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Biomedical subjects

Klaus Mewes

Publications and source records attributed to Klaus Mewes.

4 recordsLinked to original sources

Restricted ablative lesions in motor portions of GPi in primates produce extensive loss of motor-related neurons and degeneration of the lenticular fasciculus.

Deep brain stimulation (DBS) of the internal pallidum (GPi) and the subthalamic nucleus and to a lesser extent, ablative lesioning, are broadly utilized to treat patients with medically intractable Parkinson's disease and other movement disorders. Beneficial outcomes however are not uniform and adverse cognitive and behavioral are significant risks. Surgical outcomes of GPi surgeries might be improved by approaches that better account for the course of motor and non-motor pallidothalamic projections. Although several studies, including our own tracer investigations, suggest that motor projections from GPi principally form the lenticular fasciculus and non-motor projections primarily contribute to the ansa lenticularis, other schemes have perpetuated. Presently, to corroborate the course of pallidothalamic projections and to assess the feasibility of selectively targeting the motor circuit of GPi, radiofrequency lesions were placed in the motor portion of GPi in monkeys. Degenerating pallidothalamic fibers were visualized with amino cupric staining techniques and regional cell counts in GPi were compared with control hemispheres. Lesions restricted to posterior motor portions of GPi produced selective degeneration of LF and only damaged AL if the lesions extended more anteriorly. Marked secondary neuronal loss occurred well beyond the principal lesions but was mainly confined to the posterolateral motor region of GPi. These findings corroborate the original pallidothalamic outflow scheme proposed by Ranson and Ranson. Conceivably, a restrictive lesion or a DBS probe could be placed in the centroposterior portion of GPi to selectively target both local motor-related neurons and traversing pallidothalamic fibers originating from more posterior and lateral motor regions.

Animals↗

Lesions in monkey globus pallidus externus exacerbate parkinsonian symptoms.

To further define the role of the external segment of the globus pallidus (GPe) in the development of parkinsonian motor signs, two rhesus monkeys were made parkinsonian with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Behavioral assessments of bradykinesia and akinesia as well as single neuron recordings in the internal segment of the globus pallidus (GPi) were performed in both monkeys before and after ablating the sensorimotor portion of GPe. The effects of apomorphine on behavior and neuronal activity were also assessed in the parkinsonian monkeys before and after GPe ablation. We found that lesions in GPe exacerbated parkinsonian symptoms, altered neuronal activity in GPi, and reduced the therapeutic effects of apomorphine. These results support the hypothesis that GPe can influence GPi neuronal activity and is directly involved in parkinsonism. In addition, these data suggest that the inclusion of GPe in pallidotomy lesions for the treatment of Parkinson's disease can block the beneficial effects of antiparkinsonian medications and should be avoided.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Randomized trial of pallidotomy versus medical therapy for Parkinson's disease.

Thirty-six patients with Parkinson's disease (PD) were randomized to either medical therapy (N = 18) or unilateral GPi pallidotomy (N = 18). The primary outcome variable was the change in total Unified Parkinson's Disease Rating Scale (UPDRS) score at 6 months. Secondary outcome variables included subscores and individual parkinsonian symptoms as determined from the UPDRS. At the six month follow-up, patients receiving pallidotomy had a statistically significant reduction (32% decrease) in the total UPDRS score compared to those randomized to medical therapy (5% increase). Following surgery, patients' showed improvement in all the cardinal motor signs of PD including tremor, rigidity, bradykinesia, gait and balance. Drug-induced dyskinesias were also markedly improved. Although the greatest improvement occurred on the side contralateral to the lesion, significant ipsilateral improvement was also observed for bradykinesia, rigidity and drug-induced dyskinesias. A total of twenty patients have been followed for 2 years to assess the effect of time on clinical outcome. These patients have shown sustained improvement in the total UPDRS (p < 0.0001), "off" motor (p < 0.0001) and complications of therapy subscores (p < 0.0001). Sustained improvement was also seen for tremor, rigidity, bradykinesia, percent on time and drug-induced dyskinesias.

Antiparkinson Agents↗

3D visualization methods to guide surgery for Parkinson's disease.

In this paper we present 2D and 3D visualization techniques that are part of our ongoing effort to improve the accuracy of neurosurgical procedures such as 'Pallidotomy' and 'Deep Brain Stimulation' (DBS), which are performed to alleviate the symptoms of Parkinson's disease. The precise targeting and mapping of structures in the Basal Ganglia particularly the internal Globus Pallidus (GPi) using a combination of stereotactic frame- registered Magnetic Resonance Imaging (MRI) and intraoperative microelectrode recording (IMR) is key to the success of these procedures. We have designed a set of software components, including a knowledge-based system (KBS), a digital signal processing module and a 2D/3D imaging system with automated mapping paradigm, which will work in combination to improve upon the standards currently in use. The imaging system will be the focus of this publication.

Humans↗