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S Fahn

Publications and source records attributed to S Fahn.

At least 181 records · Page 10Linked to original sources
PubMed1991

The metabolic landscape of cortico-basal ganglionic degeneration: regional asymmetries studied with positron emission tomography.

Regional metabolic rate for glucose (rCMRGlc) was estimated using [18F]fluorodeoxyglucose (FDG) and positron emission tomography (PET) in five patients (four men, one woman; mean age 68; mean disease duration 2.4 years) with clinical findings consistent with the syndrome of cortico-basal ganglionic degeneration (CBGD). Left-right rCMRGlc asymmetry, (L-R)/(L + R) x 100, was calculated for 13 grey matter regions and compared with regional metabolic data from 18 normal volunteers and nine patients with asymmetrical Parkinson's disease (PD). In the CBGD group mean metabolic asymmetry values in the thalamus, inferior parietal lobule and hippocampus were greater than those measured in normal control subjects and patients with asymmetrical PD (p less than 0.02). Parietal lobe asymmetry of 5% or more was evident in all CBGD patients, whereas in PD patients and normal controls, all regional asymmetry measures were less than 5% in absolute value. Measures of frontal, parietal and hemispheric metabolic asymmetry were found to be positively correlated with asymmetries in thalamic rCMRGlc (p less than 0.05). The presence of cortico-thalamic metabolic asymmetry is consistent with the focal neuropathological changes reported in CBGD brains. Our findings suggest that metabolic asymmetries detected with FDG/PET may support a diagnosis of CBGD in life.

Aged↗
PubMed1991

Dopa-responsive dystonia: long-term treatment response and prognosis.

We report observations on the treatment of 66 patients with presumed dopa-responsive dystonia (DRD). Forty-seven of these patients had hereditary disease; 19 had disease of sporadic occurrence. Initial diagnostic confusion with "cerebral palsy" or "spastic diplegia" existed in 16 patients. Several patients benefited from anticholinergic medications and a few from carbamazepine. Levodopa was the most effective treatment in all cases. In the majority, there was an excellent response, with continued long-term clinical stability on levodopa therapy for as long as 10 to 22 years. Four men with sporadic disease and 1 woman with a sister affected with adolescent-onset parkinsonism had similar initial treatment response, but developed "wearing-off" and a less satisfactory response to levodopa within the first few years of treatment. This indicates that some patients with clinical syndromes suggestive of DRD may not have an excellent prognosis on long-term levodopa treatment and may represent misclassified cases of childhood-onset parkinsonism.

Adolescent↗
PubMed1991

Delayed-onset dystonia due to perinatal or early childhood asphyxia.

We report 10 patients with delayed-onset dystonia associated with perinatal asphyxia and 2 associated with asphyxia in childhood. In the perinatal group, the mean age of onset was 12.9 years. Among these patients, dystonia continued to progress for a mean of 7 years, and as long as 28 years. These patients had moderate motor disability; none was wheelchair-bound, and thus their prognosis was better than that of the childhood-onset idiopathic torsion dystonias. The most frequently beneficial drugs were anticholinergics. Since some of these patients closely resembled cases of idiopathic torsion dystonia, the prior occurrence of asphyxia should be used as a criterion of exclusion for that diagnosis.

Aging↗
PubMed1991

Unilateral MPTP-induced parkinsonism in monkeys. A quantitative autoradiographic study of dopamine D1 and D2 receptors and re-uptake sites.

The cynomolgus monkeys received a unilateral intracarotid injection of the neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in order to induce a chronic model of hemi-parkinsonism. The procedure was well tolerated by the animals. Unilateral injection of MPTP caused rigidity and bradykinesia of the contralateral limbs, but the animals were able to eat and drink without levodopa therapy. During spontaneous motor activity, animals rotated toward the lesioned side whereas systemic apomorphine injection stimulated circling toward the normal non-lesioned side. Twelve weeks after MPTP injection, we found a marked reduction in striatal and nigral [3H]-mazindol binding on the MPTP-injected side which is indicative of a loss in both dopaminergic nerve terminals and cell bodies. The unilateral dopaminergic denervation was associated with an ipsilateral increase in striatal and a reduction in nigral [3H]-spiperone-labelled D2 dopamine receptors; these changes are consistent with the known localization of the D2 receptors on striatal dopaminergic nerve terminals and on nigral dopaminergic cell bodies. In contrast, no changes in [3H]-SCH 23390-labelled D1 dopamine receptors were observed at the level of either the striatum or the substantia nigra. This study describes a well tolerated procedure which induces a clinical and morphological hemi-parkinsonian syndrome. This animal model may be useful in the studies of new antiparkinsonian drugs, for testing the functional efficacy of brain tissue implants and in the understanding of the physiopathogenesis of levodopa-induced dyskinesias.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1991

Torsion dystonia genes in two populations confined to a small region on chromosome 9q32-34.

Idiopathic torsion dystonia (ITD) is characterized by sustained, involuntary muscle contractions, frequently causing twisting and repetitive movements or abnormal postures. Most familial forms of ITD display autosomal dominant inheritance with reduced penetrance. Linkage analysis has been previously used to localize a dystonia gene to the 9q32-34 region in a large non-Jewish family and in a group of Ashkenazi Jewish families. Utilizing GT repeat polymorphisms from this region, here we demonstrate that the gene causing dystonia in Ashkenazi Jews can be localized to the 11-cM interval between AK1 and D9S10. Linkage analysis in the non-Jewish family is also consistent with occurrence of the gene in this region, although positive lod scores extend over a greater than 20-cM interval in that family. These results set the stage for positional cloning of the dystonia gene. Currently there are no known candidate genes in this region.

Base Sequence↗
PubMed1990

Quantitative autoradiographic changes in 5-[3H]HT-labeled 5-HT1 serotonin receptors in discrete regions of brain in the rat model of persistent dyskinesias induced by iminodipropionitrile (IDPN).

Chronic injections of iminodipropionitrile (IDPN) to rat cause a persistent motor hyperactivity, lateral and vertical sustained twisting movement of the neck, random circling and increased startle response. These abnormalities are similar to those observed after the acute administration of serotonin (5-HT) agonists in rodents. Significant changes in 5-HT concentration and in 5-HT2 receptor density in several motor-related brain regions have been observed in IDPN-treated rats. The present quantitative autoradiographic study was undertaken to assess the possibility that IDPN may also affect 5-HT1 receptors in rat brain. IDPN caused significant increases of 5-[3H]HT binding in the oriens and pyramidal layers of the CA3 field of hippocampus. In contrast, there were significant decreases of 5-[3H]HT binding in the frontal and cingulate cortices, the olfactory tubercle, the ventromedial aspect of the caudate-putamen, the nucleus accumbens, the superior colliculus, and the lateral septal nuclei. These results provide further evidence for the involvement of the 5-HT system in the development of the IDPN-induced dyskinetic syndrome.

Animals↗
PubMed1990

The metabolic anatomy of Parkinson's disease: complementary [18F]fluorodeoxyglucose and [18F]fluorodopa positron emission tomographic studies.

We studied the metabolic anatomy of typical Parkinson's disease (PD) using [18F]fluorodeoxyglucose (FDG) and [18F]fluorodopa (FDOPA) and positron emission tomography (PET). Fourteen PD patients (mean age 49 years) had FDG/PET scans, of which 11 were scanned with both FDOPA and FDG. After the injection of FDOPA, brain uptake and arterial plasma radioactivity were monitored for 2 h. Striatal FDOPA uptake was analyzed with regard to a two-compartment model, and target-to-background ratios (TBRs) and TBR-versus-time slopes were also calculated. Regional patterns of metabolic covariation were extracted from FDG/PET data using the Scaled Subprofile Model (SSM). SSM pattern weights, FDOPA uptake constants (Ki), TBRs, and TBR slopes were correlated with clinical measures for bradykinesia, rigidity, tremor, gait disturbance, left-right asymmetry, dementia, and overall disease severity. In PD patients, rate constants for FDOPA uptake correlated with individual measures of bradykinesia (p = 0.001) and gait disability (p less than 0.05). SSM analysis revealed a distinct pattern of regional metabolic asymmetries, which correlated with motor asymmetries (p less than 0.001) and left-right differences in Ki (p less than 0.01). Our data suggest that in PD patients, FDG/PET and FDOPA/PET may provide unique and complementary information about underlying disease processes.

Adult↗
PubMed1990

Autoradiography of dopamine receptors and dopamine uptake sites in the spontaneously hypertensive rat.

We examined the status of dopamine (DA) D1 and D2 receptors by using [3H]SCH 23390 and [3H]spiperone binding, respectively, and DA uptake sites by using [3H]mazindol binding in spontaneously hypertensive rats (SHR) and Sprague-Dawley (SD) rats. SHR showed significantly higher [3H]SCH 23390 and [3H]spiperone binding in the caudate-putamen (CPu), the nucleus accumbens (NAc) and the olfactory tubercle (OT) in comparison to the SD rats. There were no significant differences in [3H]mazindol-labeled DA uptake sites between the two strains. Unilateral 6-hydroxydopamine (6-OHDA) injection into the striatum resulted in more than 90% depletion of DA uptake sites in the CPu in both strains. 6-OHDA-induced DA depletion was associated with significant increases in striatal [3H]spiperone binding which were of similar magnitude in the SD rats (+64.1%) and SHR (+51.3%). There were only small decreases (-5.4%) in D1 receptor binding in the dorsolateral aspect of the CPu in the SHR, whereas there were no changes in striatal D1 receptors in the SD rats. These results indicate that, although the SHR have higher concentrations of both D1 and D2 receptors in the basal ganglia, these receptors are regulated in a fashion similar to DA receptors in SD rats after 6-OHDA-induced striatal DA depletion.

Animals↗
PubMed1990

Dopa-responsive dystonia: the spectrum of clinical manifestations in a large North American family.

We examined 106 members of a family affected with dopa-responsive dystonia (DRD), a subset of idiopathic dystonia. Ten members had unequivocal dystonia; 8 of these had generalized dystonia and the other 2 had focal dystonias (writer's cramp and spastic dysphonia). Twenty members had lesser dystonic signs and symptoms suggestive of a diagnosis of dystonia. Five members, including 1 with dystonia, had prominent parkinsonism that became symptomatic in late adulthood. All members affected with dystonia or parkinsonism had increased muscle tone (rigidity), which may represent the minimal clinical expression of DRD. Gene penetrance in families with DRD may be greater than previously suspected.

Adult↗
PubMed1990

Hemiparkinsonism-hemiatrophy syndrome: clinical and neuroradiologic features.

We evaluated 11 patients with hemiparkinson-hemiatrophy syndrome, 6 with body and contralateral cerebral hemispheric hemiatrophy, 4 with only body hemiatrophy, and 1 with just brain hemiatrophy. The mean age of symptom onset was 38.1 years (range, 18 to 54) with 5.2 +/- 3.1 (mean +/- SD) years of illness until the last follow-up visit. The presenting symptom was unilateral tremor in 6 patients, hand dystonia in 2, bradykinesia in 2, and abnormal gait in 1 patient. Three patients had a good response to levodopa, 4 had moderate response, and 2 patients had a poor response. During a mean follow-up period of 1.7 years (range, 4 months to 5 years), the Hoehn and Yahr score changed in only 3 patients: 2 gained 1.5 points and 1 gained 3 points over 2.5 years. We discuss the association between hemiparkinsonism-body hemiatrophy and contralateral hemispheric hemiatrophy, and raise the possibility of early childhood brain insult with delayed-onset parkinsonism.

Adolescent↗
PubMed1990

Double-blind, placebo-controlled trial of botulinum toxin injections for the treatment of spasmodic torticollis.

We enrolled 55 patients in a double-blind, placebo-controlled, parallel design study of the effectiveness of botulinum toxin (Botox) injections for the treatment of spasmodic torticollis. Patients received a standard series of injections, either placebo or Botox. We determined the sites of injection and dose per muscle by the nature of head deviation. Compared with placebo, Botox produced statistically significant improvement in the severity of torticollis, disability, pain, and degree of head turning. There were no serious side effects. During the double-blind phase, 61% of patients injected with Botox improved; 74% of patients subsequently improved during a later open phase at a higher dose of Botox. Direction of head turning, severity of torticollis, and presence or absence of jerky movements did not significantly influence the response rate. We conclude that Botox is a valuable treatment for spasmodic torticollis.

Analysis of Variance↗
PubMed1990

Segregation analysis of idiopathic torsion dystonia in Ashkenazi Jews suggests autosomal dominant inheritance.

The results of segregation analysis applied to a family study of idiopathic torsion dystonia in Ashkenazi Jews are reported. The study is based on 43 probands (with age at onset prior to 27 years) from 42 nuclear families; pedigrees were extended systematically through all available first- and second-degree relatives, who were directly examined and videotaped. Final diagnoses were based on exam information and blinded videotape review. Segregation analysis demonstrated that the data are consistent with autosomal dominant inheritance with 30% penetrance. Recessive and polygenic inheritance were strongly rejected. There was no evidence for sporadic cases or new mutations. The high incidence and dominant inheritance of early-onset idiopathic torsion dystonia in Ashkenazi Jews suggests genetic homogeneity within this population, making it especially useful for linkage studies of this disorder.

Adolescent↗
PubMed1989

Regional changes in brain 5-HT1A serotonin receptors in the rat model of persistent spasmodic dyskinesias induced by iminodipropionitrile.

Chronic injection of iminodipropionitrile (IDPN) to rats causes persistent motor abnormalities such as hyperactivity, lateral and vertical dyskinesia of the neck, and random circling. These behavioral changes are very similar to those observed after the acute administration of serotonin (5-HT) agonists in rodents. Moreover, some aspects of this syndrome are reproduced by stimulation of 5-HT1A receptors. The present quantitative autoradiographic study revealed a number of changes in 8-hydroxy-2-[di-n-propylamino-3H]tetralin (8-OH[3H]DPAT)-labeled 5-HT1A receptors in the brains of IDPN-treated rats. There were significant increases of 8-OH[3H]DPAT binding in the frontal cortex and in the caudate-putamen. In contrast, there were significant decreases in the interpeduncular nucleus, the pyramidal layer of the CA3 field of hippocampus, the superior colliculus and the pars reticulata of the substantia nigra. These results provide further evidence for the involvement of the 5-HT system in the development of the IDPN-induced dyskinetic syndrome.

8-Hydroxy-2-(di-n-propylamino)tetralin↗