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Biomedical subjects

W C Koller

Publications and source records attributed to W C Koller.

At least 91 records · Page 5Linked to original sources
PubMed1997

Benztropine versus clozapine for the treatment of tremor in Parkinson's disease.

Four open-label studies have reported beneficial effects of clozapine on the tremor of idiopathic Parkinson's disease (PD). We performed a double-blind crossover trial with a 2-week washout, comparing low-dose clozapine to benztropine for the treatment of tremor in PD. Twenty-two subjects enrolled and 19 completed the study. Benztropine and clozapine were equally effective in improving tremor and the motor score of the United Parkinson's Disease Rating Scale at mean doses of 3.0 and 39 mg/day, respectively. Significant adverse events were experienced with each drug, but leukopenia was not encountered. We conclude that the atypical antipsychotic drug clozapine is helpful in the treatment of tremor in PD and should be considered when all other drug therapies fail.

Adult↗
PubMed1997

High-frequency stimulation of the globus pallidus for the treatment of Parkinson's disease.

Long-term treatment of Parkinson's disease (PD) with levodopa is complicated by the development of motor fluctuations and dyskinesias. Posteroventral pallidotomy can improve tremor, bradykinesia, rigidity, and dyskinesias in PD. We performed chronic stimulation of the globus pallidus (CSGP) to duplicate the positive results of pallidotomy with reduced risk of permanent neurologic deficit in patients with advanced PD. The lead for CSGP was stereotactically implanted with the aid of microelectrode recordings in the globus pallidus pars interna. An electrical pulse generator was implanted in the subclavicular region. Stimulation settings were adjusted by computer. Five PD patients (four men, one woman) with disabling symptoms were enrolled. Three of the patients had bilateral implants. At 3 months following the last implant, four patients rated themselves as markedly improved, and one patient was moderately improved. The amount of time in the "on" state increased from 21% at baseline to 65% at 3-month follow-up (p < 0.05). There was a significant improvement in all subscales of the UPDRS (p < 0.05). One patient had an asymptomatic intracranial bleed, one patient had transient hemiparesis during surgery with stimulation, and one patient required surgical repositioning of the lead. Adverse effects caused by stimulation were minimal. CSGP is a safe and effective procedure in PD patients with motor fluctuations and dyskinesias.

Aged↗
PubMed1997

Issues in the early diagnosis of Parkinson's disease.

The clinical diagnosis of Parkinson's disease (PD) is most difficult early in the disease when the signs and symptoms are most subtle. The differential diagnosis of PD includes a number of movement disorders with similar symptomatology (e.g., essential tremor, multiple system atrophy, vascular parkinsonism). In most published studies of PD, the disease is diagnosed simply by the presence of two of the three cardinal motor signs-tremor, rigidity, and bradykinesia-or by the presence of three of the four motor signs: tremor, rigidity, bradykinesia, and postural instability. However, there is an obvious need for better diagnostic criteria. Until discrete biologic markers are developed, the use of exclusion criteria may improve the accuracy of the presumptive diagnosis of PD.

Diagnosis, Differential↗
PubMed1997

Unilateral pallidal stimulation for Parkinson's disease: neurobehavioral functioning before and 3 months after electrode implantation.

Unilateral pallidotomy is thought to have a low risk for cognitive morbidity. Nonetheless, recent research suggests that some patients experience declines in memory and language and that pallidal stimulation might be a safer treatment for Parkinson's disease (PD). We investigated the neurobehavioral effects of unilateral pallidal stimulation. Nine consecutive PD patients undergoing unilateral deep brain-stimulating electrode implantation in the globus pallidus interna were evaluated with a neuropsychological test battery approximately 1 month before and 3 months after surgery. Patients reported significantly fewer symptoms of anxiety and greater vigor after surgery. There was a trend toward fewer depressive symptoms. Semantic verbal fluency and visuoconstructional test scores declined significantly after surgery. However, among five patients showing declines in semantic verbal fluency, only one patient's score declined by more than 2 SD. No patient showed significant decline or improvement in the overall level of cognitive functioning. This study supports the relative safety, in terms of cognitive function, of unilateral pallidal stimulation in PD.

Adult↗
PubMed1996

Pharmacokinetic comparison of Sinemet and Atamet (generic carbidopa/levodopa): a single-dose study.

We compared the pharmacokinetic and motor responses of Sinemet and Atamet (generic carbidopa/levodopa) in patients with Parkinson's disease. Thirty Parkinson's disease patients (10 previously untreated, 10 with early disease, and 10 with motor fluctuations/dyskinesia) participated in a single-dose double-blind study. Following administration of an equivalent oral dose of Sinemet and Atamet on two separate days, we compared the peak plasma concentration, time to peak plasma concentration, area under the curve, total motor score, tapping score, and walking time. The mean time to peak plasma concentrations was 49 min with Sinemet and 47 min with Atamet, the mean peak plasma concentration was 1,273 ng/ml with Sinemet and 1,153 ng/ml with Atamet, and the mean area under the curve was 2,295 micrograms/ml/h with Sinemet and 2,330 micrograms/ml/h with Atamet. Similarly, there was no significant difference between total motor score, tapping score, or walking time. In this single-dose study, there were no significant differences in pharmacokinetic and motor responses between Sinemet and Atamet.

Administration, Oral↗
PubMed1996

Diagnostic testing in movement disorders.

The diagnosis of movement disorders is essentially clinical. Work-up depends on patient age, part of the body affected, drug response, and presence of other systemic or neurologic symptoms and signs. Typical Parkinson's disease, essential tremor, and tics need only minimal work-up if any. Brain magnetic resonance imaging/computed tomography, positron emission tomography and single photon emission computed tomography, and DNA studies are promising diagnostic tools. Exclusion of Wilson's disease and neuroacanthocytosis is emphasized in children and young adults with movement disorders.

Adult↗
PubMed1996

Utility of a Wisconsin Card Sorting Test short form in persons with Alzheimer's and Parkinson's disease.

The utility of administering only the first deck of 64 cards from the Wisconsin Card Sorting Test (WCST-64) in persons with Alzheimer's (AD) and Parkinson's disease (PD) was evaluated. There were 35 elderly subjects matched for gender, age, and education in each of four groups: controls, PD without dementia (PDN), PD with dementia (PDD), and AD. Additionally, the control and PDN subjects were matched for level of cognitive functioning as were the PDD and AD groups. Results revealed that demented persons performed significantly worse than nondemented subjects. The WCST-64 was also sensitive to the subtle executive deficits demonstrated by persons with PD without dementia. The findings support the use of the WCST-64 in elderly persons with AD and PD.

Aged↗
PubMed1996

Management of motor fluctuations in Parkinson's disease.

A complication of chronic levodopa therapy is a shortening of benefit of each dose. Peripheral pharmacokinetics, central pharmacokinetics, and central pharmacodynamics are involved in the pathophysiology of motor fluctuations. Strategies to improve 'wearing-off' fluctuations attempt to provide more constant plasma levodopa levels or more continuous stimulation of dopamine receptors. Controlled-release levodopa preparations are very effective for mild to moderate fluctuations. The addition of direct-acting dopamine agonists or the MAO-B inhibitor selegiline is helpful for short-term improvement. Liquid levodopa is beneficial for some patients with severe fluctuations. Apomorphine injections will provide immediate 'rescue' from 'off' states. Catechol-O-methyl transferase inhibitors are a new class of drugs which appear to improve motor fluctuations. Manipulations of dieting protein may reduce fluctuations in some patients. It is possible that motor fluctuations may be delayed by the early use of sustained release levodopa preparations or early combinations of levodopa with a dopamine agonist.

Antiparkinson Agents↗
PubMed1996

Early morning akinesia in Parkinson's disease: effect of standard carbidopa/levodopa and sustained-release carbidopa/levodopa.

We examined the effects of supplemental standard carbidopa/levodopa (Std-L) on early morning akinesia in patients with Parkinson's disease (PD) who were being treated with sustained-release carbidopa/levodopa (L-CR). We compared plasma dopa levels and clinical response in 15 PD patients after a dose of Std-L and L-CR (2 hours later) and after a dose of L-CR and placebo in a double-blind, placebo-controlled, crossover study. Plasma dopa levels, total motor score, walking time, and finger tapping time were assessed every 15 minutes for the first 2 hours and then every 30 minutes for the next 3 hours. The time of onset in clinical benefit was significantly earlier with Std-L (47 minutes, range 15 to 75 minutes) as the first dose as compared with L-CR (58 minutes, range 30 to 105 minutes). Similarly, there was a significant difference in the peak plasma dopa levels (Cmax) and the time to reach peak plasma dopa levels (Tmax) with administration of Std-L (Tmax 36 minutes; Cmax 1,501 micrograms/ml) as compared with L-CR (Tmax 111 minutes, Cmax 1,260 micrograms/ml). There was no significant difference in dyskinesias between the two treatment arms. An initial morning dose of Std-L alleviates the problem of delayed-onset clinical response that commonly occurs with L-CR.

Aged↗
PubMed1996

Multicenter, placebo-controlled trial of cabergoline taken once daily in the treatment of Parkinson's disease.

Cabergoline is a dopaminergic agonist relatively specific for the D2 receptor and much longer-acting than other dopamine agonists. We conducted a randomized, placebo-controlled, double-blind study of cabergoline in 188 levodopa/carbidopa-treated patients with suboptimally controlled Parkinson's disease (PD). The cabergoline patients had significantly better Activities of Daily Living (p = 0.032) and Motor Examination (p = 0.031) scores at the conclusion of the trial compared with the placebo group. The daily levodopa dose for the cabergoline patients decreased 18% compared with a 3% reduction for the placebo group (p < 0.001). The amount of time in the "on" state increased more in the cabergoline group (p = 0.022). The side-effect was similar to that seen with other dopamine agonists, and cabergoline was generally well tolerated. We conclude that cabergoline is an effective adjunct to levodopa for the treatment of PD.

Activities of Daily Living↗
PubMed1996

Deep brain stimulation for essential tremor.

We examined the effects and safety of deep brain stimulation (DBS) as a treatment for essential tremor (ET). Ten ET patients with disabling medication-refractory tremor underwent stereotactic implantation of a DBS lead in the left Vim thalamic nucleus and completed a 6-month follow-up. The Clinical Tremor Rating Scale and disability assessments were performed at baseline, 1-, 3-, and 6-month follow-up. There were significant improvements in dressing, drinking, eating, bathing, and handwriting as reported by the subjects. Tremor severity, writing, pouring, and spiral and line drawing were significantly improved as rated by the examiner. Improvements persisted through the 6-month follow-up period. Although global disability significantly lessened in the group as a whole, one subject with hand-finger tremor accentuated by writing had no change in disability status. In this 6-month open-label study, DBS was effective and safe in reducing tremor and functional disability in ET.

Aged↗
PubMed1996

Normal distribution of apolipoprotein E alleles in progressive supranuclear palsy.

Apolipoprotein E (Apo E) genotype is a genetic risk factor influencing the development of Alzheimer's disease (AD). Progressive supranuclear palsy (PSP), like AD, is a dementing illness with neurofibrillary tangles. We determined the frequencies of Apo E alleles in 52 PSP patients and 52 age- and gender-matched controls. The distribution of Apo E allele frequencies and genotypes showed no difference between PSP and controls. Apo E allele status does not influence the development of PSP.

Aged↗
PubMed1996

Accuracy of reported family histories of essential tremor.

We studied the accuracy of reported family histories of essential tremor (ET) by questioning the patients in our clinic and subsequently by mail and phone. For individuals who continued to report a negative family history, we mailed a screening questionnaire to their first-degree relatives to further ascertain the presence of ET. On initial assessment, 67.7% of patients reported a positive family history of ET, but following all assessments, 96.0% of patients had a positive family history. We conclude that a negative family history of ET is often inaccurate, and that ET is primarily a hereditary disease.

Family↗
PubMed1996

Methazolamide for essential voice tremor.

We studied the safety and efficacy of methazolamide (average dose 168 mg/day) in a placebo-controlled blinded investigation in nine patients with essential voice tremor. There were no significant differences for physician or patient clinical rating scores. Digital audio tape recordings showed no difference for amplitude modulation, but frequency modulation was significantly altered by methazolamide. Side effects were common with the drug. We conclude that methazolamide has limited usefulness in the treatment of essential voice tremor.

Aged↗
PubMed1996

Methods of managing levodopa-induced dyskinesias.

Levodopa-induced dyskinesias result in considerable functional impairment for patients and formidable therapeutic challenges for physicians. A practical method of treating such dyskinesias is first to classify the levodopa dyskinesias according to their temporal profile after drug administration, namely, into predictable (interdose, biphasic and 'off-period') and unpredictable ('on-off') dyskinesias. Treatment of each type of dyskinesia requires a different and relatively specific therapeutic strategy. With progression of Parkinson's disease, the threshold for interdose dyskinesia lowers, while the threshold for antiparkinsonian efficacy is unchanged; therefore, the strategy is to maintain levodopa concentrations between these 2 thresholds and avoid high concentrations. Frequent small doses of liquid levodopa preparations may be indicated. Clozapine appears to increase the threshold for dyskinesia. However, its usefulness is limited primarily by dose-related sedation and by dose-unrelated agranulocytosis. Buspirone and fluoxetine may have specific antidyskinetic benefit. Surgical treatment may aid selected patients, although criteria for selection are not fully established. The biphasic dyskinesias occur just before and just after an oral dose of levodopa. They result when levodopa concentrations fall below or rise above the threshold for therapeutic efficacy; therefore, the strategy is to maintain concentrations as nearly constant as possible above that threshold. Dopamine agonists such as subcutaneous apomorphine combined with domperidone may be particularly helpful. Thalamic stimulation can also benefit selected patients. 'Off-period' dyskinesias occur at times of predicted low concentrations of levodopa. The treatment strategy is to provide sufficient levodopa or dopaminergic stimulation during those intervals. Dopamine agonists (e.g. bromocriptine at night) may help the characteristic early foot dystonia. Anticholinergic agents may also help. The unpredictable ('on-off') dyskinesias are first analysed to establish a pattern of response. Then, on the basis of that pattern, they are treated by maintaining levodopa concentrations or dopaminergic tone during the periods that would ordinarily be 'off.' Administration of liquid levodopa preparations, addition of dopaminergic agents, restriction of treatment during the morning hours as well as restriction of the majority of dietary protein in the evening meal may provide a period of predictable good function early in the day. Clozapine, even early in treatment, appears to reduce the incidence of these dyskinesias. Rescue with apomorphine during a malignant prolonged 'off' phase is particularly valuable.

Antiparkinson Agents↗
PubMed1995

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.

Adult↗