Blood flow velocity changes induced by the focal brain activation can be assessed by using Transcranial Doppler sonography (TCD). To explore the hemispheric dominant hemodynamic effect by performing calculation, we applied TCD technique to detect cerebral blood velocity asymmetry. METHODS Twenty healthy right-handed subjects were tested. We measured mean flow velocities (MFV) in the middle and posterior cerebral arteries (MCA, PCA). Photic stimulation was given separately as a control task for calculation. RESULTS While the photic stimulation increased the blood velocity only in PCAs, performing calculation increased the velocity in MCAs. Right-left difference was noted by performing calculation with greater increase in left MCA (right: 8.8 %; left: 21.2 %). CONCLUSION Application of TCD enabled us to measure the hemodynamic changes supporting the left hemispheric dominance of calculation task. Futhermore, increase in non-dominant right hemisphere suggests the functional interaction of cerebral activity.
Blood Flow Velocity* ; Brain ; Dominance, Cerebral ; Hemodynamics ; Passive Cutaneous Anaphylaxis ; Photic Stimulation ; Posterior Cerebral Artery ; Ultrasonography, Doppler, Transcranial

Background: Renin-angiotensin systems (RAS) are involved in the physiology of migraine. Ramipril is an angiotensin-converting enzyme inhibitor. We tested whether ramipril has an effect on migraine. Methods: The study was designed as a prospective open-labeled trial in a single center. All patients were asked to maintain a headache diary. Ramipril was administered at 5mg/day (2.5mg twice a day) and subjects were checked every 4 weeks up to 12 weeks. Results: The mean number of headache days was 19.9 ± 11.2 days per month at baseline, and 12.0 ± 11.5 at 12 weeks (p<0.001 vs. baseline) with a responder rate of 41.9%. Stratified analysis by migraine frequency (15 days a month > vs. <15 days a month) did not show a difference. Mean blood pressure was not altered. Conclusions: Ramipril prevented migraine attacks independently from blood pressure. This result supports a link between renin-angiotensin system and migraine pathophysiology (Clinicaltrials.gov identifier: NCT01402479).

Migraine often runs in families and is associated with both genetic and environmental factors. Clinical and genetic heterogeneity as well as the influence of environmental factors have hampered the identification of the gene responsible for migraine disorder. Family/twin studies suggest the presence of hereditary susceptibility. Several different types of mutations or association studies with genetic polymorphism in neurotransmitters, inflammatory cytokines, homocysteine metabolism, mitochondria, or other risk genes in cerebrovascular disorders have been reported. Recently, progress of molecular genetics in familial hemiplegic migraine has provided important insights, a channelopathy, and now extending to a growing list of membrane excitability disorders. Further identification of candidate genes for migraine and exploring the correlation between phenotype and genotype are expected in the future for the understanding of migraine pathophysiology.
Cerebrovascular Disorders ; Channelopathies ; Cytokines ; Genetic Heterogeneity ; Genetics* ; Genotype ; Homocysteine ; Humans ; Membranes ; Metabolism ; Migraine Disorders* ; Migraine with Aura ; Mitochondria ; Molecular Biology ; Neurotransmitter Agents ; Phenotype ; Polymorphism, Genetic

Hyperhomocysteinemia associated with methylene terahydrofolate reductase (MTHFR) mutation can be a risk factor for idiopathic cerebral venous thrombosis. We describe the first case of MTHFR 677TT homozygote with cerebral venous thrombosis and livedo reticularis. A 45-year-old man presented with seizures and mottled-like skin lesions, that were aggravated by cold temperature. Hemorrhagic infarct in the right frontoparietal area with superior sagittal sinus thrombosis was observed. He had hyperhomocysteinemia, low plasma folate level, and MTHFR 677TT homozygote genotype, which might be associated with livedo reticularis and increase the risk for cerebral venous thrombosis.
Cold Temperature ; Folic Acid ; Genotype ; Homozygote* ; Humans ; Hyperhomocysteinemia ; Livedo Reticularis* ; Methylenetetrahydrofolate Reductase (NADPH2) ; Middle Aged ; Oxidoreductases ; Plasma ; Risk Factors ; Seizures ; Skin ; Superior Sagittal Sinus ; Thrombosis ; Venous Thrombosis*

Objective: The purpose of the present study was to screen the prevalence of aneurysms in migraineurs; to differentiate presenting features in migraineurs with and without aneurysm; and also to correlate the locations of aneurysm to the clinical features of migraine. Methods: A total of 4,416 subjects were interviewed and completed self-reported questionnaires on headache. Of these, 1,773 subjects diagnosed to have migraines based on the International Classification of Headache Disorders II (ICHD-II) criteria were screened for aneurysm by magnetic resonance angiography (MRA). When aneurysm was suspected, further investigation with trans femoral cerebral angiography (TFCA) or three dimensional computerized tomography (CT) angiography was performed. Based upon MRA findings, subjects were grouped into unruptured aneurysm migraine patients (UAMP) and no aneurysm migraine patients (NAMP). Results: The prevalence of aneurysm was 3.6% (63 of 1,773) with the mean age of 56.0 years, which were not different from those of general population. There was no difference in migraine subtypes between UAMP and NAMP. Aggravation of headache by estrogen replacement therapy during menopause (p=.039), history of migraine in young age (p= .021), diplopia (p=.026), and retroauricular pain (p=.025) were significantly associated with presence of aneurysm. Although aneurysms were detected more in anterior circulation, there was no correlation between aneurysm site and headache location. The average size of aneurysm was 3.5 ± 2.1 mm and none were ruptured. Interventional therapy of aneurysm did not alter the feature of migraine. Conclusions: The incidence of aneurysm was not different in migraine patients as compared to the general population. Some features which significantly differentiate whether migrainuers have aneurysm or not warrant further study to have a predictive and localizing value.

BACKGROUND: Migraine is commonly associated with anxiety disorder. However, whether anxiolytic medicine or changes in anxiety levels affect the migraine attack is unclear. Buspirone, the agonist for 5-HT1A receptor, is effective in treating generalized anxiety disorder. In this study, we attempted to test the efficacy of buspirone for migraine combined with anxiety disorder. METHODS: 111 outpatients aged 20 to 70 years (mean, 46.4; SD, 12.8), were analyzed. The diagnosis of migraine was made according to the HIS (International Headache Society) criteria, and the level of anxiety was rated by the Hamiton Anxiety Rating Scale (HAM-A). The migraineurs were randomly assigned to treatment with either buspirone (15 mg/day) or placebo for 6 weeks. The efficacy variables included changes in headache frequency, headache intensity, Headache Index, Headache Management Self-Efficacy Scale (HMSE), Headache Disability Inventory (HDI), and the Hamilton Anxiety Rating Scale (HAM-A). The correlation between headache improvement and the anxiolytic effect were analyzed. RESULTS: Headache frequency showed a 43.3% reduction (from 6.7/2 weeks to 3.8/2 weeks) in the buspirone-treated group, whereas a 10.3% reduction (from 6.8 to 6.1/2 weeks) in the placebo group. The Headache Index, HDI, and HAM-A were also significantly lowered in buspirone-treated patients than in placebo-treated patients. However, the headache intensity or the HMSE score were not changed. Correlation analysis between the change of Headache Index and that of HAM-A revealed no significant association. CONCLUSIONS: Buspirone is an effective prophylactic agent in migraine combined with anxiety disorder. This prophylactic effect is not secondary to the anxiolytic effect. This suggests that the agonistic action for 5-HT1A is primarily effective in migraine prophylaxis.
Anti-Anxiety Agents ; Anxiety Disorders ; Anxiety* ; Buspirone* ; Diagnosis ; Headache ; Humans ; Migraine Disorders ; Outpatients ; Receptor, Serotonin, 5-HT1A

Huntington’s disease (HD) has become a target of the first clinical trials for gene therapy among movement disorders with a genetic origin. More than 100 clinical trials regarding HD have been tried, but all failed, although there were some improvements limited to symptomatic support. Compared to other neurogenetic disorders, HD is known to have a single genetic target. Thus, this is an advantage and its cure is more feasible than any other movement disorder with heterogeneous genetic causes. In this review paper, the authors attempt to cover the characteristics of HD itself while providing an overview of the gene transfer methods currently being researched, and will introduce an experimental trial with a preclinical model of HD followed by an update on the ongoing clinical trials for patients with HD.

We present a Korean case of Hirayama disease with its typical neuroradiological findings of forward displacement of cervical dural sac and compression of the lower cervical cord during neck flexion. A 15-yr-old boy was presented with a one-year history of progressive weakness and atrophy affecting bilateral hands and forearms. The electrodiagnostic findings were compatible with the lesion of the anterior horn cells at the C7, C8, and T1 spinal segments. With neck flexion, cervical magnetic resonance imaging (MRI) showed the anterior shifting of the lower cervical dural sac resulting in the cord compression of those segments. Presumably, this disease might have been prevalent in Korea frequently under the diagnosis of "benign focal amyotrophy". In this regard, we discuss the clinical importance of cervical MRI with neck flexion and anticipate the increasing reports of the case substantiated by its characteristic radiological features.
Adolescent ; Cervical Vertebrae ; Humans ; *Magnetic Resonance Imaging ; Male ; Motor Neuron Disease/complications/pathology ; Research Support, Non-U.S. Gov't ; Spinal Cord Compression/*etiology/*pathology ; Spinal Muscular Atrophies of Childhood/*complications/*pathology

BACKGROUND: Intracellular calcium accumulation and dys-regulation is known as one of the mechanism in motor neuronal degeneration with mutations in Cu/Zn superoxide dismutase (SOD-1). METHODS: To investigate the calcium modulators and mutated SOD-1 induced neuronal death, we tested motoneuron-neuroblastoma hybrid (VSC 4.1) cells constitutively expressing human SOD-1 gene with mutations (A4V, G93A) or wild type. Calcium mobilizer through cell membrane (calcium ionophore; A23187) or endogenous calcium releaser (ryanodine, thapsigargin, cyclic ADP-ribose) was treated and cell viabilities were determined by using a 3-(4, 5-dimethylthiazole-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Apoptotic cell death was monitored by caspase enzyme assay and the Hoescht staining to check the evidence of nuclear fragmentation. RESULTS: Among agents, calcium ionophore and tharpsigargin reduced the level of survival in cells expressing mutant SOD-1. In mutant cells, caspase 3 activity was elevated and showed nuclear fragmentation. This phenomenon was blocked by caspase inhibitor. CONCLUSIONS: Our data suggest that motor neuron degeneration in familial amyotrophic lateral sclerosis with SOD-1 mutation may be mediated by calcium dys-regulation, particularly by exogenous calcium influx and this process induces caspase 3 activity which results in motor neuron death.
Amyotrophic Lateral Sclerosis ; Apoptosis ; Calcium* ; Caspase 3 ; Cell Death ; Cell Membrane ; Cell Survival ; Enzyme Assays ; Humans ; Motor Neurons ; Neurons ; Superoxide Dismutase* ; Superoxides* ; Thapsigargin

BACKGROUND: Intracellular calcium accumulation and dys-regulation is known as one of the mechanism in motor neuronal degeneration with mutations in Cu/Zn superoxide dismutase (SOD-1). METHODS: To investigate the calcium modulators and mutated SOD-1 induced neuronal death, we tested motoneuron-neuroblastoma hybrid (VSC 4.1) cells constitutively expressing human SOD-1 gene with mutations (A4V, G93A) or wild type. Calcium mobilizer through cell membrane (calcium ionophore; A23187) or endogenous calcium releaser (ryanodine, thapsigargin, cyclic ADP-ribose) was treated and cell viabilities were determined by using a 3-(4, 5-dimethylthiazole-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Apoptotic cell death was monitored by caspase enzyme assay and the Hoescht staining to check the evidence of nuclear fragmentation. RESULTS: Among agents, calcium ionophore and tharpsigargin reduced the level of survival in cells expressing mutant SOD-1. In mutant cells, caspase 3 activity was elevated and showed nuclear fragmentation. This phenomenon was blocked by caspase inhibitor. CONCLUSIONS: Our data suggest that motor neuron degeneration in familial amyotrophic lateral sclerosis with SOD-1 mutation may be mediated by calcium dys-regulation, particularly by exogenous calcium influx and this process induces caspase 3 activity which results in motor neuron death.
Amyotrophic Lateral Sclerosis ; Apoptosis ; Calcium* ; Caspase 3 ; Cell Death ; Cell Membrane ; Cell Survival ; Enzyme Assays ; Humans ; Motor Neurons ; Neurons ; Superoxide Dismutase* ; Superoxides* ; Thapsigargin