Ultra-high-dose methylcobalamin in amyotrophic lateral sclerosis: a long-term phase II/III randomised controlled study.

OBJECTIVE: To evaluate the efficacy and safety of intramuscular ultra-high-dose methylcobalamin in patients with amyotrophic lateral sclerosis (ALS). METHODS: 373 patients with ALS (El Escorial definite or probable; laboratory-supported probable; duration ≤36 months) were randomly assigned to placebo, 25 mg or 50 mg of methylcobalamin groups. The primary endpoints were the time interval to primary events (death or full ventilation support) and changes in the Revised ALS Functional Rating Scale (ALSFRS-R) score from baseline to week 182. Efficacy was also evaluated using post-hoc analyses in patients diagnosed early (entered ≤12 months after symptom onset). RESULTS: No significant differences were detected in either primary endpoint (minimal p value=0.087). However, post-hoc analyses of methylcobalamin-treated patients diagnosed and entered early (≤12 months' duration) showed longer time intervals to the primary event (p<0.025) and less decreases in the ALSFRS-R score (p<0.025) than the placebo group. The incidence of treatment-related adverse events was similar and low in all groups. CONCLUSION: Although ultra-high-dose methylcobalamin did not show significant efficacy in the whole cohort, this treatment may prolong survival and retard symptomatic progression without major side effects if started early. TRIAL REGISTRATION NUMBER: NCT00444613.

[Muro disease: amyotrophic lateral sclerosis/parkinsonism-dementia complex in Kii peninsula of Japan].

Muro disease refers to the endemic amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia complex (PDC) in the high incidence ALS focus in the Muro district of the Kii peninsula. Kii paralysis was first described in the 1680s in a folk literature, and as ALS in the medical literature by Kin-no-suke Miura in 1911. Two high-incidence ALS foci were discovered in 1960s by Kimura and Yase, and retro- and anterospective epidemiological surveys were started. Kii ALS was neuropathologically characterized by classical ALS pathology together with many neurofibrillary tangles (NFTs) in the brain, similar to Guamanian ALS. The incidence rates of ALS dramatically declined during the 1950s and 1980s, resulting in the disappearance of the high-incidence foci. In the early 1990s, however, Kuzuhara found existence of high-incidence of ALS in the region, and, in addition, of a high-incidence of PDC with abundant NFTs, similar to Guamanian PDC. The incidence rates of PDC dramatically rose during the 1980s and 1990s, and PDC replaced ALS. Unsuccessful attempts were made to identify cause and pathogenesis of the disease in minerals and environmental factors. More than 70% of patients in the endemic region had a family history of ALS or PDC; therefore, genetic factors were suspected as the cause. The authors analyzed the causative and risk candidate genes in the affected and unaffected family members, but failed to find genes related to ALS/PDC. The changing pattern of Muro disease from ALS with a younger onset and rapid progression to PDC with a later onset and longer survival suggests that some unknown environmental factor(s) might modulate the disease process, which basically might be programmed in the gene(s).

Cervical spinal cord infarction in a patient with cervical spondylosis triggered by straining during bowel movement.

An 82-year-old man experienced sudden-onset left shoulder pain and hemiparesis, which subsided on the third day. MRI revealed an ischaemic lesion at the C3-4 level together with disk herniation and cord compression from C3/4 to C6/7. On the fourth day, however, similar symptoms recurred when straining during defecation, and then progressed in a fluctuating manner and finally resulted in quadriparesis and respiratory impairment. A follow-up MRI showed fresh infarction of the anterior spinal artery (ASA) territory extending from C2 to C5. Straining during defecation may have induced the second exacerbation by elevating the venous pressure in the craniospinal axis and intervertebral disc pressure and causing minor damage and intraluminal thrombus in the ASA.

Training in mental singing while walking improves gait disturbance in Parkinson's disease patients.

Patients with Parkinson's disease (PD) have various types of gait disturbance that are thought to result from impairments in motor timing. Gait disturbances are markedly improved with the use of appropriate visual and auditory cues. In this study, patients suffering from mild to moderate PD underwent a structured music therapy session in which they were trained to walk while mentally singing. The patients were trained in 7 progressive tasks, with a final goal of walking while mentally singing. Before and after the training session, they were videotaped. The video was analyzed for time and steps while walking straight paths and while turning. After a single session of training, the time and steps were significantly improved in both situations. Follow-up interviews with the patients indicated that they effectively utilized mental singing while walking in their daily lives. We propose that singing regulates basal ganglia function and allows patients with PD to keep time regularly. The task used in the present study was simple, required no special tools, and could be utilized anytime and anyplace. Thus, walking while mentally singing has potential for improving the gait of individuals with PD.

[Music therapy and neuropsychology: a proposal to music therapy based on the cognitive processing of music].

In the last decade, a considerable number of studies have been made on the cognitive processing of music. A patient with pure amusia due to the infarction of anterior portion of bilateral temporal lobes revealed the disturbance of the discrimination of chords. Using positron emission tomography, these regions were activated when musically naive normal subjects listened to the harmony compared to the rhythm of identical music. So, we concluded that anterior temporal portion might participate in the recognition of chords. Several articles reported that the musician's brain was different from nonmusicians' functionally and anatomically. This difference was considered to be caused by the musical training for a long time. Recent studies clarified that the reorganization might occur by musical training for a few months. Melodic intonation therapy (MIT) is a method aimed to improve speech output of aphasic patients, using short melodic phrase with a word. The literatures of mental processing of music suggested that right hemisphere might participate in the expression of music, namely singing and playing instrumentals. So, it was supposed that MIT utilized the compensational function of right hemisphere for damaged left hemisphere. We also reported that mental singing improved the gait disturbance of patients with Parkinson's disease. Music therapy is changing from a social science model based on the individual experiences to a neuroscience-guided model based on brain function and cognitive processing of the perception and expression of music.