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Background Alterations in the GBA gene (NM_000157.3) are the most important genetic risk factor for Parkinson's disease (PD). Biallelic GBA mutations cause the lysosomal storage disorder Gaucher's disease. The GBA variants p.E365K and p.T408M are associated with PD but not with Gaucher's disease. The pathophysiological role of these variants needs to be further explored. Objective This study analyzed clinical, neuropsychological, metabolic, and neuroimaging phenotypes of patients with PD carrying the GBA variants p.E365K and p.T408M. Methods GBA was sequenced in 56 patients with mid-stage PD. Carriers of GBA variants were compared with noncarriers regarding clinical history and symptoms, neuropsychological features, metabolomics, and multimodal neuroimaging. Blood plasma gas chromatography coupled to mass spectrometry, 6-[18 F]fluoro-L-Dopa positron emission tomography (PET), [18 F]fluorodeoxyglucose PET, and resting-state functional magnetic resonance imaging were performed. Results Sequence analysis detected 13 heterozygous GBA variant carriers (7 with p.E365K, 6 with p.T408M). One patient carried a GBA mutation (p.N409S) and was excluded. Clinical history and symptoms were not significantly different between groups. Global cognitive performance was lower in variant carriers. Metabolomic group differences were suggestive of more severe PD-related alterations in carriers versus noncarriers. Both PET scans showed signs of a more advanced disease; [18 F]fluorodeoxyglucose PET and functional magnetic resonance imaging showed similarities with Lewy body dementia and PD dementia in carriers. Conclusions This is the first study to comprehensively assess (neuro-)biological phenotypes of GBA variants in PD. Metabolomics and neuroimaging detected more significant group differences than clinical and behavioral evaluation. These alterations could be promising to monitor effects of disease-modifying treatments targeting glucocerebrosidase metabolism. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

In Braak's model of ascending degeneration in Parkinson's disease (PD), involvement of the amygdala occurs simultaneously with substantia nigra degeneration. However, the clinical manifestations of amygdalar involvement in PD have not been fully delineated. Considered a multitask manager, the amygdala is a densely connected "hub," coordinating and integrating tasks ranging from prompt, multisensorial emotion recognition to adequate emotional responses and emotional tuning of memories. Although phylogenetically predisposed to handle fear, the amygdala handles both aversive and positive emotional inputs. In PD, neuropathological and in vivo studies suggest primarily amygdalar hypofunction. However, as dopamine acts as an inverted U-shaped amygdalar modulator, medication-induced hyperactivity of the amygdala can occur. We propose that amygdalar (network) dysfunction contributes to reduced recognition of negative emotional face expressions, impaired theory of mind, reactive hypomimia, and impaired decision making. Similarly, impulse control disorders in predisposed individuals, hallucinations, anxiety, and panic attacks may be related to amygdalar dysfunction. When available, we discuss amygdala-independent trigger mechanisms of these symptoms. Although dopaminergic agents have mostly an activation effect on amygdalar function, adaptive and compensatory network changes may occur as well, but these have not been sufficiently explored. In conclusion, our model of amygdalar involvement brings together several elements of Parkinson's disease phenomenology heretofore left unexplained and provides a framework for testable hypotheses in patients during life and in autopsy analyses. © 2015 International Parkinson and Movement Disorder Society.

Background Polysomnography (PSG) data are rare in patients who have early stage idiopathic Parkinson's disease (IPD). Methods Thirty-three patients who had IPD with a disease duration ≤3 years and 37 age-matched controls were recruited. PSG analysis was performed on current medication. Results Patients with IPD had a reduced mean percentage of muscle atonia during rapid eye movement (REM) sleep (80% vs 93%; P

Objectives: To study heart rate variability during nocturnal sleep in idiopathic Parkinson's disease. Methods: Retrospective study, using part of the data set accumulated in an earlier study, in which polysomnography was performed in 35 idiopathic Parkinson's disease patients under their usual medication and in 35 non-idiopathic Parkinson's disease controls, matched for age, gender, and amount of apneas/hypopneas per hour. R-R intervals were calculated separately for non-rapid eye movements and rapid eye movements sleep stages. R-R variability was analyzed for time and frequency domains. Selected variables considered were high frequency band (0.15–0.40 Hz) influenced by parasympathetic input and low frequency band (0.04–0.15 Hz) influenced by sympathetic input. Both frequency bands were considered in normalized units (low frequency and high frequency normalized units). Low frequency/high frequency ratio was calculated as an estimate of sympathicovagal balance. Results: All respiratory and sleep stage characteristics were similar in both groups. Low frequency normalized unit was reduced in idiopathic Parkinson's disease patients, both for non-rapid eye movements and rapid eye movements sleep (P = 0.005). Low frequency/high frequency was smaller in idiopathic Parkinson's disease for both sleep portions (P = 0.02). Conclusions: Idiopathic Parkinson's disease patients show reduced sympathetic influence on heart rate variability in both non-rapid eye movements and rapid eye movements sleep stages. We speculate that these findings are a consequence of the postganglionic noradrenergic cardiac denervation found in idiopathic Parkinson's disease patients. © 2011 Movement Disorder Society

The objective of this study was to evaluate the discriminative power of different nonmotor signs for early diagnosis of Parkinson's disease (PD). Thirty patients with PD with

The usefulness of deep brain stimulation (DBS) of thalamic nuclei in Gilles de la Tourette syndrome (GTS) has recently been advocated. We report on a 14-month follow-up study of a patient with intractable GTS in whom bilateral DBS of the internal globus pallidus was carried out. Tic frequency per minute decreased by 73% in the postoperative phase and in particular the vocal tics became less intense. Pronation/ supination bradykinesia of the left extremities was a well-tolerated, permanent side effect. Pallidal DBS could become a valuable rescue therapy for otherwise intractable GTS.

Camptocormia (CC) or pronounced forward flexion of the trunk is a common symptom of Parkinson's disease. We describe 2 patients with probable, respectively possible multiple-system atrophy and CC. Magnetic resonance imaging of the erector trunci showed focal patchy hyperintensities with gadolinium enhancement and muscle biopsy was indicative of variably pronounced focal myositis. CC was progressive and the major handicap for both patients after 1 and 1.5 years of follow-up, respectively. The therapeutic response was poor. Similarities with the dropped-head syndrome suggest that the muscle pathology may be either the primary cause of CC, a focal reaction to the CC posture, or a coincident syndrome of old age.

In PD, the impact of nocturnal respiration on sleep continuity and architecture has not been systematically investigated by polysomnography (PSG). We performed a case-control study with retrospective analysis of PSG data of 49 PD patients. After classifying the PD patients according to their apnea/hypopnea index (AHI), they were matched with 49 controls in terms of age, gender, and AHI. There were 21 PD patients (43%) who had sleep apnea syndrome (SAS), classified as mild (AHI, 5-15) in 10 patients, moderate (AHI,15-30) in 4 patients, and severe (AHI,30) in 7 patients. PD patients had more deep sleep (P = 0.02) and more nocturnal awakenings (P0.001) than the controls. Their body mass index (BMI) was lower (P = 0.04), and they maintained a more favorable respiratory profile, with higher mean and minimal oxygen saturation values (P = 0.006 and 0.01, respectively). These differences were preserved when only considering PD patients with AHI15. PD patients had less obstructive sleep apneas (P = 0.035), independently from the factor AHI. Only the respiratory changes of 4 PD patients with BMI27 and AHI15 (8%) approximated those seen in the controls. At an early or middle stage of the disease, non-obese PD patients frequently have AHI values suggesting SAS, however, without the oxygen desaturation profile of SAS. Longitudinal studies of patients with such "abortive" SAS are warranted to establish if this finding reflects benign nocturnal respiratory muscle dyskinesia or constitutes a precursor sign of dysautonomia in PD.