Hirono Ito

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.

Reversible Cerebellar Lesions Induced by Metronidazole Therapy for Helicobacter Pylori

Metronidazole is widely used for chronic or refractory infection and has recently also been used for the treatment of Helicobacter pylori. The authors report the case of a Japanese patient presenting with reversible cerebellar lesions induced by prolonged administration of metronidazole for treatment of H pylori with magnetic resonance imaging findings. Although rare, prolonged and high‐dose administration of metronidazole may induce cerebellar lesions. Increased awareness of this phenomenon is important, as these lesions are reversible with discontinuation of this drug.

Beneficial effect of pramipexole for motor function and depression in Parkinson's disease.

We examined whether pramipexole (PPX) can influence depressive scale in normal and mild depressive parkinsonian patients. In an open study of PPX as an add-on to L-dopa therapy or single administration, 36 nondemented outpatients with Parkinson’s disease (PD) were entered first. All were in the stage II or III of Hoehn and Yahr scale (H&Y). PPX were started at 0.125 mg/day and daily doses were increased to 1.5 mg/day. At 3 months after PPX treatment, patients were re-evaluated. Hamilton Depression Rating Scale (HAM-D), Unified Parkinson’s Disease Rating Scale III, H&Y stage, and freezing of gait questionnaire were compared in patients before and after PPX treatment. These scores were significantly improved after PPX administration. There were no correlations between HAM-D and those motor functions. We suggest that PPX treatment has antidepressant effects in depressive PD patients and also ameliorates HAM-D score in nondepressive PD patients in addition to motor function.

Different Variables Between Patients with Left and Right Hemispheric Ischemic Stroke

We studied whether some variables differ between patients with right and left hemispheric ischemic stroke. A total of 383 cases were obtained from our department-based records between April 2003 and March 2006. Age distribution, sex, intracranial localization of anterior (carotid artery distribution) or posterior (vertebrobasilar artery distribution) circulation, mechanism subtypes according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria, cerebrovascular risk factors, and time from clinical onset to admission were analyzed between the right and the left hemispheric ischemic stroke groups. In all, 200 patients had left hemispheric stroke and 183 patients had right hemispheric stroke. Age, sex, vascular risk profile, stroke subtypes, and mechanism subtypes were not statistically different between patients with right- and left-sided ischemic stroke. Time interval from neurologic onset to admission within 6 hours was significantly associated with left hemispheric cerebral infarction. Furthermore, patients with left-sided small-vessel occlusion visited our hospital earlier, up to 6 hours as compared with patients with right-sided small-vessel occlusion (P < .05). We suppose that patients with right-sided small-vessel occlusion may take time to be aware of neurologic deficits because of nondominant language or hand function. Our data indicate that different medical attention exists between patients with right and left hemispheric ischemic stroke. We should pay more attention to the difficulty in recognizing the neurologic deficits in patients with right hemisphere ischemic stroke, so that those patients delay hospital visit.

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.

Limb-onset amyotrophic lateral sclerosis patients visiting orthopedist show a longer time-to-diagnosis since symptom onset

BackgroundThere have been several reports concerning the survival time after symptom onset in patients with amyotrophic lateral sclerosis (ALS). However, little is known about how the choice of physician (i.e., general practitioner, neurologist, etc.) may affect the time it takes for a diagnosis of ALS to be made.MethodsWe conducted a retrospective study, covering a 20-year period, comparing the type of physician first consulted by an ALS patient at the time of initial symptoms and the amount of time that elapsed to the final diagnosis of ALS. A total of 202 patients were diagnosed and stratified according to the onset of ALS symptoms (bulbar onset [BO] and limb onset [LO]). We noted the type of physician first seen by the patient. The diagnostic interval was calculated as the time between onset of symptoms and the final diagnosis of ALS.ResultsA total of 202 ALS patients were examined. Clinical BO and LO was observed in 78 (36.6%) and in 124 (61.4%) of these patients, respectively. The type of physician examining these patients at the first symptoms of disease was as follows (BO and LO): neurologist (38.5% and 25.8%), general practitioner (14.1% and 35.5%), orthopedist (12.8% and 35.5%), otolaryngologist (15.4% and 0%), and neurosurgeon (14.1% and 3.2%). Mean diagnostic interval (standard deviation) for patients with either set of symptoms was 13.1 (6.5) months; the diagnostic interval of patients with BO and LO was 9.2 (4.5) and 15.2 (7.7) months, respectively. ALS diagnosis in LO patients was delayed by more than 10 months when the patient first consulted an orthopedist rather than a neurologist.ConclusionMore than 50% of the ALS patients included in this study did not visit a neurologist at the first symptoms of disease onset. The diagnosis of ALS was prolonged in LO patients visiting an orthopedist. We speculate that this increase in the diagnostic interval in LO patients visiting an orthopedist was due to a lack of bulbar symptoms in the early stages of this disease.

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

Brain images in ornithine transcarbamylase deficiency

Keywords: brain; circulatory disturbance; lesion topography; neuroimages; rnithine transcarbamylase deficiency

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.