Search PubMed⌕ Search

Biomedical subjects

S Fahn

Publications and source records attributed to S Fahn.

At least 91 records · Page 5Linked to original sources
PubMed1997

Fine localization of the torsion dystonia gene (DYT1) on human chromosome 9q34: YAC map and linkage disequilibrium.

The DYT1 gene, which maps to chromosome 9q34, appears to be responsible for most cases of early-onset torsion dystonia in both Ashkenazic Jewish (AJ) and non-Jewish families. This disease is inherited in an autosomal dominant mode with reduced penetrance (30%-40%). The abnormal involuntary movements associated with this disease are believed to be caused by unbalanced neural transmission in the basal ganglia. Previous linkage disequilibrium studies in the AJ population placed the DYT1 gene in a 2-cM region between the loci D9S62a and ASS. A YAC contig has now been created spanning 600 kb of this region including D9S62a. The location of the DYT1 gene has been refined within this contig using several new polymorphic loci to expand the linkage disequilibrium analysis of the AJ founder mutation. The most likely location of the DYT1 gene is within a 150 kb region between the loci D9S2161 and D9S63.

Adult↗
PubMed1997

The Washington Heights-Inwood Genetic Study of Essential Tremor: methodologic issues in essential-tremor research.

Essential tremor (ET) is the most prevalent movement disorder. It is unknown to what extent ET clusters within families, and the role of genetic susceptibility in etiology of ET has not been adequately investigated at the population level. The problem is largely methodological, with few well-designed studies. The Washington Height-Inwood Genetic Study of ET, begun in 1955, is designed to investigate the genetics of ET using a methodology that has not been applied to ET research to date. Part of the design includes a new set of clinical and electrophysiological diagnostic criteria for ET; the present paper describes this novel study design.

Case-Control Studies↗
PubMed1997

Comparison of extrapyramidal features in 31 pathologically confirmed cases of diffuse Lewy body disease and 34 pathologically confirmed cases of Parkinson's disease.

OBJECTIVE: To compare the extrapyramidal features of pathologically confirmed cases of diffuse Lewy body disease (DLBD) and Parkinson's disease (PD). BACKGROUND: The proportion of pathologically confirmed cases of DLBD diagnosed clinically as PD is as high as 88%. Few papers focus specifically on the extrapyramidal features of DLBD. Further characterization of these features might facilitate antemortem diagnosis, in particular, distinguishing DLBD from PD. METHODS: Review of prospective and retrospective clinical data on a large series of pathologically diagnosed cases of DLBD (N = 31) and PD (N = 34) seen between 1984 and 1995 at Columbia-Presbyterian Medical Center or the University of Rochester. RESULTS: Those with DLBD had an older mean age of onset (67.9 years) than PD (62.0 years) (z = 6.5, p < 0.0001). Rest tremor was more common in PD (85.0%) than DLBD (55.0%) (chi 2 = 4.3, p = 0.038). Myoclonus was more common in DLBD (18.5%) than PD (0%) (Fisher's p = 0.021). There were no differences in rigidity, bradykinesia, dystonia, or gaze palsies. Clinical response to levodopa may have been more common in PD (100%) than DLBD (70.0%) (Fisher's p = 0.059). The occurrence of any one of four clinical features (myoclonus, absence of rest tremor, no response to levodopa, or no perceived need to treat with levodopa) was 10 times more likely in DLBD than PD (odds ratio = 10.29, 95% confidence interval = 2.58-41.11). CONCLUSIONS: We demonstrated that several clinical features distinguish DLBD from PD. These features, in combination with reported differences in cognitive and psychiatric manifestations, may be used for diagnostic purposes in distinguishing DLBD from PD in prospective longitudinal cohort studies of DLBD.

Aged↗
PubMed1997

Secondary dystonia and the DYTI gene.

Early-onset (< 28 years) primary dystonia in most Ashkenazi Jews is due to a single founder mutation in the DYT1 gene on chromosome 9q34, as determined by very strong linkage disequilibrium with a haplotype of 9q34 alleles at surrounding marker loci. The role of this mutation in individuals with secondary causes for dystonia has never been tested, although environmental insults, such as neuroleptic exposure or perinatal asphyxia, are proposed to precipitate dystonia in genetically predisposed individuals. We assessed 9q34 haplotypes in 40 Ashkenazi patients with secondary dystonia; 25 had early onset of symptoms, including 15 with exposure to neuroleptic medication or perinatal asphyxia. Of the 25 patients with early onset, 9 were considered phenocopies of DYT1 having normal examinations except for dystonia, normal radiographic and other laboratory studies, and onset in a limb or the neck. Only one individual whose dystonia developed in the setting of a measles infection carried the associated haplotype. Our findings indicate that clinical diagnostic criteria that include historical information to detect tardive dystonia and perinatal asphyxia discriminate primary dystonia due to the DYT1 founder mutation. We found no evidence that the DYT1 founder mutation contributes to secondary dystonia.

Adolescent↗
PubMed1996

Delayed-onset cerebellar syndrome.

BACKGROUND: Delayed-onset involuntary movements, including dystonia and myoclonus, have been reported after stroke or head trauma. Moreover, there have been reports of delayed-onset isolated intention tremor and, in several of these cases, gait ataxia. OBJECTIVE: To further define the clinical features of a delayed-onset cerebellar syndrome. DESIGN: Subjects with cerebellar tremor and either head trauma or stroke were identified using a computerized database, providing detailed demographic and clinical information of 4002 patients with involuntary movements other than Parkinson's disease seen at our center between 1983 and 1995. Medical records and videotaped neurological examinations were retrospectively reviewed. SETTING: The Center for Parkinson's Disease and Other Movement Disorders at Columbia-Presbyterian Medical Center, New York, NY. PATIENTS: Five patients with delayed-onset cerebellar syndromes. RESULTS: Five patients with stroke or head trauma developed a cerebellar syndrome 3 weeks to 2 years after the initial insult. The syndrome, characterized by intention tremor, ataxic dysarthria, nystagmus, dysmetria, dysdiadochokinesis, and gait ataxia, was progressive in at least one patient. In four patients, lesions were present on neuroimaging in the thalamus or brain stem (especially in the midbrain). CONCLUSIONS: A delayed-onset cerebellar syndrome may follow head trauma or stroke. The syndrome is sometimes progressive and often disabling. The delayed onset implies that the syndrome is not caused by the initial lesion itself but may be caused by development of post-synaptic supersensitivity or secondary reorganization of involved pathways.

Adolescent↗
PubMed1996

Tourette syndrome.

Explore the source record for details and available documents.

Evaluation Studies as Topic↗
PubMed1996

Approach to the treatment of limb disorders with botulinum toxin A. Experience with 187 patients.

OBJECTIVE: To determine the dosing, response expectation, efficacy, and most rational strategy for using intramuscular injections of botulinum toxin A (BTX) for limb disorders. DESIGN: Open-label prospective analysis of outcome after BTX treatment in patients with limb disorders. PROCEDURE: Botulinum toxin A prepared from lyophilized botulinum toxin was injected into selected upper and lower limb muscles under electromyographic guidance. Booster injections were given every 10 to 14 days during the first month (if needed) until optimal effects were achieved. Clinical data and muscle strength testing were obtained before the first injections and repeated at each visit. Level of disability, global functional improvement, and relief of pain were evaluated 6 to 8 weeks after the first set of injections. Practical and meaningful BTX doses by muscle, limb, or condition according to specified levels of efficacy were developed. MAIN OUTCOME MEASURES: Botulinum toxin A efficacy was calculated as an arithmetic combination of changes in the 3 clinical ratings before and after administration of BTX. RESULTS: Botulinum toxin A injections were given to 187 patients with limb disorders during an 8-year period (136 with dystonia, 37 with parkinsonian, essential, and cerebellar tremors, and 14 with spasticity). Four overall outcomes from no effect to almost complete improvement in the use of the limb or relief of pain were found, and determined the strategy for follow-up injections. Average BTX efficacy for all patients was 65% and ranged from 83.5% for focal hand dystonia to 35.7% for parkinsonian tremor. Botulinum toxin A injections relieved pain, independent of motor function, in 82.7% of patients with painful muscle spasms. CONCLUSIONS: Botulinum toxin A was found to be a safe and useful treatment of various limb conditions. Botulinum toxin A was significantly more effective when only a few muscles needing low doses were injected, and tended to be more useful in dystonia and spasticity than tremor. Candidates for BTX injection could be categorized functionally into 3 groups independent of the underlying disorders. The only significant adverse effect of BTX injection in limbs was transient weakness in injected or neighboring muscles.

Adolescent↗
PubMed1996

Use of intrathecal baclofen in the treatment of patients with dystonia.

BACKGROUND: Continuous infusion of intrathecal (IT) baclofen is a highly effective standard therapy for severe spasticity of spinal origin. By contrast, there is limited clinical experience regarding the use of IT baclofen in treating patients with dystonia, and little is known regarding the indications for treatment, efficacy, and safety of IT baclofen in this disorder. OBJECTIVE: To study retrospectively the effects of IT baclofen in treating 25 patients with severe segmental or generalized dystonia. SETTING: Neurological Institute, Columbia-Presbyterian Medical Center, New York, NY. PATIENTS: Twenty-five patients with severe segmental or generalized dystonia that was refractory to oral medications underwent IT baclofen test dosing. In addition to dystonia, 17 patients had spasticity or painful spasms. Thirteen of 25 patients responded to the test doses of IT baclofen, according to unblinded neurological assessments that included the patient's subjective report; all 13 underwent implantation of a pump for continuous IT baclofen infusion. RESULTS: In contrast to reports of patients with spasticity of spinal origin, those with dystonia in the present series had a lower response rate to bolus IT baclofen doses and a smaller degree of clinical improvement. For 10 of the 13 responders to the test doses of IT baclofen, dystonia rating scale scores of videotaped examinations by blinded observers detected no significant change (P < .07) in severity of dystonia. Retrospective data from 11 of 13 patients with implantable pumps, followed up for a mean interval of 21 months after pump insertion, showed continuing efficacy in 6 individuals (55%), based on a determination of patient satisfaction; however, only 3 patients (27%) reported a sustained improvement in functional capacity. Five (38%) of the 13 patients with implantable pumps experienced severe complications that required hospitalization. CONCLUSIONS: Despite recent reports that have described the benefit in small numbers of patients with dystonia, we concluded that the role of IT baclofen in treating severe dystonia remains uncertain. Intrathecal baclofen may be more effective when dystonia is associated with spasticity or pain. In the present series, we detected no significant difference in the response to IT baclofen in patients with or without spasticity or pain, perhaps owing to the small sample size.

Baclofen↗
PubMed1996

Diagnostic guidelines in central nervous system Whipple's disease.

Many cases of central nervous system (CNS) Whipple's disease are not diagnosed until postmortem. Few reviews of CNS Whipple's disease have delineated the frequencies of abnormalities on neurological examination, cerebrospinal fluid studies, neuroimaging, and intestinal biopsy studies. Guidelines for diagnosis and treatment have not been proposed. In this review we present 3 new cases of CNS Whipple's disease and summarize the literature to determine the frequencies of neurological signs and abnormalities on diagnostic testing. We propose guidelines for diagnostic screening, selection for biopsy, and treatment. Review of the 84 cases of CNS Whipple's disease (81 in the literature, 3 new) revealed that 80% of the patients had systemic signs. Cognitive changes were frequent (71%), and 47% with cognitive changes also had psychiatric signs. Oculomasticatory myorhythmia and oculo-facial-skeletal myorhythmia, pathognomic for CNS Whipple's disease, were present in 20% of patients, and were always accompanied by a supranuclear vertical gaze palsy. Tissue biopsy was a sensitive technique; 89% of those who had biopsies had positive biopsy results. Diagnosis and treatment of definite CNS Whipple's disease should be based on the presence of pathognomic signs (oculomasticatory myorhythmia or oculo-facial-skeletal myorhythmia) or positive biopsy or polymerase chain reaction results. Possible CNS Whipple's disease should be diagnosed in the setting of unexplained systemic symptoms and neurological signs (supranuclear vertical gaze palsy, rhythmic myoclonus, dementia with psychiatric symptoms, or hypothalamic manifestations). Those with possible CNS Whipple's disease should undergo small-bowel biopsy.

Anti-Bacterial Agents↗
PubMed1996

Exclusion of the DYT1 locus in familial torticollis.

Clinical-genetic studies of idiopathic torsion dystonia (ITD) indicate that the DYT1 gene on chromosome 9q34 is responsible for most childhood limb-onset disease. The genetic basis of adult-onset ITD is less well studied. In most multiplex adult-onset ITD families, dystonia is limited to the cervical, cranial, or brachial muscles; in a few rare families, dystonia also involves the legs and trunk. Previous linkage studies have excluded the DYT1 locus in these atypical families. We studied two large non-Jewish families with adult-onset ITD limited to the cervical and brachial muscles and excluded the DYT1-containing region. This study further restricts the role of DYT1 to childhood limb-onset ITD and suggests that other genes are responsible for focal adult-onset ITD.

Adolescent↗
PubMed1996

Response to botulinum toxin F in seronegative botulinum toxin A--resistant patients.

Botulinum toxin type A (btx A) injections are the most effective treatment for most patients with focal dystonia. Some patients who improve after btx A injections and later lose response have serologic evidence of antibodies to btx A with the mouse neutralization assay (seropositive patients). Another group of patients who lose response to btx A do not have detectable antibodies (seronegative patients). Seropositive patients may improve after injections of botulinum toxin type F (btx F), an alternative serotype of botulinum toxin. We treated nine seronegative resistant patients with btx F. None of these patients had muscle atrophy after injection with btx A. Five of the nine had improvement after btx F injection that was sustained for at least three consecutive btx F injections. This observation is consistent with the hypothesis that btx resistance in seronegative patients is caused by undetected antibodies to btx A. If this be the case, then there may be techniques for preventing or reversing btx resistance, as in the case of resistance of factor VIII in the treatment of hemophilia A.

Animals↗
PubMed1996

Reliability of patient completion of the historical section of the Unified Parkinson's Disease Rating Scale.

Evaluating the reliability of self-assessed disability in patients with Parkinson's disease (PD) is important for therapeutic trials epidemiologic surveys. This is the first study to examine the interrater reliability between physician and patient in the historical section of the Unified Parkinson's Disease Rating Scale (UPDRS). Thirty consecutive subjects with idiopathic PD self-administered the historical section of a modified UPDRS. This instrument was then readministered to these 30 subjects by a neurologist. Interobserver reliability was assessed with the weighted kappa statistic (kw). The kw for each of the 17 items in the historical section of the UPDRS ranged from 0.63 to 1.0 (moderate to excellent agreement). Total kw = 0.83 (95% confidence interval = 0.79-0.87). There were no correlations between kw and age, disease duration, dose of levodopa, Hoehn and Yahr score, Schwab and England score, or modified Mini-Mental State score. Nondemented subjects with PD may reliably assess their level of disability by self-administering the historical section of the UPDRS. This has important implications for the reliable use of self-administered disability instruments for clinical research.

Activities of Daily Living↗
PubMed1996

Rapid eye movement sleep behavior disorder preceding Parkinson's disease with therapeutic response to levodopa.

Rapid eye movement (REM) sleep behavior disorder (RBD) involves complex behavior and a loss of muscle atonia occurring during REM sleep. Half of these patients with RBD have an underlying neurologic disorder including dementia, olivopontocerebellar atrophy, subarachnoid hemorrhage, and cerebrovascular disease. Clonazepam is the drug of choice for RBD. RBD has been rarely reported to precede the onset of Parkinson's disease (PD). Three patients are presented here whose RBD preceded the onset of PD by several years, and both the symptoms of PD and RBD improved with levodopa treatment. It is postulated that levodopa ameliorates RBD by suppressing REM sleep, and it remains to be seen whether levodopa can be an alternative to clonazepam in idiopathic RBD without PD.

Aged↗
PubMed1996

Oral and genital pain syndromes in Parkinson's disease.

Painful sensory complaints are known to occur in Parkinson's disease, but painful oral or genital syndromes have not been described. We report seven individuals with presumed idiopathic Parkinson's disease and one with atypical parkinsonism who experienced chronic severe oral or genital pains that appeared to be examples of a primary sensory disturbance related to the underlying parkinsonism. In each case, the pain syndrome overshadowed the other features of the parkinsonism. Five patients experienced oral pain and three patients, all women, had genital pain. No other definable organic cause was detected to explain the symptoms in any case. The genital pain tended to fluctuate in severity with the motor manifestations of the parkinsonism and could be abolished or reduced by levodopa. The recognition of painful oral or genital sensations in patients with parkinsonism should lead to further study regarding the prevalence, neurochemical basis, and treatment for these disabling symptoms.

Aged↗
PubMed1996

Cutaneous electromyographic silent period findings in brachial dystonia.

In this study we investigated the physiologic mechanisms in primary brachial dystonia by analyzing the cutaneous EMG silent period during isometric contraction of the opponens pollicis muscle. Results from the affected and unaffected arms of 11 patients with dystonia were compared to 7 patients with Parkinson's disease and 16 age-matched normal individuals (controls). The silent period onset latency, degree of EMG suppression during the silent period, and EMG rebound at the end of the silent period did not differ significantly between patients with dystonia and any other group. The duration of the silent period (the S-X interval), however, was significantly prolonged in dystonia (p<0.005) and in Parkinson's disease (p<0.001) in both affected and unaffected arms compared with controls. These findings suggest that mechanisms responsible for the initiation of the cutaneously induced silent period and the subsequent suppression depth of EMG activity are not affected in brachial dystonia, but the abnormally prolonged S-X intervals may reflect dysfunctional basal ganglia timing influences over spinal circuitry common to both dystonia and Parkinson's disease.

Adult↗