The effects of thalamic and posterior subthalamic deep brain stimulation on speech in patients with essential tremor - A prospective, randomized, doubleblind crossover study.

OBJECTIVE: To prospectively evaluate the effect of PSA- and VIM DBS on speech in ET patients. METHODS: Leads were implanted bilaterally with contacts placed in both VIM and PSA. Thirteen patients were analyzed pre- and postoperatively. Preoperative speech of ET patients was compared to healthy controls. PSA- and VIM-DBS were evaluated in a randomized, double-blind crossover phase. RESULTS: At preoperative baseline, we found reduced intelligibility. Differences in acoustic and VAS data ('ability to speak') compared to controls were gradient. Articulation rate could be predicted by disease duration. Decreased articulation rate, spirantization and voicing were found for PSA- and VIM-DBS. Targets did not differ in terms of speech deterioration. CONCLUSION: Speech in ET patients without DBS can be impaired, dependent on patient's individual characteristics. Both PSA- and VIM-DBS affect speech in a comparable way. Thus, the PSA can be considered an alternative DBS target in ET without higher risk of dysarthria.

Non-motor outcomes depend on location of neurostimulation in Parkinson's disease.

Deep brain stimulation of the subthalamic nucleus is an effective and established therapy for patients with advanced Parkinson's disease improving quality of life, motor symptoms and non-motor symptoms. However, there is a considerable degree of interindividual variability for these outcomes, likely due to variability in electrode placement and stimulation settings. Here, we present probabilistic mapping data from a prospective, open-label, multicentre, international study to investigate the influence of the location of subthalamic nucleus deep brain stimulation on non-motor symptoms in patients with Parkinson's disease. A total of 91 Parkinson's disease patients undergoing bilateral deep brain stimulation of the subthalamic nucleus were included, and we investigated NMSScale, NMSQuestionnaire, Scales for Outcomes in Parkinson's disease-motor examination, -activities of daily living, and -motor complications, and Parkinson's disease Questionnaire-8 preoperatively and at 6-month follow-up after surgery. Leads were localized in standard space using the Lead-DBS toolbox and individual volumes of tissue activated were calculated based on clinical stimulation settings. Probabilistic stimulation maps and non-parametric permutation statistics were applied to identify voxels with significant above or below average improvement for each scale and analysed using the DISTAL atlas. All outcomes improved significantly at follow-up. Significant spatial distribution patterns of neurostimulation were observed for NMSScale total score and its mood/apathy and attention/memory domains. For both domains, voxels associated with below average improvement were mainly located dorsal to the subthalamic nucleus. In contrast, above average improvement for mood/apathy was observed in the ventral border region of the subthalamic nucleus and in its sensorimotor subregion and for attention/memory in the associative subregion. A trend was observed for NMSScale sleep domain showing voxels with above average improvement located ventral to the subthalamic nucleus. Our study provides evidence that the interindividual variability of mood/apathy, attention/memory, and sleep outcomes after subthalamic nucleus deep brain stimulation depends on the location of neurostimulation. This study highlights the importance of holistic assessments of motor and non-motor aspects of Parkinson's disease to tailor surgical targeting and stimulation parameter settings to patients' personal profiles.

Nonmotor symptoms evolution during 24 months of bilateral subthalamic stimulation in Parkinson's disease.

BACKGROUND: The objective of this study was to investigate 24-month of effects of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) on nonmotor symptoms in Parkinson's disease (PD). METHODS: In this prospective, observational, multicenter, international study including 67 PD patients undergoing bilateral STN-DBS, we examined the Non-motor Symptom Scale, Non-Motor Symptoms Questionnaire, Parkinson's Disease Questionnaire-8, Scales for Outcomes in Parkinson's Disease-motor examination, -activities of daily living, and -complications, and levodopa-equivalent daily dose preoperatively and at 5 and 24-month of follow-up. After checking distribution normality, longitudinal outcome changes were investigated with Friedman tests or repeated-measures analysis of variance and Bonferroni correction for multiple comparisons using multiple tests. Post hoc, Wilcoxon signed rank t tests were computed to compare visits. The strength of clinical responses was analyzed using effect size. Explorative Spearman correlations of change scores from baseline to 24-month follow-up were calculated for all outcomes. RESULTS: The Non-motor Symptom Scale and all other outcome parameters significantly improved from baseline to the 5-month follow-up. From 5 to 24-month, partial decrements in these gains were found. Nonetheless, comparing baseline with 24-month follow-up, significant improvements were observed for the Non-motor Symptom Scale (small effect), Scales for Outcomes in PD-motor examination showed a moderate effect, and Scales for Outcomes in Parkinson's Disease-complications and levodopa-equivalent daily dose showed large effects. Non-motor Symptom Scale change scores from baseline to 24-month follow-up correlated significantly with Parkinson's Disease Questionnaire-8, Scales for Outcomes in Parkinson's Disease-activities of daily living, and -motor complications change scores. CONCLUSIONS: This study provides evidence of beneficial effects of bilateral STN-DBS on nonmotor symptoms at 24-month follow-up. The extent of nonmotor symptom improvement was directly proportionate to improvements in quality of life, activities of daily living, and motor complications. This study underlines the importance of nonmotor symptoms for holistic assessments of DBS outcomes. © 2018 International Parkinson and Movement Disorder Society.

The effects of Thalamic Deep Brain Stimulation on speech dynamics in patients with Essential Tremor: An articulographic study.

Acoustic studies have revealed that patients with Essential Tremor treated with thalamic Deep Brain Stimulation (DBS) may suffer from speech deterioration in terms of imprecise oral articulation and reduced voicing control. Based on the acoustic signal one cannot infer, however, whether this deterioration is due to a general slowing down of the speech motor system (e.g., a target undershoot of a desired articulatory goal resulting from being too slow) or disturbed coordination (e.g., a target undershoot caused by problems with the relative phasing of articulatory movements). To elucidate this issue further, we here investigated both acoustics and articulatory patterns of the labial and lingual system using Electromagnetic Articulography (EMA) in twelve Essential Tremor patients treated with thalamic DBS and twelve age- and sex-matched controls. By comparing patients with activated (DBS-ON) and inactivated stimulation (DBS-OFF) with control speakers, we show that critical changes in speech dynamics occur on two levels: With inactivated stimulation (DBS-OFF), patients showed coordination problems of the labial and lingual system in terms of articulatory imprecision and slowness. These effects of articulatory discoordination worsened under activated stimulation, accompanied by an additional overall slowing down of the speech motor system. This leads to a poor performance of syllables on the acoustic surface, reflecting an aggravation either of pre-existing cerebellar deficits and/or the affection of the upper motor fibers of the internal capsule.

Individualized current-shaping reduces DBS-induced dysarthria in patients with essential tremor.

OBJECTIVE: To investigate in patients with essential tremor (ET) treated with thalamic/subthalamic deep brain stimulation (DBS) whether stimulation-induced dysarthria (SID) can be diminished by individualized current-shaping with interleaving stimulation (cs-ILS) while maintaining tremor suppression (TS). METHODS: Of 26 patients screened, 10 reported SID and were invited for testing. TS was assessed by the Tremor Rating Scale and kinematic analysis of postural and action tremor. SID was assessed by phonetic and logopedic means. Additionally, patients rated their dysarthria on a visual analog scale. RESULTS: In 6 of the 10 patients with ET, DBS-ON (relative to DBS-OFF) led to SID while tremor was successfully reduced. When comparing individualized cs-ILS with a non-current-shaped interleaving stimulation (ILS) in these patients, there was no difference in TS while 4 of the 6 patients showed subjective improvement of speech during cs-ILS. Phonetic analysis (ILS vs cs-ILS) revealed that during cs-ILS there was a reduction of voicing during the production of voiceless stop consonants and also a trend toward an improvement in oral diadochokinetic rate, reflecting less dysarthria. Logopedic rating showed a trend toward deterioration in the diadochokinesis task when comparing ON with OFF but no difference between ILS and cs-ILS. CONCLUSION: This is a proof-of-principle evaluation of current-shaping in patients with ET treated with thalamic/subthalamic DBS and experiencing SID. Data suggest a benefit on SID from individual shaping of current spread while TS is preserved. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in patients with ET treated with DBS with SID, individualized cs-ILS reduces dysarthria while maintaining tremor control.