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Objective: To evaluate the effects of deep brain stimulation of the subthalamic nucleus (STN-DBS) on motor complications in patients with Parkinson disease (PD) beyond 15 years after surgery., Methods: Data on motor complications, quality of life (QoL), activities of daily living, Unified Parkinson's Disease Rating Scale motor scores, dopaminergic treatment, stimulation measures, and side effects of STN-DBS were retrospectively retrieved and compared before surgery, at 1 year, and beyond 15 years after bilateral STN-DBS., Results: Fifty-one patients with 17.06 ± 2.18 years STN-DBS follow-up were recruited. Compared to baseline, the time spent with dyskinesia and the time spent in the "off" state were reduced by 75% ( p < 0.001) and by 58.7% ( p < 0.001), respectively. Moreover, dopaminergic drugs were reduced by 50.6% ( p < 0.001). Parkinson's Disease Quality of Life Questionnaire total score and the emotional function and social function domains improved 13.8% ( p = 0.005), 13.6% ( p = 0.01), and 29.9% ( p < 0.001), respectively. Few and mostly manageable device-related adverse events were observed during the follow-up., Conclusions: STN-DBS is effective beyond 15 years from the intervention, notably with significant improvement in motor complications and stable reduction of dopaminergic drugs. Furthermore, despite the natural continuous progression of PD with worsening of levodopa-resistant motor and nonmotor symptoms over the years, patients undergoing STN-DBS could maintain an improvement in QoL., Classification of Evidence: This study provides Class IV evidence that, for patients with PD, STN-DBS remains effective at treating motor complications 15 years after surgery., (© 2021 American Academy of Neurology.)

Objectives: To assess the prevalence and the cumulative incidence of dementia at short-, medium- and long-term follow-up after deep brain stimulation (DBS) of the subthalamic nucleus (STN) (at 1, 5, and 10 years) and to evaluate potential risk factors for postoperative dementia., Methods: The presence of dementia (according to the DSM-V) was retrospectively evaluated at each postoperative follow-up in patients with Parkinson disease (PD) who underwent bilateral STN-DBS. Preoperative and perioperative risk factors of developing postoperative dementia were also investigated. Demographic data, disease features, medications, comorbidities, nonmotor symptoms, PD motor scales, neuropsychological scales at baseline, and perioperative complications were collected for each patient., Results: A total of 175 patients were included, and 104 were available at 10-year follow-up. Dementia prevalence was 2.3% at 1 year, 8.5% at 5 years, and 29.8% at 10 years. Dementia cumulative incidence at 1, 5, and 10 years was 2.3%, 10.9%, and 25.7%, respectively. The corresponding dementia incidence rate was 35.6 per 1,000 person-years. Male sex, higher age, hallucinations, lower frontal score at baseline, and perioperative cerebral hemorrhage were predictors of dementia., Conclusions: In patients with PD with longstanding STN-DBS, dementia prevalence and incidence are not higher than those reported in the general PD population. Except for few patients with perioperative cerebral hemorrhage, STN-DBS is cognitively safe, and does not provide dementia risk factors in addition to those reported for PD itself. Identification of dementia predictors in this population may improve patient selection and information concerning the risk of poor cognitive outcome., (© 2020 American Academy of Neurology.)

Objective: To determine the postoperative attempted and completed suicide rates after subthalamic nucleus deep brain stimulation (STN-DBS) in a single-center cohort and to determine factors associated with attempted and completed suicide., Methods: We retrospectively included all patients with Parkinson disease (PD) who underwent bilateral STN-DBS surgery at the Grenoble University Hospital between 1993 and 2016. For each patient who committed or attempted suicide, 2 patients with PD with STN-DBS without any suicidal behaviors were matched for age (±1 year), sex, and year of surgery (±2 years). Clinical data were collected from medical records. Detailed preoperative and postoperative neuropsychological evaluations, including frontal and Beck Depression Inventory (BDI) scores, were gathered., Results: A total of 534 patients with PD were included. Completed and attempted suicide percentages were 0.75% (4 of 534) and 4.11% (22 of 534), respectively. The observed suicide rate in the first postoperative year (187.20 of 100,000 per year, 1 of 534) was higher than the expected National Observatory on Suicide Risks rate adjusted for age and sex (standardized mortality ratio 8.1). This rate remained similar over the second and third postoperative years. In a comparison of the 26 patients completing/attempting suicide and the 52 controls, the first group showed more frequent history of suicidal ideation/suicide attempts and psychotic symptoms, higher percentage of family psychiatric history, higher psychiatric medication use, and higher preoperative frontal and BDI scores on neuropsychological evaluations., Conclusions: Suicide behaviors can occur after STN-DBS, especially during the first 3 years. A careful multidisciplinary assessment and long-term follow-up are recommended to recognize and treat this potentially preventable risk for mortality., (© 2019 American Academy of Neurology.)

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., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: To report on the long-term outcomes of deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus (VIM) in Parkinson disease (PD), essential tremor (ET), and dystonic tremor., Methods: One hundred fifty-nine patients with PD, ET, and dystonia underwent VIM DBS due to refractory tremor at the Grenoble University Hospital. The primary outcome was a change in the tremor scores at 1 year after surgery and at the latest follow-up (21 years). Secondary outcomes included the relationship between tremor score reduction over time and the active contact position. Tremor scores (Unified Parkinson's Disease Rating Scale-III, items 20 and 21; Fahn, Tolosa, Marin Tremor Rating Scale) and the coordinates of the active contacts were recorded., Results: Ninety-eight patients were included. Patients with PD and ET had sustained improvement in tremor with VIM stimulation (mean improvement, 70% and 66% at 1 year; 63% and 48% beyond 10 years, respectively; p < 0.05). There was no significant loss of stimulation benefit over time ( p > 0.05). Patients with dystonia exhibited a moderate response at 1-year follow-up (41% tremor improvement, p = 0.027), which was not sustained after 5 years (30% improvement, p = 0.109). The more dorsal active contacts' coordinates in the right lead were related to a better outcome 1 year after surgery ( p = 0.029). During the whole follow-up, forty-eight patients (49%) experienced minor side effects, whereas 2 (2.0%) had serious events (brain hemorrhage and infection)., Conclusions: VIM DBS is an effective long-term (beyond 10 years) treatment for tremor in PD and ET. Effects on dystonic tremor were modest and transient., Classification of Evidence: This provides Class IV evidence. It is an observational study., (© 2017 American Academy of Neurology.)

Objective: Fragile X-associated tremor ataxia syndrome (FXTAS) is defined by FMR1 premutation, cerebellar ataxia, intentional tremor, and middle cerebellar peduncle (MCP) hyperintensities. We delineate the clinical, neurophysiologic, and morphologic characteristics of FXTAS., Methods: Clinical, morphologic (brain MRI, (123)I-ioflupane SPECT), and neurophysiologic (tremor recording, nerve conduction studies) study in 22 patients with FXTAS, including 4 women., Results: A total of 43% of patients had no family history of fragile X syndrome (FXS), which contrasts with previous FXTAS series. A total of 86% of patients had tremor and 81% peripheral neuropathy. We identified 3 electroclinical tremor patterns: essential-like (35%), cerebellar (29%), and parkinsonian (12%). Two electrophysiologic patterns evocative of non-length-dependent (56%) and length-dependent sensory neuropathy (25%) were identified. Corpus callosum splenium (CCS) hyperintensity was as frequent (68%) as MCP hyperintensities (64%). Sixty percent of patients had parkinsonism and 47% abnormal (123)I-ioflupane SPECT. Unified Parkinson's Disease Rating Scale motor score was correlated to abnormal (123)I-ioflupane SPECT (p = 0.02) and to CGG repeat number (p = 0.0004). Scale for the assessment and rating of ataxia correlated with dentate nuclei hyperintensities (p = 0.03) and CCS hyperintensity was a marker of severe disease progression (p = 0.04)., Conclusions: We recommend to include in the FXTAS testing guidelines both CCS hyperintensity and peripheral neuropathy and to consider them as new major radiologic and minor clinical criterion, respectively, for the diagnosis of FXTAS. FXTAS should also be considered in women or when tremor, MCP hyperintensities, or family history of FXS are lacking. Our study broadens the spectrum of tremor, peripheral neuropathy, and MRI abnormalities in FXTAS, hence revealing the need for revised criteria.

Objective: We studied the effects of subthalamic nucleus (STN) stimulation vs levodopa on freezing of gait (FOG) and gait impairments in a large consecutive series of patients with Parkinson disease with bilateral STN stimulation., Methods: One hundred twenty-three patients performed the Stand Walk Sit Test before and 1 year after surgery both off and on levodopa and off and on stimulation., Results: Before surgery, 25 patients displayed FOG episodes and 48 were unable to complete the Stand Walk Sit Test when off levodopa. Both symptoms were alleviated by levodopa. After surgery, STN stimulation reproduced the improvement induced by levodopa before surgery in all but two patients with FOG and five others unable to walk. In 11 patients, FOG or inability to perform the test first occurred after surgery. In all patients but those experiencing FOG during the Stand Walk Sit Test before surgery, the benefit of STN stimulation did not reach that of levodopa before surgery. In patients with FOG before surgery, the effect of STN stimulation did not differ from that of levodopa either before or after surgery., Conclusions: Overall, subthalamic nucleus stimulation improved levodopa-responsive freezing of gait in most patients, although it was not always as effective as levodopa to improve gait impairments. In addition, surgery can induce gait problems in some patients.

We hypothesised that bradykinesia may be partly due to the failure of the corticomuscular system to engage in high frequency oscillatory activity in Parkinson's disease (PD). In healthy subjects such oscillations are evident in coherence between active muscles at 15--30 Hz. We therefore investigated the effects of therapeutic stimulation of the basal ganglia on this coherence and related it to changes in bradykinesia in the contralateral arm. Increases in coherence at 15--30 Hz and improvements in bradykinesia upon stimulation were correlated (r = 0.564, p < 0.001). This suggests that the basal ganglia modulate oscillatory activity in the corticomuscular system and that impairment of the motor system's ability to engage in synchronised oscillations at high frequency may contribute to bradykinesia in PD.

It remains unclear how high frequency stimulation of the subthalamic nucleus (STN) improves parkinsonism. We hypothesized that stimulation may affect the organization of the cortical drive to voluntarily activated muscle. Normally this is characterized by oscillations at 15-30 Hz, manifest in coherence between muscles in the same frequency band. We therefore investigated the effects of STN stimulation on electromyographic (EMG) activity in co-contracting distal arm muscles in nine subjects with Parkinson's disease off drugs. Without stimulation, coherence between EMG signals was diminished at 15-30 Hz compared with nine controls. STN stimulation increased coherence in the 15-30 Hz band, so that it approached that in healthy subjects. The results suggest that STN stimulation facilitates the normal cortical drive to muscles.