桑原 聡

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.

Background: In diabetic nerves, activation of the polyol pathway via an aldose reductase and the resulting impairment of the Na+-K+ pump would lead to a decreased transaxonal Na+ gradient and thereby reduced nodal Na+ currents. Objective: To investigate whether the aldose reductase inhibitor (ARI) epalrestat improves nodal Na+ currents and nerve conduction in human diabetic neuropathy. Methods: The authors conducted a 6-month, open clinical trial with an ARI, epalrestat, in 30 patients with mild-to-moderate diabetic neuropathy. The latent addition technique and measurements of the strength-duration time constant were used to estimate nodal persistent Na+ currents in median motor axons. Excitability testing and extensive nerve conduction studies including F-wave analyses were performed before and 1 and 6 months after the initiation of treatment with oral epalrestat. Results: Within a month of the start of treatment, there was a significant improvement in nerve conduction, particularly in conduction times across the carpal tunnel and F-wave latencies. The results of latent addition (p < 0.05) and strength-duration time constant (p = 0.06) suggested increased nodal persistent Na+ currents. At 6 months, nerve conduction continued to improve. Conclusions: Aldose reductase pathway inhibition could rapidly increase nodal Na+ currents and thereby improve the slowing of nerve conduction, presumably because of a restoration of the membranous Na+ gradient.

Fasciculations are a characteristic feature of amyotrophic lateral sclerosis (ALS), and can arise proximally or distally in the motor neuron, indicating a widespread disturbance in membrane excitability. Previous studies of axonal excitability properties (i.e. threshold electrotonus, strength-duration time constant) have suggested respectively that change in potassium or sodium channels may be involved. To reinvestigate these changes and explore their correlation with disease stage, multiple axonal excitability properties (threshold electrotonus, strength-duration time constant, recovery cycle and current-threshold relationship) were measured for the median nerve at the wrist in 58 ALS patients, and compared with 25 age-matched controls. In ALS, there were greater changes in depolarizing threshold electrotonus (i.e. less accommodation) (P < 0.001) and greater supernormality in the recovery cycles (P < 0.001). These abnormalities were more prominent in patients with moderately reduced CMAP (1-5 mV). Modelling the excitability changes in this group supported the hypothesis that axonal potassium conductances are reduced, resulting in increased supernormality despite membrane depolarization. The tendency for strength-duration time constant to be prolonged in ALS was only significant for patients with normal CMAP amplitude (> 5 mV). Patients with severely reduced CMAP (< 1 mV) alone showed reduced threshold changes to hyperpolarizing current. These results suggest a changing pattern of abnormal membrane properties with disease progression. First, persistent Na+ conductance increases, possibly associated with collateral sprouting, and then K+ conductances decline. Both changes cause axonal hyperexcitability, and may contribute to the generation of fasciculations. These serial changes in axonal properties could provide insights into the pathophysiology of ALS, and implications for future therapeutic options.

Objective: To investigate the effects of hyperglycemia on persistent Na+ currents in human diabetic nerves. eliminating the factors of passive membrane properties as a factor. Previous studies show that strength-duration time constant of a nerve is shortened under hyperglycemia, suggesting reduced axonal persistent Na+ currents. However, the time constant is also affected by changes in passive membrane properties. Latent addition using computerized threshold tracking is a new method that can separately evaluate Na+ currents and passive membrane properties. Methods: Latent addition was used to estimate nodal Na+ currents in median motor axons of 83 diabetic patients. Brief hyperpolarizing conditioning current pulses were delivered, and threshold changes at the conditioning-test interval of 0.2 ms were measured as an indicator of nodal persistent Na+ currents. Seventeen patients were examined before and after insulin treatment. Results: There was an inverse linear relationship between hemoglobin A1c levels and threshold changes at 0.2 ms (P=0.02); the higher hemoglobin A1c levels were associated with smaller threshold changes. After insulin treatment. there was a significant improvement in nerve conduction velocities associated with greater threshold changes at 0.2 ms (P=0.03), suggesting an increase in persistent Na+ currents. The fast component of latent addition, an indicator of passive membrane properties, was not affected by the state of glycemic control. Conclusions: Hyperglycemia could suppress nodal persistent Na+ currents, presumably because of reduced trans-axonal Na+ gradient or impaired Na+ channels, and this can be rapidly restored by glycemic control. Significance: Reduced nodal Na+ currents may partly contribute to the pathophysiology of human diabetic neuropathy. (c) 2006 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Objective: To compare site-dependent changes across the carpal tunnel in axonal persistent Na+ conductances in motor and sensory axons. Positive sensory symptoms are prominent features in carpal tunnel syndrome, and a persistent Na+ current is a major determinant of axonal excitability. Methods: The technique of latent addition was used to estimate persistent Na+ currents in median motor and sensory axons at the wrist and palm of 10 normal subjects. Brief hyperpolatizing conditioning current pulses were delivered, and threshold change at the conditioning-test interval of 0.2 ms was measured as an indicator of persistent Na+ currents. Results: Threshold changes at 0.2 ms were greater in sensory than in motor axons at both the wrist and palm. In motor axons, the threshold changes were significantly smaller at the palm (mean, 4.9%) than at the wrist (10.0%). By contrast, the threshold changes were similar at the two sites of sensory axons (12.6 and 13.1%). The passive membrane time constant was similar for motor and sensory axons at the palm and wrist. Conclusions: Nodal persistent Na+ conductances have substantial site-dependent changes decreasing distally across the carpal tunnel in median motor axons, but not in sensory axons. Significance: Whereas sensory axons generally have higher excitability than motor axons, the sensory-motor differences become more prominent across, and possibly at the carpal tunnel than the nerve trunk, and it is suggested that this contributes to the predominance of positive sensory symptoms in carpal tunnel syndrome. (c) 2006 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Background: Adhesion molecules and matrix metalloproteinases. (MMPs) are known to be relevant to the ongoing development and disappearance of areas of demyelination in the white matter of the CNS of multiple sclerosis (MS) patients. This study examined whether serum matrix metalloproteinase-3 (MMP-3) levels correlate with disease activity in MS. Methods: Serum MMP-3 levels in 47 consecutive patients with relapsing-remitting MS were measured by immunoassay every A weeks over a 15 month period. Results: During the study period, 48 clinical relapses occurred. Serum MMP-3 levels within 1 month of relapse were significantly higher than during the remission phase. Sequential analysis showed that serum MMP-3 levels had increased transiently at the time of clinical relapse but returned to the normal range within a month. Conclusions: Circulatory MMP-3 levels are correlated with disease activity in relapsing-remitting MS. This may contribute to the breakdown of the blood-brain barrier at the time of relapse.

Objective: In patients with hemifacial spasm (HFS), abnormal muscle responses (AMR) are frequently present. The objective of this study was to investigate whether the afferent input of AMR is mediated by antidromic facial nerve stimulation or orthodromic trigeminal nerve stimulation. Methods: AMR in the orbicularis oris muscle were recorded in 28 patients with HFS. When AMR were present, they were recorded after subthreshold stimulation of the facial nerve and weak stimulation delivered to the skin. Results: AMR were recordable in 24 (86%) of the patients, and usually consisted of the early constant component (mean onset latency, 10.0 ms) and late variable component (35.3 ms), similar to R1 and R2 of the blink reflex. The early or late components of AMR, or both, were frequently elicited after subthreshold stimulation of the facial nerve (43%) and skin stimulation (88%). Conclusions: AMR are likely to be mediated by trigeminal afferent inputs, rather than antidromic activation of the facial nerve, and are a type of trigeminal reflex.

Guillain-Barre syndrome (GBS) is currently divided into acute inflammatory demyelinating polyneuropathy and acute motor axonal neuropathy (AMAN). Molecular mimicry of the bacterial lipo-oligosaccharide by the human gangliosides is now considered an important cause of AMAN. Gangliosides GM1, GM1b, GD1a, and GalNAc-GD1a are likely to be the epitopes in AMAN. These antibodies initially causes reversible conduction block followed by axonal degeneration. Glycolipids are important to maintain sodium channel clustering at the nodes and tight axo-glial junction at the paranode. Disruption of axonal membrane at or near the node would result in reduced sodium currents, and loosening of the paranodal axo-glial junction leads to paranodal myelin detachment (a type of paranodal demyelination). These changes would cause nerve conduction block in AMAN.

To investigate whether thymectomy is beneficial for non-thymomatous myasthenia gravis patients with mild generalized weakness and onset age >50 years, clinical course and outcomes were compared between 10 patients receiving thymectomy and 12 without it. At the end of follow-up (mean 9.6 years after onset), the thymectomized group showed the greater percentage of clinical remission (no symptoms with or without medication; 50% versus 17%; p=0.11), and the less frequency of the presence of generalized symptoms (30% versus 75%; p<0.05). Thymectomy appears to be effective for late onset, non-thymomatous patients with generalized myasthenia gravis.

We describe a 50-year-old woman who developed chronic inflammatory demyelinating polyneuropathy ( CIDP) one year after onset of hemochromatosis. Electrodiagnostic studies showed evidence of multifocal demyelination. Marked hypergammaglobulinemia with positive anti-nuclear and anti-DNA antibodies was found. Corticosteroid treatment resulted in a significant lessening of neurological symptoms. This is the first case of CIDP with hemochromatosis. The association may be coincidental, but the altered immune system by hemochromatosis was possibly related to the development of CIDP in this patient.

Background: Little is known about long term prognosis and course after immune treatments in chronic inflammatory demyelinating polyneuropathy ( CIDP). Objective: To study long term outcomes and prognostic factors in patients with CIDP. Methods: Clinical and electrophysiological findings, responses to immune modulating treatments, and outcomes five years after the start of treatment were reviewed in 38 CIDP patients. Results: Patients were treated with corticosteroids (89%), immunoglobulin infusion (45%), or plasmapheresis (34%), and 58% received combined therapy. Five years after treatment was begun, 10 (26%) of the patients had complete remission ( lasting >2 years with normal nerve conduction studies), and 23 (61%) had partial remission ( able to walk) with ( 26%) or without ( 34%) immune treatments. The remaining five patients (13%) still had severe disability ( unable to walk) or treatment dependent relapses. Patients with complete remission more often had subacute onset, symmetrical symptoms, good response to initial corticosteroid treatment, and nerve conduction abnormalities predominant in the distal nerve terminals. In contrast, insidious onset, asymmetrical symptoms, and electrophysiological evidence of demyelination in the intermediate nerve segments were associated with refractoriness to treatment or treatment dependent relapse. Conclusions: The long term prognosis of CIDP patients was generally favourable, but 39% of patients still required immune treatments and 13% had severe disabilities. Mode of onset, distribution of symptoms, and electrophysiological characteristics may be prognostic factors for predicting a favourable outcome.

Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes syndrome is a rare multisystem disorder. Overproduction of vascular endothelial growth factor (VEGF) by plasmocytoma could be responsible for the symptoms. The authors treated four patients with high-dose chemotherapy and autologous peripheral blood stem cell transplantation. Within 6 months, symptoms associated with rapid normalization of serum VEGF levels improved.

Objective: The pattern of abnormal median-normal sural sensory nerve action potential (SNAP) is frequently found in acute/chronic inflammatory demyelinating polyneuropathy (AIDP/CIDP), whereas sural/radial SNAP amplitude ratio is sensitive to detect dying-back degeneration. To investigate whether radial SNAP and its amplitude ratio to median or sural SNAP provide additional particular patterns of sensory nerve involvement. Methods: Superficial radial, median, and sural SNAPs were recorded in 63 normal subjects and in 132 patients with AIDP/CIDP (n=22), diabetic neuropathy (n=83), or other axonal polyneuropathy (n=27). Median/radial and sural/radial amplitude ratios were examined. Results: In normal subjects, median/radial ratio was 0.96 +/- 0.05 (mean +/- SEM), and sural/radial ratio was 0.50 +/- 0.03. Compared with normal controls, the median/radial ratio was lower in patients with AIDR/CIDP (0.64 +/- 0.11; P < 0.001) or diabetic neuropathy (0.75 +/- 0.04; P=0.08), but similar in those with other neuropathy (0.94 +/- 0. 10). The sural/radial ratio was higher in the AIDP/CIDP group (0.71 +/- 0.08; P=0.10), and lower in the diabetic (0.36 +/- 0.03; P < 0.001) and other axonal neuropathy groups (0.40 +/- 0.07; P=0.08). Conclusions: AIDP/CIDP is associated with a reduced median/radial ratio and increased sural/radial ratio, probably reflecting demyelination predominant in the distal nerve terminals. Diabetic neuropathy is characterized by decreases in both median/radial and sural/radial ratios, presumably due to coexistence of carpal tunnel pathology and dying-back degeneration. Significance: Comparison of multiple SNAP amplitudes provides information about characteristic distribution patterns of sensory nerve involvement in peripheral neuropathies. (c) 2005 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

The potential therapeutic role of repetitive transcranial magnetic stimulation (rTMS) in epilepsy has been increasingly recognized. We investigated the effects of low-frequency rTMS in a patient with epilepsia partialis continua (EPC) due to cortical dysplasia. A 31-year-old female patient experienced EPC in the right upper and lower extremities, which had lasted for 15 years without generalized seizures. MRI showed focal megaencephaly around the motor cortex suggestive of cortical dysplasia. A figure of eight magnetic coil was placed over the hand motor area, and 100 stimuli with an intensity at 90% of motor threshold were given at 0.5 Hz. Immediately after rTMS, EPC was nearly abolished. The effects had continued approximately for 2 months, and the second trial resulted in the similar effects and time-course. Low-frequency rTMS was safe and well tolerated in this patient. These findings support the concept that rTMS decreases cortical excitability, and may be an effective treatment for focal partial seizures. (c) 2005 Elsevier B.V. All rights reserved.

Objective: To investigate the effects of hyperglycemia on axonal excitability and potassium conductance in human diabetic nerves. Methods: Threshold tracking was used to measure excitability indices, which depend on potassium channels (supernormality, late subnormality, threshold electrotonus, and a current/threshold relationship) in median motor axons of 96 diabetic patients. The effects of hyperglycemia on these indices were analyzed. Results: Among diabetic patients, higher serum hemoglobin Ale (HbA1c) levels were significantly associated with greater supernormality (P=0.04) and smaller late subnormality (P=0.02), suggestive of reduced nodal/paranodal potassium currents under hyperglycemia. Threshold electrotonus and current/threshold relationships did not correlate with HbA1c levels, but partly related with nerve conduction slowing. Conclusions: Hyperglycemia could reduce nodal potassium conductances, possibly due to reduced membranous potassium gradient or suppression of potassium channels. In contrast, internodal potassium conductances may be determined by both metabolic factors and structural changes such as exposure of internodal channels by demyelination. Significance: Measurements of the excitability indices could provide new insights into nodal and internodal axonal membrane properties in human diabetic neuropathy, whereas multiple factors can affect especially internodal properties. © 2005 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All fights reserved.

Background: Little is known about the long term prognosis for patients the severe acute motor axonal neuropathy (AMAN) form of Guillain-Barre syndrome (GBS), unlike those with acute inflammatory demyelinating neuropathy (AIDP). Objective: To clarify the long term prognosis for patients with AMAN. Methods: Clinical recovery and outcome in 97 consecutive GBS patients were reviewed. Results: Electrodiagnostic criteria showed that 44 patients (45%) had AMAN, 33 (34%) had AIDP, and 20 (21%) were unclassified. Most of the severely affected patients had received plasmapheresis or immunoglobulin therapy. Slow recovery (inability to walk independently at six months after onset) was found in six of the AMAN patients (14%) and in two of the AIDP patients (6%). Of the six AMAN patients, four could walk independently one year after the onset, and the other two could walk independently at 28 and 57 months after onset. Of the two AIDP patients, one could walk at nine months after the onset while the other died of pneumonia seven months after onset. Conclusions: AMAN electrodiagnosis is not always a marker of poor recovery. Almost all the severe AMAN patients who had slow recoveries over the first six months could eventually walk independently, although some required several years.

Objectives: To compare the clinical and electrophysiological features of myasthenia gravis (MG) patients with (seropositive) or without (seronegative) antibodies to acetylcholine receptor. To investigate whether antibodies to muscle specific kinase (MuSK) and ryanodine receptor (RyR) are associated with particular features. Methods: Clinical profiles and single fibre electromyography (SFEMG) in the extensor digitorum communis (EDC) were reviewed in consecutive 57 seropositive and 13 seronegative patients. Antibodies to MuSK and RyR were measured by immunoassays. Results: Of the 13 seronegative patients, four (31%) were positive for MuSK antibodies and seven (54%) were positive for RyR antibodies, including all four MuSK positive patients. Clinical features were similar at presentation for seropositive and seronegative patients, but MuSK positive patients frequently developed myasthenic crises. Despite the similar clinical severities at the time of examination, the proportion with positive jitter (93% of seropositive patients, 50% of MuSK positive patients, and 44% of MuSK negative patients) and the extent of jitter (mean consecutive difference: 76 mu s in seropositive patients, 36 ms in MuSK positive patients, and 30 ms in MuSK negative patients) were less in seronegative MG patients compared with seropositive MG patients. Conclusions: Seronegative MG is heterogeneous with respect to the presence of antibodies to MuSK. Impairment of neuromuscular synaptic transmission in EDC is less marked in seronegative than seropositive MG despite the similar clinical severity. This discrepancy may partly reflect the distribution of affected muscles in seronegative patients, but it is possible that other factors, such as impaired excitation-contraction coupling resulting from RyR antibodies, contribute to the clinical phenotype.

Putaminal hemorrhage presenting pure sensory stroke is rare. We describe a case of left putaminal hemorrhage presenting contralateral hemisensory disturbance without hemiparesis. A 52-year-old man developed analgesia and thermoanesthesia in the right half of his body, but deep sensation was relatively well preserved. Neuroradiological and somatosensory evoked potential findings suggested that thalamocortical sensory pathways to the secondary somatosensory cortex (S2) were involved, whereas those to the primary somatosensory cortex (S1) were spared. In experimental animals, spinothalamic projections from the thalamic nucleus input directly to S2. In humans, thalamocortical pathways are still a subject of debate, but results of recent functional imaging studies suggest that the pathway of pain inputs directly to S2 and that of tactile sensation to S2 via S1. Our findings support these reports. (c) 2004 Elsevier B.V. All rights reserved.

Background: In Guillain-Barré syndrome (GBS), anti-ganglioside antibodies are strongly associated with the acute motor axonal neuropathy (AMAN) form, but there are also cases of the demyelinating form of GBS (acute inflammatory demyelinating polyneuropathy [AIDP]) with anti-ganglioside antibodies. Objective: To elucidate the patterns and sequential changes in electrodiagnostic abnormalities of anti-ganglioside-positive GBS. Methods: Detailed serial electrodiagnostic findings were reviewed for 51 patients with GBS. Anti-ganglioside antibodies were measured by ELISA. Results: Antibodies to GM1, GM1b, GD1a, or GalNAc-GD1a were present in 25 patients. Of these, 12 (48%) showed the AMAN pattern, 5 (20%) the AIDP pattern, and 3 (12%) isolated F-wave absence in the first examination. All five patients with the AIDP pattern showed prolonged distal latencies, but three eventually showed the AMAN pattern or rapid normalization. The remaining two still had similarly prolonged distal latencies in weeks 4 to 6, but the serial changes were distinct from those in the anti-ganglioside-negative AIDP patients who showed progressive increases in distal latencies over 2 months after onset. Conclusions: Besides the simple axonal degeneration pattern, patients with anti-ganglioside-positive Guillain-Barré syndrome can show transient conduction slowing/block in the distal or proximal nerve segments, mimicking demyelination, but anti-ganglioside antibodies do not appear to be associated with acute inflammatory demyelinating polyneuropathy. Copyright © 2005 by AAN Enterprises, Inc.

Objective: To investigate the influences of hyperglycemia on axonal excitability in human diabetic nerves. Hyperglycemia results in decreased Na+-K+ pump function, presumably leading to intra-axonal Na+ accumulation and thereby, reduced Na+ currents. Methods: The strength-duration time constant (tau(SD)), which partly depends on persistent Na+ conductance active at the resting membrane potential, was measured in median motor axons of 79 diabetic patients. The relationship of tau(SD) with the state of glycemic control (hemoglobin A1c [HbA1c] levels) was analyzed. Results: The mean tau(SD) was longer for diabetic patients than for normal controls, but the difference was not significant. Among diabetic patients, the subgroup of patients with good glycemic control (HbA1c < 7%) had significantly longer tau(SD) than the patient group with poor control (HbA1c > 9%; P = 0.04). The mean tau(SD) was longest at the HbA1c level of 5-6%, gradually decreasing and reaching a plateau around the HbA1c level of 9%. There was an inverse relationship between HbA1c levels and tau(SD), when the HbA1c levels ranged from 5 to 9% (P 0.04). Conclusions: In diabetic nerves, tau(SD) is generally longer than normal, but hyperglycemia is associated with paradoxically shortened tau(SD), gradient, tissue acidosis, or other because of a decrease in axonal persistent Na+ conductance, possibly related to reduced membranous Na+, metabolic factors. Significance: Measurements of tau(SD) could provide a new insight into changes in ionic conductance in human diabetic nerves. (C) 2004 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Objective: To investigate acute changes in nerve conduction associated with glycemic control. In diabetes, nerve dysfunction can result from reversible metabolic factors associated with hyperglycemia, as well as structural changes. Methods: Multiple nerve conduction parameters including F-wave latencies were measured in 47 diabetic patients with prominent hyperglycemia before and after intensive insulin treatment. Results: Four weeks after the start of treatment, there was a significant improvement in minimal F-wave latencies of the median (P < 0.001) and tibial (P < 0.001) nerves, and in distal latencies (P=0.01) and sensory nerve conduction velocities (P < 0.001) of the median nerves. Amplitudes of motor and sensory responses did not change significantly. These findings were similar for patients with type 1 (n = 8) and those with type 2 (n = 39) diabetes. Patients with poorer glycemic control or milder neuropathy tended to show greater changes after treatment. Conclusions: Glycemic control quickly alters the speed of nerve conduction. F-wave latencies and conduction times across the carpal tunnel are very sensitive parameters. Significance: Serial nerve conduction studies can detect reversible slowing of nerve conduction presumably caused by metabolic factors, such as decreased Na+/K+-ATPase activity, the altered polyol pathway, and tissue acidosis. (C) 2004 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Objective: To investigate the effects of mexiletine, an analog of lidocaine, on excitability of human axons in vivo. Methods: Threshold tracking was used to measure multiple excitability indices (strength-duration time constant, rheobase, refractoriness, supernormality, and threshold electrotonus) in median motor axons of 20 patients with neuropathic pain or muscle cramping, before and 3 months after treatment with oral 300 mg mexiletine per day. Results: After treatment, there was a reduction in pain/muscle cramps, associated with decreased strength-duration time constants (P=0.01), increased rheobasic currents (P=0.06), and lower refractoriness (P=0.02), all of which were consistent with reduced nodal Na+ currents. Supernormality and threshold electrotonus did not change significantly. The changes in strength-duration properties suggest a decrease in persistent Na+ conductance. The lowered refractoriness after treatment might result from reduced transient Na+ currents, but the lack of change in supernormality and threshold electrotonus was not consistent with this hypothesis. Conclusions: Oral mexiletine in a dosage of 300 mg daily suppresses persistent Na+ currents in human motor axons. Significance: Measurements of the excitability indices can be used for non-invasive assessment and monitoring of the effects of mexiletine in patients with neuropathic pain or muscle cramps. (C) 2004 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.