Summary Normal maintenance of human motivation depends on the integrity of subcortical structures that link the prefrontal cortex with the limbic system. Structural and functional disruption of ...different networks within these circuits alters the maintenance of spontaneous mental activity and the capacity of affected individuals to associate emotions with complex stimuli. The clinical manifestations of these changes include a continuum of abnormalities in goal-oriented behaviours known as apathy. Apathy is highly prevalent in Parkinson's disease (and across many neurodegenerative disorders) and can severely affect the quality of life of both patients and caregivers. Differentiation of apathy from depression, and discrimination of its cognitive, emotional, and auto-activation components could guide an individualised approach to the treatment of symptoms. The opportunity to manipulate dopaminergic treatment in Parkinson's disease allows researchers to study a continuous range of motivational states, from apathy to impulse control disorders. Parkinson's disease can thus be viewed as a model that provides insight into the neural substrates of apathy.
Summary A dopaminergic deficiency in patients with Parkinson's disease (PD) causes abnormalities of movement, behaviour, learning, and emotions. The main motor features (ie, tremor, rigidity, and ...akinesia) are associated with a deficiency of dopamine in the posterior putamen and the motor circuit. Hypokinesia and bradykinesia might have a dual anatomo-functional basis: hypokinesia mediated by brainstem mechanisms and bradykinesia by cortical mechanisms. The classic pathophysiological model for PD (ie, hyperactivity in the globus pallidus pars interna and substantia nigra pars reticulata) does not explain rigidity and tremor, which might be caused by changes in primary motor cortex activity. Executive functions (ie, planning and problem solving) are also impaired in early PD, but are usually not clinically noticed. These impairments are associated with dopamine deficiency in the caudate nucleus and with dysfunction of the associative and other non-motor circuits. Apathy, anxiety, and depression are the main psychiatric manifestations in untreated PD, which might be caused by ventral striatum dopaminergic deficit and depletion of serotonin and norepinephrine. In this Review we discuss the motor, cognitive, and psychiatric manifestations associated with the dopaminergic deficiency in the early phase of the parkinsonian state and the different circuits implicated, and we propose distinct mechanisms to explain the wide clinical range of PD symptoms at the time of diagnosis.
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.
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.
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;
< 0.05). There was no significant loss of stimulation benefit over time (
> 0.05). Patients with dystonia exhibited a moderate response at 1-year follow-up (41% tremor improvement,
= 0.027), which was not sustained after 5 years (30% improvement,
= 0.109). The more dorsal active contacts' coordinates in the right lead were related to a better outcome 1 year after surgery (
= 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).
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.
This provides Class IV evidence. It is an observational study.
To evaluate the safety and efficacy of unilateral Gamma Knife thalamotomy (GKT) for treatment of severe tremor with a prospective blinded assessment.
Fifty patients (mean age: 74.5 years; 32 men) ...with severe refractory tremor (36 essential, 14 parkinsonian) were treated with unilateral GKT. Targeting of the ventral intermediate nucleus (Vim) was achieved with Leksell Gamma Knife with a single shot through a 4-mm collimator helmet. The prescription dose was 130 Gy. Neurologic and neuropsychological assessments including a single-blinded video assessment of the tremor severity performed by a movement disorders neurologist from another center were performed before and 12 months after treatment. MRI follow-up occurred at 3, 6, and 12 months.
The upper limb tremor score improved by 54.2% on the blinded assessment (p < 0.0001). All tremor components (rest, postural, and intention) were improved. Activities of daily living were improved by 72.2%. Cognitive functions remained unchanged. Following GKT, the median delay of improvement was 5.3 months (range 1-12 months). The only side effect was a transient hemiparesis associated with excessive edema around the thalamotomy in one patient.
This blinded prospective assessment demonstrates that unilateral GKT is a safe and efficient procedure for severe medically refractory tremor. Side effects were rare and transient in this study.
This study provides Class IV evidence that for patients with severe refractory tremor, GKT is well tolerated and effective in reducing tremor impairment.
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
ABSTRACT
Background
Although the COVID‐19 pandemic is affecting a relatively small proportion of the global population, its effects have already reached everyone. The pandemic has the potential to ...differentially disadvantage chronically ill patients, including those with Parkinson's disease (PD). The first health care reaction has been to limit access to clinics and neurology wards to preserve fragile patients with PD from being infected. In some regions, the shortage of medical staff has also forced movement disorders neurologists to provide care for patients with COVID‐19.
Objective
To share the experience of various movement disorder neurologists operating in different world regions and provide a common approach to patients with PD, with a focus on those already on advanced therapies, which may serve as guidance in the current pandemic and for emergency situations that we may face in the future.
Conclusion
Most of us were unprepared to deal with this condition given that in many health care systems, telemedicine has been only marginally available or only limited to email or telephone contacts. In addition, to ensure sufficient access to intensive care unit beds, most elective procedures (including deep brain stimulation or the initiation of infusion therapies) have been postponed. We all hope there will soon be a time when we will return to more regular hospital schedules. However, we should consider this crisis as an opportunity to change our approach and encourage our hospitals and health care systems to facilitate the remote management of chronic neurological patients, including those with advanced PD.
Abstract Analyzing irregularities in walking patterns helps detect human locomotion abnormalities that can signal health changes. Traditional observation-based assessments have limitations due to ...subjective biases and capture only a single time point. Ambient and wearable sensor technologies allow continuous and objective locomotion monitoring but face challenges due to the need for specialized expertise and user compliance. This work proposes a seismograph-based algorithm for quantifying human gait, incorporating a step extraction algorithm derived from mathematical morphologies, with the goal of achieving the accuracy of clinical reference systems. To evaluate our method, we compared the gait parameters of 50 healthy participants, as recorded by seismographs, and those obtained from reference systems (a pressure-sensitive walkway and a camera system). Participants performed four walking tests, including traversing a walkway and completing the timed up-and-go (TUG) test. In our findings, we observed linear relationships with strong positive correlations ( R 2 > 0.9) and tight 95% confidence intervals for all gait parameters (step time, cycle time, ambulation time, and cadence). We demonstrated that clinical gait parameters and TUG mobility test timings can be accurately derived from seismographic signals, with our method exhibiting no significant differences from established clinical reference systems.
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