Macroglossia in rapidly progressive inclusion body myositis.

Inclusion body myositis (IBM) is a refractory muscle disease characterized by inflammatory and degenerative features in myofibers. Macroglossia is common in systemic amyloid light chain amyloidosis; however, no reports have been published on patients with IBM. We encountered a female patient with clinicopathologically defined IBM who exhibited relatively rapid progression of dysphagia, gait disturbance, and macroglossia. Muscle biopsy demonstrated endomysial mononuclear inflammatory infiltrates, fiber necrosis and regeneration with rimmed vacuoles, and sarcoplasmic inclusions of p62. Tongue biopsy demonstrated fiber degeneration with fatty replacement and fibrosis, nonnecrotic fibers surrounded and invaded by mononuclear cells, and sarcoplasmic dotlike inclusions of p62. Based on the parotid gland, lip, and muscle biopsy, she was diagnosed as having IBM with Sjögren's syndrome. She was treated with steroid pulse and intravenous immunoglobulin therapy followed by oral administration of prednisolone, which resulted in temporary clinical improvement. Macroglossia might be an indicator of immunotherapy effectiveness.

Caregiver Burden with Duchenne and Becker Muscular Dystrophy in Japan: A Clinical Observation Study.

Objective Skeletal muscle weakness and cardiomyopathy can be seen in carriers of dystrophinopathy. Therefore, the health management of caregivers of Duchenne/Becker muscular dystrophy (DMD/BMD) patients who are themselves carriers is an important issue. However, few studies have focused on caregivers who have dystrophin mutations. Methods In this cross-sectional study conducted at five hospitals, the daily living, situation medical treatment status, genetic testing, physical assessment, care burden, and quality of life of caregivers of DMD/BMD patients were surveyed. Results The subjects were 36 main caregivers (mean age 55.7±8.4 years old), of whom 52.8% were diagnosed as carriers, 8.3% were noncarriers, and 38.9% were not confirmed. In addition, half of the caregivers were not examined regularly at medical institutions. Of all caregivers, 54.3% had muscle or cardiac symptoms, and 75% had elevated serum creatine kinase levels. The mean Zarit Caregiver Burden Interview (ZBI) total score of current caregivers was 20.9±13.1. The frequency of a ZBI total score ≥25 was significantly higher in caregivers diagnosed as carriers than in caregivers unexamined as carriers (p=0.04). The health-related quality of life score (Short Form 36; SF-36) in caregivers was slightly lower than the Japanese standard scores in the sections of physical functioning, role limitations-physical, bodily pain, and social functioning. Conclusion Some caregivers of DMD/BMD patients can themselves have muscular or cardiac symptoms and a heavy care burden. It is therefore necessary for carrier caregivers, especially women, to undergo regular health checkups and receive appropriate health management.

Renal function in amyotrophic lateral sclerosis patients on long-term treatment with edaravone.

ABSTRACT: Edaravone, a free radical-scavenger, was approved in Japan for the treatment of amyotrophic lateral sclerosis (ALS). However, the effect of the drug on renal function in ALS patients remains unclear. This study aimed to investigate renal function in ALS patients on long-term treatment with edaravone by measuring the serum estimated glomerular filtration rate based on cystatin C (eGFR-CysC).In a retrospective study, the data of ALS patients who were treated with over 10 cycles of intravenous edaravone treatment and were evaluated by eGFR-CysC before and after 10 cycles of treatment between July 2015 and June 2018 were analyzed. Then, the results were compared with those of a control ALS group that had never been treated with edaravone.There were 11 patients with ALS who received over 10 cycles of intravenous edaravone treatment. The mean interval between the first and final eGFR-CysC measurements was 18.7 ±â€Š7.9 months. Three patients (27.3%) had >20 mL/min/1.73 m2 decrease in serum eGFR-CysC. However, no patients discontinued edaravone treatment because of renal dysfunction. The average variation rate of eGFR-CysC was not different between the long-term edaravone group (0.29 ±â€Š1.07) and the control group (-0.34 ±â€Š0.40).This retrospective, single-center analysis showed no clinical exacerbation of renal function in ALS patients who received long-term treatment with edaravone.

Impact of major earthquakes on Parkinson's disease.

In April of 2016, major earthquakes occurred in Kumamoto, Japan. There is limited information on how major earthquakes affect patients with Parkinson's disease (PD). This study investigates the effect of major earthquakes on patients with PD. The participants were outpatients with PD from hospitals located in areas heavily damaged by the earthquakes. We performed an anonymous survey at nine medical institutions to investigate the condition of these patients during the month following the earthquakes. We collected questionnaires from 335 patients with PD. The mean age was 72.6, and the mean disease duration was 7.4 years. Regarding physical conditions, 29.3% of the patients worsened, 1.5% improved, and 68.1% had no change. The mental health of 35.2% of the patients worsened, 2.4% improved, and 57.9% had no change. The most frequently exacerbated neurologic symptoms included bradykinesia (56.1%), gait disturbance (51.0%), freezing of gait (40.8%), extension of "off" time (38.8%), and constipation (38.8%). The worsening mental conditions included fear of an aftershock (77.1%), anxiety (49.2%), insomnia (47.5%), melancholy feelings (45.8%), and fatigability (38.1%). Patients forced to evacuate reported significantly more physical and mental health symptoms (p < 0.01). The influences of major earthquakes on patients with PD were identified. After major earthquakes, we should consider the care required for patients' physical and mental health especially for those who experienced evacuation.

[A case of myasthenia-like symptoms induced by cibenzoline overdosage].

The present patient was an 87-year-old man who had been taking cibenzoline for tachyarrhythmia. Five years after initiation of administration, he was referred to our hospital for ptosis that worsened from midday, as well as weakness of the facial and limb muscles. He tested negative for anti-acetylcholine receptor antibody but positive in the edrophonium test, suggesting that he had myasthenia gravis. He was admitted to our hospital 3 years later due to worsening symptoms of ptosis and muscle weakness. He had hypoglycemia, cardiac conduction defect, and renal dysfunction. In addition, blood concentration of cibenzoline was markedly high (1,850 ng/ml). We terminated the administration of cibenzoline, after which the patient's neurologic symptoms improved. Our findings suggest that cibenzoline toxicity must be considered in differentiating myasthenia gravis when a patient also presents with renal dysfunction.

Long-term effects of edaravone on survival of patients with amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: Oxidative stress has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Edaravone, a free radical scavenger, was approved as a therapeutic drug for ALS in 2015 in Japan. A phase 3 clinical trial demonstrated a smaller decline in ALS functional scale scores compared with placebo. However, the long-term effects of edaravone on ALS patients remain unclear. This study aimed to retrospectively investigate the long-term effects of edaravone on the survival of ALS patients. METHODS: We retrospectively analyzed 27 consecutive patients with ALS who were treated with edaravone and 30 consecutive ALS patients who were not treated with edaravone between 2010 and 2016. RESULTS: The differences of ALSFRS-R scores from baseline to 6 months was significantly reduced in the edaravone group, compared to the control group. The changes in serum creatinine, as a possible marker of ALS severity, from baseline to 6 and 12 months were significantly improved in the edaravone group, compared to the control group. The survival rate was significantly improved in the edaravone group compared with control patients. CONCLUSION: Our retrospective single-center analysis suggests slower progression and better prognosis of ALS patients with edaravone treatment. Further investigation, including prospective multicenter analysis, is warranted to confirm the usefulness of edaravone for a better prognosis of ALS.

Utility of skinfold thickness measurement in non-ambulatory patients with Duchenne muscular dystrophy.

Nutritional disorders in Duchenne muscular dystrophy (DMD) worsen the medical condition. In particular, obesity is a serious problem that increases the risk of cardiomyopathy and affects nursing care. However, it is often difficult to evaluate body fatness in the advanced stages of DMD. Skinfold thickness measurement is a classical method to evaluate body fatness and is easily performed, even for bed-bound patients at home. We aimed to investigate the utility of skinfold thickness measurement in non-ambulatory DMD patients. Twenty-two patients with non-ambulatory, steroid-naive DMD ranging in age of 12-47 years were evaluated by body mass index (BMI), blood tests, measurement of triceps skinfold thickness (TSF), and abdominal computed tomography (CT) measurement of the areas of both subcutaneous and visceral fat. TSF showed good correlation with BMI (r = 0.80; p < 0.001), serum triglycerides (r = 0.67; p < 0.01), area of subcutaneous fat (r = 0.85; p < 0.0001), and area of visceral fat (r = 0.76; p < 0.0001). These results indicate the skinfold thickness measurement may be applicable as a screening tool in clinical practice where CT and magnetic resonance imaging assessment is often difficult in patients with advanced DMD.

Acute Multiple Cerebral Infarction in a Patient with an Accessory Mitral Valve.

A 96-year-old woman developed hemiparesis 2 weeks after orthopedic surgery. Magnetic resonance imaging revealed multiple cerebral infarctions in the bilateral hemisphere. Transthoracic echocardiography revealed a mobile structure attached to the anterior mitral leaflet that protruded toward the left ventricular outflow tract. The structure was identified as an accessory mitral valve. Doppler echocardiography showed that there was no significant left ventricular outflow obstruction. This is a rare case of a silent accessory mitral valve that was detected after multiple cerebral infarctions.

Progressive multifocal leukoencephalopathy in an HTLV-I carrier.

This report describes a previously 28-year-old healthy woman, identified as an asymptomatic human T-lymphotropic virus type I (HTLV-I) carrier, who developed both progressive multifocal leukoencephalopathy (PML) and Pneumocystis jiroveci pneumonia. For diagnostic confirmation of PML, stereotactic brain biopsy demonstrated multiple demyelinating lesions with the presence of JC viral antigen. Intramuscular alpha-interferon therapy for 2 weeks brought considerable neurologic improvement. Three years later, the patient developed lymphoma-type of adult T-cell leukemia, suggesting that HTLV-I carrier might be one of the underlying diseases of PML.

[Bilateral medial medullary infarction presenting as vertical gaze palsy].

A 79-year old man noticed paresthesia in all 4 limbs, quadriplegia and dysarthria, and then developed respiratory arrest requiring mechanical ventilation. After level of consciousness was improved, vertical gaze palsy, left hemifacial palsy (central type) and quadriplegia were noted. Brain magnetic resonance imaging (MRI) on day 9 revealed bilateral upper medial medullary infarction. In general, the vertical gaze center is thought to be present in the midbrain, including the rostral interstitial nucleus of the medial longitudinal fasciculus, posterior commissure and interstitial nucleus of Cajal. Few reports have described vertical gaze palsy due to medullary lesions. The upper medial medullary lesions, particularly the paramedian tract in the medulla, may have been responsible for vertical gaze palsy in this patient.

Life-threatening Arrhythmias in a Becker Muscular Dystrophy Family due to the Duplication of Exons 3-4 of the Dystrophin Gene.

We herein present a report of three patients with Becker muscular dystrophy in the same family who developed complete atrioventricular block or ventricular tachycardia with severe cardiomyopathy. Our cases became unable to walk in their teens, and were introduced to mechanical ventilation due to respiratory muscle weakness in their twenties and thirties. In all three cases, a medical device such as a permanent cardiac pacemaker or an implantable cardiac defibrillator was considered to be necessary. The duplication of exons 3-4 in the dystrophin gene was detected in two of the patients. In patients with Becker muscular dystrophy, complete atrioventricular block or ventricular tachycardia within a family has rarely been reported. Thus attention should be paid to the possibility of severe arrhythmias in the severe phenotype of Becker muscular dystrophy.

Chronic sensory neuronopathy associated with human T-cell lymphotropic virus type I infection.

We described two patients with chronic sensory neuronopathy who had anti-HTLV-I antibody in serum and cerebrospinal fluid but no signs of myelopathy. A sural nerve specimen revealed severe degeneration of myelinated and unmyelinated axons. The second patient had subclinical Sjögren's syndrome suggestive of a possible link among human T-cell lymphotropic virus type I (HTLV-I), Sjögren's syndrome and sensory neuronopathy, respectively. The broad spectrum of neurologic disorders associated with HTLV-I infection now would include chronic sensory neuronopathy.

Solitary metastasis of prostatic cancer to the internal auditory canal.

We report a 56-year-old man with a metastatic prostatic tumor who developed left orbital meatus syndrome as the first manifestation. Magnetic resonance imaging (MRI) showed a swollen lesion in the left internal auditory canal that was isointense on T1-weighted images, hyperintense on T2-weighted images, and marked by enhanced after the administration of gadolinium. A biopsy of the affected lesion confirmed the prostatic origin of the metastasis.

Clinical heterogeneity in dysferlinopathy.

OBJECTIVE: To clarify the clinical heterogeneity and genotype-phenotype correlation in dysferlinopathy. METHODS: We evaluated clinical parameters of 74 dysferlinopathy patients with known dysferlin gene mutations who were previously reported in the literature. RESULTS: The age at onset varied from 12 to 59 years (mean 21.7 years). Based on the initial distribution of muscle involvement, clinical phenotypes were divided into four subtypes: limb-girdle type, Miyoshi's type, distal anterior compartment type, or scapuloperoneal type. These phenotypic differences were prominent at the early stages, but were difficult to recognize later in the progression of the disease. Patients with missense mutations had significantly more severe functional status at examination and higher creatine kinase levels than those with frameshift or nonsense mutations. CONCLUSION: Dysferlinopathy exhibited marked heterogeneity in the age at onset, initial distribution of muscle involvement, and rate of disease progression. As this heterogeneity was observed even within the same family, some additional factors distinct from dysferlin might be involved.

[A case of steroid-responsive encephalopathy with positive 14-3-3 protein of the cerebrospinal fluid clinically resembling Creutzfelt-Jakob disease].

A 69-year old man developed subacutely progressive dementia, inactivity, and gait disturbance. On admission, he showed flutter-like oscillation of the bilateral eyes and myoclonus with upper extremities. Cerebrospinal fluid (CSF) analysis revealed elevation of protein (73.2mg/dl) and the positive 14-3-3 protein. An electroencephalogram (EEG) revealed diffuse slowing (2-3Hz, 80microV). Brain MRI showed high intensity lesions in the white matter and left thalamus on FLAIR and diffusion imaging. We first suspected Creutzfelt-Jakob disease (CJD), but his symptoms didn't progress and showed no PSD on EEG. Oral corticosteroid therapy (prednisolone 60mg/day) brought him remarkable recovery corresponding with improvement of CSF and EEG findings. Despite of etiology unknown, we made a diagnosis of steroid-responsive encephalopathy.

[Two cases of Duchenne muscular dystrophy over 40 years after onset].

We report two 45 year old men with Duchenne muscular dystrophy. Case 1 showed a deleted exon 50 of the dystrophin gene by MLPA analysis, and Case 2 showed deleted exons 46-52. Both patients presented with severe weakness of the skeletal muscles and respiratory dysfunction, while cardiac involvement was mild and cognitive function was almost normal. The patients are able to shop at a mall, participate in activities, and attend hobbies, although they are bedridden with artificial respiration through tracheotomy. With the progress of the respiratory care and cardiac protective therapy, the prognosis of Duchenne muscular dystrophy has improved remarkably. At present, it is possible to survive over 40 years with maintenance of quality of life, if cardiac damage is not severe.

Crossed aphasia following an infarction in the right corpus callosum.

A 68-year-old right-handed woman with no history of brain damage or familial left-handedness was admitted to our hospital due to the acute onset of speech difficulty; her speech was nonfluent. Literal and phonological paraphasias, agrammatism and paragrammatism were observed. Brain MRI revealed an acute infarction in the right anterior cerebral artery territory, involving the right corpus callosum. Moreover, cerebral blood flow was decreased not only in the area of the right corpus callosum but also in the left fronto-temporal lobe, suggesting crossed diaschisis. This is a rare case of crossed aphasia following an infarction in the right corpus callosum.

[Case of focal convexal subarachnoid hemorrhage presenting as transient ischemic attack mimic].

An 82-year-old man was suspected to have experienced a transient ischemic attack since he developed transient weakness in the right upper limb twice. On admission, neurologic examination yielded normal findings except for mild cognitive impairment. Brain CT and images showed an unexpected finding of acute focal subarachnoid hemorrhage in the left central sulcus, although MR angiography and venography did not show any abnormality. T(2)(*) weighted images showed superficial siderosis in the bilateral frontal lobes, which indicated the possibility of a recurrent subarachnoid hemorrhage. We propose that focal subarachnoid hemorrhage should be included in the differential diagnosis of transient ischemic attack.