A. Annic

Modulation of dysarthropneumophonia by low‐frequency STN DBS in advanced Parkinson's disease

Parkinsonian dysarthria (as typically characterized by hypophonia, monotony of pitch, and rhythm abnormalities) is often accompanied by gait disturbances. The long‐term effect of subthalamic nucleus deep brain stimulation (STN DBS) on dysarthria remains unclear.

Parkinsonism in Gaucher's disease type 1: ten new cases and a review of the literature.

Parkinsonism has been described in patients with Gauchers disease (GD). We reviewed the 10 cases of patients with both parkinsonism and GD recorded in the French national GD registry, as well as 49 previously published cases. Relative to the general population, parkinsonism in GD patients (1) was more frequent, (2) occurred at an earlier age, (3) responded less well to levodopa, and (4) was more frequently associated with signs of cortical dysfunction. Enzyme replacement therapy (ERT) and substrate reduction therapy (SRT) were ineffective on GD‐associated parkinsonism, suggesting that parkinsonism itself is not an indication for ERT or SRT in this setting.

Intérêts de la stimulation dopaminergique continue par Duodopa® dans la maladie de Parkinson évoluée : efficacité et tolérance

INTRODUCTION When advanced Parkinsons disease (PD) patients experience motor complications (fluctuations and dyskinesias) despite standard oral treatment, two treatment options are available: deep brain stimulation and subcutaneous apomorphine infusion with respects of indications for each strategy. Continuous intraduodenal infusion of levodopa (Duodopa) via a gastrojejunal tube may be proposed at this stage of the disease and the study of indications and clinical results with Duodopa may develop this new therapeutic alternative. PATIENTS AND METHODS Seven patients with advanced PD (dementia for all and psychiatric disorders for some of them, axial signs) were treated with Duodopa. We evaluated neuropsychological functions, all UPDRS scales, gait and quality-of-life just before Duodopa onset and six months after treatment end. Moreover, we described all adverse events (early and late) and studied daily levodopa doses before and 6 months after treatment. RESULTS We demonstrated an improvement in motor UPDRS (44%), in axial signs (40% for UPDRS part III axial subscore and 12% for gait) and a reduction of fluctuations (37.5%) and in UPDRS part IV dyskinesia (20%). These significant results are observed without any change in the quality-of-life. Adverse events were due to PEG positioning for four patients, the equipment (pump, connection, inner tube) for all patients and levodopa for four patients. Daily levodopa dose had to be increased 13.5%. CONCLUSION Duodopa can be considered as a new treatment strategy providing significant improvements in motor fluctuations, dyskinesia and severe axial signs. These results were demonstrated in very advanced PD patients, who had been excluded from previous studies, with cognitive disorders and for some of them dopaminergic psychosis well controlled by medications.

Predictive Factors for Improvement of Gait by Low-Frequency Stimulation in Parkinson's Disease

BACKGROUND After several years duration of Parkinsons disease, with or without deep brain stimulation, axial signs (such as postural instability, freezing of gait) may worsen. High-voltage, low-frequency stimulation has been shown to improve severe gait disorders in some patients. OBJECTIVE To identify predictive factors for the efficacy of low-frequency stimulation. METHODS We assessed the respective effects of low- and high-frequency stimulation using an acute stand-walk- sit test, and on motor performance in 22 patients with longstanding, bilateral sub-thalamic nucleus stimulation. We calculated the difference in the number of steps (delta steps) between high and low -frequency stimulation during the stand-walk-sit test. Our aim was to establish a profile for low-frequency responders, which was defined by a positive value for delta steps. RESULTS Low frequency responders presented higher age, a severe axial phenotype five years after surgery and a lower L-dopa responsiveness of (i) the Unified Parkinsons Disease Rating Scale part III score and its akinesia subscore before surgery and (ii) the axial subscore one year after surgery. CONCLUSION Here we defined a specific and severe axial profile of minority of patients who could benefit from low frequency stimulation parameters. Our findings challenge the conventional treatment approach (i.e. high-frequency stimulation) in patients who develop gait disorders after several years of stimulation.

Effects of Stimulus-Driven and Goal-Directed Attention on Prepulse Inhibition of Brain Oscillations

Objective: Prepulse inhibition (PPI) is an operational measure of sensory gating. PPI of cortical response to a startling pulse is known to be modulated by attention. With a time-frequency analysis, we sought to determine whether goal-directed and stimulus-driven attention differentially modulate inhibition of cortical oscillations elicited by a startling pulse. Methods: An electroencephalogram (EEG) was recorded in 26 healthy controls performing an active acoustic PPI paradigm. Startling stimuli were presented alone or either 400 or 1000 ms after one of three types of visual prepulse: to-be-attended (goal-directed attention), unexpected (stimulus-driven attention) or to-be-ignored (non-focused attention). We calculated the percentage PPI for the auditory event-related spectral perturbation (ERSP) of theta (4–7 Hz), alpha (8–12 Hz), beta1 (13–20 Hz) and beta2 (20–30 Hz) oscillations and changes in inter-trial coherence (ITC), a measure of phase synchronization of electroencephalographic activity. Results: At 400 ms: (i) PPI of the ERSP of alpha, theta and beta1 oscillation was greater after an unexpected and a to-be-attended prepulse than after a to-be-ignored prepulse; and (ii) PPI of beta2 oscillations was greater after a to-be-attended than a to-be-ignored prepulse. At 1000 ms: (i) PPI of alpha oscillations was greater after an unexpected and a to-be-attended prepulse than after a to-be-ignored prepulse; and (ii) PPI of beta1 oscillations was greater after a to-be-attended than a to-be-ignored prepulse. The ITC values did not vary according to the type of prepulse. Conclusions: In an active PPI paradigm, stimulus-driven and goal-directed attention each have differential effects on the modulation of cortical oscillations.