Lesion therapy for Parkinson's disease and other movement disorders: Update and controversies

Abstract

An analysis of the international literature on lesioning for movement disorders was undertaken to review lesion therapy for Parkinson's disease (PD) and other movement disorders and to highlight important controversies surrounding this surgical technique. Lesions have been placed throughout the neuraxis with varying approaches and success. Our understanding of the pathophysiological basis underlying the development of PD and other movement disorders has led to a better understanding of why lesioning certain portions of the nervous system should improve motor function. Advances in imaging technology and electrophysiological techniques used for localization of brain structures, such as microelectrode mapping, have improved the ability to accurately identify and lesion target structures deep in the brain. This improvement has led to an increase in the degree and consistency of clinical benefit. The major controversies in lesion therapy include: (1) which target for which disorder; (2) determination of the optimal lesion site and whether the external globus pallidus (GPe) should be included in the pallidotomy lesion for PD; (3) determination of the size of the lesion; (4) whether bilateral lesions can be placed without the high incidence of side effects reported by some investigators; (5) whether microelectrodes aid in the ability to improve clinical outcomes or increase the risk of side effects by making multiple microelectrode penetrations; (6) whether the subthalamic nucleus (STN) should be explored further as a lesioning target; and (7) whether lesioning should be abandoned entirely in favor of deep brain stimulation (DBS). Many important questions and controversies regarding lesion therapy remain unanswered. It is unlikely given the pro-DBS environment that these questions will be answered in the near future. We should, however, be careful not to abandon an effective therapy before fully exploring through randomized trials the relative effect of different surgical approaches for the treatment of patients with movement disorders.

Subthalamic Lesion or Levodopa Treatment Rescues Giant GABAergic Currents of PINK1-Deficient Striatum

“…The STN area is a well known target for surgical therapy in PD patients, either through lesion approaches or deep brain stimulation (Limousin et al, 1995;Okun and Vitek, 2004;Bronstein et al, 2011). Our observations suggest that the Pink1 Ϫ/Ϫ mice are a model for not only the electrophysiological anomalies typical of early-stage PD, they are also a useful tool to study the surgical modulation of impaired neural circuit function in PD.…”

The striatofugal fiber system in primates: A reevaluation of its organization based on single-axon tracing studies

“…These functional differences are even more obvious in the parkinsonian state, where a remarkable neuronal hyperactivity occurs in GPi but not in SNr, as noted in patients suffering from idiopathic Parkinson's disease as well as in monkeys rendered parkinsonian after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine injection (39)(40)(41). This finding explains why the GPi became the preferential target of stereotaxic surgical lesions to alleviate motor symptoms in Parkinson's disease (42). These results suggest that the cortico-caudato-nigral pathway is chiefly involved in the planning of motor acts, whereas the corticoputameno-pallidal pathway is principally concerned with their execution (Fig.…”

Network modulation by the subthalamic nucleus in the treatment of Parkinson's disease

“…In advanced PD, significant clinical benefit can be achieved with either stereotaxic lesioning or high-frequency stimulation of the STN (Lozano and Mahant, 2004;Okun and Vitek, 2004). Although the therapeutic outcome is similar for both these interventions, the mechanisms underlying STN lesioning and stimulation may be different (McIntyre et al, 2004a,b).…”