Pedunculopontine nucleus (PPN) deep brain stimulation (DBS) is an experimental treatment for Parkinson's disease (PD) which offers a fairly circumscribed benefit for gait freezing and perhaps balance ...impairment. The benefit on gait freezing is variable and typically incomplete, which may reflect that the clinical application is yet to be optimised or reflect a fundamental limitation of the therapeutic mechanism. Thus, a better understanding of the therapeutic mechanism of PPN DBS may guide the further development of this therapy. The available evidence supports that the PPN is underactive in PD due to a combination of both degeneration and excessive inhibition. Low frequency PPN DBS could enhance PPN network activity, perhaps via disinhibition. A clinical implication is that in some PD patients, the PPN may be too degenerate for PPN DBS to work. Reaction time studies report that PPN DBS mediates a very specific benefit on pre-programmed movement. This seems relevant to the pathophysiology of gait freezing, which can be argued to reflect impaired release of pre-programmed adjustments to locomotion. Thus, the benefit of PPN DBS on gait freezing could be akin to that mediated by external cues. Alpha band activity is a prominent finding in local field potential recordings from PPN electrodes in PD patients. Alpha band activity is implicated in the suppression of task irrelevant processes and thus the effective allocation of attention (processing resources). Attentional deficits are prominent in patients with PD and gait freezing and PPN alpha activity has been observed to drop out prior to gait freezing episodes and to increase with levodopa. This raises the hypothesis that PPN DBS could support or emulate PPN alpha activity and consequently enhance the allocation of attention. Although PPN DBS has not been convincingly shown to increase general alertness or attention, it remains possible that PPN DBS may enhance the allocation of processing resources within the motor system, or “motor attention”. For example, this could facilitate the ‘switching’ of motor state between continuation of pattern generated locomotion towards the intervention of pre-programmed adjustments. However, if the downstream consequence of PPN DBS on movement is limited to a circumscribed unblocking of pre-programmed movement, then this may have a similarly circumscribed degree of benefit for gait. If this is the case, then it may be possible to identify patients who may benefit most from PPN DBS. For example, those in whom pre-programmed deficits are the major contributors to gait freezing.
•Low frequency PPN DBS could disinhibit PPN network activity in PD, improving gait freezing.•Alpha band activity is prominent in local field potentials recorded from PPN electrodes.•PPN DBS could support PPN alpha activity and thus enhance the allocation of attention.•Pre-programmed movement is impaired in gait freezing and improves with PPN DBS.•PPN DBS could facilitate attentional ‘switching’ between locomotion and pre-programmed adjustments.
Summary Deep-brain stimulation (DBS) of the subthalamic nucleus (STN) is an established treatment for motor complications in Parkinson's disease. 20 years of experience with this procedure have ...contributed to improved understanding of the role of the STN in motor, cognitive, and emotional control. In Parkinson's disease, the pathological STN neuronal activity leads to motor, cognitive, and emotional inhibition. Deafferentation of the STN by DBS can reverse such behavioural inhibition. The release of this brake allows both motor and non-motor improvement, but can also be associated with excessive motor, cognitive, and emotional behavioural disinhibition. Conversely, the notable reduction in anti-parkinsonian drug dose allowed by motor improvement can unveil mesolimbic hypodopaminergic behaviours such as apathy, anxiety, or depression. Fine-tuning of stimulation parameters with dopaminergic drugs is necessary to prevent or improve pathological behaviours.
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 Parkinsonʼs 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 contactsʼ 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.
Objective
This study was undertaken to identify preoperative predictive factors of long‐term motor outcome in a large cohort of consecutive Parkinson disease (PD) patients with bilateral subthalamic ...nucleus deep brain stimulation (STN‐DBS).
Methods
All consecutive PD patients who underwent bilateral STN‐DBS at the Grenoble University Hospital (France) from 1993 to 2015 were evaluated before surgery, at 1 year (short‐term), and in the long term after surgery. All available demographic variables, neuroimaging data, and clinical characteristics were collected. Preoperative predictors of long‐term motor outcome were investigated by performing survival and univariate/multivariate Cox regression analyses. Loss of motor benefit from stimulation in the long term was defined as a reduction of less than 25% in the Movement Disorder Society–sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) part III scores compared to the baseline off‐medication scores. As a secondary objective, potential predictors of short‐term motor outcome after STN‐DBS were assessed by performing univariate and multivariate linear regression analyses.
Results
In the long‐term analyses (mean follow‐up = 8.4 ± 6.26 years, median = 10 years, range = 1–17 years), 138 patients were included. Preoperative higher frontal score and off‐medication MDS‐UPDRS part III scores predicted a better long‐term motor response to stimulation, whereas the presence of vascular changes on neuroimaging predicted a worse motor outcome. In 357 patients with available 1‐year follow‐up, preoperative levodopa response, tremor dominant phenotype, baseline frontal score, and off‐medication MDS‐UPDRS part III scores predicted the short‐term motor outcome.
Interpretation
Frontal lobe dysfunction, disease severity in the off‐medication condition, and the presence of vascular changes on neuroimaging represent the main preoperative clinical predictors of long‐term motor STN‐DBS effects. ANN NEUROL 2021;89:587–597
Reported cerebrovascular events in patients with COVID-19 are mainly ischemic, but hemorrhagic strokes and cerebral venous sinus thrombosis (CSVT), especially in critically ill patients, have also ...been described. To date, it is still not clear whether cerebrovascular manifestations are caused by direct viral action or indirect action mediated by inflammatory hyperactivation, and in some cases, the association may be casual rather than causal.
To conduct a systematic review on the cerebrovascular events in COVID-19 infection.
A comprehensive literature search on PubMed was performed including articles published from January 1, 2020, to July 23, 2020, using a suitable keyword strategy. Additional sources were added by the authors by reviewing related references. The systematic review was conducted in accordance with the PRISMA guidelines. Only articles reporting individual data on stroke mechanism and etiology, sex, age, past cardiovascular risk factors, COVID symptoms, admission NIHSS, D-dimer levels, and acute stroke treatment were selected for the review. Articles that did not report the clinical description of the cases were excluded. A descriptive statistical analysis of the data collected was performed.
From a total of 1,210 articles published from January 1, 2020, to July 23, 2020, 80 articles (275 patients), which satisfied the abovementioned criteria, were included in this review. A total of 226 cases of ischemic stroke (IS), 35 cases of intracranial bleeding, and 14 cases of CVST were found. Among patients with IS, the mean age was 64.16 ±14.73 years (range 27-92 years) and 53.5% were male. The mean NIHSS score reported at the onset of stroke was 15.23 ±9.72 (range 0-40). Primary endovascular thrombectomy (EVT) was performed in 24/168 patients (14.29%), intravenous thrombolysis (IVT) was performed in 17/168 patients (10.12%), and combined IVT+EVT was performed in 11/168 patients (6.55%). According to the reported presence of large vessel occlusion (LVO) (105 patients), 31 patients (29.52%) underwent primary EVT or bridging. Acute intracranial bleeding was reported in 35 patients: 24 patients (68.57%) had intracerebral hemorrhage (ICH), 4 patients (11.43%) had non-traumatic subarachnoid hemorrhage (SAH), and the remaining 7 patients (20%) had the simultaneous presence of SAH and ICH. Fourteen cases of CVST were reported in the literature (50% males), mean age 42.8 years ±15.47 (range 23-72). Treatment was reported only in nine patients; seven were treated with anticoagulant therapy; one with acetazolamide, and one underwent venous mechanical thrombectomy.
Cerebrovascular events are relatively common findings in COVID-19 infection, and they could have a multifactorial etiology. More accurate and prospective data are needed to better understand the impact of cerebrovascular events in COVID-19 infection.
The application of stimulators implanted directly over deep brain structures (i.e., deep brain stimulation, DBS) was developed in the late 1980s and has since become a mainstream option to treat ...several neurological conditions. Conventional DBS involves the continuous stimulation of the target structure, which is an approach that cannot adapt to patients’ changing symptoms or functional status in real-time. At the beginning of 2000, a more sophisticated form of stimulation was conceived to overcome these limitations. Adaptive deep brain stimulation (aDBS) employs on-demand, contingency-based stimulation to stimulate only when needed. So far, aDBS has been tested in several pathological conditions in animal and human models.
To review the current findings obtained from application of aDBS to animal and human models that highlights effects on motor, cognitive and psychiatric behaviors.
while aDBS has shown promising results in the treatment of Parkinson's disease and essential tremor, the possibility of its use in less common DBS indications, such as cognitive and psychiatric disorders (Alzheimer's disease, obsessive-compulsive disorder, post-traumatic stress disorder) is still challenging.
While aDBS seems to be effective to treat movement disorders (Parkinson's disease and essential tremor), its role in cognitive and psychiatric disorders is to be determined, although neurophysiological assumptions are promising.
•Conventional Deep Brain Stimulation, despite its efficacy, presents limitations.•New strategies adapting real-time DBS parameters have been tested in patients.•aDBS is effective in treating Parkinson's disease and tremor.•The evolution of technology allows to include other less common DBS indications.•Implantable devices for aDBS will be available for patients soon.
OBJECTIVES:Deep brain stimulation of the internal pallidum (GPi-DBS) is an established therapeutic option in treatment-refractory dystonia, and the identification of factors predicting surgical ...outcome is needed to optimize patient selection.
METHODS:In this retrospective multicenter study, GPi-DBS outcome of 8 patients with DYT6, 9 with DYT1, and 38 with isolated dystonia without known monogenic cause (non-DYT) was assessed at early (1–16 months) and late (22–92 months) follow-up using Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) scores.
RESULTS:At early follow-up, mean reduction of dystonia severity was greater in patients with DYT1 (BFMDRS score−60%) and non-DYT dystonia (−52%) than in patients with DYT6 dystonia (−32%; p = 0.046). Accordingly, the rate of responders was considerably lower in the latter group (57% vs >90%; p = 0.017). At late follow-up, however, GPi-DBS resulted in comparable improvement in all 3 groups (DYT6, −42%; DYT1, −44; non-DYT, −61%). Additional DBS of the same or another brain target was performed in 3 of 8 patients with DYT6 dystonia with varying results. Regardless of the genotype, patients with a shorter duration from onset of dystonia to surgery had better control of dystonia postoperatively.
CONCLUSIONS:Long-term GPi-DBS is effective in patients with DYT6, DYT1, and non-DYT dystonia. However, the effect of DBS appears to be less predictable in patients with DYT6, suggesting that pre-DBS genetic testing and counseling for known dystonia gene mutations may be indicated. GPi-DBS should probably be considered earlier in the disease course.
CLASSIFICATION OF EVIDENCE:This study provides Class IV evidence that long-term GPi-DBS improves dystonia in patients with DYT1, DYT6, and non-DYT dystonia.
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