[Therapeutic Effects of Intranasal Sumatriptan for Cluster Headache].

To clarify the associated factors for negative response to sumatriptan nasal spray in patients with cluster headache, we investigated the involvement of clinical information, such as the characteristics of headaches, before commencing sumatriptan nasal spray treatment. There were 18 male patients and 4 female patients. A total of 17 responders and 5 non-responders to sumatriptan nasal spray participated in the present study. Three factors for negative response to sumatriptan nasal spray, "young age of onset", "psychiatric disorder", and "the headache is not in the orbit," were found. Oxygen inhalation and/or subcutaneous injection were effective for nonresponsive cases. Therefore, these factors are considered to be useful for predicting therapy before applying sumatriptan nasal spray.

Accumulation of 123I-Ioflupane Is a Useful Marker of the Efficacy of Selegiline Monotherapy in Drug-Naïve Parkinson's Disease.

Background: Selegiline enhances the patient's endogenous dopamine by inhibiting dopamine metabolism. The efficacy of selegiline monotherapy for drug-naïve Parkinson's disease (PD) patients may depend on the degree of dopaminergic neuronal degeneration. 123I-Ioflupane single photon emission computed tomography (SPECT) and 123I-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy are diagnostic methods to assess the pharmacological and pathological changes in PD. Objective: We examined the utility of these imaging methods to predict the efficacy of selegiline monotherapy for motor symptoms in drug-naïve PD patients. Methods: We observed the efficacy of selegiline monotherapy in 28 drug-naïve PD patients and compared the improvement in motor function and the imaging findings. These patients received selegiline monotherapy, and the amount was increased to the optimal dose in clinical practice. Motor function was assessed using the Unified Parkinson's Rating Scale (UPDRS) at baseline and at the stable dose. Imaging was performed before treatment, and the striatal Specific Binding Ratio (SBR) of the 123I-Ioflupane SPECT and the Heart-to-Mediastinum (H/M) ratio of the 123I-MIBG myocardial scintigraphy were calculated. Both ratios were compared with improvements in scores for motor assessment using Pearson's correlation coefficient. Results: The mean UPDRS part III score significantly improved with at least 5.0 mg/day of selegiline. Further dose escalation did not improve the mean motor score. The percent improvement in the motor score from baseline showed a significant negative correlation with the SBR of average of the right and left striatum, but not with the H/M ratio. Multiple regression analysis using patient's background factors showed that percent improvement in the UPDRS part III score directly correlate with the SBR (p = 0.04), but not with the age (p = 0.72), disease duration (p = 0.31), baseline UPDRS part III (p = 0.77) and the drug dose (p = 0.26). Conclusion: PD patients with a lower accumulation of 123I-Ioflupane in the striatum can have greater improvement with selegiline monotherapy.

Efforts by Pharmacists in Community Pharmacy in Peacetime for Headache Medical Care in Emergencies, Such as Great Earthquake and Disaster.

We herein analyzed the issues that pharmacists in a community pharmacy in peacetime need to prepare for regarding headache medical care in emergencies (the state that supply of medical supplies is difficult) using a questionnaire intended for doctors and pharmacists in a community pharmacy. Recovery rates were 48.0% (96/200) for doctors and 37.3% (112/300) for pharmacists. In order to distinguish between patients for whom pharmacists need to "recommend OTC drugs" and those who need to be encouraged "to consult a hospital or clinic", doctors indicated that pharmacists need to use an "assistance tool to diagnosis headaches, such as a migraine screener" and "guidelines for chronic headaches". However, few pharmacists used these tools. Approximately 66.7% of doctors indicated that it is "meaningful" for pharmacists to distinguish patients with headaches. Moreover, doctors indicated the need for guidance by pharmacists in peacetime regarding headache medical care in emergencies. Although 73.2% of pharmacists instructed the patients with headaches of the importance of medication notebooks in emergencies, guidance ("understanding the triggers of headaches", "understanding the importance of removing the cause of the headache", "standing OTC drugs" and "standing prescription drugs") by pharmacists to prepare for an emergency was insufficient. These results provide useful information to improve the efforts by pharmacists in community pharmacies in peacetime for headache medical care in emergencies.

Clinical Response to Valproate in Patients with Migraine.

BACKGROUND AND PURPOSE: Valproate is used as a prophylactic drug for migraine, but it is not be effective in all patients. We used medical records to investigate which clinical factors affected the response to valproate in patients with migraine as an original headache, and established a scoring system for predicting the clinical response to prophylactic therapy. METHODS: We investigated clinical factors from the medical records of 95 consistent responders (CRs) and 24 inconsistent responders (IRs) to valproate. RESULTS: Multivariate stepwise logistic regression analysis revealed that a history of hyperlipidemia and hay fever and the complication of depression or other psychiatric disorder were significant factors that independently contributed to a negative response, with odds ratios of 6.024 [no vs. yes; 95% confidence interval (CI)=1.616-22.222], 2.825 (no vs. yes; 95% CI=1.046-7.634), and 2.825 (no vs. yes; 95% CI=1.052-7.576), respectively. A predictive index (PI) of the clinical response to valproate in patients with migraine was calculated using the regression coefficients of these three factors as an integer, and the index was significantly higher for IRs than for CRs (1.46±1.10 vs. 0.69±0.74, mean±SD, p<0.001). CONCLUSIONS: The obtained PI may represent an appropriate scoring system for predicting the responses in these patients.

Improvement in Language Function Correlates with Gait Improvement in Drug-naïve Parkinson's Disease Patients Taking Dopaminergic Medication.

BACKGROUND: Dopaminergic drugs, the gold standard for motor symptoms, are known to affect cognitive function in Parkinson's disease (PD) patients. OBJECTIVE: We compared the effects of dopaminergic treatment on motor and cognitive function in drug-naïve patients. METHODS: Dopaminergic medication (levodopa, dopamine agonist, selegiline) was given to 27 drug-naïve PD patients and increased to a dose optimal for improved motor symptoms. Patients were tested prior to, and 4-7 months after, drug initiation. Motor function was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS). Cognitive function was assessed using both the Japanese version of the Montreal Cognitive Assessment (MoCA-J) and the Neurobehavioral Cognitive Status Examination (COGNISTAT-J). Improvements from baseline for both motor and cognitive assessment were compared. RESULTS: Mean score of all motor assessments (UPDRS total score of Parts II and III, and sub-scores of tremor, rigidity, bradykinesia, gait, and postural instability) and certain cognitive assessments (MoCA-J total score and subscore of delayed recall) significantly improved with dopaminergic medication. Gait score improvement showed significant positive correlation with improvement in MoCA-J language domain and in language-comprehension subtests of COGNISTAT-J using Spearman's correlation coefficients. Furthermore, multiple regression analysis showed gait score improvement significantly correlated with improvements in the subtests of language-comprehension in COGNISTAT-J. CONCLUSION: There is correlated improvement in both gait and language function in de novo PD patients in response to dopaminergic drugs. Gait and language dysfunction in these patients may share a common pathophysiology linked to dopamine deficits.

[A case of migraine presenting with thunderclap headache associated with posterior reversible encephalopathy syndrome].

We report a 47-year-old woman who developed a thunderclap headache. Head axial, fluid-attenuated inversion recovery magnetic resonance imaging (FLAIR MRI) revealed high signal lesions in the left occipital and right parietal lobes. Apparent diffusion coefficient mapping showed a vasogenic edema pattern. Upon admission, the patient's blood pressure was normal and the neurological examination was unremarkable. As thunderclap headaches are associated with a repeated rise in blood pressure, we considered cerebral vasoconstriction and administered a calcium channel blocker. Thereafter, her headache with high blood pressure eased significantly and the high signal lesions on FLAIR MRI disappeared. We diagnosed the condition as posterior reversible encephalopathy syndrome (PRES). In addition, head magnetic resonance angiogram showed vasoconstriction of the right anterior cerebral artery, left middle cerebral artery, and bilateral posterior cerebral artery. Calcium channel blocker use was continued and vasoconstriction improved by day 70. In this case, the presenting symptom was thunderclap headache, which is a characteristic feature of reversible cerebral vasoconstriction syndrome (RCVS). Therefore, PRES may be caused by RCVS.

[Successful treatment with anti-epileptic-drug of an 83-year-old man with musical hallucinosis].

An 83-year-old man with 3 years symptomatic hearing loss suddenly experienced musical hallucinosis. He heard children's songs, folk songs, military songs, and the Japanese national anthem for seven months every day. He sometime had paroxysmal nausea, dull headaches and depressive mood. On examination he had no psychosis or neurological symptoms except sensorineural hearing loss in both ears. MRI brain imaging and electroencephalography showed no significant abnormalities, however 123I-IMP brain SPECT showed decreased activity in the right temporal lobe and increased activity in the left temporal and parietal lobes. Late phase 123I-iomazenil brain SPECT showed decreased accumulation in the right temporal lobe compared to the early phase. This indicates right temporal lobe epilepsy. He was diagnosed with epilepsy because of paroxysmal nausea and headache and the laterality of 123I-IMP brain SPECT and 123I-iomazenil brain SPECT. The musical hallucinosis was much reduced by carbamazepine 200mg per day. Nine months after beginning carbamazepine we detected decreased activity in the right temporal lobe and increased activity in left temporal and parietal lobes was improved. We do not believe he had epileptogenic musical hallucinosis because his musical hallusinosis was neither paroxysmal nor lateral. We diagnosed auditory Charles Bonnet syndrome with onset 3 years after sensorineural hearing loss due to reversible epileptic like discharge in temporal and parietal lobes. There is no established treatment for musical hallucinosis, but anti-epileptic drugs may be of some help.

[Orbital apex syndrome without MRI lesion caused by ANCA-associated vasculitis].

A 73-year-old man developed double vision and a progressive loss of visual acuity of the left eye over one week. Examination showed disturbances of the left II, III, IV, and VI cranial nerves, that is, an orbital apex syndrome. A brain MRI showed abnormal T2-high signals in the right maxillary sinus and the left mastoid cells without abnormalities in the left orbital apex and the surroundings. Laboratory examination showed an elevated erythrocyte sedimentation rate and a positive perinuclear anti-neutrophil cytoplasmic antibody (MPO-ANCA). After two courses of methyl-prednisolone pulse treatment, his external ophthalmoplegia fully recovered and he regained his left eye's sight. MPO-ANCA was negative and MRI abnormalities were disappeared after treatment. Two years later, the patient developed upper respiratory symptoms associated with an elevation of MPO-ANCA titer, and rapidly progressive renal failure. Renal biopsy specimen showed fibrinoid necrosis with periarteriolar neutrophil infiltration, which suggested that the patient suffered from ANCA-associated vasculitis probably of Wegener's granulomatosis or microscopic polyarteritis. ANCA-associated vasculitis may present with a focal neurological syndrome such as the orbital apex syndrome without a lesion detectable with MRI.

Influence of the Tohoku-Pacific Ocean earthquake and its aftershocks on the response to prophylactic therapy with lomerizine in patients with migraine in Tokyo: a retrospective study.

BACKGROUND: On March 11, 2011, the Tohoku-Pacific Ocean earthquake (magnitude 9.0) struck the eastern part of Japan. Despite being far from the epicenter of the catastrophic earthquake, the effects were strongly felt in Tokyo, and the aftershocks continued for several months. There are no reports regarding the influence of earthquakes on migraine medication. The aim of our study was to determine the impact of earthquakes on prophylactic therapy with lomerizine in patients with migraine in Tokyo. METHODS: The study included patients with migraine who were admitted to outpatient clinics in Tokyo between January 2010 and July 2010 or between January 2011 and July 2011 and who were prescribed lomerizine prophylactically for headache by specialists. We investigated clinical factors from the medical records for 26 of these patients. RESULTS: The study population included 10 patients in 2010 and 16 patients in 2011. The frequency of headaches was reduced to under 5 days/month during February in both the groups. Compared to 2010, the frequency of headaches significantly increased in 2011 in March, April and May. CONCLUSION: Patients with migraine were sensitive to exposure to the earthquake and their headaches worsened despite successful prophylactic treatment with lomerizine before the Tohoku-Pacific Ocean earthquake.

Characteristics of inconsistent responders to prophylaxis therapy with lomerizine in patients with migraine: a retrospective study in Japan.

Although lomerizine is used as a first-line prophylactic drug for migraines in Japan, approximately 30% of patients fail to respond to this treatment. On the basis of medical records, we investigated the involvement of clinical factors in response to lomerizine used in patients with migraine as primary headache and established a scoring system for predicting clinical responses to prophylactic therapy. Ninety-four consistent responders and 33 inconsistent responders to lomerizine were enrolled in this study. Multivariate stepwise logistic regression analysis revealed that migraine plus tension-type headache as primary headache and frequency of headache attacks were significant factors that contributed independently to negative response [odds ratio, 3.817 (no vs. yes; 95% confidence interval (CI), 1.264-11.628) and 5.814 (>15 episode days/month vs. 0-14 episode days/month; 95% CI, 2.381-14.286), respectively]. The predictive index (PI) of clinical responses to lomerizine in patients with migraine was calculated using the regression coefficients of two factors as an integer, where the score for inconsistent responders (1.00±0.71) was significantly higher than that for consistent responders (0.37±0.53, p<0.001). Sensibility of the low-scoring group (PI=0) was 75.8%, and specificity of the high-scoring group (PI=2) was 97.9%. Groups scoring low, intermediated and high included 11.6%, 35.4% and 80.0% of inconsistent responders, respectively. The PI value obtained might represent an appropriate scoring system to predict responses in these patients.

Tryptophan hydroxylase 2 gene polymorphisms in Japanese patients with medication overuse headaches.

PURPOSE: We investigated whether tryptophan hydroxylase 2 (TPH2) gene polymorphisms were involved in the aggravation of migraines due to the overuse of medication. METHODS: Forty-seven migraine patients (6 males and 41 females; 36.4 10.3 years) and 22 MOH patients (1 male and 21 females; 39.6 9.9 years) who had migraines participated in this study. The genotypes for the TPH2 gene polymorphisms (rs4565946, rs4570625, and rs4341581) were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. RESULTS: The rs4565946, rs4570625, and rs4341581 genotypes were similarly distributed between migraine patients and MOH patients. CONCLUSION: The results of this study showed no association between tryptophan TPH2 gene polymorphisms and the complication of MOH in patients with migraines.

Association between the G252A Tumor Necrosis Factor-ß Gene Polymorphism and Medication-Overuse Headache.

BACKGROUND AND PURPOSE: Migraine patients are particularly prone to the complication of medication-overuse headache (MOH). Although it has been shown that A allele carriers for the tumor necrosis factor (TNF)-ß gene G252A polymorphism are at high risk of the development of migraine without aura, the relationship between the TNF-ß gene G252A polymorphism and MOH is unknown. We investigated whether the TNF-ß gene G252A polymorphism is involved in the aggravation of migraine by overuse of medications. METHODS: Forty-seven migraine patients (6 males and 41 females; age 36.4±10.3 years, mean±SD) and 22 MOH patients (1 male and 21 females; age 39.6±9.9 years) who had migraine were included in this study. The genotype for the TNF-ß gene G252A polymorphism was determined by polymerase-chain-reaction restriction-fragment-length polymorphism analysis. RESULTS: The distribution of TNF-ß gene G252A genotype frequency differed significantly between migraine and MOH patients (p=0.013). The G/G genotype was carried by 23% of the migraine patients but it was absent in MOH patients. CONCLUSIONS: G/G genotype carriers appear to be less susceptible to the aggravation of migraine by overuse of medications. The G252A TNF-ß gene polymorphism may be one of the factors contributing to the complications of MOH in patients with migraine.

Occurrence and clinicotopographical correlates of brainstem infarction in patients with diabetes mellitus.

BACKGROUND: The goal of the study was to clarify the association between diabetes mellitus (DM) and brainstem infarctions (BSIs) and to investigate the clinicotopographic characteristics of BSIs in patients with diabetes. METHODS: Data were retrospectively reviewed for 1026 consecutive patients admitted to our hospital because of acute cerebral infarctions from January 2004 to August 2010. Acute symptomatic BSIs were explored on radiologic images and classified into multiple infarctions with BSIs, multifocal BSIs, and monofocal BSIs. Isolated BSIs were further classified based on the vertical distribution into midbrain, pontine, and medullary infarctions, and on the horizontal distribution into anterior-dominant, posterior-dominant, and anterior/posterior BSIs. Neurologic symptoms of BSIs and clinical background were compared between DM and non-DM patients. RESULTS: The prevalence of BSIs was 2.6-fold higher (P < .0001) in DM patients. Logistic regression analysis including age, sex, smoking, previous stroke, atrial fibrillation, other cardiac diseases, hypertension, hyperlipidemia, and DM showed that DM was independently associated with BSIs (odds ratio [OR] 2.814; 95% confidence interval [CI] 1.936-4.090; P < .0001). Compared with non-DM patients, DM patients showed more frequent monofocal BSIs (P < .0001) and multifocal BSIs (P = .0296). Monofocal BSIs (n = 114) more frequently involved the pons (P < .0001) and medulla (P = .0212). Anterior-dominant BSIs (P < .0001) were more common in DM patients than in non-DM patients. Symptoms of BSIs included more frequent motor paresis (P = .0180) and less frequent diplopia (P = .0298) in DM patients than in non-DM patients. CONCLUSIONS: DM is important in the development of BSIs, and the associated clinical characteristics include more frequent motor paresis and less frequent diplopia.

[Tuberculous cranial pachymeningitis presenting with long-standing diffuse brain dysfunction].

We report a 59-year-old immunocompetent man presenting with slowly progressive gait unsteadiness, dysarthria, and clumsiness in writing over 6 months. There were bilateral pyramidal signs, pseudobulbar palsy, and attention deficits. Cerebrospinal fluid examination showed mild mononuclear pleocytosis, and magnetic resonance imaging revealed pachymeningeal pattern of contrast enhancement beneath the calvarium and the posterior cranial fossa. Interferon-gamma release assay in whole blood after stimulation by specific tuberculosis antigens was positive and repeat polymerase chain reaction assay detected Mycobacterium tuberculosis genome in the cerebrospinal fluid. After combination therapy with anti-tuberculous agents and corticosteroids, the patient's pachymeningitis regressed. Tuberculous cranial pachymeningitis may present with chronic diffuse brain dysfunction without headache, fever, or cranial nerve dysfunction.

Cerebral microbleeds and dilative remodeling of the basilar artery: a magnetic resonance imaging study.

This study was conducted to examine the relationship between cerebral microbleeds (CMBs), one of the manifestations of small-vessel diseases (SVDs), and basilar artery (BA) dilatation on magnetic resonance imaging (MRI). Clinical information and MRI images were reviewed for 149 outpatients aged 46-90 years, excluding those who had a previous symptomatic cerebrovascular event. CMBs were evaluated on T2∗-weighted MRI, and BA diameters were measured as the maximal width of the flow void on axial T2-weighted MRI to assess dilatation. Patients were divided into 2 groups, with CMBs and without CMBs, and clinical information and BA diameters were compared between the groups. Regression analyses of the data also were performed. The 2 groups had significant differences in mean blood pressure (MBP), low-density lipoprotein (LDL) and uricemic acid levels, and BA diameter. Adjusted logistic regression analysis showed that MBP (odds ratio [OR], 1.059 per 1 mm Hg; 95% confidence interval [CI], 1.019-1.101; P = .0035), LDL (OR, 0.976 per 1 mg/dL; 95% CI, 0.960-0.994; P = .0072), and BA diameter (OR, 3.266 per 1 mm; 95% CI, 1.504-7.103; P = .0028) each had an independent association with the presence of CMB. Adjusted multiple regression analysis showed that only BA diameter (ß coefficient, 0.240; 95% CI, 0.775-3.734; P = .0031) was independently associated with the number of CMBs. Our data indicate that CMB, a manifestation of SVD, shows a strong association with BA dilatation.

[Intramedullary spinal cord metastasis presenting with acute onset longitudinally extensive spinal cord lesion].

A 34-year-old previously healthy man presented with acute transverse lumbar myelopathy and MRI evidence of a longitudinally extensive spinal cord lesion (LESCL) from the upper thoracic cord extending down to the conus medullaris. Gadolinium-DTPA enhancement revealed a clearly demarcated enhanced nodule confined to the level of the 11th thoracic vertebral body (T11), which might have caused longitudinally extensive edema in the spinal cord. Histopathological appearance of adenocarcinoma of the nodule led to the ultimate diagnosis of lung cancer. Intramedullary spinal cord metastasis in a young patient without previously-diagnosed malignancy is a rare disorder, but should be listed up as a cause of LESCL.

Intracranial dilative arteriopathy is associated with chronic kidney disease and small vessel diseases in the elderly.

OBJECTIVE: We sought to determine the responsible factors and clinical significance of dilatation of the internal carotid artery (ICA) and basilar artery (BA). METHODS: ICA and BA diameters were measured using magnetic resonance imaging (MRI) and their association with age, sex, conventional atherosclerotic factors, and estimated glomerular filtration rate (eGFR) were evaluated in 175 outpatients aged 40 to 89 years. The arterial diameters were measured as the maximal width of the flow void on T2-weighted MRI around the brainstem. The relationship between the arterial diameters and deep white matter hyperintensities (DWMHs) on MRI graded from 0 to 3 was also examined. Comparisons were performed between groups with diameters smaller and larger than the mean value for younger (40-69 years) and older (70-89 years) patients, and multiple regression analysis was conducted. RESULTS: Age differed significantly between the larger- and smaller-diameter groups in younger patients, but not in older patients. The larger-diameter group of older patients had a significantly lower eGFR (P = .0002 for ICA, P = .0035 for BA) and a higher DWMH grade (P = .0021 for ICA, P < .0001 for BA) compared to the smaller-diameter group. In multiple regression analysis adjusted for age and sex, a lower eGFR was an independent factor associated with larger arterial diameters (P = .0002 for ICA, P = .0021 for BA). CONCLUSION: Kidney dysfunction is an independent factor that is related to ICA and BA dilatation, which is also associated with DWMHs that reflect small vessel diseases in older patients.

Dilative arterial remodeling of the brain with different effects on the anterior and posterior circulation: an MRI study.

OBJECTIVE: The goal of the study was to investigate factors associated with dilation of the internal carotid artery (ICA) and basilar artery (BA), which reflect the anterior and posterior circulation respectively, and to examine if these arteries are affected differently by specific factors. METHODS: The diameters of ICA and BA were measured using T2-weighted magnetic resonance (MR) images at the level of the brainstem in 304 outpatients, with the maximal width of the flow void taken as the diameter for each artery. The association between the diameters and clinical data including hemoglobin A1c (HbA1c) and estimated glomerular filtration rate (eGFR) was investigated. The same analysis was performed for the BA/ICA ratio. RESULTS: Multiple regression analysis adjusted for confounding factors including gender and age showed that a lower eGFR was independently associated with dilation of both the ICA (beta coefficient -0.148, P=0.0135) and the BA (beta -0.219, P=0.0007). HbA1C was independently associated with a greater BA/ICA ratio (beta -0.183, P=0.0015) but eGFR did not show this association. Diabetes mellitus was significantly more frequent (P=0.0353) in patients with a BA/ICA ratio higher than the mean, compared to those with a lower BA/ICA ratio. CONCLUSION: Kidney dysfunction was shown to be a dilative factor for the anterior and posterior circulation as reflected by the ICA and BA diameters, respectively. The association of the BA/ICA ratio with HbA1c suggests that diabetes mellitus may affect each circulation differently.

Central pontine lesions observed with MRI in four diabetic patients.

We report four diabetic patients with a central pontine lesion on magnetic resonance imaging (MRI). All patients also had hypertension, diabetic neuropathy and nephropathy, and three had chronic hepatitis C. Their neurological symptoms were disproportionately mild compared with the MRI features, which were of high intensity on T2-weighted images, but were less prominent on T1- and diffusion-weighted images. A subclinical pontine lesion was found in two patients who had undergone MRI previously. We consider that diabetes mellitus is an important factor for developing a pontine lesion with or without symptoms, probably in association with hepato-renal problems and hypertension.