桑原 聡

Background: Callosal lesions in multiple sclerosis (MS) are usually focal, involving the inferior aspect of the corpus callosum on brain magnetic resonance imaging (MRI), but little is known about callosal lesions in neuromyelitis optica (NMO). Objective: To clarify MRI abnormalities in callosal lesions of NMO. Methods: Japanese patients with NMO (n=28) or MS (n=22) were assessed. The distributions and appearances of callosal lesions were evaluated on a brain mid-sagittal T2-weighted image (T2WI) or a fluid-attenuated inversion recovery image with a I.5T MRI scanner. Logistic regression analysis identified which characteristics of the callosal lesions were useful for discriminating NMO from MS. Results: Callosal lesions were present in 79% of NMO and 82% of MS patients. Callosal abnormalities of NMO, including splenial lesions (57% in NMO versus 27% in MS, odds ratio (OR)=4.23, p=0.04), diffusely spreading lesions from the lower to upper edges of the corpus callosum (71% versus 23%, 0R=7.18, p=0.0024), and heterogeneous T2 hyperintense lesions (71% versus 9%, 0R=44.3, p=0.0006), were feasible for discriminating NMO from MS. Conclusion: Diffuse and heterogeneous T2 hyperintense splenial lesions were characteristic of NMO. These findings could help distinguish NMO from MS on MRI.

Postprandial hypotension (PPH) is a major clinical problem in patients with autonomic failure such as that observed in multiple system atrophy (MSA). The pathophysiology of PPH remains unclear, although autonomic dysfunction and gastrointestinal vasoactive peptides have been suspected to participate in its pathogenesis. We measured blood pressure and plasma levels of glucose, insulin, noradrenaline, neurotensin, glucagon-like peptide (GLP)-1 and GLP-2 before and after meal ingestion in 24 patients with MSA to reveal the roles of the autonomic nervous system and gastrointestinal vasoactive peptides in PPH. We performed a second meal-ingestion test by administering acarbose to evaluate the effects of acarbose (an alpha-glucosidase inhibitor) on PPH and vasoactive peptides in 14 patients with MSA and PPH. We also evaluated blood pressure responses to the head-up tilt test and heart rate variability in all the patients. Severities of PPH and orthostatic hypotension were significantly correlated. Patients with PPH had significantly worse orthostatic hypotension and lower heart rate variability than those without PPH. Postprandial GLP-1 secretion was higher in patients with PPH than in those without PPH. No significant differences were observed in the postprandial increases in plasma levels of glucose, insulin, noradrenaline, neurotensin or GLP-2. Acarbose significantly attenuated postprandial hypotension and tended to decrease GLP-2 secretion. Our results indicate that autonomic failure is involved in the pathogenesis of PPH and confirm that acarbose has a preventive effect against PPH in patients with MSA. Decreased postprandial secretion of GLP-2, which increases intestinal blood pooling, may attenuate PPH in patients with MSA.

STUDY DESIGN.: Retrospective clinical study. OBJECTIVE.: To report the surgical outcomes of patients with cervical myelopathy associated with athetoid cerebral palsy and to assess whether a halo vest is necessary for postoperative external immobilization. SUMMARY OF BACKGROUND DATA.: Although a halo vest has remained the first choice for postoperative external immobilization of patients with cervical myelopathy associated with cerebral palsy, simplification of this method has been attempted in recent years. Studies focusing on postoperative external immobilization are rare. METHODS.: Since 2001, 20 patients underwent surgery with posterior instrumented fusion or posterior fixation and anterior decompression with fusion with a year or longer follow-up. Before 2004, all patients were given a halo vest for postoperative external immobilization. After 2004, halo vests were not used, and when abnormal involuntary neck movements were severe, an intramuscular injection of botulinum toxin was administered before and after surgery. Surgical outcomes, surgical methods and complications were compared between the group that used a halo vest and the group that did not use a halo vest. RESULTS.: In the halo vest group, the average Japanese Orthopedic Association score was 6.9 points before surgery and 9.3 points at 1-year follow-up. The average recovery rate was 25.0%. In the group without halo vest use, the average Japanese Orthopedic Association score was 5.8 points before surgery and 9.9 points at 1-year follow-up. The average recovery rate was 35.7%. The group without halo vest use achieved outcomes equal to those achieved in the group with halo vest use. The frequency of complications was less without halo vest use than with halo vest use. CONCLUSION.: No inferiority in clinical outcomes was seen if postoperative halo vest use was omitted. Progress in surgical instrumentation and injection of botulinum toxin may explain this result. © 2013, Lippincott Williams &amp Wilkins.

Background A GGGGCC hexanucleotide repeat expansion in C9ORF72 occurs on a chromosome 9p21 locus that is linked with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) in white populations. The diseases resulting from this expansion are referred to as 'c9FTD/ALS'. It has been suggested that c9FTD/ALS arose from a single founder. However, the existence of c9FTD/ALS in non-white populations has not been evaluated. Results We found two index familial ALS (FALS) patients with c9FTD/ALS in the Japanese population. The frequency of c9FTD/ALS was 3.4% (2/58 cases) in FALS. No patients with sporadic ALS (n=110) or control individuals (n=180) had the expansion. Neuropathological findings of an autopsy case were indistinguishable from those of white patients. Although the frequency of risk alleles identified in white subjects is low in Japanese, one patient had all 20 risk alleles and the other had all but one. The estimated haplotype indicated that the repeat expansion in these patients was located on the chromosome with the risk haplotype identified in white subjects. Conclusions C9ORF72 repeat expansions were present in a Japanese cohort of ALS patients, but they were rare. Intriguingly, Japanese patients appear to carry the same risk haplotype identified in white populations.

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.

Pseudoperipheral palsy can be caused by cerebral cortical infarctions; however, it is rarely caused by lacunar infarctions, including those in the posterior limb of the internal capsule. Meanwhile, the somatotopic localization of the corticospinal tract in the posterior limb of the internal capsule remains unknown. We herein report the case of an 81-year-old Japanese woman who presented with a left hand drop. Brain magnetic resonance imaging revealed an acute infarction as the causative lesion at the inferior level of the anteromedial portion of the posterior limb of the right internal capsule. This case report indicates the topography of hand fibers in the internal capsule.

Objective The autoimmune mechanism is considered to play an important role in the development of acquired idiopathic generalized anhidrosis (AIGA), and muscarinic M3 receptors (M3Rs) on eccrine glands are possible autoimmune targets. We investigated the existence of autoantibodies against M3Rs in AIGA patients. Methods We immunostained M3R-expressing cultured cells with the serum of 12 AIGA patients (mean age: 35.0 +/- 11.7 years, mean disease duration: 26.6 +/- 25.8 months) and 10 healthy subjects (mean age: 32.4 +/- 10.4 years). Results The surface of the M3R-expressing cells was stained by the serum obtained from one of the 12 AIGA patients but not by the serum obtained from the remaining 11 patients or healthy subjects. Conclusion The presence of M3R autoantibodies may therefore be related to the underlying mechanism of disease in a subset of AIGA patients.

Objective: To study dynamic postural balance for Parkinson's disease patients, axial mobility and center of foot pressure (COP) were recorded simultaneously during movements of a head or chest. Materials and Methods: Fifteen patients with treated Parkinson's disease and age matched 15 volunteers with no neurological disease participated in this study. Head movements were monitored with a gyroscope on the head, and COP was monitored on a force platform. The subjects were standing upright on the platform and they were asked to rotate the head only alternatively repetitively, and then asked to rotate the chest and head synchronized alternatively repetitively. Both movements were asked to do at own pace for 20 sec, respectively, gazing at a cue synchronized to the head movements. Results: Head angular velocity showed significant differences for ratios of the peak power of the power spectra by the integrated power without the peak power between groups with PD and of volunteers (P &lt 0.0001), and between movements with the head only and with the head-thorax synchronized (P &lt 0.05). COP showed significant differences for the integrated power between groups with PD and of volunteers (P &lt 0.0001) and between movements with the head only and with the head-thorax synchronized (P &lt 0.0001). Conclusion: This simple and useful measurement might give numerical evaluation of axial rigidity for Parkinson's disease patients. © 2013 Japan International Cultural Exchange Foundation &amp Japan Health Sciences University.

Fisher syndrome has been regarded peculiar inflammatory neuropathy with ophthalmoplegia, ataxia, and areflexia, whereas Bickerstaff brainstem encephalitis has been considered pure central nervous system disease characterized with ophthalmoplegia, ataxia, and consciousness disturbance. Both disorder share common features including preceding infection, albumin-cytological dissociation, and association with Guillain-Barre syndrome. The discovery of anti-GQ1b IgG antibodies further supports the view that the two disorder represent a single disease spectrum. Currently Bickerstaff brainstem encephalitis can be regarded as a variant of Fisher syndrome with central nervous system involvement.

Although the clinical symptoms of Machado-Joseph disease (MJD) vary widely, those involving the autonomic nervous system, such as cutaneous sympathetic dysfunction, have rarely been investigated. In addition, there are no reports on cutaneous vasomotor function in patients with MJD. To determine the effects of MJD on cutaneous sympathetic function, we evaluated cutaneous vasomotor and sudomotor responses in the palms of 15 patients (mean age, 49 +/- 15 years; seven men and eight women) who were genetically diagnosed with MJD as well as in the palms of 15 age-matched, healthy controls (mean age, 48 +/- 16 years; nine men and six women). Sweat response was absent in 10 (67 %) patients with MJD, and the mean amplitude of sweat response was significantly lower (p < 0.0001) in patients with MJD than in healthy controls following mental stress (mental arithmetic) and physiological stimuli. Although vasoconstrictive response was absent in three patients with MJD (20 %), there were no significant differences in the mean amplitude of vasoconstrictive response between patients with MJD and healthy controls. These results indicate that patients with MJD have reduced cutaneous sympathetic response, including severely impaired sudomotor functions and mildly affected vasomotor functions.

Spinocerebellar ataxia type 31 (SCA31) is defined by the presence of an insertion mutation containing a TGGAA repeat within the intron of the brain-expressed, associated with NEDD4 (BEAN) gene. Detecting this mutation is conventionally done by southern blotting or DNA sequencing, but these methods are technically demanding and not easily implemented in clinical diagnosis. Here, we adapted repeat-primed PCR (RP-PCR) to develop a clinical genetic test for SCA31 using only the PCR process to detect the TGGAA repeat within the insertion mutation. Pentanucleotide RP-PCR and subsequent DNA fragment analysis demonstrated characteristic ladder peaks with a 5-bp periodicity, originating from the TGGAA repeat, in 100% of samples (n=14) from SCA31 patients in whom the presence of the TGGAA repeat had been verified by DNA sequencing. No peaks were observed in a normal control and two non-SCA31 patients, in whom the TGGAA repeat was absent. This method is valuable for genetic diagnosis of SCA31 in clinical practice. © 2012 The Japan Society of Human Genetics. All rights reserved.

Aims We performed receiver operating characteristic (ROC) analysis to determine the ability of sphincter electromyography (EMG) to distinguish multiple system atrophy (MSA) from other parkinsonisms. The following was determined: (1) the appropriate motor unit potential (MUP) parameter among duration, phase, and amplitude; (2) the desirable parameter of our duration criteria; that is, more than 20% MUPs having >10?ms duration (criteria a) or mean duration >10?ms (criteria b). Methods We retrospectively reviewed 441 case records where sphincter EMG were performed in patients with parkinsonian syndromes: MSA, n?=?263; Parkinson's disease, n?=?129; dementia with Lewy bodies, n?=?25; and progressive supranuclear palsy, n?=?24. We performed ROC analysis of the data sets. Results The area under the curve used to differentiate MSA from other parkinsonian syndromes was 0.68 in duration, 0.57 in phase, and 0.51 in amplitude, respectively; these values were statistically significant. With regard to our duration criteria, area under the curve was 0.69 for the average duration of MUPs (criteria b) and 0.67 for percentage of MUPs of duration >10?ms (criteria a); these values were also statistically significant. Conclusions This study suggests that duration is appropriate parameter for the differentiation of MSA. However, the area under the curve of the mean duration was insufficient to confirm the diagnosis; sphincter EMG should be used as a supportive diagnostic tool for the diagnosis of MSA. Neurourol. Urodynam. 31:11281134, 2012. (c) 2012 Wiley Periodicals, Inc.

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.

To diagnose neuromyelitis optica (NMO), the 2006 NMO diagnostic criteria is commonly used. However, adequate studies about the time course of NMO according to the criteria have been lacking. The aim of the study was to identify the interval between disease onset and diagnosis of NMO, as well as the clinical characteristics and time course, according to the 2006 NMO diagnostic criteria in Japanese patients with NMO. Clinical progression and time course of 43 Japanese patients with NMO who fulfilled the 2006 NMO diagnostic criteria with mean disease duration of 14.2 years were investigated retrospectively. The initial inflammatory event was myelitis in 44.2% (long extensive transverse myelitis [LETM] in 14.3%), optic neuritis in 41.9%, and concurrent myelitis and optic neuritis in 9.3% of the patients. The presence of LETM and anti-aquaporin-4 antibody seropositivity by the end of the observation period was found in 85.7 and 93.0% of the patients, respectively. Among the patients whose medical information were sufficiently available, the median intervals between NMO onset and the time until development of both optic neuritis and myelitis, LETM, or fulfillment of the 2006 NMO criteria were 16.5, 35.1, and 27.8 months, respectively. The development of diagnostic method at an early stage of NMO may be needed in order to initiate early treatment.

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

A 20-year-old previously healthy man presented with prolonged consciousness alteration and severe hypertonia in the extremities after minor head trauma. Laboratory blood tests and cerebrospial fluid (CSF) tests were unremarkable except for an elevated CSF glycine concentratons. Brain MRI revealed hypoplasia of corpus callosum, enlargement of lateral cerebral ventricle and high signal intensity in the bilateral white matter on T2 weighted images. On fluid attenuated inversion recovery images, the signal intensity resembled that of CSF in the central areas of T2 alterations, surrounded by a rim of hyperintensity. These characteristic history and the results of brain MRI and CSF, the diagnosis of vanishing white matter disease (VWMD) was made. VWMD is a rare autosomal recessive leukoencephalopathy which typically begins during infancy or early childhood with a chronic progressive neurological deterioration with cerebellar ataxia and spasticity. Recently, milder variants of the disease with adult onset have been reported. VWMD should be included in the differential diagnosis of leucoencephalopathy in young adults.

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.

Atrophy of the pontine tegmentum and facial colliculus is a characteristic pathological feature of MachadoJoseph disease. We assessed whether this finding can be detected by conventional brain magnetic resonance imaging. A total of 17 patients with genetically confirmed MachadoJoseph disease, 15 disease controls (spinocerebellar ataxia type 6 and dentatorubral-pallidoluysian atrophy), and 17 normal subjects were examined using a 1.5-Tesla magnetic resonance imaging scanner. The widths of the facial colliculus, pontine tegmentum, and pontine base and the area of the fourth ventricle were measured on axial T2-weighted imaging. Pathological examination was performed in 9 MachadoJoseph disease patients. In addition, visual inspection of the facial colliculus was evaluated by receiver operating characteristic analysis. The width of the facial colliculus was significantly smaller in MachadoJoseph disease patients (0.37 +/- 0.16 mm; mean +/- standard deviation) than in normal subjects (0.73 +/- 0.30 mm; P < .01), whereas the width of the pontine tegmentum was smaller in both MachadoJoseph disease (4.85 +/- 0.58 mm) and dentatorubral-pallidoluysian atrophy (4.72 +/- 0.59) patients than in normal subjects (6.35 +/- 0.74 mm; P < .01). Visual evaluation of the facial colliculus showed sufficient area under the receiver operating characteristic curves to differentiate MachadoJoseph disease from dentatorubral-pallidoluysian atrophy (0.78) and spinocerebellar ataxia type 6 (0.87). Pathological evaluation showed significant atrophy of the facial colliculus in all MachadoJoseph disease patients. Atrophy of the facial colliculus is a feasible magnetic resonance imaging finding for diagnosing MachadoJoseph disease, and it is easily found as a flattening of the fourth ventricular floor. (c) 2012 Movement Disorder Society

Aim: We systematically performed autonomic testing on patients with polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes syndrome (POEMS) to determine whether autonomic function is preserved in such patients. Methods: We studied 17 POEMS patients, 17 diabetic neuropathy (DN) patients and 17 age-matched normal subjects. Blood pressure responses to the head-up tilt test and heart rate variability were used to evaluate cardiovascular autonomic function. Sweat responses and cutaneous vasoconstriction to several stimuli were recorded via the finger tips to estimate cutaneous sympathetic function. In addition, motor nerve conduction studies were performed. Results: Although the results of the autonomic testing were normal in POEMS patients, motor disability was severe, and motor nerve conduction studies provided evidence of extensive axonal loss. The DN patients showed significantly impaired autonomic responses despite mild motor dysfunction. Conclusions: Autonomic function was normal in POEMS patients, indicating the preservation of autonomic fibers and selective involvement of large fibers. (C) 2012 Elsevier B.V. All rights reserved.

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.

It is established that deep brain stimulation of the subthalamic nucleus improves motor function in advanced Parkinson's disease, but its effects on autonomic function remain to be elucidated. The present study was undertaken to investigate the effects of subthalamic deep brain stimulation on gastric emptying. A total of 16 patients with Parkinson's disease who underwent bilateral subthalamic deep brain stimulation were enrolled. Gastric emptying was expressed as the peak time of (CO2)-C-13 excretion (T-max) in the C-13-acetate breath test and was assessed in patients with and without administration of 100-150 mg levodopa/decarboxylase inhibitor before surgery, and with and without subthalamic deep brain stimulation at 3 months post-surgery. The pattern of (CO2)-C-13 excretion curve was analysed. To evaluate potential factors related to the effect of subthalamic deep brain stimulation on gastric emptying, we also examined the association between gastric emptying, clinical characteristics, the equivalent dose of levodopa and serum ghrelin levels. The peak time of (CO2)-C-13 excretion (T-max) values for gastric emptying in patients without and with levodopa/decarboxylase inhibitor treatment were 45.6 +/- 22.7 min and 42.5 +/- 13.6 min, respectively (P = not significant), thus demonstrating levodopa resistance. The peak time of (CO2)-C-13 excretion (T-max) values without and with subthalamic deep brain stimulation after surgery were 44.0 +/- 17.5 min and 30.0 +/- 12.5 min (P < 0.001), respectively, which showed that subthalamic deep brain stimulation was effective. Simultaneously, the pattern of the (CO2)-C-13 excretion curve was also significantly improved relative to surgery with no stimulation (P = 0.002), although the difference with and without levodopa/decarboxylase inhibitor was not significant. The difference in peak time of (CO2)-C-13 excretion (T-max) values without levodopa/decarboxylase inhibitor before surgery and without levodopa/decarboxylase inhibitor and subthalamic deep brain stimulation after surgery was not significant, although motor dysfunction improved and the levodopa equivalent dose decreased after surgery. There was little association between changes in ghrelin levels (delta ghrelin) and changes in T-max values (delta T-max) in the subthalamic deep brain stimulation trial after surgery (r = -0.20), and no association between changes in other characteristics and delta T-max post-surgery in the subthalamic deep brain stimulation trial. These results showed that levodopa/decarboxylase inhibitor did not influence gastric emptying and that subthalamic deep brain stimulation can improve the dysfunction in patients with Parkinson's disease possibly by altering the neural system that controls gastrointestinal function after subthalamic deep brain stimulation. This is the first report to show the effectiveness of subthalamic deep brain stimulation on gastrointestinal dysfunction as a non-motor symptom in Parkinson's disease.

In amyotrophic lateral sclerosis (ALS), hand muscle wasting preferentially affects the 'thenar (lateral) hand', including the abductor pollicis brevis (APB) and first dorsal interosseous (FDI) muscles, with relative sparing of the hypothenar muscles (the abductor digiti minimi (ADM)). This peculiar pattern of dissociated atrophy of the intrinsic hand muscles is termed the 'split hand' and is rarely seen in diseases other than ALS. The muscles involved in the split hand are innervated through the same spinal segments (C8 and T1), and FDI and ADM, which are differentially affected, are both ulnar nerve innervated. The physiological mechanisms underlying the split hand in ALS are incompletely understood but both cortical and spinal/peripheral mechanisms are probably involved. Motor potentials evoked by magnetic stimulation are significantly smaller when recorded from the thenar complex, compared with the hypothenar muscles, supporting a cortical mechanism. But peripheral axonal excitability studies have suggested that APB/FDI motor axons have more prominent persistent sodium currents than ADM axons, leading to higher axonal excitability and thereby more ready degeneration. Pincer or precision grip is vital to human hand function, and frequent use of thenar complex muscles may lead to greater oxidative stress and metabolic demands at both upper and lower motoneurons innervating the APB and FDI. The split hand is a useful diagnostic sign in early ALS, and recent objective studies indicate that the sign has a high degree of specificity.

Objective: The aim of this study is to establish reference values for single-fibre electromyography (SFEMG) using concentric needles in a prospective, multicentre study. Methods: Voluntary or stimulated SFEMG at the extensor digitorum communis (EDC) or frontalis (FRO) muscles was conducted in 56-63 of a total of 69 normal subjects below the age of 60 years at six Japanese institutes. The cut-off values for mean consecutive difference (MCD) of individual potentials were calculated using +2.5 SD or 95% prediction limit (one-tail) of the upper 10th percentile MCD value for individual subjects. Results: The cut-off values for individual MCD (+2.5 SD) were 56.8 mu s for EDC-V (voluntary SFEMG for EDC), 58.8 mu s for EDC-S (stimulated SFEMG for EDC), 56.8 mu s for FRO-V (voluntary SFEMG for FRO) and 51.0 mu s for FRO-S (stimulated SFEMG for FRO). The false positive rates using these cut-off values were around 2%. Conclusions: The +2.5 SD and 95% prediction limit might be two optimal cut-off values, depending on the clinical question. The obtained reference values were larger than those reported previously using concentric needles, but might better coincide with conventional values. Significance: This is the first multicentre study reporting reference values for SFEMG using concentric needles. The way to determine cut-off values and the statistically correct definition of the percentile were discussed. (C) 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

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: To report the clinical features and recovery patterns of patients with non-thyrotoxic acquired hypokalemic paralysis. Methods: The clinical and laboratory records of 11 consecutive patients with acquired non-thyrotoxic hypokalemic paralysis were reviewed and compared with those of 3 patients with thyrotoxic periodic paralysis (TPP). The causes of potassium wasting were diarrhea (n = 4), alcohol abuse (n = 2), pseudoaldosteronism (n = 2), primary aldosteronism (n = 1), distal renal tubular acidosis associated with Sjogren's syndrome (n = 1) and an unknown cause (n = 1). Results: Three of the 11 patients had prominently asymmetric limb weakness, and 2 had predominant upper limb weakness. On admission, mean serum potassium and creatine kinase (CK) levels of patients with acquired hypokalemic paralysis on admission were 1.8 mEq/L and 4,075 U/mL, respectively, and the mean duration between admission and independent walking was 6.8 days (range, 2-31 days). Despite clinical recovery, 10 patients still presented with increased CK levels after several days (mean of maximum levels, 10,519 U/mL). In addition, normalization of serum potassium levels in patients with acquired hypokalemic paralysis patients was much slower compared to that in patients with TPP. One patient with acquired hypokalemic paralysis developed ventricular fibrillation, whereas all 3 patients with TPP had symmetric proximal and lower limb-dominant weakness and exhibited complete recovery from paralysis as well as normalized serum potassium levels within 24 h. Conclusions: In patients with acquired non-thyrotoxic hypokalemic paralysis, asymmetric or upper limb-dominant weakness of the extremities is observed. Despite clinical improvement after treatment, normalization of serum potassium and CK levels is often delayed, and therefore, careful monitoring for cardiac and renal complications is required. (C) 2011 Elsevier B.V. All rights reserved.

A pivotal role of c-jun N-terminal kinase (INK) on neuronal apoptosis has been demonstrated in a rodent stroke model. MAP kinase phosphatase 1 (MKP-1) is an archetypal member of the dual-specificity protein phosphatase (DUSP) family, which inactivates mitogen-activated protein kinase (MAPK) including JNK through dephosphorylation. MKP-1, one of immediate early genes in stress conditions, was induced at transcriptional level in hypoxia/re-oxygenation (H/R) in neuroblastoma N1E115 cells, however the activation of JNK was not suppressed in the acute phase of re-oxygenation. Small interference RNA-mediated knock-down of MKP-1 enhanced phospho-JNK and neuronal death that is rescued by INK inhibitor in H/R. Conversely, conditional over-expression of MKP-1 suppressed phospho-JNK, the expression of proapoptotic genes, and neuronal death in H/R. Further the immunoreactivity of MKP-1 was detected in the neurons and partially co-localized with that of phospho-JNK in the surrounding zone of ischemia in rat MCA-O (middle cerebral artery occlusion) reperfusion model. These findings indicate that over-expression of MKP-1 could suppress neuronal death possibly through regulating JNK signaling in vitro and be a prominent neuroprotective target for the treatment of acute cerebral infarction. (C) 2011 Elsevier B.V. All rights reserved.