Kiyoko Murata

Serological Profiles of Urate, Paraoxonase-1, Ferritin and Lipid in Parkinson’s Disease: Changes Linked to Disease Progression

Background: Oxidative stress plays a role in the pathogenesis of neuronal death. Serum levels of urate or lipid were associated with the incidence of Parkinson’s disease (PD). Objective: We compared urate, paraoxonase-1 (PON1), iron, ferritin and lipid in sera of 119 PD patients and 120 healthy controls matched by age, sex and body mass index. We aimed to elucidate whether those serological data are correlated with disease progression. Results: Mean age (SD) of PD patients was 73.4 (8.7) years. Mean Yahr stage (SD) was 3.2 (0.9). Mean disease duration (SD) was 6.9 (5.1) years. Mean dose of L-DOPA (SD) was 355 (157) mg/day. As compared to controls, serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), urate and PON1 activity were significantly reduced, and serum ferritin levels were significantly increased in male and female PD patients. Serum urate levels and PON1 activities were inversely related, and serum ferritin levels were correlated with Yahr stage and PD duration in men and women. Serum levels of TC and LDL-C were inversely related to Yahr stage or PD duration in female patients. Conclusions: Our studies indicated serological profiles of urate, PON1, ferritin, TC and LDL-C in PD patients. These serological changes were linked to PD progression. Metabolism of lipid, oxidant- and antioxidant-related substances may contribute to the pathogenesis and the progression of PD.

A case of Vernet syndrome with varicella zoster virus infection.

A 40-year-old man was admitted to our department, because of sudden onset of dysphagia, hoarseness, left neck pain and headache. There were no skin lesions. On neurological examination, there were paralysis of the left soft palate and constrictor muscles of the pharynx, weakness of the left sternocleidomastoid and left upper trapezius. In cerebrospinal fluid (CSF) examination, cell count and protein concentration were elevated. Antibody titer to varicella zoster virus (VZV) was elevated in both the serum and CSF. And VZV-DNA was detected by PCR from CSF. Gd enhanced MRI showed the nodular lesion at the left jugular foramen. The diagnosis of Vernets syndrome (VS) associated with VZV infection was made. The patients symptoms were immediately improved with 30 mg of prednisone and 3 g of varaciclovir daily for 14 days. Only a few cases of VS due to VZV have been reported previously. Our case is the first case that detected VZV-DNA in CSF by PCR.

Clinically meaningful treatment responses after switching to galantamine and with addition of memantine in patients with Alzheimer’s disease receiving donepezil

Clinical trials have shown the benefits of acetylcholinesterase inhibitors, such as donepezil and galantamine, and an N-methyl-D-aspartate receptor antagonist, memantine, in patients with Alzheimer’s disease (AD). However, little is known regarding the effects of switching from donepezil 5 mg/day to galantamine 16 or 24 mg/day, or regarding the effects of adding memantine to established therapy compared with increasing the dose of donepezil. This report discusses two studies conducted to evaluate treatment with galantamine and memantine with respect to cognitive benefits and caregiver evaluations in patients with AD receiving donepezil 5 mg/day for more than 6 months. Patients with mild or moderate AD (scores 10–22 on the Mini-Mental State Examination) were enrolled in the Galantamine Switch study and switched to galantamine (maximum doses 16 mg versus 24 mg). Patients with moderate to severe AD (Mini-Mental State Examination scores 3–14) were enrolled in the Donepezil Increase versus Additional Memantine study and either had their donepezil dose increased to 10 mg/day or memantine 20 mg/day added to their existing donepezil dose. Patients received the study treatment for 28 weeks and their Disability Assessment for Dementia, Mental Function Impairment Scale, Cohen-Mansfield Agitation Inventory, and Neuropsychiatric Inventory scores were assessed with assistance from their caregivers. For the Galantamine Switch study after 8 weeks, agitation evaluated by the Cohen-Mansfield Agitation Inventory improved in both the 16 mg and 24 mg groups compared with baseline. However, there were no significant differences between the two galantamine groups. Agitation was also less in patients in the additional memantine group than in the donepezil increase group. In summary, switching to galantamine from donepezil and addition of memantine in patients with AD receiving donepezil were both safe and meaningful treatment options, and particularly efficacious for suppression of agitation.

Relationship between cervical cord 1H-magnetic resonance spectroscopy and clinoco-electromyographic profile in amyotrophic lateral sclerosis

Introduction: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motor neurons, leading to limb paralysis and respiratory failure. Methods: C1–C3 cord 1H‐magnetic resonance spectroscopy (1H‐MRS) was performed in 19 patients with ALS and 20 controls. N‐acetylaspartate (NAA), choline‐containing compounds, creatine plus phosphocreatine (Cr), and myo‐Inositol (m‐Ins) were measured. ALS Functional Rating Scale‐Revised (ALSFRS) and forced vital capacity (FVC) were assessed. The rates of decline were calculated at 6 months before and after 1H‐MRS. Results: NAA/Cr and NAA/m‐Ins were decreased significantly, and m‐Ins/Cr was increased significantly in ALS patients compared with controls. NAA/Cr and NAA/m‐Ins were correlated with ALSFRS and FVC and inversely linked to the decline rates. NAA/Cr, NAA/m‐Ins, and m‐Ins/Cr were altered markedly in 9 patients with denervation and neurogenic changes in both C2 paraspinal and upper limb muscles. Conclusions: These metabolite ratios were associated with disease progression and ongoing denervation in neck and hand muscles. C1–C3 cord 1H‐MRS might reflect anterior horn cell damage causing neck/arm weakness and respiratory dysfunction in ALS patients. Muscle Nerve, 2013

Incomplete Posterior Circle of Willis in Migraineurs With Aura

We read the article by Bugnicourt et al with great interest. Authors show that incomplete posterior circle of Willis (CW) is an independent risk factor of migraine. Our previous study disclosed that proportion of a fetal CW did not differ between migraine and control subjects. We also studied morphological changes of posterior CW in migraineurs, and we would like to compare between ours and the results of Bugnicourt et al. Among 141 migraine patients in our neurology department, 73 migraineurs (31 migraineurs with aura [MA] and 42 without aura [MO]) had brain MR imaging and angiography (MRA) using 3-dimensional time-of-flight sequence. A skilled neuroradiologist reviewed maximum intensity projection (MIP) imaging and source imaging of MRA. Complete posterior CW was defined as the presence of both posterior communicating arteries and both P1 segments of the posterior cerebral arteries. Other patterns of posterior CW were classified to incomplete type. CW morphology was compared between migraineurs and 100 age-matched control subjects (Table). Those participants who had hypertension, diabetes mellitus, dyslipidemia, or oral contraceptives were excluded. As compared with controls, migraineurs and MA sufferers significantly decreased the frequency of complete posterior CW. No significant changes of posterior CW existed between MO sufferers and controls. Posterior CW patterns were not correlated with other clinical aspects of migraineurs, including age, sex, onset age, and duration of migraine (Table). Incomplete posterior CW is associated with MA in our study whereas Bugnicourt et al showed no statistical differences of posterior CW patterns between MA and MO patients. The question arises whether incomplete posterior CW is a causative cofactor of migraine onset or whether these blood flow changes occur after migraine onset.We would like to know how onset age and duration of migraine influence posterior CW shapes in patients of Bugnicourt et al, as authors mention that their patients visit emergency department. Thirty of 47 migraineurs have atypical episodes, and 21 of 24 MA patients have prolonged aura more than 1 hour. Otherwise, our patients did not derive from emergency department. We excluded migraineurs with atypical episode or long visual aura. Posterior configuration of CW was assessed carefully by serial slices of source imaging in our subjects, besides

Preventive Treatment with Lomerizine Increases Cerebral Blood Flows during the Interictal Phase of Migraine

BACKGROUND Changes in regional cerebral blood flow (rCBF) were reported in migraineurs. However, little is known how preventive medications of migraine can influence rCBF. Lomerizine, a calcium channel blocker, has been used for migraine prophylaxis in Japan. We examined rCBF after lomerizine treatment. SUBJECTS AND METHODS Migraine was diagnosed according to the criteria of the International Classification of Headache Disorders, Third Edition beta. Migraine subtype was classified into migraine with aura (MA) and migraine without aura (MO). Lomerizine (10 mg/day, per oral) was administered for 3 months. Headache Impact Test-6 (HIT-6) and blood pressure (BP) were compared at baseline and end point. Brain single photon emission computed tomography using 99mTc-ethyl cysteinate dimer was performed at the interictal period. Brain SPECT data were analyzed according to revised version of 3-dimensional stereotaxic region of interest template. Clinic-radiological variables were analyzed by paired Students t test. RESULTS Ten migraineurs (4 men and 6 women) participated in the present study. Mean age was 54.1 (standard deviation [SD] 10.1) years. Mean duration of migraine was 25.3 (SD 9.8) years. Migraine subtype showed 4 MA and 6 MO patients. Mean score of HIT-6 was 66.3 (SD 11.7). Lomerizine treatment decreased HIT-6 scores significantly (P < .01). BP did not differ significantly after lomerizine treatment. Lomerizine treatment increased rCBF 20% approximately in the frontal, the parietal, the temporal, and the occipital region. CONCLUSIONS The present study indicated a significant increase in interictal rCBF after lomerizine treatment in migraineurs. The upregulation of rCBF could contribute to the antimigraine mechanism of lomerizine.

Domperidone effective in preventing rivastigmine-related gastrointestinal disturbances in patients with Alzheimer's disease.

Objective While acetylcholinesterase inhibitors, such as donepezil, galantamine, and rivastig-mine, are beneficial in treating behavioral symptoms of patients with Alzheimer’s disease (AD), their dose-limiting effects include gastrointestinal disturbances, such as nausea, vomiting, and diarrhea. We aimed to predict the occurrence of these gastrointestinal disturbances with rivastigmine therapy for optimal drug choice and improved compliance. Materials and methods Thirty patients with mild-to-moderate AD (scores 10–22 on the MiniMental State Examination) were administered a rivastigmine 18 mg patch with domperidone 30 mg (RWD) and without domperidone (RWOD; n = 15 each) for 20 weeks. Gastrointestinal disturbances were evaluated using a frequency scale for symptoms of gastroesophageal reflux disease (FSSG), Bristol stool form scale, laboratory data (hemoglobin, albumin, total cholesterol), body weight, and amount of food intake. Results After 12 weeks, FSSG scores were higher in the RWOD group compared to baseline scores; however, no significant differences were noted between the RWD and RWOD groups. We then subdivided each group based on high and low baseline scores; the RWOD high-score (≥4) subgroup showed increased FSSG after 12 weeks compared with the baseline score. In both RWD and RWOD groups, the low-score (≤3) subgroups showed no changes during the dose-escalation phase. Conclusion For AD patients with higher FSSG scores at baseline, domperidone was effective in preventing rivastigmine-related gastrointestinal disturbances.

WOQ-19 improves satisfaction of patients with Parkinson's disease

WCN 2013 No: 1055 Topic: 2—Movement Disorders Freezing of gait in patients with Parkinson disease is a kind of kinetic subcortical apraxia N. Skripkina, O. Levin, T. Makotrova, V. Datieva. Neurology, Russian Medical Academy of Postgraduate Education, Moscow, Russia Background: Freezing of gait is one of the late signs associated with apractic features which may be considered as a subcortical kinetic apraxia. Objective: To investigate the correlation between the frequency and severity of freezing of gait and apractic disorders. Material and methods: We examined 70 patients with PD: 39 men and 31 women (mean age—64.5 ± 8.5 years; mean disease duration —5.1 ± 3.5 years, Hoehn–Yahr stages from 2 to 4, mean UPDRS (part III) score—43.2 ± 11.6). The Gait and Balance examination was carried out with GABS (Jankovic et al., 2001) and FOG-Q (Gurevich et al., 2003) in combination with a comprehensive neuropsychological study including a 72-item apraxia scale. The apraxia scale consists of the oral, arm, leg and trunk apraxia examinations tests, and each of them includes imitation tests and tests on command. Patients were divided into 3 groups according to their FOG-Q score. Results: Freezing of gait was found in 24 (34.3%) of the PD patients. Patients with freezing had advanced stages of PD, a higher UPDRS score and more severe axial symptoms (p b 0.0001) compared with the nonfreezing patients. Patients with a higher FOG-Q score performed worse in the executive and visuospatial cognitive tests and they had a higher leg apraxia score (p b 0.05). Their performance in the apractic tests on command was worse than in the imitation tests. Conclusion: Pathophysiology of FOG in PD is unclear but a subcortical apractic defect should be considered among the possible mechanisms of its origin. doi:10.1016/j.jns.2013.07.433 Abstract—WCN 2013 No: 1058 Topic: 2—Movement Disorders WOQ-19 improves satisfaction of patients with Parkinsons diseaseWCN 2013 No: 1058 Topic: 2—Movement Disorders WOQ-19 improves satisfaction of patients with Parkinsons disease K. Kawabe, T. Takazawa, Y. Yanagihashi, Y. Ishikawa, T. Hirayama, K. Murata, O. Kano, K. Ikeda, Y. Iwasaki. Department of Neurology, Toho University Omori Medical Centre, Tokyo, Japan Objective: To analyse whether a 19-itemWearing-Off (WO) Questionnaire (WOQ-19) improves the sense of satisfaction in patients with Parkinsons disease (PD). Background: It is very difficult to comprehend all complaints of PD patients in outpatient practice. TheWO symptom is particularly underrecognized and associated with patients quality of life and sense of satisfaction.WOQ-19 has 19 simple questions and is designed to detect WO. Methods: This study included PD patients treated with l-dopa. We compared treatment satisfaction using WOQ-19 to that without using it. The sense of satisfaction was measured using a modified questionnaire for patient–physician communication, which is designed by the Office of Pharmaceutical Industry Research and can evaluate patients factors, physicians factors and the patient–physician relationship. If WO is recognized using WOQ-19, then entacapone treatment is initiated. Results: Seven PD patients enrolled for this study (two males and five females; age range, 54–88 years; mean, 75.1 years). Among them, two patients were administered entacapone on the basis of WOQ-19 results. Treatment satisfaction was improved using WOQ19, particularly for the question ‘satisfaction of the patient-centred approach’. Conclusion: WOQ-19 may improve the sense of satisfaction in PD patients and be useful for patient education. doi:10.1016/j.jns.2013.07.434 Abstract—WCN 2013 No: 1006 Topic: 2—Movement Disorders Circadian blood pressure and heart rate variations in de novo Parkinson diseaseWCN 2013 No: 1006 Topic: 2—Movement Disorders Circadian blood pressure and heart rate variations in de novo Parkinson disease Y.-S. Oh, S.B. Lee, J.-S. Kim, K.-S. Lee. Department of Neurology, The Catholic University of Korea, Seoul, Republic of Korea Background: Altered blood pressure (BP) regulation and heart rate variations are characteristic findings of cardiovascular Dysautonomia in patients with Parkinsons disease (PD). However, these variations had not been adequately investigated. Objective: The aim of this study was to investigate the patterns and characteristics of 24-hour BP variations and heart rate variations in patients with PD. Patients and methods: Case–control comparisons of 142 consecutive newly diagnosed patients with PD and 57 age-matched controls were performed. All cases underwent clinical assessments and 24-hour ambulatory BP monitoring. The associations between BP and heart rate variations and parkinsonian motor symptoms were investigated. Results: There were significant differences in the distribution of nondipping, the percent of nocturnal BP decrease, the standard deviation of heart rate and nocturnal decrease of heart rate between patients with PD and controls. However, these abnormal diurnal BP and heart rate patterns were not associated with parkinsonian motor symptoms and not related to age, gender, or disease duration. Conclusion: In conclusion, this result suggests that non-dipping and decreased nocturnal heart rate may be one of the cardiovascular autonomic dysfunctions in patients with PD, irrespective of age, disease severity, or motor symptom phenotype. doi:10.1016/j.jns.2013.07.435 Abstract—WCN 2013 No: 1027 Topic: 2—Movement Disorders Motor sequence learning and motor adaptation in primary cervical dystoniaWCN 2013 No: 1027 Topic: 2—Movement Disorders Motor sequence learning and motor adaptation in primary cervical dystonia P. Katschnig-Winter, P. Schwingenschuh, M. Davare, A. Sadnicka, R. Schmidt, J.C. Rothwell, K.P. Bhatia, M.J. Edwards. Department of Neurology, Medical University of Graz, Graz, Austria; Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, UK Background: Motor sequence learning and motor adaptation rely on overlapping circuits predominantly involving the basal ganglia and cerebellum. Given the importance of these brain regions to the pathophysiology of primary dystonia, and the previous finding of abnormal motor sequence learning in DYT1 gene carriers, we explored motor sequence learning andmotor adaptation in patientswith primary cervical dystonia. Methods: We recruited 12 patients with cervical dystonia and 11 healthy controls matched for age. Subjects used a joystick to move a cursor froma central starting point to radial targets as fast and accurately as possible. Using this device, we recorded baseline motor performance, motor sequence learning and a visuomotor adaptation task. Abstracts / Journal of the Neurological Sciences 333 (2013) e109–e151 e130