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Biomedical subjects

W C Koller

Publications and source records attributed to W C Koller.

At least 55 records · Page 3Linked to original sources
PubMed1999

Immediate-release and controlled-release carbidopa/levodopa in PD: a 5-year randomized multicenter study. Carbidopa/Levodopa Study Group.

OBJECTIVE: To compare effects of immediate-release (IR) and sustained-release (CR) carbidopa/levodopa in levodopa-naive PD patients. BACKGROUND: It was hypothesized that the long-acting preparation would be associated with fewer long-term complications. METHODS: A total of 618 patients were studied in 36 centers worldwide in a blinded, randomized parallel study. Measures of efficacy and adverse reactions were recorded at 3-month intervals for 5 years. Motor fluctuations and dyskinesias were evaluated by a patient diary and a physician-recorded questionnaire. The Nottingham Health Profile (NHP) was used to evaluate quality of life. RESULTS: Approximately 60% of patients completed the trial. After 5 years, the mean dose of IR was 426 mg/day, and the bioavailable dose of CR was 510 mg/day (mean dose, 736 mg/day). After 5 years, 20.6% of the IR group and 21.8% of the CR group had motor fluctuations or dyskinesia. Sixteen percent of both groups had changes in motor response by the questionnaire's definition. There was no significant difference between the two treatment groups. Disability scores and the motor score of the Unified Parkinson Disease Rating Scale (UPDRS) were highest at baseline, improved with therapy, and thereafter worsened over time to reach baseline scoring at the end of 5 years. The CR group was superior to IR for the Activities of Daily Living subsection of the UPDRS for all 5 years and for emotional reactivity and social isolation on the NHP; however, this may have resulted from higher doses of CR that were used. CONCLUSION: Despite the progressive nature of PD, both the immediate-release and sustained-release carbidopa/levodopa formulations maintained a similar level of control in PD after 5 years compared with baseline. Additionally, the low incidence of motor fluctuations or dyskinesia was not significantly different between the treatment groups and may be partly attributed to the relatively low doses of levodopa used throughout the 5-year study.

Activities of Daily Living↗
PubMed1999

Surgical treatment of Parkinson's disease.

Stereotaxtic surgery is an effective therapeutic maneuver in the management of advanced Parkinson's disease (PD). Thalamotomy is an effective measure to control tremor but other PD symptoms are not changed. Bilateral operations are associated with a risk of severe speech impairment. Deep brain stimulation (DBS) of the thalamus is as effective as thalamotomy and is associated with fewer side effects. Pallidotomy is effective in reducing contralateral dyskinesias and the cardinal symptoms of PD. Bilateral pallidotomy often results in cognitive dysfunction. Deep brain stimulation of the pallidum replicates the positive effects of pallidotomy and appears to be safer than ablative lesions. Subthalamic DBS is currently under investigation. This procedure may control all PD symptoms, and the dose of levodopa can often be dramatically reduced. Neurotransplantation is a promising surgical approach to PD. However, further investigation is needed to optimize this approach.

Brain Tissue Transplantation↗
PubMed1999

Abnormal performance on the PD test battery by asymptomatic first-degree relatives.

OBJECTIVE: To determine whether a sensitive and specific battery of tests (PD Battery) could identify a subset of asymptomatic first-degree relatives (FDRs) of PD patients who were significantly more impaired than age-matched normal control (NC) subjects. The PD Battery incorporates tests of motor function, olfaction, and mood. In previous studies, it has shown high specificity and sensitivity in distinguishing mildly affected PD patients from NC subjects. METHODS: The PD Battery and regression analysis-derived scoring equations were applied to asymptomatic FDRs. RESULTS: Eighty FDRs and 100 NC subjects were tested. Of the FDRs, 22.5% scored in the abnormal range, and 9% of NC subjects had abnormal scores. This difference was statistically significant. Further analysis demonstrated that FDRs with abnormal scores on the PD Battery differed on all three components of the test battery from FDRs who had normal scores. Among the sons and daughters whose scores were abnormal, there was a much higher prevalence of the affected parent being the father. CONCLUSIONS: The proportion of FDRs who demonstrated abnormal performance on the PD Battery was greater than that of NC subjects. Thus, the PD Battery may detect the asymptomatic carrier state or risk for PD. Sons and daughters whose scores were in the abnormal range were more likely to have fathers with PD.

Adult↗
PubMed1999

Efficacy of unilateral deep brain stimulation of the VIM nucleus of the thalamus for essential head tremor.

Essential tremor is a common movement disorder. Deep brain stimulation of the VIM nucleus of the thalamus has been reported to be efficacious for reducing essential hand tremor. The effect of deep brain stimulation of the thalamus on essential head tremor has not been well studied. Therefore, we evaluated the effect of DBS of the thalamus in 38 patients with essential head tremor. Head tremor scores prior to surgery were compared with scores at 3, 6, and 12 months postimplant with stimulation "on" and "off." The 3-month evaluations were blinded for 24 patients and all others were open-label. There was a significant improvement in head tremor at all postimplant evaluations compared with baseline. Essential head tremor can be reduced with deep brain stimulation of the VIM nucleus of the thalamus and, pending the results of other controlled trials, should be considered as a treatment option for patients with disabling essential head tremor unresponsive to medication.

Aged↗
PubMed1999

Cognitive outcome following staged bilateral pallidal stimulation for the treatment of Parkinson's disease.

As neurosurgical treatment of parkinsonian symptoms has become increasingly popular, concern about the cognitive morbidity which may result from such interventions has risen proportionately. Previous reports of cognitive difficulties associated with pallidotomy and thalamotomy, especially in bilateral cases, have provided the impetus for research into chronic electrical deep brain stimulation procedures which are believed to be safer than ablation. Given the lack of neurobehavioral research following bilateral deep brain stimulation procedures, this preliminary study of six Parkinson's disease patients undergoing staged bilateral pallidal stimulation was undertaken. A battery of tests assessing attention, executive function, visuomotor coordination, language, visuoperceptual function, learning memory and mood revealed no significant change in overall level of cognitive functioning after either unilateral or bilateral pallidal deep brain stimulation. No significant declines were observed about three months following bilateral stimulation, and in fact, significant gains in delayed recall and relief of anxiety symptoms were noted. It was concluded from this preliminary data that bilateral pallidal stimulation for the treatment of Parkinson's disease, at least in the absence of operative complications, offers a cognitively safe alternative to ablation.

Cognition↗
PubMed1999

Lexical, semantic, and action verbal fluency in Parkinson's disease with and without dementia.

Previous research suggests that lexical and semantic verbal fluency are differentially sensitive to the effects of cortical and subcortical dementias, but little is known about action fluency performance in dementias. The present study compared lexical, semantic, and action fluency in groups of patients with Parkinson's disease (PD) with and without dementia and an elderly control group. Findings revealed an interaction between fluency type and subject group. Although the demented PD (PDD) group performed significantly more poorly than their non-demented counterparts and normal controls on all three fluency tasks, a disproportionate disparity in scores was noted on the action fluency task. The findings suggest that action fluency may be particularly sensitive to PD-associated dementia and may be an early indicator of the conversion from PD to PDD. As reported elsewhere, PD without dementia was not associated with significant impairment on any of the fluency tasks.

Aged↗
PubMed1998

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.

Aged↗
PubMed1998

Neuroprotection for Parkinson's disease.

Levodopa is the most effective drug available for the treatment of Parkinson's disease (PD). As a precursor of dopamine, levodopa causes an increase in brain dopamine, which is depleted in PD. However, long-term levodopa therapy is associated with complications such as dyskinesias, motor fluctuations, and mental status changes. The treatment of these side effects is a major challenge for the clinician.

Antiparkinson Agents↗
PubMed1998

Clozapine use in Parkinson's disease: a retrospective analysis of a large multicentered clinical experience.

We conducted a multicentered, retrospective review of clozapine's (CZP) effects on a range of psychiatric, sleep, cognitive, motor, and sensory disorders in Parkinson's disease (PD). Therapeutic outcomes and adverse events were compared with varying prescribing practices at participating sites. The medical records of 172 consecutive PD patients treated with CZP at four movement disorder clinics were reviewed. Low-dose CZP improved psychiatric symptoms of psychosis, anxiety, depression, hypersexuality, sleep disturbance, and akathisia. Tremor, torticollis, limb dystonia, and pain showed modest rates of improvement. Twenty-three percent of patients withdrew as a result of adverse events or treatment failure. Inpatient CZP initiation did not improve therapeutic efficacy, or reduce adverse events or the withdrawal rate. Low-dose CZP in the outpatient setting is generally an effective and well-tolerated treatment for many of the psychiatric, sleep, motor, and sensory disturbances common to late-stage PD.

Aged↗
PubMed1998

Double-blind controlled trial of gabapentin in essential tremor.

Gabapentin has been reported to be effective for essential tremor (ET) based on open-label trials. We studied gabapentin (1800 mg/day) and placebo in a double-blind crossover design in 20 ET patients. Eighteen patients completed the study and two patients dropped out as a result of adverse effects which resolved when the medication was discontinued. Tremor was assessed at baseline and after 2 weeks of gabapentin and placebo treatment. One patient was mildly improved and another was moderately improved with placebo. Similarly, one patient reported mild improvement and another patient had marked improvement with gabapentin. All the remaining patients either reported no change or were worse with both treatment arms. There was no significant difference for total tremor score, hand tremor score, handwriting scores, or pouring scores. Sickness Impact Profile scores were no different between placebo and gabapentin. Our results suggest that as an adjuvant therapy in ET, gabapentin has limited benefit.

Acetates↗
PubMed1998

Improvements in daily functioning after deep brain stimulation of the thalamus for intractable tremor.

Deep brain stimulation (DBS) of the thalamus reduces tremor in patients with essential tremor (ET). However, few studies have determined the degree of improvement in daily functioning associated with DBS. We developed a self-report Tremor Activities of Daily Living Scale (TADLS) to compare daily functioning with the stimulator turned on and off. Patients rated their performance on the 30 items of the TADLS with the stimulator turned off and then on. They also performed 10 activities under the supervision of a clinician who rated their functional ability with stimulation off and then on. There was a 58% improvement in self-rated TADLS scores in patients with DBS with the stimulator on compared with stimulation off. When activities were rated by the clinician, the average improvement in functioning with the stimulator on was 54%. There were reasonably high correlations between patient and clinician ratings of functioning. ET patients have a marked improvement in daily functioning with thalamic DBS.

Activities of Daily Living↗
PubMed1998

Pharmacologic treatment of tremor.

Tremor is a common neurologic symptom that can also be incapacitating to the patient, so effective therapy is needed. The causes of tremor are heterogeneous. Essential tremor (ET) and the tremor associated with Parkinson's disease (PD) are the most common encountered in clinical practice. Beta-adrenergic blockers and primidone remain the mainstay of treatment for ET, whereas carbidopa/levodopa and anticholinergics are most beneficial in PD. However, the efficacy of various other medications has been studied in ET and PD, and also in patients with tremor resulting from other conditions, with varying results.

Humans↗
PubMed1998

Chronic electrical stimulation of the left ventrointermediate (Vim) thalamic nucleus for the treatment of pharmacotherapy-resistant Parkinson's disease: a differential impact on access to semantic and episodic memory?

Thalamotomy for medically refractory Parkinson's disease (PD) is considered to be efficacious and relatively safe. Because a minority of patients experience decrements in language and memory (often mild and transient) after thalamotomy, chronic thalamic deep brain stimulation (DBS) might be a safer treatment given its reversibility and the modifiability of stimulation parameters. Two preliminary studies support the relative cognitive safety of unilateral DBS of the ventral intermediate (Vim) thalamic nucleus, but it is unclear whether possibly subtle changes in language and memory represent effects of "microthalamotomy" or of stimulation per se. This report provides preliminary data concerning effects of left thalamic stimulation on information processing speed, semantic memory (verbal fluency and visual confrontation naming), and verbal episodic memory in a patient with PD. In addition to being evaluated before and 3 and 6 months after surgery, the patient was tested 18 months after surgery either on or off medications and with the stimulator turned either on or off (order counterbalanced across medication conditions). Test performance differences between the stimulation conditions were attenuated "off" as compared to "on" medication. Vim stimulation consistently, albeit subtly, improved semantic verbal fluency but interfered with immediate recall of word lists. Parallels to findings from acute, intraoperative thalamic stimulation studies are explored. The hypothesis is offered that left Vim stimulation might facilitate access to semantic memory, but interfere with episodic memory processes.

Adult↗
PubMed1998

Quality of life and Parkinson's disease: the CR FIRST Study.

Quality of life is an important issue in the treatment of Parkinson's disease. Both general and disease specific quality of life scales are now being used in interventional trials. In the Sinemet CR First trial, the long-acting preparation was found to be superior to the immediate release preparation in several measures of the Nottingham Health Profile, a generic quality of life scale. In particular social isolation and emotional reactivity was better with Sinemet CR. The long acting drug was also superior for all five years of the study, for activities of daily living subscale of the UPDRS. It is concluded the Sinemet CR may have advantages over the immediate release preparation on Quality of life issues in PD.

Antiparkinson Agents↗
PubMed1998

Pallidotomy lesion locations: significance of microelectrode refinement.

OBJECTIVE: To determine whether stereotactic pallidotomy requires refinement using microelectrode recording to ensure proper lesion placement. METHODS: The experiment approach was based on retrospective comparisons of microelectrode-refined radiofrequency lesion locations with hypothetical unrefined lesion positions. Actual and hypothetical pallidotomy lesions were classified based on their lesion center (thermocoagulative zone) locations and their total lesion areas (surrounding edematous zone) relative to the pallidal target. Assessments were made using postoperative T2-weighted magnetic resonance axial images, which showed both the lesion and globus pallidus (GP). The magnitude of microelectrode refinement from an initial preoperative starting point determined by computed tomography was calculated using stereotactic coordinates and included corrections for the lesioning tract trajectory angle. RESULTS: In all 25 patients, the center of the actual pallidotomy lesion was within the GP. Without microelectrode refinement, 13 of 25 hypothetical lesion positions would have been localized such that the lesion center would not have remained in the GP. In eight cases, microelectrode refinement resulted in no significant change in lesion location, but in one case, microelectrode refinement resulted in lesion center placement away from the GP. CONCLUSION: Kinesthetically driven microelectrode refinement in pallidotomy lesioning seems to be required to ensure proper lesion location within the GP.

Adult↗
PubMed1998

Gene-toxin interaction as a putative risk factor for Parkinson's disease with dementia.

We had previously examined environmental, sociodemographic and clinical variables as predictors for Parkinson's disease with dementia (PD + D) and found that lower educational attainment, greater motor impairment and advanced age at disease onset were more common in PD + D than in subjects with Parkinson's disease without dementia (PD-D). We now explore the hypothesis that genetic traits coupled with nongenetic factors may raise the risk of development of PD + D. The study cohort of 43 PD + D and 51 PD-D subjects was analyzed examining environmental, sociodemographic and clinical variables along with 3 candidate gene markers: poor debrisoquine metabolizer allele (CYP 2D6 29B+), monoamine oxidase B allele 1, and apolipoprotein E epsilon 4 allele. Variables were initially entered into a multivariate model singly. Again lower education, age at onset and motor impairment appeared as predictors of PD + D while other variables (including allele status) failed to emerge as significant individual risk factors for dementia. We then examined environmental and genetic variables analyzed in tandem to look for potential variable interactions. Subjects who had pesticide exposure and at least 1 copy of the CYP 2D6 29B+ allele had 83% predicted probability of PD + D (stepwise logistic regression model: p = 0.0491). This case-control study provides preliminary evidence that a gene-toxin interaction may play an etiological role in PD + D. Further assessment of the role of these putative risk factors in incident dementia in PD is indicated.

Aged↗
PubMed1998

Comparison of actual pallidotomy lesion location with expected stereotactic location.

Accuracy of pallidotomy lesion placement was assessed by comparing actual lesion locations with expected pallidotomy lesion locations based on stereotaxy. Actual and expected lesions were compared in anteroposterior, dorsoventral and lateral axes. In 22 pallidotomies, actual lesion locations were determined using axial MR images. Expected lesion locations were calculated using a starting point derived from preoperative computerized tomography, displacements from the starting point based on microelectrode-driven electrophysiological refinement, and the trajectory angle of the lesioning tract relative to the anterior-posterior commissural plane. On average, actual lesion locations were found 2.91 +/- 2.23 mm posterior, 3.22 +/- 2.49 mm ventral, and 0.05 +/- 1.80 mm lateral compared to the expected lesion location. Discrepancies between the actual lesion and expected lesion locations may be mostly accounted for by posterior and ventral lesion spread from the exposed electrode tip, in-plane and volume averaging effects associated with MR images, and possible brain shifting during surgery. However, despite the remaining small differences between actual and expected lesion location, good clinical outcome of reduced dyskinesias and 'off' time along with UPDRS-based improvement in mentation, motor and activity of daily living measures was observed.

Aged↗