Subthalamic deep brain stimulation and impulse control in Parkinson's disease.

BACKGROUND AND PURPOSE: Experimental studies suggest that deep brain stimulation (DBS) of the subthalamic nucleus (STN) induces impulsivity in patients with Parkinson's disease (PD). The purpose of this study was to assess various measures of impulse control in PD patients with STN DBS in comparison to patients receiving medical therapy. METHODS: In a cross-sectional evaluation, 53 consecutively eligible patients were assessed for impulsivity with the Barratt Impulsiveness Scale, for impulse control disorders (ICDs) using the Minnesota Impulsive Disorders Interview, and for obsessive-compulsive symptoms using the Maudsley Obsessional-Compulsive Inventory. RESULTS: Independent samples t-tests revealed that compulsivity scores were not different between DBS patients and patients without DBS. However, impulsivity scores were significantly higher in DBS patients. Additionally, ICDs were observed in 3 of 16 (19%) DBS patients and in 3 of 37 (8%) medically treated patients. No association was found between the use of dopamine agonists and impulsivity in DBS patients. CONCLUSIONS: Our data suggest that screening for impulsivity and ICDs should be performed prior to DBS, and that patients should be monitored for these problems during follow-up. Prospective trials are needed to confirm the findings of this exploratory study and to elucidate the reasons of a possible induction of impulsivity by STN DBS.

Pharmacologic trials in the treatment of cerebellar tremor.

We studied the effect of long-term administration of propranolol hydrochloride and isoniazid and the acute action of ethyl alcohol on cerebellar tremor in patients with multiple sclerosis and primary cerebellar degeneration in a placebo-controlled double-blind crossover test. None of the drugs decreased the severity of either static or kinetic cerebellar tremors.

Dose-response relationship of propranolol in the treatment of essential tremor.

The effect of doses of propranolol hydrochloride, 80 to 800 mg/day, was investigated in 15 patients with essential tremor. The dose was increased by 80 mg weekly. Tremor was recorded by an accelerometer and its amplitude and frequency was determined by spectral analysis. Serum propranolol level was measured by radioreceptor assay. Tremor control varied greatly from complete suppression at 80 mg/day to no reduction at 800 mg/day. Mean serum propranolol levels increased with increasing dosage, but they did not correlate with tremor suppression. Five patients did not tolerate doses higher than 640 mg/day. Maximum tremor suppression occurred within a dose range between 160 and 320 mg/day. Higher doses did not cause additional tremor reduction.

Pharmacologic treatment of parkinsonian tremor.

The relative efficacy of trihexiphenidyl hydrochloride, amantadine hydrochloride, and low-dose carbidopa-levodopa in reducing parkinsonian tremor was investigated using objective techniques. Trihexiphenidyl and carbidopa-levodopa decreased tremor by greater than 50%. Some patients responded to one drug but not to the other. Amantadine decreased tremor less than 25%. Monotherapy with trihexiphenidyl or carbidopa-levodopa should be the initial treatment for the tremor of Parkinson's disease.

Dysfluency (stuttering) in extrapyramidal disease.

Acquired stuttering in the adult is rare and is usually associated with trauma or vascular disease. A recent patient had adult-onset dysfluency, and, subsequently, signs of progressive supranuclear palsy developed. A review of cases of extrapyramidal disease identified five parkinsonian patients with stutteringlike behavior. Dysfluencies were of slow onset and were an early symptom. Speech was characterized by repetitions/prolongations on initial syllables, which occurred on both small grammatical and substantive words. Dysfluency was found mostly in self-formulated speech. There was a positive adaptation effect. No secondary motor symptoms occurred and behavioral response to dysfluency was minimal. Speech characteristics of dysfluency associated with extrapyramidal disease differ from both developmental dysfluency and acquired dysfluency secondary to vascular or traumatic insults. In patients with adult-onset stutteringlike dysfluencies it is important to consider extrapyramidal disease.

Adjuvant therapy of parkinsonian tremor.

The effect of long-acting propranolol hydrochloride (160 mg/d), primidone (250 mg at night), and clonazepam (4 mg/d) on the resting, postural, and kinetic component of tremor was investigated in ten parkinsonian patients in a double-blind crossover design. Tremor was assessed by patient opinion, clinical scoring, and accelerometer recordings. The amplitude and frequency of tremorgrams were determined by spectral analysis. Most patients preferred long-acting propranolol and chose to continue taking the drug. The mean clinical score for resting and postural tremor was significantly decreased by long-acting propranolol but not by primidone or clonazepam. Long-acting propranolol reduced the mean amplitude of resting tremor by 70% and the mean amplitude of postural tremor by 50%. Mean tremor amplitudes were not changed by primidone or clonazepam. Tremor frequency was unaltered by the drugs. No side effects occurred with long-acting propranolol but adverse reactions were common with primidone and clonazepam. Long-acting propranolol is a useful adjuvant therapy for the tremors associated with Parkinson's disease.

Metoprolol compared with propranolol in the treatment of essential tremor.

We analyzed effects of metoprolol tartrate and propranolol hydrochloride on 23 patients with essential tremor. Tremor was assessed by patient self-evaluation, clinical scoring, and tremorgrams. Ten of 20 patients had tremor reduction with propranolol. Metoprolol decreased tremor in 13 of 23 patients, including three patients with asthma in whom propranolol had caused respiratory distress. Adverse reactions were infrequent. Individual patients either responded to both propranolol and metoprolol or to neither drug. Patient age, duration of tremor, tremor frequency, family history, or response to intravenous ethyl alcohol did not distinguish responders from nonresponders.

Combined resting-postural tremors.

We studied eight patients with combined resting-postural tremors, which are classified as a subtype of essential tremor. Trihexyphenidyl hydrochloride, levodopa, and propranolol hydrochloride therapy were not effective in reducing these tremors.

Pharmacologic probe with progabide of GABA mechanisms in essential tremor.

Progabide, a gamma-aminobutyric acid agonist, was given to ten patients with essential tremor in a double-blind, placebo-controlled crossover study. The effect of progabide did not differ from that of placebo. Alterations in gamma-aminobutyric acid neurotransmission do not appear to be involved in the pathogenesis of essential tremor.

Psychogenic parkinsonism.

BACKGROUND: Parkinsonism resulting from a primary psychiatric disorder has not been well characterized previously. We had been impressed that this was a rare but definite cause of parkinsonism in patients presenting to our subspecialty movement disorders clinics. OBJECTIVE: To define the clinical characteristics of "psychogenic parkinsonism" to assist in the differentiation of these patients from those with "organic" parkinsonian disorders. DESIGN: Retrospective chart reviews of patients seen at three large movement disorders centers. PATIENTS: Seven men and seven women were diagnosed as having "documented" or "clinically established" psychogenic parkinsonism after repeated assessments. RESULTS: Tremor (12 patients) was present at rest but continued without the usual transient dampening on taking up a posture and persisted with action. Tremor frequency and rhythmicity varied markedly. Tremor could often be entrained to the frequency of other movements or subsided with distraction. Rigidity (six patients) had features of voluntary resistance, often decreasing with distraction and/or activating synkinetic movements in opposite limbs. Arm swing was usually diminished or absent on the affected side; however, the arm could be held tightly to the side or cradled in front of the patient. Slowness of movement (all 14 patients) usually lacked the typical decrementing amplitude feature of bradykinesia. The slowness, ambulatory abnormalities, and postural instability (12 patients) often had bizarre, inconsistent, or incongruous features. Functional "give-way" weakness and nonorganic sensory disturbances were common (10 patients). Spontaneous remissions and remissions with placebo treatment or psychotherapy and response fluctuations related to unusual interventions were occasionally seen (five patients). Underlying psychological factors varied considerably. Most patients had been seen by several physicians and had undergone multiple unrevealing investigations. Fluorodopa F 18 (F-dopa) positron emission tomographic scanning yielded normal findings in three patients. Abnormal positron emission tomographic scanning results in a fourth patient, whose signs and symptoms had improved with psychotherapy and haloperidol therapy, emphasizes the possibility that prominent psychogenic features may be superimposed on organic parkinsonism in some patients. CONCLUSION: Psychogenic parkinsonism occurs rarely. It is a diagnosis of exclusion that should be made only by physicians with considerable experience in the care and treatment of patients with parkinsonism.

Dapsone-induced peripheral neuropathy.

Peripheral neuropathy is a rare complication of dapsone therapy. This neuropathy appears primarily to be of the motor type, and recovery occurs on discontinuation of the drug therapy. The patient in this report developed a marked motor deficit as well as a selective marked loss of vibration sense shortly after the initiation of a relatively low dose of dapsone. Recovery was rapid on cessation of the therapy. This patient was found to be a slow acetylator of isoniazid, and therefore is probably a slow acetylator of dapsone. The possible mechanisms of the neurotoxicity of dapsone and the role of altered metabolism are discussed.

Neuropsychological impairment in Parkinson's disease with and without depression.

OBJECTIVES: To compare quantitative and qualitative aspects of neuropsychological test performance in patients with Parkinson's disease who currently had depression (PDD) and those without depression (PDN) so as to evaluate the influence of depression on cognition in Parkinson's disease. DESIGN: Cross-sectional comparisons among PDN, PDD, and normal control (NC) groups. The setting was a neurodegenerative disease research center in a teaching hospital. Groups consisted of 44 patients with PDN and 44 patients with PDD matched for age, education, gender, age at onset of disease, disease duration, and disease severity; a group of 44 NC subjects matched for age, education, and gender; and a second set of comparisons between 15 patients with PDN and 15 patients with PDD also matched for overall severity of cognitive impairment. MEASURES: The neuropsychological measures used were the Mattis Dementia Rating Scale, Beck Depression Inventory, Wisconsin Card Sorting Test, Controlled Oral Word Association Test, Logical Memory subtest of the Wechsler Memory Scale-Revised, Digit Span subtest of the Wechsler Adult Intelligence Scale-Revised, and the Boston Diagnostic Aphasia Examination's Animal Naming test and Boston Naming Test. RESULTS: Relative to the NC group, both PDN and PDD groups demonstrated impairments in immediate and delayed verbal recall, semantic fluency, and problem solving. When PDN and PDD groups were matched for demographic and disease variables, only the PDD group evidenced impairment relative to NC in visual confrontation naming, and in lexical and semantic fluency. In addition, impairments on immediate recall and semantic fluency in the PDD group were more pronounced than those in the PDN group. However, when PDN and PDD groups were also matched for overall severity of cognitive impairment, no significant differences emerged among the two groups' neuropsychological test performances. CONCLUSIONS: Depression exacerbates some memory and language impairments associated with PD, even when the PDN and PDD groups are matched for demographic and disease variables. However, the extent and pattern of cognitive impairment is similar in PDN and PDD when the groups are also matched also for overall severity of cognitive impairment. Depression influences the quantity rather than the quality of cognitive impairment associated with Parkinson's disease.

Posttraumatic torticollis.

We report six cases of torticollis precipitated by neck trauma. The dystonia began 1 to 4 days after the trauma and differed clinically from idiopathic torticollis by marked limitation of range of motion, lack of improvement after sleep ("honeymoon period"), and absence of geste antagonistique. Worsening with action was not present; nor was there improvement with support as seen with idiopathic torticollis. Onset of pain immediately after the trauma and marked spasms of the paracervical muscles were other predominant features. Anticholinergic therapy was without benefit; however, some improvement occurred with botulinum toxin injection. It is concluded that torticollis can be caused by peripheral trauma and that it has unique clinical characteristics.

Environmental risk factors in siblings with Parkinson's disease.

To investigate possible risk factors in Parkinson's disease, we conducted a case-controlled study of 19 families having two or more siblings with Parkinson's disease. Demographic data were collected, including lifetime histories of places of residence; sources of drinking water; occupations, such as farming; and exposure to herbicides and pesticides. Rural living and drinking well water, but not farming and herbicide exposure, were significantly increased in 38 parkinsonians compared with 38 normal control subjects. A comparison of parkinsonian siblings with siblings with essential tremor revealed no differences in any risk factors for the years of shared environment. These data suggest that living in a rural environment and drinking well water are risk factors for Parkinson's disease and that the total life exposure to an environmental toxin may be more important than exposure in early life.

Diagnostic validity of the dementia questionnaire for Alzheimer disease.

OBJECTIVE: To determine the sensitivity and specificity of postmortem dementia diagnoses based on a retrospective informant interview by comparison with criterion standard neuropathological diagnoses and the results of previous clinical examinations. SETTING: Three university-based academic research centers. SUBJECTS: Fifty-four deceased elderly persons with Alzheimer disease, another dementing disorder, a neurologic disease resulting in functional impairment but no dementia, or no neurologic disorder. METHODS: Blinded nonclinician interviewers administered the Dementia Questionnaire (DQ) by telephone to informants, typically close relatives, who were familiar with the intellectual and functional status of the subjects before death. Two senior clinicians (LJ.T. and C.K.) rated each DQ for the presence or absence of a dementia syndrome during life and for the specific disorders causing the dementia, if present. Raters were blinded to the neuropathological findings and based their assessments only on data provided by responses to the DQ. Comparison was made with diagnoses based on neuropathological assessment. In most cases, the results of antemortem clinical examinations were also available as a check on the clinical diagnosis of the dementia syndrome. Sensitivity and specificity of the DQ diagnoses were computed, and chance-corrected agreement measures were calculated for the 2 independent DQ raters (LJ.T. and C.K.). RESULTS: Compared with antemortem clinical diagnosis, the average sensitivity of the DQ for the clinical syndrome of dementia was 92.8%, the specificity was 89.5%, and the interrater agreement was 98% (kappa = 0.96). Among 7 subjects with mild dementia (Mini-Mental State Examination score > or = 24 at the last clinical examination), 5 (71%) were correctly identified using the DQ. The DQ correctly indicated the absence of dementia in 8 (80%) of 10 subjects with other neurologic disorders causing functional impairment. Compared with the neuropathological diagnoses, the DQ differentiated Alzheimer disease from other primary causes of dementia with a sensitivity of 89% and a specificity of 72%. The interrater agreement was 93.8% (kappa = 0.85). CONCLUSIONS: Compared with the results of the antemortem clinical examinations, the DQ was sensitive to the presence of dementia, detected most cases of mild dementia, and discriminated dementia from other neurologic disorders causing functional impairment. Compared with the neuropathological diagnoses, the ability of the DQ to differentiate Alzheimer disease from other dementing disorders indicates that it may be useful as a research tool.

Levodopa in the treatment of Parkinson's disease.

Levodopa is the most effective drug available for the symptomatic treatment of Parkinson's disease (PD) and is the gold standard with which other therapies must be compared. Levodopa improves most parkinsonian symptoms and is associated with an apparent decrease in mortality rate. However levodopa usage is also associated with both acute and chronic side effects which compromise treatment. Levodopa is metabolized by both decarboxylase and catechol-O-methyl transferase enzymes. It is routinely administered in combination with a decarboxylase inhibitor to prevent the peripheral accumulation of dopamine and associated side effects such as nausea and vomiting. More recent studies suggest that combination of levodopa with an inhibitor of catechol-O-methyl transferase prolongs the duration of effect of the drug and can prolong the duration of motor response in fluctuating patients. This article will review the safety and efficacy of levodopa treatment.

Sensory symptoms in Parkinson's disease.

Nineteen of 50 Parkinson patients had sensory complaints of numbness, coldness, burning, or pain. There was no objective sensory loss, and sensory symptoms did not correlate with specific motor or autonomic signs. Symptoms were frequently restricted to the hemiparkinson side and sometimes preceded motor symptoms. Nerve conduction and somatosensory evoked potential studies were normal.

Propranolol therapy for essential tremor of the head.

The effect of propranolol on essential tremor affecting the head was studied in a placebo-controlled trial. Clinical tremor scores and tremor amplitude as measured by an accelerometer were significantly decreased for both head and hand tremor by 160-mg/d and 320-mg/d doses of propranolol. Placebo and 80 mg/d were without effect. In individual patients, the responsiveness of head tremor tended to parallel that of hand tremor. The head tremor of essential tremor can be treated successfully with propranolol therapy.

How accurately can Parkinson's disease be diagnosed?

The clinical picture of Parkinson's disease (PD) can be so varied that absolute clinical diagnosis may not always be possible. Several diverse entities (including toxins, pharmacologic agents, and multisystem atrophies and other degenerative diseases) can produce clinical syndromes almost indistinguishable from those of PD. Nevertheless, a sufficient number of guiding criteria--such as the presence of at least two of three motor signs (tremor, bradykinesia, and rigidity), persistence of these signs for several years, and responsiveness to levodopa--may serve to clarify and specify diagnosis, at least until such time as a biologic marker of PD is discovered. However, currently the clinical diagnosis of PD remains difficult.

Alternate day levodopa therapy in parkinsonism.

Chronic high dose levodopa therapy in Parkinson disease is associated with an apparent loss of efficacy and an increased prevalence of side effects which limit is effectiveness. The use of minimum dosage has therefore been recommended. We found that los-dose alternate-day levodopa provided adequate control of early but not late parkinsonism. Stable clinical responses occurred both on the day of drug administration and on the following day, although plasma dopa levels were negligible on the day when the drug was not given. Alternate-day therapy results in less cumulative dosage and may better preserve existing compensatory striatal activity, leading to more effective long-term treatment.