Assistant Professor of Clinical Neurology, Weill Cornell Medical College
Dr. Sarva reports no financial relationships relevant to this field of study.
SYNOPSIS: Mood, cognitive, and behavioral changes in tremor-predominant Parkinson’s disease patients, three and 12 months after receiving MRI-guided focused ultrasound thalamotomy, were correlated with quality of life more than the severity of tremor reduction.
SOURCE:Sperling SA, Shah BB, Barrett MJ, et al. Focused ultrasound thalamotomy in Parkinson’s disease: Nonmotor outcomes and quality of life. Neurology 2018;91:e1275-e1284.
Magnetic resonance imaging-guided focused ultrasound (MRIgFUS) lesioning of the VIM thalamus is effective in treating appendicular essential tremor and now is being investigated to assess its efficacy in Parkinson’s disease (PD) tremor. Although initial studies of PD tremor have been encouraging, the long-term cognitive, behavioral, and quality-of-life effects of the thalamotomy are unknown. In this study, cognition, behavioral changes, and mood were assessed three months after MRIgFUS thalamotomy for tremor-predominant PD. Secondary outcomes included changes in these domains after three and 12 months. Postoperative quality-of-life assessments were performed to understand the effects of non-motor symptoms and tremor reduction on patient well-being. The sample group of subjects (n = 27) were derived from the investigators’ pilot randomized, sham-controlled MRIgFUS thalamotomy study for PD tremor, which was published in 2017. Twenty subjects were assigned to active treatment and seven to sham. After the three-month crossover period, six from the sham arm crossed over to the active group. In addition to PD and tremor rating scales, the patients underwent a comprehensive neuropsychological battery, which included tests for verbal fluency, frontal dysfunction, and quality of life.
Baseline demographic, motor, and non-motor characteristics were not statistically significant between the active and sham groups. There were no differences in overall cognitive performance or assessments of mood from baseline at three months and at 12 months. There were no statistically significant differences in cognitive or psychiatric assessments between those who received the treatment initially compared to the six who crossed over after receiving sham, but verbal fluency declined. Quality of life improved postoperatively at three months and at 12 months. However, quality-of-life changes did not correlate to tremor severity but with mood disorders, level of functionality, and Unified Parkinson’s Disease Rating Scale motor subscale scores, which accounts for all motor features of PD.
COMMENTARY
Prior literature describing neuropsychiatric effects following lesioning procedures has been mixed, with some showing decline and others no decline. This study demonstrates cognitive and psychiatric stability in patients receiving MRIgFUS thalamotomy for PD tremor both at three and 12 months post-procedure. Although this is encouraging, there are several important considerations. The sample size was small. Tremor-predominant PD patients who were not afflicted with a fast cognitive decline, in comparison to the postural instability gait disorder subtypes, were studied. Thus, it would be important to study this latter subtype, which more commonly is associated with cognitive decline, to allow for generalizability of these data. A number of patients were lost to follow-up at 12 months, further reducing predictability in cognition and mood at longer time points. With the use of more advanced MRI technology, such as tractography and other functional imaging, as well as the detailed neuropsychological battery and longer follow-up, subsequent studies may provide a better assessment of the non-motor effects of this lesioning procedure. The lesion target (thalamus vs. pallidum) also may play a role in determining neuropsychiatric stability long term, but further data are required.
Although MRIgFUS thalamotomy has been shown to be safe in essential tremor, its overall effects on cognition in PD are unknown, despite the preliminary positive results. Thus, larger studies involving complete neuropsychological batteries are necessary to determine the long-term sequelae of noninvasive lesioning procedures in PD.