The occurrence of cognitive deficits that have been reported with thalamotomy and pallidotomy, and the failure of thalamotomy to improve features other than tremor, has driven an interest in trying to find alternative targets to lesion, especially for patients who require bilateral procedures and are not suitable for DBS.
The realization that the neurons of the STN in parkinsonian monkeys are over-active led to an interest in this nucleus as a possible target for PD (98). Surgeons had previously avoided the STN given the long-standing awareness that lesions of the normal STN in normal primates can cause hemiballism (99), and this is a well known consequence of infarcts and hemorrhages in this region in humans. In contrast, it has been shown that excitotoxic (100) or thermocoagulation (101) lesions of the pathological STN in MPTP-treated primates can alleviate parkinsonism. However, these thermocoagulation lesions also involved the internal capsule, ansa lenticularis, and globus pallidus (101,102), and so the clinical benefit in these cases may not have been solely due to deactivation of the STN. Early studies of deactivation of the subthalamic area by lesioning cannot be used to provide good quality evidence by today's standards because the lesions in this region of the brain were not anatomically well defined (103). When the STN became a logical target in the surgical treatment of PD, concern over the possibility of introducing chorea/ballism led neurosurgeons to apply stimulation rather than electrocoagulation to this site since the former can be successful and yet is more reversible (104). However, the relatively high technological demands and costs of DBS have encouraged some groups to attempt subthalamic nucleotomy.
There have been a few open-labeled, nonrandomized reports of the use of unilateral subthalamic nucleotomy in PD. The target in one study was the sensorimo-tor region of the dorsal STN, defined by semi-microrecordings and stimulation (18). These authors showed a sustained reduction in off motor UPDRS scores by 50% in 10/11 patients and this effect was maintained in 4/11 patients for two years. UPDRS on scores and ADL scores also improved. Ipsilateral bradykinesia improved by 20%, but this effect was not sustained at 12 months. Axial scores for gait and postural instability showed marked and sustained improvements. Dyskinesia was seen in the contralateral limbs of five patients during lesioning and lasted up to 12 hours before abating spontaneously. One patient developed transient delayed chorea. Another patient developed a postoperative infarction affecting the area of the lesioned STN, zona incerta, and ventral thalamus. This resulted in severe contralateral dyskinesia that persisted despite cessation of all levodopa and eventually required treatment with a pallidotomy on the same side as the subthalamotomy. Apart from this patient, the dose of medication was maintained for 12 months, unlike cases of bilateral STN DBS in which medication doses can be reduced significantly.
In the second series, the target was the central area of the subthalamus in nine patients and lesioning was guided by macrostimulation (17). Efficacy results were not reported but only one patient developed chorea postoperatively, which initially required medical treatment but then subsided spontaneously to only mild movements. Four subjects had their medication doses reduced. In the series of Gill and Heywood (105), five patients had unilateral and five had bilateral small subthalam-otomies with improved parkinsonism and only one case had mild dyskinesia. This group's larger report on 17 tremor-predominant, unilaterally operated patients followed for two years suggested improvement in all the features of parkinsonism, but greatest for tremor, with a 50% reduction in dopaminergic medication (106). Similar results were reported by Su et al. (107).
The target lesion in one series included the dorsolateral STN and pallidufugal fibers (Forel's field H2). Postoperative chorea was mild and transient, except in one patient in whom the lesion was confined to the STN only. The chorea in this instance was controlled by the subsequent insertion of a deep brain stimulator in the field H2 fibers and zona incerta. A similar phenomenon was described by comparison of two cases by Chen et al. (108); that is, a subthalamotomy that included the dorsal extranuclear fibers of the zona incerta led to less dyskinesia than a lesion confined to the STN only. Tseng et al. (109) described another patient with a lesion large enough to have included all of the STN, zona incerta, and lenticular fasciculus that caused delayed onset but permanent hemiballism that eventually led to death. The optimal target for lesions in the subthalamic area therefore needs further careful confirmation. It could be hypothesized, for example, that discrete small lesions confined to the nucleus (i.e., subthalamic nucleotomy) may be more likely to lead to chorea, whereas modest lesions which include the dorsolateral STN but also extend dorsally (i.e., subthalamic nucleotomy with additional interruption of the ansa lenticularis, zona incerta, and lenticular fasciculus) may be less likely to induce chorea since any potential to induce chorea may be counteracted by the concurrent interruption of these efferent fibers from the internal pallidum.
A somewhat unique side effect of unilateral subthalamotomy is leaning away from the side of the lesion. This can be responsive to dopaminergic medication, but in one report (110), the postural asymmetry resolved following a further subthalam-otomy on the other side. This observation is reminiscent of the asymmetric benefit that becomes apparent in bilaterally affected patients with akinetic-rigid symptoms following unilateral pallidotomy, and indicates that for these patients a bilateral procedure—typically bilateral STN DBS—should usually be offered. Currently, therefore, the exact location and role of unilateral lesions of the subthalamic region in clinical practice remains unclear.
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