Parkinson Disease: Yokochi F

Miziuno Y, Okuma Y, Kikuchi S, Kuno S, Hashimoto T, Hasegawa K, Mano Y, Miwa H, Murata M, Yamamoto M, Yokochi F, Okiyama R, Kanazawa A, Shinpo K, Chuma T, Higashi T, Maruyama T, Mizuta E, Yamazaki S, Anonymous00188. · Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan · Rinsho Shinkeigaku. · Pubmed #12708433 No free full text.

This publication has no abstract.

Yokochi F. · Department of Neurology, Tokyo Metropolitan Neurological Hospital, 2-6-1 Musashidai, Fuchu-shi, Tokyo 183-0042, Japan. · Brain Nerve. · Pubmed #19378817 No free full text.

Abstract: Deep brain stimulation (DBS) has proved highly effective in the treatment for Parkinson's disease and dystonia. Presently, many types of dopamine agonists, monoamine oxidase B (MAOB) inhibitors, catechol-O-methyltransferase (COMT) inhibitor or other antiparkinsonian drugs are being developed. However, it is still very difficult to medically treat motor complications associated with levodopa therapy. Surgical intervention using DBS was possible to stimulate the subthalamic nucleus as the treatment of Parkinson's disease. Stimulation of the subthalamic nucleus improves the cardinal parkinsonian symptoms and motor complication associated with levodopa treatment. DBS is a reversible treatment and the original status could be observed by turning off the stimulation. This procedure enables the observation of clinical outcomes or brain mechanisms under both the conditions of turned on and turned off stimulations. On the other hand, dystonia is heterogeneous and refractory and hence, it has been difficult to medically treat it. Since there was no effective treatment available for patients with generalized dystonia, these patients became disabled. However, recently, bilateral pallidal DBS has been shown to markedly improve the conditions of patients with generalized dystonia, and it has proven to be a reliable treatment. There are two characteristic clinical effects of pallidal DBS on dystonia. It improves primary hereditary generalized dystonia, particularly DYT 1, more prominently than secondary dystonia and its beneficial effects are observed over a period of time course. The beneficial effects of pallidal DBS in patients with dystonia are not immediate but progress over weeks to months. The brain mechanism underlying the improvement of pallidal DBS in dystonia has been unclear. Many studies on DBS in Parkinson's disease and dystonia have been carried out to elucidate the clinical outcomes and/or the underlying neurophysiological mechanisms. In this review, the clinical outcomes of DBS for Parkinson's disease and dystonia will be focused on.

Yokochi F. · Department of Neurology, Tokyo Metropolitan Neurological Hospital, 2-1-16 Musashidai, Fuchu, Tokyo, 184-0032, Japan. · J Neurol. · Pubmed #17131222 No free full text.

Abstract: Various types of abnormal posture are observed in Parkinson's disease (PD). Lateral flexion is very common and frequent among them. The clinical characteristics of lateral flexion in PD vary and are classified into two types, the chronic and subchronic types. The chronic type of lateral flexion in PD appears subclinically and worsens, which is related to the laterality of parkinsonian symptoms and the progression of the disease. The subchronic type of lateral flexion in PD develops subacutely and worsens rapidly in several months. An atypical and rare type of tonic truncal dystonia, Pisa syndrome, may be induced following the intake of neuroleptics. The clinical features of the subchronic type of lateral flexion in PD are similar to those of Pisa syndrome. Differences between lateral flexion in PD and Pisa syndrome are described.

Shichi T, Okiyama R, Yokochi F, Taniguchi M, Takahashi H, Hamada I. · Department of Neurology, Tokyo Metropolitan Neurological Hospital, 2-6-1, Musashidai, Fuchu, Tokyo 183-0042, Japan. · No To Shinkei. · Pubmed #16026045 No free full text.

Abstract: According to evidenced-based criteria, surgical treatment with subthalamic stimulation is indicated for advanced Parkinson's disease with severe motor complications. Currently, the treatment is indicated for patients in whom medical treatment has failed even if the patient is still in an early stage. This study investigated the efficacy and safety of unilateral subthalamic stimulation for patients with early-stage Parkinson's disease. We evaluated the Unified Parkinson's Disease Rating Scale (UPDRS) and the Schwab England ADL score before and 6 months after this treatment in 6 patients with early-stage Parkinson's disease demonstrating predominantly unilateral parkinsonian symptoms. We implanted a stimulation electrode (model 3387 or 3389) unilaterally on the side showing dominate symptoms, using both MRI and electrophysiological guidance. Six months after the beginning of stimulation, the UPDRS motor score without medication was improved by 64% and the Schwab England ADL score was improved by 23%. There were no adverse events except for asymptomatic intra-ventricular hemorrhage in one patient. Unilateral subthalamic stimulation is a useful treatment for patients with early-stage Parkinson's disease showing predominantly unilateral parkinsonian symptoms. However, long-term results of subthalamic stimulation for early-stage patients remain unclear.

Yokochi F. · Department of Neurology, Tokyo Metropolitan Neurological Hospital. · Nippon Rinsho. · Pubmed #15462385 No free full text.

Abstract: The aim of stereotactic operation for Parkinson's disease is to improve or keep daily activity or quality of life by ablation or improvement of some parkinsonian symptoms. All of parkinsonian symptoms are not improved by stereotactic operation and classify roughly into three categories. The symptoms which are definitely improved are tremor, rigidity, L-dopa-induced dyskinesia, bradykinesia (secondary bradykinesia caused by rigidity) and wearing off phenomenon. Freezing gait, postural instability or postural abnormality is improved in some patients, but not always. Disturbance of speech or swallowing, L-dopa non-responsive akinesia, psychiatric symptoms or autonomic disturbances are not expected to be improved. Before stereotactic operation symptoms which cause disabilities of patients should be carefully examined. Aim of stereotactic operation should make clear and not ambiguous.

Yokochi F. · Department of Neurology, Tokyo Metropolitan Neurological Hospital. · Nippon Rinsho. · Pubmed #11068452 No free full text.

Abstract: Tremor is the most common initial symptom and one of the cardinal features of Parkinson's disease. Mild tremor causes only minimal disability, but severe tremor causes more significant disability and distress for the patient than rigidity and/or bradykinesia. Anticholinergic agents, levodopa/DCI and dopamine agonists are most common and beneficial in parkinsonian tremor, but efficacies of these medications are variable among patients. Rigidity and bradykinesia are more responsive to levodopa/DCI therapy than tremor. Clozapine is an atypical neuroleptic agent, not on the market in Japan, and has been reported to decrease or ameliorate parkinsonian tremor through the studies of open label and double blind crossover as a new drug for parkinsonian tremor.

Arai N, Yokochi F, Ohnishi T, Momose T, Okiyama R, Taniguchi M, Takahashi H, Matsuda H, Ugawa Y. · Dept. of Neurology, Division of Neuroscience, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. · J Neurol. · Pubmed #18563467 No free full text.

Abstract: Bilateral symptoms and signs of Parkinson's disease (PD) are often improved by unilateral subthalamic nucleus deep brain stimulation (STN-DBS). However, the mechanism for such bilateral effects is unknown. This study was intended to examine effects of unilateral STN-DBS using positron emission computed tomography (PET) and to elucidate mechanisms for bilateral improvement achieved by unilateral stimulation.We conducted (18)F-fluorodeoxyglucose ((18)FDG) and (18)F-fluorodopa ((18)F-DOPA ) PET scans in PD patients whose bilateral limb symptoms and axial symptoms were improved by unilateral DBS. Two scans were performed in each PET study: when DBS was on and off. We compared those images using statistic parametric mapping (SPM) 99.The significant clinical improvement obtained by unilateral DBS was shown as improvements in bilateral motor limb, axial, and gait subscores of the Unified PD Rating Scale (UPDRS). Moreover, (18)FDG PET revealed significant metabolic increases in the ipsilateral ventrolateral thalamic areas and metabolic decrease at the contralateral globus pallidus interna (GPi). In contrast, (18)F-DOPA PET showed no significant differences between DBS on and off.Ipsilateral thalamic activation might induce ipsilateral motor cortical activation, which explains the improvement of contralateral limb symptoms. Furthermore, deactivation of the contralateral GPi might disinhibit the thalamus and contralateral motor cortex, which explains reduction of ipsilateral limb symptoms. These results suggest the mechanisms for bilateral improvement achieved by unilateral DBS.

Yokochi F. · No affiliation provided · No To Shinkei. · Pubmed #11968820 No free full text.

This publication has no abstract.

Terao T, Yokochi F, Taniguchi M, Kawasaki T, Okiyama R, Hamada I, Nishikawa N, Izawa N, Shin M, Kumada S, Takahashi H. · Department of Neurosurgery, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan. · Acta Neurochir (Wien). · Pubmed #18615234 No free full text.

Abstract: A 64-year-old woman with Parkinson is disease had a severe resting tremor that was not completely relieved by right-sided gamma knife thalamotomy (GKT). We performed bilateral staged thalamic deep brain stimulation (DBS) and compared the right and left ventral intermediate nucleus (Vim) of the thalamus including the frequency of single units recorded with microelectrodes, and also the somatotopical distribution of kinaesthetic cells (Ki). The average frequency of units for the presumed left Vim exceeded that of the right (22.6 +/- 19.2 Hz vs. 14.3 +/- 8.8 Hz). Regarding the somatotopic distribution of Ki, the receptive field for the leg, which is usually situated in the dorsolateral Vim, was more widely scattered in the right Vim than the non-lesioned left side. Our findings raise the possibility that the specific properties of the neurons changed due to partial coagulation by GKT within both the coagulated and the surrounding thalamic lesions.

Kumazawa R, Tomiyama H, Li Y, Imamichi Y, Funayama M, Yoshino H, Yokochi F, Fukusako T, Takehisa Y, Kashihara K, Kondo T, Elibol B, Bostantjopoulou S, Toda T, Takahashi H, Yoshii F, Mizuno Y, Hattori N. · Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan. · Arch Neurol. · Pubmed #18541801 links to  free full text

Abstract: OBJECTIVES: To determine the frequency, distribution, and clinical features of Parkinson disease (PD) with PINK1 mutations. DESIGN: Retrospective clinical and genetic review. SETTING: University hospital. PATIENTS: We performed extensive mutation analyses of PINK1 in 414 PD patients negative for parkin mutations (mean [SD] age at onset, 42.8 [14.3] years), including 391 unrelated patients (190 patients with sporadic PD and 201 probands of patients with familial PD) from 13 countries. RESULTS: We found 10 patients with PD from 9 families with PINK1 mutations and identified 7 novel mutations (2 homozygous mutations [p.D297MfsX22 and p.W437R] and 5 single heterozygous mutations [p.A78V, p.P196QfsX25, p.M342V, p.W437R, and p.N542S]). No compound heterozygous mutations were found. The frequency of homozygous mutations was 4.26% (2 of 47) in families with autosomal recessive PD and 0.53% (1 of 190) in patients with sporadic PD. The frequency of heterozygous mutations was 1.89% (2 of 106) in families with potential autosomal dominant PD and 1.05% (2 of 190) in patients with sporadic PD. The mean (SD) age at onset in patients with single heterozygous mutations (53.6 [11.1] years; range, 39-69 years) was higher than that in patients with homozygous mutations (34.0 [20.3] years; range, 10-55 years). Myocardial iodine-123 metaiodobenzylguanidine uptake was low in patients with heterozygous mutations but not in those with homozygous mutations. CONCLUSIONS: Our results suggest that homozygous PINK1 mutations tend to be diagnosed as the early-onset autosomal recessive form of PD. Single heterozygous mutations may contribute to the development of sporadic PD and also could be an additional genetic predisposition for developing familial PD. The reduced myocardial iodine-123 metaiodobenzylguanidine uptake observed in patients with single heterozygous PINK1 mutations is similar to that seen in patients with sporadic PD.

Waragai M, Nakai M, Wei J, Fujita M, Mizuno H, Ho G, Masliah E, Akatsu H, Yokochi F, Hashimoto M. · Laboratory for Chemistry and Metabolism, Tokyo Metropolitan Institute for Neuroscience, Tokyo 183-8526, Japan. · Neurosci Lett. · Pubmed #17720313 No free full text.

Abstract: DJ-1 is a multifunctional protein whose loss of function by gene mutations may play a causative role for familial Parkinson's disease (PD). A recent study has shown that the expression of this molecule is upregulated in both brains and cerebrospinal fluids (CSF) in various neurological disorders, including sporadic PD, Alzheimer's disease (AD) and stroke, raising a possibility that DJ-1 could be a potential biomarker for these diseases. In this context, the main objective of the present study was to determine if DJ-1 was increased in the plasma of PD patients. For this purpose, blood plasma samples collected from sporadic PD patients, dementia with Lewy bodies (DLB) and healthy age-matched controls were analyzed by immunoblotting and enzyme-linked immunosorbent assay. The results showed that the plasma DJ-1 levels in PD (n=104) were higher than those in control (n=80) (p<0.05). Moreover, the plasma DJ-1 levels in the advanced stage of PD (n=52, Yahr III-IV) were higher than those in the early stage of PD (n=52, Yahr I-II) (p<0.05), demonstrating that the plasma DJ-1 was correlated with the disease severity in PD. Plasma DJ-1 levels were also significantly higher in DLB (n=30) compared with both controls and early stage of PD (p<0.01). Taken together, these results suggest that the plasma DJ-1 could be a useful biomarker for the evaluation of the disease severity in PD and possibly in other Lewy body diseases.

Taniguchi M, Takahashi H, Kawasaki T, Terao T, Iwamuro H, Yokochi F, Okiyama R, Shichi T, Hamada I. · Department of Neurosurgery, Tokyo Metropolitan Neurological Hospital, Fuchu, Japan. · No Shinkei Geka. · Pubmed #15352636 No free full text.

This publication has no abstract.

Kondo T, Takubo H, Yokochi F, Okuma Y, Mizuno Y. · Department of Neurology, Juntendo University School of Medicine, Japan. · No To Shinkei. · Pubmed #12599519 No free full text.

Abstract: We herein report on the outcome of 5 year-treatment of Parkinson's disease patients with selegiline hydrochloride. The subjects participated in this study were 10 patients whose treatment had been maintained consecutively by administration of this agent even after completion of the Phase II trial (all cases under adjunct therapy with L-DOPA/DCI). The daily dose of selegiline hydrochloride was 6.6 +/- 2.5 mg in average at the end and/or termination of the study. As for L-DOPA, its daily dose decreased from 410 +/- 160 mg to 365 +/- 133 mg at the 6th month, but the dose reduction level after 9 months was not determinable due to an increase in dropouts. Regarding alteration in the scores for individual symptoms, improvement in wearing-off symptom was pronounced during the treatment period of 3 to 51 months. The Global Improvement Rate and Usefulness Rate remained stable during the period of 18 to 30 months treatment although these rates declined after 36 months probably because of exacerbation in disease conditions. This study may assure tolerability of selegiline hydrochloride in a long-term treatment of Parkinson's disease patients.

Okiyama R, Yokochi F, Taniguchi M, Takahashi H, Hasegawa N, Hamada I. · Department of Neurology, Tokyo Metropolitan Neurological Hospital, 2-6-1 Musashidai, Fuchu-shi, Tokyo 183-0042, Japan. · No To Shinkei. · Pubmed #12476577 No free full text.

Abstract: Chronic stimulation of subthalamus nucleus (STN) is effective in treating severe motor fluctuation and levodopa induced dyskinesia as well as parkinsonian motor symptoms. The improvement of peak-dose/diphasic dyskinesias of STN stimulation is considered to be due to the decrease in the daily dosage of antiparkinsonian drugs. However one report pointed out that STN stimulation improved directly levodopa induced dyskinesia. Moreover the timing of the improvement for levodopa induced dyskinesia is not yet obvious. In the present study, we have assessed variance in the latency of improvement of levodopa induced dyskinesia due to STN stimulation. In addition, we would clarify an issue which cite of STN stimulation improved parkinsonian symptoms and motor complication (motor dyskinesias and motor fluctuation). We have studied seven patients diagnosed with advanced idiopathic Parkinson's disease with motor fluctuations and levodopa induced dyskinesias. Before and after the implantation of stimulating electrode, patients were assessed by the Unified Parkinson's Disease Rating Scale and % 'OFF' motor state. The dosage of the antiparkinsonian medication was not modified for one month prior to implantation. Following implantation, dosage of the medication and strength of stimulation was adjusted, if necessary. Symptoms of motor fluctuation and dyskinesia improved in all patients six month after surgery. The mean off-time duration and dyskinesia disability improved compared with presurgical conditions. However, the time course of the improvement of dyskinesias was not the same among patients. Contralateral limb dyskinesias in three patients improved immediately after the stimulation without modification of medication. In contrast, the stimulation worsened contralateral limb dyskinesias in other three patients immediately following the surgery. In two of the three patients, dyskinesias gradually improved within one month after surgery without reducing the dosage of medication. Dyskinesias of the other patient improved following a reduction in the dosage of medication one month after the surgery. Improvement of parkinsonian symptoms of the patients with longer latency of stimulation effect for dyskinesias was better than that of the patients with shorter latency. Stimulation cite of the former group appeared to locate more central than that of the latter group. Latency and strength of the effects of STN stimulation are variable.

Yokochi F, Okiyama R, Taniguchi M, Takahashi H, Hasegawa N, Hamada I. · Department of Neurology, Tokyo Metropolitan Neurological Hospital, Fucyu, Japan. · J Neurol. · Pubmed #11697686 No free full text.

Abstract: The relationships between lesion location and clinical outcome following posteroventral pallidotomy for Parkinson's disease were studied. Forty-four patients were operated forty-six times and studied with neurological and psychological examinations before and after pallidotomy. Lesion location was confirmed using films with a coagulation electrode which were X-rayed during the operation. Changes of intelligence were observed in the patients with anteromedial lesions. Wearing-off phenomenon in four patients and dopa-induced dyskinesia in three patients were not improved following pallidotomy in twenty patients with severe wearing-off and dyskinesia. Lesions in the patients with no improvement of wearing off were located more lateral and those in the patients with sustained severe dyskinesia were located more dorsal in the internal part of the globus pallidus. It may be concluded that clinical outcome is related to lesion location.