摘要:

AbstractNumerous advances in in vivo and ex vivo gene‐therapy approaches to Parkinson's disease offer promise for direct clinical trials in patients in the next several years. These systems are predicated on introducing genes that encode enzymes responsible for dopamine biosynthesis or neurotrophic factors that may delay nigrostriatal degeneration or facilitate regeneration. We review the current status of experimental approaches to gene therapy for Parkinson's disease. Comparative advantages and disadvantages of each system are enumerated, and preclinical trials of some of the systems are evaluated. Although the specific in vivo or ex vivo methods used for gene transfer into the brain are likely to be supplanted by newer technology over the next decade, the principles and approaches developed in current studies likely will remain the sam

ISSN:0885-3185    

DOI:10.1002/mds.870110502

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractTremor can be particularly disabling in patients with multiple sclerosis (MS) and is mildly improved by drug treatment. The efficiency of stereotactic thalamotomy has been reported in a small number of patients but was counterbalanced by severe postoperative complications. Stimulation of the thalamic ventral intermediate nucleus, which is a less aggressive surgical method, is efficient in essential and in parkinsonian tremors. We report here the results of thalamic stimulation in 13 patients with MS with tremor. All patients were subjected to clinical examination, videorecording, and quantification of the functional disability before surgery and 3 months postoperatively. The surgical intervention was well tolerated in all cases. A clear improvement of the tremor was observed in 69.2% of the patients. Functional improvement was more varied and depended on the severity of tremor and coexistence of other neurological symptoms. Of the eight most severely affected patients, seven recovered the possibility to easily catch an object and use it. The results indicate that thalamic stimulation may be useful in the treatment of severe postural cerebellar tremor in MS.

ISSN:0885-3185    

DOI:10.1002/mds.870110503

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractCabergoline is a long‐acting D2dopamine (DA) agonist. We conducted an open study to investigate the effectiveness and tolerability of cabergoline, administered once a day orally, in 50 consecutive patients with Parkinson's disease complicated by motor fluctuations and dyskinesias. In 15 patients cabergoline replaced another direct DA agonist. Evaluation after 6 months of treatment (also including patients who dropped out during this period), showed an improvement in off or on hours, or both, in excess of 50% in 27 patients, comprising 20 of the 35 patients (57%) previously untreated with DA agonists and seven of the 15 patients (47%) already on DA agonists when the study began. Of the 22 patients who received the treatment for 1 year, the improvement was maintained up to final evaluation in the patients not on DA agonists at admission (n = 16), whereas a slight deterioration in clinical condition was observed in the patients already on DA agonists at admission (n = 6). Only six patients showed a detectable increase in dyskinesias. The most common side effects were gastric upset (n = 12), orthostatic hypotension (n = 3), and ankle edema (n = 3), all mild; also observed were two cases of pleural effusion/pulmonary fibrosis. Twenty patients (40%) failed to complete the treatment; of these, five (10% of total) dropped out because of adverse effects. It is concluded that once‐daily administrations of cabergoline are useful for treating patients with Parkinson's disease with motor fluctuations and may advantageously substitute other DA agonists. The side effects of the drug are generally mild, although two cases involving pleuropulmonary complications did eme

ISSN:0885-3185    

DOI:10.1002/mds.870110504

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractUntil now the clinical criteria for the diagnosis of vascular parkinsonism (VP) have been disputed. The purpose of the present study is to investigate whether quantitative gait analysis can differentiate between the gait pattern of patients with VP and the gait pattern of patients with idiopathic Parkinson's disease (PD). Twelve patients with VP, 12 patients with PD, and 10 neurologically nondiseased controls were examined by quantitative gait analysis. Patients with VP, having a similar gait velocity and stride length, showed relatively preserved arm swing with markedly more anteflexion in the shoulder on the forward sway of the arm swing than patients with PD. Patients with VP also showed less flexion dystonic posture of the elbow, hip, knee, and trunk than did patients with PD. There was no significant difference in the excursions and coordination of arm swing in the patients with VP compared with the control group. Both patient groups showed reduced leg movements, reduced hip extension, and reduced knee flexion and extension as compared with the controls.

ISSN:0885-3185    

DOI:10.1002/mds.870110505

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractIt is still unclear why balance impairment in Parkinson's disease (PD) often responds insufficiently to dopaminergic medication. We have studied this issue in 23 patients with idiopathic PD and 24 healthy controls. Our specific purposes were (a) to investigate the contribution of abnormal automatic postural responses to balance impairment in PD and (b) to assess the influence of dopaminergic medication on abnormal automatic postural responses and balance impairment. Standing subjects received 4° “toe‐up” rotational perturbations of a supporting forceplate. We bilaterally recorded posturally destabilizing medium latency (ML) responses from the stretched gastrocnemius muscles and functionally corrective long latency (LL) responses from the shortened tibialis anterior (TA) muscles. We also assessed changes in the center of foot pressure (CFP) and the center of gravity (COG). All patients were tested “off” and “on” phase. All controls were tested and retested after 1 h. During the off phase, we found enlarged ML amplitudes and diminished LL amplitudes in patients, together with a markedly increased posterior displacement of the COG. The abnormal ML and LL responses were partially responsible for the increased body sway in patients because the initial forward (destabilizing) displacement of the CFP was increased, while the subsequent backward displacement of the CFP (a measure of the corrective braking action of LL responses) was delayed. Abnormal late automatic or possibly more voluntary postural corrections also contributed substantially to the increased body sway. During the on phase, ML amplitudes were reduced in patients but remained increased compared with controls. LL amplitudes no longer differed between both groups due to a modest, possibly dopamine‐related in crease in patients and a simultaneous decrease in controls. The abnormal CFP displacement was only partially improved by dopaminergic medication. The later postural corrections were not improved at all. Consequently, the increased posterior COG displacement was not ameliorated during the on phase. We conclude that (a) a combination of abnormal automatic and perhaps more voluntary postural corrections contributes to increased body sway in PD and (b) dopaminergic medication fails to improve balance impairment in PD because early automatic postural responses are only partially corrected, while later occurring postural corrections are not improved at all. These electrophysiological results support clinical observations and suggest that nondopaminergic lesions play a significant role in the pathophysiology of postural abn

ISSN:0885-3185    

DOI:10.1002/mds.870110506

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractWe have developed a rodent model of striatonigral degeration, one of the core pathologies underlying the disease multiple system atrophy (MSA). 6‐Hydroxydopamine (6‐OHDA) was administered into the left medial forebrain bundle of male Wistar rats, followed 3–4 weeks later by intrastriatal injection of quinolinic acid into the ipsilateral stratum. The 6‐OHDA lesion resulted in ipsilateral rotation to (+)‐amphetamine and contralateral rotation to apomorphine. Following the subsequent striatal lesion, amphetamine‐induced ipsilateral rotation persisted, but apomorphine‐induced contralateral rotation was reduced or abolished. Subsequently, the lesioned striatum was implanted with fetal CNS allografts consisting of cell suspensions derived from striatal primordium alone or combined with cografts of ventral mesencephalon. Cografted rats showed a reduction or reversal of amphetamine‐induced rotation. This was not observed in animals receiving striatal grafts alone. Apomorphine‐induced contralateral rotation was restored after striatal grafts alone, but only partially in animals receiving sham or cografts. Tyrosine hydroxylase (TH) and dopamine‐ and cyclic adenosine 3′:5′‐monophosphate‐regulated phosphoprotein (DARPP 32) immunocytochemistry showed mesencephalic and striatal graft survival in most animals. However, dopaminergic outgrowth was restricted to the graft deposit. The latter was surrounded by a markedly gliotic glial fibrillary acidic protein‐positive capsule continuous with corpus callosum. Dopaminergic reinnervation of denervated and lesioned adult striatum itself was absent, suggesting that rotational recovery was due to diffuse dopamine release. The study shows that combined unilateral lesioning of rodent medial forebrain bundle and striatum results in a characterstic drug‐induced rotational response that can be partly restored by

ISSN:0885-3185    

DOI:10.1002/mds.870110507

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractWe describe the first Danish family with dentatorubral‐pallidoluysian atrophy (DRPLA), containing 16 clinically affected individuals in five generations. Inheritance is autosomal dominant. The disorder was diagnosed as Huntington's (HD), but analysis of the IT15 gene for HD revealed normal alleles. The diagnosis of DRPLA was based on the finding of elongated CAG repeats in the B37 gene on chromosome 12 in affected individuals. The age at onset ranged from 13 to 60 years, with most severe clinical picture being associated with onset in childhood. Clinical features included varying combinations of dementia, euphoria, visuomotor disturbances, speech problems, ataxia, tremor, epilepsy, and involuntary movements presenting as chorea, athetosis, and dystonia. We discuss characteristics of DRPLA that may enable the differentiation from HD on a clinical basis. In conclusion, DRPLA should be considered and DNA analysis is recommended in patients manifesting varying combinations of extrapyramidal and cerebellar symptoms, especially when clinical features show pronounced intrafamilial variability, and dyscoordination, tremor, myoclonus, epilepsy, and euphoria are part of the syndrom

ISSN:0885-3185    

DOI:10.1002/mds.870110508

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractThis is a retrospective review of 97 Huntington disease (HD) patients living in long‐term care facilities in the Twin Cities. The purpose of the study was to describe the demographic features, patterns of behavior, weight change, nursing issues medication use, and hospitalization in this population. On admission to the nursing home, the “average” HD patient was of either sex, 45 years old, previously employed, a high school graduate, and not married. One third had severe behavior problems. Half gained and half lost weight; weight loss was not a predictor of death. Almost all used central nervous system‐active drugs, most commonly neuroleptics. Eighty‐four percent were ambulatory on admission, but 88% of those who died were nonambulatory at the time of death. We concluded that (a) HD patients are demographically different from other residents of long‐term care facilities, (b) weight gain can occur in some late‐stage patients, (c) negative behavior is a significant problem but is restricted to a subset of patients, and (d) adapting creatively to increasing multifaceted disability is the greatest challenge to the staff in facilities caring fo

ISSN:0885-3185    

DOI:10.1002/mds.870110509

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractOne hundred patients with clinically diagnosed Huntington's disease (HD) were randomized to either idebenone, an antioxidant and enhancer of oxidative metabolism, or placebo, in a 1‐year, double‐blind, parallel‐group study aimed at slowing the rate of progression of the disease. Ninety‐one patients completed the study. There were no significant differences between groups on the primary outcome measures of the Huntington's Disease Activities of Daily Living Scale (ADL—an index of functional status) and the Quantified Neurologic Examination (QNE). Sample size calculations based on progression of the ADL and QNE in this study group revealed that a larger study group is necessary to detect any differences less than an almost complete halting of the disease. This argues for multicenter efforts for future therapeutic tri

ISSN:0885-3185    

DOI:10.1002/mds.870110510

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractWe report two patients with subacute diffuse encephalopathy characterized by confusion, myoclonic encephalopathy, and mild akineto‐rigid extrapyramidal signs in one case and by apathy, memory deficit, and partial complex seizures in the other. Hashimoto's thyroiditis with high titers of antithyroglobulin antibodies was diagnosed in both patients, who were unresponsive to anticonvulsant medication, but showed rapid neurological improvement following steroid treatment. On neuropsychological examination, predominant frontotemporal dysfunction was noted. Electroencephalographic activity was remarkable for its rhythmical delta activity, unresponsive to, or even paradoxically increased by, anticonvulsant treatment. On magnetic resonance imaging, atrophy with temporal predominance was found. These observations support the idea that this potentially treatable dementia and movement disorder should be classified as a separate clinical entit

ISSN:0885-3185    

DOI:10.1002/mds.870110511

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY