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1

Genetics Home Reference: Hereditary sensory neuropathy type 1  

MedlinePLUS

... Genetic disorder catalog Conditions > Hereditary sensory neuropathy type 1 On this page: Description Genetic changes Inheritance Diagnosis ... December 2009 What is hereditary sensory neuropathy type 1? Hereditary sensory neuropathy type 1 is a condition ...

2

Genetics Home Reference: Hereditary sensory and autonomic neuropathy type V  

MedlinePLUS

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

3

Genetics Home Reference: Hereditary sensory and autonomic neuropathy type IE  

MedlinePLUS

... addition of methyl groups, consisting of one carbon atom and three hydrogen atoms, to DNA molecules. In particular, the enzyme helps ... understanding hereditary sensory and autonomic neuropathy type IE? atom ; autonomic nervous system ; autosomal ; autosomal dominant ; cell ; cytosine ; ...

4

Genes for Hereditary Sensory and Autonomic Neuropathies: A Genotype-Phenotype Correlation  

ERIC Educational Resources Information Center

Hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders characterized by axonal atrophy and degeneration, exclusively or predominantly affecting the sensory and autonomic neurons. So far, disease-associated mutations have been identified in seven genes: two genes for autosomal dominant ("SPTLC1"…

Rotthier, Annelies; Baets, Jonathan; De Vriendt, Els; Jacobs, An; Auer-Grumbach, Michaela; Levy, Nicolas; Bonello-Palot, Nathalie; Kilic, Sara Sebnem; Weis, Joachim; Nascimento, Andres; Swinkels, Marielle; Kruyt, Moyo C.; Jordanova, Albena; De Jonghe, Peter; Timmerman, Vincent

2009-01-01

5

Assessment and evaluation of hereditary sensory and autonomic neuropathies with autonomic and neurophysiological examinations  

Microsoft Academic Search

The five different types of the rare hereditary sensory and autonomic neuropathies (HSAN) are classified by their mode of inheritance, pathology, natural history, biochemical, neurophysiologic and autonomic abnormalities. Clinically, the different types of HSANs can be identified by a detailed history and examination and 'bedside' tests of sympathetic or parasympathetic function such as active standing, metronomic breathing or the Valsalva

Max J. Hilz

2002-01-01

6

Talectomy for Equinovarus Deformity in Family Members with Hereditary Motor and Sensory Neuropathy Type I  

PubMed Central

The treatment of severe rigid neurogenic clubfoot deformities still remains a challenging problem in modern paediatric orthopaedics. In those cases, in spite of being a palliative procedure, talectomy has been advocated for the correction of the deformity thus providing a stable plantigrade foot which allows pain-free walking with standard footwear. Herein, we present the results after talectomy in two patients (brother and sister) affected by a hereditary motor and sensory neuropathy type I, with rigid severe pes equinovarus deformities. PMID:25610681

Georgiev, Hristo

2014-01-01

7

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

PubMed Central

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

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

2014-01-01

8

Genetics of congenital insensitivity to pain with anhidrosis (CIPA) or hereditary sensory and autonomic neuropathy type IV  

Microsoft Academic Search

Summary Congenital insensitivity to pain with anhidrosis (CIPA) or hereditary sensory and autonomic neuropathy type IV (HSAN-IV) is an autosomal recessive disorder characterized by recurrent episodic fevers, anhidrosis (inability to sweat), absence of reaction to noxious (or painful) stimuli, self-mutilating behavior and mental retardation. The anomalous pain and temperature sensation and anhidrosis in CIPA are due to the absence of

Yasuhiro Indo

2002-01-01

9

Response to Immunosuppressive Therapy in Patients with Hereditary Motor and Sensory Neuropathy and Associated Dysimmune Neuromuscular Disorders  

Microsoft Academic Search

We encountered 2 patients with hereditary motor and sensory neuropathy (HMSN) type I who had marked weakness developing during several months superimposed on chronic peroneal muscular atrophy. Further studies disclosed a chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in one patient and CIDP associated with polymyositis in the other. Both patients responded to prednisone and azathioprine with substantial improvement. Patients with HMSN

Galen W. Mitchell; E. Peter Bosch; Michael N. Hart

1987-01-01

10

Hereditary sensory and autonomic neuropathy type 1 (HSANI) caused by a novel mutation in SPTLC2  

PubMed Central

Objective: To describe the clinical and neurophysiologic phenotype of a family with hereditary sensory and autonomic neuropathy type 1 (HSANI) due to a novel mutation in SPTLC2 and to characterize the biochemical properties of this mutation. Methods: We screened 107 patients with HSAN who were negative for other genetic causes for mutations in SPTLC2. The biochemical properties of a new mutation were characterized in cell-free and cell-based activity assays. Results: A novel mutation (A182P) was found in 2 subjects of a single family. The phenotype of the 2 subjects was an ulcero-mutilating sensory-predominant neuropathy as described previously for patients with HSANI, but with prominent motor involvement and earlier disease onset in the first decade of life. Affected patients had elevated levels of plasma 1-deoxysphingolipids (1-deoxySLs). Biochemically, the A182P mutation was associated with a reduced canonical activity but an increased alternative activity with alanine, which results in largely increased 1-deoxySL levels, supporting their pathogenicity. Conclusion: This study confirms that mutations in SPTLC2 are associated with increased deoxySL formation causing HSANI. PMID:23658386

Murphy, Sinéad M.; Ernst, Daniela; Wei, Yu; Laurŕ, Matilde; Liu, Yo-Tsen; Polke, James; Blake, Julian; Winer, John; Houlden, Henry; Hornemann, Thorsten

2013-01-01

11

Hereditary sensory and autonomic neuropathy type V: Report of a rare case  

PubMed Central

Hereditary sensory and autonomic neuropathy (HSAN) type V is a rare inherited disease caused by a mutation in the neurotrophic tyrosine kinase receptor, type 1 gene located on chromosome 1 (1q21-q22). It is characterized by pain insensitivity, partial anhydrosis without mental retardation and unimpaired touch and pressure sensitivity. Self-mutilation injury involving the teeth, lips, tongue, ears, eyes, nose, and fingers are invariable feature of this disorder. The purpose of this paper was to discuss the diagnosis and oral management of 18-month-old girl with HSAN type V, having typical oral manifestation of bitten tongue and auto-extraction of primary teeth. Modified bite guard was given to the patient to prevent further self-mutilating injuries to the tongue.

Kalaskar, Ritesh; Kalaskar, Ashita

2015-01-01

12

Hereditary sensory and autonomic neuropathy type V: Report of a rare case.  

PubMed

Hereditary sensory and autonomic neuropathy (HSAN) type V is a rare inherited disease caused by a mutation in the neurotrophic tyrosine kinase receptor, type 1 gene located on chromosome 1 (1q21-q22). It is characterized by pain insensitivity, partial anhydrosis without mental retardation and unimpaired touch and pressure sensitivity. Self-mutilation injury involving the teeth, lips, tongue, ears, eyes, nose, and fingers are invariable feature of this disorder. The purpose of this paper was to discuss the diagnosis and oral management of 18-month-old girl with HSAN type V, having typical oral manifestation of bitten tongue and auto-extraction of primary teeth. Modified bite guard was given to the patient to prevent further self-mutilating injuries to the tongue. PMID:25684922

Kalaskar, Ritesh; Kalaskar, Ashita

2015-01-01

13

[Hereditary optic neuropathies].  

PubMed

Hereditary optic neuropathies are a group of heterogeneous conditions affecting both optic nerves, with an autosomal dominant, autosomal recessive, X-related or mitochondrial transmission. The two most common non-syndromic hereditary optic neuropathies (Leber's hereditary optic neuropathy and autosomal dominant optic atrophy) are very different in their clinical presentation and their genetic transmission, leading however to a common, non-specific optic nerve atrophy. Beyond the optic atrophy-related visual loss, which is the clinical hallmark of this group of diseases, other associated neurological signs are increasingly recognized. PMID:22989781

Milea, D; Verny, C

2012-10-01

14

Genetic aspects of hereditary motor and sensory neuropathy (types I and II)  

PubMed Central

The genetic features of a series of 227 patients with hereditary motor and sensory neuropathy (HMSN) have been analysed. The series comprised 119 index cases from 110 families in which 108 affected relatives were identified. The cases were classified as having type I or type II HMSN on the basis of nerve conduction studies. Inheritance in the type I cases was autosomal dominant in 139 (45 families) and autosomal recessive in eight (four families) with 26 single cases. For the type II cases, 35 (17 families) were autosomal dominant and three (two families) autosomal recessive with 16 single cases. A significant excess of males was present in the combined single and recessive type I cases and in the type I index cases. No X linked pedigrees were identified. The correlation coefficients for motor nerve conduction velocity between the index cases and their relatives suggested further genetic heterogeneity in the type I cases. Parent-offspring and sib-sib correlation coefficients for age of onset in the dominantly inherited type I cases were less than 0·5. There was therefore no strong suggestion of genetic heterogeneity in terms of age of onset. The severity of muscle weakness did not differ between the dominantly inherited type I and type II cases. In both types males had higher weakness scores than females, but there was no difference for either type in relation to the sex of the affected parent. Segration analysis suggested that approximately 70% of the single generation type I cases were of autosomal recessive inheritance, whereas only about 25% of the single generation type II cases were recessive. Biological fitness was reduced in type II HMSN, which would support a higher proportion of new dominant mutations among the single cases of this type than in type I. Despite the excess of males in the type I single case/recessive category, a contribution of cases with X linked recessive inheritance is improbable. Single cases of HMSN, especially the type II form in view of its later onset, are likely to be unrecognised clinically and will be classified as `cryptogenic' neuropathy. As in many affected subjects the degree of disability is minimal, a careful scrutiny of the relatives is merited in such instances. PMID:7218272

Harding, A E; Thomas, P K

1980-01-01

15

The electrophysiological profile of hereditary motor and sensory neuropathy–Lom  

PubMed Central

Clinical findings: Onset was in early childhood with gait difficulty related to progressive lower limb weakness. Upper limb weakness developed later. Bulbar involvement was present in one third of the patients, and deafness appeared during the second or third decades. Electrophysiological findings: Electromyographic evidence of denervation was progressive, more severe distally, and greater in the legs, being total in distal lower limb muscles in most patients. Sensory action potentials were absent and motor nerve conduction was severely slowed. This included proximal upper limb (musculocutaneous and axillary), hypoglossal, and facial nerves. The severity of slowing increased during childhood. M waves, often multiple, were recorded in all affected individuals. The blink reflex showed an unusual three component response. The latencies of all three components were prolonged. Conclusions: HMSN-L is shown to be a demyelinating neuropathy involving severe and early axonal loss. The progressive slowing of nerve conduction during childhood differs from the static reduction seen in type I HMSN. PMID:15897517

Ishpekova, B; Christova, L; Alexandrov, A; Thomas, P

2005-01-01

16

Genetics Home Reference: Hereditary neuropathy with liability to pressure palsies  

MedlinePLUS

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

17

Genetics of the Charcot-Marie-Tooth disease in the Spanish Gypsy population: the hereditary motor and sensory neuropathy-Russe in depth.  

PubMed

Four private mutations responsible for three forms demyelinating of Charcot-Marie-Tooth (CMT) or hereditary motor and sensory neuropathy (HMSN) have been associated with the Gypsy population: the NDRG1 p.R148X in CMT type 4D (CMT4D/HMSN-Lom); p.C737_P738delinsX and p.R1109X mutations in the SH3TC2 gene (CMT4C); and a G>C change in a novel alternative untranslated exon in the HK1 gene causative of CMT4G (CMT4G/HMSN-Russe). Here we address the findings of a genetic study of 29 Gypsy Spanish families with autosomal recessive demyelinating CMT. The most frequent form is CMT4C (57.14%), followed by HMSN-Russe (25%) and HMSN-Lom (17.86%). The relevant frequency of HMSN-Russe has allowed us to investigate in depth the genetics and the associated clinical symptoms of this CMT form. HMSN-Russe probands share the same haplotype confirming that the HK1 g.9712G>C is a founder mutation, which arrived in Spain around the end of the 18th century. The clinical picture of HMSN-Russe is a progressive CMT disorder leading to severe weakness of the lower limbs and prominent distal sensory loss. Motor nerve conduction velocity was in the demyelinating or intermediate range. PMID:22978647

Sevilla, T; Martínez-Rubio, D; Márquez, C; Paradas, C; Colomer, J; Jaijo, T; Millán, J M; Palau, F; Espinós, C

2013-06-01

18

Genetics Home Reference: Leber hereditary optic neuropathy  

MedlinePLUS

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

19

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

PubMed

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

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

2014-01-01

20

[Review of the recent literature on hereditary neuropathies].  

PubMed

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

Birouk, N

2014-12-01

21

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

PubMed Central

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

Ceranic, B; Luxon, L

2004-01-01

22

Distal hereditary motor neuropathy type II (distal HMN II): mapping of a locus to chromosome 12q24  

Microsoft Academic Search

The distal hereditary motor neuropathy (distal HMN) or the spinal form of Charcot-Marie-Tooth (CMT) disease is an exclusively motor disorder of the peripheral nerv- ous system. The disorder clinically resembles the her- editary motor and sensory neuropathies (HMSN) type I and type II or CMT type 1 and type 2. Distal HMN might also be related to the spinal muscular

Vincent Timmerman; Peter De Jonghe; Sandra Simokovic; Ann Löfgren; Joke Beuten; Eva Nelis; Chantal Ceuterick; Jean-Jacques Martin; Christine Van Broeckhoven

1996-01-01

23

Hereditary optic neuropathies share a common mitochondrial coupling defect.  

PubMed

Hereditary optic neuropathies are heterogeneous diseases characterized by the degeneration of retinal ganglion cells leading to optic nerve atrophy and impairment of central vision. We found a common coupling defect of oxidative phosphorylation in fibroblasts of patients affected by autosomal dominant optic atrophy (mutations of OPA1), autosomal dominant optic atrophy associated with cataract (mutations of OPA3), and Leber's hereditary optic neuropathy, a disorder associated with point mutations of mitochondrial DNA complex I genes. Interestingly, the energetic defect was significantly more pronounced in Leber's hereditary optic neuropathy and autosomal dominant optic atrophy patients with a more complex phenotype, the so-called plus phenotype. PMID:18496845

Chevrollier, Arnaud; Guillet, Virginie; Loiseau, Dominique; Gueguen, Naďg; de Crescenzo, Marie-Anne Pou; Verny, Christophe; Ferre, Marc; Dollfus, Hélčne; Odent, Sylvie; Milea, Dan; Goizet, Cyril; Amati-Bonneau, Patrizia; Procaccio, Vincent; Bonneau, Dominique; Reynier, Pascal

2008-06-01

24

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.?? PMID:9576536

Moretto, A.; Lotti, M.

1998-01-01

25

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

26

Inherited Neuropathies  

Microsoft Academic Search

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

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

2011-01-01

27

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

PubMed Central

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

2014-01-01

28

[Autoimmune autonomic ganglionopathy and acute autonomic and sensory neuropathy].  

PubMed

Autonomic neuropathies may occur primarily or secondarily to various underlying diseases. Primary autonomic neuropathies are divided into pure autonomic neuropathy, autonomic neuropathy with sensory impairment, and autonomic neuropathy with sensory and motor impairment based on the concomitance or absence of sensory or motor dysfunctions. Autoimmune autonomic ganglionopathy refers to a pure autonomic neuropathy, which typically affects both cholinergic and adrenergic functions. About a half of the patients with autoimmune autonomic ganglionopathy are positive for anti-ganglionic acetylcholine receptor antibodies. The mode of progression widely ranges from acute to chronic, including that mimicking pure autonomic failure. The number of unmyelinated fibers in the sural nerve biopsy specimens tends to decrease with the duration of disease become longer. Immunomodulatory treatments are suggested to be effective for autoimmune autonomic ganglionopathy. Acute autonomic and sensory neuropathy is characterized by autonomic and sensory impairment without motor dysfunction that reaches its nadir within a short period of time mimicking the progression of Guillain-Barré syndrome. The monophasic clinical course and frequent presence of a history of antecedent infections suggests a participation of immune mechanisms. The initial symptoms are those related to autonomic disturbance or superficial sensory impairment, while deep sensory impairment accompanied by sensory ataxia subsequently appears in some patients. Sural nerve biopsy specimens reveal small-fiber predominant axonal loss, and autopsy cases show neuronal loss in the thoracic sympathetic and dorsal root ganglia. Hence, small neurons in the autonomic and sensory ganglia may be affected in the initial phase and, subsequently, large neurons in the sensory ganglia are damaged in acute autonomic and sensory neuropathy. PMID:24291976

Koike, Haruki; Sobue, Gen

2013-01-01

29

Hereditary Neuropathy with Liability to Pressure Palsy: A Recurrent and Bilateral Foot Drop Case Report  

PubMed Central

Hereditary neuropathy with liability to pressure palsy is characterized by acute, painless, recurrent mononeuropathies secondary to minor trauma or compression. A 16-year-old boy had the first episode of right foot drop after minor motorcycle accident. Electromyography revealed conduction block and slowing velocity conduction of the right deep peroneal nerve at the fibular head. After motor rehabilitation, he fully recovered. Six months later he had the second episode of foot drop in the opposite site after prolonged squatting position. Electromyography revealed sensorimotor polyneuropathy of left peroneal, sural, posterior tibial, and deep peroneal nerves and also of ulnar, radial, and median nerves of both upper limbs. Histological examination revealed sensory nerve demyelination and focal thickenings of myelin fibers. The diagnosis of hereditary neuropathy with liability to pressure palsy was confirmed by PMP22 deletion of chromosome 17p11.2. He started motor rehabilitation and avoidance of stressing factors with progressive recovery. After one-year followup, he was completely asymptomatic. Recurrent bilateral foot drop history, “sausage-like” swellings of myelin in histological examination, and the results of electromyography led the authors to consider the diagnosis despite negative family history. The authors highlight this rare disease in pediatric population and the importance of high index of clinical suspicion for its diagnosis. PMID:24251057

Flor-de-Lima, Filipa; Taipa, Ricardo; Melo-Pires, Manuel; Rodrigues, Maria Lurdes

2013-01-01

30

Sensory neuropathy as part of the cerebellar ataxia neuropathy vestibular areflexia syndrome  

PubMed Central

Objective: The syndrome of cerebellar ataxia with bilateral vestibulopathy was delineated in 2004. Sensory neuropathy was mentioned in 3 of the 4 patients described. We aimed to characterize and estimate the frequency of neuropathy in this condition, and determine its typical MRI features. Methods: Retrospective review of 18 subjects (including 4 from the original description) who met the criteria for bilateral vestibulopathy with cerebellar ataxia. Results: The reported age at onset range was 39–71 years, and symptom duration was 3–38 years. The syndrome was identified in one sibling pair, suggesting that this may be a late-onset recessive disorder, although the other 16 cases were apparently sporadic. All 18 had sensory neuropathy with absent sensory nerve action potentials, although this was not apparent clinically in 2, and the presence of neuropathy was not a selection criterion. In 5, the loss of pinprick sensation was virtually global, mimicking a neuronopathy. However, findings in the other 11 with clinically manifest neuropathy suggested a length-dependent neuropathy. MRI scans showed cerebellar atrophy in 16, involving anterior and dorsal vermis, and hemispheric crus I, while 2 were normal. The inferior vermis and brainstem were spared. Conclusions: Sensory neuropathy is an integral component of this syndrome. It may result in severe sensory loss, which contributes significantly to the disability. The MRI changes are nonspecific, but, coupled with loss of sensory nerve action potentials, may aid diagnosis. We propose a new name for the condition: cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS). Neurology® 2011;76:1903–1910 PMID:21624989

Waterston, J.A.; Halmagyi, G.M.; Mossman, S.; Chancellor, A.M.; McLean, C.A.; Storey, E.

2011-01-01

31

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

32

Diagnosis and new treatments in genetic neuropathies  

Microsoft Academic Search

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

M M Reilly; M E Shy

2009-01-01

33

[Denny-Brown sensory neuropathy disclosing a bilateral ovarian adenocarcinoma].  

PubMed

The authors report the case of a 76 year-old woman examined because of occurrence of a paraneoplastic sensory neuropathy. Three months later, she developed a left inguinal adenopathy, metastasis of a bilateral ovarian adenocarcinoma. This case of particular interest in view of the way the neoplasm was discovered. The sensory neuropathy was previously reported to be associated with an ovarian cancer in only one case of the literature. Besides the tumor masse only limited to a left inguinal adenopathy, in this case emphasizes the ability of these rare metastasis. The ovarian cancer-associated antigen CA 125 is particularly useful for the diagnosis when high levels are found. In the absence of a pelvic tumor masse, the paraneoplastic sensory neuropathy, as well as the high levels of CA 125, have resulted in an exploratory laparotomy with extemporaneous examination of the ovaries, enabling to make the diagnosis of bilateral ovarian adenocarcinoma. PMID:3206097

Humbert, P; Mas, J; Monnier, G; Carbillet, J P; Chatelain, F; Montcuquet, P; Dupond, J L

1988-11-01

34

[Analysis of the clinical, electrophysiological and genetic features of a family affected with hereditary neuropathy with liability to pressure palsies].  

PubMed

OBJECTIVE To delineate the clinical, electrophysiological and genetics features of a family where 4 members were affected with hereditary neuropathy with liability to pressure palsies (HNPP). METHODS Clinical features of the 4 patients were summarized. Electrophysiological examination and genetic analysis were carried out. RESULTS All of the patients showed recurrent motor and sensory disturbances after minor traction or constriction. Electrophysiology study revealed that the prolonged latency and reduced conduction velocity of peripheral nerve were general and with multiple sites of affection. The nerve locations liable to entrapment showed conduction block. A deletion mutation of peripheral myelin protein 22 (PMP22) gene was identified by genetic analysis. CONCLUSION HNPP usually affects areas where nerves are liable to entrapment, and presents with motor and sensory disturbances of the innervated areas. Electrophysiological study reveals general nervous demyelination. Genetic analysis can clarify the diagnosis of HNPP. PMID:25636095

Qi, Faying; Che, Fengyuan

2015-02-10

35

Pathological features of ganglioradiculitis (sensory neuropathy) in two dogs.  

PubMed

Canine ganglioradiculitis (sensory neuropathy) was examined pathologically in two dogs (dog Nos. 1 and 2). The affected dogs had 1 and 2 years clinical courses from the onset, respectively. As common clinical signs, both cases showed progressive ataxia, difficulty in prehending food, visual deficit, and several sensory abnormalities. Gross observation after tissue fixation revealed whitish discoloration in the dorsal column of the spinal cords. The histological lesions were mainly distributed in the spinal dorsal roots, ganglions, and dorsal columns. In the spinal dorsal roots and ganglions, there were striking myelin loss, mild infiltration of mononuclear cells, and proliferation of small spindle cells. In the dorsal funiculus, there were moderate to severe diffuse myelin-loss and axonal degeneration. Immunohistochemistry for substance P (SP) revealed marked reduction of SP-immunopositive granules in the spinal substantia gelatinosa of affected dogs. By immunohistochemistry, CD3-positive cells were observed in the dorsal roots of dog No. 2, while CD3-positive cells were rare in those of dog No. 1. In the spinal ganglion of dog No. 1 there were many CD3- and MHC class II-positive cells. By indirect immunofluorescence assay using sera from affected dogs, no autoantibodies against canine nerve tissues were detected. The clinicopathological features of the present cases are almost consistent with those in previous reports of canine sensory neuropathies, while the etiology remains unclear. PMID:18176020

Funamoto, Miwako; Nibe, Kazumi; Morozumi, Motoji; Edamura, Kazuya; Uchida, Kazuyuki

2007-12-01

36

Anti-histone antibodies in subacute sensory neuropathy.  

PubMed

We investigated the levels of anti-histone antibodies in the sera of 7 patients with subacute sensory neuropathy. IgG antibodies to histones H1 and H3 were significantly elevated in 4 of these patients. The anti-H1 antibodies reacted mainly with determinants located in the central globular and the carboxy-terminal domain of the H1 molecule. We also observed reactivity of these sera with histone H1 zero, a variant found in terminally-differentiated cells such as neurons. This study suggests a potential for histones to serve as autoantigens in humorally-mediated paraneoplastic diseases. PMID:1655989

Monestier, M; Fasy, T M; Bohm, L; Lieberman, F S

1991-08-01

37

THE ROLE OF GLYOXALASE I IN HYPERGLYCEMIA-INDUCED SENSORY NEURON DAMAGE AND DEVELOPMENT OF DIABETIC SENSORY NEUROPATHY SYMPTOMS  

E-print Network

Diabetic neuropathy is the most common and debilitating complication of diabetes mellitus with over half of all patients developing altered sensation as a result of damage to peripheral sensory neurons. Hyperglycemia results in altered nerve...

Jack, Megan Marie

2011-08-31

38

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. PMID:24369379

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

39

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

40

Hereditary motor and sensory neuropathy type I and type II  

Microsoft Academic Search

In an attempt to clearly identify the different HMSN subgroups, we prospectively evaluated 128 subjects (46 index cases, 39 affected and 43 unaffected relatives) on clinical, genetic and electrophysiological grounds. The diagnosis of HMNS I or II was made in 77 patients. Differential diagnosis between type I and II patients was impossible on clinical grounds alone, but nerve conduction study

A. Sghirlanzoni; D. Pareyson; V. Scaioli; R. Marazzi; L. Pacini

1990-01-01

41

Genetics Home Reference: Hereditary sensory and autonomic neuropathy type II  

MedlinePLUS

... Patients and Families Resources for Health Professionals What glossary definitions help with understanding HSAN2? acids ; apnea ; apoptosis ; ... many other terms in the Genetics Home Reference Glossary . See also Understanding Medical Terminology . References (9 links) ...

42

Cannabis in painful HIV-associated sensory neuropathy: A randomized placebo-controlled trial  

Microsoft Academic Search

Objective: To determine the effect of smoked cannabis on the neuropathic pain of HIV-associated sensory neuropathy and an experimental pain model. Methods: Prospective randomized placebo-controlled trial conducted in the inpatient General Clinical Research Center between May 2003 and May 2005 involving adults with painful HIV- associated sensory neuropathy. Patients were randomly assigned to smoke either cannabis (3.56% tetrahydrocannabinol) or identical

D. I. Abrams; C. A. Jay; S. B. Shade; H. Vizoso; H. Reda; M. E. Kelly; M. C. Rowbotham; K. L. Petersen

2007-01-01

43

Partial Gene Deletions of PMP22 Causing Hereditary Neuropathy with Liability to Pressure Palsies  

PubMed Central

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal neuropathy that is commonly caused by a reciprocal 1.5?Mb deletion on chromosome 17p11.2, at the site of the peripheral myelin protein 22 (PMP22) gene. Other patients with similar phenotypes have been shown to harbor point mutations or small deletions, although there is some clinical variation across these patients. In this report, we describe a case of HNPP with copy number changes in exon or promoter regions of PMP22. Multiplex ligation-dependent probe analysis revealed an exon 1b deletion in the patient, who had been diagnosed with HNPP in the first decade of life using molecular analysis. PMID:25506001

Cho, Sun-Mi; Kim, Yoonjung; Lee, Sang Guk; Yang, Jin-Young

2014-01-01

44

Leber hereditary optic neuropathy - Historical report in comparison with the current knowledge.  

PubMed

Leber hereditary optic neuropathy (LHON) is a genetic, maternally inherited disease caused by point mutations in the mitochondrial genome. LHON patients present with sudden, painless and usually bilateral loss of vision caused by optic nerve atrophy. The first clinical description of the disease was made by Theodor Leber, a German ophthalmologist, in 1871. Here we present his thorough notes about members of four families and their pedigrees. We also provide insights into the current knowledge about LHON pathology, genetics and treatment in comparison with Leber's findings. PMID:25261848

Piotrowska, Agnieszka; Korwin, Magdalena; Bartnik, Ewa; To?ska, Katarzyna

2015-01-15

45

Mitochondrial DNA variation and HIV-associated sensory neuropathy in CHARTER.  

PubMed

HIV-associated sensory neuropathy remains an important complication of combination antiretroviral therapy and HIV infection. Mitochondrial DNA haplogroups and single nucleotide polymorphisms (SNPs) have previously been associated with symptomatic neuropathy in clinical trial participants. We examined associations between mitochondrial DNA variation and HIV-associated sensory neuropathy in CNS HIV Antiretroviral Therapy Effects Research (CHARTER). CHARTER is a USA-based longitudinal observational study of HIV-infected adults who underwent a structured interview and standardized examination. HIV-associated sensory neuropathy was determined by trained examiners as ?1 sign (diminished vibratory and sharp-dull discrimination or ankle reflexes) bilaterally. Mitochondrial DNA sequencing was performed and haplogroups were assigned by published algorithms. Multivariable logistic regression of associations between mitochondrial DNA SNPs, haplogroups, and HIV-associated sensory neuropathy were performed. In analyses of associations of each mitochondrial DNA SNP with HIV-associated sensory neuropathy, the two most significant SNPs were at positions A12810G [odds ratio (95 % confidence interval)?=?0.27 (0.11-0.65); p?=?0.004] and T489C [odds ratio (95 % confidence interval)?=?0.41 (0.21-0.80); p?=?0.009]. These synonymous changes are known to define African haplogroup L1c and European haplogroup J, respectively. Both haplogroups were associated with decreased prevalence of HIV-associated sensory neuropathy compared with all other haplogroups [odds ratio (95 % confidence interval)?=?0.29 (0.12-0.71); p?=?0.007 and odds ratio (95 % confidence interval)?=?0.42 (0.18-1.0); p?=?0.05, respectively]. In conclusion, in this cohort of mostly combination antiretroviral therapy-treated subjects, two common mitochondrial DNA SNPs and their corresponding haplogroups were associated with a markedly decreased prevalence of HIV-associated sensory neuropathy. PMID:23073667

Holzinger, Emily R; Hulgan, Todd; Ellis, Ronald J; Samuels, David C; Ritchie, Marylyn D; Haas, David W; Kallianpur, Asha R; Bloss, Cinnamon S; Clifford, David B; Collier, Ann C; Gelman, Benjamin B; Marra, Christina M; McArthur, Justin C; McCutchan, J Allen; Morgello, Susan; Simpson, David M; Franklin, Donald R; Rosario, Debralee; Selph, Doug; Letendre, Scott; Grant, Igor

2012-12-01

46

Oxidative phosphorylation differences between mitochondrial DNA haplogroups modify the risk of Leber's hereditary optic neuropathy.  

PubMed

Leber's hereditary optic neuropathy is a maternally inherited optic atrophy caused by mitochondrial DNA point mutations. Previous epidemiological studies have shown that individuals from mitochondrial genetic backgrounds (haplogroups) J/Uk and H have a higher and a lower risk, respectively, of suffering this disorder. To analyze the bases of these associations at cellular and molecular levels, functional studies with cybrids provide high quality evidence. Cybrids from haplogroup J contain less mitochondrial deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) and synthesize a smaller amount of mitochondrial DNA-encoded polypeptides than those from haplogroup H. Haplogroup J cybrids also display lower oxygen consumption, mitochondrial inner membrane potential and total adenosine-5'-triphosphate (ATP) levels. Moreover, mitochondrial DNA levels correlate with many parameters of the oxidative phosphorylation system. These results suggest that the mitochondrial DNA amount determines oxidative phosphorylation capacity and, along with other recently published observations, support the possibility that mitochondrial DNA levels may be responsible for the bias of the disorder toward males, for the incomplete penetrance of mutations causing Leber's hereditary optic neuropathy and for the association of the disease with particular mitochondrial DNA haplogroups. PMID:22561905

Gómez-Durán, Aurora; Pacheu-Grau, David; Martínez-Romero, Ińigo; López-Gallardo, Ester; López-Pérez, Manuel J; Montoya, Julio; Ruiz-Pesini, Eduardo

2012-08-01

47

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

48

Relative Contribution of Mutations in Genes for Autosomal Dominant Distal Hereditary Motor Neuropathies: A Genotype-Phenotype Correlation Study  

ERIC Educational Resources Information Center

Distal hereditary motor neuropathy (HMN) is a clinically and genetically heterogeneous group of disorders affecting spinal alpha-motor neurons. Since 2001, mutations in six different genes have been identified for autosomal dominant distal HMN; "glycyl-tRNA synthetase (GARS)," "dynactin 1 (DCTN1)," "small heat shock 27 kDa protein 1 (HSPB1),"…

Dierick, Ines; Baets, Jonathan; Irobi, Joy; Jacobs, An; De Vriendt, Els; Deconinck, Tine; Merlini, Luciano; Van den Bergh, Peter; Rasic, Vedrana Milic; Robberecht, Wim; Fischer, Dirk; Morales, Raul Juntas; Mitrovic, Zoran; Seeman, Pavel; Mazanec, Radim; Kochanski, Andrzej; Jordanova, Albena; Auer-Grumbach, Michaela; Helderman-van den Enden, A. T. J. M.; Wokke, John H. J.; Nelis, Eva; De Jonghe, Peter; Timmerman, Vincent

2008-01-01

49

Achalasia, chronic sensory neuropathy, and N-type calcium channel autoantibodies: beneficial response to IVIG  

Microsoft Academic Search

Autoimmune gastrointestinal dysmotility (AGID) can result from paraneoplastic onconeuronal antibodies. Patients may present\\u000a with regional hypomotility anywhere along the gastrointestinal tract. We report a case of a woman who developed an insidious\\u000a sensory neuropathy and achalasia. She was found to have a high-titer of N-type voltage gated-calcium channel (VGCC) antibodies.\\u000a She demonstrated clinical and electrophysiological improvement of her neuropathy, as

Hugh J. McMillan; Jayashri Srinivasan

2010-01-01

50

Arnold’s nerve cough reflex: evidence for chronic cough as a sensory vagal neuropathy  

PubMed Central

Arnold’s nerve ear-cough reflex is recognised to occur uncommonly in patients with chronic cough. In these patients, mechanical stimulation of the external auditory meatus can activate the auricular branch of the vagus nerve (Arnold’s nerve) and evoke reflex cough. This is an example of hypersensitivity of vagal afferent nerves, and there is now an increasing recognition that many cases of refractory or idiopathic cough may be due to a sensory neuropathy of the vagus nerve. We present two cases where the cause of refractory chronic cough was due to sensory neuropathy associated with ear-cough reflex hypersensitivity. In both cases, the cough as well as the Arnold’s nerve reflex hypersensitivity were successfully treated with gabapentin, a treatment that has previously been shown to be effective in the treatment of cough due to sensory laryngeal neuropathy (SLN). PMID:25383210

Gibson, Peter G.; Birring, Surinder S.

2014-01-01

51

Pure sensory neuropathy in patients with primary Sjögren's syndrome: clinical, immunological, and electromyographic findings.  

PubMed Central

A pure sensory neuropathy caused by lymphocytic infiltration of the dorsal root ganglia has been reported in a few patients with Sjögren's syndrome. The clinical, immunological, and electromyographic findings of five patients with this type of neuropathy and primary Sjögren's syndrome were reviewed. Typical clinical indications were the presence of a chronic asymmetrical sensory deficit, initial disease in the hands with a predominant loss of the vibratory and joint position senses, and an association with Adie's pupil syndrome or trigeminal sensory neuropathy. The simultaneous impairment of the central and peripheral evoked cortical potentials suggested that there was a lesion of the neuronal cell body. The neuropathy preceded the diagnosis of Sjögren's syndrome in four patients. Four patients were positive for Ro antibodies, but systemic vasculitis or malignancy was not found after a mean follow up of six years. These findings indicate that in patients with a sensory neuropathy the diagnosis of Sjögren's syndrome has to be considered, even if the patient denies the presence of sicca symptoms, and that appropriate tests must be carried out. PMID:2173499

Font, J; Valls, J; Cervera, R; Pou, A; Ingelmo, M; Graus, F

1990-01-01

52

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

PubMed

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

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

2015-01-12

53

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

54

Diagnostic challenges in movement disorders: Sensory Ataxia Neuropathy Dysarthria and Ophthalmoplegia (SANDO) syndrome.  

PubMed

A woman in her early 60s presented to our Movement Disorders Centre with a 5-year history of progressive peripheral neuropathy, gait instability with falls, blurred vision, cognitive impairment and tremors. The patient was found to have profound sensory ataxia, chronic ophthalmoplegia, dementia with significant deficits in registration and construction and bilateral resting tremor of the hands. Investigations revealed an unremarkable MRI of the brain, negative cerebrospinal fluid studies, and unremarkable chemistries. Nerve conduction studies found a severe sensorimotor axonal polyneuropathy. Genetic testing revealed a compound heterozygous mutation in the POLG1 gene consistent with the diagnosis of Sensory Ataxia Neuropathy Dysarthria and Ophthalmoplegia (SANDO) syndrome. PMID:23997076

Lovan, Alyson; Ihtsham ul Haq; Balakrishnan, Nikhil

2013-01-01

55

A locus for axonal motor-sensory neuropathy with deafness and mental retardation maps to Xq24-q26  

SciTech Connect

DNA markers on the X chromosome were used to map the locus for an unusual form of X-linked recessive hereditary motor and sensory neuropathy with associated deafness and mental retardation in a three-generation family that was originally reported by Towchock et al. This family included seven affected males, three obligate carrier females, and four unaffected males. The patients were severely affected within the first few years of life with distal weakness, muscle atrophy, sensory loss, areflexia, pes cavus, and hammer toes. Five of the seven affected males showed associated deafness, and three of these five individuals also presented with mental retardation or social development delay. Motor nerve conduction velocitites in affected males were normal to mildly delayed, and sensory conduction was markedly abnormal. Heterozygous females were asymptomatic. Close linkage to the Xg blood group locus (Xp22) and the PGK locus (Xq13) was previously excluded in this family, while weak linkage of the disease gene to DXYS1 (Xq21.3) was suggested. Our current linkage studies and haplotype analysis of 19 microsatellite markers on the long arm of the X chromosome demonstrate that DXS425 (Xq24) and HPRT (Xq26.1) are flanking markers and that the disease gene is closely linked to the markers DSX1122, DXS994, DXS737, DXS100, DXS1206, and DXS1047. 27 refs., 1 fig., 2 tabs.

Priest, J.M.; Nouri, N.; Keats, B.J.B. [Louisiana State Univ. Medical Center, New Orleans, LA (United States)] [and others

1995-09-20

56

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

PubMed Central

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

Barohn, Richard J.; Katz, Jonathan

2014-01-01

57

A locus for axonal motor-sensory neuropathy with deafness and mental retardation maps to Xq26-q27  

SciTech Connect

Twenty-two DNA markers spanning the X chromosome have been analyzed for linkage to the locus causing an unusual form of X-linked recessive hereditary motor and sensory neuropathy in a Pennsylvania family of Italian ancestry. This 3 generation family which was originally reported by Cowchock includes 7 affected males, 3 obligate carrier females, and 4 unaffected males. Males are severely affected at birth or within the first few years of life with areflexia, slowly progressive axonal atrophy, and absence of large myelinated fibers, and they all develop pes cavus and hammer toes. Five of the 7 affected males show associated deafness and 3 of these 5 individuals also presented with mental retardation or social developmental delay. Motor nerve conduction velocities in affected males are normal to mildly delayed and sensory conduction velocities are markedly abnormal. Heterozygous females are asymptomatic. Close linkage to the Xg blood group locus (Xp22) was previously excluded in this family while weak linkage of the disease gene to DXYS1 (Xq13-q21) was suggested. The current study excludes the short arm and the proximal long arm of the X chromosome. Haplotype analysis of markers on the long arm demonstrates that HPRT is a proximal flanking marker and that the disease gene is closely linked to the marker DXS984. Further microsatellite markers are being studied in order to refine the region of the distal long arm of the X chromosome containing the gene causing the motor-sensory neuropathy in this family. This is the first such gene assigned to the distal region of Xq.

Priest, J.M.; Nouri, N.; Keats, B.J.B. [Louisiana State Univ. Medical Center, New Orleans, LA (United States)] [and others

1994-09-01

58

Molecular screening of 980 cases of suspected hereditary optic neuropathy with a report on 77 novel OPA1 mutations.  

PubMed

We report the results of molecular screening in 980 patients carried out as part of their work-up for suspected hereditary optic neuropathies. All the patients were investigated for Leber's hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA), by searching for the ten primary LHON-causing mtDNA mutations and examining the entire coding sequences of the OPA1 and OPA3 genes, the two genes currently identified in ADOA. Molecular defects were identified in 440 patients (45% of screened patients). Among these, 295 patients (67%) had an OPA1 mutation, 131 patients (30%) had an mtDNA mutation, and 14 patients (3%), belonging to three unrelated families, had an OPA3 mutation. Interestingly, OPA1 mutations were found in 157 (40%) of the 392 apparently sporadic cases of optic atrophy. The eOPA1 locus-specific database now contains a total of 204 OPA1 mutations, including 77 novel OPA1 mutations reported here. The statistical analysis of this large set of mutations has led us to propose a diagnostic strategy that should help with the molecular work-up of optic neuropathies. Our results highlight the importance of investigating LHON-causing mtDNA mutations as well as OPA1 and OPA3 mutations in cases of suspected hereditary optic neuropathy, even in absence of a family history of the disease. PMID:19319978

Ferré, Marc; Bonneau, Dominique; Milea, Dan; Chevrollier, Arnaud; Verny, Christophe; Dollfus, Hélčne; Ayuso, Carmen; Defoort, Sabine; Vignal, Catherine; Zanlonghi, Xavier; Charlin, Jean-Francois; Kaplan, Josseline; Odent, Sylvie; Hamel, Christian P; Procaccio, Vincent; Reynier, Pascal; Amati-Bonneau, Patrizia

2009-07-01

59

SPTLC1 and RAB7 mutation analysis in dominantly inherited and idiopathic sensory neuropathies  

PubMed Central

Objective: To screen persons with dominantly inherited HSAN I and others with idiopathic sensory neuropathies for known mutations of SPTLC1 and RAB7. Patients: DNA was examined from well characterised individuals of 25 kindreds with adult onset HSAN I for mutations of SPTLC1 and RAB7; 92 patients with idiopathic sensory neuropathy were also screened for known mutations of these genes. Results: Of the 25 kindreds, only one had a mutation (SPTLC1 399T?G). This kindred, and 10 without identified mutations, had prominent mutilating foot injuries with peroneal weakness. Of the remainder, 12 had foot insensitivity with injuries but no weakness, one had restless legs and burning feet, and one had dementia with hearing loss. No mutation of RAB7 was found in any of these. No known mutations of SPTLC1 or RAB7 were found in cases of idiopathic sensory neuropathy. Conclusions: Adult onset HSAN I is clinically and genetically heterogeneous and further work is required to identify additional genetic causes. Known SPTLC1or RAB7 mutations were not found in idiopathic sensory neuropathy. PMID:15965219

Klein, C; Wu, Y; Kruckeberg, K; Hebbring, S; Anderson, S; Cunningham, J; Dyck, P; Klein, D; Thibodeau, S; Dyck, P

2005-01-01

60

Sporadic bulbospinal muscle atrophy with facial-onset sensory neuropathy.  

PubMed

We report a case of idiopathic severe facial-onset sensorimotor neuropathy with no evidence of Kennedy's disease, familial amyotrophic lateral sclerosis, amyloidosis, Tangier disease, sarcoidosis, chronic basilar meningitis, or Sjögren's syndrome. Clinical and neurophysiological features of this patient resemble those of four recently reported patients who were affected with facial-onset sensorimotor neuropathy (FOSMN), a probably novel disease. The present report provides information about a further patient with FOSMN in order to better characterize the clinical and laboratory features of this disease. PMID:18335469

Isoardo, Gianluca; Troni, Walter

2008-05-01

61

Corneal confocal microscopy reveals trigeminal small sensory fiber neuropathy in amyotrophic lateral sclerosis  

PubMed Central

Although subclinical involvement of sensory neurons in amyotrophic lateral sclerosis (ALS) has been previously demonstrated, corneal small fiber sensory neuropathy has not been reported to-date. We examined a group of sporadic ALS patients with corneal confocal microscopy, a recently developed imaging technique allowing in vivo observation of corneal small sensory fibers. Corneal confocal microscopy (CCM) examination revealed a reduction of corneal small fiber sensory nerve number and branching in ALS patients. Quantitative analysis demonstrated an increase in tortuosity and reduction in length and fractal dimension of ALS patients’ corneal nerve fibers compared to age-matched controls. Moreover, bulbar function disability scores were significantly related to measures of corneal nerve fibers anatomical damage. Our study demonstrates for the first time a corneal small fiber sensory neuropathy in ALS patients. This finding further suggests a link between sporadic ALS and facial-onset sensory and motor neuronopathy (FOSMN) syndrome, a rare condition characterized by early sensory symptoms (with trigeminal nerve distribution), followed by wasting and weakness of bulbar and upper limb muscles. In addition, the finding supports a model of neurodegeneration in ALS as a focally advancing process. PMID:25360111

Ferrari, Giulio; Grisan, Enrico; Scarpa, Fabio; Fazio, Raffaella; Comola, Mauro; Quattrini, Angelo; Comi, Giancarlo; Rama, Paolo; Riva, Nilo

2014-01-01

62

SENSORY NEURON INSULIN SIGNALING AND ITS ROLE IN DIABETIC NEUROPATHY  

E-print Network

is multifactorial and the majority of research currently focuses on the toxic pathways induced by hyperglycemia. Interestingly though, insulin has been recently characterized to have direct effects on sensory neurons and is now believed to be a neurotrophic factor...

Grote, Caleb W.

2013-05-31

63

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

PubMed Central

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

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

2014-01-01

64

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

SciTech Connect

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

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

2009-11-20

65

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

SciTech Connect

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

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

2009-06-05

66

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. PMID:19893645

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

2008-01-01

67

?? T cells infiltrating sensory nerve biopsies from patients with inflammatory neuropathy  

Microsoft Academic Search

Sensory nerve biopsy specimens from patients with Guillain Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy\\u000a (CIDP), and controls consisting of other neuropathies, were examined in order to characterise the nature and intensity of\\u000a any inflammatory infiltrate. In order to establish whether ?? T cells were present in these infiltrates we examined the expression\\u000a of ?? and ?? T cell receptors

John Winer; Sharon Hughes; Joanne Cooper; Anne Ben-Smith; Caroline Savage

2002-01-01

68

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

PubMed Central

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

2014-01-01

69

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. PMID:24319328

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

2013-01-01

70

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

PubMed Central

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

2014-01-01

71

A very large Brazilian pedigree with 11778 Leber's hereditary optic neuropathy.  

PubMed Central

PURPOSE: We conducted extensive epidemiological, neuro-ophthalmological, psychophysical, and blood examinations on a newly discovered, very large pedigree with molecular analysis showing mtDNA mutation for Leber's hereditary optic neuropathy (LHON). METHODS: Four patients representing four index cases from a remote area of Brazil were sent to Sao Paulo, where complete ophthalmological examinations strongly suggested LHON. Molecular analysis of their blood demonstrated that they were LHON, homoplasmic 11778, J-haplogroup. They had an extensive family that all lived in one rural area in Brazil. To investigate this family, we drew on a number of international experts to form a team that traveled to Brazil. This field team also included several members of the Federal University of Sao Paulo, and together we evaluated 273 of the 295 family members that were still alive. We conducted epidemiological interviews emphasizing possible environmental risk factors, comprehensive neuro-ophthalmological examinations, psychophysical tests, Humphrey visual field studies, fundus photography, and blood testing for both mitochondrial genetic analysis and nuclear gene linkage analysis. RESULTS: The person representing the first-generation case immigrated from Verona, Italy, to Colatina. Subsequent generations demonstrated penetrance rates of 71%, 60%, 34%, 15%, and 9%. The percentages of males were 60%, 50%, 64%, 100%, and 100%. Age at onset varied from 10 to 64 years, and current visual acuities varied from LP to 20/400. CONCLUSIONS: Almost 95% of a nearly 300-member pedigree with LHON 11778 were comprehensively studied. Analysis of environmental risk factors and a nuclear modifying factor from this group may help address the perplexing mystery of LHON: Why do only some of the genetically affected individuals manifest the disease? This fully described database may also provide an excellent opportunity for future clinical trials of any purported neuroprotective agent. PMID:12545691

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

2002-01-01

72

Neuron-Specific Enolase Is Elevated in Asymptomatic Carriers of Leber's Hereditary Optic Neuropathy  

PubMed Central

Purpose. Neuron-specific enolase (NSE) is a biomarker for neuronal stress. Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease affecting retinal ganglion cells (RGC). These RGCs and their axons in the retinal nerve fiber layer (RNFL) and optic nerve head may show subclinical pathology in unaffected mutation carriers, or undergo cell death in affected patients. We hypothesize that increased levels of blood NSE may characterize LHON carriers as a biomarker of ongoing RGC stress. Methods. Serum was obtained from 74 members of a Brazilian pedigree with LHON carrying the homoplasmic 11778/ND4 mitochondrial DNA mutation. Classified by symptoms and psychophysical metrics, 46/74 patients were unaffected mutation “carriers,” 14/74 were “affected,” and 14/74 were “off-pedigree” controls. Serum NSE levels were determined by ELISA specific for the ? subunit of NSE. Results. Serum NSE concentrations in carriers (27.17 ± 39.82 ?g/L) were significantly higher than affected (5.66 ± 4.19 ?g/L; P = 0.050) and off-pedigree controls (6.20 ± 2.35 ?g/L; P = 0.047). Of the 14/46 (30.4 %) carriers with significantly elevated NSE levels (mean = 75.8 ± 42.3 ?g/L), 9/14 (64.3%) were male. Furthermore, NSE levels were nearly three times greater in asymptomatic male carriers (40.65 ± 51.21 ?g/L) than in asymptomatic female carriers (15.85 ± 22.27 ?g/L; P = 0.034). Conclusions. Serum NSE levels are higher in LHON carriers compared with affected and off-pedigree individuals. A subgroup of mostly male carriers had significantly elevated serum NSE levels. Thus, male carriers are at higher risk for LHON-related neuronal stress. PMID:22893673

Yee, Kenneth M.; Ross-Cisneros, Fred N.; Lee, Jeong Goo; Da Rosa, Arlon Bastos; Salomao, Solange R.; Berezovsky, Adriana; Belfort, Rubens; Chicani, Filipe; Moraes-Filho, Milton; Sebag, Jerry; Carelli, Valerio; Sadun, Alfredo A.

2012-01-01

73

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

PubMed Central

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

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

2006-01-01

74

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. PMID:23060142

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

75

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

PubMed

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

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

2012-05-01

76

The relationship of nerve fibre pathology to sensory function in entrapment neuropathy  

PubMed Central

Surprisingly little is known about the impact of entrapment neuropathy on target innervation and the relationship of nerve fibre pathology to sensory symptoms and signs. Carpal tunnel syndrome is the most common entrapment neuropathy; the aim of this study was to investigate its effect on the morphology of small unmyelinated as well as myelinated sensory axons and relate such changes to somatosensory function and clinical symptoms. Thirty patients with a clinical and electrophysiological diagnosis of carpal tunnel syndrome [17 females, mean age (standard deviation) 56.4 (15.3)] and 26 age and gender matched healthy volunteers [18 females, mean age (standard deviation) 51.0 (17.3)] participated in the study. Small and large fibre function was examined with quantitative sensory testing in the median nerve territory of the hand. Vibration and mechanical detection thresholds were significantly elevated in patients with carpal tunnel syndrome (P < 0.007) confirming large fibre dysfunction and patients also presented with increased thermal detection thresholds (P < 0.0001) indicative of C and A?-fibre dysfunction. Mechanical and thermal pain thresholds were comparable between groups (P > 0.13). A skin biopsy was taken from a median nerve innervated area of the proximal phalanx of the index finger. Immunohistochemical staining for protein gene product 9.5 and myelin basic protein was used to evaluate morphological features of unmyelinated and myelinated axons. Evaluation of intraepidermal nerve fibre density showed a striking loss in patients (P < 0.0001) confirming a significant compromise of small fibres. The extent of Meissner corpuscles and dermal nerve bundles were comparable between groups (P > 0.07). However, patients displayed a significant increase in the percentage of elongated nodes (P < 0.0001), with altered architecture of voltage-gated sodium channel distribution. Whereas neither neurophysiology nor quantitative sensory testing correlated with patients’ symptoms or function deficits, the presence of elongated nodes was inversely correlated with a number of functional and symptom related scores (P < 0.023). Our findings suggest that carpal tunnel syndrome does not exclusively affect large fibres but is associated with loss of function in modalities mediated by both unmyelinated and myelinated sensory axons. We also document for the first time that entrapment neuropathies lead to a clear reduction in intraepidermal nerve fibre density, which was independent of electrodiagnostic test severity. The presence of elongated nodes in the target tissue further suggests that entrapment neuropathies affect nodal structure/myelin well beyond the focal compression site. Interestingly, nodal lengthening may be an adaptive phenomenon as it inversely correlates with symptom severity. PMID:25348629

Schmid, Annina B.; Bland, Jeremy D. P.; Bhat, Manzoor A.

2014-01-01

77

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. PMID:22879922

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

78

Phosphorylated neurofilament heavy chain is a marker of neurodegeneration in Leber hereditary optic neuropathy (LHON)  

PubMed Central

Purpose To determine the profile of neurodegeneration in Leber hereditary optic neuropathy (LHON). Methods We quantitated serum levels of phosphorylated neurofilament heavy chain (pNF-H) in a Brazilian pedigree of 16 affected patients and 59 carriers with LHON, both molecularly characterized as harboring the G to A mutation at nucleotide 11,778 of the mitochondrial genome. The association of subject characteristics to pNF-H levels was studied with multiple regression; pNF-H data were square-root transformed to effect normality of distribution of residuals. Relationships between the square-root of pNF-H and age and sex were investigated within groups with Pearson correlation and the two-sample t-test. Linear regression was used to assess the difference between groups and to determine if the relationship of age was different between affected individuals and carriers. Results of plotting pNF-H levels by age suggested a nonlinear, quadratic association so age squared was used in the statistical analysis. ANCOVA was used to assess the influence of age and group on pNF-H levels. Results In the carrier group, there was a significant correlation of square-root pNF-H (mean=0.24 ng/ml2) with age (r=0.30, p=0.022) and a stronger correlation with quadratic age (r=0.37, p=0.003). With a higher mean pNF-H (0.33 ng/ml2) for the affected group, correlations were of similar magnitude, although they were not statistically significant: age (r=0.22, p=0.42), quadratic age (r=0.22, p=0.45). There was no correlation between age and pNF-H levels (mean=0.34 ng/ml2) in the off-pedigree group: age (r=0.03, p=0.87), quadratic age (r=0.04, p=0.84). There was no difference between sexes and pNF-H levels in any of the groups (affected, p=0.65; carriers, p=0.19; off-pedigree, p=0.93). Conclusions Elevated pNF-H released into the serum of some affected LHON patients may suggest that axonal degeneration occurs at some point after loss of visual function. Increases in pNF-H levels of carriers with increasing age, not seen in off-pedigree controls, may suggest subtle subclinical optic nerve degeneration. PMID:19104679

Shaw, Gerry; Ross-Cisneros, Fred N.; Quiros, Peter; Salomao, Solange R.; Berezovsky, Adriana; Carelli, Valerio; Feuer, William J.; Sadun, Alfredo A.

2008-01-01

79

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

PubMed Central

Purpose Leber hereditary optic neuropathy (LHON) is a common cause of inherited blindness, primarily due to one of three mitochondrial DNA (mtDNA) mutations. These mtDNA pathogenic mutations have variable clinical penetrance. Recent linkage evidence raised the possibility that the nuclear gene optic atrophy 1 (OPA1) determines whether mtDNA mutation carriers develop blindness. To validate these findings we studied OPA1 in three independent LHON cohorts: sequencing the gene in discordant male sib pairs, carrying out a family-based association study of common functional genetic variants, and carrying out a population-based association study of the same genetic variants. Methods We tested 3 hypothesis in three separate study groups. Study group 1: Direct sequencing of OPA1 coding regions was performed using sequencing methodologies (Applied Biosystems, Foster City, CA). Chromatograms were compared with the GenBank reference sequence NM_015560.1. Splice-site prediction was performed using GeneSplicer. Study group 2: Genotyping for rs166850 and rs10451941 was performed by restriction fragment length polymorphism (RFLP) analysis with specific primers for both genotypes, using The restriction enzymes RsaI and FspBI to discriminate genotypes. Study group 3: Genotyping for rs166850 and rs10451941 was performed by primer extension of allele-specific extensions products by matrix-associated laser desorption/ionisation time-of-flight (MALDI-TOF, Seqeunom, San Diego, CA) mass spectrometry. Allele and genotype frequencies were compared using Pearson’s chi-square test. Multiple logistic regression was performed to look for interactions between the variables. All analyses were performed using SPSS software version 17.0 (SPSS Inc.). Results In all three groups we were unable to find an association between OPA1 genetic variation and visual failure in LHON mtDNA mutation carriers. Conclusions Our findings suggest that genetic variation in OPA1 is unlikely to make a major contribution to the risk of blindness in LHON mutation carriers. PMID:21203403

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

2010-01-01

80

A Genome-Wide Association Study Identifies Novel Loci for Paclitaxel-Induced Sensory Peripheral Neuropathy in CALGB 40101  

PubMed Central

Purpose Sensory peripheral neuropathy is a common and sometimes debilitating toxicity associated with paclitaxel therapy. This study aims to identify genetic risk factors for development of this toxicity. Experimental Design A prospective pharmacogenetic analysis of primary breast cancer patients randomized to the paclitaxel arm of CALGB 40101 was used to identify genetic predictors of the onset and severity of sensory peripheral neuropathy. A genome-wide association study in 855 subjects of European ancestry was performed and findings were replicated in additional European (n = 154) and African American (n = 117) subjects. Results A single nucleotide polymorphism in FGD4 was associated with the onset of sensory peripheral neuropathy in the discovery cohort (rs10771973; HR, 1.57; 95% CI, 1.30–1.91; P = 2.6 × 10?6) and in a European (HR, 1.72; 95% CI, 1.06–2.80; P = 0.013) and African American (HR, 1.93; 95% CI, 1.13-3.28; P = 6.7 × 10?3) replication cohort. There is also evidence that markers in additional genes, including EPHA5 (rs7349683) and FZD3 (rs10771973), were associated with the onset or severity of paclitaxel-induced sensory peripheral neuropathy. Conclusions A genome-wide association study has identified novel genetic markers of paclitaxel-induced sensory peripheral neuropathy, including a common polymorphism in FGD4, a congenital peripheral neuropathy gene. These findings suggest that genetic variation may contribute to variation in development of this toxicity. Validation of these findings may allow for the identification of patients at increased risk of peripheral neuropathy and inform the use of an alternative to paclitaxel and/or the clinical management of this toxicity. PMID:22843789

Baldwin, R. Michael; Owzar, Kouros; Zembutsu, Hitoshi; Chhibber, Aparna; Kubo, Michiaki; Jiang, Chen; Watson, Dorothy; Eclov, Rachel J.; Mefford, Joel; McLeod, Howard L.; Friedman, Paula N.; Hudis, Clifford A.; Winer, Eric P.; Jorgenson, Eric M.; Witte, John S.; Shulman, Lawrence N.; Nakamura, Yusuke; Ratain, Mark J.; Kroetz, Deanna L.

2012-01-01

81

Amplitude of sensory nerve action potential in early stage diabetic peripheral neuropathy: an analysis of 500 cases  

PubMed Central

Early diagnosis of diabetic peripheral neuropathy is important for the successful treatment of diabetes mellitus. In the present study, we recruited 500 diabetic patients from the Fourth Affiliated Hospital of Kunming Medical University in China from June 2008 to September 2013: 221 cases showed symptoms of peripheral neuropathy (symptomatic group) and 279 cases had no symptoms of peripheral impairment (asymptomatic group). One hundred healthy control subjects were also recruited. Nerve conduction studies revealed that distal motor latency was longer, sensory nerve conduction velocity was slower, and sensory nerve action potential and amplitude of compound muscle action potential were significantly lower in the median, ulnar, posterior tibial and common peroneal nerve in the diabetic groups compared with control subjects. Moreover, the alterations were more obvious in patients with symptoms of peripheral neuropathy. Of the 500 diabetic patients, neural conduction abnormalities were detected in 358 cases (71.6%), among which impairment of the common peroneal nerve was most prominent. Sensory nerve abnormality was more obvious than motor nerve abnormality in the diabetic groups. The amplitude of sensory nerve action potential was the most sensitive measure of peripheral neuropathy. Our results reveal that varying degrees of nerve conduction changes are present in the early, asymptomatic stage of diabetic peripheral neuropathy. PMID:25221597

Zhang, Yunqian; Li, Jintao; Wang, Tingjuan; Wang, Jianlin

2014-01-01

82

A Case of Acute Motor and Sensory Axonal Neuropathy Following Hepatitis A Infection  

PubMed Central

Acute motor and sensory axonal neuropathy (AMSAN) are recently described subtypes of Guillain-Barre syndrome characterized by acute onset of distal weakness, loss of deep tendon reflexes, and sensory symptoms. A 21-yr-old male was transferred to our hospital due to respiration difficulties and progressive weakness. In laboratory findings, immunoglobulin M antibodies against hepatitis A were detected in blood and cerebrospinal fluid. The findings of motor nerve conduction studies showed markedly reduced amplitudes of compound muscle action potentials in bilateral peroneal, and posterior tibial nerves, without evidence of demyelination. Based on clinical features, laboratory findings, and electrophysiologic investigation, the patient was diagnosed the AMSAN following acute hepatitis A viral infection. The patient was treated with intravenous immunoglobulin and recovered slowly. Clinicians should consider this rare but a serious case of AMSAN following acute hepatitis A infection. PMID:24339719

Jo, Yoon-Sik; Han, Sang-Don; Choi, Jin-Yong; Kim, Ick Hee; Kim, Yong-Duk

2013-01-01

83

Sonographic Evaluation of the Peripheral Nerves in Hereditary Neuropathy With Liability to Pressure Palsies: A Case Report  

PubMed Central

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominantly inherited disorder that affects peripheral nerves by repeated focal pressure. HNPP can be diagnosed by clinical findings, electrodiagnostic studies, histopathological features, and genetic analysis. Ultrasonography is increasingly used for the diagnosis of neuromuscular diseases; however, sonographic features of HNPP have not been clearly defined. We report the sonographic findings and comparative electrodiagnostic data in a 73-year-old woman with HNPP, confirmed by genetic analysis. The cross-sectional areas of peripheral nerves were enlarged at typical nerve entrapment sites, but enlargement at non-entrapment sites was uncommon. These sonographic features may be helpful for diagnosis of HNPP when electrodiagnostic studies are suspicious of HNPP and/or gene study is not compatible. PMID:24639934

Kim, Se Hwa; Yoon, Joon Shik; Park, Bum Jun

2014-01-01

84

Electrophysiological characterisation of motor and sensory tracts in patients with hereditary spastic paraplegia (HSP)  

PubMed Central

Background Hereditary spastic paraplegias (HSPs) are characterised by lower limb spasticity due to degeneration of the corticospinal tract. We set out for an electrophysiological characterisation of motor and sensory tracts in patients with HSP. Methods We clinically and electrophysiologically examined a cohort of 128 patients with genetically confirmed or clinically probable HSP. Motor evoked potentials (MEPs) to arms and legs, somato-sensory evoked potentials of median and tibial nerves, and nerve conduction studies of tibial, ulnar, sural, and radial nerves were assessed. Results Whereas all patients showed clinical signs of spastic paraparesis, MEPs were normal in 27% of patients and revealed a broad spectrum with axonal or demyelinating features in the others. This heterogeneity can at least in part be explained by different underlying genotypes, hinting for distinct pathomechanisms in HSP subtypes. In the largest subgroup, SPG4, an axonal type of damage was evident. Comprehensive electrophysiological testing disclosed a more widespread affection of long fibre tracts involving peripheral nerves and the sensory system in 40%, respectively. Electrophysiological abnormalities correlated with the severity of clinical symptoms. Conclusions Whereas HSP is primarily considered as an upper motoneuron disorder, our data suggest a more widespread affection of motor and sensory tracts in the central and peripheral nervous system as a common finding in HSP. The distribution patterns of electrophysiological abnormalities were associated with distinct HSP genotypes and could reflect different underlying pathomechanisms. Electrophysiological measures are independent of symptomatic treatment and may therefore serve as a reliable biomarker in upcoming HSP trials. PMID:24107482

2013-01-01

85

Hyperglycemia- and neuropathy-induced changes in mitochondria within sensory nerves  

PubMed Central

Objective This study focused on altered mitochondrial dynamics as a potential mechanism for diabetic peripheral neuropathy (DPN). We employed both an in vitro sensory neuron model and an in situ analysis of human intraepidermal nerve fibers (IENFs) from cutaneous biopsies to measure alterations in the size distribution of mitochondria as a result of hyperglycemia and diabetes, respectively. Methods Neurite- and nerve-specific mitochondrial signals within cultured rodent sensory neurons and human IENFs were measured by employing a three-dimensional visualization and quantification technique. Skin biopsies from distal thigh (DT) and distal leg (DL) were analyzed from three groups of patients; patients with diabetes and no DPN, patients with diabetes and confirmed DPN, and healthy controls. Results This analysis demonstrated an increase in mitochondria distributed within the neurites of cultured sensory neurons exposed to hyperglycemic conditions. Similar changes were observed within IENFs of the DT in DPN patients compared to controls. This change was represented by a significant shift in the size frequency distribution of mitochondria toward larger mitochondria volumes within DT nerves of DPN patients. There was a length-dependent difference in mitochondria within IENFs. Distal leg IENFs from control patients had a significant shift toward larger volumes of mitochondrial signal compared to DT IENFs. Interpretation The results of this study support the hypothesis that altered mitochondrial dynamics may contribute to DPN pathogenesis. Future studies will examine the potential mechanisms that are responsible for mitochondrial changes within IENFs and its effect on DPN pathogenesis. PMID:25493271

Hamid, Hussein S; Mervak, Colin M; Münch, Alexandra E; Robell, Nicholas J; Hayes, John M; Porzio, Michael T; Singleton, J Robinson; Smith, A Gordon; Feldman, Eva L; Lentz, Stephen I

2014-01-01

86

Mutations in HINT1 are one of the most frequent causes of hereditary neuropathy among Czech patients and neuromyotonia is rather an underdiagnosed symptom.  

PubMed

Mutations in the HINT1 gene were recently discovered as being the major cause of autosomal recessive axonal neuropathy with neuromyotonia. This combination was clinically recognized and described previously in a few reports but is generally unknown. We aimed to establish the importance of HINT1 mutations as the cause of hereditary neuropathy and particularly hereditary motor neuropathy/axonal Charcot-Marie-Tooth (HMN/CMT2) among Czech patients. Overall, mutations in the HINT1 gene seem to be a surprisingly frequent cause of inherited neuropathy in our group of patients. Biallelic pathogenic mutations were found in 21 patients from 19 families. The prevalent mutation in the Czech population is the p.R37P (95 % of pathogenic alleles). Clinically, all patients with biallelic mutations presented with early onset of symptoms at the end of the first decade. Foot/toe extension weakness to plegia was present in almost all patients. Neuromyotonia was present in all but two patients. However, it had been properly recognized in only three patients prior to molecular genetic diagnosis. HINT1 mutations seem to be one of the most frequent causes of inherited neuropathy and are probably the most frequent cause of HMN in Czech patients. We suggest all HMN/CMT2 patients be tested for the presence of the prevalent mutation, the p.R37P. PMID:25342199

Laššuthová, P; Brožková, D Šafka; Kr?tová, M; Neupauerová, J; Haberlová, J; Mazanec, R; Dvo?á?ková, N; Goldenberg, Z; Seeman, P

2015-01-01

87

Application of multiplex ligation-dependent probe analysis to define a small deletion encompassing PMP22 exons 4 and 5 in hereditary neuropathy with liability to pressure palsies  

Microsoft Academic Search

Hereditary neuropathy with liability to pressure palsies arises as a result of defects at the chromosome 17p11.2-12 locus and in 84% of cases a 1.5Mb deletion containing the PMP22 gene is detected by analysis that utilises polymorphic (CA)n repeat markers which flank this gene. We report the clinical and electrophysiological findings observed in a kindred with three members affected by

Ian J Sutton; A Paul Mocroft; Victoria H Lindley; Richard M Barber; R Jane Bryon; John B Winer; Fiona MacDonald

2004-01-01

88

Molecular genetic analysis of the 17p11.2 region in patients with hereditary neuropathy with liability to pressure palsies (HNPP)  

Microsoft Academic Search

Hereditary neuropathy with liability to pressure palsies (HNPP) is in most cases associated with an interstitial deletion of the same 1.5-Mb region at 17p11.2 that is duplicated in Charcot-Marie-Tooth type 1A (CMT1A) patients. Unequal crossing-over following misalignment at flanking repeat sequences (CMT1A-REP), either leads to tandem duplication in CMT1A patients or deletion in HNPP patients. With the use of polymorphic

Vincent Timmerman; Ann Löfgren; Eric Guern; Ping Liang; Peter Jonghe; Jean-Jacques Martin; Damienne Verhalle; Wim Robberecht; Riadh Gouider; Alexis Brice; Christine Broeckhoven

1996-01-01

89

Excitability of A? sensory neurons is altered in an animal model of peripheral neuropathy  

PubMed Central

Background Causes of neuropathic pain following nerve injury remain unclear, limiting the development of mechanism-based therapeutic approaches. Animal models have provided some directions, but little is known about the specific sensory neurons that undergo changes in such a way as to induce and maintain activation of sensory pain pathways. Our previous studies implicated changes in the A?, normally non-nociceptive neurons in activating spinal nociceptive neurons in a cuff-induced animal model of neuropathic pain and the present study was directed specifically at determining any change in excitability of these neurons. Thus, the present study aimed at recording intracellularly from A?-fiber dorsal root ganglion (DRG) neurons and determining excitability of the peripheral receptive field, of the cell body and of the dorsal roots. Methods A peripheral neuropathy was induced in Sprague Dawley rats by inserting two thin polyethylene cuffs around the right sciatic nerve. All animals were confirmed to exhibit tactile hypersensitivity to von Frey filaments three weeks later, before the acute electrophysiological experiments. Under stable intracellular recording conditions neurons were classified functionally on the basis of their response to natural activation of their peripheral receptive field. In addition, conduction velocity of the dorsal roots, configuration of the action potential and rate of adaptation to stimulation were also criteria for classification. Excitability was measured as the threshold to activation of the peripheral receptive field, the response to intracellular injection of depolarizing current into the soma and the response to electrical stimulation of the dorsal roots. Results In control animals mechanical thresholds of all neurons were within normal ranges. A? DRG neurons in neuropathic rats demonstrated a mean mechanical threshold to receptive field stimulation that were significantly lower than in control rats, a prolonged discharge following this stimulation, a decreased activation threshold and a greater response to depolarizing current injection into the soma, as well as a longer refractory interval and delayed response to paired pulse electrical stimulation of the dorsal roots. Conclusions The present study has demonstrated changes in functionally classified A? low threshold and high threshold DRG neurons in a nerve intact animal model of peripheral neuropathy that demonstrates nociceptive responses to normally innocuous cutaneous stimuli, much the same as is observed in humans with neuropathic pain. We demonstrate further that the peripheral receptive fields of these neurons are more excitable, as are the somata. However, the dorsal roots exhibit a decrease in excitability. Thus, if these neurons participate in neuropathic pain this differential change in excitability may have implications in the peripheral drive that induces central sensitization, at least in animal models of peripheral neuropathic pain, and A? sensory neurons may thus contribute to allodynia and spontaneous pain following peripheral nerve injury in humans. PMID:22289651

2012-01-01

90

Noninvasive Peroneal Sensory and Motor Nerve Conduction Recordings in the Rabbit Distal Hindlimb: Feasibility, Variability and Neuropathy Measure  

PubMed Central

The peroneal nerve anatomy of the rabbit distal hindlimb is similar to humans, but reports of distal peroneal nerve conduction studies were not identified with a literature search. Distal sensorimotor recordings may be useful for studying rabbit models of length-dependent peripheral neuropathy. Surface electrodes were adhered to the dorsal rabbit foot overlying the extensor digitorum brevis muscle and the superficial peroneal nerve. The deep and superficial peroneal nerves were stimulated above the ankle and the common peroneal nerve was stimulated at the knee. The nerve conduction studies were repeated twice with a one-week intertest interval to determine measurement variability. Intravenous vincristine was used to produce a peripheral neuropathy. Repeat recordings measured the response to vincristine. A compound muscle action potential and a sensory nerve action potential were evoked in all rabbits. The compound muscle action potential mean amplitude was 0.29 mV (SD ± 0.12) and the fibula head to ankle mean motor conduction velocity was 46.5 m/s (SD ± 2.9). The sensory nerve action potential mean amplitude was 22.8 ?V (SD ± 2.8) and the distal sensory conduction velocity was 38.8 m/s (SD ± 2.2). Sensorimotor latencies and velocities were least variable between two test sessions (coefficient of variation ?=? 2.6–5.9%), sensory potential amplitudes were intermediate (coefficient of variation ?=? 11.1%) and compound potential amplitudes were the most variable (coefficient of variation ?=?19.3%). Vincristine abolished compound muscle action potentials and reduced sensory nerve action potential amplitudes by 42–57% while having little effect on velocity. Rabbit distal hindlimb nerve conduction studies are feasible with surface recordings and stimulation. The evoked distal sensory potentials have amplitudes, configurations and recording techniques that are similar to humans and may be valuable for measuring large sensory fiber function in chronic models of peripheral neuropathies. PMID:24658286

Hotson, John R.

2014-01-01

91

Autonomic neuropathy, II: Specific peripheral neuropathies.  

PubMed

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

McDougall, A J; McLeod, J G

1996-06-01

92

Role of TNF block genetic variants in HIV-associated sensory neuropathy in black Southern Africans.  

PubMed

HIV-associated sensory neuropathy (HIV-SN) is a common neurological complication of HIV infection. The TNF block is a region within the central MHC that contains many immunoregulatory genes. Polymorphisms and haplotypes of the TNF block have been associated with increased risk of HIV-SN in Asians and whites. Here we investigated genetic associations with HIV-SN in 342 black Southern Africans (190 cases and 152 neuropathy-free controls) using single nucleotide polymorphisms (SNPs) spanning the TNF block and a set of haplotypes defined by 31 SNPs in Asian and white populations (denoted FVa). We included population-appropriate tagSNPs derived from an African population (Yoruban, YRI, HapMap) and derived extended haplotypes comprising 61 SNPs (denoted FVa_ext b). We found no association between HIV-SN and carriage of two SNPs (TNF-1031/rs1799964*C and BAT1 (intron10)/rs9281523*C) associated with HIV-SN in whites and Asians. Additionally, a haplotype containing TNF-1031/rs1799964*C associated with increased risk of HIV-SN in Asians, but was not present in this African population. However, alleles of seven SNPs associated with reduced risk of HIV-SN (corrected for age, height and multiple comparisons). These were rs11796*A, rs3130059*G, rs2071594*C, NFKBIL1-62/rs2071592*A, rs2071591*A, LTA+252/rs909253*G, rs1041981*C. One haplotype (FV18_ext1), not containing these alleles, was associated with increased risk of HIV-SN after correction for age, height and multiple comparisons. Our results confirm the involvement of genes in the TNF block in altering risk for HIV-SN, but genotypes critical in this African population differed from those affecting HIV-SN in whites and Asians. These differences support the need for genetic association studies in diverse populations. PMID:24896147

Wadley, Antonia L; Hendry, Liesl M; Kamerman, Peter R; Chew, Constance Sn; Price, Patricia; Cherry, Catherine L; Lombard, Zané

2015-03-01

93

Mitochondrial abnormality in sensory, but not motor, axons in paclitaxel-evoked painful peripheral neuropathy in the rat  

PubMed Central

The dose-limiting side effect of the anti-neoplastic agent, paclitaxel, is a chronic distal symmetrical peripheral neuropathy that produces sensory dysfunction (hypoesthesia and neuropathic pain) but little or no distal motor dysfunction. Similar peripheral neuropathies are seen with chemotherapeutics in the vinca alkaloid, platinum-complex, and proteasome inhibitor classes. Studies in rats suggest that the cause is a mitotoxic effect on axonal mitochondria. If so, then the absence of motor dysfunction may be due to mitotoxicity that affects sensory axons but spares motor axons. To investigate this, paclitaxel exposure levels in the dorsal root, ventral root, dorsal root ganglion, peripheral nerve, and spinal cord were measured, and the ultrastructure and the respiratory function of mitochondria in dorsal roots and ventral roots were compared. Sensory and motor axons in the roots and nerve had comparably low exposure to paclitaxel and exposure in the spinal cord was negligible. However, sensory neurons in the dorsal root ganglion had a very high and remarkably persistent (up to10 days or more after the last injection) exposure to paclitaxel. Paclitaxel evoked a significant increase in the incidence of swollen and vacuolated mitochondria in the myelinated and unmyelinated sensory axons of the dorsal root (as seen previously in the peripheral nerve) but not in the motor axons of the ventral root. Stimulated mitochondrial respiration in the dorsal root was significantly depressed in paclitaxel-treated animals examined 2-4 weeks after the last injection, whereas respiration in the ventral root was normal. We conclude that the absence of motor dysfunction in paclitaxel-evoked peripheral neuropathy may be due to the absence of a mitotoxic effect in motor neuron axons, while the sensory dysfunction may be due to a mitotoxic effect resulting from the primary afferent neuron's cell body being exposed to high and persistent levels of paclitaxel. PMID:22037390

Xiao, Wen Hua; Zheng, Huaien; Zheng, Felix Y.; Nuydens, Rony; Meert, Theo F.; Bennett, Gary J.

2011-01-01

94

Evidence of GLP-1-mediated neuroprotection in an animal model of pyridoxine-induced peripheral sensory neuropathy  

PubMed Central

Pyridoxine (vitamin B6) intoxicated rodents develop a peripheral neuropathy characterized by sensory nerve conduction deficits associated with disturbances of nerve fiber geometry and axonal atrophy. To investigate the possibility that glucagon-like peptide-1 (7-36)-amide (GLP-1) receptor agonism may influence axonal structure and function through neuroprotection neurotrophic support, effects of GLP-1 and its long acting analog, Exendin-4 (Ex4) treatment on pyridoxine-induced peripheral neuropathy were examined in rats using behavioral and morphometric techniques. GLP-1 is an endogenous insulinotropic peptide secreted from the gut in response to the presence of food. GLP-1 receptors (GLP-1R) are coupled to the cAMP second messenger pathway, and are expressed widely throughout neural tissues of humans and rodents. Recent studies have established that GLP-1 and Ex4, have multiple synergistic effects on glucose-dependent insulin secretion pathways of pancreatic ?-cells and on neural plasticity. Data reported here suggest that clinically relevant doses of GLP-1 and Ex4 may offer some protection against the sensory peripheral neuropathy induced by pyridoxine. Our findings suggest a potential role for these peptides in the treatment of neuropathies, including that associated with type II diabetes mellitus. PMID:17125767

Perry, TracyAnn; Holloway, Harold W.; Weerasuriya, Ananda; Mouton, Peter R.; Duffy, Kara; Mattison, Julie A.; Greig, Nigel H.

2007-01-01

95

Sensory, psychological, and metabolic dysfunction in HIV-associated peripheral neuropathy: A cross-sectional deep profiling study.  

PubMed

HIV-associated sensory neuropathy (HIV-SN) is a frequent complication of HIV infection and a major source of morbidity. A cross-sectional deep profiling study examining HIV-SN was conducted in people living with HIV in a high resource setting using a battery of measures which included the following: parameters of pain and sensory symptoms (7day pain diary, Neuropathic Pain Symptom Inventory [NPSI] and Brief Pain Inventory [BPI]), sensory innervation (structured neurological examination, quantitative sensory testing [QST] and intraepidermal nerve fibre density [IENFD]), psychological state (Pain Anxiety Symptoms Scale-20 [PASS-20], Depression Anxiety and Positive Outlook Scale [DAPOS], and Pain Catastrophizing Scale [PCS], insomnia (Insomnia Severity Index [ISI]), and quality of life (Short Form (36) Health Survey [SF-36]). The diagnostic utility of the Brief Peripheral Neuropathy Screen (BPNS), Utah Early Neuropathy Scale (UENS), and Toronto Clinical Scoring System (TCSS) were evaluated. Thirty-six healthy volunteers and 66 HIV infected participants were recruited. A novel triumvirate case definition for HIV-SN was used that required 2 out of 3 of the following: 2 or more abnormal QST findings, reduced IENFD, and signs of a peripheral neuropathy on a structured neurological examination. Of those with HIV, 42% fulfilled the case definition for HIV-SN (n=28), of whom 75% (n=21) reported pain. The most frequent QST abnormalities in HIV-SN were loss of function in mechanical and vibration detection. Structured clinical examination was superior to QST or IENFD in HIV-SN diagnosis. HIV-SN participants had higher plasma triglyceride, concentrations depression, anxiety and catastrophizing scores, and prevalence of insomnia than HIV participants without HIV-SN. PMID:24973717

Phillips, Tudor J C; Brown, Matthew; Ramirez, Juan D; Perkins, James; Woldeamanuel, Yohannes W; Williams, Amanda C de C; Orengo, Christine; Bennett, David L H; Bodi, Istvan; Cox, Sarah; Maier, Christoph; Krumova, Elena K; Rice, Andrew S C

2014-09-01

96

Characteristic features of hereditary neuropathy with liability to pressure palsy (HNPP) presenting with brachial plexopathy in soldiers.  

PubMed

A brachial plexus lesion is not common in hereditary neuropathy with liability to pressure palsy (HNPP). We report the clinical and electrodiagnostic features of young soldiers with HNPP presenting with brachial plexopathy. By reviewing 2year medical records from Korean military hospitals, we identified soldiers with brachial plexus lesions. Among them, patients diagnosed with HNPP were determined and clinical and electrophysiological findings were compared between HNPP and non-HNPP patients with a brachial plexus lesion. Thirteen patients (6.8%) were diagnosed with HNPP among 189 patients with a brachial plexus lesion. Push-ups, as either a punishment or an exercise, was the most frequent preceding event in HNPP patients (76.9%), whereas it was rare in non-HNPP patients. The distal motor latency of the median nerve showed the highest sensitivity (90.9%) and specificity (100%) for HNPP in patients with a brachial plexus lesion. In conclusion, HNPP should be suspected in patients with brachial plexopathy if brachial plexopathy develops after push-ups or if the distal motor latency of median nerves is prolonged. PMID:25175852

Kim, Kyoung-Eun

2014-11-15

97

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

SciTech Connect

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

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

2006-08-18

98

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

SciTech Connect

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

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

2006-02-03

99

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

100

Psychophysical analysis of contrast processing segregated into magnocellular and parvocellular systems in asymptomatic carriers of 11778 Leber's hereditary optic neuropathy.  

PubMed

We examined achromatic contrast discrimination in asymptomatic carriers of 11778 Leber's hereditary optic neuropathy (LHON 18 controls) and 18 age-match were also tested. To evaluate magnocellular (MC) and Parvocellular (PC) contrast discrimination, we used a version of Pokorny and Smith's (1997) pulsed/steady-pedestal paradigms (PPP/SPP) thought to be detected via PC and MC pathways, respectively. A luminance pedestal (four 1 degree x 1 degree squares) was presented on a 12 cd/m2 surround. The luminance of one of the squares (trial square, TS) was randomly incremented for either 17 or 133 ms. Observers had to detect the TS, in a forced-choice task, at each duration, for three pedestal levels: 7, 12, 19 cd/m2. In the SPP, the pedestal was fixed, and the TS was modulated. For the PPP, all four pedestal squares pulsed for 17 or 133 ms, and the TS was simultaneously incremented or decremented. We found that contrast discrimination thresholds of LHON carriers were significantly higher than controls' in the condition with the highest luminance of both paradigms, implying impaired contrast processing with no evidence of differential sensitivity losses between the two systems. Carriers' thresholds manifested significantly longer temporal integration than controls in the SPP, consistent with slowed MC responses. The SPP and PPP paradigms can identify contrast and temporal processing deficits in asymptomatic LHON carriers, and thus provide an additional tool for early detection and characterization of the disease. PMID:18598420

Gualtieri, M; Bandeira, M; Hamer, R D; Costa, M F; Oliveira, A G F; Moura, A L A; Sadun, F; De Negri, A M; Berezovsky, A; Salomăo, S R; Carelli, V; Sadun, A A; Ventura, D F

2008-01-01

101

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

PubMed Central

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

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

2013-01-01

102

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

PubMed Central

We report here the clinical, genetics and molecular characterization of a five-generation Han Chinese family with Leber’s hereditary optic neuropathy (LHON). Strikingly, this family exhibits very high penetrance and occurrence of optic neuropathy. In particular, twenty-five (10 males/15 females) of 30 matrilineal relatives exhibited the variable severity, ranging from profound to mild of visual impairment. This penetrance of optic neuropathy in this Chinese family is much higher than those in many families with LHON worldwide. The age-at-onset for visual impairment in matrilineal relatives in this Chinese family varied from 7 to 24 years old, with the average of 15 years old. Furthermore, the ratio between affected male and female matrilineal relatives is 1:1.5 in the Chinese family. This observation is in contrast with the typical features in LHON pedigrees that there was predominance of affected males in LHON in many families from different ethnic origins. Molecular analysis of mitochondrial genome identified the known ND4 G11778A mutation and 51 variants, belonging to Asian haplogroup C4a1. The absence of other known secondary LHON-associated and functionally significant mtDNA mutations in this Chinese family suggested that mitochondrial variants may not play an important role in the phenotypic manifestation of the G11778A mutation in this Chinese family. Therefore, nuclear modifier gene(s) may be responsible for very high penetrance and occurrence of optic neuropathy in this Chinese pedigree. PMID:20627642

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

2010-01-01

103

Peripheral neuropathies of childhood.  

PubMed

This article has provided a brief overview of the most common inherited and acquired peripheral nerve diseases encountered in childhood. The diagnostic approach of peripheral neuropathies in children often relies on some combination of careful history taking, physical examination findings, a careful determination of family history, electrodiagnostic studies, molecular genetic studies, sural nerve biopsy, and occasionally metabolic laboratory studies. Although pediatric mononeuropathies may have different causes than those observed in adults, the clinical presentations, diagnostic evaluation, and management of mononeuropathies are frequently similar in adults and children. Encouraging progress is being made in the management of acute inflammatory demyelinating polyneuropathy (AIDP), which is the most common acquired neuropathy of childhood. Rapid advances in molecular genetics over the past decade have had a significant impact on our diagnostic approach to hereditary motor sensory neuropathy in particular. In the future it is likely that the sequencing of genes, characterization of protein structure and function, and further elucidation of pathophysiology will have significant impacts on the treatment of many inherited peripheral neuropathies of childhood. PMID:11345019

McDonald, C M

2001-05-01

104

AMYLOID NEUROPATHIES  

PubMed Central

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

Shin, Susan C.; Robinson-Papp, Jessica

2012-01-01

105

Neurophysiological evidence for generalized sensory neuronopathy in cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS).  

PubMed

Introduction: Cerebellar Ataxia with Neuropathy and bilateral Vestibular Areflexia Syndrome (CANVAS) is a recently described multi-system ataxia defined by the presence of cerebellar ataxia, bilateral vestibulopathy, and a somatic sensory deficit. The characteristic clinical sign is an abnormal visually enhanced vestibulo-ocular reflex. The somatic sensory deficit contributes to a significant level of disability in CANVAS. Methods & results: Neurophysiological investigation in 14 patients revealed uniformly absent sensory nerve action potentials in all limbs, abnormal blink reflexes in 13/14, and abnormal masseter reflexes in 6/11. Tibial H-reflexes were absent in 11/14. Somatosensory evoked potentials were abnormal in 10/11 tested, and brainstem audiometry evoked responses were abnormal in 3/8. Cutaneous silent period responses were abnormal in 7/14. Discussion: We suggest that a sensory neuronopathy should be sought in cerebellar and/or vestibular ataxias, particularly where the degree of ataxia is out of proportion to the clinically identified cerebellar and/or vestibular dysfunction. © 2014 Wiley Periodicals, Inc. PMID:25130975

Szmulewicz, David J; Seiderer, Linda; Halmagyi, G Michael; Storey, Elsdon; Roberts, Leslie

2014-08-16

106

The Role of Cutaneous Innervation in the Sensory Abnormalities Associated with Diabetic Neuropathy  

E-print Network

Diabetes-induced nerve damage results in cutaneous denervation, nerve conduction slowing, suppressed regenerative responses, and debilitating painful or insensate sensory symptoms. The increasing prevalence of diabetic ...

Johnson, Megan Sarah

2008-05-05

107

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

PubMed Central

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

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

2012-01-01

108

Sensory-motor axonal peripheral neuropathy in an advanced breast cancer patient treated with ixabepilone  

Microsoft Academic Search

Ixabepilone is a novel microtubule-stabilising agent used as monotherapy or in combination with capecitabine to treat taxane-\\u000a and anthracycline-refractory breast cancer. We report the case of a patient who experienced an unusual motor neuropathy after\\u000a the first cycle. This is a very uncommon secondary effect, but it must be taken into account as a possible complication of\\u000a treatment with ixabepilone.

Joaquim Bosch-Barrera; Jaime Espinós; Asier Gómez-Ibáńez; Jaime Gállego Pérez-Larraya; Jorge Iriarte

2009-01-01

109

Prospective study of paclitaxel-induced peripheral neuropathy with quantitative sensory testing  

Microsoft Academic Search

Background. Paclitaxel-induced peripheral neuropathy (PN) may be severeand dose-limiting at initial doses = 275 mg\\/M2, but itsneurotoxicity at doses = 250 mg\\/M2 has been incompletelycharacterized. The purposes of this study were to characterize and quantifypaclitaxel-induced PN and to determine the utility of quantitative sensorytesting (QST). Methods. We prospectively examined clinically and by QST 37women with metastatic breast cancer, treated with

Peter a. Forsyth; Casilda Balmaceda; Kendra Peterson; Andrew D. Seidman; Penny Brasher; Lisa M. Deangelis

1997-01-01

110

CHARACTERIZATION & TREATMENT OF LARGE SENSORY FIBER PERIPHERAL NEUROPATHY IN DIABETIC MICE  

E-print Network

Patients with large-fiber diabetic sensorimotor polyneuropathy (DPN) can develop altered sensorimotor function. Gait and balance control are regulated, in part, through large sensory nerves innervating muscle spindles. The overall goal...

Muller, Karra

2008-11-17

111

Neuromuscular manifestations in hereditary haemochromatosis.  

PubMed

Involvement of peripheral nerves and skeletal muscles has been reported in the course of hereditary haemochromatosis (HH) but a systematic study is lacking. However, patients with HH report symptoms suggesting a possible polyneuropathy or myopathy. In this study patients with DNA proven HH were recruited from a large general teaching hospital. First, all patients were clinically examined using a structured interview and neurological exam. After reviewing these data an expert panel reached consensus about the presence of a possible neuropathy or myopathy and made recommendations for ancillary investigations (nerve conduction studies, electromyography, thermal threshold tests, laboratory tests). After a second meeting consensus was reached about the final diagnosis. Patients who had a neuropathy or myopathy of which the origin was still unclear were referred to an independent neurologist for further evaluation. Ultimately, of 46 patients included, 25 had no myopathy or neuropathy, 5 an axonal sensory motor polyneuropathy of which the cause was found (diabetes in 2, combination of diabetes and chemotherapy in 1, Charcot Marie Tooth type 2 in 1, Morbus Sjögren in 1), 9 an idiopathic axonal sensory motor polyneuropathy, 3 an idiopathic small fiber polyneuropathy and 4 a carpal tunnel syndrome. There were no cases of proven myopathy. We conclude that an idiopathic polyneuropathy was diagnosed in a relative large number of patients with HH (26%), but the causal relationship needs to be confirmed in larger (case-control) series. PMID:20358215

Wouthuis, S F; van Deursen, C Th B M; te Lintelo, M P; Rozeman, C A M; Beekman, R

2010-09-01

112

Mice with a mutation in the dynein heavy chain 1 gene display sensory neuropathy but lack motor neuron disease.  

PubMed

In neurons, cytoplasmic dynein functions as a molecular motor responsible for retrograde axonal transport. An impairment of axonal transport is thought to play a key role in the pathogenesis of neurodegenerative diseases such as amyotrophic lateral sclerosis, the most frequent motor neuron disease in the elderly. In this regard, previous studies described two heterozygous mouse strains bearing missense point mutations in the dynein heavy chain 1 gene that were reported to display late-onset progressive motor neuron degeneration. Here we show, however, that one of these mutant strains, the so-called Cra mice does not suffer from motor neuron loss, even in aged animals. Consistently, we did not observe electrophysiological or biochemical signs of muscle denervation, indicative of motor neuron disease. The "hindlimb clasping" phenotype of Cra mice could rather be due to the prominent degeneration of sensory neurons associated with a loss of muscle spindles. Altogether, these findings show that dynein heavy chain mutation triggers sensory neuropathy rather than motor neuron disease. PMID:18952079

Dupuis, Luc; Fergani, Anissa; Braunstein, Kerstin E; Eschbach, Judith; Holl, Nathalie; Rene, Frédérique; Gonzalez De Aguilar, Jose-Luis; Zoerner, Björn; Schwalenstocker, Birgit; Ludolph, Albert C; Loeffler, Jean-Philippe

2009-01-01

113

Painful Peripheral Neuropathies  

PubMed Central

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

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

2006-01-01

114

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

PubMed Central

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

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

2009-01-01

115

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

PubMed

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

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

2014-09-01

116

Neurotrophin3 Administration Attenuates Deficits of Pyridoxine-Induced Large-Fiber Sensory Neuropathy  

Microsoft Academic Search

Chronic treatment of adult rats for 2-3 weeks with high doses of pyridoxine (vitamin B6) produced a profound proprioceptive loss, similar to that found in humans overdosed with this vita- min or treated with the chemotherapeutic agent cisplatin. Pyr- idoxine toxicity was manifest as deficits in simple and precise locomotion and sensory nerve function and as degeneration of large-diameter\\/large-fiber spinal

Maureen E. Helgren; Kenneth D. Cliffer; Kim Torrento; Chris Cavnor; Rory Curtis; Peter S. DiStefano; Stanley J. Wiegand; Ronald M. Lindsay

1997-01-01

117

Sensory Ataxic Neuropathy in Golden Retriever Dogs Is Caused by a Deletion in the Mitochondrial tRNATyr Gene  

PubMed Central

Sensory ataxic neuropathy (SAN) is a recently identified neurological disorder in golden retrievers. Pedigree analysis revealed that all affected dogs belong to one maternal lineage, and a statistical analysis showed that the disorder has a mitochondrial origin. A one base pair deletion in the mitochondrial tRNATyr gene was identified at position 5304 in affected dogs after re-sequencing the complete mitochondrial genome of seven individuals. The deletion was not found among dogs representing 18 different breeds or in six wolves, ruling out this as a common polymorphism. The mutation could be traced back to a common ancestor of all affected dogs that lived in the 1970s. We used a quantitative oligonucleotide ligation assay to establish the degree of heteroplasmy in blood and tissue samples from affected dogs and controls. Affected dogs and their first to fourth degree relatives had 0–11% wild-type (wt) sequence, while more distant relatives ranged between 5% and 60% wt sequence and all unrelated golden retrievers had 100% wt sequence. Northern blot analysis showed that tRNATyr had a 10-fold lower steady-state level in affected dogs compared with controls. Four out of five affected dogs showed decreases in mitochondrial ATP production rates and respiratory chain enzyme activities together with morphological alterations in muscle tissue, resembling the changes reported in human mitochondrial pathology. Altogether, these results provide conclusive evidence that the deletion in the mitochondrial tRNATyr gene is the causative mutation for SAN. PMID:19492087

Baranowska, Izabella; Jäderlund, Karin Hultin; Nennesmo, Inger; Holmqvist, Erik; Heidrich, Nadja; Larsson, Nils-Göran; Andersson, Göran; Wagner, E. Gerhart H.; Hedhammar, Ĺke; Wibom, Rolf; Andersson, Leif

2009-01-01

118

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. PMID:24568867

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

2014-01-01

119

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. PMID:19733221

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

120

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

SciTech Connect

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

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

1991-09-15

121

Hip dysplasia associated with a hereditary sensorimotor polyneuropathy mimics a myopathic process  

PubMed Central

Some orthopedic complications have been reported in the hereditary neuropathies. However, the association of the hip dysplasia with this category of neuropathy is rarely recognized. We present a 13-year-old boy with the progressive weakness of the lower extremities, difficulty in walking, climbing stairs, and rising from floor; a wide-based, hyper-extended and waddling gait similar to a myopathic process. Hip radiography showed dysplastic acetabulae with hip subluxation, broken Shenton's lines, and valgus femoral necks. In electrodiagnosis, there was a significant neuropathic process (absent all evoked sensory potentials, abnormal evoked motor responses, and neurogenic electeromyography) which eventually was found to be a hereditary mixed axonal and demyelinating sensorimotor polyneuropathy with concomitant hip dysplasia confirmed with thorough physical examination and the electrodiagnostic study. In patients with gait difficulties such as waddling gait mimicking a myopathic process, hereditary polyneuropathy complicated with hip dysplasia should be considered as well. PMID:22919197

Hadianfard, Mohammad Javad; Ashraf, Alireza

2012-01-01

122

Paraneoplastic neuropathy.  

PubMed

Recent progress in serological screening of paraneoplastic antibodies and in diagnostic imaging techniques to detect malignancies has enabled a broadening of the concept of paraneoplastic neurological syndromes by integrating nonclassic clinical features. The peripheral nervous system is frequently involved in patients with paraneoplastic syndrome and may be seen alone or in combination with involvement of other areas of the nervous system. Destruction of dorsal root ganglion cells due to lymphocytic infiltration, especially with CD8-positive cytotoxic T cells, has been postulated to mediate the classic syndrome of subacute sensory neuronopathy. However, the motor and autonomic nervous systems are frequently affected. Indeed, patients can develop clinical features compatible with Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, or brachial plexopathy. Other forms of paraneoplastic neuropathy are vasculitic neuropathy, autoimmune autonomic ganglionopathy, and chronic intestinal pseudo-obstruction. Various onconeural antibodies, including anti-Hu, anti-CV2/CRMP-5, and anti-ganglionic acetylcholine receptor antibodies, are associated with neuropathy. Somatic neuropathy is the most common manifestation in patients with anti-Hu and anti-CV2/CRMP-5 antibodies, while anti-ganglionic acetylcholine receptor antibody is associated with autonomic neuropathies. A whole-body fluorodeoxyglucose positron emission tomography scan may be useful to detect malignancy in patients with unremarkable conventional radiological findings. Recognition and diagnosis of paraneoplastic neuropathy is important, as neuropathic symptoms usually precede the identification of the primary tumor, and treatment at an earlier stage provides better chances of good outcomes. PMID:23931811

Koike, Haruki; Sobue, Gen

2013-01-01

123

Gastrodin inhibits allodynia and hyperalgesia in painful diabetic neuropathy rats by decreasing excitability of nociceptive primary sensory neurons.  

PubMed

Painful diabetic neuropathy (PDN) is a common complication of diabetes mellitus and adversely affects the patients' quality of life. Evidence has accumulated that PDN is associated with hyperexcitability of peripheral nociceptive primary sensory neurons. However, the precise cellular mechanism underlying PDN remains elusive. This may result in the lacking of effective therapies for the treatment of PDN. The phenolic glucoside, gastrodin, which is a main constituent of the Chinese herbal medicine Gastrodia elata Blume, has been widely used as an anticonvulsant, sedative, and analgesic since ancient times. However, the cellular mechanisms underlying its analgesic actions are not well understood. By utilizing a combination of behavioral surveys and electrophysiological recordings, the present study investigated the role of gastrodin in an experimental rat model of STZ-induced PDN and to further explore the underlying cellular mechanisms. Intraperitoneal administration of gastrodin effectively attenuated both the mechanical allodynia and thermal hyperalgesia induced by STZ injection. Whole-cell patch clamp recordings were obtained from nociceptive, capsaicin-sensitive small diameter neurons of the intact dorsal root ganglion (DRG). Recordings from diabetic rats revealed that the abnormal hyperexcitability of neurons was greatly abolished by application of GAS. To determine which currents were involved in the antinociceptive action of gastrodin, we examined the effects of gastrodin on transient sodium currents (I(NaT)) and potassium currents in diabetic small DRG neurons. Diabetes caused a prominent enhancement of I(NaT) and a decrease of potassium currents, especially slowly inactivating potassium currents (I(AS)); these effects were completely reversed by GAS in a dose-dependent manner. Furthermore, changes in activation and inactivation kinetics of I(NaT) and total potassium current as well as I(AS) currents induced by STZ were normalized by GAS. This study provides a clear cellular basis for the peripheral analgesic action of gastrodin for the treatment of chronic pain, including PDN. PMID:22761855

Sun, Wei; Miao, Bei; Wang, Xiu-Chao; Duan, Jian-Hong; Ye, Xin; Han, Wen-Juan; Wang, Wen-Ting; Luo, Ceng; Hu, San-Jue

2012-01-01

124

Gastrodin Inhibits Allodynia and Hyperalgesia in Painful Diabetic Neuropathy Rats by Decreasing Excitability of Nociceptive Primary Sensory Neurons  

PubMed Central

Painful diabetic neuropathy (PDN) is a common complication of diabetes mellitus and adversely affects the patients’ quality of life. Evidence has accumulated that PDN is associated with hyperexcitability of peripheral nociceptive primary sensory neurons. However, the precise cellular mechanism underlying PDN remains elusive. This may result in the lacking of effective therapies for the treatment of PDN. The phenolic glucoside, gastrodin, which is a main constituent of the Chinese herbal medicine Gastrodia elata Blume, has been widely used as an anticonvulsant, sedative, and analgesic since ancient times. However, the cellular mechanisms underlying its analgesic actions are not well understood. By utilizing a combination of behavioral surveys and electrophysiological recordings, the present study investigated the role of gastrodin in an experimental rat model of STZ-induced PDN and to further explore the underlying cellular mechanisms. Intraperitoneal administration of gastrodin effectively attenuated both the mechanical allodynia and thermal hyperalgesia induced by STZ injection. Whole-cell patch clamp recordings were obtained from nociceptive, capsaicin-sensitive small diameter neurons of the intact dorsal root ganglion (DRG). Recordings from diabetic rats revealed that the abnormal hyperexcitability of neurons was greatly abolished by application of GAS. To determine which currents were involved in the antinociceptive action of gastrodin, we examined the effects of gastrodin on transient sodium currents (INaT) and potassium currents in diabetic small DRG neurons. Diabetes caused a prominent enhancement of INaT and a decrease of potassium currents, especially slowly inactivating potassium currents (IAS); these effects were completely reversed by GAS in a dose-dependent manner. Furthermore, changes in activation and inactivation kinetics of INaT and total potassium current as well as IAS currents induced by STZ were normalized by GAS. This study provides a clear cellular basis for the peripheral analgesic action of gastrodin for the treatment of chronic pain, including PDN. PMID:22761855

Ye, Xin; Han, Wen-Juan; Wang, Wen-Ting; Luo, Ceng; Hu, San-Jue

2012-01-01

125

Leber's Hereditary Optic Neuropathy is Associated with Compound Primary Mutations of Mitochondrial ND1 m.3635G?>?A and ND6 m.14502 T?>?C.  

PubMed

Abstract Purpose: To describe the clinical and molecular characteristics of a Chinese Leber hereditary optic neuropathy (LHON) pedigree with compound mitochondrial DNA (mtDNA) mutations of m.3635G?>?A and m.14502T?>?C. Methods: A total of 22 individuals (2 affected, 20 unaffected) from a five-generation Chinese family with LHON underwent comprehensive ophthalmic examination, including visual acuity, slit lamp examination, fundoscopy, visual field examination and visual evoked potentials (VEP). The complete mtDNA genome of the two patients were amplified by polymerase chain reaction, sequenced using a Bigdye terminator v3.1 cycle sequencing kit and analyzed on an ABI 3700XL Genetic Analyzer. Results: Two LHON patients in the family presented typical features of LHON: painless and progressive deterioration of bilateral vision, bilateral optic atrophy, centrocecal scotomata in both eyes and significant prolonged P100 latency and low amplitude potential in VEP. Compound primary mtDNA mutations of m.3635G?>?A and m.14502T?>?C were identified in these two patients and another 12 living matrilineal members of the pedigree. Haplogroup analysis showed the patients in this LHON family belonged to the N9b1 haplogroup. Modeled mutant structure showed the mutations altered the molecular local space conformation on the surface of ND1 and ND6. Conclusions: Compound mtDNA mutations of m.3635G?>?A and m.14502T?>?C presented with low penetration, and the patients with these compound mutations exhibited mild visual impairment. The biological information analysis suggested that m.14502T?>?C might play a protective role in LHON associated with m.3635G?>?A. The haplogroup analysis indicated that the mtDNA haplogroup might be an important factor affecting the expression of LHON associated with m.3635G?>?A and/or m.14502T?>?C. PMID:24417559

Jin, Xin; Wang, Lifeng; Gong, Yan; Chen, Bing; Wang, Yanhua; Chen, Tingjun; Wei, Shihui

2014-01-13

126

Diabetic neuropathy enhances voltage-activated Ca2+ channel activity and its control by M4 muscarinic receptors in primary sensory neurons.  

PubMed

Painful neuropathy is one of the most serious complications of diabetes and remains difficult to treat. The muscarinic acetylcholine receptor (mAChR) agonists have a profound analgesic effect on painful diabetic neuropathy. Here we determined changes in T-type and high voltage-activated Ca(2+) channels (HVACCs) and their regulation by mAChRs in dorsal root ganglion (DRG) neurons in a rat model of diabetic neuropathy. The HVACC currents in large neurons, T-type currents in medium and large neurons, the percentage of small DRG neurons with T-type currents, and the Cav3.2 mRNA level were significantly increased in diabetic rats compared with those in control rats. The mAChR agonist oxotremorine-M significantly inhibited HVACCs in a greater proportion of DRG neurons with and without T-type currents in diabetic than in control rats. In contrast, oxotremorine-M had no effect on HVACCs in small and large neurons with T-type currents and in most medium neurons with T-type currents from control rats. The M(2) and M(4) antagonist himbacine abolished the effect of oxotremorine-M on HVACCs in both groups. The selective M(4) antagonist muscarinic toxin-3 caused a greater attenuation of the effect of oxotremorine-M on HVACCs in small and medium DRG neurons in diabetic than in control rats. Additionally, the mRNA and protein levels of M(4), but not M(2), in the DRG were significantly greater in diabetic than in control rats. Our findings suggest that diabetic neuropathy potentiates the activity of T-type and HVACCs in primary sensory neurons. M(4) mAChRs are up-regulated in DRG neurons and probably account for increased muscarinic analgesic effects in diabetic neuropathic pain. PMID:21883220

Cao, Xue-Hong; Byun, Hee Sun; Chen, Shao-Rui; Pan, Hui-Lin

2011-11-01

127

Chemotherapy-induced peripheral neuropathy  

Microsoft Academic Search

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

Stefan Quasthoff; Hans Peter Hartung

2002-01-01

128

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  

PubMed Central

OBJECTIVES—Leber'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 magnetisation transfer imaging (MTI), and (b) the presence and extent of macroscopic and microscopic pathology in the brain and cervical cord, using MRI and MT ratio (MTR) and mean diffusivity (&Dmacr;) histogram analysis.?METHODS—Ten patients with LHON, four with LHON-MS, and 20 age and sex matched healthy controls were studied. For the optic nerve and the brain, dual-echo turbo spin echo (TSE), T1 weighted spin echo, and MT images were obtained. For the brain, fast fluid attenuated inversion recovery (fast FLAIR) and diffusion weighted images were also obtained. For the cervical cord, fast short tau inversion recovery (STIR) and MT images were obtained. The volume and the average MTR value of both the optic nerves were measured. MTR and &Dmacr; histograms of the normal appearing brain tissue (NABT) and MTR histograms of the whole cervical cord tissue were created.?RESULTS—The mean values of optic nerve volumes and MTR were significantly lower in patients with LHON than in healthy controls. Mean NABT-MTR histogram peak height was significantly lower in patients with LHON than in controls, whereas no significant difference was found for any of the cervical cord MTR histogram derived measures. Average diffusivity (&Dmacr;) was higher in patients with LHON than in controls. Optic nerve volume and MTR value and mean NABT-MTR were lower in patients with LHON-MS than in those with LHON.?CONCLUSIONS—The severity of optic nerve pathology in LHON is measurable in vivo using MRI and MTI. MTR and &Dmacr; histogram analysis suggests that microscopic brain damage occurs in LHON and that it is more severe in the MS-like form of the disease.?? PMID:11254765

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

2001-01-01

129

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. PMID:24860645

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

2014-01-01

130

Diabetic Neuropathy  

MedlinePLUS

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

131

Overlap Phenotype between CMT1A and Hereditary Neuropathy with Liability to Pressure Palsies Caused by the Novel Small In-frame Deletion c.407_418del12 in PMP22 Gene.  

PubMed

We report monozygotic twins, who presented with a clinical picture of Charcot-Marie-Tooth disease type 1 (CMT1) with bilateral foot drop, pes cavus, thoracic kyphosis, and scoliosis. Hereditary neuropathy with liability to pressure palsies (HNPP) showed up in one of them. Neurography showed demyelinating neuropathy, typical for CMT1, and transient conduction block in the ulnar nerve correlating with clinical ulnar palsy due to minor mechanical stress in only one of them. Genetic analysis revealed novel small de novo deletion c.407_418del12 in the PMP22 gene. Our patient shows the rarely reported combination of CMT1A and HNPP, caused by an in-frame deletion in the PMP22 gene. HNPP is in the majority of cases correlated with heterozygous deletion of the whole PMP22 gene or other mutations leading to functional haploinsufficiency. The cases give further evidence that pathogenesis of HNPP is not completely understood and can obviously result from existence of a defective protein, too. The intrafamiliar phenotypic variability, even in monozygotic twins, confirms the well-known fact that factors apart from genetics contribute to the clinical course. PMID:25265422

Vill, Katharina; Kuhn, Marius; Gläser, Dieter; Müller-Felber, Wolfgang

2015-02-01

132

Charcot-Marie-Tooth disease type 1A and hereditary neuropathy with liability to pressure palsies: a SacI polymorphism in the proximal CMT1A-REP elements may lead to genetic misdiagnosis.  

PubMed

A male patient with clinical signs and symptoms of a demyelinating neuropathy was shown to have a duplication of the 1.5-Mb region on chromosome 17p11.2 by means of two-color fluorescence in situ hybridization (FISH). This duplication is typical for the vast majority of Charcot-Marie-Tooth type 1A (CMT1A) cases. Analysis of DNA extracted from peripheral blood used to detect an EcoRI/SacI 3. 2-kb junction fragment with probe pLR7.8 confirmed the CMT1A duplication, but also revealed a 7.8-kb fragment usually observed in patients with a hereditary neuropathy with liability to pressure palsies (HNPP). Both fragments observed in one patient canot result from one unequal crossover. In EcoRI/SacI Southern hybridization experiments with probe pLR7.8 DNA of his healthy parents also revealed a 7.8-kB restriction fragment. A subsequent two-color FISH analysis, however, indicated a normal status for interphase nuclei of the parents. Hence we hypothesize that the 7.8-kb fragment observed in our patient and his parents is not the product of unequal crossover during meiosis but due to a polymorphism of the SacI site in a proximal CMT1A-REP element. PMID:9933299

Fuchs, C; Liehr, T; Ozbey, S; Ekici, A; Grehl, H; Rautenstrauss, B

1998-12-01

133

Targeting of CaV3.2 T-type calcium channels in peripheral sensory neurons for the treatment of painful diabetic neuropathy.  

PubMed

Pain-sensing sensory neurons (nociceptors) of the dorsal root ganglion (DRG) can become sensitized (hyperexcitable) in response to pathological conditions such as diabetes, which in turn may lead to the development of painful peripheral diabetic neuropathy (PDN). Because of insufficient knowledge about the mechanisms for this hypersensitization, current treatment for painful PDN has been limited to somewhat nonspecific systemic drugs having significant side effects or potential for abuse. Recent studies have established that the CaV3.2 isoform of T-channels makes a previously unrecognized contribution to sensitization of pain responses by enhancing excitability of nociceptors in animal models of type 1 and type 2 PDN. Furthermore, it has been reported that the glycosylation inhibitor neuraminidase can inhibit the native and recombinant CaV3.2 T-currents in vitro and completely reverse mechanical and thermal hyperalgesia in diabetic animals with PDN in vivo. Understanding details of posttranslational regulation of nociceptive channel activity via glycosylation may facilitate development of novel therapies for treatment of painful PDN. Pharmacological targeting the specific pathogenic mechanism rather than the channel per se may cause fewer side effects and reduce the potential for drug abuse in patients with diabetes. PMID:24482063

Todorovic, Slobodan M; Jevtovic-Todorovic, Vesna

2014-04-01

134

Neuropathy Association  

MedlinePLUS

... FIND US ON Boston Skyscraper Shines Purple and Gold for Millions Living With Neuropathy! Photo Credit: Michael ... Tower in Boston, MA lit up, purple and gold, for over 20 million people living with neuropathy. ...

135

Hereditary myelopathies.  

PubMed

Hereditary myelopathies comprise a diverse group of disorders whose signs and symptoms include progressive spasticity, limb ataxia without additional cerebellar signs, impaired vibration and positional sensation, and a variable degree of neurogenic weakness, all suggesting spinal cord impairment. Recent progress in the understanding of hereditary myelopathies has revealed that many are systemic processes with widespread axonal degeneration. However, the concept of hereditary myelopathies remains clinically helpful in differentiating hereditary myelopathies from other potentially treatable myelopathies. In this article, hereditary myelopathies are divided into four categories: hereditary spastic paraplegias, motor neuron disorders, spinocerebellar and spastic ataxias, and metabolic disorders, including leukodystrophies. PMID:22810932

Hedera, Peter

2011-08-01

136

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

PubMed Central

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

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

2014-01-01

137

Leprous neuropathy.  

PubMed

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

de Freitas, Marcos R G; Said, Gérard

2013-01-01

138

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. PMID:23642713

Barohn, Richard J; Amato, Anthony A.

2014-01-01

139

Clinicopathological and genetic study of early-onset demyelinating neuropathy  

Microsoft Academic Search

Summary Autosomal recessive demyelinating Charcot-Marie- Tooth disease (CMT4), Dejerine-Sottas disease and congenital hypomyelinating neuropathy are variants of hereditary demyelinating neuropathy of infancy, a geneti- cally heterogeneous group of disorders. To explore the spectrum of early-onset demyelinating neuropathies further, we studied the clinicopathological and genetic aspects of 20 patients born to unaffected parents. In 19 families out of 20, consanguinity between

Yesim Parman; Ibrahim Bars; Birdal Bilir; Muruvvet Poyraz; Nisrine Bissar-Tadmouri; Anna Williams; Nadia Ammar; Eva Nelis; Vincent Timmerman; Feza Deymeer; Piraye Serdaro; Peter J. Brophy

2004-01-01

140

Chemotherapy induced neuropathy in clinical practice Neuropatía inducida por quimioterapia en la práctica clínica  

Microsoft Academic Search

SUMMARY Neuropathic pain is a common symptom amongst patients with chemotherapy induced peripheral nerve neurotoxicity, and symptoms are indistinguishable from those seen with toxic neuropathy from other causes. The neuropathy is predominantly sensory and follows a glove-stocking distribution and associates with burning pain. Autonomic neuropathy manifested as constipation frequently occurs. There are some risk factors for neuropathy caused by chemotherapy:

Camilo E. Fadul

141

Colour vision defects in asymptomatic carriers of the Leber's hereditary optic neuropathy (LHON) mtDNA 11778 mutation from a large Brazilian LHON pedigree: a case?control study  

PubMed Central

Aims To determine if asymptomatic carriers from a previously identified large pedigree of the Leber's hereditary optic neuropathy (LHON) 11778 mtDNA mutation have colour vision deficits. Methods As part of a comprehensive analysis of over 200 members of a large Brazilian LHON pedigree spanning seven generations, colour vision tests were obtained from 91 members. Colour vision was tested one eye at a time using the Farnsworth?Munsell 100 (FM?100) hue colour vision test. The test was administered under uniform conditions, taking into account: ambient light levels, daylight colour temperature of 6700?kelvin, and neutral uniform background. Tests were scored using the FM?100 MS?Excel computer scoring program. Defects were determined and categorised as tritan, deutan, or protan. Categorisation of each dyschromatopsia was based on review of demonstrated axis computer generated plots and age adjusted error scores which coincided with Verriest 95% confidence intervals. Only the axis with the greatest magnitude error score was used to classify the defect. 55 of the 91 test subjects were LHON mtDNA 11778 J haplotype mutation carriers, proved by mtDNA analysis. The remaining 36 subjects were age matched non?blood relatives (off pedigree), who served as controls. Results 27 of 55 carriers (49.10%) were shown to have colour vision defects in one or both eyes. 13 of the 27 (48%) abnormal tests in the carrier group were tritan defects and the remaining 14 (52%) were deutan defects. Nine of the 27 (33%) abnormals in the carrier group were identified as having bilateral defects. Six of these were deutan, and the remaining three were tritan dyschromatopsias. Only six of the 36 (16.66%) age matched controls were found to have any type of dyschromatopsia. Five (83.3%) of these were deutan defects. The remaining one was a tritan defect. The difference between the two groups using a ?2 test with one degree of freedom was statistically significant with a p value less that 0.001. Conclusions Until now, LHON has always been characterised by a sudden, devastating vision loss. Asymptomatic carriers, those without vision loss, were considered unaffected by the disease. It now appears that asymptomatic carriers of the LHON mutation are affected by colour vision defects and may manifest other subtle, yet chronic, changes. PMID:16424523

Quiros, P A; Torres, R J; Salomao, S; Berezovsky, A; Carelli, V; Sherman, J; Sadun, F; De Negri, A; Belfort, R; Sadun, A A

2006-01-01

142

The neuropathy of erectile dysfunction  

Microsoft Academic Search

These studies were intended to explore the relationship between autonomic neuropathy and erectile dysfunction (ED). Sensory thresholds reflecting the integrity of both large diameter, myelinated neurons (ie pressure, touch, vibration) and small diameter axons (ie hot and cold thermal sensation) were determined on the penis and finger. Data were compared across subjects with and without ED, controlling for age, hypertension

CB Bleustein; JC Arezzo; H Eckholdt; A Melman

2002-01-01

143

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

PubMed

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

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

2014-01-01

144

In vivo silencing of the Ca V3.2 T-type calcium channels in sensory neurons alleviates hyperalgesia in rats with streptozocin-induced diabetic neuropathy  

Microsoft Academic Search

Earlier, we showed that streptozocin (STZ)-induced type 1 diabetes in rats leads to the development of painful peripheral diabetic neuropathy (PDN) manifested as thermal hyperalgesia and mechanical allodynia accompanied by significant enhancement of T-type calcium currents (T-currents) and cellular excitability in medium-sized dorsal root ganglion (DRG) neurons. Here, we studied the in vivo and in vitro effects of gene-silencing therapy

Richard B. Messinger; Ajit K. Naik; Miljen M. Jagodic; Michael T. Nelson; Woo Yong Lee; Won Joo Choe; Peihan Orestes; Janelle R. Latham; Slobodan M. Todorovic; Vesna Jevtovic-Todorovic

2009-01-01

145

Autonomic neuropathies  

NASA Technical Reports Server (NTRS)

A limited autonomic neuropathy may underlie some unusual clinical syndromes, including the postural tachycardia syndrome, pseudo-obstruction syndrome, heat intolerance, and perhaps chronic fatigue syndrome. Antibodies to autonomic structures are common in diabetes, but their specificity is unknown. The presence of autonomic failure worsens prognosis in the diabetic state. Some autonomic neuropathies are treatable. Familial amyloid polyneuropathy may respond to liver transplantation. There are anecdotal reports of acute panautonomic neuropathy responding to intravenous gamma globulin. Orthostatic hypotension may respond to erythropoietin or midodrine.

Low, P. A.

1998-01-01

146

Peripheral Neuropathy  

MedlinePLUS

... have been studied for PN caused by diabetes: B vitamins. Several B vitamins are useful in treating diabetic neuropathy. These include biotin, choline, inositol, and thiamine. They appear to improve nerve function. Alpha-lipoic ...

147

Treatment of Diabetic Sensory Polyneuropathy  

Microsoft Academic Search

Opinion statement  No current disease-modifying treatments have been shown definitively in randomized clinical trials to reduce or reverse diabetic\\u000a sensory polyneuropathy (DSP). It is increasingly recognized that individuals with “prediabetes” or impaired glucose regulation\\u000a can already have a “small-fiber” neuropathy, or mild DSP, in which sensory axons of both small and larger diameter are damaged.\\u000a Small-fiber neuropathy is frequently associated with

Lindsay Zilliox; James W. Russell

2011-01-01

148

Hereditary Hemochromatosis  

MedlinePLUS

... high iron levels may have skin with a bronze or gray color. Their lab tests may be ... recommended for children younger than 18 years of age. Treatment How is hereditary hemochromatosis treated? The goal ...

149

Peripheral systems: neuropathy.  

PubMed

Long-term, excessive consumption of alcoholic beverages produces a peripheral neuropathy with symptoms of decreased superficial sensation, hyperalgesia, and weakness. Alcoholic neuropathy is characterized by axonal degeneration with reduced density of both small and large fibers and axonal sprouting. Electrophysiologic studies reveal a marked reduction in the amplitude of sensory potentials and moderate slowing of nerve conduction, mainly in the lower extremities. Dietary deficiency of vitamins, which are often associated with chronic alcoholism, can contribute to the pathogenesis. Recent studies using animal models have identified several mechanisms by which ethanol impacts peripheral nerve function. Ethanol can exert direct neurotoxic effects on peripheral nerves via its metabolite acetaldehyde and by enhancing oxidative stress. Ethanol activation of protein kinase C? signaling in primary afferent nociceptors plays an important role in lowering nociceptive threshold. Further, ethanol causes cytoskeletal dysfunction and inhibits both anterograde and retrograde axonal transport. Alcoholic neuropathy is potentially reversible and treatments include abstinence from alcoholic beverages and consumption of a nutritionally balanced diet supplemented with B vitamins. However, response to these treatment strategies can be variable, which underscores the need for novel therapeutic strategies. In this review, we provide an overview of the clinical findings and insights on molecular mechanisms from animal models. PMID:25307593

Maiya, Rajani P; Messing, Robert O

2014-01-01

150

Suprascapular neuropathy.  

PubMed

Suprascapular neuropathy has often been overlooked as a source of shoulder pain. The condition may be more common than once thought as it is being diagnosed more frequently. Etiologies for suprascapular neuropathy may include repetitive overhead activities, traction from a rotator cuff tear, and compression from a space-occupying lesion at the suprascapular or spinoglenoid notch. Magnetic resonance imaging is useful for visualizing space-occupying lesions, other pathological entities of the shoulder, and fatty infiltration of the rotator cuff. Electromyography and nerve conduction velocity studies remain the standard for diagnosis of suprascapular neuropathy; however, data on interobserver reliability are limited. Initial treatment of isolated suprascapular neuropathy is typically nonoperative, consisting of physical therapy, nonsteroidal anti-inflammatory drugs, and activity modification; however, open or arthroscopic operative intervention is warranted when there is extrinsic nerve compression or progressive pain and/or weakness. More clinical data are needed to determine if treatment of the primary offending etiology in cases of traction from a rotator cuff tear or compression from a cyst secondary to a labral tear is sufficient or whether concomitant decompression of the nerve is warranted for management of the neuropathy. PMID:20926731

Boykin, Robert E; Friedman, Darren J; Higgins, Laurence D; Warner, Jon J P

2010-10-01

151

Hereditary Hemochromatosis (For Parents)  

MedlinePLUS

Hereditary Hemochromatosis Hereditary hemochromatosis is a genetic disease that causes the body to absorb and store too much iron . ... and in rare cases, children. Causes of Hereditary Hemochromatosis Although many people have never heard of hereditary ...

152

Hereditary Pheochromocytoma.  

PubMed

Introduction. Pheochromocytomas (PHEO) and paragangliomas (PGL) are rare neuroendocrine tumors with an estimated occurrence of 2 to 5 patients per million per year and an incidence of about 1 per 100 000 in the general population. These tumors may arise sporadically or be associated to various syndromes, namely multiple endocrine neoplasia type 2, neurofibromatosis type 1, Von Hippel-Lindau syndrome, and hereditary paraganglioma-pheochromocytoma syndromes. Objectives. This article aims to review the current epidemiology, pathogenesis, clinical presentation, and genetic aspects of syndromes associated with hereditary PHEO/PGL. Methods. The literature research, conducted at PubMed database, included review articles, published from February 2009 to February 2014, written in English or Portuguese, using as query: "Hereditary AND Pheochromocytoma." Conclusion. These tumors can be part of a myriad hereditary conditions that are not yet fully understood. Nevertheless, important systemic symptoms and even fatal outcomes can occur. Knowledge of these hereditary conditions can ensure a more efficient detection, treatment, and even prevention of these neuroectodermal tumors, thus new tests and studies should be conducted. PMID:24903423

Santos, Pedro; Pimenta, Tiago; Taveira-Gomes, Antonio

2014-06-01

153

Auditory Neuropathy  

MedlinePLUS

... of organizations that can answer questions and provide printed or electronic information on auditory neuropathy. Please see the list of organizations at www.nidcd.nih.gov/directory . Use the following keywords ... a printed list of organizations, contact: NIDCD Information Clearinghouse 1 ...

154

Hereditary Hyperlipoproteinemias  

ERIC Educational Resources Information Center

Evidence and research indicate that the majority of cases of coronary artery disease represent familial disorders which are best explained by a polygenic hereditary predisposition interacting with emotional triggers such as diet and stress. Early identification is judged necessary. (Authors/JA)

Nora, James J.; And Others

1973-01-01

155

Hereditary hemochromatosis  

Microsoft Academic Search

Hereditary hemochromatosis is an autosomal recessive disorder, the gene for which occurs in approximately 10% of Americans, most of whom are unaffected heterozygotes. Approximately 51000 white Americans are homozygous and at risk of developing severe and potentially lethal hemochromatosis. The disorder affects numerous organ systems, but the most common symptoms are fatigue, palpitations, joint pains, and impotence; the most common

David L. Witte; William H. Crosby; Corwin Q. Edwards; Virgil F. Fairbanks; Frank A. Mitros

1996-01-01

156

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

157

Diabetic Neuropathies  

Microsoft Academic Search

Clinical trials of agents for the treatment of diabetic neuropathy have been confronted with a lack of agreement on appropriate\\u000a endpoints and have generated controversy on why ample demonstration of efficacy of an agent in animal studies has not been\\u000a readily translated into success in human clinical trials. There has been a failure to recognize that the relief of symptoms

Aaron I. Vinik

158

Suprascapular neuropathy.  

PubMed

Suprascapular neuropathy is an uncommon cause of shoulder pain and weakness and therefore may be overlooked as an etiologic factor. The suprascapular nerve is vulnerable to compression at the suprascapular notch as well as at the spinoglenoid notch. Other causes of suprascapular neuropathy include traction injury at the level of the transverse scapular ligament or the spinoglenoid ligament and direct trauma to the nerve. Sports involving overhead motion, such as tennis, swimming, and weight lifting, may result in traction injury to the suprascapular nerve, leading to dysfunction. The diagnosis of suprascapular neuropathy is based on clinical findings and abnormal electrodiagnostic test results, after the exclusion of other causes of shoulder pain and weakness. Magnetic resonance imaging may provide an anatomic demonstration of nerve entrapment and muscle atrophy. With this modality, ganglion cysts are recognized with increasing frequency as a source of external compression of the suprascapular nerve. Without evidence of a discrete lesion compressing the nerve, nonoperative treatment should include physical therapy and avoidance of precipitating activities. When nonoperative treatment fails to alleviate symptoms or when a discrete lesion such as a ganglion cyst is present, surgical decompression is warranted. Decompression gives reliable pain relief, but recovery of shoulder function and restoration of atrophied muscle tissue may be incomplete. PMID:11497489

Romeo, A A; Rotenberg, D D; Bach, B R

1999-01-01

159

Recombination hot spot in 3.2-kb region of the Charcot-Marie Tooth type 1A repeat sequences: New tools for molecular diagnosis of hereditary neuropathy with liability to pressure palsies and of Charcot-Marie-Tooth type 1A  

SciTech Connect

Charcot-Marie-Tooth type 1A (CMT1A) disease and hereditary neuropathy with liability to pressure palsies (HNPP) are autosomal dominant neuropathies, associated, respectively, with duplications and deletions of the same 1.5-Mb region on 17p11.2-p12. These two rearrangements are the reciprocal products of an unequal meiotic crossover between the two chromosome 17 homologues, caused by the misalignment of the CMT1A repeat sequences (CMT1A-REPs), the homologous sequences flanking the 1.5-Mb CMT1A/HNPP monomer unit. In order to map recombination breakpoints within the CMT1A-REPs, a 12.9-kb restriction map was constructed from cloned EcoRI fragments of the proximal and distal CMT1A-REPs. Only 3 of the 17 tested restriction sites were present in the proximal CMT1A-REP but absent in the distal CMT1A-REP, indicating a high degree of homology between these sequences. The rearrangements were mapped in four regions of the CMT1A-REPs by analysis of 76 CMT1A index cases and 38 HNPP patients, who were unrelated. A hot spot of crossover breakpoints located in a 3.2-kb region accounted for three-quarters of the rearrangements, detected after EcoRI/SacI digestion, by the presence of 3.2-kb and 7.8-kb junction fragments in CMT1A and HNPP patients, respectively. These junction fragments, which can be detected on classical Southern blots, permit molecular diagnosis. Other rearrangements can also be detected by gene dosage on the same Southern blots. 25 refs., 4 figs., 2 tabs.

Lopes, J.; LeGuern, E.; Gouider, R.; Tardieu, S.; Abbas, N. [Hopital de la Salpetriere, Paris (France)] [and others

1996-06-01

160

Suprascapular neuropathy.  

PubMed

Suprascapular neuropathy is a relatively uncommon but significant cause of shoulder pain and dysfunction. The suprascapular nerve follows a tortuous course from the neck to the posterior shoulder. There are several potential causes of nerve entrapment along this path, particularly at the vulnerable suprascapular and spinoglenoid notches, where nerve excursion is limited by bony and ligamentous constraints. Additional extrinsic compression may be caused by glenohumeral joint-related ganglion cysts or soft-tissue masses. Traction neuropathy may occur following excessive nerve excursion during overhead sports or as a result of massive, retracted rotator cuff tears in older patients. Diagnosis is based on a careful history, physical examination, focused imaging, and electrodiagnostic studies. In the absence of a clear structural compression or overtensioning of the nerve, treatment initially should be nonsurgical, with activity modification and physical therapy. Discrete nerve compression or failure of nonsurgical measures warrants early surgical intervention. Arthroscopic alternatives to the traditional open suprascapular and/or spinoglenoid notch decompressions have the benefit of simultaneously diagnosing and addressing intra-articular and/or subacromial pathology while minimizing morbidity. In most patients, both open and arthroscopic approaches provide reliable pain relief and improvements in function; return of strength and muscle bulk is less predictable. PMID:19880677

Piasecki, Dana P; Romeo, Anthony A; Bach, Bernard R; Nicholson, Gregory P

2009-11-01

161

Idiopathic Small Fiber Neuropathy: Phenotype, Etiologies, and the Search for Fabry Disease  

PubMed Central

Background and Purpose The etiology of small fiber neuropathy (SFN) often remains unclear. Since SFN may be the only symptom of late-onset Fabry disease, it may be underdiagnosed in patients with idiopathic polyneuropathy. We aimed to uncover the etiological causes of seemingly idiopathic SFN by applying a focused investigatory procedure, to describe the clinical phenotype of true idiopathic SFN, and to elucidate the possible prevalence of late-onset Fabry disease in these patients. Methods Forty-seven adults younger than 60 years with seemingly idiopathic pure or predominantly small fiber sensory neuropathy underwent a standardized focused etiological and clinical investigation. The patients deemed to have true idiopathic SFN underwent genetic analysis of the alpha-galactosidase A gene (GLA) that encodes the enzyme alpha-galactosidase A (Fabry disease). Results The following etiologies were identified in 12 patients: impaired glucose tolerance (58.3%), diabetes mellitus (16.6%), alcohol abuse (8.3%), mitochondrial disease (8.3%), and hereditary neuropathy (8.3%). Genetic alterations of unknown clinical significance in GLA were detected in 6 of the 29 patients with true idiopathic SFN, but this rate did not differ significantly from that in healthy controls (n=203). None of the patients with genetic alterations in GLA had significant biochemical abnormalities simultaneously in blood, urine, and skin tissue. Conclusions A focused investigation may aid in uncovering further etiological factors in patients with seemingly idiopathic SFN, such as impaired glucose tolerance. However, idiopathic SFN in young to middle-aged Swedish patients does not seem to be due to late-onset Fabry disease. PMID:24829596

Kostulas, Konstantinos; Vrethem, Magnus; Rolfs, Arndt; Press, Rayomand

2014-01-01

162

Persisting nutritional neuropathy amongst former war prisoners.  

PubMed Central

Of 898 former Far East prisoners of war, assessed between 1968 and 1981, 49 (5.5%) had evidence of persisting symptomatic neurological disease dating back to their periods of malnutrition in captivity. The commonest syndromes were peripheral neuropathy (often of "burning foot" type), optic atrophy, and sensori-neural deafness. Though nutritional neuropathies disappeared soon after release in most ex-Far East prisoners of war, in some they have persisted up to 36 years since exposure to the nutritional insult. PMID:6292369

Gill, G V; Bell, D R

1982-01-01

163

The spectrum of immune-mediated autonomic neuropathies: insights from the clinicopathological features.  

PubMed

Although autonomic neuropathy may occur as a secondary consequence of various diseases, other patients without any obvious underlying diseases show profound autonomic dysfunctions from the early phase of the disease. These idiopathic or primary cases are divided into pure autonomic neuropathy, autonomic neuropathy with sensory impairment, and autonomic neuropathy with sensory and motor impairment based on the concomitance or absence of sensory or motor dysfunctions. The discovery of the antiganglionic acetylcholine receptor antibody suggested the involvement of immune mechanisms in idiopathic cases, especially in those cases with pure autonomic neuropathy. The ability to test for the presence of this antibody has significantly expanded the concept of autonomic neuropathy to include cases with a chronic progressive course that mimics pure autonomic failure. Recent work based on the antiganglionic acetylcholine receptor antibody has established autoimmune autonomic ganglionopathy as an isolated nosological entity. Other forms of primary autonomic neuropathies include acute autonomic and sensory neuropathy and acute autonomic sensory and motor neuropathy, although the nosological relationship of the latter to Guillain-Barré syndrome should be discussed. Although the possibility of infectious, metabolic or toxic aetiologies should be carefully excluded in these forms of autonomic neuropathy, the monophasic clinical course and the presence of antecedent infections suggest the involvement of immune mechanisms similar to Guillain-Barré syndrome. Neuronopathy in the autonomic ganglia is considered to be a common pathology in these autonomic neuropathies. In addition, clinically significant autonomic neuropathy may be associated with pre-existing immunological diseases such as paraneoplastic syndrome and Sjögren's syndrome. An overlap with autoimmune autonomic ganglionopathy has been suggested in these settings. PMID:22906617

Koike, Haruki; Watanabe, Hirohisa; Sobue, Gen

2013-01-01

164

Pathogenesis and Treatment of Immune-Mediated Neuropathies  

PubMed Central

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.; zu Horste, Gerd Meyer; Kieseier, Bernd C.

2009-01-01

165

Comparison of the complete mtDNA genome sequences of human cell lines--HL-60 and GM10742A--from individuals with pro-myelocytic leukemia and leber hereditary optic neuropathy, respectively, and the inclusion of HL-60 in the NIST human mitochondrial DNA standard reference material--SRM 2392-I.  

PubMed

Forensic and clinical laboratories benefit from DNA standard reference materials (SRMs) that provide the quality control and assurance that their results from sequencing unknown samples are correct. Therefore, the mitochondrial DNA (mtDNA) genome of HL-60, a promyelocytic leukemia cell line, has been completely sequenced by four laboratories and will be available to the forensic and medical communities in the spring of 2003; it will be called National Institute of Standards and Technology (NIST) SRM 2392-I. NIST human mtDNA SRM 2392 will continue to be available and includes the DNA from two apparently healthy individuals. Both SRM 2392 and 2392-I contain all the information (e.g. the sequences of 58 unique primer sets) needed to use these SRMs as positive controls for the amplification and sequencing any DNA. Compared to the templates in SRM 2392, the HL-60 mtDNA in SRM 2392-I has two tRNA differences and more polymorphisms resulting in amino acid changes. Four of these HL-60 mtDNA polymorphisms have been associated with Leber Hereditary Optic Neuropathy (LHON), one as an intermediate mutation and three as secondary mutations. The mtDNA from a cell line (GM10742A) from an individual with LHON was also completely sequenced for comparison and contained some of the same LHON mutations. The combination of these particular LHON associated mutations is also found in phylogenetic haplogroup J and its subset, J2, and may only be indicative that HL-60 belongs to haplogroup J, one of nine haplogroups that characterize Caucasian individuals of European descent or may mean that haplogroup J is more prone to LHON. Both these mtDNA SRMs will provide enhanced quality control in forensic identification, medical diagnosis, and single nucleotide polymorphism detection. PMID:16120335

Levin, Barbara C; Holland, Koren A; Hancock, Diane K; Coble, Michael; Parsons, Thomas J; Kienker, Laura J; Williams, Diana W; Jones, Marypat; Richie, Kristy L

2003-06-01

166

Diabetic radiculoplexus neuropathies.  

PubMed

Diabetic radiculoplexus neuropathies (DRPN) are neuropathies clinically and pathologically distinct from the neuropathy typically associated with diabetes (DPN). DRPN are usually subacute in onset, painful, and often demonstrate a monophasic course with incomplete recovery. Pathologically, these neuropathies are due to ischemic injury from altered immunity and often have features suggestive or diagnostic of microvasculitis. Unlike DPN, immune therapy may be helpful in treatment of these conditions given their pathological substrate and therefore are important to identify early and distinguish from other neuropathies that occur in patient with diabetes. PMID:25410213

Laughlin, Ruple S; Dyck, P James B

2014-01-01

167

Peripheral neuropathy associated with primary Sjögren's syndrome.  

PubMed Central

Clinical and electrophysiological signs of peripheral neuropathy were found in 10 of 46 patients (21.7%) with primary Sjögren's syndrome, symmetric polyneuropathy in seven (mainly sensory in five, mainly autonomic in two), sensory neuronopathy in two patients, and mononeuropathy multiplex in one patient. Peripheral neuropathy was the presenting manifestation in five patients (10.9%). Onset of the disease after 50 years was significantly more common in the polyneuropathy group (six of seven) than in non-neuropathic patients with primary Sjögren's syndrome (14 of 36; p = 0.034). No other difference in clinical or laboratory variables between neuropathic and non-neuropathic patients with primary Sjogren's syndrome was found. Neurophysiological study showed variable findings predominantly suggesting an axonopathy. Nerve biopsy showed moderate remyelination and regeneration in four patients, and fibre loss, mainly of large size, in three. Necrotising vasculitis was not seen but alterations of the endoneurial microvessels were prominent. PMID:8057125

Gemignani, F; Marbini, A; Pavesi, G; Di Vittorio, S; Manganelli, P; Cenacchi, G; Mancia, D

1994-01-01

168

Motor neuropathy due to docetaxel and paclitaxel.  

PubMed

Paclitaxel and docetaxel are novel chemotherapeutic agents that promote the polymerization and inhibit the depolymerization of microtubules. Sensory neuropathy is common with these agents, particularly paclitaxel. We evaluated 64 patients treated with these drugs; 54 were followed prospectively. Eleven (17%, including six of the 54 prospectively followed patients) developed muscle weakness that was predominantly proximal. The weakness was idiosyncratic, occurring at any stage of treatment, had a variable course, and was reversible upon cessation of drug. All patients developed symptoms or signs of taxane-induced sensory neuropathy. Weakness was likely neuropathic in origin; electrodiagnostic studies suggested a distal axonopathy in some patients and proximal denervation (anterior horn cell or nerve root) in other. PMID:8710063

Freilich, R J; Balmaceda, C; Seidman, A D; Rubin, M; DeAngelis, L M

1996-07-01

169

Is Pancreatic Cancer Hereditary?  

MedlinePLUS

... Board Patient Education / Basics of Pancreatic Cancer Is pancreatic cancer hereditary? Cancer of the pancreas is a genetic ... found in cigarette smoke. The genetics of hereditary pancreatic cancer is a focus of research at Johns Hopkins. ...

170

The variable clinical manifestations of ulnar neuropathies at the elbow.  

PubMed Central

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

Stewart, J D

1987-01-01

171

Peripheral neuropathies in Sjögren's syndrome: a critical update on clinical features and pathogenetic mechanisms.  

PubMed

Sjögren's syndrome is a systemic autoimmune disease that, apart from exocrine glands, may affect every organ or system. Involvement of different sections of the peripheral nervous system results in a wide spectrum of neuropathic manifestations. Based on distinct clinical, electrophysiological and histological criteria, the types of neuropathies seen in Sjögren's syndrome include: a) pure sensory which presents with distal symmetric sensory loss due to axonal degeneration of sensory fibers; sensory ataxia due to loss of proprioceptive large fibers (ganglionopathy); or with painful dysethesias (small fiber sensory neuropathy) due to degeneration of cutaneous axons. The latter appears to be the most common neuropathy in Sjögren's syndrome and requires skin biopsy for diagnosis to document loss or reduction of nerve fiber density; b) sensorimotor polyneuropathy affecting sensory and motor axons, often associated with severe systemic or pro-lymhomatous manifestations, such as palpable purpura and cryoglobulinemia, and c) rare types that include autoimmune demyelinating neuropathy, mononeuropathy, mononeuropathy multiplex and autonomic neuropathy. In this review, the frequency, prevalence and diagnostic criteria for each neuropathy subset are discussed and possible pathogenetic mechanisms are outlined. PMID:22318209

Pavlakis, P P; Alexopoulos, H; Kosmidis, M L; Mamali, I; Moutsopoulos, H M; Tzioufas, A G; Dalakas, M C

2012-08-01

172

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. PMID:23642725

Saporta, Mario A.; Shy, Michael E.

2013-01-01

173

Bilateral Optic Neuropathy with Bilateral Putaminal Lesions: A Case Report.  

PubMed

Bilateral optic neuropathy with bilateral putaminal lesions may be caused by methanol or cyanide poisoning or mitochondrial disorders including Leber hereditary optic neuropathy and Leigh syndrome. We report the case of a 34-year-old Japanese man who developed bilateral visual loss 5 days after the development of gastrointestinal symptoms. Magnetic resonance imaging of the brain on admission revealed high-intensity signal areas in the bilateral putamina on diffusion-weighted and T2-weighted images as well as a high-intensity signal area in the left middle cerebellar peduncle that had been identified 3 years previously. We diagnosed bilateral optic neuropathy with bilateral putaminal lesions caused by preceding infection-triggered demyelination. We administered methylprednisolone, but his vision did not recover. PMID:25052423

Togawa, Jumpei; Ohi, Takekazu

2014-07-23

174

Etiologic Spectrum of Biopsy-Proven Peripheral Neuropathies in Childhood from a Resource-Poor Setting.  

PubMed

There are only a few studies describing the etiologic spectrum of biopsy-proven peripheral neuropathies in children. This study reviewed the clinical, electrophysiological, and pathologic profile of 239 children (?18 years of age) who have undergone nerve biopsy in a tertiary care centre for neurologic disorders and analyzed the etiologic spectrum and utility of nerve biopsy. The clinical profile, neuropathologic findings, and other investigations were combined to infer the final diagnosis. Neuropathy was detected in 199 biopsies; axonal pathology in 43%; demyelination in 41%; mixed pattern in 8%; and nonspecific findings in 8%. The major diagnostic categories included hereditary neuropathies (48%), heredodegenerative and metabolic disorders (27%), and inflammatory neuropathies (12%). Nerve biopsy proved most helpful in diagnosis of demyelinating and inflammatory neuropathies, reiterating its usefulness in specific situations. PMID:25038122

Krishnan, Pramod; Mahadevan, Anita; Bindu, Parayil Sankaran; Chickabasaviah, Yasha T; Taly, Arun B

2014-07-17

175

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

176

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. PMID:3003254

Hallett, M; Tandon, D; Berardelli, A

1985-01-01

177

Evaluation of neuropathy during intensive vincristine chemotherapy for non-Hodgkin's lymphoma and Acute Lymphoblastic Leukemia  

PubMed Central

Back ground: Vincristine (VCR), is a chemotherapy drug, useful in the treatment of leukemia, lymphoma and solid tumor and it is a potent neurotoxin and sensory neuropathy drug which a common behavioral toxicity of this drug. Neuropathy is common squeal of intensive chemotherapy protocols that contain vincristine and corticosteroids. Materials and Methods: This study was a retrospective and descriptive study of neuropathy during in chemotherapy program with vincristine for patients with non-Hodgkin's lymphoma (NHL) and Acute Lymphoblastic Leukemia (ALL). Data was analyzed by spss Version16 software. Results: From total of 51 cases, 23 patients had vincristine neuropathy (45%). Patients with visceral neuropathy have shown ileus, constipation in 13 patients (25%), occasionally severe diarrhea 11 (21%), mild diarrhea 7 (13.7%) and transient diarrhea in 16 patients (31%). Motor neuropathy were found in one patient with Bell, s palsy (1.9%) and one patient with Hoarseness. 12 patients (23.5%) had some type of complication together with sensory peripheral neuropathy. Conclusion: Almost half of patients with vincristin chemotherapy had neuropathy and the mean age of patients with neuropathy was 12.3 years. PMID:24575286

Dorchin, M; Masoumi Dehshiri, R; Soleiman, S; Manashi, M

2013-01-01

178

Nonsyndromic Hereditary Hearing Loss  

Microsoft Academic Search

The etiology of hereditary hearing loss is extraordinarily complex. More than 400 genetic syndromes are associated with hearing loss and more than 140 genetic loci associated with nonsyndromic hearing loss have been mapped, with more than 60 genes identified to date. Hereditary hearing loss can be inherited as an autosomal dominant, autosomal recessive, X-linked or mitochondrial (maternally inherited) condition. The

Raye L. Alford

2011-01-01

179

Genetics Home Reference: Distal hereditary motor neuropathy, type V  

MedlinePLUS

... the hand brought on by exposure to cold temperatures are often the initial symptom. The characteristic features ... of glycyl-tRNA synthetase. A reduction in the activity of this enzyme may impair transmission of nerve impulses. As a ...

180

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

PubMed

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

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

2013-12-01

181

Multifocal Motor Neuropathy  

MedlinePLUS

... Funding Information Research Programs Training & Career Awards Enhancing Diversity Find People About NINDS NINDS Multifocal Motor Neuropathy ... News From NINDS | Find People | Training | Research | Enhancing Diversity Careers@NINDS | FOIA | Accessibility Policy | Contact Us | Privacy ...

182

Nuclear matrix proteins and hereditary diseases.  

PubMed

The review summarizes literature data on alterations of structure or expression of different nuclear matrix proteins in hereditary syndromes. From the point of view of involvement of nuclear matrix proteins in etiology and pathogenesis of the disease hereditary pathologies can be classified in pathologies with pathogenesis associated with defects of nuclear matrix proteins and pathologies associated to changes of the nuclear matrix protein spectrum. The first group includes laminopathies, hereditary diseases with abnormal nuclear-matrix associated proteins and triplet extension diseases associated with accumulation of abnormal proteins in the nuclear matrix. Laminopathies are hereditary diseases coupled to structural defects of the nuclear lamina. These diseases include Emery-Dreifuss muscular dystrophy, limb girdle muscular dystrophy, dilated cardiomyopathy (DCM) with conduction system disease, familial partial lipodystrophy (FPLD), autosomal recessive axonal neuropathy (Charcot-Marie-Tooth disorder type 2, CMT2), mandibuloacral dysplasia (MAD), Hutchison Gilford Progeria syndrome (HGS), Greenberg Skeletal Dysplasia, and Pelger-Huet anomaly (PHA). Most of them are due to mutations in the lamin A/C gene, one - to mutations in emerin gene, some are associated with mutations in Lamin B receptor gene. In Werner's, Bloom's, Cockayne's syndromes, Fanconi anemia, multiple carboxylase deficiency mutations in nuclear matrix protein or enzyme gene lead to deficient DNA repair, abnormal regulation of cell growth and differentiation or other specific metabolic functions. Proteins with a long polyglutamic tract synthesized in the cells of patients with dentato-rubral and pallido-luysian atrophy, myotonic dystrophy and Huntington disease interfere with transcription on the nuclear matrix. Down's syndrome is a representative of the group of diseases with altered nuclear matrix protein spectrum. PMID:15865282

Sjakste, N; Sjakste, T

2005-03-01

183

Neuropathological alterations in diabetic truncal neuropathy: evaluation by skin biopsy  

PubMed Central

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

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

1998-01-01

184

Peripheral neuropathy and cancer  

Microsoft Academic Search

Peripheral neuropathy has a major impact on quality of life and may limit the amount of treatment patients can receive. Neurotoxic\\u000a agents are used increasingly in oncologic practice, yet clinicians are often unaware of the protean manifestations of neuropathy\\u000a and find its management troubling. Recent knowledge about the mechanisms of neuropathic disease and new treatments may help\\u000a to minimize the

Arthur D. Forman

2004-01-01

185

Asymptomatic Vasculitic Neuropathy.  

PubMed

Objectives: We did a retrospective analysis of the clinical, pathological, and electrophysiological features of 21 cases of asymptomatic vasculitic neuropathy (AsVN). Methods: Among 270 patients with biopsy proven vasculitic neuropathy, we identified 21 (7.8%) who had asymptomatic neuropathy. Results: Of the 21 patients with AsVN, 11 were women and 10 were men. The mean age was 62.5 years. Referring physicians suspected systemic vasculitis on the basis of clinical and laboratory features, but none of the patients had neuropathy by examination. Screening nerve conduction studies identified neuropathy in all, leading us to perform a sural nerve, biopsy which confirmed the diagnosis of vasculitis. Twelve patients had active (Type I), 6 had inactive (Type II), and 3 had probable (Type III) vasculitis. Vasculitis was primary in 10 patients and secondary in 11. Conclusions: Nerve conduction study is an important tool for identifying AsVN, a sub-type of vasculitic neuropathy. © 2014 Wiley Periodicals, Inc. PMID:25354330

Kurt, Semiha; Alsharabati, Mohammad; Lu, Liang; Claussen, Gwendolyn C; Oh, Shin J

2014-10-29

186

Painful diabetic neuropathy.  

PubMed

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

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

2014-01-01

187

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. PMID:24864250

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

188

Mitotoxicity and bortezomib-induced chronic painful peripheral neuropathy.  

PubMed

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

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

2012-12-01

189

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. PMID:23818897

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

2013-01-01

190

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

191

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

192

Genome-Wide Screen Identifies Drug-Induced Regulation of the Gene Giant Axonal Neuropathy (Gan) in a Mouse Model of Antiretroviral-Induced Painful Peripheral Neuropathy  

PubMed Central

Painful peripheral neuropathy is a debilitating complication of the treatment of HIV with nucleoside reverse transcriptase inhibitors (NRTIs). Patients are living longer with these drugs; however many develop excruciating, unremitting, and often treatment-limiting neuropathy that is resistant to conventional pain management therapies. Improving patient comfort and quality of life is paramount and depends on a clearer understanding of this devastating side effect. The mechanisms underlying the development of NRTI-induced neuropathy, however, remain unclear. Using a mouse model of NRTI-induced neuropathy, the authors conducted an unbiased whole-genome microarray screen to identify molecular targets in the spinal dorsal horn, which is the location where integration of ascending sensory transmission and descending modulatory effects occur. Analysis of the microarray data identified a change in the gene giant axonal neuropathy 1 (Gan1). Mutation of this gene has been linked to the development of giant axonal neuropathy (GAN), a rare autosomal recessive condition characterized by a progressive sensorimotor neuropathy. Gan1 has not been previously linked to nerve pathologies in other populations. In this study, downregulation of the Gan1 gene and the gene protein product, gigaxonin, was validated via quantitative polymerase chain reaction ([qPCR] gene expression) and Western blot analyses (protein level). Our report is the first to suggest that Gan1 might be a novel molecular target in the development of NRTI-induced peripheral neuropathy with implications for new therapeutic approaches to preventing or reducing a significant side effect of HIV treatment. PMID:19398414

Dorsey, Susan G.; Leitch, Carmen C.; Renn, Cynthia L.; Lessans, Sherrie; Smith, Barbara A.; Wang, Xiao M.; Dionne, Raymond A.

2012-01-01

193

Genome-wide screen identifies drug-induced regulation of the gene giant axonal neuropathy (Gan) in a mouse model of antiretroviral-induced painful peripheral neuropathy.  

PubMed

Painful peripheral neuropathy is a debilitating complication of the treatment of HIV with nucleoside reverse transcriptase inhibitors (NRTIs). Patients are living longer with these drugs; however many develop excruciating, unremitting, and often treatment-limiting neuropathy that is resistant to conventional pain management therapies. Improving patient comfort and quality of life is paramount and depends on a clearer understanding of this devastating side effect. The mechanisms underlying the development of NRTI-induced neuropathy, however, remain unclear. Using a mouse model of NRTI-induced neuropathy, the authors conducted an unbiased whole-genome microarray screen to identify molecular targets in the spinal dorsal horn, which is the location where integration of ascending sensory transmission and descending modulatory effects occur. Analysis of the microarray data identified a change in the gene giant axonal neuropathy 1 (Gan1). Mutation of this gene has been linked to the development of giant axonal neuropathy (GAN), a rare autosomal recessive condition characterized by a progressive sensorimotor neuropathy. Gan1 has not been previously linked to nerve pathologies in other populations. In this study, downregulation of the Gan1 gene and the gene protein product, gigaxonin, was validated via quantitative polymerase chain reaction ([qPCR] gene expression) and Western blot analyses (protein level). Our report is the first to suggest that Gan1 might be a novel molecular target in the development of NRTI-induced peripheral neuropathy with implications for new therapeutic approaches to preventing or reducing a significant side effect of HIV treatment. PMID:19398414

Dorsey, Susan G; Leitch, Carmen C; Renn, Cynthia L; Lessans, Sherrie; Smith, Barbara A; Wang, Xiao M; Dionne, Raymond A

2009-07-01

194

[Entrapment neuropathies in sports medicine].  

PubMed

The more frequent entrapment neuropathies related to sport are described: thoracic outlet syndrome in aquatic athletes and pitchers, long thoracic neuropathy in tennis players, suprascapular neuropathy in volleyball and tennis players, ulnar nerve entrapment at the elbow in pitchers and at the wrist in cyclists, Morton's syndrome in runners and dancers. PMID:11475937

Wang, F C; Crielaard, J M

2001-05-01

195

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

PubMed Central

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

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

2013-01-01

196

Motor Branch Biopsy of the Pronator Teres Muscle in a Patient with Painful Forearm Neuropathy  

PubMed Central

Histological evaluation of a peripheral nerve is often the final diagnostic work-up for a neuropathy of unknown origin, and a distal sensory nerve is usually biopsied. Here, we report the case of a female patient with painful unilateral neuropathy in the upper arm. According to the histological evaluation of the pronator teres motor branch, vasculitis seemed to be the most probable cause of the condition, and steroid therapy improved the patients’ symptoms. A biopsy of the motor branch of the pronator teres muscle nerve may be considered a valuable diagnostic option in selected cases with neuropathy affecting the upper limb, when performed in cooperation with neurologists and orthopedic surgeons. PMID:25232332

Kinoshita, Tomomi; Fukushima, Kazuhiro; Abe, Ryu-ta; Ogawa, Yuka; Nakagawa, Michitaka; Katoh, Nagaaki; Yoshida, Takuhiro; Kato, Hiroyuki; Ikeda, Shu-ichi

2014-01-01

197

Infantile peripheral neuropathy, deafness, and proximal tubulopathy associated with a novel mutation of the RRM2B gene  

PubMed Central

Mitochondrial DNA depletion syndromes are a group of autosomal recessive hereditary disorders characterized by reduction of the amount of mitochondrial DNA in the affected tissue (muscle, liver, brain, or kidneys). We report a case of an infant with myopathy, deafness, peripheral neuropathy, nephrocalcinosis, proximal renal tubulopathy, moderate lactic acidosis, and a novel mutation of the RRM2B gene. PMID:24382854

Stojanovi?, Vesna; Mayr, Johannes A.; Sperl, Wolfgang; Bariši?, Nenad; Doronjski, Aleksandra; Milak, Gordana

2013-01-01

198

Gene Testing for Hereditary Ataxia  

MedlinePLUS

... FAQ NATIONAL ATAXIA FOUNDATION FREQUENTLY ASKED QUESTIONS ABOUT... Gene Testing for Hereditary Ataxia This fact sheet provides ... onset. For which of the hereditary ataxias is gene testing available? Discovery of specific ataxia genes makes ...

199

CaV3.2 T-type calcium channels in peripheral sensory neurons are important for mibefradil-induced reversal of hyperalgesia and allodynia in rats with painful diabetic neuropathy.  

PubMed

We recently showed that streptozotocin (STZ) injections in rats lead to the development of painful peripheral diabetic neuropathy (PDN) accompanied by enhancement of CaV3.2 T-type calcium currents (T-currents) and hyperexcitability in dorsal root ganglion (DRG) neurons. Here we used the classical peripherally acting T-channel blocker mibefradil to examine the role of CaV3.2 T-channels as pharmacological targets for treatment of painful PDN. When administered intraperitoneally (i.p.), at clinically relevant doses, mibefradil effectively alleviated heat, cold and mechanical hypersensitivities in STZ-treated diabetic rats in a dose-dependent manner. We also found that CaV3.2 antisense (AS)-treated diabetic rats exhibit a significant decrease in painful PDN compared with mismatch antisense (MIS)-treated diabetic rats. Co-treatment with mibefradil (9 mg/kg i.p.) resulted in reversal of heat, cold and mechanical hypersensitivity in MIS-treated but not in AS-treated diabetic rats, suggesting that mibefradil and CaV3.2 AS share the same cellular target. Using patch-clamp recordings from acutely dissociated DRG neurons, we demonstrated that mibefradil similarly blocked T-currents in diabetic and healthy rats in a voltage-dependent manner by stabilizing inactive states of T-channels. We conclude that antihyperalgesic and antiallodynic effects of mibefradil in PDN are at least partly mediated by inhibition of CaV3.2 channels in peripheral nociceptors. Hence, peripherally acting voltage-dependent T-channel blockers could be very useful in the treatment of painful symptoms of PDN. PMID:24705276

Obradovic, Aleksandar Lj; Hwang, Sung Mi; Scarpa, Joseph; Hong, Sung Jun; Todorovic, Slobodan M; Jevtovic-Todorovic, Vesna

2014-01-01

200

CaV3.2 T-Type Calcium Channels in Peripheral Sensory Neurons Are Important for Mibefradil-Induced Reversal of Hyperalgesia and Allodynia in Rats with Painful Diabetic Neuropathy  

PubMed Central

We recently showed that streptozotocin (STZ) injections in rats lead to the development of painful peripheral diabetic neuropathy (PDN) accompanied by enhancement of CaV3.2 T-type calcium currents (T-currents) and hyperexcitability in dorsal root ganglion (DRG) neurons. Here we used the classical peripherally acting T-channel blocker mibefradil to examine the role of CaV3.2 T-channels as pharmacological targets for treatment of painful PDN. When administered intraperitoneally (i.p.), at clinically relevant doses, mibefradil effectively alleviated heat, cold and mechanical hypersensitivities in STZ-treated diabetic rats in a dose-dependent manner. We also found that CaV3.2 antisense (AS)-treated diabetic rats exhibit a significant decrease in painful PDN compared with mismatch antisense (MIS)-treated diabetic rats. Co-treatment with mibefradil (9 mg/kg i.p.) resulted in reversal of heat, cold and mechanical hypersensitivity in MIS-treated but not in AS-treated diabetic rats, suggesting that mibefradil and CaV3.2 AS share the same cellular target. Using patch-clamp recordings from acutely dissociated DRG neurons, we demonstrated that mibefradil similarly blocked T-currents in diabetic and healthy rats in a voltage-dependent manner by stabilizing inactive states of T-channels. We conclude that antihyperalgesic and antiallodynic effects of mibefradil in PDN are at least partly mediated by inhibition of CaV3.2 channels in peripheral nociceptors. Hence, peripherally acting voltage-dependent T-channel blockers could be very useful in the treatment of painful symptoms of PDN. PMID:24705276

Obradovic, Aleksandar Lj.; Hwang, Sung Mi; Scarpa, Joseph; Hong, Sung Jun; Todorovic, Slobodan M.; Jevtovic-Todorovic, Vesna

2014-01-01

201

Measurement of somatic neuropathy for clinical practice and clinical trials  

Microsoft Academic Search

Distal sensory polyneuropathy is a common and unpleasant complication of diabetes mellitus. It is the main initiating factor\\u000a for foot ulceration. The increasing prevalence of diabetes has important associated health implications, both in terms of\\u000a morbidity and mortality, and results in the consumption of scarce medical resources. Identification of somatic neuropathy\\u000a in clinical practice is therefore important for targeted educational

Vern A. La Scott; Solomon Tesfaye

2001-01-01

202

Periaxin mutations cause a broad spectrum of demyelinating neuropathies  

Microsoft Academic Search

Previous studies have demonstrated that apparent loss-of-function mutations in the periaxin gene cause autosomal re- cessive Dejerine-Sottas neuropathy or severe demyelinating Charcot-Marie-Tooth disease. In this report, we extend the associated phenotypes with the identification of two additional families with novel periaxin gene mutations (C715X and R82fsX96) and provide detailed neuropathology. Each patient had marked sensory involvement; two siblings with a

Hiroshi Takashima; Cornelius F. Boerkoel; Peter De Jonghe; Chantal Ceuterick; Jean-Jacques Martin; Thomas Voit; Anna Williams; Peter J. Brophy; Vincent Timmerman; James R. Lupski

2002-01-01

203

Hereditary elliptocytic anaemia  

PubMed Central

A sibship with four cases of hereditary elliptocytic anaemia is described. The condition in this family may have arisen as a mutation in the mother of the sibship; affected members were unable to taste phenylthiocarbamide while normal members were tasters. Experiments with 32P-orthophosphate in vitro did not show any evidence of biochemical upset as found in hereditary spherocytosis; thus a combination of congenital spherocytosis and elliptocytosis cannot be supported as the cause of the haemolytic state. Clinical evidence of haemolytic disease was accompanied by a tendency to excessive lysis in vitro. Infection may play a part in the precipitation of anaemic crises in this as in other hereditary haemolytic anaemias. Images PMID:13883803

Davidson, R. J. L.; Strauss, W. T.

1961-01-01

204

[Hereditary coproporphyria. 7 cases].  

PubMed

Hereditary coprophyria, known since 1955, is a rare variety of hepatic porphyria. The clinical picture is similar to that of acute intermittent porphyria with certain minor differences; neurological manifestations being rarer in particular. The essential biological characteristic is the massive excretion, in the urine and faeces, of coproporphyrins whilst the excretion of porphobilinogen and delta-amino-laevulinic acid is only slightly increased. As in acute intermittent porphyria, certain medications have an adverse effect, especially the barbiturates. The exact nature of the biochemical lesion is not understood but its hereditary nature has been demonstrated. 25 families have been reported in the literature up to the present time. The authors report two cases of hereditary coproporphyria with peripheral paralysis and respiratory failure, the outcome being fatal in one case. Study of the families led to the discovery of 3 other cases in the second family and 2 latent forms in the first. PMID:1196884

Jaeger, A; Tempe, J D; Geisler, F; Nordmann, Y; Mantz, J M

1975-11-15

205

Peripheral neuropathy induced by combination chemotherapy of docetaxel and cisplatin.  

PubMed Central

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

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

1997-01-01

206

Hereditary Spastic Paraplegia  

MedlinePLUS

... help maintain the function of axons in the spinal cord. Understanding how mutations of these genes cause HSP should lead to ways to prevent, treat, and cure HSP. NIH Patient Recruitment for Hereditary Spastic Paraplegia Clinical Trials At NIH Clinical Center Throughout the U.S. and ...

207

Hereditary Hearing Loss.  

ERIC Educational Resources Information Center

This article discusses inheritance patterns in hearing loss, epidemiology, clues to genetic causes, locating genes that cause hereditary disorders, genes related to hearing loss disorders in individuals with Usher syndrome, Waardenburg syndrome, Treacher-Collins syndrome, Branchio-oto-renal and Pendred syndromes, and the significance of finding…

Tran, LenhAnh P.; Grundfast, Kenneth M.

1997-01-01

208

Hereditary coproporphyria and epilepsy  

Microsoft Academic Search

A 9-year-old boy with mental deterioration and epilepsy suffered an acute attack of hereditary coproporphyria associated with worsening of seizure control. Leucocyte coproporphyrinogen oxidase activity was undetectable in the patient during this attack, and was reduced in his mother, a latent case. The complex relationship between porphyria, epilepsy, and anticonvulsant drugs is discussed.

A B Houston; M J Brodie; M R Moore; G G Thompson; J B Stephenson

1977-01-01

209

Human hereditary hepatic porphyrias  

Microsoft Academic Search

The human hereditary hepatic porphyrias are diseases due to marked deficiencies of enzymes in the heme biosynthetic pathway. Porphyrias can be classified as either hepatic or erythroid, depending on the major production site of porphyrins or their precursors. The pathogenesis of inherited hepatic porphyrias has now been defined at the molecular level. Some gene carriers are vulnerable to a range

Yves Nordmann; Hervé Puy

2002-01-01

210

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 PMID:6273507

Satchell, P M; McLeod, J G

1981-01-01

211

Emerging toxic neuropathies and myopathies.  

PubMed

Psychiatrists in practice encounter patients abusing alcohol and street drugs such as cocaine that can lead to toxic myopathies or neuropathies. Psychiatrists also encounter patients with neuropsychiatric systemic lupus erythematosus who are treated with myotoxic medications (e.g., Hydroxychloroquine). Thus a well-rounded knowledge of toxic myopathies and neuropathies is extremely useful. The differential diagnosis of toxic myopathies and neuropathies is expanding rapidly and practical knowledge of these entities is becoming important. PMID:23688688

Kushlaf, Hani A

2013-06-01

212

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

213

[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

214

Carcinoma associated paraneoplastic peripheral neuropathies in patients with and without anti-onconeural antibodies  

PubMed Central

OBJECTIVE—When to suspect a paraneoplastic disorder is a puzzling problem that has not recently been studied in a large series of patients referred for peripheral neuropathy.?METHODS—From 422 consecutive patients with peripheral neuropathy, 26 were analysed who concomitantly had carcinoma but no tumorous infiltration, drug toxicity, or cachexia. Their clinical, pathological, and electrophysiological data were analysed according to the presence of anti-onconeural antibodies, the latency between presentation and cancer diagnosis, and the incidence of carcinoma in the corresponding types of neuropathy of the population of 422patients.?RESULTS—Seven patients (group I) had anti-onconeural antibodies (six anti-Hu, one anti-CV2) and 19 did not (groups IIA and B). In group I, subacute sensory neuropathy (SSN) was the most frequent but other neuropathies including demyelinating neuropathies were present. Patients in group II A had a short latency (mean 7.88months), and a rapidly and usually severe neuropathy which corresponded in 11/14 to an established inflammatory disorder including neuropathy with encephalomyelitis, mononeuritis multiplex, and acute or chronic inflammatory demyelinating polyneuropathy (CIDP). Patients in group IIB had a long latency (mean 8.4 years) and a very chronic disorder corresponding in four of five to an axonal non-inflammatory polyneuropathy. In this population, the incidence of carcinoma occurring with a short latency was 47% in sensory neuronopathy, 1.7% in Guillain-Barré syndrome, 10% in mononeuritis multiplex and CIDP, and 4.5% in axonal polyneuropathy.?CONCLUSIONS—Paraneoplastic neuropathies associated with carcinoma are heterogeneous disorders. Neuropathies occurring with a long latency with tumours probably resulted from a coincidental association. Neuropathies which occurred within a few years of the tumour evolved rapidly and corresponded mostly to inflammatory disorders. As dysimmune neuropathies are probably paraneoplastic in a limited number of cases, patients with these disorders should probably not be investigated systematically for carcinoma in the absence of anti-onconeural antibodies, except when the neuropathy is associated with encephalomyelitis and probably with vasculitis. Questions remain concerning CIDP.?? PMID:10369814

Antoine, J.; Mosnier, J.; Absi, L.; Convers, P.; Honnorat, J.; Michel, D.

1999-01-01

215

Optic neuropathy caused by Propionibacterium acnes pachymeningitis.  

PubMed

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

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

2014-09-01

216

Effect of High-Fat Diet on Peripheral Neuropathy in C57BL/6 Mice  

PubMed Central

Objective. Dyslipidemia may contribute to the development of peripheral neuropathy, even in prediabetics; however, few studies have evaluated vascular dysfunction and oxidative stress in patients with peripheral neuropathy. Methods. Using high-fat diet- (HFD-) induced prediabetic C57BL/6 mice, we assessed motor and sensory nerve conduction velocity (NCV) using a BIOPAC System and thermal algesia with a Plantar Test (Hargreaves' method) Analgesia Meter. Intraepidermal nerve fiber density and mean dendrite length were tested following standard protocols. Vascular endothelial growth factor-A (VEGF-A) and 12/15-lipoxygenase (12/15-LOX) were evaluated by immunohistochemistry and Western blot, respectively. Results. HFD-fed mice showed deficits in motor and sensory NCV, thermal hyperalgesia, reduced mean dendrite length, and VEGF-A expression in the plantar skin and increased 12/15-LOX in the sciatic nerve (P < 0.05 compared with controls). Conclusion. HFD may cause large myelinated nerve and small sensory nerve fiber damage, thus leading to neuropathy. The mean dendrite length may be a more sensitive marker for early detection of peripheral neuropathy. Reduced blood supply to the nerves and increased oxidative stress may contribute to the development and severity of peripheral neuropathy. PMID:25404943

Xu, Lingling; Tang, Dou; Guan, Meiping; Xie, Cuihua; Xue, Yaoming

2014-01-01

217

The pattern and diagnostic criteria of sensory neuronopathy: a case–control study  

PubMed Central

Acquired sensory neuronopathies encompass a group of paraneoplastic, dysimmune, toxic or idiopathic disorders characterized by degeneration of peripheral sensory neurons in dorsal root ganglia. As dorsal root ganglia cannot easily be explored, the clinical diagnosis of these disorders may be difficult. The question as to whether there exists a common clinical pattern of sensory neuronopathies, allowing the establishment of validated and easy-to-use diagnostic criteria, has not yet been addressed. In this study, logistic regression was used to construct diagnostic criteria on a retrospective study population of 78 patients with sensory neuronopathies and 56 with other sensory neuropathies. For this, sensory neuronopathy was provisionally considered as unambiguous in 44 patients with paraneoplastic disorder or cisplatin treatment and likely in 34 with a dysimmune or idiopathic setting who may theoretically have another form of neuropathy. To test the homogeneity of the sensory neuronopathy population, likely candidates were compared with unambiguous cases and then the whole population was compared with the other sensory neuropathies population. Criteria accuracy was checked on 37 prospective patients referred for diagnosis of sensory neuropathy. In the study population, sensory neuronopathy showed a common clinical and electrophysiological pattern that was independent of the underlying cause, including unusual forms with only patchy sensory loss, mild electrical motor nerve abnormalities and predominant small fibre or isolated lower limb involvement. Logistic regression allowed the construction of a set of criteria that gave fair results with the following combination: ataxia in the lower or upper limbs + asymmetrical distribution + sensory loss not restricted to the lower limbs + at least one sensory action potential absent or three sensory action potentials <30% of the lower limit of normal in the upper limbs + less than two nerves with abnormal motor nerve conduction study in the lower limbs. PMID:19506068

Camdessanché, Jean-Philippe; Jousserand, Guillemette; Ferraud, Karine; Vial, Christophe; Petiot, Philippe; Honnorat, Jérôme

2009-01-01

218

Hormonally exacerbated hereditary angioedema.  

PubMed

Hereditary angioedema is a rare disorder which is associated with an inherited deficiency of the inhibitor of the activated first component of complement. Genetic transmission occurs in an autosomal dominant manner. Affected patients are heterozygotes, and their deficiency is incomplete, many of them having up to 20% of the normal amount of the inhibitor. We describe two cases of C1 esterase inhibitor deficiency occurring in a mother and daughter in whom the symptoms appeared to be related to the menstrual cycle or the taking of the oral contraceptive pill. Although both features have been mentioned in the literature, to the best of our knowledge premenstrual exacerbations have not been documented previously. We examined the likely basis of hormonally exacerbated hereditary angioedema. PMID:1445091

Yip, J; Cunliffe, W J

1992-01-01

219

Human hereditary hepatic porphyrias.  

PubMed

The human hereditary hepatic porphyrias are diseases due to marked deficiencies of enzymes in the heme biosynthetic pathway. Porphyrias can be classified as either hepatic or erythroid, depending on the major production site of porphyrins or their precursors. The pathogenesis of inherited hepatic porphyrias has now been defined at the molecular level. Some gene carriers are vulnerable to a range of exogenous and endogenous factors, which may trigger neuropsychiatric and/or cutaneous symptoms. Early diagnosis is of prime importance since it makes way for counselling. In this article we present an overview of recent advances on hepatic porphyrias: 5-aminolevulinic acid dehydratase deficiency porphyria, acute intermittent porphyria (AIP), porphyria cutanea tarda (PCT), hereditary coproporphyria (HC), and variegate porphyria (VP). PMID:12367763

Nordmann, Yves; Puy, Hervé

2002-11-01

220

Non HFE related hereditary haemochromatosis.  

PubMed

Hereditary hemochromatosis (HH) is manifested as iron overload in different organs due to homozygosity of a single autosomal mutation. Two different mutations C282Y and H63D in the HFE gene have been associated with hereditary hemochromatosis cases. This disease is seen in northern european populations, but in India it is a rare disease. We report a young male with severe abnormalty of liver functions due to Non HFE related Hereditary Hemochromatosis. PMID:25327073

Sharma, S K; Mangudkar, Sangram; Rathod, Mehul; Verma, Amrita; Phanikumar, R L V; Garg, Subodh; Dhakne, Ajinkya; Barure, Ramdas

2014-03-01

221

Characterizing Neuropathies Associated With Monoclonal Gammopathy of Undetermined Significance (MGUS): A Framework Consistent With Classifying Injuries According to Fiber Size  

Microsoft Academic Search

Neuropathies associated with monoclonal gammopathy of undetermined significance (MGUS) occur frequently in the elderly. Data from 42 consecutive elderly patients with a MGUS-associated neuropathy—12 patients with IgM MGUS, 25 patients with IgG MGUS, 5 patients with IgA MGUS—were evaluated prospectively using quantifiable clinical criteria and quantitative sensory testing. Results consistent with preferential injury to large fibers were found in patients

Morris A. Fisher; John R. Wilson

2002-01-01

222

Genetics Home Reference: Hereditary hemorrhagic telangiectasia  

MedlinePLUS

... to hereditary hemorrhagic telangiectasia? Mutations in the ACVRL1 , ENG , and SMAD4 genes cause hereditary hemorrhagic telangiectasia. Hereditary ... 1 is caused by mutations in the gene ENG . Type 2 is caused by mutations in the ...

223

Sympathetic Blocks Provided Sustained Pain Relief in a Patient with Refractory Painful Diabetic Neuropathy  

PubMed Central

The sympathetic nervous system has been implicated in pain associated with painful diabetic neuropathy. However, therapeutic intervention targeted at the sympathetic nervous system has not been established. We thus tested the hypothesis that sympathetic nerve blocks significantly reduce pain in a patient with painful diabetic neuropathy who has failed multiple pharmacological treatments. The diagnosis of small fiber sensory neuropathy was based on clinical presentations and confirmed by skin biopsies. A series of 9 lumbar sympathetic blocks over a 26-month period provided sustained pain relief in his legs. Additional thoracic paravertebral blocks further provided control of the pain in the trunk which can occasionally be seen in severe diabetic neuropathy cases, consequent to extensive involvement of the intercostal nerves. These blocks provided sustained and significant pain relief and improvement of quality of life over a period of more than two years. We thus provided the first clinical evidence supporting the notion that sympathetic nervous system plays a critical role in painful diabetic neuropathy and sympathetic blocks can be an effective management modality of painful diabetic neuropathy. We concluded that the sympathetic nervous system is a valuable therapeutic target of pharmacological and interventional modalities of treatments in painful diabetic neuropathy patients. PMID:22606406

Cheng, Jianguo; Daftari, Anuj; Zhou, Lan

2012-01-01

224

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

225

Deletion of KCC3 in parvalbumin neurons leads to locomotor deficit in a conditional mouse model of peripheral neuropathy associated with agenesis of the corpus callosum.  

PubMed

Hereditary motor and sensory neuropathy associated with agenesis of the corpus callosum (HMSN/ACC or ACCPN) is an autosomal recessive disease caused by the disruption of the SLC12A6 gene, which encodes the K-Cl cotransporter-3 (KCC3). A ubiquitous deletion of KCC3 in mice leads to severe locomotor deficits similar to ACCPN patients. However, the underlying pathological mechanism leading to the disease remains unclear. Even though a recent study suggests that the neuropathic features of ACCPN are mostly due to neuronal loss of KCC3, the specific cell type responsible for the disease is still unknown. Here we established four tissue specific KCC3 knockout mouse lines to explore the cell population origin of ACCPN. Our results showed that the loss of KCC3 in parvalbumin-positive neurons led to significant locomotor deficit, suggesting a crucial role of these neurons in the development of the locomotor deficit. Interestingly, mice in which KCC3 deletion was driven by the neuron-specific enolase (NSE) did not develop any phenotype. Furthermore, we demonstrated that nociceptive neurons targeted with Nav1.8-driven CRE and Schwann cells targeted with a desert hedgehog-driven CRE were not involved in the development of ACCPN. Together, these results establish that the parvalbumin-positive neuronal population is an important player in the pathogenic development of ACCPN. PMID:25116249

Ding, Jinlong; Delpire, Eric

2014-11-01

226

Metabolic neuropathies and myopathies.  

PubMed

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

D'Amico, Adele; Bertini, Enrico

2013-01-01

227

Hereditary spastic paraplegia: clinico-pathologic features and emerging molecular mechanisms  

PubMed Central

Hereditary spastic paraplegia (HSP) is a syndrome designation describing inherited disorders in which lower extremity weakness and spasticity are the predominant symptoms. There are more than 50 genetic types of HSP. HSP affects individuals diverse ethnic groups with prevalence estimates ranging from 1.2 to 9.6 per 100,000 [39, 70, 77, 154, 185]. Symptoms may begin at any age. Gait impairment that begins after childhood usually worsens very slowly over many years. Gait impairment that begins in infancy and early childhood may not worsen significantly. Post mortem studies consistently identify degeneration of corticospinal tract axons (maximal in the thoracic spinal cord) and degeneration of fasciculus gracilis fibers (maximal in the cervico-medullary region). HSP syndromes thus appear to involve motor-sensory axon degeneration affecting predominantly (but not exclusively) the distal ends of long central nervous system (CNS) axons. In general, proteins encoded by HSP genes have diverse functions including axon transport (e.g. SPG30/KIF1A, SPG10/KIF5A and possibly SPG4/Spastin); endoplasmic reticulum morphology (e.g. SPG3A/Atlastin, SPG4/Spastin, SPG12/reticulon 2, and SPG31/REEP1, all of which interact); mitochondrial function (e.g. SPG13/chaperonin 60/heat shock protein 60, SPG7/paraplegin; and mitochondrial ATP6; 4) myelin formation (e.g. SPG2/Proteolipid protein and SPG42/Connexin 47); 5) protein folding and ER-stress response (SPG6/NIPA1, SPG8/K1AA0196 (Strumpellin), SGP17/BSCL2 (Seipin) [113-115], “mutilating sensory neuropathy with spastic paraplegia” due to CcT5 mutation and presumably SPG18/ERLIN2); 6) corticospinal tract and other neurodevelopment (e.g. SPG1/L1 cell adhesion molecule and SPG22/thyroid transporter MCT8); 7) fatty acid and phospholipid metabolism (e.g. SPG28/DDHD1, SPG35/FA2H, SPG39/NTE, SPG54/DDHD2, and SPG56/CYP2U1); and 8) endosome membrane trafficking and vesicle formation (e.g. SPG47/AP4B1, SPG48/KIAA0415, SPG50/AP4M1, SPG51/AP4E, SPG52/AP4S1, and VSPG53/VPS37A). The availability of animal models (including bovine, murine, zebrafish, Drosophila, and C. elegans) for many types of HSP permits exploration of disease mechanisms and potential treatments. This review highlights emerging concepts of this large group of clinically similar disorders. For recent review of HSP including historical descriptions, differential diagnosis, and additional references see [78]. PMID:23897027

Fink, John K.

2014-01-01

228

Hereditary spastic paraplegia: clinico-pathologic features and emerging molecular mechanisms.  

PubMed

Hereditary spastic paraplegia (HSP) is a syndrome designation describing inherited disorders in which lower extremity weakness and spasticity are the predominant symptoms. There are more than 50 genetic types of HSP. HSP affects individuals of diverse ethnic groups with prevalence estimates ranging from 1.2 to 9.6 per 100,000. Symptoms may begin at any age. Gait impairment that begins after childhood usually worsens very slowly over many years. Gait impairment that begins in infancy and early childhood may not worsen significantly. Postmortem studies consistently identify degeneration of corticospinal tract axons (maximal in the thoracic spinal cord) and degeneration of fasciculus gracilis fibers (maximal in the cervico-medullary region). HSP syndromes thus appear to involve motor-sensory axon degeneration affecting predominantly (but not exclusively) the distal ends of long central nervous system (CNS) axons. In general, proteins encoded by HSP genes have diverse functions including (1) axon transport (e.g. SPG30/KIF1A, SPG10/KIF5A and possibly SPG4/Spastin); (2) endoplasmic reticulum morphology (e.g. SPG3A/Atlastin, SPG4/Spastin, SPG12/reticulon 2, and SPG31/REEP1, all of which interact); (3) mitochondrial function (e.g. SPG13/chaperonin 60/heat-shock protein 60, SPG7/paraplegin; and mitochondrial ATP6); (4) myelin formation (e.g. SPG2/Proteolipid protein and SPG42/Connexin 47); (5) protein folding and ER-stress response (SPG6/NIPA1, SPG8/K1AA0196 (Strumpellin), SGP17/BSCL2 (Seipin), "mutilating sensory neuropathy with spastic paraplegia" owing to CcT5 mutation and presumably SPG18/ERLIN2); (6) corticospinal tract and other neurodevelopment (e.g. SPG1/L1 cell adhesion molecule and SPG22/thyroid transporter MCT8); (7) fatty acid and phospholipid metabolism (e.g. SPG28/DDHD1, SPG35/FA2H, SPG39/NTE, SPG54/DDHD2, and SPG56/CYP2U1); and (8) endosome membrane trafficking and vesicle formation (e.g. SPG47/AP4B1, SPG48/KIAA0415, SPG50/AP4M1, SPG51/AP4E, SPG52/AP4S1, and VSPG53/VPS37A). The availability of animal models (including bovine, murine, zebrafish, Drosophila, and C. elegans) for many types of HSP permits exploration of disease mechanisms and potential treatments. This review highlights emerging concepts of this large group of clinically similar disorders. PMID:23897027

Fink, John K

2013-09-01

229

Pathophysiology of Hereditary Angioedema  

PubMed Central

The genetic deficiency of the C1 inhibitor is responsible for hereditary angioedema (HAE), which is a disease transmitted as an autosomal dominant trait. More than 200 point mutations in the C1 inhibitor gene have been found to be associated with HAE. Patients with this disease suffer from recurrent angioedema, which is mediated by bradykinin derived from activation of the contact system. This system is physiologically controlled at several steps by the C1 inhibitor. In this review, we describe known mechanisms for the development of angioedema in patients with C1 inhibitor deficiency.

Caccia, Sonia; Suffritti, Chiara

2014-01-01

230

Pediatric hereditary angioedema  

PubMed Central

Hereditary angioedema (HAE) is a lifelong illness characterized by recurrent swelling of the skin, intestinal tract, and, ominously, the upper airway. It is caused by inadequate activity of the protein C1-inhibitor, with dysfunction in the kallikrein/bradykinin pathway underlying the clinical symptoms. In addition to the physical symptoms, patients experience significant decrements in vocational and school achievement as well as in overall quality of life. Symptoms often begin in childhood and occur by age 20 in most patients, but life-threatening attacks are uncommon in the pediatric population. The availability of new therapies has transformed the management of HAE. PMID:24313851

MacGinnitie, Andrew J

2014-01-01

231

Acute motor axonal neuropathy in a child with atypical presentation: a case report.  

PubMed

Acute motor axonal neuropathy (AMAN) is a variant of Guillain-Barre syndrome. It has been reported to have no sensory symptoms and is diagnosed by typical electrophysiological findings of low-amplitude or unobtainable compound muscle action potentials with normal sensory nerve action potentials. However, the authors experienced atypical case of general electrophysiological findings of AMAN with pain and paresthesia and presented it. This case implies that clinician should be on the alert to atypical sensory symptoms from the classical presentation of AMAN even if the patient is diagnosed with AMAN electrophysiologically and should consider proper treatment options based on clinical presentations. PMID:25621680

Lee, Kyung Soo; Han, Seung Hoon

2015-01-01

232

Neuropathy and levodopa in Parkinson's disease: evidence from a multicenter study.  

PubMed

The objectives of this study were to evaluate the risk of neuropathy in patients with Parkinson's disease (PD) and to evaluate the role of levodopa exposure as a potential risk factor. A multicenter study of 330 patients with PD and 137 healthy controls with a comparable age distribution was performed. With respect to levodopa exposure, 144 patients had long exposure (? 3 years) to levodopa (LELD), 103 patients had short exposure (<3 years) to levodopa (SELD), and 83 patients had no exposure to levodopa (NOLD). Nerve function was evaluated using the reduced total neuropathy score. Right sural sensory antidromic and peroneal motor nerve conduction studies were performed by neurophysiologists who were blinded to the existence of neuropathy clinical features or PD treatment. Overall, 19.40% of patients in the LELD group, 6.80% in the SELD group, 4.82% in the NOLD group, and 8.76% in the control group were diagnosed with neuropathy (axonal, predominantly sensory). Multivariate logistic analysis indicated that the risk of neuropathy was not influenced by disease duration, severity, or sex. The risk of neuropathy increased by approximately 8% for each year of age (P < 0.001; odds ratio [OR], 1.08; 95% confidence interval [CI], 1.037-1.128). The risk of neuropathy was 2.38 higher in the LELD group than in the control group (P = 0.022; OR, 2.38; 95% CI, 1.130-5.014). In a comparison between patients with and without neuropathy (Student's t test), the levodopa dose was higher (P < 0.0001), serum vitamin B12 levels were lower (P = 0.0102), and homocysteine levels were higher (P < 0.001) in the patients with neuropathy. Our results demonstrate that the duration of exposure to levodopa, along with age, is the main risk factor for the development of neuropathy. Screening for homocysteine and vitamin B12 levels and clinical-neurophysiological monitoring for neuropathy may be advisable in patients with PD who are receiving treatment with levodopa. PMID:23836370

Ceravolo, Roberto; Cossu, Giovanni; Bandettini di Poggio, Monica; Santoro, Lucio; Barone, Paolo; Zibetti, Maurizio; Frosini, Daniela; Nicoletti, Valentina; Manganelli, Fiore; Iodice, Rosa; Picillo, Marina; Merola, Aristide; Lopiano, Leonardo; Paribello, Alessandra; Manca, Davide; Melis, Maurizio; Marchese, Roberta; Borelli, Paolo; Mereu, Alessandra; Contu, Paolo; Abbruzzese, Giovanni; Bonuccelli, Ubaldo

2013-09-01

233

Hereditary palmoplantar keratodermas.  

PubMed

Hereditary palmoplantar keratodermas (PPK) comprise a clinically and genetically heterogeneous group of genodermatoses, which share impaired epidermal differentiation resulting in prominent palmoplantar hyperkeratosis. Classically, keratodermas have been separated according to their clinical appearance into diffuse, focal, and as a feature of ectodermal dysplasias and many other syndromes. Since molecular genetic analyses have helped characterize the underlying genetic defects in an increasing number of hereditary PPK over the last two decades, a pathophysiological separation seems more reasonable. Today PPK can be classified based on defects in keratins, loricrin, desmosomes, connexins, and cathepsins. Although these proteins have different structures and functions, all of them influence epidermal differentiation and cornified envelope assembly. Depending on tissue distribution and location of mutation with a certain gene, the clinical spectrum of PPK range from a pure palmoplantar restricted skin abnormality to a complex combination of symptoms with dental anomalies, deafness, progressive cardiomyopathy and even cancer. Solely for those reasons, a correct diagnosis based on molecular genetic analyses is mandatory, although a causal therapy is still not available. Instead, several therapeutic modalities including topical ointments, surgical interventions and systemic retinoids help to reduce the patients' symptoms. PMID:19341430

Braun-Falco, Markus

2009-11-01

234

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

235

Therapy-related peripheral neuropathy in multiple myeloma patients.  

PubMed

This review discusses the most common issues concerning multiple myeloma (MM)-related peripheral neuropathy (PN). This is an important MM complication, observed in up to 54% of newly diagnosed patients, caused by the disease itself or its treatment. Although its aetiology is largely unknown, a number of mechanisms are suspected. It is important to know the neurological status of a patient, as many new antimyeloma medicines can trigger or exacerbate any pre-existing neuropathy. Examples include thalidomide-induced and bortezomib-induced PN (TiPN and BiTN, respectively), which are key MM treatment options. TiPN is usually sensory and sensorimotor, whereas BiPN is typically sensory. The mechanisms of chemotherapy-induced neurotoxicity in MM are well known; thalidomide seems to induce PN through its antiangiogenic properties, whereas bortezomib neurotoxicity is connected with disrupted calcium homeostasis. TiPN incidence ranges from 25% to 75%, and its prevalence and severity appears to be dose-dependent. BiPN incidence is almost 40% and is dose-related as well. Poor (25%) reversibility of TiPN prompted the recommendations for dose and exposure reduction, whereas BiPN cases are mostly reversible (64%). Peripheral sensory neuropathy is very rare in patients receiving bendamustine monotherapy. Because of this favourable toxicity profile, bendamustine may be considered a promising option for combination therapies in pre-existing PN in myeloma patients. Considering the lack of curative therapy for treatment-emergent PN, prevention is a key management strategy in MM patients. All patients should be evaluated for PN before the administration of a neurotoxic drug, and those under treatment should be closely monitored by a neurologist. Copyright © 2014 John Wiley & Sons, Ltd. PMID:25399783

Morawska, Marta; Grzasko, Norbert; Kostyra, Magdalena; Wojciechowicz, Jolanta; Hus, Marek

2014-11-14

236

Preventing Chemotherapy-Induced Neuropathy  

Cancer.gov

In this trial, researchers are testing the ability of an antioxidant supplement called alpha-lipoic acid to prevent peripheral neuropathy caused by the platinum-containing drugs cisplatin and oxaliplatin.

237

Chemotherapy-Induced Peripheral Neuropathy  

Cancer.gov

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

238

Glutamate Carboxypeptidase II Inhibition Behaviorally and Physiologically Improves Pyridoxine-Induced Neuropathy in Rats  

PubMed Central

Pyridoxine is used as a supplement for treating conditions such as vitamin deficiency as well as neurological disorders such as depression, epilepsy and autism. A significant neurologic complication of pyridoxine therapy is peripheral neuropathy thought to be a result of long-term and high dose usage. Although pyridoxine-induced neuropathy is transient and can remit after its withdrawal, the process of complete recovery can be slow. Glutamate carboxypeptidase II (GCP II) inhibition has been shown to improve symptoms of both chemotherapy- and diabetic-induced neuropathy. This study evaluated if GCP II inhibition could behaviorally and physiologically improve pyridoxine-induced neuropathy. In the current study, high doses of pyridoxine (400 mg/kg, twice a day for seven days) were used to induce neuropathy in rats. An orally bioavailable GCP II inhibitor, 2-(3-mercaptopropyl) pentanedioic acid (2-MPPA), was administered daily at a dose of 30 mg/kg starting from the onset of pyridoxine injections. Body weight, motor coordination, heat sensitivity, electromyographical (EMG) parameters and nerve morphological features were monitored. The results show beneficial effects of GCP II inhibition including normalization of hot plate reaction time, foot fault improvements and increased open field distance travelled. H wave frequency, amplitude and latency as well as sensory nerve conduction velocity (SNCV) were also significantly improved by 2-MPPA. Lastly, GCP II inhibition resulted in morphological protection in the spinal cord and sensory fibers in the lumbar region dorsal root ganglia (DRG). In conclusion, inhibition of GCP II may be beneficial against the peripheral sensory neuropathy caused by pyridoxine. PMID:25254647

Potter, Michelle C.; Wozniak, Krystyna M.; Callizot, Noelle; Slusher, Barbara S.

2014-01-01

239

Control of uremic neuropathy by equilibrium peritoneal dialysis.  

PubMed

Motor nerve conduction velocity (MNCV), sensory nerve conduction velocity (SNVC) and distal motor latencies times (DMLT) were evaluated both in upper and lower limbs in three groups of 15 patients of comparable age, treated respectively by extracorporeal dialysis (HD), continuous ambulatory peritoneal dialysis (CAPD) and combined peritoneal dialysis (CPD) for comparable sufficiently long periods. Moreover, MNCV was monitored longitudinally in two groups of patients shifted from CAPD to HD and vice versa. The results show a significant superiority of peritoneal dialysis and particularly of CAPD with respect to HD in controlling uremic neuropathy. PMID:6329962

Buoncristiani, U; Mazzotta, G; Carobi, C; Gallai, V; Cozzari, M; Di Paolo, N N

1984-03-01

240

Distinct lymphocytes subsets in IgM-related neuropathy: clinical-immunological correlations.  

PubMed

IgM-related neuropathy generally presents as a late-onset demyelinating polyneuropathy with predominant sensory loss and ataxia. However, we recently reported the clinical, neurophysiological and pathological findings from our cohort and identified in about a third of patients an atypical phenotype. We analyzed by flow cytometry the different lymphocytes subsets in the peripheral blood of patients affected by IgM-related neuropathy, chronic inflammatory demyelinating polyneuropathy (CIDP), monoclonal gammopathy of undetermined significance and healthy subjects, to investigate whether different immunological patterns may differentiate the classical phenotype from atypical forms. IFN-gamma producing CD4+ and CD8+ T lymphocytes, as well as CD4+ and CD8+ T cells expressing T-bet (T-helper type 1, Th1) were increased in CIDP patients. The percentage of circulating CD4+ and CD8+ T cells producing IL-10 as well as the percentage of CD19+ cells expressing Blimp-1 were higher in patients with IgM-neuropathy. We did not find any significant differences in the different lymphocytes subsets in the IgM-related neuropathy between patients with classical and atypical phenotype. Th1 cells are increased in CIDP patients while a T helper type 2-phenotype seems to prevail in patients with IgM-neuropathy. Further studies involving a larger patient population are needed to evaluate if different lymphocytes subset may be involved in different clinical phenotypes of IgM-related neuropathy. PMID:25192662

Iorio, Raffaele; Sabatelli, Mario; Del Grande, Alessandra; Bisogni, Giulia; Damato, Valentina; Plantone, Domenico; Marti, Alessandro; Frisullo, Giovanni; Romano, Angela; Rossini, Paolo Maria; Luigetti, Marco

2015-02-01

241

A sensory-integrative approach to familial dysautonomia.  

PubMed

Familial dysautonomia, a relatively rare hereditary condition, consists of a baffling array of nervous system malfunctions that seriously disturb the lives of the young victims and their families. Since several of the deficits can be identified as sensory-integrative and as such have been successfully treated in other contexts, it is suggested that sensory integration therapy may benefit these children. Results of a ten-month-old Isralei child appear to support this conjecture and suggest further exploration of the sensory integration approach in evaluation and treatment of dysautonomia and related conditions. PMID:517362

Speier, T

1979-11-01

242

Fibromyalgia and neuropathic pain - differences and similarities. A comparison of 3057 patients with diabetic painful neuropathy and fibromyalgia  

Microsoft Academic Search

Background  Patients with diabetic neuropathy (DPN) and fibromyalgia differ substantially in pathogenetic factors and the spatial distribution\\u000a of the perceived pain. We questioned whether, despite these obvious differences, similar abnormal sensory complaints and pain\\u000a qualities exist in both entities. We hypothesized that similar sensory symptoms might be associated with similar mechanisms\\u000a of pain generation. The aims were (1) to compare epidemiological

Jana Koroschetz; Stefanie E Rehm; Ulrich Gockel; Mathias Brosz; Rainer Freynhagen; Thomas R Tölle; Ralf Baron

2011-01-01

243

Genetics Home Reference: Hereditary hyperekplexia  

MedlinePLUS

... that is connected to the spinal cord (the brainstem). Approximately 80 percent of cases of hereditary hyperekplexia ... to transmit signals in the spinal cord and brainstem. Mutations in the other four genes account for ...

244

Genetics Home Reference: Hereditary spherocytosis  

MedlinePLUS

... in 1 in 2,000 individuals of Northern European ancestry. This condition is the most common cause of inherited anemia in that population. The prevalence of hereditary spherocytosis in people of ...

245

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

PubMed Central

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

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

2010-01-01

246

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

PubMed

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

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

2010-08-01

247

Marie-Unna Hereditary Hypotrichosis  

PubMed Central

Marie-Unna type of hereditary hypotrichosis is a rare autosomal dominant disorder that has a distinctive type of hair loss pattern that varies with child's age. It is characterized by sparse or absent hair at birth with regrowth of coarse, wiry twisted hair from childhood, followed by progressive loss on approaching puberty. We report a 12-year-old male child with characteristic clinical features suggestive of hereditary hypotrichosis of Marie-Unna type. PMID:25368478

Srinivas, Sahana M; Hiremagalore, Ravi

2014-01-01

248

Retinoic acid reduces chemotherapy-induced neuropathy in an animal model and patients with lung cancer  

PubMed Central

Objective: To evaluate the effect of all-trans retinoic acid (ATRA) as treatment for chemotherapy-induced peripheral neuropathy in an experimental animal model and in a randomized, double-blinded, controlled trial in patients with non-small-cell lung cancer (NSCLC). Methods: Forty male Wistar rats were randomized in 5 groups: group A, control; groups B and C, treated with cisplatin; and groups D and E, treated with paclitaxel. ATRA (20 mg/kg PO) was administered for 15 days in groups C and E. We evaluated neuropathy and nerve regeneration–related morphologic changes in sciatic nerve, the concentration of nerve growth factor (NGF), and retinoic acid receptor (RAR)–? and RAR-? expression. In addition, 95 patients with NSCLC under chemotherapy treatment were randomized to either ATRA (20 mg/m2/d) or placebo. Serum NGF, neurophysiologic tests, and clinical neurotoxicity were assessed. Results: The experimental animals developed neuropathy and axonal degeneration, associated with decreased NGF levels in peripheral nerves. Treatment with ATRA reversed sensorial changes and nerve morphology; this was associated with increased NGF levels and RAR-? expression. Patients treated with chemotherapy had clinical neuropathy and axonal loss assessed by neurophysiology, which was related to decreased NGF levels. ATRA reduced axonal degeneration demonstrated by nerve conduction velocity and clinical manifestations of neuropathy grades ?2. Conclusions: ATRA reduced chemotherapy-induced experimental neuropathy, increased NGF levels, and induced RAR-? expression in nerve. In patients, reduction of NGF in serum was associated with the severity of neuropathy; ATRA treatment reduced the electrophysiologic alterations. Classification of evidence: This study provides Class II evidence that ATRA improves nerve conduction in patients with chemotherapy-induced peripheral neuropathy. Neurology® 2011;77:987–995 PMID:21865574

Hernández-Pedro, N.; Fernández-González- Aragón, M.C.; Saavedra-Pérez, D.; Campos-Parra, A.D.; Ríos-Trejo, M.Á.; Cerón-Lizárraga, T.; Martínez-Barrera, L.; Pineda, B.; Ordóńez, G.; Ortiz-Plata, A.; Granados-Soto, V.; Sotelo, J.

2011-01-01

249

Crucifixion and median neuropathy  

PubMed Central

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

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

2013-01-01

250

Peripheral neuropathy in pediatric systemic lupus erythematosus  

Microsoft Academic Search

Peripheral neuropathy is an uncommon manifestation of systemic lupus erythematosus and has not yet been characterized in pediatric patients. We report the clinical and electrophysiologic features of peripheral neuropathy in one child and three adolescents with lupus erythematosus. There were three females and one male. The peripheral neuropathy followed the onset of lupus erythematosus by a mean of 3 years.

Liora Harel; Masha Mukamel; Riva Brik; Hannah Blau; Rachel Straussberg

2002-01-01

251

Hereditary Renal Cancer Syndromes  

PubMed Central

Inherited susceptibility to kidney cancer is a fascinating and complex topic. Our knowledge about types of genetic syndromes associated with an increased risk of disease is continually expanding. Currently, there are 10 syndromes associated with an increased risk of all types of renal cancer, which are reviewed herein. Clear cell renal cancer is associated with von Hippel Lindau disease, chromosome 3 translocations, PTEN hamartomatous syndrome and mutations in BAP1, as well as several of the genes encoding the proteins comprising the succinate dehydrogenase complex (SDHB/C/D). Type 1 papillary renal cancers arise in conjunction with germline mutations in MET and type 2 as part of Hereditary Leiomyomatosis and Renal Cell Cancer (FH mutations). Chromophone and oncocytic renal cancers are predominantly associated with Birt Hogg Dubé syndrome. Angiomyolipomas are commonly and their malignant counterpart epitheliod angiomyolipomas rarely are found in patients with Tuberous Sclerosis Complex. The targeted therapeutic options for the renal cancer associated with these diseases are just starting to expand, and are an area of active clinical research. PMID:24359990

Haas, Naomi B.

2013-01-01

252

Emerging toxic neuropathies and myopathies.  

PubMed

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

Kushlaf, Hani A

2011-08-01

253

Validation of Michigan neuropathy screening instrument for diabetic peripheral neuropathy  

Microsoft Academic Search

ObjectiveThe reliability and accuracy of the Michigan neuropathy screening instrument (MNSI) have been discussed recently. As a result of the difficulties of performing and analyzing nerve biopsy as a standard diagnostic test, electromyography and neuronography is used as the best alternative diagnostic procedure. The objective of this study was to determine the diagnostic performance of the test characteristics and cut-off

Ali Moghtaderi; Alireza Bakhshipour; Homayra Rashidi

2006-01-01

254

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

255

Canadian hereditary angioedema guideline.  

PubMed

Hereditary angioedema (HAE) is a disease which is associated with random and often unpredictable attacks of painful swelling typically affecting the extremities, bowel mucosa, genitals, face and upper airway. Attacks are associated with significant functional impairment, decreased Health Related Quality of Life, and mortality in the case of laryngeal attacks. Caring for patients with HAE can be challenging due to the complexity of this disease. The care of patients with HAE in Canada is neither optimal nor uniform across the country. It lags behind other countries where there are more organized models for HAE management, and where additional therapeutic options are licensed and available for use. The objective of this guideline is to provide graded recommendations for the management of patients in Canada with HAE. This includes the treatment of attacks, short-term prophylaxis, long-term prophylaxis, and recommendations for self-administration, individualized therapy, quality of life, and comprehensive care. It is anticipated that by providing this guideline to caregivers, policy makers, patients and their advocates, that there will be an improved understanding of the current recommendations regarding management of HAE and the factors that need to be considered when choosing therapies and treatment plans for individual patients. The primary target users of this guideline are healthcare providers who are managing patients with HAE. Other healthcare providers who may use this guideline are emergency physicians, gastroenterologists, dentists and otolaryngologists, who will encounter patients with HAE and need to be aware of this condition. Hospital administrators, insurers and policy makers may also find this guideline helpful. PMID:25352908

Betschel, Stephen; Badiou, Jacquie; Binkley, Karen; Hébert, Jacques; Kanani, Amin; Keith, Paul; Lacuesta, Gina; Yang, Bill; Aygören-Pürsün, Emel; Bernstein, Jonathan; Bork, Konrad; Caballero, Teresa; Cicardi, Marco; Craig, Timothy; Farkas, Henriette; Longhurst, Hilary; Zuraw, Bruce; Boysen, Henrik; Borici-Mazi, Rozita; Bowen, Tom; Dallas, Karen; Dean, John; Lang-Robertson, Kelly; Laramée, Benoît; Leith, Eric; Mace, Sean; McCusker, Christine; Moote, Bill; Poon, Man-Chiu; Ritchie, Bruce; Stark, Donald; Sussman, Gordon; Waserman, Susan

2014-01-01

256

Subdural Hemorrhage Mimicking Peripheral Neuropathy  

PubMed Central

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

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

2014-01-01

257

Study on Corporate Hereditary Central Dogma  

Microsoft Academic Search

Based on analyzing the central dogma of biology, this paper raises hypothesis, using the analogism method to set up the corporate hereditary central dogma. It analyzes the differences between the Corporate hereditary central dogma and the central dogma of biology, which explains the significance of research on Corporate hereditary central dogma; it discusses the meanings of all factors of Corporate

Li Xianbai

2010-01-01

258

TRIGLYCERIDE, NEFA, AND PREDIABETIC NEUROPATHY: ROLE FOR OXIDATIVE-NITROSATIVE STRESS  

PubMed Central

Peripheral neuropathy develops in human subjects with prediabetes and metabolic syndrome, prior to overt hyperglycemia. The contributions of impaired glucose tolerance and insulin signaling, hypertriglyceridemia and/or increased NEFA, and hypercholesterolemia to this condition remain unknown. Niacin and its derivatives alleviate dyslipidemia with a minor effect on glucose homeostasis. This study evaluated the roles of impaired glucose tolerance versus dyslipidemia in prediabetic neuropathy using Zucker fatty (fa/fa) rats and the niacin derivative acipimox, as well as the interplay of hypertriglyceridemia, increased NEFA, and oxidative-nitrosative stress. 16 wk-old Zucker fatty rats with impaired glucose tolerance, obesity, hyperinsulinemia, hypertriglyceridemia, hypercholesterolemia, and increased NEFA, displayed sensory nerve conduction velocity deficit, thermal and mechanical hypoalgesia, and tactile allodynia. Acipimox (100 mgkg?1d?1, 4 weeks) reduced serum insulin, NEFA, and triglyceride concentrations without affecting glucose tolerance and hypercholesterolemia. It alleviated sensory nerve conduction velocity deficit, changes in behavioral measures of sensory function, and corrected oxidative-nitrosative stress, but not impaired insulin signaling, in peripheral nerve. Elevated NEFA increased total and mitochondrial superoxide production and NAD(P)H oxidase activity in cultured human Schwann cells. In conclusion, hypertriglyceridemia and/or increased NEFA concentrations cause prediabetic neuropathy through oxidative-nitrosative stress. Lipid-lowering agents and antioxidants may find use in management of this condition. PMID:22366714

Lupachyk, Sergey; Watcho, Pierre; Hasanova, Nailia; Julius, Ulrich; G.Obrosova, Irina

2012-01-01

259

Enriching the diet with menhaden oil improves peripheral neuropathy in streptozotocin-induced type 1 diabetic rats.  

PubMed

The purpose of this study was to determine the effect of supplementing the diet of type 1 diabetic rats with menhaden oil on diabetic neuropathy. Menhaden oil is a natural source for n-3 fatty acids, which have been shown to have beneficial effects in cardiovascular disease and other morbidities. Streptozotocin-induced diabetic rats were used to examine the influence of supplementing their diet with 25% menhaden oil on diabetic neuropathy. Both prevention and intervention protocols were used. Endpoints included motor and sensory nerve conduction velocity, thermal and mechanical sensitivity, and innervation and sensitivity of the cornea and hindpaw. Diabetic neuropathy as evaluated by the stated endpoints was found to be progressive. Menhaden oil did not improve elevated HbA1C levels or serum lipid levels. Diabetic rats at 16-wk duration were thermal hypoalgesic and had reduced motor and sensory nerve conduction velocities, and innervation and sensitivity of the cornea and skin were impaired. These endpoints were significantly improved with menhaden oil treatment following the prevention or intervention protocol. We found that supplementing the diet of type 1 diabetic rats with menhaden oil improved a variety of endpoints associated with diabetic neuropathy. These results suggest that enriching the diet with n-3 fatty acids may be a good treatment strategy for diabetic neuropathy. PMID:25376787

Coppey, Lawrence J; Davidson, Eric P; Obrosov, Alexander; Yorek, Mark A

2015-02-01

260

Why Are Sensory Axons More Vulnerable for Ischemia than Motor Axons?  

PubMed Central

Objective In common peripheral neuropathies, sensory symptoms usually prevail over motor symptoms. This predominance of sensory symptoms may result from higher sensitivity of sensory axons to ischemia. Methods We measured median nerve compound sensory action potentials (CSAPs), compound muscle action potentials (CMAPs), and excitability indices in five healthy subjects during forearm ischemia lasting up to disappearance of both CSAPs and CMAPs. Results Ischemia induced: (1) earlier disappearance of CSAPs than CMAPs (mean ± standard deviation 30±5 vs. 46±6 minutes), (2) initial changes compatible with axonal depolarization on excitability testing (decrease in threshold, increase in strength duration time constant (SDTC) and refractory period, and decrease in absolute superexcitability) which were all more prominent in sensory than in motor axons, and (3) a subsequent decrease of SDTC reflecting a decrease in persistent Na+ conductance during continuing depolarisation. Interpretation Our study shows that peripheral sensory axons are more vulnerable for ischemia than motor axons, with faster inexcitability during ischemia. Excitability studies during ischemia showed that this was associated with faster depolarization and faster persistent Na+ channel inactivation in sensory than in motor axons. These findings might be attributed to differences in ion channel composition between sensory and motor axons and may contribute to the predominance of sensory over motor symptoms in common peripheral neuropathies. PMID:23840596

Hofmeijer, Jeannette; Franssen, Hessel; van Schelven, Leonard J.; van Putten, Michel J. A. M.

2013-01-01

261

Angiogenesis and Hereditary Hemorrhagic Telangiectasia  

Microsoft Academic Search

To date much of the recent work on pathological angiogenesis has focused on inflammatory diseases, diabetes and cancer in particular. Hereditary hemorrhagic telangiectasia or Rendu-Osler-Weber disease provides an example of the genetic disorder of angiogenesis in which a multisystemic angiodysplasia is responsible for severe hemorrhage. The disease pathogenesis is partially explained by a defect in the TGF-? signaling system, although

Carlo Sabbŕ; Anna Cirulli; Rita Rizzi; Giovanna Pasculli; Mauro Gallitelli; Giorgina Specchia; Vincenzo Liso

2001-01-01

262

[Hereditary angioneurotic edema (author's transl)].  

PubMed

Hereditary angioneurotic edema is a rare autosomally-inherited disease, which is caused by a deficiency or functional inactivation of C-1 inactivator in the complement system. The poor prognosis of the disease mandates that an early diagnosis be made and drug therapy begun to prevent a lethal outcome. The pathogenesis, clinical course and therapies available are detailed. PMID:7462039

Löhle, E; Mann, W

1980-01-01

263

Drug therapy for hereditary cancers  

PubMed Central

Tumors arising in patients with hereditary cancer syndromes may have distinct drug sensitivity as compared to their sporadic counterparts. Breast and ovarian neoplasms from BRCA1 or BRCA2 mutation carriers are characterized by deficient homologous recombination (HR) of DNA, that makes them particularly sensitive to platinum compounds or inhibitors of poly (ADP-ribose) polymerase (PARP). Outstandingly durable complete responses to high dose chemotherapy have been observed in several cases of BRCA-related metastatic breast cancer (BC). Multiple lines of evidence indicate that women with BRCA1-related BC may derive less benefit from taxane-based treatment than other categories of BC patients. There is virtually no reports directly assessing drug response in hereditary colorectal cancer (CRC) patients; studies involving non-selected (i.e., both sporadic and hereditary) CRC with high-level microsatellite instability (MSI-H) suggest therapeutic advantage of irinotecan. Celecoxib has been approved for the treatment of familial adenomatous polyposis (FAP). Hereditary medullary thyroid cancers (MTC) have been shown to be highly responsive to a multitargeted tyrosine kinase inhibitor vandetanib, which exerts specific activity towards mutated RET receptor. Given the rapidly improving accessibility of DNA analysis, it is foreseen that the potential predictive value of cancer-associated germ-line mutations will be increasingly considered in the future studies. PMID:21819606

2011-01-01

264

Clinical phenotype of patients with neuropathy associated with monoclonal gammopathy: a comparative study and a review of the literature.  

PubMed

The objective of this study was to investigate if the clinical and electrophysiological phenotype of patients with polyneuropathy associated with IgM monoclonal gammopathy (IgM-PNP) is related to the presence of antibodies against gangliosides or myelin-associated glycoprotein (MAG). We compared clinical and nerve conduction study (NCS) characteristics of 11 IgM-PNP patients with antibodies against asialo-GM1 or gangliosides (GM1, GD1a, GD1b, GM2 or GQ1b) to 11 consecutive IgM-PNP patients with anti-MAG neuropathy and to 9 IgM-PNP patients without antibodies against either MAG or gangliosides. Patients with anti-ganglioside antibodies could not be differentiated from those with anti-MAG antibodies based on clinical characteristics. However, within the group of anti-ganglioside antibody positive patients, antibodies against GD1b and GQ1b were associated with a purely sensory neuropathy (p = 0.002), while asymmetric weakness with symmetric sensory loss was associated with anti-asialo-GM1 antibodies. In conclusion, polyneuropathy associated with IgM monoclonal gammopathy and anti-ganglioside antibodies clinically resembles anti-MAG neuropathy. Pure sensory neuropathy and marked asymmetry may suggest the presence of anti-ganglioside rather than anti-MAG antibodies. PMID:24781837

Stork, Abraham C J; van der Pol, W-Ludo; Franssen, Hessel; Jacobs, Bart C; Notermans, Nicolette C

2014-07-01

265

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

PubMed

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

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

1988-09-27

266

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

267

Taxane-induced peripheral neuropathy has good long-term prognosis: a 1- to 13-year evaluation.  

PubMed

Taxane-induced neuropathy is a frequent complication, in particular in women with breast cancer. The incidence can be variable and ranges from 11 to 87%, depending on the taxane used and identified risk factors, such as cumulative dose, additional neurotoxic chemotherapy agents and previous nerve fragility. However, little is known about long-term outcome and interference with daily life activities. The objective of this study was to assess clinical and electrophysiological neurological evaluation (ENMG) in a cohort of patients, 1-13 years (median 3 years) after the end of the last cure. Sixty-nine women were enrolled in the lymphology unit of Cognacq-Jay's Hospital. They were 58 ± 9 years old (mean age ± SD) and had been treated by docetexel (n = 56), paclitaxel (n = 10) or both (n = 3), 1-13 years before. Sensory neuropathy occurred in 64% and totally disappeared within months for only 14% after cessation of treatment. However, if symptoms were still present at the time of examination, they were considered as minor by almost all patients, with no interference with daily life activities (grade 2 CTCAE v.3.0). ENMG was accepted by 14 patients; it was normal in 7, and showed sensory axonal neuropathy in 5 and sensory-motor neuropathy in 2. The incidence of taxane-induced neuropathy is high, more frequent with paclitaxel than docetaxel, and is characterized by minor or moderate axonal sensory polyneuropathy. When persistent, it is extremely well tolerated by the patient. When clinical motor signs occur, the patient should be referred to a neurologist. PMID:22349867

Osmani, Karima; Vignes, Stéphane; Aissi, Mouna; Wade, Fatou; Milani, Paolo; Lévy, Bernard I; Kubis, Nathalie

2012-09-01

268

The Influence of Peripheral Neuropathy, Gender, and Obesity on the Postural Stability of Patients with Type 2 Diabetes Mellitus  

PubMed Central

Aim. To assess the influence of peripheral neuropathy, gender, and obesity on the postural stability of patients with type 2 diabetes mellitus. Methods. 151 patients with no history of otology, neurology, or orthopaedic or balance disorders accepted to participate in the study. After a clinical interview and neuropathy assessment, postural stability was evaluated by static posturography (eyes open/closed on hard/soft surface) and the “Up & Go” test. Results. During static posturography, on hard surface, the length of sway was related to peripheral neuropathy, gender, age, and obesity; on soft surface, the length of sway was related to peripheral neuropathy, gender, and age, the influence of neuropathy was larger in males than in females, and closing the eyes increased further the difference between genders. The mean time to perform the “Up & Go” test was 11.6 ± 2.2 sec, with influence of peripheral neuropathy, gender, and age. Conclusion. In order to preserve the control of static upright posture during conditions with deficient sensory input, male patients with type 2 diabetes mellitus with no history of balance disorders may be more vulnerable than females, and obesity may decrease the static postural control in both males and females. PMID:25258716

Herrera-Rangel, Aline; Aranda-Moreno, Catalina; Mantilla-Ochoa, Teresa; Zainos-Saucedo, Lylia; Jáuregui-Renaud, Kathrine

2014-01-01

269

Animal Models of Autoimmune Neuropathy  

PubMed Central

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

Soliven, Betty

2014-01-01

270

Focal neuropathies following percutaneous nephrolithotomy (PCNL) – preliminary study  

PubMed Central

Introduction: Postoperative neurological complications in pelvic and renal surgery are a well-known clinical problem and their morbidities are important. We designed this study to determine prevalence and risk factors of such complications after percutaneous nephrolithotomy (PCNL) surgery. Material and methods: A cross-sectional study was performed during February and July 2011 on 68 PCNL cases. Demographic data and surgery reports were gathered and comprehensive neurological physical examination carried out before and after surgery. Then, data was analyzed using software SPSS 18. Results: The ultimate sample included 30 (46.2%) male and 35 (53.8%) female patients with a mean age of 47.9 ± 11.47 years. In intercostal and lumbosacral plexus area, sensory neurological complications occurred in 8 patients (12.31%), 4 men and 4 women. The most common involved dermatomes and nerves were T12 (8 cases). There was a significant correlation between prolonged duration of surgery and prevalence of sensory complications (p<0.010). The highest hemoglobin value drop after surgery occurred in patients with neurological complications (p<0.001). There were no correlations between age, tracts used, diabetes mellitus, BMI, hypertension, positioning of patients and side of surgery with incidence of sensory neurological complications. No motor neurological complications occurred. Conclusion: Prolonged duration of PCNL and increased value of hemoglobin drop may lead to increased risk of neuropathy. Larger prospective studies with retroperitoneal imagings and patients’ follow up is suggested for better understanding of this complication. PMID:23798911

Nasseh, Hamidreza; Pourreza, Farshid; Saberi, Alia; Kazemnejad, Ehsan; Kalantari, Behnam Behmardi; Falahatkar, Siavash

2013-01-01

271

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

272

Peripheral neuropathy associated with capecitabine.  

PubMed

5-fluorouracil (5-FU)-associated peripheral neuropathy is an uncommon event. Capecitabine (CAP) is a pro-drug of 5-FU and peripheral neuropathy associated with CAP has not been reported. During analysis of 28 patients receiving CAP with concomitant radiation (XRT) for pancreatic cancer (resected or locally advanced), two patients developed signs and symptoms consistent with peripheral neuropathy. Patients received CAP 1200-1600 mg/m2 in two divided doses with XRT (total 5040-5400 Gy) x 6 weeks, followed by 4 weeks rest, then 6 cycles of CAP 2000-2500 mg/m2 in two divided doses x 14 days every (q) 3 weeks. Patients were assessed weekly during CAP-XRT and q 3 weeks during CAP alone. Patient A reported right leg weakness (foot drop) during week 4 of CAP-XRT (1600 mg/m2). Patient B developed perioral and upper extremity paresthesias during the fourth cycle of CAP alone (2500 mg/m2). Dihydropyrimidine dehydrogenase (DPD) activity was measured by radioisotopic assay using lysates of peripheral blood mononuclear cells. Neurologic examination revealed right foot drop in Patient A and was unremarkable in Patient B. Central nervous system imaging was negative. Electromyogram and nerve conduction studies showed sensorimotor peripheral neuropathy in both patients. DPD activity was normal in both patients. There was no evidence of disease progression. Neurologic symptoms resolved after stopping CAP for 4 weeks in Patient A, with no recurrence after reinitiating CAP alone at 2000 mg/m2. Patient B continued at 80% of standard dose (2000 mg/m2) and symptoms resolved without further intervention. We conclude peripheral neuropathy with 5-FU is rare. Neurotoxicity occurs most often with intermittent high dose 5-FU as bolus injection or 24- to 48-h infusions. The etiology of neurotoxicity in our two patients remains unclear; however, as CAP is rapidly metabolized to 5-FU in patients with normal liver function, it is likely that 5-FU or its active metabolites (fluoro-beta-alanine) were contributing factors. Knowledge regarding potential adverse effects of CAP is paramount and dose modification is indicated with development of neurotoxicity. PMID:15494638

Saif, M Wasif; Wood, Tina E; McGee, Philip J; Diasio, Robert B

2004-09-01

273

Intramuscular viral delivery of paraplegin rescues peripheral axonopathy in a model of hereditary spastic paraplegia  

PubMed Central

Degeneration of peripheral motor axons is a common feature of several debilitating diseases including complicated forms of hereditary spastic paraplegia. One such form is caused by loss of the mitochondrial energy-dependent protease paraplegin. Paraplegin-deficient mice display a progressive degeneration in several axonal tracts, characterized by the accumulation of morphological abnormal mitochondria. We show that adenoassociated virus–mediated (AAV-mediated) intramuscular delivery of paraplegin halted the progression of neuropathological changes and rescued mitochondrial morphology in the peripheral nerves of paraplegin-deficient mice. One single injection before onset of symptoms improved the motor performance of paraplegin-deficient mice for up to 10 months, indicating that the peripheral neuropathy contributes to the clinical phenotype. This study provides a proof of principle that gene transfer may be an effective therapeutic option for patients with paraplegin deficiency and demonstrates that AAV vectors can be successfully employed for retrograde delivery of an intracellular protein to spinal motor neurons, opening new perspectives for several hereditary axonal neuropathies of the peripheral nerves. PMID:16357941

Pirozzi, Marinella; Quattrini, Angelo; Andolfi, Gennaro; Dina, Giorgia; Malaguti, Maria Chiara; Auricchio, Alberto; Rugarli, Elena I.

2006-01-01

274

Hereditary colorectal cancer in china.  

PubMed

The purpose of this article is to review basic research as well as clinical studies on Chinese hereditary colorectal cancer. Hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) accounts for 2.2% of all colorectal cancer, and Chinese criteria for suspected HNPCC have been developed. Germline mutations as well as large genomic rearrangements of mismatch repair (MMR) genes are responsible for this syndrome. Gastric cancer is the second most common cancer in Chinese HNPCC patients. Contrary to sporadic colorectal cancer in the Chinese population, HNPCC does not typically present with rectal cancer. Incidence of familial adenomatous polyposis (FAP) in China is approximately 1.5/100,000. Polyps in Chinese FAP patients can emerge as early as 16 months old, but malignant transformation usually occurs in the third and fourth decade. Total resection of the colon and rectum is necessary in FAP patients. For unresectable duodenal polyps, chemopreventive agents may be used. PMID:20223042

Shu, Zheng; Yanqin, Huang; Ying, Yuan

2005-01-01

275

Placebo-controlled trial of rituximab in IgM anti-myelin–associated glycoprotein neuropathy  

PubMed Central

Objective: To determine whether rituximab 375 mg/m2 was efficacious in patients with immunoglobulin M (IgM) anti-myelin–associated glycoprotein antibody demyelinating neuropathy (IgM anti-MAG demyelinating neuropathy). Methods: Fifty-four patients with IgM anti-MAG demyelinating neuropathy were enrolled in this randomized, double-blind, placebo-controlled trial. The inclusion criteria were inflammatory neuropathy cause and treatment (INCAT) sensory score (ISS) ?4 and visual analog pain scale >4 or ataxia score ?2. The primary outcome was mean change in ISS at 12 months. Results: Twenty-six patients were randomized to a group receiving 4 weekly infusions of 375 mg/m2 rituximab, and 28 patients to placebo. Intention-to-treat analysis, with imputation of missing ISS values by the last observation carried forward method, showed a lack of mean change in ISS at 12 months, 1.0 ± 2.7 in the rituximab group, and 1.0 ± 2.8 in the placebo group. However, changes were observed, in per protocol analysis at 12 months, for the number of patients with an improvement of at least 2 points in the INCAT disability scale (p = 0.027), the self-evaluation scale (p = 0.016), and 2 subscores of the Short Form–36 questionnaire. Conclusions: Although primary outcome measures provide no evidence to support the use of rituximab in IgM anti-MAG demyelinating neuropathy, there were improvements in several secondary outcomes in per protocol analysis. Level of evidence: This study provides Class I evidence that rituximab is ineffective in improving ISS in patients with IgM anti-MAG demyelinating neuropathy. PMID:23667063

Viala, Karine; Nicolas, Guillaume; Créange, Alain; Vallat, Jean-Michel; Pouget, Jean; Clavelou, Pierre; Vial, Christophe; Steck, Andreas; Musset, Lucile; Marin, Benoit

2013-01-01

276

[Hereditary drusen in Bruch's membrane].  

PubMed

The left eye of a 71-year-old patient who had suffered from choroiditis guttata was removed immediately after death by enucleation. Histopathological studies revealed numerous nodular (hard) drusen, a wide variety of senile alterations of the pigment epithelium and Bruch's membrane, and the presence of multiple corpora arenacea in the subarachnoid space of the optic nerve. A new hypothesis concerning the development of hereditary drusen is advanced, postulating a disturbance of the lysosomal enzyme/inhibitor balance. PMID:2437356

Cagianut, B; Theiler, K

1987-01-01

277

Structural basis of hereditary coproporphyria  

Microsoft Academic Search

Hereditary coproporphyria is an autosomal dominant disorder resulting from the half-normal activity of coproporphyrinogen oxidase (CPO), a mitochondrial enzyme catalyzing the antepenultimate step in heme biosynthesis. The mechanism by which CPO catalyzes oxidative decarboxylation, in an extraordinary metal- and cofactor-independent manner, is poorly understood. Here, we report the crystal structure of human CPO at 1.58-Ĺ resolution. The structure reveals a

Dong-Sun Lee; Eva Flachsová; Michaela Bodnárová; Borries Demeler; Pavel Martásek; C. S. Raman

2005-01-01

278

Pathology of hereditary breast cancer  

Microsoft Academic Search

Background  Hereditary breast cancer runs in families where several members in different generations are affected. Most of these breast\\u000a cancers are caused by mutations in the high penetrance genes BRCA1 and BRCA2 accounting for about 5% of all breast cancers. Other genes that include CHEK2, PTEN, TP53, ATM, STK11\\/LKB1, CDH1, NBS1, RAD50, BRIP1 and PALB2 have been described to be high

Petra van der Groep; Elsken van der Wall; Paul J. van Diest

2011-01-01

279

Monilethrix: a rare hereditary condition.  

PubMed

Monilethrix is a rare hereditary condition generally considered to be an autosomal-dominant disorder with variable penetrance. Here, we report a case of monilethrix in a 13-year-old boy with an affected sibling. A therapeutic trial with oral N-acetyl cysteine was attempted. There was slight improvement after 2 months of therapy. The hair density, however, did not show any further improvement subsequently. Monilethrix remains as a therapeutic challenge for dermatologists. PMID:23723505

Vikramkumar, Adaikalampillai Ganapathy; Kuruvila, Sheela; Ganguly, Satyaki

2013-05-01

280

Guideline of transthyretin-related hereditary amyloidosis for clinicians  

PubMed Central

Transthyretin amyloidosis is a progressive and eventually fatal disease primarily characterized by sensory, motor, and autonomic neuropathy and/or cardiomyopathy. Given its phenotypic unpredictability and variability, transthyretin amyloidosis can be difficult to recognize and manage. Misdiagnosis is common, and patients may wait several years before accurate diagnosis, risking additional significant irreversible deterioration. This article aims to help physicians better understand transthyretin amyloidosis—and, specifically, familial amyloidotic polyneuropathy—so they can recognize and manage the disease more easily and discuss it with their patients. We provide guidance on making a definitive diagnosis, explain methods for disease staging and evaluation of disease progression, and discuss symptom mitigation and treatment strategies, including liver transplant and several pharmacotherapies that have shown promise in clinical trials. PMID:23425518

2013-01-01

281

Peripheral Neuropathy – Clinical and Electrophysiological Considerations  

PubMed Central

This article is a primer on the pathophysiology and clinical evaluation of peripheral neuropathy for the radiologist. Magnetic resonance neurography (MRN) has utility in the diagnosis of many focal peripheral nerve lesions. When combined with history, examination, electrophysiology, and laboratory data, future advancements in high-field MRN may play an increasingly important role in the evaluation of patients with peripheral neuropathy. PMID:24210312

Chung, Tae; Prasad, Kalpana; Lloyd, Thomas E.

2013-01-01

282

Disulfiram-induced neuropathy: a case report.  

PubMed

Disulfiram is widely used for aversive treatment of alcoholism. Neuropathy is one of the most severe side effects of disulfiram therapy. We report the case of a young man who developed a neuropathy following disulfiram administration, with a virtually complete recovery within 2 months. PMID:25445071

Mohapatra, Satyakam; Sahoo, Manas Ranjan; Rath, Neelmadhav

2014-10-01

283

[Axonal involvement in dysimmune neuropathies].  

PubMed

Dysimmune neuropathies, in common with other neuropathies, comprise an axonal impairment that it is primary or secondary to a demyelinating process. We consider here axonal impairment in the course of certain dysimmune neuropathies, such as the Guillain Barré syndrome, chronic inflammatory demyelinating polyradiculoneuritis and multiple conduction block neuropathy. We mention the fact that it is not always easy to evidence the axonal impairment, its severity and its potential for regeneration. The mechanisms of the axonal lesions stem essentially from the special and tight bonds between the axon and the Schwann cell, which in the central central nervous system are mirrored by the bonds between axons and oligodendrocytes. Indeed, myelinating Schwann cells modify the properties of the axon in the normal peripheral nervous system, and abnormal Schwann cells induce pathological modifications. The periods of appearance of the axonal impairment are nevertheless quite variable depending on the type of the dysimmune neuropathy: acute or chronic. Some Guillain-Barré syndromes may be distinguished by a severe axonal impairment, now well documented and referred to as AMSAN and AMAN. Various mechanisms of axonal impairment are discussed. The bond between axon and myelin means that any pathological process in Schwann cells leads to axonal impairment, with inflammatory processes having a direct impact on the axon: mechanism of typical 'by-stander effect', repressive role of endoneurial edema, direct dysimmune attack on axonal epitopes on the corresponding axolemma, especially on the GM1 gangliosides, intra-axonal accumulation of sodium and calcium due to disruption the voltage-dependent sodium/potassium ion channels, slow retrograde progression to anterior horn neurons and possibly also to posterior spinal cords. The treatment of the axonal impairment is not straightforward; it is based, in a first instance, on the direct relation between the severity of the demyelinating lesions and the axonal impairment. For the acute forms of typical Guillain-Barré syndrome, the value of plasma exchanges and intravenous immunoglobulins has demonstrated in double blind, randomized trials. For the chronic demyelinating inflammatory polyradiculoneuritis, corticotherapy, along with plasma exchange and the immunoglobulins, have also been shown to be effective. Immunosuppressor treatment has benefits, but it is hard to prove objectively. It is generally recognized that it is only useful if applied for a period of weeks, although this is currently a matter of debate. Other therapeutic options have been discussed and proposed, although to date there is a lack of proven efficiency: such treatments include neuroprotective agents and drugs which block sodium/potassium ion channels. It is increasingly difficult to propose new treatments with validated efficiency, due to the small number of patients presenting dysimmune neuropathies of the type discussed here that are both typical and suitable for inclusion in medium to long term studies. PMID:18087224

Vallat, J-M

2007-09-01

284

Diabetic neuropathy and foot complications.  

PubMed

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

Boulton, Andrew J M

2014-01-01

285

Management of ischemic optic neuropathies  

PubMed Central

Ischemic optic neuropathies (IONs) consist primarily of two types: anterior ischemic optic neuropathy (AION) and posterior ischemic optic neuropathy (PION). AION comprises arteritic AION (A-AION: due to giant cell arteritis) and non-arteritic AION (NA-AION: due to other causes). PION consists of arteritic PION (A-PION: due to giant cell arteritis), non-arteritic PION (NA-PION: due to other causes), and surgical PION (a complication of several systemic surgical procedures). These five types of ION are distinct clinical entities etiologically, pathogenetically, clinically and from the management point of view. In the management of AION, the first crucial step with patients aged 50 and over is to identify immediately whether it is arteritic or not because A-AION is an ophthalmic emergency and requires urgent treatment with high-dose steroid therapy to prevent any further visual loss in one or both eyes. Patients with NA-AION, when treated with systemic corticosteroid therapy within first 2 weeks of onset, had significantly better visual outcome than untreated ones. Systemic risk factors, particularly nocturnal arterial hypotension, play major roles in the development of NA-AION; management of them is essential in its prevention and management. NA-PION patients, when treated with high-dose systemic steroid therapy during the very early stages of the disease, showed significant improvement in visual acuity and visual fields, compared to untreated eyes. A-PION, like A-AION, requires urgent treatment with high-dose steroid therapy to prevent any further visual loss in one or both eyes. There is no satisfactory treatment for surgical PION, except to take prophylactic measures to prevent its development. PMID:21350282

Hayreh, Sohan Singh

2011-01-01

286

Peripheral neuropathies from chemotherapeutics and targeted agents: diagnosis, treatment, and prevention  

PubMed Central

Peripheral neuropathies induced by chemotherapy (CIPN) are an increasingly frequent problem. Contrary to hema­tologic adverse effects, which can be treated with hematopoetic growth factors, neither prophylaxis nor spe­cific treatment is available, and only symptomatic treatment can be offered. Neurotoxic drugs are becoming a major dose-limiting factor. The epidemiology is still unclear. Several drug-dependent pathogenetic mechanisms exist. CIPN are predominately sensory, length-dependent neuropathies that develop after a typical cumulative dose. Usually, the appearance of CIPN is dose dependent, although in at least 2 drugs (oxaliplatin and taxanes), immediate toxic effects occur. The most frequent substances causing CIPN are platin compounds, vinka alkaloids, taxanes, and bortezomib and thalidomide. The role of synergistic neurotoxicity caused by previously given chemo­therapies and concomitant chemotherapies and the role pre-existent neuropathy on the development of a CIPN is not clear. As the number of long-term cancer survivors increases and a new focus on long-term effects of chemotherapy-induced neuropathies emerge, concepts of rehabili­tation need to be implemented to improve the patients’ functions and quality of life. PMID:23095830

Grisold, Wolfgang; Cavaletti, Guido; Windebank, Anthony J.

2012-01-01

287

A Novel and Selective Poly (ADP-Ribose) Polymerase Inhibitor Ameliorates Chemotherapy-Induced Painful Neuropathy  

PubMed Central

Background Chemotherapy-induced neuropathy is the principle dose limiting factor requiring discontinuation of many chemotherapeutic agents, including cisplatin and oxaliplatin. About 30 to 40% of patients receiving chemotherapy develop pain and sensory changes. Given that poly (ADP-ribose) polymerase (PARP) inhibition has been shown to provide neuroprotection, the current study was developed to test whether the novel PARP inhibitor compound 4a (analog of ABT-888) would attenuate pain in cisplatin and oxaliplatin-induced neuropathy in mice. Results An established chemotherapy-induced painful neuropathy model of two weekly cycles of 10 intraperitoneal (i.p.) injections separated by 5 days rest was used to examine the therapeutic potential of the PARP inhibitor compound 4a. Behavioral testing using von Frey, paw radiant heat, cold plate, and exploratory behaviors were taken at baseline, and followed by testing at 3, 6, and 8 weeks from the beginning of drug treatment. Conclusion Cisplatin-treated mice developed heat hyperalgesia and mechanical allodynia while oxaliplatin-treated mice exhibited cold hyperalgesia and mechanical allodynia. Co-administration of 50 mg/kg or 25 mg/kg compound 4a with platinum regimen, attenuated cisplatin-induced heat hyperalgesia and mechanical allodynia in a dose dependent manner. Similarly, co-administration of 50 mg/kg compound 4a attenuated oxaliplatin-induced cold hyperalgesia and mechanical allodynia. These data indicate that administration of a novel PARP inhibitor may have important applications as a therapeutic agent for human chemotherapy-induced painful neuropathy. PMID:23326593

Ta, Lauren E.; Schmelzer, James D.; Bieber, Allan J.; Loprinzi, Charles L.; Sieck, Gary C.; Brederson, Jill D.; Low, Philip A.; Windebank, Anthony J.

2013-01-01

288

Differential Transcriptome Profile of Peripheral White Cells to Identify Biomarkers Involved in Oxaliplatin Induced Neuropathy  

PubMed Central

Anticancer chemotherapy (CT) produces non-desirable effects on normal healthy cells and tissues. Oxaliplatin is widely used in the treatment of colorectal cancer and responsible for the development of sensory neuropathy in varying degrees, from complete tolerance to chronic neuropathic symptoms. We studied the differential gene expression of peripheral leukocytes in patients receiving oxaliplatin-based chemotherapy to find genes and pathways involved in oxaliplatin-induced peripheral neuropathy. Circulating white cells were obtained prior and after three cycles of FOLFOX or CAPOX chemotherapy from two groups of patients: with or without neuropathy. RNA was purified, and transcriptomes were analyzed. Differential transcriptomics revealed a total of 502 genes, which were significantly up- or down-regulated as a result of chemotherapy treatment. Nine of those genes were expressed in only one of two situations: CSHL1, GH1, KCMF1, IL36G and EFCAB8 turned off after CT, and CSRP2, IQGAP1, GNRH2, SMIM1 and C5orf17 turned on after CT. These genes are likely to be associated with the onset of oxaliplatin-induced peripheral neuropathy. The quantification of their expression in peripheral white cells may help to predict non-desirable side effects and, consequently, allow a better, more personalized chemotherapy.

Morales, Manuel; Ávila, Julio; González-Fernández, Rebeca; Boronat, Laia; Soriano, María Luisa; Martín-Vasallo, Pablo

2014-01-01

289

Electrodiagnostic evaluation of ulnar neuropathy and other upper extremity mononeuropathies.  

PubMed

Upper extremity mononeuropathies are some of the common disorders seen in neurophysiology laboratories. Electrophysiologic studies rely on accurate localization based on knowledge of applicable anatomy and features of history and physical examination. Careful electrodiagnostic studies provide an accurate diagnosis, help localize the lesion site, exclude alternate diagnoses, reveal unsuspected diagnoses, determine pathophysiology of lesions, and assess severity, timeframe, and prognosis of lesions. This article discusses the electrodiagnostic approach to ulnar neuropathy, proximal median neuropathy, radial neuropathy, musculocutaneous neuropathy, axillary neuropathy, suprascapular neuropathy, and long thoracic neuropathy. Pertinent aspects of the history and physical examination, nerve conduction studies, and electromyography are presented. PMID:22361371

Dimberg, Elliot L

2012-05-01

290

Autonomic neuropathy in diabetes mellitus.  

PubMed

Diabetic autonomic neuropathy (DAN) is a serious and common complication of diabetes, often overlooked and misdiagnosed. It is a systemic-wide disorder that may be asymptomatic in the early stages. The most studied and clinically important form of DAN is cardiovascular autonomic neuropathy defined as the impairment of autonomic control of the cardiovascular system in patients with diabetes after exclusion of other causes. The reported prevalence of DAN varies widely depending on inconsistent definition, different diagnostic method, different patient cohorts studied. The pathogenesis is still unclear and probably multifactorial. Once DAN becomes clinically evident, no form of therapy has been identified, which can effectively stop or reverse it. Prevention strategies are based on strict glycemic control with intensive insulin treatment, multifactorial intervention, and lifestyle modification including control of hypertension, dyslipidemia, stop smoking, weight loss, and adequate physical exercise. The present review summarizes the latest knowledge regarding clinical presentation, epidemiology, pathogenesis, and management of DAN, with some mention to childhood and adolescent population. PMID:25520703

Verrotti, Alberto; Prezioso, Giovanni; Scattoni, Raffaella; Chiarelli, Francesco

2014-01-01

291

Current understanding of auditory neuropathy.  

PubMed

Auditory neuropathy is defined by the presence of normal evoked otoacoustic emissions (OAE) and absent or abnormal auditory brainstem responses (ABR). The sites of lesion could be at the cochlear inner hair cells, spiral ganglion cells of the cochlea, synapse between the inner hair cells and auditory nerve, or the auditory nerve itself. Genetic, infectious or neonatal/perinatal insults are the 3 most commonly identified underlying causes. Children usually present with delay in speech and language development while adult patients present with hearing loss and disproportionately poor speech discrimination for the degree of hearing loss. Although cochlear implant is the treatment of choice, current evidence show that it benefits only those patients with endocochlear lesions, but not those with cochlear nerve deficiency or central nervous system disorders. As auditory neuropathy is a disorder with potential long-term impact on a child's development, early hearing screen using both OAE and ABR should be carried out on all newborns and infants to allow early detection and intervention. PMID:19904452

Boo, Nem-Yun

2008-12-01

292

Suprascapular neuropathy: diagnosis and management.  

PubMed

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

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

2012-02-01

293

Methyltestosterone therapy in hereditary angioedema.  

PubMed

In a double-blind study of four patients with hereditary angioedema, the efficacy of methyltestosterone (taken daily in 10-mg linguet form) in preventing attacks was shown. There were 19 episodes during 11.8 months of placebo administration, compared with only four attacks during the 46 months of cumulative methyltestosterone treatment (P less than 0.001). The mean serum C4 protein level was twice as high in all patients when they were taking the drug (176 +/- 36 mug/ml) as compared with the placebo (84 +/- 21 mug/ml), and rose to normal range in three of four patients. PMID:320930

Sheffer, A L; Fearon, D T; Austen, K F

1977-03-01

294

'Pseudocirrhosis' in hereditary haemorrhagic telangiectasia.  

PubMed Central

Telangiectasia-associated hepatic fibrosis (TAHF) in a 68-year-old woman with hereditary haemorrhagic telangiectasia (HHT) is described. The patient died of oat-cell carcinoma of the lung. In addition to the structural alterations which have been described previously in HHT, the liver exhibited focal midlobular hepatocytic necrosis and tumour metastases. The possibility that treatment of HHT was causally related to some of the hepatic abnormalities found in our patient and the differentiation of TAHF from true cirrhosis are discussed. Images PMID:203609

Cooney, T; Sweeney, E C; Coll, R; Greally, M

1977-01-01

295

Hereditary Phosphofructokinase Deficiency in Wachtelhunds  

PubMed Central

Hereditary phosphofructokinase (PFK) deficiency was diagnosed in two Wachtelhund dogs and suspected in three related Wachtelhund dogs with exercise intolerance, hemolytic anemia, and pigmenturia. Severe, persistent reticulocytosis in light of only mild anemia together with hemoglobinuria after strenuous exercise suggested PFK deficiency. Low erythrocyte PFK activity together with low 2,3-diphosphoglycerate concentrations and a high hemoglobin-oxygen affinity confirmed the diagnosis. The PFK deficiency is due to a single missense mutation in the muscle-type PFK M-PFK gene in English springer and American cocker spaniels, whippets, and mixed-breed dogs; however, these PFK-deficient Wachtelhunds do not have the same PFK mutation. PMID:21311071

Hillström, Anna; Tvedten, Harold; Rowe, André; Giger, Urs

2011-01-01

296

ON (STRONGLY) GORENSTEIN (SEMI)HEREDITARY RINGS  

E-print Network

Abstract. In this paper, we introduce and study the rings of Gorenstein homological dimensions small or equal than 1, which we call Gorenstein (semi)hereditary rings, specially particular cases of these rings, which we call strongly Gorenstein (semi)hereditary rings. 1.

Najib Mahdou; Mohammed Tamekkante

297

On (Strongly) Gorenstein (Semi)Hereditary Rings  

Microsoft Academic Search

In this paper, we introduce and study the rings of Gorenstein homological dimensions less than or equal to 1. We call these\\u000a Gorenstein (semi)hereditary rings and call a particular subclass of these strongly Gorenstein (semi)hereditary rings.

Najib Mahdou; Mohammed Tamekkante

2011-01-01

298

On (strongly) Gorenstein (semi)hereditary rings  

Microsoft Academic Search

In this paper, we introduce and study the rings of Gorenstein homological dimensions small or equal than 1, which we call Gorenstein (semi)hereditary rings, specially particular cases of these rings, which we call strongly Gorenstein (semi)hereditary rings.

Najib Mahdou; Mohammed Tamekkante

2008-01-01

299

Hereditary ovarian cancer in Ashkenazi Jews  

Microsoft Academic Search

Ovarian cancer is the fourth leading cause of cancer deaths among American women. While women in both the Ashkenazi and non-Ashkenazi populations have an estimated 1.7% lifetime risk of acquiring malignancy, the proportion of hereditary ovarian cancer is much higher in the Ashkenazim. Most of this increased proportion of hereditary ovarian cancer risk is accounted for by inherited mutations in

Luis Robles-díaz; Deborah J Goldfrank; Noah D Kauff; Mark Robson; Kenneth Offit

2004-01-01

300

Diabetic neuropathy: structural analysis of nerve hydration by Magnetic Resonance Spectroscopy  

SciTech Connect

The water content of the sural nerve of diabetic patients was quantitatively defined by magnetic resonance proton imaging as a putative reflection of activity of the aldose-reductase pathway. Thirty-nine patients were evaluated, comparing group A, symptomatic diabetic men with sensory neuropathy; group B, similarly symptomatic diabetic men treated aldose-reductase inhibition; group C, neurologically asymptomatic diabetic men; and group D, control nondiabetic men. Marked increase in hydration of the sural nerve was seen in more than half of the symptomatic diabetic patients. Two of 11 neurologically asymptomatic diabetics had increased nerve hydration, suggesting a presymptomatic alteration of the nerve. Symptomatic diabetics treated with aldose-reductase inhibitors had normal nerve water levels. Increased level of peripheral nerve water represents a new finding in diabetes mellitus. It seems to be related to aldose-reductase activity, involved in the development of neuropathy, and similar to events that occur in other target tissue in human diabetes.

Griffey, R.H.; Eaton, P.; Sibbitt, R.R.; Sibbitt, W.L. Jr.; Bicknell, J.M.

1988-11-18

301

Novel Compound Heterozygous Nonsense PRX Mutations in a Korean Dejerine-Sottas Neuropathy Family  

PubMed Central

Background Mutations in the gene encoding periaxin (PRX) are known to cause autosomal recessive Dejerine-Sottas neuropathy (DSN) or Charcot-Marie-Tooth disease type 4F. However, there have been no reports describing Korean patients with these mutations. Case Report We examined a Korean DSN patient with an early-onset, slowly progressive, demyelinating neuropathy with prominent sensory involvement. Whole-exome sequencing and subsequent capillary sequencing revealed novel compound heterozygous nonsense mutations (p.R392X and p.R679X) in PRX. One mutation was transmitted from each of the patient's parents. No unaffected family member had both mutations, and the mutations were not found in healthy controls. Conclusions We believe that these novel compound heterozygous nonsense mutations are the underlying cause of DSN. The clinical, electrophysiologic, and pathologic phenotypes in this family were similar to those described previously for patients with PRX mutations. We have identified the first PRX mutation in a Korean patient with DSN.

Choi, Ye Ji; Hyun, Young Se; Nam, Soo Hyun; Koo, Heasoo; Hong, Young Bin

2015-01-01

302

Cutaneous nociceptors lack sensitisation, but reveal ?-opioid receptor-mediated reduction in excitability to mechanical stimulation in neuropathy  

PubMed Central

Background Peripheral nerve injuries often trigger a hypersensitivity to tactile stimulation. Behavioural studies demonstrated efficient and side effect-free analgesia mediated by opioid receptors on peripheral sensory neurons. However, mechanistic approaches addressing such opioid properties in painful neuropathies are lacking. Here we investigated whether opioids can directly inhibit primary afferent neuron transmission of mechanical stimuli in neuropathy. We analysed the mechanical thresholds, the firing rates and response latencies of sensory fibres to mechanical stimulation of their cutaneous receptive fields. Results Two weeks following a chronic constriction injury of the saphenous nerve, mice developed a profound mechanical hypersensitivity in the paw innervated by the damaged nerve. Using an in vitro skin-nerve preparation we found no changes in the mechanical thresholds and latencies of sensory fibres from injured nerves. The firing rates to mechanical stimulation were unchanged or reduced following injury. Importantly, ?-opioid receptor agonist [D-Ala2,N-Me-Phe4,Gly5]-ol-enkephalin (DAMGO) significantly elevated the mechanical thresholds of nociceptive A? and C fibres. Furthermore, DAMGO substantially diminished the mechanically evoked discharges of C nociceptors in injured nerves. These effects were blocked by DAMGO washout and pre-treatment with the selective ?-opioid receptor antagonist Cys2-Tyr3-Orn5-Pen7-amide. DAMGO did not alter the responses of sensory fibres in uninjured nerves. Conclusions Our findings suggest that behaviourally manifested neuropathy-induced mechanosensitivity does not require a sensitised state of cutaneous nociceptors in damaged nerves. Yet, nerve injury renders nociceptors sensitive to opioids. Prevention of action potential generation or propagation in nociceptors might represent a cellular mechanism underlying peripheral opioid-mediated alleviation of mechanical hypersensitivity in neuropathy. PMID:23116256

2012-01-01

303

Obstructive Sleep Apnea and Diabetic Neuropathy  

PubMed Central

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

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

2012-01-01

304

Surgical and postpartum hereditary brachial plexus attacks and prophylactic immunotherapy  

PubMed Central

Introduction Surgery and childbirth can trigger attacks of hereditary brachial plexus neuropathy (HBPN), and inflammation was suggested as a component of the pathogenesis. Methods HBPN patients who underwent surgery or parturition from Jan.1,1996 to Dec.31,2009 were studied. Results Twenty-five HBPN patients underwent 48 surgeries or parturitions. Seventeen patients (68%) had attacks, including 13 periprocedural and 7 postpartum by varied anesthesia types. Three patients who had 8 earlier combined attacks (after thyroidectomy, laminectomy, and Caesarean section) were given prophylactic immunosuppressive therapy (corticosteroids ± immunoglobulin). None suffered postoperative attacks, which is uncharacteristic of their prior experience. Five had perioperative attacks as their first HBPN manifestation. Median follow-up was 11(3-48) months. Attacks occurred in the operated limb (n=6) or distant (n=7) to surgical sites. All attacks interfered with daily living, with frequent incomplete recovery. Five patients had a SEPT9 mutation. Conclusions Corticosteroid may prevent parturition and surgical HBPN attacks in some patients. Diverse surgeries, anesthesia and childbirth frequently trigger HBPN attacks. PMID:23042485

Klein, Christopher J.; Barbara, David W.; Sprung, Juraj; Dyck, Peter J.; Weingarten, Toby N.

2012-01-01

305

Structural basis of hereditary coproporphyria  

PubMed Central

Hereditary coproporphyria is an autosomal dominant disorder resulting from the half-normal activity of coproporphyrinogen oxidase (CPO), a mitochondrial enzyme catalyzing the antepenultimate step in heme biosynthesis. The mechanism by which CPO catalyzes oxidative decarboxylation, in an extraordinary metal- and cofactor-independent manner, is poorly understood. Here, we report the crystal structure of human CPO at 1.58-Ĺ resolution. The structure reveals a previously uncharacterized tertiary topology comprising an unusually flat seven-stranded ?-sheet sandwiched by ?-helices. In the biologically active dimer (KD = 5 × 10-7 M), one monomer rotates relative to the second by ?40° to create an intersubunit interface in close proximity to two independent enzymatic sites. The unexpected finding of citrate at the active site allows us to assign Ser-244, His-258, Asn-260, Arg-262, Asp-282, and Arg-332 as residues mediating substrate recognition and decarboxylation. We favor a mechanism in which oxygen serves as the immediate electron acceptor, and a substrate radical or a carbanion with substantial radical character participates in catalysis. Although several mutations in the CPO gene have been described, the molecular basis for how these alterations diminish enzyme activity is unknown. We show that deletion of residues (392-418) encoded by exon six disrupts dimerization. Conversely, harderoporphyria-causing K404E mutation precludes a type I ?-turn from retaining the substrate for the second decarboxylation cycle. Together, these findings resolve several questions regarding CPO catalysis and provide insights into hereditary coproporphyria. PMID:16176984

Lee, Dong-Sun; Flachsová, Eva; Bodnárová, Michaela; Demeler, Borries; Martásek, Pavel; Raman, C. S.

2005-01-01

306

The Neuropathies of Waldenström’s Macroglobulinemia (WM) and IgM-MGUS  

PubMed Central

Background Neuropathy is common in Waldenström’s macroglobulinemia (WM, an IgM-associated lymphoplasmacytic lymphoma) and in IgM-monoclonal gammopathy of undetermined significance (IgM-MGUS). Paraneoplastic or paraimmune mechanisms are thought to be involved in the pathogenesis of these neuropathies. Attempts at distinguishing WM and IgM-MGUS neuropathies are lacking especially among bone marrow (BM) confirmed patients. Methods Retrospective analyses were performed on BM confirmed WM (N=30) and IgM-MGUS (N=73) neuropathy patients with neurologic assessments and hematologic features. Results The presence of anemia and quantity of IgM monoclonal protein were significantly greater in WM. Based on multiple neurologic assessments differences were not found for: 1) length of time from neurologic symptom onset to evaluation; 2) chief complaint of painless loss of feeling in the feet, Romberg’s sign and tremor; and 3) clinical motor, sensory and reflex abnormalities. Autonomic testing was normal in both diseases. Using nerve conduction (NCS) criteria for demyelination, 62% of IgM-MGUS and 27% of WM met this criteria (p=0.013). IgM MGUS patients had greater terminal conduction slowing by ulnar residual latency calculation (<0.01). The degree of axonal loss as measured by summated compound muscle action potentials and available nerve biopsy was not significantly different between diseases. Conclusion Although WM and IgM-MGUS must be distinguished for hematologic prognosis and treatment, clinical neuropathy presentations of WM and IgM-MGUS are similar and likely related to comparable axonal loss in both conditions. Despite these similarities, evidence of demyelination was found by electrophysiologic studies much more commonly in IgM-MGUS. This difference may reflect varied immune mechanism(s) in the two disorders. PMID:21320835

Klein, Christopher J.; Moon, Joon-Shik; Mauermann, Michelle L.; Zeldenrust, Steven R.; Wu, Yanhong; Dispenzieri, Angela; Dyck, Peter J.

2014-01-01

307

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. PMID:24891949

Rajbhandari, Satyan

2014-01-01

308

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. PMID:24088636

Karuppannasamy, Divya; Raghuram, Andavar; Sundar, Devisundaram

2014-01-01

309

Uses of Skin Biopsy for Sensory and Autonomic Nerve Assessment  

PubMed Central

Skin biopsy is a valuable diagnostic tool for small-fiber-predominant neuropathy by the quantification of intra-epidermal nerve fiber density (IENFD). It has the unique advantage of being a minimally invasive procedure with the potential for longitudinal evaluation of both sensory and autonomic fibers. Unmyelinated small fibers are not otherwise quantified objectively with such a level of sensitivity as has been reported with IENFD. Recent advances include an expansion of the skin punch biopsy technique to evaluate larger myelinated fibers and mechanoreceptors, and recent work has also focused on additional methods of quantifying dermal fibers and densely innervated autonomic structures. This review discusses current work using skin biopsy for the pathologic analysis of peripheral nerve fibers in neuropathy of various causes as well as its use in clinical trials. PMID:23250768

Myers, M. Iliza; Peltier, Amanda C.

2013-01-01

310

Symplectic structures, their Bäcklund transformations and hereditary symmetries  

Microsoft Academic Search

It is shown that compatible symplectic structures lead in a natural way to hereditary symmetries. (We recall that a hereditary symmetry is an operator-valued function which immediately yields a hierarchy of evolution equations, each having infinitely many commuting symmetries all generated by this hereditary symmetry. Furthermore this hereditary symmetry usually describes completely the soliton structure and the conservation laws of

B. Fuchssteiner; A. S. Fokas

1981-01-01

311

Bicycling induced pudendal nerve pressure neuropathy.  

PubMed

Pudendal neuropathies are well recognised as part of more generalised peripheral neuropathies; however, focal abnormalities of the pudendal nerve due to cycling-related injuries have been infrequently reported. We describe two patients who developed pudendal neuropathies secondary to pressure effects on the perineum from racing-bicycle saddles. Both were male competitive athletes, one of whom developed recurrent numbness of the penis and scrotum after prolonged cycling; the other developed numbness of the penis, an altered sensation of ejaculation, with disturbance of micturition and reduced awareness of defecation. Both patients improved with alterations in saddle position and riding techniques. We conclude that pudendal nerve pressure neuropathy can result from prolonged cycling, particularly when using a poor riding technique. PMID:1821826

Silbert, P L; Dunne, J W; Edis, R H; Stewart-Wynne, E G

1991-01-01

312

INHERITED NEUROPATHIES: CLINICAL OVERVIEW AND UPDATE  

PubMed Central

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.

2014-01-01

313

Fatigue in immune-mediated neuropathies.  

PubMed

Fatigue, a highly debilitating symptom, is reported in most patients with immune-mediated neuropathies, particularly in Guillain-Barré syndrome, chronic immune-mediated demyelinating polyradiculoneuropathy, monoclonal gammopathy of undetermined significance related polyneuropathy, and multifocal motor neuropathy. Aspects like the degree of known fatigue in these disorders, its impact on daily functioning and quality of life, the suggested underlying mechanisms, and possible therapeutic interventions for fatigue will be addressed in this review. PMID:23182640

Merkies, Ingemar S J; Faber, Catharina G

2012-12-01

314

Cigarette smoking and neuropathy in diabetic patients.  

PubMed

We studied whether lifetime cigarette smoking is associated with the presence of diabetic neuropathy. The research design consisted of a case-control study conducted from a referral-based diabetes clinic at a major medical center. The patients were a 65% sample (163 insulin-dependent diabetes mellitus [IDDM] and 166 non-insulin-dependent diabetes mellitus [NIDDM] patients) of all patients admitted during a 26-mo period. Neuropathy was diagnosed on the basis of signs and symptoms. Smoking history was obtained by mailed questionnaire (66% response rate). Diabetes duration, HbA1, age, sex, peripheral vascular disease, hypertension history, and lifetime alcohol consumption were measured as covariates. The prevalence of neuropathy was 49 and 38% in IDDM (n = 113) and NIDDM (n = 104) patients, respectively. In IDDM, but not NIDDM, current or ex-smokers were significantly more likely to have neuropathy than individuals who had never smoked (odds ratio 2.46, P = 0.02), and the prevalence of neuropathy increased with increasing number of pack-years smoked (P less than 0.001). After adjustment for covariates, IDDM patients smoking greater than or equal to 30 pack-yr were 3.32 times more likely to have neuropathy than patients smoking less than this amount (95% confidence interval 1.15-9.58, P = 0.026). Cigarette smoking was associated with the presence of neuropathy in this clinic-based population of IDDM patients. The hypothesis that cigarette smoking is associated with diabetic neuropathy should be investigated further, both prospectively and in a more representative population. PMID:2318103

Mitchell, B D; Hawthorne, V M; Vinik, A I

1990-04-01

315

Genetics Home Reference: Hereditary neuralgic amyotrophy  

MedlinePLUS

... neuralgic amyotrophy also have unusual physical characteristics including short stature, excess skin folds on the neck and arms, ... immune system ; inherited ; isoforms ; neuropathy ; palate ; prevalence ; protein ; short stature ; sign ; spontaneous ; stature ; stress ; surgery ; syndactyly ; tissue ; uvula ; ...

316

Pure sensory Guillain-Barré syndrome: A case report and review of the literature.  

PubMed

Sensory Guillain-Barré syndrome (GBS) is an acute demyelinating neuropathy that presents clinically with involvement of the sensory peripheral nerve only. To date, <10 cases of pure sensory GBS have been reported; thus, the clinical and pathological features of sensory variant GBS are yet to be well characterized. The current study reports the case of a 43-year-old female that presented with acute, symmetric and monophasic sensory neuropathy, without motor weakness. Patient history, clinical examination, routine nerve conduction studies and sural nerve biopsy were reviewed. All the observations were consistent with a diagnosis of pure sensory GBS. In particular, the pathological features of the sural nerve biopsy revealed that the form of regenerated nerve fibers have complete structure of myelinated nerve fascicles, and these myelinated nerve fibers are thicker than other parts of the biopsy. The patient received small-dose (20 mg/day) prednisone initially, but without any benefit. Satisfactory improvements were observed with one course of intravenous immunoglobulin. PMID:25289029

Yang, Jingjing; Huan, Mingming; Jiang, Huajun; Song, Chunli; Zhong, Lin; Liang, Zhanhua

2014-11-01

317

HEREDITARY ACHONDROPLASIA IN THE RABBIT  

PubMed Central

Hereditary achondroplasia (chondrodystrophia foetalis) in the rabbit has been described in the present and preceding papers (1, 2). It is the first instance of this abnormality in rodents to be reported. The variation arose in pure bred Havana stock. The abnormality is determined by the expression of a simple recessive unit factor, affected individuals being homozygous for the factor. Females are somewhat more frequently affected than males, but the character is not sex-linked. Rabbits heterozygous for the factor as determined by appropriate breeding tests have a perfectly normal appearance at birth and in later life. The condition appears to be determined solely by the genetic constitution of the animal. Attention was drawn to the fact that although the development of the achondroplastic form proceeds to birth at term, death regularly occurs at the time of or very shortly after parturition. This feature of the condition is briefly discussed. PMID:19871500

Pearce, Louise; Brown, Wade H.

1945-01-01

318

Imaging of Hereditary Hemorrhagic Telangiectasia  

SciTech Connect

This pictorial review is based on our experience of the follow-up of 120 patients at our multidisciplinary center for hereditary hemorrhagic telangiectasia (HHT). Rendu-Osler-Weber disease or HHT is a multiorgan autosomal dominant disorder with high penetrance, characterized by epistaxis, mucocutaneous telangiectasis, and visceral arteriovenous malformations (AVMs). The research on gene mutations is fundamental and family screening by clinical examination, chest X-ray, research of pulmonary shunting, and abdominal color Doppler sonography is absolutely necessary. The angioarchitecture of pulmonary AVMs can be studied by unenhanced multidetector computed tomography; however, all other explorations of liver, digestive bowels, or brain require administration of contrast media. Magnetic resonance angiography is helpful for central nervous system screening, in particular for the spinal cord, but also for pulmonary, hepatic, and pelvic AVMs. Knowledge of the multiorgan involvement of HHT, mechanism of complications, and radiologic findings is fundamental for the correct management of these patients.

Carette, Marie-France, E-mail: marie-france.carette@tnn.aphp.fr; Nedelcu, Cosmina; Tassart, Marc [AP-HP Tenon Hospital, Radiology Department (France); Grange, Jean-Didier; Wislez, Marie [Centre d'Accueil de la Maladie de Rendu Osler de Tenon (CAMROT) (France); Khalil, Antoine, E-mail: antoine_khalil@yahoo.f [AP-HP Tenon Hospital, Radiology Department (France)

2009-07-15

319

Structural basis of hereditary coproporphyria.  

PubMed

Hereditary coproporphyria is an autosomal dominant disorder resulting from the half-normal activity of coproporphyrinogen oxidase (CPO), a mitochondrial enzyme catalyzing the antepenultimate step in heme biosynthesis. The mechanism by which CPO catalyzes oxidative decarboxylation, in an extraordinary metal- and cofactor-independent manner, is poorly understood. Here, we report the crystal structure of human CPO at 1.58-A resolution. The structure reveals a previously uncharacterized tertiary topology comprising an unusually flat seven-stranded beta-sheet sandwiched by alpha-helices. In the biologically active dimer (K(D) = 5 x 10(-7) M), one monomer rotates relative to the second by approximately 40 degrees to create an intersubunit interface in close proximity to two independent enzymatic sites. The unexpected finding of citrate at the active site allows us to assign Ser-244, His-258, Asn-260, Arg-262, Asp-282, and Arg-332 as residues mediating substrate recognition and decarboxylation. We favor a mechanism in which oxygen serves as the immediate electron acceptor, and a substrate radical or a carbanion with substantial radical character participates in catalysis. Although several mutations in the CPO gene have been described, the molecular basis for how these alterations diminish enzyme activity is unknown. We show that deletion of residues (392-418) encoded by exon six disrupts dimerization. Conversely, harderoporphyria-causing K404E mutation precludes a type I beta-turn from retaining the substrate for the second decarboxylation cycle. Together, these findings resolve several questions regarding CPO catalysis and provide insights into hereditary coproporphyria. PMID:16176984

Lee, Dong-Sun; Flachsová, Eva; Bodnárová, Michaela; Demeler, Borries; Martásek, Pavel; Raman, C S

2005-10-01

320

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

PubMed

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

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

2004-01-01

321

Sensory neuronopathy complicating systemic lupus erythematosus: a case report  

PubMed Central

Introduction Systemic lupus erythematosus is a multi-system connective tissue disorder. Peripheral neuropathy is a known and underestimated complication in systemic lupus erythematosus. Ganglionopathy manifests when neuronal cell bodies in the dorsal root ganglion are involved. Autoimmune disorders are a known etiology, with systemic lupus erythematosus being a rare cause. Case presentation A 32-year-old South Asian woman presented with oral ulceration involving her lips following initiation of treatment for a febrile illness associated with dysuria. She had a history of progressively worsening numbness over a period of 4 months involving both the upper and lower limbs symmetrically while sparing the trunk. Her vibration sense was impaired, and her reflexes were diminished. For the past 4 years, she had had a bilateral, symmetrical, non-deforming arthritis involving the upper and lower limbs. Her anti-nuclear antibody and anti-double-stranded deoxyribonucleic acid status were positive. Although her anti-Ro antibodies were positive, she did not have clinical features suggestive of Sjögren syndrome. Nerve conduction studies revealed sensory neuronopathy. A diagnosis of systemic lupus erythematosus complicated by sensory neuronopathy was made. Treatment with intravenous immunoglobulin resulted in clinical and electrophysiological improvement. Conclusion Peripheral neuropathy in systemic lupus erythematosus can, by itself, be a disabling feature. Nerve conduction studies should be considered when relevant. Neuropathy in systemic lupus erythematosus should be given greater recognition, and rarer forms of presentation should be entertained in the differential diagnosis when the clinical picture is atypical. Intravenous immunoglobulin may have role in treatment of sensory neuronopathy in systemic lupus erythematosus. PMID:24884917

2014-01-01

322

Genetic Testing for Hereditary Colorectal Cancer  

MedlinePLUS

... this? Submit What's this? Submit Button CDC Features Genetic Testing for Hereditary Colorectal Cancer Language: English Espańol ( ... new podcast about genetic testing for Lynch syndrome . Genetic Testing for Lynch Syndrome Genetic testing is used ...

323

Haem arginate in acute hereditary coproporphyria  

Microsoft Academic Search

An 11 year old boy presented with severe acute hereditary coproporphyria. Despite supportive measures his condition deteriorated after admission. Haem arginate, started two days after presentation, produced appreciable inhibition of porphyrin precursor overproduction and clinical improvement.

D J Manning; T A Gray

1991-01-01

324

Haem arginate in acute hereditary coproporphyria.  

PubMed Central

An 11 year old boy presented with severe acute hereditary coproporphyria. Despite supportive measures his condition deteriorated after admission. Haem arginate, started two days after presentation, produced appreciable inhibition of porphyrin precursor overproduction and clinical improvement. PMID:2053800

Manning, D J; Gray, T A

1991-01-01

325

Genetics Home Reference: Hereditary diffuse gastric cancer  

MedlinePLUS

... Patients and Families Resources for Health Professionals What glossary definitions help with understanding hereditary diffuse gastric cancer? ... many other terms in the Genetics Home Reference Glossary . See also Understanding Medical Terminology . References (9 links) ...

326

Genetics Home Reference: Hereditary multiple exostoses  

MedlinePLUS

... Patients and Families Resources for Health Professionals What glossary definitions help with understanding hereditary multiple exostoses? autosomal ; ... many other terms in the Genetics Home Reference Glossary . See also Understanding Medical Terminology . References (7 links) ...

327

Treating Hereditary Thyroid Cancer in Children  

Cancer.gov

In this clinical trial, doctors are testing a new drug called vandetanib (Zactima) in young patients with advanced hereditary medullary thyroid cancer. Vandetanib targets the specific genetic defect responsible for these tumors.

328

Peroneal nerve palsy caused by popliteal pseudoaneurysm in a child with hereditary multiple exostosis.  

PubMed

A 12-year-old boy with a family history of hereditary multiple exostosis presented with a 3-week history of progressive knee swelling. The clinical examination revealed drop foot and a loss of extension in his right knee. Evaluation with color duplex ultrasonography, computed tomography angiography, and magnetic resonance imaging revealed a popliteal artery pseudoaneurysm associated with exostosis from the distal femur. This patient was diagnosed as having peroneal neuropathy caused by popliteal artery pseudoaneurysm compressing the nerve in the right popliteal fossa. The pseudoaneurysm was repaired primarily, and the exostosis was excised during the operation. Pain and knee contracture resolved after surgery. The patient was then referred to physical therapy for the management of drop foot. PMID:24326060

Onan, Burak; Onan, Ismihan Selen; Guner, Yesim; Yeniterzi, Mehmet

2014-05-01

329

Signaling by Sensory Receptors  

PubMed Central

Sensory systems detect small molecules, mechanical perturbations, or radiation via the activation of receptor proteins and downstream signaling cascades in specialized sensory cells. In vertebrates, the two principal categories of sensory receptors are ion channels, which mediate mechanosensation, thermosensation, and acid and salt taste; and G-protein-coupled receptors (GPCRs), which mediate vision, olfaction, and sweet, bitter, and umami tastes. GPCR-based signaling in rods and cones illustrates the fundamental principles of rapid activation and inactivation, signal amplification, and gain control. Channel-based sensory systems illustrate the integration of diverse modulatory signals at the receptor, as seen in the thermosensory/pain system, and the rapid response kinetics that are possible with direct mechanical gating of a channel. Comparisons of sensory receptor gene sequences reveal numerous examples in which gene duplication and sequence divergence have created novel sensory specificities. This is the evolutionary basis for the observed diversity in temperature- and ligand-dependent gating among thermosensory channels, spectral tuning among visual pigments, and odorant binding among olfactory receptors. The coding of complex external stimuli by a limited number of sensory receptor types has led to the evolution of modality-specific and species-specific patterns of retention or loss of sensory information, a filtering operation that selectively emphasizes features in the stimulus that enhance survival in a particular ecological niche. The many specialized anatomic structures, such as the eye and ear, that house primary sensory neurons further enhance the detection of relevant stimuli. PMID:22110046

Julius, David; Nathans, Jeremy

2012-01-01

330

Refsum's disease: a peroxisomal disorder affecting phytanic acid a-oxidation  

Microsoft Academic Search

Refsum's disease (hereditary motor sensory neuropathy type IV, heredopathia atactica polyneuritiformis) is an auto- somal recessive disorder the clinical features of which include retinitis pigmentosa, blindness, anosmia, deafness, sensory neuropathy, ataxia and accumulation of phytanic acid in plasma- and lipid-containing tissues. The transport and bio- chemical pathways of phytanic acid metabolism have recently been defined with the cloning of two

Anthony S. Wierzbicki; Matthew D. Lloyd; Christopher J. Schofield; Michael D. Feher; F. Brian Gibberd

331

Peripheral neuropathy in mice with neuronal nitric oxide synthase gene deficiency  

PubMed Central

Evidence for the important role of the potent oxidant peroxynitrite in peripheral diabetic neuropathy and neuropathic pain is emerging. This study evaluated the contribution of neuronal nitric oxide synthase (nNOS) to diabetes-induced nitrosative stress in peripheral nerve and dorsal root ganglia, and peripheral nerve dysfunction and degeneration. Control and nNOS?/? mice were made diabetic with streptozotocin, and maintained for 6 weeks. Peroxynitrite injury was assessed by nitrotyrosine and poly(ADP-ribose) immunoreactivities. Peripheral diabetic neuropathy was evaluated by measurements of sciatic motor and hind-limb digital sensory nerve conduction velocities, thermal algesia, tactile allodynia, and intraepidermal nerve fiber density. Control nNOS?/? mice displayed normal motor nerve conduction velocity and thermal response latency, whereas sensory nerve conduction velocity was slightly lower compared with non-diabetic wild-type mice, and tactile response threshold and intraepidermal nerve fiber density were reduced by 47 and 38%, respectively. Both diabetic wild-type and nNOS?/? mice displayed enhanced nitrosative stress in peripheral nerve. In contrast to diabetic wild-type mice, diabetic nNOS?/? mice had near normal nitrotyrosine and poly(ADP-ribose) immunofluorescence in dorsal root ganglia. Both diabetic wild-type and nNOS?/? mice developed motor and sensory nerve conduction velocity deficits and thermal hypoalgesia although nNOS gene deficiency slightly reduced severity of the three disorders. Tactile response thresholds were similarly decreased in control and diabetic nNOS?/? mice compared with non-diabetic wild-type mice. Intraepidermal nerve fiber density was lower by 27% in diabetic nNOS?/? mice compared with the corresponding non-diabetic group, and by 20% in diabetic nNOS?/? mice compared with diabetic wild-type mice. In conclusion, nNOS is required for maintaining the normal peripheral nerve function and small sensory nerve fibre innervation. nNOS gene deficiency does not protect from development of nerve conduction deficit, sensory neuropathy and intraepidermal nerve fiber loss. PMID:19360314

VARENIUK, IGOR; PACHER, PAL; PAVLOV, IVAN A.; DREL, VIKTOR R.; OBROSOVA, IRINA G.

2009-01-01

332

Treatment of painful diabetic neuropathy.  

PubMed

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

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

2015-01-01

333

Mouse Models of Diabetic Neuropathy  

PubMed Central

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

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

2014-01-01

334

Treatment of painful diabetic neuropathy  

PubMed Central

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

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

2015-01-01

335

Suprascapular neuropathy in volleyball players.  

PubMed

Entrapment neuropathy of the suprascapular nerve (SNE), although a recognised clinical entity, is a relatively rare cause of shoulder pain and subjective weakness in the athlete involved in overhead sports like volleyball and badminton. This study deals with the presentation and management of four unusual cases of suprascapular nerve entrapment in volleyball players. Four male volleyball players presented to our department with intractable shoulder pain and subjective sensation of shoulder weakness. They all had visible wasting of both supraspinatus and infraspinatus muscles, together with weakness of abduction and external rotation of the arm. They all responded temporarily to a diagnostic injection of local anaesthetic. MR imaging was useful in diagnosing space occupying lesions in three cases and the presence of a hypertrophic suprascapular ligament in one case. Due to failure of non- operative treatment, which included activity modification, rest, analgesics and rehabilitation programme over 6 months, surgery was then required to decompress the suprascapular nerve. All patients were symptom free at 6 months postoperatively and after an intensive rehabilitation programme, they were able to return to their normal level of activity including sport. PMID:16035699

Dramis, Asterios; Pimpalnerkar, Ashvin

2005-06-01

336

PHENYLMETHYLSULFONYL FLUORIDE PROTECTS RATS FROM MIPAFOX-INDUCED DELAYED NEUROPATHY  

EPA Science Inventory

Initiation of organophosphorus-induced delayed neuropathy (OPIDN) is thought to consist of two molecular events involving the phosphorylation of the target enzyme, neurotoxic esterase or neuropathy target enzyme (NTE), and a subsequent 'aging' reaction which transforms the inhibi...

337

Peripheral Neuropathy in Rats Exposed to Dichloroacetate  

PubMed Central

The use of dichloroacetate (DCA) for treating patients with mitochondrial diseases is limited by the induction of peripheral neuropathy. The mechanisms of DCA-induced neuropathy are not known. Oral DCA treatment (50–500 mg/kg/day for up to 16 weeks) induced tactile allodynia in both juvenile and adult rats; concurrent thermal hypoalgesia developed at higher doses. Both juvenile and adult rats treated with DCA developed nerve conduction slowing that was more pronounced in adult rats. No overt axonal or glial cell abnormalities were identified in peripheral nerves or spinal cord of any DCA-treated rats but morphometric analysis identified a reduction of mean axonal caliber of peripheral nerve myelinated fibers. DCA treatment also caused accumulation of oxidative stress markers in the nerves. These data indicate that behavioral, functional and structural indices of peripheral neuropathy may be induced in both juvenile and adult rats treated with DCA at doses similar to those in clinical use. DCA-induced peripheral neuropathy primarily afflicts axons and involves both metabolic and structural disorders. The DCA-treated rat may provide insight into the pathogenesis of peripheral neuropathy and facilitate development of adjuvant therapeutics to prevent this disorder that currently restricts the clinical use of DCA. PMID:19680144

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

2009-01-01

338

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

339

NEUROPHYSIOLOGICAL EVALUATION OF SENSORY SYSTEMS'  

EPA Science Inventory

Exposure to many neurotoxic compounds has been shown to produce a sensory system dysfunction. Neurophysiological assessment of sensory function in humans and animal models often uses techniques known as sensory evoked potentials. Because both humans and animals show analogous res...

340

The hereditary autoinflammatory disorders uncovered.  

PubMed

There is a thriving interest in the field of hereditary autoinflammatory disorders (HAID), a gamut of heterogeneous conditions deriving from an aberrant orchestration of innate immunity, unified by the common feature of seemingly unprovoked inflammation, which might be systemic or occur in localized niches of the organism. Recurrent fever and episodic inflammation in the joints, serosal membranes, skin, gut, and other organs are the common denominator of HAID. Mutations in the inflammasome-related genes have been associated with different HAID, showing the intimate link existing between interleukin-1 (IL-1)-structured inflammasome and their pathogenesis. Differential diagnosis of HAID can be challenging, as there are no universally accepted diagnostic protocols, and near half of patients may remain without any genetic abnormality identified. The use of IL-1-antagonists has been associated with beneficial effects in a large number of HAID associated with excessive IL-1 signalling, such as cryopyrin-associated periodic syndromes, familial Mediterranean fever, and deficiency of IL-1 receptor antagonist. This review will discuss about the key-clues of HAID which might guide for an early recognition and drive decisions for treatment. PMID:25149390

Rigante, Donato; Vitale, Antonio; Lucherini, Orso Maria; Cantarini, Luca

2014-09-01

341

Molecular basis of hereditary pancreatitis.  

PubMed

Hereditary pancreatitis (HP) is an autosomal dominant disease. Two heterozygous missense mutations, R122H (R117H) and N29I (N21I), in the cationic trypsinogen gene have been clearly associated with HP. The 'self-destruct' model proposed for the R122H mutation is discussed in connection with the existing theory of pancreatitis, and the basic biochemistry and physiology of trypsinogen, with particular reference to R122 as the primary autolysis site of the cationic trypsinogen. Two different genetic mechanisms are identified which cause the R122H mutation, and gene conversion is the likely cause of the N29I mutation. A unifying model, which highlights an indirect impairment on the R122 autolysis site is hypothesised for the N29I mutation. Possible predisposition to pancreatitis by additional DNA variants in the gene, such as the A16V signal peptide cleavage site mutation and the K23R activation peptide cleavage site mutation is suspected, but not proven. Evidence of genetic heterogeneity of HP is reviewed and cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations detected in HP families are re-evaluated. Finally, large scale association studies are expected to clarify the additional variants' role in pancreatitis and to identify new HP genes. PMID:10909845

Chen, J M; Ferec, C

2000-07-01

342

HEREDITARY OSTEOPETROSIS OF THE RABBIT  

PubMed Central

The results of x-ray, hematologic, and chemical studies on cases of hereditary osteopetrosis of the rabbit are described and the resemblance of the findings to those of the severe juvenile form of human osteopetrosis is pointed out. The outstanding feature of the x-ray examinations was the homogeneous dense appearance of the entire skeleton. This condition was present at birth. In older cases there was evidence of some differentiation of bone structure. The hematologic studies showed that the disease was characterized by the development of a macrocytic anemia, thrombocytopenia, and a moderate myeloid leucocytosis. Other abnormal findings included high reticulocyte and normoblast counts, anisocytosis and poikllocytosis, and degenerative changes of the neutrophiles and lymphocytes. The chemical studies showed very low serum calcium values; serum phosphorus values were low during the first 4 weeks of life but were somewhat higher than normal levels in older cases. The serum phosphatase values were elevated. The blood sugar content was generally low. The blood cholesterol values were generally high. The liver glycogen values were small especially in older cases and those for muscle glycogen were somewhat smaller than normal values. PMID:18103398

Pearce, Louise

1948-01-01

343

Expenditures in the elderly with peripheral neuropathy  

PubMed Central

Summary To optimize care in the evaluation of peripheral neuropathy, we sought to define which tests drive expenditures and the role of the provider type. We investigated test utilization and expenditures by provider type in those with incident neuropathy in a nationally representative elderly, Medicare population. Multivariable logistic regression was used to determine predictors of MRI and electrodiagnostic utilization. MRIs of the neuroaxis and electrodiagnostic tests accounted for 88% of total expenditures. Mean and aggregate diagnostic expenditures were higher in those who saw a neurologist. Patients who saw a neurologist were more likely to receive an MRI and an electrodiagnostic test. MRIs and electrodiagnostic tests are the main contributors to expenditures in the evaluation of peripheral neuropathy, and should be the focus of future efficiency efforts. PMID:24175158

Callaghan, Brian C.; Burke, James F.; Rodgers, Ann; McCammon, Ryan; Langa, Kenneth M.; Feldman, Eva L.; Kerber, Kevin A.

2013-01-01

344

Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) - a case report and review of literature.  

PubMed

CANVAS (cerebellar ataxia with neuropathy and vestibular areflexia syndrome) is a rare neurological syndrome of unknown etiology. The main clinical features include bilateral vestibulopathy, cerebellar ataxia and sensory neuropathy. An abnormal visually enhanced vestibulo-ocular reflex is the hallmark of the disease. We present a case of 58-year-old male patient who has demonstrated gait disturbance, imbalance and paresthesia of feet for 2 years. On examination ataxia of gait, diminished knee and ankle reflexes, absence of plantar reflexes, fasciculations of thigh muscles, gaze-evoked downbeat nystagmus and abnormal visually enhanced vestibulo-ocular reflex were found. Brain magnetic resonance imaging revealed cerebellar atrophy. Vestibular function testing showed severely reduced horizontal nystagmus in response to bithermal caloric stimulation. Nerve conduction study revealed loss of upper and lower limb sensory nerve action potentials. The course of illness was progressive with ataxic gait and unsteadiness as the most disabling symptoms. We report 4-year follow-up of the patient since the beginning of the disease. PMID:25440017

Figura, Monika; Gawe?, Ma?gorzata; Kolasa, Anna; Janik, Piotr

2014-01-01

345

The chemotherapy-induced peripheral neuropathy outcome measures standardization study: from consensus to the first validity and reliability findings  

PubMed Central

Background Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and dose-limiting complication of cancer treatment. Thus far, the impact of CIPN has not been studied in a systematic clinimetric manner. The objective of the study was to select outcome measures for CIPN evaluation and to establish their validity and reproducibility in a cross-sectional multicenter study. Patients and methods After literature review and a consensus meeting among experts, face/content validity were obtained for the following selected scales: the National Cancer Institute-Common Toxicity Criteria (NCI-CTC), the Total Neuropathy Score clinical version (TNSc), the modified Inflammatory Neuropathy Cause and Treatment (INCAT) group sensory sumscore (mISS), the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, and CIPN20 quality-of-life measures. A total of 281 patients with stable CIPN were examined. Validity (correlation) and reliability studies were carried out. Results Good inter-/intra-observer scores were obtained for the TNSc, mISS, and NCI-CTC sensory/motor subscales. Test–retest values were also good for the EORTC QLQ-C30 and CIPN20. Acceptable validity scores were obtained through the correlation among the measures. Conclusion Good validity and reliability scores were demonstrated for the set of selected impairment and quality-of-life outcome measures in CIPN. Future studies are planned to investigate the responsiveness aspects of these measures. PMID:22910842

Cavaletti, G.; Cornblath, D. R.; Merkies, I. S. J.; Postma, T. J.; Rossi, E.; Frigeni, B.; Alberti, P.; Bruna, J.; Velasco, R.; Argyriou, A. A.; Kalofonos, H. P.; Psimaras, D.; Ricard, D.; Pace, A.; Galič, E.; Briani, C.; Dalla Torre, C.; Faber, C. G.; Lalisang, R. I.; Boogerd, W.; Brandsma, D.; Koeppen, S.; Hense, J.; Storey, D.; Kerrigan, S.; Schenone, A.; Fabbri, S.; Valsecchi, M. G.; Mazzeo, A.; Pace, A.; Pessino, A.; Schenone, A.; Toscano, A.; Argyriou, A.A.; Brouwer, B.; Frigeni, B.; Piras, B.; Briani, C.; Dalla Torre, C.; Dominguez Gonzalez, C.; Faber, C. G.; Tomasello, C.; Binda, D.; Brandsma, D.; Cortinovis, D.; Psimaras, D.; Ricard, D.; Storey, D.; Cornblath, D.R.; Galič, E.; Lindeck Pozza, E.; Rossi, E.; Vanhoutte, E.K.; Lanzani, F.; Pastorelli, F.; Altavilla, G.; Cavaletti, G.; Granata, G.; Kalofonos, H.P.; Ghignotti, I.; Merkies, I.S.J.; Bruna, J.; Hense, J.; Heimans, J.J.; Mattavelli, L.; Padua, L.; Reni, L.; Bakkers, M.; Boogerd, M.; Campagnolo, M.; Cazzaniga, M.; Eurelings, M.; Leandri, M.; Lucchetta, M.; Penas Prado, M.; Russo, M.; Valsecchi, M.G.; Piatti, M.L.; Alberti, P.; Bidoli, P.; Grant, R.; Plasmati, R.; Velasco, R.; Lalisang, R.I.; Meijer, R.J.; Fabbri, S.; Dorsey, S. G.; Galimberti, S.; Kerrigan, S.; Koeppen, S.; Postma, T.J.; Boogerd, W.; Grisold, W.

2013-01-01

346

Evaluation of PMI-5011, an ethanolic extract of Artemisia dracunculus L., on peripheral neuropathy in streptozotocin-diabetic mice.  

PubMed

We previously reported that PMI-5011, an ethanolic extract of Artemisia dracunculus L., alleviates peripheral neuropathy in high fat diet-fed mice, a model of prediabetes and obesity developing oxidative stress and pro-inflammatory changes in the peripheral nervous system. This study evaluated PMI-5011 on established functional, structural, and biochemical changes associated with Type I diabetic peripheral neuropathy. C57Bl6/J mice with streptozotocin-induced diabetes of a 12-week duration, developed motor and sensory nerve conduction velocity deficits, thermal and mechanical hypoalgesia, tactile allodynia, and intra-epidermal nerve fiber loss. PMI-5011 (500 mg/kg/day for 7 weeks) alleviated diabetes-induced nerve conduction slowing, small sensory nerve fiber dysfunction, and increased intra-epidermal nerve fiber density. PMI-5011 blunted sciatic nerve and spinal cord 12/15-lipoxygenase activation and oxidative-nitrosative stress, without ameliorating hyperglycemia or reducing sciatic nerve sorbitol pathway intermediate accumulation. In conclusion, PMI-5011, a safe and non-toxic botanical extract, may find use in the treatment of diabetic peripheral neuropathy. PMID:21225225

Watcho, Pierre; Stavniichuk, Roman; Tane, Pierre; Shevalye, Hanna; Maksimchyk, Yury; Pacher, Pal; Obrosova, Irina G

2011-03-01

347

Neurologic dysfunction from exposure to 2-t-butylazo-2-hydroxy-5-methylhexane (BHMH): a new occupational neuropathy.  

PubMed Central

Seven cases of subacute central and peripheral neurologic dysfunction developed in 18 workers employed in the manufacture of reinforced plastic bathtubs. Cases were characterized by weight loss, dizziness, paresthesias, muscle weakness, incontinence, memory loss, and loss of peripheral, color, and night vision. Neuropathies began distally, involved both sensory and motor function, and were associated with prolonged sensory latency, muscle fibrillation, and reduced numbers of functioning motor units. One patient developed posterior lenticular cataracts. Slow improvement occurred on removal from exposure, but residual neuropathies persisted for as long as two years. Epidemiologic investigation disclosed that the first case developed approximately two weeks after introduction of a new plastic foaming agent, 2-t-butylazo-2-hydroxy-5-methylhexane (BHMH). All cases occurred in workers exposed directly to BHMH. No new cases developed after use of BHMH was discontinued. A survey of the firm which produced BHMH and of 68 user firms found two additional clusters of mild neuropathy which may have been caused by BHMH. BHMH was withdrawn from distribution following discovery of these cases. Subsequently, BHMH has been shown in rats to be a potent neurotoxin. Adequate premarket testing could have averted this outbreak. PMID:3985240

Horan, J M; Kurt, T L; Landrigan, P J; Melius, J M; Singal, M

1985-01-01

348

Na+/H+ exchanger 1 inhibition reverses manifestation of peripheral diabetic neuropathy in type 1 diabetic rats.  

PubMed

Evidence for an important role for Na(+)/H(+) exchangers in diabetic complications is emerging. The aim of this study was to evaluate whether Na(+)/H(+) exchanger 1 inhibition reverses experimental peripheral diabetic neuropathy. Control and streptozotocin-diabetic rats were treated with the specific Na(+)/H(+) exchanger 1 inhibitor cariporide for 4 wk after 12 wk without treatment. Neuropathy end points included sciatic motor and sensory nerve conduction velocities, endoneurial nutritive blood flow, vascular reactivity of epineurial arterioles, thermal nociception, tactile allodynia, and intraepidermal nerve fiber density. Advanced glycation end product and markers of oxidative stress, including nitrated protein levels in sciatic nerve, were evaluated by Western blot. Rats with 12-wk duration of diabetes developed motor and sensory nerve conduction deficits, thermal hypoalgesia, tactile allodynia, and intraepidermal nerve fiber loss. All these changes, including impairment of nerve blood flow and vascular reactivity of epineurial arterioles, were partially reversed by 4 wk of cariporide treatment. Na(+)/H(+) exchanger 1 inhibition was also associated with reduction of diabetes-induced accumulation of advanced glycation endproduct, oxidative stress, and nitrated proteins in sciatic nerve. In conclusion, these findings support an important role for Na(+)/H(+) exchanger 1 in functional, structural, and biochemical manifestations of peripheral diabetic neuropathy and provide the rationale for development of Na(+)/H(+) exchanger 1 inhibitors for treatment of diabetic vascular and neural complications. PMID:23736542

Lupachyk, Sergey; Watcho, Pierre; Shevalye, Hanna; Vareniuk, Igor; Obrosov, Alexander; Obrosova, Irina G; Yorek, Mark A

2013-08-01

349

Phenotypic Changes in Diabetic Neuropathy Induced by a High-Fat Diet in Diabetic C57Bl/6 Mice  

PubMed Central

Emerging evidence suggests that dyslipidemia is an independent risk factor for diabetic neuropathy (DN) (reviewed by Vincent et al. 2009). To experimentally determine how dyslipidemia alters DN, we quantified neuropathic symptoms in diabetic mice fed a high-fat diet. Streptozotocin-induced diabetic C57BL/6 mice fed a high-fat diet developed dyslipidemia and a painful neuropathy (mechanical allodynia) instead of the insensate neuropathy (mechanical insensitivity) that normally develops in this strain. Nondiabetic mice fed a high-fat diet also developed dyslipidemia and mechanical allodynia. Thermal sensitivity was significantly reduced in diabetic compared to nondiabetic mice, but was not worsened by the high-fat diet. Moreover, diabetic mice fed a high-fat diet had significantly slower sensory and motor nerve conduction velocities compared to nondiabetic mice. Overall, dyslipidemia resulting from a high-fat diet may modify DN phenotypes and/or increase risk for developing DN. These results provide new insight as to how dyslipidemia may alter the development and phenotype of diabetic neuropathy. PMID:22144990

Guilford, B. L.; Ryals, J. M.; Wright, D. E.

2011-01-01

350

The clinical approach to small fibre neuropathy and painful channelopathy  

PubMed Central

Small fibre neuropathy (SFN) is characterised by structural injury selectively affecting small diameter sensory and/or autonomic axons. The clinical presentation is dominated by pain. SFN complicates a number of common diseases such as diabetes mellitus and is likely to be increasingly encountered. The diagnosis of SFN is demanding as clinical features can be vague and nerve conduction studies normal. New diagnostic techniques, in particular measurement of intraepidermal nerve fibre density, have significantly improved the diagnostic efficiency of SFN. Management is focused on the treatment of the underlying cause and analgesia, as there is no neuroprotective therapy. A recent and significant advance is the finding that a proportion of cases labelled as idiopathic SFN are in fact associated with gain of function mutations of the voltage-gated sodium channels Nav1.7 and Nav1.8 (encoded by the genes SCN9A and SCN10A, respectively). There is a further group of heritable painful conditions in which gain of function mutations in ion channels alter excitability of sensory neurones but do not cause frank axon degeneration; these include mutations in Nav1.7 (causing erythromelalgia and paroxysmal extreme pain disorder) and TRPA1 (resulting in familial episodic pain disorder). These conditions are exceptionally rare but have provided great insight into the nociceptive system as well as yielding potential analgesic drug targets. In patients with no pre-existing risk factor, the investigation of an underlying cause of SFN should be systematic and appropriate for the patient population. In this review, we focus on how to incorporate recent developments in the diagnosis and pathophysiology of SFN into clinical practice. PMID:24778270

Themistocleous, Andreas C; Ramirez, Juan D; Serra, Jordi; Bennett, David L H

2014-01-01

351

Ischemic Neuropathy Associated with Livedoid Vasculitis  

PubMed Central

Background Livedoid vasculitis is a chronic dermatological problem with an unclear etiology. Clinical findings are petechiae with painful ulcers in both lower extremities, which heal to become hyperpigmented and porcelain-white satellite lesions. There are only a few reported cases of livedoid vasculitis presenting in combination with peripheral neuropathy. Case Report We report the first case of a Korean patient presenting with mononeuritis multiplex combined with livedoid vasculitis, which was confirmed by electrophysiological and pathological studies. Conclusions Our report supports the possible vaso-occlusive etiology of livedoid vasculitis in multifocal ischemic neuropathy. PMID:22259622

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

2011-01-01

352

Sympathetic neuropathy and dysphagia following doxycycline sclerotherapy.  

PubMed

This case report demonstrates neurologic sequela following treatment with doxycycline sclerotherapy. A six-week-old child presented with respiratory distress from a macrocystic lymphatic malformation, extending from the skull base to the anterior mediastinum. Following doxycycline sclerotherapy, the airway symptoms resolved; however, the child developed silent aspiration and Horner's syndrome. Two months following treatment the patient resumed oral diet and at one year post-intervention there has been no recurrence of symptoms, with only mild ptosis remaining. While neuropathies following doxycycline sclerotherapy have been described, aspiration has never been documented. This case demonstrates a single patient's clinical course and resolution of their neuropathies. PMID:23931985

Wang, Kevin L; Chun, Robert H; Kerschner, Joseph E; Sulman, Cecille G

2013-09-01

353

Inhibition of TFG function causes hereditary axon degeneration by impairing endoplasmic reticulum structure  

PubMed Central

Hereditary spastic paraplegias are a clinically and genetically heterogeneous group of gait disorders. Their pathological hallmark is a length-dependent distal axonopathy of nerve fibers in the corticospinal tract. Involvement of other neurons can cause additional neurological symptoms, which define a diverse set of complex hereditary spastic paraplegias. We present two siblings who have the unusual combination of early-onset spastic paraplegia, optic atrophy, and neuropathy. Genome-wide SNP-typing, linkage analysis, and exome sequencing revealed a homozygous c.316C>T (p.R106C) variant in the Trk-fused gene (TFG) as the only plausible mutation. Biochemical characterization of the mutant protein demonstrated a defect in its ability to self-assemble into an oligomeric complex, which is critical for normal TFG function. In cell lines, TFG inhibition slows protein secretion from the endoplasmic reticulum (ER) and alters ER morphology, disrupting organization of peripheral ER tubules and causing collapse of the ER network onto the underlying microtubule cytoskeleton. The present study provides a unique link between altered ER architecture and neurodegeneration. PMID:23479643

Beetz, Christian; Johnson, Adam; Schuh, Amber L.; Thakur, Seema; Varga, Rita-Eva; Fothergill, Thomas; Hertel, Nicole; Bomba-Warczak, Ewa; Thiele, Holger; Nürnberg, Gudrun; Altmüller, Janine; Saxena, Renu; Chapman, Edwin R.; Dent, Erik W.; Nürnberg, Peter; Audhya, Anjon

2013-01-01

354

Bortezomib-Induced Painful Peripheral Neuropathy: An Electrophysiological, Behavioral, Morphological and Mechanistic Study in the Mouse  

PubMed Central

Bortezomib is the first proteasome inhibitor with significant antineoplastic activity for the treatment of relapsed/refractory multiple myeloma as well as other hematological and solid neoplasms. Peripheral neurological complications manifesting with paresthesias, burning sensations, dysesthesias, numbness, sensory loss, reduced proprioception and vibratory sensitivity are among the major limiting side effects associated with bortezomib therapy. Although bortezomib-induced painful peripheral neuropathy is clinically easy to diagnose and reliable models are available, its pathophysiology remains partly unclear. In this study we used well-characterized immune-competent and immune-compromised mouse models of bortezomib-induced painful peripheral neuropathy. To characterize the drug-induced pathological changes in the peripheral nervous system, we examined the involvement of spinal cord neuronal function in the development of neuropathic pain and investigated the relevance of the immune response in painful peripheral neuropathy induced by bortezomib. We found that bortezomib treatment induced morphological changes in the spinal cord, dorsal roots, dorsal root ganglia (DRG) and peripheral nerves. Neurophysiological abnormalities and specific functional alterations in A? and C fibers were also observed in peripheral nerve fibers. Mice developed mechanical allodynia and functional abnormalities of wide dynamic range neurons in the dorsal horn of spinal cord. Bortezomib induced increased expression of the neuronal stress marker activating transcription factor-3 in most DRG. Moreover, the immunodeficient animals treated with bortezomib developed a painful peripheral neuropathy with the same features observed in the immunocompetent mice. In conclusion, this study extends the knowledge of the sites of damage induced in the nervous system by bortezomib administration. Moreover, a selective functional vulnerability of peripheral nerve fiber subpopulations was found as well as a change in the electrical activity of wide dynamic range neurons of dorsal horn of spinal cord. Finally, the immune response is not a key factor in the development of morphological and functional damage induced by bortezomib in the peripheral nervous system. PMID:24069168

Bardini, Michela; Fazio, Grazia; Chiorazzi, Alessia; Meregalli, Cristina; Oggioni, Norberto; Shanks, Kathleen; Quartu, Marina; Serra, Maria Pina; Sala, Barbara; Cavaletti, Guido; Dorsey, Susan G.

2013-01-01

355

Bortezomib-induced painful peripheral neuropathy: an electrophysiological, behavioral, morphological and mechanistic study in the mouse.  

PubMed

Bortezomib is the first proteasome inhibitor with significant antineoplastic activity for the treatment of relapsed/refractory multiple myeloma as well as other hematological and solid neoplasms. Peripheral neurological complications manifesting with paresthesias, burning sensations, dysesthesias, numbness, sensory loss, reduced proprioception and vibratory sensitivity are among the major limiting side effects associated with bortezomib therapy. Although bortezomib-induced painful peripheral neuropathy is clinically easy to diagnose and reliable models are available, its pathophysiology remains partly unclear. In this study we used well-characterized immune-competent and immune-compromised mouse models of bortezomib-induced painful peripheral neuropathy. To characterize the drug-induced pathological changes in the peripheral nervous system, we examined the involvement of spinal cord neuronal function in the development of neuropathic pain and investigated the relevance of the immune response in painful peripheral neuropathy induced by bortezomib. We found that bortezomib treatment induced morphological changes in the spinal cord, dorsal roots, dorsal root ganglia (DRG) and peripheral nerves. Neurophysiological abnormalities and specific functional alterations in A? and C fibers were also observed in peripheral nerve fibers. Mice developed mechanical allodynia and functional abnormalities of wide dynamic range neurons in the dorsal horn of spinal cord. Bortezomib induced increased expression of the neuronal stress marker activating transcription factor-3 in most DRG. Moreover, the immunodeficient animals treated with bortezomib developed a painful peripheral neuropathy with the same features observed in the immunocompetent mice. In conclusion, this study extends the knowledge of the sites of damage induced in the nervous system by bortezomib administration. Moreover, a selective functional vulnerability of peripheral nerve fiber subpopulations was found as well as a change in the electrical activity of wide dynamic range neurons of dorsal horn of spinal cord. Finally, the immune response is not a key factor in the development of morphological and functional damage induced by bortezomib in the peripheral nervous system. PMID:24069168

Carozzi, Valentina A; Renn, Cynthia L; Bardini, Michela; Fazio, Grazia; Chiorazzi, Alessia; Meregalli, Cristina; Oggioni, Norberto; Shanks, Kathleen; Quartu, Marina; Serra, Maria Pina; Sala, Barbara; Cavaletti, Guido; Dorsey, Susan G

2013-01-01

356

Organophosphates induce distal axonal damage, but not brain oedema, by inactivating neuropathy target esterase  

SciTech Connect

Single doses of organophosphorus compounds (OP) which covalently inhibit neuropathy target esterase (NTE) can induce lower-limb paralysis and distal damage in long nerve axons. Clinical signs of neuropathy are evident 3 weeks post-OP dose in humans, cats and chickens. By contrast, clinical neuropathy in mice following acute dosing with OPs or any other toxic compound has never been reported. Moreover, dosing mice with ethyloctylphosphonofluoridate (EOPF) - an extremely potent NTE inhibitor - causes a different (subacute) neurotoxicity with brain oedema. These observations have raised the possibility that mice are intrinsically resistant to neuropathies induced by acute toxic insult, but may incur brain oedema, rather than distal axonal damage, when NTE is inactivated. Here we provide the first report that hind-limb dysfunction and extensive axonal damage can occur in mice 3 weeks after acute dosing with a toxic compound, bromophenylacetylurea. Three weeks after acutely dosing mice with neuropathic OPs no clinical signs were observed, but distal lesions were present in the longest spinal sensory axons. Similar lesions were evident in undosed nestin-cre:NTEfl/fl mice in which NTE had been genetically-deleted from neural tissue. The extent of OP-induced axonal damage in mice was related to the duration of NTE inactivation and, as reported in chickens, was promoted by post-dosing with phenylmethanesulfonylfluoride. However, phenyldipentylphosphinate, another promoting compound in chickens, itself induced in mice lesions different from the neuropathic OP type. Finally, EOPF induced subacute neurotoxicity with brain oedema in both wild-type and nestin-cre:NTEfl/fl mice indicating that the molecular target for this effect is not neural NTE.

Read, David J.; Li Yong [MRC Toxicology Unit, University of Leicester, Hodgkin Building, Lancaster Road, Leicester LE1 9HN (United Kingdom); Chao, Moses V. [Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016 (United States); Cavanagh, John B. [Department of Clinical Neuroscience, Institute of Psychiatry, London SE5 8AF (United Kingdom); Glynn, Paul, E-mail: pg8@le.ac.u [MRC Toxicology Unit, University of Leicester, Hodgkin Building, Lancaster Road, Leicester LE1 9HN (United Kingdom)

2010-05-15

357

Genetics Home Reference: Infantile-onset ascending hereditary spastic paralysis  

MedlinePLUS

... with a small number of reported cases. What genes are related to infantile-onset ascending hereditary spastic paralysis? Mutations in the ALS2 gene cause infantile-onset ascending hereditary spastic paralysis. The ...

358

Pathobiology of cancer chemotherapy-induced peripheral neuropathy (CIPN)  

PubMed Central

Chemotherapy induced peripheral neuropathy (CIPN) is a type of neuropathic pain that is a major dose-limiting side-effect of potentially curative cancer chemotherapy treatment regimens that develops in a “stocking and glove” distribution. When pain is severe, a change to less effective chemotherapy agents may be required, or patients may choose to discontinue treatment. Medications used to alleviate CIPN often lack efficacy and/or have unacceptable side-effects. Hence the unmet medical need for novel analgesics for relief of this painful condition has driven establishment of rodent models of CIPN. New insights on the pathobiology of CIPN gained using these models are discussed in this review. These include mitochondrial dysfunction and oxidative stress that are implicated as key mechanisms in the development of CIPN. Associated structural changes in peripheral nerves include neuronopathy, axonopathy and/or myelinopathy, especially intra-epidermal nerve fiber (IENF) degeneration. In patients with CIPN, loss of heat sensitivity is a hallmark symptom due to preferential damage to myelinated primary afferent sensory nerve fibers in the presence or absence of demyelination. The pathobiology of CIPN is complex as cancer chemotherapy treatment regimens frequently involve drug combinations. Adding to this complexity, there are also subtle differences in the pathobiological consequences of commonly used cancer chemotherapy drugs, viz platinum compounds, taxanes, vincristine, bortezomib, thalidomide and ixabepilone, on peripheral nerves. PMID:24385965

Han, Yaqin; Smith, Maree T.

2013-01-01

359

High doses of cobalt induce optic and auditory neuropathy.  

PubMed

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

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

2013-09-01

360

Pathobiology of cancer chemotherapy-induced peripheral neuropathy (CIPN).  

PubMed

Chemotherapy induced peripheral neuropathy (CIPN) is a type of neuropathic pain that is a major dose-limiting side-effect of potentially curative cancer chemotherapy treatment regimens that develops in a "stocking and glove" distribution. When pain is severe, a change to less effective chemotherapy agents may be required, or patients may choose to discontinue treatment. Medications used to alleviate CIPN often lack efficacy and/or have unacceptable side-effects. Hence the unmet medical need for novel analgesics for relief of this painful condition has driven establishment of rodent models of CIPN. New insights on the pathobiology of CIPN gained using these models are discussed in this review. These include mitochondrial dysfunction and oxidative stress that are implicated as key mechanisms in the development of CIPN. Associated structural changes in peripheral nerves include neuronopathy, axonopathy and/or myelinopathy, especially intra-epidermal nerve fiber (IENF) degeneration. In patients with CIPN, loss of heat sensitivity is a hallmark symptom due to preferential damage to myelinated primary afferent sensory nerve fibers in the presence or absence of demyelination. The pathobiology of CIPN is complex as cancer chemotherapy treatment regimens frequently involve drug combinations. Adding to this complexity, there are also subtle differences in the pathobiological consequences of commonly used cancer chemotherapy drugs, viz platinum compounds, taxanes, vincristine, bortezomib, thalidomide and ixabepilone, on peripheral nerves. PMID:24385965

Han, Yaqin; Smith, Maree T

2013-01-01

361

DIABETIC NEUROPATHY PART 1: OVERVIEW AND SYMMETRIC PHENOTYPES  

PubMed Central

Diabetes is the most common cause of neuropathy in US and neuropathies are the most common complication of diabetes mellitus affecting up to 50% of patients with type 1 and type 2 diabetes mellitus. Various types of neuropathies can be associated with diabetes mellitus.1 Symptoms usually include numbness, tingling, pain and weakness. Dizziness with postural changes can be seen with autonomic neuropathy. Metabolic, vascular and immune theories have been proposed for the pathogenesis of diabetic neuropathy. Pathologically axonal damage and segmental demyelination can be seen with diabetic neuropathies. Management of diabetic neuropathy should begin at the initial diagnosis of diabetes and mainly requires tight and stable glycemic control. Many medications are available for the treatment of neuropathic pain. PMID:23642717

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

2014-01-01

362

Human sensory subsystems emulator.  

PubMed

Last year this author presented his design for a computerized human nervous system function emulator for use in an android robot. This paper describes that emulator's sensory subsystems in more detail and adds new functions. Topics covered include sensor types, signal conditioning, data handling in the afferent pathways and interpretation of sensory information. Physiological sensory modalities (including: temperature, pressure, acceleration, humidity, sound and light stimuli) as well as nonphysiological (including: magnetic, radio, infrared, ultrasound and satellite GPS) are elucidated. The relationship of a primitive stimulus (i.e.: heat) to a high level sensation (i.e.: pain) is explored. PMID:11347421

Frenger, P

2001-01-01

363

Sensory Characteristics in ASD  

PubMed Central

In this paper, we review evidence regarding differences in the types of sensory experiences of persons with ASD with respect to both unisensory and multisensory processing. We discuss selfreports, carer questionnaires as well as perceptual processing differences found in the laboratory. Incoming information is processed through one or more of our senses and fundamental differences in the processing of information from any sensory modality or combination of sensory modalities are likely to have cascading effects on the way individuals with ASD experience the world around them, effects that can have both positive and negative impact on a individual with ASD’s quality of life. PMID:21264053

Stewart, Mary E.; Russo, Natalie; Banks, Jennifer; Miller, Louisa; Burack, Jacob A.

2009-01-01

364

Concomitant occurrence of cervical myelopathy, cerebral infarction, and peripheral neuropathy in systemic lupus erythematosus: a case report.  

PubMed

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease characterized by multiorgan involvement with diverse clinical presentations. Central nervous system involvement in neuropsychiatric syndromes of SLE (NPSLE), such as cerebrovascular disease and myelopathy, is a major cause of morbidity and mortality in SLE patients. The concomitant occurrence of myelopathy, cerebrovascular disease, and peripheral neuropathy in a patient with SLE has not yet been reported. We report on a 41-year-old woman with SLE who showed motor and sensory impairment with urinary retention and was diagnosed with cervical myelopathy and acute cerebral infarction by spine and brain magnetic resonance imaging and peripheral neuropathy by electrodiagnostic examination. Even though pathogenesis of NPSLE is not well elucidated, we assume that increased antibodies of anti-double stranded DNA (anti-dsDNA), presence of lupus anticoagulant and hypertension are risk factors that have caused neuropsychiatric lupus in this patient. PMID:24855622

Kim, So-Yeon; Yoon, Tae-Sik; Suh, Jee-Hyun

2014-04-01

365

International Neuropathy Workshop of 2009: introduction to the final reports.  

PubMed

Neuropathies are amongst the most common of the long-term complications of diabetes, affecting up to 50% of patients. Their clinical features vary immensely and patients may present with a wide spectrum of specialties, from neurology to urology, for example, or from cardiology to podiatry. Neuropathies are typically characterized by a progressive loss of nerve fibres which may affect both of the principal divisions of the peripheral nervous system. The epidemiology and natural history of the diabetic neuropathies remain poorly defined. The International Consensus Workshop in Toronto in 2009 arose from the fact that at the moment there are no clear, universally accepted guidelines regarding the definition of diabetic neuropathies. This has resulted in a massive variation in how neuropathy is diagnosed in different centres and countries. A preliminary summary report of the Toronto meeting was published in 2010. The series of papers published in this issue of Diabetes/Metabolism Research and Reviews are the detailed reports that came from each sub-group of this Consensus panel. These reviews cover the problems with definitions and classification of neuropathy, the management of painful neuropathy and then the sub-group of small fibre neuropathies. There are also 3 papers on the autonomic neuropathies, covering cardiovascular autonomic neuropathies, as well as other areas of the autonomic neuropathies including gastrointestinal, urogenital and pseudomotor neuropathies. This series of papers will give the reader detailed information on the diverse aspects of diabetic neuropathies, their measurement and management, and will also assist in the selection of appropriate measures of both autonomic and somatic nerve function in clinical trials. This is clearly work in progress as diagnostic criteria for diabetic neuropathies are likely to evolve with developments in the field. PMID:21695765

Boulton, Andrew J M; Valensi, Paul; Tesfaye, Solomon

2011-10-01

366

Systemic corticosteroids in nonarteritic ischemic optic neuropathy  

PubMed Central

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

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

2014-01-01

367

Genetics Home Reference: Giant axonal neuropathy  

MedlinePLUS

... What if I still have specific questions about giant axonal neuropathy? Ask the Genetic and Rare Diseases Information Center . Where can I find general ... Health Professionals What glossary definitions help with understanding giant axonal ... (11 links) The resources on this site should not be used as a substitute for ...

368

CANCER GENETICS & PREVENTION HEREDITARY BREAST AND OVARIAN CANCER  

E-print Network

(called "triple negative") breast cancers. Below are the estimated lifetime risks of cancer in peopleCANCER GENETICS & PREVENTION HEREDITARY BREAST AND OVARIAN CANCER SYNDROME (HBOC) ­ BRCA1 PATIENT INFORMATION What is Hereditary Breast and Ovarian Cancer syndrome? Hereditary Breast and Ovarian Cancer

Liu, Xiaole Shirley

369

Benign Hereditary Chorea: Clinical, Neuroimaging, and Genetic Findings  

Microsoft Academic Search

Benign hereditary chorea is an autosomal dominant disease with an early onset of symptoms. In some families, symptoms tend to decrease in adulthood, suggesting that the disorder results from a developmental disturbance in the brain. Individuals with benign hereditary chorea, a nonprogressive disease, have normal or slightly below normal intelligence. The locus for benign hereditary chorea is on chromosome 14.

Muhammad Mahajnah; Dov Inbar; Adam Steinmetz; Peter Heutink; G. J. Breedveld; Rachel Straussberg

2007-01-01

370

Hereditary Ovarian Cancer: Molecular Genetics and Clinical Implications  

Microsoft Academic Search

Epidemiologic data support the existence of two discrete manifestations of hereditary ovarian carcinoma: the breast and ovarian cancer syndrome and the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome. Genetic linkage analyses reveal that the majority of breast and ovarian cancer families are linked to theBRCA1gene, while some cases of hereditary ovarian cancer are also apparent in breast cancer families linked to

Jeff Boyd; Stephen C. Rubin

1997-01-01

371

Diagnosis and management of hereditary hemochromatosis.  

PubMed

Hereditary hemochromatosis is a rare genetic disorder that can have significant clinical consequences. Hemochromatosis is associated with iron overload, and can initially be recognized through laboratory testing for serum ferritin and transferrin saturation. Genetic testing for the HFE mutation can be performed in patients with elevated iron indices and a suspicion for hemochromatosis or liver disease. The main pathway resulting in iron overload is through altered hepcidin levels. Treatment of patients with the clinical phenotype of hereditary hemochromatosis is commonly through phlebotomy for removal of excess iron stores. This article highlights the current information and data regarding the diagnosis and management of hemochromatosis. PMID:25454304

Salgia, Reena J; Brown, Kimberly

2015-02-01

372

Neuromorphic sensory systems.  

PubMed

Biology provides examples of efficient machines which greatly outperform conventional technology. Designers in neuromorphic engineering aim to construct electronic systems with the same efficient style of computation. This task requires a melding of novel engineering principles with knowledge gleaned from neuroscience. We discuss recent progress in realizing neuromorphic sensory systems which mimic the biological retina and cochlea, and subsequent sensor processing. The main trends are the increasing number of sensors and sensory systems that communicate through asynchronous digital signals analogous to neural spikes; the improved performance and usability of these sensors; and novel sensory processing methods which capitalize on the timing of spikes from these sensors. Experiments using these sensors can impact how we think the brain processes sensory information. PMID:20493680

Liu, Shih-Chii; Delbruck, Tobi

2010-06-01

373

Peripheral nerve findings in hereditary coproporphyria  

Microsoft Academic Search

In spite of several cases reported in the literature, the exact pathogenetic mechanism of neuropathic changes in porphyric neuropathy remains uncertain. Various authors have ascribed the neuropathologic findings to either a dying-back axonal degeneration or segmental demyelination. In recent years, the hypothesis of an axonal and myelinic disorder has received support by the demonstration of a combined and simultaneous involvement

G. Trapani; C. Casali; P. Tonali; G. C. Topi

1984-01-01

374

Ozone partially prevents diabetic neuropathy in rats.  

PubMed

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

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

2015-02-01

375

HEREDITARY ACHONDROPLASIA IN THE RABBIT  

PubMed Central

Pathological observations on hereditary achondroplasia in the rabbit have been described. At autopsy, the chief features of interest are: reduced size with disproportionately shortened extremities and large head, cutaneous and subcutaneous edema of variable degree and distribution, small shortened bones with a cartilaginous appearance and texture, immature teeth, and cleft palate in one-fourth the cases; blood-stained fluid in the thoracic and abdominal cavities; a comparatively small heart pointing to the right of the midline, a very large firm thymus, a large pale soft spleen, a large swollen liver with red mottling, and a stomach distended with thin greenish mucus but no milk. The mean relative weights of all organs in terms of the net body weight were larger than those of normal new-born litter mates. The mean actual weights of the kidneys, the brain, and especially the spleen and the thymus were also larger than their respective normal values, those of the heart, liver, and adrenals were slightly smaller, while that of the pituitary was the same. Histologically, all endochondral cartilages show marked abnormalities of differentiation with pronounced deficiency of ossification. Calcification of membranous bones is likewise deficient. The histological abnormalities of the long bones are very similar to, if not identical with, those characteristic of human fetal chondrodystrophy, the creeper fowl condition, the "bull-dog" calf, and achondroplasia of the dog. No histological evidence was found in any organ which would suggest a basis for a responsible causal agent of the abnormality. Minor to marked vascular dilatation and congestion and edema is a variable feature but is fairly widely distributed. The changes in the thyroid indicate an active gland. The cellular pattern of the pituitary is characterized by some increase in basophilic cells. The lymphoid elements of the spleen are more or less depleted. The hemopoietic tissue in the spleen and liver is reduced in amount. In blood obtained from the heart, there is a reduction in the numbers of red and white cells and platelets and in the hemoglobin content as well; immature cells and particularly normoblasts are comparatively numerous. PMID:19871499

Pearce, Louise; Brown, Wade H.

1945-01-01

376

Effects of treatments for symptoms of painful diabetic neuropathy: systematic review  

Microsoft Academic Search

Objective To evaluate the effects of treatments for the symptoms of painful diabetic neuropathy. Design Systematic review. Data sources Articles (English and full text) on double blind randomised trials found by searching with the key words anticonvulsant, antidepressant, non-steroidal antiinflammatory drugs, tramadol, opioid, ion channel blocker, diabetic neuropathy, diabetic peripheral neuropathy, peripheral neuropathy, and neuropathy. The search included Medline, Embase,

Man-chun Wong; Joanne W Y Chung; Thomas K S Wong

2007-01-01

377

Hereditary pancreatitis. Gene defects and their implications.  

PubMed

Hereditary pancreatitis is a rare condition characterized by acute and chronic pancreatitis transmitted in an autosomal dominant fashion. There also is an epidemiologic link to pancreatic cancer in some affected families. Failure of a secondary brake mechanism responsible for inactivation of prematurely activated cationic trypsin in acinar cells seems to be the fundamental defect in type I hereditary pancreatitis (R117H cationic trypsin), and also may explain the pathogenesis of type II hereditary pancreatitis (N211 cationic trypsin). The diagnosis is made based on clinical history and, in certain cases, by molecular diagnostic testing for these gene defects. Medical management of acute and chronic hereditary pancreatitis currently does not differ from that of nonhereditary AP. As in nonhereditary pancreatitis, the surgical approach must be tailored to the individual problem, with an understanding that disease restricted to the head of the gland is atypical and that residual acinar tissue continues to drive the disease state. Although diagnosis and management of pancreatic adenocarcinoma are similar in this cohort, the increased age-accumulated risk suggests that thoughtful screening protocols eventually may be clinically and cost-effective. PMID:10470321

Gates, L K; Ulrich, C D; Whitcomb, D C

1999-08-01

378

Cerebellar learning distinguishes inflammatory neuropathy with and without tremor  

PubMed Central

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

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

2013-01-01

379

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

Federal Register 2010, 2011, 2012, 2013

...neuropathies, regardless of whether they are transient or persistent in nature. In 1996, NAS...occurrence of ``acute and subacute transient peripheral neuropathy.'' In subsequent...description of the condition to ``early onset transient peripheral neuropathy.'' This...

2012-08-10

380

Sjögren Syndrome-Associated Small Fiber Neuropathy: Characterization From a Prospective Series of 40 Cases.  

PubMed

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

Sčne, Damien; Cacoub, Patrice; Authier, François-Jérôme; Haroche, Julien; Créange, Alain; Saadoun, David; Amoura, Zahir; Guillausseau, Pierre-Jean; Lefaucheur, Jean-Pascal

2013-08-26

381

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

PubMed

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

Kuntzer, T

2014-12-01

382

Suprascapular neuropathy: what does the literature show?  

PubMed

Suprascapular neuropathy remains a rare, albeit increasingly recognized, diagnosis. Despite its relatively low prevalence, it must be kept in the shoulder surgeon's mind as a potential cause of shoulder pain, particularly in patients where the history, physical examination, and imaging studies do not adequately explain a patient's symptoms or disability. Although challenging to identify, suprascapular neuropathy can be successfully treated. The current literature shows that the location and mechanism of nerve injury are the most important factors guiding management. Different treatment strategies are required, depending on the specific location and type of nerve injury. Controversy regarding if and when to perform an isolated suprascapular nerve release continues. Furthermore, no recommendations regarding suprascapular nerve release in conjunction with rotator cuff repair can be made at this time, and further research is necessary to better delineate the indications in the future. PMID:22445163

Moen, Todd C; Babatunde, Oladapo M; Hsu, Stephanie H; Ahmad, Christopher S; Levine, William N

2012-06-01

383

Other Autonomic Neuropathies Associated with Ganglionic Antibody  

PubMed Central

The acetylcholine receptor ganglionic (G-AchR) antibody is a very specific serologic test for autoimmune autonomic ganglionopathy. The spectrum of autoimmune (or presumed to be autoimmune) autonomic disorders, however, is quite broad and positivity to this antibody has been reported in a variety of other conditions, albeit infrequent and with low titer. This review describes the autonomic neuropathies most frequently encountered in clinical practice in which an autoimmune etiology is suspected. They include a chronic form (pure autonomic failure) and limited autonomic neuropathies with predominant involvement of one neurotransmitter type (i.e., cholinergic vs. adrenergic) or one system (such as the gastrointestinal system) or a distal small fiber dysfunction. In each of these conditions, occasional positivity to the G-AchR antibody has been found, but the pathogenetic significance of such finding is still uncertain. Other antigens and antibodies yet to be identified are more likely to be responsible in these disorders. PMID:19058765

Sandroni, Paola; Low, Phillip A.

2009-01-01

384

Other autonomic neuropathies associated with ganglionic antibody.  

PubMed

The acetylcholine receptor ganglionic (G-AchR) antibody is a very specific serologic test for autoimmune autonomic ganglionopathy. The spectrum of autoimmune (or presumed to be autoimmune) autonomic disorders, however, is quite broad and positivity to this antibody has been reported in a variety of other conditions, albeit infrequent and with low titer. This review describes the autonomic neuropathies most frequently encountered in clinical practice in which an autoimmune etiology is suspected. They include a chronic form (pure autonomic failure) and limited autonomic neuropathies with predominant involvement of one neurotransmitter type (i.e., cholinergic vs. adrenergic) or one system (such as the gastrointestinal system) or a distal small fiber dysfunction. In each of these conditions, occasional positivity to the G-AchR antibody has been found, but the pathogenetic significance of such finding is still uncertain. Other antigens and antibodies yet to be identified are more likely to be responsible in these disorders. PMID:19058765

Sandroni, Paola; Low, Phillip A

2009-03-12

385

Chemotherapy-induced peripheral neuropathy: What do we know about mechanisms?  

PubMed

Cisplatin, oxaliplatin, paclitaxel, vincristine and bortezomib are some of the most effective drugs successfully employed (alone or in combinations) as first-line treatment for common cancers. However they often caused severe peripheral neurotoxicity and neuropathic pain. Structural deficits in Dorsal Root Ganglia and sensory nerves caused symptoms as sensory loss, paresthesia, dysaesthesia and numbness that result in patient' suffering and also limit the life-saving therapy. Several scientists have explored the various mechanisms involved in the onset of chemotherapy-related peripheral neurotoxicity identifying molecular targets useful for the development of selected neuroprotective strategies. Dorsal Root Ganglia sensory neurons, satellite cells, Schwann cells, as well as neuronal and glial cells in the spinal cord, are the preferential sites in which chemotherapy neurotoxicity occurs. DNA damage, alterations in cellular system repairs, mitochondria changes, increased intracellular reactive oxygen species, alterations in ion channels, glutamate signalling, MAP-kinases and nociceptors ectopic activation are among the events that trigger the onset of peripheral neurotoxicity and neuropathic pain. In the present work we review the role of the main players in determining the pathogenesis of anticancer drugs-induced peripheral neuropathy. PMID:25459280

Carozzi, V A; Canta, A; Chiorazzi, A; Cavaletti, G

2014-10-22

386

Autonomic dysfunction is a major feature of cerebellar ataxia, neuropathy, vestibular areflexia 'CANVAS' syndrome.  

PubMed

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a recently recognized neurodegenerative ganglionopathy. Prompted by the presence of symptomatic postural hypotension in two patients with CANVAS, we hypothesized that autonomic dysfunction may be an associated feature of the syndrome. We assessed symptoms of autonomic dysfunction and performed autonomic nervous system testing among 26 patients from New Zealand. After excluding three patients with diabetes mellitus, 83% had evidence of autonomic dysfunction; all patients had at least one autonomic symptom and 91% had more than two symptoms. We also found a higher rate of downbeat nystagmus (65%) than previously described in CANVAS. We confirmed that sensory findings on nerve conduction tests were consistent with a sensory ganglionopathy and describe two patients with loss of trigeminal sensation consistent with previous pathological descriptions of trigeminal sensory ganglionopathy. Our results suggest that autonomic dysfunction is a major feature of CANVAS. This has implications for the management of patients with CANVAS as the autonomic symptoms may be amenable to treatment. The findings also provide an important differential diagnosis from multiple system atrophy for patients who present with ataxia and autonomic failure. PMID:25070514

Wu, Teddy Y; Taylor, Jennifer M; Kilfoyle, Dean H; Smith, Andrew D; McGuinness, Ben J; Simpson, Mark P; Walker, Elizabeth B; Bergin, Peter S; Cleland, James C; Hutchinson, David O; Anderson, Neil E; Snow, Barry J; Anderson, Tim J; Paermentier, Laura A F; Cutfield, Nick J; Chancellor, Andrew M; Mossman, Stuart S; Roxburgh, Richard H

2014-10-01

387

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

388

Suprascapular neuropathy related to a glenohumeral joint cyst.  

PubMed

A man with shoulder pain and complaints of weakness had examination findings consistent with a suprascapular neuropathy with predominant involvement of the infraspinatus muscle. Electrodiagnostic studies confirmed an axon-loss suprascapular neuropathy with greater involvement of the infraspinatus muscle. Magnetic resonance imaging (MRI) demonstrated a large ganglion cyst originating from the glenohumeral joint. The clinical, electrodiagnostic, and radiologic evaluation of suprascapular neuropathy is discussed. PMID:10366233

McCluskey, L; Feinberg, D; Dolinskas, C

1999-06-01

389

Nerve Growth Factor and Diabetic Neuropathy  

PubMed Central

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

Vinik, Aaron

2003-01-01

390

Other autonomic neuropathies associated with ganglionic antibody  

Microsoft Academic Search

The acetylcholine receptor ganglionic (G-AchR) antibody is a very specific serologic test for autoimmune autonomic ganglionopathy. The spectrum of autoimmune (or presumed to be autoimmune) autonomic disorders, however, is quite broad and positivity to this antibody has been reported in a variety of other conditions, albeit infrequent and with low titer.This review describes the autonomic neuropathies most frequently encountered in

Paola Sandroni; Phillip A. Low

2009-01-01

391

Optic disk excavation in nonarteritic anterior ischemic optic neuropathy.  

PubMed

Most ischemic optic neuropathies are attributed to interference of blood flow originating within the posterior ciliary circulation. In patients with the most common type of ischemic optic neuropathy, nonarteritic anterior ischemic optic neuropathy (NAION), the microvascular ischemia predominantly affects the intraocular portion of the optic nerve. NAION most commonly occurs in eyes with small, "crowded" optic disks and usually does not result in optic disk excavation. We report a patient who presented with NAION and subsequently developed optic disc excavation typical of glaucomatous optic neuropathy. PMID:20436358

Punjabi, Omar S; Tanna, Angelo P; Rosenberg, Michael A

2011-02-01

392

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. PMID:24088641

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

2014-01-01

393

Hereditary pancreatitis: new insights, new directions.  

PubMed

Hereditary pancreatitis is an unusual form of acute and chronic pancreatitis with a familial predisposition. Recently, the gene mutations causing most cases of hereditary pancreatitis have been identified in the cationic trypsinogen gene. The known mutations are trypsinogen R117H and N211. These may predispose to acute pancreatitis by eliminating one of the fail-safe mechanisms used by the pancreas to eliminate prematurely activated trypsin. Accumulation of active trypsin mutants are hypothesized to initiate a digestive enzyme activation cascade in the pancreatic acinar cells leading to autodigestion, an intense inflammatory response, and acute pancreatitis. The observation that these patients also develop typical chronic pancreatitis and may later develop pancreatic cancer provides strong evidence that these conditions are linked. Knowledge of the pathophysiological conditions leading to acute and chronic pancreatitis and the development of a transgenic mouse expressing the mutant human trypsinogen genes will provide directions and tools necessary for the effective treatment or prevention of this human disease. PMID:11030605

Whitcomb, D C; Ulrich, C D

1999-07-01

394

Albright hereditary osteodystrophy: a case report.  

PubMed

A dental practitioner with an eagle's eye can diagnose many hidden disease through careful examination of the oral cavity. One such hereditary metabolic disorder is Albright hereditary osteodystrophy (AHO). Characteristic presentations in an individual affected by AHO were short stature, obesity and brachydactyly especially of 4(th) and 5(th) digits, which are the phenotypic features of genetic mutation. Pseudohypoparathyroidism (PHP) is characterized by inability of the body to respond appropriately to parathormone, mainly characterized by hypocalcemia, increased serum parathormone concentration, insensitivity to the biological activity of parathormone and hyperphosphatemia. AHO when seen in association with resistance to parathormone (PTH), it is called PHP. Here is, a case report of 32-year-old male patient with AHO with distinctive physical characteristics and oral manifestations. PMID:25478468

Hugar, Deepa; Sajjanshetty, Sangameshwar; Hugar, Santosh; Kadani, Megha

2014-10-01

395

Albright Hereditary Osteodystrophy: A Case Report  

PubMed Central

A dental practitioner with an eagle’s eye can diagnose many hidden disease through careful examination of the oral cavity. One such hereditary metabolic disorder is Albright hereditary osteodystrophy (AHO). Characteristic presentations in an individual affected by AHO were short stature, obesity and brachydactyly especially of 4th and 5th digits, which are the phenotypic features of genetic mutation. Pseudohypoparathyroidism (PHP) is characterized by inability of the body to respond appropriately to parathormone, mainly characterized by hypocalcemia, increased serum parathormone concentration, insensitivity to the biological activity of parathormone and hyperphosphatemia. AHO when seen in association with resistance to parathormone (PTH), it is called PHP. Here is, a case report of 32-year-old male patient with AHO with distinctive physical characteristics and oral manifestations. PMID:25478468

Sajjanshetty, Sangameshwar; Hugar, Santosh; Kadani, Megha

2014-01-01

396

Early Retinal Arteriolar Changes and Peripheral Neuropathy in Diabetes  

PubMed Central

OBJECTIVE To examine the association between early retinal arteriolar abnormalities and diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS Data from 608 people (aged 40–80 years) with diabetes from the population-based Singapore Malay Eye Study were analyzed. Participants underwent binocular two-field digital retinal photography and quantitative sensory testing. DPN was defined as an abnormal response to a monofilament or neurothesiometer test. Quantitative changes of retinal vascular caliber and arteriolar bifurcation geometry were measured using a computer-based program. Qualitative retinal signs of retinopathy and retinal arteriolar wall signs were graded by standardized methods. RESULTS DPN was present in 155 people (25.5%). After adjusting for age, sex, diabetes duration, HbA1c, cardiovascular risk factors, antihypertensive medication use, and peripheral arterial disease, people with suboptimal arteriolar caliber (odds ratio 1.94 [95% CI 1.22–3.10]), larger arteriolar branching coefficient (1.58 [1.03–2.42]), diabetic retinopathy (1.82 [1.20–2.75]), and focal arteriolar narrowing (2.92 [1.48–5.76]) were more likely to have DPN. Participants with a greater number of retinal microvascular signs were more likely to have DPN than those without retinal changes (6.11 [2.11–17.71] for two or more signs and 3.47 [1.18–10.21] for one sign compared with none). CONCLUSIONS Individuals with diabetes with early retinal arteriolar abnormalities are more likely to have DPN, independent of hyperglycemia and major vascular risk factors. These data support the hypothesis that early microvascular dysfunction, evident in the retina, is an independent risk factor for DPN. PMID:22374638

Ding, Jie; Cheung, Carol Y.; Ikram, M. Kamran; Zheng, Ying-Feng; Cheng, Ching-Yu; Lamoureux, Ecosse L.; Tai, E. Shyong; Subramaniam, Tavintharan; Wong, Tien Yin

2012-01-01

397

Environmental Awareness (Sensory Awareness).  

ERIC Educational Resources Information Center

Capitalizing on the resources available within a city block, this resource guide for the emotionally handicapped (K-6) describes methods and procedures for developing sensory awareness in the urban out-of-doors. Conceptual focus is on interdependency ("living things are interdependent"). Involvement in the environment (observing, thinking, doing)…

Carpenter, Marian

398

Recording Sensory Words  

ERIC Educational Resources Information Center

From children's viewpoints, what they experience in the world is what the world is like--for everyone. "What do others experience with their senses when they are in the same situation?" is a question that young children can explore by collecting data as they use a "feely box," or take a "sensory walk." There are many ways to focus the children's…

Ashbrook, Peggy

2007-01-01

399

Structured Sensory Trauma Interventions  

ERIC Educational Resources Information Center

This article features the National Institute of Trauma and Loss in Children (TLC), a program that has demonstrated via field testing, exploratory research, time series studies, and evidence-based research studies that its Structured Sensory Intervention for Traumatized Children, Adolescents, and Parents (SITCAP[R]) produces statistically…

Steele, William; Kuban, Caelan

2010-01-01

400

Hereditary auto-inflammatory disorders and biologics  

Microsoft Academic Search

The term auto-inflammatory disorders has been coined to describe a group of conditions characterized by spontaneously relapsing and remitting bouts of systemic\\u000a inflammation without apparent involvement of antigen-specific T cells or significant production of auto-antibodies. The hereditary\\u000a periodic fever syndromes are considered as the prototypic auto-inflammatory diseases, and genetic studies have yielded important\\u000a new insights into innate immunity. DNA analysis

Leigh D. Church; Sarah M. Churchman; Philip N. Hawkins; Michael F. McDermott

2006-01-01

401

Hereditary coproporphyria and chronic tubulointerstitial nephritis  

Microsoft Academic Search

A 41-year-old woman was admitted to our hospital because of abdominal pain, limb weakness, and red-wine-colored urine. Laboratory\\u000a data showed renal insufficiency and hyperchloremic metabolic acidosis due to type 4 renal tubular acidosis. Clinical manifestations\\u000a and investigation of porphyrins in her urine, erythrocytes, and feces established the diagnosis of hereditary coproporphyria\\u000a (HCP). Renal biopsy revealed chronic tubulointerstitial nephritis. She was

Kenji Osafune; Takayuki Yoshinaga; Makoto Tadano; Hiroya Takeoka; Yasufumi Kageyama; Rokuro Mimura; Hiroshi Saita; Keiji Ichikawa; Kazuro Kanatsu

2000-01-01

402

X-linked bulbospinomuscular atrophy (Kennedy's disease) masquerading as lead neuropathy.  

PubMed

A 43-year-old male was referred by a veterinarian who evaluated his dog for a seizure and suspected a toxic lead exposure for both. He refurbished houses, removing old paint, and complained of decreased cognition, fatigue, and muscle cramps. He had a depressed affect, postural tremor, right arm weakness with partial denervation on EMG, and borderline-low sensory nerve action potential (SNAP) amplitudes. A mild anemia and elevated serum and urine lead levels supported a diagnosis of lead neuropathy. Chelation therapy increased urine lead excretion without symptomatic improvement. His brother worked part-time with him and developed similar findings, but also had difficulty chewing, dysphagia, perioral twitching, gynecomastia, and multifocal denervation of extremity and facial muscles. His lead levels were not elevated, but an androgen receptor mutation identified on the X chromosome for both brothers confirmed the diagnosis of X-linked bulbospinomuscular atrophy (Kennedy's disease). PMID:8170488

Albers, J W; Bromberg, M B

1994-04-01

403

Peripheral nerve function in patients with painful diabetic neuropathy treated with continuous subcutaneous insulin infusion.  

PubMed Central

In order to study the effects of improved metabolic control on painful diabetic polyneuropathy, 15 patients were treated with continuous subcutaneous insulin infusion over a 12 month period. Polyneuropathy was assessed by pain score, neurological examinations, nerve conduction studies and determination of sensory thresholds and cardiovascular reflexes. Improved metabolic control was confirmed by significantly improved levels of glycosylated haemoglobin (11.7 +/- 0.3% at entry to the study, to 8.7 +/- 0.3% after 12 months; mean +/- SEM). Symptomatic relief was confirmed by significantly improved pain scores. Thresholds for thermal cutaneous sensation improved significantly from 6.0 +/- 0.8 degrees C at entry to the study to 2.7 +/- 0.7 degrees C after 12 months (mean +/- SEM). These findings suggest a selective improvement of peripheral small nerve fibre function after continuous subcutaneous insulin infusion. The importance of quantitating thermal cutaneous sensation in longitudinal studies of patients with diabetic neuropathy was confirmed. PMID:3681313

Bertelsmann, F W; Heimans, J J; Van Rooy, J C; Dankmeijer, H F; Visser, S L; Van der Veen, E A

1987-01-01

404

Understanding Sensory Integration. ERIC Digest.  

ERIC Educational Resources Information Center

This brief paper summarizes what is known about sensory integration and sensory integration dysfunction (DSI). It outlines evaluation of DSI, treatment approaches, and implications for parents and teachers, including compensatory strategies for minimizing the impact of DSI on a child's life. Review of origins of sensory integration theory in the…

DiMatties, Marie E.; Sammons, Jennifer H.

405

Sensory Integration in Mental Health  

Microsoft Academic Search

Lorna Jean King is interviewed concerning the present status of sensory integration as a treatment modality in the area of mental health. Topics covered are: use of sensory integration techniques with adults and adolescents in both chronic and acute mental health settings; goals and expected outcomes of using sensory integration techniques; cost-effectiveness of these techniques; differences between occupational therapy and

Barbara W. Posthuma

1983-01-01

406

The role of miR-146a in dorsal root ganglia neurons of experimental diabetic peripheral neuropathy  

PubMed Central

Sensory neurons mediate diabetic peripheral neuropathy. Using a mouse model of diabetic peripheral neuropathy (db/db mice) and cultured dorsal root ganglion (DRG) neurons, the present study showed that hyperglycemia downregulated miR-146a expression and elevated interleukin-1 receptor activated kinase (IRAK1) and tumor necrosis factor receptor-associated factor 6 (TRAF6) levels in DRG neurons. In vitro, elevation of miR-146a by miR-146a mimics in DRG neurons increased neuronal survival under high glucose conditions. Downregulation and elevation of miR-146a in DRG neurons, respectively, were inversely related to IRAK1 and TRAF6 levels. Treatment of diabetic peripheral neuropathy with sildenafil, a phosphodiesterase type 5 inhibitor, augmented miR-146a expression and decreased levels of IRAK1 and TRAF6 in the DRG neurons. In vitro, blockage of miR-146a in DRG neurons abolished the effect of sildenafil on DRG neuron protection and downregulation of IRAK1 and TRAF6 proteins under hyperglycemia. Our data provide the first evidence showing that miR-146a plays an important role in mediating DRG neuron apoptosis under hyperglycemic conditions. PMID:24316060

Wang, Lei; Chopp, Michael; Szalad, Alexandra; Zhang, Yi; Wang, Xinli; Zhang, RuiLan; Liu, Xianshuang; Jia, Longfei; Zhang, Zheng Gang

2014-01-01

407

The role of miR-146a in dorsal root ganglia neurons of experimental diabetic peripheral neuropathy.  

PubMed

Sensory neurons mediate diabetic peripheral neuropathy. Using a mouse model of diabetic peripheral neuropathy (BKS.Cg-m+/+Lepr(db)/J (db/db) mice) and cultured dorsal root ganglion (DRG) neurons, the present study showed that hyperglycemia downregulated miR-146a expression and elevated interleukin-1 receptor-activated kinase (IRAK1) and tumor necrosis factor receptor-associated factor 6 (TRAF6) levels in DRG neurons. In vitro, elevation of miR-146a by miR-146a mimics in DRG neurons increased neuronal survival under high-glucose conditions. Downregulation and elevation of miR-146a in DRG neurons, respectively, were inversely related to IRAK1 and TRAF6 levels. Treatment of diabetic peripheral neuropathy with sildenafil, a phosphodiesterase type 5 inhibitor, augmented miR-146a expression and decreased levels of IRAK1 and TRAF6 in the DRG neurons. In vitro, blockage of miR-146a in DRG neurons abolished the effect of sildenafil on DRG neuron protection and downregulation of IRAK1 and TRAF6 proteins under hyperglycemia. Our data provide the first evidence showing that miR-146a plays an important role in mediating DRG neuron apoptosis under hyperglycemic conditions. PMID:24316060

Wang, L; Chopp, M; Szalad, A; Zhang, Y; Wang, X; Zhang, R L; Liu, X S; Jia, L; Zhang, Z G

2014-02-14

408

Loss of Fig4 in both Schwann cells and motor neurons contributes to CMT4J neuropathy  

PubMed Central

Mutations of FIG4 are responsible for Yunis-Varón syndrome, familial epilepsy with polymicrogyria, and Charcot-Marie-Tooth type 4J neuropathy (CMT4J). Although loss of the FIG4 phospholipid phosphatase consistently causes decreased PtdIns(3,5)P2 levels, cell-specific sensitivity to partial loss of FIG4 function may differentiate FIG4-associated disorders. CMT4J is an autosomal recessive neuropathy characterized by severe demyelination and axonal loss in human, with both motor and sensory involvement. However, it is unclear whether FIG4 has cell autonomous roles in both motor neurons and Schwann cells, and how loss of FIG4/PtdIns(3,5)P2-mediated functions contribute to the pathogenesis of CMT4J. Here, we report that mice with conditional inactivation of Fig4 in motor neurons display neuronal and axonal degeneration. In contrast, conditional inactivation of Fig4 in Schwann cells causes demyelination and defects in autophagy-mediated degradation. Moreover, Fig4-regulated endolysosomal trafficking in Schwann cells is essential for myelin biogenesis during development and for proper regeneration/remyelination after injury. Our data suggest that impaired endolysosomal trafficking in both motor neurons and Schwann cells contributes to CMT4J neuropathy. PMID:25187576

Vaccari, Ilaria; Carbone, Antonietta; Previtali, Stefano Carlo; Mironova, Yevgeniya A.; Alberizzi, Valeria; Noseda, Roberta; Rivellini, Cristina; Bianchi, Francesca; Del Carro, Ubaldo; D'Antonio, Maurizio; Lenk, Guy M.; Wrabetz, Lawrence; Giger, Roman J.; Meisler, Miriam H.; Bolino, Alessandra

2015-01-01

409

Vitamin A increases nerve growth factor and retinoic acid receptor beta and improves diabetic neuropathy in rats.  

PubMed

All-trans retinoic acid (ATRA) promotes the endogenous expression of both nerve growth factor (NGF) and retinoic acid receptor beta (RAR-?). We have previously shown that the administration of ATRA partly reverts the damage induced by diabetic neuropathy (DN). In this investigation, we evaluated the effects of vitamin A, a commercial, inexpensive compound of retinoic acid, on the therapy of DN. A total of 70 rats were randomized into 4 groups. Group A was the control, and groups B, C, and D received a total dose of 60 mg/kg streptozotocin intraperitoneally. When signs of DN developed, groups C and D were treated either with vitamin A (20,000 IU) or with ATRA 25 mg/kg for 60 days. Plasma glucose, contents of NGF, thermal and nociceptive tests, and RAR-? expression were evaluated. All diabetic rats developed neuropathy. The treatment with vitamin A and ATRA reverted similarly the sensorial disturbances, which was associated with increased contents of NGF and RAR-? expression. Our results indicate that the administration of vitamin A has the same therapeutic effect as ATRA on peripheral neuropathy and suggest its potential therapeutic use in patients with diabetes. PMID:24768685

Hernández-Pedro, Norma; Granados-Soto, Vinicio; Ordońez, Graciela; Pineda, Benjamin; Rangel-López, Edgar; Salazar-Ramiro, Aleli; Arrieta, Oscar; Sotelo, Julio

2014-09-01

410

Loss of Fig4 in both Schwann cells and motor neurons contributes to CMT4J neuropathy.  

PubMed

Mutations of FIG4 are responsible for Yunis-Varón syndrome, familial epilepsy with polymicrogyria, and Charcot-Marie-Tooth type 4J neuropathy (CMT4J). Although loss of the FIG4 phospholipid phosphatase consistently causes decreased PtdIns(3,5)P2 levels, cell-specific sensitivity to partial loss of FIG4 function may differentiate FIG4-associated disorders. CMT4J is an autosomal recessive neuropathy characterized by severe demyelination and axonal loss in human, with both motor and sensory involvement. However, it is unclear whether FIG4 has cell autonomous roles in both motor neurons and Schwann cells, and how loss of FIG4/PtdIns(3,5)P2-mediated functions contribute to the pathogenesis of CMT4J. Here, we report that mice with conditional inactivation of Fig4 in motor neurons display neuronal and axonal degeneration. In contrast, conditional inactivation of Fig4 in Schwann cells causes demyelination and defects in autophagy-mediated degradation. Moreover, Fig4-regulated endolysosomal trafficking in Schwann cells is essential for myelin biogenesis during development and for proper regeneration/remyelination after injury. Our data suggest that impaired endolysosomal trafficking in both motor neurons and Schwann cells contributes to CMT4J neuropathy. PMID:25187576

Vaccari, Ilaria; Carbone, Antonietta; Previtali, Stefano Carlo; Mironova, Yevgeniya A; Alberizzi, Valeria; Noseda, Roberta; Rivellini, Cristina; Bianchi, Francesca; Del Carro, Ubaldo; D'Antonio, Maurizio; Lenk, Guy M; Wrabetz, Lawrence; Giger, Roman J; Meisler, Miriam H; Bolino, Alessandra

2015-01-15

411

Treatment with anti-TNF alpha protects against the neuropathy induced by the proteasome inhibitor bortezomib in a mouse model.  

PubMed

Bortezomib (BTZ), a proteasome inhibitor, is an effective anti-neoplastic drug used in the treatment of multiple myeloma and mantle cell lymphoma. However, it can induce a reversible peripheral neuropathy that may lead to treatment discontinuation. The mechanism through which BTZ exerts toxic effects in peripheral neurons is not clear. Release of proinflammatory cytokines after nerve damage can induce neurodegeneration, but the effects of BTZ on cytokine expression in neurons are unknown, although BTZ modulates the expression of cytokines, such as TNF-? and IL-6, in tumor cells. The aim of this study was to evaluate the expression and the role of these cytokines on the course of BTZ induced neuropathy in mice. IL-6, TNF-?, TGF-?1 and IL-1? were up-regulated in dorsal root ganglia but TNF-? and IL-6 increased faster and higher. Then, we studied the potential neuroprotective effect of selective antibodies anti-TNF-? and anti-IL-6 on the evolution of the neuropathy. Treatment with anti-TNF-? but not with anti-IL-6 significantly prevented the decrease of sensory nerve action potentials amplitude and the loss of myelinated and unmyelinated fibers. We conclude that monoclonal antibodies directed against TNF-? may be a suitable neuroprotective therapy against the neurotoxicity induced by BTZ. PMID:24406455

Alé, Albert; Bruna, Jordi; Morell, Marta; van de Velde, Helgi; Monbaliu, Johan; Navarro, Xavier; Udina, Esther

2014-03-01

412

Transferrin receptor function in hereditary hemochromatosis  

SciTech Connect

The binding of /sup 125/I-diferric transferrin to cultured skin fibroblasts and phytohemagglutinin-stimulated lymphocytes was studied in cells derived from individuals homozygous for hereditary hemochromatosis and from normal individuals. Receptors with a high affinity for diferric transferrin were present on all cells. Transferrin receptor number decreased by more than 50% when fibroblasts from both normal and hemochromatotic subjects were maintained in iron-supplemented medium. The number of transferrin receptors expressed by normal and hemochromatotic lymphocytes after mitogen stimulation in iron-supplemented media was less than 50% that of lymphocytes which were mitogen stimulated in standard medium. No change in the affinity of the receptors of diferric transferrin was seen in cells maintained in iron-supplemented medium. Competition experiments in the presence of deferoxamine suggested that the transferrin receptors of fibroblasts and mitogen-stimulated lymphocytes have a 70- to 100-fold higher affinity for diferric transferrin than for apotransferrin. No differences in the properties of transferrin receptors were found between patients with hereditary hemochromatosis and normal individuals. Although transferrin binding decreases when cells are exposed to high levels of iron in the medium, the failure to totally abolish transferrin binding to the receptor suggests that the concentration of diferric transferrin to which cells are exposed may be a major determinant of cellular iron loading in hereditary hemochromatosis.

Ward, J.H.; Kushner, J.P.; Ray, F.A.; Kaplan, J.

1984-02-01

413

Sensory analysis of lipstick.  

PubMed

Sensory analysis of lipstick product by trained panellists started with recruiting female panels who are lipstick users, in good health condition and willing to be a part of sensory members. This group of people was further scrutinized with duo-trio method using commercial lipstick samples that are commonly used among them. About 40% of the 15 panels recruited were unable to differentiate the lipstick samples they usually use better than chance. The balance of nine panels that were corrected at least with 65% across all trials in panels screening process was formed a working group to develop sensory languages as a means of describing product similarities and differences and a scoring system. Five sessions with each session took about 90 min were carried out using 10 types of lipsticks with different waxes mixture ratio in the formulation together with six commercial lipsticks that are the most common to the panels. First session was focus on listing out the panels' perception towards the characteristic of the lipstick samples after normal application on their lips. Second session was focus on the refining and categorizing the responses gathered from the first session and translated into sensory attributes with its definition. Third session was focus on the scoring system. Fourth and fifth sessions were repetition of the third session to ensure consistency. In a collective effort of the panels, sensory attributes developed for lipstick were Spreadability, Off flavour, Hardness, Smoothness, Moist, Not messy, Glossy and Greasy. Analysis of variance was able to provide ample evidence on gauging the panel performance. A proper panels selecting and training was able to produce a reliable and sensitive trained panel for evaluating the product based on the procedures being trained. PMID:21272038

Yap, K C S; Aminah, A

2011-06-01