澁谷 和幹

Objective: To elucidate the features of sensory nerve involvement in Fisher syndrome (FS), this study extensively investigated sensory electrophysiology. Methods: In 47 consecutive FS patients, results of sensory nerve conduction studies in the median, ulnar and sural nerves, soleus H-reflexes, and median or tibial somatosensory-evoked potentials (SEP) were reviewed. Because of the large effects of age on amplitude of sensory nerve action potentials (SNAP), we strictly defined reduction of SNAP amplitudes by using a nomogram which age and amplitude obtained from 87normal subjects. Results: In routine nerve conduction studies, SNAP amplitude was reduced only in 32% of the patients, and conduction velocity was decreased in 2%. In contrast, soleus H-reflexes were frequently absent or reduced (67%). SEPs were abnormal only in 17%. Conclusions: In FS, absent soleus H-reflexes are the most frequent electrophysiologic abnormalities, whereas SNAPs amplitudes are rarely affected. The pattern is characterized by predominant involvement of group Ia afferents with relatively preserved cutaneous afferents without evidence suggestive of demyelination. Significance: The major targets of immune attack by anti-GQ1b antibodies in FS appear to be group Ia neurons in the dorsal root ganglia, and this is presumably responsible for ataxia and areflexia in FS. (C) 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is a multisystem disorder associated with plasma cell dyscrasia. Elevated serum levels of vascular endothelial growth factor (VEGF), which strongly promotes neovascularization and vasopermeability, are considered to be responsible for the characteristic symptoms such as angiomata, pleural effusion/ascites, edema, and organomegaly in the disorder. To study whether other angiogenetic factors are upregulated in POEMS syndrome, we measured serum levels of basic fibroblast growth factor and hepatocyte growth factor (HGF), as well as VEGF, in 17 patients with POEMS syndrome. All these factors were significantly upregulated in the POEMS syndrome patients. After the treatment with anti-VEGF antibody, the levels of HGF did not change, suggesting that elevation of HGF levels is not secondary to VEGF overproduction. These results suggest that different angiogenetic factors might contribute to the pathogenesis of POEMS syndrome, and this fact might contribute to the insufficient clinical effects obtained by suppression of VEGF alone.

Adult-onset Alexander disease (AOAD) has been increasingly recognized since the identification of the glial fibrillary acidic protein gene mutation in 2001. We report on a 56-year-old man who was genetically confirmed as AOAD with the glial fibrillary acidic protein mutation of p.M74T. He developed spastic tetraparesis, sensory disturbances in four limbs, and mild cognitive impairment without apparent dysarthria and dysphagia. The case was characterized by severe atrophy of the medulla oblongata and upper cervical cord with intramedullary signal intensity changes on magnetic resonance imaging. While AOAD is diverse in clinical presentation, the peculiar magnetic resonance imaging findings of marked atrophy of the medulla oblongata and cervical cord are thought to be highly suggestive of the diagnosis of AOAD.

Objective: To systematically study abnormalities in cytokine profiles in polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome, which has been increasingly recognized as a cause of demyelinating neuropathy associated with plasma cell dyscrasia and elevated serum level of vascular endothelial growth factor (VEGF). Methods: In this case-control study, we measured serum levels of 27 cytokines in patients with POEMS syndrome using a multiplex suspension array system, and compared them with those of controls. In 10 patients, serial changes after treatment were analyzed. Results: Interleukin (IL)-12 as well as VEGF levels were markedly increased (p < 0.0001) in all the patients (n = 23). Ten kinds of other proinflammatory cytokines such as IL-6 and tumor necrosis factor-alpha were also significantly increased in the POEMS syndrome group, but in some patients the serum levels of such cytokines remained within the normal ranges. After treatments, the IL-12 as well as VEGF levels significantly decreased with clinical improvements (p > 0.01 and p > 0.05, respectively). Conclusions: Our findings suggest that serum IL-12 is a biomarker of the disease activity in POEMS syndrome. The overproduction of IL-12, as well as VEGF, is likely to play an important role in the pathogenesis of the disorder, and could contribute to the peripheral nerve demyelination in POEMS syndrome. Neurology (R) 2012;79:575-582

Objective: The aim of this study was to investigate differences in excitability properties of human median and superficial radial sensory axons (e. g., axons innervating the glabrous and hairy skin in the hand). Previous studies have shown that excitability properties differ between motor and sensory axons, and even among sensory axons between median and sural sensory axons. Methods: In 21 healthy subjects, threshold tracking was used to examine excitability indices such as strength-duration time constant, threshold electrotonus, supernormality, and threshold change at the 0.2 ms inter-stimulus interval in latent addition. In addition, threshold changes induced by ischemia for 10 min were compared between median and superficial radial sensory axons. Results: Compared with radial sensory axons, median axons showed shorter strength-duration time constant, greater threshold changes in threshold electrotonus (fanning-out), greater supernormality, and smaller threshold changes in latent addition. Threshold changes in both during and after ischemia were greater for median axons. Conclusions: These findings suggest that membrane potential in human median sensory axons is more negative than in superficial radial axons, possibly due to greater activity of electrogenic Na+/K+ pump. These results may reflect adaptation to impulses load carried by median axons that would be far greater with a higher frequency. Significance: Biophysical properties are not identical in different human sensory axons, and therefore their responses to disease may differ. (C) 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Objective The aim of this study was to investigate whether axonal excitability indices are associated with survival in patients with amyotrophic lateral sclerosis (ALS). Previous nerve excitability studies suggested increased persistent sodium currents in motor axons of patients with ALS, which lead to axonal hyperexcitability and potentially enhance neuronal death. Methods 112 patients with sporadic ALS were followed up until endpoint (death or tracheostomy). Multivariate analyses were performed using the Cox proportional hazard model. Threshold tracking was used to measure multiple axonal excitability indices in median motor axons, such as strength-duration time constant (SDTC; a measure of nodal persistent sodium current). Latent addition was also used to estimate the magnitude of persistent sodium currents. Results The overall median tracheostomy-free survival from onset was 37 months. Prolonged SDTC was strongly associated with shorter survival (adjusted HR 4.07; 95% CI 1.7 to 9.8; p=0.0018) compared with older onset age (>60 years; HR=1.80) and bulbar onset (HR=1.80). Estimated median survival was 34 months in the longer SDTC group and 51 months in the shorter SDTC group. This index was highly statistically significant even after multiple testing adjustments with age and site of onset (bulbar or limb). Latent addition study results were consistent with these findings. Conclusions Axonal persistent sodium currents, estimated by SDTC and latent addition, are strong and independent predictors for shorter survival in patients with ALS. Membrane hyperexcitability is possibly associated with motor neuronal death, and modulation of excessive sodium currents could be a novel therapeutic option for ALS.

Background POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes) syndrome, a rare cause of demyelinating neuropathy associated with multiorgan involvement, has been increasingly recognised. Polyneuropathy is often an initial manifestation and therefore the disorder can be misdiagnosed as chronic inflammatory demyelinating polyneuropathy (CIDP). Objective To elucidate whether POEMS syndrome and CIDP are differentiated based on profiles of neuropathy. Methods Clinical and electrophysiological data were reviewed in consecutive POEMS syndrome (n=51) and typical CIDP (n=46) patients in a single Japanese hospital between 2000 and 2010. Results Both POEMS and CIDP patients showed symmetric polyneuropathy, physiological evidence of demyelination (70% of POEMS patients fulfilled the electrodiagnostic criteria for definite CIDP) and albuminocytological dissociation; 49% of the POEMS syndrome patients had neuropathy onset and 60% of them were initially diagnosed as having CIDP by neurologists. Clinically, POEMS neuropathy more frequently showed severe leg pain (76% vs 7%; p < 0.001), muscle atrophy (52% vs 24%; p=0.005) and distal dominant muscle weakness. Electrophysiologically, POEMS syndrome was characterised by less prolonged distal motor latency (mean 5.6 ms vs 8.1 ms; p < 0.001) and higher terminal latency index (0.42 vs 0.33; p=0.006) in the median nerves, and unrecordable tibial and sural responses (p < 0.001), suggesting demyelination predominant in the nerve trunk rather than in the distal nerve terminals, and axonal loss in the lower limb nerves. Conclusions Before development of typical systemic manifestations, POEMS neuropathy can be distinguished from CIDP by the clinical profile and patterns of nerve conduction abnormalities. Recognition of these features leads to early diagnosis and proper treatment for POEMS syndrome.

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease characterized by progressive motoneuron loss. Redistribution of transactive response deoxyribonucleic acid-binding protein 43 from the nucleus to the cytoplasm and the presence of cystatin C-positive Bunina bodies are considered pathological hallmarks of amyotrophic lateral sclerosis, but their significance has not been fully elucidated. Since all reported rodent transgenic models using wild-type transactive response deoxyribonucleic acid-binding protein 43 failed to recapitulate these features, we expected a species difference and aimed to make a non-human primate model of amyotrophic lateral sclerosis. We overexpressed wild-type human transactive response deoxyribonucleic acid-binding protein 43 in spinal cords of cynomolgus monkeys and rats by injecting adeno-associated virus vector into the cervical cord, and examined the phenotype using behavioural, electrophysiological, neuropathological and biochemical analyses. These monkeys developed progressive motor weakness and muscle atrophy with fasciculation in distal hand muscles first. They also showed regional cytoplasmic transactive response deoxyribonucleic acid-binding protein 43 mislocalization with loss of nuclear transactive response deoxyribonucleic acid-binding protein 43 staining in the lateral nuclear group of spinal cord innervating distal hand muscles and cystatin C-positive cytoplasmic aggregates, reminiscent of the spinal cord pathology of patients with amyotrophic lateral sclerosis. Transactive response deoxyribonucleic acid-binding protein 43 mislocalization was an early or presymptomatic event and was later associated with neuron loss. These findings suggest that the transactive response deoxyribonucleic acid-binding protein 43 mislocalization leads to alpha-motoneuron degeneration. Furthermore, truncation of transactive response deoxyribonucleic acid-binding protein 43 was not a prerequisite for motoneuronal degeneration, and phosphorylation of transactive response deoxyribonucleic acid-binding protein 43 occurred after degeneration had begun. In contrast, similarly prepared rat models expressed transactive response deoxyribonucleic acid-binding protein 43 only in the nucleus of motoneurons. There is thus a species difference in transactive response deoxyribonucleic acid-binding protein 43 pathology, and our monkey model recapitulates amyotrophic lateral sclerosis pathology to a greater extent than rodent models, providing a valuable tool for studying the pathogenesis of sporadic amyotrophic lateral sclerosis.

Objective: To assess whether Awaji criteria improve the sensitivity of diagnosis for amyotrophic lateral sclerosis (ALS). In Awaji ALS criteria, fasciculation potentials are regarded as evidence of acute denervation in the presence of chronic neurogenic changes on needle electromyography. Methods: We reviewed clinical and neurophysiological data of 113 consecutive patients who were suspected as suffering ALS. The six muscles (trapezius, biceps, first dorsal interosseous, T10-paraspinalis, vastus lateralis, and tibialis anterior muscles) were examined by EMG, focusing on the presence of fasciculation potentials. The sensitivity of revised El Escorial (R-EEC) and Awaji criteria was compared. Results: Probable or definite ALS was diagnosed in 61% of the patients by R-EEC and 71% by Awaji criteria. By applying Awaji criteria; (1) 17 of the 44 patients categorized as possible ALS by R-EEC reached to probable/definite ALS, 11 of whom had bulbar onset, (2) in 48 patients with bulbar onset, the proportion of probable/definite ALS increased from 59% to 82%, (3) in 62 patients with limb onset, the proportion of probable/definite ALS was 61% (63% by R-EEC). Conclusions: Awaji criteria improve the sensitivity of ALS diagnosis in patients with bulbar onset, but not in those with limb onset. Significance: Accepting fasciculation potentials as evidence of acute denervation increases the diagnostic sensitivity of ALS, particularly in patients with bulbar onset, and contributes to early diagnosis. (C) 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Objective: The aim of this study is to develop a novel method to assess activity-dependent hyperpolarization in human single motor axons at a constant stimulus frequency by using intra-muscular axonal stimulating single fiber electromyography (s-SFEMG). Methods: We performed s-SFEMG in the extensor digitorum communis (EDC) muscle of 10 normal subjects, and measured changes in latencies for single muscle fiber action potentials (MAPs) during 500 stimuli delivered at 5, 10 and 20 Hz. The data were analyzed with a repeated measurement analysis, and multiple comparisons were performed. Results: A total of 585 MAPs were examined at 5 Hz (n = 190), 10 Hz (n = 210), and 20 Hz (n = 185) steady stimulation. There was a progressive linear prolongation of latencies, as the stimulus rate increased (F = 95.6, p < 0.001); the least square means (SEM) of latency change were 100.7 (0.28)% at 5 Hz, 102.3 (0.27)% at 10 Hz and 105.3 (0.28)% at 20 Hz. There were statistically significant differences between frequencies by Tukey-Kramer's method. Despite the significant latency prolongation, no activity-dependent conduction block developed. A 20 Hz electric stimulation to intramuscular axons was well-tolerated in all the subjects. Conclusions: Tetanic stimulation at a constant rate results in significant latency increase in single human motor axons, the extent of which depends on the stimulus frequency. The findings imply that physiological discharge rates will activate the Na(+)/K(+) pump and thereby produce axonal hyperpolarization in single motor axons. Significance: This technique may detect activity-dependent conduction block if the safety margin of impulse transmission is significantly reduced by demyelination or increased branching due to collateral sprouting in a variety of neuromuscular disorders. (C) 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Fasciculations are characteristic features of amyotrophic lateral sclerosis (ALS), suggesting abnormally increased excitability of motor axons. Previous nerve excitability studies have shown reduced axonal potassium currents in ALS patients that may contribute to the hyperexcitability and thereby generation of fasciculations. To clarify changes in axonal ion channel expression in motor axons of ALS, we performed immunohistochemistry of potassium and sodium channels in the C7 and L5 ventral/dorsal roots obtained from five autopsy cases of sporadic ALS. Compared to controls, the immunoreactivity of potassium channels (Kv1.2) was markedly reduced in the ventral roots, but normal in the dorsal roots of all the ALS patients. Nodal sodium channel expression was not significantly different in ALS patients and control subjects. Our results show prominently reduced expression of axonal potassium channels, and provide the neuropathological and biological basis for decreased accommodative potassium currents in motor axons of ALS patients. The axonal hyperexcitability would lead to generation of fasciculations, and possibly enhances motor neuron death in ALS. (C) 2011 Elsevier Inc. All rights reserved.

Objectives: To study the utility of muscle ultrasound (US) for detection of fasciculations and its contribution to diagnosis in amyotrophic lateral sclerosis (ALS). Fasciculations are characteristic features of ALS, and US can detect them easily and reliably. New diagnostic criteria for ALS, the Awaji algorithm, reintroduced fasciculations as evidence of acute denervation equivalent to that of fibrillations and positive sharp waves. Methods: In 81 consecutive patients with sporadic ALS, we prospectively performed needle EMG and US in 6 muscles (tongue, biceps brachii, first dorsalis interosseous, paraspinalis, vastus lateralis, and tibialis anterior), and diagnostic category were determined by revised El Escorial criteria and Awaji criteria. Results: Fasciculations were much more frequently detected by US than by EMG in the tongue (60% vs 0%), biceps brachii (88% vs 60%), and tibialis anterior muscles (83% vs 45%). The proportion of the patients with definite or probable ALS was 48% by revised El Escorial criteria and 79% by Awaji criteria using US. Conclusions: Muscle US is a practical and efficient tool to detect fasciculations, particularly in the tongue. A combination of US and EMG substantially increases the diagnostic sensitivity of ALS. Neurology (R) 2011;77:1532-1537

TAR DNA binding protein of 43 kDa (TDP-43) is likely to be the major pathogenetic protein in amyotrophic lateral sclerosis (ALS). A previous study has shown that levels of TDP-43 in CSF measured by an ELISA are significantly higher for ALS patients than for controls. The aim of this study was to investigate whether elevated CSF TDP-43 levels are specific to ALS, and are associated with clinical profiles in ALS patients. We measured CSF TDP-43 levels by the same ELISA in 27 ALS patients and 50 neurodegenerative or inflammatory disease controls such as Parkinson's disease, multiple sclerosis, and Guillain-Barre, syndrome. Results showed that the CSF TDP-43 levels were increased only in ALS patients. Receiver operating characteristic (ROC) analyses showed a sensitivity of 59.3% and a specificity of 96.0%. We also found that lower CSF TDP-43 levels may be associated with shorter survival time. In conclusion, the CSF TDP-43 is a potential biomarker that supports a diagnosis of ALS. Moreover, among ALS patients, lower levels of CSF TDP-43 may reflect the accumulation of TDP-43 in the cortical and spinal motor neurons and thereby shorter survival time, although this should be confirmed in larger prospective studies.

Nerve conduction slowing in amyotrophic lateral sclerosis (ALS) is usually caused by loss of fast motor axons. We studied the frequency, extent, and distribution of prominently prolonged distal motor latencies in ALS. We reviewed results of median, ulnar, and tibial nerve conduction studies in 91 patients with ALS, 24 with lower motor neuron disorders, and 36 with axonal neuropathy. Coincidental carpal tunnel syndrome was found for 4 (4.4%) of the ALS patients who were excluded from analyses. Markedly prolonged distal latencies (>125% of the upper limit of normal) were found only in the median nerve of ALS patients (9%), and in none of the disease controls. Excitability studies suggested membrane depolarization in some ALS patients. Our results show that approximately 10% of ALS patients shows prominently prolonged median distal latency, which cannot be explained by axonal loss and carpal tunnel lesion. The distal nerve conduction slowing may partly be caused by membrane depolarization possibly due to motor neuronal degeneration in ALS. We suggest that recognition of the pattern of distal motor axonal dysfunction predominant in the median nerve is clinically important, and could provide additional insights into the pathophysiology of ALS. (C) 2010 Elsevier B.V. All rights reserved.

Objective: Juvenile muscular atrophy of distal upper extremity (Hirayama disease) is characterized by juvenile-onset of asymmetric amyotrophy, but the pathophysiology has not been fully clarified. "Cold paresis", aggravation of muscle weakness with exposure to cold, is a characteristic feature of this disease. The aim of this study was to investigate changes in axonal excitability properties in Hirayama disease. Methods: Threshold tracking was used to measure strength-duration time constant (SDTC), threshold electrotonus, refractoriness, and supernormality in median motor axons at the wrist of 14 patients and 10 age-matched normal controls. The measurements were performed at room temperature and after cooling. Results: Patients showed prolonged SDTC, fanning-out of threshold electrotonus curves, and increased refractoriness and supernormality. After cooling, there were similar changes in patients and normal subjects, compatible with axonal depolarization possibly due to paralysis of sodium-potassium pump. Conclusions: Motor axonal excitability in Hirayama disease were characterized by increased persistent sodium currents, and dysfunction of transient sodium and potassium channels possibly associated with prominent collateral sprouting in young individuals. Further studies will be required to elucidate mechanisms for cold paresis. Significance: Assessment of axonal excitability could provide characteristic features of ionic mechanisms in diseases with neurogenic amyotrophy such as Hirayama disease. (C) 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

慢性炎症性脱髄性多発ニューロパチー（CIDP）の臨床病型は近位筋と遠位筋が同様に障害される典型的CIDPと，遠位対称型（DADS）などの非典型的CIDPに分けられる．下肢遠位のしびれ感と脱力が緩徐に進行した治療抵抗性のDADS型CIDPの72歳男性例を報告する．発症4年目に近位筋をふくむ四肢筋力低下が急速に進行したが，プラスマフェレーシスにより著明に改善し，以後はステロイドにより寛解が維持できた．本例は当初DADS型の特徴を有していたが，経過中に典型的CIDPの病態が重層し，CIDPの病態の多様性を示唆すると考えられた．<br>

Objective To study the utility of CT for detection of small bone lesions in POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome. For patients with a solitary bone lesion, irradiation is a first-line treatment, whereas systemic chemotherapy is indicated for patients with multiple bone lesions. Therefore it is important to correctly identify the number of bone lesions. Methods We studied the sensitivity of chest/abdomen/pelvic CT to detect bone lesions in 28 patients with POEMS syndrome. 99mTc-HMDP bone scintigraphy was performed in 14 patients, and the results were compared with CT. Results CT showed multiple bone lesions in 68% of the 28 patients, and 71% of the lesions had a diameter &lt; 10 mm. In 14 patients who underwent both CT and scintigraphy, bone lesions were detected in 57% by CT and in 79% by scintigraphy, but the location and nature of the identified lesions were considerably different; CT frequently showed small lesions (diameter &lt; 10 mm) in the vertebrae and pelvis, which were not detected by scintigraphy, whereas scintigraphy could show lesions in the skull and long bones. Overall, by using both examinations, multiple bone lesions were found for 86% of patients. Conclusion CT is particularly useful to detect small bone lesions. CT and bone scintigraphy are complementary, and therefore both should be performed for bone survey in POEMS syndrome.

Objective: To investigate changes in axonal persistent Na(+) currents in patients with neuropathic pain and the effects of mexiletine, an analogue of lidocaine, on axonal excitability properties. Methods: The technique of latent addition was used to estimate nodal persistent Na(+) currents in superficial radial sensory axons of 17 patients with neuropathic pain/paresthesias before and after mexiletine treatment. Brief hyperpolarizing conditioning currents were delivered, and threshold change at the conditioning-test interval of 0.2 ms was measured as an indicator of the magnitude of persistent Na(+) currents. Results: Threshold changes at 0.2 ms in latent addition were greater in the neuropathic patients than in the normal controls (p &lt; 0.001). After mexiletine treatment, there was a reduction in clinical pain scores (p &lt; 0.001), associated with decreased threshold changes at 0.2 ms (p &lt; 0.001). Conclusions: In patients with neuropathy, nodal persistent Na(+) currents in large sensory fibers increase, and the abnormal currents can be suppressed by mexiletine. Pain reduction after mexiletine treatment raises the possibility that excessive Na(+) currents are also suppressed in small fibers mediating neuropathic pain. Significance: Latent addition can be used for indirect in vivo monitoring of nodal Na(+) currents in large sensory fibers, and future studies using this approach in small fibers would provide new insights into the peripheral mechanism of neuropathic pain. (C) 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Peripheral neuropathy is a rare manifestation of sarcoidosis, and previous studies have shown axonal degeneration as the main pathology. We herein report three patients with sarcoidosis who presented with multiple mononeuropathy as the initial manifestation. Nerve conduction studies showed prominent multifocal conduction blocks in the intermediate nerve trunk. In all three patients, corticosteroid treatment resulted in a dramatic clinical improvement associated with rapid resolution of conduction blocks. The sequential electrodiagnostic findings suggest that demyelinative or ischemic-functional conduction block is responsible for their neuropathy. To date, only three cases of acute conduction block neuropathy associated with sarcoidosis have been reported, but it may occur more frequently than expected.

Peripheral nerve injury alters function and expression of voltage gated Na(+) channels on the axolemma, leading to ectopic firing and neuropathic pain/paresthesia. Hyperglycemia also affects nodal Na(+) currents, presumably due to activation of polyol pathway and impaired Na(+)-K(+) pump. We investigated changes in nodal Na(+) currents in peripheral sensory axons and their relation with pain in human diabetic neuropathy. Latent addition using computerized threshold tracking was used to estimate nodal persistent Na(+) currents in radial sensory axons of 81 diabetic patients. Of these, 36 (44%) had chronic neuropathic pain and severe paresthesia. Compared to patients without pain, those with pain had greater nodal Na(+) currents (p = 0.001), smaller amplitudes of sensory nerve action potentials (SNAP) (p = 0.0003), and lower hemoglobin A1c levels (p = 0.006). Higher axonal Na(+) conductance was associated with smaller SNAP amplitudes (p = 0.03) and lower hemoglobin A1c levels (p = 0.008). These results suggest that development of neuropathic pain depends on axonal hyperexcitability due to increased nodal Na(+) currents associated with structural changes, but the currents could also be affected by the state of glycemic control. Our findings support the view that altered Na(+) channels could be responsible for neuropathic pain/paresthesia in diabetic neuropathy.

Objective: Previous studies have shown that age, gender, and body mass index (BMI) affect amplitude of sensory nerve action potentials (SNAP), but the total effects of multiple factors or the most prominently affected nerves have not been elucidated. This study systematically investigated effects of these factors. Methods: Amplitude of SNAP of the median, ulnar, superficial radial, superficial peroneal, and sural nerves was measured in 105 healthy subjects. The effects of age, gender, and BMI on each nerve were estimated by multivariate linear regression analysis. Results: SNAP amplitude decreased with age in all five nerves. Women had greater SNAP amplitude than men in the upper limb nerves (median, ulnar, and radial), but not in the lower limb nerves (peroneal and sural). Similarly, greater BMI was associated with smaller amplitudes in the upper limb nerves, but not in the lower limb nerves. Multivariate analyses showed the three factors explained 50% of the variation in the median nerve, 46% in the ulnar nerve, and 22-32% in the remaining nerves. Conclusions: The effects of age, gender, and BMI on SNAP amplitudes are not identical in different sensory nerves. Age was strongly correlated with SNAP amplitude in the nerves tested, whereas gender and BMI affect amplitudes only in the upper limb nerves. Significance: Age, gender, and BMI should be taken into account in clinical practice, but the extent of influence depends on the sensory nerves examined. (C) 2009 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

To assess the significance of distal compound muscle action potential (CMAP) duration for diagnosis of demyelinating neuropathies, electrophysiologic data were reviewed from 471 subjects, including 145 normal controls, 60 patients with chronic inflammatory demyelinating polyneuropathy (CIDP), 205 with other neuropathy, and 61 with amyotrophic lateral sclerosis (ALS). The duration of distally evoked CMAP was measured in the median, ulnar, tibial, and peroneal nerves. Optimal cut-off values were calculated with receiver-operating characteristic (ROC) curves. In comparison of normal controls and CIDP patients, ROC analyses showed the sufficient area under the curves (82-93%). When the cut-off values in the detection of demyelination were determined as the point with 98% specificity vs. normal on the ROC curves (median, 6.6 ms; ulnar, 6.7 ms; peroneal, 7.6 ms; tibial, 8.8 ms), the sensitivity was 77% for CIDP, with a specificity of 90% vs. ALS and 95% vs. diabetic neuropathy. The distal CMAP duration is a useful index for the detection of distal demyelination. We suggest the above cut-off values for each nerve as one of the electrodiagnostic criteria for demyelinating neuropathies, preferentially affecting the distal nerve terminals, such as CIDP.

Objective: The threshold tracking technique is a new approach to non-invasively assess biophysical properties of axonal membrane in human subjects. The aim of this study was to evaluate the effects of age and gender on excitability properties of human motor axons. Methods: Computerized threshold tracking was used to measure multiple excitability indices in median motor axons of 93 normal subjects (50 men; age, 20-86 years). Results: Regression analyses showed that the higher age was associated with longer strength-duration time constant (p = 0.03), smaller threshold changes in depolarizing threshold electrotonus (p = 0.02), smaller super-normality (p = 0.01), and steeper slope of the current-threshold relationship for hyperpolarizing currents (p &lt; 0.001). There were slight sex differences in rheobase, threshold electrotonus, supernormality, late subnormality, and current-threshold slope, though they were significant only in the subgroup with age &lt;50 years. Conclusions: Aging may increase persistent sodium cut-rents, inward rectification, and possibly, outward potassium currents. The combination of changes raises the possibility of slight membrane depolarization in elderly people. For the sex-related differences, further studies will be required with the evaluation of sex hormonal effects. Significance: Age-related effects on excitability properties are subtle, but should be taken into consideration in the clinical application of nerve excitability testing, particularly in elderly subjects. (c) 2008 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.

Cortical dysplasia has been increasingly recognized as a cause of epilepsy. We describe herein a 31-year-old female patient with epilepsia partialis continua (EPC) in the right extremities, which had lasted for 15 years without generalized seizures and other neurological deteriorations. MRI showed a focal thickening around the left motor area, indicative of cortical dysplasia, with adjacent subcortical abnormal T2 high intensity, suggestive of dysmyelination. Transcranial magnetic stimulation revealed low motor thresholds and markedly prolonged latencies of motor-evoked potentials (MEP) of the affected side, consistent with hyperexcitability of the cortical motoneurons accompanied by dysmyelination. This case demonstrates that motor cortex dysplasia can result in a mild and non-progressive form of epilepsia partialis continua, associated with the characteristic MRI and MEP abnormalities. (C) 2004 Elsevier B.V. All rights reserved.