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Charcot-Marie-Tooth (CMT) disease is a complex of peripheral nervous system disorders. CMT type 2U (CMT2U) is an autosomal dominant (AD) disease caused by mutations in the MARS gene encoding methionyl-tRNA synthetase; this disease has thus been newly called AD-CMTax- MARS. A few families with mutations in the MARS gene have been reported, without detailed histopathological findings. We describe a 70-year-old woman who had bilateral dysesthesia of the soles since the age of 66 years. Sural nerve biopsy showed a decrease in the density of large myelinated nerve fibers. Increased clusters of regenerating myelinated nerve fibers were noted. Electron microscopic analyses revealed degeneration of unmyelinated nerves. There was no vasculitis or inflammatory cell infiltration. Genetic analysis identified a heterozygous p.P800T mutation, a reported mutation in the MARS gene. We report the detailed histopathological findings in a patient with CMT2U/AD-CMTax- MARS. The findings are similar to those found in CMT2D caused by mutations in the GARS gene, encoding glycyl-tRNA synthetase. [ABSTRACT FROM AUTHOR]

The aim of this study was to clarify the differences in the pathogenesis of neuropathy between myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-positive and -negative patients with Churg-Strauss syndrome (CSS). Eight MPO-ANCA-positive and 14 MPO-ANCA-negative patients were included. In addition to the standard histology, nerve biopsies were examined, employing immunohistochemistry for eosinophil major basic protein and electron microscopy. The groups did not differ significantly in clinical profiles, including the peak disability score and number of blood eosinophils. In nerve biopsies, necrotizing vasculitis was found in 63% (5/8) of the ANCA-positive and 21% (3/14) of the ANCA-negative patients. Fibrinoid necrosis of vessel walls was noted in 4 ANCA-positive patients (50%), and in one ANCA-negative patient ( p = 0039). In contrast, a large number of eosinophilic infiltrations in the epineurium was shown in 36% (5/14) of the ANCA-negative patients, with no eosinophilic infiltrations shown in ANCA-positive patients. In 3 ANCA-negative patients, endoneurial eosinophils were seen where focal axonal loss and capillary dilatation were occasionally noted. There may be 2 pathogenetic mechanisms of neuropathy with CSS: ANCA-related vascular fibrinoid necrosis, and a toxic eosinophilic effect on nerve fibers which is independent of ANCA. Therapy targeting activated eosinophils may be a possible treatment for intractable neuropathy of CSS. [ABSTRACT FROM AUTHOR]

Neuromuscular biopsy is still an essential method for diagnosing vasculitic neuropathy, although its diagnostic sensitivity is at most 60%. Our objective was to examine the expression of hypoxia-inducible factor 1α (HIF-1α) in peripheral nerves and to evaluate its usefulness in diagnosing vasculitic neuropathy, especially for discrimination from other axonal neuropathies. Forty-one patients with vasculitic neuropathy consisting of 20 definite, 14 probable and seven possible diagnoses, 15 patients with metabolic neuropathy, five with motor neuron disease and six with chronic inflammatory demyelinating polyneuropathy were included. Nerve biopsy specimens were immunohistochemically examined for HIF-1α and various cell markers. Distinct immunoreactivity (IR) was observed in nuclei of endoneurial cells in 54% (22/41) of vasculitic patients, while specimens from metabolic neuropathies showed less nuclear IR and the difference of mean density of HIF-1α-positive nuclei was significant. Two patients with possible vasculitis who showed HIF-1α-positive nuclei in endoneurium, were later confirmed to have vasculitis by skin biopsies. Most of the cells expressing HIF were demonstrated to be Schwann cells. There was a trend in the vasculitic patients with early phase nerve damage to display higher endoneurial HIF-1α-IR. HIF-1α may be an immunohistochemical marker for vasculitic neuropathy, especially when the observed section contains no vasculitic lesions. [ABSTRACT FROM AUTHOR]

Abstract: Phenotypic variations have been reported in Charcot-Marie-Tooth disease type 2 (CMT2) including age-at-onset, disease progression and severity. Sporadic cases with CMT2 have also been demonstrated by genetic test. We here report a patient with late-onset CMT2 without family history, who developed gait disturbance at the age of 68. Sequence analysis revealed a novel heterozygous Arg198Gly mutation in the cytoplasmic domain of the major peripheral myelin protein zero (MPZ). The mutation is located in the protein kinase C (PKC) alpha substrate motif (RSTK) of MPZ, presumably leading to the loss of PKC-mediated phosphorylation in adhesion. Routine genetic test for CMT is not recommended for every patient with late-onset peripheral neuropathy without known causes, however, the genetic test may be taken into consideration if the patient shows a clinical phenotype similar to that of CMT, and the possibility of a de novo mutation cannot be excluded. [ABSTRACT FROM AUTHOR]

Background: We intended to clarify the phenotypic and molecular diversities of spinocerebellar ataxia type 2 (SCA2) in Japan. Methods: DNA was extracted from the peripheral blood of 436 patients, including 126 patients with chronic neuropathy, 108 with amyotrophic lateral sclerosis, and 202 with cerebellar ataxia. We then PCR-amplified and sequenced the ATXN2 gene. The biopsied sural nerves of mutation-positive patients were subjected to light-microscopic and electron-microscopic analyses. Transfection analyses were performed using a Schwann cell line, IMS32. Results: We found PCR-amplified products potentially corresponding to expanded CAG repeats in four patients. Two patients in the chronic neuropathy group had a full repeat expansion or an intermediate expansion (39 or 32 repeats), without limb ataxia. The sural nerve biopsy findings of the two patients included axonal neuropathy and mixed neuropathy (axonal changes with demyelination). Schwann cells harbored either cytoplasmic or nuclear inclusions on electron microscopic examination. Both patients recently exhibited pyramidal signs. In the third patient in the cerebellar ataxia group, we identified a novel 21-base duplication mutation near 22 CAG repeats (c.432_452dup). The transfection study revealed that the 21-base-duplication mutant Ataxin-2 proteins aggregated in IMS32 and rendered cells susceptible to oxidative stress, similar to a CAG-expanded mutant. The fourth patient, with 41 repeats, had ataxia and spasticity. The two patients with cerebellar ataxia also had peripheral neuropathy. Conclusions: Patients with expanded CAG repeats can exhibit a neuropathy-dominant phenotype not described previously. The novel 21-base-duplication mutant seems to share the aggregation properties of polyglutamine-expanded mutants. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Vascular thrombosis is prevalent among patients with polyneuropathy, organomegaly, endocrinopathy M‐protein, and skin changes (POEMS) syndrome. The endothelial cells in the endoneurium are often hypertrophied and the lumen is frequently occluded. Consequent local hypoxia may increase vascular endothelial growth factor (VEGF), which induces hypercoagulation and vascular permeability. Methods: This study presents two patients in the fifth decade of life, who had rare nerve biopsy findings of vascular occlusion mainly by platelets. Before the cases presented here, we encountered nine confirmed POEMS patients whose nerve biopsies did not show similar findings. Results: A small artery and a vein were occluded, but no atherosclerotic changes were observed. The endothelial cells that adhered to the packed platelets lost their junctions. Discussion: Platelet aggregation, degranulation, and ischemia may cause a loose endothelial barrier and leak proinflammatory cytokines, such as interleukin‐12. This may increase production of VEGF and may cause nerve demyelination. Small vessel platelet thrombosis may contribute to the pathogenesis of this disorder. [ABSTRACT FROM AUTHOR]

Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) has recently been attributed to biallelic repeat expansions in RFC1. More recently, the disease entity has expanded to atypical phenotypes, including chronic neuropathy without cerebellar ataxia or vestibular areflexia. Very recently, RFC1 expansions were found in patients with Sjögren syndrome who had neuropathy that did not respond to immunotherapy. In this study RFC1 was examined in 240 patients with acute or chronic neuropathies, including 105 with Guillain-Barré syndrome or Miller Fisher syndrome, 76 with chronic inflammatory demyelinating polyneuropathy, and 59 with other types of chronic neuropathy. Biallelic RFC1 mutations were found in three patients with immune-mediated neuropathies, including Guillain-Barré syndrome, idiopathic sensory ataxic neuropathy, or anti-myelin-associated glycoprotein (MAG) neuropathy, who responded to immunotherapies. In addition, a patient with chronic sensory autonomic neuropathy had biallelic mutations, and subclinical changes in Schwann cells on nerve biopsy. In summary, we found CANVAS-related RFC1 mutations in patients with treatable immune-mediated neuropathy or demyelinating neuropathy. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Vascular thrombosis is prevalent among patients with polyneuropathy, organomegaly, endocrinopathy M‐protein, and skin changes (POEMS) syndrome. The endothelial cells in the endoneurium are often hypertrophied and the lumen is frequently occluded. Consequent local hypoxia may increase vascular endothelial growth factor (VEGF), which induces hypercoagulation and vascular permeability. Methods: This study presents two patients in the fifth decade of life, who had rare nerve biopsy findings of vascular occlusion mainly by platelets. Before the cases presented here, we encountered nine confirmed POEMS patients whose nerve biopsies did not show similar findings. Results: A small artery and a vein were occluded, but no atherosclerotic changes were observed. The endothelial cells that adhered to the packed platelets lost their junctions. Discussion: Platelet aggregation, degranulation, and ischemia may cause a loose endothelial barrier and leak proinflammatory cytokines, such as interleukin‐12. This may increase production of VEGF and may cause nerve demyelination. Small vessel platelet thrombosis may contribute to the pathogenesis of this disorder. [ABSTRACT FROM AUTHOR]

Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) has recently been attributed to biallelic repeat expansions in RFC1. More recently, the disease entity has expanded to atypical phenotypes, including chronic neuropathy without cerebellar ataxia or vestibular areflexia. Very recently, RFC1 expansions were found in patients with Sjögren syndrome who had neuropathy that did not respond to immunotherapy. In this study RFC1 was examined in 240 patients with acute or chronic neuropathies, including 105 with Guillain-Barré syndrome or Miller Fisher syndrome, 76 with chronic inflammatory demyelinating polyneuropathy, and 59 with other types of chronic neuropathy. Biallelic RFC1 mutations were found in three patients with immune-mediated neuropathies, including Guillain-Barré syndrome, idiopathic sensory ataxic neuropathy, or anti-myelin-associated glycoprotein (MAG) neuropathy, who responded to immunotherapies. In addition, a patient with chronic sensory autonomic neuropathy had biallelic mutations, and subclinical changes in Schwann cells on nerve biopsy. In summary, we found CANVAS-related RFC1 mutations in patients with treatable immune-mediated neuropathy or demyelinating neuropathy. [ABSTRACT FROM AUTHOR]

Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) has recently been attributed to biallelic repeat expansions in RFC1. More recently, the disease entity has expanded to atypical phenotypes, including chronic neuropathy without cerebellar ataxia or vestibular areflexia. Very recently, RFC1 expansions were found in patients with Sjögren syndrome who had neuropathy that did not respond to immunotherapy. In this study RFC1 was examined in 240 patients with acute or chronic neuropathies, including 105 with Guillain-Barré syndrome or Miller Fisher syndrome, 76 with chronic inflammatory demyelinating polyneuropathy, and 59 with other types of chronic neuropathy. Biallelic RFC1 mutations were found in three patients with immune-mediated neuropathies, including Guillain-Barré syndrome, idiopathic sensory ataxic neuropathy, or anti-myelin-associated glycoprotein (MAG) neuropathy, who responded to immunotherapies. In addition, a patient with chronic sensory autonomic neuropathy had biallelic mutations, and subclinical changes in Schwann cells on nerve biopsy. In summary, we found CANVAS-related RFC1 mutations in patients with treatable immune-mediated neuropathy or demyelinating neuropathy. [ABSTRACT FROM AUTHOR]

Introduction: Neurofascin155 (NF155) is a target antigen for autoantibodies in a subset of chronic inflammatory demyelinating polyneuropathy (CIDP).Methods: We report the cases of 4 patients with anti-NF155 immunoglobulin G4 (IgG4) antibody-positive CIDP who underwent sural nerve biopsies.Results: All patients were relatively young at onset. Three patients experienced tremors, and 2 patients had severe ataxia. Although the response to intravenous immunoglobulin was poor in all patients, plasma exchange and corticosteroids were at least partially effective. Immunoadsorption plasmapheresis was performed in 1 patient but was ineffective. Electron microscopic examination of sural nerve biopsies revealed loss of paranodal transverse bands in all patients.Discussion: Anti-NF155 IgG4 antibody-positive CIDP shows distinctive clinicopathological features, indicating that the IgG4 antibody is directly associated with the pathogenic mechanisms of anti-NF155 IgG4 antibody-positive CIDP. Muscle Nerve 57: 498-502, 2018. [ABSTRACT FROM AUTHOR]

The article describes the case of a 43-year-old male industrial worker with 1-bromopropane-induced neurotoxicity. His use of 1-bromopropane as a cleaning agent for metal parts at the workplace without proper protection is described. The patient's development of pain, muscle weakness, gait disturbance and numbness is mentioned. Axonal damage was shown in a histopathologic examination of sural nerve biopsy. Symptoms improved gradually when he was kept away from exposure to the solvent. INSET: 260.

Objective: Eosinophils are tissue‐dwelling immune cells. Accumulating evidence indicates that a type of cell death termed ETosis is an important cell fate involved in the pathophysiology of inflammatory diseases. Although the critical role of eosinophils in eosinophilic granulomatosis with polyangiitis (EGPA; formerly Churg‐Strauss syndrome) is well established, the presence of eosinophil ETosis (EETosis) is poorly understood. We undertook this study to better understand the characteristics of EETosis. Methods: In vitro studies using blood‐derived eosinophils were conducted to characterize EETosis. The occurrence of EETosis in tissues from patients with EGPA was studied by immunostaining and electron microscopy. Serum concentrations of eosinophil‐derived proteins in healthy controls, patients with asthma, and EGPA patients with active disease or with disease in remission (n = 15 per group) were examined. Results: EETosis was reliant on reactive oxygen species and peptidylarginine deiminase type 4–dependent histone citrullination, resulting in the cytolytic release of net‐like eosinophil extracellular traps, free galectin‐10, and membrane‐bound intact granules. The signature of EETosis, including loss of cytoplasmic galectin‐10 and deposition of granules, was observed in eosinophils infiltrating various tissues from EGPA patients. Serum eosinophil granule proteins and galectin‐10 levels were increased in EGPA and positively correlated with disease activity as assessed by the Birmingham Vasculitis Activity Score (r = 0.8531, P < 0.0001 for galectin‐10). When normalized to blood eosinophil counts, this correlation remained for galectin‐10 (r = 0.7168, P < 0.0001) but not for granule proteins. Galectin‐10 levels in active EGPA positively correlated with serum interleukin‐5 levels. Conclusion: Eosinophils infiltrating diseased tissues in EGPA undergo EETosis. Considering the exclusive expression and large pool of cytoplasmic galectin‐10 in eosinophils, elevated serum galectin‐10 levels in patients with EGPA might reflect the systemic occurrence of cytolytic EETosis. [ABSTRACT FROM AUTHOR]

To clarify the roles of neutrophils in anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitic neuropathy, we studied neutrophil extracellular traps (NETs) in peripheral nerve vasculitis. Stored nerve samples from 17 patients with microscopic polyangiitis (MPA) were immunohistochemically analyzed using antibodies for citrullinated histone H3 (citH3) and various neutrophil enzymes. We defined merged citH3 and extracellularly released myeloperoxidase (MPO) as NET formation. We also compared NET formation between MPO-ANCA-positive/negative MPA and rheumatoid arthritis (RA)-associated vasculitic neuropathy. NETs were identified mostly in vasculitic small arterioles of 6 of 12 MPO-ANCA-positive MPA patients, and their frequency was higher ( p < 0.05) than in ANCA-negative patients. NETs were not found in vasculitic neuropathy with RA or patients with chronic inflammatory demyelinating polyradiculoneuropathy. NETs were also observed in the peripheral nervous system of MPA patients as well as in the lung and kidney. These results suggest that NETs may be involved in the pathogenesis of MPA neuropathy. [ABSTRACT FROM AUTHOR]

Antibodies to Contactin-1 and Neurofascin 155 (Nfasc155) have recently been associated with subsets of patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Contactin-1 and Nfasc155 are cell adhesion molecules that constitute the septate-like junctions observed by electron microscopy in the paranodes of myelinated axons. Antibodies to Contactin-1 have been shown to affect the localization of paranodal proteins both in patient nerve biopsies and in animal models after passive transfer. However, it is unclear whether these antibodies alter the paranodal ultrastructure. We examined by electron microscopy sural nerve biopsies from two patients presenting with anti-Nfasc155 antibodies, and also four patients lacking antibodies, three normal controls, and five patients with other neuropathies. We found that patients with anti-Nfasc155 antibodies presented a selective loss of the septate-like junctions at all paranodes examined. Further, cellular processes penetrated into the expanded spaces between the paranodal myelin loops and the axolemma in these patients. These patients presented with important nerve conduction slowing and demyelination. Also, the reactivity of anti-Nfasc155 antibodies from these patients was abolished in neurofascin -deficient mice, confirming that the antibodies specifically target paranodal proteins. Our data indicate that anti-Nfasc155 destabilizes the paranodal axo-glial junctions and may participate in conduction deterioration. [ABSTRACT FROM AUTHOR]

Introduction: Adult-onset Krabbe disease is clinically rare and usually affects the pyramidal tracts in the central nervous system. Patients develop a spastic gait, and peripheral neuropathy sometimes occurs simultaneously.Methods: A 55-year-old woman with consanguineous parents developed slowly progressive, asymmetric muscle weakness and atrophy in her forearms, while her ability to walk remained unaffected without pyramidal tract signs after onset at age 51 years.Results: Nerve conduction studies demonstrated an asymmetric demyelinating-type peripheral neuropathy, and sural nerve biopsy documented reduced myelinated nerve fiber density with uniformly thin myelin sheaths, suggesting hypomyelination. Brain MRI demonstrated minor white-matter injury along the optic radiations, which was associated with asymptomatic, mild, prolonged latency on visual evoked potentials. Laboratory analysis documented low enzyme activity of galactocerebrosidase (GALC) and a known mutation of the GALC gene.Conclusion: Isolated peripheral neuropathy occurs very rarely in adult-onset Krabbe disease. Muscle Nerve 54: 152-157, 2016. [ABSTRACT FROM AUTHOR]

Objective To investigate anti-neurofascin 155 ( NF155) antibody-positive chronic inflammatory demyelinating polyneuropathy ( CIDP). Methods Sera from 50 consecutive CIDP patients diagnosed in our clinic, 32 patients with multiple sclerosis, 40 patients with other neuropathies including 26 with Guillain-Barré syndrome ( GBS)/Fisher syndrome, and 30 healthy controls were measured for anti- NF antibodies by flow cytometry using HEK293 cell lines stably expressing human NF155 or NF186. Four additional CIDP patients with anti- NF155 antibodies referred from other clinics were enrolled for clinical characterization. Results The positivity rate for anti- NF155 antibodies in CIDP patients was 18% (9/50), who all showed a predominance of IgG4 subclass. No other subjects were positive, except one GBS patient harboring IgG1 anti- NF155 antibodies. No anti- NF155 antibody carriers had anti- NF186 antibodies. Anti- NF155 antibody-positive CIDP patients had a significantly younger onset age, higher frequency of drop foot, gait disturbance, tremor and distal acquired demyelinating symmetric phenotype, greater cervical root diameter on magnetic resonance imaging neurography, higher cerebrospinal fluid protein levels, and longer distal and F-wave latencies than anti- NF155 antibody-negative patients. Marked symmetric hypertrophy of cervical and lumbosacral roots/plexuses was present in all anti- NF155 antibody-positive CIDP patients examined by neurography. Biopsied sural nerves from two patients with anti- NF155 antibodies demonstrated subperineurial edema and occasional paranodal demyelination, but no vasculitis, inflammatory cell infiltrates, or onion bulbs. Among anti- NF155 antibody-positive patients, treatment responders more frequently had daily oral corticosteroids and/or immunosuppressants in addition to intravenous immunoglobulins than nonresponders did. Interpretation Anti- NF155 antibodies occur in a subset of CIDP patients with distal-dominant involvement and symmetric nerve hypertrophy. [ABSTRACT FROM AUTHOR]

Charcot-Marie-Tooth disease (CMT), the most common hereditary neuropathy, has been classified into two types, demyelinating and axonal types. We previously analyzed the genes causing dominant demyelinating CMT in 227 Japanese patients to identify the genetic background, but could not find any mutations in 110 patients. To investigate the frequency of patients with autosomal recessive demyelinating CMT (CMT4) mutations, we analyzed the coding sequence of known causative genes of CMT4 in 103 demyelinating CMT patients, excluding seven patients owing to lack of specimens. We found one patient with a GDAP1 mutation, one patient with an MTMR2 mutation, two patients with SH3TC2/KIAA1985 mutations and three patients with FGD4 mutations. Twelve patients, including five previously detected patients with PRX mutations, were diagnosed as CMT4, accounting for 5.5% of demyelinating CMT. In the patient with GDAP1 mutation, only one mutation inherited from his mother was detected by genomic sequencing. Analysis by reverse transcription polymerase chain reaction using messenger RNA (mRNA) from the patient's leukocytes revealed the absence of transcription from the allele inherited from his father, suggesting the existence of one more mutation leading to a lack or destabilization of mRNA. Most patients carrying CMT4 gene mutations present with early-onset and slowly progressive symptoms, which may be associated with the function of mutants. We could not identify the disease-causing gene in 96 patients (about 45%). Further studies including studies with next-generation sequencers will be required to identify the causative gene in Japanese CMT. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the prevalence and clinical correlates of apathy and depression in Parkinson disease (PD), and to clarify whether apathy can be dissociated from depression. One hundred fifty patients with PD completed the Beck Depression Inventory Second Edition (BDI-II), Starkstein's Apathy Scale (AS), and a quality of life (QOL) battery. Hoehn and Yahr (HY) staging, the Unified Parkinson's Disease Rating Scale (UPDRS), and the Mini-Mental State Examination (MMSE) were performed on the same day. Apathy (AS score ≥ 16) was diagnosed in 60% of patients and depression (BDI-II score ≥ 14) in 56%. Apathy coexisted with depression in 43% of patients, compared with depression without apathy in 13% and apathy without depression in 17%. Apathy scale score was significantly correlated with UPDRS scores, HY stage, and age, whereas BDI-II score was correlated only with UPDRS scores. Both AS and BDI-II scores were negatively correlated with QOL. However, multiple regression analysis revealed that depression was strongly and negatively associated with emotional well-being and communication, whereas apathy was mainly associated with cognition and stigma. These findings suggest that apathy and depression may be separable in PD, although both are common in patients with PD and are associated with QOL. [ABSTRACT FROM AUTHOR]

The neurofilament light chain polypeptide (NEFL) forms the major intermediate filament in neurons and axons. NEFL mutation is a cause of axonal or demyelinating forms of dominant Charcot–Marie–Tooth disease (CMT). We investigated NEFL in 223 Japanese CMT patients who were negative for PMP22, MPZ, GJB1, LITAF, EGR2, GDAP1, MTMR2 and PRX in the demyelinating form and negative for MFN2, MPZ, GJB1, HSP27, HSP22 and GARS in the axonal form. We detected four heterozygous missense mutations—Pro8Leu, Glu90Lys, Asn98Ser and Glu396Lys––in five unrelated patients and a homozygous nonsense mutation, Glu140Stop, in one other patient. All patients had mildly to moderately delayed nerve conduction velocities, possibly caused by a loss of large diameter fibers. This is the first report of a homozygous nonsense mutation of NEFL. Results of our study show that nonsense NEFL mutations probably cause a recessive phenotype, in contrast to missense mutations, which cause a dominant phenotype.Journal of Human Genetics (2009) 54, 94–97; doi:10.1038/jhg.2008.13; published online 16 January 2009 [ABSTRACT FROM AUTHOR]

Abstract: A 45-year-old man with insulin-dependent diabetic mellitus developed progressive asymmetrical weakness and atrophy of both shoulder girdle muscles within 1 year. In the last month, he also developed slight weakness of both thighs. Neuropathology of the sural nerve showed an axonal degeneration and perivascular inflammation and electromyography revealed neurogenic changes. Because of a diagnosis of suspected diabetic amyotrophy, intravenous immunoglubulin was administered. This treatment produced marked improvement. Physicians should take into account the possibility of diabetic amyotrophy in patients with diabetic mellitus showing primary involvement of shoulder girdle muscles marked by weakness and atrophy. [Copyright &y& Elsevier]

We report two siblings who presented with non-progressive marked sensory ataxia associated with arthrogryposis multiplex congenita (AMC). Deep tendon reflexes and H reflex were completely absent, but F waves were preserved. The sensory nerve conduction studies indicated the presence of relatively mild sensory polyneuropathy. The conventional somatosensory evoked potentials (SEPs) showed mildly prolonged latency for both the peripheral and cortical responses, suggesting a slowed conduction through the peripheral as well as central pathway. However, the ‘proprioceptive SEPs’ were absent, in conformity with complete loss of joint sense. Sural nerve biopsy revealed only mild thinning of myelin in the younger sister but was entirely normal in her brother. Taken together with the characteristic electrophysiological findings, the symptoms were considered to be due to predominant involvement of a selective population of somatosensory ganglions. The present cases showed no progression of the neurological deficit what-so-ever since birth, which strongly suggests a developmental anomaly or aplasia of a limited population of peripheral sensory neurons. [ABSTRACT FROM AUTHOR]

Abstract: We report the case of a 68-year-old man who developed hepatitis B virus (HBV)-related vasculitis, manifesting as mononeuritis multiplex, 8 days after influenza vaccination. The patient was a carrier of wild-type HBV, and had never received influenza vaccination. Histologic examination of the left sural nerve revealed necrotising vasculitis predominantly involving small blood vessels. HbsAg deposits were observed at a high density around the epineurial blood vessels of the sural nerve. He was treated with prednisone and Lamivudine. His condition improved gradually. However, seroconversion of HBs and HBe Ag was not detected. At the last follow-up 2 years later, his vascilitis did not recur. On the basis of the time of onset of vasculitis, the presumptive immune-mediated pathology of this disorder suggests a possible etiologic link with influenza vaccine. To our knowledge, our case is the first to show vasculitis of peripheral nerves proven pathologically after influenza vaccination. [Copyright &y& Elsevier]

• Mutations in FBLN5 gene cause Charcot-Marie-Tooth disease type 1 (CMT). • We recently detected the rare mutation c.1117C > T in FBLN5 in Japanese familial cases. • Few reports have described the peripheral nerve pathology in CMT1 with FBLN5 mutation. • Our case study exhibited vasculitis of small vessels on sural nerve pathology. • Here we describe the clinical information of two familial patients in detail. [ABSTRACT FROM AUTHOR]

Peripheral neuropathy is an uncommon complication of idiopathic thrombocytopenic purpura (ITP). We report a 61-year-old man with ITP who developed acute-onset mononeuropathy multiplex. An electrophysiologic study revealed active axonal degenerative alteration, and a sural nerve biopsy showed axonal degeneration. Intraneural hemorrhage was suggested to be the most likely cause.Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]