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Biomedical subjects

S Fahn

Publications and source records attributed to S Fahn.

At least 253 records · Page 14Linked to original sources
PubMed1987

Localized injections of botulinum toxin for the treatment of focal dystonia and hemifacial spasm.

Medical treatment of dystonia usually results in an incomplete response and is frequently unsuccessful. Peripheral surgical therapy is available for some focal dystonias, but may only offer temporary relief and may have unacceptable complications. We have used local injections of botulinum toxin into the appropriate muscles for treatment of disabling focal or segmental dystonia in 93 patients with torticollis, blepharospasm, oromandibular dystonia (OMD), limb dystonia, lingual dystonia, and dystonia adductor dysphonia, in addition to four patients with hemifacial spasm. Significant relief of motor symptoms was seen in 69% of the patients with blepharospasm and 64% of patients with torticollis; 74% of the latter group with pain experience relief. Relief of symptoms was noted in most patients with OMD and limb dystonia, and all with lingual dystonia, dystonic adductor spastic dysphonia, and those with hemifacial spasm. Benefit averaged 2 1/2-3 months initially; however some patients experienced longer relief with subsequent injections. Adverse effects were transient, although 2 patients developed antibodies against the toxin, and we documented evidence for distant effects in others. This approach of chemically weakening contracting muscles in focal dystonia offers many advantages over pharmacotherapy and surgical therapy. Additional experience is needed to explore the proper doses, and potential for long term adverse effects.

Adult↗
PubMed1987

The effect of intracerebroventricular infusion of (+)-4-propyl-9-hydroxynapthoxacine (PHNO) through a totally implanted drug delivery system in rats with dopamine deficiency.

Rats with experimentally induced DA deficiency were treated with intracerebroventricular administration of (+)-4-propyl-9-hydroxynaphthoxacine (PHNO) through a totally implanted chronic delivery system which delivered PHNO, 0.9 microgram/h, continuously for up to 2 weeks. Rats with 6-OH-DA induced unilateral nigrostriatal lesion showed, after PHNO infusion, a potent and persistent contralateral turning behavior (8-11 turns/min) which was not present in vehicle-infused animals. The intensity of spontaneous and apomorphine-induced rotation did not decrease after 2 weeks of continuous infusion, suggesting that tolerance to PHNO or to other dopamine agonists did not develop. The magnitude of the spontaneous turning behavior in PHNO-infused animals correlated well with the baseline response to apomorphine (r = 0.505, p less than 0.025). Rats implanted with pumps delivering PHNO or vehicle were treated with reserpine, 0.5 mg/kg/day for 14 days. Vehicle-infused, reserpinized animals had a severe akinesia and weight loss during the experimental period (motor activity, measured in counts per minute was reduced to 5-10% of baseline levels, and body weight to 50% of baseline levels). PHNO-infusion partially restored activity to 60% of baseline counts and reduced the severity of weight loss. PHNO effects were observed for as long as the infusion was maintained. No side effects were observed. Intracerebroventricular infusion of PHNO may be an alternative experimental approach to untreatable motor fluctuations in Parkinson's disease.

Animals↗
PubMed1987

Systemic therapy of dystonia.

A number of pharmacologic agents have been found to be effective for the dystonias. Anticholinergic drugs have been shown to be the most effective in terms of percentage of subjects who receive moderate to marked benefit. About 50% of children and 40% of adults obtain such improvement. Peripheral adverse effects are usually overcome by pyridostigmine. It may be necessary to utilize pilocarpine eyedrops for blurred vision. Central adverse effects, such as forgetfulness, can be reduced only by a reduction in dosage of the anticholinergic. In comparing trihexyphenidyl and ethopropazine, we found that children tend to have better tolerance of the former and adults tend to have better tolerance of the latter. The antidopaminergics are the group of drugs that were found to be the next most effective agents in terms of percentage of patients who respond. However, these drugs, particularly the dopamine receptor blockers, have the capacity to induce tardive dyskinesia and tardive dystonia. Tardive syndromes are difficult to treat and can persist indefinitely. Other agents that have shown usefulness in controlling dystonia are levodopa, baclofen, carbamazepine, and the benzodiazepines, either alone or in combination with each other and with the anticholinergics. Stereotactic thalamotomy is particularly useful in contralateral hemidystonia. The risk of adverse effects is less than with bilateral thalamotomy, which may need to be employed when generalized dystonia is severely disabling and not responsive to pharmacotherapy.

Adolescent↗
PubMed1987

Transient dystonia as a complication of varicella.

A case of transient post-varicella lingual-mandibular dystonia is presented. This case was compared with the eight previously reported instances of involuntary movement disorders which rarely follow varicella infection.

Adolescent↗
PubMed1987

Study of movement disorders and brain iron by MR.

Heavily T2-weighted high-field MR images provide a unique opportunity for the evaluation of the extrapyramidal motor system. The images are affected by the presence of small amounts of naturally occurring paramagnetic substances--principally iron--that delineate the neostriatum (caudate and putamen), globus pallidus, red nucleus, substantia nigra, and dentate nucleus, primarily by a decrease in signal secondary to the T2* effect. Movement disorders are associated with either increased or decreased signal or both in these structures, depending on the pathologic process. In the initial evaluation of 113 patients with a variety of movement disorders, good correlation of imaging abnormalities can be made with a simplified schema of the extrapyramidal pathways and a system of classification of abnormal movements, parkinsonism/tremor, dystonia, chorea, myoclonus, and hemiballismus. Parkinsonisms are characterized by abnormalities of the cortico-ponto-cerebello-dentato-rubro-thalamo-cortico-spinal tract or the nigrostriatal tract. Dystonias are characterized by abnormalities of the neostriatum predominantly affecting the putamen. Choreas are also characterized by abnormalities of the neostriatum but predominantly affecting the caudate nucleus. Hemiballismus is characterized by lesions affecting the subthalamic nucleus or associated pathway.

Adult↗
PubMed1986

Reserpine-induced up-regulation of dopamine D2 receptors in the rat striatum is enhanced by denervation but not by chronic receptor blockade.

Compensatory increases in the density of dopamine (DA) D2 receptors in the rat striatum occur following chronic interruption of dopaminergic neurotransmission. Substantia nigra lesions, DA depletion with reserpine and D2 receptor blockade by neuroleptics increase the number of striatal D2 receptors as identified with the D2 ligand, [3H]spiperone [( 3H]SPIP). Chronic administration of haloperidol to substantia nigra-lesioned rats causes an additive increase in binding over levels obtained with one treatment alone. In this study we have found a similar response when lesioned animals are treated with reserpine. However, compensatory increases in the number of [3H]SPIP binding sites found after combined administration of reserpine and haloperidol to intact rats do not exceed levels obtained following administration of either drug alone. The data suggest that up-regulation of striatal D2 binding sites occurring after substantia nigra lesions is unique relative to other forms of up-regulation and may involve the loss of a presynaptic regulatory factor other than DA.

Animals↗
PubMed1986

Chronic treatment with bromocriptine induces behavioral supersensitivity in rats.

Chronic treatment of rotating rats with equipotent doses of the dopamine (DA) agonists apomorphine (APO), 3-(3,4-dihydroxyphenyl)-1-n-propylpyrrolidine hydrobromide (DPPP) and bromocriptine (BRO) for four weeks resulted in marked differences in rotational activity following acute administration of these agonists. Whereas chronic treatment with APO and DPPP failed to produce any significant changes in agonist-induced rotational behavior, chronic BRO treatment induced a progressive increase in rotational activity up to a mean 200% increase over controls at four weeks. These findings may, in part, explain the long-term clinical efficacy of bromocriptine in patients with Parkinson's disease.

Animals↗
PubMed1986

Correlates of early disability in Huntington's disease.

Functional disability in Huntington's disease usually results from a combination of the movement disorder, intellectual decline, and psychopathological changes, but the unique contribution of each element has never been investigated. The Shoulson-Fahn functional capacity rating scale measures independence in such daily activities as eating, dressing, and managing personal finances, and is used to stage the illness and follow its progression. To determine which problems contribute most to reduced functional capacity as the disease evolves, we reviewed the records of 48 consecutive patients who were evaluated for intellectual and emotional status and motor disability. Each patient was staged and rated for functional capacity at the time of the examinations. Thirty-three of these patients were followed over several years with repeat evaluations at 6-month intervals. Intellectual impairment and depression correlated significantly with reduced functional capacity. However, when the somatic symptoms of depression were eliminated from the analysis, its relationship to functional capacity was no longer significant. Duration of illness, motor disability, and age at onset also had little impact. Neuropsychological test performance and functional capacity deteriorated over time. Our data suggest that intellectual impairment is a major factor in reducing functional capacity in the early stages of Huntington's disease.

Activities of Daily Living↗
PubMed1986

Tics in a patient with Parkinson's disease.

A patient with Gilles de la Tourette syndrome later developed Parkinson's disease in middle age. This was accompanied by a marked reduction in the frequency of tics but levodopa toxicity exacerbated the tics. The dopamine hypothesis of tic disorders is supported by this observation.

Humans↗
PubMed1986

Opioid responsiveness in patients with neuroleptic-induced akathisia.

Five patients with either acute or tardive neuroleptic-induced akathisia (5 weeks to 1 1/2 years duration) were videotaped before, during, and after a 2-week trial of propoxyphene (Darvon), 100 mg q.i.d., or acetaminophen (Tylenol) with 30 mg codeine, two tabs, q.i.d. Three "blinded" observers, experienced in movement disorders, rated the involuntary movements shown on the videotapes and agreed that, on opioids, all patients showed substantial to complete improvement of their stereotyped restless akathitic movements. Matching placebo was not beneficial. One patient who had improved on opioids was challenged with naloxone while on the opioids. There was a brief but severe reactivation of the akathisia. Our results suggest that opioids offer a selective therapy for patients with neuroleptic-induced akathisia and further suggest that the endogenous opiate system may be involved in patients with neuroleptic-induced akathisia.

Acetaminophen↗
PubMed1986

Analysis of the clinical course of non-Jewish, autosomal dominant torsion dystonia.

We have analyzed the clinical course of non-Jewish, autosomal dominant torsion dystonia in 41 patients among 15 families. The median age of onset was 8 years, with a range of 0.8-57 years. The body regions most frequently affected at the onset were the legs and arms. There was a relationship between age of onset and site of onset; at earlier ages the legs were more frequently affected, whereas at later ages, the arms and cranial structures were more frequently affected. Fifty-three percent of patients developed generalized dystonia within a median time of 1 year. Two factors strongly associated with the occurrence of generalized dystonia are: early age of onset, and onset in the legs. Our results are similar to those of prior studies of non-Jewish and Jewish patients with torsion dystonia. Whether there are clinical distinctions between the Jewish and non-Jewish forms of dystonia, as proposed in the past, must be reinvestigated in patients within the same referral base.

Adolescent↗
PubMed1986

Natural history and treatment of tardive dystonia.

We retrospectively reviewed the clinical course and response to treatment of 67 patients with tardive dystonia. The age at onset ranged from 13 to 72 years without predilection to any particular age group or sex. Patients developed tardive dystonia even after relatively short duration of exposure to dopamine antagonists (21% within one year). Five of 42 patients withdrawn from these drugs remitted. Overall clinical improvement occurred in 52% of patients. Tetrabenazine and reserpine were most effective (greater than 50% response rate) in controlling dystonia. Anticholinergic drugs diminished dystonia in 46% of patients.

Adolescent↗
PubMed1986

Pharmacologic evaluation of dopaminergic receptor blockade by metoclopramide.

The occurrence of adverse extrapyramidal effects following metoclopramide (MCP) therapy has been well documented in humans. In rats, MCP produced catalepsy and inhibited apomorphine-induced stereotypy, locomotor activity, and rotational behavior. MCP also accelerated dopamine turnover, potently stimulated prolactin release, and, at high concentrations, inhibited [3H]spiperone binding to striatal membranes. These behavioral and biochemical effects induced by MCP were similar to those observed with haloperidol. We conclude that MCP possesses most of the pharmacological properties of neuroleptic agents.

Animals↗