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The current study aimed to evaluate whether cerebrospinal fluid (CSF) neuron-specific enolase (NSE) levels are elevated in amyotrophic lateral sclerosis (ALS) and are effective in distinguishing ALS from cervical spondylotic myelopathy (CSM). We retrospectively evaluated 45 patients with ALS, 23 with CSM, 28 controls, and 10 with Parkinson’s disease (PD) who underwent analysis of CSF NSE levels. The control group comprised patients aged above 45 years who underwent lumbar puncture because of suspected neurological disorders that were ruled out after extensive investigations. CSF NSE levels were evaluated using the electro-chemiluminescent immunoassay. The ALS group had significantly higher CSF NSE levels than the CSM and control groups (P

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) often causes peripheral nervous system impairments. However, little is known about subclinical involvements of the central nervous system in AAV. We investigated the frequency and progression of cerebral small vessel disease (SVD) in patients with AAV. This single-center, case–control study comprised 56 patients with myeloperoxidase (MPO)-ANCA-positive AAV. Cerebral SVD presenting periventricular and deep white matter hyperintensities was assessed using brain magnetic resonance imaging (MRI). Seventy-five patients with non-stroke-associated neurological diseases were employed as controls. At clinical diagnosis of MPO-ANCA-positive AAV, the frequency of periventricular hyperintensities in the AAV group was significantly higher than that in the control group (P = 0.014). Shinohara and Fazekas grades of periventricular hyperintensities in the AAV group were significantly higher than those in the control group (P = 0.019 and 0.020, respectively). In the AAV group, atherosclerosis-related factors, such as age and hypertension, were not associated with the Shinohara grades of periventricular hyperintensities, whereas serum CRP levels were significantly associated (odds ratio = 6.000, 95% confidence interval 1.648–21.840, P = 0.004). MRI changes were followed in 23 patients with AAV until 2 years after 6 months of diagnosis. Six of these patients worsened the grades of periventricular hyperintensities, while two of 27 in the control group worsened the grades (P = 0.013). Inflammatory events are associated with the occurrence of cerebral SVD before clinical diagnosis of MPO-ANCA-positive AAV. The patients may be continuously exposed to the risk of cerebral SVD after immunosuppressive therapy.

Introduction In myasthenia gravis (MG) therapy, achieving Myeasthenia Gravis Foundation of America minimal manifestation (MM) or better status is proposed as a desirable target. However, this level of control often is not achieved and clinical factors affecting prognosis remain unclear. Methods Participants were 104 consecutive patients with MG who visited Osaka Medical College Hospital. We retrospectively assessed the association of clinical and laboratory features at baseline with prognosis. Eighty patients who achieved MM or better status were classified as the good outcome group and the remaining 24 patients were classified as the poor outcome group. Results The rate of dysphagia at baseline was significantly higher in the poor outcome group than in the good outcome group (p = 0.002). The levels of serum total protein and albumin at baseline were both significantly lower in the poor outcome group than in the good outcome group (p = 0.036 and p = 0.014, respectively). Additionally, Controlling Nutritional Status scores at baseline were significantly higher in the poor outcome group than in the good outcome group (p = 0.043). Multivariate analysis using a Cox proportional hazards model showed that dysphagia (hazard ratio [HR], 6.92; 95% confidence interval [CI], 1.49-40.31) and hypoalbuminemia (HR, 2.57; 95% CI, 1.04-6.57) at baseline were risk factors that predicted prognosis. Discussion These findings suggest that dysphagia and hypoalbuminemia at baseline are associated with outcomes and are predictive risk factors for poorer outcomes in patients with MG.

We herein report the case of a 53-year-old man with cerebellar ataxia with anti-glutamic acid decarboxylase antibody (GAD-Ab) who mimicked Miller Fisher syndrome (MFS). He developed ophthalmoplegia, diplopia, and gait ataxia for one week. The serum and cerebrospinal fluid GAD-Ab titers were greatly increased, and the GAD-Ab index suggesting intrathecal antibody synthesis was elevated, while GQ1b-Ab was negative. After steroid pulse therapy and following prednisolone, his symptoms dramatically improved over the course of 11 months with the simultaneous decline of GAD-Ab titers. This case indicates that cerebellar ataxia with GAD-Ab can present with acute neurological findings mimicking MFS, and that steroid therapy has an excellent therapeutic effect.

Introduction: Patient-reported outcomes recently have been used to assess treatment outcomes. The Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) is a particularly convenient and useful tools. However, data on the normative values of Japanese population are lacking, so the present study was conducted to gather this information. Methods: We assessed 1098 volunteers over 18 years of age (363 men and 735 women, average 50 years old) who had not received upper limb treatment in a medical facility. These participants included our institution’s staff, their family members, and the participants in the group meetings held by institution’s staff. Their occupations were also examined. We divided occupations into nonmanual and manual labor. These factors of the participants were then analyzed to clarify which (if any) influenced the QuickDASH. Results: Valid answers were obtained from 961 subjects (87.5%). The median score was 2 (mean: 4.8) in the overall population, 0 (mean: 2.6) in men, and 2.5 (mean: 6.0) in women. The scores increased with age and were higher in women than in men. There were no significant differences by manual labor. Female sex and older age were identified as factors that influenced the QuickDASH score in the multiple regression analysis. There were high correlations among QuickDASH, work and sports/music scores. Conclusions: The present study provided QuickDASH scores for Japanese volunteers who had not received upper limb treatment in a medical facility. The scores were associated with older age and female sex. This study helps us to know the degree of potential upper limb impairment in the general population, and will help in populational strategies as primary and secondary preventive medicine for upper limb-related diseases.

To determine clinical features of neurologic disorders associated with anti-glutamic acid decarboxylase antibodies (anti-GAD-Ab), we examined titers and time-dependent changes of anti-GAD-Ab. Six patients, stiff person syndrome (2), cerebellar ataxia (1), limbic encephalitis (1), epilepsy (1), brainstem encephalitis (1), were compared with 87 type I diabetes mellitus (T1DM) patients without neurologic disorders. Anti-GAD-Ab titers and index were higher in neurologic disorders than in T1DM, suggesting intrathecal antibody synthesis. Anti-GAD-Ab titers in T1DM decreased over time, whereas they remained high in neurologic disorders. Immunotherapy improved neurological disorders and anti-GAD-Ab titers and index provide clinically meaningful information about their diagnostic accuracy.

Objective To evaluate the factors related to the choice of a tracheostomy and invasive ventilation in amyotrophic lateral sclerosis patients and to determine survival time after a tracheostomy at a single institute in Japan between 1990 and 2010. Methods Data for survival time until death or tracheostomy were obtained from 160 patients. Fifty-two patients (33%) underwent tracheostomy/mechanical ventilation. Results Tracheostomy and invasive ventilation prolonged median survival time (74 months), as did non-invasive ventilation (48 months) when compared to a non-ventilation-supported control group (32 months; p 65 years old significantly increased after 1999 (27%) compared to earlier years (10%, p = 0.002). Cox proportional modeling confirmed an age of ≤ 65 years as advantageous for long-term survival after a tracheostomy. In univariate logistic regression analysis, factors related to the decision to perform a tracheostomy included an age of ≤ 65 years, greater use of non-invasive ventilation, the presence of a spouse, interval and speed from disease onset to diagnosis/tracheostomy and preservation of motor function. In multivariate logistic regression analysis, age, shorter duration from disease onset until tracheostomy and the presence of a spouse were independently associated with the decision to perform a tracheostomy. Kaplan–Meier plots revealed longer survival times in patients who resided at home after a tracheostomy compared to patients who stayed at a hospital (p = 0.007). Conclusions Tracheostomy and invasive ventilation are frequently used in Japan. Various factors impact patients' decisions to have these procedures. This study identified factors related to the decision-making process and post-tracheostomy survival.

A Japanese randomized controlled study showed that Interferon â (IFN-â1b) therapy is clinically effective in decreasing the frequency of attacks in multiple sclerosis (MS), even in optico-spinal MS (OSMS). However, recent studies have shown that IFN-â (IFN-â1a/IFN-â1b) treatment was not effective in neuromyelitis optica (NMO) patients and that the diminished benefit of IFN-â treatment in NMO may be due to different immune responses to IFN-â. We determined longitudinally the expression of CCR5, CXCR3 and CCR4 on CD4+ T and CD8+ T cells in the blood from patients with NMO and MS treated with IFN-â1b. During a 12-month period of IFN-â1b therapy, the annualized relapse rate decreased in MS patients but not in NMO patients. There was no significant difference in the expression of the chemokine receptors between NMO and MS at baseline. The percentages of CD4+CCR5+ and CD4+CXCR3+ T cells, representative of the Th1 response, were decreased in both NMO and MS after treatment. The percentage of CD4+CCR4+ T cells, representative of the Th2 response, was decreased in MS, but those for NMO was significantly increased compared with the pretreatment levels. Our results indicate that IFN-â1b-induced up-modulation of the Th2 response in NMO patients may be the source of differences in the therapeutic response to IFN-â1b therapy. In the present study, Th2 predominance is involved in the pathogenesis of NMO.

Osteochondroma of the carpal is rare. We found only 1 case of osteochondroma of the trapezium in the literature. We present a case of a 52-year-old woman with an osteochondroma of the left trapezium and trapeziometacarpal arthritis.

Guillain–Barre syndrome (GBS) is an acute, post-infectious, inflammatory, autoimmune peripheral neuropathy with a highly diverse clinical course and outcome. We classified GBS on the basis of patients’ first nerve conduction and validated this system to be associated with outcome on the basis of electrophysiological characteristics during the acute phase of GBS. We retrospectively evaluated 40 GBS patients who underwent their first electrophysiological study within 14 days of onset and classified GBS into four patterns: (1) acute inflammatory demyelinating polyneuropathy (AIDP) pattern with sensory nerve conduction abnormalities (motor–sensory AIDP: MS-AIDP), (2) AIDP pattern without sensory nerve conduction abnormalities (motor AIDP: M-AIDP), (3) acute motor axonal neuropathy (AMAN) pattern, and (4) minor abnormalities pattern. We compared the clinical, electrophysiological, and laboratory findings between groups and determined subgroups associated with poor outcome. The MS-AIDP and AMAN patterns more frequently exhibited prolonged recovery compared with the M-AIDP and minor abnormalities patterns and were associated with prolonged recovery (specificity, 100 %; sensitivity, 73 %; P < 0.001). The period of inability to walk independently was significantly longer in the MS-AIDP and AMAN patterns than in the M-AIDP and minor abnormalities patterns (median 85 vs. 10 days; P < 0.001). In conclusion, our classification of GBS using a single nerve conduction study in the early phase of disease is associated with outcomes. This classification can be used to counsel individual patients and guide decision-making with respect to treatment.

Background Pulmonary thromboembolism is a common cause of death in patients with autopsy-confirmed Parkinsonism. This study investigated the incidence of leg deep vein thrombosis in Parkinson’s disease and relationships between deep vein thrombosis and clinical/laboratory findings, including postural abnormalities as assessed by photographic measurements. Methods This cross-sectional study assessed the presence of deep vein thrombosis using bilateral leg Doppler ultrasonography in 114 asymptomatic outpatients with Parkinson’s disease. Results Deep vein thrombosis was detected in 23 patients (20%) with Parkinson’s disease. Deep vein thrombosis was located in the distal portion in 18 patients and in the proximal portion in 5 patients. No significant differences in age, sex, body mass index, disease duration, Hoehn-Yahr stage, anti-Parkinson’s drugs, or daily levodopa-equivalent dose were seen between deep vein thrombosis-positive and -negative groups. Univariate analysis for developing deep vein thrombosis in patients with Parkinson’s disease identified the following markers: long-term wheelchair use, bent knee, bent spine, and D-dimer elevation. Bending angles were significantly greater in the deep vein thrombosis-positive group at the knee and spine than in the deep vein thrombosis-negative group. Half of Parkinson’s disease patients with camptocormia had deep vein thrombosis. Among diabetes mellitus cases, long-term wheelchair use, bent knee over 15°, camptocormia, D-dimer elevation, the more risk markers were associated with a higher incidence of DVT. The presence of risk markers contributed to the development of deep vein thrombosis. On multivariate logistic regression analysis, a bent knee posture was strongly associated with an increased risk of deep vein thrombosis. Conclusion Presence of leg deep vein thrombosis correlated with postural abnormalities in Parkinson’s disease. We recommend non-invasive ultrasonographic screening for leg deep vein thrombosis in these high-risk patients with Parkinson’s disease.

Matrix metalloproteinase-9 (MMP-9) plays an important role in some neuroinflammatory diseases through the blood-brain barrier (BBB) disruption. To investigate the pathogenicity of MMP-9 in neuromyelitis optica (NMO), serum and CSF MMP-9 concentrations were measured in 13 NMO and 15 multiple sclerosis (MS) patients and 14 healthy controls, and correlated with clinical and laboratorial parameters. Serum MMP-9 concentrations were significantly higher in NMO than MS and controls, and correlated with EDSS score, CSF/serum albumin ratio, and CSF IL-8 concentrations. Our results indicate that MMP-9, promoted by elevated IL-8 activation, plays a crucial role in the pathogenesis of NMO through the BBB disruption.

Anhedonia has been proposed as a specific mood disorder related to the dopaminergic nerve dysfunction seen in Parkinson's disease (PD). This study examined hedonic tone in patients with PD using the Snaith-Hamilton Pleasure Scale (SHAPS) and investigated the associations with depressive mood by the Self-Rating Questionnaire for Depression (SRQ-D).This study examined 100 patients with PD and 111 age-matched controls (C2) recruited from 300 healthy subjects (C1) to compare the frequency of anhedonia and to clarify whether anhedonia in PD is associated with depression and anti-Parkinson medication.Forty-six percent of PD patients revealed possible/probable depression and 10 patients (10%) with PD showed anhedonia as compared to 3.3% in C1 and 2.7% in C2. The reduction in hedonic tone was related to depression in PD. Among 10 PD patients with anhedonia, seven were in anhedonia with depression and three were in anhedonia without depression. There was no sex difference in anhedonia and depression. No patients treated with pramipexole showed anhedonia but also the highest proportion of normal hedonic tone was found in patients treated with pramipexole among PD patients. In analysis of each SHAPS item, no significant difference was seen on social interaction scores in contrast to the significant reduction of interest/pastimes and sensory experience and food/drink scores between PD patients and C1/C2.Anhedonia may overlap depressive syndrome but some PD patients without depression presented anhedonia. Pramipexole could maintain hedonic tone. The PD patients could enjoy attracting attention and wish to do things helpful for others.

Respiratory insufficiency is a problem that develops in nearly all people diagnosed with amyotrophic lateral sclerosis (ALS). A 46-year-old man with ALS, who had been in a bedridden state with tracheal ventilation support, complained of faintness and dyspnea. The airway pressure of the ventilator had increased, and bleeding from the trachea had occurred several times. A fiberoptic bronchoscopy showed granulation located on the anterior wall of the trachea and severe airway obstruction of the tracheostomy tube. Although a long tracheostomy tube had been intubated for the initial management of the tracheal granulation, a tumor on the posterior tracheal wall had relapsed and occluded the tracheal lumen. A self-expandable metallic airway stent was placed into the tracheal stenosis. After stenting, his symptoms of dyspnea and syncope imploved, and the increased airway pressure of the ventilator was normalized. We speculated that the tracheal granuloma had occurred due to a tracheal mucosal injury related to endotracheal suctioning. We should pay attention to complaints of dyspnea in ALS patients with tracheostomy and make a careful consideration to airway care including suction management.

To determine which of the three motor functions (bulbar, upper extremities, lower extremities) was normally preserved at the time that respiratory symptoms occurred in amyotrophic lateral sclerosis (ALS).Respiratory failure is the major cause of death in ALS. The course of the disease progression to the onset of subjective respiratory symptom can vary from patient to patient and the diversity of this progression in ALS patients is not well understood.The subjects were 120 Japanese patients with sporadic ALS who were followed-up at our hospital or for whom precise information was available regarding death or the time that the patient required tracheotomy or ventilation assistance. Symptoms started: in the upper limbs in 47 patients; in the lower limbs in 44 patients; in the bulbar region in 22 patients; as the combined type (two regions involved simultaneously on initial presentation) in 6 patients; and with respiratory symptoms in 1 patient.At the time of the appearance of respiratory symptoms, 43 patients (35.8%) had some normally preserved motor function. Significantly fewer patients with progressive bulbar palsy maintained one or more normal motor functions (14%) compared to patients whose disease started in the extremities (43%). Patients were divided into two groups depending on whether they had significant bulbar involvement at the time of the appearance of respiratory symptoms: 88 patients had significant bulbar involvement (B type), and 32 patients did not (R type). Based on the Kaplan-Meier survival curves, no significant difference in the median survival time was noted between the two groups (R type, 29.4 months vs. B type, 32.5 months; p = 0.06). We could not find any difference about clinical characteristics such as gender, onset age, initial site between R and B group. The motor functions that were preserved at the time of respiratory symptom onset included: bulbar function in 32 patients (26.7%); lower extremity function in 12 patients (10%); and upper extremity function in only 3 patients (2.5%). The use of mechanical ventilation in ALS patients with one or more preserved motor functions was significantly higher than in those without any normally preserved motor function (p = 0.03).From a low rate of upper extremity motor function preservation, respiratory function deterioration appears to be related to upper-limb involvement, likely due to a possible link to diaphragmatic function. Advanced directives should carefully address the use of mechanical ventilation in patients without bulbar symptoms.

Two patients presented with malignant hypertension associated with encephalopathy predominantly manifesting as brainstem lesion. T(2)-weighted and fluid-attenuated inversion recovery magnetic resonance (MR) imaging revealed diffuse hyperintense areas in the pons and scattered lesions in the cerebellum, basal ganglia, and cerebral subcortex without parieto-occipital lesions. Diffusion-weighted MR imaging demonstrated these lesions as normal intensity, indicating vasogenic edema. These lesions resolved rapidly once hypertension was controlled. Review of clinical findings for 14 other patients with hypertensive brainstem encephalopathy without parieto-occipital lesions suggested that anterior circulation structures supplied by the carotid artery are frequently involved in such patients.

An intensive combination chemotherapy regimen supported by granulocyte colony-stimulating factor (G-CSF) was evaluated in adult T-cell leukemia/lymphoma (ATLL) patients in a multiinstitutional, cooperative study. Vincristine 1 mg/m2 i.v. day 1, Adriamycin 40 mg/m2 i.v. day 1, cyclophosphamide 400 mg/m2 i.v. day 1, prednisolone 40 mg/m2 i.v. days 1 to 3 and 8 to 10, etoposide 35 mg/m2 i.v. days 1 to 8, vindesine 2 mg/m2 i.v. day 8, ranimustine 50 mg/m2 i.v. day 8, mitoxantrone 7 mg/m2 i.v. day 8, and G-CSF 50 mg/m2 s.c. days 9 to 21 were given for 2 to 4 courses every 3 weeks to 83 patients with ATLL. Complete remission (CR) and partial remission (PR) were achieved in 35.8 and 38.3 percent, respectively, of 81 evaluable patients. The median survival of all patients was 8.5 months, with a predicted 3-year survival of 13.5 percent by the Kaplan-Meier method. The median duration of response was 7.6 months (range 0.2-42.7), and 13 patients were alive. Their median survival time was 29.1 months (range 19.2-44.7). In 67.6 percent of courses, white blood cell (WBC) nadirs were1.0 x 10(9)/L. Days required for the recovery of WBC from the nadir to1.0 x 10(9)/L were5 days in 71.4 percent of the treatment courses. The G-CSF supported an intensified chemotherapy regimen for ATLL and yielded better response rate and longer survival compared to previous reports in Japan. Because duration of remission is still short, further studies of postremission therapy or other strategies are warranted.