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Biomedical subjects

S Fahn

Publications and source records attributed to S Fahn.

At least 109 records · Page 6Linked to original sources
PubMed1995

Factors predictive of the need for levodopa therapy in early, untreated Parkinson's disease. The Parkinson Study Group.

OBJECTIVE: To identify characteristics of patients with early, untreated Parkinson's disease that are the most important predictors of rapid functional decline. DESIGN: Prospective observational study of a cohort of 800 patients with early, untreated Parkinson's disease who were involved in a multicenter, randomized, double-blind, controlled clinical trial of selegiline hydrochloride (L-deprenyl) and vitamin E (alpha-tocopherol). PRIMARY OUTCOME VARIABLE: Time from randomization to the onset of disability that necessitated levodopa therapy (end point), as judged by the enrolling investigator. METHODS: Stepwise Cox regression was used in combination with clinical judgment to identify the most important independent baseline predictors of the primary end point among a host of variables, including treatment with selegiline and vitamin E, global and specific clinical measures of disease severity, demographic variables, and neuropsychological test results. RESULTS: In addition to selegiline treatment and global disease severity measures, such as the stage according to the criteria of Hoehn and Yahr, impaired domestic capacity, and the activities of daily living score, the complex of postural instability/gait difficulty and bradykinesia were found to be the factors that were most highly associated with the risk of reaching the end point. CONCLUSIONS: The findings suggest that patients with Parkinson's disease whose early clinical presentation includes either postural instability/gait difficulty or bradykinesia are at high risk for rapid functional decline.

Adult↗
PubMed1995

Psychogenic parkinsonism.

BACKGROUND: Parkinsonism resulting from a primary psychiatric disorder has not been well characterized previously. We had been impressed that this was a rare but definite cause of parkinsonism in patients presenting to our subspecialty movement disorders clinics. OBJECTIVE: To define the clinical characteristics of "psychogenic parkinsonism" to assist in the differentiation of these patients from those with "organic" parkinsonian disorders. DESIGN: Retrospective chart reviews of patients seen at three large movement disorders centers. PATIENTS: Seven men and seven women were diagnosed as having "documented" or "clinically established" psychogenic parkinsonism after repeated assessments. RESULTS: Tremor (12 patients) was present at rest but continued without the usual transient dampening on taking up a posture and persisted with action. Tremor frequency and rhythmicity varied markedly. Tremor could often be entrained to the frequency of other movements or subsided with distraction. Rigidity (six patients) had features of voluntary resistance, often decreasing with distraction and/or activating synkinetic movements in opposite limbs. Arm swing was usually diminished or absent on the affected side; however, the arm could be held tightly to the side or cradled in front of the patient. Slowness of movement (all 14 patients) usually lacked the typical decrementing amplitude feature of bradykinesia. The slowness, ambulatory abnormalities, and postural instability (12 patients) often had bizarre, inconsistent, or incongruous features. Functional "give-way" weakness and nonorganic sensory disturbances were common (10 patients). Spontaneous remissions and remissions with placebo treatment or psychotherapy and response fluctuations related to unusual interventions were occasionally seen (five patients). Underlying psychological factors varied considerably. Most patients had been seen by several physicians and had undergone multiple unrevealing investigations. Fluorodopa F 18 (F-dopa) positron emission tomographic scanning yielded normal findings in three patients. Abnormal positron emission tomographic scanning results in a fourth patient, whose signs and symptoms had improved with psychotherapy and haloperidol therapy, emphasizes the possibility that prominent psychogenic features may be superimposed on organic parkinsonism in some patients. CONCLUSION: Psychogenic parkinsonism occurs rarely. It is a diagnosis of exclusion that should be made only by physicians with considerable experience in the care and treatment of patients with parkinsonism.

Adult↗
PubMed1995

Spread of symptoms in idiopathic torsion dystonia.

We reviewed the histories of 115 patients who had idiopathic dystonia and who were 21 years of age and younger at onset of symptoms and 472 patients with onset older than age 21. Patients with onset in the lower extremities tended to be younger at onset (mean age 8.4 years), have rapid spread of symptoms to other body parts, and to develop generalized dystonia. Patients with onset in the upper extremities tended to be older at onset (mean age 11.2 years) and were less likely to develop generalized dystonia, but were more likely to experience spread of symptoms many years after the disease began. Almost 20% of patients younger than age 22 began with torticollis, and 67% of these remained focal after a mean 14.9 years. In adults, dystonic symptoms remained focal in the majority, but approximately 15-30% of patients presenting with blepharospasm, torticollis, laryngeal or brachial dystonia eventually experienced dystonia outside the initially involved segment. Almost 50% of children and adolescents with dystonia reported a family history of dystonia, compared with approximately 10-13% of patients with torticollis, laryngeal or brachial dystonia. Less than 3% of patients with blepharospasm reported a family history of dystonia. There were only minor differences in the pattern of spread of dystonic symptoms between Jewish and non-Jewish patients. Although younger patients were more likely to report a family history of dystonia, patterns of spread were the same for familial and sporadic patients in the same age range.

Adolescent↗
PubMed1995

Parkinsonian features of eight pathologically diagnosed cases of diffuse Lewy body disease.

Premortem diagnosis of diffuse Lewy body disease (DLBD) is difficult, and knowledge of the parkinsonian features of DLBD might facilitate the diagnosis. In this study, we compared the parkinsonian syndrome of DLBD and Parkinson's disease (PD). We retrospectively reviewed the charts of Columbia-Presbyterian Medical Center (CPMC) Brain Bank cases (1989-1993) with pathologically diagnosed DLBD or PD, and the literature on the parkinsonian features in DLBD patients presenting with parkinsonism. Parkinsonism accompanied or preceded cognitive/psychiatric changes in most CPMC cases (DLBD 100%, PD 88%). DLBD had an earlier mean age of onset than PD did (57 versus 64 years), a similar male:female ratio (1.7:1 versus 1.9:1), and similar mean disease duration (12-13 years). Cognitive/psychiatric changes were less frequent in PD than in DLBD (65 versus 100%) (p = 0.025). Rest tremor was specifically mentioned in 29% of DLBD versus 56% of PD (p = 0.10). Bradykinesia was less common in PD (56% versus 86%) (p = 0.05). All those with PD responded to L-Dopa, as did all those with DLBD who received L-Dopa. In conclusion, there are subtle differences between PD and DLBD in age of onset, frequency of cognitive/psychiatric changes, bradykinesia, and rest tremor. However, even when taken together, these cannot be used to distinguish these entities.

Age of Onset↗
PubMed1995

Teaching tape for the motor section of the unified Parkinson's disease rating scale.

We developed a teaching tape of the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS) to provide investigators with a visual document of three raters' interpretations of the scoring system for each item except rigidity. The rate of agreement for the selected samples was always significant, with Kendall's coefficient of concordance W ranging between 0.97 and 0.62. We also provided full UPDRS ratings on sample patients that may be used for training and for multicenter studies to assure uniformity of rating. The study identified several items of the UPDRS motor examination for which written instructions were vague, including speech, action tremor, finger taps, rapid alternating movements, and postural stability. Future versions of the scale should address these problems and correct ambiguities. This project offers the first attempt to provide a visual analog for the UPDRS.

Audiovisual Aids↗
PubMed1995

Antiparkinsonian therapies and brain mitochondrial complex I activity.

Alterations in complex I activity, one of the enzymatic units of the mitochondrial respiratory chain, have been demonstrated in different tissues from patients with Parkinson's disease (PD). Subsequently, we showed that the chronic administration of levodopa can cause alterations in mitochondrial respiratory chain activity in rats, which suggests that the observed deficit in complex I activity in PD might be, at least in part, related to chronic levodopa therapy. Our study assessed the in vitro effects of different antiparkinsonian agents on complex I activity in rat brain. As previously reported, both levodopa and dopamine inhibit complex I activity in a dose-dependent manner. In contrast, the two major metabolites of dopamine, homovanillic acid and 3,4-dihydroxyphenylacetic acid as well as 3-O-methyl-dopa, had little or no effect on complex I activities. Bromocriptine, pergolide, trihexyphenidyl, molindone, and clozapine were all without significant inhibitory effects on mitochondrial function. Although vitamin C and deprenyl did not alter complex I activity, they did prevent the inhibitory effect of both levodopa and dopamine on complex I activity. This work indicates that among the different and usual antiparkinsonian agents, only levodopa and dopamine induced reductions in complex I activity. It also indicates that vitamin C and deprenyl are both effective in preventing the levodopa-induced complex I inhibition. This latter finding provides further support to the use of antioxidants and monoamine oxidase inhibitors as therapeutic strategies in attempts to slow the progression of PD.

Animals↗
PubMed1995

Dystonia in a patient with deletion of 18q.

This is the first reported case of dystonia with a partial deletion of the long arm (q) of chromosome 18. Neurologic findings in the 18q- syndrome include mental retardation, seizures, nystagmus, incoordination, tremor, and chorea. A 36-year-old woman with an 18q terminal deletion [karyotype 46,XX,del(18)(q22.2)] had hypothyroidism, diabetes mellitus, borderline intelligence, short stature, short neck, sensorineural hearing loss, and sensorimotor axonal neuropathy. Parents' karyotypes were normal. She had had incoordination and writing difficulty since childhood. Posturing and tremor of the head began at age 16, followed by arm tremors. She had jaw deviation and tremor, neck tremor with retrocollis, involuntary pronation of the right arm, coarse postural and severe action tremor, and tight pen grip with dystonic wrist extension on writing. The 18q- syndrome should be added to the list of genetic causes of secondary dystonia. A karyotype analysis should be considered in secondary dystonias, particularly when there are associated features such as short stature and endocrinopathies.

Adult↗
PubMed1995

Speech dysfunction in early Parkinson's disease.

The purpose of this study is to determine if subjects in the early stages of untreated Parkinson's disease (PD) or PD treated with deprenyl alone suffer from motor speech abnormalities. Speech defects are common in advanced PD, including disturbances of respiration, phonation, and articulation. We studied 12 subjects with early PD (Hoehn and Yahr stage < or = 2, mean duration disease 3.2 years) who were not taking symptomatic therapy and tested them under two conditions: on and off deprenyl. None of the subjects was depressed or demented (Mini Mental Status mean 29.9/30; Hamilton Depression Rating mean 2.7/52). All functioned independently (Schwab and England Activities of Daily Living mean 93.1/100). Acoustic and speech productions were assessed using the DSP Sona-Graph 5500 and an evaluation of dysarthria. All 12 had at least two characteristics of dysarthria on examination, although 8 were not aware of it. Vocal tremor was identified on narrow band spectrogram for four subjects. Deprenyl did not have a consistent effect on speech. Ten subjects had no detectable change in speech on deprenyl, one was worse, and one was improved.

Adult↗
PubMed1995

Generalized chorea in an infant with semilobar holoprosencephaly.

We report chorea in an infant with holoprosencephaly. Congenital structural brain disease has not been a reported cause of chorea. Cranial magnetic resonance imaging revealed small, fused frontal lobes with hypoplastic caudates. Our patient responded to symptomatic treatment with dopamine-depleting agents. It is likely that the mechanism for the chorea was a dysfunction of the striatum. The differential diagnosis of childhood chorea should include holoprosencephaly.

Child, Preschool↗
PubMed1995

Genetic analysis of idiopathic torsion dystonia in Ashkenazi Jews and their recent descent from a small founder population.

We have examined data on six closely linked microsatellite loci on chromosome 9q34 from 59 Ashkenazi Jewish families with idiopathic torsion dystonia (ITD). Our data show that the vast majority (> 90%) of early-onset ITD cases in the Ashkenazi population are due to a single founder mutation, which we estimate first appeared approximately 350 years ago. We also show that carriers preferentially originate from the northern part of the historic Jewish Pale of settlement (Lithuania and Byelorussia). The recent origin of this dominant mutation and its current high frequency (between 1/6,000 and 1/2,000) suggest that the Ashkenazi population descends from a limited group of founders, and emphasize the importance of genetic drift in determining disease allele frequencies in this population.

Alleles↗
PubMed1995

The metabolic topography of idiopathic torsion dystonia.

We used [18F]fluorodeoxyglucose (FDG) and PET with a statistical model of regional metabolic covariation to study brain topographic organization in idiopathic torsion dystonia (ITD). We studied 11 patients with predominantly right-sided ITD and 11 age-matched controls, and measured global, regional cerebral and normalized metabolic rates for glucose (GMR, rCMRGlc, rCMRGlc/GMR). The Scaled Subprofile Model was applied to the combined rCMRGlc dataset to identify topographic covariance profiles associated with ITD. We found that global and regional metabolic rates were normal in ITD. The SSM analysis of the combined groups of ITD patients and normals revealed a significant topographic profile characterized by relative bilateral increases in the metabolic activity of the lateral frontal and paracentral cortices, associated with relative covariate hypermetabolism of the contralateral lentiform nucleus, pons and midbrain. Subject scores for this profile correlated significantly with Fahn-Marsden disease severity ratings (r = 0.67, P < 0.02). In contrast to parkinsonism, lentiform and thalamic metabolism were dissociated in dystonia. We conclude that ITD is characterized by relative metabolic overactivity of the lentiform nucleus and premotor cortices. The presence of lentiform thalamic metabolic dissociation suggests that in this disorder hyperkinetic movements may arise through excessive activity of the direct putameno-pallidal inhibitory pathway.

Adult↗
PubMed1995

Adult onset idiopathic torsion dystonia is excluded from the DYT 1 region (9q34) in a Swedish family.

A gene (DYT1) for early onset idiopathic torsion dystonia was mapped to chromosome 9q34 in non-Jewish and Jewish families. The DYT1 gene region has been excluded in other families with adult onset and cervical or cranial onset idiopathic torsion dystonia from the United States, Great Britain, and France. The role of DYT1 in a Swedish family with adult onset idiopathic torsion dystonia in four generations was examined. The disease seems to be inherited in an autosomal dominant mode with reduced penetrance in this family. There were 10 affected family members, with a mean age of onset of 27 (range 18 to 50) years. The disease showed variable expression, with focal, multifocal, and generalised forms of dystonia in different family members. Genetic analysis excluded the chromosomal region containing the DYT1 locus as being responsible for dystonia in this family.

Adolescent↗
PubMed1995

Early differential diagnosis of Parkinson's disease with 18F-fluorodeoxyglucose and positron emission tomography.

Early-stage Parkinson's disease (EPD) is often clinically asymmetric. We used 18F-fluorodeoxyglucose (FDG) and PET to assess whether EPD can be detected by a characteristic pattern of regional metabolic asymmetry. To identify this pattern, we studied 10 EPD (Hoehn and Yahr stage I) patients (mean age 61.1 +/- 11.1 years) using 18F-FDG and PET to calculate regional metabolic rates for glucose. The scaled subprofile model (SSM) was applied to metabolic asymmetry measurements for the combined group of EPD patients and normal subjects to identify a specific covariation pattern that discriminated EPD patients from normal subjects. To determine whether this pattern could be used diagnostically, we studied a subsequent group of five presumptive EPD patients (mean age 50.9 +/- 18.3), five normal subjects (mean age 44.6 +/- 15.3), and nine patients with atypical drug-resistant early-stage parkinsonism (APD) (mean age 44.6 +/- 14.0). In each member of this prospective cohort, we calculated the expression of the EPD-related covariation pattern (subject scores) on a case-by-case basis. We also studied 11 of the EPD patients, five patients with APD, and 10 normal subjects with 18F-fluorodopa (FDOPA) and PET to measure presynaptic nigrostriatal dopaminergic function, and we assessed the accuracy of differential diagnosis with both PET methods using discrimination analysis. SSM analysis disclosed a significant topographic contrast profile characterized by covariate basal ganglia and thalamic asymmetries. Subject scores for this profile accurately discriminated EPD patients from normal subjects and APD patients (p < 0.0001). Group assignments into the normal or parkinsonian categories with FDG/PET were comparable to those achieved with FDOPA/PET, although APD and EPD patients were not differentiable by the latter method. Metabolic brain imaging with FDG/PET may be useful in the differential diagnosis of EPD.

Adult↗
PubMed1995

Peripherally induced EMG silent periods. Normal physiology and disorders of motor control.

Periods of relative or absolute EMG suppression induced by peripheral stimulation have been described using a variety of experimental paradigms in normal subjects and in conditions of abnormal motor control. Peripherally induced silent periods represent complex inhibitory modulations of muscle activity and can be reproducibly evoked by cutaneous or mixed nerve electrical or mechanical stimuli. Features of the electromyographic suppression which most easily permit analysis include the degree of EMG inhibition, the latency and duration of the response, and the timing of the return of normal EMG activity following the stimulus, or S-X interval. When exteroceptive reflexes in craniocervical muscles are studied, alternating periods of EMG inhibition and facilitation have been described. Experiments designed to isolate the various contributants to EMG silence have not revealed a unitary electrophysiological basis for all of the silent period responses elicited by peripheral means. Thus, silent periods share a multifactorial origin that depends upon segmental spinal mechanisms which are heavily influenced by descending suprasegmental pathways. Because these mechanisms are affected in a variety of central disorders of motor control, study of peripherally induced silent periods may provide a window on the abnormal physiology of selected CNS diseases. Further study is required to elucidate the electrophysiology of peripherally induced silent periods, and to clarify the alterations in these negative motor phenomena that occur in central disorders of motor control.

Dystonia↗
PubMed1994

Dystonia in Ashkenazi Jews: clinical characterization of a founder mutation.

A gene (DYT1) for idiopathic torsion dystonia maps to chromosome 9q34 in Ashkenazi Jewish families with early onset of symptoms. Further, there is linkage disequilibrium between DYT1 and a particular haplotype of alleles at 9q34 loci in this population. This implies that a large proportion of early-onset idiopathic torsion dystonia in Ashkenazi Jews is due to a founder mutation in DYT1. To characterize the phenotypic range of this mutation, we studied 174 Ashkenazi Jewish individuals affected with idiopathic torsion dystonia. We used GT(n) markers on chromosome 9q34 (D9S62, D9S63, and ASS) and classified individuals as having ("carriers"), not having ("noncarriers"), or being ambiguous with respect to a DYT1-associated haplotype. We assessed clinical features and found marked clinical differences between haplotype carriers and noncarriers. There were 90 carriers, 70 noncarriers, and 14 ambiguous individuals. The mean age at onset of symptoms was significantly lower in carriers than in noncarriers (12.5 +/- 8.2 vs 36.5 +/- 16.4 years). In 94% of carriers, symptoms began in a limb (arm or leg equally); rarely the disorder started in the neck (3.3%) or larynx (2.2%). In contrast, the neck, larynx, and other cranial muscles were the sites of onset in 79% of noncarriers; onset in the arms occurred in 21% and onset in the legs never occurred. Limb onset, leg involvement in the course of disease, and age at onset distinguished haplotype carriers from noncarriers with 90% accuracy. In conclusion, there are clinical differences between Ashkenazi Jewish individuals with idiopathic torsion dystonia who do or do not have a unique DYT1 mutation, as determined by a DYT1-associated haplotype of 9q34 alleles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗