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Biomedical subjects

Kazuko Hasegawa

Publications and source records attributed to Kazuko Hasegawa.

15 recordsLinked to original sources
PubMed2007

Zonisamide improves motor function in Parkinson disease: a randomized, double-blind study.

OBJECTIVE: To evaluate the efficacy, safety and tolerability of daily doses of 25, 50, and 100 mg of zonisamide (ZNS) administered as adjunctive treatment in patients with Parkinson disease (PD). METHODS: We conducted a multicenter, randomized, double-blind, parallel-treatment, placebo-controlled study in Japan. Patients with PD who showed insufficient response to levodopa treatment were given placebo for 2 weeks and then treated for 12 weeks with 25, 50, or 100 mg/day of ZNS or placebo, in addition to levodopa, followed by a 2-week dose-reduction period. The primary endpoint was change from baseline in the total score of the Unified Parkinson's Disease Rating Scale (UPDRS) Part III at the final assessment point. Secondary endpoints included changes from baseline in total daily "off" time; total scores of UPDRS Parts I, II, and IV; and Modified Hoehn and Yahr Scale score. Safety analysis was based on the incidence of adverse events. RESULTS: There was significant improvement in the primary endpoint in the 25-mg and 50-mg groups vs placebo. The duration of "off" time was significantly reduced in the 50-mg and 100-mg groups vs placebo. Dyskinesia was not increased in ZNS groups. The incidence of adverse effects was similar between the 25-mg, 50-mg, and placebo groups but higher in the 100-mg group. CONCLUSIONS: Zonisamide is safe, effective and well tolerated at 25 to 100 mg/day as an adjunctive treatment in patients with Parkinson disease.

Adult↗
PubMed2006

Pathological heterogeneity of the precentral gyrus in Pick's disease: a study of 16 autopsy cases.

This report concerns the upper motor neuron involvement in 16 autopsy cases of Pick disease with Pick bodies, including 11 cases reported by us previously. Prominent, circumscribed atrophy of the precentral gyrus, conspicuously in the lower portion, was noted in one case. Loss of Betz cells and astrocytosis of the precentral gyrus layer V were encountered in 15 cases (94%) and eight cases (50%), respectively. Appearance of Pick bodies and ballooned neurons in the precentral gyrus layer V was confirmed in seven cases (44%). Degeneration of the pyramidal tract in the medulla oblongata was noted in all 15 cases in which this structure was examined. Pyramidal signs were observed in four (67%) of the six cases that were neurologically sufficiently examined: hyperreflexia in four cases (67%), spasticity in one case (17%). Babinski sign was not encountered in any of the six cases. In all four cases having pyramidal signs, degeneration of the pyramidal tract was observed. In contrast, two cases having degeneration of the pyramidal tract did not develop pyramidal signs. In Pick's disease with Pick bodies, obvious involvement of the precentral gyrus and pyramidal tract was not previously noticed. Furthermore, we suggest that pyramidal signs in Pick's disease with Pick bodies have been underestimated.

Aged↗
PubMed2006

Novel mutations in the guanosine triphosphate cyclohydrolase 1 gene associated with DYT5 dystonia.

OBJECTIVES: To better understand the relationship between mutation of the guanosine triphosphate cyclohydrolase I (GCH1) gene and the etiology of DYT5 dystonia and to accumulate data on the mutation in the Japanese population for genetic diagnosis of the disease. SETTING: Japanese population. Patients Eight Japanese patients with suspected DYT5 dystonia were analyzed. Intervention Direct genomic sequencing of 6 exons of GCH1 was performed. MAIN OUTCOME MEASURES: For patients who did not exhibit any abnormality in the sequence analysis, the possibility of exon deletions was examined. In cases for which cerebrospinal fluid was available, the concentrations of neopterin and biopterin were measured as an index of GCH1 enzyme activity. RESULTS: In 2 patients, we found a new T106I mutation in exon 1 of GCH1, a position involved in the helix-turn-helix structure of the enzyme. In the third patient, we found a new mutation (a 15-base pair nucleotide deletion) in exon 5 that may cause a frameshift involving the active site. In the fourth patient, we detected a known nucleotide G>A substitution in the splice site of intron 5, which has been reported to produce exon 5-skipped messenger RNA. The concentrations of both neopterin and biopterin in the cerebrospinal fluid of the third and fourth patients were markedly lower than the normal range, indicating that the GCH1 enzyme was functionally abnormal in these mutations. Gene dosage analysis showed that the fifth patient had a deletion of both exon 3 and exon 4, whereas the sixth patient had a deletion of exon 3. CONCLUSIONS: We found several novel, as well as known, GCH1 mutations in Japanese patients with DYT5 dystonia. In some of them, the GCH1 enzyme activity was proved to be impaired.

Adolescent↗
PubMed2006

Clinicogenetic study of mutations in LRRK2 exon 41 in Parkinson's disease patients from 18 countries.

We screened LRRK2 mutations in exon 41 in 904 parkin-negative Parkinson's disease (PD) patients (868 probands) from 18 countries across 5 continents. We found three heterozygous missense (novel I2012T, G2019S, and I2020T) mutations in LRRK2 exon 41. We identified 11 (1.3%) among 868 PD probands, including 2 sporadic cases and 8 (6.2%) of 130 autosomal dominant PD families. The LRRK2 mutations in exon 41 exhibited relatively common and worldwide distribution. Among the three mutations in exon 41, it has been reported that Caucasian patients with G2019S mutation have a single-founder effect. In the present study, Japanese patients with G2019S were unlikely to have a single founder from the Caucasian patients. In contrast, I2020T mutation has a single-founder effect in Japanese patients. Clinically, patients with LRRK2 mutations had typical idiopathic PD. Notably, several patients developed dementia and psychosis, and one with I2020T had low cardiac (123)I-metaiodobenzylguanidine (MIBG) heart/mediastinum ratio, although the ratio was not low in other patients with I2020T or G2019S. Clinical phenotypes including psychosis, dementia, and MIBG ratios are also heterogeneous, similar to neuropathology, in PD associated with LRRK2 mutations.

Antiparkinson Agents↗
PubMed2006

[A survey about the accessibility to botulinum toxin therapy for dystonia].

We investigated the accessibility of the therapy with botulinum toxin for blepharospasm or cervical dystonia in Japan. Based on the administration sheet for Botox sent to the Japan Branch of Allergan Co. Ltd. (Tokyo, Japan), the survey was performed about how many institutions treated 3 or more patients with botulinum toxin in each of February, 2003, and February, 2005, for each disease entity. Among 369 secondary medical zones covering all the areas of Japan, 73 zones had 103 institutions that met our criteria for blepharospasm in 2003, and the number slightly increased to 77 zones and 109 institutions in 2005. For cervical dystonia, 25 zones had 32 institutions in 2003, and the number increased to 36 zones and 48 institutions in 2005. Although medical zones with larger population tended to have more institutions, there was great inequality in the accessibility of patients among medical zones. Besides, the number of institutions was thought to be quite insufficient especially for cervical dystonia in most areas of Japan. Larger number of institutions in any region of Japan should be preferably able to treat focal dystonia with botulinum toxin in order to improve patients' accessibility, because this safe and effective therapy can be now regarded as the first line for both blepharospasm and cervical dystonia.

Anti-Dyskinesia Agents↗
PubMed2005

An LRRK2 mutation as a cause for the parkinsonism in the original PARK8 family.

We detected a missense mutation in the kinase domain of the LRRK2 gene in members with autosomal dominant Parkinson's disease of the Japanese family (the Sagamihara family) who served as the basis for the original defining of the PARK8 Parkinson's disease locus. The results of the Sagamihara family, in combination with the unique pathological features characterized by pure nigral degeneration without Lewy bodies, provided us with valuable information for elucidating the protein structure-pathogenesis relationship for the gene product of LRRK2. We did not detect this mutation or other known mutations of the LRRK2 gene in Japanese patients with sporadic Parkinson's disease.

Amino Acid Sequence↗
PubMed2005

[Therapy of dystonia in Japan].

A questionnaire about the treatment of dystonia was sent out to 585 councilors of Societas Neurologica Japonica. One hundred and sixty-eight replies (28.7%) were collected, although some of them were excluded from the analysis because of inappropriateness. 1) The number of patients previously experienced was < 10; 37 respondents (22.7%), 10-50; 83 (50.9%), 50-100; 26 (16.0%), and > 100; 17 (10.4%). 2) Oral medication was most often the first line treatment in either of generalized dystonia, blapharospasm, cervical dystonia, and writer's cramp. Botulinum toxin injection was the first or the second line treatment in 147 (87.5%) and 116 (69.0%) respondents for blepharospasm and cervical dystonia, respectively. In these two conditions, the more experienced doctors tended to prefer botulinum toxin injection to the other treatments as the first choice (Cochran-Armitage analysis; p = 0.003 for blepharospasm and p = 0.002 for cervical dystonia). 3) Among the oral drugs, anticholinergics, especially trihexyphenidyl, were the most frequent choice in generalized dystonia, cervical dystonia, and writer's cramp. For blepharospasm, clonazepam was most favored. Sedatives, especially diazepam, were also often the drug of choice in either of these disorders. The favored drugs were not related to the respondent's experience. 4) The success rate of treatment, designated as the percentage of patients who improved through any treatment so much that the respondent was satisfied with it, was the highest in blepharospasm (65.4 +/- 24.1; mean +/- SD), followed by cervical dystonia (41.2 +/- 23.4), writer's cramp (32.9 +/- 22.5), and generalized dystonia (20.4 +/- 19.8). Only in cervical dystonia, the rate was significantly higher in more experienced respondents (regression analysis; p = 0.008). In blepharospasm (p < 0.001) and cervical dystonia (p = 0.002), regression analysis indicated that the success rate was higher in the group who preferred botulinum toxin injection to oral medication as the first line treatment. These results indicate that in Japan the treatment of choice for dystonia does not always follow the therapeutic guidelines for dystonia proposed in some foreign countries. Adopting more evidence-based rationale of treatment is encouraged, because the recent progress about the treatment of dystonia, e.g. botulinum toxin injection or the stereotaxic surgery, is reshaping dystonia from a devastating to a treatable disorder.

Anticonvulsants↗
PubMed2005

[Efficient use and problems associated with "home remote medical support system"--utilization of videophones for homecare patients].

"Home Remote Medical Support System" (the support system) is an interactive real time communication system, consisting of a vital health measuring device and a near-television quality home digital videophone installed at a residence, to connect a primary medical care institution and a homecare patient by information communication lines. Exclusive use of a telephone, vital health measuring device, TV monitor and camera are installed as home devices to communicate with a primary personal computer at the medical institution to manage patient's data and to have video phone health consultations. We employed and conducted the support system with a help from "the remote medical assistant task" operated by the local government since April 2004. Two patients actually used the support system in the first year although we initially planned to have three. In conclusion, the support system appears to have been useful for the health management of patients with stable conditions. Meanwhile, we have to reassess the application of the support system and to balance its accountability among the user efficiency, the content of the support provider and user expenses.

Home Care Services↗
PubMed2004

[Sleep disorders in Parkinson's disease].

Approximately 74-94% patients with Parkinson's disease have sleep disorders: such as frequent awakening, excessive daytime sleepiness, nightmares, nocturnal cramps, REM sleep behavior disorders and so on. In contrast, the relationship between physiological mechanism of sleep and the dopamine systems are still obscure, because the dopamine systems are not directly related neither initiating or maintaining sleep system nor awaking system. However, most of all the dopaminergic drugs were reported to induce sleepiness or sleep attacks in the patients with Parkinson's disease. So, physicians must inform patients with Parkinson's disease warning the excessive daytime sleepiness and sleep attack. In this article, I suggest the mechanisms of sleep disorders on Parkinson's disease from the physiological points of view, and how to manage these problems.

Humans↗
PubMed2002

A new locus for Parkinson's disease (PARK8) maps to chromosome 12p11.2-q13.1.

We performed genomewide linkage analysis of a Japanese family with autosomal dominant parkinsonism, which exhibits clinical features compatible with those of common Parkinson's disease. Parametric two-point linkage analysis yielded a highest log odds (LOD) score of 4.32 at D12S345 (12p11.21). Parametric multipoint linkage analysis of the 13.6cM interval around this marker yielded LOD scores almost uniformly of >4.0 with a Z(max) of 4.71 at D12S85 (12q12). Haplotype analysis detected two obligate recombination events at D12S1631 and D12S339 and defined the disease-associated haplotype in the 13.6cM interval in 12p11.2-q13.1. This haplotype was shared by all the patients and by some unaffected carriers, suggesting that disease penetration in this family is incomplete. This low penetrance suggests that environmental or other genetic factors modify expression of the disease. Nonparametric two-point and multipoint linkage analyses, which are penetrance-independent, yielded Z(max) LOD scores of 14.2 and 24.9 at D12S345, respectively, strongly supporting the mapping of the parkinsonism locus in this family to 12p11.23-q13.11. This chromosome region is different from any known locus for hereditary parkinsonism, in keeping with the unique genetic features of the parkinsonism in this family. The nomenclature of PARK8 was assigned to the new locus.

Adult↗