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Biomedical subjects

W C Koller

Publications and source records attributed to W C Koller.

At least 37 records · Page 2Linked to original sources
PubMed2001

Parkinson's disease. Update in diagnosis and symptom management.

Parkinson's disease (PD) is a progressive neurodegenerative disorder with a high burden of morbidity. Because no diagnostic test exists for PD, clinical knowledge and skill are key to making an early, accurate diagnosis. Diagnostic criteria for PD require at least two of three motor signs: tremor, rigidity, or bradykinesia. Levodopa and the dopamine agonists are considered first-line drug therapy. Recent studies have shown a lower incidence of dyskinesia in patients who began therapy with a dopamine agonist, although levodopa may be better tolerated by patients age 70 or older. Combinations of medications and rehabilitative, alternative, and surgical therapies can often help patients achieve adequate control of PD motor symptoms and maintain a high quality of independent living.

Aged↗
PubMed2000

Early detection of probable idiopathic Parkinson's disease: II. A prospective application of a diagnostic test battery.

We developed a battery of tests, incorporating motor function, olfaction, and mood, that distinguishes between early mild, probable idiopathic Parkinson's disease (iPD), and normal control subjects. Here, we determined the PD Battery's ability to prospectively identify which patients with symptoms and signs suggestive of, but not yet diagnostic of, iPD who would subsequently be diagnosed as having iPD. Of 212 enrolled patients, 194 have been followed for at least 1 year. Among these 194, 59 were diagnosed with iPD, 40 as neurologically normal, and the remaining 106 with other neurologic conditions such as essential tremor. The test battery was 92% specific and 68% sensitive for iPD. The area under the Receiver Operating Characteristics curve was 0.88 for predicting which participants would subsequently be diagnosed as having iPD or as being neurologically normal.

Adult↗
PubMed2000

Motor initiation and execution in essential tremor and Parkinson's disease.

Clinical differentiation of essential tremor (ET) from idiopathic Parkinson's disease (iPD) is based on the lack of akinesia and bradykinesia. Nevertheless, early tremor-predominant iPD often is difficult to distinguish from ET. Motor initiation and execution in ET, iPD, and normal control (NC) subjects were investigated. Individuals with iPD, ET and NC performed a reaction-time wrist flexion and extension task. Motor performances were similar between ET and iPD and both were different than normal control subjects. Both the patients with iPD and ET had longer reaction times and slower movement velocities than NC subjects. This may help to explain some of the difficulties in distinguishing patients with these two diseases. The similarities of motor performance suggest that while ET and iPD may be separate disease entities, they may share similar pathogenic motor mechanisms from the perspective of an integrated motor system that drives the motor cortex.

Adult↗
PubMed2000

Health-related quality of life in Parkinson's disease after pallidotomy and deep brain stimulation.

This study explored the multidimensional outcome of three neurosurgical interventions for Parkinson's disease (PD): pallidotomy (N = 23), pallidal deep brain stimulation (DBS) (N = 9), and thalamic DBS (N = 7). All patients completed the Sickness Impact Profile (SIP) and the Beck Depression Inventory. Pallidotomy patients also completed the Profile of Mood States, the Beck Anxiety Inventory, and a disease-specific quality of life (QOL) measure, the Parkinson's Disease Questionnaire (PDQ-39). Three months after surgery, all neurosurgical groups showed significant improvements in mood and function, including physical, psychosocial, and overall functioning. Pallidal DBS and pallidotomy patients who completed additional QOL measures reported decreased anxiety and tension, increased vigor, improved mobility and ability to perform activities of daily living, and decreased perceived stigma. Psychosocial dysfunction scores from the SIP were related to depressed mood both at baseline (r = .42) and at followup (r = .45), but the physical dysfunction subscale was not related to mood at either time point, suggesting that disruption of social relationships due to PD may have more impact on affective distress than physical symptoms alone. Results suggest that neurosurgical interventions for PD improve disabling PD motor symptoms and also improve several domains of quality of life.

Activities of Daily Living↗
PubMed2000

The behavioral complications of pallidal stimulation: a case report.

We report a case of recurrent manic episodes associated with chronic deep brain stimulation (DBS) targeting globus pallidus (GP) in the treatment of Parkinson's disease (PD). Cardinal PD symptoms and dyskinesia improved with DBS, and neuropsychological testing found improvements in visuospatial measures associated with left DBS and in verbal memory with right DBS when compared to the patient's preoperative baseline. Under conditions of right, left, and bilateral DBS, the patient experienced bouts of mania and hypomania lasting several days at a time. Positron emission tomography (PET) with (15)O-labeled water was performed after his first manic episode under four conditions: no stimulation, right DBS, left DBS, and bilateral DBS. Although no manic switch occurred during the course of the PET study, all three DBS conditions were associated with decreases in regional flow in the left parahippocampus and hippocampus and right mid-cingulate gyrus. Increases in flow in left inferior frontal area, bilateral insula, dorsolateral prefrontal cortex, and cuneus were common to all DBS conditions. GP stimulation in PD may be associated with behavioral and cognitive effects. Distributed blood flow changes observed with pallidal DBS support a role for the pallidum in cognition and affective regulation.

Adult↗
PubMed2000

Pallidotomy microelectrode targeting: neurophysiology-based target refinement.

OBJECTIVE: Microelectrode recording can refine targeting for stereotactic radiofrequency lesioning of the globus pallidus to treat Parkinson's disease. Multiple intraoperative microelectrode recording/stimulating tracks are searched and assessed for neuronal activity, presence of tremor cells, visual responses, and responses to kinesthetic input. These physiological data are then correlated with atlas-based anatomic data to approximate electrode location. On the basis of these physiological properties, one or more tracks are selected for lesioning. This study analyzes the track physiological factors that seem most significant in determining the microelectrode recording track(s) that will be chosen for pallidal lesioning. METHODS: Thirty-six patients with Parkinson's disease underwent microelectrode-guided pallidotomy. Between one and five microelectrode recording tracks were made per patient. Usually, one (n = 23) or two (n = 12) of these tracks were lesioned. Electrode positions in the x (mediolateral) and y (anteroposterior) axes were recorded and related to track neurophysiological findings and final lesion location. The stereotactic location and sequence of microelectrode tracks were recorded and plotted to illustrate individual search patterns. These patterns were then compared with those noted in other patients. Neurophysiological data obtained from recording tracks were analyzed. A retrospective analysis of track electrophysiology was performed to determine the track characteristics that seemed most important in the surgeon's choice of the track to lesion. Track physiological properties included general cell spike amplitude, tremor synchronous neuronal firing, kinesthetically responsive neuronal firing, and optic track responses (either phosphenes reported by the patient during track microstimulation or neuronal firing in response to light stimulus into the patient's eyes). Orthogonally corrected postoperative magnetic resonance images were used to confirm the anatomic lesion locations. RESULTS: In patients who had a single mapped track lesioned, specific track electrophysiological characteristics identified the track that would be lesioned most of the time (20 of 24 patients). Tracks that exhibited a combination of tremor synchronous firing, joint kinesthesia, and visual responsivity were lesioned 17 (85%) of 20 times. Analysis of intraoperative electrode movement in the x and y axes indicated a significant subset of moves but did not result in microelectrode positioning closer to the subsequently lesioned track. Accuracy of initial electrode movement in the x and y axes was most highly correlated with a measure of first-track electrophysiological activity. The number of microelectrode recording tracks did not correlate with clinical outcome. Anatomic analysis, using postoperative magnetic resonance imaging, revealed that all lesions were placed in the globus pallidus. Most patients (35 of 36) improved after surgery. CONCLUSION: The level of electrophysiological activity in the first track was the best predictive factor in determining whether the next microelectrode move would be closer to the ultimately lesioned track. The analysis of electrode track location and neurophysiological properties yields useful information regarding the effectiveness of microelectrode searching in the x and y axes. Within an institution, the application of this modeling method may increase the efficiency of the microelectrode refinement process.

Aged↗
PubMed2000

Early Parkinson's disease: what is the best approach to treatment.

Early and correct diagnosis and treatment of Parkinson's disease (PD) are crucial for the patient's well being. At the first visit, it is important to deal with the patient's misconceptions of the disease and its course, to offer sources of information and to suggest exercises. To make a correct initial diagnosis of PD we need to assess the course of the initial levodopa responsiveness. The most frequent challenges in diagnosing PD are the conditions of essential tremor and multiple system atrophy. PD has 3 stages of development: (i) early--from the onset of symptoms to the appearance of motor fluctuations; (ii) middle--from motor fluctuations to the appearance of moderate-to-severe disability; and (iii) advanced--when moderate-to-severe disability is present. The medical treatment of early PD should be started when functional disability appears, which is a different threshold for each patient. For patients below 65 years old, or above 65 years old but with preserved mental function and with no severe comorbidity, initial monotherapy with a dopamine agonist is advisable. This approach appears to delay the appearance and reduce the amount of late motor complications with subsequent levodopa treatment. All dopamine agonists have similar efficacy, which is less than that of levodopa. It is important to consider the adverse effect profile when a choice for initial or adjunctive therapy is made. When levodopa therapy is started as an adjunct in younger patients or as initial monotherapy in older patients, sustained-release levodopa preparations are preferred. They have a longer half-life and possibly stimulate the dopamine receptors more continuously. Anticholinergic drugs are appropriate for younger patients with tremor-dominant PD. Amantadine is mainly used for dyskinesia control. Catechol-O-methyl-transferase inhibitors and neurosurgery are not treatments of choice for early PD but can be very effective for more advanced disease. The presence of presymptomatic markers of PD, such as changes in odour detection, handwriting, speech, movement time of self-initiated motor acts, personality traits, presence of antibodies against dopaminergic neurons, pattern of positron emission tomography results, appearance of mitochondrial DNA mutation profiles, etc., appear to be very important in the light of the emerging neuroprotective therapies. Neuroprotection is aimed at slowing the rate of disease progression. Selegiline has been shown to cause a mild delay in the need for levodopa, possibly suggesting some protection. However, this initial benefit was not sustained in long term studies. Currently, there is no neuroprotective drug for PD.

Animals↗
PubMed2000

Early detection of probable idiopathic Parkinson's disease: I. Development of a diagnostic test battery.

We developed a test battery as an inexpensive and objective aid for the early diagnosis of idiopathic Parkinson's disease (iPD) and its differential diagnoses. The test battery incorporates tests of motor function, olfaction, and mood. In the motor task, a wrist flexion-and-extension task to different targets, movement velocities were recorded. Olfaction was tested with the University of Pennsylvania Smell Identification Test. Mood was assessed with the Beck Depression Inventory. An initial regression model was developed from the results of 19 normal control subjects and 18 patients with early, mild, probable iPD. Prospective application to an independent validation set of 122 normal control subjects and 103 patients resulted in an 88% specificity rate and 69% sensitivity rate, with an area under the Receiver Operator Characteristic curve of 0.87.

Adult↗
PubMed2000

Time course of loss of clinical benefit following withdrawal of levodopa/carbidopa and bromocriptine in early Parkinson' s disease.

Putative neuroprotective agents for Parkinson's disease can be assessed in untreated patients using progression of clinical disability as an index of disease progression. To avoid the confound associated with symptomatic therapy, progression of the underlying disease can be assessed by evaluating the progression of clinical disability from an untreated baseline to a final visit following wash-out of symptomatic medication. In this type of analysis it is critical to use a washout of sufficient duration to ensure elimination of symptomatic effects. To assess the time course of resolution of symptomatic effects, we evaluated 31 patients at days 1, 8, and 15 following discontinuation of levodopa/carbidopa and bromocriptine. Mean total Unified Parkinson's Disease Rating Scale scores (+/- standard error) increased (worsened) by 7.4+/-1.5 from day 1 to day 15 (p <0.0001), 4.5+/-1.2 from day 1 to day 8 (p = 0.0009), and 2.9+/-1.0 from day 8 to day 15 (p = 0.01). We conclude that a wash-out of at least 2 weeks is required to eliminate the symptomatic effects of levodopa/carbidopa and bromocriptine in patients with early Parkinson's disease.

Aged↗
PubMed2000

Pharmacologic treatment of essential tremor.

Essential tremor (ET) is a common movement disorder that often causes functional disability, potentially leading to physical and emotional difficulties. The paucity of data available regarding the underlying pathophysiologic mechanism of ET hinders the development of innovative approaches to pharmacotherapeutic treatments. Options for drug therapy include the use of primidone, beta-adrenergic blockers, such as propranolol, alcohol, and other drugs, such as benzodiazepines, gabapentin, carbonic anhydrase inhibitors, clozapine, flunarizine, clonidine, and the methylxanthine derivative theophylline. Chemodenervation with botulinum toxin type A may be a therapeutic option for selected patients with ET. Each drug is classified as to the quality of evidence for efficacy and the suggested strength of therapeutic recommendation. In general clinical practice, primidone and propranolol have proven efficacy in ET.

Aged↗
PubMed2000

Surgical treatment of essential tremor.

Surgical treatment for essential tremor (ET) has been used since the early 1950s. Initially, different areas were targeted for tremor control. However, the optimal target was eventually determined to be the ventralis intermedius (VIM) nucleus of the thalamus. Thalamotomy improves contralateral tremor in more than 90% of patients. Long-term studies of thalamotomy indicate that the benefits continue in most patients. Persistent morbidity associated with thalamotomy, which occurs in less than 10% of patients, includes dysarthria, dysequilibrium, weakness, and cognitive impairment. Bilateral thalamotomy is associated with substantial morbidity and is usually avoided. Studies demonstrate that chronic stimulation of the VIM is safe and effective for tremor. Adverse effects of chronic stimulation include paresthesia, dysarthria, dysequilibrium, and localized pain. In many patients, bilateral thalamic stimulation is performed without a substantial increase in morbidity. ET patients with disabling medication-resistant tremor are reasonable candidates for these stereotactic procedures.

Essential Tremor↗
PubMed2000

Linear pharmacokinetic behavior of ropinirole during multiple dosing in patients with Parkinson's disease.

The objectives of this study were to measure the pharmacokinetics of ropinirole at steady state when the drug is used as an adjunct to L-dopa and evaluate the long-term tolerability of ropinirole in this indication. Twenty-four patients who were taking L-dopa for Parkinson's disease and experiencing a lack of symptomatic control were recruited. Patients received open-label adjunctive treatment with ropinirole for up to 2 years. The starting dose was 0.5 mg bid, which could be titrated to a maximum of 6.0 mg tid. Ropinirole demonstrated approximately dose-linear pharmacokinetics at steady state; corresponding values were higher during tid than bid dosing. A reduction in mean L-dopa dose was maintained throughout the trial. The combination of L-dopa and ropinirole was generally well tolerated, with only 1 patient withdrawing from treatment because of adverse events. Thus, ropinirole shows approximately linear steady-state pharmacokinetics and a good safety profile when administered with L-dopa.

Adult↗
PubMed2000

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.

Humans↗
PubMed2000

Deep brain stimulation of the Vim nucleus of the thalamus for the treatment of tremor.

The surgical treatment of tremor has evolved considerably in the past few years. Of the several conditions associated with severe tremor, the most common are Parkinson's disease (PD) and essential tremor (ET). Levodopa therapy reduced drastically the number of patients with PD who require surgery because of inadequate control. However, there remains a small number of "tremor dominant" PD patients for whom surgical treatment is often the best option. The ventralis intermediate nucleus (Vim) of the thalamus has been the preferred surgical target for the treatment of parkinsonian tremor for many years, but this is now challenged by the subthalamic nucleus (STN). Deep brain stimulation (DBS) of either target possesses high therapeutic efficacy against tremor in PD. ET may be difficult to treat pharmacologically. Thalamotomy is an effective surgical procedure for ameliorating ET but may be associated with persistent neurologic deficits. DBS of the thalamus is also a highly effective means of reducing ET. DBS appears to be safer than thalamotomy and is now the recommended surgical procedure.

Electric Stimulation Therapy↗
PubMed1999

Neuropsychological and quality of life outcome after thalamic stimulation for essential tremor.

OBJECTIVE: To evaluate short-term effects of unilateral thalamic deep brain stimulation (DBS) on cognition, mood state, and quality of life in patients with essential tremor (ET). BACKGROUND: Unilateral thalamotomy and thalamic DBS are effective in alleviating refractory tremor contralateral to the side of surgery. Thalamotomy can lead to cognitive morbidity, and DBS might be a preferable surgical intervention given potential avoidance or reversibility of such morbidity. Although unilateral thalamic DBS is cognitively safe and leads to quality of life improvement in PD, its neurobehavioral effects in ET are unknown. METHODS: Forty patients with ET were administered a broad neuropsychological test battery, measures of mood state, and generic and disease-specific quality of life measures approximately 1 month before and 3 months after surgery (left hemisphere, 38 patients). RESULTS: Unilateral thalamic DBS was associated with significant improvements in tremor and dominant-hand fine visuomotor coordination. Statistically significant but clinically modest gains were observed on tasks of visuoperceptual and constructional ability, visual attention, delayed word list recognition, and prose recall. Only lexical verbal fluency declined significantly after surgery. Patients rated themselves as less anxious after surgery, and they perceived their quality of life as improved significantly. In particular, patients reported improved quality of life with respect to activities of daily living, stigma, emotional well-being, and communication. CONCLUSIONS: Unilateral thalamic DBS for ET is cognitively safe and associated with improvements in anxiety and quality of life in the near term and in the absence of operative complications. Patients were better able to carry out activities of daily living after surgery, and they reported improvement in several psychosocial domains of quality of life.

Aged↗
PubMed1999

Bilateral thalamic stimulation for the treatment of essential tremor.

OBJECTIVE: To determine the safety and efficacy of bilateral thalamic stimulation in the treatment of essential tremor (ET). METHODS: Nine ET patients with disabling tremor refractory to pharmacotherapy underwent bilateral staged implants. Tremor was assessed by the Fahn-Tolosa-Marin Tremor Rating Scale at baseline 1 (before first implant), baseline 2 (before second implant), and at 6-month and 1-year follow-up. Blinded evaluations were performed at 3 months. Associated changes in speech were evaluated in six patients. There were seven men and two women with a mean age of 73.8 years. RESULTS: There was a significant improvement in the mean total tremor score from a baseline of 66.1+/-11.6 to 28.4+/-12.8 12 months after the second surgery. Similarly, the mean motor tremor subscore was 20.1+/-5.0 before the first surgery and improved significantly to 14.1+/-3.6 before the second surgery. Motor tremor scores 6 months after the second surgery (6.0+/-3.7) and 12 months after the second surgery (7.5+/-3.9) also improved significantly relative to the preoperative scores. The mean activities of daily living (ADL) subscore at baseline was 18.2+/-2.9 and improved significantly before the second surgery to 9.0+/-3.2. These ADL scores further improved 6 months (6.2+/-5.2) and 12 months (7.9+/-5.7) following the second surgery, but these gains were not significant. Blinded evaluations also revealed a similar degree of improvement. Complications were noted in five patients: asymptomatic intracranial hematoma (1), postoperative seizures (1), a hematoma over the implanted pulse generator (IPG) (1), lead repositioning (1), and IPG malfunction (1). Adverse effects related to stimulation were mild and resolved with adjustment of the stimulation parameters. Three of the six patients demonstrated worsening of dysarthria with both stimulators on. CONCLUSIONS: Bilateral thalamic stimulation is effective in reducing tremor and functional disability in ET; however, dysarthria is a possible complication.

Activities of Daily Living↗