Yusaku Nakamura

Treatment of Kearns‐Sayre syndrome with coenzyme Q10

We studied the metabolism of coenzyme Q10 (CoQ) and the effects of CoQ therapy in five patients with Kearns-Sayre syndrome (KSS). Although the mitochondrial fraction was increased in muscles from KSS patients, CoQ content was slightly low. CoQ synthesis was normal in fibroblasts from KSS patients. Administration of 120 to 150 mg/d of CoQ improved abnormal metabolism of pyruvate and NADH oxidation in skeletal muscle. CoQ therapy decreased CSF protein concentration and CSF lactate/pyruvate ratio. ECG abnormalities and neurologic symptoms also improved.

Long‐term coenzyme Q10 therapy for a mitochondrial encephalomyopathy with cytochrome c oxidase deficiency A 31P NMR study

For 2 years we administered high doses of coenzyme Q10 (CoQ) to a patient having mitochondrial encephalomyopathy with cytochrome c oxidase deficiency. Abnormal elevation of the serum lactate per pyruvate ratio and the increased concentration of serum lactate plus pyruvate induced by exercise decreased with CoQ treatment. This therapeutic effect continued for 2 years. 31P nuclear magnetic resonance spectroscopy showed acceleration of the postexercise recovery of the ratio of phosphocreatine to inorganic phosphate in muscle during CoQ treatment. These observations support the beneficial effect of CoQ on the impaired mitochondrial oxidative metabolism in muscle. Also, impaired central and peripheral nerve conductivities consistently improved during CoQ treatment. These results indicate that CoQ has clinical value in the long-term management of patients with mitochondrial encephalomyopathies, even though there are clinical limitations to the effects of this therapy.

Improvement of abnormal pyruvate metabolism and cardiac conduction defect with coenzyme Ql0 in Kearns‐Sayre syndrome

In a patient with Kearns-Sayre syndrome, concentration of coenzyme Ql0, a component of the mito-chondrial electron transport system, was decreased in serum and in the mitochondrial fraction of skeletal muscle. Serum concentrations of lactate and pyruvate were abnormally high, especially after exercise or oral glucose loading. Levels of folic acid in plasma and CSF were decreased. ECG showed a first-degree atrioventricular block. After administration of coenzyme Ql0 60 to 120 mg daily for 3 months, serum levels of lactate and pyruvate became normal, with improvement of atrioventricular block and ocular movements.

Daily repetitive transcranial magnetic stimulation of primary motor cortex for neuropathic pain: a randomized, multicenter, double-blind, crossover, sham-controlled trial.

&NA; The double‐blinded randomized controlled trial showed that daily repetitive transcranial magnetic stimulation of primary motor cortex provided short‐term positive effect on neuropathic pain without serious adverse events. &NA; There is little evidence for multisession repetitive transcranial magnetic stimulation (rTMS) on pain relief in patients with neuropathic pain (NP), although single‐session rTMS was suggested to provide transient pain relief in NP patients. We aimed to assess the efficacy and safety of 10 daily rTMS in NP patients. We conducted a randomized, double‐blind, sham‐controlled, crossover study at 7 centers. Seventy NP patients were randomly assigned to 2 groups. A series of 10 daily 5‐Hz rTMS (500 pulses/session) of primary motor cortex (M1) or sham stimulation was applied to each patient with a follow‐up of 17 days. The primary outcome was short‐term pain relief assessed using a visual analogue scale (VAS). The secondary outcomes were short‐term change in the short form of the McGill pain questionnaire (SF‐MPQ), cumulative changes in the following scores (VAS, SF‐MPQ, the Patient Global Impression of Change scale [PGIC], and the Beck Depression Inventory [BDI]), and the incidence of adverse events. Analysis was by intention to treat. This trial is registered with the University hospital Medical Information Network Clinical Trials Registry. Sixty‐four NP patients were included in the intention‐to‐treat analysis. The real rTMS, compared with the sham, showed significant short‐term improvements in VAS and SF‐MPQ scores without a carry‐over effect. PGIC scores were significantly better in real rTMS compared with sham during the period with daily rTMS. There were no significant cumulative improvements in VAS, SF‐MPQ, and BDI. No serious adverse events were observed. Our findings demonstrate that daily high‐frequency rTMS of M1 is tolerable and transiently provides modest pain relief in NP patients.

Mutations in the gene encoding p62 in Japanese patients with amyotrophic lateral sclerosis

Objective: The purpose of this study was to find mutations in the SQSTM1 gene encoding p62 in Japanese patients with amyotrophic lateral sclerosis (ALS), since this gene has been recently identified as a causative gene for familial and sporadic ALS in the United States. Methods: We sequenced this gene in 61 Japanese patients with sporadic and familial ALS. To our knowledge, we describe for the first time the clinical information of such mutation-positive patients. Results: We found novel mutations, p.Ala53Thr and p.Pro439Leu, in 2 patients with sporadic ALS. The clinical picture of the mutation-positive patients was that of typical ALS with varied upper motor neuron signs. Although this gene is causative for another disease, Paget disease of bone (PDB), none of our patients showed evidence of concomitant PDB. Conclusion: The presence of mutations in this racial population suggests worldwide, common involvement of the SQSTM1 gene in ALS.

Functional magnetic resonance imaging to word generation task in a patient with Broca’s aphasia

Abstract We describe the findings of functional magnetic resonance imaging (fMRI) in a patient with Broca’s aphasia. The patient was a 45-year-old, right-handed woman who developed Broca’s aphasia after infarction in the left frontal lobe. The first fMRI showed no signals in the left frontal lobe during verbal tasks, 2 weeks after the onset of infarction. Four weeks later, when the patient’s symptom had improved, the second fMRI showed some increase in the fMRI signals in the left frontal lobe. Seven months later, she had completely recovered the ability to speak. The last fMRI then showed that the increment in signal activity in the left frontal lobe during verbal tasks had recovered to the level seen in normal subjects. There was a good correlation between the increase in task-related signals in Broca’s area and the recovery of language function. Our findings show that fMRI has can be important in assessing cognitive functions in patients with Broca’s aphasia.

VCP gene analyses in Japanese patients with sporadic amyotrophic lateral sclerosis identify a new mutation

Accumulating evidence has proven that mutations in the VCP gene encoding valosin-containing protein (VCP) cause inclusion body myopathy with Paget disease of the bone and frontotemporal dementia. This gene was later found to be causative for amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, occurring typically in elderly persons. We thus sequenced the VCP gene in 75 Japanese patients with sporadic ALS negative for mutations in other genes causative for ALS and found a novel mutation, p.Arg487His, in 1 patient. The newly identified mutant as well as known mutants rendered neuronal cells susceptible to oxidative stress. The presence of the mutation in the Japanese population extends the geographic region for involvement of the VCP gene in sporadic ALS to East Asia.

Rotigotine Transdermal Patch Improves Swallowing in Dysphagic Patients with Parkinson's Disease.

Abnormal swallowing, dysphagia, is a potentially fatal symptom in Parkinson’s disease (PD) and is characterized by frequent silent aspiration, an unrecognized risk of suffocation and aspiration pneumonia. Several studies have reported that the injection of apomorphine, a dopamine agonist, alleviated dysphagia in some patients with PD. The effects of other antiparkinson medications against dysphagia remain controversial. Rotigotine is another dopamine agonist with non-oral administration, i.e., a transdermal patch. Its noninvasiveness seems to render this medicine even more suitable than apomorphine for dysphasic patients. However, no direct evidence has been reported. In the present retrospective open-label study, we for the first time objectively showed that rotigotine improved swallowing on videofluoroscopic examination in dysphagic patients with PD.

Refractory acute disseminated encephalomyelitis with anti-galactocerebroside antibody

Acute disseminated encephalomyelitis causes multifocal demyelination in the central nerve system. Although this disease generally responds well to steroid therapy, it is occasionally steroid-resistant, leading to poor outcomes. Serological markers of prognosis are currently unavailable. We measured anti-glycolipid antibodies in 25 consecutive patients with acute disseminated encephalomyelitis, and found that four patients were positive for anti-galactocerebroside antibodies. All four patients had a poor response to steroids. We summarize clinical information on these four patients and three similar patients reported previously. This is the first report to describe concomitant involvement of the central nerve system and peripheral nervous system in anti-galactocerebroside antibody-associated acute disseminated encephalomyelitis, consistent with the location of galactocerebroside, and to document a dramatic response to repeated intravenous immunoglobulin therapy after unsuccessful steroid treatment in one patient.

A case of anti-N-methyl-D-aspartate receptor encephalitis with multiple sclerosis-like demyelinated lesions

OBJECTIVE To describe an unusual case of a male patient with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis who presented with multiple white matter lesions. Brain biopsy of the patient was performed, and follow-up evaluation of the cerebrospinal fluid (CSF) NMDAR antibody titer was implemented. DESIGN Case report. SETTING University hospital. PATIENT A 35-year-old man with anti-NMDAR encephalitis initially presented with fever and psychiatric symptoms. After an initial attack of anti-NMDAR encephalitis, 2 atypical relapses occurred, which presented with myelitis and multifocal white matter lesions; the lesions were open-ring-shaped and partially enhanced. INTERVENTION Analysis of the brain biopsy specimen revealed the presence of demyelinated lesions with discrete borders. Subsequent intravenous methylprednisolone therapy resulted in improvement in the brain lesions. Prednisolone and cyclophosphamide were orally administered thereafter. Clinical progression of the disease paralleled observed changes in the CSF NMDAR antibody titer. CONCLUSION The demyelinated lesions observed in this case were similar to lesions found in multiple sclerosis. On the basis of our finding that the clinical progression of the disease and the associated symptoms paralleled changes in the CSF NMDAR antibody titer, we speculate that the lesions formed as a result of anti-NMDAR encephalitis.