Parkinson disease following COVID-19: Report of six cases.

BACKGROUND AND PURPOSE: Core clinical manifestations of COVID-19 include influenza-like and respiratory symptoms. However, it is now evident that neurological involvement may occur during SARS-CoV-2 infection, covering an extensive spectrum of phenotypical manifestations. A major challenge arising from this pandemic is represented by detecting emerging neurological complications following recovery from SARS-CoV-2 infection. To date, a few post-COVID-19-infected subjects diagnosed with Parkinson disease (PD) have been described, raising the possibility of a connection between the infection and neurodegenerative processes. Here, we describe a case series of six subjects who developed PD after COVID-19. METHODS: Patients were observed at Scientific Institute for Research and Health Care Mondino Foundation Hospital, Pavia (Italy), and San Paolo University Hospital of Milan (Italy) between March 2021 and June 2022. In all subjects, SARS-CoV-2 infection was confirmed by means of reverse transcriptase polymerase chain reaction from a nasopharyngeal swab. Subjects underwent an accurate neurological evaluation, and neuroimaging studies were performed. RESULTS: We describe six subjects who developed PD with an average time window after SARS-CoV-2 infection of 4-7 weeks. Apparently, no relationship with COVID-19 severity emerged, and no overt structural brain abnormalities were found. All subjects experienced unilateral resting tremor at onset and showed a satisfactory response to dopaminergic treatment. CONCLUSIONS: Immune responses to SARS-CoV-2 infection have been shown to shape the individual susceptibility to develop long-term consequences. We hypothesize that, in these subjects, COVID-19 has unmasked a latent neurodegenerative process. Characterization of the neuroinflammatory signatures in larger cohorts is warranted, which might provide novel insights into the pathogenesis of PD.

Risk factors for post-COVID cognitive dysfunctions: the impact of psychosocial vulnerability.

BACKGROUND: Cognitive dysfunction is a well-established manifestation of the post-COVID syndrome. Psychological vulnerability to stressors can modify disease trajectories, causing long-term risk for negative outcomes. Nonetheless, how premorbid risk factors and response to stressor affect neuropsychological changes is still incompletely understood. In this study, we explored the impact of psychosocial variables on cognitive functioning in a post-COVID sample. METHODS: All subjects were submitted to a comprehensive neuropsychological battery and an assessment of perceived loneliness, post-traumatic stress, and changes in anxiety and depression levels. A social vulnerability index was also calculated. The set of psycho-social variables was reduced to two Principal Component Analysis (PCA) components: distress and isolation. RESULTS: Forty-five percent of individuals showed cognitive impairments, with predominant memory and executive deficits. Post-traumatic stress disorder was clinically relevant in 44% of the sample. Social vulnerability scores of the sample were comparable to those of general population. The individual performance in learning and response initiation/suppression was directly related to distress component, encasing anxiety, stress, and depression measures. CONCLUSION: These findings suggest that psychosocial assessment of post-COVID patients can detect fragile individuals at risk of cognitive impairments. Dedicated psychological support services may play a useful role in the prevention of post-COVID cognitive dysfunction.

Artificial Intelligence-Based Voice Assessment of Patients with Parkinson's Disease Off and On Treatment: Machine vs. Deep-Learning Comparison.

Parkinson's Disease (PD) is one of the most common non-curable neurodegenerative diseases. Diagnosis is achieved clinically on the basis of different symptoms with considerable delays from the onset of neurodegenerative processes in the central nervous system. In this study, we investigated early and full-blown PD patients based on the analysis of their voice characteristics with the aid of the most commonly employed machine learning (ML) techniques. A custom dataset was made with hi-fi quality recordings of vocal tasks gathered from Italian healthy control subjects and PD patients, divided into early diagnosed, off-medication patients on the one hand, and mid-advanced patients treated with L-Dopa on the other. Following the current state-of-the-art, several ML pipelines were compared usingdifferent feature selection and classification algorithms, and deep learning was also explored with a custom CNN architecture. Results show how feature-based ML and deep learning achieve comparable results in terms of classification, with KNN, SVM and naïve Bayes classifiers performing similarly, with a slight edge for KNN. Much more evident is the predominance of CFS as the best feature selector. The selected features act as relevant vocal biomarkers capable of differentiating healthy subjects, early untreated PD patients and mid-advanced L-Dopa treated patients.

Interplay between endocannabinoids and dopamine in the basal ganglia: implications for pain in Parkinson's disease.

Pain is a complex phenomenon, and basal ganglia circuitry integrates many aspects of pain including motor, emotional, autonomic, and cognitive responses. Perturbations in dopamine (DA) signaling are implicated in the pathogenesis of chronic pain due to its involvement in both pain perception and relief. Several lines of evidence support the role of endocannabinoids (eCBs) in the regulation of many electrical and chemical aspects of DAergic neuron function including excitability, synaptic transmission, integration, and plasticity. However, eCBs play an even more intricate and intimate relationship with DA, as indicated by the adaptive changes in the eCB system following DA depletion. Although the precise mechanisms underlying DA control on pain are not fully understood, given the high correlation of eCB and DAergic system, it is conceivable that eCBs may be part of these mechanisms.In this brief survey, we describe the reciprocal regulation of eCB-DA neurotransmission with a particular emphasis on the actions of eCBs on ionic and synaptic signaling in DAergic neurons mediated by CB receptors or independent on them. Furthermore, we analyze the eCB-DA imbalance which characterizes pain condition and report the implications of reduced DA levels for pain in Parkinson's disease. Lastly, we discuss the potential of the eCB-DA system in the development of future therapeutic strategies for the treatment of pain.

Pseudo-Orthostatic Tremor in Graves' Disease: A Possible Early Sign of Parkinsonism?

Background: Pseudo-orthostatic tremor is a hyperkinetic movement disorder usually associated with other neurological comorbidities, mainly Parkinson's disease. Case report: A 65-year-old male presented with unsteadiness and leg tremor while standing. Electrophysiological evaluation confirmed the presence of pseudo-orthostatic tremor. Blood test showed an undiagnosed Graves' disease. A complete remission of tremor was achieved with methimazole. Dopamine transporter scintigraphy showed a mild reduction of the striatal binding, bilaterally. Discussion: Graves' disease can be associated with pseudo-orthostatic tremor. Thyroid function should be assessed in patients complaining of unsteadiness. The causative role of hyperthyroidism in determining dopaminergic degeneration and uncovering subclinical parkinsonism warrants further investigations.