桑原 聡

Objective: To evaluate the degree of blood-brain barrier disruption in patients with neuromyelitis optica (NMO) and to clarify whether the levels of soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular cell adhesion molecule 1 (sVCAM-1) in patients with NMO can be useful biomarkers for blood-brain barrier breakdown. Design: Descriptive historical cohort. Setting: Department of Neurology, Graduate School of Medicine, Chiba University. Patients: The levels of sICAM-1 and sVCAM-1 in 25 patients with NMO, 21 patients with multiple sclerosis, and 20 patients with other noninflammatory neurologic disorders in the serum and cerebrospinal fluid (CSF) were measured using a multiplexed fluorescent magnetic bead-based immunoassay. Main Outcome Measures: Levels of the soluble adhesion molecules in serum and CSF and their associations with blood-brain barrier disruption. Results: The CSF levels of sICAM-1 and sVCAM-1 increased in patients with NMO compared with patients with multiple sclerosis and other noninflammatory neurologic disorders (P < .001), and serum levels of sICAM-1 increased in patients with NMO compared with healthy control individuals (P = .003). The CSF sICAM-1 levels from patients with NMO were correlated with the albumin quotient (P = .02) and the presence of lesions detected via gadolinium-enhanced magnetic resonance imaging. Conclusions: Severe blood-brain barrier breakdown occurs in patients with NMO. Measuring adhesion molecules is useful to evaluate this barrier disruption.

The neuromuscular junction (NMJ) is a specialized synapse with a complex structural organization. Muscle contraction involves several steps: (1) nerve conduction to depolarize the motor nerve terminals, (2) opening of voltage-gated calcium channels (VGCCs) in the presynaptic membrane, (3) generation of endplate potential in the postsynaptic membrane via acetylcholine receptors, (4) depolarization of muscle sodium channels, and (5) excitation-contraction (E-C) coupling. Each step can be affected by various diseases. Guillain-Barre syndrome involves distal axons and possibly the presynaptic NMJ. The abnormalities can be detected by nerve conduction studies and single-fiber electromyography (SFEMG). Myasthenia gravis (MG) with anti-acetylcholine receptor (AChR) antibodies, is the most common NMJ disorder, and ∼5% of myasthenia patients are positive for anti-muscle specific kinase (MuSK) antibodies. Patterns and severity of neuromuscular transmission failure detected by repetitive nerve stimulation test and SFEMG are somewhat different in AChR-MG and MuSK-MG. Excitation-contraction (E-C) coupling can be affected by MG, possibly via antibodies against ryanodine receptors. The E-C coupling time can be assessed with an accelerometer. Lambert-Eaton myasthenic syndrome is caused by antibodies against presynaptic VGCCs. This review will focus on neurophysiological testing, including SFEMG, and measurements of E-C coupling time with an accelerometer. In addition to confirming or excluding the diagnosis, these techniques can provide new insights into the pathophysiology of a variety of neuromuscular disorders.

POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes) syndrome is a rare cause of demyelinating neuropathy with monoclonal plasma cell proliferation, and POEMS neuropathy is usually chronically progressive. Herein, the authors report a 34-year-old woman with POEMS syndrome presenting as acute polyneuropathy. Within 2 weeks of disease onset, she became unable to walk with electrodiagnostic features of demyelination and was initially diagnosed as having Guillan-Barre syndrome. Other systemic features (oedema and skin changes) developed later, and an elevated serum level of vascular endothelial growth factor led to the diagnosis of POEMS syndrome. She received high-dose chemotherapy with autologous peripheral blood stem cell transplantation, resulting in good recovery. The authors also reviewed patterns and speed of progression of neuropathy in the 30 patients with POEMS syndrome; 22 (73%) of them were unable to walk independently with the median period of 9.5 months from POEMS onset (range 0.5-51 months). Whereas the speed of neuropathy progression varies considerably among patients, some POEMS patients can show acute or subacute polyneuropathy. The early diagnosis and treatment could result in rapid improvement as shown in the present patient.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is currently classified into "typical CIDP" and other variants, such as "multifocal acquired demyelinating sensory and motor neuropathy (MADSAM)". Typical CIDP is a classic form, clinically characterized by symmetric proximal and distal muscle weakness and motor-dominant manifestation. In typical CIDP, demyelination predominantly affects the distal nerve terminals and nerve roots, presumably because of the lack of the blood-nerve barrier in these regions, and this could be responsible for the "non-nerve length-dependent" distribution of muscle weakness. Furthermore, the safety factor of impulse transmission is physiologically lowered by axonal branching in the intramuscular motor nerves, and therefore, conduction block develops more readily in motor axons than in sensory axons, leading to motor-dominant polyneuropathy in typical CIDP. These findings suggest the importance of humoral immunity in typical CIDP. In contrast, MADSAM is characterized by multifocal demyelination in the intermediate nerve trunks with preservation of the nerve terminals/roots, and such distribution of lesions should result in multiple mononeuropathy or asymmetric polyneuropathy. In MADSAM neuropathy, cellular immunity might be predominantly involved in the breakdown of the blood-nerve barrier at the site of the conduction block. Clinical features are likely to be determined by the distribution of demyelinative lesions, and probably reflect the different immunopathogenesis of each CIDP subtype. This review focuses on clinical-electrophysiological correlation in the subtypes of CIDP. © 2011 Japanese Society for Neuroimmunology.

Objective: Pathological studies showed both pontine transverse (cortico-ponto-cerebellar) and longitudinal (corticospinal) fibers degenerate in MSA. The objective was to investigate the association between the development of cross sign, degenerations of pontine fibers, and the frequency of pyramidal signs in MSA. Methods: Patients with MSA (n = 26) and healthy subjects (n = 27) were enrolled in this study. Whole pontine transverse and longitudinal fibers were individually traced by diffusion tensor tractography. FA was calculated along each entire tractography. Cross sign was graded as: 0, no cross sign; 1, anterior-posterior line only; and 2, complete cross sign. T2-hyperintense MCPs was graded as: 0, no change; 1, slight signal change; and 2, severe signal change. FA of pontine fibers in MSA patients and that in healthy subjects was statistically evaluated by ANOVA with an overall statistical significance level of 0.05. The frequency of pyramidal signs in MSA was compared between each cross and MCP grade. Results: FA of pontine transverse fibers in MSA patients decreased with the development of cross sign. FA of Cross 2 was significantly lower than that of healthy subjects (p = 0.003). As regards pontine longitudinal fibers, FA decreased when cross sign was completed. The frequency of pyramidal signs in MCP 2 and 1 was higher than that in MCP 0. Conclusion: Pontine transverse fibers degenerate as cross sign develop, and degenerations of pontine longitudinal fibers begin, or even accelerate when cross sign becomes apparent. Pyramidal signs are frequently present when T2-hyperintense MCPs are clearly observed. (C) 2011 Elsevier B.V. All rights reserved.

In multiple sclerosis, activated CD4(+) T cells initiate an immune response in the brain and spinal cord, resulting in demyelination, degeneration and progressive paralysis. Repulsive guidance molecule-a (RGMa) is an axon guidance molecule that has a role in the visual system and in neural tube closure. Our study shows that RGMa is expressed in bone marrow-derived dendritic cells (BMDCs) and that CD4(+) T cells express neogenin, a receptor for RGMa. Binding of RGMa to CD4(+) T cells led to activation of the small GTPase Rap1 and increased adhesion of T cells to intracellular adhesion molecule-1 (ICAM-1). Neutralizing antibodies to RGMa attenuated clinical symptoms of mouse myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) and reduced invasion of inflammatory cells into the CNS. Silencing of RGMa in MOG-pulsed BMDCs reduced their capacity to induce EAE following adoptive transfer to naive C57BL/6 mice. CD4(+) T cells isolated from mice treated with an RGMa-specific antibody showed diminished proliferative responses and reduced interferon-gamma (IFN-gamma), interleukin-2 (IL-2), IL-4 and IL-17 secretion. Incubation of PBMCs from patients with multiple sclerosis with an RGMa-specific antibody reduced proliferative responses and pro-inflammatory cytokine expression. These results demonstrate that an RGMa-specific antibody suppresses T cell responses, and suggest that RGMa could be a promising molecular target for the treatment of multiple sclerosis.

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.

Fisher syndrome is characterized by the clinical triad of ophthalmoplegia, ataxia, and areflexia. It is considered a variant form of Guillain-Barre syndrome, which is associated with anti-GQ1b antibodies. During initial examinations of patients, physicians must rule out other neurologic disorders or conditions that resemble Fisher syndrome, such as vitamin B1 deficiency (Wernicke's encephalopathy), vascular disease, multiple sclerosis, collagen disease, Behcet disease, sarcoidosis, neoplasm of the brainstem, and infectious diseases such as diphtheria, botulism, and viral infections (eg, herpes encephalitis). The acute phase of Fisher syndrome should be carefully observed to see if it occurs concomitantly with Guillain-Barre syndrome or if there is development to Bickerstaff brainstem encephalitis, as these require specific immune treatments. Typically, Fisher syndrome has a fairly good natural course. Although several reports have suggested the possible efficacy of immunotherapies such as plasmapheresis and intravenous immunoglobulins (IVIg) in treating Fisher syndrome, there have been no randomized controlled studies. Large retrospective studies have suggested that neither plasmapheresis nor IVIg alters the clinical outcome of patients with Fisher syndrome, probably because of the good spontaneous recovery in these patients. Therefore, Fisher syndrome alone does not necessarily require immunotherapy. To accelerate the start of recovery, IVIg can be given, but it is important to first obtain informed consent from patients after the potential risks of blood products are explained. When overlap with Guillain-Barre syndrome or development to Bickerstaff brainstem encephalitis occurs, plasma exchange or IVIg should be administered as early as possible because Guillain-Barre syndrome can cause respiratory failure or severe weakness with axonal degeneration, and Bickerstaff brainstem encephalitis may not have as good a natural course as Fisher syndrome alone. There have been no prospective, controlled studies (randomized or nonrandomized) of the use of immunotherapy to treat Fisher syndrome. To evaluate the efficacy of immunotherapies used to treat Fisher syndrome, large prospective studies are required.

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.

Lidocaine unmasks silent symptoms and eases neuropathic pain in multiple sclerosis patients however, the effects of lidocaine in neuromyelitis optica have never been reported. We describe the case of a 59-year-old Japanese woman with neuromyelitis optica spectrum disorder who developed optic neuritis 1 day after intravenous lidocaine injection for treating allodynia. Her symptom seemed to result from a relapse of neuromyelitis optica induced by lidocaine administration, and not because of the transient effects of intravenous lidocaine administration. The possibility that lidocaine administration results in relapse of neuromyelitis optica due to its immunomodulating effects cannot be ruled out. Copyright © 2011 Akiyuki Uzawa et al.

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 < 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 < 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.

Aims: It is usually difficult to distinguish between idiopathic Parkinson's disease (PD) and parkinsonian-type multiple system atrophy (MSA-P) in the early stage. However, it is important to make a careful early-stage diagnosis. Therefore, we determined whether an examination of pelvic organ dysfunction would be helpful to distinguish between PD and MSA-P. Methods: We recruited 61 patients with PD and 54 patients with MSA-P who were examined at our neurology clinic. The mean ages of the patients with PD and MSA-P were 67 and 64 years, respectively. The mean disease duration of both groups was 3.2 years. We administered a questionnaire on pelvic organ dysfunction to the PD and MSA-P groups. The questionnaire had sections focusing on bladder, bowel, and sexual function. Dysfunction, as described in the responses, was evaluated as normal, mild (> once a month), moderate (> once a week), or severe (> once a day). The Mann-Whitney U-test was used for statistical analysis. Results: Compared with the PD group, the prevalence and severity of pelvic dysfunction in the MSA-P group was significantly higher for urinary urgency (MSA-P 76%, PD 58%, P<0.05), retardation in initiating urination (79%, 48%, P<0.05), prolongation in urination (79%, 72%, P<0.05), and constipation (58%, 31%, P<0.05). The quality-of-life index among pelvic organ dysfunctions indicated that urinary and bowel function was significantly more impaired in the MSA-P group than in the PD group. Conclusions: Urinary urgency, retardation in initiating urination, prolongation in urination, and constipation are more prevalent and severe in MSA-P compared to PD. Neurourol. Urodynam. 30: 102-107, 2011. (C) 2010 Wiley-Liss, Inc.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is classified into typical type that is characterized by proximal weakness and atypical type that include demyelinating acquired distal symmetric (DADS) type. DADS type CIDP is characterized by slowly progressive clinical course, motor and sensory involvement dominant in the leg and resistance to therapy. We report the case of a 72 year-old man with DADS type CIDP, who have dysesthesia and weakness dominant in distal of limbs. Disease progression was resistant to therapy for prednisolone and intravenous immunoglobulin, but slowly progressive for 4 years. Subacute exacerbation that was accompanied by proximal weakness was occurred at 4 years later from onset. Nerve conduction study revealed markedly prolonged distal latencies and slowing of conduction velocities. Double filtration plasmapheresis improved symptom, after oral prednisolone kept remission. This case had characteristic of DADS type CIDP at the onset, but changed into typical CIDP also for the therapy in the clinical course. This case indicate the multiplicity of CIDP.

Fasciculation is a characteristic feature of ALS. Nerve excitability studies have shown increased persistent sodium currents and reduced potassium currents in motor axons of ALS patients, both of which lead to axonal hyperexcitability and thereby generation of fasciculations. The present study was undertaken to investigate whether abnormal axonal excitability indices are correlated with survival in ALS patients. A total of 112 consecutive patients with sporadic ALS were followed-up until endpoint (death or tracheostomy). Univariate analyses revealed longer strength-duration time constant (SDTC) was associated with a shorter survival. In multivariate analyses using the Cox proportional hazard model, onset age&gt 60 years and longer SDTC were strong predictors of shorter survival. Assuming that SDTC depends on nodal persistent sodium conductances, our results showed that an increased persistent sodium current is strong and independent predictor for short survival of ALS patients. These findings support the hypothesis that membrane hyperexcitability would contribute to motor neuronal death in ALS.

Background: Neuromyelitis optica (NMO) is assumed to be immunologically distinct from multiple sclerosis (MS). Adequate studies about cytokines and chemokines in NMO have been lacking. Objective: To investigate the contribution of cytokines/chemokines in the pathogenesis of NMO. Methods: We measured 27 cytokines/chemokines and Th17 cell-associated cytokines in the cerebrospinal fluid (CSF) of 31 NMO, 29 MS and 18 other non-inflammatory neurological disorders patients. The serum levels of some cytokines/chemokines were also measured. The correlations between clinical characteristics/laboratory findings and levels of cytokines/chemokines in NMO were examined. Results: The CSF levels of interleukin (IL)-1 receptor antagonist, IL-6, IL-8, IL-13 and granulocyte colony-stimulating factor were significantly increased in NMO, while IL-9, fibroblast growth factor-basic, granulocyte macrophage colony-stimulating factor, macrophage inflammatory protein-1-beta and tumor necrosis factor-alpha were increased in MS. IL-10 and interferon-gamma-inducible protein-10 were elevated in NMO and MS. In serum analyses, only the IL-6 level showed significant elevation in NMO. The CSF IL-6 level had a significant correlation with the CSF glial fibrillary acidic protein level and CSF cells, and a weak correlation with anti-aquaporin-4 antibody titers. Conclusions: Different immunological status and pathophysiologies exist between NMO and MS, and IL-6 may play important roles in the pathogenesis of NMO.

Background: The role of different chemokine receptors in the pathogenesis of multiple sclerosis (MS) has been extensively investigated; however, little is known about the difference in the role of chemokine receptors between the pathogenesis of neuromyelitis optica (NMO) and MS. Therefore, we examined the expression of chemokine receptors on peripheral blood lymphocytes (PBL) in MS and NMO. Methods: We used flow cytometry to analyse lymphocyte subsets in 12 patients with relapsing NMO, 24 with relapsing-remitting MS during relapse, 3 with NMO and 5 with MS during remission. Results: Compared with healthy controls (HC), the percentage of lymphocytes in white blood cells was significantly lower in NMO and MS patients. The percentage of T cells expressing CD4(+)CD25(+) and CD4(+)CD45RO(+) was higher, while that of CD4(+)CC chemokine receptor (CCR)3(+) (T helper 2, Th2) was significantly lower in MS patients than in HC. The ratios of CD4(+)CXC chemokine receptors (CXCR)3(+)/CD4(+)CCR3(+) (Th1/Th2) and CD8(+)CXCR3(+)/CD8(+)CCR4(+) (T cytotoxic 1, Tc1/Tc2) were higher in MS patients than in HC. The percentage of CD8(+)CXCR3(+) T cell (Tc1) and CD4(+)CXCR3(+) T cell (Th1) decreased significantly during remission in MS patients (P <0.05). No significant differences were identified in the expression of the chemokine receptors on PBL in NMO patients compared with MS patients and HC. Conclusions: Th1 dominance of chemokine receptors on blood T cells and the correlation between CXCR3(+) T cell (Th1 and Tc1) and disease activity in MS patients were confirmed by analysing chemokines receptors on PBL. In contrast, deviation in the Th1/Th2 balance was not observed in NMO patients.

It is essential to perform electromyography and nerve-conduction studies for diagnosis amyotrophic lateral sclerosis (ALS), but these conventional electrophysiologic methods cannot be used for studies on the mechanism underlying ALS. The recently developed nerve-excitability test can provide new insights into the pathophysiology of this disease. Fasciculation is one of the characteristic features of ALS. Ectopic firing of motor units originates usually from the motor nerve terminals and occasionally from the motor neurons, indicating a widespread abnormality in axonal excitability. ALS is a multifactorial disease in which some genetic abnormalities and environmental factors lead to cell death through a complex cascade, which includes oxidative stress, mitochondrial dysfunction, excitotoxicity, and impaired axonal transport. It is important to elucidate the pathophysiology of axonal excitability in ALS because increased axonal excitability enhances oxidative stress and excitotoxicity, ultimately contributing to motor neuron death. To date, 2 axonal ion channel abnormalities have been identified: (1) increased persistent sodium currents and (2) reduced potassium currents both abnormalities cause an increase in axonal excitability and are responsible for fasciculations. The results for excitability testing in such patients are characterized by the following features: (1) a prolonged strength-duration time constant, which suggests increased persistent sodium currents (2) greater threshold changes in depolarizing threshold electrotonus and (3) greater supernormality, which suggests impaired potassium channels. The altered axonal properties in patients with ALS may provide new insights into the pathophysiology of ALS and have implications for the development of ion channel modulators as therapeutic options for patients with ALS.

Corticobasal syndrome, progressive supranuclear palsy and frontotemporal dementia are all part of a disease spectrum that includes common cognitive impairment and movement disorders. The aim of this study was to characterize brain cholinergic deficits in these disorders. We measured brain acetylcholinesterase activity by [(11)C] N-methylpiperidin-4-yl acetate and positron emission tomography in seven patients with corticobasal syndrome (67.6 +/- 5.9 years), 12 with progressive supranuclear palsy (68.5 +/- 4.1 years), eight with frontotemporal dementia (59.8 +/- 6.9 years) and 16 healthy controls (61.2 +/- 8.5 years). Two-tissue compartment three-parameter model and non-linear least squares analysis with arterial input function were performed. k(3) value, an index of acetylcholinesterase activity, was calculated voxel-by-voxel in the brain of each subject. The k(3) images in each disease group were compared with the control group by using Statistical Parametric Mapping 2. Volume of interest analysis was performed on spatially normalized k(3) images. The corticobasal syndrome group showed decreased acetylcholinesterase activity (k(3) values) in the paracentral region, frontal, parietal and occipital cortices (P < 0.05, cluster corrected). The group with progressive supranuclear palsy had reduced acetylcholinesterase activity in the paracentral region and thalamus (P < 0.05, cluster corrected). The frontotemporal dementia group showed no significant differences in acetylcholinesterase activity. Volume of interest analysis showed mean cortical acetylcholinesterase activity to be reduced by 17.5% in corticobasal syndrome (P < 0.001), 9.4% in progressive supranuclear palsy (P < 0.05) and 4.4% in frontotemporal dementia (non-significant), when compared with the control group. Thalamic acetylcholinesterase activity was reduced by 6.4% in corticobasal syndrome (non-significant), 24.0% in progressive supranuclear palsy (P < 0.03) and increased by 3.3% in frontotemporal dementia (non-significant). Both corticobasal syndrome and progressive supranuclear palsy showed brain cholinergic deficits, but their distribution differed somewhat. Significant brain cholinergic deficits were not seen in frontotemporal dementia, which may explain the unresponsiveness of this condition to cholinergic modulation therapy.

We describe a 64-year-old woman who developed spinal myoclonus around the left scapula after long thoracic nerve injury by mastectomy. Involuntary muscle twitching was semi-rhythmic, and ultrasonography identified contraction of the serratus anterior, teres major, and rhomboid muscles. FDG-PET imaging revealed markedly increased glucose uptake only in the serratus anterior. Lidocaine injection into this muscle resulted in complete cessation of the involuntary movement, and then she was successfully treated with botulinum toxin type A. These findings raise the possibility that the myoclonus was primarily caused by ectopic firing of the injured long thoracic nerve, then spreading to adjacent muscles possibly via a central mechanism mediated by group la afferents. The new imaging tools, such as FDG-PET and ultrasonography, were useful to determine the therapeutic target muscle. (C) 2010 Published by Elsevier B.V.

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 < 0.001). After mexiletine treatment, there was a reduction in clinical pain scores (p < 0.001), associated with decreased threshold changes at 0.2 ms (p < 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.

Background: Although the benefit of treatment for relapsing-remitting multiple sclerosis (MS) is firmly established, whether interferon beta-1b (IFNB-1b) therapy is efficacious for neuromyelitis optica (NMO) has been debated. Methods: We reviewed the responses to IFNB-1b treatment in 18 patients with relapsing NMO and compared the results with those from 38 patients with relapsing-remitting MS. We compared clinical characteristics, the annualized relapse rate (ARR) and the probability of being relapse free before and after IFNB-1b treatment in patients with NMO and MS. Results: The proportion of patients with more than 50% increase in the ARR after IFNB-1b treatment was much higher in NMO than in MS (P = 0.046). ARR was significantly lower in patients with MS after IFNB-1b administration than before (P = 0.015), but not in NMO. Kaplan-Meier and log-rank statistical analyses revealed that relapse-free rates were lower in NMO than MS after IFNB-1b treatment (P = 0.032). The analyses also showed lower relapse-free rates during the pre-IFNB-1b treatment period than the post-IFNB-1b treatment period in MS (P < 0.001), but not in NMO. Conclusion: IFNB-1b treatment does not appear to be effective for preventing relapse in NMO likely because of differences between the immune-pathogenesis of NMO and MS.

Objective: Tachycardia is a clinical feature of Machado-Joseph disease (MJD), and it may be attributable to cardiac autonomic dysfunction. We investigated heart rate variability in MJD patients to reveal heart rate dysregulation in MJD. Methods: Power spectral analysis of successive R-R intervals (300 beats) was performed in 10 genetically diagnosed MJD patients and 10 healthy control subjects to obtain frequency-domain measures, including high- (HF: 0.15-0.4 Hz) and low frequency power (LF; 0.04-0.15 Hz) and the ratio of LF to HF (LF/HF) of heart rate variability. In addition, the coefficient of R-R intervals (CV(R-R)) was calculated as a time-domain measure. Results: HF in the MJD patients (26.2 +/- 25.3 ms(2)) was lower than that in the controls (82.1 +/- 82.6 ms(2), p = 0.004). LF was also lower in the MJD patients (70.6 +/- 69.4 ms(2)) than in the controls (106.9 +/- 81.3 ms(2); p = 0.029). There was no significant difference in LF/HF or CV(R-R) between the groups. Conclusion: HF, which is modulated by parasympathetic vagal activity, was low in our MJD patients. The reduced parasympathetic activity may be a cause of tachycardia in MJD patients. (C) 2009 Elsevier B.V. All rights reserved.

The forebrain is one of the important suprapontine micturition centres. Previous studies have shown that electrical stimulation of the frontal lobe and the anterior cingulate gyrus elicited either inhibition or facilitation of bladder contraction. Patients with frontal lobe tumours and aneurysms showed micturition disorders. Functional brain imaging studies showed that several parts of the forebrain are activated during bladder filling. We aimed to examine neuronal activities of forebrain structures with respect to bladder contraction in cats. In 14 adult male cats under ketamine anaesthesia in which a spontaneous isovolumetric bladder-contraction/relaxation cycle had been generated, we carried out extracellular single-unit recording in forebrain with respect to the contraction/relaxation cycles in the bladder. We recorded 112 neurons that were related to the bladder-contraction/relaxation cycles. Ninety-four neurons were found to be tonically activated during the bladder-relaxation phase, whereas the remaining 18 neurons were tonically activated during the bladder-contraction phase. Both types of neuron were widely distributed around the cruciate sulcus. Most were located medially (medial and superior frontal gyrus) and the rest were located laterally (middle and inferior frontal gyrus). Neurons recorded in forebrain structures were activated with respect to the contraction/relaxation cycles in the bladder. Forebrain structures may have a significant role in regulating bladder contraction in cats. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

To detect serum biomarkers associated with disease activity in relapsing-remitting multiple sclerosis (MS). We Studied serum low-molecular peptide profiling of MS patients and normal controls comprehensively by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Serum level of 1741 Da peptide was increased at the time of clinical relapse in patients than in normal controls and returned toward normal during remission. Tandem mass spectrometry analysis revealed that the peptide was a fragment of complement C4 (NGFKSHALQLNNRQI). This fragment peptide could be a possible marker of disease activity. It may reflect complement activation in the pathogenesis of MS. (C) 2009 Elsevier B.V. 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.