Comparison of erector spinae fatigability between female patients with Parkinson's disease and healthy individuals: a cross sectional pilot study.

BACKGROUND: Postural abnormality is one of the main symptoms of Parkinson's disease (PD). The erector spinae muscles play an important role in maintaining an upright posture, but the fatigability of the erector spinae in patients with PD is unknown. The purpose of this study was to compare the trunk extension maximum voluntary contraction (MVC) and the fatigability of the erector spinae between female patients with PD and healthy volunteers. METHODS: Th participants of this cross-sectional pilot study comprised 19 patients with PD and nine healthy volunteers matched for sex, age, and physical characteristics as a control group. The MVC of all participants was measured, and after sufficient rest, the Sørensen back endurance test was conducted to the point of exhaustion. The muscle activity of the erector spinae during the Sørensen back endurance test was measured using surface electromyography. The median frequency (MF) slope, which is an index of fatigability, was calculated from the recorded surface muscle activity by means of power spectrum analysis using a Fast Fourier transformation. RESULTS: Nine of the 19 patients with PD were unable to perform the Sørensen back endurance test, and a lower proportion of the PD group were able to perform it compared with the control group. The MVC of those patients with PD who were able to perform the Sørensen back endurance test was lower than that of the control group, and the time for which the pose could be maintained was shorter. There was no significant difference between the MF slope on the left and right side in the PD group, and it was higher on both sides than in the control group. CONCLUSION: This is the first study to demonstrate a reduction of maximum muscle strength and great fatigability of the erector spinae in patients with PD. This discovery strongly underlines the need for paraspinal muscle training from an early stage with the aim of preventing the progression of postural abnormality in patients with PD.

Increased large-scale inter-network connectivity in relation to impulsivity in Parkinson's disease.

Impulsivity is a neuropsychiatric feature of Parkinson's disease (PD). We investigated the pathophysiology of impulsivity in PD using resting-state functional magnetic resonance imaging (rs-fMRI). We investigated 45 patients with idiopathic PD and 21 healthy controls. Based on Barratt Impulsiveness Scale (BIS-11) score, PD patients were classified as higher (PD-HI) or lower impulsivity (PD-LI). Functional connectivity (FC) between various large-scale brain networks were analysed using the CONN toolbox. FC between the right frontoparietal network (FPN) and medial visual network (MVN) was significantly higher in PD-HI patients than PD-LI patients (false discovery rate [FDR]-adjusted p = 0.0315). FC between the right FPN and MVN had a significant positive correlation with total BIS-11 score (FDR-adjusted p = 0.010) and the attentional impulsivity (FDR-adjusted p = 0.046) and non-planning impulsivity subscale scores (FDR-adjusted p = 0.018). On the other hand, motor impulsivity subscale score had a significant negative correlation with the FC between the default-mode and salience networks (right supramarginal gyrus, FDR-adjusted p = 0.018; anterior cingulate cortex, FDR-adjusted p = 0.027); this trend was observed in healthy controls. The attentional and non-planning impulsivity, regarded as 'cognitive' impulsivity, may be associated with dysfunction in integration of perceptual information and flexible cognitive control in PD.

The updated retrospective questionnaire study of sporadic inclusion body myositis in Japan.

BACKGROUND: Sporadic inclusion body myositis (sIBM) is the most prevalent muscle disease in elderly people, affecting the daily activities. sIBM is progressive with unknown cause and without effective treatment. In 2015, sIBM was classified as an intractable disease by the Japanese government, and the treatment cost was partly covered by the government. This study aimed to examine the changes in the number of patients with sIBM over the last 10 years and to elucidate the cross-sectional profile of Japanese patients with sIBM. METHODS: The number of sIBM patients was estimated through a reply-paid postcard questionnaire for attending physicians. Only patients diagnosed as "definite" or "probable" sIBM by clinical and biopsy sIBM criteria were included in this study (Lancet Neurol 6:620-631, 2007, Neuromuscul Disord 23:1044-1055, 2013). Additionally, a registered self-administered questionnaire was also sent to 106 patients who agreed to reply via their attending physician, between November 2016 and March 2017. RESULTS: The number of patients diagnosed with sIBM for each 5-year period was 286 and 384 in 2011 and 2016, respectively. Inability to stand-up, cane-dependent gait, inability to open a plastic bottle, choking on food ingestion, and being wheelchair-bound should be included as sIBM milestones. Eight patients were positive for anti-hepatitis C virus antibody; three of them were administered interferon before sIBM onset. Steroids were administered to 33 patients (31.1%) and intravenous immunoglobulin to 46 patients (43.4%). From 2016 to 2017, total of 70 patients applied for the designated incurable disease medical expenses subsidy program. Although the treatment cost was partly covered by the government, many patients expressed psychological/mental and financial anxieties. CONCLUSIONS: We determined the cross-sectional profile of Japanese patients with sIBM. Continuous support and prospective surveys are warranted.

Superficial siderosis associated with duplicated dura mater detected by CISS reverse MRI.

Superficial siderosis (SS) of the central nervous system is a rare disease caused by chronic or repeated hemorrhages in the subarachnoid space. Closure of dural defects is an effective therapy for SS. Conventional magnetic resonance imaging (MRI), however, cannot sufficiently detect dural tears. To better detect these defects, we analyzed the clinical data of consecutive patients admitted to our department with SS and performed constructive interference in steady-state (CISS) reverse MRI of the brain and spinal cord. CISS reverse method emphasizes the contrast between the dura and cerebrospinal fluid, enabling detection of dural defects better than usual T2-weighted MRI. CISS reverse MRI detected fluid-filled collections in five of the seven SS patients we studied. These images showed that the fluid-filled collections were packed within duplicated dura mater. In three of the five, dural defects were confirmed intraoperatively. We postulate that fluid-filled collections are actually derived from dissection of the dura mater. In accordance with the Monro-Kellie hypothesis, we propose that CSF transferal into the fluid-filled collections via dural defects induces an increase in blood volume and promotes the exudation of blood from engorged vessels. In patients with SS, it is very important to repair dural defects to prevent further associated neurological impairment. CISS reverse MRI is useful for detecting such dural defects.

Anti-ganglionic AChR antibodies in Japanese patients with motility disorders.

BACKGROUND: The existence of several autoantibodies suggests an autoimmune basis for gastrointestinal (GI) dysmotility. Whether GI motility disorders are features of autoimmune autonomic ganglionopathy (AAG) or are related to circulating anti-ganglionic acetylcholine receptor (gAChR) antibodies (Abs) is not known. The aim of this study was to determine the associations between autonomic dysfunction, anti-gAChR Abs, and clinical features in patients with GI motility disorders including achalasia and chronic intestinal pseudo-obstruction (CIPO). METHODS: First study: retrospective cohort study and laboratory investigation. Samples from 123 patients with seropositive AAG were obtained between 2012 and 2017. Second study: prospective study. Samples from 28 patients with achalasia and 14 patients with CIPO were obtained between 2014 and 2016, and 2013 and 2017, respectively. In the first study, we analyzed clinical profiles of seropositive AAG patients. In the second study, we compared clinical profiles, autonomic symptoms, and results of antibody screening between seropositive, seronegative achalasia, and CIPO groups. RESULTS: In the first study, we identified 10 patients (8.1%) who presented with achalasia, or gastroparesis, or paralytic ileus. In the second study, we detected anti-gAChR Abs in 21.4% of the achalasia patients, and in 50.0% of the CIPO patients. Although patients with achalasia and CIPO demonstrated widespread autonomic dysfunction, bladder dysfunction was observed in the seropositive patients with CIPO as a prominent clinical characteristic of dysautonomia. CONCLUSIONS: These results demonstrate a significant prevalence of anti-gAChR antibodies in patients with achalasia and CIPO. Anti-gAChR Abs might mediate autonomic dysfunction, contributing to autoimmune mechanisms underlying these GI motility disorders.

Multicenter questionnaire survey for sporadic inclusion body myositis in Japan.

BACKGROUND: Sporadic inclusion body myositis (sIBM) is the most prevalent acquired muscle disease in the elderly. sIBM is an intractable and progressive disease of unknown cause and without effective treatment. The etiology of sIBM is still unknown; however, genetic factors, aging, lifestyles, and environmental factors may be involved. The purpose of this study is to elucidate the cross-sectional profile of patients affected by sIBM in Japan. METHODS: We surveyed patient data for 146 cases diagnosed at a number of centers across Japan. We also issued a questionnaire for 67 patients and direct caregivers to further elucidate the natural history of the disease. RESULTS: The mean age at the onset was 63.4 ± 9.2 years. The mean length of time from the onset to diagnosis was 55.52 ± 49.72 months, suggesting that there is a difficulty in diagnosing this disease with long-term consequences because of late treatment. 73 % described the psychological/mental aspect of the disease. The most popular primary caregiver was the patient's spouse and 57 % patients mentioned that they were having problems managing the finances. CONCLUSIONS: Through these surveys, we described the cross-sectional profiles of sIBM in Japan. Many patients described psychological/mental and financial anxiety because of the aged profile of sIBM patients. The profiles of sIBM patients are similar to those in Western countries.

Anti-U3 ribonucleoprotein antibody-positive inflammatory myopathy: a case report.

BACKGROUND: The discovery of myositis-specific autoantibodies and myositis-associated autoantibodies has led to a new serological classification. Human U3 RNP, which consists of the U3 small nucleolar RNA and anti-U3 RNP antibody, is directed against one of the subunits. Anti-U3 RNP antibodies have been detected in 5-8 % of patients with systemic sclerosis, and antibody-positive patients with systemic sclerosis have shown more frequent skeletal muscle involvement than that of antibody-negative patients with systemic sclerosis. CASE PRESENTATION: A 74-year-old Japanese man positive for anti-U3 RNP antibody was referred to our hospital because of gait disturbance and dysphagia. His serum myoglobin and creatine kinase levels were elevated, and myopathic changes were observed in his proximal legs by needle electromyography. A muscle biopsy was performed at the quadriceps femoris muscle, which showed high signal intensity on fat-suppressed and T2-weighted magnetic resonance images. The patient was diagnosed with probable polymyositis because CD8-positive lymphocytes had invaded only the endomysium and not into the muscle fibers. Severe proliferation of the interstitial connective tissue and edematous changes were observed. Oral prednisolone therapy was started, and the patient's muscle weakness of the proximal limbs improved remarkably within 1 month. Dysphagia caused by incomplete function of the cricopharyngeal muscle persisted for 5 years. CONCLUSIONS: Our findings indicate that mild muscle weakness with steroid-resistant dysphagia may be a clinical feature of patients with anti-U3 RNP antibody-positive inflammatory myopathy.

Fatigue-related differences in erector spinae between prepubertal children and young adults using surface electromyographic power spectral analysis.

BACKGROUND: The erector spinae is more resistant to fatigue in adult women than men. However, no study has reported the sex differences in back muscle fatigue in children. OBJECTIVE: The aim of this study was to evaluate the fatigability of erector spinae in prepubertal children and adults, in both males and females. METHODS: Fourteen prepubertal boys, 13 prepubertal girls, 14 adult men, and 13 adult women performed the Sørensen back isometric endurance test until exhaustion. The results of electromyographic (EMG) power spectral analysis of erector spinae were compared between both age groups and sexes. RESULTS: The slopes of EMG power spectral median and mean power frequency were significantly higher in males than in females, in both age groups. Furthermore, the slopes were significantly lower in prepubertal children than in adults, in both males and females. CONCLUSIONS: Our results showed major differences in the fatigue threshold of the erector spinae between boys and girls and children and adults. The muscle fatigued faster in prepubertal boys and adult men than in prepubertal girls and adult women. In both sexes, a lower slope of EMG power spectrum parameters of the erector spinae was noted during endurance test in prepubertal children compared to adults.

Methotrexate myelopathy after intrathecal chemotherapy: a case report.

INTRODUCTION: Methotrexate is often administered intrathecally or into the cerebral ventricles, particularly in patients with central nervous system tumors. However, in addition to chemical arachnoiditis, methotrexate can induce severe myelopathy. CASE PRESENTATION: A 59-year-old Japanese man with diffuse B-cell lymphoma who underwent systemic chemotherapy including methotrexate and 20 Gy of radiotherapy received intrathecal methotrexate for recurrence. Flaccid paresis of his lower limbs and fecal and urinary incontinence appeared 1 month later. All sensations were impaired below the Th10 dermatome level. Although the clinical symptoms were compatible with transverse myelitis, T2-weighted imaging of his thoracic spinal cord demonstrated signal hyperintensity localized to the posterior and lateral funiculi, which resembled subacute combined degeneration. His serum vitamin B12, folic acid, and total homocysteine levels were within normal limits, but total homocysteine levels in his cerebrospinal fluid were elevated, suggesting spinal cord demyelination. CONCLUSIONS: Little is known of the pathogenesis of methotrexate myelopathy. A possible mechanism of methotrexate myelopathy with demyelination was suggested by the increased homocysteine levels in the cerebrospinal fluid.

Statins and myotoxic effects associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies: an observational study in Japan.

Statins have a variety of myotoxic effects and can trigger the development of inflammatory myopathies or myasthenia gravis (MG) mediated by immunomodulatory properties. Autoantibodies to 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) have been identified in patients with statin-associated myopathy. The purpose of the present study is to develop an enzyme-linked immunosorbent assay (ELISA) of anti-HMGCR antibodies and to elucidate the clinical significance of anti-HMGCR antibodies in Japanese patients with inflammatory myopathies or MG. We enrolled 75 patients with inflammatory myopathies, who were all negative for anti-signal recognition particle and anti-aminoacyl transfer RNA synthetase antibodies. They were referred to Keio University and National Center of Neurology and Psychiatry between October 2010 and September 2012. We also studied 251 patients with MG who were followed at the MG Clinic at Keio University Hospital. Anti-HMGCR antibodies were detected by ELISA. We investigated demographic, clinical, radiological, and histological findings associated with anti-HMGCR antibodies. We established the anti-HMGCR ELISA with the recombinant protein. Protein immunoprecipitation detected autoantigens corresponding to HMGCR. Immunohistochemistry using muscle biopsy specimens revealed regenerating muscle fibers clearly stained by polyclonal anti-HMGCR antibodies and patients' serum. Anti-HMGCR autoantibodies were specifically detected in 8 patients with necrotizing myopathy. The seropositivity rate in the necrotizing myopathy patients was significantly higher than those in the patients with other histological diagnoses of inflammatory myopathies (31% vs 2%, P = 0.001). Statins were administered in only 3 of the 8 anti-HMGCR-positive patients. Myopathy associated with anti-HMGCR antibodies showed mild limb weakness and favorable response to immunotherapy. All 8 patients exhibited increased signal intensities on short T1 inversion recovery of muscle MRI. Of the 251 patients with MG, 23 were administered statins at the onset of MG. One late-onset MG patient experienced MG worsening after 4-wk treatment with atorvastatin. However, anti-HMGCR antibodies were not detected in the 251 MG patients except for one early-onset MG patient with no history of statin therapy. Anti-HMGCR antibodies are a relevant clinical marker of necrotizing myopathy with or without statin exposure, but they are not associated with the onset or deterioration of MG.

[The etiology and pathogenesis of sporadic inclusion body myositis].

Sporadic inclusion body myositis (sIBM) is the most common acquired muscle disease in older individuals. Muscle weakness and atrophy in the quadriceps, wrist flexor, and finger flexors are the typical clinical findings in sIBM. The etiology and pathogenesis of sIBM are still poorly understood; however, genetic factors, aging, and environmental factors might possibly play a role. The pathological characteristics of sIBM include two unique features: inflammatory changes in muscle fibers, and cytoplasmic and intranuclear inclusions containing several Alzheimer-type proteins. Based on these pathological findings, there is a continuing debate on whether sIBM is primarily a T cell-mediated inflammatory myositis or a myodegenerative disorder characterized by abnormal protein aggregation, presence of inclusions bodies, and secondary inflammation. Unfortunately, sIBM is also generally refractory to immune therapy.

Methylmercury exposure and neurological outcomes in Taiji residents accustomed to consuming whale meat.

Methylmercury (MeHg) is a major environmental neurotoxicant that causes damage to the central nervous system. In Japan, industrial emission of MeHg has resulted in MeHg intoxication in Minamata and Niigata, the so-called Minamata disease. Humans are exposed to MeHg derived from natural sources, primarily fish and fish predators. Therefore, MeHg continues to be an environmental risk to human health, particularly in susceptible populations that frequently consume substantial amounts of fish or fish predators such as whale. This study aimed to investigate the health effects of MeHg exposure in adults. The subjects were 194 residents (117 males, 77 females; age 20-85 years) who resided in the coastal town of Taiji, the birthplace of traditional whaling in Japan. We analyzed hair for mercury content and performed detailed neurological examinations and dietary surveys. Audiometry, magnetic resonance imaging, and electromyography were performed to diagnose neurological defects. Whole blood mercury and selenium (Se) levels were measured in 23 subjects. The geometric mean of the hair mercury levels was 14.9 µg/g. Twelve subjects revealed hair mercury levels >50 µg/g (NOAEL) set by WHO. Hair mercury levels significantly correlated with daily whale meat intake. These results suggested that residents in Taiji were highly exposed to MeHg by ingesting MeHg-contaminated whale meat. Multivariate regression analysis demonstrated no significant correlations between hair mercury levels and neurological outcomes, whereas some of the findings significantly correlated with age. A significantly positive correlation between whole blood mercury and Se levels was observed and the whole blood mercury/Se molar ratios of all subjects were <1. These findings suggested that sufficient Se intake might be one of causes of the absence of adverse effects of MeHg exposure in this study.

Chronic inflammatory demyelinating polyneuropathy associated with primary biliary cirrhosis.

We report a patient with chronic inflammatory demyelinating polyneuropathy associated with primary biliary cirrhosis (PBC). Except for minimal biochemical abnormalities, clinical symptoms of PBC were not observed, and we diagnosed our patient with asymptomatic PBC from the results of a liver biopsy. Although the patient noticed little muscle weakness, an electrophysiological study demonstrated slow conduction velocities and prolonged distal latencies, with definite conduction blocks in the median, ulnar, and tibial nerves. The disturbed sensory pattern was asymmetrical, and sensory nerve action potentials were not evoked. From these observations, we diagnosed this patient with chronic inflammatory demyelinating polyneuropathy. Neuropathy associated with PBC is very rare. We must differentiate demyelinating neuropathy with PBC in patients with asymmetrical sensory dominant neuropathy with high immunoglobulin M titers, and investigate for the presence of anti-mitochondrial antibodies to rule out a complication of asymptomatic PBC.

Balloon dilation in sporadic inclusion body myositis patients with Dysphagia.

Here, we describe balloon catheter dilation at the upper esophageal sphincter (UES) in three sporadic inclusion body myositis (s-IBM) patients with dysphagia. Initially, we performed IVIg therapy, and, three months later, switched to balloon dilation therapy. A 12-Fr balloon catheter was inserted from the mouth under fluoroscopy and the balloon inflated at the UES. The catheter was pulled back and re-inserted several times. We examined videofluoroscopy (VF) and pressure at the oropharynx, hypopharynx and UES using computed pharyngoesophageal manometry (CPM). Before both therapies, the VF study revealed a very small amount of barium paste passing through the UES. After balloon dilation therapy, as well as IVIg, subjective complaints of dysphagia disappeared and the VF study revealed an increased amount of barium paste passing through the UES. We conclude that balloon dilation therapy is a complementary method for conventional dysphagia therapies in s-IBM patients with dysphagia.

Myelin-associated glycoprotein-related neuropathy associated with psoriasis: a case report.

INTRODUCTION: Psoriasis vulgaris is a common inflammatory disease of the skin, and myelin-associated glycoprotein-related neuropathy is a chronic sensory-predominant polyneuropathy. Although both of these diseases are considered autoimmune diseases, psoriasis with concomitant myelin-associated glycoprotein-related neuropathy is very rare. Here, we report a case of myelin-associated glycoprotein-related neuropathy associated with psoriasis. CASE PRESENTATION: A 66-year-old Japanese man, having experienced sternocostoclavicular pain for ten years, was admitted to our hospital because of gait disturbance and numbness of the limbs. Our patient had normal cranial nerve function and normal limb muscle strength. His vibratory and position sense was severely impaired and his touch, temperature and pinprick sensations were mildly disturbed in a glove and stocking distribution. A myelin-associated glycoprotein western blot analysis showed the presence of a 91 to 94kDa band using purified human myelin-associated glycoprotein antigen. His skin lesions were moderately pruritic and Auspitz's sign was positive. Our patient also showed osteitis of his clavicle and manubrium. We diagnosed our patient with myelin-associated glycoprotein-related neuropathy associated with psoriatic arthritis. Five days after intravenous immunoglobulin therapy, his deep sensory impairment began to improve and his sternocostoclavicular pain diminished dramatically. CONCLUSIONS: Because myelin-associated glycoprotein-related neuropathy and psoriatic arthritis are both considered autoimmune diseases, we conclude that intravenous immunoglobulin therapy is very effective for patients with an association of these diseases.

A dysphagia study in patients with sporadic inclusion body myositis (s-IBM).

The nature of the swallowing impairment in patients with sporadic inclusion body myositis (s-IBM) has not been well characterized. In this study, we examined ten consecutive s-IBM patients using videofluoroscopy (VF) and computed pharyngoesophageal manometry (CPM). The patients were divided into two groups: patients with complaint and without complaint of dysphagia. VF results indicated pharyngeal muscle propulsion (PP) at the hypopharyngeal and upper esophagus sphincter (UES) in all s-IBM patients. Patients without complaint of dysphagia showed a mild degree of PP, whereas a severe form of PP was observed in patients with complaint of dysphagia. CPM revealed that negative pressure during UES opening was not observed in the s-IBM patients with complaint of dysphagia. Incomplete opening and PP at the UES were observed in all s-IBM patients. These results indicate that the dysphagic processes occur subclinically in s-IBM patients who may not report swallowing impairments.