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Migraine is the sixth most common cause of disability worldwide. Historically, three theories regarding the etiology of headache have been suggested: vascular, neuronal, and trigeminovascular. However, the mechanism of migraine is still unknown. The advantages of studying the premonitory phase are several as it is the earliest clinical change during a migraine attack, and hence, is likely to disclose brain areas involved right at the beginning. Studying this phase may also allow to reveal the generator of migraine. In human neurophysiology, human functional neuroimaging, and preclinical biochemical studies, the relationship between the premonitory phase and hypothalamus has been suggested. On the other hand, calcitonin gene-related peptide (CGRP) has now been firmly established as a key player in migraine. Trigeminal CGRP and its roles in vasodilation, neurogenic inflammation, and peripheral sensitization are likely to be the most relevant peripheral actions causing the condition. CGRP could also be acting as a neuromodulator of light aversion, central sensitization, and cortical spreading depression (CSD).

Background We studied the relationship between survival prognosis and the functional outcome at discharge from acute-care hospitals in each subtype of ischemic stroke patients. Methods A total of 853 consecutive patients with first-ever ischemic stroke, recruited from December 1999 to November 2002, were followed for 725.8 ± 430.0 days. Functional outcome was scored using the modified Rankin scale (mRS). Survival analysis was performed using Kaplan-Meier curves, log rank test, and Cox regression model. Results The respective mortality of the groups with mRS scores of 0-2, 3, 4, and 5 were 13.1%, 25.0%, 47.2% (p

Aim: We assessed the long-term prognosis of patients with large subcortical infarctions (LSCI). Methods: We defined LSCI as lesions ≥15 mm confined to deep penetrating arteries without a cardioembolic or atherothrombotic source. Patients with acute ischemic strokes were consecutively registered and followed for 751 ± 441 days. The clinical characteristics and long-term prognoses of patients with LSCI were compared to those of patients with lacunar (LACI), atherothrombotic (ATI) and cardioembolic infarctions (CEI). Results: At discharge from the hospital, the proportion of good outcomes (modified Rankin Scale ≤2) for patients with LSCI (52.1%) was similar to that for ATIs (47.2%), but worse than that for LACIs (73.2%). After a 3-year follow-up period, the mortality rates from LSCI, LACIs, ATIs and CEIs were 8.4, 8.2, 22.3 and 41.1%, respectively; the recurrence rates were 9.3, 14.1, 16.6 and 23.8%, respectively. Conclusions: The short-term prognosis of functional outcomes for LSCI was worse than that for LACIs, but similar to acute-phase ATI outcomes. The long-term prognosis after a LSCI is good, and recurrence tends to be lower than for LACIs.

Objectives – To identify determinants of recurrence after ischemic stroke in the Japanese population. Materials and methods – We enrolled 885 patients with acute ischemic stroke that had been admitted to our community hospitals. A total of 831 cases were followed for 1 year after the index stroke. Patients were assigned to one of the ischemic stroke subtype groups based on the NINDS Stroke Data Bank criteria. Results – Rates of stroke recurrence were significantly different among stroke subtype groups: 14.4% in cardioembolic infarction, 7.3% in atherothrombotic infarction (ATI), 6.2% in lacunar infarction (LI) and 7.8% in infarction of uncertain cause. Previous history of stroke was the predictor of stroke recurrence for the groups of ATI and LI patients, and diabetes mellitus was the predictor of recurrence for the group of LI patients. Conclusion – The rate of recurrence and risk factors for stroke recurrence are different by stroke subtypes.

We identify the prevalence and genetic features of Charcot-Marie-Tooth disease (CMT) in Yonago and Sakaiminato, western Japan. From information in registered records and questionnaires, definite or candidate CMT patients were examined. Eleven families with 19 patients (7 female and 12 male) were identified and the prevalence was 10.8 per 100,000 in April 2000. Eleven patients in 6 families showed a Thr124Met mutation of the MPZ gene, in 2 families duplication of the PMP22 gene was suggested and no abnormalities were found in 2 families. To identify the occurrence of mildly affected CMT, the exhaustive region-matched and family study was necessary.

Seventy-eight patients with tension-type headache (TH) were treated with tizanidine hydrochloride (tizanidine). Plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) and serum free fatty acids (FFA) levels in these patients were determined before the treatment with tizanidine. Eighteen healthy volunteers composed the control group. Four weeks after the treatment with tizanidine 24 (31%) of 78 patients showed excellent improvement (excellent group); 28 (35%) showed moderate improvement (moderate group); 18 (23%) showed mild improvement (mild group); 7 (10%) showed no improvement and one (1%) showed worsening of her headache (no change and worsened group). The plasma MHPG levels in the excellent group were significantly higher than in the other groups, including the control group. The serum FFA levels in the excellent group were significantly higher than in the controls. In this study, 66% of the patients reported improvement in their headaches. Some patients with TH had high plasma MHPG levels and these patients in particular showed excellent improvement after the administration of tizanidine. Though there may be a placebo response to some extent, the clinical usefulness of tizanidine for TH seems to be excellent. Further study is necessary concerning the pharmacological effect of tizanidine and plasma MHPG levels in patients with TH.

Through an epidemiological survey, we observed 3 types of clinical courses among patients with senile dementia of the Alzheimer type (SDAT). The mental ability of the patients declined rapidly (Group A; n = 11), gradually (Group B; n = 6), or showed extremely slow changes (Group C; n = 9). The acetylcholinesterase (AChE) activity and somatostatin (SRIF) concentration of the cerebrospinal fluid (CSF) were measured in patients with Alzheimer's disease (AD) and 3 types of SDAT. Both AChE activity and SRIF concentration of CSF were significantly lower in Group A and among patients with AD compared with age-matched control subjects. Both AChE activity and SRIF concentration of CSF were not significantly different in Groups B and C. This biochemical study confirmed our epidemiological finding that only the patients in Group A with SDAT closely resembled the clinical course of AD and may belong to the category of neurodegenerative disorders.

The serum levels of apolipoprotein B, C-II and the ratio of apolipoprotein B/A-I were found to be significantly higher in multiinfarct dementia than in dementia of the Alzheimer type. The high serum levels of apolipoprotein B, C-II and the high ratio of apolipoprotein B/A-I may cause multiinfarct dementia. The large difference between the groups suggests that the serum levels of apolipoprotein B, C-II and the ratio of apolipoprotein B/A-I may be useful in differential diagnosis of these two kinds of dementia.