桑原 聡

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.

Although immunosuppressive effects of antiepileptic drug are well known, serious complications of antiepileptic drug are rare. We report a case of hypogammaglobulinemia associated with aplasia of B lymphocytes after carbamazepine treatment. Despite repeated intravenous immunoglobulin replacement therapy, this condition persisted for more than three months. The present case suggested that routine monitoring of the blood cell count and serum levels of immunoglobulin are important in patients treated with carbamazepine, and a lymphocyte subpopulation study is valuable in cases of hypogammaglobulinemia.

There are significant advances in immune-modulating treatments for Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) in the past 20 years. GBS, however, is still a serious disease with a mortality rate of 8% and 20% of the patients being unable to walk independently a year after onset. For CIDP and related disorders such as multifocal motor neuropathy, and demyeinating neuropathy with antimyelin-associated-glycoprotein (MAG) antibody, treatments should be based on individual pathophysiology. Rituximab could be a promising agent for the subtypes of CIDP refractory to conventional immune treatments. Crow-Fukase syndrome is a rare cause of demyelinating neuropathy with multiorgan involvement. Overproduction of vascular endothelial growth factor (VEGF), probably mediated by monoclonal proliferation of plasma cells, is likely to be responsible for most of the characteristic symptoms. There is no established treatment regimen for Crow-Fukase syndrome. In appropriate candidates, high-dose chemotherapies with autologous peripheral blood stem cell transplantation is highly recommended, because this treatment could result in obvious improvement in neuropathy as well as other symptoms. Indication of this treatment has not yet been established, and long-term prognosis is unclear at present. Treatments that should be considered as future therapy against Crow-Fukase syndrome include thalidomide, and anti-VEGF monoclonal antibody (bevacizumab).

Guillain–Barré syndrome is currently classified into 2 major forms based on pathologic and electrophysiologic criteria: (1) acute inflammatory demyelinating polyneuropathy (AIDP), by far the most common form in western countries and (2) acute motor axonal neuropathy (AMAN), which is more prevalent in East Asia (China and Japan). AMAN is characterized by electrophysiologic and pathologic evidence of axonal degeneration of the motor nerves as well as functional conduction failure or other pathophysiology. It is possibly associated with anti-ganglioside antibodies in particular, IgG antibodies to the gangliosides GM1, GM1b, GD1a and GalNAc-GD1a, which may be induced by particular infectious agents such as Campylobacter jejuni or Haemophilus influenza. Although AMAN appears to be similar to AIDP, there are important clinical differences. AMAN is a pure motor syndrome, with infrequent and mild involvement of the autonomic nervous system. When sensory fibres are also affected, this axonal subtype is called acute motor and sensory axonal neuropathy. Patients with AMAN often show hyperreflexia in the recovery phase. AMAN has a rapid progression in its early stage and has an earlier nadir than AIDP. AMAN has 2 patterns of clinical recovery, rapid and prolonged, in contrast to the relatively uniform recovery seen in AIDP. Electrophysiologic evidence of axonal degeneration is thought to be an indicator of poor prognosis. However, the most severely disabled AMAN patients are able to walk independently within a few years, indicating that electrodiagnosis of AMAN is not always a marker of poor recovery. This review provides an update on the clinical features, recovery pattern and long-term prognosis in AMAN patients.

Crow-Fukase syndrome, also called POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome, is a rare cause of demyelinating and axonal mixed neuropathy with multiorgan involvement. The pathogenesis of Crow-Fukase syndrome is not well understood, but overproduction of vascular endothelial growth factor (VEGF), probably mediated by monoclonal proliferation of plasma cells, is likely to be responsible for most of the characteristic symptoms. There is no established treatment regimen. In appropriate candidates, high-dose chemotherapies with autologous peripheral blood stem cell transplantation is highly recommended, because this treatment could result in obvious improvement in neuropathy as well as other symptoms, with a significant decrease in serum VEGF levels. Indication of this treatment has not yet been established, and long-term prognosis is unclear at present. Thalidomide should be considered for patients who are not indicated for transplantation therapy. Treatments that should be considered as future therapy include lenalidomide, bortezomib, and anti-VEGF monoclonal antibody (bevacizumab).

To investigate differences in helper T cell immune responses in cerebrospinal fluid (CSF) between neuromyelitis optica (NMO) and multiple sclerosis (MS), we measured CSF levels of interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-alpha and interferon-gamma at the time of relapse in 17 NMO patients and 21 MS patients using fluorescence-activated cell sorting. CSF IL-6 levels were significantly higher in NMO patients than in patients with MS (P = 0.001) and other neurological diseases (P = 0.001). The other cytokines tested were undetectable. Elevated CSF levels of IL-6 in only NMO supports the view of different pathophysiologies of NMO and MS. CSF IL-6 levels may be useful in the differential diagnosis of the two disorders.

We describe 2 patients who developed anti-aquaporin-4 antibody-positive neuromyelitis optica (NMO) following the development of anti-acetylcholine receptor antibody-positive myasthenia gravis (MG). A literature review of 13 similar cases in addition to the present 2 cases of NMO with MG showed predominance among Asian women and frequent development of NMO following thymectomy for MG. Moreover, in one of our patients, serial assays of anti-aquaporin-4 antibody and anti-acetylcholine receptor antibody were performed. Accumulating evidence for the coexistence of NMO and MG suggests that a common immunopathogenesis of NMO and MG may exist, and the association of NMO with MG may be more frequent than hitherto believed. (C) 2009 Elsevier B.V. All rights reserved.

Few cases of dopamine agonist-induced antecollis in Parkinson's disease (PD) have been reported. Literature review of 16 PD patients including our 3 cases with dopamine agonist-induced antecollis showed predominance of (1) Japanese, (2) women, and (3) Hoehn-Yahr stage of >= 3. We experienced three Japanese PD patients who subacutely exhibited antecollis following increased dopamine agonist dose that improved just after withdrawal of the agonist. One patient developed antecollis during increasing pramipexole dose in combination with cabergoline. Antecollis in another patient appeared during increasing pramipexole dose; it worsened after substituting pergolide for pramipexole, but improved after withdrawal of pergolide. Our cases indicate that there is no specific dopamine agonist causing antecollis, and it is possibly caused by a number of single dopamine agonists or a combination of them. Dopamine agonist-induced antecollis should be considered when encountering antecollis in PD patients being treated with dopamine agonists and withdrawal of the agonist can improve symptoms. (C) 2009 Movement Disorder Society

To evaluate the effects of bromocriptine on bladder function in Parkinson's disease (PD) patients and compare these effects with those of (L-dopa). We recruited 8 patients with PD. Urodynamic study (UDS) was performed before and I hour after administering 100 mg L-dopa/decarboxylase inhibitor (DCI) and 2.5 hours after administering 7.5 mg bromocriptine. After the bromocriptine administration, urinary urgency aggravated. UDS revealed a decreased bladder volume at which detrusor overactivity (DO) was initiated, a decreased bladder volume at first sensation of bladder filling (FSV) (P < 0.05), an increased maximum Watts Factor value (WFmax) (detrusor contractility), a decreased Abrams-Griffiths (AG) number (urethral obstruction), and a decreased postvoid residual (PVR) (P < 0.01). Similarly, after the L-dopa administration, urinary urgency aggravated. UDS revealed an aggravated DO (P < 0.05), a decreased FSV and bladder capacity (P < 0.01, 0.05), an increased WFmax (P < 0.05), an increased AG number, and a decreased PVR (P < 0.01). A single dose of bromocriptine proved to exacerbate urinary urgency and DO in the storage phase, and improve bladder emptying through increased detrusor contractility and decreased bladder outlet obstruction, within hours. With the exception of bladder outlet obstruction, these effects of bromocriptine are similar to the effects of L-dopa, albeit slightly less pronounced. (C) 2009 Movement Disorder Society

Clinical course and prognosis are variable among patients with chronic inflammatory demyelinating polyneuropathy (CIDP), whereas the extent of axonal degeneration is the major prognostic factor. We studied the effects of sera from CIDP patients on axonal growth in cultured mouse dorsal root ganglion neurons. Compared with control sera, CIDP sera prominently Suppressed axonal Outgrowth of dorsal root ganglion neurons and shortened axonal length. The inhibitory activity was abolished by adding Y27632, a Rho-kinase inhibitor. These findings suggest that CIDP sera inhibit axonal elongation by Rho-kinase activation, and some serum factors may be responsible for development of axonal degeneration in CIDP.

Background: Several different missense mutations in the voltage-gated sodium channel subunit gene SCN1A have been identified in epileptic patients with benign phenotype and patients with severe phenotype. However, the reason why similar missense mutations in SCN1A result in different phenotypes has not yet been fully clarified. Objective: To clarify the phenotype-genotype relationship in SCN1A, a meta-analysis was performed to quantitatively determine the effect of amino acid substitutions in SCN1A on epilepsy severity phenotype using physicochemical property indices of the amino acid, and to discuss in the context of the molecular evolution of the proteins. Methods: PubMed was searched for articles and information was extracted on localisation and types of SCN1A missense mutations in patients with benign and severe epileptic syndromes; detailed information was also extracted. Results: Meta-analysis quantitatively revealed that the physicochemical properties of several amino acids significantly affected epilepsy phenotype severity. It showed that missense mutations that decreased protein hydrophobicity were significantly associated with severe epilepsy phenotypes. It also showed that the phenotype severity of SCN1A missense mutations in the transmembrane domains of SCN1A (128/155; 82.6%)could be predicted with high sensitivity and positive predictive values using the physicochemical property changes, indicating the possibility of phenotype prediction for entirely new missense mutations using analytical methods. Conclusions: The results show that changes in the physicochemical properties of amino acids affected both the phenotype and clinical symptoms of patients with SCN1A missense mutations. This meta-analysis study provides new insights into SCN1A gene functions and a new strategy for genetic diagnosis, genetic counselling and epilepsy treatment.

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.

Neuromyelitis optica (NMO) is presumably mediated by all autoantibody against aquaporin-4 densely expressed at the blood-brain barrier. In 18 patients with NMO, brain magnetic resonance imaging (MRI) findings were systematically, reviewed. Brain MRI abnormalities were found for 89% of the patients, and the most prominent feature was "cloud-like enhancement," multiple patchy enhancing lesions with blurred margin, found in 90% of the patients with positive contrast enhancement. In NMO, brain MRI abnormalities are frequent, and cloud-like enhancement appears to be an MRI finding specific to NMO, possibly caused by primary involvement of the blood-brain barrier by the autoantibodies.

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.

The effects of anti-parkinsonian drugs on bladder function have been controversial; namely, some aggravated while others alleviated bladder dysfunction in patients with Parkinson disease. These studies, however, did not consider the close- and time-dependent effects. Therefore, we investigated these effects of apomorphine, an anti-parkinsonian drug and a nonselective dopamine receptor agonist, on the bladder function using normal conscious rats. Consecutive cycles of micturition were analyzed for 30-min periods before and after (over a 4-h period) s.c. administration of a single dose of 0.01 (low), 0.05 (medium), 0.5 (high) mg/kg of apomorphine or saline to the rats. Apomorphine administration produced various effects in relevant urodynamic parameters, although the monitored parameters remained unchanged in saline-administered rats. During filling, low-dose apomorphine induced initial decreases in voiding frequency (VF; defined as the number of voidings during a 15-min period). However, medium- and high-dose apomorphine dose-dependently induced initial increases in VF, and was followed by decreases in VF. These doses also induced initial increase in threshold pressure. During voiding, low-dose apomorphine induced initial increases in micturition volume (MV), which reflected an increase in bladder capacity (BC). However, medium- and high-dose apomorphine dose-dependently induced initial decreases in MV, and was followed by increases in MV. These doses also dose-dependently induced an initial increase in maximum bladder contraction pressure during the early phase after administration. The present study demonstrated that apomorphine displayed a close- and time-dependent biphasic effect on the normal bladder filling function. These pharmacodynamic characteristics of apomorphine could be applicable to other anti-parkinsonian drugs such as levodopa and nonselective dopamine receptor agonists, and may account for the previous reported conflicting effects of anti-parkinsonian drugs on bladder dysfunction in patients with Parkinson disease, although it needs to be evaluated in disease status. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.

Objective: To characterize brain cholinergic deficits in Parkinson disease (PD), PD with dementia (PDD), and dementia with Lewy bodies (DLB). Methods: Participants included 18 patients with PD, 21 patients with PDD/DLB, and 26 healthy controls. The PD group consisted of nine patients with early PD, each with a disease duration of less than 3 years, five of whom were de novo PD patients, and nine patients with advanced PD, each with a disease duration greater than or equal to 3 years. The PDD/DLB group consisted of 10 patients with PDD and 11 patients with DLB. All subjects underwent PET scans with N-[(11)C]-methyl-4-piperidyl acetate to measure brain acetylcholinesterase (AChE) activity. Brain AChE activity levels were estimated voxel-by-voxel in a three-compartment analysis using the arterial input function, and compared among our subject groups through both voxel-based analysis using the statistical parametric mapping software SPM5 and volume-of-interest analysis. Results: Among patients with PD, AChE activity was significantly decreased in the cerebral cortex and especially in the medial occipital cortex (% reduction compared with the normal mean = -12%) (false discovery rate-corrected p value &lt;0.01). Patients with PDD/DLB, however, had even lower AChE activity in the cerebral cortex (% reduction = -27%) (p &lt; 0.01). There was no significant difference between early PD and advanced PD groups or between DLB and PDD groups in the amount by which regional AChE activity in the brain was reduced. Conclusions: Brain cholinergic dysfunction occurs in the cerebral cortex, especially in the medial occipital cortex. It begins in early Parkinson disease, and is more widespread and profound in both Parkinson disease with dementia and dementia with Lewy bodies. Neurology (R) 2009; 73: 273-278

The first dorsal interosseclus (FDI) and abductor digiti minimi (ADM) muscles are innervated by the same ulnar nerve, but studies have shown that the former is much more severely affected in amyotrophic lateral sclerosis. In this study, threshold tracking was used to investigate whether membrane properties differ between FDI and ADM motor axons. In 12 normal subjects, compound muscle action potentials were recorded from FDI and ADM after ulnar nerve stimulation at the wrist. The strength-duration time constant was significantly longer in the FDI axons than in the ADM axons, and latent addition studies showed greater threshold changes at the conditioning-test stimulus of 0.2 ms in FDI than in ADM axons. These findings suggest that nodal persistent sodium conductances are more prominent in FDI axons than in ADM axons, and therefore excitability is physiologically higher in FDI axons. Even in the same nerve at the same sites, membrane properties of FDI and ADM motor axons differ significantly, and thus their axonal/neuronal responses to disease may also differ. Muscle Nerve 39: 350-354, 2009

Needle electromyography (EMG) of the tongue is traditionally used as a key to the diagnosis of amyotrophic lateral sclerosis (ALS), although relaxation of the tongue is often difficult to achieve. Recently, frequent abnormalities in the EMGs of the sternocleidomastoid (SCM) and upper trapezius muscles in ALS have been reported. To elucidate the diagnostic utility of these muscles we performed a multicenter prospective study to examine EMGs of the tongue (genioglossus), SCM, and trapezius in 104 ALS or suspected ALS patients. We also examined EMGs of the SCM and trapezius in 32 cervical spondylosis (CS) patients. We mainly evaluated fibrillation potentials/positive sharp waves (Fib/PSWs) and fasciculation potentials. Complete relaxation was achieved in 85% of ALS patients in the trapezius, but in only 6% of patients in the tongue. Fib/PSWs were observed in 8%, 13%, and 45% of ALS patients in the tongue, SCM, and trapezius, respectively, whereas fasciculation potentials were observed in 1%, 7%, and 39%, respectively. Abnormal spontaneous activity of any type was found in 9%, 17%, and 63% of patients, respectively. The high frequency of abnormal spontaneous activity in the trapezius was similar among the different diagnostic categories, and even 72% of clinically suspected ALS (progressive muscular atrophy) patients showed them in their trapezius. We did not observe Fib/PSWs or fasciculation potentials in any of our CS patients, thus these findings have excellent specificity. Tongue EMG added little utility over the clinical sign of tongue atrophy. Abnormal spontaneous activity in the trapezius would be more useful for the early diagnosis of ALS.

MRI findings of sarcoidosis are usually intraparenchymal granuloma with leptomeningeal lesions. This appearance is dependent upon leptomeningeal lesions subsequently infiltrating to parenchyma. We describe a 52-year-old man with slowly progressive paresthesias and weakness in his legs. MRI showed diffuse leptomeningeal lesions throughout the brainstem and spinal cord without intraparenchymal lesions. A diagnosis of sarcoidosis was confirmed by cervical lymph node biopsy which detected noncaseating granuloma. Only leptomeningeal lesions throughout the brainstem and spinal cord could be observed in sarcoidosis.

Background: Some patients with Fisher syndrome (FS) developed subsequent descending tetraparesis (Fisher/Guillain-Barre overlapping syndrome: FS/GBS). The assumption is that such descending progression may frequently lead to respiratory failure. Objective: To investigate whether patients with FS/GBS more often require artificial ventilation than those with typical GBS and which clinical and serological findings are useful predictors. Methods: Medical records were reviewed of patients who had acute ophthalmoplegia, ataxia and areflexia, as well as subsequent tetraparesis with monophasic course. Forty-five patients fulfilled the FS/GBS criteria. Clinical and serological features were analysed, and clinical predictors of mechanical ventilation were investigated. Results: FS/GBS patients more frequently required mechanical ventilation than did GBS patients (24% vs 10%, p = 0.04). The former also needed artificial ventilation earlier than the latter (p = 0.03), but none of the FS patients required it. As the initial symptom, ventilated FS/GBS patients more frequently showed titubation than non-ventilated patients (55% vs 18%, p = 0.04). During the course of the illness, descending tetraparesis was more common in 11 ventilated FS/GBS patients than in the other 34 non-ventilated patients (64% vs 21%, p = 0.02). The need for artificial ventilation was not associated with anti-GQ1b IgG antibodies, mono-specific anti-GT1a IgG antibodies or IgG antibodies to various ganglioside complexes. Conclusions: FS/GBS patients significantly needed mechanical ventilation more often. Such patients showing titubation and descending tetraparesis need to be carefully monitored as the illness progresses because those clinical features are helpful predictors of respiratory failure.

Autoantibodies against voltage-gated potassium channels (VGKC-Abs) are associated with acquired neuromyotonia (Isaacs' syndrome) and related disorders such as Morvan's syndrome and some cases of limbic encephalitis. The mechanisms underlying the various phenotypes induced by VGKC-Abs are not fully understood. Recently, we reported a case of LE with VGKC-Abs accompanied by severe intestinal pseudo-obstruction and thymoma. Thymectomy and immunosuppressive therapy induced dramatic clinical improvement of LE symptoms, and VGKC-Abs titers decreased from 1254 pM to 549 pM (normal &gt; 100 pM). Seventeen months later, the patient developed progressive generalized muscle cramping, paresthesias in his lower extremities, excessive sweating, and severe constipation. There was no recurrence of the LE. Electromyography showed fasciculation potentials and myokymic discharges, and the plasma VGKC-Abs titer was again elevated to 879 pM. Here we report a case of Isaacs' syndrome after complete remission of LE with VGKC-Abs that may provide an insight into a possible link among VGKC-Abs associated syndromes. (C) 2008 Elsevier B.V. All rights reserved

Background: Polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes (POEMS) syndrome is a rare multi-system disorder associated with plasma-cell dyscrasia. Several case series and reports have suggested that high-dose chemotherapy with autologous peripheral blood stem-cell transplantation is efficacious treatment, but this transplantation is not indicated for elderly patients and patients with renal failure. Objective: To investigate the effects of thalidomide treatment for POEMS syndrome. Methods: Nine patients, who were not indicated for high-dose chemotherapy, were treated with thalidomide. Neurological disability scores, nerve conduction studies and serum levels of vascular endothelial growth factor (VEGF) were prospectively examined. VEGF levels were measured by an enzyme-linked immunosorbent assay. Results: During follow-up periods of 8-23 months (mean, 15 months), all patients showed substantial clinical improvement (n = 6) or stabilisation of symptoms (n = 3). Serum VEGF levels decreased in all patients and were normalised in five patients. Nerve conduction velocities in the median nerve increased in seven patients. There were no serious adverse effects, including thalidomide neuropathy. Conclusion: Thalidomide treatment should be further studied as a treatment for POEMS syndrome, particularly for patients who are not indicated for transplantation therapy.

Background: Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is a rare multisystem disorder associated with plasma cell dyscrasia. There is increasing evidence that high-dose chemotherapy with autologous peripheral blood stem cell transplantation (Auto-PBSCT) is an efficacious treatment. Objective: To elucidate the extent and time course of neurologic improvement after Auto-PBSCT in patients with POEMS syndrome. Methods: Clinical and electrophysiologic findings in nine patients were reviewed. The median follow-up period was 20 months (range, 8 to 49 months). Serum levels of vascular endothelial growth factor (VEGF) were measured by ELISA. Results: Serum VEGF levels rapidly decreased a month after Auto-PBSCT. Within 3 months, neurologic improvement began, and all the patients showed substantial neurologic recovery during the next 3 months. Particularly, three initially chairbound patients regained ability to walk at 6 months. Nerve conduction studies showed significant increases in conduction velocities and amplitudes within 6 months of treatment. At the end of follow-up periods, neuropathy was still improving, and no patients had recurrence of symptoms. Conclusion: Autologous peripheral blood stem cell transplantation results in obvious neurologic improvement within 6 months, presumably by extensive axonal regeneration and remyelination. This therapy could be considered as a first line treatment for patients with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes syndrome with younger onset even if they are tetraplegic. Neurology (R) 2008;71:1691-1695

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.

Objective and methods: To characterise the epidemiological features of chronic inflammatory demyelinating polyneuropathy (CIDP) in the Japanese population, this study performed a nationwide assessment of the prevalence and incidence rates in Japan. Results: The prevalence rate per 100 000 was 1.61 in the total population 2.01 in males and 1.23 in females. The age dependent prevalence rates were 0.23 in juveniles (&lt 15 years old), 1.50 in young adults (15-55 years) and 2.31 in elderly adults (&gt 55 years). The sex and age dependent prevalence rates were 0.22 in males and 0.24 in females in juveniles, 1.81 in males and 1.19 in females in young adults, and 3.12 in males and 1.64 in females in elderly adults. The annual incidence rate per 100 000 was 0.48 in the total population, 0.58 in males and 0.38 in females. The age dependent incidence rate was 0.06 in juveniles, 0.40 in young adults and 0.73 in elderly adults. The sex and age dependent incidence rate was 0.05 in males and 0.08 in females in juveniles, 0.50 in males and 0.30 in females in young adults, and 0.93 in males and 0.58 in females in elderly adults. Both the prevalence and incidence rates were very similar throughout the eight geographical areas studied, from the northern to the southern parts of Japan. Conclusions: The prevalence and incidence rates were similar to those reported in the Caucasian population. The pathogenic background is suggested to be common throughout the different races and geographic areas, while gender and age effects should be taken into account in the pathogenesis of CIDP.