Shukla, Aparna Wagle

Deep brain stimulation (DBS) is an effective neuromodulatory therapy for Parkinson’s disease (PD). Early studies using globus pallidus internus (GPi) DBS for PD profiled the nucleus as having two functional zones. This concept disseminated throughout the neuromodulation community as the “GPi triangle”. Although our understanding of the pallidum has greatly evolved over the past 20 years, we continue to reference the triangle in our clinical decision-making process. We propose a new direction, termed the spatial boundary hypothesis, to build upon the 2-dimensional outlook on GPi DBS. We believe an updated 3-D GPi model can produce more consistent, positive patient outcomes.

AbstractBackground and purposeSeveral clinical and demographic factors relate to anatomic spread of adult‐onset isolated dystonia, but a predictive model is still lacking. The aims of this study were: (i) to develop and validate a predictive model of anatomic spread of adult‐onset isolated dystonia; and (ii) to evaluate whether presence of tremor associated with dystonia influences model predictions of spread.MethodsAdult‐onset isolated dystonia participants with focal onset from the Dystonia Coalition Natural History Project database were included. We developed two prediction models, one with dystonia as sole disease manifestation (“dystonia‐only”) and one accepting dystonia OR tremor in any body part as disease manifestations (“dystonia OR tremor”). Demographic and clinical predictors were selected based on previous evidence, clinical plausibility of association with spread, or both. We used logistic regressions and evaluated model discrimination and calibration. Internal validation was carried out based on bootstrapping.ResultsBoth predictive models showed an area under the curve of 0.65 (95% confidence intervals 0.62–0.70 and 0.62–0.69, respectively) and good calibration after internal validation. In both models, onset of dystonia in body regions other than the neck, older age, depression and history of neck trauma were predictors of spread.ConclusionsThis predictive modeling of spread in adult‐onset isolated dystonia based on accessible predictors (demographic and clinical) can be easily implemented to inform individuals’ risk of spread. Because tremor did not influence prediction of spread, our results support the argument that tremor is a part of the dystonia syndrome, and not an independent or coincidental disorder.

AbstractThe pathophysiology of dystonic tremor and essential tremor remains partially understood. In patients with medication-refractory dystonic tremor or essential tremor, deep brain stimulation (DBS) targeting the thalamus or posterior subthalamic area has evolved into a promising treatment option. However, the optimal DBS targets for these disorders remains unknown. This retrospective study explored the optimal targets for DBS in essential tremor and dystonic tremor using a combination of volumes of tissue activated estimation and functional and structural connectivity analyses. We included 20 patients with dystonic tremor who underwent unilateral thalamic DBS, along with a matched cohort of 20 patients with essential tremor DBS. Tremor severity was assessed preoperatively and approximately 6 months after DBS implantation using the Fahn-Tolosa-Marin Tremor Rating Scale. The tremor-suppressing effects of DBS were estimated using the percentage improvement in the unilateral tremor-rating scale score contralateral to the side of implantation. The optimal stimulation region, based on the cluster centre of gravity for peak contralateral motor score improvement, for essential tremor was located in the ventral intermediate nucleus region and for dystonic tremor in the ventralis oralis posterior nucleus region along the ventral intermediate nucleus/ventralis oralis posterior nucleus border (4 mm anterior and 3 mm superior to that for essential tremor). Both disorders showed similar functional connectivity patterns: a positive correlation between tremor improvement and involvement of the primary sensorimotor, secondary motor and associative prefrontal regions. Tremor improvement, however, was tightly correlated with the primary sensorimotor regions in essential tremor, whereas in dystonic tremor, the correlation was tighter with the premotor and prefrontal regions. The dentato-rubro-thalamic tract, comprising the decussating and non-decussating fibres, significantly correlated with tremor improvement in both dystonic and essential tremor. In contrast, the pallidothalamic tracts, which primarily project to the ventralis oralis posterior nucleus region, significantly correlated with tremor improvement only in dystonic tremor. Our findings support the hypothesis that the pathophysiology underpinning dystonic tremor involves both the cerebello-thalamo-cortical network and the basal ganglia-thalamo-cortical network. Further our data suggest that the pathophysiology of essential tremor is primarily attributable to the abnormalities within the cerebello-thalamo-cortical network. We conclude that the ventral intermediate nucleus/ventralis oralis posterior nucleus border and ventral intermediate nucleus region may be a reasonable DBS target for patients with medication-refractory dystonic tremor and essential tremor, respectively. Uncovering the pathophysiology of these disorders may in the future aid in further improving DBS outcomes.

AbstractBackgroundLimited tools are available for the assessment of orthostatic tremor severity and disability.ObjectivesTo develop and validate a self‐administered orthostatic tremor scale.MethodsAfter expert consensus and literature review generating a list of 42 items, the scale was developed and modified for validation after a patient focus group, multiple rounds of Delphi panels, and cognitive interviews. Clinimetric evaluations included assessing content validity, internal consistency, measurement error and reliability, construct validity, and concurrent validity anchored on the examiner's Clinical Global Impression score.ResultsEleven items ranked on a Likert scale from 0 (no disability/severity) to 5 (maximal disability/severity) were evaluated in 54 orthostatic tremor patients (16 men and 38 women; mean age: 69.17 ± 9.64 years; disease duration: 13.83 ± 11.24 years) to probe severity and disability over the preceding 1‐week period. The 11‐item scale showed good internal consistency (Cronbach's alpha = 0.863) and acceptable (>0.40) item‐to‐total correlation. However, one item was removed at the final Delphi panel because of significant floor effect, poor item‐to‐total correlation, and poor factor‐loading, leaving the scale with 10 items (10‐item Orthostatic Tremor Severity and Disability Scale). Test‐retest reliability at 2 weeks was excellent (two‐way random intraclass correlation coefficient > 0.90), and the individual item test‐retest reliability showed good agreement, with a threshold weighted kappa >0.60 for all items. Exploratory factor analyses revealed a parsimonious two‐factor construct accounting for 57.7% of the scale's variance. The 10‐item Orthostatic Tremor Severity and Disability Scale scores correlated with the CGI.ConclusionsThe self‐administered 10‐item Orthostatic Tremor Severity and Disability Scale scale is valid and reliable for capturing orthostatic tremor–related severity and disability. © 2020 International Parkinson and Movement Disorder Society

AbstractBackgroundWe report the accumulated experience with ventral intermediate nucleus deep brain stimulation for medically refractory orthostatic tremor.MethodsData from 17 patients were reviewed, comparing presurgical, short‐term (0‐48 months), and long‐term (≥48 months) follow‐up. The primary end point was the composite activities of daily living/instrumental activities of daily living score. Secondary end points included latency of symptoms on standing and treatment‐related complications.ResultsThere was a 21.6% improvement (P = 0.004) in the composite activities of daily living/instrumental activities of daily living score, which gradually attenuated (12.5%) in the subgroup of patients with an additional long‐term follow‐up (8 of 17). The latency of symptoms on standing significantly improved, both in the short‐term (P = 0.001) and in the long‐term (P = 0.018). Three patients obtained no/minimal benefit from the procedure.ConclusionsDeep brain stimulation of the ventral intermediate nucleus was, in general, safe and well tolerated, yielding sustained benefit in selected patients with medically refractory orthostatic tremor. © 2017 International Parkinson and Movement Disorder Society