ON/OFF non-motor evaluation: a new way to evaluate non-motor fluctuations in Parkinson's disease.

BACKGROUND: NMF are currently poorly evaluated in therapeutic decisions. A quantification of their severity would facilitate their integration. The objective of this study was to validate an autoquestionnaire evaluating the severity of non-motor fluctuations (NMF) in Parkinson's disease (PD). METHODS: Patients with PD were included in presurgical situation for deep brain stimulation of subthalamic nuclei. They participated in the PREDISTIM cohort (a study evaluating the predictive factors for therapeutic response of subthalamic stimulation in PD) in 17 centres in France. Our questionnaire, resulting from previous phases of development, included 11 non-motor symptoms (NMS). Their severity ranged from 0 to 10 and was assessed in OFF and then ON-Dopa to study their fluctuations. RESULTS: 310 patients were included, of whom 98.8% had NMS and 98.0% had NMF. Each NMS was significantly improved by L-Dopa (decrease in severity score ranging from 43.1% to 69.9%). Fatigue was the most frequent and most severe NMS. NMS were considered more bothersome than motor symptoms by 37.5% of patients in OFF-Dopa and 34.9% in ON-Dopa. CONCLUSIONS: This is the first questionnaire allowing a real-time quantification of the severity of NMS and their fluctuation with levodopa. It was able to confirm and measure the effect of L-dopa and show differences according to the patients and the NMS. It differs from other questionnaires by its measurement at a precise moment of the severity of the NMS, allowing its use during pretherapeutic assessments.Our questionnaire has been validated to measure the severity of NMF. It will be able to quantify the non-motor effect of anti-parkinsonian treatments and could facilitate the integration of NMF in therapeutic decisions.

Dynamic functional changes upon thalamotomy in essential tremor depend on baseline brain morphometry.

Patients with drug-resistant essential tremor (ET) may undergo Gamma Knife stereotactic radiosurgical thalamotomy (SRS-T), where the ventro-intermediate nucleus of the thalamus (Vim) is lesioned by focused beams of gamma radiations to induce clinical improvement. Here, we studied SRS-T impacts on left Vim dynamic functional connectivity (dFC, n = 23 ET patients scanned before and 1 year after intervention), and on surface-based morphometric brain features (n = 34 patients, including those from dFC analysis). In matched healthy controls (HCs), three dFC states were extracted from resting-state functional MRI data. In ET patients, state 1 spatial stability increased upon SRS-T (F1,22 = 19.13, p = 0.004). More frequent expression of state 3 over state 1 before SRS-T correlated with greater clinical recovery in a way that depended on the MR signature volume (t6 = 4.6, p = 0.004). Lower pre-intervention spatial variability in state 3 expression also did (t6 = - 4.24, p = 0.005) and interacted with the presence of familial ET so that these patients improved less (t6 = 4.14, p = 0.006). ET morphometric profiles showed significantly lower similarity to HCs in 13 regions upon SRS-T (z ≤ - 3.66, p ≤ 0.022), and a joint analysis revealed that before thalamotomy, morphometric similarity and states 2/3 mean spatial similarity to HCs were anticorrelated, a relationship that disappeared upon SRS-T (z ≥ 4.39, p < 0.001). Our results show that left Vim functional dynamics directly relates to upper limb tremor lowering upon intervention, while morphometry instead has a supporting role in reshaping such dynamics.

Exploring the heterogeneous morphometric data in essential tremor with probabilistic modelling.

Essential tremor (ET) is a prevalent movement disorder characterized by marked clinical heterogeneity. Here, we explored the morphometric underpinnings of this cross-subject variability on a cohort of 34 patients with right-dominant drug-resistant ET and 29 matched healthy controls (HCs). For each brain region, group-wise morphometric data was modelled by a multivariate Gaussian to account for morphometric features' (co)variance. No group differences were found in terms of mean values, highlighting the limits of more basic group comparison approaches. Variance in surface area was higher in ET in the left lingual and caudal anterior cingulate cortices, while variance in mean curvature was lower in the right superior temporal cortex and pars triangularis, left supramarginal gyrus and bilateral paracentral gyrus. Heterogeneity further extended to the right putamen, for which a mixture of two Gaussians fitted the ET data better than a single one. Partial Least Squares analysis revealed the rich clinical relevance of the ET population's heterogeneity: first, increased head tremor and longer symptoms' duration were accompanied by broadly lower cortical gyrification. Second, more severe upper limb tremor and impairments in daily life activities characterized the patients whose morphometric profiles were more atypical compared to the average ET population, irrespective of the exact nature of the alterations. Our results provide candidate morphometric substrates for two different types of clinical variability in ET. They also demonstrate the importance of relying on analytical approaches that can efficiently handle multivariate data and enable to test more sophisticated hypotheses regarding its organization.

Deep Brain Stimulation-Withdrawal Syndrome in Parkinson's Disease: Risk Factors and Pathophysiological Hypotheses of a Life-Threatening Emergency.

BACKGROUND AND OBJECTIVES: Subthalamic nucleus deep brain stimulation (DBS) is the most common therapeutic surgical procedure for patients with Parkinson's disease with motor fluctuations, dyskinesia, or tremor. Routine follow-up of patients allows clinicians to anticipate replacement of the DBS battery reaching the end of its life. Patients who experience a sudden stop of the DBS battery experience a rapid worsening of symptoms unresponsive to high dose of levodopa, in a life-threatening phenomenon called "DBS-withdrawal syndrome." In the current context of the COVID-19 pandemic, in which many surgeries are being deprogrammed, it is of utmost importance to determine to what extent DBS battery replacement surgeries should be considered an emergency. In this study, we attempt to identify risk factors of DBS-withdrawal syndrome and provide new insights about pathophysiological hypotheses. We then elaborate on the optimal approach to avoid and manage such a situation. MATERIALS AND METHODS: We conducted a systematic review of the literature on the subject and reported the cases of 20 patients (including five from our experience) with DBS-withdrawal syndrome, comparing them with 15 undisturbed patients (including three from our experience), all having undergone neurostimulation discontinuation. RESULTS: A long disease duration at battery removal and many years of DBS therapy are the main potential identified risk factors (p < 0.005). In addition, a trend for older age at the event and higher Unified Parkinson's Disease Rating Scale motor score before initial DBS implantation (evaluated in OFF-drug condition) was found (p < 0.05). We discuss several hypotheses that might explain this phenomenon, including discontinued functioning of the thalamic-basal ganglia loop due to DBS-stimulation cessation in a context in which cortical-basal ganglia loop had lost its cortical input, and possible onset of a severe bradykinesia through the simultaneous occurrence of an alpha and high-beta synchronized state. CONCLUSIONS: The patients' clinical condition may deteriorate rapidly, be unresponsive to high dose of levodopa, and become life-threatening. Hospitalization is suggested for clinical monitoring. In the context of the current COVID-19 pandemic, it is important to widely communicate the replacement of DBS batteries reaching the end of their life. More importantly, in cases in which the battery has stopped, there should be no delay in performing replacement as an emergent surgery.

Results of a Randomized Clinical Trial of Speech After Early Neurostimulation in Parkinson's Disease.

BACKGROUND: The EARLYSTIM trial demonstrated for Parkinson's disease patients with early motor complications that deep brain stimulation of the subthalamic nucleus (STN-DBS) and best medical treatment (BMT) was superior to BMT alone. OBJECTIVE: This prospective, ancillary study on EARLYSTIM compared changes in blinded speech intelligibility assessment between STN-DBS and BMT over 2 years, and secondary outcomes included non-speech oral movements (maximum phonation time [MPT], oral diadochokinesis), physician- and patient-reported assessments. METHODS: STN-DBS (n = 102) and BMT (n = 99) groups underwent assessments on/off medication at baseline and 24 months (in four conditions: on/off medication, ON/OFF stimulation-for STN-DBS). Words and sentences were randomly presented to blinded listeners, and speech intelligibility rate was measured. Statistical analyses compared changes between the STN-DBS and BMT groups from baseline to 24 months. RESULTS: Over the 2-year period, changes in speech intelligibility and MPT, as well as patient-reported outcomes, were not different between groups, either off or on medication or OFF or ON stimulation, but most outcomes showed a nonsignificant trend toward worsening in both groups. Change in oral diadochokinesis was significantly different between STN-DBS and BMT groups, on medication and OFF STN-DBS, with patients in the STN-DBS group performing slightly worse than patients under BMT only. A signal for clinical worsening with STN-DBS was found for the individual speech item of the Unified Parkinson's Disease Rating Scale, Part III. CONCLUSION: At this early stage of the patients' disease, STN-DBS did not result in a consistent deterioration in blinded speech intelligibility assessment and patient-reported communication, as observed in studies of advanced Parkinson's Disease. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Graph Theoretical Analysis of Structural Covariance Reveals the Relevance of Visuospatial and Attentional Areas in Essential Tremor Recovery After Stereotactic Radiosurgical Thalamotomy.

Essential tremor (ET) is the most common movement disorder. Its pathophysiology is only partially understood. Here, we leveraged graph theoretical analysis on structural covariance patterns quantified from morphometric estimates for cortical thickness, surface area, and mean curvature in patients with ET before and one year after (to account for delayed clinical effect) ventro-intermediate nucleus (Vim) stereotactic radiosurgical thalamotomy. We further contrasted the observed patterns with those from matched healthy controls (HCs). Significant group differences at the level of individual morphometric properties were specific to mean curvature and the post-/pre-thalamotomy contrast, evidencing brain plasticity at the level of the targeted left thalamus, and of low-level visual, high-level visuospatial and attentional areas implicated in the dorsal visual stream. The introduction of cross-correlational analysis across pairs of morphometric properties strengthened the presence of dorsal visual stream readjustments following thalamotomy, as cortical thickness in the right lingual gyrus, bilateral rostral middle frontal gyrus, and left pre-central gyrus was interrelated with mean curvature in the rest of the brain. Overall, our results position mean curvature as the most relevant morphometric feature to understand brain plasticity in drug-resistant ET patients following Vim thalamotomy. They also highlight the importance of examining not only individual features, but also their interactions, to gain insight into the routes of recovery following intervention.

The Contribution of Subthalamic Nucleus Deep Brain Stimulation to the Improvement in Motor Functions and Quality of Life.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN-DBS) effectively treats motor symptoms and quality of life (QoL) of advanced and fluctuating early Parkinson's disease. Little is known about the relation between electrode position and changes in symptom control and ultimately QoL. OBJECTIVES: The relation between the stimulated part of the STN and clinical outcomes, including the motor score of the Unified Parkinson's Disease Rating Scale (UPDRS) and the quality-of-life questionnaire, was assessed in a subcohort of the EARLYSTIM study. METHODS: Sixty-nine patients from the EARLYSTIM cohort who underwent DBS, with a comprehensive clinical characterization before and 24 months after surgery, were included. Intercorrelations of clinical outcome changes, correlation between the affected functional parts of the STN, and changes in clinical outcomes were investigated. We further calculated sweet spots for different clinical parameters. RESULTS: Improvements in the UPDRS III and Parkinson's Disease Questionnaire (PDQ-39) correlated positively with the extent of the overlap with the sensorimotor STN. The sweet spots for the UPDRS III (x = 11.6, y = -13.1, z = -6.3) and the PDQ-39 differed (x = 14.8, y = -12.4, z = -4.3) ~3.8 mm. CONCLUSIONS: The main influence of DBS on QoL is likely mediated through the sensory-motor basal ganglia loop. The PDQ sweet spot is located in a posteroventral spatial location in the STN territory. For aspects of QoL, however, there was also evidence of improvement through stimulation of the other STN subnuclei. More research is necessary to customize the DBS target to individual symptoms of each patient. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Morphometric features of drug-resistant essential tremor and recovery after stereotactic radiosurgical thalamotomy.

Essential tremor (ET) is the most common movement disorder. Its neural underpinnings remain unclear. Here, we quantified structural covariance between cortical thickness (CT), surface area (SA), and mean curvature (MC) estimates in patients with ET before and 1 year after ventro-intermediate nucleus stereotactic radiosurgical thalamotomy, and contrasted the observed patterns with those from matched healthy controls. For SA, complex rearrangements within a network of motion-related brain areas characterized patients with ET. This was complemented by MC alterations revolving around the left middle temporal cortex and the disappearance of positive-valued covariance across both modalities in the right fusiform gyrus. Recovery following thalamotomy involved MC readjustments in frontal brain centers, the amygdala, and the insula, capturing nonmotor characteristics of the disease. The appearance of negative-valued CT covariance between the left parahippocampal gyrus and hippocampus was another recovery mechanism involving high-level visual areas. This was complemented by the appearance of negative-valued CT/MC covariance, and positive-valued SA/MC covariance, in the right inferior temporal cortex and bilateral fusiform gyrus. Our results demonstrate that different morphometric properties provide complementary information to understand ET, and that their statistical cross-dependences are also valuable. They pinpoint several anatomical features of the disease and highlight routes of recovery following thalamotomy.

Subthalamic stimulation breaks the balance between distal and axial signs in Parkinson's disease.

In Parkinson's disease (PD), the effects of both Ldopa and subthalamic deep brain stimulation (STN-DBS) are known to change cost-valuation. However, this was mostly studied through reward-effort task involving distal movements, while axial effort, less responsive to treatments, have been barely studied. Thus, our objective was to compare the influence of both Ldopa and STN-DBS on cost-valuation between two efforts modalities: vowel production (as an example of axial movement) and hand squeezing (as an example of distal movement). Twelve PD patients were recruited to participate in this study. The task consisted in deciding whether to accept or reject trials based on a reward-effort trade-off. Participants performed two blocks with hand squeezing, and two with vowel production, in the four treatment conditions (Ldopa On/Off; STN-DBS On/Off). We found that STN-DBS changed the ratio difference between hand and phonation efforts. Vowel production effort was estimated easier to perform with STN-DBS alone, and harder when associated with Ldopa. The difference between hand and phonation efforts was correlated with quality of life in Off/Off and On Ldopa alone conditions, and with impulsive assessment On STN-DBS alone. We highlighted that STN-DBS could introduce an imbalance between the actual motor impairments and their subjective costs. With this finding, we also suggest paying particular attention to the different treatment effects that should be expected for axial and distal movement dysfunctions.

Early atypical signs and insula hypometabolism predict survival in multiple system atrophy.

OBJECTIVE: We aim to search for predictors of survival among clinical and brain 18F-FDG positron emission tomography (PET) metabolic features in our cohort of patients with multiple system atrophy (MSA). METHODS: We included patients with a 'probable' MSA diagnosis for whom a clinical evaluation and a brain PET were performed early in the course of the disease (median 3 years, IQR 2-5). A retrospective analysis was conducted using standardised data collection. Brain PET metabolism was characterised using the Automated Anatomical Labelling Atlas. A Cox model was applied to look for factors influencing survival. Kaplan-Meier method estimated the survival rate. We proposed to develop a predictive 'risk score', categorised into low-risk and high-risk groups, using significant variables entered in multivariate Cox regression analysis. RESULTS: Eighty-five patients were included. The overall median survival was 8 years (CI 6.64 to 9.36). Poor prognostic factors were orthostatic hypotension (HR=6.04 (CI 1.58 to 23.12), p=0.009), stridor (HR=3.41 (CI 1.31 to 8.87), p=0.012) and glucose PET hypometabolism in the left insula (HR=0.78 (CI 0.66 to 0.92), p=0.004). Good prognostic factors were time to diagnosis (HR=0.68 (CI 0.54 to 0.86), p=0.001) and use of selective serotonin reuptake inhibitor (SSRI) (HR=0.17 (CI 0.06 to 0.46), p<0.001). The risk score revealed a 5-year gap separating the median survival of the two groups obtained (5 years vs 10 years; HR=5.82 (CI 2.94 to 11.49), p<0.001). CONCLUSION: The clinical prognosis factors we have described support published studies. Here, we also suggest that brain PET is of interest for prognosis assessment and in particular in the search for left insula hypometabolism. Moreover, SSRIs are a potential drug candidate to slow the progression of the disease.

The Brain Connectome after Gamma Knife Radiosurgery of the Ventro-Intermediate Nucleus for Tremor: Marseille-Lausanne Radiobiology Study Protocol.

Essential tremor (ET) is the most common movement disorder. Deep brain stimulation is the current gold standard for drug-resistant tremor, followed by radiofrequency lesioning. Stereotactic radiosurgery by Gamma Knife (GK) is considered as a minimally invasive alternative. The majority of procedures aim at the same target, thalamic ventro-intermediate nucleus (Vim). The primary aim is to assess the clinical response in relationship to neuroimaging changes, both at structural and functional level. All GK treatments are uniformly performed in our center using Guiot's targeting and a radiation dose of 130 Gy. MR neuroimaging protocol includes structural imaging (T1-weighted and diffusion-weighted imaging [DWI]), resting-state functional MRI, and 18F-fluorodeoxyglucose-positron emission tomography. Neuroimaging changes are studied both at the level of the cerebello-thalamo-cortical tract (using the prior hypothesis based upon Vim's circuitry: motor cortex, ipsilateral Vim, and contralateral cerebellar dentate nucleus) and also at global brain level (no prior hypothesis). This protocol aims at using modern neuroimaging techniques for studying Vim GK radiobiology for tremor, in relationship to clinical effects, particularly in ET patients. In perspective, using such an approach, patient selection could be based upon a specific brain connectome profile.

Musical sonification improves motor control in Parkinson's disease: a proof of concept with handwriting.

A growing number of studies postulate the use of music to improve motor control in patients with Parkinson's disease (PD). The effects of music are greatly variable from one individual to the other and do not always reach the expected benefits. This study aimed to optimize the use of music in the management of movement disorders inherent to PD in a handwriting task. We developed and tested musical sonification (MS), a method that transforms in real-time kinematic variables into music. Twelve patients with PD, on medication, and 12 healthy controls were recruited in a pretest/training/posttest design experiment. Three training sessions were compared, for which participants were asked to produce graphomotor exercises: one session with music (unrelated to handwriting), one with MS (controlled by handwriting), and one in silence. Results showed that the performance in training was better under MS than under silence or background music, for both groups. After training, the benefits of MS were still present for both groups, with a higher effect for PD patients than for control group. Our results provide a proof of concept to consider MS as a relevant auditory guidance strategy for movement rehabilitation in patients with PD.

Deep Brain Stimulation for Freezing of Gait in Parkinson's Disease With Early Motor Complications.

BACKGROUND: Effects of DBS on freezing of gait and other axial signs in PD patients are unclear. OBJECTIVE: Secondary analysis to assess whether DBS affects these symptoms within a large randomized controlled trial comparing DBS of the STN combined with best medical treatment and best medical treatment alone in patients with early motor complications (EARLYSTIM-trial). METHODS: One hundred twenty-four patients were randomized in the stimulation group and 127 patients in the best medical treatment group. Presence of freezing of gait was assessed in the worst condition based on item-14 of the UPDRS-II at baseline and follow-up. The posture, instability, and gait-difficulty subscore of the UPDRS-III, and a gait test including quantification of freezing of gait and number of steps, were performed in both medication-off and medication-on conditions. RESULTS: Fifty-two percent in both groups had freezing of gait at baseline based on UPDRS-II. This proportion decreased in the stimulation group to 34%, but did not change in the best medical treatment group at 24 months (P = 0.018). The steps needed to complete the gait test decreased in the stimulation group and was superior to the best medical treatment group (P = 0.016). The axial signs improved in the stimulation group compared to the best medical treatment group (P < 0.01) in both medication-off and medication-on conditions. CONCLUSIONS: Within the first 2 years of DBS, freezing of gait and other axial signs improved in the medication-off condition compared to best medical treatment in these patients. © 2019 International Parkinson and Movement Disorder Society.

Multiple System Atrophy: Phenotypic spectrum approach coupled with brain 18-FDG PET.

OBJECTIVE: The 2008 diagnostic criteria classify Multiple System Atrophy (MSA) patients in a predominantly parkinsonian (MSA-P) or cerebellar (MSA-C) type. Phenotypic descriptions have since highlighted a clinical heterogeneity among patients (e.g., mixed-type, cognitive impairment, atypical longer survival). This study attempts to identify different phenotypes of patients with MSA and to describe corresponding brain 18-FDG Positron Emission Tomography (PET) patterns. METHODS: Patients with a "probable" MSA diagnosis for whom a brain 18-FDG PET was performed were included. A retrospective analysis (from 2006 to 2017) was conducted using standardized data collection. We used Latent Class Analysis (LCA), an innovative statistical approach, to identify profiles of patients based on common clinical characteristics. Brain metabolism of different groups was studied at rest. RESULTS: Eighty-five patients were included. Three different profiles were revealed (entropy = 0.835): 1. extrapyramidal, axial, laryngeal-pharyngeal involvement (LPI) and cerebellar symptoms (n = 46, 54.1%); 2. cerebellar and LPI symptoms (n = 30, 35.3%); 3. cerebellar and cognitive symptoms (n = 9, 10.6%). Brain metabolism analyses (k > 89; p < 0.001) showed hypometabolism of the basal ganglia, frontal/prefrontal, temporal cortices and left posterior cerebellum in profile 1. In profile 2 there was hypometabolism of the medulla, prefrontal, temporal, cingular cortices, putamen and bilateral cerebellar hemispheres. In profile 3 there was hypometabolism of bilateral posterior cerebellar hemispheres and vermis. CONCLUSION: Beyond the two most common phenotypes of MSA, a third and particularly atypical profile with cerebellar and cognitive symptoms but without LPI involvement is described. These profiles are supported by different brain metabolic abnormalities which could be useful for diagnostic purposes.

Programming parameters of subthalamic deep brain stimulators in Parkinson's disease from a controlled trial.

BACKGROUND: Programming algorithms have never been tested for outcome. The EARLYSTIM study showed superior outcomes of deep brain stimulation of the subthalamic nucleus (STN-DBS) over best medical treatment in early Parkinson's disease (PD). Patients were programmed according to common guidelines but customized for each patient. METHODS: Stimulation parameters were systematically documented at 1, 5, 12, and 24 month in the cohort of 114 patients who had bilateral STN-DBS at 24 month. We investigated the influence of atypical programming, changes of stimulated electrode contacts and stimulation energy delivered. Outcomes were the Unified Parkinson's Disease Rating Scale (UPDRS) motor and ADL-subscores, health-related quality of life (PDQ-39) summary index and mobility- and ADL-subscores. RESULTS: At 1/5/12/24 months follow up, mean amplitude (1.8/2.5/2.6/2.8 V), impedance (1107/1286/1229/1189 Ω) and TEED (33.7/69.0/84.4/93.0 V2*µs*Hz/Ω) mainly increased in the first 5 months, while mean pulse width (60.0/62.5/65.1/65.8 µs), frequency (130/137.7/139.1/142.7 Hz) remained relatively stable. Typical programming (single monopolar electrode contact) was used in 80.7% of electrodes. Double monopolar (11/114) and bipolar (2/114) stimulation was only rarely required. There was no significant difference in clinical outcomes between the patient groups requiring contact changes (n = 32/28.1%) nor between typical (n = 83/72.8%) versus non-typical programming. Energy used for STN-DBS was higher for the dominant side of PD. CONCLUSION: In the first 5 months an increase in amplitude is required to compensate for various factors. Monopolar stimulation is sufficient in 80% of patients at 24 months. Homogeneous stimulation strategies can account for the favorable outcomes reported in the Earlystim study.

Normalization of aberrant pretherapeutic dynamic functional connectivity of extrastriate visual system in patients who underwent thalamotomy with stereotactic radiosurgery for essential tremor: a resting-state functional MRI study.

OBJECTIVE: The tremor circuitry has commonly been hypothesized to be driven by one or multiple pacemakers within the cerebello-thalamo-cortical pathway, including the cerebellum, contralateral motor thalamus, and primary motor cortex. However, previous studies, using multiple methodologies, have advocated that tremor could be influenced by changes within the right extrastriate cortex, at both the structural and functional level. The purpose of this work was to evaluate the role of the extrastriate cortex in tremor generation and further arrest after left unilateral stereotactic radiosurgery thalamotomy (SRS-T). METHODS: The authors considered 12 healthy controls (HCs, group 1); 15 patients with essential tremor (ET, right-sided, drug-resistant; group 2) before left unilateral SRS-T; and the same 15 patients (group 3) 1 year after the intervention, to account for delayed effects. Blood oxygenation level-dependent functional MRI during resting state was used to characterize the dynamic interactions of the right extrastriate cortex, comparing HC subjects against patients with ET before and 1 year after SRS-T. In particular, the authors applied coactivation pattern analysis to extract recurring whole-brain spatial patterns of brain activity over time. RESULTS: The authors found 3 different sets of coactivating regions within the right extrastriate cortex in HCs and patients with pretherapeutic ET, reminiscent of the "cerebello-visuo-motor," "thalamo-visuo-motor" (including the targeted thalamus), and "basal ganglia and extrastriate" networks. The occurrence of the first pattern was decreased in pretherapeutic ET compared to HCs, whereas the other two patterns showed increased occurrences. This suggests a misbalance between the more prominent cerebellar circuitry and the thalamo-visuo-motor and basal ganglia networks. Multiple regression analysis showed that pretherapeutic standard tremor scores negatively correlated with the increased occurrence of the thalamo-visuo-motor network, suggesting a compensatory pathophysiological trait. Clinical improvement after SRS-T was related to changes in occurrences of the basal ganglia and extrastriate cortex circuitry, which returned to HC values after the intervention, suggesting that the dynamics of the extrastriate cortex had a role in tremor generation and further arrest after the intervention. CONCLUSIONS: The data in this study point to a broader implication of the visual system in tremor generation, and not only through visual feedback, given its connections to the dorsal visual stream pathway and the cerebello-thalamo-cortical circuitry, with which its dynamic balance seems to be a crucial feature for reduced tremor. Furthermore, SRS-T seems to bring abnormal pretherapeutic connectivity of the extrastriate cortex to levels comparable to those of HC subjects.

Quality of life predicts outcome of deep brain stimulation in early Parkinson disease.

OBJECTIVE: To investigate predictors for improvement of disease-specific quality of life (QOL) after deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson disease (PD) with early motor complications. METHODS: We performed a secondary analysis of data from the previously published EARLYSTIM study, a prospective randomized trial comparing STN-DBS (n = 124) to best medical treatment (n = 127) after 2 years follow-up with disease-specific QOL (39-item Parkinson's Disease Questionnaire summary index [PDQ-39-SI]) as the primary endpoint. Linear regression analyses of the baseline characteristics age, disease duration, duration of motor complications, and disease severity measured at baseline with the Unified Parkinson's Disease Rating Scale (UPDRS) (UPDRS-III "off" and "on" medications, UPDRS-IV) were conducted to determine predictors of change in PDQ-39-SI. RESULTS: PDQ-39-SI at baseline was correlated to the change in PDQ-39-SI after 24 months in both treatment groups (p < 0.05). The higher the baseline score (worse QOL) the larger the improvement in QOL after 24 months. No correlation was found for any of the other baseline characteristics analyzed in either treatment group. CONCLUSION: Impaired QOL as subjectively evaluated by the patient is the most important predictor of benefit in patients with PD and early motor complications, fulfilling objective gold standard inclusion criteria for STN-DBS. Our results prompt systematically including evaluation of disease-specific QOL when selecting patients with PD for STN-DBS. CLINICALTRIALSGOV IDENTIFIER: NCT00354133.