Early Surgical Experiments

The Parkinson's-Reversing Breakthrough

Treatment for Parkinson Disease

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Early attempts to treat tremor by open resection of motor and premotor cortex resulted in the substitution of disabling extrapyramidal symptoms with disabling hemiparesis (1,2). A major advance came about with the publications of Russell Meyers in 1942 and 1951, showing that surgical resection of the head of the caudate nucleus and pallidofugal fibers (3,4) could resolve tremor and rigidity without inducing paresis. This paved the way for the next 20 years of experimental basal ganglia lesion surgery as a treatment for extrapyramidal syndromes. Surgical precision was improved and comorbidity was reduced with the development of the stereo-taxic technique (5). Subsequently, stereotaxic chemopallidectomy using procaine oil (6), alcohol (7), and pallidal electrocoagulation (8,9) were reported to effectively improve tremor and rigidity.

At that time, results were not reported in an objective manner and lesion locations within the pallidum were not precisely documented. The target was the anterodorsal pallidum, a target now proposed to be part of the associative circuits involved in motor control (10). The benefit of a more ventral lesion had already been documented with lesions that included the ansa lenticularis (11). Benefit was also reported from more posterior lesions in five patients who had gained only temporary relief from tremor from anterodorsal pallidotomy, but gained sustained antitremor benefits when their lesions were extended by 4 to 6 mm posteriorly (12).

Svennilson et al. (13) varied the position of their lesions in the first 32 cases from their cohort of 81 patients between 1953 and 1957 and showed sustained improvements in rigidity (79%) and tremor (82%) when the lesion was in the pos-teromedial aspect of the pallidum. They also reported additional benefit to general motor function, as assessed by their patients' ability to return to work (25%) or become independent in activities of daily living (37%).

Lesion locations were varied, not just within the pallidum but within the basal ganglia. Some early evidence suggested the superiority of thalamotomy in resolving tremor and rigidity (7,14). These reports were later extended to specify ventrolateral (VL) and ventral intermediate thalamotomy (15,16). In 1967, the introduction of levodopa (17) led to a worldwide reduction in the use of pallido-tomy and thalamotomy to treat parkinsonism. Lesion surgery later re-emerged with a new role as a result of identification of new indications and new targets within the basal ganglia (18), although it has largely been replaced by deep brain stimulation (DBS) (19,20).

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