Search

The term trigeminal autonomic cephalalgias (TACs) was introduced in the 2

Objectives To assess the impacts of social situation changes due to the coronavirus disease 2019 (COVID-19) pandemic on headache-related disability and other symptoms in patients with migraine in Japan. Methods We conducted a multicentre, cross-sectional study including 659 outpatients with migraine diagnosed by headache specialists. The participants were asked about the impacts of the first wave of the COVID-19 pandemic on headache-related disability, headache days, headache intensity, stress, physical activity, hospital access and their work and home lives. For headache-related disability, the total Migraine Disability Assessment (MIDAS) score and part A and B scores were analysed. Multivariate stepwise linear regression analysis was performed to identify the clinical predictors of changes in the total MIDAS score before and during the COVID-19 pandemic. Logistic regression analysis was performed to determine the factors related to new-onset headache during the COVID-19 pandemic. Results Finally, 606 migraine patients (73 M/533 F; age, 45.2 ± 12.0 years) were included in the study, excluding those with incomplete data. Increased stress, substantial concern about COVID-19 and negative impacts of the first wave of the COVID-19 pandemic on daily life were reported in 56.8 %, 55.1 and 45.0 % of the participants, respectively. The total MIDAS and A and B scores did not significantly change after the first wave of the COVID-19 pandemic. New-onset headache, which was observed in 95 patients (15.7 %), was associated with younger age and worsened mood and sleep in the logistic regression analysis. The multivariate stepwise linear regression analysis of changes in the total MIDAS score before and during the first wave of COVID-19 pandemic identified worsened sleep, increased acute medication use, increased stress, medication shortages, comorbidities, the absence of an aura and new-onset headache were determinants of an increased total MIDAS score during the first wave of the COVID-19 pandemic. Conclusions In this multicentre study, clinical factors relevant to headache-related disability, such as new-onset headache, stress and sleep disturbances, were identified, highlighting the importance of symptom management in migraine patients during the first wave of the COVID-19 pandemic.

The calcitonin gene-related peptide (CGRP) has been shown to play a major role in the pathophysiology of migraine in recent years. Studies have suggested that blocking CGRP signaling is an effective preventive and therapeutic strategy in patients with migraine. Triptans, considered the mainstay of antimigraine treatment cause vasoconstriction; however, gepants and ditans (two novel classes of therapeutic agents) inhibit CGRP release but do not show a vasoconstrictor effect. Both these drugs are awaiting clinical approval in Japan as antimigraine medications that can be administered to patients with cardiovascular risk factors and to those with triptan-refractory migraine.

Cowden syndrome is a rare autosomal dominant disorder characterized by multiple hamartomas of the ectoderm and brain. A 36-year-old Japanese man presented with right facial seizure during sleep and was admitted to our hospital. He showed cobblestoning over the tongue and palmar pitting but no neurological abnormalities while he was not having a seizure. Brain magnetic resonance imaging showed focal cortical dysplasia in the left frontal lobe. Electroencephalography showed sharp waves over the left frontal lesion. A genetic analysis revealed a novel mutation of PTEN. The administration of carbamazepine ended the seizures. This is the first Japanese case of Cowden syndrome with a novel PTEN gene mutation and cortical dysplasia.

Aim An association between body mass index (BMI) and stroke outcome have been reported, but the results are controversial. The aim of the present study was to evaluate whether BMI is associated with ischemic stroke outcome. Methods Consecutive Japanese acute ischemic stroke patients were analyzed. BMI was categorized as underweight (BMI

High plasma levels of brain natriuretic peptide (BNP) may also be observed in patients with non-cardioembolic infarction (CEI). We aimed to evaluate the relation between plasma BNP level, clinical parameters, and functional outcome in patients with and without CEI.This study analyzed consecutive Japanese patients with acute ischemic stroke. Correlations between plasma BNP level and conventional risk factors for ischemic stroke were examined. Values of P less than .05 were considered statistically significant.This study analyzed 718 acute ischemic stroke patients (445 men and 273 women; mean age, 73.9 years). Mean plasma level of BNP was significantly higher for CEI (366.6 pg/ml) than for non-CEI (105.6 pg/ml; P.01). Poor outcome (modified Rankin Scale score ≥3) at hospitalization and discharge were associated with significantly higher plasma BNP level than good outcome (modified Rankin Scale score ≤2) for both CEI and non-CEI. On multiple regression analysis, log-BNP was significantly associated with female sex, smoking, triglyceride, and creatinine clearance in CEI. In non-CEI, log-BNP was significantly associated with systolic/diastolic blood pressure, triglyceride, high-density lipoprotein cholesterol, and creatinine clearance.Irrespective of the presence of CEI, plasma BNP offers a marker of prognostic functional outcome. We clarified the characteristics and differences associated with plasma BNP in CEI and non-CEI, and our results suggest that plasma BNP can provide a useful marker of brain damage and neurohumoral dynamics in acute ischemic stroke.

Cowden syndrome is a rare autosomal dominant disorder characterized by multiple hamartomas of the ectoderm and brain. A 36-year-old Japanese man presented with right facial seizure during sleep and was admitted to our hospital. He showed cobblestoning over the tongue and palmar pitting but no neurological abnormalities while he was not having a seizure. Brain magnetic resonance imaging showed focal cortical dysplasia in the left frontal lobe. Electroencephalography showed sharp waves over the left frontal lesion. A genetic analysis revealed a novel mutation of PTEN. The administration of carbamazepine ended the seizures. This is the first Japanese case of Cowden syndrome with a novel PTEN gene mutation and cortical dysplasia.

BACKGROUND AND PURPOSE: Branch atheromatous disease is a stroke subtype considered a risk factor for early neurologic deterioration. Meanwhile, crossed cerebellar diaschisis is thought to be influenced by the degree and location of supratentorial perfusion abnormalities and is associated with the clinical outcome in the case of an ischemic stroke. In this article, our aim was to clarify the utility of using a whole-brain 3D pulsed continuous arterial spin-labeling method as an imaging biomarker for predicting neurologic severity in branch atheromatous disease. MATERIALS AND METHODS: Twenty-three patients with branch atheromatous disease in the lenticulostriate artery territory were enrolled. All patients underwent MR imaging, including DWI, 3D-TOF-MRA, and 3D-arterial spin-labeling. We measured the asymmetry index of CBF in the affected area (branch atheromatous disease), the asymmetry index of the contralateral cerebellar hemisphere (crossed cerebellar diaschisis), and the DWI infarct volume in the lenticulostriate artery territory. We also compared each parameter with the initial NIHSS score with the Pearson correlation coefficient. RESULTS: Among the 23 patients, we found no correlation between NIHSS score and the asymmetry index of CBF in the affected area (branch atheromatous disease) (r = −0.027, P = .724), whereas the asymmetry index of the contralateral cerebellar hemisphere (crossed cerebellar diaschisis) and DWI infarct volumes were significantly correlated with NIHSS score (r = 0.515, P = .012; r = 0.664, P = .001, respectively). CONCLUSIONS: In patients with branch atheromatous disease, 3D-arterial spin-labeling can detect crossed cerebellar diaschisis, which is correlated with the degree of neurologic severity.

Background An association between serum uric acid and outcomes of ischemic stroke has been reported, but the results are controversial. The aim of this study is to clarify how uric acid may affect activities of daily living after acute ischemic stroke. Methods Consecutive Japanese patients with acute ischemic stroke were analyzed. Serum uric acid quartiles and activities of daily living at hospitalization and discharge in men and women were examined. Activities of daily living were evaluated using the modified Rankin scale score, and a score of 3 or higher was defined as poor activities of daily living. P values less than .05 were considered significant. Results A total of 987 patients with acute ischemic stroke (591 men; mean age, 72.3 years) were analyzed in this study. We observed a U-shaped relationship between serum uric acid and poor activities of daily living in both men and women at hospitalization and discharge. Multivariate analysis demonstrated that the first quartile group of serum uric acid was significantly associated with poor activities of daily living in both men and women, using the third quartile group as the reference. Conclusions Lower serum uric acid can be a marker for predicting poor activities of daily living in patients with acute ischemic stroke, irrespective of sex.

Background The congestion of spin-labeled blood at large-vessel occlusion can present as hyperintense signals on perfusion magnetic resonance imaging with 3-dimensional pseudo-continuous arterial spin labeling (proximal bright vessel sign). The purpose of this study was to clarify the difference between proximal bright vessel sign and susceptibility vessel sign in acute cardioembolic cerebral infarction. Methods Forty-two patients with cardioembolic cerebral infarction in the anterior circulation territory underwent magnetic resonance imaging including diffusion-weighted imaging, 3-dimensional pseudo-continuous arterial spin labeling perfusion magnetic resonance imaging, T2*-weighted imaging, and 3-dimensional time-of-flight magnetic resonance angiography using a 3-T magnetic resonance scanner. Visual assessments of proximal bright vessel sign and the susceptibility vessel sign were performed by consensus of 2 experienced neuroradiologists. The relationship between these signs and the occlusion site of magnetic resonance angiography was also investigated. Results Among 42 patients with cardioembolic cerebral infarction, 24 patients showed proximal bright vessel sign (57.1%) and 25 showed susceptibility vessel sign (59.5%). There were 19 cases of proximal bright vessel sign and susceptibility vessel sign-clear, 12 cases of proximal bright vessel sign and susceptibility vessel sign-unclear, and 11 mismatched cases. Four out of 6 patients with proximal bright vessel sign-unclear and susceptibility vessel sign-clear showed distal middle cerebral artery occlusion, and 2 out of 5 patients with proximal bright vessel sign-clear and susceptibility vessel sign-unclear showed no occlusion on magnetic resonance angiography. Conclusions Proximal bright vessel sign is almost compatible with susceptibility vessel sign in patients with cardioembolic cerebral infarction.

Background Progressive supranuclear palsy (PSP) is a neurodegenerative disorder that is sometimes confused with Parkinson's disease, multiple system atrophy, and other disorders. The typical clinical features are categorized as Richardson's syndrome (RS), but other clinical subtypes include PSP-parkinsonism (PSP-P) and PSP-pure akinesia with gait freezing (PSP-PAGF). In this study, we determined the prevalence of PSP in a Japanese rural area compared to our previous 1999 report. Methods We collected data in Yonago City from 2009 to 2014 using a service-based study of PSP. We collected case history data from PSP patients in the area from our hospital. The crude prevalence and 95% confidence interval (CI) were calculated using the population demographics on the prevalence day of 1 October 2010. Age- and sex-adjusted prevalence was calculated by direct standardization to the population demographics in Yonago City on the prevalence day of 1 April 1999. Material and Results We identified 25 patients: 16 with probable RS, 4 with possible RS, 3 with clinical PSP-P, and 2 with clinical PSP-PAGF. The prevalence per 100,000 was 17.90 (male = 18.05; female = 17.76). The prevalence of PSP in Yonago in 2010 increased compared to the measurements from 1999. Conclusion The prevalence of PSP in Japan increased from 1999 to 2010.

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

It is generally believed that cortical spreading depression (CSD) demonstrated by Leao underlie migraine aura and migraine headache depends on the activation of the trigeminovascular pain pathway proposed by Moskowitz. The onset of migraine attack and the association between CSD and the trigeminovascular pain pathway have remained largely unknown. Recent animal studies indicate that CSD can activate trigeminal nociception and thus trigger headache mechanism. Meanwhile, the nature and mechanism of migraine without aura is still an open question. It is considered that the pain in migraineur is affected by hereditary factors, internal factors such as female sex hormone, and external factors as medication, meal, weather, stress, etc. We review here the current understanding of the migraine pathophysiology, focusing on recent advance regarding cortical spreading depression and pain.

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.

Background/Aim: To determine the prevalence and incidence of Parkinson’s disease (PD) and compare them with results from our previous studies. Methods: We examined epidemiological characteristics of PD patients using a service-based study in Yonago City, and a door-to-door study in Daisen Town. The prevalence days were April 1, 2004 in Yonago, and April 1, 2003 in Daisen. Results: In Yonago, we identified 254 PD patients. The crude prevalence was 180.3 (95% CI, 158.1–202.4) per 100,000 population. The adjusted prevalence was 145.8 (95% CI, 145.2–146.5) in 1980, 147.0 (95% CI, 146.3–147.6) in 1992, and 166.8 (95% CI, 166.1–167.5) in 2004, when calculated using the Japanese population in 2004. The crude incidence was 18.4 (95% CI, 11.3–25.5) per 100,000 population per year. The crude incidence in 1980 was 10.2 (95% CI, 4.6–15.8), and the adjusted incidence was 9.8 (95% CI, 4.3–15.3) in 1992, and 10.3 (95% CI, 4.7–15.9) in 2004, when calculated using the population in Yonago in 1980. In Daisen, there were 21 PD patients. The crude prevalence was 306.6 (95% CI, 175.7–437.6) and the adjusted prevalence was 192.6 (95% CI, 191.9–193.8). Conclusions: The prevalence of PD had increased, primarily because the population had aged. Differences in prevalence between these adjacent areas may have resulted from differences in the methods of investigation.

Objective In order to examine a possible role of serum heart-fatty acid binding protein (H-FABP) in patients with Lewy body disease, we measured serum levels of H-FABP in patients with dementia with Lewy bodies (DLB), Parkinson's disease (PD), and Alzheimer's disease (AD). Methods Serum levels of H-FABP were measured using a solid-phase enzyme-linked immunoassay. Iodine-123 metaiodobenzylguanidine ( 123 I-MIBG) cardiac scintigraphy was performed on each patient and the heart to mediastinum (H/M) ratio was calculated. Receiver operating characteristic (ROC) analysis was used to calculate the optimal cutoff values of the H-FABP between DLB and AD patients. Independent predictive variables for serum H-FABP levels were analyzed using multivariate regression analysis. Results Serum levels of H-FABP were significantly higher in DLB patients and PD patients than in AD patients. H/M ratios of the DLB and PD patients were significantly lower than those of AD patients. The diagnostic value of the serum H-FABP levels between AD and DLB patients was inferior to that of the delayed H/M ratio of 123 I-MIBG cardiac scintigraphy. Multivariate regression analysis revealed that the delayed H/M ratio predicted serum H-FABP levels in the PD patients. Conclusions Examination of serum H-FABP levels did not allow discrimination between DLB and AD patients. Cardiac sympathetic nerve dysfunction may be associated with elevation of serum H-FABP in Lewy body disease patients.

A 49-year-old man noticed a resting tremor in his right hand and was diagnosed with Parkinson's disease (PD) at the age of 43. Soon thereafter, he noticed a right neck mass that only appeared when he swallowed and was accompanied by an uncomfortable sensation. At the age of 49, he was admitted to our hospital to adjust his medication for PD and to examine the neck mass. The subcutaneous mass was round, soft, and approximately 3 cm in diameter. The symptoms in his neck showed no progression. Resting tremors and rigidity due to his PD were predominantly observed on his right side, but his postural reflex was intact. Cervical echogram revealed that the mass was the belly of the OM itself. Thus, the patient was diagnosed with omohyoid muscle syndrome (OMS). It can be surmised that some susceptibility of the OM itself and/or structural fragility in the surrounding tissues would be involved in the pathogenesis of OMS. In this case, considering that OMS occurred soon after symptoms of PD appeared, we speculated that muscle tone abnormalities due to PD played a role in the development of OMS.

Substance P (SP), calcitonin gene-related peptide (CGRP), and angiotensin converting enzyme (ACE) may have roles in trigeminovascular nociceptive mechanisms. We investigated interictal levels of SP, CGRP, ACE activity, and their correlation, in a sample of migraineurs. Forty-one patients su!ering from migraine with aura (MA), 54 without aura (MO), and 52 non-headache subjects (controls) participated in this study. Blood samples were collected from cubital veins. Plasma levels of SP and CGRP were measured by enzyme immunoassay. Plasma ACE activities were measured spectrophotometrically. SP levels in MA (6.6 ± 3.7 pg/ml; mean ± SD) and MO (6.6 ± 3.2 pg/ml) were significantly higher than in controls (4.8 ± 2.4 pg/ml) (P < 0.01). CGRP levels in MA (18.8 ± 8.8 pg/ml) and MO (19.1 ± 9.4 pg/ml) were also significantly higher than in controls (13.4 ± 4.4 pg/ml) (P < 0.01). ACE activities in MA (34.6 ± 19.0 U/l) were significantly higher than in MO (25.3 ± 13.2 U/l) and controls (27.0 ± 20.4 U/l) (P < 0.05). There was a significant correlation between SP and CGRP levels (P < 0.05). In MA, SP and CGRP showed a tendency toward positive correlation, which was not significant. There was a weak, but significant positive correlation between SP levels and ACE activities (P < 0.01). However, a relationship between ACE activities and CGRP levels was not observed. The data suggest that SP, CGRP, and ACE are relevant to migraine pathophysiology, and that they may interact. ! 2006 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

An association between body mass index (BMI) and stroke outcome have been reported, but the results are controversial. The aim of the present study was to evaluate whether BMI is associated with ischemic stroke outcome.Consecutive Japanese acute ischemic stroke patients were analyzed. BMI was categorized as underweight (BMI18.5 kg/mA total of 1206 acute ischemic stroke patients (760 men; mean age 72.5 years) were analyzed in the present study. There were 111 underweight cases (9.2%), 785 normal weight cases (65.1%) and 310 obese cases (25.7%). The underweight group had a significantly higher rate of poor short and long-term outcomes than the normal weight group. The outcomes of the obese group were not significantly different from those of the normal weight group. Recurrence was not significantly different among the groups.Lower BMI might be a predictor of poorer short-term and long-term stroke outcomes. Geriatr Gerontol Int 2017; 17: 369-374.

We report the case of an 18-year-old Japanese woman with cobalamin (cbl) C disease. She was born between non- consanguineous parents, and had easy fatigability from a childhood. At 14 years old, she developed renal failure, and had repeated psychosis during 2 years. At 16 old, she developed her gait disturbance and her symptoms fluctuated, but the cause of gait disturbance was unclear. At 18 years old, she was admitted with worsening of gait disturbance. Physical examination revealed spastic paraparesis and bilateral peroneal nerve paralyses. Homocystinuria and methylmalonic aciduria were detected, although serum vitamin B12 was within normal range. Gene mutation analysis revealed Gly147Asp (440G>A) and Trp157Ser (470G>C) in the MMACHC gene as a compound heterozygous mutation. We diagnosed her as having late-onset cbl C disease, and her gait disturbance and renal failure improved after intramuscular hydroxocobalamin administration. Although late-onset cbl C disease is rare in Japan, it an important to consider this congenital disease because symptoms are expected to improve by medical intervention.

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.

Early onset familial Alzheimer's disease with spastic paraparesis (FAD-SP) has been associated with mutations of the presenilin 1 gene (PSEN1). We report a pedigree of FAD-SP due to a novel missense mutation of PSEN1 (Y154N). The symptoms of the proband were characterized by presenile dementia in her 40s, preceded by spastic paraparesis in her 30s, whereas the mother of the proband presented with spastic paraparesis in her 40s, followed by symptoms of dementia in her mid 60s. The mutation was found only in the proband, and not in a normal family member, normal Japanese control subjects, patients with sporadic Alzheimer's disease or patients with familial spastic paraparesis without dementia. Thus, Y154N is a novel PSEN1 mutation responsible for FAD-SP of Japanese origin.

Methylenetetrahydrofolate reductase (MTHFR) is the only route for the synthesis of 5-methyltetrahydrofolate, which is utilized to convert homocysteine to methionine. In this study, we measured the enzyme activity of a mutant MTHFR that was detected in a patient with hyperhomocysteinemia. The 428C>T mutation in exon 2 of the MTHFR gene is a novel mutation, while the [458G>T+459C>T] mutation in exon 2 is a previously reported mutation. The activity of mutant enzymes containing the 428C>T, [458G>T+459C>T] and 677C>T mutations was 12.7±4.7%, 48.1±18.8%, and 43.6±14.4%, respectively, of that of the wild type enzyme. Our results suggest that these two variants each result in a severe MTHFR deficiency, which causes a developmental delay and cerebral vascular disease.

Epidemiological studies have shown that elevated plasma homocysteine (Hcy) levels play an important role in the pathogenesis of Alzheimer's disease (AD). In spite of the evidence that a C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene elevates plasma Hcy levels, the impact of the C677T polymorphism on the development of AD is controversial. Here, we performed a genetic case-control study in a Japanese population to investigate whether three polymorphisms of the MTHFR gene, C677T (Ala222Val), A1298C (Glu429Ala), and A1793G (Arg594Gln), are associated with the development of late-onset AD (LOAD). In our study, the MTHFR gene had four major regional haplotypes: Haplotype A (677C-1298A-1793G), Haplotype B (677T-1298A-1793G), Haplotype C (677C-1298C-1793G), and Haplotype D (677C-1298C-1793A). The frequency of Haplotype C in LOAD was significantly lower than that in control group. Furthermore, the benefit conferred by the presence of at least one Haplotype C was stronger in LOAD patients who lacked the ApoE 4 allele (OR=0.293; 95% CI=0.115-0.744; P=0.010). The results indicate that Haplotype C of the MTHFR gene is protective against the development of LOAD.

Recent epidemiological studies have emphasized the impact of elevated blood homocysteine levels on the pathogenesis of Alzheimer’s disease (AD). In spite of a significant impact of a MTHFR C677T polymorphism on the blood homocysteine levels, the association between the C677T polymorphism and AD remains controversial. Therefore, other unidentified genetic factor(s) that regulate blood homocysteine levels may exist. Here, we have analyzed the 5′-upstream region of the MTHFR gene and examined AD patients (n = 223) and nondemented individuals (n = 323) for polymorphisms in the 5′-upstream region of the MTHFR gene. We identified two polymorphisms (–713G/A and –393C/A, upstream of the start codon). We found no significant relationship between AD and the 5′-upstream region polymorphisms of the MTHFR gene. Thus, our study does not reinforce the hypothesis of an independent involvement of the MTHFR gene upstream region polymorphisms in AD risk.

Migraine is considered to be a polygenic multifactorial disease with various environmental and genetic etiologies. We investigated glutathione S-transferase (GST) P1 Ile105Val, T1 and M1 polymorphisms in 174 Japanese headache sufferers and 372 Japanese controls. The headache group consisted of 38 cases of migraine with aura, 95 migraine without aura (MWOA) and 41 tension-type headache sufferers. The M1 homozygous deletion genotype was significantly higher in MWOA (64%) compared with controls (46%; p < 0.01; odds ratio = 2.18, 95% confidence interval: 1.32–3.61, adjusted for age and gender). In a comparison of the current smokers, the M1 null frequencies in MWOA were further increased. GSTM1 may be one of the genetic risk factors for MWOA in the Japanese population.

Cortical spreading depression (CSD) is a slowly propagated wave of depolarization of neurons and glial cells, followed by a subsequent sustained suppression of spontaneous neuronal activity. Functional imaging studies of migraine patients have shown dramatic changes in blood flow and brain activity whose characteristics are similar to those of CSD, implicated in migraine visual aura. Although the trigeminal nerve innervates the meninges and participates in the genesis of migraine headaches, triggering mechanisms remain controversial and poorly understood. It is demonstrated by animal models that CSD activates trigeminovascular afferents and evokes a series of cortical meningeal and brainstem events consistent with the development of headache. Three familial hemiplegic migraine, a rare monogenic subtype of migraine with aura, genes have been identified, which all encode ion transporters, suggesting that disturbances in ion and neurotransmitter balances in the brain are responsible for this migraine type. Additional molecular insight into the pathophysiology of migraine may come from other monogenic syndromes such as CADASIL, RVCL. Several genetic associations with candidate migraine genes like ESR1, MTHFR, and INSR, have been convincingly replicated. The genome-wide association studies may be a successful strategy toward identification of migraine susceptibility genes.

The vestibulospinal system was evaluated using a stabilometric method in patients with migraine and episodic tension-type headache during headache-free periods. Migraine patients often complain of dizziness or vertigo during headache attacks and some exhibit these symptoms between attacks. Computerized static stabilometry is a reliable and non-invasive technique to evaluate the equilibrium function in various diseases. The subjects consisted of 21 patients with migraine, 12 patients with episodic tension-type headache and, age- and sex-matched controls. We performed two sets of static stabilometric measurements with eyes open (EO) and eyes closed (EC) for 30 s. The averages of two sessions of the following six stabilometric parameters were used for the analysis: locus length (LNG), environmental area (ENV-AREA), rectangle area (REC-AREA), locus length per second, locus length per environ area (L/E), and root mean square area. Romberg quotients (EC/EO) of these six parameters were also analyzed. The mean values of LNG, ENV-AREA and REC-AREA in the EC session in the migraine group were significantly greater than those in the controls (P < 0.05, Mann-Whitney rank sum test). Romberg quotients of all stabilometric parameters except the L/E in the migraine group were significantly greater than in the controls. Patients with episodic tension-type headache did not show any differences in the stabilometric study from the controls. The present findings suggest that patients with migraine show a significant increase of the body sway during the EC session, which indicates an underlying dysfunction in the vestibulospinal system.

Migraine is one of the common diseases, suffering 8.4 million patients in Japan. Recently conditions associated with chronic migraine were considered to be worse than episodic migraine in socio-economic status, health-related quality of life, and headache-related burden. Preventing the chronification, and improving treatment and management, the natural disease course could give us some clues. Several reports suggested that a population prevalence of chronic migraine is about 2% and approximately 2.5% of patients with episodic migraine develop new-onset chronic migraine each year. The risk factors for converting episodic to chronic migraine were demonstrated as follows: age, low education/socioeconomic status, head injury, attack frequency, obesity, medication overuse, stressful life events, caffeine overuse, snoring, other pain syndromes, allodynia, proinflammatory states, prothrombotic states, and specific genes. It was also focused in comobidity with chronic migraine, such as depression, anxiety, chronic pain, asthma, bronchitis, hypertension, and so on. The ratio converting in reverse was reported as a fourth in two years. We should recognize the burden of migraine patients, and improve patients' outcome under reducing risk factors and assessing the effect of treatment on headache progression.

Chronification of migraine headache is one of the major issues to resolve urgently. The prevalence of chronic migraine is close to 2％, and the chronification occurs in approximately 2.5％ of episodic cases annually.The pathophysiology of transformation from episodic to chronic migraine is still unclear. It is considered that there are several risk factors for migraine chronification; 1) non-modifiable: age, low education/socioeconomic status, and head injury, 2) modifiable: attack frequency, obesity, medication overuse, stressful life events, caffeine overuse, snoring, and other pain syndrome, 3) currently putative: allodynia, proinflammatory states, prothrombotic states, and specific genes.There were a few clinical reports concerning to the migraine transformation from abroad, but few data from Japan. The prevalence of chronic daily headache in our headache clinic in Japan was 20-30％. The medication overuse headache was the most prevalent form in the highest attack frequency (>15 days/month) grope. Discontinuation of overused medication and administration of prophylactic medication were effective, and 40％ of followed cases kept out of MOH at two years later.

Objective.—To clarify whether the circadian rhythm of heart rate variability parameters can be identified in patients with migraine during a headache-free period and to identify any specific pattern of the circadian rhythm of heart rate variability, using time-domain and spectral analysis and cosinor rhythm analysis of heart rate variability during normal daily activity. Methods.—Forty-eight–hour Holter electrocardiograms were recorded for 27 patients with migraine during headache-free periods and 24 healthy controls during free activity. The circadian rhythms of heart rate fluctuation parameters, that is, mean interval, standard deviation, root-mean-square successive differences (RMSSD), %RR50, and low (0.020 to 0.150 Hz) and high frequency (0.150 to 0.400 Hz) heart rate fluctuations were analyzed with the group mean cosinor method. Results.—The group mean cosinor analysis and the acrophase-amplitude analysis demonstrated significant differences in circadian rhythm in SD, RMSSD, %RR50, and high frequency between the group with migraine and controls. The amplitudes of SD, RMSSD, %RR50, and high frequency in the group with migraine were smaller than those in controls, which implied parasympathetic hypofunction in migraineurs. There were no significant differences in the MESOR (midline estimating statistic of rhythms) of the analyzed heart rate parameters except for low frequency. The MESOR of low frequency in the migraineurs was significantly smaller than that in the controls. Conclusions.—Patients with migraine have hypofunction in the parasympathetic nervous system during normal daily activity in the headache-free period.

We examined the expression of presenilin 1 (PS-1) mRNA in cultured skin fibroblasts taken from living patients with Alzheimer’s disease (AD) and human brains taken postmortem from AD patients by RT-PCR analysis. The donors of fibroblasts consisted of 28 cases with AD and 19 neurological patient without dementia (CTL). The brains came from 17 cases with AD and 23 cases with CTL. We found that PS-1 mRNA levels in skin fibroblasts of AD patients were significantly higher than those of CTL patients (p < 0.0001). Moreover, we found that PS-1 mRNA levels in human brains with AD were significantly higher than in those with CTL (p < 0.0001). These findings suggest that high levels of PS-1 mRNA in AD may play an important role in developing AD and that the examination of PS-1 mRNA in skin fibroblasts may be helpful for the diagnosis of AD.

Objectives – The goal of this study is to clarify the association between migraine and Serotonin 2C receptor Cys23Ser polymorphism in Japanese population. Materials and method – This study included 37 individuals with migraine with aura (MWA), 80 with migraine without aura, 43 with tension type headache (TH) and 360 with controls. The genotypes of Cys23Ser polymorphism were confirmed by polymerase chain reaction-restriction fragment length polymorphism techniques. Results – The Ser allele frequency in control subjects is much less than that in Caucasian population. The Ser allele frequency in patients with MWA was higher than that in control subjects. Conclusion – The present study provides that 5HTR2c Cys23Ser polymorphism may be associated with MWA in Japanese population.

It has been reported that the cholinesterase inhibitor, donepezil, improves cognitive decline in patients with Parkinson's disease dementia (PDD). However, this improvement was dominant for frontal lobe dysfunction, and the increase in the Mini-Mental State Examination (MMSE) score was minimal. We report a PDD patient with a decline of regional cerebral blood flow (rCBF) in the posterior cingulate cortex, precunei, and bilateral parietotemporal association cortex, as determined by single-photon emission computed tomography (SPECT) using the easy Z-scores imaging system (e-ZIS). Upon administration of donepezil, both the rCBF and MMSE score increased. The effectiveness of donepezil may vary based on the rCBF pattern in PDD.

Dementia with Lewy bodies (DLB) is the second most common senile degenerative dementia after Alzheimer's disease (AD). The presentation of overlapping symptoms between these two disorders leads to difficulties in the determination of clinical entities. Serum samples were subjected to surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) analysis in order to identify a diagnostic marker for DLB. Four putative protein peaks (m/z 3,883, 4,964, 7,761 and 10,534) were differentially expressed in DLB patients compared to AD patients and control subjects. Receiver operating characteristics (ROC) analysis of a multivariate logistic model of the combination of three peaks (m/z 3,883, 7,761 and 10,534) exhibited the highest discriminatory ability of DLB subjects from non-DLB subjects with a sensitivity of 83.3%, a specificity of 95.8%, a positive predictive value of 90.9% and a negative predictive value of 92.0%. SELDI-TOF MS profiling, therefore, has revealed a serum signature with high diagnostic potential for DLB.

We report a 71-year-old man presenting with paraneoplastic cerebellar degeneration (PCD) associated anti-Yo antibody after surgery for gastric adenocarcinoma. Seven months after partial gastrectomy, he deviated to the right on walking. Furthermore, a feeling of dysarthria appeared and he was unable to sit after 2 months. When he was hospitalized, he showed a disturbance of his eye movement on lower gaze, a nystagmus on lateral gaze, saccadic eye movement on smooth pursuit, cerebellar ataxia, and decreasing of muscle tonus in his extremities. However, no atrophic findings of the brainstem and cerebellum were revealed by brain MRI. He responded poorly to treatment with high-dose methylprednisolone, high-dose immunoglobulin, double filtration plasmapheresis and rehabilitation. There was a strong anti-Yo immunohistochemical staining of the cytoplasm in both the patient's tumor cells and normal cerebellar Purkinje cells. These findings suggest that PCD associated with anti-Yo antibody triggered by adenocarcinoma might occur in this male patient.

Contains fulltext : 50540.pdf (Publisher’s version ) (Closed access) OBJECTIVE: Migraine with aura is associated with increased risk of stroke. The MTHFR C677T genotype has been associated with increased risk of migraine in selected clinical samples and with elevated homocysteine, a risk factor for stroke. We assessed the association of the MTHFR C677T variant with migraine and the mediating effect of cardiovascular risk factors and metabolic markers of genotype status. METHODS: We compared adult migraineurs with aura (MA; n = 187), without aura (MO; n = 226), and nonmigraineurs (n = 1,212) from the population-based Genetic Epidemiology of Migraine study. RESULTS: Compared with the wild-type genotype, the T/T genotype was associated with increased odds of MA (odds ratio [OR], 2.05; 95% confidence interval, 1.2-3.4; p < 0.006), with a trend of increasing numbers of T alleles (OR, 1.40; 95% confidence interval, 1.1-1.8; p < 0.007). ORs were slightly attenuated after adjusting for homocysteine. INTERPRETATION: Risk of MA is associated with MTHFR C674T homozygosity, independent of other cardiovascular risk factors.

Migraine is one of the common diseases suffering 8.4 million patients in Japan. The pathophysiology of migraine remains unclear. The genetic and basic studies of the familial hemiplegic migraine, a specific subtype of migraine with aura, have demonstrated the dysfunction of mutant brain-expressed calcium ion channel and/or the Na+/K+ ion transporter and suggested the association between cortical spreading depression (CSD) and migraine with aura. It is suggested that the CSD, neurogenic inflammation and vasodilatation caused by unknown triggers may activate the 'brainstem migraine generator' and amplified back way. In consequence, headache and/or aura will be appeared and strengthened. Our etiological data of headache in Daisen located in Western Japan clarified as follows; 1) Overall prevalence of migraine in Daisen was 6.0%. Women observed a 5.9-fold higher risk of migraine than men. 2) Fatigue, mental stress, and lack of sleep were the main headache triggers. 3) Only 7.3% of those with migraine with aura and 5.3% of those with migraine without aura had consulted a physician. 4) Migraineurs consume significantly more fatty/oily foods, coffee, and tea than nonheadache subjects of the same community. Migraineurs consume significantly fewer fish than nonheadache residents. As a conclusion, only a few Japanese migraineurs receive benefits of medical services and recent advances of headache medicine. The Japanese guideline for chronic headache treatment has declared in 2002. The International Classification of headache disorders has reedited to the 2nd edition. Public education concerning headaches is one of the most urgent issues in Japan.

Migraine is a common form of the chronic headache syndromes. Although the pathogenesis of migraine still remains enigmatic, there have been remarkable progress in headache research. Point mutations of P/Q-type Ca2+ channel alpha 1 subunit (CACNA1A) gene have been identified in familial hemiplegic migraine (FHM), which linked to chromosome 19 (FHM-1, OMIM 141500). Na-K ATPase alpha2 gene has been identified as the causative gene for FHM linked to 1q21-23 (FHM-2, OMIM 602481). Common forms of migraine (i.e. migraine with and without aura) seems to be caused from multifactorial genetic factors and environmental factors. An association study of allelic variation at Codon 23 (Cys or Ser) of 5HT2C-R gene in Japanese samples revealed that the Ser allele frequency in migraine with aura was significantly higher than that in the non-headache controls. However, negative association of this polymorphism have been reported in Caucasian migrainures. The C677T allelic variation of 5,10-methylenetetrahydrofolate reductase (MTHFR) are focused on in association with the coronary heart diseases and the cerebrovascular diseases. The T allelic frequency in migraine sufferers was significantly higher than that in controls. The C677T mutation of MTHFR is one of the genetic risk factors for migraine. These observations are confirmed in Turkish, Australian and Spanish samples. Positive associations of angiotensin converting enzyme (ACE) gene, endotheline receptor-A (ET-A) gene, and insulin receptor gene have been reported. Using the genomewide screen technology, significant linkage between the migraine with aura and a marker on 4q24 has been reported in Finnish families. The genome wide screen analysis will be one of the powerful strategies on exploring migraine gene. Genetic study of migraine headache is a promised and fruitful field and will provide deep understanding to migraine headache. Discovery of new responsible or susceptible genes to migraine will also open an avenue to develop new therapeutic strategy of migraine.

Recently, several angiotensin I-converting enzyme (ACE) inhibitors and an angiotensin II receptor blocker were demonstrated to have a clinically important prophylactic effect in migraine. ACE is one of the key enzymes in the rennin-angiotensin-aldosterone system, which modulates vascular tension and blood pressure. In humans, serum ACE levels are strongly genetically determined. Individuals who were homozygous for the deletion (D) allele showed increased ACE activity levels. To investigate the role of ACE polymorphism in headache, we analyzed the ACE insertion (I)/deletion (D) genotypes of 54 patients suffering from migraine with aura (MwA), 122 from migraine without aura, 78 from tension-type headache (TH), and 248 non-headache healthy controls. The ACE D allele were significantly more frequent in the MwA than controls (p