桑原 聡

Objective: To elucidate the frequency of peripheral nerve demyelination in multiple sclerosis (MS). There are a number of case reports describing MS patients associated with demyelinating neuropathy, but its frequency in a whole MS population is unknown. Methods: Extensive nerve conduction studies were prospectively performed in 60 consecutive patients with relapsing-remitting MS. Multiple excitability measurements using threshold tracking were also performed in median motor axons and superficial radial sensory axons. Results: Nerve conduction abnormalities suggestive of demyelination were found for 3 (5%) of the patients. Two of them developed clinically evident neuropathy, whereas the remaining one had only generalized areflexia in addition to MS symptoms/signs. In all the three, MS preceded demyelinating neuropathy by several years. Excitability testing showed that supernormality and threshold electrotonus at the tested sites (median motor axons at the wrist, and radial sensory axons at the mid-forearm) were similar in the normal and MS groups. Conclusions: MS patients do not generally have peripheral nerve demyelination, but approximately 5% of patients develop demyelinating neuropathy. The association could result from a common pathogenesis possibly due to epitope spreading during the long course of MS. Significance: Association of chronic inflammatory demyelinating polyneuropathy with MS is not frequent, but needs to be recognized as a treatable condition. (c) 2008 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

POEMS syndrome is a rare plasma cell disorder characterized by peripheral neuropathy, monoclonal gammopathy, and high levels of serum vascular endothelial growth factor, the pathogenesis of which remains unclear. A unique feature of this syndrome is that the proliferating monoclonal plasma cells are essentially restricted. Here we determined complete nucleotide sequences of monoclonal immunoglobulin lambda light chain (IGL) variable regions in 11 patients with POEMS syndrome. The V-region of the Ig lambda gene of all 11 patients was restricted to the V lambda 1 subfamily. Searching for homologies with IGL germlines revealed that 2 germlines, IGLV1-44*01 (9/11) and IGLV1-40*01 (2/10), were identified, with an average homology of 91.1%. The IGLJ3*02 gene was used in 11 of 11 rearrangements with an average homology of 92.2%. These data suggest that the highly restricted use of IGL V lambda 1 germlines plays an important role in the pathogenesis of POEMS syndrome.

Aims: Some physical or arousal stimuli induce a rise in sweat secretion (sympathetic sweat response or SSwR) and a reduction in skin blood flow (skin vasomotor reflex or SkVR) to the palm. We recorded SSwRs and SkVRs in diabetic patients and assessed the usefulness of these parameters for evaluating autonomic dysfunction in diabetes. Methods: We studied 42 diabetic patients (58+/-12 years) and 42 normal control subjects (59+/-11 years). Focal sweat secretion and skin blood flow were measured on the palm by a sudorometer and a Doppler flowmeter, respectively. SSwRs and SkVRs to deep inspiration, mental arithmetic, and isotonic exercise were recorded. SSwR amplitude was measured from baseline to peak, and SkVR amplitude (reduction rate) was calculated as: (blood flow reduction/basal blood flow) x 100%. We also conducted head-up tilt tests and R-R interval variation tests (coefficient of variation of R-R intervals or CVR-R). Results: The SSwR or SkVR amplitudes in the diabetic group were significantly lower than those in the control group for any stimulus. CVR-R in the diabetic group was significantly less than that in the control group. The diabetic group showed a significantly greater reduction in systolic blood pressure during head-up tilt compared with the control group. in the diabetic group, there were significant correlations in SSwR or SkVR amplitudes versus blood pressure falls during the head-up tilt test, and CVR-R values. Conclusion: We believe that SSwR and SkVR are useful indexes for the evaluation of autonomic involvement in diabetic patients. (C) 2008 Elsevier Inc. All rights reserved.

Objective: To investigate cutaneous sympathetic functions in carpal tunnel syndrome (CTS) using sympathetic sweat responses (SSwRs) and skin vasomotor reflexes (SVmRs). Methods: In 29 hands (20 patients) with idiopathic CTS, SSwRs were recorded with a sudorometer from the thenar eminence, and SVmRs were used to measure cutaneous blood flow using a Doppler flowmeter placed on the index finger tip. Normal data were obtained from 15 volunteers of similar age. Results: SSwRs or SVmRs were abnormal in 23 (80%) hands; SSwRs were absent in 38%, whereas SVmRs were abnormally decreased in 59%. Autonomic symptoms were present in 18 (62%) hands; finger edema (38%) and dry hand (35%) were frequent symptoms. Autonomic symptoms, and abnormal SSwRs and SVmRs did not correlate with results of nerve conduction studies. Conclusions: Skin sudomotor or vasomotor sympathetic function is frequently impaired in CTS. Susceptibility to compression ischemia may be different in sympathetic unmyelinated and large myelinated fibers. (c) 2008 Elsevier B.V. All rights reserved.

Background and purpose: The presence of a projection from the primary motor cortex to the ipsilateral muscles has been established in human, but whether this pathway contributes to functional recovery after stroke is unclear. We investigated whether the ipsilateral tract is activated in hemiparetic stroke. Methods: Motor-evoked potentials (MEPs) were simultaneously recorded from the bilateral trapezius or abductor digiti minimi (ADM) muscles after magnetic stimulation to the motor cortex in 40 acute stroke patients. Results: At rest, ipsilateral trapezius MEPs were recordable in none of the 24 normal controls, and in 38% of the patients after stimulation to the non affected hemisphere (P < 0.001). With voluntary contraction, ipsilateral trapezius MEPs were elicited in 21% of the normal controls and 73% of the patients (P < 0.001). Ipsilateral ADM MEPs were rarely recordable in both controls (0%) and patients (3%). The presence of ipsilateral trapezius MEPs was associated with less severe paresis in the trapezius (P = 0.04) and deltoid (P = 0.07), but not in the more distal muscles. Conclusions: The ipsilateral cortico-spinal tract is acutely facilitated after stroke in the trunk or proximal muscles, but not in the hand muscles. Activation of such pathway appears to partly compensate motor dysfunction of the trunk/ proximal muscles.

A subgroup of limbic encephalitis is associated with antibodies against voltage-gated potassium channels (VGKC), and responds well to immuno-modulating therapies. Anti-VGKC antibodies are also found in Isaacs' syndrome and Morvan's syndrome, both of which are sometimes complicated by thymoma. We describe a 52-years-old man with limbic encephalitis, thymoma, and anti-VGKC antibodies, who presented with autonomic dysfunctions such as severe intestinal pseudo-obstruction, hyperhidrosis and hypertension. Thymectomy and corticosteroid therapy remarkably improved his symptoms. Brain magnetic resonance imaging showed hypothalamic lesions, in addition to the bilateral involvement of the medial temporal lobes. This patient had severe autonomic dysfunctions resembling those of Morvan's syndrome. This case may represent a subgroup of VGKC-antibody associated syndromes with a wide spectrum of symptoms, including Isaacs' syndrome, Morvan's syndrome, and limbic encephalitis. (C) 2008 Published by Elsevier B.V.

Patients with peripheral neuropathy frequently suffer from positive sensory (pain and paresthesias) and motor (muscle cramping) symptoms even in the recovery phase of the disease. To investigate the pathophysiology of increased axonal excitability in peripheral nerve regeneration, we assessed the temporal and spatial expression of voltage-gated Na+ channels as well as nodal persistent Na+ currents in a mouse model of Wallerian degeneration. Crushed sciatic nerves of 8-week-old C57/BL6J male mice underwent complete Wallerian degeneration at 1 week. Two weeks after crush, there was a prominent increase in the number of Na+ channel clusters per unit area, and binary or broad Na+ channel clusters were frequently found. Excess Na+ channel clusters were retained up to 20 weeks post-injury. Excitability testing using latent addition suggested that nodal persistent Na+ currents markedly increased beginning at week 3, and remained through week 10. These results suggest that axonal regeneration is associated with persistently increased axonal excitability resulting from increases in the number and conductance of Na+ channels.

POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome is a rare cause of demyelinating and axonal mixed neuropathy with multiorgan involvement. This syndrome is potentially fatal progressive neuropathy and/or massive peripheral edema or pleural effusion/ascites deteriorate patients' quality of life. Serious complications such as multiorgan failure due to capillary leak syndrome and thromboembolic events may occur, resulting in poor prognosis. The pathogenesis of POEMS syndrome is not well understood, but overproduction of vascular endothelial growth factor (VEGF), probably secreted by plasmacytoma, may be responsible for most of its characteristic symptoms. Many case reports and series have described patients who have been treated with irradiation, resection of plasmacytoma, chemotherapies, corticosteroids, plasmapheresis, and intravenous immunoglobulin infusion however, there is no established treatment regimen. In suitable cases, high-dose chemotherapies with autologous peripheral blood stem cell transplantation is highly recommended because this treatment could result in obvious improvement in neuropathy as well as other symptoms, with a significant decrease in the serum VEGF levels. However, from pooled data of published experience, the transplant-related mortality is reported is 5%. At present, indications of this treatment have not yet been established and long-term prognosis is unclear. Treatments with thalidomide or lenalidomide, and anti-VEGF monoclonal antibody (bevacizumab) should be considered as future therapies.

Objective: The aim of this study was to investigate changes in excitability properties associated with axonal regeneration in human neuropathy and a mouse Wallerian degeneration model. Methods: Threshold tracking was used to measure axonal excitability indices such as strength-duration time constant (SDTC), threshold electrotonus, supernormality in median motor axons at the wrist of 13 patients with vasculitic neuropathy in their recovery phase, and in tibial motor axons at the ankle of mice with sciatic nerve crush. In the mouse model, excitability testing was performed 4, 8, 12, and 20 weeks after the nerve crush. Results: In patients, there were longer SDTC, greater threshold changes at 0.2 ms in latent addition, and greater threshold changes in depolarizing and hyperpolarizing threshold electrotonus, compared with controls. The pattern of changes in excitability indices was similar to those in experimental nerve crush, in which the indices remained abnormal for 20 weeks after the crush. These changes suggest an increase in nodal persistent sodium currents, whereas multiple factors may also contribute to changes in excitability properties, such as axonal hyperpolarization, increased internodal resistance, and altered potassium currents. Conclusions: Excitability properties in regenerating axons are characterized by increased nodal persistent currents with variable combination of changes in passive properties, membrane potential, and potassium currents. Significance: Increased persistent sodium currents are potential reasons for positive symptoms in patients with,axonal neuropathy. Sodium channel blockers could be considered a treatment option. (c) 2008 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Twenty-eight patients suffered Campylobacter jejuni enteritis after eating raw chicken. Among them, only one patient developed Bickerstaff's brainstem encephalitis, who carried anti-GQ1b IgG antibodies. In contrast, none of the others did the autoantibodies. C. jejuni was cultured from all stool samples from five patients with enteritis alone. All the isolates had the same genotype, cst-II (Asn51), which are characteristic of strains isolated from Bickerstaff's brainstem encephalitis. These findings suggest that host susceptibility may play a role in inducing the production of anti-ganglioside antibodies and the development of Bickerstaff's brainstem encephalitis. (C) 2008 Elsevier B.V. All rights reserved.

NMO-IgG, a disease-specific autoantibody for neuromyelitis optica, recognizes aquaporin-4 (AQP4) and has been examined by indirect immunofluorescence assay. We developed an enzyme-linked immunosorbent assay (ELISA) to detect anti-AQP4 antibodies by establishing methods for expression in a baculovirus system and purification of recombinant AQP4 as antigen. Elevated anti-AQP4 antibody titers in serum were found in 15 (71%) of 21 patients with neuromyelitis optica, 4.3% of 46 patients with multiple sclerosis, none of 51 normal controls, and 2.6% of 115 patients with other neurological diseases. The ELISA system can be substituted for the conventional NMO-IgG assay. (C) 2008 Published by Elsevier B.V.

Whether Bickerstaff's brainstem encephalitis (BBE) is a distinct disease or a subtype of Fisher syndrome (FS) is unclear as there have been no clinical studies with sufficiently large numbers of patients with FS or BBE. Our aim was to clarify the nosological relationship. Medical records of patients suffering acute ophthalmoplegia and ataxia within four weeks of onset were reviewed. BBE was the diagnosis for patients with impaired consciousness, FS for those with clear consciousness and areflexia. Clinical features, neuroimages, and laboratory findings were analyzed. Patients were grouped as having BBE (n = 53), FS (n = 466), or as unclassified (n = 62). The BBE and FS groups had similar features; positive serum anti-GQ1b IgG antibody (68% versus 83%), antecedent Campylobacter jejuni infection (23% versus 21%), CSF albuminocytological dissociation (46% versus 76%), brain MRI abnormality (11% versus 2%), and abnormal EEG findings (57% versus 25%). BBE (n = 4) and FS (n = 28) subgroups underwent detailed electrophysiological testing. Both groups frequently showed absent soleus H-reflexes, but normal sensory nerve conduction (75% versus 74%) and a 1-Hz power spectrum peak on postural body sway analysis (67% versus 72%). Common autoantibodies, antecedent infections, and MRI and neurophysiological results found in this large study offer conclusive evidence that Bickerstaff's brainstem encephalitis and Fisher syndrome form a continuous spectrum with variable CNS and PNS involvement.

Previous studies suggest that in amyotrophic lateral sclerosis (ALS) the abductor pollicis brevis (APB) and first dorsal interosseous (FDI) are more severely involved than abductor digiti minimi (ADM). To elucidate the pattern, frequency, extent, and specificity of such dissociated muscle atrophy in ALS, compound muscle action potentials recorded from APB, FDI, and ADM were analyzed in 77 ALS patients, 171 normal controls, and 196 disease controls. Compared with normal controls, ALS patients had a reduced APB/ADM amplitude ratio (P < 0.001) and FDI/ADM ratio (P < 0.001), whereas patients with other anterior horn diseases showed similar APB/ADM and FDI/ADM ratios to normal values. Decreased APB/ADM ratio was found in 41% of ALS patients, 5% of normal controls, and 4% of disease controls. Prominent muscle atrophy in APB and FDI, with relatively preserved ADM, appears to be specific to ALS. Dissociated hand muscle atrophy presumably reflects part of the pathophysiology and supports the diagnosis of ALS.

We describe a patient with Huntington's disease (HD) who showed asymmetrical upper limb amyotrophy as a main manifestation. Chorea and psychiatric symptoms were not prominent. Electromyography revealed generalized active and chronic denervation and fasciculations. A genetic test showed 46 CAG repeats in the huntingtin gene. Asymmetrical amyotrophy restricted to the upper limb has been reported in some patients with progressive chorea and amyotrophy without acanthocytosis, but genetically proven cases of HD have rarely been reported. It is not known why only a few HD patients show the motor neuronal loss; however, certain as-yet-unidentified genetic factors combined with some environment factors and the underlying cellular dysfunctions by polyglutamine aggregation could be responsible for the motor neuronal loss similar to that in amyotrophic lateral sclerosis. (c) 2008 Movement Disorder Society.

Background POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome is a rare cause of demyelinating and axonal mixed neuropathy with multiorgan involvement and monoclonal plasma cell-proliferative disorder. The pathogenesis of POEMS syndrome is not well understood, but overproduction of vascular endothelial growth factor (VEGF), probably secreted by plasmacytomas, is likely to be responsible for most of the characteristic symptoms. POEMS syndrome is a potentially fatal disease, and patients' quality of life deteriorates because of progressive neuropathy, massive pleural effusion or ascites, or thromboembolic events. There is a need for efficacious therapy to improve prognosis. Objectives To provide the best available evidence from randomised controlled trials on treatment for POEMS syndrome. Search strategy We searched the Cochrane Neuromuscular Disease Group Trials Register (March 2008), MEDLINE (from January 1966 to March 2008), EMBASE ( from January 1980 to March 2008) and CINAHL (from January 1982 to March 2008) for randomized controlled trials, quasi-randomized trials, historically controlled studies, and trials with concurrent controls. We adapted this strategy to search MEDLINE from 1966 and EMBASE from 1980 for comparative cohort studies, case-control studies and trials, and case series. Selection criteria All randomized and quasi-randomized controlled trials, and non-randomized controlled studies were sought. Since we discovered no such clinical trials, we assessed and summarized all retrospective case series including five or more patients in the 'Discussion' section. Data collection and analysis Two authors independently reviewed and extracted details of all potentially relevant trials with any treatment for POEMS syndrome. We then collated and summarized information on the outcome. Main results We found no randomized or non-randomized prospective controlled trials of treatment for POEMS syndrome. We summarized the results of retrospective case series containing five or more patients in the Discussion section. Authors' conclusions There are no randomized or quasi-randomized controlled clinical trials of treatment for POEMS syndrome on which to base practice.

Objectives: This study aims to investigate whether thymectomy is beneficial for late-onset (>50 years) myasthenia gravis patients with no thymoma, particularly for those with mild generalized weakness. Patients and methods: A total of 34 patients were included in the study. The clinical course and long-term outcomes over 2 years were reviewed in 20 patients who underwent thymectomy and in 14 without. thymectomy. Results: Of the 34 patients, 20 (59%) underwent thymectomy. Thymectomized patients had more severe disability at entry than non-thymectomized patients, but outcome measures did not significantly differ between the two patient groups. Moreover, subgroup analyses including 22 patients with mild generalized weakness at entry showed that the thymectomized group (n = 10) showed a greater percentage of clinical remission (no symptoms; 50% versus 17%; p = 0.11) and a lower frequency of the presence of generalized symptoms (30% versus 75%; p<0.05) than the non-thymectomized group (n = 12) at the end of follow-up (means 9.6 years after onset). Conclusions: Thymectomy is a potentially effective treatment for late onset, non-thymomatous patients with mild generalized myasthenia gravis. (C) 2007 Elsevier B.V. All rights reserved.

Acute motor axonal neuropathy (AMAN), an axonal subtype of Guillain-Barre syndrome (GBS), is characterized by pure motor involvement, frequent antecedent infection by Campylobacter jejuni, association with anti-GM1 or anti-GD1a immunoglobulin G (IgG) antibodies, and the electrophysiological features of axonal degeneration and reversible conduction block. Molecular mimicry exists between GM1 and GD1a gangliosides and lipooligosaccharides (LOSs) of C. jejuni isolates from AMAN. Sensitization of rabbits with GM1 or C. jejuni LOS induces anti-GM1 IgG antibodies and subsequent flaccid paralysis. Pathological changes seen in rabbit model peripheral nerves are identical to those in human AMAN. Immunohistochemistry of AMAN rabbits shows disruption of nodal sodium channel clusters and detachment of paranodal myelin terminal loops, similar to paranodal demyelination, which would significantly reduce the safety factor for impulse transmission and might be responsible for the rapidly reversible conduction block frequently present in human AMAN. C. jejuni sialyltransferase (Cst-II), which functions in the biosynthesis of ganglioside-like LOSs, determines the transferase activity. Strains with cst-II (Thr51) express GM1 and GD1a epitopes, whereas GBS patients infected with cst-II (Thr51) strains have anti-GM1 or anti-GD1a IgG antibodies. The cst-II gene is responsible for the development of GBS. Immunological, pathological, electrophysiological, and bacteriological studies have provided strong evidence of carbohydrate mimicry being a cause of AMAN and clarified the mechanisms of nerve conduction failure in AMAN.

Anti-ganglioside GQ1b antibody induces neuromuscular blocking on mouse phrenic nerve-diaphragm preparations. Several reports suggest that patients with this antibody show abnormal neuromuscular transmission in the facial or limb muscles, but limb muscle weakness is unusual in Miller Fisher syndrome that is often associated with anti-GQ1b antibody. To determine whether anti-GQ1b sera affect neuromuscular transmission in human limb muscles, axonal-stimulating single fiber electromyography was performed in the forearm muscle of seven patients with anti-GQ1b antibody. All showed normal jitter and no blocking. Anti-GQ1b antibody does not affect neuromuscular transmission in human limb muscles. The different findings in mouse and human may be explained by the extent of expression of GQ1b on the motor nerve terminals in the muscle examined. (C) 2007 Elsevier B.V. All rights reserved.

Patients with acute motor axonal neuropathy (AMAN) generally recover well. We reviewed clinical and electrophysiologic recovery in 13 patients for up to 5 years. Twelve patients showed rapid recovery over 12 months, whereas in the remaining one the recovery was slow and incomplete at 5 years. In AMAN, axonal degeneration appears to develop predominantly in the motor nerve terminals, and only occasionally more proximally in the nerve roots. Nerve terminal degeneration-regeneration presumably provides a mechanism for good recovery.

Objective: Median-ulnar comparative studies (MUCS) play an important role in the electrodiagnosis of carpal tunnel syndrome, but in diabetes concomitant involvement of Guyon's canal (ulnar nerve compression at the wrist) would reduce the sensitivity of MUGS. This study tested the utility of median-radial comparative studies (MRCS) in diabetic patients. Methods: Anti-dromic MUCS and MRCS were prospectively performed in 120 patients with diabetes, and 64 normal controls. In 28 diabetic patients, latent addition using threshold tracking was performed in superficial radial sensory axons to estimate persistent nodal sodium currents. Results: MUCS was abnormal in 49% of the diabetic patients, and MRCS was abnormal in 58%. Median motor distal latencies were prolonged in 38%, and median sensory nerve conduction velocities were slowed in 40%. The longer latency differences in MRCS were associated with smaller persistent sodium currents, suggesting that intra-axonal sodium accumulation mediated by hyperglycemia enhances nerve compression. Conclusions: MRCS appears to be the most sensitive electrodiagnostic test in the detection of median neuropathy at the wrist in diabetic patients. Nerve conduction slowing across the carpal tunnel may be associated with metabolic abnormalities under hyperglycemia. Significance: Assessment of nerve conduction across the common entrapment sites could provide new insights into the pathophysiology of diabetic neuropathy related to metabolic factors. (C) 2007 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Objective: To investigate whether excitation-contraction (E-C) coupling of muscle is impaired in patients with myasthenia gravis (MG). Methods: In 51 patients with generalized MG and 35 normal subjects, compound muscle action potentials (CMAPs) of the abductor pollicis brevis, and movement-related potentials using an accelerometer placed at the thumb tip were simultaneously recorded after median nerve stimulation at the wrist. The E-C coupling time (ECCT) was estimated by a latency difference between CMAP and movement-related potential. Antibodies against acetylcholine receptor (AChR), ryanodine receptor (RyR), and muscle specific receptor tyrosine kinase (MuSK) were measured by immunoassays. Results: The mean ECCT was significantly longer in patients with MG (mean SEM; 2.79 +/- 0.1 ms; p = 0.002) than in normal controls (2.52 +/- 0.1 ms). Among MG patients, the mean ECCT was longer for patients with thymoma than for those without it (P = 0.04), and was shorter for patients treated with FK506 (an immunosuppressant and also an enhancer of RyR related Ca2+ release) than for those not receiving this treatment (p = 0.04). ECCT had no significant correlation with anti-AChR, anti-RyR, or anti-MuSK antibodies. Conclusions: In MG, E-C coupling appears to be impaired, particularly in patients with thymoma, and FK506 possibly facilitates E-C coupling. Significance: The functional implication of impaired E-C coupling is not established, but it may contribute to muscle weakness in patients with MG. (c) 2007 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Paranodal axo-glial junctions are important for ion channel clustering and rapid action potential propagation in myelinated nerve fibers. Paranode formation depends on the cell adhesion molecules neurofascin (NF) 155 in glia, and a Caspr and contactin heterodimer in axons. We found that antibody to ganglioside GM1 labels paranodal regions. Autoantibodies to the gangliosides GM1 and GD1a are thought to disrupt nodes of Ranvier in peripheral motor nerves and cause Guillain-Barre syndrome, an autoimmune neuropathy characterized by acute limb weakness. To elucidate ganglioside function at and near nodes of Ranvier, we examined nodes in mice lacking gangliosides including GM1 and GD1a. In both peripheral and central nervous systems, some paranodal loops failed to attach to the axo-lemma, and immunostaining of Caspr and NF155 was attenuated. K+ channels at juxtaparanodes were mislocalized to paranodes, and nodal Na+ channel clusters were broadened. Abnormal immunostaining at paranodes became more prominent with age. Moreover, the defects were more prevalent in ventral than dorsal roots, and less frequent in mutant mice lacking the b-series gangliosides but with excess GM1 and GD1a. Electrophysiological studies revealed nerve conduction slowing and reduced nodal Na+ current in mutant peripheral motor nerves. The amounts of Caspr and NF155 in low density, detergent insoluble membrane fractions were reduced in mutant brains. These results indicate that gangliosides are lipid raft components that contribute to stability and maintenance of neuron-glia interactions at paranodes. (c) 2007 Wiley-Liss, Inc.

We analyzed clinical recovery of 92 patients with Miller Fisher syndrome who had been treated with IV immunoglobulin (IVIg; n = 28), plasmapheresis (n = 23), and no immune treatment (n = 41). IVIg slightly hastened the amelioration of ophthalmoplegia and ataxia, but the times of the disappearances of those symptoms were similar among three groups. In Miller Fisher syndrome, IVIg and plasmapheresis seem not to have influenced patients' outcomes, presumably because of good natural recovery.

Objective: Previous axonal excitability studies suggest hyperkalemia or hypokalemia can significantly alter membrane potential and thereby, excitability properties. We studied whether physiological fluctuation of serum potassium levels affects axonal excitability in normal human axons. Methods: Threshold tracking was used to measure strength-duration properties, refractory periods, supernormality, and threshold electrotonus in median motor axons of 12 normal volunteers. In each subject, the excitability indices and serum potassium levels were measured three times (baseline, 2 h later, and 2 weeks later). Results: The pooled data (n = 36) showed significant correlation of the relative refractory period, supernormality, and depolarizing threshold electrotonus with potassium levels. Among each trial (12 subjects) the correlation did not reach statistical significance occasionally. Strength-duration properties, refractoriness, late subnormality, and hyperpolarizing threshold electrotonus were not significantly affected by serum potassium levels. Conclusions: Even in the normal range, serum potassium levels could slightly alter axonal excitability of human axons. Among excitability indices, the relative refractory period, supernormality, and threshold electrotonus are sensitive to potassium levels. Significance: Physiological fluctuation of serum potassium levels could partly be responsible for inter- and intra-subject variability of excitability indices. (c) 2006 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

The presence of antibodies against muscle-specific receptor tyrosine kinase (MuSK) appears to define a subgroup of patients with myasthenia gravis (MG) characterized by weakness predominant in bulbar, facial and neck muscles compared with anti-acetylcholine receptor (AChR) antibody-positive MG. To investigate the patterns and severity of neuromuscular transmission failure in different muscles in MuSK-positive MG, we performed single fiber electromyography (SFEMG) in the facial (frontalis) and limb (extensor digitorum communis, EDC) muscles in three anti-Musk-positive patients, and compared results with those of 11 anti-AChR-positive patients. Only one of the three MuSK-positive patients had abnormal jitter in EDC, but all the three showed clearly increased jitter in the frontalis. By contrast, the AChR-positive patients showed similarly abnormal jitter for the two muscles. These results suggest that when the diagnosis of anti-MuSK-positive MG is suspected, SFEMG should be performed in most prominently affected muscles.

We present the case of a 71-year-old woman with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome. Overproduction of vascular endothelial growth factor (VEGF), secreted by plasmacytoma, is considered responsible for the characteristic symptoms, and therefore anti-VEGF monoclonal antibody (bevacizumab) could be a therapeutic option. The patient was treated with bevacizumab 7 years after onset. Despite a dramatic decrease in serum VEGF levels, there was no clinical improvement, possibly because aberrant angiogenesis had already developed systemically. We suggest that careful consideration should be taken for indication of bevacizumab therapy, and this agent may be used in selected patients with a short duration POEMS syndrome.

Objective: To investigate the changes in nodal persistent Na+ currents in human neuropathy and motor neuron disease. In human motor axons, approximately 1.0% of total Na+ channels are active at rest, termed "persistent" Na+ channels, and the conductance can be noninvasively estimated by the technique of latent addition in vivo. Methods: Latent addition was performed in median motor axons of 93 patients with axonal neuropathy (n = 38), lower motor neuron disorder (LMND; n = 19) or amyotrophic lateral sclerosis (ALS; n = 36) and in 27 age-matched normal subjects. Brief hyperpolarizing conditioning current pulses were delivered, and threshold change at the conditioning-test interval of 0.2 ms was measured as an estimator of the magnitude of persistent Na+ currents. Threshold electrotonus and supernormality were also measured as indicators of resting membrane potential. Results: Threshold changes at 0.2ms were significantly greater in patients with neuropathy or LMND (p < 0.05), and tended to be greater in ALS patients (p = 0.075) than in normal controls. Threshold electrotonus and supernormality did not differ in each patient group and normal controls, suggesting that membrane potential is not altered in patients. In the recovery phase of axonal neuropathy, the threshold changes increased in parallel with an increase in amplitudes of compound muscle action potential. Conclusions: Persistent Na+ currents appear to increase commonly in disorders involving lower motor neurons, possibly associated with axonal regeneration or collateral sprouting or changes in Na+ channel gating. Significance: The increased axonal excitability could partly be responsible for positive motor symptoms such as muscle cramping frequently seen in lower motor neuron disorders. (c) 2006 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

In injured adult neurons, the process of axonal regrowth and reestablishment of the neuronal function have to be activated. We assessed in this study whether RhoA, a key regulator of neurite elongation, is activated after injury to the peripheral nervous system. RhoA is activated in motoneurons but not in Schwann cells after mouse sciatic nerve injury. To examine whether the activation of RhoA and its effector, Rho-kinase, retards axon regeneration of injured motoneurons, we employed a Rho-kinase inhibitor, fasudil. Amplitudes of distally evoked compound muscle action potentials are increased significantly faster after axonal injury in mice treated with fasudil compared with controls. Histological analysis shows that fasudil treatment increases the number of regenerating axons with large diameter, suggesting that axon maturation is facilitated by Rho-kinase inhibition. In addition, fasudil does not suppress the myelination of regenerating axons. These findings suggest that RhoA/Rho-kinase may be a practical molecular target to enhance axonal regeneration in human peripheral neuropathies.

The authors reported the neurological disease spectrum associated with autoantibodies against minor gangliosides GM1b and Ga1NAc-GD1a. IgG and IgM antibody reactivity against gangliosides GM1, GM2, GM1b, GDla, Ga1NAc-GD1a and GQ1b was investigated in sera from 7000 consecutive patients who had various neurological conditions. The clinical diagnoses for 456 anti-GM1b-positive patients were Guillain-Barre syndrome (GBS, 71%), atypical GBS with preserved deep tendon reflexes (12%), Fisher syndrome (10%), Bickerstaff's brainstem encephalitis (2%), ataxic GBS (2%) and acute ophthalmoparesis (1%). For 193 anti-GalNAc-GD I a-positive patients, the diagnoses were GBS (70%), atypical GBS (16%), Fisher syndrome (10%) and Bickerstaff's brainstem encephalitis (3%). Of the patients with GBS or atypical GBS, 28% of 381 anti-GM1b-positive and 31% of 166 anti-GalNAc-GD1a-positive patients had neither anti-GM1 nor anti-GDla antibodies. Of those patients with Fisher syndrome, Bickerstaff's brainstem encephalitis, ataxic GBS or acute ophthalmoparesis, 33% of 67 anti-GM1b-positive, and 52% of 25 anti-GalNAc-GD1a-positive patients had no anti-GQ1b antibodies. Autoantibodies against GM1b and GalNAc-GD1a are associated with GBS, Fisher syndrome and related conditions. These antibodies should provide useful serological markers for identifying patients who have atypical GBS with preserved deep tendon reflexes, ataxic GBS, Bickerstaff's brainstem encephalitis or acute ophthalmoparesis, especially for those who have no antibodies to GM 1, GD1a or GM1b. A method to prepare GM1b was developed. (c) 2006 Elsevier B.V. All rights reserved.

Objective: Previous axonal excitability studies in amyotrophic lateral sclerosis (ALS) have suggested that impaired potassium channel function could be responsible for the generation of fasciculations, but the ectopic activity arises predominantly from the motor nerve terminals. This study tested the hypothesis that dysfunction of potassium channels is more pronounced in the more distal parts of axons. Methods: Threshold electrotonus was used to compare accommodation at the motor point of abductor pollicis brevis, and at the wrist portion of the median nerve, between 22 patients with ALS and 19 normal subjects. As target responses for motor point stimulation, movement-related potentials were recorded using an accelerometer. Results: Compared to normal subjects, ALS patients showed greater threshold changes to depolarizing conditioning currents at both the motor point and wrist, suggesting less accommodation by potassium currents. Differences in the threshold electrotonus curves between the normal and ALS groups were much more prominent at the motor point than at the wrist. Conclusions: In ALS, axonal potassium channels are impaired more prominently in distal portions of axons than at the nerve trunk, and this is consistent with evidence that fasciculations mostly arise from the nerve terminals. Significance: Excitability testing at the motor point provides additional information about the pathophysiology of ALS. (c) 2006 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.