The right amygdala and migraine: Analyzing volume reduction and its relationship with symptom severity.

This study aimed to explore the relationship between gray matter volume changes and various clinical parameters in patients with migraine, focusing on symptom severity, quality of life, and states of depression and anxiety. Using a case-control design, we examined 33 patients with migraine, with or without aura, and 27 age-matched healthy subjects. We used magnetic resonance imaging to assess the volumes of 140 bilateral brain regions. Clinical evaluations included the Migraine Disability Assessment, the Migraine Specific Quality of Life Questionnaire, the Center for Epidemiologic Studies Depression scale, Spielberger's State and Trait Anxiety scales, and the Japanese version of the Montreal Cognitive Assessment. We compared the scores of these measures between migraine patients and healthy controls to examine the interplay between brain structure and clinical symptoms. Significant volumetric differences were observed in the pallidum and amygdala between migraine patients and healthy individuals. The reduction in the right amygdala volume correlated significantly with migraine severity as measured by the Migraine Disability Assessment. Path analysis revealed a model where Migraine Disability Assessment scores were influenced by Migraine Specific Quality of Life Questionnaire outcomes, which were further affected by depression, anxiety, and a low right pallidum volume. Our findings suggest that the chronicity and severity of migraine headaches specifically affect the right amygdala. Our path model suggests a complex relationship whereby migraine disability is strongly influenced by quality of life, which is, in turn, affected by psychological states, such as anxiety and depression.

[A case study of a patient with myotonic dystrophy type 1 whose gait disturbance was improved by gait training with hybrid assistive limbs].

A Japanese woman first noticed dysarthria at the age of 23. She visited a hospital at the age of 32 and was diagnosed as having myotonic dystrophy clinically. She was diagnosed genetically as having myotonic dystrophy type 1 at 47 years old with 160-270 CTG repeats on the DMPK gene. At the age of 48, she needed non-invasive positive pressure ventilation because of hypoxia at night. Her gait function also deteriorated. She could not stand up from the supine position by herself. However, when she stood, she could walk without a cane for a short distance. She was admitted to our hospital to receive rehabilitation against progressive gait disturbance at the age of 53. She received gait training with hybrid assistive limb® (HAL®). We evaluated some parameters such as walking distance of 2-minute walk test (2MWT), gait speed /cadence/stride length of 10-meter walk test (10MWT), before and just after the course. The first course was performed in September 2017 and the second was done in May 2018 so the interval was about six months. After two courses of HAL® gait training, the distance on the 2-minute walk test increased from 111 m to 154 m, the average speed and the cadence of 10MWT improved from 2.01 m/s to 2.78 m/s and from 2.21 steps/s to 3.05 steps/s respectively. The score of the muscular disability quality of life (QOL) rating scale was also improved. The factors including "defecation," "breathing," and "ADL" suggest that the patient's physical abilities improved and she could move easily. Other factors such as "hope", "activity" and "human relationship" suggest that patient's mood improved after the HAL® training.It was suggested that HAL® gait training could improve QOL as well as gait function in patients with progressive neuromuscular disorder.

Bile acid abnormality induced by intestinal dysbiosis might explain lipid metabolism in Parkinson's disease.

Intestinal dysbiosis refers to an imbalance in the intestinal flora. The concept of small intestinal bacterial overgrowth (SIBO), a condition of abnormal proliferation of the small intestine microbiota, has been proposed as a form of small intestine dysbiosis. In Parkinson's disease patients, weight loss and metabolic disorders such as lipid abnormalities are frequently encountered. This was a prospective investigation of the presence of SIBO using the lactulose breath test, Parkinson's disease symptoms, medications, abdominal symptoms, and blood data involving 39 Parkinson's disease patients. Of the 39 patients, 19 were positive for SIBO, 16 were negative, and 4 were equivocal. SIBO-positive patients had a significantly smaller dopaminergic drug load (dopamine replacement of Parkinson's disease drug potency) (P = 0.009) and significantly lower serum triglyceride (TG) (P = 0.024) and total bilirubin (P = 0.019) levels. No relationship was seen between the presence or absence of SIBO and motor or abdominal symptoms. The following hypothesis was developed with regard to the possibility that intestinal bacterial overgrowth has various effects that are exhibited via bile acid metabolism in Parkinson's disease patients. Serum bilirubin levels become higher as bilirubin metabolism declines with decreases in the intestinal bacteria. At the same time, bile acid is broken down due to increased intestinal bacteria, and lipid absorption decreases. This induces low serum TG levels and leads to weight loss. By a similar mechanism, there is less absorption of vitamin D as bile acid levels decrease, leading to osteoporosis and fractures. The possibility that some of the non-motor manifestations accompanying Parkinson's disease are caused by intestinal dysbiosis needs to be considered.

Increased number of mitochondria in capillaries distributed in stroke-like lesions of two patients with MELAS.

We investigated two autopsy cases of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) using immunohistochemical staining with an anti-mitochondrial antibody against translocase of the outer membrane 20 (TOMM20). In case 1, the patient was a 42-year-old man with a disease duration of 53 days, and in case 2, the patient was a 62-year-old woman with a disease duration of 27 months. In both the cases autopsy revealed moderate atrophy of the cerebrum and cerebellum and multifocal necrotizing lesions, irrespective of the vascular territory. Case 1 showed multiple areas with total necrosis in the cortex, accompanied by increases in number of protoplasmic astrocytes and acidophilic neurons as well as axonal swelling, suggestive of acute or subacute stage stroke-like lesions (SLLs). In case 2, most of the SLLs displayed laminar spongy change in a rarefied cortex, and were considered to be at the chronic stage. In both the cases, capillary proliferation was noted within the SLLs, particularly in the acute phase. Endothelial cells of proliferating capillaries were strongly positive for TOMM20. In the cortex outside the SLLs, microvessels displayed only a fine granular immunoreactivity, as is seen in the controls. Although smooth muscle cells and endothelial cells in pial arteries and arterioles were also strongly positive for TOMM20, the territories of the affected pial arteries and arterioles did not correlate with the distribution of the SLLs. Although MELAS is characterized by recurrent stroke-like episodes (SLEs), the pathogenetic relationship between SLEs and mitochondrial angiopathy remains unknown. An aberrant increase of mitochondria in the capillary endothelial cells of SLLs may disturb endothelial function, thus playing a role in the formation or development of SLLs.

A Pilot Study of Tranilast for Cardiomyopathy of Muscular Dystrophy.

Objective Heart failure is currently the most serious complication of muscular dystrophy. The transient receptor potential cation channel, subfamily V, member 2 (TRPV2) is a stretch-sensitive Ca channel. In damaged myocytes or cardiomyocytes, TRPV2 translocates to the cytoplasmic membrane and enhances Ca influx, triggering cell damage. Evidence suggests that the inhibition of TRPV2 may be a new therapeutic target in heart failure. We found that tranilast, which is widely used as an anti-allergic drug, inhibits TRPV2. A pilot study was conducted to assess the safety and efficacy of tranilast in muscular dystrophy patients with cardiomyopathy. Methods After obtaining informed consent, two muscular dystrophy patients with advanced heart failure took tranilast (300 mg/day) for three months. Blood tests, echocardiography, electrocardiography (ECG), Holter ECG, analyses of the TRPV2 expression in peripheral mononuclear cells, and circulating micro ribonucleic acid profiling were performed to assess the safety and efficacy of tranilast. Results The brain natriuretic peptide levels decreased after treatment. The expression of TRPV2 on the cytoplasmic membrane of peripheral mononuclear cells was enhanced before treatment and was decreased after treatment. Some heart-related micro ribonucleic acids (miR-208a-5p, miR-223-3p) were elevated and then decreased after treatment. Some adverse events, including the potentiation of warfarin, the worsening of renal dysfunction, an increased heart rate and premature ventricular contractions, were observed. Conclusion Tranilast can inhibit TRPV2 and can be effective for treating heart failure, even in patients with muscular dystrophy. Although careful attention is needed, the inhibition of TRPV2 can be a new treatment target for cardiomyopathy. A multi-center trial is planned.

A case of Brugada syndrome which developed status epilepticus.

A 35-year-old man showed a convulsive attack with consciousness loss and was suspected of having Brugada syndrome 6 months prior to admission to our hospital. At the initial examination, the patient showed conjugate deviation, followed by left limb convulsions and consciousness loss. He regained consciousness after 1 minute, though cardiac arrest from ventricular fibrillation was noted during an electroencephalography (EEG) examination. Sinus rhythm recovered with defibrillation, though the convulsions persisted and a Status Epilepticus developed. The patient was diagnosed with Brugada syndrome and received implantable cardioverter defibrillator (ICD). After ICD, he has suffered no further convulsive attacks. Brugada syndrome is an inheritable cardiac disease causing sudden death by ventricular fibrillation. It is important to consider both epilepsy and arrhythmia in diagnosis of the seizures.

The Motor Unit Number Index of Subclinical Abnormality in Amyotrophic Lateral Sclerosis.

PURPOSE: Diagnosis of amyotrophic lateral sclerosis (ALS) at an early stage is challenging, thus making the enrollment of these patients in clinical trials infeasible. In this study, we investigated the potential usability of motor unit number index (MUNIX) to detect denervation of clinically intact muscles of ALS patients. METHODS: Thirty-two first dorsal interosseous muscles of 26 ALS patients were evaluated with both MUNIX and needle electromyography. RESULTS: The mean MUNIX value of first dorsal interosseous muscles was 131 in the control group, whereas it was 48, 34, 15, and 8 for Medical Research Council scales of 5, 4, 3, and 2, respectively, in the ALS patients. The optimal cutoff point gave a sensitivity of 0.89 and a specificity of 1.0. Among 9 intact first dorsal interosseous muscles of the ALS patients, 8 showed MUNIX values below the cutoff point, whereas only 2 first dorsal interosseous muscles showed denervation on needle electromyography. CONCLUSIONS: MUNIX could serve as a sensitive technique to detect denervation of clinically intact muscles of ALS patients.

[A case of limb-girdle muscular dystrophy 2M diagnosed by the occurence of dilated cardiomyopathy].

We report a 24-year-old Japanese man initially suspected to have Becker's muscular dystrophy at the age of 6 years, because of a high level of creatine kinase in serum, though he discontinued visiting the hospital. At the age of 23, he was admitted to the hospital for severe dilated cardiomyopathy, and subsequently diagnosed with limb-girdle muscular dystrophy2M (LGMD2M) based on muscle biopsy and gene analysis. It was recently reported that some patients with fukutinopathy develop LGMD. Most of the cases reported in Japan showed mild skeletal muscle involvement despite serious cardiomyopathy, which may sometimes the initial symptom of the disease. Since muscular dystrophy patients can develop severe cardiac failure, irrespective of the severity of skeletal muscle involvement, regular examinations of cardiopulmonary function are necessary.