Assessing REM sleep behaviour disorder: from machine learning classification to the definition of a continuous dissociation index

Objectives: Rapid Eye Movement Sleep Behaviour Disorder (RBD) is regarded as a pro-drome of neurodegeneration, with a high conversion rate to α–synucleinopathies such as Parkinson’s Disease (PD). The clinical diagnosis of RBD co–exists with evidence of REM Sleep Without Atonia (RSWA), a parasomnia that features loss of physiological muscular atonia during REM sleep. The objectives of this study are to implement an automatic detection of RSWA from polysomnographic traces, and to propose a continuous index (the Dissociation Index) to assess the level of dissociation between REM sleep stage and atonia. This is performed using Euclidean distance in proper vector spaces. Each subject is assigned a dissociation degree based on their distance from a reference, encompassing healthy subjects and clinically diagnosed RBD patients at the two extremes. Methods: Machine Learning models were employed to perform automatic identification of patients with RSWA through clinical polysomnographic scores, together with variables derived from electromyography. Proper distance metrics are proposed and tested to achieve a dissociation measure. Results: The method proved efficient in classifying RSWA vs. not-RSWA subjects, achieving an overall accuracy, sensitivity and precision of 87%, 93% and 87.5%, respectively. On its part, the Dissociation Index proved to be promising in measuring the impairment level of patients. Conclusions: The proposed method moves a step forward in the direction of automatically identifying REM sleep disorders and evaluating the impairment degree. We believe that this index may be correlated with the patients’ neurodegeneration process; this assumption will undergo a robust clinical validation process involving healthy, RSWA, RBD and PD subjects

Pure autonomic failure versus prodromal dysautonomia in Parkinson’s disease: Insights from the bedside

Autonomic failure may include orthostatic hypotension, supine hypertension, bowel and bladder disturbances, impaired thermal regulation, and sexual dysfunction, all of which can be features of Parkinson's disease (PD) and other a‐synucleinopathies. All patients with pure autonomic failure, most patients with multiple system atrophy, and 18% of patients with PD will develop symptomatic orthostatic hypotension. However, the extent of central and peripheral norepinephrine deficiency, parasympathetic nuclei degeneration, and arterial baroreflex failure may be differentially impaired in these disorders. Consequently, clinical features and prognostic implications of autonomic dysfunction in a‐synucleinopathies may be more complex than previously envisioned. The case described in this report highlights the clinical similarities between PD and pure autonomic failure, raising the question of whether pure autonomic failure represents a restricted Lewy body synucleinopathy or an early manifestation of PD

SARS-CoV-2 vaccination, Parkinson's disease, and other movement disorders: case series and short literature review

BACKGROUND: Several neurological complications have been reported following SARS-Cov-2 vaccination, without a clear causal relationship ever being verified, including some cases of worsening of Parkinson’s disease (PD) symptoms and new onset of movement disorders in non-parkinsonian patients. METHODS: We describe two new cases of PD patients treated with device-aided therapy who developed worsening of parkinsonian symptoms after receiving the third vaccine dose (booster). We also conducted a short review of the cases reported in literature of PD symptoms worsening and new onset of movement disorders in non-parkinsonian patients after SARS-Cov-2 vaccination. RESULTS: The first patient, a 46-year-old man implanted with bilateral Subthalamic Deep Brain Stimulation, experienced temporary motor and non-motor symptoms worsening after mRNA-1273 booster, improved after stimulation settings modification. The second patient, a 55-year-old man implanted with percutaneous endoscopic transgastric jejunostomy (PEG-J) for levodopa-carbidopa intestinal gel (LCIG) infusion experienced severe temporary worsening of dyskinesia and managed through temporary LCIG dose reduction. Other seven cases of vaccine-related movement disorder are currently reported in literature, four describing PD symptoms worsening and three the onset of new movement disorders in otherwise healthy people. CONCLUSION: Both our patients and the cases described so far completely recovered after few days with parkinsonian therapy modification, symptomatic treatment, or even spontaneously, underlining the transient and benign nature of side effects from vaccine. Patients should be reassured about these complications, manageable through a prompt evaluation by the reference neurologist. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10072-022-06182-w

Home monitoring of motor fluctuations in Parkinson's disease patients

In Parkinson's disease, motor fluctuations (worsening of tremor, bradykinesia, freezing of gait, postural instability) affect up to 70% of patients within 9 years of \textsc {l}-dopa therapy. Nevertheless, the assessment of motor fluctuations is difficult in a medical office, and is commonly based on poorly reliable self-reports. Hence, the use of wearable sensors is desirable. In this preliminary trial, we have investigated bradykinesia and freezing of gait—FOG—symptoms by means of inertial measurement units. To this purpose, we have employed a single smartphone on the patient's waist for FOG experiment (38 patients), and on patient thigh for LA (93 subjects). Given the sound performance achieved in this trial (AUC = 0.97 for FOG and AUC = 0.92 for LA), motor fluctuations may be estimated in domestic environments. To this end, we plan to perform measures and data processing on SensorTile, a tiny IoT module including several sensors, a microcontroller, a BlueTooth low-energy interface and microSD card, implementing an electronic diary of motor fluctuations, posture and dyskinesia during activity of daily living

verification of a parkinson s disease protein signature in t lymphocytes by multiple reaction monitoring

Diagnosis of Parkinson's disease, the second most common neurodegenerative disease, is based on the appearance of motor symptoms. A panel of protein biomarkers in the T-lymphocyte proteome was previously proposed as a Parkinson's disease signature. Here, we designed an LC–MS based method to quantitatively evaluate this protein signature by multiple reaction monitoring (MRM) in T-lymphocytes and peripheral blood mononuclear cells from a new cohort of nine patients with Parkinson's disease and nine unaffected subjects. Patients were classified using the discriminant function obtained from two-dimensional electrophoresis and protein amounts measured by MRM, thus assigning seven controls out of nine as true negatives and nine patients out of nine as true positives. A good discriminant power was obtained by selecting a subset of peptides from the protein signature, with an area under the receiver operating characteristic curve of 0.877. A similar result is achieved by evaluating all peptides of a selected pane..