, the remarkable length of their processes, and the rapid changes in metabolic requirements arising from their intrinsic excitability render these cells particularly dependent on effective mitochondrial function and positioning. The rules that govern these changes and their functional significance are not fully understood, yet the dysfunction of mitochondrial dynamics has been implicated as a pathogenetic factor in a number of diseases, including disorders of the central and peripheral nervous systems. Recent Advances: In recent years, a number of mutations of genes encoding proteins that play important roles in mitochondrial dynamics and function have been discovered in patients with Charcot-Marie-Tooth (CMT) disease, a hereditary peripheral neuropathy. These findings have directly linked mitochondrial pathology to the pathology of peripheral nerve and have identified certain aspects of mitochondrial dynamics as potential early events in the pathogenesis of CMT. In addition, mitochondrial dysfunction has now been implicated in the pathogenesis of noninherited neuropathies, including diabetic and inflammatory neuropathies. Critical Issues: The role of mitochondria in peripheral nerve diseases has been mostly examined in vitro, and less so in animal models. Future Directions: This review examines available evidence for the role of mitochondrial dynamics in the pathogenesis of peripheral neuropathies, their relevance in human diseases, and future challenges for research in this field. Antioxid. Redox Signal. 21, 601-620. PMID:24386984

Sajic, Marija

2014-08-01

260

Pudendal neuropathy in evacuatory disorders  

Microsoft Academic Search

PURPOSE: Aims of the present study were to assess frequency of pudendal neuropathy in patients with constipation and fecal incontinence, to determine its correlation with clinical variables, anal electromyographic assessment, and anal manometric pressures, and to determine usefulness of the pudendal nerve terminal motor latency assessment in evaluation of these evacuatory disorders. METHODS: From 1988 to 1993, 395 patients (constipated,

Carlos A. Vaccaro; Denis M. O. Cheong; Steven D. Wexner; Juan J. Nogueras; Virgilio D. Salanga; Maurice R. Hanson; Reginald C. Phillips

1995-01-01

261

[Femoral neuropathy in urological surgery].  

PubMed

We present four cases of femoral neuropathy due to urological surgery, first case happened after right lumbotomy twenty years ago and the other three cases in the last four years after iliac incision. We review lesion production mecanism, evolution, treatment and prevention of this rare neurological complication. We do a literature review about this pathology related with urological activity. PMID:18020214

Pastor Guzmán, J M; Pastor Navarro, H; Donate Moreno, M J; Pardal Fernández, J M; Carrión López, P; Salinas Sánchez, A; Virseda Rodríguez, J A

2007-09-01

262

Peripheral Neuropathy Following Chloroquine Therapy  

PubMed Central

Four patients were observed who developed similar episodes of peripheral neuropathy following prolonged treatment with chloroquine phosphate. This previously unreported toxic reaction consisted of bilateral loss of knee and ankle reflexes and weakness of the quadriceps muscles. Gradual return to normal followed withdrawal of the chloroquine. Other toxic reactions to the drug are reviewed.

Loftus, Lawrence R.

1963-01-01

263

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

2009-01-01

264

Not all neuropathy in diabetes is of diabetic etiology: Differential diagnosis of diabetic neuropathy  

Microsoft Academic Search

Diabetic peripheral neuropathy is the most common peripheral neuropathy in the developed world; however, not all patients\\u000a with diabetes and peripheral nerve disease have a peripheral neuropathy caused by diabetes. Several (although not all) studies\\u000a have drawn attention to the presence of other potential causes of a neuropathy in individuals with diabetes; 10% to 50% of\\u000a individuals with diabetes may

Roy Freeman

2009-01-01

265

Papilloedema and the optic disc.  

PubMed

The anatomy and blood supply of the optic nerve head are reviewed along with the variations in normal appearance and the aetiology of so-called pseudo-papilloedema. The clinical features and causes of papilloedema due to increased intra-cranial pressure are discussed along with optic disc oedema from other causes. The conditions of optic neuritis, neuropathy and the ischaemic optic neuropathies are also evaluated. PMID:2751237

Cullen, J F

1989-03-01

266

Drug-induced peripheral neuropathies.  

PubMed

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

Argov, Z; Mastaglia, F L

1979-03-10

267

AIDS and AIDS-treatment neuropathies  

Microsoft Academic Search

AIDS and AIDS-treatment neuropathies are common in individuals infected with HIV. As patients live longer due to improved\\u000a antiretroviral therapies, the impact of painful neuropathy on patients’ lives may increase. Several antiretroviral medications\\u000a are known to cause toxic neuropathy in AIDS patients, but this may be outweighed by the beneficial effects of viral suppression.\\u000a Current theories on the pathogenesis of

Derek Williams; Anthony Geraci; David M. Simpson

2001-01-01

268

AIDS and AIDS-treatment neuropathies  

Microsoft Academic Search

AIDS and AIDS-treatment neuropathies are common in individuals infected with HIV. As patients live longer due to improved\\u000a antiretroviral therapies, the impact of painful neuropathy on patients’ lives may increase. Several antiretroviral medications\\u000a are known to cause toxic neuropathy in patients with AIDS, but this may be outweighed by the beneficial effects of viral suppression.\\u000a Current theories on the pathogenesis

Derek Williams; Anthony Geraci; David M. Simpson

2002-01-01

269

Oxaliplatin induced-neuropathy in digestive tumors.  

PubMed

Oxaliplatin is one of the main drugs used in digestive tumors treatment. Peripheral neuropathy is a well-recognized dose-limiting toxicity of OXL. Two types of neuropathy have been described with this agent: acute or transient and chronic or persistent, with different etiology, clinical manifestations and prognosis. This paper is an exhaustive review about the main aspects of oxaliplatin induced peripheral neuropathy, focus in clinical features, treatment, prevention strategies and future approach. PMID:24029604

Sereno, María; Gutiérrez-Gutiérrez, Gerardo; Gómez-Raposo, César; López-Gómez, Miriam; Merino-Salvador, Maria; Tébar, Francisco Zambrana; Rodriguez-Antona, Cristina; Casado, Enrique

2014-01-01

270

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

271

Neuromuscular ultrasound in common entrapment neuropathies.  

PubMed

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

Cartwright, Michael S; Walker, Francis O

2013-11-01

272

Vestibular involvement in peripheral neuropathy: A review.  

PubMed

Abstract Objective: This paper reviews the current literature on involvement of the vestibular division of the eighth cranial nerve in peripheral neuropathies. The literature abounds with references to auditory neuropathy, which is frequently related to more generalized neuropathies, but there is a marked paucity of work regarding vestibular neuropathy. A brief overview of neuropathies and the anatomy of the vestibulocochlear nerve provide the background for a review of the literature of vestibular nerve involvement in a range of neuropathies. Design: A literature search including textbooks, and peer-reviewed published journal articles in online bibliographic databases was conducted. Study sample: Two databases for medical research were included in this review. Results: The review of the literature indicates that vestibular involvement is a common and consistent finding in many peripheral neuropathies of different aetiologies. Specifically, if patients present unsteadiness/ataxia out of proportion to objective signs of somatosensory loss or muscle weakness. Conclusion: This review concludes that vestibular neuropathy, is common in peripheral neuropathy and should be identified to optimize patient management and rehabilitation. PMID:24588465

Buetti, Belinda; Luxon, Linda M

2014-06-01

273

Perineurium talin immunoreactivity decreases in diabetic neuropathy  

Microsoft Academic Search

We studied the immunolocalization of Dp116 (a 116 kDa protein product of the dystrophin gene), vinculin, talin, vimentin, desmin, spectrin and titin in the sural nerve biopsies of 25 patients with peripheral neuropathies of different origin. 4 patients presented with HMSN type 1, 4 with HMSN type 2, 2 with HNPP, 4 with CIDP, 5 with chronic axonal neuropathy of

Anna Mazzeo; Carmelo Rodolico; Maria C Monici; Alba Migliorato; M'hammed Aguennouz; Giuseppe Vita

1997-01-01

274

Pregabalin for painful diabetic peripheral neuropathy  

Microsoft Academic Search

Painful symptoms of diabetic peripheral neuropathy have been shown to be improved by treatment with the antiepileptic drug pregabalin. Freeman et al. performed a meta-analysis of 7 randomized, placebo-controlled trials that evaluated the efficacy and safety of pregabalin treatment for painful diabetic peripheral neuropathy. The trials were consistent in their inclusion and exclusion criteria, but involved a variety of doses

Lee C Rogers; David G Armstrong

2008-01-01

275

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.

2000-01-01

276

Suprascapular neuropathy in volleyball players  

PubMed Central

Background—Suprascapular nerve entrapment with isolated paralysis of the infraspinatus muscle is uncommon. However, this pathology has been reported in volleyball players. Despite a lack of scientific evidence, excessive strain on the nerve is often cited as a possible cause of this syndrome. Previous research has shown a close association between shoulder range of motion and strain on the suprascapular nerve. No clinical studies have so far been designed to examine the association between excessive shoulder mobility and the presence of this pathology. Aim—To study the possible association between the range of motion of the shoulder joint and the presence of suprascapular neuropathy by clinically examining the Belgian male volleyball team with respect to several parameters. Methods—An electromyographic investigation, a clinical shoulder examination, shoulder range of motion measurements, and an isokinetic concentric peak torque shoulder internal/external rotation strength test were performed in 16 professional players. Results—The electrodiagnostic study showed a severe suprascapular neuropathy in four players which affected only the infraspinatus muscle. In each of these four players, suprascapular nerve entrapment was present on the dominant side. Except for the hypotrophy of the infraspinatus muscle, no significant differences between the affected and non-affected players were observed on clinical examination. Significant differences between the affected and non-affected players were found for range of motion measurements of external rotation, horizontal flexion and forward flexion, and for flexion of the shoulder girdle (protraction); all were found to be higher in the affected players than the non-affected players. Conclusions—This study suggests an association between increased range of motion of the shoulder joint and the presence of isolated paralysis of the infraspinatus muscle in volleyball players. However, the small number of patients in this study prevents definite conclusions from being drawn. Key Words: suprascapular neuropathy; infraspinatus muscle; volleyball; shoulder mobility

Witvrouw, E; Cools, A; Lysens, R; Cambier, D; Vanderstraeten, G; Victor, J; Sneyers, C; Walravens, M

2000-01-01

277

[Wernicke encephalopathy accompanying linitis plastica].  

PubMed

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

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

2014-01-01

278

Peripheral neuropathy incidence in inflammatory bowel disease  

PubMed Central

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

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

2013-01-01

279

Autonomic neuropathy in mixed cryoglobulinemia.  

PubMed

A retrospective, cross-sectional study was performed on a series of HCV-related mixed cryoglobulinemia (HCV-MC) patients to assess autonomic neuropathy (AN) and its relation to peripheral neuropathy (PN). Thirty consecutive patients affected by HCV-MC underwent clinical, neurological and electrodiagnostic examinations. Autonomic nervous system (ANS) involvement was assessed by functional cardiovascular tests and sympathetic skin response (SSR) evaluation. Sural nerve biopsy was performed in 10 patients with PN. All patients received steroids, 15 also received recombinant interferon-alpha2b (RIfn-alpha2b). PN occurred in 27 patients (90.0%) and AN in 4 (13.3 %) all with signs of PN. SSR was the autonomic test more frequently altered. Biopsy disclosed axonal degeneration more evident in the 4 patients with AN. Three out of 4 patients with AN received steroids and rIFN-alpha2b and 1 steroids alone. In our study on HCV-MC, it was concluded that AN can occur also without dysautonomic symptoms, SSR appears to be one of the optional tests to use together with dysautonomic tests to identify AN and finally PN and AN do not seem to be positively influenced by addition of rIFN-alpha2b to steroid treatment. PMID:17334955

Ammendola, A; Sampaolo, S; Migliaresi, S; Ambrosone, L; Ammendola, E; Ciccone, G; Di Iorio, G

2007-02-01

280

Peroneal neuropathy after weight loss.  

PubMed

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

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

2000-06-01

281

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

PubMed

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

2012-02-17

282

Impaired bronchomotor responses to field stimulation in guinea-pigs with cisplatin-induced neuropathy.  

PubMed

Pre-treatment with cisplatin (3 mg/kg) i.p. once a day over 6 days induced sensory neuropathy as confirmed by femoral nerve conduction velocity test and significantly decreased contractions induced by electrical field stimulation (100 stimuli, 20 V, 0.1 ms, 20 Hz) in isolated main bronchial rings from guinea-pigs. The field stimulation-induced non-adrenergic, non-cholinergic (NANC) relaxations, however, were amplified in rings from animals with cisplatin neuropathy. The NANC relaxation response was completely blocked by 30 microM N(G)-nitro-L-arginine methyl ester in preparations from both control and cisplatin-treated animals. Superoxide dismutase (40 units/ml) was without effect on NANC relaxation in control rings, however, it substantially decreased NANC relaxation in preparations from animals with cisplatin neuropathy. These results show that cisplatin-induced sensory neuropathy is accompanied by attenuation of neural bronchoconstriction and an enhanced NANC relaxation. The latter is in part attained by an increased peripheral superoxide production. PMID:10973628

Szilvássy, J; Sziklai, I; Racz, T; Horvath, P; Rabloczky, G; Szilvassy, Z

2000-09-01

283

Pathogenesis of Painful Diabetic Neuropathy  

PubMed Central

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

Rajbhandari, Satyan

2014-01-01

284

Diabetic Neuropathies: The Nerve Damage of Diabetes  

MedlinePLUS

... may include numbness, tingling, or pain in the toes, feet, legs, hands, arms, and fingers wasting of ... causes pain or loss of feeling in the toes, feet, legs, hands, and arms. Autonomic neuropathy causes ...

285

Genetics Home Reference: Ataxia neuropathy spectrum  

MedlinePLUS

... part of a group of conditions called the POLG -related disorders. The conditions in this group feature ... neuropathy spectrum is caused by mutations in the POLG gene or, rarely, the C10orf2 gene. The POLG ...

286

Inherited neuropathies: clinical overview and update.  

PubMed

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

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

2013-10-01

287

Genetics Home Reference: Giant axonal neuropathy  

MedlinePLUS

... and Families Resources for Health Professionals What glossary definitions help with understanding giant axonal neuropathy? autosomal ; autosomal ... system ; proteasome ; protein ; recessive ; ubiquitin You may find definitions for these and many other terms in the ...

288

Pattern Recognition Approach to Neuropathy and Neuronopathy  

PubMed Central

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

Barohn, Richard J; Amato, Anthony A.

2014-01-01

289

Idiopathic trigeminal sensory neuropathy. A case report.  

PubMed

Idiopathic trigeminal sensory neuropathy is a rare clinical condition characterized by sensory disturbances on the face. Its symptoms may be permanent or temporary and a wide variety of diagnostic procedures is usually required to establish the diagnosis. Frequently, it is the first manifestation of a systemic disorder. In the majority of cases causal treatment is not possible, even though patients with trigeminal sensory neuropathy should be carefully monitored by physicians. PMID:24166572

Szczudlik, P; Kierdaszuk, B; Bako?, L; Maj, E; Kami?ska, A

2013-01-01

290

Peroneal Neuropathy after Tibio-Fibular Fracture  

PubMed Central

Objective To investigate the injury mechanism in patients who had peroneal neuropathy after a tibio-fibular fracture and the correlation between tibio-fibular fracture location and the severity of the peroneal neuropathy by using electrodiagnosis. Method Thirty-four patients with peroneal neuropathy after a tibio-fibular fracture were recruited for this study. Their medical records, radiologic and electrodiagnostic findings were investigated retrospectively. They were divided into 2 groups according to the existence of a fibular head fracture. The group of patients without the fibular head fracture was further classified according to the criteria of Orthopedic Trauma Association (OTA) classification. The differences between the two groups in the severity of the neuropathy and electrodiagnostic findings were evaluated. Results Nine cases (26.5%) had tibio-fibular fractures with a coexisting fibular-head fracture and 25 cases (73.5%) had tibio-fibular fractures without fractures in the fibular-head area. There was no statistical significance in the correlation between the existence of the fibular head fracture and the severity of the electrodiagnostic findings. Neither was there any statistically significant relationship between the site of the tibio-fibular fracture and the severity of the peroneal neuropathy (p>0.05). Conclusion This study showed there were numerous cases with common peroneal neuropathy after tibiofibular fracture without a coexisting fibular-head fracture, which shows the importance of indirect nerve injury mechanisms as well as that of direct nerve injury as a cause of peroneal neuropathy. In addition, this study showed that there was no statistically significant correlation between the site of tibio-fibular fracture and the severity of peroneal neuropathy.

Kim, Ye Chan

2011-01-01

291

[Median nerve neuropathy after perilunate dislocation injuries].  

PubMed

Purpose: The purpose of this retrospective study was to investigate the frequency and appearance of median nerve neuropathy following perilunate dislocation injuries with respect to the preceding surgical decompression and the clinical outcome. Patients and Methods: 32 patients were followed for a mean of 65 months after surgery for perilunate dislocation, including carpal tunnel release in 13 patients. 10 of 11 patients with clinical symptoms of median nerve affection at follow-up had additionally an electrophysiological examination. Median neuropathy was assumed if 2 or more parameters were pathologic. Patients with and without median neuropathy were compared. The DASH score, pain, wrist motion, grip strength and the Mayo wrist score were used to rate the outcome. Results: In 6 patients, neuropathy of the median nerve persisted since injury in spite of carpal tunnel release in 5 of them. 3 patients showed secondary, delayed median nerve affection. Patients with median neuropathy had a worse result with regard to pain at rest, grip force, the DASH score, and the Mayo wrist score. The difference was statistically significant for pain with activities. Conclusion: Median neuropathy following perilunar dislocation injuries is frequent. It appears rather like a chronic neural lesion than a typical compression syndrome. A primary carpal tunnel release cannot always prevent persistent neural disorders. PMID:24940631

Mühldorfer-Fodor, M; Hohendorff, B; Saalabian, A A; Hahne, M; van Schoonhoven, J; Prommersberger, K-J

2014-06-01

292

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.

2010-01-01

293

Insulin resistance occurres in parallel with sensory neuropathy in STZ-induced diabetes in rats; differential response to early vs late insulin supplementation  

Microsoft Academic Search

Objective: We investigated whether progressive sensory neuropathy was accompanied by changes in whole body insulin sensitivity in rats made diabetic by streptozotocin (STZ). The effects of early and late insulin supplementation were also studied. Materials\\/Methods: The STZ-treated rats failed to gain weight and exhibited stable hyperglycaemia and low plasma insulin levels with a decrease in nerve conduction velocity (NCV) measured

Zoltan Szilvássy; Joseph Nemeth; Péter Kovács; György Paragh; Réka Sári; László Vígh; Barna Peitl

294

Genetics Home Reference: Hereditary sensory and autonomic neuropathy type V  

MedlinePLUS

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

295

Goiter and Laryngeal Sensory Neuropathy  

PubMed Central

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

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

2013-01-01

296

Mouse Models of Diabetic Neuropathy  

PubMed Central

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

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

2007-01-01

297

Abnormal calcium homeostasis in peripheral neuropathies  

PubMed Central

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

Fernyhough, Paul; Calcutt, Nigel A.

2010-01-01

298

[Original articles on axonal neuropathy in 2010].  

PubMed

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

2011-12-01

299

Molecularly Targeted Therapies for Dysimmune Neuropathies  

PubMed Central

Conventional treatment options, including corticosteroids, intravenous immunoglobulin, or plasma exchange, often fail to treat dysimmune neuropathies, such as chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and monoclonal gammopathy with its subtypes. Therefore, a significant percentage of patients require adjunctive immunosuppressive therapies. Considering that even immunosuppressive agents often are ineffective and/or associated with significant toxicities, the need for the development of safe and effective new treatment options is rising. Currently, several monoclonal antibodies (MAbs) have been tested in open-label small-sized studies or even in single cases so as to establish future directions in the therapy of diseases of the peripheral nervous system (PNS). Rituximab, an MAb targeting against the B cell surface membrane protein CD20, is the most widely used and promising MAb for the treatment of dysimmune neuropathies, especially for those in which immunoglobulin M (IgM) autoantibodies are pathogenetically involved. The efficacy of alemtuzumab, bevacizumab, and etanercept to treat various forms of dysimmune neuropathies is currently under investigation. This review looks critically at recent developments in molecularly targeted therapies for dysimmune neuropathies and also highlights areas of future research to pursue.

Argyriou, Andreas A

2009-01-01

300

Porphyric neuropathy: prevention of progression using haeme-arginate.  

PubMed

We report on a patient with acute intermittent porphyria (AIP) who, during treatment with hypertonic glucose, developed peripheral neuropathy. Once haeme-arginate was started, the progression of the neuropathy was attenuated. This suggests that hypertonic glucose may be inadequate in preventing the development of neuropathy in a patient with porphyria. However, haeme-arginate, if started early, can attenuate the progression of porphyric neuropathy. PMID:8258754

Muthane, U B; Vengamma, B; Bharathi, K C; Mamatha, P

1993-12-01

301

Atypical Traumatic Pneumorrhachis Accompanied by Paraparesis  

PubMed Central

Pneumorrhachis, caused by intraspinal air, is an exceptional but important radiographic finding that is accompanied by different etiologies. Pneumorrhachis, by itself, is usually asymptomatic and gets reabsorbed spontaneously. Therefore, the patients with pneumorrhachis are mostly managed conservatively. We encountered a unique case of atypical traumatic pneumorrhachis accompanied by paraparesis.

Kim, Kweon Young; Kang, Jung Hun; Lee, Min Hong; Han, Yong

2014-01-01

302

Reversible peripheral neuropathy in idiopathic hypoparathyroidism.  

PubMed

We describe a 40-year-old male with idiopathic hypoparathyroidism presenting with tetany, proximal weakness, signs of hypocalcaemia including Chvostek and Trousseau's and diminished tendon reflexes in the upper and lower limbs. Electrophysiological studies revealed a sensory-motor neuropathy, predominantly axonal as evidenced by decreased CMAP amplitudes, with normal distal latencies-velocites, except for median nerve where a prolonged distal latency was observed. Serial nerve conduction studies were performed at repeated intervals for 2 years, while he received treatment for hypoparathyroidism (calcium and vitamin D supplementation). A progressive improvement in neuropathy both clinical and on electrophysiological studies was observed. Occurrence of peripheral neuropathy in hypocalcaemic states such as hypoparathyroidism and its reversibility after normalization of calcium homeostasis lend proof to the role of critical Ca2+ ion concentration in the normal functioning of the peripheral axons. PMID:11903124

Goswami, R; Bhatia, M; Goyal, R; Kochupillai, N

2002-02-01

303

Dyslipidemia-Induced Neuropathy in Mice  

PubMed Central

OBJECTIVE Neuropathy is a frequent and severe complication of diabetes. Multiple metabolic defects in type 2 diabetic patients result in oxidative injury of dorsal root ganglia (DRG) neurons. Our previous work focused on hyperglycemia clearly demonstrates induction of mitochondrial oxidative stress and acute injury in DRG neurons; however, this mechanism is not the only factor that produces neuropathy in vivo. Dyslipidemia also correlates with the development of neuropathy, even in pre-diabetic patients. This study was designed to explore the contribution of dyslipidemia in neuropathy. RESEARCH DESIGN AND METHODS Mice (n = 10) were fed a control (10% kcal %fat) or high-fat (45% kcal %fat) diet to explore the impact of plasma lipids on the development of neuropathy. We also examined oxidized lipid–mediated injury in cultured DRG neurons from adult rat using oxidized LDLs (oxLDLs). RESULTS Mice on a high-fat diet have increased oxLDLs and systemic and nerve oxidative stress. They develop nerve conduction velocity (NCV) and sensory deficits prior to impaired glucose tolerance. In vitro, oxLDLs lead to severe DRG neuron oxidative stress via interaction with the receptor lectin-like oxLDL receptor (LOX)-1 and subsequent NAD(P)H oxidase activity. Oxidative stress resulting from oxLDLs and high glucose is additive. CONCLUSIONS Multiple metabolic defects in type 2 diabetes directly injure DRG neurons through different mechanisms that all result in oxidative stress. Dyslipidemia leads to high levels of oxLDLs that may injure DRG neurons via LOX-1 and contribute to the development of diabetic neuropathy.

Vincent, Andrea M.; Hayes, John M.; McLean, Lisa L.; Vivekanandan-Giri, Anuradha; Pennathur, Subramaniam; Feldman, Eva L.

2009-01-01

304

Diabetes, peripheral neuropathy, and old age disability.  

PubMed

The purpose of this study was to determine whether peripheral neuropathy explains the apparent association between diabetes and disability in old age, and to evaluate the utility of lower extremity function tests in older diabetic adults with and without neuropathy. We evaluated 39 adults, aged 70-79 years, for pressure sensation (log(10)g), vibration perception threshold (VPT; microns), and electrophysiologic function of the peroneal nerve. The subjects included patients with established diabetic neuropathy (DN; n = 14), diabetic controls without neuropathy (DC; n = 13), and nondiabetic controls (NDC; n = 12). Nonparametric statistical methods were used to relate neuropathy measures to performance in tests of walking speed, static and dynamic balance, coordination, and ankle strength (kilograms). Significant age-adjusted correlations were observed between measures of sensory neuropathy and a variety of performance measures, and electrophysiologic measures were related to static balance. DN subjects had significantly higher pressure sensation than NDC (5.17 vs 3.38g, P < 0.05), higher VPT (62.5 vs 21.7 microm, P < 0.05), and lower peroneal motor response amplitudes at multiple sites. Pressure sensation and nerve conduction measures did not differ between DC and NDC. Compared with NDC, DN subjects performed significantly worse on tests of walking speed (0.99 vs 1.34 m/s; P < 0.05), static balance (4.9 vs 20.4 s; P < 0.05), dynamic balance (9.23 vs 25.52 s; P < 0.05), and coordination (6.73 vs 4.76 s; P < 0.05). No differences were observed in these measures between DC and NDC. Observed differences in physical abilities between older diabetic and nondiabetic adults may have been due to the subset of diabetic individuals with peripheral neuropathy. Quantitative measures of sensory and motor nerve function have distinct effects on physical performance. Interventions aimed at reducing the impact of diabetes-associated disability in old age may have the greatest impact among people with peripheral neuropathy. PMID:11754184

Resnick, Helaine E; Stansberry, Kevin B; Harris, Tamara B; Tirivedi, Mahdvi; Smith, Kimberly; Morgan, Polly; Vinik, Aaron I

2002-01-01

305

Optical Coherence Tomography in Glaucoma  

NASA Astrophysics Data System (ADS)

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

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

306

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

PubMed

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

2013-02-25

307

Acetylcarnitine and neuropathy: call for information.  

PubMed

AIDS Treatment News is seeking information from people who have used acetylcarnitine, a substance available in health food stores. The substance is in clinical trials as a possible treatment for diabetic neuropathy. There has been little scientific or anecdotal evidence related to its use in HIV patients. Contact information is included. PMID:11365469

1998-06-01

308

Poisoning by organophosphorus insecticides and sensory neuropathy  

PubMed Central

OBJECTIVES—Poisoning by organophosphate insecticides causes cholinergic toxicity. Organophosphate induced delayed polyneuropathy (OPIDP) is a sensory-motor distal axonopathy which usually occurs after ingestion of large doses of certain organophosphate insecticides and has so far only been reported in patients with preceding cholinergic toxicity. Surprisingly, it was recently reported by other authors that an exclusively sensory neuropathy developed in eight patients after repeated unquantified exposures to chlorpyrifos, which did not cause clear-cut cholinergic toxicity. The objective was to assess whether an exclusively sensory neuropathy develops in patients severely poisoned by various OPs.?METHODS—Toxicological studies and electrophysiological measurements were performed in peripheral motor and sensory nerves in 11 patients after acute organophosphate poisoning among which two subjects were poisoned with chlorpyrifos.?RESULTS—Three patients developed OPIDP, including one poisoned by chlorpyrifos. Exclusively sensory neuropathy was never seen after either single or repeated acute organophosphate poisoning. A mild sensory component was associated with a severe motor component in two of the three cases of OPIDP, the other was an exclusively motor polyneuropathy.?CONCLUSION—A sensory-motor polyneuropathy caused by organophosphate insecticides might occur after a severe poisoning and the sensory component, if present, is milder than the motor one. Bearing in mind the toxicological characteristics of these organophosphate insecticides, other causes should be sought for sensory peripheral neuropathies in patients who did not display severe cholinergic toxicity a few weeks before the onset of symptoms and signs.??

Moretto, A.; Lotti, M.

1998-01-01

309

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

1999-01-01

310

Impaired laryngeal mobility and entrapment neuropathies.  

PubMed

Entrapment neuropathies are rarely mentioned in phoniatrics because a definite diagnosis is very difficult to make. However, several clinical examples described here strongly support this etiology, which should now be considered in the diagnosis of both partial and complete laryngeal immobility as well as in minor neuromuscular disorders. PMID:21077411

Roch, J B; Piron, A

2010-01-01

311

Poisoning by organophosphorus insecticides and sensory neuropathy  

Microsoft Academic Search

OBJECTIVESPoisoning by organophosphate insecticides causes cholinergic toxicity. Organophosphate induced delayed polyneuropathy (OPIDP) is a sensory-motor distal axonopathy which usually occurs after ingestion of large doses of certain organophosphate insecticides and has so far only been reported in patients with preceding cholinergic toxicity. Surprisingly, it was recently reported by other authors that an exclusively sensory neuropathy developed in eight patients after

Angelo Moretto; Marcello Lotti

1998-01-01

312

Alpha-Lipoic Acid and Diabetic Neuropathy  

PubMed Central

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.

Vallianou, Natalia; Evangelopoulos, Angelos; Koutalas, Pavlos

2009-01-01

313

Proximal sensory neuropathies of the Leg.  

PubMed

This article addresses the proximal sensory neuropathies of the leg, concentrating on those nerves that are purely sensory or have a predominately sensory onset. These include the lateral femoral cutaneous nerve, the ilioinguinal nerve, the genitofemoral nerve, and the posterior femoral cutaneous nerve. The obturator and femoral nerves are also summarily mentioned with respect to their sensory symptoms. PMID:10393758

Reid, V; Cros, D

1999-08-01

314

Perineurium talin immunoreactivity decreases in diabetic neuropathy.  

PubMed

We studied the immunolocalization of Dp116 (a 116 kDa protein product of the dystrophin gene), vinculin, talin, vimentin, desmin, spectrin and titin in the sural nerve biopsies of 25 patients with peripheral neuropathies of different origin. 4 patients presented with HMSN type 1, 4 with HMSN type 2, 2 with HNPP, 4 with CIDP, 5 with chronic axonal neuropathy of unknown origin, 3 with vasculitic neuropathy, 3 with diabetic neuropathy. Expression and localization of Dp116, vinculin, vimentin, desmin, spectrin and titin did not differ from normal control cases. Spectrin and titin immunoreactivities were absent and desmin was occasionally found in few epineurial vessels. A thin rim of Dp116 binding surrounded the outermost layer of myelin sheaths. Perineurium and epineurial vessels stained deeply for vinculin. Vimentin immunoreactivity was seen in all endoneurial, perineurial and epineurial cells. Immunoreactivity for talin was normally found at endoneurial and epineurial vessel walls, perineurial cells and epineurial fibroblasts in all the sural nerves except diabetic nerves. In the latter, whereas talin binding was normal in the vessel walls and epineurial fibroblasts, it was markedly reduced in the perineurium. On immunoblot, two bands at 235 and 190 kDa were found in the sural nerves with the antibody anti-talin, and both were reduced only in the patients with diabetic neuropathy. We postulate that decreased perineurium talin in diabetic polyneuropathy may be related to the known alterations of the tight junctions of the perineurial cells, which have been proposed to be a contributory factor to impaired permeability barrier properties. PMID:9077489

Mazzeo, A; Rodolico, C; Monici, M C; Migliorato, A; Aguennouz, M; Vita, G

1997-02-27

315

Mutations in VRK1 Associated With Complex Motor and Sensory Axonal Neuropathy Plus Microcephaly  

PubMed Central

IMPORTANCE Patients with rare diseases and complex clinical presentations represent a challenge for clinical diagnostics. Genomic approaches are allowing the identification of novel variants in genes for very rare disorders, enabling a molecular diagnosis. Genomics is also revealing a phenotypic expansion whereby the full spectrum of clinical expression conveyed by mutant alleles at a locus can be better appreciated. OBJECTIVE To elucidate the molecular cause of a complex neuropathy phenotype in 3 patients by applying genomic sequencing strategies. DESIGN, SETTING, AND PARTICIPANTS Three affected individuals from 2 unrelated families presented with a complex neuropathy phenotype characterized by axonal sensorimotor neuropathy and microcephaly. They were recruited into the Centers for Mendelian Genomics research program to identify the molecular cause of their phenotype. Whole-genome, targeted whole-exome sequencing, and high-resolution single-nucleotide polymorphism arrays were performed in genetics clinics of tertiary care pediatric hospitals and biomedical research institutions. MAIN OUTCOMES AND MEASURES Whole-genome and whole-exome sequencing identified the variants responsible for the patients’ clinical phenotype. RESULTS We identified compound heterozygous alleles in 2 affected siblings from 1 family and a homozygous nonsense variant in the third unrelated patient in the vaccinia-related kinase 1 gene (VRK1). In the latter subject, we found a common haplotype on which the nonsense mutation occurred and that segregates in the Ashkenazi Jewish population. CONCLUSIONS AND RELEVANCE We report the identification of disease-causing alleles in 3 children from 2 unrelated families with a previously uncharacterized complex axonal motor and sensory neuropathy accompanied by severe nonprogressive microcephaly and cerebral dysgenesis. Our data raise the question of whether VRK1 mutations disturb cell cycle progression and may result in apoptosis of cells in the nervous system. The application of unbiased genomic approaches allows the identification of potentially pathogenic mutations in unsuspected genes in highly genetically heterogeneous and uncharacterized neurological diseases.

Gonzaga-Jauregui, Claudia; Lotze, Timothy; Jamal, Leila; Penney, Samantha; Campbell, Ian M.; Pehlivan, Davut; Hunter, Jill V.; Woodbury, Suzanne L.; Raymond, Gerald; Adesina, Adekunle M.; Jhangiani, Shalini N.; Reid, Jeffrey G.; Muzny, Donna M.; Boerwinkle, Eric; Lupski, James R.; Gibbs, Richard A.; Wiszniewski, Wojciech

2014-01-01

316

Hairy cell leukemia accompanied by Evans syndrome.  

PubMed

We report a case of Western type hairy cell leukemia (HCL), a very rare leukemia in Japan. In this malignancy, leukemic cells in a peripheral blood film may be missed due in part to accompanying pancytopenia and in part to loss of typical cytoplasmic projections if prepared in a conventional Japanese way using forced air-drying. Our present patient also had a variety of autoantibodies and the clinical picture was primarily that of Evans syndrome (ES), suggesting disturbed immune responses associated with the HCL. Although HCL accompanied by either AIHA or ITP has been reported, the occurrence of ES in HCL is extremely rare. PMID:24850460

Ebara, Shigeyuki; Kagosima, Mizuho; Marumo, Mikio; Ito, Yasusi; Tatumi, Eiji; Mitsutani, Susumu

2014-04-01

317

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

PubMed

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

2013-09-01

318

Localization of [3H]octylphosphonyl-labeled neuropathy target esterase by chicken nervous tissue autoradiography.  

PubMed

Neuropathy target esterase (NTE) undergoes phosphorylation and aging as the initial steps in organophosphorus (OP)-induced delayed neuropathy (OPIDN). Localization of NTE is an important step in characterizing the mechanism of OPIDN. Earlier histochemical immunoreactivity or esterase assays localized NTE in areas of the brain and spinal cord rich in neuronal cell bodies and in the dorsal root ganglion. We use a more direct and quantitative autoradiographic approach of forming phosphorylated and aged [3H]octylphosphonyl-NTE on treatment with the highly potent [octyl-3H]octyl-4H-1,3,2-benzodioxaphosphorin 2-oxide to determine NTE as the labeling site resistant to the non-neuropathic paraoxon and sensitive to the neuropathic mipafox. NTE is observed in the cerebral cortical layer, some layers of the optic tectum, the gray matter of the spinal cord and the sensory neurons of the dorsal root ganglion to a higher extent than in adjacent areas. PMID:10505626

Kamijima, M; Casida, J E

1999-10-01

319

Diabetic neuropathy: new strategies for treatment.  

PubMed

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

2008-02-01

320

Bilateral brachial plexus compressive neuropathy (crutch palsy).  

PubMed

Brachial plexus compressive neuropathy following the use of axillary crutches (crutch palsy) is a rare but well-recognized entity. Most reported cases involve the posterior cord of the brachial plexus in children and have resolved spontaneously within 8-12 weeks. We recently treated a 36-year-old man who was using axillary crutches for mobilization after a supracondylar femoral fracture. Bilateral posterior cord (predominantly radial nerve) compressive neuropathy subsequently developed, with lesser involvement of the ulnar and median nerves. The patient had little to no improvement clinically 8 weeks after the estimated onset of the palsy, and an electromyogram at that time confirmed the presence of a severe axonotmesis lesion of the radial, median, and ulnar nerves bilaterally. The patient was treated with static cock-up wrist splinting and discontinuation of the axillary crutches. Return of sensory and motor function was delayed but occurred within 9 months. PMID:9057152

Raikin, S; Froimson, M I

1997-01-01

321

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

2004-01-01

322

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

1998-01-01

323

Cytoskeleton, Axonal Transport, and the Mechanisms of Axonal Neuropathy  

Microsoft Academic Search

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

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

324

Evaluation of Ulnar neuropathy on hemodialysis patients  

PubMed Central

Background: Ulnar nerve entrapment at the elbow is the second most common upper extremity nerve involvement after median nerve involvement at the wrist or carpal tunnel syndrome (CTS) considering the frequency of occurrence in the upper limb with variable causes. Hemodialysis, because of elbow positioning during dialysis, upper extremity vascular-access, and underlying disease is one cause of ulnar entrapment. This study considers evaluating the effect of elbow positioning on ulnar involvement prevalence during dialysis. Materials and Methods: This cross-sectional study started in June 2011 and completed in December 2011. The patients receiving dialysis with at least one symptom or sign of ulnar nerve involvement underwent nerve conduction studies. Electromyography testing (EMG) performed to confirm the ulnar neuropathy. To review the ulnar nerve, patients must be in supine position with arm in 90° abduction and elbow in 135° flexion. We stimulated the ulnar nerve at three different points, including 6 cm above and 4 cm below the elbow and over the wrist. According to the electrophysiological data, the intensity of nerve entrapment and possibility of associated polyneuropathy determined. Results: Clinically and electrodiagnostically, evidence confirmed that ulnar neuropathy was present in 11 (27.5%) of 40 hemodialysis patients and in 10 (25%) of 40 peritoneal patients (P value: 0.83). Also, the prevalence of median neuropathy in hemodialysis and peritoneal dialysis patients was 14 (35%) and 10 (25%), respectively (P value: 0.33). Conclusion: The frequency of median and ulnar neuropathy in hemodialysis patients is more than peritoneal dialysis, but this different is not significant. In addition, comparing sitting position with prolonged elbow flexion and supine position with elbow extension during hemodialysis, recommended doing hemodialysis in later position with using an elbow pad.

Vahdatpour, Babak; Maghroori, Razieh; Mortazavi, Mojgan; Khosrawi, Saeid

2012-01-01

325

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

2010-01-01

326

Somatic DNA Damages in Cardiovascular Autonomic Neuropathy  

Microsoft Academic Search

Cardiovascular autonomic neuropathy (CAN) is one of the most clinically significant complications of diabetes mellitus. Even\\u000a though many ethological factors have been attributed for the pathogenesis of this disease no attempts were made to correlate\\u000a DNA damage as a causative factor. Hence the present study was undertaken to asses the extent of somatic DNA damages by cytokinesis-block\\u000a micronuclei assay (CBMN).

A. Supriya SimonD; D. Dinesh Roy; V. Jayapal; T. Vijayakumar

2011-01-01

327

A Case of Unilateral Auditory Neuropathy  

Microsoft Academic Search

We report a case of unilateral auditory neuropathy (AN) showing improvement in both pure tone hearing (PTA) and speech discrimination\\u000a scores (SDS) with time. Some reports have documented the findings of auditory examination in patients with unilateral AN,\\u000a and a few reports have documented the time-related changes in these findings for the same patients. A 3-year-old Japanese\\u000a boy was referred

Yuki Saito; Mitsuya Suzuki; Tunemasa Sato

328

Pathogenesis of pain in peripheral diabetic neuropathy  

Microsoft Academic Search

Recent advances in understanding the pain associated with diabetic neuropathy are likely to provide significant mechanistic\\u000a insights and offer better therapies. In clinical research, new tools for measuring neuropathic pain and validation of histologic\\u000a and other biomarkers will provide the foundation for research advances, and new clinical trial designs will allow better discrimination\\u000a of beneficial treatments and may reveal underlying

Nigel A. Calcutt; Miroslav Misha Backonja

2007-01-01

329

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

PubMed

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

Delval, Arnaud; Stojkovic, Tanya; Vermersch, Patrick

2006-02-01

330

Chemotherapy-induced neuropathy: A comprehensive survey.  

PubMed

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

Miltenburg, N C; Boogerd, W

2014-08-01

331

A reversible functional sensory neuropathy model.  

PubMed

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

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

2014-06-13

332

PMP22 related congenital hypomyelination neuropathy.  

PubMed

The peripheral myelin protein 22 (PMP22) is a tetraspan membrane protein which is localised in the compact myelin of the peripheral nerves. In fibroblasts, where it was originally identified as growth arrest related factor 3 (Gas3), PMP22 has been shown to modulate cell proliferation; in the peripheral nervous system its roles are still debated. The duplication of PMP22 is the most common cause of the demyelinating form of the autosomal dominant Charcot-Marie-Tooth neuropathy (CMT1A); rarer missense mutations of PMP22 also cause CMT1A or severe dehypomyelinating neuropathies of infancy grouped under the heading of Dejerine-Sottas syndrome (DSS). Here, a sporadic patient affected with DSS is described; nerve biopsy disclosed a picture of hypomyelination/amyelination with basal laminae onion bulbs and no florid demyelination and it was consistent with congenital hypomyelination neuropathy (CHN); molecular analysis disclosed a novel point mutation of PMP22 that causes a non-conservative arginine for cysteine substitution at codon 109, in the third transmembrane domain. CHN is the rarest and severest form of DSS and it is thought to reflect dysmyelination rather than demyelination. The reported case suggests that missense point mutations may alter a putative role of PMP22 in modulating Schwann cell growth and differentiation. PMID:11118262

Fabrizi, G M; Simonati, A; Taioli, F; Cavallaro, T; Ferrarini, M; Rigatelli, F; Pini, A; Mostacciuolo, M L; Rizzuto, N

2001-01-01

333

Inherited peripheral neuropathies due to mitochondrial disorders.  

PubMed

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

Cassereau, J; Codron, P; Funalot, B

2014-05-01

334

Childhood steroid-responsive acute erythromelalgia with axonal neuropathy of large myelinated fibers: a dysimmune neuropathy?  

PubMed

A 12-year-old girl developed acute erythromelalgia of distal extremities. Physical, imaging and laboratory examinations failed to find an infective, systemic autoimmune, metabolic, endocrine, and vascular origin. The severe pain and allodynia indicated small-fiber neuropathy but muscle weakness suggested an involvement of large myelinated nerve fibers. This was confirmed by electrophysiological testing. High-dose then slowly tapered methylprednisolone resulted in rapid remission of painful erythromelalgia and complete electrophysiological recovery. Our case may suggest an additional variant to recently described steroid-responsive erythromelalgia with small-fiber axonopathy and may denote a transitory variant to Guillain-Barré syndrome or chronic dysimmune neuropathies. PMID:19056270

Pfund, Zoltan; Stankovics, Jozsef; Decsi, Tamas; Illes, Zsolt

2009-01-01

335

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.

2010-01-01

336

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

PubMed

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. PMID:21176122

Santarelli, Rosamaria

2010-01-01

337

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

PubMed Central

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.

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

2013-01-01

338

Purple pigments: the pathophysiology of acute porphyric neuropathy.  

PubMed

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

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

2011-12-01

339

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

2011-01-01

340

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

PubMed

Approximately 1 in 2500 Americans suffer from Charcot-Marie-Tooth (CMT) disease. The underlying disease mechanisms are unique in most forms of CMT, with many point mutations on various genes causing a toxic accumulation of misfolded proteins. Symptoms of the disease often present within the first two decades of life, with CMT1A patients having reduced compound muscle and sensory action potentials, slow nerve conduction velocities, sensory loss, progressive distal weakness, foot and hand deformities, decreased reflexes, bilateral foot drop and about 5% become wheelchair bound. In contrast, the ultra-rare disease Giant Axonal Neuropathy (GAN) is frequently described as a recessively inherited condition that results in progressive nerve death. GAN usually appears in early childhood and progresses slowly as neuronal injury becomes more severe and leads to death in the second or third decade. There are currently no treatments for any of the forms of CMTs or GAN. We suggest that further clinical studies should analyse electrical impedance myography as an outcome measure for CMT. Further, additional quality of life (QoL) assessments for these CMTs are required, and we need to identify GAN biomarkers as well as develop new genetic testing panels for both diseases. We propose that using the Global Registry of Inherited Neuropathy (GRIN) could be useful for many of these studies. Patient advocacy groups and professional organizations (such as the Hereditary Neuropathy Foundation (HNF), Hannah's Hope Fund (HHF), The Neuropathy Association (TNA) and the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) can play a central role in educating clinicians and patients. Undertaking these studies will assist in the correct diagnosis of disease recruiting patients for clinical studies, and will ultimately improve the endpoints for clinical trials. By addressing obstacles that prevent industry investment in various forms of inherited neuropathies, we can envision treatment options for these rare diseases in the near future. PMID:24860645

Sames, Lori; Moore, Allison; Arnold, Renee; Ekins, Sean

2014-01-01

341

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

PubMed Central

Approximately 1 in 2500 Americans suffer from Charcot-Marie-Tooth (CMT) disease. The underlying disease mechanisms are unique in most forms of CMT, with many point mutations on various genes causing a toxic accumulation of misfolded proteins. Symptoms of the disease often present within the first two decades of life, with CMT1A patients having reduced compound muscle and sensory action potentials, slow nerve conduction velocities, sensory loss, progressive distal weakness, foot and hand deformities, decreased reflexes, bilateral foot drop and about 5% become wheelchair bound. In contrast, the ultra-rare disease Giant Axonal Neuropathy (GAN) is frequently described as a recessively inherited condition that results in progressive nerve death. GAN usually appears in early childhood and progresses slowly as neuronal injury becomes more severe and leads to death in the second or third decade. There are currently no treatments for any of the forms of CMTs or GAN. We suggest that further clinical studies should analyse electrical impedance myography as an outcome measure for CMT. Further, additional quality of life (QoL) assessments for these CMTs are required, and we need to identify GAN biomarkers as well as develop new genetic testing panels for both diseases. We propose that using the Global Registry of Inherited Neuropathy (GRIN) could be useful for many of these studies. Patient advocacy groups and professional organizations (such as the Hereditary Neuropathy Foundation (HNF), Hannah's Hope Fund (HHF), The Neuropathy Association (TNA) and the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) can play a central role in educating clinicians and patients. Undertaking these studies will assist in the correct diagnosis of disease recruiting patients for clinical studies, and will ultimately improve the endpoints for clinical trials. By addressing obstacles that prevent industry investment in various forms of inherited neuropathies, we can envision treatment options for these rare diseases in the near future.

Ekins, Sean

2014-01-01

342

[Photochromotherapy of experimental compression-ischemic neuropathy].  

PubMed

Effects of monochrome light of the green and red spectra (mean wave length 540 and 670 nm, respectively) were studied on experimental rat model of compression-ischemic neuropathy (40 animals). The nerve under compression was exposed to green and red light using light-diode physiotherapeutic unit "Spectr-LC" with different intensity. Electromyographic parameters of the compressed nerve improved significantly after exposure to monochrome green light with intensity 500 mJ/cm2. The effect was dose dependent. Green light produced better effect. PMID:12852016

Guzalov, P I; Kir'ianova, V V; Zhulev, N M; Veselovski?, A B; Vlasov, T D; Zhulev, S N; Ziganshina, D P; Korniushin, O V

2003-01-01

343

Hyperglycemia-Initiated Mechanisms in Diabetic Neuropathy  

Microsoft Academic Search

Peripheral diabetic neuropathy (PDN) is one of the most devastating complications of diabetes mellitus. The pathogenesis of\\u000a PDN involves hyperglycemia-initiated mechanisms as well as other factors, i.e., impaired insulin signaling, hypertension,\\u000a disturbances of fatty acid and lipid metabolism. This review describes new findings in animal and cell culture models:\\u000a \\u000a \\u000a \\u000a 1. \\u000a \\u000a Supporting the importance of previously established hyperglycemia-initiated mechanisms, such as

Irina G. Obrosova

344

Chronic ataxic neuropathy mimicking dorsal midbrain syndrome  

PubMed Central

We describe the clinical course, with special attention to the disturbance of eye movements, of a 29?year?old man with chronic ataxic neuropathy with ophthalmoplegia, IgM paraprotein, cold agglutinins and anti?GD1b disialosyl antibodies (CANOMAD). Using the magnetic search coil technique, we documented convergence during upward saccades and other features suggestive of dorsal midbrain syndrome. Thus, in common with Miller Fisher syndrome, CANOMAD may present with clinical findings implicating involvement of the central nervous system, which contains ganglioside antigens to anti?GD1b antibodies.

Arbogast, S D; Khanna, S; Koontz, D W; Tomsak, R L; Katirji, B; Leigh, R J

2007-01-01

345

Chronic ataxic neuropathy mimicking dorsal midbrain syndrome.  

PubMed

We describe the clinical course, with special attention to the disturbance of eye movements, of a 29-year-old man with chronic ataxic neuropathy with ophthalmoplegia, IgM paraprotein, cold agglutinins and anti-GD1b disialosyl antibodies (CANOMAD). Using the magnetic search coil technique, we documented convergence during upward saccades and other features suggestive of dorsal midbrain syndrome. Thus, in common with Miller Fisher syndrome, CANOMAD may present with clinical findings implicating involvement of the central nervous system, which contains ganglioside antigens to anti-GD1b antibodies. PMID:17504882

Arbogast, S D; Khanna, S; Koontz, D W; Tomsak, R L; Katirji, B; Leigh, R J

2007-11-01

346

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

1988-01-01

347

Early diabetic neuropathy: Triggers and mechanisms  

PubMed Central

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

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

2007-01-01

348

Mitotoxicity in distal symmetrical sensory peripheral neuropathies.  

PubMed

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

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

2014-06-01

349

Computer aided diagnosis of diabetic peripheral neuropathy  

NASA Astrophysics Data System (ADS)

Diabetic peripheral neuropathy (DPN) refers to the nerve damage that can occur in diabetes patients. It most often affects the extremities, such as the feet, and can lead to peripheral vascular disease, deformity, infection, ulceration, and even amputation. The key to managing diabetic foot is prevention and early detection. Unfortunately, current existing diagnostic techniques are mostly based on patient sensations and exhibit significant inter- and intra-observer differences. We have developed a computer aided diagnostic (CAD) system for diabetic peripheral neuropathy. The thermal response of the feet of diabetic patients following cold stimulus is captured using an infrared camera. The plantar foot in the images from a thermal video are segmented and registered for tracking points or specific regions. The temperature recovery of each point on the plantar foot is extracted using our bio-thermal model and analyzed. The regions that exhibit abnormal ability to recover are automatically identified to aid the physicians to recognize problematic areas. The key to our CAD system is the segmentation of infrared video. The main challenges for segmenting infrared video compared to normal digital video are (1) as the foot warms up, it also warms up the surrounding, creating an ever changing contrast; and (2) there may be significant motion during imaging. To overcome this, a hybrid segmentation algorithm was developed based on a number of techniques such as continuous max-flow, model based segmentation, shape preservation, convex hull, and temperature normalization. Verifications of the automatic segmentation and registration using manual segmentation and markers show good agreement.

Chekh, Viktor; Soliz, Peter; McGrew, Elizabeth; Barriga, Simon; Burge, Mark; Luan, Shuang

2014-03-01

350

The mechanism of atomization accompanying solid injection  

NASA Technical Reports Server (NTRS)

A brief historical and descriptive account of solid injection is followed by a detailed review of the available theoretical and experimental data that seem to throw light on the mechanism of this form of atomization. It is concluded that this evidence indicates that (1) the atomization accompanying solid injection occurs at the surface of the liquid after it issues as a solid stream from the orifice; and (2) that such atomization has a mechanism physically identical with the atomization which takes place in an air stream, both being due merely to the formation, at the gas-liquid interface, of fine ligaments under the influence of the relative motion of gas and liquid, and to their collapse, under the influence of surface tension, to form the drops in the spray.

Castleman, R A , Jr

1933-01-01

351

Lithium attenuates peripheral neuropathy induced by paclitaxel in rats.  

PubMed

As a cancer chemotherapeutic agent, paclitaxel (Taxol® ) causes dose-related peripheral neuropathy in human beings. The mechanisms underlying this toxicity are currently unknown, and there are no validated treatments for its prevention or control. To assess whether lithium as a pre-treatment and at subtherapeutic dose could prevent the peripheral neuropathy produced by it, rats were treated with paclitaxel (2?mg/kg i.p. every other day for a total of 16 times) and/or lithium chloride (300?mg/l) via water supply. General toxicity and body-weight were measured regularly during the experiment. To evaluate the sensory and motor neuropathy hot-plate, open-field test and nerve conduction velocity were used. In rats treated with only paclitaxel, there was behavioural, electrophysiological and histological evidence of a mixed sensorimotor neuropathy after 16 injections. Lithium robustly reduced the rate of mortality and general toxicity. Paclitaxel-induced sensorimotor neuropathy was significantly improved as indicated by changes in hotplate latency, total distance moved and a significant increase in sciatic, sural and tail sensory or motor nerve conduction velocity. The same results were observed in histopathological examinations; however, dorsal root ganglion neurons did not significantly change in the paclitaxel-treated groups. These results suggest that lithium, at subtherapeutic doses, can prevent both motor and sensory components of paclitaxel neuropathy in rats. Thus, lithium at these doses, as an inexpensive and relatively safe salt, may be useful clinically in preventing the neuropathy induced by paclitaxel treatment. PMID:21917116

Pourmohammadi, Nasir; Alimoradi, Houman; Mehr, Shahram Ejtemaei; Hassanzadeh, Gholamreza; Hadian, Mohammad Reza; Sharifzadeh, Mohammad; Bakhtiarian, Azam; Dehpour, Ahmad Reza

2012-03-01

352

Auditory neuropathy: unexpectedly common in a screened newborn population.  

PubMed

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

2009-08-01

353

Increased biosynthesis of endoneurial oligohexosylceramides in human peripheral neuropathy.  

PubMed

Studying in vitro incorporation of [3H]galactose into biopsied sural endoneurium, we have demonstrated biosynthesis of glucocerebroside and its homologs, lactosylceramide, trihexosylceramide, and tetrahexosylceramide, in normal adult human sural nerve. Such in vitro biosynthesis of oligohexosylceramides is markedly increased in biopsied sural nerve from patients with various types of peripheral neuropathy. Since this altered glycosphingolipid biosynthesis occurs in several diversely caused polyneuropathies, it presumably relates to degenerative or regenerative events characteristic of neuropathy rather than a specific variety of neuropathy. PMID:2840613

Yao, J K; Dyck, P J

1987-12-01

354

Motor neuron disease due to neuropathy target esterase gene mutation: clinical features of the index families.  

PubMed

Recently, we reported that mutations in the neuropathy target esterase (NTE) gene cause autosomal recessive motor neuron disease (NTE-MND). We describe clinical, neurophysiologic, and neuroimaging features of affected subjects in the index families. NTE-MND subjects exhibited progressive lower extremity spastic weakness that began in childhood and was later associated with atrophy of distal leg and intrinsic hand muscles. NTE-MND resembles Troyer syndrome, except that short stature, cognitive impairment, and dysmorphic features, which often accompany Troyer syndrome, are not features of NTE-MND. Early onset, symmetry, and slow progression distinguish NTE-MND from typical amyotrophic lateral sclerosis. NTE is implicated in organophosphorus compound-induced delayed neurotoxicity (OPIDN). NTE-MND patients have upper and lower motor neuron deficits that are similar to OPIDN. Motor neuron degeneration in subjects with NTE mutations supports the role of NTE and its biochemical cascade in the molecular pathogenesis of OPIDN and possibly other degenerative neurologic disorders. PMID:21171093

Rainier, Shirley; Albers, James W; Dyck, Peter J; Eldevik, O Petter; Wilcock, Sandra; Richardson, Rudy J; Fink, John K

2011-01-01

355

Spinal subarachnoid hemorrhage accompanied with intraventricular hemorrhage.  

PubMed

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. PMID:23961296

Fatehi, Farzad; Basiri, Keivan; Ghorbani, Askar

2013-03-01

356

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

2013-01-01

357

Falcotentorial meningioma accompanied by temporal lobe hematoma.  

PubMed

We report a case of a falcotentorial meningioma accompanied by hematoma in the temporal lobe. A healthy 51 year-old-female with no history of hypertension presented with sudden onset of consciousness disturbance and right hemiparesis. Computed tomography revealed a hematoma 5.5 cm in diameter surrounded by thick edematous brain in the left temporal lobe and a tumor 3.5 cm in diameter in the pineal region. Bilateral carotid angiography detected occlusion of the Galenic vein and straight sinus. No causative abnormality of hemorrhage was apparent. However, the left basal vein of Rosenthal had disappeared, and anastomotic venous channels could be observed in the medial left temporal lobe, contiguous to the hematoma. Emergency craniotomy failed to detect any abnormality which could cause hemorrhage in the brain parenchyma surrounding the hematoma. Subtotal removal of the tumor, histologically diagnosed as fibrous meningioma, was achieved three months later employing an occipital transtentorial approach. Venous congestion caused by compression due to the tumor was considered to be one of possible causes of the hemorrhage. PMID:11720166

Ohba, S; Kurisu, K; Arita, K; Sugiyama, K; Inoue, T; Satoh, H; Hibino, S

2001-09-01

358

Surface decomposition accompanying the perception of transparency.  

PubMed

At the retina, each location can have only one value of luminance or color. When transparency is perceived, however, different surface qualities can be redistributed to two or more apparently superimposed layers. The experiments described here explored the characteristics of this surface decomposition. It is shown that the surface decomposition occurs rapidly, it affects even early stages of visual processing, and it involves attributes such as texture and motion as well as color and brightness. In the first experiment, the recognition advantage for transparent overlapping digits demonstrated that the surface decomposition accompanying transparency occurs within 60 ms. In the second, the separation of overlying orthogonal grids due to surface decomposition was found to influence the strength of the McCollough effect, an effect attributed to early cortical processing. Finally, when a transparent surface appears to extend over areas that are physically identical to the background, qualities of the transparent overlay such as texture and motion, as well as color or brightness (e.g., the neon color effect) appear to spread to the illusory overlay. PMID:8347552

Watanabe, T; Cavanagh, P

1993-01-01

359

Review: Regional land subsidence accompanying groundwater extraction  

USGS Publications Warehouse

The extraction of groundwater can generate land subsidence by causing the compaction of susceptible aquifer systems, typically unconsolidated alluvial or basin-fill aquifer systems comprising aquifers and aquitards. Various ground-based and remotely sensed methods are used to measure and map subsidence. Many areas of subsidence caused by groundwater pumping have been identified and monitored, and corrective measures to slow or halt subsidence have been devised. Two principal means are used to mitigate subsidence caused by groundwater withdrawal—reduction of groundwater withdrawal, and artificial recharge. Analysis and simulation of aquifer-system compaction follow from the basic relations between head, stress, compressibility, and groundwater flow and are addressed primarily using two approaches—one based on conventional groundwater flow theory and one based on linear poroelasticity theory. Research and development to improve the assessment and analysis of aquifer-system compaction, the accompanying subsidence and potential ground ruptures are needed in the topic areas of the hydromechanical behavior of aquitards, the role of horizontal deformation, the application of differential synthetic aperture radar interferometry, and the regional-scale simulation of coupled groundwater flow and aquifer-system deformation to support resource management and hazard mitigation measures.

Galloway, Devin L.; Burbey, Thomas J.

2011-01-01

360

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

PubMed Central

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.

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

2013-01-01

361

Ophthalmoplegic migraine: a recurrent demyelinating neuropathy?  

PubMed

The demonstration by magnetic resonance imaging (MRI) scanning of thickening and enhancement of the cisternal part of the oculomotor nerve in patients diagnosed as "ophthalmoplegic migraine" prompts reconsideration of this uncommon disorder. The case histories of five patients, three male and two female, varying in age from 6 to 30 years, are presented here. Recurrent painful ophthalmoplegia started in infancy in two cases, childhood in two instances and adult life in one. One child had his first attacks at 3, 5 and 12 months of age, on each occasion 10 days after an injection of triple vaccine. The possibility of this condition being a recurrent demyelinating neuropathy is considered and its possible relationship to migraine explored. PMID:11422088

Lance, J W; Zagami, A S

2001-03-01

362

Entrapment neuropathies of the lower extremity.  

PubMed

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

Craig, Anita

2013-05-01

363

Peripheral neuropathy: pathogenic mechanisms and alternative therapies.  

PubMed

Peripheral neuropathy (PN), associated with diabetes, neurotoxic chemotherapy, human immunodeficiency virus (HIV)/antiretroviral drugs, alcoholism, nutrient deficiencies, heavy metal toxicity, and other etiologies, results in significant morbidity. Conventional pain medications primarily mask symptoms and have significant side effects and addiction profiles. However, a widening body of research indicates alternative medicine may offer significant benefit to this patient population. Alpha-lipoic acid, acetyl-L-carnitine, benfotiamine, methylcobalamin, and topical capsaicin are among the most well-researched alternative options for the treatment of PN. Other potential nutrient or botanical therapies include vitamin E, glutathione, folate, pyridoxine, biotin, myo-inositol, omega-3 and -6 fatty acids, L-arginine, L-glutamine, taurine, N-acetylcysteine, zinc, magnesium, chromium, and St. John's wort. In the realm of physical medicine, acupuncture, magnetic therapy, and yoga have been found to provide benefit. New cutting-edge conventional therapies, including dual-action peptides, may also hold promise. PMID:17176168

Head, Kathleen A

2006-12-01

364

Hereditary sensory radicular neuropathy: defective neurogenic inflammation.  

PubMed

Hereditary sensory radicular neuropathy exhibits autosomal dominant inheritance with complete penetrance in males and incomplete penetrance in females. Newer tests of small sensory nerve function were used in screening 8 family members aged between 14 and 66 years. All exhibited some frequent features of the disorder with an onset in the 2nd or 3rd decade, foot ulceration, foot callus, loss of pin prick, thermal and light touch sensation, and some reduction in vibration acuity and proprioception in the lower limbs. The hands were involved in 3 of 8, muscle involvement was present in 5 of 8, but deafness was not detected by audiometry. Nerve conduction velocity, sensory action potentials, latency and amplitude, thermal acuity, vibration acuity and axon reflex flares were measured in all patients. One sural nerve biopsy confirmed the presence of peripheral fibre loss in this predominantly sensory neuropathy. Chemically evoked axon reflex tests were used to evaluate the extent of primary sensory nerve fibre involvement. All patients were tested using a Moor MBF 3-D dual channel laser Doppler velocimeter. Acetylcholine or phenylephrine iontophoretically applied as 16 mC doses evoked absent or tiny axon reflexes in areas of impaired pin prick sensation. By contrast, direct microvascular dilator responses to nitroprusside (smooth muscle dependent) and acetylcholine (endothelium-dependent) were present but somewhat reduced in areas with defective neurogenic inflammation. These results differ significantly from the responses obtained in age-matched healthy controls (P < 0.05). Foot pressure analysis was performed for orthoses in 2 affected members with foot ulceration using the Musgrave Footprint system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1343862

Westerman, R A; Block, A; Nunn, A; Delaney, C A; Hahn, A; Dennett, X; Carr, R W

1992-01-01

365

Genetics Home Reference: Neuropathy, ataxia, and retinitis pigmentosa  

MedlinePLUS

... Read more about Leigh syndrome . What are the genetic changes related to NARP? Neuropathy, ataxia, and retinitis ... Center . Where can I find general information about genetic conditions? The Handbook provides basic information about genetics ...

366

Examination and clinical care of the patient with neuropathy.  

PubMed

Examination of a patient with peripheral neuropathy starts with careful questioning of the patient about the history of symptoms and signs and of a possible familial disorder. Several steps are required during examination of the patient with peripheral neuropathy: first the pattern of neuropathy and site of lesions should be determined: roots, nerve trunks, focal, multifocal, length-dependent generalized polyneuropathy, the type of nerve fibers predominantly affected, the association with trophic changes and autonomic dysfunction, the course of the disease ranging from acute inflammatory polyneuritis or fulminant multifocal neuropathy to an extremely slow progression as in Charcot-Marie-Tooth syndromes. At the end of this first contact with the patient, the neurologist must decide which investigations seem necessary and their timing including electrophysiological tests, imaging, CSF examination, blood tests, nerve and muscle biopsy, DNA testing, etc. In some cases, life-threatening manifestations, including weakness of respiratory muscles or swallowing difficulty, or autonomic dysfunction, require urgent therapeutic decisions. PMID:23931783

Said, Gérard

2013-01-01

367

Cisplatin induced neuropathy: central, peripheral and autonomic nerve involvement.  

PubMed

A prospective study was performed in patients treated with cisplatin to evaluate the occurrence and degree of central, peripheral and autonomic neuropathy and to determine the most accurate method to study this neuropathy. Twelve patients were examined before, during and after treatment. Evaluation included neurologic examination, conventional nerve conduction studies of the median and peroneal nerves and short latency somatosensory evoked potentials (SSER) after median and tibial nerve stimulation. Valsalva maneuvers before and during treatment were performed in 11 patients. Symptoms of peripheral neuropathy paralleled clinical signs. Conventional nerve conduction studies did not seem to be more accurate than clinical examination in determining peripheral neuropathy. SSER appeared to be the most sensitive method for the detection of peripheral nerve impairment. A slowing of central conduction velocity occurred after cumulative doses of 200-400 mg/m2 as measured by SSER. In two patients also some involvement of the autonomic nerves was suggested. PMID:2128320

Boogerd, W; ten Bokkel Huinink, W W; Dalesio, O; Hoppenbrouwers, W J; van der Sande, J J

1990-12-01

368

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

2010-01-01

369

Reversal of optic neuropathy secondary to voluntary globe luxation.  

PubMed

Luxation of the globe is rare in the general population and may be spontaneous, voluntary, or traumatic. Spontaneous or voluntary globe luxation results from shallow orbit, floppy eyelids, lax orbital ligaments, backward displacement of orbital septum, or proptotic eyes due to orbital tumors or infiltrative processes, as in Grave's ophthalmopathy. The authors report a case with unilateral voluntary globe luxation presented with unilateral progressive visual loss. PMID:19157936

Yaman, Aylin; Ozturk, Taylan; Soylev, Meltem F

2009-04-01

370

Pathogenesis and treatment of immune-mediated neuropathies.  

PubMed

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

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

2009-07-01

371

Peripheral Neuropathy Associated With Nucleoside Reverse Transcriptase Inhibitor Therapy  

Microsoft Academic Search

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

Bruce A. Cohen; Russell Bartt

372

Peripheral neuropathy with essential mixed cryoglobulinemia: biopsies from 5 cases  

Microsoft Academic Search

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

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

1988-01-01

373

Assessment of Recovery from Burn Related Neuropathy by Electrodiagnostic Testing  

PubMed Central

The purpose of this study was to investigate the recovery of burn related neuropathies by electrodiagnostic testing. Burn patients who presented to an American Burn Association verified burn center were interviewed and examined for clinical evidence of peripheral neuropathies by a physiatrist. Patients whom consented to participate were tested for electrodiagnostic evidence of peripheral neuropathy. Repeated studies were performed to assess for evidence of recovery. A total of 370 patients were screened. 36 (9.73%) patients had clinical evidence of neuropathy. Eighteen male patients with a mean total body surface area burn of 42% had nerve conduction studies performed. Etiologies of the injuries included 8 flame, 8 electrical and 3 others. Seventy three nerve conduction studies were performed and 58 of the tests were abnormal. The most commonly affected nerve was the median sensory (10). For patients with repeated tests, the mean time between tests was 169 days (SD 140 days). There was a significant difference between the initial and follow up test (McNemar’s change test p=0.009). In subset analysis of motor and sensory abnormalities, there was no significant difference (p=0.07). The most common neuropathy identified in this cohort was the median sensory. Overall, there was improvement in the nerve conduction abnormalities examined. This study suggests that the prognosis for recovery after burn related neuropathy is good.

Gabriel, Vincent; Kowalske, Karen J.; Holavanahalli, Radha K.

2009-01-01

374

Peripheral neuropathy with nucleoside antiretrovirals: risk factors, incidence and management.  

PubMed

Distal symmetrical peripheral neuropathy is a common adverse experience in persons with HIV infection. This condition, which presents as a pain, numbness. burning and/or dysaethesia initially in the feet, is often multi-factorial in its origin. Nucleoside analogue reverse transcriptase inhibitors represent an important contributor to peripheral neuropathy. Specifically, around 10% of patients receiving stavudine or zalcitabine and 1 to 2% of didanosine recipients may have to discontinue therapy with these agents due to neuropathy. Prompt withdrawal of these therapies enables gradual resolution of signs and symptoms in most patients, although a period of symptom intensification may occur shortly after withdrawal. Risk factors for developing peripheral neuropathy during nucleoside analogue therapy include low CD4+ cell count (<100 cells/mm3), a prior history of an AIDS defining illness or neoplasm, a history of peripheral neuropathy, use of other neurotoxic agents including high alcohol (ethanol) consumption and nutritional deficiencies such as low serum hydroxocobalamin levels. Thus, patients at increased risk of peripheral neuropathy should potentially avoid the use of the neurotoxic nucleoside analogues or be more carefully monitored during therapy. Management of this problem includes patient education. prompt withdrawal of the likely causative agent (giving consideration not to leave the patient on a sub-optimal therapy regimen) and simple analgesia. with augmentation with tricyclic antidepressants or anticonvulsant agents when pain is severe. New agents that may assist in managing this condition include levacecarnine (acetyl-L-carnitine) and nerve growth factors such as recombinant human nerve growth factor. PMID:9880091

Moyle, G J; Sadler, M

1998-12-01

375

The Association between Autoantibodies and Peripheral Neuropathy in Lupus Nephritis  

PubMed Central

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

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

2014-01-01

376

Animal models of peripheral neuropathy due to environmental toxicants.  

PubMed

Despite the progress in our understanding of pathogeneses and the identification of etiologies of peripheral neuropathy, idiopathic neuropathy remains common. Typically, attention to peripheral neuropathies resulting from exposure to environmental agents is limited relative to more commonly diagnosed causes of peripheral neuropathy (diabetes and chemotherapeutic agents). Given that there are more than 80,000 chemicals in commerce registered with the Environmental Protection Agency and that at least 1000 chemicals are known to have neurotoxic potential, very few chemicals have been established to affect the peripheral nervous system (mainly after occupational exposures). A wide spectrum of exposures, including pesticides, metals, solvents, nutritional sources, and pharmaceutical agents, has been related, both historically and recently, to environmental toxicant-induced peripheral neuropathy. A review of the literature shows that the toxicity and pathogeneses of chemicals adversely affecting the peripheral nervous system have been studied using animal models. This article includes an overview of five prototypical environmental agents known to cause peripheral neuropathy-namely, organophosphates, carbon disulfide, pyridoxine (Vitamin B6), acrylamide, and hexacarbons (mainly n-hexane, 2,5-hexanedione, methyl n-butyl ketone). Also included is a brief introduction to the structural components of the peripheral nervous system and pointers on common methodologies for histopathologic evaluation of the peripheral nerves. PMID:24615445

Rao, Deepa B; Jortner, Bernard S; Sills, Robert C

2014-01-01

377

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

1996-01-01

378

Bilateral nonarteritic anterior ischemic neuropathy following acute angle-closure glaucoma in a patient with iridoschisis: case report.  

PubMed

A 55-year-old woman was referred to our clinic because of a one-week history of visual loss and raised intraocular pressure in the left eye followed 4 days later by visual loss in the right eye. Slit-lamp examination showed bilateral conjunctival hyperemia, slight diffuse corneal edema, shallow anterior chamber and fixed and dilated pupil in both eyes. Splitting of the anterior layers of the iris with fibrillar degeneration extending for approximately one quadrant inferiorly was presented in each eye. Fundus examination showed optic disc edema with no vascular tortuosity and no cup in both eyes. The condition was treated as bilateral acute angle-closure glaucoma in a patient with irisdoschisis. After medical treatment and improvement of visual acuity, perimetry revealed a significant visual field defect especially in left eye; this case represents a rare concurrence of acute angle-closure glaucoma and bilateral nonarteritic ischemic optic neuropathy. Although most cases of elevated intraocular pressure, including acute angle-closure glaucoma, do not result in optic disc edema and irreversible vision loss, variations in the vascular supply of the nerve optic head along with others ocular systemic risk factors, may predispose certain individuals to nonarteritic ischemic optic neuropathy during periods of elevated intraocular pressure. PMID:21670912

Torricelli, André; Reis, Alexandre Soares Castro; Abucham, Julio Zaki; Suzuki, Ricardo; Malta, Roberto Freire Santiago; Monteiro, Mário Luiz R

2011-01-01

379

NEUROPATHY TARGET ESTERASE INHIBITION BY ORGANOPHOSPHORUS ESTERS IN HUMAN NEUROBLASTOMA CELLS  

EPA Science Inventory

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

380

Management of chemotherapy-induced peripheral neuropathy.  

PubMed

Recent advances in the development and administration of chemotherapy for malignant diseases have been rewarded with prolonged survival rates. The cost of progress has come at a price and the nervous system is frequently the target of chemotherapy-induced neurotoxicity. Unlike more immediate toxicities that effect 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 toxicity is directed against the peripheral nerve, resulting in chemotherapy-induced peripheral neuropathy (CIPN). Chemotherapeutic agents used to treat hematologic and solid tumors target a variety of structures and functions in the peripheral nervous system, including the neuronal cell body, the axonal transport system, the myelin sheath, and glial support structures. Each agent exhibits a spectrum of toxic effects unique to its mechanism of toxic injury, and recent study in this field has yielded clearer ideas on how to mitigate injury. Combined with the call for a greater recognition of the potentially devastating ramifications of CIPN on quality of life, basic and clinical researchers have begun to investigate therapy to prevent neurotoxic injury. Preliminary studies have shown promise for some agents including glutamine, glutathione, vitamin E, acetyl-L-carnitine, calcium, and magnesium infusions, but final recommendations await prospective confirmatory studies. PMID:16834943

Stillman, Mark; Cata, Juan P

2006-08-01

381

Diabetic neuropathy: mechanisms, emerging treatments, and subtypes.  

PubMed

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

Albers, James W; Pop-Busui, Rodica

2014-08-01

382

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

2013-01-01

383

Diabetic neuropathy and oxidative stress: therapeutic perspectives.  

PubMed

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

2013-01-01

384

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

1988-01-01

385

Subclinical Ulnar Neuropathy at the Elbow in Diabetic Patients  

PubMed Central

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

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

2014-01-01

386

Peripheral neuropathy in survivors of childhood acute lymphoblastic leukemia.  

PubMed

Acute lymphoblastic leukemia (ALL) is the most common form of cancer in children. Recent advances in treatment have led to dramatically improved survival rates. Standard ALL treatment includes multiple administrations of the chemotherapeutic drug vincristine, which is a known neurotoxic agent. Although peripheral neuropathy is a well-known toxicity among children receiving vincristine acutely, the long-term effects on the peripheral nervous system in these children are not clear. The objective of this study was to determine the prevalence of neuropathy and its impact on motor function and quality of life (QOL) among children who survived ALL. Thirty-seven survivors of childhood ALL aged 8-18 underwent evaluation for neuropathy through self-reported symptoms, standardized examinations, and nerve conduction studies (NCS). Functional impact of neuropathy was assessed using the Bruininks-Oseretsky test of Motor Proficiency (BOT-2). QOL was assessed using the PedsQL. Nerve conduction study abnormalities were seen in 29.7% of children who were longer than 2 years off therapy for ALL. Most children with an abnormal examination or NCS did not have subjective symptoms. Although overall motor function was below population norms on the BOT-2, presence of neuropathy did not significantly correlate with motor functional status or QOL. PMID:19909482

Ramchandren, Sindhu; Leonard, Marcia; Mody, Rajen J; Donohue, Janet E; Moyer, Judith; Hutchinson, Raymond; Gurney, James G

2009-09-01

387

Endoplasmic reticulum stress contributes to prediabetic peripheral neuropathy.  

PubMed

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

2013-09-01

388

PGC-1? regulation of mitochondrial degeneration in experimental diabetic neuropathy.  

PubMed

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

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

2014-04-01

389

HIV-Related Peripheral Neuropathy and Glucose Dysmetabolism: Study of a Public Dataset  

Microsoft Academic Search

Aims and Methods: The authors analyzed the public dataset of Multicenter AIDS Cohort Study to examine the association of glucose dysmetabolism with HIV-related peripheral neuropathy. Results: Among 5,622 participants in the data, 282 (5%) had peripheral neuropathy, of which 225 had sensory neuropathy. Of 225 participants with sensory neuropathy, 191 (84.8%) had exposure to highly active antiretroviral therapy. Of 225

Soham G. Sheth; Chitharanjan V. Rao; Alexandros Tselis; Richard A. Lewis

2007-01-01

390

NEUROPATHY AND QUALITY OF LIFE IN DIABETIC CONTINUOUS AMBULATORY PERITONEAL DIALYSIS PATIENTS  

Microsoft Academic Search

RoyalInfirmary, Renal Unit, Manchester, U.K. Oiabetes mellitus is the commonest cause of end -stage renal failure and is associated with considerable morbidity. Neuropathy is one of the most serious complications of diabetes, linked to the incidence of nephropathy and retinopathy. The prevalence of neuropathy increases with age and duration of diabetes. Peripheral sensorimotor neuropathy is the main manifestation of neurological

Theofanis Apostolou; Ram Gokal Manchester

391

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

PubMed

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

2010-06-01

392

Assessing corneal nerve structure and function in diabetic neuropathy.  

PubMed

The accurate detection and quantification of human diabetic peripheral neuropathy are important to define at-risk patients, anticipate deterioration and assess new therapies. Two emerging ophthalmic techniques, namely, corneal confocal microscopy and corneal aesthesiometry, demonstrate the ability to diagnose, quantify severity and assess therapeutic benefit in diabetic peripheral neuropathy. Corneal confocal microscopy allows quantification of corneal nerve morphology and non-contact corneal aesthesiometry assesses corneal sensitivity. The present review provides a detailed critique of the rationale, practical application in terms of the instruments used to capture images and the basis on which images are interpreted and analysed. We also critically evaluate how these two new non-invasive ophthalmic tests can be deployed to diagnose diabetic and other peripheral neuropathies. PMID:22594548

Tavakoli, Mitra; Petropoulos, Ioannis N; Malik, Rayaz A

2012-05-01

393

Pyridoxine induced neuropathy by subcutaneous administration in dogs  

PubMed Central

To construct a sensory neuropathy model, excess pyridoxine (150 mg/kg s.i.d.) was injected subcutaneously in dogs over a period of 7 days. During the administrations period, the dogs experienced body weight reduction and proprioceptive loss involving the hindquarters. After pyridoxine administration was completed, electrophysiological recordings showed that the M wave remained at a normal state, but the H-reflex of the treated dogs disappeared at 7 days. The dorsal funiculus of L4 was disrupted irregularly in the axons and myelin with vacuolation. The dorsal root ganglia of L4, and sciatic and tibial nerves showed degenerative changes and vacuolation. However, the lateral and ventral funiculi of L4 showed a normal histopathologic pattern. Although this subcutaneous administration method did not cause systemic toxicity and effectively induced sensory neuropathy, this study confirmed the possibility of producing a pyridoxine-induced sensory neuropathy model in dogs with short-term administration.

Chung, Jin-Young; Choi, Jung-Hoon; Hwang, Cheol-Yong

2008-01-01

394

Validation of bedside methods in evaluation of diabetic peripheral neuropathy  

PubMed Central

Background & objectives: Vibration perception threshold (VPT) is considered as a gold standard for diagnosis of diabetic peripheral neuropathy. However, the data are sparse comparing the VPT with commonly used bedside modalities. This study was carried out to evaluate the usefulness of simple bed side screening modalities for peripheral neuropathy in patients with diabetes mellitus. Methods: A total of 1044 patients with diabetes mellitus attending the Diabetes clinic from January 2007 to May 2008, were included in this study. All subjects had a detailed clinical assessment including Diabetic Neuropathy Symptom (DNS) score, Diabetic Neuropathy Examination (DNE) score, ankle reflex, vibration sensation with a 128 Hz tuning fork, 10g Semmes-Weinstein monofilament and vibration perception threshold (VPT). Results: The prevalence of peripheral neuropathy was 34.9 per cent with VPT. Foot care practices were followed by only 214 (20.5%) of the study population. When compared with VPT, ankle reflex was the most sensitive (90.7%) but least specific (37.3%). The tuning fork and monofilament tests respectively had lower sensitivity (62.5 and 62.8%) but better specificity (95.3 and 92.9%) and accuracy (78.9 and 77.9%). Significant correlations were observed between the VPT score and the DNE (r = 0.532, P<0.001) and DNS (r = 0.546, P<0.001) scores and absent tuning fork sensation (r= 0.590; P<0.001), monofilament sensation (r= 0.573; P<0.001) and ankle reflex (r = 0.377, P= 0.01). Interpretation & conclusions: The present findings show that simple bed side tests are useful for assessing peripheral diabetic neuropathy, even in those subjects in whom foot care practices are not followed.

Jayaprakash, P.; Bhansali, Anil; Bhansali, Shobhit; Dutta, Pinaki; Anantharaman, R.; Shanmugasundar, G.; Ravikiran, M.

2011-01-01

395

Effects of sorbinil therapy in diabetic patients with painful peripheral neuropathy and autonomic neuropathy.  

PubMed

Clinical investigations with the aldose reductase inhibitor sorbinil in patients with peripheral neuropathy due to diabetes are described. After an improvement in motor and sensory nerve conduction velocities was demonstrated in asymptomatic diabetic patients taking sorbinil (compared with velocities during a placebo period), 11 patients with painful diabetic neuropathy were treated with sorbinil for three weeks without alterations in diabetic management or control. Therapy was placebo-controlled in a single-blind fashion in eight patients. Pain (assessed by or on a zero to 20 rating scale), which had been constant for many months before entry into the study and unresponsive to numerous medications, improved from a mean score of 16 to 8 and returned when the drug was discontinued. Objective improvement in sensation and strength were observed in some cases. Improvements in nerve conduction velocity and cardiac autonomic function were also documented. Cardiac autonomic neuropathy was studied in 36 patients in a double-blind, placebo-controlled, randomized, noncrossover trial. Patients received one 250-mg sorbinil tablet or one placebo tablet daily for six weeks, after a one-week baseline period. Glycemic control did not change during the study period, as indicated by unaltered glycohemoglobin levels. Response was assessed by expiration-inspiration ratios, obtained on electrocardiography during six cycles per minute respiration, and by resting minimal heart rate, both measures of vagal function. In the sorbinil-treated group, expiration-inspiration ratios improved from 1.074 +/- 0.012 to 1.096 +/- 0.020 (p less than 0.03). There was a slight decrease in the ratios in the placebo-treated group, from 1.112 +/- 0.023 to 1.105 +/- 0.023 (not significant). The difference between the Week 0 to Week 6 changes in each group was significant (p less than 0.01). Resting minimal heart rate decreased in the sorbinil-treated group from 76.4 +/- 2.3 to 66.8 +/- 2.8 +/- 2.4 beats per minute (p less than 0.001), with a mean change of 10 +/- 2. In the placebo-treated group, heart rate was unchanged (77.9 +/- 3.9 to 77.5 +/- 3.3 beats per minute). The two-sample t test of the within-group differences was also significant (p less than 0.001). The changes in both expiration-inspiration ratios and resting minimal heart rate are consistent with a sorbinil-related improvement in cardiac parasympathetic nerve function. Several isolated cases of apparent sorbinil-related improvements in autonomic symptoms have been observed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:3000176

Jaspan, J B; Herold, K; Bartkus, C

1985-11-15

396

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

PubMed

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

Chimenti, Peter C; Hammert, Warren C

2013-08-01

397

The haematic thiamine level in the course of alcoholic neuropathy.  

PubMed

The specific roles of ethanol and malnutrition in the pathogenesis of neurological disorders of chronic alcoholism remain unclear. We measured plasmatic thiamine levels and erythrocyte transketolase activity in 30 alcoholics with peripheral neuropathy and in 4 with a Wernicke-Korsakoff (W-K) syndrome. Thiamine levels in the first group were comparable to those of normal subjects while a significantly lower concentration was found in W-K syndrome. Transketolase activity was lower for both groups in comparison with normal subjects. We suggest that a defect in thiamine utilization is involved in peripheral neuropathy of alcoholics, rather than a lack of thiamine itself. PMID:3032641

Paladin, F; Russo Perez, G

1987-01-01

398

Multifocal motor neuropathy presenting as chronic progressive proximal leg weakness.  

PubMed

We report on a 47-year-old man with a 12-year history of progressive and ultimately severe proximal weakness of his right lower limb. Motor conduction block at the unaffected tibial nerve and positive IgM antibodies against GM1 gangliosides lead us to suggest a diagnosis of oligosymptomatic multifocal motor neuropathy. He rapidly responded to intravenous immunoglobulins, with complete remission lasting 4 weeks, and had a repeated treatment response to intravenous immunoglobulins during subsequent exacerbations. The proximal involvement may represent another unusual clinical manifestation of multifocal motor neuropathy. PMID:15145341

Mäurer, Mathias; Stoll, Guido; Toyka, Klaus V

2004-06-01

399

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

PubMed Central

Hereditary neuropathy with liability to pressure palsies (HNPP) is an uncommon diagnosis that should be considered in patients with multiple compressive neuropathies. We present the case of a woman who presented with bilateral hand numbness and weakness. Electrodiagnostic testing revealed bilateral carpal tunnel syndrome, bilateral ulnar neuropathy at the elbow, left peroneal neuropathy at the fibular head, and a primarily demyelinating generalized sensorimotor neuropathy. Subsequent genetic testing identified a deletion at chromosome 17p11.2 to confirm the diagnosis of HNPP. Treatment of this largely self-limiting disease is controversial, and this patient suffered minimal disability with treatment including splinting and surgical releases.

Feinberg, Joseph; DiCarlo, Edward F.; Birchansky, Sherri B.; Wolfe, Scott W.

2007-01-01

400

Impact of cytokines on the pathomechanism of diabetic and alcoholic neuropathies.  

PubMed

Diabetic and alcoholic neuropathies are heterogeneous groups with variable lesions of axons or myelin. Their pathogenesis is complex and involves multiple pathways. To elucidate the impact of immunological factors in development of these neuropathies the expression of some cytokines in serum was studied: tumour necrosis factor a (TNF-a), monocyte chemotactic protein-1 (MCP-1) and growth-regulated oncogene alpha (GRO-alpha; CXCL1). 29 patients with type 2 diabetes, 31 with chronic alcohol abuse and 20 healthy controls were included in the study. The type of neuropathy (involvement of axon or myelin) was evaluated by electrophysiological methods (EMG and nerve conduction velocity). The cytokine level was determined by ELISA method. For statistical comparison the nonparametric Mann-Whitney test was used. The evaluated material was divided according to clinical duration of neuropathy and electrophysiological pattern. Expression of TNF-alpha in both types of neuropathy does not differ from the control material. Expression of MCP-1 was higher, but insignificantly, in patients with alcoholic neuropathy. The same concerns the demyelinating form versus axonal diabetic neuropathy. Serum level of GRO-alpha; was significantly higher in patients with alcoholic neuropathy and in cases with demyelinating form of diabetic neuropathy than in control subjects. GRO-alpha; is a potent neutrophil chemoattractant playing an important role in various primary and secondary inflammatory processes. The results suggest that GRO-alpha; may contribute to the mechanism of alcoholic neuropathy and in demyelinating form of diabetic neuropathy. PMID:17594598

Micha?owska-Wender, Grazyna; Adamcewicz, Grazyna; Wender, Mieczys?aw

2007-01-01

401

Peripheral neuropathy as a component of the neuroleptic malignant syndrome.  

PubMed

The neuroleptic malignant syndrome, an idiosyncratic reaction to antipsychotic medication, is defined by the tetrad of autonomic dysfunction, rigidity, fever, and altered mental status. Two patients in whom this syndrome developed acquired severe peripheral neuropathies during the course of their illness. This demyelinative polyneuropathy has not been reported previously as occurring in the neuroleptic malignant syndrome. PMID:3026179

Anderson, S A; Weinschenk, K

1987-01-01

402

Cubital Tunnel Reconstruction For Ulnar Neuropathy In Osteoarthritic Elbows  

Microsoft Academic Search

We operated on 16 patients for ulnar neuropathy associated with osteoarthritis of the elbow. They were all male manual workers, with an average age of 51 years at the time of surgery. The severity of the symptoms was McGowan grade 1 in five patients, grade 2 in nine and grade 3 in two. The mean follow-up was 36 months. The

Akihito Tsujino; Yoshiyasu Itoh; Koichiro Hayashi; Mitsuyoshi Uzawa

1997-01-01

403

Diabetic neuropathies: clinical manifestations and current treatment options  

Microsoft Academic Search

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

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

2006-01-01

404

The Haematic Thiamine Level in the Course of Alcoholic Neuropathy  

Microsoft Academic Search

The specific roles of ethanol and malnutrition in the pathogenesis of neurogical disorders of chronic alcoholism remain unclear. We measured plasmatic thiamine levels and erythrocyte transketolase activity in 30 alcoholics with peripheral neuropathy and in 4 with a Wernicke-Korsakoff (W-K) syndrome. Thiamine levels in the first group were comparable to those of normal subjects while a significantly lower concentration was

F. Paladin; Russo Perez

1987-01-01

405