Amphetamine-induced dopaminergic hypersensitivity in guinea pigs. Implications in psychosis and human movement disorders.

Following chronic amphetamine pretreatment, guinea pigs demonstrate an increased sensitivity to both d-amphetamine sulfate- and apomorphine hydrochloride-induced stereotyped behavior. This observation suggests that chronic exposure to high doses of a dopamine agonist (d-amphetamine) alters the response of the brain to the subsequent administration of both indirect (d-amphetamine) and direct (apomorphine) dopamine agonists. This altered response may be due to the development of dopamine receptor site hypersensitivity. Clinical evidence suggests that a similar agonist-induced hypersensitivity may play a role in the development of dyskinetic movement disorders and psychoses in humans following the chronic use of such dopamine agonists as amphetamine and levodopa.

Physostigmine for cardiac and neurologic manifestations of phenothiazine poisoning.

Psychotropic drugs such as the phenothiazine neuroleptics and tricyclic antidepressants are known to cause electrocardiographic abnormalities as well as a central anticholinergic syndrome. Physostigmine is known to reverse the central muscarinic anticholinergic manifestations by inhibition of the enzyme cholinesterase. An unusual case of trifluoperazine overdose, in which the patient presented with cardiac arrhythmias and a central anticholinergic syndrome, is presented. Treatment with physostigmine reversed the central anticholinergic syndrome as well as the electrocardiographic abnormalities. Effects of phenothiazines on altering cardiac status are also discussed.

Reversal of tricyclic-overdosage-induced central anticholinergic syndrome by physostigmine.

Although there is evidence that the delirium, stupor, coma, and seizure-like activity seen in overdosage with tricyclic antidepressants and antiparkinson drugs are due to the central anticholinergic activity of these agents, patients with overdosage of these drugs are still frequently misdiagnosed. The authors present a case of reversal of anticholinergic-drug-induced prolonged coma, myoclonus, and choreoathetosis by physostigmine. This report supports the anticholinergic basis of the clinical manifestations of such overdosages, provides information on the role of acetylcholine and dopamine in psychiatric and movement disorders, and illustrates dramatically the need for accurate diagnosis and treatment.

Levodopa-induced psychosis: a kindling phenomenon.

Of 88 patients with idiopathic Parkinson's disease, without prior psychotic symptoms, and without significant dementia, nearly half had experienced vivid dreams, hallucinations, illusions, and nonconfusional as well as confusional psychoses as side effects of chronic levodopa therapy within the previous year of treatment. It was found that 61.3% of all hallucinations were associated with preexistent or concurrent vivid dream phenomena, that all psychotic states were associated with preexistent or concurrent vivid dreams and/or hallucinations, and that nonconfusional psychotic states tended to become confusional. These findings raise the possibility that chronic levodopa therapy may result in dopaminergic kindling and support the hypothesis that chronic dopaminergic agonism may, via such a kindling mechanism, play a role in the development of some types of psychoses.

Tardive dyskinesia: review and update.

Tardive dyskinesia is an extrapyramidal syndrome associated with the chronic administration of major neuroleptic agents. The pathogenesis of the disorder appears to relate to chronic striatal dopaminergic receptor site blockade; the pathophysiology of tardive dyskinesia appears to relate to the resultant denervation hypersensitivity. Agents that deplete the brain of dopamine are the mainstay of therapy for tardive dyskinesia. Cholinergic agents that potentially modulate the balance between dopamine and acetycholine in the striatum offer possible additional therapeutic options. Clearly, resumption of neuroleptic therapy is treatment with the presumed pathogenic agent and is to be avoided whenever possible.

Pharmacology of hallucinations induced by long-term drug therapy.

The authors studied 20 patients with Parkinson's disease and prominent hallucinations related to dopaminergic or anticholinergic therapy. The character of the hallucinations appeared distinct from the classic description of either acute anticholinergic or acute aminergic hallucinatory states. Manipulation of either kind of drug could precipitate or relieve hallucinations in a given patient, which suggests that the dopaminergic/cholinergic systems are reciprocally active in the pathophysiology of long-term drug-induced hallucinatory states in this population.

Recurrence of childhood multiple tic in late adult life.

In contrast to the lifelong persistence of symptoms characteristic of Gilles de la Tourette's syndrome, multiple tic of childhood is considered to be a self-limited disorder that remits by early adulthood. We describe four patients who had a history of multiple tic of childhood, complete absence of tics throughout most of their adult lives, and recurrence of tics in late adult life. All four had multiple tics that began before the age of 9 years and included both motor and vocal tics that changed in location and severity over time. None of the patients exhibited coprolalia. All tics subsided before the age of 20 years, only to recur after the age of 60 years, once again including both motor and vocal tics that changed in location and severity slowly over time. The one patient who was severely bothered by the recurrence of motor and vocal tics responded well to haloperidol. Although they do not fit into any accepted diagnostic category for multiple tic, these patients suggest that multiple tic of childhood can recur in adult life. This suggests that Gilles de la Tourette's syndrome may be a continuum for chronic multiple tic of childhood to full-blown classic Gilles de la Tourette's syndrome.

Meiges disease: a clinical form of facial convulsion, bilateral and medial.

In 1910 the French neurologist Henry Meige described in detail a disorder characterized chiefly by symmetric dystonic spasms of the facial muscles, which he called "spasm facial median." Cases with this disorder are rare, and frequently misdiagnosed and inappropriately treated. We report here a translation of Meige's original description of "spasm facial median." We hope that this translation will make it easier to recognize and diagnose this disorder and that it will stimulate greater interest in this unusual syndrome.

Levodopa-induced myoclonus.

Twelve parkinsonian patients on long-term levodopa therapy developed intermittent, myoclonic body jerks. The movements consisted of single unilateral or bilateral abrupt jerks of the extremities and occurred most frequently during sleep. Although directly related to daily dosage of levodopa, the myoclonus was specifically blocked by the serotonin antagonist, methysergide. Levodopa-induced myoclonus may be related to intermittent increases of activity of serotonin in the brain and results from levodopa-induced dysregulation of serotonin activity.

Dystonic foot response of Parkinsonism.

One third of a patient population with idiopathic parkinsonism was found to suffer from debilitating, painful dystonic movements of the lower extremities. The prevalence of this involuntary movement disorder was found to be positively correlated with the duration of dopaminergic treatment, but it also occurred occasionally in untreated persons. We suggest that the "dystonic foot response of parkinsonism" is a distinct clinical entity that has no localizing value in frontal lobe disorders and is associated with extrapyramidal disease. This disorder, though exacerbated by dopaminergic therapy, also differs from well-accepted dopaminergic side-effects and does not predictably respond to manipulation of antiparkinsonian medications. Although the precise pathophysiology of this movement disorder is unknown, its response to baclofen therapy suggests that neurotransmitter systems other than cholinergic or dopaminergic ones may be implicated.

Paradoxial response to dopaminergic agents in parkinsonism.

A patient with the classical stigmata of parkinsonism was treated on three separate occasions with levodopa, a combination of levodopa and carbidopa, and lergotrile mesylate, a direct-acting dopamine-receptor agonist. All three treatment regimens resulted in dose-related increases in parkinsonian features. To our knowledge, this response has not been previously described. Lergotrile did not alter CSF homovanillic acid concentration. It is suggested that this rare paradoxical motor response to dopaminergic agents may be associated with dysfunction of the postsynaptic dopamine receptor site.

Pergolide in Parkinson's disease.

Twenty-two patients received pergolide mesylate for Parkinson's disease for one year. Improvement was maximal at six months, but average functional scores were still better at 12 months than at pretreatment evaluation. On-off fluctuations were reduced in severity, and two of 18 patients experienced full resolution. Pergolide is an effective and safe ongoing medication for Parkinson's disease.

Fluphenazine and multifocal tic disorders.

In a five-year study, 21 patients with multiple tic disorder intolerant of haloperidol therapy were treated with fluphenazine hydrochloride. Sixteen of these patients had fewer side effects with fluphenazine and had either equivalent (five patients) or better (11 patients) tic control. Fluphenazine can be an effective treatment for multiple tics in patients with dose-limiting side effects related to haloperidol.

A pure parkinsonian syndrome following acute carbon monoxide intoxication.

A 50-year-old woman with carbon monoxide (CO)-induced parkinsonism was found to have bilateral lucencies of the globus pallidus on computed tomographic (CT) scan consistent with old necrotic lesions. She showed no clinical response to levodopa therapy, although she did improve with anticholinergic therapy. It is suggested that the parkinsonism in this patient is due to the pallidal lesions demonstrated on CT scan, and that such pallidal-related parkinsonism may not respond to dopaminergic therapy.

Autologous transplantation of adrenal medulla in Parkinson's disease. 18-month results.

Eighteen of 19 patients who underwent autologous adrenal medullary transplantation to the right caudate nucleus have been followed up for 18 months. During the course of this study, a statistically significant improvement was noted in percent "on" time, percent "on" time without dyskinesia, activity of daily living (ADL) scores during the "on" stages, and ADL, motor, and Schwab-England scores during the "off" stages. Benefits tended to be maximal at 6 months and to gradually lessen thereafter, although statistically significant improvement in comparison with baseline was still present at 18 months for ADL, motor, and Hoehn-Yahr scores during the "off" stages. Almost all parameters had deteriorated by 18 months compared with 12 months, including those remaining significantly improved in comparison with baseline. These patterns were similar for each of the three participating centers. Complications were largely restricted to the perioperative period.

Hemiparkinsonism as a late complication of hemiatrophy: a new syndrome.

Four men with evidence of hemiatrophy resulting from early-life hemispheral injury developed unilateral hemiparkinsonism on the side of the hemiatrophy. The parkinsonism began in the fourth decade and has remained unilateral for 5 to 35 years. In all four patients, the parkinsonism was slowly progressive, but the clinical response to levodopa was minimal, suggesting that the parkinsonism might have a postsynaptic striatal component. The clinical similarities of these four patients suggest that this is a distinct syndrome in which hemiparkinsonism is a late sequela of hemiatrophy. Identification of this syndrome has prognostic significance, because it seems to have a stereotyped course, remaining unilateral and only slowly progressive.

Prevalence of spontaneous lingual-facial-buccal dyskinesias in the elderly.

The prevalence of spontaneous lingual-facial-buccal movements was determined in 661 patients between the ages of 50 and 79 without neuroleptic exposure or known CNS disease. The prevalence was 0.8% between ages 50 and 59, 6% between ages 60 and 69, and 7.8% between ages 70 and 79.

On the mechanism of sudden death in Moersch-Woltman syndrome.

A patient dying in the hospital with Moersch-Woltman Stiff-person syndrome (MWS) suffered from episodic, severe, uncompensated metabolic acidosis. Possible explanations for the acid-base abnormalities in this neurologic disorder are proposed.

Deanol in the treatment of levodopa-induced dyskinesias.

Levodopa-induced dyskinesias frequently limit the clinical efficacy of levodopa therapy in Parkinson's disease. Deanol recently has been reported to be of value in relieving the dyskinesias by acting through a central cholinergic mechanism. Seventeen outpatients with levodopa-induced dyskinesias were given deanol in dosages of 300 to 900 mg per day. The dyskinesias improved in four of the patients, remained unchanged in five, and worsened in eight. In all four patients who showed improvement after institution of deanol therapy, the improvement continued after the patients were switched to a placebo. One of these patients also demonstrated improvement in his parkinsonism, while two others experienced a worsening in their parkinsonism. Deanol does not appear to be effective in the treatment of levodopa-induced dyskinesias.

Calcification of the basal ganglia as a cause of levodopa-resistant parkinsonism.

We present a patient with levodopa-resistant parkinsonism due to basal ganglia calcification related to surgically-induced hypoparathyroidism. The calcification was seen on computerized axial tomography but not on skull x-rays. Such calcification should be looked for in all cases of levodopa-resistant parkinsonism, since it is possible that treatment of hypoparathyroidism may halt progression of the disease. This case with similar ones from the literature suggest that striatal disease itself can cause parkingonism and that the parkinsonism in such patients tends to be less responsive or nonresponsive to levodopa.