Dynamic Cerebral Microdialysis during Pallidotomy and Thalamotomy in Parkinson’s Disease: A Preliminary Neurochemical Study

In Parkinson’s disease (PD), dopaminergic neurons reduce the regulation of glutamatergic (glutamate-Glu) input from the cortex to neostriatum (caudate and putamen nuclei) consequently leading to a hyperactivity of globus pallidus internae (GPi) neurons that release gamma-amino-butyric acid (GABA) into the thalamic ventrolateral (VL) nucleus. The objective of the present experiment was to measure changes in GABA and Glu in the caudate and the thalamus of 2 patients during the application of electrical stimuli following either a pallidotomy or a thalamotomy. Proper insertion of the electrode was tested by applying high frequency electrical pulses (HFEP). During these procedures, we obtained neurochemical information placing cerebral (CMD) microdialysis probes in caudate nucleus and VL nucleus of ipsi- and contra-lateral thalamus. In VL thalamus, extracellular GABA decreased during HFEP, tending to reach previous levels once HFEP was finalized. Following the pallido- or thalamotomy GABA decreased again. Similarly, in the contralateral VL thalamus, extracellular GABA levels showed a similar but less pronounced profile but did not show any decrement after the lesion. Caudate Glu decreases when HFEP is applied to the GPi and recovers to previous levels after HFEP, but did not decrease again after lesion (GPi-tomy), instead it continued to rise. These results suggest that HFEP exerts a similar but reversible biochemical effect as thermopallido- or thermothalamotomy on GABA extracellular concentration in the ipsilateral VL thalamus. We also observe a distant effect of HFEP, but not of thermolesion, on contralateral thalamic GABA and ipsilateral caudate Glu.

Magnetic resonance-guided focused ultrasound for essential tremor:a prospective,single center,single-arm study

The safety and effectiveness of magnetic resonance-guided focused ultrasound thalamotomy has been broadly established and validated for the treatment of essential tremor.In 2018,the first magnetic resonance-guided focused ultrasound system in Chinese mainland was installed at the First Medical Center of the PLA General Hospital.This prospective,single center,open-label,single-arm study was part of a worldwide prospective multicenter clinical trial(ClinicalTrials.gov Identifier:NCT03253991)conducted to confirm the safety and efficacy of magnetic resonance-guided focused ultrasound for treating essential tremor in the local population.From 2019 to 2020,10 patients with medication refractory essential tremor were recruited into this open-label,single arm study.The treatment efficacy was determined using the Clinical Rating Scale for Tremor.Safety was evaluated according to the incidence and severity of adverse events.All of the subjects underwent a unilateral thalamotomy targeting the ventral intermediate nucleus.At the baseline assessment,the estimated marginal mean of the Clinical Rating Scale for Tremor total score was 58.3±3.6,and this improved after treatment to 23.1±6.4 at a 12-month follow-up assessment.A total of 50 adverse events were recorded,and 2 were defined as serious.The most common intraoperative adverse events were nausea and headache.The most frequent postoperative adverse events were paresthesia and equilibrium disorder.Most of the adverse events were mild and usually disappeared within a few days.Our findings suggest that magnetic resonance-guided focused ultrasound for the treatment of essential tremor is effective,with a good safety profile,for patients in Chinese mainland.

Current surgical treatments for Parkinson's disease and potential therapeutic targets

Currently, the most common surgical treatment for Parkinson＇s disease is deep brain stimulation（DBS）. This treatment strategy is typically reserved for bradykinesia, rigidity and tremor in patients who no longer respond to medication in a predictable manner or who suffer medication-induced dyskinesias. In addition to DBS, ablative procedures like radiofrequency, radiosurgery and focused ultrasound are also utilized for select tremor symptoms. In this review, we discuss evolving surgical techniques, targets, and emerging technology. In addition, we evaluate potential paradigm shifts in treatment, including gene therapy, immunotherapy and cell transplantation. While these new techniques and treatment options are still in their infancy, advances in Parkinson＇s disease treatment are rapidly expanding.