[Therapeuetic aspects of cluster headache in the practical clinical site].

The therapeutic procedures of cluster headache begin from the precise diagnose. Because cluster headache is usually accompanied with teeth pain and/or neck pain, some patients aren't able to consult adequate medical institutions. In this lecture I showed the some male and female patients as examples. The female patient was suffered from menstruation related migraine in her period of cluster headache. From the view point of treatment, preventive medicines are essential. They not just reduce severity and also improve the length of headache-period. Suitable preventive medicines may avoid the whole severe attacks. We reported therapeutic experiences of valproate, gabapentin and amitriptyline with verapamil in 2010 at general meeting of Societas Neurologica Japonica. Steroids are not indispensable. As for triptans rapid-type one are usually used. If the attacks are severe, sumatriptan subcutaneous injection kit (SSI) needs to be introduced. The expert nurses who are skilled in the procedures of SSI improve both patients' adherence and therapeutic efficiency. We held a first educational meeting of SSI in Tokyo 2012. Because cluster headache is formidable, the integrated therapy which is composed of precise diagnosis, preventive medicine and adequate medicines for headache attacks is essential and needed.

An analysis of risk factors for asymptomatic cerebral infarction.

OBJECTIVE: The aim of this study is to identify risk factors for asymptomatic cerebral infarction (ACI) in the general Japanese population. MATERIALS AND METHODS: A total of 634 subjects (272 men aged 55.4+/-8.8 years and 362 women aged 55.2+/-8.5 years) who visited the Health Management Center at Aoyama Hospital (Tokyo, Japan) from January 2004 through January 2005 for an annual brain dry dock examination were analyzed. We evaluated 21 risk factors for ACI by multivariate logistic regression analysis. RESULTS: Abnormal or potentially abnormal conditions were detected in 258 subjects (40.7% of all subjects who had an annual check-up program for brain disease). The most frequent abnormal finding was ACI, which was observed in 208 subjects. The significant risk factors for ACI, as determined by multivariate logistic analysis, were age (P <0.01), hypertension (P <0.01), and hypertensive vascular changes in the fundus (P <0.05). CONCLUSION: The hypertensive vascular abnormalities in the fundus might be a risk factor for ACI independent of age and hypertension.

An autosomal dominant cerebellar ataxia linked to chromosome 16q22.1 is associated with a single-nucleotide substitution in the 5' untranslated region of the gene encoding a protein with spectrin repeat and Rho guanine-nucleotide exchange-factor domains.

Autosomal dominant cerebellar ataxia (ADCA) is a group of heterogeneous neurodegenerative disorders. By positional cloning, we have identified the gene strongly associated with a form of degenerative ataxia (chromosome 16q22.1-linked ADCA) that clinically shows progressive pure cerebellar ataxia. Detailed examination by use of audiogram suggested that sensorineural hearing impairment may be associated with ataxia in our families. After restricting the candidate region in chromosome 16q22.1 by haplotype analysis, we found that all patients from 52 unrelated Japanese families harbor a heterozygous C-->T single-nucleotide substitution, 16 nt upstream of the putative translation initiation site of the gene for a hypothetical protein DKFZP434I216, which we have called "puratrophin-1" (Purkinje cell atrophy associated protein-1). The full-length puratrophin-1 mRNA had an open reading frame of 3,576 nt, predicted to contain important domains, including the spectrin repeat and the guanine-nucleotide exchange factor (GEF) for Rho GTPases, followed by the Dbl-homologous domain, which indicates the role of puratrophin-1 in intracellular signaling and actin dynamics at the Golgi apparatus. Puratrophin-1--normally expressed in a wide range of cells, including epithelial hair cells in the cochlea--was aggregated in Purkinje cells of the chromosome 16q22.1-linked ADCA brains. Consistent with the protein prediction data of puratrophin-1, the Golgi-apparatus membrane protein and spectrin also formed aggregates in Purkinje cells. The present study highlights the importance of the 5' untranslated region (UTR) in identification of genes of human disease, suggests that a single-nucleotide substitution in the 5' UTR could be associated with protein aggregation, and indicates that the GEF protein is associated with cerebellar degeneration in humans.

Glycosphingolipid composition of primary cultured human brain microvascular endothelial cells.

Glycosphingolipid (GSL) antigens have been considered to be involved in the pathogenesis of autoimmune neurologic disorders including multiple sclerosis. To establish the GSL pattern specific for endothelial cells forming blood-brain barrier (BBB), we established a method to yield sufficient quantities of highly purified human brain microvascular endothelial cells (HBMECs) and compared their GSL composition to that of human umbilical cord vein endothelial cells (HUVECs), as the representative of endothelial cells not forming BBB. The major gangliosides were GM3 and sialyl paragloboside (LM1), and the major neutral GSLs were lactosylceramide (LacCer), globotriaosylceramide (Gb3), and globoside (Gb4). Trace amounts of GM1, GD1a, GD1b, GT1b, and sulfoglucuronosyl paragloboside (SGPG) could be detected by the high performance thin layer chromatography-overlay method. SGPG was detected only at a nonconfluent state in an amount almost 1/30 that of in nonconfluent HUVECs. Conversely, GM3 and LM1 increased significantly after confluency. The amount of Gb3 in HBMECs was almost as twice that in HUVECs. The significance of these differences in GSL content between HBMECs and HUVECs and between confluent and nonconfluent states is obscure. It might be related, however, to the defense mechanism at the BBB and to the susceptibility of the central nervous system in some disorders that target cell surface GSL, such as hemolytic uremic syndrome.

Efficacy of candesartan in the treatment of migraine in hypertensive patients.

Triptans are usually administered for migraine, but cannot be given to patients with malfunctioning cardiac or cerebral vascular systems, which commonly accompany hypertension. This article focuses on 8 cases in which treatment with candesartan was successful in reducing both the incidence and severity of headache in hypertensive patients with migraine. The cases reported in this article showed a mean improvement in Migraine Disability Assessment score from 29.4 to 9 points and in blood pressure from 154.9/90.4 to 129.5/81.9mmHg, suggesting that candesartan is an extremely attractive option for the treatment of migraine. Although recent studies have reported the efficacy of candesartan for treating migraine, there has been no description of its potential advantages over other prophylactic drugs. The present study included patients who could not tolerate triptans for whom triptans were contraindicated, several patients for whom other migraine prophylactic drugs showed little or no effect, and one patient for whom candesartan was prescribed initially for hypertension, but was also found to be therapeutic for migraines. Thus candesartan is considered to be a unique, attractive choice of prophylactic agent for migraine complicated by hypertension.

Motor weakness and cerebellar ataxia in Sjögren syndrome--identification of antineuronal antibody: a case report.

We report here a combination of rare neurological manifestations of primary Sjögren syndrome (SS), such as motor-dominant motor weakness of peripheral origin, cerebellar ataxia and depression, in a Japanese female patient. An autoantibody in her serum and cerebrospinal fluid immunolabelled spinal motor neurons and cerebellar Purkinje cells. On Western blot, this antibody reacted with a protein of 34 kDa from the extract of spinal cord, dorsal root ganglion, or cerebellar cortex, which might correspond to motor weakness and cerebellar ataxia, respectively. The absence of its reactivity to the liver tissue indicates that this autoantibody targets an antigen represented exclusively in the neural tissues. Although it remains to be proved how autoantibodies, sometimes associated with SS, are involved in the development of clinical pictures, some of them are present in the cerebrospinal fluid and exhibit an exclusive affinity to neural tissues, which indicates its plausible link to neurological manifestations. Recognition of these antineuronal antibodies in SS will potentially provide a chance to treat these patients by removing or inactivating the antibody.