Computer skills in patients with movement disorders.

BACKGROUND: Electronic communication is important in healthcare, but the level of computer proficiency among patients with neurological disorders is unknown. OBJECTIVE: This study sought to determine the proportion of a movement disorder clinic population that was able to perform basic computer skills, and the effect of specific cognitive and motor features on computer proficiency. METHODS: One hundred and four movement disorder patients participated. Seventy-four completed both paper and computerized questionnaires to evaluate data entry skills and thirty subjects completed paper questionnaires only. Basic e-mail messaging and Internet skills were evaluated. Demographic information, Mini-Mental Status Examination (MMSE) score, and Hoehn and Yahr stage were assessed. RESULTS: Ninety-six percent of subjects successfully completed computerized data entry tasks, and over 70% completed e-mail and Internet tasks. Computer data entry had an average accuracy of nearly 95% when compared to paper data entry. Poorer performance on computer tasks was associated with older age, less education, and cognitive impairment. Computer performance was reduced in subjects with a history of parkinsonism and when both tremor and dyskinesia were present during task performance. Nearly three-quarters of subjects have access to a computer. Subjects who completed the paper questionnaire but refused to complete the computer questionnaire were older, less educated and more cognitively impaired. CONCLUSION: The majority of patients visiting a tertiary movement disorders center were able to perform computer data entry, e-mail messaging and Internet usage. These results reinforce the potential value of electronic communication and information systems in neurology practice.

Parkinson's disease. Diagnosis and the initiation of therapy.

Parkinson's disease (PD) is the most common cause of parkinsonism. Parkinsonism is characterized by resting tremor, bradykinesia, rigidity and gait impairment. There is no specific diagnostic test for PD and it is important for clinicians to understand the clinical signs which help to distinguish PD from parkinsonism. It is equally important to be aware of the clinical signs which can be an indication that the diagnosis is not PD. These so-called Parkinson-plus syndromes include progressive supranuclear palsy (PSP), multiple systems atrophy (MSA), corticobasal degeneration (CBD), vascular parkinsonism (VP) and parkinsonism with dementia (Lewy body dementia, LBD). The differential diagnosis of parkinsonism will be discussed. Initiating pharmacologic therapy for PD must take into consideration the degree of dysfunction the patient is experiencing, the question of neuroprotection, the degree of motor response required, and the potential complications of long-term treatment. Neuropro-tective trials of coenzyme Q10 (CoQ), vitamin C, vitamin E, monoamine oxidase B inhibitors (MAO-I) and dopamine agonists do not support the use of any of these drugs for a neuroprotective effect. There is recent supportive evidence that levodopa may have a neuroprotective effect. Either dopamine agonists or levodopa may be initiated. Dopamine agonists are associated with fewer motor fluctuations and dyskinesias, while levodopa is associated with better motor performance. Initiation of therapy should be tailored to individual patients with the emphasis on symptom control, with the hope that new approaches to treatment of PD (including neuroprotection) will be forthcoming.

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.

Pramipexole in progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disorder with no effective treatment. Dopaminergic agents occasionally produce transient symptomatic improvement. The authors report the results of pramipexole treatment (4.5 mg daily) in six patients with PSP (average disease duration, 4.4 years). Patients were treated for 2 months. Patients were evaluated with the Unified Parkinson's Disease Rating Scale, Hoehn and Yahr stage, and Schwab and England Activities of Daily Living Scale at baseline and 2 months. Pramipexole was not efficacious for the symptoms of PSP.

Psychosis as the initial manifestation of adult-onset Niemann-Pick disease type C.

Niemann-Pick disease type C (NPC) is a neurometabolic genetic disorder that is distinguished from Niemann-Pick disease by its later onset, more insidious progression, variable visceromegaly, and abnormalities of intracellular cholesterol metabolism. We describe a patient who presented with an 8-year history of psychosis requiring chronic neuroleptic therapy for a presumed diagnosis of schizophrenia. He was subsequently diagnosed with NPC as the emerging features of dementia, ataxia, dysarthria, and vertical supranuclear ophthalmoplegia were recognized. The characteristic features of adult-onset NPC and the obstacles to early diagnosis are reviewed.

Methylphenidate-induced chorea: case report and pharmacologic implications.

In a child with minimal brain dysfunction, we found that chorea was related to the major central effect of methylphenidate and probably to the effect of the drug on central catecholaminergic systems. Also, after 3 weeks of treatment with methylphenidate, guinea pigs showed a hypersensitive response to apomorphine, suggesting that chronic administration of methylphenidate leads to hypersensitivity of receptor sites. Chorea beginning shortly after initiation of methylphenidate therapy probably is related to the central dopaminergic effect of the drug; when choreic movements appear after chronic methylphenidate administration, altered responsiveness of striatal dopamine receptor sites may be responsible.

The effect of levodopa, lergotrile, and bromocriptine on brain iron, manganese, and copper.

Chronic administration of a levodopa-carbidopa combination, bromocriptine, or lergotrile produced alterations of essential metal concentrations in the guinea pig caudate nucleus, frontal cortex, and cerebellar hemisphere. All long-term treatment regimens resulted in significantly increased concentrations of manganese in all brain areas, and these same regimens resulted in almost universally decreased copper concentrations. Since the long-term administration of these dopamine agonists in man results in extrapyramidal dysfunction, these observations suggest that alterations of trace metal concentrations in the brain may be related to the chronic toxicity of these dopamine agonists.

Elderly inpatients: postural reflex impairment.

We examined postural reflexes in 50 patients in a geriatric care facility. Patients aged 60 years and older who did not have orthostatic hypotension were subjected to a standing postural perturbation, and the degree of postural instability was recorded. Sixteen patients with leg amputations, recent stroke, and leg deformities were excluded. Of the remaining 34 patients, 44% had severe postural reflex impairment, and 24% had moderate impairment. Although the etiology for postural reflex impairment may be multivariant, the high percentage suggests that postural reflex dysfunction may be an important cause of unexplained falls in the elderly.

Meige syndrome (blepharospasm-oromandibular dystonia) after long-term neuroleptic therapy.

Two patients developed either blepharospasm or blepharospasm-oromandibular dystonia following chronic therapy with chlorpromazine, haloperidol, or thioridazine. In one patient, appearance of the movement disorder was associated with neuroleptic withdrawal, and in the other patient, the movement disorder began while neuroleptic therapy continued. Because of the age of one patient and the severe intermittent psychosis in the other, these Meige-like symptoms were attributed to chronic neuroleptic use rather than to spontaneously occurring Meige syndrome. The symptoms occurring as part of a tardive dyskinesia suggest that dopaminergic mechanisms play a role in idiopathic Meige syndrome.

Amantadine-induced peripheral neuropathy.

We report a 48-year-old woman with a 17-year history of PD who developed a peripheral sensory-motor neuropathy secondary to chronic administration (8 years) of amantadine. Discontinuation of amantadine resulted in resolution of trophic skin ulcers, paresthesias, and distal weakness. Amantadine may be hazardous to patients with severe and chronic livedo reticularis.

Cognitive impairments associated with early Parkinson's disease.

We administered a battery of cognitive tests to 41 recently diagnosed Parkinson patients and 41 controls to assess the early neuropsychological changes associated with Parkinson's disease (PD). Parkinson subjects did as well as controls on tasks assessing attention and select language and visuospatial measures. However, PD subjects did significantly worse on embedded figures, facial recognition, proverbs, and verbal and figural memory measures, and made more perseverative responses on a set shifting task. A discriminant function of measures of proverbs, embedded figures, and memory accounted for 22% of the variance between groups. These data suggest that the cognitive changes in early PD are more pervasive than originally described and may reflect the onset of a more widespread pathologic process.

Levodopa, melanoma, and Parkinson's disease.

Previous reports and the Physicians' Desk Reference caution against the use of levodopa in Parkinson's disease (PD) patients with melanoma. A critical review of the literature reveals only anecdotal evidence to support a link between levodopa and melanoma. In fact, levodopa has an antitumor effect on melanoma. We report nine patients with PD and melanoma who were treated with levodopa/carbidopa (L/C). Current evidence suggests that L/C can be used safely in PD patients with a history of melanoma.

HIV encephalitis presenting with severe generalized chorea.

We report a case of rapidly progressive encephalopathy and generalized chorea due to HIV encephalitis. The patient was a 24-year-old man known to be HIV-seropositive for 4 years. The severity of the movement disorder resulted in rhabdomyolysis. Sepsis developed and he died after a 21-day hospitalization. Pathologic study revealed prominent neuronal loss and gliosis of subcortical regions. Acute encephalopathy with generalized chorea may be a rare consequence of HIV encephalitis.

Dopaminergic antagonism of L-5-hydroxytryptophan-induced myoclonic jumping behavior.

We studied the effect of dopamine agonists (levodopa, apomorphine, lergotrile, and M-7 [2(dimethylamino)5,6-dihydroxytetralin] on myoclonic jumping behavior in young male guniea pigs. All these agents had a significant antagonistic effect on the frequency of this serotonin-mediated behavior. The duration of the antagonism corresponded in all cases to the duration of stereotyped chewing behavior induced by these agents alone. The dopamine antagonist haloperidol potentiated jumping behavior. Therefore myoclonic jumping behavior is influenced by dopaminergic mechanisms, and this behavior may be the result of interaction between dopaminergic and serotonergic activity. The role of dopaminergic mechanisms in human myoclonic disorders needs further clarification.

Sydenham chorea: an update.

To document possible changing characteristics of Sydenham chorea, we reviewed records of 240 patients with this diagnosis who were seen between 1951 and 1976. A dramatic progressive decline in the number of cases was observed. The syndrome occurred mainly in childhood. Female predominance was apparent only after the 10. There was a high femilial incidence for both chorea and rheumatic fever. Most patients had generalized chorea, and fewer than 20% had hemichorea. Dysarthria, probably of extrapyramidal origin, was frequent but neurologic abnormalities other than diffuse encephalopathy were rare. One-third of the patients had coexisting heart disease. Repeat attacks of Sydenham chorea occurred, but the recurrence rate was much less than noted in previous studies.

Drug holiday and management of Parkinson disease.

Chronic treatment of parkinsonism with levodopa or levodopa/carbidopa is associated with problems that include dyskinesia, on-off phenomena, hallucinosis, and possible loss of therapeutic efficacy. We studied the effects of a period of transient drug withdrawal (drug holiday) in 16 patients who manifested these complications of chronic levodopa therapy. Patients were evaluated daily before, during, and after the period of drug withdrawal. Eleven of the 16 patients exhibited enhanced motor responsiveness after the holiday and required only half of the initial daily dose for improved motor performance. Most levodopa-induced side effects decreased after the holiday. Hallucinosis was ameliorated in all cases. The frequency of on-off phenomena and myoclonus also diminished. Sensitivity to levodopa-induced dyskinesia was not affected by the drug holiday. Because most patients required lower dosage after the holiday, dyskinesias were no longer present. These observations suggest that parkinsonian patients who suffer complications of chronic levodopa therapy may benefit from a period of drug withdrawal.

Bromocriptine-induced behavioral hypersensitivity: implications for the therapy of parkinsonism.

Bromocriptine (CB-154) is a direct-acting dopamine agonist of proven clinical efficacy in parkinsonism. The capacity of bromocriptine to induce receptor site hypersensitivity was investigated utilizing a behavioral model in guinea pigs. Following 4 weeks of bromocriptine treatment, animals demonstrated a subsequent long-lasting hypersensitivity to amphetamine and apomorphine. The data suggest that chronic use of bromocriptine can induce receptor site hypersensitivity. These results may be an indication that, because of a similar propensity to side effects during chronic therapy, direct-acting dopamine agonists will offer no long-term advantage over current antiparkinsonian drugs. The observed phenomena suggest that chronic dopaminergic agonism may not be an ideal therapy for parkinsonism.

Lergotrile in the treatment of parkinsonism.

Lergotrile mesylate, a direct-acting dopamine agonist, was administered for up to 10 months to 25 patients with Parkinson disease. Of six patients not receiving levodopa concurrently, five showed definite improvement in parkinsonian signs and symptoms. These results are the first clear indication that lergotrile is efficacious, independently of any interaction with levodopa, in the treatment of Parkinson disease. The drug was also effective in relieving some complications of long-term levodopa therapy. Lergotrile was more effective in alleviating on-off problems than in reversing loss of levodopa efficacy. Side effects of lergotrile included exacerbation of hallucinations, dyskinesias, hypotension, and alterations in liver function tests.

Amphetamine-induced hypersensitivity in guinea pigs.

Chronic administration of d-amphetamine to young guinea pigs results in an increased behavioral response to this drug. After 6 months of daily amphetamine exposure, animals demonstrated behavioral hypersensitivity and developed full amphetamine-induced stereotyped behavior with decreased latency. The data suggest that chronic agonism with amphetamine can produce dopaminergic hypersensitivity, a behavior that contrasts with the development of drug tolerance to other pharmacologic agents. The mechanism of this induced hypersensitivity was studied by comparing brain amphetamine levels after acute and chronic amphetamine treatment. The two groups of guinea pigs showed no significant difference in amphetamine levels or drug distribution. These results suggest that altered amphetamine metabolism cannot account for the hypersensitivity seen after amphetamine exposure. Guinea pigs chronically pretreated with d-amphetamine were hypersensitive to another dopaminergic agonist whose metabolic pathway is distinct from that of amphetamine. These results have therapeutic implications in the management of clinical conditions related to chronic agonist-induced hypersensitivity.

Chorea induced by oral contraceptives.

A rare complication of oral contraceptive therapy is the induction of chorea. We here describe five cases of chorea in patients receiving low- or high-dose estrogen-containing contraceptives. All patients were nulliparous, young (average age 19 years), and became symptomatic shortly (average of 5 weeks) after initiation of contraceptive therapy. Two patients previously suffered an episode of Syndenham chorea; one experienced chorea in the course of Henoch-Schönlein purpura; and two had a history of congenital cyanotic heart disease without chorea. Dyskinesia resolved in all patients upon discontinuing the medication. Patients with preexisting striatal abnormalities appear more susceptible to oral contraceptive-induced chorea which is reversible on drug discontinuation. The mechanism of oral contraceptive-induced chorea is unknown, but clinical and experimental data suggest that it involves altered central dopaminergic activity.

PIP: It is known that chorea is a rarely-occurring complication of oral contrceptive therapy. 5 case histories of chorea in patients receiving either low- or high-dose estrogen-containing contraceptives are reviewed. All the patients were young and nulliparous. They developed the symptoms within an average of 5 weeks after therapy initiation. Dyskinesia ceased upon cessation of the oral contraceptive therapy. A summary of 17 previously-reported cases of oral contraceptive-associated chorea is also presented in tabular form. These cases plus the 5 reviewed in this paper suggest that chorea arises in women with abnormalities of the basal ganglia of various etiologies and will probably not occur in normal individuals. Studies with animals have indicated that female sex hormones may enhance central dopaminergic sensitivity, bringing on chorea in oral contraceptive patients. In the 3 of 5 patients here described who had previously experienced an episode of chorea, the contraceptive-induced disorders, i.e., asymmetries, orofacial involvement, and personality changes, were similar to the original movement disorders. The other 2 cases studied here had not experienced a chorea episode but did have a history of neonatal cyanosis.