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1

Hereditary sensory neuropathy type I  

Microsoft Academic Search

Hereditary sensory neuropathy type I (HSN I) is a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset. The exact prevalence is unknown, but is estimated as very low. Disease onset varies between the 2nd and 5th decade of life. The main clinical feature of HSN I

Michaela Auer-Grumbach

2008-01-01

2

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 ...

3

Autosomal recessive forms of hereditary motor and sensory neuropathy  

Microsoft Academic Search

Six families are described with hereditary motor and sensory neuropathy (HMSN) of probable autosomal recessive inheritance. Four of these were classified as HMSN type I and two as type II. The consanguinity rate in this series was high, suggesting that these recessive genes are rare. In comparison with the dominantly inherited forms of these disorders, the mean age of onset

A E Harding; P K Thomas

1980-01-01

4

A case of hereditary sensory autonomic neuropathy type IV.  

PubMed

Hereditary sensory autonomic neuropathy type IV (HSAN -IV), also known as congenital insensitivity to pain with anhidrosis, is a very rare condition that presents in infancy with anhidrosis, absence of pain sensation and self -mutilation. Developmental delay and mental retardation are usually present. Ultrastructural study of the peripheral nerves demonstrates loss of the unmyelinated and small myelinated fibers. We here report a 8 year -old boy with HSAN IV with typical clinical features where the diagnosis was supported by nerve biopsy findings. However, our case was unusual since mental development was normal. PMID:22566729

Prashanth, G P; Kamate, Mahesh

2012-04-01

5

A case of hereditary sensory autonomic neuropathy type IV  

PubMed Central

Hereditary sensory autonomic neuropathy type IV (HSAN -IV), also known as congenital insensitivity to pain with anhidrosis, is a very rare condition that presents in infancy with anhidrosis, absence of pain sensation and self -mutilation. Developmental delay and mental retardation are usually present. Ultrastructural study of the peripheral nerves demonstrates loss of the unmyelinated and small myelinated fibers. We here report a 8 year -old boy with HSAN IV with typical clinical features where the diagnosis was supported by nerve biopsy findings. However, our case was unusual since mental development was normal. PMID:22566729

Prashanth, G. P.; Kamate, Mahesh

2012-01-01

6

Cardiac arrest after anesthetic management in a patient with hereditary sensory autonomic neuropathy type IV  

PubMed Central

Hereditary sensory autonomic neuropathy type IV is a rare disorder with an autosomal recessive transmission and characterized by self-mutilation due to a lack in pain and heat sensation. Recurrent hyperpyrexia and anhydrosis are seen in patients as a result of a lack of sweat gland innervation. Self-mutilation and insensitivity to pain result in orthopedic complications and patients undergone recurrent surgical interventions with anesthesia. However, these patients are prone to perioperative complications such as hyperthermia, hypothermia, and cardiac complications like bradycardia and hypotension. We report a 5-year-old boy with hereditary sensory autonomic neuropathy type IV, developing hyperpyrexia and cardiac arrest after anesthesia. PMID:21655028

Ergul, Yakup; Ekici, Baris; Keskin, Sabiha

2011-01-01

7

Palmoplantar keratoderma, nail dystrophy, and hereditary motor and sensory neuropathy: an autosomal dominant trait  

Microsoft Academic Search

Autosomal dominant inheritance of a syndrome comprising palmoplantar keratoderma, nail dystrophy, and hereditary motor and sensory neuropathy (HMSN) was observed in three generations of one family. Nail dystrophy affected the toe and fingernails; it was present at birth or developed during early childhood. Palmoplantar keratoderma became apparent in later childhood. Each subject with nail dystrophy and keratoderma also had clinical

J L Tolmie; D E Wilcox; R McWilliam; A Assindi; J B Stephenson

1988-01-01

8

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

Microsoft Academic Search

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

A E Harding; P K Thomas

1980-01-01

9

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

10

Recent Advances in the Genetics of Hereditary Axonal Sensory-Motor Neuropathies Type 2  

Microsoft Academic Search

Hereditary axonal motor and sensory neuropathies or Charcot-Marie-Tooth disease type 2 (CMT2) are characterized clinically\\u000a by distal muscle weakness and atrophy, sensory loss, and foot deformities. Conduction velocities are usually in the normal\\u000a range or mildly slowed. The majority of CMT2 are autosomal-dominant but autosomal-recessive forms have been described. The\\u000a number of genes associated with CMT2 have significantly increased in

Senda Ajroud-Driss; Han-Xiang Deng; Teepu Siddique

2011-01-01

11

Novel mutations in the HSN2 gene causing hereditary sensory and autonomic neuropathy type II.  

PubMed

Hereditary sensory and autonomic neuropathy type II (HSAN-II) is caused by recessive mutations in the HSN2 gene assigned to chromosome 12p13.33. The authors report three unrelated HSAN-II families with homozygous or compound heterozygous mutations resulting in the truncation of the HSN2 protein. Genotype-phenotype correlations indicated that HSN2 mutations are associated with an early childhood onset of a predominantly sensory neuropathy, complicated by acromutilations in both upper and lower limbs. PMID:16534117

Coen, K; Pareyson, D; Auer-Grumbach, M; Buyse, G; Goemans, N; Claeys, K G; Verpoorten, N; Laurà, M; Scaioli, V; Salmhofer, W; Pieber, T R; Nelis, E; De Jonghe, P; Timmerman, V

2006-03-14

12

Clinical Features: Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum (HMSN/ACC) [OMIM #218000  

E-print Network

1/13 Clinical Features: Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus sensorimotor neuropathy resulting in hypotonia, areflexia and amyotrophy, variable degrees of dysgenesis Neuropathy with Agenesis of the Corpus Callosum #12;1/13 Prenatal testing for a known mutation Sample

Ober, Carole

13

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.

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

2014-01-01

14

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

PubMed

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; Kang, Sa-Yoon

2014-09-01

15

[Hereditary neuropathy: recent advance].  

PubMed

Hereditary neuropathies are classified into Charcot-Marie-Tooth disease (CMT), familial amyloid polyneuropathy (FAP), hereditary motor neuropathies (HMN) and hereditary sensory (and autonomic) neuropathies (HSAN). CMTs are furthermore classified into demyelinating neuropathies (CMT1), axonal neuropathies (CMT2) and intermediate form. Duplication of PMP22 (CMT1A) accounts for about 70% of CMT1 and MFN2 mutations account for 25% of CMT2. Genes involved in phosphoinositide regulation cause CMT4; MTMR2 mutation in CMT 4B1 and MTMR13/SBF2 mutation in CMT4B2. In addition to these genes, FIG4, which is a causative gene of pale tremor mouse, is newly identified as a gene for CMT4J. MFN2 and GDAP1 cause CMT2 or CMT4. These genes regulate mitochondrial fusion and fission. Altered axonal mitochondrial transport is suggested as the pathogenesis of the CMT. In animal model with pmp22 duplication, ascorbic acid seems to be effective to prevent disease progression. Nationwide trial of ascorbic acid therapy for CMT1A is now ongoing by the intractable neuropathy study group. Curcumin treatment educes apoptosis of cells that express PMP22 point mutation and partially mitigates the severe neuropathy phenotype of Trembler-J mouse model in a dose-dependent manner. Curcumin treatment may have a potential therapeutic role in CMT with PMP22 point mutation in humans. The high throughput system of diagnosis for CMT has been developed by employing a resequencing array system. PMID:19198150

Nakagawa, Masanori

2008-11-01

16

Hereditary sensory neuropathy type 1 in a Portuguese family-electrodiagnostic and autonomic nervous system studies.  

PubMed

Hereditary sensory and autonomic neuropathy type 1 (HSAN 1) is a dominantly inherited disorder; its gene locus is mapped on chromosome 9q22. Three different missense mutations (C133Y, C133W and V144D) have been described in 11 families from Australia, England and Austria. Common clinical features have been found in these families. We report the clinical and electrophysiological features of three members of a large Portuguese family with HSAN 1 and the C133Y missense mutation. The affected members showed typical clinical features. Electrophysiological findings were consistent with a distal axonal predominantly sensory neuropathy with motor involvement, in three different severity stages. No autonomic involvement was detected in sudomotor and cardiovascular tests. This report documents the lesion of the motor nerve fibers in this disease, as well as the preservation of the autonomic nervous system function, therefore suggesting that HSNA is an inappropriate name for this disorder. PMID:15546589

Geraldes, Ruth; de Carvalho, Mamede; Santos-Bento, Mariana; Nicholson, Garth

2004-12-15

17

Hereditary motor and sensory neuropathy--Lom, a novel demyelinating neuropathy associated with deafness in gypsies. Clinical, electrophysiological and nerve biopsy findings  

Microsoft Academic Search

Summary A previously unrecognized neuropathy was identified in Bulgarian gypsies, and was designated hereditary motor and sensory neuropathy-Lom (HMSNL) after the town where the initial cases were found. It was subsequently identified in other gypsy communities. The disorder, which is of autosomal recessive inheritance, was mapped to chromosome 8q24. It begins consistently in the first decade of life with gait

Luba Kalaydjieva; Amelia Nikolova; Ivo Turnev; Julia Petrova; Anna Hristova; Boryana Ishpekova; Iva Petkova; Alexander Shmarov; Stella Stancheva; L. Middleton; Luciano Merlini; A. Trogu; J. R. Muddle; R. H. M. King; P. K. Thomas

1998-01-01

18

[Update on hereditary neuropathy].  

PubMed

Hereditary neuropathies are classified into several subtypes according to clinical, electrophysiologic and pathologic findings. Recent genetic studies have revealed their phenotypic and genetic diversities. In the primary peripheral demyelinating neuropathies (CMT1), at least 15 genes have been associated with the disorders; altered dosage or point mutation of PMP22, GJB1, MPZ, EGR2, MTMR2, NDRG1, PRX, SOX10, GDAP1 and MTMR13/SBF2. In the primary peripheral axonal neuropathies (CMT2), at least 10 genes have been associated with these disorders; NEFL, KIF1B, MFN2, GAN1, LMNA, RAB7, GARS, TDP1, APTX, and SETX. In addition, some mutations in GJB1, MPZ, GDAP1 and NEFL also present with clinical and electrophysiologic findings of CMT2. Patients with TDP1, APTX or SETX mutations share common clinical findings; autosomal recessive inheritance, cerebellar ataxia, and axonal neuropathy. These genes are suspected to be related to DNA/RNA repair and induce cell death especially in neuronal cells. In addition to the above diseases, we have reported a new type of NMSNP (MIM# * 604484) characterized by proximal dominant neurogenic atrophy, obvious sensory nerve involvement and the gene locus on 3q12.3. Here, we summarize the genetic bases of hereditary neuropathies and attempt to highlight significant genotype-phenotype correlations with a special interest in nonsense-mediated mRNA decay pathway. PMID:15651351

Nakagawa, Masanori; Takashima, Hiroshi

2004-11-01

19

Genes for hereditary sensory and autonomic neuropathies: a genotype-phenotype correlation.  

PubMed

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 and RAB7) and five genes for autosomal recessive forms of HSAN (WNK1/HSN2, NTRK1, NGFB, CCT5 and IKBKAP). We performed a systematic mutation screening of the coding sequences of six of these genes on a cohort of 100 familial and isolated patients diagnosed with HSAN. In addition, we screened the functional candidate gene NGFR (p75/NTR) encoding the nerve growth factor receptor. We identified disease-causing mutations in SPTLC1, RAB7, WNK1/HSN2 and NTRK1 in 19 patients, of which three mutations have not previously been reported. The phenotypes associated with mutations in NTRK1 and WNK1/HSN2 typically consisted of congenital insensitivity to pain and anhidrosis, and early-onset ulcero-mutilating sensory neuropathy, respectively. RAB7 mutations were only found in patients with a Charcot-Marie-Tooth type 2B (CMT2B) phenotype, an axonal sensory-motor neuropathy with pronounced ulcero-mutilations. In SPTLC1, we detected a novel mutation (S331F) corresponding to a previously unknown severe and early-onset HSAN phenotype. No mutations were found in NGFB, CCT5 and NGFR. Overall disease-associated mutations were found in 19% of the studied patient group, suggesting that additional genes are associated with HSAN. Our genotype-phenotype correlation study broadens the spectrum of HSAN and provides additional insights for molecular and clinical diagnosis. PMID:19651702

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

2009-10-01

20

Genes for hereditary sensory and autonomic neuropathies: a genotype-phenotype correlation  

PubMed Central

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 and RAB7) and five genes for autosomal recessive forms of HSAN (WNK1/HSN2, NTRK1, NGFB, CCT5 and IKBKAP). We performed a systematic mutation screening of the coding sequences of six of these genes on a cohort of 100 familial and isolated patients diagnosed with HSAN. In addition, we screened the functional candidate gene NGFR (p75/NTR) encoding the nerve growth factor receptor. We identified disease-causing mutations in SPTLC1, RAB7, WNK1/HSN2 and NTRK1 in 19 patients, of which three mutations have not previously been reported. The phenotypes associated with mutations in NTRK1 and WNK1/HSN2 typically consisted of congenital insensitivity to pain and anhidrosis, and early-onset ulcero-mutilating sensory neuropathy, respectively. RAB7 mutations were only found in patients with a Charcot-Marie-Tooth type 2B (CMT2B) phenotype, an axonal sensory-motor neuropathy with pronounced ulcero-mutilations. In SPTLC1, we detected a novel mutation (S331F) corresponding to a previously unknown severe and early-onset HSAN phenotype. No mutations were found in NGFB, CCT5 and NGFR. Overall disease-associated mutations were found in 19% of the studied patient group, suggesting that additional genes are associated with HSAN. Our genotype–phenotype correlation study broadens the spectrum of HSAN and provides additional insights for molecular and clinical diagnosis. PMID:19651702

Rotthier, Annelies; Baets, Jonathan; Vriendt, Els De; 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

2009-01-01

21

Strength training in patients with myotonic dystrophy and hereditary motor and sensory neuropathy: A randomized clinical trial  

Microsoft Academic Search

A randomized clinical trial on the effects of strength training was performed in myotonic dystrophy (MyD) patients and patients with hereditary motor and sensory neuropathy (HMSN). Training and most measurement tools involved the proximal lower extremity muscles. The participants trained 3 times a week for 24 weeks with weights adapted to their force. Strength was evaluated by isokinetically measured knee

Eline Lindeman; Pieter Leffers; Frank Spaans; Jan Drukker; Jos Reulen; Maria Kerckhoffs; Albere Köke

1995-01-01

22

From genes to pain: nerve growth factor and hereditary sensory and autonomic neuropathy type V.  

PubMed

Hereditary sensory and autonomic neuropathy type V (HSAN V) is an autosomal recessive disorder characterized by the loss of deep pain perception. The anomalous pain and temperature sensations are due to the absence of nociceptive sensory innervation. The neurotrophin nerve growth factor (NGF), by binding to tropomyosin receptor A (TrkA) and p75NTR receptors, is essential for the development and survival of sensory neurons, and for pain perception during adulthood. Recently a homozygous missense mutation (R100W) in the NGF gene has been identified in HSAN V patients. Interestingly, alterations in NGF signalling, due to mutations in the NGF TRKA gene, have also been involved in another congenital insensitivity to pain, HSAN IV, characterized not only by absence of reaction to painful stimuli, but also anhidrosis and mental retardation. These symptoms are absent in HSAN V patients. Unravelling the mechanisms that underlie the differences between HSAN IV and V could assist in better understanding NGF biology. This review highlights the recent key findings in the understanding of HSAN V, including insights into the molecular mechanisms of the disease, derived from genetic studies of patients with this disorder. PMID:24494679

Capsoni, Simona

2014-02-01

23

Immunological study of hereditary motor and sensory neuropathy type 1a (HMSN1a)  

PubMed Central

Objectives: Fifty three patients were studied to investigate whether autoimmune or inflammatory mechanisms could explain the phenotypic heterogeneity of patients with hereditary motor and sensory neuropathy type 1a (HMSN1a). Methods: Serum samples were examined for antibodies to peripheral nerve myelin protein 22 (PMP22), ganglioside GM1 and cauda equina homogenate, and interleukin-6 (IL-6) and soluble tumour necrosis factor receptor 1 (sTNF R1) concentrations. Serological results were compared with those from patients with other neuropathies (ONPs, n=30) and with normal subjects (n=51). Results: In the group as a whole, no relation emerged between clinical severity and any immune parameters. Immunohistochemical examination of four sural nerve biopsies did not show significant inflammatory infiltration. In a subset of 12 patients who experienced stepwise progression of disease, there was a trend towards a higher proportion having anti-PMP22 antibodies (33% v 15% of those with gradual disease progression, 3% ONPs, and no normal controls) and complement fixing antibodies to human cauda equina (25% v 5% with gradual progression, 8.6% ONPs, 3.9% normal controls, p=0.07). Conclusions: Patients with HMSN1a and a stepwise disease progression may have an inflammatory, autoimmune component superimposed on the genetic condition. PMID:11796774

Gabriel, C; Gregson, N; Wood, N; Hughes, R

2002-01-01

24

Misclassification and linkage of hereditary sensory and autonomic neuropathy type 1 as Charcot-Marie-Tooth disease, Type 2B  

SciTech Connect

Recently Kwon et al. published in the Journal their work describing linkage of a single large family with an inherited axonal neuropathy to chromosome 3, which they suggest is a second locus for Charcot-Marie-Tooth (CMT) type 2 and subsequently named {open_quotes}CMT2B.{close_quotes} We think that the diagnostic classification of this family as CMT2 is incorrect, since the subjects have a severe sensory neuropathy that fits within the hereditary sensory and autonomic neuropathy (HSAN) type 1 classification of Dyck (1993). Abnormal sensory findings in CMT2 separate it from distal spinal muscular atrophy but are a minor component of clinical symptoms in most CMT patients, as CMT is primarily a motor neuropathy. When Kwon et al. state that {open_quotes}all [patients] had characteristic findings in their physical examinations, including... evidence of foot sores that were slow to heal, or amputated limbs related to the poorly healing foot ulcers,{close_quotes} it suggests that a different diagnosis is more appropriate. In our experience collecting data on >950 individuals in >60 CMT1, CMT2, CMTX and CMT4 families, we have not seen foot ulcers, osteomyelitis, or amputations. Ulcerations leading to osteomyelitis and amputations are usually associated with severe sensory neuropathies. 16 refs., 1 tab.

Vance, J.M.; Speer, M.C.; Stajich, J.M. [Duke Univ. Medical Center, Durham, NC (United States)

1996-07-01

25

Frequency of mutations in the genes associated with hereditary sensory and autonomic neuropathy in a UK cohort  

PubMed Central

The hereditary sensory and autonomic neuropathies (HSAN, also known as the hereditary sensory neuropathies) are a clinically and genetically heterogeneous group of disorders, characterised by a progressive sensory neuropathy often complicated by ulcers and amputations, with variable motor and autonomic involvement. To date, mutations in twelve genes have been identified as causing HSAN. To study the frequency of mutations in these genes and the associated phenotypes, we screened 140 index patients in our inherited neuropathy cohort with a clinical diagnosis of HSAN for mutations in the coding regions of SPTLC1, RAB7, WNK1/HSN2, FAM134B, NTRK1 (TRKA) and NGFB. We identified 25 index patients with mutations in six genes associated with HSAN (SPTLC1, RAB7, WNK1/HSN2, FAM134B, NTRK1 and NGFB); 20 of which appear to be pathogenic giving an overall mutation frequency of 14.3%. Mutations in the known genes for HSAN are rare suggesting that further HSAN genes are yet to be identified. The p.Cys133Trp mutation in SPTLC1 is the most common cause of HSAN in the UK population and should be screened first in all patients with sporadic or autosomal dominant HSAN. PMID:22302274

Davidson, G. L.; Murphy, S. M.; Polke, J. M.; Laura, M.; Salih, M. A. M.; Muntoni, F.; Blake, J.; Brandner, S.; Davies, N.; Horvath, R.; Price, S.; Donaghy, M.; Roberts, M.; Foulds, N.; Ramdharry, G.; Soler, D.; Lunn, M. P.; Manji, H.; Davis, M. B.; Houlden, H.; Reilly, M. M.

2013-01-01

26

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

PubMed

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 maneuver, sensory and motor nerve conduction studies, quantitative sensory testing of thermal and vibratory perception, and the analysis of sudomotor function by recordings of the sympathetic skin response (SSR) or the sweat output during quantitative sudomotor axon reflex testing (QSART). The slowly progressive, symmetrical HSAN type I manifests between the second and fourth decade with ulcers or mutilations of the lower extremities, low normal sensory and motor nerve conduction velocities, but abnormal warm, cold and heat pain perception and distal anhidrosis. In HSAN type II, symptoms occur already in infancy, trophic alterations affect fingers and toes. There are acral anhidrosis and various autonomic dysfunctions such as tonic pupils, eating and swallowing difficulties, constipation, episodic fever, profound hypotonia and episodes of apnea. Sensory perception is severely impaired and accounts for elevated vibratory but also thermal perception thresholds. Sensory nerve conduction is highly abnormal while motor nerve conduction studies are almost normal. Type III, the autosomal recessive familial dysautonomia (FD), is the most common of the HSANs. FD is characterized by pronounced autonomic, primarily sympathetic dysregulation with severe orthostatic hypotension, repeated episodes of autonomic crises with excessive arterial hypertension, profuse sweating, skin blotching, puffy hands and behavioral abnormalities. FD manifests only in children of Ashkenazi Jewish ancestry. Cardinal findings are diminished deep tendon reflexes, absence of overflow tears, absence of fungi-form papillae of the tongue and of axon flare response following intradermal histamine injection. Thermal and vibratory testing show pronounced impairment of temperature and pain but also of vibratory perception. Children with HSAN IV, 'congenital insensitivity to pain with anhidrosis' experience repeated episodes of high fevers during high environmental temperature due to anhidrosis. The anhidrosis of the hyperkeratotic skin accounts for absence of the SSR or lack of sweat output during QSART. The patients' insensitivity to superficial as well as deep, visceral pain can be demonstrated e. g. by quantitative heat pain testing. Patients develop severe mutilations e. g. of the tip of their tongue, they might have severe burn injuries and multiple, unnoticed fractures with neuropathic joints. Children with the very rare HSAN type V respond normally to tactile, vibratory or thermal stimuli, but have a selective loss of pain perception with otherwise normal neurological examination. Painful stimuli reveal no signs of discomfort. PMID:12102461

Hilz, Max J

2002-05-01

27

Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing loss  

PubMed Central

DNA methyltransferase 1 (DNMT1) is crucial for maintenance of methylation, gene regulation and chromatin stability1-3. DNA mismatch repair, cell cycle regulation in post-mitotic neurons4,5 and neurogenesis6 are influenced by DNA methylation. Here we show mutations in DNMT1 cause both central and peripheral neurodegeneration in one form of hereditary sensory and autonomic neuropathy (HSAN1) with dementia and hearing loss7,8. Exome sequencing led to the identification of DNMT1 mutation c.A1484G (p.Tyr495Cys) in two American and one Japanese kindreds and a triple nucleotide change c.1470TCC-1472ATA (p.Asp490Glu-Pro491Tyr) in one European kindred. All mutations are within the targeting sequence (TS) domain of DNMT1. These mutations cause premature degradation of mutant proteins, reduced methyltransferase activity and impaired heterochromatin binding during the G2 cell cycle phase, leading to global hypomethylation and site specific hypermethylation. Our study demonstrates DNMT1 mutations cause aberrant methylation implicated in complex pathogenesis. The discovered DNMT1 mutations provide a new framework for the study of neurodegenerative diseases. PMID:21532572

Klein, Christopher J.; Botuyan, Maria-Victoria; Wu, Yanhong; Ward, Christopher J.; Nicholson, Garth A.; Hammans, Simon; Hojo, Kaori; Yamanishi, Hiromitch; Karpf, Adam R.; Wallace, Douglas C.; Simon, Mariella; Lander, Cecilie; Boardman, Lisa A.; Cunningham, Julie M.; Smith, Glenn E.; Litchy, William J.; Boes, Benjamin; Atkinson, Elizabeth J.; Middha, Sumit; Dyck, P. James; Parisi, Joseph E.; Mer, Georges; Smith, David I.; Dyck, Peter J.

2011-01-01

28

Epidemiology of hereditary sensory and autonomic neuropathy type IV and V in Japan.  

PubMed

Hereditary sensory and autonomic neuropathy (HASN) refers to a group of rare congenital disorders characterized by loss of pain sensation and other sensory or autonomic abnormalities. Among them, a relatively large proportion of patients with HSAN type IV, which is accompanied by anhidrosis and intellectual disability, are reported from Israel and Japan. HSAN type V, with normal sweating and mental development, is rarely reported in Japan. In 2009, we founded a research group for congenital insensitivity to pain and performed the first epidemiological survey of HSAN types IV and V in Japan. Questionnaires were sent to a total of 3,488 certified training institutions of five nationwide medical societies comprising pediatricians, neurologists, orthopedic surgeons, and dentists. Answers were obtained from 1,610 institutions, and 192 HSAN patients (152 with type IV and 28 with type V) were reported from 105 institutions. After excluding duplicated patients, we identified a total of 62 current, 36 past, and five deceased patients for HSAN-IV, and a total of 14 current, 13 past, and 0 deceased patients for HSAN-V. Using these figures, we estimated that the number of Japanese patients with HSAN types IV and V as 130-210 and 30-60 patients, respectively. We identified no gender differences, and patients with a family history of the disorder were limited to affected siblings in both conditions. Most patients with HSAN-IV were 5-40 years of age, whereas half of the patients with HSAN-V were 40 years or older. PMID:23495212

Haga, Nobuhiko; Kubota, Masaya; Miwa, Zenzo

2013-04-01

29

Exclusion of p75NGFR and other candidate genes in a family with hereditary sensory neuropathy type II.  

PubMed

Hereditary sensory neuropathy Type II (HSN II) is an autosomal recessive disorder characterized by the loss of peripheral sensory modalities in individuals with otherwise normal development. Patients with HSN II often have chronic ulceration of the fingers and toes, autoamputation of the distal phalanges, and neuropathic joint degeneration associated with loss of pain sensation. Recent descriptions of a similar phenotype in mice carrying a targeted mutation in the low affinity nerve growth factor receptor, p75NGFR, suggested the possibility that mutations in this gene or other members of the nerve growth factor (NGF) family of genes and their receptors might be responsible for this human disorder. In this study candidate genes were evaluated by their inheritance pattern in two sisters affected with HSN II, their unaffected sister and mother in a consanguineous family. The segregation of polymorphic alleles at and around loci for p75NGFR, TRKA, TRKB, BDNF, and familial dysautonomia (another hereditary sensory neuropathy having features in common with HSN II) virtually excluded these genes as the cause of HSN II in this family. Further evaluation of loci for other neurotrophic factors and their receptors, which will be possible when mapping information on their loci becomes available, may permit the identification of the gene responsible for HSN II. PMID:8895241

Davar, G; Shalish, C; Blumenfeld, A; Breakfield, X O

1996-09-01

30

KIF1A, an Axonal Transporter of Synaptic Vesicles, Is Mutated in Hereditary Sensory and Autonomic Neuropathy Type 2  

PubMed Central

Hereditary sensory and autonomic neuropathy type II (HSANII) is a rare autosomal-recessive disorder characterized by peripheral nerve degeneration resulting in a severe distal sensory loss. Although mutations in FAM134B and the HSN2 exon of WNK1 were associated with HSANII, the etiology of a substantial number of cases remains unexplained. In addition, the functions of WNK1/HSN2 and FAM134B and their role in the peripheral nervous system remain poorly understood. Using a yeast two-hybrid screen, we found that KIF1A, an axonal transporter of synaptic vesicles, interacts with the domain encoded by the HSN2 exon. In parallel to this screen, we performed genome-wide homozygosity mapping in a consanguineous Afghan family affected by HSANII and identified a unique region of homozygosity located on chromosome 2q37.3 and spanning the KIF1A gene locus. Sequencing of KIF1A in this family revealed a truncating mutation segregating with the disease phenotype. Subsequent sequencing of KIF1A in a series of 112 unrelated patients with features belonging to the clinical spectrum of ulcero-mutilating sensory neuropathies revealed truncating mutations in three additional families, thus indicating that mutations in KIF1A are a rare cause of HSANII. Similarly to WNK1 mutations, pathogenic mutations in KIF1A were almost exclusively restricted to an alternatively spliced exon. This study provides additional insights into the molecular pathogenesis of HSANII and highlights the potential biological relevance of alternative splicing in the peripheral sensory nervous system. PMID:21820098

Riviere, Jean-Baptiste; Ramalingam, Siriram; Lavastre, Valerie; Shekarabi, Masoud; Holbert, Sebastien; Lafontaine, Julie; Srour, Myriam; Merner, Nancy; Rochefort, Daniel; Hince, Pascale; Gaudet, Rebecca; Mes-Masson, Anne-Marie; Baets, Jonathan; Houlden, Henry; Brais, Bernard; Nicholson, Garth A.; Van Esch, Hilde; Nafissi, Shahriar; De Jonghe, Peter; Reilly, Mary M.; Timmerman, Vincent; Dion, Patrick A.; Rouleau, Guy A.

2011-01-01

31

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

32

Aberrant signature methylome by DNMT1 hot spot mutation in hereditary sensory and autonomic neuropathy 1E.  

PubMed

DNA methyltransferase 1 (DNMT1) is essential for DNA methylation, gene regulation and chromatin stability. We previously discovered DNMT1 mutations cause hereditary sensory and autonomic neuropathy type 1 with dementia and hearing loss (HSAN1E; OMIM 614116). HSAN1E is the first adult-onset neurodegenerative disorder caused by a defect in a methyltransferase gene. HSAN1E patients appear clinically normal until young adulthood, then begin developing the characteristic symptoms involving central and peripheral nervous systems. Some HSAN1E patients also develop narcolepsy and it has recently been suggested that HSAN1E is allelic to autosomal dominant cerebellar ataxia, deafness, with narcolepsy (ADCA-DN; OMIM 604121), which is also caused by mutations in DNMT1. A hotspot mutation Y495C within the targeting sequence domain of DNMT1 has been identified among HSAN1E patients. The mutant DNMT1 protein shows premature degradation and reduced DNA methyltransferase activity. Herein, we investigate genome-wide DNA methylation at single-base resolution through whole-genome bisulfite sequencing of germline DNA in 3 pairs of HSAN1E patients and their gender- and age-matched siblings. Over 1 billion 75-bp single-end reads were generated for each sample. In the 3 affected siblings, overall methylation loss was consistently found in all chromosomes with X and 18 being most affected. Paired sample analysis identified 564,218 differentially methylated CpG sites (DMCs; P<0.05), of which 300?134 were intergenic and 264?084 genic CpGs. Hypomethylation was predominant in both genic and intergenic regions, including promoters, exons, most CpG islands, L1, L2, Alu, and satellite repeats and simple repeat sequences. In some CpG islands, hypermethylated CpGs outnumbered hypomethylated CpGs. In 201 imprinted genes, there were more DMCs than in non-imprinted genes and most were hypomethylated. Differentially methylated region (DMR) analysis identified 5649 hypomethylated and 1872 hypermethylated regions. Importantly, pathway analysis revealed 1693 genes associated with the identified DMRs were highly associated in diverse neurological disorders and NAD+/NADH metabolism pathways is implicated in the pathogenesis. Our results provide novel insights into the epigenetic mechanism of neurodegeneration arising from a hotspot DNMT1 mutation and reveal pathways potentially important in a broad category of neurological and psychological disorders. PMID:25033457

Sun, Zhifu; Wu, Yanhong; Ordog, Tamas; Baheti, Saurabh; Nie, Jinfu; Duan, Xiaohui; Hojo, Kaori; Kocher, Jean-Pierre; Dyck, Peter J; Klein, Christopher J

2014-08-01

33

HIV Associated Sensory Neuropathy  

PubMed Central

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

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

2014-01-01

34

Hereditary and acquired amyloid neuropathies  

Microsoft Academic Search

Amyloid neuropathies occur in a context of hereditary (FAP) or acquired amyloidosis. They present usually as severe and progressive\\u000a polyneuropathy and carry a poor prognosis. Most FAP are associated with endoneurial deposits of variant transthyretin (TTR)\\u000a with substitution of one aminoacid and are secondary to a point mutation of the TTR gene. Portugal is the main endemic area\\u000a of TTR-FAP,

David Adams

2001-01-01

35

Identification of a Novel Gene (HSN2) Causing Hereditary Sensory and Autonomic Neuropathy Type II through the Study of Canadian Genetic Isolates  

PubMed Central

Hereditary sensory and autonomic neuropathy (HSAN) type II is an autosomal recessive disorder characterized by impairment of pain, temperature, and touch sensation owing to reduction or absence of peripheral sensory neurons. We identified two large pedigrees segregating the disorder in an isolated population living in Newfoundland and performed a 5-cM genome scan. Linkage analysis identified a locus mapping to 12p13.33 with a maximum LOD score of 8.4. Haplotype sharing defined a candidate interval of 1.06 Mb containing all or part of seven annotated genes, sequencing of which failed to detect causative mutations. Comparative genomics revealed a conserved ORF corresponding to a novel gene in which we found three different truncating mutations among five families including patients from rural Quebec and Nova Scotia. This gene, termed “HSN2,” consists of a single exon located within intron 8 of the PRKWNK1 gene and is transcribed from the same strand. The HSN2 protein may play a role in the development and/or maintenance of peripheral sensory neurons or their supporting Schwann cells. PMID:15060842

Lafreniere, Ronald G.; MacDonald, Marcia L. E.; Dube, Marie-Pierre; MacFarlane, Julie; O'Driscoll, Mary; Brais, Bernard; Meilleur, Sebastien; Brinkman, Ryan R.; Dadivas, Owen; Pape, Terry; Platon, Christele; Radomski, Chris; Risler, Jenni; Thompson, Jay; Guerra-Escobio, Ana-Maria; Davar, Gudarz; Breakefield, Xandra O.; Pimstone, Simon N.; Green, Roger; Pryse-Phillips, William; Goldberg, Y. Paul; Younghusband, H. Banfield; Hayden, Michael R.; Sherrington, Robin; Rouleau, Guy A.; Samuels, Mark E.

2004-01-01

36

Oral l-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1  

PubMed Central

Hereditary sensory and autonomic neuropathy type 1 (HSAN1) causes sensory loss that predominantly affects the lower limbs, often preceded by hyperpathia and spontaneous shooting or lancinating pain. It is caused by several missense mutations in the genes encoding 2 of the 3 subunits of the enzyme serine palmitoyltransferase (SPT). The mutant forms of the enzyme show a shift from their canonical substrate l-serine to the alternative substrate l-alanine. This shift leads to increased formation of neurotoxic deoxysphingolipids (dSLs). Our initial analysis showed that in HEK cells transfected with SPTLC1 mutants, dSL generation was modulated in vitro in the presence of various amino acids. We therefore examined whether in vivo specific amino acid substrate supplementation influenced dSL levels and disease severity in HSAN1. In mice bearing a transgene expressing the C133W SPTLC1 mutant linked to HSAN1, a 10% l-serine–enriched diet reduced dSL levels. l-serine supplementation also improved measures of motor and sensory performance as well as measures of male fertility. In contrast, a 10% l-alanine–enriched diet increased dSL levels and led to severe peripheral neuropathy. In a pilot study with 14 HSAN1 patients, l-serine supplementation similarly reduced dSL levels. These observations support the hypothesis that an altered substrate selectivity of the mutant SPT is key to the pathophysiology of HSAN1 and raise the prospect of l-serine supplementation as a first treatment option for this disorder. PMID:22045570

Garofalo, Kevin; Penno, Anke; Schmidt, Brian P.; Lee, Ho-Joon; Frosch, Matthew P.; von Eckardstein, Arnold; Brown, Robert H.; Hornemann, Thorsten; Eichler, Florian S.

2011-01-01

37

Taking Pain Out of NGF: A "Painless" NGF Mutant, Linked to Hereditary Sensory Autonomic Neuropathy Type V, with Full Neurotrophic Activity  

PubMed Central

During adulthood, the neurotrophin Nerve Growth Factor (NGF) sensitizes nociceptors, thereby increasing the response to noxious stimuli. The relationship between NGF and pain is supported by genetic evidence: mutations in the NGF TrkA receptor in patients affected by an hereditary rare disease (Hereditary Sensory and Autonomic Neuropathy type IV, HSAN IV) determine a congenital form of severe pain insensitivity, with mental retardation, while a mutation in NGFB gene, leading to the aminoacid substitution R100W in mature NGF, determines a similar loss of pain perception, without overt cognitive neurological defects (HSAN V). The R100W mutation provokes a reduced processing of proNGF to mature NGF in cultured cells and a higher percentage of neurotrophin secreted is in the proNGF form. Moreover, using Surface Plasmon Resonance we showed that the R100W mutation does not affect NGF binding to TrkA, while it abolishes NGF binding to p75NTR receptors. However, it remains to be clarified whether the major impact of the mutation is on the biological function of proNGF or of mature NGF and to what extent the effects of the R100W mutation on the HSAN V clinical phenotype are developmental, or whether they reflect an impaired effectiveness of NGF to regulate and mediate nociceptive transmission in adult sensory neurons. Here we show that the R100 mutation selectively alters some of the signaling pathways activated downstream of TrkA NGF receptors. NGFR100 mutants maintain identical neurotrophic and neuroprotective properties in a variety of cell assays, while displaying a significantly reduced pain-inducing activity in vivo (n?=?8–10 mice/group). We also show that proNGF has a significantly reduced nociceptive activity, with respect to NGF. Both sets of results jointly contribute to elucidating the mechanisms underlying the clinical HSAN V manifestations, and to clarifying which receptors and intracellular signaling cascades participate in the pain sensitizing action of NGF. PMID:21387003

Capsoni, Simona; Covaceuszach, Sonia; Marinelli, Sara; Ceci, Marcello; Bernardo, Antonietta; Minghetti, Luisa; Ugolini, Gabriele; Pavone, Flaminia; Cattaneo, Antonino

2011-01-01

38

Novel frameshift and splice site mutations in the neurotrophic tyrosine kinase receptor type 1 gene (NTRK1) associated with hereditary sensory neuropathy type IV.  

PubMed

Congenital insensitivity to pain with anhidrosis or hereditary sensory and autonomic neuropathy type IV (HSAN IV) is the first human genetic disorder implicated in the neurotrophin signal transduction pathway. HSAN IV is characterized by absence of reaction to noxious stimuli, recurrent episodes of fever, anhidrosis, self-mutilating behavior and often mental retardation. Mutations in the neurotrophic tyrosine kinase, receptor, type 1 (NTRK1) are associated with this disorder. Here we report four homozygous mutations, two frameshift (p.Gln626fsX6 and p.Gly181fsX58), one missense (p.Arg761Trp) and one splice site (c.359+5G>T) mutation in four HSAN IV patients. The splice site mutation caused skipping of exons 2 and 3 in patient's mRNA resulting in an in-frame deletion of the second leucine-rich motif. NTRK1 mutations are only rarely reported in the European population. This report extends the spectrum of NTRK1 mutations observed in patients diagnosed with HSAN IV. PMID:16373086

Verpoorten, Nathalie; Claeys, Kristl G; Deprez, Liesbet; Jacobs, An; Van Gerwen, Veerle; Lagae, Lieven; Arts, Willem Frans; De Meirleir, Linda; Keymolen, Kathelijn; Ceuterick-de Groote, Chantal; De Jonghe, Peter; Timmerman, Vincent; Nelis, Eva

2006-01-01

39

Novel NTRK1 mutations cause hereditary sensory and autonomic neuropathy type IV: demonstration of a founder mutation in the Turkish population.  

PubMed

Hereditary sensory and autonomic neuropathy type IV (HSAN IV), or congenital insensitivity to pain with anhidrosis, is an autosomal recessive disorder characterized by insensitivity to noxious stimuli, anhidrosis from deinnervated sweat glands, and delayed mental and motor development. Mutations in the neurotrophic tyrosine kinase receptor type 1 (NTRK1), a receptor in the neurotrophin signaling pathway phosphorylated in response to nerve growth factor, are associated with this disorder. We identified six families from Northern Central Turkey with HSAN IV. We screened the NTRK1 gene for mutations in these families. Microsatellite and single nucleotide polymorphism (SNP) markers on the Affymetrix 250K chip platform were used to determine the haplotypes for three families harboring the same mutation. Screening for mutations in the NTRK1 gene demonstrated one novel frameshift mutation, two novel nonsense mutations, and three unrelated kindreds with the same splice-site mutation. Genotyping of the three families with the identical splice-site mutation revealed that they share the same haplotype. This report broadens the spectrum of mutations in NTRK1 that cause HSAN IV and demonstrates a founder mutation in the Turkish population. PMID:18322713

Tüysüz, Beyhan; Bayrakli, Fatih; DiLuna, Michael L; Bilguvar, Kaya; Bayri, Yasar; Yalcinkaya, Cengiz; Bursali, Aysegul; Ozdamar, Elif; Korkmaz, Baris; Mason, Christopher E; Ozturk, Ali K; Lifton, Richard P; State, Matthew W; Gunel, Murat

2008-05-01

40

Transit Defect of Potassium-Chloride Co-transporter 3 Is a Major Pathogenic Mechanism in Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum*  

PubMed Central

Missense and protein-truncating mutations of the human potassium-chloride co-transporter 3 gene (KCC3) cause hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC), which is a severe neurodegenerative disease characterized by axonal dysfunction and neurodevelopmental defects. We previously reported that KCC3-truncating mutations disrupt brain-type creatine kinase-dependent activation of the co-transporter through the loss of its last 140 amino acids. Here, we report a novel and more distal HMSN/ACC-truncating mutation (3402C?T; R1134X) that eliminates only the last 17 residues of the protein. This small truncation disrupts the interaction with brain-type creatine kinase in mammalian cells but also affects plasma membrane localization of the mutant transporter. Although it is not truncated, the previously reported HMSN/ACC-causing 619C?T (R207C) missense mutation also leads to KCC3 loss of function in Xenopus oocyte flux assay. Immunodetection in Xenopus oocytes and in mammalian cultured cells revealed a decreased amount of R207C at the plasma membrane, with significant retention of the mutant proteins in the endoplasmic reticulum. In mammalian cells, curcumin partially corrected these mutant protein mislocalizations, with more protein reaching the plasma membrane. These findings suggest that mis-trafficking of mutant protein is an important pathophysiological feature of HMSN/ACC causative KCC3 mutations. PMID:21628467

Salin-Cantegrel, Adele; Riviere, Jean-Baptiste; Shekarabi, Masoud; Rasheed, Sarah; DaCal, Sandra; Laganiere, Janet; Gaudet, Rebecca; Rochefort, Daniel; Lesca, Gaetan; Gaspar, Claudia; Dion, Patrick A.; Lapointe, Jean-Yves; Rouleau, Guy A.

2011-01-01

41

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

42

Medical management of hereditary optic neuropathies.  

PubMed

Hereditary optic neuropathies are diseases affecting the optic nerve. The most common are mitochondrial hereditary optic neuropathies, i.e., the maternally inherited Leber's hereditary optic neuropathy (LHON) and dominant optic atrophy (DOA). They both share a mitochondrial pathogenesis that leads to the selective loss of retinal ganglion cells and axons, in particular of the papillo-macular bundle. Typically, LHON is characterized by an acute/subacute loss of central vision associated with impairment of color vision and swelling of retinal nerve fibers followed by optic atrophy. DOA, instead, is characterized by a childhood-onset and slowly progressive loss of central vision, worsening over the years, leading to optic atrophy. The diagnostic workup includes neuro-ophthalmologic evaluation and genetic testing of the three most common mitochondrial DNA mutations affecting complex I (11778/ND4, 3460/ND1, and 14484/ND6) for LHON and sequencing of the nuclear gene OPA1 for DOA. Therapeutic strategies are still limited including agents that bypass the complex I defect and exert an antioxidant effect (idebenone). Further strategies are aimed at stimulating compensatory mitochondrial biogenesis. Gene therapy is also a promising avenue that still needs to be validated. PMID:25132831

La Morgia, Chiara; Carbonelli, Michele; Barboni, Piero; Sadun, Alfredo Arrigo; Carelli, Valerio

2014-01-01

43

Neuropathic pain in hereditary peripheral neuropathy  

PubMed Central

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

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

2013-01-01

44

Experimental therapeutics in hereditary neuropathies: the past, the present, and the future.  

PubMed

Hereditary neuropathies represent approximately 40% of undiagnosed neuropathies in a tertiary clinic setting. The Charcot-Marie-Tooth neuropathies (CMT) are the most common. Mutations in more than 40 genes have been identified to date in CMT. Approximately 50% of CMT cases are accounted for by CMT type 1A, due to a duplication within the peripheral myelin protein 22 gene (PMP22). Mutations in the gap junction beta 1 gene (GJB1), the myelin protein zero gene (MPZ), and the mitofusin 2 gene (MFN2) account for a substantial proportion of other genetically definable CMT. Some 15% of demyelinating CMT and 70% of axonal CMT await genetic clarification. Other hereditary neuropathies include the hereditary sensory and autonomic neuropathies, the familial amyloid polyneuropathies, and multisystem disorders (e.g., lipid storage diseases and inherited ataxias) that have peripheral neuropathy as a major or minor component. This review surveys the challenges of developing effective therapies for hereditary neuropathies in terms of past, present, and future experimental therapeutics in CMT. PMID:19019301

Herrmann, David N

2008-10-01

45

Genetics Home Reference: Distal hereditary motor neuropathy, type V  

MedlinePLUS

... indicate that misfolded seipin proteins accumulate in the endoplasmic reticulum, which is a structure inside the cell that ... type V? atrophy ; autosomal ; autosomal dominant ; cell ; distal ; endoplasmic reticulum ; enzyme ; gait ; gene ; hereditary ; incidence ; inherited ; motor ; neuropathy ; ...

46

Atypical hereditary neuropathy with liability to pressure palsies (HNPP): the value of direct DNA diagnosis.  

PubMed Central

We report two patients with suspected hereditary liability to pressure palsies. Neurophysiological studies showed a mixed axonal-demyelinating sensory-motor polyneuropathy with focal slowing of conduction velocities at the common sites of entrapment. Morphological studies on sural nerve biopsy from the proband showed active axonal regeneration without typical tomacula. Molecular analysis confirmed the presence of a deletion of chromosome 17p11.2 in both patients. Our observation confirms the heterogeneity of hereditary liability to pressure palsies and the relevance of DNA testing for the diagnosis of this hereditary neuropathy. Images PMID:9391880

Sessa, M; Nemni, R; Quattrini, A; Del Carro, U; Wrabetz, L; Canal, N

1997-01-01

47

Genetics of congenital insensitivity to pain with anhidrosis (CIPA) or hereditary sensory and autonomic neuropathy type IV. Clinical, biological and molecular aspects of mutations in TRKA(NTRK1) gene encoding the receptor tyrosine kinase for nerve growth factor.  

PubMed

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 afferent neurons activated by tissue-damaging stimuli and a loss of innervation of eccrine sweat glands, respectively. Nerve growth factor (NGF) supports the survival of nociceptive sensory and autonomic sympathetic neurons as well as cholinergic neurons of the basal forebrain. The human TRKA (NTRKI) gene located on chromosome 1 (1q21-q22) encodes a receptor tyrosine kinase (RTK) which is autophosphorylated in response to NGF, thus, activating various pathways of intracellular signal transduction. We earlier identified the genetic basis of CIPA by detecting mutations in TRKA gene of patients. Defects in NGF signal transduction at its receptor lead to failure to survive as various NGF dependent neurons are not maintained, most probably due to apoptosis during development. TRKA mutations are distributed in an extracellular domain involved in NGF binding, as well as in the intracellular signal-transduction domain. Missense mutations with loss of function provide considerable insight into the structure-function relationship in the RTK family. In view of the fact that defects in TRKA cause CIPA, the molecular pathology of CIPA provides unique opportunities to explore critical roles of the NGF-TRKA receptor system. Thus, CIPA can serve as a useful model to determine mechanisms of development and maintenance of NGF-dependent neurons in autonomic, sensory and central nervous systems, as well as the physiology of these neurons in humans. PMID:12102460

Indo, Yasuhiro

2002-05-01

48

Foot Pad Skin Biopsy in Mouse Models of Hereditary Neuropathy  

PubMed Central

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

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

2010-01-01

49

Genetic spectrum of hereditary neuropathies with onset in the first year of life  

PubMed Central

Early onset hereditary motor and sensory neuropathies are rare disorders encompassing congenital hypomyelinating neuropathy with disease onset in the direct post-natal period and Dejerine–Sottas neuropathy starting in infancy. The clinical spectrum, however, reaches beyond the boundaries of these two historically defined disease entities. De novo dominant mutations in PMP22, MPZ and EGR2 are known to be a typical cause of very early onset hereditary neuropathies. In addition, mutations in several other dominant and recessive genes for Charcot–Marie–Tooth disease may lead to similar phenotypes. To estimate mutation frequencies and to gain detailed insights into the genetic and phenotypic heterogeneity of early onset hereditary neuropathies, we selected a heterogeneous cohort of 77 unrelated patients who presented with symptoms of peripheral neuropathy within the first year of life. The majority of these patients were isolated in their family. We performed systematic mutation screening by means of direct sequencing of the coding regions of 11 genes: MFN2, PMP22, MPZ, EGR2, GDAP1, NEFL, FGD4, MTMR2, PRX, SBF2 and SH3TC2. In addition, screening for the Charcot–Marie–Tooth type 1A duplication on chromosome 17p11.2-12 was performed. In 35 patients (45%), mutations were identified. Mutations in MPZ, PMP22 and EGR2 were found most frequently in patients presenting with early hypotonia and breathing difficulties. The recessive genes FGD4, PRX, MTMR2, SBF2, SH3TC2 and GDAP1 were mutated in patients presenting with early foot deformities and variable delay in motor milestones after an uneventful neonatal period. Several patients displaying congenital foot deformities but an otherwise normal early development carried the Charcot–Marie–Tooth type 1A duplication. This study clearly illustrates the genetic heterogeneity underlying hereditary neuropathies with infantile onset. PMID:21840889

Baets, Jonathan; Deconinck, Tine; De Vriendt, Els; Zimon, Magdalena; Yperzeele, Laetitia; Van Hoorenbeeck, Kim; Peeters, Kristien; Spiegel, Ronen; Parman, Yesim; Ceulemans, Berten; Van Bogaert, Patrick; Pou-Serradell, Adolf; Bernert, Gunther; Dinopoulos, Argirios; Auer-Grumbach, Michaela; Sallinen, Satu-Leena; Fabrizi, Gian Maria; Pauly, Fernand; Van den Bergh, Peter; Bilir, Birdal; Battaloglu, Esra; Madrid, Ricardo E.; Kabzinska, Dagmara; Kochanski, Andrzej; Topaloglu, Haluk; Miller, Geoffrey; Jordanova, Albena; Timmerman, Vincent

2011-01-01

50

Visual Rehabilitation of Persons with Leber's Hereditary Optic Neuropathy.  

ERIC Educational Resources Information Center

This article presents results of a noncontrolled clinical study of 20 persons with Leber's hereditary optic neuropathy who were treated from 1976 to 1990 at the Low Vision Centre of the Finnish Federation of the Visually Handicapped. The importance of early functional visual rehabilitation is emphasized, as is the use of low vision aids to help…

Rudanko, S.-L.

1995-01-01

51

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

52

[Mitochondrial DNA mutation in Leber's hereditary optic neuropathy in China].  

PubMed

Leber's hereditary optic neuropathy (LHON), a typical maternally inherited disease, is caused by a single nucleotide change of G to A at the site of nucleotide 11,788 of mtDNA. We used PCR method to analysis mtDNA from 102 individuals of nineteen pedigrees. The results showed that 67% of the patients (30/45) and 55% (29/53) of the maternal relatives have such a mutation, while no mutation exists in the four normal individuals. The results show that Wallace's mutation is a main cause of LHON in China. PMID:7994643

Zhang, L S; Huang, Y; Li, F Y

1994-06-01

53

Mitochondrial DNA Mutation Associated with Leber's Hereditary Optic Neuropathy  

NASA Astrophysics Data System (ADS)

Leber's hereditary optic neuropathy is a maternally inherited disease resulting in optic nerve degeneration and cardiac dysrhythmia. A mitochondrial DNA replacement mutation was identified that correlated with this disease in multiple families. This mutation converted a highly conserved arginine to a histidine at codon 340 in the NADH dehydrogenase subunit 4 gene and eliminated an Sfa NI site, thus providing a simple diagnostic test. This finding demonstrated that a nucleotide change in a mitochondrial DNA energy production gene can result in a neurological disease.

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

1988-12-01

54

Genetic evaluation of inherited motor/sensory neuropathy.  

PubMed

Inherited disorders of peripheral nerves represent a common group of neurologic diseases. Charcot-Marie-Tooth neuropathy type 1 (CMT1) is a genetically heterogeneous group of chronic demyelinating polyneuropathies with loci mapping to chromosome 17 (CMT1A), chromosome 1 (CMT1B), chromosome 16 (CMT1C) and chromosome 10 (CMT1D). CMT1A is most often associated with a tandem 1.5-megabase (Mb) duplication in chromosome 17p11.2-p12. In rare patients it may result from a point mutation in the peripheral myelin protein-22 (PMP22) gene. CMT1B is associated with point mutations in the myelin protein zero (Po or MPZ) gene. Mutations in the SIMPLE gene cause CMT1C, and CMT1D is the result of mutations in the early response 2 (ERG2 or Krox-20) gene. An X-linked form of CMT1 (CMT1X) maps to Xq13 and is associated with mutations in the connexin32 (Cx32) gene. Charcot-Marie-Tooth neuropathy type 2 (CMT2) is an axonal neuropathy that maps to chromosome 1p35-p36 (CMT2A), chromosome 3q13-q22 (CMT2B), chromosome 7p14 (CMT2D), chromosome 8p21 (CMT2E), chromosome 1q22-q23 (CMT2F) or chromosome 3q13 (CMT2G). Two X-linked forms of CMT2 have been reported (CMT2XA and CMT2XB), but the genes remain unidentified. An area that has recently expanded is the identification of autosomal recessive forms of CMT type 1 and 2. Of the eight recessive forms of CMT1 that have been identified to date, only two have been fully characterized at the molecular level (CMT1 AR B 1 and CMT1 AR D). Point mutations were found in the myotubularin-related protein-2 (MTM2) gene for CMT1 AR B1. CMT1 AR D is the result of point mutations in the N-myc downstream-regulated gene 1 (NDRG1). Dejerine-Sottas disease (DSD), also called hereditary motor and sensory neuropathy type III (HMSNIII), is a severe, infantile-onset demyelinating polyneuropathy syndrome that may be associated with point mutations in either the PMP22 gene, PO gene, EGR2 gene or the PRX gene (for the recessive form). It shares considerable clinical and pathological features with CMT1. Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder that results in a recurrent, episodic demyelinating neuropathy. HNPP is associated with a 1.5-Mb deletion in chromosome 17p11.2-p12 that results in reduced expression of the PMP22 gene. CMT1A and HNPP are reciprocal duplication/deletion syndromes that originate from unequal crossover during germ cell meiosis. Other rare forms of demyelinating peripheral neuropathies map to chromosome 8q, 10q and 11q. PMID:16106622

Chance, Phillip F

2004-01-01

55

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

PubMed

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

Hayashi, Shintaro; Okamoto, Koichi

2011-10-01

56

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

57

Epidemiology and penetrance of Leber hereditary optic neuropathy in Finland.  

PubMed

We have performed an entire-population-based survey of the epidemiology and penetrance of Leber hereditary optic neuropathy (LHON) in Finland - a country that is among the best-studied genetic isolates in the world. During our long-term clinical follow-up period since 1970, we have so far identified 36 LHON families in Finland, comprised of almost 1000 family members. Counting the unaffected family members has been possible thanks to accessible genealogical records, and this has improved the accuracy of our penetrance figures by minimizing the sample bias. Our results, although confirming some well-known features of LHON, indicate that the overall penetrance of LHON is lower than previously estimated, and that affected females have a higher incidence of affected offspring compared to the unaffected females. The prevalence of LHON in Finland is 1:50 000, and one in 9000 Finns is a carrier of one of the three LHON primary mutations. PMID:17406640

Puomila, Anu; Hämäläinen, Petra; Kivioja, Sanna; Savontaus, Marja-Liisa; Koivumäki, Satu; Huoponen, Kirsi; Nikoskelainen, Eeva

2007-10-01

58

Therapeutic strategies for Leber's hereditary optic neuropathy: A current update  

PubMed Central

Summary Leber's hereditary optic neuropathy (LHON) is a rare mitochondrial retinopathy, caused by mutations in subunits of complex I of the respiratory chain, which leads to elevated levels of oxidative stress and an insufficient energy supply. This molecular pathology is thought to be responsible for the dysfunction and eventual apoptotic loss of retinal ganglion cells in the eye, which ultimately results in blindness. Many strategies, ranging from neuroprotectants, antioxidants, anti-apoptotic- and anti-inflammatory compounds have been tested with mixed results. Currently, the most promising compounds are short-chain quinones that have been shown to protect the vision of LHON patients during the early stages of the disease. This commentary gives a brief overview on the current status of tested therapeutics and also addresses future developments such as the use of gene therapy that hopefully will provide safe and efficient therapy options for all LHON patients. PMID:25343117

Faldu, Dharmesh

2013-01-01

59

Leber's Hereditary Optic Neuropathy: The Mitochondrial Connection Revisited  

PubMed Central

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

Abu-Amero, Khaled K.

2011-01-01

60

Leber's Hereditary Optic Neuropathy: The Mitochondrial Connection Revisited.  

PubMed

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

Abu-Amero, Khaled K

2011-01-01

61

Defective Presynaptic Choline Transport Underlies Hereditary Motor Neuropathy  

PubMed Central

The neuromuscular junction (NMJ) is a specialized synapse with a complex molecular architecture that provides for reliable transmission between the nerve terminal and muscle fiber. Using linkage analysis and whole-exome sequencing of DNA samples from subjects with distal hereditary motor neuropathy type VII, we identified a mutation in SLC5A7, which encodes the presynaptic choline transporter (CHT), a critical determinant of synaptic acetylcholine synthesis and release at the NMJ. This dominantly segregating SLC5A7 mutation truncates the encoded product just beyond the final transmembrane domain, eliminating cytosolic-C-terminus sequences known to regulate surface transporter trafficking. Choline-transport assays in both transfected cells and monocytes from affected individuals revealed significant reductions in hemicholinium-3-sensitive choline uptake, a finding consistent with a dominant-negative mode of action. The discovery of CHT dysfunction underlying motor neuropathy identifies a biological basis for this group of conditions and widens the spectrum of disorders that derive from impaired NMJ transmission. Our findings compel consideration of mutations in SLC5A7 or its functional partners in relation to unexplained motor neuronopathies. PMID:23141292

Barwick, Katy E.S.; Wright, Jane; Al-Turki, Saeed; McEntagart, Meriel M.; Nair, Ajith; Chioza, Barry; Al-Memar, Ali; Modarres, Hamid; Reilly, Mary M.; Dick, Katherine J.; Ruggiero, Alicia M.; Blakely, Randy D.; Hurles, Matt E.; Crosby, Andrew H.

2012-01-01

62

Sensory neuropathy with bone destruction due to a mutation in the membrane-shaping atlastin GTPase 3.  

PubMed

Many neurodegenerative disorders present with sensory loss. In the group of hereditary sensory and autonomic neuropathies loss of nociception is one of the disease hallmarks. To determine underlying factors of sensory neurodegeneration we performed whole-exome sequencing in affected individuals with the disorder. In a family with sensory neuropathy with loss of pain perception and destruction of the pedal skeleton we report a missense mutation in a highly conserved amino acid residue of atlastin GTPase 3 (ATL3), an endoplasmic reticulum-shaping GTPase. The same mutation (p.Tyr192Cys) was identified in a second family with similar clinical outcome by screening a large cohort of 115 patients with hereditary sensory and autonomic neuropathies. Both families show an autosomal dominant pattern of inheritance and the mutation segregates with complete penetrance. ATL3 is a paralogue of ATL1, a membrane curvature-generating molecule that is involved in spastic paraplegia and hereditary sensory neuropathy. ATL3 proteins are enriched in three-way junctions, branch points of the endoplasmic reticulum that connect membranous tubules to a continuous network. Mutant ATL3 p.Tyr192Cys fails to localize to branch points, but instead disrupts the structure of the tubular endoplasmic reticulum, suggesting that the mutation exerts a dominant-negative effect. Identification of ATL3 as novel disease-associated gene exemplifies that long-term sensory neuronal maintenance critically depends on the structural organisation of the endoplasmic reticulum. It emphasizes that alterations in membrane shaping-proteins are one of the major emerging pathways in axonal degeneration and suggests that this group of molecules should be considered in neuroprotective strategies. PMID:24459106

Kornak, Uwe; Mademan, Inès; Schinke, Marte; Voigt, Martin; Krawitz, Peter; Hecht, Jochen; Barvencik, Florian; Schinke, Thorsten; Gießelmann, Sebastian; Beil, F Timo; Pou-Serradell, Adolf; Vílchez, Juan J; Beetz, Christian; Deconinck, Tine; Timmerman, Vincent; Kaether, Christoph; De Jonghe, Peter; Hübner, Christian A; Gal, Andreas; Amling, Michael; Mundlos, Stefan; Baets, Jonathan; Kurth, Ingo

2014-03-01

63

Reversible isolated sensory axonal neuropathy due to cobalamin deficiency.  

PubMed

Vitamin B(12) deficiency causes a wide range of hematological, gastrointestinal, and neurological manifestations. The most common neurological complication is subacute combined degeneration, sometimes associated with polyneuropathy. Isolated peripheral neuropathy due to cyanocobalamin deficiency is less frequent, and thus it may be overlooked. We describe 2 patients with isolated sensory axonal neuropathy secondary to vitamin B(12) deficiency who had complete clinical and electrophysiological recovery after cyanocobalamin replacement. Testing for serum vitamin B(12) and its metabolites should be done in any distal symmetric neuropathy. PMID:22334179

Dalla Torre, Chiara; Lucchetta, Marta; Cacciavillani, Mario; Campagnolo, Marta; Manara, Renzo; Briani, Chiara

2012-03-01

64

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

65

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

PubMed

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

Gallenmüller, C; Klopstock, T

2014-03-01

66

Novel therapeutic approaches for Leber's hereditary optic neuropathy.  

PubMed

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

Iyer, Shilpa

2013-03-01

67

Phenotypic heterogeneity in hereditary motor neuropathy type V: a new case report series.  

PubMed

Previous studies have revealed a wide phenotypic heterogeneity in hereditary motor neuropathy type V in which upper and lower motor neurons and peripheral motor axons are variously affected, even within the same family. In this case series, we describe the genetic, clinical and electrophysiological features of patients belonging to a four-generation Italian family. Because of a possible anticipation phenomenon, the disorder became apparent at an earlier age as it passed to the next generation, with a median age of onset of 65 years for the first 2 generations, 32 for the third, and 13.5 for the fourth. The symptoms at onset varied considerably among the sufferers, with a predominant impairment of the hands in seven cases, the impairment of the four limbs in one patient and only of the lower limbs in another. Also muscle atrophy was variable, from very mild to severe (wasting of the distal muscles of the limbs). Moreover, electrophysiological results were heterogeneous, including cases with isolated and with diffuse axonal motor neuropathy, and one case of motor sensory polyneuropathy. A novel polymorphism G?T was also found in the Berardinelli-Seip congenital lipodystrophy 2 gene on intron 4. This broad phenotypic and genotypic spectrum calls the clinician attention to this rare and still insufficiently known disease. PMID:22427291

Pennisi, Manuela; Raggi, Alberto; Barone, Rita; Muglia, Maria; Citrigno, Luigi; Cantone, Mariagiovanna; Lanza, Giuseppe; Pennisi, Giovanni; Ferri, Raffaele; Bella, Rita

2012-03-01

68

Pyridoxine-induced sensory ataxic neuronopathy and neuropathy: revisited.  

PubMed

High dose pyridoxine is neurotoxic. Previous case reports were sparse and little is known about the clinical and electrodiagnostic findings. Three patients with pyridoxine-induced sensory ataxic neuropathy were studied and a review of the involved literature was performed. Three patients, aged 80, 83 and 83 years old, presented with sensory ataxia for 3-8 months. Examination showed signs of polyneuropathy and sensory ataxia. Six hundred milligrams of pyridoxine was consumed each day for 3-10 years, in the form of vitamin B1-6-12 combination tablet. Investigations for other causes of neuropathy were unremarkable. Blood levels of vitamin B6 were markedly elevated at 104.6, 81.4 and 66.9 times of upper normal limits. Electrodiagnostic tests showed symmetric axonal sensory polyneuropathy in two patients. Two years after vitamin discontinuation, all patients showed no significant improvement in the neuropathy and gait. In conclusion, consumption of high dose pyridoxine can cause sensory neuronopathy and axonal sensorimotor polyneuropathy, leading to sensory ataxia which may not be reversible. PMID:25056196

Kulkantrakorn, Kongkiat

2014-11-01

69

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

PubMed Central

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

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

2012-01-01

70

Rapid genetic screening of Charcot-Marie-Tooth disease type 1A and hereditary neuropathy with liability to pressure palsies patients?  

PubMed Central

We used the allele-specific PCR-double digestion method on peripheral myelin protein 22 (PMP22) to determine duplication and deletion mutations in the proband and family members of one family with Charcot-Marie-Tooth disease type 1 and one family with hereditary neuropathy with liability to pressure palsies. The proband and one subclinical family member from the Charcot-Marie-Tooth disease type 1 family had a PMP22 gene duplication; one patient from the hereditary neuropathy with liability to pressure palsies family had a PMP22 gene deletion. Electron microscopic analysis of ultrathin sections of the superficial peroneal nerve from the two probands demonstrated demyelination and myelin sheath hyperplasia, as well as an ‘onion-like’ structure in the Charcot-Marie-Tooth disease type 1A patient. We observed an irregular thickened myelin sheath and ‘mouse-nibbled’-like changes in the patient with hereditary neuropathy with liability to pressure palsies. In the Charcot-Marie-Tooth disease type 1A patient, nerve electrophysiological examination revealed moderate-to-severe reductions in the motor and sensory conduction velocities of the bilateral median nerve, ulnar nerve, tibial nerve, and sural nerve. Moreover, the compound muscle action potential amplitude was decreased. In the patient with hereditary neuropathy with liability to pressure palsies, the nerve conduction velocity of the bilateral tibial nerve and sural nerve was moderately reduced, and the nerve conduction velocity of the median nerve and ulnar nerve of both upper extremities was slightly reduced. PMID:25337104

Li, Xiaobo; Zi, Xiaohong; Li, Lin; Zhan, Yajing; Huang, Shunxiang; Li, Jin; Li, Xuning; Li, Xigui; Hu, Zhengmao; Xia, Kun; Tang, Beisha; Zhang, Ruxu

2012-01-01

71

Inherited focal, episodic neuropathies  

Microsoft Academic Search

Hereditary neuropathy with liability to pressure palsies (HNPP; also called tomaculous neuropathy) is an autosomal-dominant\\u000a disorder that produces a painless episodic, recurrent, focal demyelinating neuropathy. HNPP generally develops during adolescence,\\u000a and may cause attacks of numbness, muscular weakness, and atrophy. Peroneal palsies, carpal tunnel syndrome, and other entrapment\\u000a neuropathies may be frequent manifestations of HNPP. Motor and sensory nerve conduction

Phillip F. Chance

2006-01-01

72

Thermally induced transient trigeminal sensory neuropathy: imaging findings.  

PubMed

We report the clinical and imaging features of a patient with transient partial trigeminal sensory neuropathy thought to have been induced by thermal injury to the tongue. Abnormal thickening and enhancement of the mandibular division of the trigeminal nerve was revealed by MR imaging. The diagnostic considerations for mass-like enlargement of the trigeminal nerve should include transient/inflammatory processes, as well as more common and sinister conditions, such as tumor. PMID:10669251

Chan, L L; DeMonte, F; Ginsberg, L E

2000-01-01

73

Mitochondrial dysfunction in distal axons contribute to HIV sensory neuropathy  

PubMed Central

Objective Accumulation of mitochondrial DNA (mtDNA) damage has been associated with aging and abnormal oxidative metabolism. We hypothesized that in human immunodeficiency virus associated sensory neuropathy (HIV-SN), damaged mtDNA accumulates in distal nerve segments and that a spatial pattern of mitochondrial dysfunction contribute to the distal degeneration of sensory nerve fibers. Methods We measured levels of common deletion mutations in mtDNA and expression levels of mitochondrial respiratory chain complexes of matched proximal and distal nerve specimens from patients with and without HIV-SN. In mitochondria isolated from peripheral nerves of simian immunodeficiency virus (SIV) infected macaques, a model of HIV-SN, we measured mitochondrial function and generation of reactive oxygen species. Results We identified increased levels of mtDNA common deletion mutation in post-mortem sural nerves of patients with HIV-SN as compared to uninfected patients or HIV patients without sensory neuropathy. Furthermore, we found that common deletion mutation in mtDNA was more prevalent in distal sural nerves compared to dorsal root ganglia. In a primate model of HIV-SN, freshly isolated mitochondria from sural nerves of macaques infected with a neurovirulent strain of SIV showed impaired mitochondrial function compared to mitochondria from proximal nerve segments. Interpretation Our findings suggest that mtDNA damage accumulates in distal mitochondria of long axons, especially in patients with HIV-SN, and that this may lead to reduced mitochondrial function in distal nerves relative to proximal segments. Although our findings are based on HIV-SN, if confirmed in other neuropathies, these observations could explain the length-dependent nature of most axonal peripheral neuropathies. PMID:21280080

Lehmann, Helmar C.; Chen, Weiran; Borzan, Jasenka; Mankowski, Joseph; Hoke, Ahmet

2010-01-01

74

Genetics Home Reference: Distal hereditary motor neuropathy, type II  

MedlinePLUS

... role in the tensing of muscle fibers (muscle contraction). Heat shock protein beta-1 and heat shock ... atrophy ; autosomal ; autosomal dominant ; axons ; big toe ; cell ; contraction ; cytoskeleton ; diameter ; distal ; gene ; hereditary ; infection ; inflammation ; inherited ; ...

75

Neurotrophic factors and their receptors in human sensory neuropathies.  

PubMed

Neurotrophic factors may play key roles in pathophysiological mechanisms of human neuropathies. Nerve growth factor (NGF) is trophic to small-diameter sensory fibers and regulates nociception. This review focuses on sensory dysfunction and the potential of neurotrophic treatments. Genetic neuropathy. Mutations of the NGF high-affinity receptor tyrosine kinase A (Trk A) have been found in congenital insensitivity to pain and anhidrosis; these are likely to be partial loss-of-function mutations, as axon-reflex vasodilatation and sweating can be elicited albeit reduced, suggesting rhNGF could restore nociception in some patients. Leprous neuropathy. Decreased NGF in leprosy skin may explain cutaneous hypoalgesia even with inflammation and rhNGF may restore sensation, as spared nerve fibers show Trk A-staining. Diabetic neuropathy. NGF is depleted in early human diabetic neuropathy skin, in correlation with dysfunction of nociceptor fibers. We proposed rhNGF prophylaxis may prevent diabetic foot ulceration. Clinical trials have been disappointed, probably related to difficulty delivering adequate doses and need for multiple trophic factors. NGF and glial cell line-derived neurotrophic factor (GDNF) are both produced by basal keratinocytes and neurotrophin (NT-3) by suprabasal keratinocytes: relative mRNA expression was significantly lower in early diabetic neuropathy skin compared to controls, for NGF (P < 0.02), BDNF (P < 0.05), NT-3 (P < 0.05), GDNF (< 0.02), but not NT4/5, Trk A or p75 neurotrophin receptor (all P > 0.05). Posttranslational modifications of mature and pro-NGF may also affect bioactivity and immunoreactivity. A 53 kD band that could correspond to a prepro-NGF-like molecule was reduced in diabetic skin. Traumatic neuropathy and pain. While NGF levels are acutely reduced in injured nerve trunks, neuropathic patients with chronic skin hyperalgesia and allodynia show marked local increases of NGF levels; here anti-NGF agents may provide analgesia. Physiological combinations of NGF, NT-3 and GDNF, to mimic a 'surrogate target organ', may provide a novel 'homeostatic' approach to prevent the development and ameliorate intractable neuropathic pain (e.g., at painful amputation stumps). PMID:14699981

Anand, Praveen

2004-01-01

76

A family with distal hereditary motor neuropathy and a K141Q mutation of small heat shock protein HSPB1.  

PubMed

We herein describe a Japanese family with distal hereditary motor neuropathy carrying a K141Q mutation of small heat shock protein HSPB1. Two patients among them had late onset disease (older than 50 years). The muscles of the distal legs were weak and atrophic. Sensory and autonomic dysfunction were not seen. Even eight years after onset, one patient could still walk without support. A nerve conduction study revealed axonal degeneration of the motor nerves of the legs. A heterozygous K141Q mutation was detected in the affected patients. The late onset and mild clinical phenotype might reflect the mild biochemical alteration of HSP27 induced by the K141Q mutation. PMID:25088881

Maeda, Kengo; Idehara, Ryo; Hashiguchi, Akihiro; Takashima, Hiroshi

2014-01-01

77

An epidemic in Cuba of optic neuropathy, sensorineural deafness, peripheral sensory neuropathy and dorsolateral myeloneuropathy.  

PubMed

An epidemic outbreak of peripheral neuropathy affected Cuba in 1992-93 resulting in 50,862 cases (national cumulative incidence rate (CIR) 461.4 per 100,000). Clinical forms included retrobulbar optic neuropathy, sensory and dysautonomic peripheral neuropathy, dorsolateral myeloneuropathy, sensorineural deafness, dysphonia and dysphagia, spastic paraparesis, and mixed forms. For epidemiological purposes, cases were classified as optic forms (CIR 242.39) or peripheral forms (CIR 219.25). Increased risk was found among smokers (odds ratio (OR) 4.9), those with history of missing meals (OR 4.7) resulting in lower intake of animal protein, fat, and foods that contain B-vitamins, combined drinking and smoking (OR 3.5), weight loss (OR 2.8), excessive sugar consumption (OR 2.7) and heavy drinking (OR 2.3). Optic neuropathy was characterized by decreased vision, bilateral and symmetric central or cecocentral scotomata, and loss of color vision due to selective lesion of the maculopapillary bundles. Peripheral neuropathy was a distal axonopathy lesion affecting predominantly large myelinated axons. Deafness produced selective high frequency (4-8 kHz) hearing loss. Myelopathy lesions combined dorsal column deficits and pyramidal involvement of lower limbs with spastic bladder. Clinical features were those of Strachan syndrome and beriberi. Intensive search for neurotoxic agents, in particular organophosphorus esters, chronic cyanide, and trichloroethylene intoxication, yielded negative results. Treatment of patients with B-group vitamins and folate produced rewarding results. Most patients improved significantly and less than 0.1% of them remained with sequelae; there were no fatal cases. Supplementation of multivitamins to the entire Cuban population resulted in curbing of the epidemic. Overt malnutrition was not present, but a deficit of micronutrients, in particular thiamine, cobalamine, folate and sulfur amino acids appears to have been a primary determinant of this epidemic. PMID:7699385

Román, G C

1994-12-01

78

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

PubMed

Major advances in understanding the pathogenesis of inherited metabolic disease caused by mitochondrial DNA mutations have yet to translate into treatments of proven efficacy. Leber's hereditary optic neuropathy is the most common mitochondrial DNA disorder causing irreversible blindness in young adult life. Anecdotal reports support the use of idebenone in Leber's hereditary optic neuropathy, but this has not been evaluated in a randomized controlled trial. We conducted a 24-week multi-centre double-blind, randomized, placebo-controlled trial in 85 patients with Leber's hereditary optic neuropathy due to m.3460G>A, m.11778G>A, and m.14484T>C or mitochondrial DNA mutations. The active drug was idebenone 900 mg/day. The primary end-point was the best recovery in visual acuity. The main secondary end-point was the change in best visual acuity. Other secondary end-points were changes in visual acuity of the best eye at baseline and changes in visual acuity for both eyes in each patient. Colour-contrast sensitivity and retinal nerve fibre layer thickness were measured in subgroups. Idebenone was safe and well tolerated. The primary end-point did not reach statistical significance in the intention to treat population. However, post hoc interaction analysis showed a different response to idebenone in patients with discordant visual acuities at baseline; in these patients, all secondary end-points were significantly different between the idebenone and placebo groups. This first randomized controlled trial in the mitochondrial disorder, Leber's hereditary optic neuropathy, provides evidence that patients with discordant visual acuities are the most likely to benefit from idebenone treatment, which is safe and well tolerated. PMID:21788663

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

2011-09-01

79

Mitochondrial mutations of Leber's hereditary optic neuropathy: a risk factor for multiple sclerosis  

Microsoft Academic Search

Multiple sclerosis (MS) and Leber's hereditary optic neuropathy (LHON) have been found to occur in combination. Based on\\u000a an extensive literature search and on a clinical analysis of 55 LHON pedigrees (103 patients) and 40 patients with definite\\u000a MS, this study concludes that the association of LHON and MS is more than a coincidence, and that carrying a primary LHON

Ludo Vanopdenbosch; Bénédicte Dubois; Marie-Béatrice D'Hooghe; Françoise Meire; Herwig Carton

2000-01-01

80

Weighted needle pinprick sensory thresholds: a simple test of sensory function in diabetic peripheral neuropathy.  

PubMed Central

A simple device is described, consisting of 12 weighted 23 gauge disposable needles (0.2 to 5.2 g), for testing sensation in busy diabetic clinics. The pinprick sensory threshold (PPT) is the lightest weighted needle which consistently elicits a sharp sensation. The subjects were 48 healthy controls (hospital staff), 44 diabetic patients without neuropathic symptoms, and 35 diabetic patients with chronic painful neuropathy. In the controls, the mean PPT from the right hand and foot obtained on two test occasions a week apart did not differ significantly. In diabetic patients without symptomatic neuropathy, the mean PPT in the right hand and right foot were significantly higher than in the controls. The diabetic patients with painful neuropathy had clearly increased mean PPT in the right hand and foot compared with controls. Marstock thermal limen in diabetic patients with painful neuropathy correlated significantly with PPT determinations. PPT and thermal thresholds probably give comparable information on small fibre dysfunction in diabetic patients with symptomatic neuropathy. Compared with thermal threshold determinations however, the weighted needle apparatus is inexpensive, simple, and rapid to use. PMID:1312581

Chan, A W; MacFarlane, I A; Bowsher, D; Campbell, J A

1992-01-01

81

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

82

Genetics Home Reference: Hereditary sensory and autonomic neuropathy type II  

MedlinePLUS

HSAN2 Related Gene(s) Related Condition(s) References Quick links to this topic MedlinePlus Health information Additional NIH Resources National Institutes of Health Educational resources Information pages Patient support ...

83

Mouse mtDNA mutant model of Leber hereditary optic neuropathy  

PubMed Central

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

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

2012-01-01

84

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

85

Papilloedema and MRI enhancement of the prechiasmal optic nerve at the acute stage of Leber hereditary optic neuropathy  

Microsoft Academic Search

The authors report a case of one patient from a family carrying the homoplasmic Leber hereditary optic neuropathy (LHON) G11778A mitochondrial DNA mutation with papilloedema 9 months prior to the acute stage of LHON and still present at the onset of visual loss. During the vision loss, the MRI demonstrated a T2 hyperintensity and an enhancement of the prechiasmal left

Cédric Lamirel; Julien Cassereau; Isabelle Cochereau; Catherine Vignal-Clermont; Olivier Pajot; Jean-Yves Tanguy; Xavier Zanlonghi; Pascal Reynier; Patrizia Amati-Bonneau; Frédéric Dubas; Dominique Bonneau; Christophe Verny

2010-01-01

86

Functional alterations of the mitochondrially encoded ND4 subunit associated with Leber's hereditary optic neuropathy.  

PubMed

Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease associated with point mutations in mitochondrial DNA. The most frequent of these mutations is the G-to-A substitution at nucleotide position 11,778 which changes an evolutionarily conserved arginine with a histidine at position 340 in subunit ND4 of NADH:ubiquinone reductase (respiratory complex I). We report that this amino acid substitution alters the affinity of complex I for the ubiquinone substrate and induces resistance towards its potent inhibitor rotenone in mitochondria of LHON patients. Such changes could reflect a substantial loss in the energy conserving function of NADH:ubiquinone reductase and thus explain the pathological effect of the ND4/11,778 mutation. PMID:7926004

Degli Esposti, M; Carelli, V; Ghelli, A; Ratta, M; Crimi, M; Sangiorgi, S; Montagna, P; Lenaz, G; Lugaresi, E; Cortelli, P

1994-10-01

87

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

PubMed Central

Leber Hereditary Optic Neuropathy (LHON) is an important cause of inherited mitochondrial blindness among young adults. The majority of patients carry one of three mitochondrial DNA (mtDNA) point mutations: m.3460G>A, m.11778G>A and m.14484T>C, all of which affect critical complex I subunits of the mitochondrial respiratory chain. LHON is characterised by marked incomplete penetrance, clearly implying that the mtDNA mutation is insufficient on its own to trigger retinal ganglion cell dysfunction and visual loss. In this case series of three affected patients harbouring the m.11778G>A mutation, we provide evidence suggesting that raised intraocular pressure could be a risk factor triggering visual loss in at-risk LHON carriers. PMID:23667621

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

2013-01-01

88

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

SciTech Connect

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

Chalmers, R.M.; Davis, M.B.; Sweeney, M.G.; Wood, N.W.; Harding, A.E. [Inst. of Neurology, London (United Kingdom)

1996-07-01

89

Single-cell analysis of intercellular heteroplasmy of mtDNA in Leber hereditary optic neuropathy  

SciTech Connect

The authors have investigated the distribution of mutant mtDNA molecules in single cells from a patient with Leber hereditary optic neuropathy (LHON). LHON is a maternally inherited disease that is characterized by a sudden-onset bilateral loss of central vision, which typically occurs in early adulthood. More than 50% of all LHON patients carry an mtDNA mutation at nucleotide position 11778. This nucleotide change converts a highly conserved arginine residue to histidine at codon 340 in the NADH-ubiquinone oxidoreductase subunit 4 (ND4) gene of mtDNA. In the present study, the authors used PCR amplification of mtDNA from lymphocytes to investigate mtDNA heteroplasmy at the single-cell level in a LHON patient. They found that most cells were either homoplasmic normal or homoplasmic mutant at nucleotide position 11778. Some (16%) cells contained both mutant and normal mtDNA.

Kobayashi, Y.; Sharpe, H.; Brown, N.

1994-07-01

90

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

91

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

92

Multifocal motor neuropathy with conduction block with sensory fibre involvement in a diabetic patient. Case report.  

PubMed

Multifocal motor neuropathy with conduction block (MMNcb) is a relatively rare disease characterized clinically by asymmetric limb weakness with spared sensation and electrophysiologically by persistent focal motor conduction block. We present the case of a 40-year-old male patient with six-year history of progressive, asymmetric weakness of upper and lower extremities without sensory symptoms. Electroneurography revealed definite or probable motor conduction block in several nerves. However, features of axonal lesion of sensory fibres were also found. Laboratory studies were unremarkable apart from an abnormal glucose tolerance test, and type 2 diabetes was diagnosed. In the presented case the differential diagnosis should take into consideration MMNcb with coexisting diabetic sensory polyneuropathy and multifocal acquired demyelinating sensory and motor neuropathy (MADSAM). PMID:18651334

Fila, Micha?; Szadkowska, Iwona; Hasiec, Tomasz; Bogucki, Andrzej

2008-01-01

93

[Mixed neuropathies in rheumatoid arthritis. Motor and sensory nerve conduction velocities].  

PubMed

Nerve conduction studies and analysis of the sensory action potential (110 nerves investigated) demons treated abnormalities in 15 to 20 patients with rheumatoid arthritis. It is concluded that moderate, often subclinical peripheral neuropathy is a common complication in rheumatoid arthritis. PMID:184511

Frenay, J; Goor, C; Kievitis, J H; Endtz, J

1976-01-01

94

Successful immunosuppressant therapy of severe progressive cerebellar degeneration and sensory neuropathy: a case report  

Microsoft Academic Search

A 56 year old woman had a 19 month history of a severe subacute progressive cerebellar degeneration, peripheral sensory neuropathy, and urinary incontinence. She was confined to a wheelchair, needed assistance with eating, and her speech was almost unintelligible. No underlying cancer was found despite repeated investigations, and no autoantibodies were demonstrated. She received a 3-month course of intensive immunosuppressant

Nima Mowzoon; Walter G Bradley

2000-01-01

95

Human extraocular muscles in mitochondrial diseases: comparing chronic progressive external ophthalmoplegia with Leber’s hereditary optic neuropathy  

Microsoft Academic Search

Aims: To compare the ultrastructural aspects of human extraocular muscles in two types of mitochondrial disease: chronic progressive external ophthalmoplegia (CPEO) and Leber’s hereditary optic neuropathy (LHON).Methods: Muscle samples of the medial rectus obtained from surgery in a sporadic case of CPEO associated with deleted mitochondrial DNA, and post mortem in a case of 3460\\/ND1 LHON were processed for electron

A Carta; V Carelli; T D’Adda; F N Ross-Cisneros; A A Sadun

2005-01-01

96

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

PubMed Central

A rare form of Leber hereditary optic neuropathy (LHON) that is associated with hereditary spastic dystonia has been studied in a large Dutch family. Neuropathy and ophthalmological lesions were present together in some family members, whereas only one type of abnormality was found in others. mtDNA mutations previously reported in LHON were not present. Sequence analysis of the protein-coding mitochondrial genes revealed two previously unreported mtDNA mutations. A heteroplasmic A-->G transition at nucleotide position 11696 in the ND4 gene resulted in the substitution of an isoleucine for valine at amino acid position 312. A second mutation, a homoplasmic T-->A transition at nucleotide position 14596 in the ND6 gene, resulted in the substitution of a methionine for the isoleucine at amino acid residue 26. Biochemical analysis of a muscle biopsy revealed a severe complex I deficiency, providing a link between these unique mtDNA mutations and this rare, complex phenotype including Leber optic neuropathy. PMID:8644732

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

1996-01-01

97

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

SciTech Connect

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

De Vries, D.D.; Oost, B.A. van [Univ. Hospital Nijmegen (Netherlands); Went, L.N.; Bruyn, G.W. [Univ. of Leiden (Netherlands)] [and others

1996-04-01

98

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

99

The mitochondrial DNA mutation at position 11778 in Chinese families with Leber's hereditary optic neuropathy.  

PubMed

We amplified the 340 bp of mitochondrial DNA (mtDNA) by PCR including the recognized sequence of restriction enzyme of SfaN I. After amplification and digestion of SfaN I, two bands of 190 bp and 150 bp appeared in the mtDNA of four normal individuals but only one band of 340 bp appeared in the mtDNA with the mutation of G to A at the site of the nucleotide 11778 because such mutation destroyed the recognized sequence of SfaN I. We studied the mtDNAs of the patients with Leber's hereditary optic neuropathy from 19 Chinese families and their maternal relatives as well as the normal individuals i. e. the husbands of the female members of the pedigrees. The results show that 66.7% of the patients (30/45) and 54.7% of the maternal relatives (29/53) have such a mutation, while no such a mutation exists in the four normal individuals. So, we conclude that the mutation of mitochondrial DNA at position 11,778 is also a major cause of LHON in China. PMID:7744206

Zhang, L; Huang, Y; Li, F; Wang, S; Zhu, B; Zhang, Z; Tong, Y; Gao, J

1994-09-01

100

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

SciTech Connect

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

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

1993-10-01

101

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

102

Diagnosis and new treatments in genetic neuropathies.  

PubMed

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 has revolutionised our understanding of the peripheral nervous system and allowed the development of rational approaches to therapy. The first therapeutic trials in CMT are currently underway. This review will suggest an approach to the diagnosis of these disorders and provide an update on new therapies. PMID:19917815

Reilly, M M; Shy, M E

2009-12-01

103

Polygenic inheritance of paclitaxel-induced sensory peripheral neuropathy driven by axon outgrowth gene sets in CALGB 40101 (Alliance).  

PubMed

Peripheral neuropathy is a common dose-limiting toxicity for patients treated with paclitaxel. For most individuals, there are no known risk factors that predispose patients to the adverse event, and pathogenesis for paclitaxel-induced peripheral neuropathy is unknown. Determining whether there is a heritable component to paclitaxel-induced peripheral neuropathy would be valuable in guiding clinical decisions and may provide insight into treatment of and mechanisms for the toxicity. Using genotype and patient information from the paclitaxel arm of CALGB 40101 (Alliance), a phase III clinical trial evaluating adjuvant therapies for breast cancer in women, we estimated the variance in maximum grade and dose at first instance of sensory peripheral neuropathy. Our results suggest that paclitaxel-induced neuropathy has a heritable component, driven in part by genes involved in axon outgrowth. Disruption of axon outgrowth may be one of the mechanisms by which paclitaxel treatment results in sensory peripheral neuropathy in susceptible patients. PMID:24513692

Chhibber, A; Mefford, J; Stahl, E A; Pendergrass, S A; Baldwin, R M; Owzar, K; Li, M; Winer, E P; Hudis, C A; Zembutsu, H; Kubo, M; Nakamura, Y; McLeod, H L; Ratain, M J; Shulman, L N; Ritchie, M D; Plenge, R M; Witte, J S; Kroetz, D L

2014-08-01

104

Early infantile sensory-motor neuropathy with late onset respiratory distress.  

PubMed

Children with spinal muscular atrophy with respiratory distress (SMARD1) usually present within their first year of life, with respiratory failure due to diaphragmatic paralysis and progressive distal limb weakness. We present a child with a confirmed compound heterozygous IGHMBP2 mutation c.[676G>T];[2083A>T] in whom severe sensory-motor neuropathy preceded diaphragmatic paralysis by almost 3years. Autonomic system involvement with neurogenic bladder and urine retention were found at 3years. In summary, our patient highlights the broad spectrum of phenotypes observed in SMARD1. Currently, no prediction of phenotype according to genotype is possible, suggesting that yet unknown factors cause the observed phenotypic variation. Even in the absence of obvious diaphragmatic weakness, SMARD1 should be considered in severe infantile onset neuropathies. High throughput techniques, such as next generation sequencing, will possibly offer a useful approach in the heterogeneous group of inherited neuropathies. PMID:24342282

Blaschek, Astrid; Gläser, Dieter; Kuhn, Marius; Schroeder, Andreas Sebastian; Wimmer, Cornelius; Heimkes, Bernd; Schön, Carola; Müller-Felber, Wolfgang

2014-03-01

105

Canine inherited motor and sensory neuropathies: An updated classification in 22 breeds and comparison to Charcot–Marie–Tooth disease  

Microsoft Academic Search

Canine inherited neuropathies form a group of degenerative diseases affecting motor and\\/or sensory and autonomic peripheral nerves. There is now a large number of inherited motor and sensory neuropathies (IMSN) reported in the veterinary literature, for which clinical, electrophysiological, histopathological and mode of inheritance data are available. Their resemblance with Charcot–Marie–Tooth disease in humans is suggested, although direct comparison is

Nicolas Granger

2011-01-01

106

Peripheral sensory neuropathy observed in children with cerebral palsy: is chronic afferent excitation from muscle spindles a possible cause?  

Microsoft Academic Search

Introduction  Peripheral sensory neuropathy is known to be associated with several medical conditions; however, it has not been reported\\u000a in patients with cerebral palsy. Authors have observed pathological changes in the sensory nerve rootlets taken during selective\\u000a dorsal rhizotomy. This paper reports a possible novel cause of peripheral sensory neuropathy: the chronic afferent excitations\\u000a from muscle spindles.\\u000a \\u000a \\u000a \\u000a \\u000a Case report  Sensory nerve rootlets

Toru Fukuhara; Yoichiro Namba; Ichiro Yamadori

2010-01-01

107

Sensory ataxic neuropathy due to a novel C10Orf2 mutation with probable germline mosaicism.  

PubMed

The authors describe siblings with progressive external ophthalmoplegia (PEO) due to a novel heterozygous A to G transition at nucleotide 955 of C10Orf2 (Twinkle). The mutation was not identified in parents' blood, hair follicles, buccal mucosa, or urinary epithelium, indicating germ line mosaicism. One sibling presented with sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO), a phenotype previously associated with the POLG1 gene, highlighting the clinical overlap in autosomal PEO. PMID:15668446

Hudson, G; Deschauer, M; Busse, K; Zierz, S; Chinnery, P F

2005-01-25

108

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

109

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

110

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

111

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

PubMed Central

Background: The authors investigated the correlation of protan and tritan color vision with disease characteristics in Leber hereditary optic neuropathy (LHON). The authors also characterized the therapeutic potential of idebenone in protecting patients from developing dyschromatopsia in LHON. Methods: Color contrast data of 39 LHON patients participating in a randomized, double-blind placebo-controlled intervention study were evaluated. Patients reported disease onset <5 years before enrolment and were genetically confirmed. Protan and tritan color contrast sensitivity was measured using a computer graphics method in patients receiving idebenone (Catena; 900 mg/d; N = 28) or placebo (N = 11) for 6 months. Results: Mean age of patients was 28.1 years, 87.2% were men, 76.9% carried the m11778G>A mutation, and mean duration since onset was 2 years. Assessing protan and tritan color vision at baseline revealed a high degree of color confusion even in young patients (<25 years) and with a short history of disease (<1 year). Treatment with idebenone improved tritan color vision compared with placebo (P = 0.008 at week 24); a similar trend was seen for protan. The effect of idebenone was most prominent in patients with discordant visual acuity (interocular difference of logMAR >0.2). In this subgroup, the treatment effect at week 24 was 20.4% (P = 0.005) in favor of idebenone for the tritan color domain and 13.5% (P = 0.067) for the protan domain. Conclusion: This study confirms that protan and tritan color confusion is an early symptom in LHON. Treatment with idebenone can protect from loss of color vision, particularly in patients who are at imminent risk of further vision loss. PMID:23263355

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

2013-01-01

112

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

PubMed Central

Objective: To determine whether the association between multiple sclerosis (MS) and Leber hereditary optic neuropathy (LHON) (known as “Harding disease”) is a chance finding, or the 2 disorders are mechanistically linked. Methods: We performed a United Kingdom–wide prospective cohort study of prevalent cases of MS with LHON mitochondrial DNA (mtDNA) mutations. The new cases were compared with published cases, enabling a comprehensive clinical description. We also performed a meta-analysis of studies screening patients with MS for LHON mtDNA mutations to find evidence of a genetic association. Results: Twelve new patients were identified from 11 pedigrees, and 44 cases were identified in the literature. The combined cohort had the following characteristics: multiple episodes of visual loss, predominance for women, and lengthy time interval before the fellow eye is affected (average 1.66 years), which is very atypical of LHON; conversely, most patients presented without eye pain and had a poor visual prognosis, which is unusual for optic neuritis associated with MS. The number of UK cases of LHON-MS fell well within the range predicted by the chance occurrence of MS and the mtDNA mutations known to cause LHON. There was no association between LHON mtDNA mutations and MS in a meta-analysis of the published data. Conclusions: Although the co-occurrence of MS and LHON mtDNA mutations is likely to be due to chance, the resulting disorder has a distinct phenotype, implicating a mechanistic interaction. Patients with LHON-MS have a more aggressive course, and prognostication and treatment should be guarded. PMID:24198293

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

2013-01-01

113

Retinal Ganglion Cell Dysfunction in Asymptomatic G11778A: Leber Hereditary Optic Neuropathy  

PubMed Central

Purpose. To report the serial evaluation of asymptomatic eyes of subjects with mutated G11778A mitochondrial DNA. Methods. Forty-five asymptomatic G11778A Leber hereditary optic neuropathy (LHON) carriers and two patients with the mutation who developed unilateral visual loss underwent testing that included visual acuity, automated visual field, pattern electroretinogram (PERG), and spectral-domain optical coherence tomography every 6 months between September 2008 and March 2012. Results. Visual acuity, visual fields, and retinal nerve fiber layer thickness remained stable within the normal range. Mean PERG amplitudes of carriers dropped progressively by ?40% from baseline to 36 months. In addition, comparisons with the fellow eyes of patients with unilateral optic neuritis revealed a 3.4 ETDRS (Early Treatment Diabetic Retinopathy Study) letter loss in the LHON carriers. A single carrier developed visual loss, with PERG amplitudes dropping by half. In one of two LHON cases who presented with unilateral visual loss, visual acuity in the asymptomatic eye was ?20/40 at baseline. The PERG amplitude of this eye was reduced to ?30% of normal. Six months later, his visual acuity had dropped to ?20/500. A second patient who was ?20/20 and had a visual field defect in the asymptomatic eye at baseline remained at this level for the 18 months of follow-up. His PERG amplitudes were similar to those of asymptomatic carriers, with 0.78 ?V at baseline that did not decline with follow-up. Conclusions. Declines of the PERG amplitude suggest subclinical retinal ganglion cell dysfunction in asymptomatic G11778A subjects, which is progressive. PMID:24398093

Guy, John; Feuer, William J.; Porciatti, Vittorio; Schiffman, Joyce; Abukhalil, Fawzi; Vandenbroucke, Ruth; Rosa, Potyra R.; Lam, Byron L.

2014-01-01

114

Analysis of dynein intermediate chains, light intermediate chains and light chains in a cohort of hereditary peripheral neuropathies.  

PubMed

The cytoplasmic dynein heavy chain (DYNC1H1) gene has been increasingly associated with neurodegenerative disorders including axonal Charcot-Marie-Tooth disease (CMT2), intellectual disability and malformations of cortical development. In addition, evidence from mouse models (Loa, catabolite repressor-activator (Cra) and Sprawling (Swl)) has shown that mutations in Dync1h1 cause a range of neurodegenerative phenotypes with motor and sensory neuron involvement. In this current study, we examined the possible contribution of other cytoplasmic dynein subunits that bind to DYNC1H1 as a cause of inherited peripheral neuropathy. We focused on screening the cytoplasmic dynein intermediate, light intermediate and light chain genes in a cohort of families with inherited peripheral neuropathies. Nine genes were screened and ten variants were detected, but none was identified as pathogenic, indicating that cytoplasmic dynein intermediate, light intermediate and light chains are not a cause of neuropathy in our cohort. PMID:25028179

Tey, Shelisa; Ahmad-Annuar, Azlina; Drew, Alexander P; Shahrizaila, Nortina; Nicholson, Garth A; Kennerson, Marina L

2014-10-01

115

A quantitative sensory analysis of peripheral neuropathy in colorectal cancer and its exacerbation by oxaliplatin chemotherapy.  

PubMed

Peripheral neuropathy caused by cytotoxic chemotherapy, especially platins and taxanes, is a widespread problem among cancer survivors that is likely to continue to expand in the future. However, little work to date has focused on understanding this challenge. The goal in this study was to determine the impact of colorectal cancer and cumulative chemotherapeutic dose on sensory function to gain mechanistic insight into the subtypes of primary afferent fibers damaged by chemotherapy. Patients with colorectal cancer underwent quantitative sensory testing before and then prior to each cycle of oxaliplatin. These data were compared with those from 47 age- and sex-matched healthy volunteers. Patients showed significant subclinical deficits in sensory function before any therapy compared with healthy volunteers, and they became more pronounced in patients who received chemotherapy. Sensory modalities that involved large A? myelinated fibers and unmyelinated C fibers were most affected by chemotherapy, whereas sensory modalities conveyed by thinly myelinated A? fibers were less sensitive to chemotherapy. Patients with baseline sensory deficits went on to develop more symptom complaints during chemotherapy than those who had no baseline deficit. Patients who were tested again 6 to 12 months after chemotherapy presented with the most numbness and pain and also the most pronounced sensory deficits. Our results illuminate a mechanistic connection between the pattern of effects on sensory function and the nerve fiber types that appear to be most vulnerable to chemotherapy-induced toxicity, with implications for how to focus future work to ameloirate risks of peripheral neuropathy. Cancer Res; 74(21); 5955-62. ©2014 AACR. PMID:25183707

de Carvalho Barbosa, Mariana; Kosturakis, Alyssa K; Eng, Cathy; Wendelschafer-Crabb, Gwen; Kennedy, William R; Simone, Donald A; Wang, Xin S; Cleeland, Charles S; Dougherty, Patrick M

2014-11-01

116

Inherited autonomic neuropathies.  

PubMed

Inherited autonomic neuropathies are a rare group of disorders associated with sensory dysfunction. As a group they are termed the "hereditary sensory and autonomic neuropathies" (HSAN). Classification of the various autonomic and sensory disorders is ongoing. In addition to the numerical classification of four distinct forms proposed by Dyck and Ohta (1975), additional entities have been described. The best known and most intensively studied of the HSANs are familial dysautonomia (Riley-Day syndrome or HSAN type III) and congenital insensitivity to pain with anhidrosis (HSAN type IV). Diagnosis of the HSANs depends primarily on clinical examinations and specific sensory and autonomic assessments. Pathologic examinations are helpful in confirming the diagnosis and in differentiating between the different disorders. In recent years identification of specific genetic mutations for some disorders has aided diagnosis. Replacement or definitive therapies are not available for any of the disorders so that treatment remains supportive and directed toward specific symptoms. PMID:15088259

Axelrod, Felicia B; Hilz, Max J

2003-12-01

117

A case of rare recessive oculopharyngeal muscular dystrophy (OPMD) coexisting with hereditary neuropathy with liability to pressure palsies (HNPP).  

PubMed

Oculopharyngeal muscular dystrophy (OPMD) is typically inherited in an autosomal dominant fashion and is characterized by late onset proximal muscle weakness, ptosis and difficulty swallowing. It is caused by expansion mutations in the PABPN1 gene on chromosome 14q11. There is also a rare recessive form of the disease caused by homozygosity of a very small expansion mutation in the same gene. Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder characterized by recurrent peripheral monofocal neuropathies. In this report a patient with both recessive OPMD and HNPP is described. The presence of two genetically unlinked neurological diagnoses in the same individual is a rare event and may have delayed the diagnoses. PMID:18358598

Marsh, Eleanor A; Robinson, David O

2008-05-01

118

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

PubMed

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

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

2012-03-01

119

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

PubMed Central

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

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

2000-01-01

120

Pan-American mDNA haplogroups in Chilean patients with Leber's hereditary optic neuropathy  

PubMed Central

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

Romero, Pablo; Fernandez, Veronica; Slabaugh, Mark; Seleme, Nicolas; Reyes, Nury; Gallardo, Patricia; Herrera, Luisa; Pena, Luis; Pezo, Patricio; Moraga, Mauricio

2014-01-01

121

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

PubMed

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; Bennett, David L H

2014-12-01

122

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

123

Hyperosmolar solutions selectively block action potentials in rat myelinated sensory fibers: implications for diabetic neuropathy.  

PubMed

Diabetic neuropathy is a common complication of diabetes mellitus patients. It is a wide range of abnormalities affecting proximal and distal peripheral sensory and motor nerves. Although plasma hyperosmolality is a common finding in diabetes mellitus, the effects of hyperosmolality on conduction of various sensory signal components have not been addressed in detail. Here we show that in rat dorsal root ganglion (DRG) preparations from normal rats, hyperosmolar solutions (360 mmol/kg, containing increased glucose, sucrose, NaCl, or mannitol) produce a selective block of signal propagation in myelinated sensory A-fibers. In compound action potential (CAP) recordings with suction electrodes, peak A-fiber CAP amplitude was selectively decreased (20%), while the C-fiber peak remained intact or was slightly increased. Hyperosmolar solutions had smaller effects on conduction velocity (CV) of both A- and C-fibers (approximately 5% decrease). Hyperosmolality-induced CAP changes could not be observed during recordings from isolated spinal nerves but were evident during recordings from desheathed spinal nerves. In intracellular recordings, hyperosmolar solutions produced a block of spinal nerve-evoked action potential invasion into the somata of some A-fiber neurons. Removal of extracellular calcium completely prevented the hyperosmolality-induced CAP decreases. Based on these data, we propose that the decreased CAP amplitudes recorded in human patients and in animal models of diabetes are in part due to the effects of hyperosmolality and would depend on the extracellular osmolality at the time of sensory testing. We also hypothesize that hyperosmolality may contribute to both the sensory abnormalities (paresthesias) and the chronic pain symptoms of diabetic neuropathy. PMID:13679399

Matsuka, Yoshizo; Spigelman, Igor

2004-01-01

124

Poly(ADP-Ribose) Polymerase Inhibition Alleviates Experimental Diabetic Sensory Neuropathy  

PubMed Central

Poly(ADP-ribose) polymerase (PARP) activation is emerging as a fundamental mechanism in the pathogenesis of diabetes complications including diabetic neuropathy. This study evaluated the role of PARP in diabetic sensory neuropathy. The experiments were performed in control and streptozotocin-induced diabetic rats treated with or without the PARP inhibitor 1,5-isoquinolinediol (ISO; 3 mg · kg?1 · day?1 i.p.) for 2 weeks after 2 weeks without treatment. Diabetic rats developed thermal hyperalgesia (assessed by paw-withdrawal and tail-flick tests), mechanical hyperalgesia (von Frey anesthesiometer/rigid filaments and Randall-Sellito tests), tactile allodynia (flexible von Frey filaments), and increased flinching behavior in phases 1 and 2 of the 2% formalin pain test. They also had clearly manifest increase in nitrotyrosine and poly(ADP-ribose) immunoreactivities in the sciatic nerve and increased superoxide formation (hydroxyethidine method) and nitrotyrosine immunoreactivity in vasa nervorum. ISO treatment alleviated abnormal sensory responses, including thermal and mechanical hyperalgesia and tactile allodynia as well as exaggerated formalin flinching behavior in diabetic rats, without affecting the aforementioned variables in the control group. Poly(ADP-ribose) and, to a lesser extent, nitrotyrosine abundance in sciatic nerve, as well as superoxide and nitrotyrosine formation in vasa nervorum, were markedly reduced by ISO therapy. Apoptosis in dorsal root ganglion neurons (transferase-mediated dUTP nick-end labeling assay) was not detected in any of the groups. In conclusion, PARP activation contributes to early diabetic sensory neuropathy by mechanisms that may include oxidative stress but not neuronal apoptosis. PMID:16731831

Ilnytska, Olga; Lyzogubov, Valeriy V.; Stevens, Martin J.; Drel, Viktor R.; Mashtalir, Nazar; Pacher, Pal; Yorek, Mark A.; Obrosova, Irina G.

2008-01-01

125

Poly(ADP-ribose) polymerase inhibition alleviates experimental diabetic sensory neuropathy.  

PubMed

Poly(ADP-ribose) polymerase (PARP) activation is emerging as a fundamental mechanism in the pathogenesis of diabetes complications including diabetic neuropathy. This study evaluated the role of PARP in diabetic sensory neuropathy. The experiments were performed in control and streptozotocin-induced diabetic rats treated with or without the PARP inhibitor 1,5-isoquinolinediol (ISO; 3 mg x kg(-1) x day(-1) i.p.) for 2 weeks after 2 weeks without treatment. Diabetic rats developed thermal hyperalgesia (assessed by paw-withdrawal and tail-flick tests), mechanical hyperalgesia (von Frey anesthesiometer/rigid filaments and Randall-Sellito tests), tactile allodynia (flexible von Frey filaments), and increased flinching behavior in phases 1 and 2 of the 2% formalin pain test. They also had clearly manifest increase in nitrotyrosine and poly(ADP-ribose) immunoreactivities in the sciatic nerve and increased superoxide formation (hydroxyethidine method) and nitrotyrosine immunoreactivity in vasa nervorum. ISO treatment alleviated abnormal sensory responses, including thermal and mechanical hyperalgesia and tactile allodynia as well as exaggerated formalin flinching behavior in diabetic rats, without affecting the aforementioned variables in the control group. Poly(ADP-ribose) and, to a lesser extent, nitrotyrosine abundance in sciatic nerve, as well as superoxide and nitrotyrosine formation in vasa nervorum, were markedly reduced by ISO therapy. Apoptosis in dorsal root ganglion neurons (transferase-mediated dUTP nick-end labeling assay) was not detected in any of the groups. In conclusion, PARP activation contributes to early diabetic sensory neuropathy by mechanisms that may include oxidative stress but not neuronal apoptosis. PMID:16731831

Ilnytska, Olga; Lyzogubov, Valeriy V; Stevens, Martin J; Drel, Viktor R; Mashtalir, Nazar; Pacher, Pal; Yorek, Mark A; Obrosova, Irina G

2006-06-01

126

Medical Marijuana for HIV-Associated Sensory Neuropathy: Legal and Ethical Issues.  

PubMed

The number of states legalizing medical marijuana is increasing. Medical marijuana is possibly effective therapy for HIV-associated sensory neuropathy. Despite legalization at the state level, however, the current and contradictory federal drug enforcement policy creates the risk that physicians who recommend medical marijuana to their patients will lose their ability to prescribe medications. The federal-state tension has legal and ethical implications for neurologists who receive a request for medical marijuana from their patients since neurologists must strive to both relieve suffering and obey relevant laws. Recommendation of medical marijuana by neurologists to their patients is ethically permissible but is not ethically mandatory. PMID:25299291

Larriviere, Daniel G

2014-10-01

127

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

128

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

129

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

SciTech Connect

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

Obermaier-Kusser, B.; Schubring, S.; Paprotta, A.; Meitinger, T.; Jaksch, M.; Gerbitz, K.D. [Univ. of Munich (Germany); Lorenz, B. [Univ. of Rogensburgh (Germany); Zerres, K. [Univ. of Bonn (Germany); Meire, F. [Univ. of Ghent (Belgium); Cochaux, P. [Univ. of Brussels (Belgium)] [and others

1994-11-01

130

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

PubMed Central

IMPORTANCE Patients with rare diseases and complex clinical presentations represent a challenge for clinical diagnostics. Genomic approaches are allowing the identification of novel variants in genes for very rare disorders, enabling a molecular diagnosis. Genomics is also revealing a phenotypic expansion whereby the full spectrum of clinical expression conveyed by mutant alleles at a locus can be better appreciated. OBJECTIVE To elucidate the molecular cause of a complex neuropathy phenotype in 3 patients by applying genomic sequencing strategies. DESIGN, SETTING, AND PARTICIPANTS Three affected individuals from 2 unrelated families presented with a complex neuropathy phenotype characterized by axonal sensorimotor neuropathy and microcephaly. They were recruited into the Centers for Mendelian Genomics research program to identify the molecular cause of their phenotype. Whole-genome, targeted whole-exome sequencing, and high-resolution single-nucleotide polymorphism arrays were performed in genetics clinics of tertiary care pediatric hospitals and biomedical research institutions. MAIN OUTCOMES AND MEASURES Whole-genome and whole-exome sequencing identified the variants responsible for the patients’ clinical phenotype. RESULTS We identified compound heterozygous alleles in 2 affected siblings from 1 family and a homozygous nonsense variant in the third unrelated patient in the vaccinia-related kinase 1 gene (VRK1). In the latter subject, we found a common haplotype on which the nonsense mutation occurred and that segregates in the Ashkenazi Jewish population. CONCLUSIONS AND RELEVANCE We report the identification of disease-causing alleles in 3 children from 2 unrelated families with a previously uncharacterized complex axonal motor and sensory neuropathy accompanied by severe nonprogressive microcephaly and cerebral dysgenesis. Our data raise the question of whether VRK1 mutations disturb cell cycle progression and may result in apoptosis of cells in the nervous system. The application of unbiased genomic approaches allows the identification of potentially pathogenic mutations in unsuspected genes in highly genetically heterogeneous and uncharacterized neurological diseases. PMID:24126608

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

2014-01-01

131

Modulating molecular chaperones improves sensory fiber recovery and mitochondrial function in diabetic peripheral neuropathy  

PubMed Central

Quantification of intra-epidermal nerve fibers (iENFs) is an important approach to stage diabetic peripheral neuropathy (DPN) and is a promising clinical endpoint for identifying beneficial therapeutics. Mechanistically, diabetes decreases neuronal mitochondrial function and enhancing mitochondrial respiratory capacity may aid neuronal recovery from glucotoxic insults. We have proposed that modulating the activity and expression of heat shock proteins (Hsp) may be of benefit in treating DPN. KU-32 is a C-terminal Hsp90 inhibitor that improved thermal hypoalgesia in diabetic C57Bl/6 mice but it was not determined if this was associated with an increase in iENF density and mitochondrial function. After 16 weeks of diabetes, Swiss Webster mice showed decreased electrophysiological and psychosensory responses and a >30% loss of iENFs. Treatment of the mice with ten weekly doses of 20 mg/kg KU-32 significantly reversed pre-existing deficits in nerve conduction velocity and responses to mechanical and thermal stimuli. KU-32 therapy significantly reversed the pre-existing loss of iENFs despite the identification of a sub-group of drug-treated diabetic mice that showed improved thermal sensitivity but no increase in iENF density. To determine if the improved clinical indices correlated with enhanced mitochondrial activity, sensory neurons were isolated and mitochondrial bioenergetics assessed ex vivo using extracellular flux technology. Diabetes decreased maximal respiratory capacity in sensory neurons and this deficit was improved following KU-32 treatment. In conclusion, KU-32 improved physiological and morphologic markers of degenerative neuropathy and drug efficacy may be related to enhanced mitochondrial bioenergetics in sensory neurons. PMID:22465570

Urban, Michael J.; Pan, Pan; Farmer, Kevin L.; Zhao, Huiping; Blagg, Brian S.J.; Dobrowsky, Rick T.

2012-01-01

132

Sensory ataxic neuropathy with dysarthria/dysphagia and ophthalmoplegia (SANDO). Two case reports  

E-print Network

Case histories of two unrelated patients suffering from sensory ataxic neuropathy, dysarthria / dysphagia and external ophthalmoplegia (SANDO) are reported. Both patients showed compound heterozygosity for POLG1 gene mutations, and presented with symptom of the clinical characteristics of SANDO. A patient with a p.A467T and p.W748S, well-known mutations showed a progressive course with early onset and multisystem involvement, including symptoms characteristics for mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). The second patient showed a less well-known p.T251I and p.G848S mutations with late onset and dysphagia/dysarthria dominated, moderate symptoms. This later is the second published case history, when these POLG1 gene mutations are the possible background of late onset SANDO, dominantly presenting with bulbar symptoms. Key words: SANDO, heterozygote POLG1 mutations

István Gáti; Olof Danielsson; Jon Jonasson; Anne-marie Landtblom

133

[Hereditary spastic paraplegia associated with congenital cataracts, mental retardation and peripheral neuropathy].  

PubMed

A 16-year-old male patient was admitted to our hospital with mental retardation and a gradually increasing gait disturbance. He fell easily at age 6, and lost the ability to jump at age 12. At age 13, he lost the ability to run, and developed pes cavus and hammer toes. Spastic paraplegia with mental retardation, congenital cataracts, hyper reflexia, dysarthria, callosal hypogenesis and peripheral neuropathy were evident at age 16. Laboratory examinations did not reveal any underlying disorders. He was diagnosed as having complex spastic paraplegia with cataracts, mental retardation and peripheral neuropathy that might comprise a genetically distinct entity that is unique to Japan, because all prior reports of this combination have been generated only from Japan. PMID:21077357

Hattori, Ayako; Sasaki, Masayuki; Sakuma, Hiroshi; Saito, Yoshiaki; Komaki, Hirofumi; Nakagawa, Eiji; Sugai, Kenji

2010-11-01

134

Acute motor-sensory axonal neuropathy associated with active systemic lupus erythematosus and anticardiolipin antibodies.  

PubMed

Acute motor-sensory axonal neuropathy (AMSAN) is an axonal variant of Guillian-Barré syndrome (GBS) that presents with acute ascending quadriparesis. This has generally been described in association with Campylobacter jejuni infections or with anti-ganglioside antibodies. Known cases have shown a slow recovery and a poor prognosis. We report a case with clinical and electrophysiological evidence of AMSAN in association with active systemic lupus erythematosus (SLE) and anticardiolipin antibodies but not the other associations, with a rapid response to combination immunosuppressant and intravenous immunoglobulin (IVIg) therapy. The association between AMSAN and SLE has not been previously described. This case illustrates that early recognition and the utilization of electrophysiologic techniques may be beneficial in the diagnosis and management of GBS associated with SLE. Fulminant or rapidly progressive cases should be managed in specialized intensive care units. Combination therapy of immunosuppressants and IVIg may be beneficial in non-vasculitic axonal radiculo-neuropathies associated with SLE, resulting in good outcomes. PMID:17039164

Ubogu, E E; Zaidat, O O; Suarez, J I

2001-10-01

135

The utility of clinical neurophysiological and quantitative sensory testing for trigeminal neuropathy.  

PubMed

This article reviews the utility of neurophysiological recordings and quantitative sensory testing (QST) in providing sensitive, quantitative, and objective tests for the diagnosis and localization of damage to the trigeminal nerve. Electromyography and recordings of the masseter reflex and compound muscle action potential evoked by transcranial magnetic stimulation or direct electrical stimulation of the masseteric nerve can be of value in evaluating the function of a motor neurons supplying the muscles of mastication. Orthodromic recording of the sensory action potential and trigeminal somatosensory-evoked potential recording with the near-nerve stimulation technique are sensitive tools for the investigation of trigeminal sensory Abeta afferents, whereas recordings of polysynaptic trigeminal brainstem reflexes and tactile QST are less sensitive. At late stages of recovery, the blink reflex and masseter inhibitory reflex are often normal, but at earlier stages, the blink reflex recording has good prognostic value, and the presence of a reflex response may confirm continuity of the nerve trunk after partial laceration. Trigeminal small-fiber function (Adelta and C) can be studied with thermal QST of the cool, warm, heat pain, and cold pain detection thresholds or with laser-evoked potential recording. Thermal QST may remain abnormal years after axonal damage and aids in the diagnosis of late sequelae of trigeminal nerve injury. In a study of the diagnostic value of neurography, blink reflex and thermal QST, and various commonly used clinical sensory tests, neurophysiologic tests and thermal QST had better sensitivity (50% to 88% vs 40% to 59%) and negative predictive values (78% to 100% vs 70% to 74%) compared to clinical examination, whereas the specificity (55% to 100%) and positive predictive values (48% to 73%) were similar. At 1 year after trigeminal nerve injury, the risk of a false negative finding with clinical sensory testing was 94%, whereas the combination of nerve conduction recordings and thermal QST increased the diagnostic yield to 100% in patients with long-standing postsurgical sensory alteration. In conclusion, clinical neurophysiological recordings and QST improve the diagnostic accuracy for trigeminal neuropathy. PMID:15636020

Jääskeläinen, Satu K

2004-01-01

136

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

SciTech Connect

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

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

1992-12-01

137

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

138

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

139

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

PubMed

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

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

2014-03-01

140

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

PubMed

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

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

2012-01-01

141

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

PubMed Central

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

2013-01-01

142

Immune-mediated components of hereditary demyelinating neuropathies: lessons from animal models and patients.  

PubMed

Most demyelinating forms of Charcot-Marie-Tooth type 1 (CMT1) neuropathy are slowly progressive and do not respond to anti-inflammatory treatment. In nerve biopsy samples, overt lymphocytic infiltration is absent, but pathological features typical of macrophage-related demyelination have been reported. In mouse models of CMT1, demyelination was substantially reduced when the mutants were backcrossed into an immunodeficient genetic background. A few individual patients with CMT1 respond to anti-inflammatory treatment; however, unlike most patients with CMT1, these patients show accelerated worsening of symptoms, inflammatory infiltrates in nerve biopsies, and clinical features resembling chronic inflammatory demyelinating polyneuropathy as well as CMT1. We conclude that in patients with typical CMT1 and in animal models, a cryptic and mild inflammatory process not responsive to standard anti-inflammatory treatment fosters genetically mediated demyelination. PMID:15261606

Martini, Rudolf; Toyka, Klaus V

2004-08-01

143

c-Jun activation in Schwann cells protects against loss of sensory axons in inherited neuropathy.  

PubMed

Charcot-Marie-Tooth disease type 1A is the most frequent inherited peripheral neuropathy. It is generally due to heterozygous inheritance of a partial chromosomal duplication resulting in over-expression of PMP22. A key feature of Charcot-Marie-Tooth disease type 1A is secondary death of axons. Prevention of axonal loss is therefore an important target of clinical intervention. We have previously identified a signalling mechanism that promotes axon survival and prevents neuron death in mechanically injured peripheral nerves. This work suggested that Schwann cells respond to injury by activating/enhancing trophic support for axons through a mechanism that depends on upregulation of the transcription factor c-Jun in Schwann cells, resulting in the sparing of axons that would otherwise die. As c-Jun orchestrates Schwann cell support for distressed neurons after mechanical injury, we have now asked: do Schwann cells also activate a c-Jun dependent neuron-supportive programme in inherited demyelinating disease? We tested this by using the C3 mouse model of Charcot-Marie-Tooth disease type 1A. In line with our previous findings in humans with Charcot-Marie-Tooth disease type 1A, we found that Schwann cell c-Jun was elevated in (uninjured) nerves of C3 mice. We determined the impact of this c-Jun activation by comparing C3 mice with double mutant mice, namely C3 mice in which c-Jun had been conditionally inactivated in Schwann cells (C3/Schwann cell-c-Jun(-/-) mice), using sensory-motor tests and electrophysiological measurements, and by counting axons in proximal and distal nerves. The results indicate that c-Jun elevation in the Schwann cells of C3 nerves serves to prevent loss of myelinated sensory axons, particularly in distal nerves, improve behavioural symptoms, and preserve F-wave persistence. This suggests that Schwann cells have two contrasting functions in Charcot-Marie-Tooth disease type 1A: on the one hand they are the genetic source of the disease, on the other, they respond to it by mounting a c-Jun-dependent response that significantly reduces its impact. Because axonal death is a central feature of much nerve pathology it will be important to establish whether an axon-supportive Schwann cell response also takes place in other conditions. Amplification of this axon-supportive mechanism constitutes a novel target for clinical intervention that might be useful in Charcot-Marie-Tooth disease type 1A and other neuropathies that involve axon loss. PMID:25216747

Hantke, Janina; Carty, Lucy; Wagstaff, Laura J; Turmaine, Mark; Wilton, Daniel K; Quintes, Susanne; Koltzenburg, Martin; Baas, Frank; Mirsky, Rhona; Jessen, Kristján R

2014-11-01

144

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

145

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

SciTech Connect

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

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

1996-02-01

146

Electrical Stimulation as an Adjunctive Treatment of Painful and Sensory Diabetic Neuropathy  

PubMed Central

Background The objective of this review is to evaluate the use of electrical stimulation to treat diabetic neuropathy. Application of electrical stimulation may provide a novel treatment option for large and small fiber neuropathy in persons with diabetes. Large and small nerve neuropathy alters pain, proprioception, touch perception, and motor function, which cause burning foot pain and serve as protective mechanisms from ulcerations. Methods A content search for clinical trials involving electrical stimulation, neuropathy, and diabetes was conducted through PubMed. Randomized clinical trials and prospective studies with outcome measures affecting the lower extremity function were selected for review. Results We identified eight studies in which electrical stimulation was used to treat diabetic neuropathy. Six studies evaluated small fiber neuropathy. Two studies evaluated patients with both small and large fiber neuropathy and reported significant improvement in vibration and monofilament testing and reduction in symptoms in the electrical stimulation treatment group. Six of the eight painful neuropathy studies identified significant improvement in symptoms. There were no studies that evaluated electrical stimulation to treated diabetic motor neuropathy, fall prevention or postural instability. Conclusions Electrical stimulation may be an effective alternative and adjunctive therapy to current interventions for diabetic peripheral neuropathy. PMID:24124947

Thakral, Gaurav; Kim, Paul J.; LaFontaine, Javier; Menzies, Robert; Najafi, Bijan; Lavery, Lawrence A.

2013-01-01

147

Disturbed sensory perception of changes in thermoalgesic stimuli in patients with small fiber neuropathies.  

PubMed

The assessment of functional deficits in small fibre neuropathies (SFN) requires using ancillary tests other than conventional neurophysiological techniques. One of the tests with most widespread use is thermal threshold determination, as part of quantitative sensory testing. Thermal thresholds typically reflect one point in the whole subjective experience elicited by a thermal stimulus. We reasoned that more information could be obtained by analyzing the subjective description of the ongoing sensation elicited by slow temperature changes (dynamic thermal testing, DTT). Twenty SFN patients and 20 healthy subjects were requested to describe, by using an electronic visual analog scale system, the sensation perceived when the temperature of a thermode was made to slowly change according to a predetermined pattern. The thermode was attached to the left ventral forearm or the distal third of the left leg and the stimulus was either a monophasic heat or cold stimuli that reached 120% of pain threshold and reversed to get back to baseline at a rate of 0.5 °C/s. Abnormalities seen in patients in comparison to healthy subjects were: (1) delayed perception of temperature changes, both at onset and at reversal, (2) longer duration of pain perception at peak temperature, and (3) absence of an overshoot sensation after reversal, ie, a transient perception of the opposite sensation before the temperature reached again baseline. The use of DTT increases the yield of thermal testing for clinical and physiological studies. It adds information that can be discriminant between healthy subjects and SFN patients and shows physiological details about the process of activation and inactivation of temperature receptors that may be abnormal in SFN. PMID:23806653

Medici, Conrado; Barraza, Gonzalo; Castillo, Carlos D; Morales, Merche; Schestatsky, Pedro; Casanova-Mollà, Jordi; Valls-Sole, Josep

2013-10-01

148

Peripheral Neuropathy  

MedlinePLUS

... and chronic forms can exhibit a pattern of alternating remission and relapse. Acute inflammatory demyelinating neuropathy, better known as Guillain-Barré syndrome, can damage motor, sensory, and autonomic nerve fibers. Most people recover ...

149

Acute motor and sensory axonal neuropathy in Burkitt-like lymphoma.  

PubMed

Immune-mediated neuropathies associated with non-Hodgkin's lymphoma are rare and can be difficult to delineate from neuropathies of other etiologies. We report the clinical and pathological findings of a 36-year-old patient with fulminant quadriplegic neuropathy, left facial nerve palsy, and Burkitt-like lymphoma. Features of the neuropathy, which occurred during induction chemotherapy with a total cumulative dose of 4 mg vincristine, suggested axonal Guillain-Barré syndrome. There was no evidence of direct malignant infiltration of the peripheral nervous system. We hypothesize that immune mechanisms triggered by the lymphoma initiated damage to the peripheral nervous system and enhanced its vulnerability to the toxic effects of vincristine. PMID:16671108

Wanschitz, Julia; Dichtl, Wolfgang; Budka, Herbert; Löscher, Wolfgang N; Boesch, Sylvia

2006-10-01

150

Schwann cells and the pathogenesis of inherited motor and sensory neuropathies (Charcot-Marie-Tooth disease).  

PubMed

Over the last 15 years, a number of mutations in a variety of genes have been identified that lead to inherited motor and sensory neuropathies (HMSN), also called Charcot-Marie-Tooth disease (CMT). In this review we will focus on the molecular and cellular mechanisms that cause the Schwann cell pathologies observed in dysmyelinating and demyelinating forms of CMT. In most instances, the underlying gene defects alter primarily myelinating Schwann cells followed by secondary axonal degeneration. The first set of proteins affected by disease-causing mutations includes the myelin components PMP22, P0/MPZ, Cx32/GJB1, and periaxin. A second group contains the regulators of myelin gene transcription EGR2/Krox20 and SOX10. A third group is composed of intracellular Schwann cells proteins that are likely to be involved in the synthesis, transport and degradation of myelin components. These include the myotubularin-related lipid phosphatase MTMR2 and its regulatory binding partner MTMR13/SBF2, SIMPLE, and potentially also dynamin 2. Mutations affecting the mitochondrial fission factor GDAP1 may indicate an important contribution of mitochondria in myelination or myelin maintenance, whereas the functions of other identified genes, including NDRG1, KIAA1985, and the tyrosyl-tRNA synthase YARS, are not yet clear. Mutations in GDAP1, YARS, and the pleckstrin homology domain of dynamin 2 lead to an intermediate form of CMT that is characterized by moderately reduced nerve conduction velocity consistent with minor myelin deficits. Whether these phenotypes originate in Schwann cells or in neurons, or whether both cell types are directly affected, remains a challenging question. However, based on the advances in systematic gene identification in CMT and the analyses of the function and dysfunction of the affected proteins, crucially interconnected pathways in Schwann cells in health and disease have started to emerge. These networks include the control of myelin formation and stability, membrane trafficking, intracellular protein sorting and quality control, and may extend to mitochondrial dynamics and basic protein biosynthesis. PMID:16856148

Berger, Philipp; Niemann, Axel; Suter, Ueli

2006-09-01

151

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

SciTech Connect

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

Sweeney, M.G.; Davis, M.B.; Lashwood, A.; Brockington, M.; Harding, A.E. (Institute of Neurology, Queen Square, London (United Kingdom)); Toscano, A. (Clinica Neurologica, Messina (Italy))

1992-10-01

152

A mitochondrial DNA variant, identified in Leber hereditary optic neuropathy patients, which extends the amino acid sequence of cytochrome c oxidase subunit I.  

PubMed Central

A G-to-A transition at nucleotide pair (np) 7444 in the mtDNA was found to correlate with Leber hereditary optic neuropathy (LHON). The mutation eliminates the termination codon of the cytochrome c oxidase subunit I (COI) gene, extending the COI polypeptide by three amino acids. The mutation was discovered as an XbaI restriction-endonuclease-site loss present in 2 (9.1%) of 22 LHON patients who lacked the np 11778 LHON mutation and in 6 (1.1%) of 545 unaffected controls. The mutant polypeptide has an altered mobility on SDS-PAGE, suggesting a structural alteration, and the cytochrome c oxidase enzyme activity of patient lymphocytes is reduced approximately 40% relative to that in controls. These data suggest that the np 7444 mutation results in partial respiratory deficiency and thus contributes to the onset of LHON. Images Figure 1 Figure 3 PMID:1322638

Brown, M D; Yang, C C; Trounce, I; Torroni, A; Lott, M T; Wallace, D C

1992-01-01

153

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

PubMed Central

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

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

2012-01-01

154

Role of the DNA Base Excision Repair Protein, APE1 in Cisplatin, Oxaliplatin, or Carboplatin Induced Sensory Neuropathy  

PubMed Central

Although chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect of platinum drugs, the mechanisms of this toxicity remain unknown. Previous work in our laboratory suggests that cisplatin-induced CIPN is secondary to DNA damage which is susceptible to base excision repair (BER). To further examine this hypothesis, we studied the effects of cisplatin, oxaliplatin, and carboplatin on cell survival, DNA damage, ROS production, and functional endpoints in rat sensory neurons in culture in the absence or presence of reduced expression of the BER protein AP endonuclease/redox factor-1 (APE1). Using an in situ model of peptidergic sensory neuron function, we examined the effects of the platinum drugs on hind limb capsaicin-evoked vasodilatation. Exposing sensory neurons in culture to the three platinum drugs caused a concentration-dependent increase in apoptosis and cell death, although the concentrations of carboplatin were 10 fold higher than cisplatin. As previously observed with cisplatin, oxaliplatin and carboplatin also increased DNA damage as indicated by an increase in phospho-H2AX and reduced the capsaicin-evoked release of CGRP from neuronal cultures. Both cisplatin and oxaliplatin increased the production of ROS as well as 8-oxoguanine DNA adduct levels, whereas carboplatin did not. Reducing levels of APE1 in neuronal cultures augmented the cisplatin and oxaliplatin induced toxicity, but did not alter the effects of carboplatin. Using an in vivo model, systemic injection of cisplatin (3 mg/kg), oxaliplatin (3 mg/kg), or carboplatin (30 mg/kg) once a week for three weeks caused a decrease in capsaicin-evoked vasodilatation, which was delayed in onset. The effects of cisplatin on capsaicin-evoked vasodilatation were attenuated by chronic administration of E3330, a redox inhibitor of APE1 that serendipitously enhances APE1 DNA repair activity in sensory neurons. These outcomes support the importance of the BER pathway, and particularly APE1, in sensory neuropathy caused by cisplatin and oxaliplatin, but not carboplatin and suggest that augmenting DNA repair could be a therapeutic target for CIPN. PMID:25188410

Kelley, Mark R.; Jiang, Yanlin; Guo, Chunlu; Reed, April; Meng, Hongdi; Vasko, Michael R.

2014-01-01

155

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

PubMed Central

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

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

2013-01-01

156

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

SciTech Connect

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

Oostra, R.J.; Bleeker-Wagemakers, E.M.; Zwart, R. [Ophthalmic Research Institute, Amsterdam (Netherlands)] [and others

1995-10-01

157

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

PubMed

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

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

2014-04-01

158

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

159

Localization of a gene responsible for autosomal recessive demyelinating neuropathy with focally folded myelin sheaths to chromosome 11q23 by homozygosity mapping and haplotype sharing  

Microsoft Academic Search

Hereditary motor and sensory neuropathy (HMSN) with focally folded myelin sheaths, or Charcot-Marie-Tooth type 4B (CMT4B), is a distinct clinical entity belonging to the heterogeneous group of autosomal recessive demyelinating neuropathies. We first described a large pedigree with CMT4B, which showed a high consanguinity level and an autosomal recessive pattern of inheritance. Through conventional linkage analysis, we excluded linkage of

Alessandra Bolino; Valeria Brancolini; Francesco Bono; Amalia Bruni; Antonio Gambardella; Giovanni Romeo; Aldo Quattrone; Marcella Devoto

1996-01-01

160

A 1.5-Mb deletion in 17p11.2-p12 is frequently observed in Italian families with hereditary neuropathy with liability to pressure palsies.  

PubMed Central

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder characterized by recurrent mononeuropathies. A 1.5-Mb deletion in chromosome 17p11.2-p12 has been associated with HNPP. Duplication of the same 1.5-Mb region is known to be associated with Charcot-Marie-Tooth disease type 1 (CMT1A), a more severe peripheral neuropathy characterized by symmetrically slowed nerve conduction velocity (NCV). The CMT1A duplication and HNPP deletion appear to be the reciprocal products of a recombination event involving a repeat element (CMT1A-REP) that flanks the 1.5-Mb region involved in the duplication/deletion. Patients from nine unrelated Italian families who were diagnosed with HNPP on the basis of clinical, electrophysiological, and histological evaluations were analyzed by molecular methods for DNA deletion on chromosome 17p. In all nine families, Southern analysis using a CMT1A-REP probe detected a reduced hybridization signal of a 6.0-kb EcoRI fragment mapping within the distal CMT1A-REP, indicating deletion of one copy of CMT1A-REP in these HNPP patients. Families were also typed with a polymorphic (CA)n repeat and with RFLPs corresponding to loci D17S122, D17S125, and D17S61, which all map within the deleted region. Lack of allelic transmission from affected parent to affected offspring was observed in four informative families, providing an independent indication for deletion. Furthermore, pulsed-field gel electrophoresis analysis of SacII-digested genomic DNA detected junction fragments specific to the 1.5-Mb HNPP deletion in seven of nine Italian families included in this study. These findings suggest that a 1.5-Mb deletion on 17p11.2-p12 is the most common mutation associated with HNPP. Images Figure 2 Figure 4 Figure 5 PMID:7825607

Lorenzetti, D; Pareyson, D; Sghirlanzoni, A; Roa, B B; Abbas, N E; Pandolfo, M; Di Donato, S; Lupski, J R

1995-01-01

161

A 1.5-Mb deletion in 17p11.2-p12 is frequently observed in Italian families with hereditary neuropathy with liability to pressure palsies  

SciTech Connect

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder characterized by recurrent mononeuropathies. A 1.5-Mb deletion in chromosome 17p11.2-p12 has been associated with HNPP. Duplication of the same 1.5-Mb region is known to be associated with Charcot-Marie-Tooth disease type 1 (CMT1A), a more severe peripheral neuropathy characterized by symmetrically slowed nerve conduction velocity (NCV). The CMT1A duplication and HNPP deletion appear to be the reciprocal products of a recombination event involving a repeat element (CMT1A-REP) that flanks the 1.5-Mb region involved in the duplication/deletion. Patients from nine unrelated Italian families who were diagnosed with HNPP on the basis of clinical, electrophysiological, and histological evaluations were analyzed by molecular methods for DNA deletion on chromosome 17p. In all nine families, Southern analysis using a CMT1A-REP probe detected a reduced hybridization signal of a 6.0-kb EcoRI fragment mapping within the distal CMT1A-REP, indicating deletion of one copy of CMT1A-REP in these HNPP patients. Families were also typed with a polymorphic (CA){sub n} repeat and with RFLPs corresponding to loci D17S122, D17S125, and D17S61, which all map within the deleted region. Lack of allelic transmission from affected parent to affected offspring was observed in four informative families, providing an independent indication for deletion. Furthermore, pulsed-field gel electrophoresis analysis of SacII-digested genomic DNA detected junction fragments specific to the 1.5-Mb HNPP deletion in seven of nine Italian families included in this study. These findings suggest that a 1.5-Mb deletion on 17p11.2-p12 is the most common mutation associated with HNPP. 51 refs., 5 figs., 1 tab.

Lorenzetti, D.; Pandolfo, M. [Istituto Nazionale Neurologico, Milan (Italy)]|[Baylor College of Medicine, Houston, TX (United States); Pareyson, D.; Sghirlanzoni, A.; Di Donato, S. [Istituto Nazionale Neurologico, Milan (Italy); Roa, B.B.; Abbas, N.E.; Lupski, J.R. [Baylor College of Medicine, Houston, TX (United States)

1995-01-01

162

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

163

Cell therapy using retinal progenitor cells shows therapeutic effect in a chemically-induced rotenone mouse model of Leber hereditary optic neuropathy.  

PubMed

Primary mitochondrial disorders occur at a prevalence of one in 10?000; ?50% of these demonstrate ocular pathology. Leber hereditary optic neuropathy (LHON) is the most common primary mitochondrial disorder. LHON results from retinal ganglion cell pathology, which leads to optic nerve degeneration and blindness. Over 95% of cases result from one of the three common mutations in mitochondrial genes MTND1, MTND4 and MTND6, which encode elements of the complex I respiratory chain. Various therapies for LHON are in development, for example, intravitreal injection of adeno-associated virus carrying either the yeast NDI1 gene or a specific subunit of mammalian Complex I have shown visual improvement in animal models. Given the course of LHON, it is likely that in many cases prompt administration may be necessary before widespread cell death. An alternative approach for therapy may be the use of stem cells to protect visual function; this has been evaluated by us in a rotenone-induced model of LHON. Freshly dissected embryonic retinal cells do not integrate into the ganglion cell layer (GCL), unlike similarly obtained photoreceptor precursors. However, cultured retinal progenitor cells can integrate in close proximity to the GCL, and act to preserve retinal function as assessed by manganese-enhanced magnetic resonance imaging, optokinetic responses and ganglion cell counts. Cell therapies for LHON therefore represent a promising therapeutic approach, and may be of particular utility in treating more advanced disease. PMID:24569607

Mansergh, Fiona C; Chadderton, Naomi; Kenna, Paul F; Gobbo, Oliviero L; Farrar, G Jane

2014-11-01

164

Motor and sensory nerve conduction velocity in the baboon: normal values and changes during acrylamide neuropathy  

PubMed Central

Nerve conduction velocity and the amplitude of nerve and muscle action potentials have been measured in the median and anterior tibial nerves of normal adult and infant baboons. The effect of altered temperature on velocity has also been investigated. Seven adult baboons were intoxicated with acrylamide. In animals given 10-15 mg/kg/day, the gradual development of a peripheral neuropathy was accompanied by a decline in the amplitude of both muscle and nerve action potentials. There was also a gradual fall in conduction velocity. In some cases maximal motor velocity in the median nerve fell by as much as 34%, and in the anterior tibial nerve by as much as 49%, the largest falls being seen in animals showing the greatest reductions in response amplitude. Histological studies, reported elsewhere, have shown that the main pathological change in our animals was a degeneration of the peripheral nerves, with little demyelination. Fibre diameter histograms indicated that large fibres were particularly severely affected, and it seems likely that the reduced maximal conduction velocities were due to this selective loss of large-diameter fibres. PMID:4328885

Hopkins, A. P.; Gilliatt, R. W.

1971-01-01

165

Ciliary neurotrophic factor activates NF-?B to enhance mitochondrial bioenergetics and prevent neuropathy in sensory neurons of streptozotocin-induced diabetic rodents  

PubMed Central

Diabetes causes mitochondrial dysfunction in sensory neurons that may contribute to peripheral neuropathy. Ciliary neurotrophic factor (CNTF) promotes sensory neuron survival and axon regeneration and prevents axonal dwindling, nerve conduction deficits and thermal hypoalgesia in diabetic rats. In this study, we tested the hypothesis that CNTF protects sensory neuron function during diabetes through normalization of impaired mitochondrial bioenergetics. In addition, we investigated whether the NF-?B signal transduction pathway was mobilized by CNTF. Neurite outgrowth of sensory neurons derived from streptozotocin (STZ)-induced diabetic rats was reduced compared to neurons from control rats and exposure to CNTF for 24 h enhanced neurite outgrowth. CNTF also activated NF-?B, as assessed by Western blotting for the NF-?B p50 subunit and reporter assays for NF-?B promoter activity. Conversely, blockade of NF-?B signaling using SN50 peptide inhibited CNTF-mediated neurite outgrowth. Studies in mice with STZ-induced diabetes demonstrated that systemic therapy with CNTF prevented functional and structural indices of peripheral neuropathy along with deficiencies in dorsal root ganglion (DRG) NF-?B p50 expression and DNA binding activity. DRG neurons derived from STZ-diabetic mice also exhibited deficiencies in maximal oxygen consumption rate and associated spare respiratory capacity that were corrected by exposure to CNTF for 24 h in an NF-?B-dependent manner. We propose that the ability of CNTF to enhance axon regeneration and protect peripheral nerve from structural and functional indices of diabetic peripheral neuropathy is associated with targeting of mitochondrial function, in part via NF-?B activation, and improvement of cellular bioenergetics. PMID:23022047

Saleh, Ali; Roy Chowdhury, Subir K.; Smith, Darrel R.; Balakrishnan, Savitha; Tessler, Lori; Martens, Corina; Morrow, Dwane; Schartner, Emily; Frizzi, Katie E.; Calcutt, Nigel A.; Fernyhough, Paul

2012-01-01

166

Leber's hereditary optic neuropathy: biochemical effect of 11778/ND4 and 3460/ND1 mutations and correlation with the mitochondrial genotype.  

PubMed

To clarify the bioenergetic relevance of mtDNA mutations in Leber's hereditary optic neuropathy (LHON), we investigated affected individuals and healthy carriers from six Italian LHON families harboring the 11778/ND4 and the 3460/ND1 mtDNA mutations. The enzymatic activities of mitochondrial complex I and its sensitivity to the potent inhibitors rotenone and rolliniastatin-2 were studied in mitochondrial particles from platelets, in correlation with mtDNA analysis of platelets and leukocytes. In platelets homoplasmic for mutant mtDNA, both 11778/ND4 and 3460/ND1 mutations induced resistance to rotenone and the 3460/ND1 mutation also provoked a marked decrease in the specific activity of complex I. Individuals heteroplasmic in platelets for either mutation showed normal biochemical features, indicating functional complementation of wild-type mtDNA. There was no correlation between the clinical status and mtDNA homo/heteroplasmy in platelets, but the biochemical features correlated with the mitochondrial genotype of platelets. In some cases, the degree of mtDNA heteroplasmy differed in platelets and leukocytes from the same individual with a prevalence of wild-type mtDNA in the platelets. These results imply that biochemical studies on mitochondrial diseases should always be integrated with mtDNA analysis of the same tissue investigated and also suggest that the mtDNA analysis on the leukocyte fraction, as usually performed in LHON, does not necessarily reflect the mutant genotype level of other tissues. The differential tissue heteroplasmy may be more relevant than previously thought in determining disease penetrance. PMID:9191778

Carelli, V; Ghelli, A; Ratta, M; Bacchilega, E; Sangiorgi, S; Mancini, R; Leuzzi, V; Cortelli, P; Montagna, P; Lugaresi, E; Degli Esposti, M

1997-06-01

167

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

PubMed

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

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

2013-12-01

168

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

PubMed

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

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

2012-08-01

169

Genetic axonal neuropathies and neuronopathies of pre-natal and infantile onset.  

PubMed

The infantile-onset axonal neuropathies and neuronopathies are an uncommon and heterogeneous group of conditions causing weakness, wasting, and developmental delay in early childhood. Many are associated with central nervous system or other systemic manifestations and cause early mortality. We review the axonal Charcot-Marie-Tooth subtypes with onset in infancy, spinal muscular atrophy, and related syndromes of early infancy, giant axonal neuropathy, infantile neuroaxonal dystrophy, hereditary motor and sensory neuropathy with agenesis of the corpus callosum, early-onset neuropathies associated with mitochondrial disorders, and other less well-delineated clinical entities. Useful clinical and neuropathologic features in the diagnostic work-up of these conditions are also presented. PMID:22971091

Yiu, Eppie M; Ryan, Monique M

2012-09-01

170

Reduced intraepidermal nerve fiber density in HIV-associated sensory  

E-print Network

diagnostic tool in idiopathic small-fiber sensory neuropathy3,4 and diabetic neuropathy,5 but has not yetReduced intraepidermal nerve fiber density in HIV-associated sensory neuropathy M. Polydefkis, MD nerve fiber (IENF) density in HIV-associated sensory neuropathy (HIV-SN) to measurements of neuropathy

Steinbach, Joe Henry

171

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

PubMed

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

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

2014-04-01

172

Induction of monocyte chemoattractant protein-1 (MCP-1) and its receptor CCR2 in primary sensory neurons contributes to paclitaxel-induced peripheral neuropathy  

PubMed Central

The use of paclitaxel (Taxol®), a microtubule stabilizer, for cancer treatment is often limited by its associated peripheral neuropathy (chemotherapy-induced peripheral neuropathy, CIPN) which predominantly results in sensory dysfunction including chronic pain. Here we show that paclitaxel CIPN was associated with an induction of chemokine monocyte chemoattractant protein-1 (MCP-1) and its cognate receptor CCR2 in primary sensory neurons of dorsal root ganglia (DRG). Immunostaining revealed that MCP-1 was mainly expressed in small nociceptive neurons while CCR2 was expressed in large and medium-sized myelinated neurons. Direct application of MCP-1 consistently induced intracellular calcium increases in DRG large and medium-sized but not small neurons mainly dissociated from paclitaxel- but not vehicle-treated animals. Paclitaxel also induced increased expression of MCP-1 in spinal astrocytes but no CCR2 signal was detected in spinal cord. Local blockade of MCP-1/CCR2 signaling by anti-MCP-1 antibody or CCR2 antisense oligodeoxynucleotides significantly attenuated paclitaxel CIPN phenotypes including mechanical hypersensitivity and loss of intraepidermal nerve fibers (IENFs) in hindpaw glabrous skin. These results suggest that activation of paracrine MCP-1/CCR2 signaling between DRG neurons plays a critical role in the development of paclitaxel CIPN and targeting MCP-1/CCR2 signaling could be a novel therapeutic approach. PMID:23726937

Zhang, Haijun; Boyette-Davis, Jessica A.; Kosturakis, Alyssa K.; Li, Yan; Yoon, Seo-Yeon; Walters, Edgar T.; Dougherty, Patrick M.

2013-01-01

173

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

174

Axonal Neuropathy-associated TRPV4 Regulates Neurotrophic Factor-derived Axonal Growth*  

PubMed Central

Spinal muscular atrophy and hereditary motor and sensory neuropathies are characterized by muscle weakness and atrophy caused by the degenerations of peripheral motor and sensory nerves. Recent advances in genetics have resulted in the identification of missense mutations in TRPV4 in patients with these hereditary neuropathies. Neurodegeneration caused by Ca2+ overload due to the gain-of-function mutation of TRPV4 was suggested as the molecular mechanism for the neuropathies. Despite the importance of TRPV4 mutations in causing neuropathies, the precise role of TRPV4 in the sensory/motor neurons is unknown. Here, we report that TRPV4 mediates neurotrophic factor-derived neuritogenesis in developing peripheral neurons. TRPV4 was found to be highly expressed in sensory and spinal motor neurons in early development as well as in the adult, and the overexpression or chemical activation of TRPV4 was found to promote neuritogenesis in sensory neurons as well as PC12 cells, whereas its knockdown and pharmacologic inhibition had the opposite effect. More importantly, nerve growth factor or cAMP treatment up-regulated the expression of phospholipase A2 and TRPV4. Neurotrophic factor-derived neuritogenesis appears to be regulated by the phospholipase A2-mediated TRPV4 pathway. These findings show that TRPV4 mediates neurotrophic factor-induced neuritogenesis in developing peripheral nerves. Because neurotrophic factors are essential for the maintenance of peripheral nerves, these findings suggest that aberrant TRPV4 activity may lead to some types of pathology of sensory and motor nerves. PMID:22187434

Jang, Yongwoo; Jung, Jooyoung; Kim, Hyungsup; Oh, Jungeun; Jeon, Ji Hyun; Jung, Saewoon; Kim, Kyung-Tai; Cho, Hawon; Yang, Dong-Jin; Kim, Sung Min; Kim, In-Beom; Song, Mi-Ryoung; Oh, Uhtaek

2012-01-01

175

Coexistence of Charcot-Marie-Tooth disease type 1A and anti-MAG neuropathy.  

PubMed

At age 35, a man with a genetic diagnosis of Charcot-Marie-Tooth disease type 1A (CMT1A) but no family history of neuropathy and no clinical symptoms developed rapidly progressive loss of balance, distal limb numbness, loss of manual dexterity, and hand tremor. Five years later, he walked with support and had mild pes cavus, marked sensory ataxia, severe leg and hand weakness, absent deep tendon reflexes (DTRs), severe sensory loss, and hand tremor. He had dramatically reduced motor nerve conduction velocity (MNCV), strikingly prolonged motor distal latencies, absent sensory action potentials and lower limb compound muscle action potentials. CMT1A duplication was reconfirmed but the dramatic change in his clinical course suggested a superimposed acquired neuropathy. An IgM-kappa monoclonal gammopathy of uncertain significance (MGUS) with high titer anti-myelin associated glycoprotein (anti-MAG) activity was found. Nerve biopsy showed severe loss of myelinated fibers with onion bulbs, no evidence of uncompacted myelin, and few IgM deposits. Rituximab was given and he improved. It is very likely that this is a chance association of two rare and slowly progressive neuropathies; rapidly worsening course may have been due to a "double hit". Interestingly, there are reports of possible superimposition of dysimmune neuropathies on hereditary ones, and the influence of the immune system on inherited neuropathies is matter for debate. PMID:23781967

Piscosquito, Giuseppe; Salsano, Ettore; Ciano, Claudia; Palamara, Luisa; Morbin, Michela; Pareyson, Davide

2013-06-01

176

Clinical Features: Charcot Marie Tooth Disease is a group of inherited neuropathies characterized by chronic motor and sensory  

E-print Network

1/13 Clinical Features: Charcot Marie Tooth Disease is a group of inherited neuropathies-499-9264 Email: info@charcot-marie-tooth.org http://www.charcot-marie-tooth.org/ The Muscular Dystrophy Association 3300 E. Sunrise Drive Tucson, AZ 85718 800-572-1717 http://www.mda.org/ European Charcot-Marie-Tooth

Ober, Carole

177

Clinical Features: Charcot Marie Tooth Disease is a group of inherited neuropathies characterized by chronic motor and sensory  

E-print Network

10/08 Clinical Features: Charcot Marie Tooth Disease is a group of inherited neuropathies-499-9264 Email: info@charcot-marie-tooth.org http://www.charcot-marie-tooth.org/ The Muscular Dystrophy Association 3300 E. Sunrise Drive Tucson, AZ 85718 800-572-1717 http://www.mda.org/ European Charcot-Marie-Tooth

Gilad, Yoav

178

Clinical Features: Charcot Marie Tooth Disease is a group of inherited neuropathies characterized by chronic motor and sensory  

E-print Network

6/11 Clinical Features: Charcot Marie Tooth Disease is a group of inherited neuropathies-499-9264 Email: info@charcot-marie-tooth.org http://www.charcot-marie-tooth.org/ The Muscular Dystrophy Association 3300 E. Sunrise Drive Tucson, AZ 85718 800-572-1717 http://www.mda.org/ European Charcot-Marie-Tooth

Ober, Carole

179

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

PubMed

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

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

2014-01-01

180

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

181

Diabetic Neuropathy  

MedlinePLUS

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

182

Sciatic neuropathy as first sign of metastasising prostate cancer  

Microsoft Academic Search

Peripheral neuropathies are among the most common neurological diseases and have numerous causes, including diabetes, alcohol, hereditary, toxic, metabolic, infectious, inflammatory, ischaemic and paraneoplastic. Often, however, no definitive cause is identified and the condition is termed idiopathic neuropathy. Here we describe a patient who was initially diagnosed with idiopathic sciatic neuropathy but who was eventually diagnosed with prostate cancer. This

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

2010-01-01

183

A 1.5 Mb submicroscopic deletion in 17p11.2-p12 is frequently observed in Italian families with hereditary neuropathy with liability to pressure palsies  

SciTech Connect

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder characterized by recurrent mononeuropathies that was recently associated with a 1.5 Mb deletion in chromosome 17p11.2-p12. Duplication of the same region is known to be associated with Charcot-Marie-Tooth disease type 1A (CMT1A), a more severe peripheral neuropathy characterized by symmetrically slowed nerve conduction velocity. The CMT1A duplication and HNPP deletion are reciprocal recombination products involving a repeat element (CMT1A-REP) which flanks the 1.5 Mb region involved in the duplication/deletion. Patients from 9 unrelated HNPP Italian families were clinically, electrophysiologically and histologically evaluated. Families were typed with a polymorphic (CA){sub n} repeat and with RFLPs corresponding to loci D17S122, D17S125 and D17S61, which all map within the deleted region. Lack of allelic transmission from affected parent to affected offspring was observed in four informative families, suggesting the presence of deletion. Southern blot analysis of EcoRI digested genomic DNA from HNPP patients and control subjects was performed using a probe mapping within the CMT1A-REP elements. A reduced hybridization signal of a 6.0 kb EcoRI fragment, mapping within the distal CMT1A-REP, was observed in all HNPP patients suggesting the loss of one copy of this fragment in the HNPP-deleted chromosome. PFGE analysis of SacII digested genomic DNA from selected HNPP subjects showed the presence of a junction fragment which has previously been found in association with the 1.5 Mb HNPP deletion. Evidence for deletion could be demonstrated in all 9 families suggesting that the 17p11.2-p12 deletion is commonly associated with HNPP.

Lorenzetti, D.; Roa, B.B.; Abbas, N.E. [Baylor College of Medicine, Houston, TX (United States)] [and others

1994-09-01

184

Dominant mutations in the cation channel gene transient receptor potential vanilloid 4 cause an unusual spectrum of neuropathies  

PubMed Central

Hereditary neuropathies form a heterogeneous group of disorders for which over 40 causal genes have been identified to date. Recently, dominant mutations in the transient receptor potential vanilloid 4 gene were found to be associated with three distinct neuromuscular phenotypes: hereditary motor and sensory neuropathy 2C, scapuloperoneal spinal muscular atrophy and congenital distal spinal muscular atrophy. Transient receptor potential vanilloid 4 encodes a cation channel previously implicated in several types of dominantly inherited bone dysplasia syndromes. We performed DNA sequencing of the coding regions of transient receptor potential vanilloid 4 in a cohort of 145 patients with various types of hereditary neuropathy and identified five different heterozygous missense mutations in eight unrelated families. One mutation arose de novo in an isolated patient, and the remainder segregated in families. Two of the mutations were recurrent in unrelated families. Four mutations in transient receptor potential vanilloid 4 targeted conserved arginine residues in the ankyrin repeat domain, which is believed to be important in protein–protein interactions. Striking phenotypic variability between and within families was observed. The majority of patients displayed a predominantly, or pure, motor neuropathy with axonal characteristics observed on electrophysiological testing. The age of onset varied widely, ranging from congenital to late adulthood onset. Various combinations of additional features were present in most patients including vocal fold paralysis, scapular weakness, contractures and hearing loss. We identified six asymptomatic mutation carriers, indicating reduced penetrance of the transient receptor potential vanilloid 4 defects. This finding is relatively unusual in the context of hereditary neuropathies and has important implications for diagnostic testing and genetic counselling. PMID:20460441

Zimo?, Magdalena; Baets, Jonathan; Auer-Grumbach, Michaela; Berciano, José; Garcia, Antonio; Lopez-Laso, Eduardo; Merlini, Luciano; Hilton-Jones, David; McEntagart, Meriel; Crosby, Andrew H.; Barisic, Nina; Boltshauser, Eugen; Shaw, Christopher E.; Landouré, Guida; Ludlow, Christy L.; Gaudet, Rachelle; Houlden, Henry; Reilly, Mary M.; Fischbeck, Kenneth H.; Sumner, Charlotte J.; Timmerman, Vincent; Jordanova, Albena

2010-01-01

185

Peripheral neuropathy associated with the sicca syndrome.  

PubMed Central

Three patients with the sicca syndrome and chronic sensory neuropathy are described; in two of them neuropathy was the presenting feature of the disease. The sicca syndrome can give rise to a characteristic neurological syndrome comprising areflexia and asymmetrical sensory loss, particularly of proprioception, in the limbs. This is often associated with tonic pupils and trigeminal anaesthesia. PMID:3007674

Kennett, R P; Harding, A E

1986-01-01

186

Yield of the sural/radial ratio versus the medial plantar nerve in sensory neuropathies with a normal sural response.  

PubMed

The electrodiagnostic yield of the medial plantar nerve action potential (NAP) amplitude versus the sural/radial amplitude ratio (SRAR) was determined in 110 consecutive patients with clinically diagnosed distal sensory polyneuropathy (SN) and normal sural responses. Forty-five consecutive patients with clinically diagnosed lumbosacral radiculopathy served as disease controls. Of the 110 SN patients, 32 were classified clinically as SN with large-fiber involvement (SN-LFI), whereas 78 had clinically pure small-fiber SN. Plantar NAP amplitudes were abnormal in 18 of 32 patients (56%) with SN-LFI, and 15 of 78 (19%) with small-fiber SN. A SRAR <0.21 (fifth percentile of normal) was found in 7 of 32 patients (22%) with SN-LFI and 8 of 78 (10%) with small-fiber SN. In the control group, the medial plantar NAP was normal in all 45 subjects (100%), whereas the SRAR was >0.21 in 43 subjects (96%). Thus, for a 50% pretest probability of SN-LFI, the positive predictive value of an abnormal medial plantar was 100% versus 85% for a SRAR <0.21. The medial plantar NAP amplitude is a more useful measure of SN, than is the SRAR, in patients under age 70, with suspected SN-LFI. The yield of the SRAR and plantar NAP amplitude is poor when clinical signs of large-fiber sensory dysfunction are lacking. PMID:18340276

Sullivan, John P; Logigian, Eric L; Kocharian, Naira; Herrmann, David N

2008-04-01

187

Electrophysiological studies in diabetic neuropathy  

Microsoft Academic Search

In 30 patients with diabetic neuropathy sensory potentials in the median nerve, motor conduction in the lateral popliteal and median nerves, and electromyographic findings in distal and proximal muscles were compared with the severity of symptoms and signs. All patients had abnormalities in at least one of the electrophysiological parameters. The sensory potentials were the most sensitive indicator of subclinical

Albert Lamontagne; Fritz Buchthal

1970-01-01

188

The expansion of 300 CTG repeats in myotonic dystrophy transgenic mice does not induce sensory or motor neuropathy.  

PubMed

Although many studies have been carried out to verify the involvement of the peripheral nervous system (PNS) in dystrophia myotonica (DM1) patients, the results remain controversial. The generation of DM1 transgenic mice displaying the human DM1 phenotype provides a useful tool to investigate the type and incidence of structural abnormalities in the PNS. In the present study, the morphological and morphometric analysis of semi-thin sections of sciatic and sural nerves, lumbar dorsal root ganglia (DRG) and lumbar spinal cords revealed that in DM1 transgenic mice carrying 300 CTG repeats, there is no change in the number and diameter of myelinated axons compared to wild type. Only a non-significant reduction in the percentage of thin myelinated axons was detected in electron micrographs of ultra-thin sciatic nerve sections. Analysis of the number of neurons did not reveal a loss in number of either sensory neurons in the lumbar DRG or motor neurons in the lumbar spinal cord in these DM1 mice. Furthermore, in hind limb muscle sections, stained with a neurofilament antibody and alpha-bungarotoxin, the intramuscular axon arborization appeared normal in DM1 mice and undistinguishable from that in wild-type mice. Moreover, in DM1 mice, there was no irregularity in the structure or an increase in the endplate area. Also statistical analysis did not show an increase in endplate density or in the concentration of acetylcholine receptors. Altogether, these results suggest that 300 CTG repeats are not sufficient to induce axonopathy, demyelination or neuronopathies in this transgenic mouse model. PMID:17318633

Gantelet, E; Kraftsik, R; Delaloye, S; Gourdon, G; Kuntzer, T; Barakat-Walter, I

2007-08-01

189

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

190

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

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

191

Neuropathy Association  

MedlinePLUS

... 18: Boston's Prudential Tower Will Glow Purple and Gold for Neuropathy Awareness REGISTER NOW! December 13: "Your ... May 20: Boston's Zakim Bridge Shines Purple and Gold for Millions Living with Neuropathy! May 15-16: ...

192

Diabetic Neuropathy  

MedlinePLUS

... levels damage the blood vessels and nerves. That's why people who don't control (or can't control) their blood sugar very ... neuropathy treated? There is no cure for diabetic neuropathy. Treatment focuses on slowing the development ...

193

Metabolic neuropathies  

MedlinePLUS

... are at the highest risk of nerve damage ( diabetic neuropathy ) from diabetes include: Those with damage to the ... A, Ward K. Neuropathic Pain: A Review of Diabetic Neuropathy. US Pharm . 2010;35(5):HS8-HS15.

194

Inherited mitochondrial optic neuropathies  

PubMed Central

Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (DOA) are the two most common inherited optic neuropathies and they result in significant visual morbidity among young adults. Both disorders are the result of mitochondrial dysfunction: LHON from primary mitochondrial DNA (mtDNA) mutations affecting the respiratory chain complexes; and the majority of DOA families have mutations in the OPA1 gene, which codes for an inner mitochondrial membrane protein critical for mtDNA maintenance and oxidative phosphorylation. Additional genetic and environmental factors modulate the penetrance of LHON, and the same is likely to be the case for DOA which has a markedly variable clinical phenotype. The selective vulnerability of retinal ganglion cells (RGCs) is a key pathological feature and understanding the fundamental mechanisms that underlie RGC loss in these disorders is a prerequisite for the development of effective therapeutic strategies which are currently limited. PMID:19001017

Yu-Wai-Man, P; Griffiths, P G; Hudson, G; Chinnery, P F

2009-01-01

195

Chronic dysimmune neuropathies: Beyond chronic demyelinating polyradiculoneuropathy  

PubMed Central

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

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

2011-01-01

196

Effectiveness of Real-Time Quantitative PCR Compare to Repeat PCR for the Diagnosis of Charcot-Marie-Tooth Type 1A and Hereditary Neuropathy with Liability to Pressure Palsies  

PubMed Central

The majority of cases of Charcot-Marie-Tooth type 1A (CMT1A) and of hereditary neuropathy with a liability to pressure palsies (HNPP) are the result of heterozygosity for the duplication or deletion of peripheral myelin protein 22 gene (PMP22) on 17p11.2. Southern blots, pulsed-field gel electrophoresis (PFGE), fluorescence in situ hybridization (FISH) and polymorphic marker analysis are currently used diagnostic methods. But they are time-consuming, labor-intensive and have some significant limitations. We describe a rapid realtime quantitative PCR method for determining gene copy number for the identification of DNA duplication or deletion occurring in CMT1A or HNPP and compare the results obtained with REP-PCR. Six patients with CMT1A and 14 patients with HNPP [confirmed by Repeat (REP)-PCR], and 16 patients with suspicious CMT1A and 13 patients with suspicious HNPP [negative REP-PCR], and 15 normal controls were studied. We performed REP-PCR, which amplified a 3.6 Kb region (including a 1.7 Kb recombination hotspot), using specific CMT1A-REP and real-time quantitative PCR on the LightCycler system. Using a comparative threshold cycle (Ct) method and ?-globin as a reference gene, the gene copy number of the PMP22 gene was quantified. The PMP22 duplication ratio ranged from 1.35 to 1.74, and the PMP22 deletion ratio from 0.41 to 0.53. The PMP22 ratio in normal controls ranged from 0.81 to 1.12. All 6 patients with CMT1A and 14 patients with HNPP confirmed by REP-PCR were positive by real-time quantitative PCR. Among the 16 suspicious CMT1A and 13 suspicious HNPP with negative REP-PCR, 2 and 4 samples, respectively, were positive by real-time quantitative PCR. Real-time quantitative PCR is a more sensitive and more accurate method than REP-PCR for the detection of PMP22 duplications or deletions, and it is also faster and easier than currently available methods. Therefore, we believe that the real-time quantitative method is useful for diagnosing CMT1A and HNPP. PMID:15988805

Choi, Jong Rak; Lee, Woon Hyoung; Sunwoo, Il Nam; Lee, Eun Kyung; Lee, Chang Hoon

2005-01-01

197

Diabetic Neuropathy  

Microsoft Academic Search

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

Solomon Tesfaye

198

[Vasculitic peripheral neuropathy].  

PubMed

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

Oya, Yasushi

2013-11-01

199

Neuropathy in Wolfram syndrome.  

PubMed

Wolfram syndrome (WFS) is a degenerative disease with neurological and endocrine disorders, characterized by the association of juvenile diabetes mellitus and bilateral optic atrophy. A polyneuropathy was exceptionally described but its characteristics are not well-established. In addition to our observation, we searched all case reports of patients with WFS in the medical literature (more than 600), and selected patients who underwent an EMG: twenty-one patients underwent an EMG, which was considered as abnormal in only 8 cases. The common profile was axonal sensory-motor polyneuropathy, sometimes with marked decrease of motor conduction velocities. This neuropathy could be due to diabetes mellitus, even though microangiopathic and macroangiopathic complications are rare in WFS. Another origin for this neuropathy could be a degenerative process in relationship with WFS. PMID:20888932

Mathis, Stéphane; Maisonobe, Thierry; Neau, Jean-Philippe

2011-01-01

200

Congenital giant axonal neuropathy.  

PubMed

Giant axonal neuropathy (GAN) is a distal sensorimotor neuropathy, characterized by neurofilamentous axonal swellings, with usual onset at 2 to 3 years of age. We report a case of congenital GAN with hypotonia at birth. At 7 months of age, nerve conduction studies showed almost complete lack of sensory and motor responses in the lower extremities. A sural nerve biopsy specimen disclosed absence of myelinated axons. Autopsy, following death at 15 months of age, revealed axonal swellings in peripheral nerves and distal degeneration of long spinal cord tracts. The neurofilamentous content of the axonal swellings was confirmed by Glees-Marsland staining and immunoperoxidase reaction with antibodies to neurofilaments. Axonal swellings did not stain with periodic acid-Schiff and were not seen in the cerebral cortex or brain stem, distinguishing this process from infantile neuroaxonal dystrophy. This patient illustrates congenital GAN with subsequent rapid progression. PMID:2990373

Kinney, R B; Gottfried, M R; Hodson, A K; Autilio-Gambetti, L; Graham, D G

1985-07-01

201

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

202

[Neuropathies and almitrine. 14 cases].  

PubMed

Previously reported cases of peripheral neuropathies occurring during almitrine therapy had only a few weeks follow-up after having stopped the drug. We have studied clinical and electrophysiological data 6 to 12 months after almitrine had been given up in 9 patients from a group of 14 whose epidemiologic, clinical, electrophysiological and pathological data had been registered. In 7 of them, without any chronic respiratory deficiency, almitrine was administered as almitrine bismésilate and raubasine, and in 7 others (6 with chronic respiratory deficiency) as almitrine bismesilate alone. In patients who had another possible cause of neuropathy, clinical disorders appeared after a lesser total quantity of almitrine (p less than 0.05). Clinical data were suggestive of sensory peripheral neuropathies of feet and lower third of legs. Electrophysiological data suggested distal axonopathy in spite of the absence of denervation: amplitudes of sensory potentials were reduced and nerve conduction velocities were moderately decreased. Biopsies revealed mild neurogenic atrophy of muscles and distal axonopathy. Clinical improvement was very slow and 6 to 12 months later, most of the patients still presented decreased vibration sense and ankle reflexes loss, but all of them were still improving. Amplitudes of sensory potentials and sensory nerve conduction velocities were significantly improved (p less than 0.05) but motor nerve conduction velocities were not (p greater than 0.05). Our study shows: 1) clinical, electrophysiological and pathological data similar to those previously reported; 2) subclinical disturbances of motor functions in lower limbs and sensory functions in upper limbs; 3) some patients presented with unusual signs: posture tremor (3 cases), painful legs and moving toes (1 case); 4) peripheral neuropathies may occur during almitrine therapy even in patients without any chronic respiratory insufficiency; 5) peripheral neuropathies occurred with lower doses in patients with other factors predisposing to neuropathies; 6) patients' improvement was very slow; 7) in 9 cases the imputability of these peripheral neuropathies to almitrine is plausible. We suggest not to prescribe almitrine without caution, especially in patients with other factors of neuropathy. Treatment should be regularly interrupted. PMID:2889253

Petit, H; Leys, D; Hurtevent, J F; Parent, M; Caron, J; Salomez, J L; Krivosic, I

1987-01-01

203

Alcoholic neuropathy  

MedlinePLUS

... this condition. In severe cases, nerves that regulate internal body functions (autonomic nerves) may be involved. Risks of alcoholic neuropathy include: Long-term, heavy alcohol use Alcoholism that is present for 10 years or more

204

[Hereditary hemochromatosis].  

PubMed

The case of a 43-year-old male is presented, with diagnosed diabetes mellitus,heart failure, skin pigmentation, hepatic cirhosis, and hereditary hemochromatosis confirmed by liver biopsy. The objective of this publication is to have hemochromatosis in mind as a differential diagnosis in a middle-aged patient with several pathologies and organs involved. PMID:14716426

Landa Garrido, Lidia; Huamán Muñante, José; Valencia Caballero, Víctor; Lozano Miranda, Zenaida; Nago Nago, Augusto

2003-01-01

205

Facioscapulohumeral muscular dystrophy and Charcot-Marie-Tooth neuropathy 1A - evidence for "double trouble" overlapping syndromes  

PubMed Central

Background We report on a patient with genetically confirmed overlapping diagnoses of CMT1A and FSHD. This case adds to the increasing number of unique patients presenting with atypical phenotypes, particularly in FSHD. Even if a mutation in one disease gene has been found, further genetic testing might be warranted in cases with unusual clinical presentation. Case presentation The reported 53 years old male patient suffered from walking difficulties and foot deformities first noticed at age 20. Later on, he developed scapuloperoneal and truncal muscle weakness, along with atrophy of the intrinsic hand and foot muscles, pes cavus, claw toes and a distal symmetric hypoesthesia. Motor nerve conduction velocities were reduced to 20 m/s in the upper extremities, and not educible in the lower extremities, sensory nerve conduction velocities were not attainable. Electromyography showed both, myopathic and neurogenic changes. A muscle biopsy taken from the tibialis anterior muscle showed a mild myopathy with some neurogenic findings and hypertrophic type 1 fibers. Whole-body muscle MRI revealed severe changes in the lower leg muscles, tibialis anterior and gastrocnemius muscles were highly replaced by fatty tissue. Additionally, fatty degeneration of shoulder girdle and straight back muscles, and atrophy of dorsal upper leg muscles were seen. Taken together, the presenting features suggested both, a neuropathy and a myopathy. Patient’s family history suggested an autosomal dominant inheritance. Molecular testing revealed both, a hereditary motor and sensory neuropathy type 1A (HMSN1A, also called Charcot-Marie-Tooth neuropathy 1A, CMT1A) due to a PMP22 gene duplication and facioscapulohumeral muscular dystrophy (FSHD) due to a partial deletion of the D4Z4 locus (19 kb). Conclusion Molecular testing in hereditary neuromuscular disorders has led to the identification of an increasing number of atypical phenotypes. Nevertheless, finding the right diagnosis is crucial for the patient in order to obtain adequate medical care and appropriate genetic counseling, especially in the background of arising curative therapies. PMID:24041033

2013-01-01

206

Aesthesiometry : Quantification of cutaneous pressure sensation in diabetic peripheral neuropathy  

Microsoft Academic Search

The Semmes-Weinstein pressure aesthesi- ometer, which measures cutaneous pressure sensation, was used for quantifying sensory loss in diabetic periph- eral neuropathy . Eighty subjects comprising four groups were tested : nondiabetic controls (Group C) ; non- neuropathic, diabetic controls (Group DC) ; diabetic subjects with neuropathy and without a history of pedal ulcerations (Group DN) ; and, diabetic subjects with

JOHN J. HOLEWSKI; RICHARD M. STESS; PETER M. GRAF; CARL GRUNFELD

207

Association Between Arsenic Exposure and a Measure of Subclinical Sensory  

E-print Network

Association Between Arsenic Exposure and a Measure of Subclinical Sensory Neuropathy in Bangladesh between arsenic exposure and signs of subclinical peripheral neuropathy. Abstract Objectives: We examined the association between arsenic exposure and peripheral neuropathy in Bangladesh, where the population has been

van Geen, Alexander

208

Multifocal Motor Neuropathy  

MedlinePLUS

... Enhancing Diversity Find People About NINDS NINDS Multifocal Motor Neuropathy Information Page Table of Contents (click to ... being done? Clinical Trials Organizations What is Multifocal Motor Neuropathy? Multifocal motor neuropathy is a progressive muscle ...

209

[Hereditary hemochromatosis].  

PubMed

Hereditary hemochromatosis is an inherited autosomal recessive disease, associated to a mutation in the recently described HFE gene, which is located on the short arm of chromosome 6. The product of this gene combines with the beta-2-microglobulin and the ferritin receptor, and regulates the iron absorption in the small intestine crypt cells. It is possible that the mutation may cause the increased iron uptake by the intestinal cells. The disease is very much common in men after the forties, and its expression is influenced by concomitant alcoholism, iron rich diet, oral and parenteral iron administration, menstrual blood loss or abnormal hemorrhages, blood donations, pregnancy, lactation, and iron malabsorption clinical conditions, like celiac disease. Many patients are asymptomatic, and the diagnosis may be suspected by hepatomegaly of unknown cause, abnormal iron metabolism tests, increased serum aminotransferase levels, diabetes mellitus, and anonymous arthropathy. Less commonly hereditary hemochromatosis presented by symptoms and signs of chronic liver disease, or by the classic triad described by Trousseau skin pigmentation, hepatomegaly and diabetes mellitus. The diagnosis is confirmed by the increased serum ferritin levels and transferrin saturation, and the stainable iron in hepatocytes, measured by scale devised by Scheuer et al, or the measurement of the hepatic iron. The C282Y mutation was found in 64 to 100% of patients; eventually, subjects with hepatic iron overload identical to hereditary hemochromatosis has no mutation, and homozygous for the C282Y mutation do not express iron overload. Iron is best and quickly removed by weekly or twice-weekly phlebotomy of 500 ml, containing approximately 250 mg iron. One to 3 years of weekly phlebotomy may be required to reduce stores to normal. As a guide to long-term maintenance therapy, is recommended phlebotomy every 3 months and the serum ferritin level should be maintained by less than 50 ng/ml. PMID:12170286

Dantas, W

2001-01-01

210

Recombination hot spot in a 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. French CMT Collaborative Research Group.  

PubMed Central

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 where 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. Images Figure 2 Figure 3 PMID:8651299

Lopes, J.; LeGuern, E.; Gouider, R.; Tardieu, S.; Abbas, N.; Birouk, N.; Gugenheim, M.; Bouche, P.; Agid, Y.; Brice, A.

1996-01-01

211

Diagnosis and Management of Diabetic Peripheral Neuropathy  

Microsoft Academic Search

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

Isabel Illa

1999-01-01

212

Peripheral neuropathies during treatment with almitrine: report of 46 cases  

Microsoft Academic Search

Almitrine bismesylate is thought to cause sensory peripheral neuropathy. Forty-six patients are reported who received almitrine bismesylate alone for chronic respiratory failure or in combination with raubasine for various cerebrovascular diseases. Polyneuropathy appeared between 9 and 25 months after the onset of treatment. Sensory signs and symptoms were confined to the distal parts of the lower limbs and involved large

P. Bouche; L. Lacomblez; J. M. Leger; M. P. Chaunu; H. Ratinahirana; P. Brunet; J. J. Hauw; H. P. Cathala; D. Laplane

1989-01-01

213

Nerve biopsy and conduction studies in diabetic neuropathy  

Microsoft Academic Search

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

F Behse; F Buchthal; F Carlsen

1977-01-01

214

Neuropathy Target Esterase Is Required for Adult Vertebrate Axon Maintenance  

PubMed Central

The enzyme neuropathy target esterase (NTE) is present in neurons and deacylates the major membrane phospholipid, phosphatidylcholine (PtdCho). Mutation of the NTE gene or poisoning by neuropathic organophosphates—chemical inhibitors of NTE—causes distal degeneration of long spinal axons in humans. However, analogous neuropathological changes have not been reported in nestin-cre:NTEfl/fl mice with NTE-deficient neural tissue. Furthermore, altered PtdCho homeostasis has not been detected in NTE-deficient vertebrates. Here, we describe distal degeneration of the longest spinal axons in ?3-week-old nestin-cre:NTEfl/fl mice and in adult C57BL/6J mice after acute dosing with a neuropathic organophosphate: in both groups early degenerative lesions were followed by swellings comprising accumulated axoplasmic material. In mice dosed acutely with organophosphate, maximal numbers of lesions, in the longest spinal sensory axon tract, were attained within days and were preceded by a transient rise in neural PtdCho. In nestin-cre:NTEfl/fl mice, sustained elevation of PtdCho over many months was accompanied by progressive degeneration and massive swelling of axons in sensory and motor spinal tracts and by increasing hindlimb dysfunction. Axonal lesion distribution closely resembled that in hereditary spastic paraplegia (HSP). The importance of defective membrane trafficking in HSP and the association of NTE with the endoplasmic reticulum—the starting point for the constitutive secretory pathway and transport of neuronal materials into axons—prompted investigation for a role of NTE in secretion. Cultured NTE-deficient neurons displayed modestly impaired secretion, consistent with neuronal viability and damage in vivo initially restricted to distal parts of the longest axons. PMID:19759306

Read, David J.; Li, Yong; Chao, Moses V.; Cavanagh, John B.

2009-01-01

215

Diabetic Neuropathy (Beyond the Basics)  

MedlinePLUS

... diabetes mellitus Type 2 diabetes mellitus Patient information: Diabetic neuropathy (Beyond the Basics) Author Eva L Feldman, MD, ... MD, PhD Find Print Contents of this article DIABETIC NEUROPATHY OVERVIEW DIABETIC NEUROPATHY RISK FACTORS DIABETIC NEUROPATHY SYMPTOMS ...

216

Inherited Neuropathies  

PubMed Central

With a prevalence of 1 in 2500 people, inherited peripheral nerve diseases, collectively called Charcot-Marie-Tooth disease (CMT), are among the most common inherited neurologic disorders. Patients with CMT typically present with chronic muscle weakness and atrophy in limbs, sensory loss in the feet and hands, and foot deformities. Clinical similarities between patients often require genetic testing to achieve a precise diagnosis. In this article, the author reviews the clinical and pathologic features of CMT, and demonstrates how electrodiagnostic and genetic tools are used to assist in the diagnosis and symptomatic management of the diseases. Several cases are presented to illustrate the diagnostic processes. PMID:23117945

Li, Jun

2013-01-01

217

Congenital hypomyelinating neuropathy.  

PubMed Central

Two patients with congenital hypomyelinating neuropathy are reported with details of sural nerve pathology. The resemblance of this condition to the hypomyelinating neuropathy of Trembler mice is discussed and the pertinent medical literature reviewed. Images PMID:4087003

Harati, Y; Butler, I J

1985-01-01

218

Neuropathy secondary to drugs  

MedlinePLUS

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

219

Sciatic neuropathy as first sign of metastasising prostate cancer  

PubMed Central

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

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

2010-01-01

220

[Acrodystrophic neuropathy in an alcoholic].  

PubMed

The patient was a 48-year-old alcoholic man with no contributory family history. At age 36 he had developed sensory dominant polyneuropathy with highly impaired temperature sensation and deep sensation in the lower extremities, recurrent ulcers of the toes, and sexual impotence. A sural nerve biopsy at this time revealed marked loss of myelinated fibers with relative preservation of the population of unmyelinated fibers. Subsequently, he developed muscle atrophy of the lower thighs, urinary incontinence, and Wernicke's encephalopathy, and became non-ambulatory at age 44. The peripheral nerve conduction findings suggested predominantly axonal degeneration. The entire course was characterized by alternative progression and partial recovery influenced by his alcohol intake and nutritional state. Alcoholic neuropathy is a major cause of solitary acrodystrophic neuropathy (ADN). Manifestations of autonomic and motor neuropathy are more marked in alcoholic ADN than in HSAN-I, and central nervous system involvement is the hallmark of alcoholic ADN. In the treatment of patients with alcoholic ADN, attention should be paid to diabetes mellitus, malnutritional state, and vitamin deficiency, which frequently complicate alcoholism. PMID:8386536

Yamamura, Y; Hironaka, M; Shimoyama, M; Toyota, Y; Kurokawa, M; Kohriyama, T; Nakamura, S

1993-01-01

221

Peripheral neuropathies 1988  

SciTech Connect

The authors present results and experience in sixteen specific disciplines related to the study of nerve physiopathology, diagnosis and treatment. Twenty-two different peripheral neuropathies are presented, and different models related to health care strategies are discussed. The authors report on Inflammatory and autoimmune neuropathies and Genetic neuropathies.

Assal, J.P.; Liniger, C.

1990-01-01

222

[Molecular genetics of inherited neuropathies].  

PubMed

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

Takashima, Hiroshi

2006-01-01

223

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

224

Childhood-onset multifocal motor neuropathy with conduction blocks.  

PubMed

Multifocal motor neuropathy (MMN) is an acquired disorder with onset in adulthood. The authors describe a patient with a slowly progressing distal upper limb motor neuropathy since age 6 years, in whom definite conduction blocks in upper limbs, outside common entrapment sites, and no sensory involvement were consistent with MMN. IV immunoglobulin treatment produced marked muscle strength improvement and conduction block disappearance. MMN diagnosis should also be considered in childhood. PMID:16567714

Moroni, I; Bugiani, M; Ciano, C; Bono, R; Pareyson, D

2006-03-28

225

Evaluation of thermal and vibration sensation in diabetic neuropathy  

Microsoft Academic Search

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

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

1985-01-01

226

Abnormal calcium homeostasis in peripheral neuropathies  

PubMed Central

Abnormal neuronal calcium (Ca2+) homeostasis has been implicated in numerous diseases of the nervous system. The pathogenesis of two increasingly common disorders of the peripheral nervous system, namely neuropathic pain and diabetic polyneuropathy, has been associated with aberrant Ca2+ channel expression and function. Here we review the current state of knowledge regarding the role of Ca2+ dyshomeostasis and associated mitochondrial dysfunction in painful and diabetic neuropathies. The central impact of both alterations of Ca2+ signalling at the plasma membrane and also intracellular Ca2+ handling on sensory neuron function is discussed and related to abnormal endoplasmic reticulum performance. We also present new data highlighting sub-optimal axonal Ca 2+ signalling in diabetic neuropathy and discuss the putative role for this abnormality in the induction of axonal degeneration in peripheral neuropathies. The accumulating evidence implicating Ca2+ dysregulation with both painful and degenerative neuropathies, along with recent advances in understanding of regional variations in Ca2+ channel and pump structures, makes modulation of neuronal Ca2+ handling an increasingly viable approach for therapeutic interventions against the painful and degenerative aspects of many peripheral neuropathies. PMID:20034667

Fernyhough, Paul; Calcutt, Nigel A.

2010-01-01

227

Disease mechanisms in inherited neuropathies  

Microsoft Academic Search

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

Steven S. Scherer; Ueli Suter

2003-01-01

228

Differential diagnosis of Charcot-Marie-Tooth disease and related neuropathies  

Microsoft Academic Search

The diagnosis of Charcot-Marie-Tooth disease (CMT) and related neuropathies (e. g. Déjèrine-Sottas disease; hereditary neuropathy with liability to pressure palsies) appears to be easy. However, the incredible advances in molecular genetics have greatly complicated the classification of these disorders, and the proper diagnosis of the CMT subtype may be important for correct genetic counselling and prognosis. Moreover, these diseases may

D. Pareyson

2004-01-01

229

Symptomatic treatment of peripheral diabetic neuropathy with carbamazepine (Tegretol ® ): Double blind crossover trial  

Microsoft Academic Search

Summary  A double blind crossover study with placebo and carbamazepine was done in 30 diabetic patients who presented diverse clinical types of peripheral diabetic neuropathy. The active drug offered symptomatic relief of all sensory manifestations in 28 cases. No effort was made to assess the action of carbamazepine upon motor or visceral manifestations of neuropathy. There were two complete failures. Untoward

J. A. Rull; R. Quibrera; H. González-Millán; O. Lozano Castañeda

1969-01-01

230

HIV neuropathy: Insights in the pathology of HIV peripheral nerve disease  

Microsoft Academic Search

HIV-associated neuropathies (HIV-N) have become the most frequent neuro- logical disorder associated with HIV infection. The most common forms of HIV-N are the distal sensory polyneuropathy (DSP) and antiretroviral toxic neuropathies (ATN), disorders characterized mostly by sensory symptoms that include spontaneous or evoked pain that follow a subacute or chronic course. The main pathological features that characterize DSP and ATN

Carlos A. Pardo; Justin C. McArthur; John W. Griffin

2001-01-01

231

Hereditary Papillary Renal Cell Carcinoma  

MedlinePLUS

... Carcinoma Request Permissions Download PDF Hereditary Papillary Renal Cell Carcinoma This section has been reviewed and approved ... Board , 10/2013 What is hereditary papillary renal cell carcinoma? Hereditary papillary renal cell carcinoma (HPRCC) is ...

232

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

233

[A diabetic visceral neuropathy].  

PubMed

The article concentrates on an issue of a diabetic autonomous neuropathy (DAN) in the gastrointestinal tract (GIT). It points out etiopathogenesis of diabetic polyneuropathy. It presents autonomous neuropathy in an overview where it also in more detail discusses this issue in the GIT. It highlights clinical picture and possible diagnostic and therapeutic ways of affecting individual parts of the gastrointestinal tract. PMID:15305631

Olsovský, J

2004-05-01

234

Nutritional optic neuropathy.  

PubMed

Nutritional optic neuropathy (aka deficiency optic neuropathy) is a dysfunction of the optic nerve resulting from improper dietary content of certain nutrients essential for normal functioning of the nerve fibers. Most commonly, it results from folic acid and vitamin B complex deficiency associated with malnutrition or poor dietary habits, incorrectly applied vegetarian diet, or chronic alcohol abuse. Obese patients after bariatric surgery constitute another risk group of optic neuropathy. Nutritional optic neuropathy is characterized by painless, gradually progressing, bilateral and symmetrical decrease in visual acuity, which can be accompanied by the color vision dysfunction. Progression of the neuropathy is associated with optic nerve atrophy, manifesting as complete disc pallor. Treatment of nutritional neuropathy includes dietary supplementation, aimed at compensating for the deficient nutrients. The treatment is mostly based on folic acid, vitamin B complex, and protein replacement, as well as eliminating risk factors of neuropathy. Early treatment commencement, prior to irreversible optic nerve atrophy, is a prerequisite of effective treatment. We would like to highlight this problem by presenting the case of a young woman in whom chronic use "water-based" diet resulted in anemia and bilateral nutritional optic neuropathy. PMID:25345287

Sawicka-Pierko, Anna; Obuchowska, Iwona; Mariak, Zofia

2014-01-01

235

[Molecular genetics of inherited neuropathies].  

PubMed

To clarify the specific features and molecular mechanisms of five diseases that we previously reported, we reviewed recent progress in HMSN-P linked to chromosome 3, CMT4F caused by PRX, CMT4A caused by GDAP1, CMT4B2 caused by SBF2/MTMR13F, and SCAN1 caused by TDP1. HMSN-P is characterized by late onset, proximal dominant severe muscle weakness, fasciculations, muscle cramp and sensory involvement. HMSN-P is a primary neuronopathy. Mutations in periaxin are associated with a broad spectrum of demyelinating neuropathies including DSS, a sensory dominant form and early onset slowly progressive CMT. Pathologically, loss of myelinated fibers, demyelination, small onion bulb formations, tomacula formation and myelin foldings were seen in sural nerves. Absence of septate like junction in the paranodal loop suggests that periaxin could be required for the adhesion complex. GDAP1 is a relatively common cause of CMT4. Half of reported patients showed the demyelinating form, while the rest showed the axonal form. The typical feature of CMT4A is paresis of the vocal cords and diaphragm. CMT4B2 is characterized by autosomal recessive, juvenile onset glaucoma and focally folded myelin in sural nerves. SBF2/MTMR13 mutations cause CMT4B2. Early onset glaucoma was seen in patients with nonsense mutations. SBF2/MTMR13 and MTMR2, which is the cause of CMT4B1, could be acting on the same 3-phosphoinositide signaling pathway. Clinical phenotypes of patients with SCAN1 showed cerebellar ataxia and axonal neuropathy. TDP1 acts on the single strand break repair pathway, and works specifically on topoisomerase I related SSBR. Disruption of TDP1 could induce a delay in the transcription process. The low rate of protein supply could lead to deaths of large neuronal cell. PMID:17432174

Takashima, Hiroshi

2006-11-01

236

Leprosy late-onset neuropathy: an uncommon presentation of leprosy.  

PubMed

Clinical and pathological findings in leprosy are determined by the natural host immune response to Mycobacterium leprae. We previously described cases of painful neuropathy (PN) with no concurrent cause apart from a past history of leprosy successfully treated. Four leprosy previously treated patients who developed a PN years after multidrug therapy (MDT) are reported. The mean patient age was 52.75 years (47-64). The mean time interval of the recent neuropathy from the previous MDT was 19 years (12-26). A painful multiplex neuritis or polyneuropathy were observed respectively in two cases. Electrophysiological studies disclosed a sensory axonal neuropathy in two cases. Microvasculitis with no bacilli was seen in nerve biopsy. Neuropathic symptoms were improved with prednisone. We consider these cases as being a leprosy late-onset neuropathy (LLON) form of presentation. A delayed immune reaction could explain the late appearance of LLON. PMID:22699535

Nascimento, Osvaldo J M; Freitas, Marcos R G de; Escada, Tania; Marques Junior, Wilson; Cardoso, Fernando; Pupe, Camila; Duraes, Sandra

2012-06-01

237

The natural history of acute painful neuropathy in diabetes mellitus  

Microsoft Academic Search

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

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

1983-01-01

238

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

239

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

240

Animal models for inherited peripheral neuropathies  

PubMed Central

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

MARTINI, RUDOLF

1997-01-01

241

Cognition in hereditary ataxia  

Microsoft Academic Search

Apart from motor control the cerebellum has been implicated in higher cortical functions such as memory, fronto-executive\\u000a functions, visuoconstructive skills and emotion. Clinical descriptions of hereditary ataxias mention cognitive impairment\\u000a to a variable extent. Systematic neuropsychological studies are limited. Regarding the neuropathological pattern in different\\u000a SCA types, cognitive deficits in hereditary ataxias are not likely to be contingent upon cerebellar

Katrin Burk

2007-01-01

242

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

PubMed Central

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

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

2012-01-01

243

[Diabetes mellitus and autoimmune neuropathy].  

PubMed

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

Deguchi, Takahisa; Nishio, Yoshihiko; Takashima, Hiroshi

2014-02-01

244

Inherited demyelinating neuropathies with micromutations of peripheral myelin protein 22 gene.  

PubMed

The peripheral myelin protein 22 gene (PMP22) encodes an intrinsic membrane protein of compact myelin. Duplication or deletion of PMP22 causes the most common autosomal dominant neuropathies, Charcot-Marie-Tooth disease type 1A or hereditary neuropathy with liability to pressure palsies. Charcot-Marie-Tooth disease type 1A is a hypertrophic de-remyelinating neuropathy manifesting with peroneal muscular atrophy and uniform, marked, slowing of nerve conduction velocities. Hereditary neuropathy with liability to pressure palsies is a recurrent focal neuropathy with sausage-like myelin thickening (tomacula) and non-uniform nerve conduction velocity changes. Missense or nonsense mutations also cause more severe Charcot-Marie-Tooth disease type 1A forms of infancy or hereditary neuropathy with liability to pressure palsies, but they are presumably very rare. We performed a mutational scanning of PMP22 in 229 index patients (46 familial, 183 isolated) referred for suspected inherited neuropathy. The series included 125 cases with hereditary neuropathy with liability to pressure palsies (mean age 42.5 years), 47 cases with Charcot-Marie-Tooth disease type 1A (motor nerve conduction velocities at median nerve below 38 m/s) (mean age 40.7 years) and 57 cases with Charcot-Marie-Tooth with unknown nerve conduction velocities (mean age 43 years). Preliminary molecular studies ruled out PMP22 duplication or deletion or mutations in a comprehensive panel of Charcot-Marie-Tooth genes. Mutational scanning of PMP22 was done by denaturing high performance liquid chromatography and automated nucleotide sequencing. To investigate the molecular basis of phenotype-to-genotype correlations, we performed a transcriptional analysis of PMP22 using reverse-transcriptase polymerase chain reaction and quantitative real-time polymerase chain reaction in two phenotypically divergent nerve biopsies. Ten patients harboured eight micromutations of PMP22 including four novel changes. In six familial and three sporadic cases, detected mutations caused premature or delayed stop codons and were associated with hereditary neuropathy with liability to pressure palsies; the related pathological pictures ranged from classical tomaculous neuropathy to a mild demyelinating neuropathy with atypical non-tomaculous myelin thickenings. In a single family a c.179-2A> G mutation affecting the splice acceptor site of intron 2 cosegregated with a Charcot-Marie-Tooth disease type 1A-like syndrome and a peculiar pathological picture of demyelinating neuropathy without Charcot-Marie-Tooth disease type 1A-like classical onion bulbs or tomacula. Transcriptional analysis of a novel c.174_178?+?7delAAACGGTGAGGC deletion involving exon 2 and intron 2 demonstrated an unstable mutant transcript leading to a p.Asn59GlyfsX12 change; the mutation represented a null allele and caused a typical tomaculous hereditary neuropathy with liability to pressure palsies. The Charcot-Marie-Tooth disease type 1-like c.179-2A >?G allele led to a stable transcript with an in-frame deletion of exon 3 (p.Glu60_Ala106del); the predicted shorter protein could exert variable molecular effects. In conclusion, micromutations of PMP22 cause a clinical and pathological continuum of demyelinating neuropathies that may include atypical phenotypes. PMID:21252112

Taioli, Federica; Cabrini, Ilaria; Cavallaro, Tiziana; Acler, Michele; Fabrizi, Gian Maria

2011-02-01

245

Dystonin/Bpag1 is a necessary endoplasmic reticulum/nuclear envelope protein in sensory neurons  

SciTech Connect

Dystonin/Bpag1 proteins are cytoskeletal linkers whose loss of function in mice results in a hereditary sensory neuropathy with a progressive loss of limb coordination starting in the second week of life. These mice, named dystonia musculorum (dt), succumb to the disease and die of unknown causes prior to sexual maturity. Previous evidence indicated that cytoskeletal defects in the axon are a primary cause of dt neurodegeneration. However, more recent data suggests that other factors may be equally important contributors to the disease process. In the present study, we demonstrate perikaryal defects in dorsal root ganglion (DRG) neurons at stages preceding the onset of loss of limb coordination in dt mice. Abnormalities include alterations in endoplasmic reticulum (ER) chaperone protein expression, indicative of an ER stress response. Dystonin in sensory neurons localized in association with the ER and nuclear envelope (NE). A fusion protein ofthe dystonin-a2 isoform, which harbors an N-terminal transmembrane domain, associated with and reorganized the ER in cell culture. This isoform also interacts with the NE protein nesprin-3{alpha}, but not nesprin-3{beta}. Defects in dt mice, as demonstrated here, may ultimately result in pathogenesis involving ER dysfunction and contribute significantly to the dt phenotype.

Young, Kevin G. [Ottawa Health Research Institute, 501 Smyth Road, Ottawa, Ontario, K1H 8L6 (Canada); University of Ottawa Center for Neuromuscular Disease, University of Ottawa, Ottawa, Ontario (Canada); Kothary, Rashmi [Ottawa Health Research Institute, 501 Smyth Road, Ottawa, Ontario, K1H 8L6 (Canada); University of Ottawa Center for Neuromuscular Disease, University of Ottawa, Ottawa, Ontario (Canada); Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario (Canada); Department of Medicine, University of Ottawa, Ottawa, Ontario (Canada)], E-mail: rkothary@ohri.ca

2008-09-10

246

Autosomal dominant sensory ataxia: a neuroaxonal dystrophy  

Microsoft Academic Search

Autosomal dominant sensory ataxia (ADSA), a rare hereditary ataxia, is characterized by progressive dysfunction of central\\u000a sensory pathways. Its pathological features have not been previously documented. We report a case of a 61-year-old man with\\u000a ADSA who died of congestive heart failure. Autopsy specimens of brain, thoracolumbar spinal cord, peripheral nerve and skeletal\\u000a muscle were examined. There was no abnormality

Jeremy J. Moeller; Robert J. B. Macaulay; Paul N. Valdmanis; Lyle E. Weston; Guy A. Rouleau; Nicolas Dupré

2008-01-01

247

[Ultrasonographic diagnosis of inflammatory neuropathies].  

PubMed

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

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

2014-03-01

248

Compressive neuropathies related to ganglions of the wrist and hand.  

PubMed

Ganglions of the wrist and hand causing compressive neuropathies are rare clinical entities. Compression of the ulnar and median nerves in their respective fibro-osseous tunnels lead to characteristic patterns of motor and/or sensory deficits, which are directly related to the location of the lesion. We present a unique case of a "dumbbell" shaped ganglion invading both Guyon's canal and the carpal tunnel causing a dual compressive neuropathy of the ulnar and median nerve. We discuss the patho-anatomy, clinical assessment, investigation and surgical treatment of this condition. PMID:24641752

Jayakumar, Prakash; Jayaram, Vijay; Nairn, David S

2014-01-01

249

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

250

Hereditary multiple exostosis.  

PubMed

Hereditary multiple exostosis is an intriguing genetic condition with a clinical impact in the field of orthopaedics, paediatrics and oncology. In this review we highlight the current knowledge about this condition from a clinical and scientific point of view. This gives us more insight into the molecular mechanisms and current models on which therapeutic agents are based. It allows for a multidisciplinary approach to the management of this complex condition. There is currently no exact pathological model that can accurately describe all the findings in the research on Hereditary Multiple Exostosis. Promising treatments with blocking agents are currently under investigation. PMID:24563962

Ryckx, Andries; Somers, Jan F A; Allaert, Lieven

2013-12-01

251

Natura non facit saltus in anti-ganglioside antibody-mediated neuropathies.  

PubMed

Natura non facit saltus (Latin for "nature does not make jumps") is a maxim expressing the idea that natural things and properties change gradually, in a continuum, rather than suddenly. In biomedical sciences, for taxonomic purposes, we make jumps that emphasize differences more than similarities. Among the dysimmune neuropathies, 2 disorders, characterized by the presence of antibodies to gangliosides GM1 and GD1a and a peculiar, exclusive motor involvement, have been identified: acute motor axonal neuropathy (AMAN) and multifocal motor neuropathy (MMN). However, anti-GM1 or -GD1a antibodies are also associated with acute motor and sensory axonal motor neuropathy (AMSAN). We review the results of recent clinical and experimental studies showing that AMAN and MMN are not exclusively motor. We discuss the possible explanations for the greater resistance of sensory fibers to antibody attack to finally suggest that AMAN, AMSAN, and MMN belong to a continuous spectrum with a common pathophysiological mechanism. PMID:23625341

Uncini, Antonino; Notturno, Francesca; Capasso, Margherita

2013-10-01

252

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

253

Acute and chronic ataxic neuropathies with disialosyl antibodies: a continuous clinical spectrum and a common pathophysiological mechanism.  

PubMed

Acute ataxic neuropathies with disialosyl antibodies include Fisher syndrome, ataxic Guillain-Barré syndrome (GBS), and acute sensory ataxic neuropathy. Fisher syndrome and ataxic GBS are more strongly associated with IgG anti-GQ1b and anti-GT1a than with anti-GD1b antibodies, whereas the association is reversed in the case of acute sensory ataxic neuropathy. Chronic ataxic neuropathy with disialosyl antibodies is associated with IgM paraprotein to GD1b and GQ1b, which occasionally reacts with GT1a. The clinical, electrophysiological, and pathological features, along with experimental findings, suggest that acute and chronic ataxic neuropathies with disialosyl antibodies form a continuous clinical and pathophysiological spectrum characterized by a complement-mediated disruption at the nodal region and are better classified in the new category of nodo-paranodopathies. PMID:24477718

Yuki, Nobuhiro; Uncini, Antonino

2014-05-01

254

Ischemic optic neuropathy.  

PubMed

Ischemic optic neuropathy is the most frequent cause of vision loss in middle age. Clinical and laboratory research studies have begun to clarify the natural history, clinical presentation, diagnostic criteria and pathogenesis of various ischemic nerve injuries. As a result, physicians are acquiring new tools to aid in the diagnosis and potential treatment of ischemic nerve injury. The aim of this review is to examine recent data on anterior and posterior ischemic optic neuropathy and to provide a framework for physicians to manage and counsel affected individuals. PMID:18826805

Athappilly, Geetha; Pelak, Victoria S; Mandava, Naresh; Bennett, Jeffrey L

2008-10-01

255

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

256

Myelin protein zero Arg36Gly mutation with very late onset and rapidly progressive painful neuropathy.  

PubMed

Mutations in myelin protein zero (MPZ) protein result in a wide spectrum of peripheral neuropathies, from congenital hypomyelinating to late onset sensory and motor axonal forms. In some patients, neuropathic pain can be a prominent symptom, making the diagnosis challenging mainly in those with other risk factors for neuropathy. We describe a 77-year-old woman with impaired glucose tolerance presenting with rapidly progressive axonal neuropathy leading to excruciating pain and severe weakness of lower limbs within 2?years from the onset. Her son abruptly complained of similar painful symptoms at the age of 47 years. Molecular analysis revealed a novel heterozygous missense mutation (c.106A>G) in MPZ exon 2, causing the substitution of arginine-36 with glycine in the extracellular domain. Our observation suggests that MPZ-related neuropathy should be considered in the diagnostic work up of patients with painful axonal neuropathy even presenting with rapid progression and at a very late age of onset. PMID:23279346

Dacci, Patrizia; Taroni, Franco; Bella, Eleonora Dalla; Milani, Micaela; Pareyson, Davide; Morbin, Michela; Lauria, Giuseppe

2012-12-01

257

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

258

Immune modulation therapy in the management of bortezomib-induced peripheral neuropathy  

PubMed Central

Peripheral neuropathy (PN) is one of the most common side effects of bortezomib therapy. The majority of bortezomib-related PN is a sensory neuropathy of mild to moderate degree, and is reversible after dose reduction or discontinuation. However, occasionally bortezomib-induced neuropathy can be severe and affects motor and/or autonomic nerves, and may be mediated by immune process. The role of immune modulation therapy in the management of bortezomib-induced PN was not well established. Here, we reported a case of bortezomib-induced severe PN that responded well to plasma exchange and steroid treatment. PMID:23211009

2012-01-01

259

Diabetic autonomic neuropathy  

Microsoft Academic Search

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

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

1979-01-01

260

Peripheral neuropathy in patients treated with almitrine dimesylate.  

PubMed

Sensory peripheral neuropathy developed in 5 patients treated with almitrine dimesylate, 60-100 mg/day. Onset was insidious, beginning symmetrically in the legs with stocking sensory loss and loss of ankle-jerks. Cerebrospinal fluid protein levels were slightly increased and there was electrophysiological and histological evidence of distal axonopathy. The interval between the first dose of almitrine dimesylate and onset of symptoms ranged from 2 to 4 months in 4 patients. All patients had noted a recent weight loss of 4-15 kg which may have resulted in release of previously bound drug. PMID:2860446

Gherardi, R; Louarn, F; Benvenuti, C; Perrier, M; Lejonc, J L; Schaeffer, A; Degos, J D

1985-06-01

261

Peripheral neuropathies during treatment with almitrine: report of 46 cases.  

PubMed

Almitrine bismesylate is thought to cause sensory peripheral neuropathy. Forty-six patients are reported who received almitrine bismesylate alone for chronic respiratory failure or in combination with raubasine for various cerebrovascular diseases. Polyneuropathy appeared between 9 and 25 months after the onset of treatment. Sensory signs and symptoms were confined to the distal parts of the lower limbs and involved large and small fibres. Histological and electrophysiological findings indicated axonal degeneration. Respiratory failure could have caused the polyneuropathy in some cases but many had no chest disease. Patients began to improve between 3 and 6 months after withdrawal of the drug. Recovery was usually complete after 12 months. PMID:2536801

Bouche, P; Lacomblez, L; Leger, J M; Chaunu, M P; Ratinahirana, H; Brunet, P; Hauw, J J; Cathala, H P; Laplane, D

1989-01-01

262

[Hereditary hemorrhagic telangiectasia].  

PubMed

Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) is a development disorder of the vasculature characterized by telangiectases and arteriovenous malformations in specific locations. Among monogenic disorders, it is one of the most common, though affected individuals are widely underdiagnosed. The most common features of this disorder, nosebleeds, and telangiectases on the lips, hands, and oral mucosa are often quite subtle. Mutations in at least five genes may result in hereditary hemorrhagic telangiectasia, but mutations in two genes (ENG and ACVRL1/ALK1) account for approximately 85% of cases. Optimal management requires understanding the specific clinical patterns of these vascular malformations, especially their locations and timing during life. Therapeutic modulation of angiogenesis may be an effective therapy. PMID:23517771

Duffau, P; Lazarro, E; Viallard, J-F

2014-01-01

263

Hereditary Nonmelanoma Skin Cancer  

PubMed Central

Cutaneous basal and squamous cell carcinomas are among the most frequent malignancies in the white population, with the annual incidence estimates ranging from 1 million to 3.5 million cases in the United States. These tumors can occur either sporadically or in the context of hereditary genodermatoses with cancer predisposition, such as basal cell nevus syndrome, xeroderma pigmentosum, epidermolysis bullosa, or oculocutaneous albinism. Different genes and signaling pathways have been shown to play a central role in the development and growth of these tumors. This article overviews the clinical features, diagnostic criteria, and the most recent data on genetic routes of the major hereditary syndromes predisposed to the development of nonmelanoma skin cancer. PMID:23174490

Nikolaou, Vasiliki; Stratigos, Alexander J.; Tsao, Hensin

2013-01-01

264

Hereditary Haemorrhagic Telangiectasia  

Microsoft Academic Search

\\u000a Hereditary Haemorrhagic Telangiectasia (HHT, Osler–Weber–Rendu syndrome) exemplifies diseases which have catalysed advances\\u000a in the understanding of fundamental pathophysiological mechanisms. The hallmark of HHT is the development of abnormal blood\\u000a vessels, involving the lung in approximately 50% of cases. This chapter will focus on the molecular mechanisms that underlie\\u000a their generation. While not all clinical problems in HHT can be directly

Claire Shovlin; S. Paul Oh

265

Hereditary haemorrhagic telangiectasia  

Microsoft Academic Search

Summary. Hereditary haemorrhagic telangiectasia (also known as Osler-Weber-Rendu syndrome) is a relatively common, under-recognized autosomal- dominant disorder that results from multisystem vascular dysplasia. It is characterized by telangiecta- ses and arteriovenous malformations of skin, mucosa and viscera. This article summarizes the clinical manifestations and the management of this disorder and its management. This review underscores an urgent need to conduct

A. S HAPIRO

2008-01-01

266

Diabetic Neuropathy: Mechanisms to Management  

PubMed Central

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

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

2014-01-01

267

Motor and functional evaluation of patients with spastic paraplegia, optic atrophy, and neuropathy (SPOAN).  

PubMed

Spastic paraplegia, optic atrophy, and neuropathy (SPOAN) is an autosomal recessive complicated form of hereditary spastic paraplegia, which is clinically defined by congenital optic atrophy, infancy-onset progressive spastic paraplegia and peripheral neuropathy. In this study, which included 61 individuals (age 5-72 years, 42 females) affected by SPOAN, a comprehensive motor and functional evaluation was performed, using modified Barthel index, modified Ashworth scale, hand grip strength measured with a hydraulic dynamometer and two hereditary spastic paraplegia scales. Modified Barthel index, which evaluate several functional aspects, was more sensitive to disclose disease progression than the spastic paraplegia scales. Spasticity showed a bimodal distribution, with both grades 1 (minimum) and 4 (maximum). Hand grip strength showed a moderate inverse correlation with age. Combination of early onset spastic paraplegia and progressive polyneuropathy make SPOAN disability overwhelming. PMID:20339643

Graciani, Zodja; Santos, Silvana; Macedo-Souza, Lucia Inês; Monteiro, Carlos Bandeira de Mello; Veras, Maria Isabel; Amorim, Simone; Zatz, Mayana; Kok, Fernando

2010-02-01

268

Myelin disorders: Causes and perspectives of Charcot-Marie-Tooth neuropathy.  

PubMed

Charcot-Marie-Tooth (CMT) disease is a common hereditary neuropathy that causes progressive distally pronounced muscle weakness and can lead to life-long disability in patients. In most cases, the disorder has been associated with a partial duplication of human chromosome 17 (CMT1A), causing 1.5-fold overexpression of the peripheral myelin protein 22 kDa (PMP22). Increased PMP22 gene dosage results in demyelination, secondary axonal loss, and neurogenic muscle atrophy. Experimental therapeutic approaches based on the role of progesterone and ascorbic acid in myelin formation recently have reached preclinical proof-of-principle trials in rodents. It was shown that progesterone receptor antagonists can reduce PMP22 overexpression and clinical severity in a CMT1A rat model. Furthermore, ascorbic acid treatment reduced premature death and demyelination in a CMT1A mouse model. Thus, basic research has opened up new vistas for the understanding and treatment of hereditary neuropathies. PMID:16632877

Meyer zu Hörste, Gerd; Prukop, Thomas; Nave, Klaus-Armin; Sereda, Michael W

2006-01-01

269

Genetics Home Reference: Giant axonal neuropathy  

MedlinePLUS

... literature OMIM Genetic disorder catalog Conditions > Giant axonal neuropathy On this page: Description Genetic changes Inheritance Diagnosis ... definitions Reviewed October 2007 What is giant axonal neuropathy? Giant axonal neuropathy is an inherited condition involving ...

270

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

271

Sensory syndromes.  

PubMed

Somatosensory deficit syndromes represent a common impairment following stroke and have a prevalence rate of around 80% in stroke survivors. These deficits restrict the ability of survivors to explore and manipulate their environment and are generally associated with a negative impact on quality of life and personal safety. Sensory impairments affect different sensory modalities in diverse locations at varying degrees, ranging from complete hemianesthesia of multiple modalities to dissociated impairment of somatosensory submodalities within a particular region of the body. Sensory impairments induce typical syndromal patterns which can be differentiated by means of a careful neurological examination, allowing the investigator to deduce location and size of the underlying stroke. In particular, a stroke located in the brainstem, thalamus, and the corticoparietal cortex result in well-differentiable sensory syndromes. Sensory function following stroke can be regained during rehabilitation even without specific sensory training. However, there is emerging evidence that specialized sensory interventions can result in improvement of somatosensory and motor function. Herein, we summarize the clinical presentations, examination, differential diagnoses, and therapy of sensory syndromes in stroke. PMID:22377851

Klingner, Carsten M; Witte, Otto W; Günther, Albrecht

2012-01-01

272

Drug-induced peripheral neuropathy.  

PubMed

Peripheral neuropathy can be caused by medication, and various descriptions have been applied for this condition. In this MiniReview, the term 'drug-induced peripheral neuropathy' (DIPN) is used with the suggested definition: Damage to nerves of the peripheral nervous system caused by a chemical substance used in the treatment, cure, prevention or diagnosis of a disease. Optic neuropathy is included in this definition. A distinction between DIPN and other aetiologies of peripheral neuropathy is often quite difficult and thus, the aim of this MiniReview is to discuss the major agents associated with DIPN. PMID:24786912

Vilholm, Ole Jakob; Christensen, Alex Alban; Zedan, Ahmed Hussein; Itani, Mustapha

2014-08-01

273

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

PubMed Central

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

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

2014-01-01

274

Sensory deprivation versus sensory variation  

Microsoft Academic Search

Compared verbal and physiological reactions to sensory deprivation (SD) and extreme sensory variation (SV). 22 male undergraduates were confined to a cubicle for 8 hr. in each condition on 2 different occasions. 2 other 8-hr sessions were spent in a relatively normal, nonconfined condition. Ss found SD more boring, dislikable, and anxiety and depression provoking than SV. More unreality stress

Marvin Zuckerman; Harold Persky; Lynne Miller; Bernard Levine

1970-01-01

275

Inflammatory autoimmune neuropathy, presumably induced by bortezomib, in a patient suffering from multiple myeloma.  

PubMed

Bortezomib is a proteasome inhibitor demonstrating substantial activity in multiple myeloma. One of its key toxicities is peripheral neuropathy, which is reversible in most patients. The possibility that bortezomib might in rare cases induce severe neuropathies by auto-inflammatory mechanisms remains controversial. We report here the case of a 65-year-old female myeloma patient who was initially treated with bortezomib, doxorubicin, and dexamethasone (PAD). At the end of the second cycle of PAD, the patient presented with a rapid and severe onset of paresis of the left arm, accompanied by progressive sensory neuropathy and increasing neuropathic pain. After an extensive neurological work-up, including electrophysiological and laboratory evaluations as well as magnet resonance tomography imaging, we diagnosed an inflammatory autoimmune neuropathy, presumably induced by bortezomib, with accentuation of the left arm nerve plexus. We subsequently initiated regular treatment with polyvalent immunoglobulins, which gradually improved the neurological symptoms. In conclusion, the identification of an inflammatory autoimmune neuropathy, presumably associated with bortezomib, is a rare but important complication. An extensive neurological examination should be performed in patients who develop severe or unusual sensory or motor deficits under therapy with bortezomib, so as to differentiate autoimmune from toxic neuropathies, as therapeutic strategies differ for each. PMID:21553020

Schmitt, Stefan; Goldschmidt, H; Storch-Hagenlocher, B; Pham, M; Fingerle-Rowson, G; Ho, A D; Neben, K

2011-06-01

276

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.

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

2014-01-01

277

[Antiganglioside antibodies in neuropathies and motor neuronopathies].  

PubMed

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

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

1996-12-01

278

Autonomic and sensory nerve dysfunction in primary biliary cirrhosis  

Microsoft Academic Search

AIM: Cardiovascular autonomic and peripheral sensory neuropathy is a known complication of chronic alcoholic and non-alcoholic liver diseases. We aimed to assess the prevalence and risk factors for peripheral sensory nerve and autonomic dysfunction using sensitive methods in patients with primary biliary cirrhosis (PBC). METHODS: Twenty-four AMA M2 positive female patients with clinical, biochemical and histological evidence of PBC and

Katalin Keresztes; Ildikó Istenes; Aniko Folhoffer; Peter L Lakatos; Andrea Horvath; Timea Csak; Peter Varga; Peter Kempler; Ferenc Szalay; Lakatos PL

279

Auditory neuropathy and cochlear implantation  

Microsoft Academic Search

This work was undertaken to study the prevalence of auditory neuropathy among deaf subjects “as diagnosed by objective tests for peripheral neuropathy” together with their performance using the cochlear implant (CI) device. Thirty-five adult CI subjects versus twenty subjects with sensorineural hearing loss of both genders and of variable etiology of hearing loss were included. Electrophysiological testing of peripheral nerves

S Soliman; N Kamal; S Ashour

2003-01-01

280

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

281

Sensory Nerve Conduction in Demyelinating and Axonal Guillain-Barré Syndromes  

Microsoft Academic Search

Guillain-Barré syndrome is divided into acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN) based on motor nerve conduction studies. We investigated whether sensory nerve conduction studies contribute to the electrodiagnosis of AIDP and AMAN. In consecutive 59 patients with AIDP (n = 26) or AMAN (n = 33), results of sensory nerve conduction studies in the median,

Satoshi Kuwabara; Kazue Ogawara; Sonoko Misawa; Keiko Mizobuchi; Jia-Ying Sung; Yukiko Kitano; Masahiro Mori; Takamichi Hattori

2004-01-01

282

Revisiting the evidence for neuropathy caused by pyridoxine deficiency and excess.  

PubMed

Pyridoxine deficiency and excess have been implicated as a cause for peripheral neuropathy. As a result, unrelated neuropathies are often treated with pyridoxine based on questionable evidence. However, neurological practitioners frequently discourage patients from taking pyridoxine in excess of 50 mg/d given concerns around the development of a toxic sensory neuronopathy. There is no systematic review to support either of the 2 practices. To address this gap in knowledge, we reviewed the available literature on neuropathy attributed to pyridoxine deficiency and excess. Based on the current limited data, it can be concluded that very low doses of daily pyridoxine are required to prevent peripheral neuropathy. There is inadequate evidence to support routine pyridoxine supplementation in patients with disorders of peripheral nervous system. Supplementation with pyridoxine at doses greater than 50 mg/d for extended duration may be harmful and should be discouraged. PMID:25137514

Ghavanini, Amer A; Kimpinski, Kurt

2014-09-01

283

Hypothesis on the pathogenesis of vacuolar myelopathy, dementia, and peripheral neuropathy in AIDS  

Microsoft Academic Search

Certain aspects of the clinical syndrome of dementia, cerebral atrophy, predominantly sensory neuropathy, and vacuolar myelopathy in AIDS resemble those seen in vitamin B12 deficiency. Pathologically, there are similarities not only in the changes in the spinal cord, but also in the brain and peripheral nerves. The pathogenesis of vacuolar myelopathy may be secondary to a combination of immune mediated

S V Tan; R J Guiloff

1998-01-01

284

Benign joint hypermobility with neuropathies: Documentation and mechanism of median, sciatic, and common peroneal nerve compression  

Microsoft Academic Search

Summary  We report three patients in whom carpal tunnel syndrome was due to neurapraxis as a consequence of unusual sleep postures enabled by their benign joint hypermobility syndrome (BJHS). A fourth patient also had bilateral sensory sciatic neuropathy and a common peroneal palsy, similarly due to regularly adopted unusual postures. Recognition of such cause-effect mechanisms and their simple solution in BJHS

L. M. March; H. Francis; J. Webb

1988-01-01

285

Severe neuropathy in a patient with acquired immune deficiency syndrome (AIDS)  

Microsoft Academic Search

A patient with acquired immune deficiency syndrome (AIDS) developed a progressive neuromuscular disorder which included a sensory component, severe weakness and muscle wasting, and fasciculations. At autopsy, there was evidence of severe peripheral neuropathy, as well as widespread cytomegalovirus (CMV) infection within the central and peripheral nervous system. Although the anterior horn cell complement within the spinal cord appeared normal,

M. E. Robert; J. J. Geraghty; S. A. Miles; M. E. Cornford; H. V. Vinters

1989-01-01

286

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

287

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

288

Vascular risk factors and diabetic neuropathy  

Microsoft Academic Search

background Other than glycemic control, there are no treatments for diabetic neuropathy. Thus, identifying potentially modifiable risk factors for neuropathy is crucial. We studied risk factors for the development of distal symmetric neuropathy in 1172 patients with type 1 diabetes mellitus from 31 centers participating in the European Diabetes (EURODIAB) Prospective Complications Study. methods Neuropathy was assessed at baseline (1989

Solomon Tesfaye; Nish Chaturvedi; Simon E. M. Eaton

2005-01-01

289

Hereditary gingival fibromatosis  

PubMed Central

Hereditary gingival fibromatosis (HGF) is a rare condition that can occur as an isolated disease, chromosomal abnormality, or as part of a number of syndromes. The gingival enlargement in HGF can be so severe that it can cover the crowns of teeth completely, causing severe functional derangement and facial disfigurement. Through review of literature revealed that HGF is usually an autosomal dominant condition, however the recessive forms are also reported. The hyperplastic gingiva is firm on palpation and has normal color with abundant stippling on the adjacent gingiva. The buccal and lingual gingiva may be involved in both the mandible and maxilla. The degrees of gingival enlargement show both intra- and interindividual variations. Here, an interesting case report of massive HGF has been presented.

Chaurasia, Akhilanand

2014-01-01

290

Upper gastrointestinal sensory-motor dysfunction in diabetes mellitus  

PubMed Central

Gastrointestinal (GI) sensory-motor abnormalities are common in patients with diabetes mellitus and may involve any part of the GI tract. Abnormalities are frequently sub-clinical, and fortunately only rarely do severe and life-threatening problems occur. The pathogenesis of abnormal upper GI sensory-motor function in diabetes is incompletely understood and is most likely multi-factorial of origin. Diabetic autonomic neuropathy as well as acute suboptimal control of diabetes has been shown to impair GI motor and sensory function. Morphological and biomechanical remodeling of the GI wall develops during the duration of diabetes, and may contribute to motor and sensory dysfunction. In this review sensory and motility disorders of the upper GI tract in diabetes is discussed; and the morphological changes and biomechanical remodeling related to the sensory-motor dysfunction is also addressed. PMID:16718808

Zhao, Jing-Bo; Fr?kjaer, Jens Br?ndum; Drewes, Asbj?rn Mohr; Ejskjaer, Niels

2006-01-01

291

Molecular diagnosis of PMP22 -associated neuropathies using fluorescence in situ hybridization (FISH) on archival peripheral nerve tissue preparations  

Microsoft Academic Search

Charcot-Marie-Tooth (CMT) syndrome type 1 and tomaculous neuropathy, also called hereditary neuropathy with liability to\\u000a pressure palsies (HNPP), represent two groups of neurological disorders with different subtypes, which can be distinguished\\u000a at the molecular level. It is known that a 1.5-mb region on chromosome 17p11.2– 12, which includes the gene for the peripheral\\u000a myelin protein 22 kDa (PMP22), is duplicated

Thomas Liehr; Holger Grehl; Bernd Rautenstrauss

1997-01-01

292

Diabetic autonomic neuropathy.  

PubMed

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

Vinik, Aaron I; Erbas, Tomris

2013-01-01

293

Genetics Home Reference: Hereditary hyperekplexia  

MedlinePLUS

... inheritance is that fathers cannot pass X-linked traits to their sons. Where can I find information ... definitions help with understanding hereditary hyperekplexia? autosomal ; autosomal dominant ; autosomal recessive ; brainstem ; cell ; chromosome ; congenital ; epilepsy ; familial ; ...

294

Genetics Home Reference: Hereditary spherocytosis  

MedlinePLUS

... the eyes and skin (jaundice), and an enlarged spleen (splenomegaly). Most newborns with hereditary spherocytosis have severe ... are removed from circulation and taken to the spleen for destruction. Within the spleen, the red blood ...

295

Cardiac Involvement in Hereditary Ataxias  

PubMed Central

Although much attention has been focused on the neurological sequelae of the hereditary ataxias, patients with these conditions also may develop cardiac complications that represent a significant cause of disability and even death. In this paper, we describe the hereditary ataxias with known cardiac involvement, discuss underlying causes, and review guidelines for screening and treatment. Continued progress will require coordinated clinical trial networks, interdisciplinary care teams, and team science. PMID:22764180

Moore, Sean; Raman, Subha V.

2013-01-01

296

NSE, a Potential Biomarker, Is Closely Connected to Diabetic Peripheral Neuropathy  

PubMed Central

OBJECTIVE To explore the relationship between serum neuron-specific enolase (NSE) levels and diabetic neuropathy. RESEARCH DESIGN AND METHODS Type 1 or 2 diabetic and healthy control subjects (n = 568) were randomly enrolled in a cross-sectional study. Diabetic neuropathy status was documented by the presence of clinical symptoms or signs, electromyography, quantitative sensory tests, and cardiac autonomic neuropathy tests. The severity of the neuropathy was staged by composite scores. Serum NSE was measured using electrochemiluminescence immunoassay. The demographic and clinical variables were obtained through an interviewer questionnaire. RESULTS Serum NSE levels increased slightly in diabetic subjects compared with normal subjects (9.1 [1.5] vs. 8.7 [1.7], P = 0.037), and the levels increased greatly in diabetic subjects with neuropathy compared with those without (10.8 [2.8] vs. 9.1 [1.5], P = 0.000). The association of NSE with diabetic neuropathy was independent of the hyperglycemic state (fasting blood glucose, HbA1c, duration, and the type of diabetes) and other potential confounders affecting NSE levels (e.g., age, sex, and renal status) (odds ratio 1.48 [1.13–1.74], P = 0.001). In addition, NSE levels increased with and were closely correlated to the stages of neuropathy (r = 0.63 [0.52–0.74], P = 0.000). The optimal cutoff point for serum NSE levels to distinguish patients with diabetic neuropathy from those without was 10.10 ?g/L, with a sensitivity of 66.3% and a specificity of 72.5%. CONCLUSIONS Serum NSE levels are closely associated with peripheral neuropathy in patients with diabetes. Future studies are warranted to clarify the relationship. PMID:23846809

Li, Jianbo; Zhang, Hongman; Xie, Min; Yan, Lingfei; Chen, Jiawei; Wang, Hongxing

2013-01-01

297

Trigeminal small-fiber sensory neuropathy causes burning mouth syndrome  

Microsoft Academic Search

Burning mouth syndrome is a common disorder that frequently affects women in the 5th–7th decade. It is characterized by persisting painful symptoms mainly involving the anterior two-thirds of the tongue. For several years it has been attributed to psychological causes. We investigated the innervation of the epithelium of the tongue to assess whether damage of peripheral nerve fibers underlies the

Giuseppe Lauria; Alessandra Majorana; Monica Borgna; Raffaella Lombardi; Paola Penza; Alessandro Padovani; Pierluigi Sapelli

2005-01-01

298

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.

299

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.

300

Giant axonal neuropathy: clinical and genetic study in six cases  

PubMed Central

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

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

2005-01-01

301

Effect of Atibalamula and Bhumyamalaki on thirty-three patients of diabetic neuropathy.  

PubMed

Diabetic neuropathy is a relatively early and common complication affecting approximately 30% of diabetic patients. According to Ayurvedic principles there is involvement of Vata and Pitta Dosa in diabetic neuropathy. Bhumyamalaki (Phyllanthus niruri) is a plant which shows possibility to pacify these two Dosas. Another plant Atibala (Abutilon indicum) has also Vata pacifying qualities. Present study has been carried out to study the effects of Bhumyamalaki and Atibala on 33 patients of diabetic neuropathy. All the patients have been given Bhumyamalaki Churna 3 g twice a day and decoction of 10 g of Atibala-mula twice a day for 30 days. Neuropathy analyzer machine has been used for exact recording of sensory perception of vibration, cold and hot sensations before and after treatment. Changes in numbness, tingling, burning sensation and pain in lower limbs have also been assessed before and after treatment. Results have been analyzed statistically by applying the 't' test. It can be stated from the results that use of Bhumyamalaki and Atibalamula in the patients of diabetic neuropathy can revert the diminished sensory perception and can reduce the symptoms significantly. PMID:22529650

Patel, Kalapi; Patel, Manish; Gupta, S N

2011-07-01

302

Effect of Atibalamula and Bhumyamalaki on thirty-three patients of diabetic neuropathy  

PubMed Central

Diabetic neuropathy is a relatively early and common complication affecting approximately 30% of diabetic patients. According to Ayurvedic principles there is involvement of Vata and Pitta Dosa in diabetic neuropathy. Bhumyamalaki (Phyllanthus niruri) is a plant which shows possibility to pacify these two Dosas. Another plant Atibala (Abutilon indicum) has also Vata pacifying qualities. Present study has been carried out to study the effects of Bhumyamalaki and Atibala on 33 patients of diabetic neuropathy. All the patients have been given Bhumyamalaki Churna 3 g twice a day and decoction of 10 g of Atibala-mula twice a day for 30 days. Neuropathy analyzer machine has been used for exact recording of sensory perception of vibration, cold and hot sensations before and after treatment. Changes in numbness, tingling, burning sensation and pain in lower limbs have also been assessed before and after treatment. Results have been analyzed statistically by applying the ‘t’ test. It can be stated from the results that use of Bhumyamalaki and Atibalamula in the patients of diabetic neuropathy can revert the diminished sensory perception and can reduce the symptoms significantly. PMID:22529650

Patel, Kalapi; Patel, Manish; Gupta, S N

2011-01-01

303

Hereditary ataxias: overview.  

PubMed

The hereditary ataxias are a highly heterogeneous group of disorders phenotypically characterized by gait ataxia, incoordination of eye movements, speech, and hand movements, and usually associated with atrophy of the cerebellum. There are more than 35 autosomal dominant types frequently termed spinocerebellar ataxia and typically having adult onset. The most common subtypes are spinocerebellar ataxia 1, 2, 3, 6, and 7, all of which are nucleotide repeat expansion disorders. Autosomal recessive ataxias usually have onset in childhood; the most common subtypes are -Friedreich, ataxia-telangiectasia, ataxia with oculomotor apraxia type 1, and ataxia with oculomotor apraxia type 2. Four autosomal recessive types have dietary or biochemical treatment modalities (ataxia with vitamin E deficiency, cerebrotendinous xanthomatosis, Refsum, and coenzyme Q10 deficiency), whereas there are no specific treatments for other ataxias. Diagnostic genetic testing is complicated because of the large number of relatively uncommon subtypes with extensive phenotypic overlap. However, the best testing strategy is based on assessing relative frequencies, ethnic predilections, and recognition of associated phenotypic features such as seizures, visual loss, or associated movement abnormalities. PMID:23538602

Jayadev, Suman; Bird, Thomas D

2013-09-01

304

Mitochondrial optic neuropathies - Disease mechanisms and therapeutic strategies  

PubMed Central

Leber hereditary optic neuropathy (LHON) and autosomal-dominant optic atrophy (DOA) are the two most common inherited optic neuropathies in the general population. Both disorders share striking pathological similarities, marked by the selective loss of retinal ganglion cells (RGCs) and the early involvement of the papillomacular bundle. Three mitochondrial DNA (mtDNA) point mutations; m.3460G>A, m.11778G>A, and m.14484T>C account for over 90% of LHON cases, and in DOA, the majority of affected families harbour mutations in the OPA1 gene, which codes for a mitochondrial inner membrane protein. Optic nerve degeneration in LHON and DOA is therefore due to disturbed mitochondrial function and a predominantly complex I respiratory chain defect has been identified using both in vitro and in vivo biochemical assays. However, the trigger for RGC loss is much more complex than a simple bioenergetic crisis and other important disease mechanisms have emerged relating to mitochondrial network dynamics, mtDNA maintenance, axonal transport, and the involvement of the cytoskeleton in maintaining a differential mitochondrial gradient at sites such as the lamina cribosa. The downstream consequences of these mitochondrial disturbances are likely to be influenced by the local cellular milieu. The vulnerability of RGCs in LHON and DOA could derive not only from tissue-specific, genetically-determined biological factors, but also from an increased susceptibility to exogenous influences such as light exposure, smoking, and pharmacological agents with putative mitochondrial toxic effects. Our concept of inherited mitochondrial optic neuropathies has evolved over the past decade, with the observation that patients with LHON and DOA can manifest a much broader phenotypic spectrum than pure optic nerve involvement. Interestingly, these phenotypes are sometimes clinically indistinguishable from other neurodegenerative disorders such as Charcot-Marie-Tooth disease, hereditary spastic paraplegia, and multiple sclerosis, where mitochondrial dysfunction is also thought to be an important pathophysiological player. A number of vertebrate and invertebrate disease models has recently been established to circumvent the lack of human tissues, and these have already provided considerable insight by allowing direct RGC experimentation. The ultimate goal is to translate these research advances into clinical practice and new treatment strategies are currently being investigated to improve the visual prognosis for patients with mitochondrial optic neuropathies. PMID:21112411

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

2011-01-01

305

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

306

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

PubMed

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

307

A novel NGF mutation clarifies the molecular mechanism and extends the phenotypic spectrum of the HSAN5 neuropathy  

PubMed Central

Background Nerve growth factor ? (NGF?) and tyrosine kinase receptor type A (TRKA) are a well studied neurotrophin/receptor duo involved in neuronal survival and differentiation. The only previously reported hereditary sensory neuropathy caused by an NGF mutation, c.661C>T (HSAN5), and the pathology caused by biallelic mutations in the TRKA gene (NTRK1) (HSAN4), share only some clinical features. A consanguineous Arab family, where five of the six children were completely unable to perceive pain, were mentally retarded, did not sweat, could not discriminate temperature, and had a chronic immunodeficiency, is reported here. The condition is linked to a new homozygous mutation in the NGF gene, c.[680C>A]+[681_682delGG]. Methods Genetic linkage and standard sequencing techniques were used to identify the causative gene. Using wild-type or mutant over-expression constructs transfected into PC12 and COS-7 cells, the cellular and molecular consequences of the mutations were investigated. Results The mutant gene produced a precursor protein V232fs that was unable to differentiate PC12 cells. V232fs was not secreted from cells as mature NGF?. Conclusions Both the clinical and cellular data suggest that the c.[680C>A]+[681_682delGG] NGF mutation is a functional null. The HSAN5 phenotype is extended to encompass HSAN4-like characteristics. It is concluded that the HSAN4 and HSAN5 phenotypes are parts of a phenotypic spectrum caused by changes in the NGF/TRKA signalling pathway. PMID:20978020

Carvalho, Ofelia P; Thornton, Gemma K; Hertecant, Joseph; Houlden, Henry; Nicholas, Adeline K; Cox, James J; Rielly, Mary; Al-Gazali, Lihadh

2010-01-01

308

[Hereditary prostate cancer].  

PubMed

Prostate cancer (PC) is one of the most common cancers affecting men. It may soon become the main cancer--caused mortality among men all over the world. The genetic basis of prostate cancer is very complex and its etiology is poorly understood. The genes associated with hereditary predisposition to prostate cancer remain largely unknown. Family history of PC, particularly at a young age, is a strong risk factor. Through linkage analysis, numerous prostate cancer susceptibility chromosomal loci have been identified, including: HPC1 (1q24-25), PCaP (1q42.2-43), HPCX (Xq27-28), CAPB (1p36), HPC2 (17p12), HPC20 (20q13). However, it turned out that any of these genes is not a high-risk prostate cancer susceptibility gene. According to literature data HPC is associated with genes involved in androgen metabolism, including androgen receptor gene--AR, SRD5A2 and CYP17, genes involved in the DNA damage repair, including BRCA1, BRCA2, NBS1 and MLH1 or some developmental genes as HOXB13. Identification of PC high predisposition susceptibility genes is very important, because the ascertainment of a higher risk of prostate cancer development in mutation carriers enable to develop and implement in clinical practice suitable prophylactic programs which could prevent the disease or detect it in an early stage. It seems that better knowledge of the molecular pathology of prostate cancer could make it easier to discover new drugs of chemopreventive and chemotherapeutic activity. There are many cellular pathways associated with PC cancerogenesis, which may become a potential goal for such drugs in the future. PMID:24864115

Heise, Marta; Haus, Olga

2014-01-01

309

[Hereditary syndromes of neuroendocrine tumours].  

PubMed

Diffuse localised neuroendocrinal cells represent the largest population of endocrinally active cells and can degenerate to malignant neuroendocrine tumours (NET). In this review the most important hereditary syndromes that predispose for endocrine and neuroendocrine tumours are presented and discussed. NET occur mainly as sporadic tumours. Current investigations on the pathogenesis of sporadic neuroendocrine tumours have revealed a close relationship between hereditary and sporadic neuroendocrine tumours. In the course of hereditary syndromes, such as multiple endocrine neoplasia, endocrine and neuroendocrine tumours as well as non-endocrine neoplasias can occur. In order to recognise these syndromes in good time a knowledge of the predisposing syndromes and their cardinal symptoms is essential. In this way not only individualised diagnosis and therapy can be planned but also an appropriate early management of first degree relatives can be initiated. PMID:24327486

Kaemmerer, D; Posorski, N; Hommann, M; Baum, R P; Hörsch, D

2014-08-01

310

Genetics Home Reference: Hereditary antithrombin deficiency  

MedlinePLUS

... that promote blood clotting, especially a protein called thrombin. Most of the mutations that cause hereditary antithrombin ... gene ; hereditary ; inherited ; protein ; pulmonary ; pulmonary embolism ; surgery ; thrombin ; thrombosis ; veins You may find definitions for these ...

311

Mixed or immune complex cryoglobulinaemia and neuropathy  

PubMed Central

Three patients with peripheral neuropathy and mixed or immune complex cryoglobulinaemia are reported. The significance of mixed cryoglobulinaemia and the pathogenesis of the peripheral neuropathy are discussed. Images PMID:4360402

Cream, J. J.; Hern, J. E. C.; Hughes, R. A. C.; Mackenzie, I. C. K.

1974-01-01

312

Update on medication-induced peripheral neuropathy  

Microsoft Academic Search

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

Louis H. Weimer; Noor Sachdev

2009-01-01

313

Peripheral neuropathy in mitochondrial disorders.  

PubMed

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

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

2013-10-01

314

Mechanically-evoked C-fiber activity in painful alcohol and AIDS therapy neuropathy in the rat  

Microsoft Academic Search

While altered activities in sensory neurons were noticed in neuropathic pain, caused by highly diverse insults to the peripheral nervous system, such as diabetes, alcohol ingestion, cancer chemotherapy and drugs used to treat AIDS, other infections and autoimmune diseases, as well as trauma, our understanding of how these various peripheral neuropathies manifest as altered neuronal activity is still rudimentary. The

Xiaojie Chen; Jon D Levine

2007-01-01

315

Alpha-lipoic acid: Antioxidant potency against lipid peroxidation of neural tissues in vitro and implications for diabetic neuropathy  

Microsoft Academic Search

Nerve lipid peroxidation is increased in experimental diabetic neuropathy, and ?-lipoic acid will prevent the deficits in nerve blood flow, oxidative stress, and distal sensory conduction. Because these alterations can occur by mechanisms other than augmenting lipid peroxidation in vivo, and because both pro-oxidant and antioxidant effects of the agent have been reported, we undertook studies of in vitro lipid

Kim K. Nickander; Benjamin R. Mcphee; Phillip A. Low; Hans Tritschler

1996-01-01

316

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

317

Treatment of oxaliplatin-induced peripheral neuropathy by intravenous mangafodipir  

PubMed Central

Background. The majority of patients receiving the platinum-based chemotherapy drug oxaliplatin develop peripheral neurotoxicity. Because this neurotoxicity involves ROS production, we investigated the efficacy of mangafodipir, a molecule that has antioxidant properties and is approved for use as an MRI contrast enhancer. Methods. The effects of mangafodipir were examined in mice following treatment with oxaliplatin. Neurotoxicity, axon myelination, and advanced oxidized protein products (AOPPs) were monitored. In addition, we enrolled 23 cancer patients with grade ?2 oxaliplatin-induced neuropathy in a phase II study, with 22 patients receiving i.v. mangafodipir following oxaliplatin. Neuropathic effects were monitored for up to 8 cycles of oxaliplatin and mangafodipir. Results. Mangafodipir prevented motor and sensory dysfunction and demyelinating lesion formation. In mice, serum AOPPs decreased after 4 weeks of mangafodipir treatment. In 77% of patients treated with oxaliplatin and mangafodipir, neuropathy improved or stabilized after 4 cycles. After 8 cycles, neurotoxicity was downgraded to grade ?2 in 6 of 7 patients. Prior to enrollment, patients received an average of 880 ± 239 mg/m2 oxaliplatin. Patients treated with mangafodipir tolerated an additional dose of 458 ± 207 mg/m2 oxaliplatin despite preexisting neuropathy. Mangafodipir responders managed a cumulative dose of 1,426 ± 204 mg/m2 oxaliplatin. Serum AOPPs were lower in responders compared with those in nonresponders. Conclusion. Our study suggests that mangafodipir can prevent and/or relieve oxaliplatin-induced neuropathy in cancer patients. Trial registration. Clinicaltrials.gov NCT00727922. Funding. Université Paris Descartes, Ministère de la Recherche et de l’Enseignement Supérieur, and Assistance Publique-Hôpitaux de Paris. PMID:24355920

Coriat, Romain; Alexandre, Jerome; Nicco, Carole; Quinquis, Laurent; Benoit, Evelyne; Chereau, Christiane; Lemarechal, Herve; Mir, Olivier; Borderie, Didier; Treluyer, Jean-Marc; Weill, Bernard; Coste, Joel; Goldwasser, Francois; Batteux, Frederic

2013-01-01

318

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

319

Pelvic floor neuropathy: a comparative study of diabetes mellitus and idiopathic faecal incontinence.  

PubMed

Twenty one patients with diabetic peripheral neuropathy, 18 with idiopathic faecal incontinence and 11 normal controls were studied with techniques of mucosal electrosensitivity, rectal distension for the quantitative assessment of anorectal sensation, and manometric and electromyographic tests for the assessment of anorectal motor function. An asymptomatic sensorimotor deficit was found in the anal canal of patients with diabetic peripheral neuropathy. Mucosal electrosensitivity thresholds in the anal canal were significantly higher (p less than 0.01 v controls) and fibre density of the external anal sphincter significantly raised (p less than 0.0001 v controls). Anal manometry and pudendal nerve terminal motor latencies were similar to controls. In patients with idiopathic faecal incontinence the tests of sensory and motor function also showed a sensorimotor neuropathy; compared with controls, mucosal electrosensitivity thresholds were significantly higher (p less than 0.002), anal canal resting and maximum squeeze pressures were significantly lower (p less than 0.05 and p less than 0.002 respectively), and pudendal nerve terminal motor latencies and fibre density of the external anal sphincter were significantly raised (both p less than 0.05). Sensory thresholds to rectal distension were similar in all groups. Pelvic floor sensorimotor neuropathy in diabetic patients has several features in common with that of patients with idiopathic faecal incontinence but its functional significance remains uncertain. PMID:3384360

Rogers, J; Levy, D M; Henry, M M; Misiewicz, J J

1988-06-01

320

Peripheral Neuropathy Following Chloroquine Therapy  

PubMed Central

Four patients were observed who developed similar episodes of peripheral neuropathy following prolonged treatment with chloroquine phosphate. This previously unreported toxic reaction consisted of bilateral loss of knee and ankle reflexes and weakness of the quadriceps muscles. Gradual return to normal followed withdrawal of the chloroquine. Other toxic reactions to the drug are reviewed. PMID:14052974

Loftus, Lawrence R.

1963-01-01

321

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.

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

2014-01-01

322

Screening for HIV-Associated Peripheral Neuropathy in Resource-Limited Settings  

PubMed Central

INTRODUCTION Peripheral neuropathy is the most common neurological complication of HIV but is widely under-diagnosed in resource-limited settings. We investigated the utility of screening tools administered by non-physician health care workers (HCW) and quantitative sensory testing (QST) administered by trained individuals for identification of moderate/severe neuropathy. METHODS We enrolled 240 HIV-infected outpatients using two-stage cluster randomized sampling. HCWs administered the several screening tools. Trained study staff performed QST. Tools were validated against a clinical diagnosis of neuropathy. RESULTS Participants were 65% women, mean age 36.4 years, median CD4 324 cells/?L. 65% were taking antiretrovirals, and 18% had moderate/severe neuropathy. The screening tests were 76% sensitive in diagnosing moderate/severe neuropathy with negative predictive values of 84–92%. QST was less sensitive but more specific. DISCUSSION Screening tests administered by HCW have excellent negative predictive values and are promising tools for scale-up in resource-limited settings. QST shows promise for research use. PMID:24037693

Cettomai, Deanna; Kwasa, Judith K.; Birbeck, Gretchen L.; Price, Richard W.; Cohen, Craig R.; Bukusi, Elizabeth A.; (OB/Gyn), MMed; Kendi, Caroline; Meyer, Ana-Claire L.

2014-01-01

323

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

324

Triglyceride, nonesterified fatty acids, and prediabetic neuropathy: role for oxidative-nitrosative stress.  

PubMed

Peripheral neuropathy develops in human subjects with prediabetes and metabolic syndrome before overt hyperglycemia. The contributions of impaired glucose tolerance and insulin signaling, hypertriglyceridemia and/or increased nonesterified fatty acids (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. Sixteen-week-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 mg kg(-1) day(-1), 4 weeks) reduced serum insulin, NEFA, and triglyceride concentrations without affecting glucose tolerance and hypercholesterolemia. It alleviated sensory nerve conduction velocity deficit and 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 a use in the management of this condition. PMID:22366714

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

2012-04-15

325

A modified peripheral neuropathy scale: the Overall Neuropathy Limitations Scale  

PubMed Central

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

Graham, R C; Hughes, R A C

2006-01-01

326

A novel Refsum-like disorder that maps to chromosome 20  

E-print Network

with signs of peripheral neuropathy (pes cavus, tendoachilles contracture). Hearing loss and cataract become motor and sensory neuropathy; IBD identical by descent; NARP neuropathy, ataxia, and retinitis pigmentosa; SCA7 spinocerebellar ataxia type 7. The hereditary neuropathies constitute a heterogeneous group

Majewski, Jacek

327

Management of hereditary angioedema in pediatric patients.  

PubMed

Hereditary angioneurotic edema is a rare disorder caused by the congenital deficiency of C1 inhibitor. Recurring angioedematous paroxysms that most commonly involve the subcutis (eg, extremities, face, trunk, and genitals) or the submucosa (eg, intestines and larynx) are the hallmarks of hereditary angioneurotic edema. Edema formation is related to reduction or dysfunction of C1 inhibitor, and conventional therapy with antihistamines and corticosteroids is ineffective. Manifestations occur during the initial 2 decades of life, but even today there is a long delay between the onset of initial symptoms and the diagnosis of hereditary angioneurotic edema. Although a variety of reviews have been published during the last 3 decades on the general management of hereditary angioneurotic edema, little has been published regarding management of pediatric hereditary angioneurotic edema. Thus, we review our experience and published data to provide an approach to hereditary angioneurotic edema in childhood. PMID:17724112

Farkas, Henriette; Varga, Lilian; Széplaki, Gábor; Visy, Beáta; Harmat, George; Bowen, Tom

2007-09-01

328

Pediatric neuropathic arthropathy initially masquerading as inflammatory arthritis.  

PubMed

We describe a case of neuropathic arthropathy in the knees of a child eventually diagnosed with a hereditary sensory and autonomic neuropathy. The child was initially treated for rheumatologic disease at an outside institution. History and neurological workup revealed a neuropathy most consistent with hereditary sensory and autonomic neuropathy type II. Hereditary sensory and autonomic neuropathy should be considered in the differential diagnosis of children with joint abnormalities whose workup for an inflammatory arthropathy is negative and who exhibit diminished pain sensation on examination. PMID:25275767

Zei, Markus G; Meyers, Arthur B; Vora, Sheetal

2014-10-01

329

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

330

Animal models of autoimmune neuropathy.  

PubMed

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

331

Rituximab in cryoglobulinemic peripheral neuropathy  

Microsoft Academic Search

Type II mixed cryoglobulinemia is sustained by an oligoclonal production of IgM sharing rheumatoid activity and can be associated\\u000a with renal, cutaneous, rheumatologic or neurological manifestations. Peripheral neuropathy is a major cause of morbidity in\\u000a hepatitis C virus-associated mixed cryoglobulinemia and is often refractory to any treatment. Rituximab induces a selective\\u000a depletion of IgM-producing B cells, and both case reports

Roberto Cavallo; Dario Roccatello; Elisa Menegatti; Carla Naretto; Franca Napoli; Simone Baldovino

2009-01-01

332

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

333

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; Jauregui-Renaud, Kathrine

2014-01-01

334

Novel systems for in vivo monitoring and microenvironmental investigations of diabetic neuropathy in a murine model.  

PubMed

Peripheral neuropathy is a devastating complication of diabetes conferring vast morbidity and mortality. Despite prolonged efforts to elucidate the mechanisms underlying diabetic related neuropathic phenomena and develop effective therapies, current treatment is for the most part glycemic control and symptomatic care. This is partially due to the intricate pathophysiology of diabetic neuropathy and the scarcity of valid experimental models. The aim of the study was to establish novel systems enabling monitoring and dissection of significant processes in the development of diabetic neuropathy. In a non-invasive in vivo model, two-photon microscopy is applied to evaluate mechanoreceptors (Meissner corpuscles) within an intact footpad of transgenic mice expressing a fluorescent neuronal tracer. By applying this advanced technology, which couples potent tissue penetration with superb resolution, we documented qualitative and quantitative diabetes-specific alterations in these sensory structures. Detection of such changes previously required laborious invasive histopathological techniques. In parallel, we present an ex vivo system that mimics the native microenvironment of the nerve ending via a unique co-culture of primary sensory neurons and thin skin slices. In conjunction with innovative high-throughput digital axonal measurements and computerized quantification tools, this method enables an unbiased exploration of neuronal autonomous and non-autonomous malfunctions. Using this setup we demonstrate that while the diabetic nerve retains a near-normal growth and regeneration capacities, the diabetic skin exhibits a decreased ability to support axonal outgrowth. Thus, an early target organ failure rather than intrinsic neuronal failure may initiate the neuropathy. Overall, the illustrated experimental platforms may greatly facilitate the holistic investigation of diabetic neuropathy. PMID:22592935

Amit, Sharon; Yaron, Avraham

2012-11-01

335

Genetics Home Reference: Hereditary leiomyomatosis and renal cell cancer  

MedlinePLUS

... providers. Gene Review: Hereditary Leiomyomatosis and Renal Cell Cancer Genetic Testing Registry: Hereditary leiomyomatosis and renal cell cancer MedlinePlus Encyclopedia: Renal Cell Carcinoma You might also ...

336

[New treatments of hereditary blindness].  

PubMed

Ongoing clinical trials are targeting several previously intractable hereditary causes of blindness of congenital, childhood or early adulthood onset, mainly in the optic nerve and retina. The intended stage of initiation of the new therapeutic approaches ranges from neonatal life and a structurally intact retinal tissue to adult life with a complete loss of photoreceptors. It must be assumed that some of the trials will succeed in producing new therapies and action must be taken to refine and accelerate diagnostics and to preserve therapeutic potential in blind people. PMID:23992912

Bertelsen, Mette; Rosenberg, Thomas; Larsen, Michael

2013-09-01

337

Nuclear matrix proteins and hereditary diseases  

Microsoft Academic Search

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

N. Sjakste; T. Sjakste

2005-01-01

338

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

PubMed Central

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

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

2014-01-01

339

Entrapment neuropathies in chronic stroke patients.  

PubMed

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

Hunkar, Remziye; Balci, Kemal

2012-02-01

340

Diagnosis and treatment in inflammatory neuropathies  

Microsoft Academic Search

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

M P T Lunn; H J Willison

2009-01-01

341

Medial arterial calcification and diabetic neuropathy  

Microsoft Academic Search

X-ray examinations of the feet, knees, and hands were performed on 20 diabetics with severe neuropathy and 20 diabetics with no evidence of neuropathy but with a similar mean age and duration of diabetes. All were under 53 years old with no clinical evidence of peripheral vascular disease. Medial arterial calcification was much more common and extensive in the patients

M E Edmonds; N Morrison; P J Watkins

1982-01-01

342

Gastric emptying in diabetic autonomic neuropathy  

Microsoft Academic Search

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

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

1977-01-01

343

Blood flow patterns in painful diabetic neuropathy  

Microsoft Academic Search

Summary  Peripheral blood flow is known to be qualitatively increased in diabetic patients with neuropathy. We have measured the actual blood flow in the feet of diabetic patients with neuropathy using non-invasive mercury strain gauge plethysmography and Doppler sonogram techniques and shown that it is increased on average five times above normal at an ambient temperature of 20 °–22 °C. Moreover,

A. G. Archer; V. C. Roberts; P. J. Watkins

1984-01-01

344

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

345

Giant axonal neuropathy: MRS findings.  

PubMed

Giant axonal neuropathy (GAN) is a rare genetic disease of childhood involving the central and peripheral nervous systems. Axonal loss with several giant axons filled with neurofilaments is the main histopathological feature of peripheral nerve biopsies in this disease. Routine neuroimaging studies reveal diffuse hyperintensities in cerebral and cerebellar white matter. In this case report, the authors present the brain magnetic resonance spectroscopic features (normal N-acetylaspartate/creatine and increased choline/creatine and myoinositol/creatine ratios), which might indicate the absence of neuroaxonal loss and the presence of significant demyelination and glial proliferation in white matter, of an 11-year-old boy diagnosed with GAN. PMID:14569833

Alkan, Alpay; Kutlu, Ramazan; Sigirci, Ahmet; Baysal, Tamer; Altinok, Tayfun; Yakinci, Cengiz

2003-10-01

346

Spinocerebellar Ataxia with Axonal Neuropathy  

Microsoft Academic Search

\\u000a \\u000a Spinocerebellar ataxia with axonal neuropathy (SCAN1) is an autosomal recessive disorder caused by a specific point mutation\\u000a (c.1478A>G, p.H493R) in the tyrosyl-DNA phosphodiesterase (TDP1) gene. Functional and genetic studies suggest that this mutation, which disrupts the active site of the Tdp1 enzyme, causes\\u000a disease by a combination of decreased catalytic activity and stabilization of the normally transient covalent Tdp1-DNA intermediate.

Cheryl Walton; Heidrun Interthal; Ryuki Hirano; Mustafa A. M. Salih; Hiroshi Takashima; Cornelius F. Boerkoel

347

A variant of multifocal motor neuropathy with acute, generalised presentation and persistent conduction blocks  

PubMed Central

Objective:Multifocal motor neuropathy with persistent conduction blocks is classically described as a chronic neuropathy with progressive onset, and acute forms have not previously been characterised. We report four cases of severe motor impairment with acute and generalised onset and with persistent motor conduction blocks. Patients and results:An acute tetraparesis with diffuse areflexia but little or no sensory disturbance was the clinical picture. Serial electrophysiological tests showed persistent multifocal motor conduction blocks with absent F waves in most tested motor nerves. No or minor abnormalities of the sensory nerve action potentials were observed. Cerebrospinal fluid contained normal or mildly increased protein levels (<1 g/l) without cells. Campylobacter jejuni serology was negative in three patients and consistent with past infection in one patient. Anti-ganglioside antibodies were positive in three patients. A five day course of intravenous immunoglobulins produced nearly complete symptom resolution in three patients and was ineffective in one patient. Conclusion:Because of the persistence of multifocal motor conduction blocks for several weeks or months as the isolated electrophysiological feature, these cases could not be consistent with Guillain–Barré syndrome or chronic inflammatory demyelinating polyneuropathy. They suggest an original variant of multifocal motor neuropathy with an acute and generalised initial presentation and persistent motor conduction blocks affecting all four limbs. PMID:14617715

Lefaucheur, J; Gregson, N; Gray, I; von Raison, F; Bertocchi, M; Creange, A

2003-01-01

348

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

349

[Hereditary angioedema. A therapeutic guide].  

PubMed

Hereditary angioedema (HAE) is a rare autosomal dominant disease, characterized by episodes of edema involving the skin, gastrointestinal tract and larynx. HAE has a historical asphyxia mortality of 15% to 50%. It is the consequence of functional C1 inhibitor deficiency. The identification of bradykinin as the principal mediator of the disease has lead to the development of new drugs for its treatment. HAE management and treatment are agreed by international consensus decision. A therapeutic guide for the treatment of the disease is important to improve diagnosis and treatment. We here describe the pharmacology of drugs available for the treatment of HAE in Argentina: plasma derived C1 Inhibitor, the bradykinin antagonist: icatibant, the attenuated androgen danazol and the anti-fibrinolytic agents epsilonaminocaproic acid and tranexamic acid. Furthermore, we describe drug use and adverse effects control, as well as the last international consensus document recommendations applicable to Argentina to conform a first guide to HAE treatment in our country. PMID:22522852

Malbrán, Alejandro; Fernández Romero, Diego S; Menéndez, Alejandra

2012-01-01

350

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

351

Mitochondrial stress and the pathogenesis of diabetic neuropathy  

PubMed Central

Diabetic neuropathy is a major complication of diabetes that affects the sensory and autonomic nervous systems and leads to significant morbidity and impact on quality of life of patients. Mitochondrial stress has been proposed as a major mediator of neurodegeneration in diabetes. This review briefly summarizes the nature of sensory and autonomic nerve dysfunction and presents these findings in the context of diabetes-induced nerve degeneration mediated by alterations in mitochondrial ultrastructure, physiology and trafficking. Diabetes-induced dysfunction in calcium homeostasis is discussed at length and causative associations with sub-optimal mitochondrial physiology are developed. It is clear that across a range of complications of diabetes that mitochondrial physiology is impaired, in general a reduction in electron transport chain capability is apparent. This abnormal activity may predispose mitochondria to generate elevated reactive oxygen species (ROS), although experimental proof remains lacking, but more importantly will deleteriously alter the bioenergetic status of neurons. It is proposed that the next five years of research should focus on identifying changes in mitochondrial phenotype and associated cellular impact, identifying sources of ROS in neurons and analyzing mitochondrial trafficking under diabetic conditions. PMID:20729997

Fernyhough, Paul; Roy Chowdhury, Subir K.; Schmidt, Robert E.

2010-01-01

352

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) ...

353

Genetics Home Reference: Hereditary folate malabsorption  

MedlinePLUS

... the production of DNA and its chemical cousin, RNA. Infants with hereditary folate malabsorption are born with ... anemia ; microvilli ; neurological ; platelets ; prevalence ; protein ; proton ; recessive ; RNA ; susceptibility ; thrombocytopenia ; vitamins ; white blood cells You may ...

354

Linezolid-induced optic neuropathy.  

PubMed

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

Karuppannasamy, Divya; Raghuram, Andavar; Sundar, Devisundaram

2014-04-01

355

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

356

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

357

Domination in distance-hereditary graphs  

Microsoft Academic Search

The domination problem and its variants have been extensively studied in the literature. In this paper we investigate the domination problem in distance-hereditary graphs. In particular, we give a linear-time algorithm for the domination problem in distance-hereditary graphs by a labeling approach. We actually solve a more general problem,called the L-domination problem, which also includes the total domination problem as

Maw-shang Chang; Shaur-ching Wu; Gerard J. Chang; Hong-gwa Yeh

2002-01-01

358

Pegylated Interferon Alpha-Associated Optic Neuropathy  

PubMed Central

A 52-year-old man with chronic hepatitis C presented with painless, bilateral, simultaneous non-arteritic anterior ischemic optic neuropathy (NAION) and peripheral neuropathy. Symptoms began 19 weeks after starting peginterferon alpha-2a. The peripheral neuropathy and vision of the right eye improved, but the vision of the left eye worsened after stopping interferon. We identified 23 additional cases of NAION during interferon alpha therapy. At least 12 of these patients suffered bilateral NAION. Patients lost vision 1–40 weeks after initiating therapy. Of 21 eyes that had documented initial and follow-up acuities, 8 improved, 1 worsened, and the rest remained stable. One patient had a painful peripheral neuropathy. Treatment with interferon alpha may result in NAION. Discontinuation of therapy deserves consideration after weighing individual risks and benefits. PMID:20351572

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

2013-01-01

359

Current and future treatment of amyloid neuropathies.  

PubMed

Amyloid neuropathies of acquired or genetic origin are disabling and life-threatening, until recently there were few treatment options available. Poor prognosis is related to progressive neuropathy and associated, although often underdiagnosed, cardiac involvement in specific transthyretin (TTR) gene mutations. Recent progress has modified prognosis and management of amyloid neuropathies. In TTR-familial amyloidosis with polyneuropathy, major changes have occurred over the last 30 years: better knowledge concerning genetics, phenotypes and epidemiology, and the advent of possible treatments. Liver transplantation, first performed in 1990, stopped disease progression, thus doubling survival in early onset V30M patients. More recently tetramer stabilizers (Tafamidis and Diflunisal) showed a significant reduction of progression of neuropathic scores; Tafamidis is now recommended in Stage I patients. Two multicentric clinical trials are now ongoing to evaluate TTR gene silencing by antisense Oligonucleotides (ASO) or siRNA. In the near future we should have new therapeutical options for patients with amyloid neuropathy. PMID:25416603

Adams, David; Cauquil, Cecile; Theaudin, Marie; Rousseau, Antoine; Algalarrondo, Vincent; Slama, Michel S

2014-12-01

360

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

361

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

362

Sudoscan, a Noninvasive Tool for Detecting Diabetic Small Fiber Neuropathy and Autonomic Dysfunction  

PubMed Central

Abstract Objective Sudomotor dysfunction may be an early detectable abnormality in diabetic small fiber neuropathy. The aim of this study was to evaluate the efficacy of Sudoscan™ (Impeto Medical, Paris, France) in detecting diabetic neuropathy (DN), in comparison with other standardized tests, in patients with diabetes mellitus (DM). Subjects and Methods Sudoscan measures electrochemical skin conductance (ESC) of hands and feet through reverse iontophoresis. We evaluated 83 DM patients with and without DN and 210 healthy controls (HCs). Neuropathy Impairment Score—Lower Legs (NIS-LL), quantitative autonomic function testing (QAFT), and quantitative sensory testing (QST) were performed. Symptomatic pain was recorded using a visual analog scale. Receiver-operator characteristic (ROC) curves were calculated to evaluate the efficacy of Sudoscan in detecting DN compared with traditional modalities. Results Diabetes patients with DN had significantly worse ESCs of feet and hands than DM patients without DN and HCs (respectively, 56.3±3 vs. 75.9±5.5 and 84.4±0.9 [P<0.0001] for feet and 51.9±2.4 vs. 67.5±4.3 and 73.1±0.8 [P<0.0001] for hands). Increasing NIS-LL scores were associated with decreasing ESC values. ESCs correlated significantly with clinical (NIS-LL), somatic (QST), and autonomic (QAFT) measures of neuropathy and with pain scores. ROC curve analysis showed significant results for both hands and feet ESC (area under the curve of 0.86 and 0.88, respectively; P<0.0001) with sensitivity of 78% and specificity of 92% for feet to detect DN. Conclusions Sudoscan is a promising, sensitive tool to detect neuropathy in patients with DM. This is a very simple, easy-to-perform test that can be done in the clinical setting in 3–5?min. PMID:23889506

Casellini, Carolina M.; Parson, Henri K.; Richardson, Margaret S.; Nevoret, Marie L.

2013-01-01

363

Modulation of Nociception in Painful Diabetic Neuropathy  

E-print Network

to alleviate symptoms of painful diabetic neuropathy [45]. Repeated application of 0.05-0.075% capsaicin cream, which effectively depletes the pain-inducing neuropeptide substance P, along with other pro-nociceptive molecules, from cutaneous peripheral nerve... endings has mixed outcomes. Recently, use of a single high-dose (8%) capsaicin patch has shown promising results in post-herpetic neuralgia (PHN) and human immunodeficiency virus (HIV)-induced neuropathy [33, 34, 41, 46, 47]. Topical lidocaine...

Katz, Natalie

2014-05-31

364

[Visceral diabetic neuropathy of the urogenital tract].  

PubMed

The article deals with issues of diabetic autonomous neuropathy (DAN) in the urogenital tract (UGT), and brings attention to the ethiopathogenesis of diabetic polyneuropathy. It provides a synopsis of autonomous neuropathy and deals, in more detail, with its manifestations in the UGT. The different symptoms of the disorder are addressed, the need for timely diagnosis is pointed out as the prerequisite for a successful therapy, and the necessity for interdisciplinary cooperation in dealing with this health issue is exposed. PMID:18630632

Olsovský, J

2008-05-01

365

Optic neuropathy following retrobulbar injection: a review.  

PubMed

Abstract A retrobulbar block is a regional anesthetic nerve block in the retrobulbar space. Optic neuropathy following retrobulbar injection is a well-recognized and rare complication of the procedure with an unknown incidence. This article reviews the relevant literature regarding vision loss following this procedure. Mechanisms of injury to the optic nerve as well as methods that can be employed to minimize the risk of optic neuropathy will be explored, including alternatives to retrobulbar anesthesia. PMID:25325871

Gross, Andrew; Cestari, Dean M

2014-11-01

366

Peripheral neuropathy: clinical and electrophysiological considerations.  

PubMed

This article is a primer on the pathophysiology and clinical evaluation of peripheral neuropathy for the radiologist. Magnetic resonance neurography 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 magnetic resonance neurography may play an increasingly important role in the evaluation of patients with peripheral neuropathy. PMID:24210312

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

2014-02-01

367

Combined sensory and motor deficit in primary neuropathic faecal incontinence.  

PubMed

Eleven patients with idiopathic faecal incontinence (IFI) and nine normal controls were studied with techniques of mucosal electrosensitivity and rectal distention for the quantitative assessment of anal and rectal sensation and with manometric and electromyographic tests for the assessment of anorectal motor function. The tests of motor function showed pelvic floor motor neuropathy in the patients with IFI, compared with controls, anal canal resting and voluntary contraction pressures were significantly (p less than 0.05, p less than 0.002) lower, pudendal nerve terminal motor latency and external anal sphincter fibre density were significantly (p less than 0.05, p less than 0.05) raised. The results of mucosal electrosensitivity (MES) disclosed a sensory deficit in the anal canal in patients with IFI, compared with controls, MES threshold was significantly (p less than 0.002) higher. Sensory thresholds to rectal distension were similar in the two groups. This study shows that sensory deficit of the anal canal occurs in combination with the motor neuropathy of the anal canal musculature in primary neuropathic faecal incontinence. PMID:3343013

Rogers, J; Henry, M M; Misiewicz, J J

1988-01-01

368

The pathophysiology of hereditary angioedema.  

PubMed

Hereditary angioedema (HAE) causes recurrent episodes of angioedema that may be very severe and are frequently associated with significant morbidity and even mortality. Understanding the pathophysiology of this disease is crucial for proper diagnosis and management of these patients. HAE is caused by mutations in the SERPING1 gene that result in decreased plasma levels of functional C1 inhibitor. A large number of different mutations have been described that result in HAE. About 15% of patients have a mutation at or near the active site of the reactive mobile loop, resulting in a protein that lacks functional activity (type II HAE). Type I HAE is caused by a diverse range of mutations, some of which cause the nascent protein to misfold and thus to be unable to enter the secretory pathway. The primary mediator of swelling in HAE is bradykinin, a product of the plasma contact system. Bradykinin induces increased vascular permeability by activating the bradykinin B2 receptor, which results in phosphorylation of vascular endothelial cadherin. The regulation of both the bradykinin B2 receptor and peptidases that degrade bradykinin may influence HAE disease severity. HAE results from mutations in the SERPING1 gene that lead to a loss of functional C1 inhibitor. Attacks of angioedema result from generation of bradykinin, which acts on bradykinin B2 receptors to enhance vascular permeability. PMID:23282866

Zuraw, Bruce L

2010-09-01

369

[Hereditary Sipple syndrome (author's transl)].  

PubMed

This entity, isolated by Gorlin, is characterized by the presence of cutaneous and mucous neuromas, facial disfiguration resembling acromegalia as well as morphological changes to the extremities similar to those produced by Marfan's disease. These factors are also associated with multiple endocrinological neoplasms type II of Sipple's syndrome. In other words, malignant tumors developing from thyroid "C" cells as well as from bilateral benign pheochromocytoma (neoplasias which derive from the A.P.U.D. system). It is considered to be hereditary in nature and transmitted as a dominant trait. Its evolution is triphasic, and the prognosis is extremely dismal. There may exist incomplete or benign forms, in the course of which the endocrinological neoplasms may appear very late or not at all. Generally, the diagnosis is easy. This entity can be calssified with other diseases stemming from the neural ridge, in other words "neurocristopathies" but in spite of these similarities with disease of the same embryological origin, it would seem that this particular entity is genetically autonomous. The only effective treatment is surgical, for thyroid neoplasms, as well as neoplasms occurring in the medullo-adrenal glands. It should be noted that this line of treatment must be undertaken with the utmost precaution. PMID:869445

Bazex, A; Boulard, C; Delsol, G; Bazex, J; Louvet, J L

1977-02-01

370

Sensory Conversion Devices  

NASA Astrophysics Data System (ADS)

The human body has five basic sensory functions: touch, vision, hearing, taste, and smell. The effectiveness of one or more of these human sensory functions can be impaired as a result of trauma, congenital defects, or the normal ageing process. Converting one type of function into another, or translating a function to a different part of the body, could result in a better quality of life for a person with diminished sensorial capabilities.

Medelius, Pedro

371

An autosomal recessive cerebellar ataxia syndrome with upward gaze palsy, neuropathy, and seizures.  

PubMed

The authors describe three siblings born to consanguineous parents with early onset ataxia, dysarthria, myoclonic, generalized tonic clonic seizures, upward gaze palsy, extensor plantar reflexes, sensory neuropathy, and normal cognition. Direct screening excluded mutations in FRDA, TDP1,and SACS genes and at 8344, 3243, and 8993 positions of mitochondrial DNA. Linkage analysis excluded AOA-1, EPM1, EPM2A, EPM2B, CAMOS, and recessive ataxias linked to chromosome 9q34-9qter. This clinical constellation may represent a distinct form of early onset cerebellar ataxia. PMID:15642921

Straussberg, R; Basel-Vanagaite, L; Kivity, S; Dabby, R; Cirak, S; Nurnberg, P; Voit, T; Mahajnah, M; Inbar, D; Saifi, G M; Lupski, J R; Delague, V; Megarbane, A; Richter, A; Leshinsky, E; Berkovic, S F

2005-01-11

372

Pure sensory Guillain-Barr? syndrome: A case report and review of the literature  

PubMed Central

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.

YANG, JINGJING; HUAN, MINGMING; JIANG, HUAJUN; SONG, CHUNLI; ZHONG, LIN; LIANG, ZHANHUA

2014-01-01

373

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

374

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

375

The co-occurrence of myocardial dysfunction and peripheral insensate neuropathy in a streptozotocin-induced rat model of diabetes  

PubMed Central

Background Cardiomyopathy and distal symmetrical polyneuropathy (DSPN), including sensory and autonomic dysfunction, often co-occur in diabetic mellitus (DM) patients. However, the temporal relationship and progression between these two complications has not been investigated. Using a streptozotocin DM animal model that develops insensate neuropathy, our aim was to examine in parallel the development of DSPN and DM-associated changes in cardiac structure and function as well as potential mechanisms, such as autonomic dysfunction, evaluated by changes in urinary and myocardial norepinephrine content and myocardial neuronal markers. Methods Sensory neuropathy was measured by behavioral tests using Von Frey filaments and Hargreaves methods. Echocardiography was used to evaluate myocardial structure and function. Autonomic function was evaluated by measuring urinary and myocardial norepinephrine (NE) levels by enzyme-linked immunosorbent assay and high-performance liquid chromatography/mass spectrometry. Quantitative immunohistochemistry was used to measure the myocardial neuronal markers, calcitonin gene-related peptide (CGRP) and general neuronal protein gene product 9.5 (PGP 9.5). Results The DM group developed tactile and thermal insensate neuropathy 4–5 weeks after DM onset. Cardiovascular changes were found between 4 and 12 weeks after DM onset and included bradycardia, diastolic and systolic dysfunction and cardiac dilation. There was a 2.5-fold reduction in myocardial NE levels and a 5-fold increase in urinary NE levels in the DM group. Finally, there was a 2.3-fold increase in myocardial CGRP levels in the DM group and no change in PGP9.5 levels. Conclusions Cardiovascular structural and functional changes developed early in the course of DM and in combination with insensate neuropathy. In parallel, signs of cardiac autonomic dysfunction were also found and included decreased myocardial NE levels and altered CGRP levels. These results may indicate the need for early cardiovascular evaluation in DM patients with insensate neuropathy. PMID:24410801

2014-01-01

376

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

PubMed Central

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

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

2012-01-01

377

[Sensory Systems of Infants.  

ERIC Educational Resources Information Center

This newsletter contains six articles: (1) "Early Flavor Experiences: When Do They Start?" Julie A. Mennella and Gary K. Beauchamp); (2) "Infant Massage" (Tiffany Field); (3) "The Infant's Sixth Sense: Awareness and Regulation of Bodily Processes" (Stephen W. Porges); (4) "Sensory Contributions to Action: A Sensory Integrative Approach" (Marie E.…

Zero To Three, 1993

1993-01-01

378

Genetics Home Reference: Congenital cataracts, facial dysmorphism, and neuropathy  

MedlinePLUS

... Research studies OMIM Genetic disorder catalog Conditions > Congenital cataracts, facial dysmorphism, and neuropathy (often shortened to CCFDN ) ... definitions Reviewed April 2010 What is CCFDN? Congenital cataracts, facial dysmorphism, and neuropathy (CCFDN) is a rare ...

379

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...

380

[Hereditary essential myoclonus. Report of a family].  

PubMed

The occurrence of myoclonic and dystonic movements as an isolated expression of a neurologic condition of hereditary pattern have been scarcely described in literature. For this entity some authors proposed the denomination "hereditary myoclonic dystonia" while others prefer the use of the expression "hereditary essential myoclonus". We present a family in which this unusual association of abnormal movements affected several members in three generations. The propositus patient is a 14-year-old girl who have noticed the dystonic movements by 7 years of age and the myoclonic ones by 13 years of age, with a slow progression. There was no reference about the effect of alcohol (abstemious patient). There was a family history of similar cases. The supplementary investigation (seric dosage of cupper, ceruloplasmine, T3, T4, TSH; acanthocytes search; CSF examination; CT scan and MRI of the head) did not show any abnormality. Clonazepam was the only medication that lead to a clinical improvement, reducing both movements. PMID:7893218

Alves, R S; Barbosa, E R; Limongi, J C; Silva, L J

1994-09-01

381

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 ...

382

Ischemic optic neuropathies - where are we now?  

PubMed

Ischemic optic neuropathy is of two types: anterior and posterior. Non-arteritic anterior ischemic optic neuropathy (NA-AION) is the most common type of ischemic optic neuropathy. There are three major misconceptions about NA-AION: (1) that its pathogenesis is not known, (2) that NA-AION and ischemic cerebral stroke are similar in nature, pathogenetically and in management, and (3) that there is no treatment. All these misconceptions are based on lack of in-depth knowledge of the subject. They are discussed in the light of our current scientific knowledge. The pathogenesis of NA-AION is known but is highly complex. NA-AION and ischemic cerebral stroke are very different clinical entities, pathogenetically and in management. Aspirin has no beneficial effect. Corticosteroid therapy during the initial stages can be beneficial. To reduce the risk of development of NA-AION in the other eye or of further visual loss in the same eye, it is essential to reduce as many risk factors as possible. Management of arteritic anterior ischemic optic neuropathy and of posterior ischemic optic neuropathy is discussed. PMID:23821118

Hayreh, Sohan Singh

2013-08-01

383

The Center for Peripheral Neuropathy Department of Neurology  

E-print Network

control. While certain conditions may contribute to the development of peripheral neuropathy--diabetes#12;The Center for Peripheral Neuropathy Department of Neurology The University of Chicago 5841 South Maryland Avenue, MC2030 Chicago, Illinois 60637 Director, Center for Peripheral Neuropathy Brian

Sherman, S. Murray

384

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

PubMed Central

To elucidate the cause(s) of acute or subacute bilateral simultaneous optic neuropathy (BSON) in adult life, a follow up study of 23 patients was performed with clinical assessment, brain MRI, HLA typing, and mitochondrial DNA analysis. The results of CSF electrophoresis were available from previous investigations in 11 patients. At follow up, five (22%) had developed clinically definite multiple sclerosis, four (17%) had mitochondrial DNA point mutations indicating a diagnosis of Leber's hereditary optic neuropathy (LHON). The remaining 14 patients (61%) still had clinically isolated BSON a mean of 50 months after the onset of visual symptoms: three of 14 (21%) had multiple MRI white matter lesions compatible with multiple sclerosis, three of 14 (21%) had the multiple sclerosis associated HLA-DR15/DQw6 haplotype, and one of seven tested had CSF oligoclonal IgG bands; in total only five (36%) had one or more of these risk factors. The low frequency of risk factors for the development of multiple sclerosis in these 14 patients suggests that few will develop multiple sclerosis with more prolonged follow up. It is concluded that: (a) about 20% of cases of BSON without affected relatives are due to LHON; (b) multiple sclerosis develops after BSON in at least 20% of cases, but the long term conversion rate is likely to be considerably less than the rate of over 70% seen after an episode of acute unilateral optic neuritis in adult life. PMID:7823072

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

1995-01-01

385

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

386

Delayed Pneumocephalus-Induced Cranial Neuropathy  

PubMed Central

Pneumocephalus is a common occurrence after cranial surgery, with patients typically remaining asymptomatic from a moderate amount of intracranial air. Postsurgical pneumocephalus rarely causes focal neurological deficits; furthermore, cranial neuropathy from postsurgical pneumocephalus is exceedingly uncommon. Only 3 cases have been previously reported that describe direct cranial nerve compression from intracranial air resulting in an isolated single cranial nerve deficit. The authors present a patient who developed dysconjugate eye movements from bilateral oculomotor nerve palsy. Direct cranial nerve compression occurred as a result of postoperative pneumocephalus in the interpeduncular cistern. The isolated cranial neuropathy gradually recovered as the intracranial air was reabsorbed. PMID:24151506

Marupudi, Neena I.

2013-01-01

387

[Ischemic optic neuropathy after lumbar spine surgery].  

PubMed

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

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

2007-12-01

388

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

PubMed Central

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.

2013-01-01

389

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

390

The Role of DNA Methylation in Aging, Rejuvenation, and Age-Related Disease  

E-print Network

, such as a hereditary form of sensory neuropathy accompanied by dementia, are directly caused by methylomic changes the methylome and demonstrate great promise with regard to rejuvenation. Introduction Epigenetic regulation

de Magalhães, João Pedro

391

Role of nitrosative stress in early neuropathy and vascular dysfunction in streptozotocin-diabetic rats.  

PubMed

Evidence for important roles of the highly reactive oxidant peroxynitrite in diabetic complications is emerging. We evaluated the role of peroxynitrite in early peripheral neuropathy and vascular dysfunction in STZ-diabetic rats. In the first dose-finding study, control and STZ-diabetic rats were maintained with or without the potent peroxynitrite decomposition catalyst Fe(III)tetrakis-2-(N-triethylene glycol monomethyl ether) pyridyl porphyrin (FP15) at 3, 5, or 10 mg.kg(-1).day(-1) in the drinking water for 4 wk after an initial 2 wk without treatment for assessment of early neuropathy. In the second study with similar experimental design, control and STZ-diabetic rats were maintained with or without FP15, 5 mg.kg(-1).day(-1), for vascular studies. Rats with 6-wk duration of diabetes developed motor and sensory nerve conduction velocity deficits, mechanical hyperalgesia, and tactile allodynia in the absence of small sensory nerve fiber degeneration. They also had increased nitrotyrosine and poly(ADP-ribose) immunofluorescence in the sciatic nerve and dorsal root ganglia. All these variables were dose-dependently corrected by FP15, with minimal differences between the 5 and 10 mg.kg(-1).day(-1) doses. FP15, 5 mg.kg(-1).day(-1), also corrected endoneurial nutritive blood flow and nitrotyrosine, but not superoxide, fluorescence in aorta and epineurial arterioles. Diabetes-induced decreases in acetylcholine-mediated relaxation by epineurial arterioles and coronary and mesenteric arteries, as well as bradykinin-induced relaxation by coronary and mesenteric arteries, were alleviated by FP15 treatment. The findings reveal the important role of nitrosative stress in early neuropathy and vasculopathy and provide the rationale for further studies of peroxynitrite decomposition catalysts in long-term diabetic models. PMID:17911342

Obrosova, Irina G; Drel, Viktor R; Oltman, Christine L; Mashtalir, Nazar; Tibrewala, Jyoti; Groves, John T; Yorek, Mark A

2007-12-01

392

Hereditary disorders of renal phosphate wasting  

Microsoft Academic Search

Inherited diseases of renal phosphate handling lead to urinary phosphate wasting and depletion of total body phosphorus stores. Clinical sequelae of inherited disorders that are associated with increased urinary phosphate excretion are deleterious and can lead to abnormal skeletal growth and deformities. This Review describes hereditary disorders of renal phosphate wasting taking into account developments in our understanding of renal

Robert F. Reilly; Amir S. Alizadeh Naderi

2010-01-01

393

Prevention and therapy in hereditary retinal degenerations  

Microsoft Academic Search

A survey of the present state of developments concerning prevention and therapy of hereditary retinal diseases is given. In recent years the techniques of molecular genetics have led to a rapid identification of a great number of cloned or mapped genes responsible for such diseases. Moreover, further progress has been made in the understanding of disease mechanisms by describing the

Dorothea Besch; Eberhart Zrenner

2003-01-01

394

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

395

DIABETIC NEUROPATHY PART 2: PROXIMAL AND ASSYMMETRIC PHENOTYPES  

PubMed Central

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

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

2014-01-01

396

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

397

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

Microsoft Academic Search

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

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

1989-01-01

398

[Autonomic neuropathy of the gastrointestinal tract].  

PubMed

The paper focuses on the issues of diabetic autonomic neuropathy in the gastrointestinal tract. It describes the aethiopathogenesis of diabetic polyneuropathy. More detailed discussion is then provided with respect to gastrointestinal tract. The clinical picture and options available for the diagnosis and treatment when various parts of the gastrointestinal tract are involvement are examined. PMID:21612065

Olsovský, J

2011-04-01

399

Auditory Neuropathy Spectrum Disorder: A Review  

ERIC Educational Resources Information Center

Purpose: Auditory neuropathy spectrum disorder, or ANSD, can be a confusing diagnosis to physicians, clinicians, those diagnosed, and parents of children diagnosed with the condition. The purpose of this review is to provide the reader with an understanding of the disorder, the limitations in current tools to determine site(s) of lesion, and…

Norrix, Linda W.; Velenovsky, David S.

2014-01-01

400

Magnetic resonance imaging of radiation optic neuropathy  

SciTech Connect

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

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

1990-10-15

401

Peripheral neuropathy: pattern recognition for the pragmatist  

Microsoft Academic Search

Long lists of causes of peripheral neuropathy make peripheral nerve disease a dry and uninspiring subject. A simple scheme based on the answers to just six questions should enable the clinician to recognise characteristic patterns, investigate relevant subgroups appropriately, and identify treatable disorders quickly: which systems are involved? What is the distribution of weakness? What is the nature of the

James R Overell

2011-01-01

402

Speech Perception in Individuals with Auditory Neuropathy  

ERIC Educational Resources Information Center

Purpose: Speech perception in participants with auditory neuropathy (AN) was systematically studied to answer the following 2 questions: Does noise present a particular problem for people with AN: Can clear speech and cochlear implants alleviate this problem? Method: The researchers evaluated the advantage in intelligibility of clear speech over…

Zeng, Fan-Gang; Liu, Sheng

2006-01-01

403

Chlamydia in Anterior Ischemic Optic Neuropathy  

Microsoft Academic Search

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

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

2002-01-01

404

Pupillary signs in diabetic autonomic neuropathy  

Microsoft Academic Search

Pupillary function was investigated in 36 insulin-dependent diabetics and 36 controls matched for age and sex. About half of the diabetics had evidence of peripheral somatic or autonomic neuropathy, or both. The diabetic patients had abnormally small pupil diameters in the dark and less fluctuation in pupil size (hippus) during continuous illumination than the controls. They also had reduced reflex

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

1978-01-01

405

Epidemic neuropathy in Cuba: a plea to end the United States economic embargo on a humanitarian basis.  

PubMed

During 1992-1993, an epidemic of neurologic disease in Cuba affected 50,862 patients with optic neuropathy, sensorineural deafness, predominantly sensory peripheral neuropathy, and dorsolateral myelopathy. The clinical syndromes were identical to those of prisoners of war subjected to nutritional restriction in tropical prison camps during World War II (Strachan's disease). A dietary deficiency of group B vitamins and sulfur-containing amino acids appears to have been the primary cause of the epidemic. This was a consequence of economic and