A trial of scheduled deep brain stimulation for Tourette syndrome: moving away from continuous deep brain stimulation paradigms.

OBJECTIVE: To collect the information necessary to design the methods and outcome variables for a larger trial of scheduled deep brain stimulation (DBS) for Tourette syndrome. DESIGN: We performed a small National Institutes of Health-sponsored clinical trials planning study of the safety and preliminary efficacy of implanted DBS in the bilateral centromedian thalamic region. The study used a cranially contained constant-current device and a scheduled, rather than the classic continuous, DBS paradigm. Baseline vs 6-month outcomes were collected and analyzed. In addition, we compared acute scheduled vs acute continuous vs off DBS. SETTING: A university movement disorders center. PATIENTS: Five patients with implanted DBS. MAIN OUTCOME MEASURE: A 50% improvement in the Yale Global Tic Severity Scale (YGTSS) total score. RESULTS Participating subjects had a mean age of 34.4 (range, 28-39) years and a mean disease duration of 28.8 years. No significant adverse events or hardware-related issues occurred. Baseline vs 6-month data revealed that reductions in the YGTSS total score did not achieve the prestudy criterion of a 50% improvement in the YGTSS total score on scheduled stimulation settings. However, statistically significant improvements were observed in the YGTSS total score (mean [SD] change, -17.8 [9.4]; P=.01), impairment score (-11.3 [5.0]; P=.007), and motor score (-2.8 [2.2]; P=.045); the Modified Rush Tic Rating Scale Score total score (-5.8 [2.9]; P=.01); and the phonic tic severity score (-2.2 [2.6]; P=.04). Continuous, off, and scheduled stimulation conditions were assessed blindly in an acute experiment at 6 months after implantation. The scores in all 3 conditions showed a trend for improvement. Trends for improvement also occurred with continuous and scheduled conditions performing better than the off condition. Tic suppression was commonly seen at ventral (deep) contacts, and programming settings resulting in tic suppression were commonly associated with a subjective feeling of calmness. CONCLUSIONS: This study provides safety and proof of concept that a scheduled DBS approach could improve motor and vocal tics in Tourette syndrome. Refinements in neurostimulator battery life, outcome measure selection, and flexibility in programming settings can be used to enhance outcomes in a future larger study. Scheduled stimulation holds promise as a potential first step for shifting movement and neuropsychiatric disorders toward more responsive neuromodulation approaches. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01329198.

DBS candidates that fall short on a levodopa challenge test: alternative and important indications.

INTRODUCTION: Candidacy for deep brain stimulation (DBS) in Parkinson disease (PD) is typically assessed by the preoperative motor response to levodopa along with an interdisciplinary evaluation. However, recent cases treated at our institution have achieved good outcomes with DBS despite a sub-30% improvement in motor scores. The aim of this study was to examine the outcomes of DBS in a subset of patients who failed to reach the 30% motor improvement threshold. METHODS: A review of all DBS patients treated at the University of Florida Movement Disorders Center between 2002 and 2009 was performed utilizing a DBS database. All patients with sub-30% improvement in Unified Parkinson Disease Rating Scale Part III after dopaminergic medication administration were included. RESULTS: Nine patients were identified; DBS was performed for severe dyskinesia (n=5), "on/off motor" fluctuations (n=1) and medication-refractory tremor (n=3). The target symptoms were improved in all patients. Postoperatively, scores on the Unified Parkinson Disease Rating Scale Part II and III and subscores on Parkinson disease questionnaire-39 improved (P<0.05). CONCLUSIONS: Although motor response to levodopa remains the primary selection criteria for DBS candidacy in Parkinson disease, patients who do not meet the 30% threshold and have disabling symptoms may still benefit from DBS. Select patients with severe dyskinesia, "on/off" motor fluctuations, and/or medication-refractory tremor may experience significant benefits from DBS and should be considered on a case by case basis through an interdisciplinary team evaluation.

Inappropriate crying and laughing in Parkinson disease and movement disorders.

OBJECTIVE: To examine in a pilot study inappropriate crying and laughing (also termed pseudobulbar affect (PBA)) and underlying mood disturbances in a large clinic based population of Parkinson's disease and movement disorder patients. BACKGROUND: PBA is characterized by uncontrollable laughter without mirth, or alternatively crying without the feeling of sadness. It is a common condition affecting more than one million people with neurological diseases. While PBA has been studied in many neurological diseases, little is known about its prevalence in movement disorders, or its relationship to more chronic mood disturbances. We carried out this pilot study to examine this relationship. METHODS: Seven hundred and nineteen out of 860 consecutive patients who visited our Movement Disorders Center met inclusion criteria (i.e. > or = 18 years of age, formal diagnosis by a movement disorder specialist, completion of PBA questionnaire, and absence of brain surgery including deep brain stimulation). All subjects were interviewed for symptoms of PBA during their visit. In addition, 661 of these patients completed both the Visual Analog Mood Scale (VAMS) and Beck Depression Inventory I (BDI-I). RESULTS: Thirty-seven of the 719 reported PBA symptoms; 75.7% (28/37) had pathological 'crying', 13.5% (5/37) had pathological 'laughing' and 10.8% (4/37) had both. The prevalence of PBA in individual diagnostic categories was: 4.7% (18/387) of idiopathic Parkinson's disease (PD), 2.7% (2/74) of primary dystonia, 3.1% (2/65) of essential tremor (ET), 7.8% (8/108) of patients with other forms of Parkinsonism, 21.7% (5/23) of psychogenic movement disorders, 0% (0/18) of patients with combined PD and ET, and 4.5% (2/44) of other movement disorders. Patients with PBA had a higher total BDI score (P=0.0278) and VAMS 'tiredness' score (P=0.0109). In patients on antidepressant therapy the prevalence of PBA was 7.1% compared to 2.7% in the group not on therapy (P=0.0094). CONCLUSION: PBA was present in most movement disorders, but especially prevalent in parkinsonism. PBA patients in this cohort had more chronic depressive symptoms and tiredness.