Acute and reversible parkinsonism due to organophosphate pesticide intoxication: five cases.

OBJECTIVE: To describe five patients who developed acute and reversible parkinsonism following organophosphate (OP) pesticide exposure, and to consider whether this syndrome represents a rare sequela of such exposure in genetically susceptible individuals. BACKGROUND: Several toxins are known to produce parkinsonism following acute exposure. Although case-control studies have implicated OP pesticides in the etiology of PD, acute parkinsonism following brief pesticide exposure has never been reported. METHODS: The authors describe the clinical syndrome affecting five patients who presented with recent OP exposure and symptoms of an acute akinetic-rigid syndrome. RESULTS: All patients developed parkinsonism that resembled PD clinically except for poor response to levodopa. Three genetically related patients were exposed to pesticides in a common environment before onset of parkinsonism; other family members remained unaffected. Other secondary causes of parkinsonism were excluded. Four patients recovered completely without treatment, and one patient was lost to follow-up. One patient experienced repeated episodes of parkinsonism with inadvertent reexposure to a pesticide-contaminated environment. CONCLUSION: The clinical course of these five patients suggests their syndrome represents a heretofore undescribed toxic effect of OP pesticides. Our observations strengthen epidemiologic studies implicating OP pesticides in the etiology of PD. A genetic susceptibility to OP pesticide-induced parkinsonism may account for three family members developing this syndrome.

Paroxysmal exercise-induced dystonia: eight new sporadic cases and a review of the literature.

We report eight new sporadic cases of paroxysmal dystonia induced by prolonged or sustained exercise and review an additional seven previously reported cases. The attacks in our patients lasted from a few minutes to up to 2 h, and patient age at onset ranged from 2 to 30 years. Four of the eight patients had hemidystonic attacks, both legs were involved in two other cases, and the remaining two patients had involvement of the right foot only. We propose that such cases should be classified as paroxysmal exercise-induced dystonia.

Evidence for a dopaminergic deficit in sporadic amyotrophic lateral sclerosis on positron emission scanning.

Although rare, the chronic neurodegenerative disorders amyotrophic lateral sclerosis (ALS) and idiopathic parkinsonism coexist to a greater degree than expected by chance. This suggests that patients with ALS may have subclinical lesions of the nigrostriatal dopaminergic pathway. To study this hypothesis, we did positron emission tomography with 6-fluorodopa on 16 patients with sporadic ALS and without extrapyramidal disease, and compared the results with age-matched controls. We found a significant progressive fall in 6-fluorodopa uptake with time since diagnosis, and reduced dopaminergic function in 3 patients with ALS of long duration. This supports the hypothesis that ALS and IP may share pathogenesis and, perhaps, aetiology.

The causalgia-dystonia syndrome.

We report 18 patients (16 women and two men) with causalgia and dystonia, triggered by peripheral injuries in 15 cases and occurring spontaneously in three. The injury was often trivial, and did not cause overt peripheral nerve lesions. The mean age at presentation was 28.5 years. None had a family history of dystonia. The leg was affected initially in 12 patients, the arm in the remaining six cases. All had burning pain, allodynia and hyperpathia, along with vasomotor, sudomotor and trophic changes. All developed dystonic muscle spasms in the affected part. Dystonia always appeared at the same time or after the causalgia. The spasms were typically sustained, producing a 'fixed' dystonic posture, in contrast to the mobile spasms characteristics of idiopathic torsion dystonia. There was spread of the causalgia and of the dystonia from its initial site both in the affected limb and to other extremities, the latter in hemiplegic, transverse and triplegic distribution. All investigations were normal. All modes of conventional treatment failed to relieve either the pain or the dystonia, but two patients recovered spontaneously. At present it is impossible to decide whether this distressing syndrome is a true functional disorder of the central nervous system, or is of psychogenic origin.

Time course of postanoxic akinetic-rigid and dystonic syndromes.

Twelve previously normal patients with anoxic brain damage due to various causes are described. The mean age at anoxia was 27.4 years. Six patients, in their fourth decade or older, developed an early akinetic-rigid syndrome; the mean interval between anoxia and akinetic-rigid syndrome was 3.1 months (range, less than 1 week to 12 months). Four of these six patients also developed dystonia, usually after some months. Six other patients, all children or young adults, developed a pure dystonic syndrome; the mean interval between anoxia and dystonia was 9.7 months (range, 1 week to 36 months). Dystonia was generalized and progressed over a mean period of 21.9 months (range, 3 to 96 months). Severe bulbar involvement was common. Age determined whether an akinetic-rigid or a dystonic syndrome developed in our patients and those reported in the literature. Many, but not all, patients had lesions on brain imaging (or at autopsy). In those with visible lesions in the basal ganglia, those with dystonia tended to have damage in putamen, while those with an akinetic-rigid syndrome tended to have damage in the globus pallidus. There were exceptions.

Rapidly progressive autosomal dominant parkinsonism and dementia with pallido-ponto-nigral degeneration.

We describe a family with nearly 300 members over 8 generations with 32 affected individuals who have an autosomal dominant neurodegenerative disease characterized by progressive parkinsonism with dystonia unrelated to medications, dementia, ocular motility abnormalities, pyramidal tract dysfunction, frontal lobe release signs, perseverative vocalizations, and urinary incontinence. The course is exceptionally aggressive; symptom onset and death consistently occur in the fifth decade. Positron emission tomographic studies with [18F]6-fluoro-L-dopa (6FD) were performed in 4 patients and 7 individuals at risk for development of the disease. All affected subjects had markedly reduced striatal uptake of 6FD (p less than 0.001). All individuals at risk had normal striatal uptake, but high 6FD uptake rate constants were noted in 3 of the 7 studied. Autopsy findings revealed severe neuronal loss with gliosis in substantia nigra, pontine tegmentum, and globus pallidus, with less involvement of the caudate and the putamen. There were no plaques, tangles, Lewy bodies, or amyloid bodies. This kindred appears to represent a neurodegenerative disease not heretofore described. We propose the following name for this new genetic disease: autosomal dominant parkinsonism and dementia with pallido-ponto-nigral degeneration.

Bilateral striopallidodentate calcinosis: cerebrospinal fluid, imaging, and electrophysiological studies.

We report the genetic, clinical, electrophysiological, and imaging studies in a family with bilateral striopallidodentate calcinosis (Fahr's disease). The intracerebral calcium deposits occurred before onset of the symptoms in the third decade of life. Progressive neurological deterioration occurred in the fifth decade of life in the proband. Cerebrospinal fluid homocarnosine, a central nervous system-specific peptide, was increased twofold in patients with autosomal dominant bilateral stripallidodentate calcinosis; in sporadic cases, there was no detectable homocarnosine and a decreased level of histidine. With advancing age, the amount of calcification increases, but it has not been determined if a critical amount must be reached before symptoms occur. Computerized tomography is superior to magnetic resonance imaging for radiological diagnosis. Despite diffuse striatal calcification, striatal 6-[18F]fluoro-L-dopa uptake did not reveal any difference between patients and control subjects, from which we infer persisting integrity of the nigrostriatal dopaminergic pathway.

Pleuropulmonary disease associated with dopamine agonist therapy.

Artificial dopamine agonists are widely employed for the treatment of idiopathic parkinsonism. Pleuropulmonary disease has previously been reported to occur with the use of bromocriptine and mesulergine. We report similar adverse effects induced by the newer agonists lisuride and cabergoline. All these agents are tetracyclic ergot derivatives. This suggests a causal link between ergot-derived dopamine agonists and pleuropulmonary disease.

Positron emission tomography suggests that the rate of progression of idiopathic parkinsonism is slow.

We performed sequential positron emission tomography scans with 6-[18F]fluoro-L-dopa in 9 patients with idiopathic parkinsonism and 7 age-matched normal control subjects to compare changes in the nigrostriatal dopaminergic pathway over time. The mean interval between the scans was 3.3 years for the group with idiopathic parkinsonism and 3.9 years for the control subjects. The scans were analyzed by calculating the ratio of striatal to background radioactivity. Both groups showed statistically significant reductions of striatal uptake over the interval. The rate of decrease was almost identical in each group (p = 0.6). We infer that the usual rate of loss of integrity of the dopaminergic nigrostriatal pathway in patients with idiopathic parkinsonism is slow and the rate of change between the two groups was comparable.

Positron emission tomography in progressive supranuclear palsy.

Positron emission tomography with 6-[18F]fluoro-L-dopa (6-FD) provides in vivo information on the function of nigrostriatal dopaminergic neurons. We used 6-FD and positron emission tomography to investigate the integrity of the nigrostriatal system in seven patients with progressive supranuclear palsy. All patients had axial hypertonia, vertical gaze palsy, and parkinsonian features. Dementia, pyramidal signs, and ataxia were seen in varying proportions. We analyzed the scans with a graphic method to calculate a steady-state 6-FD uptake rate constant for the whole striatum. Results were compared with those obtained in seven age-matched controls. As a group, the patients with progressive supranuclear palsy had reduced 6-FD uptake constants. The 6-FD uptake constant correlated inversely with the duration of the disease. Normal positron emission tographic findings in one patient with the shortest duration of symptoms suggests that in early progressive supranuclear palsy, parkinsonism may relate to dysfunction distal to the dopaminergic neurons.

Treatment of spasticity with botulinum toxin: a double-blind study.

We studied the effect of botulinum-A toxin on spasticity of the leg adductors in 9 patients who were either chair-bound or bed-bound with chronic stable multiple sclerosis. We injected botulinum toxin (400 mouse units) or placebo into the adductor muscles in a randomized, crossover, double-blind design. Two physicians, who were unaware of the treatment order, used an objective rating scale and independently assessed the patients; interobserver correlation was excellent (r = 0.93-0.81). We found that botulinum toxin produced a significant reduction in spasticity (p = 0.009) and a significant improvement in the ease of nursing care (p = 0.009). There were no adverse effects during this short-term trial. This is the first demonstration of the beneficial effect of botulinum toxin on focal spastic muscle contractions.

Positron emission tomography in Shy-Drager syndrome.

We studied the nigrostriatal dopaminergic pathway in 3 patients with Shy-Drager syndrome, by using positron emission tomography and [18F]6-fluoro-1-dopa to determine whether their parkinsonism correlated with impaired functional integrity of the presynaptic nigrostriatal pathway. One patient had short duration of disease, mild parkinsonism, and a normal positron emission tomographic scan, suggesting pathological changes functionally distal to the nigrostriatal pathway. Two patients with longer duration of disease had more severe parkinsonism and reduced [18F]6-fluoro-1-dopa uptake, suggesting impaired nigrostriatal dopaminergic function with progression of Shy-Drager syndrome.

Clinical neurophysiological examination of deafness associated with juvenile motor neurone disease.

Three patients with the syndrome of progressive severe deafness, associated with juvenile onset of motor neurone disease, were examined using conventional audiometry and brainstem auditory evoked response (BAER) recordings, and electrocochleographic recordings were made in two of them. Findings indicate that the deafness had resulted from loss of acoustic nerve fibers and/or sensory cells of the spiral ganglion.