Hirotaka Katoh

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.

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.

Association between the G252A Tumor Necrosis Factor-β 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)-β gene G252A polymorphism are at high risk of the development of migraine without aura, the relationship between the TNF-β gene G252A polymorphism and MOH is unknown. We investigated whether the TNF-β 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-β gene G252A polymorphism was determined by polymerase-chain-reaction restriction-fragment-length polymorphism analysis. Results The distribution of TNF-β 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-β gene polymorphism may be one of the factors contributing to the complications of MOH in patients with migraine.

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.

A Cyclooxygenase 2 Gene Polymorphism is a Risk Factor for the Complication of Medication Overuse Headaches in Patients with Migraines

We determined whether cyclooxygenase-2 (COX-2) gene polymorphisms were involved in the aggravation of migraines due to the overuse of medication. Polymorphisms in the COX-2 (rs20417, rs689466) gene were examined. Forty-seven patients with migraine (6 males and 41 females; 5 with migraines with aura (MA), 36 with migraines without aura (MO), 6 with MA + MO; 1 with MA and 21 with MO; 36.4 ± 10.3 years) and 22 patients with medication overuse headache (MOH) (1 male and 21 females; 39.6 ± 9.9 years) who had migraines participated in this study. The genotypes of each polymorphism were analyzed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) methods. No significant differences were observed in the genotypic distributions of rs20417 (C/C + G/C vs. G/G, p=0.220) between migraine patients and MOH patients. The frequencies of the rs689466 G/G genotype were significantly higher in patients with MOH than in patients with migraines (G/G vs. A/A+A/G, p=0.008). Furthermore, the frequencies of the rs689466 G/G genotype were significantly higher in patients with MOH who had migraines without aura (MO) than in patients with MO (G/G vs. A/A+A/G, p=0.001). The results of this study showed that the COX-2 polymorphism (rs689466) was independently related with the complication of MOH in patients with MO.

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.

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.

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 (β 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.

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.

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 Parkinsons 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 Parkinsons 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 Spearmans 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.