The impact of the COVID-19 pandemic on neuropsychiatric and sleep disorders, and quality of life in individuals with neurodegenerative and demyelinating diseases: a systematic review and meta-analysis of observational studies.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has affected the mental health, sleep and quality of life, especially in individuals with chronic disease. Therefore, the purpose of this systematic review and meta-analysis was to investigate the impact of the COVID-19 pandemic on neuropsychiatric disorders (depression, anxiety, stress), sleep disorders (sleep quality, insomnia) and quality of life in individuals with Parkinson's disease (PD), Multiple Sclerosis (MS) and Alzheimer's disease (AD) compared to healthy controls. METHODS: Seven databases (Medline, Embase, ScienceDirect, Web of Science, The Cochrane Library, Scielo and Lilacs) were searched between March 2020 and December 2022. Observational studies (i.e., cross-sectional, case-control, cohort) were included. GRADE approach was used to assess the quality of evidence and strength of the recommendation. Effect size was calculated using standardized mean differences (SMD; random effects model). A customized Downs and Black checklist was used to assess the risk of bias. RESULTS: Eighteen studies (PD = 7, MS = 11) were included. A total of 627 individuals with PD (healthy controls = 857) and 3923 individuals with MS (healthy controls = 2432) were analyzed. Twelve studies (PD = 4, MS = 8) were included in the meta-analysis. Individuals with PD had significantly elevated levels of depression (very low evidence, SMD = 0.40, p = 0.04) and stress (very low evidence, SMD = 0.60, p < 0.0001). There was no difference in anxiety (p = 0.08). Individuals with MS had significantly higher levels of depression (very low evidence, SMD = 0.73, p = 0.007) and stress (low evidence, SMD = 0.69, p = 0.03) and low quality of life (very low evidence, SMD = 0.77, p = 0.006). There was no difference in anxiety (p = 0.05) and sleep quality (p = 0.13). It was not possible to synthesize evidence in individuals with AD and sleep disorder (insomnia). CONCLUSION: In general, the COVID-19 pandemic negatively impacted individuals with PD and MS. Individuals with PD showed significantly higher levels of depression and stress; and individuals with MS presented significantly higher depression and stress levels, as well as significantly lower quality of life when compared to healthy controls. Further studies are needed to investigate the impact of the COVID-19 pandemic in individuals with AD.

Improving work life balance among female educationists during the COVID-19 lockdown.

BACKGROUND: The entire education industry switched from offline to online modes as a result of the coronavirus outbreak. Numerous teachers who were diagnosed with musculoskeletal, psychological, and other neurodegenerative diseases have reported increased exhaustion, lack of sleep, a decline in quality of life (QoL), a decrease in physical activity, and excessive stress from online classes during the COVID-19 lockdown, especially women. OBJECTIVE: The aim of this study is to evaluate the effectiveness of three-modal exercise on fatigue, sleep, QoL as well as to determine the relationship between age, disease severity, disease stage and working years with women diagnosed with Parkinson's disease (PD). METHODS: In this randomized controlled trial, 44 female educators in stages I-II with PD who were between the ages of 40 and 60 volunteered. For a total of 36 sessions over the course of six weeks, Group A received a three-modal fitness program through online video sessions, whereas Group B received Nordic walking. The outcome measures included the Fatigue Severity Scale, Parkinson's Disease Sleep Scale, and Parkinson's Disease Quality of Life Questionnaire-39. RESULTS: Age, Hoehn and Yahr scale, working years, and PD in years did not correlate with each other (p > 0.50). The three-modal exercise experimental Group A showed statistically significant improvement in QoL (p 0.001), sleep (p 0.001), and fatigue (p 0.001). CONCLUSION: Women in the field of education who participated in a three-modal exercise programme for PD reported a significant improvement in their level of exhaustion, sleep patterns, and quality of life.

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.

Impact of COVID­19 infection in patients with neurodegenerative diseases with particular focus on Alzheimer's and Parkinson's disease.

Neurodegenerative disorders (NDD) are chronic neurological diseases characterized by loss and/or damage to neurons along with the myelin sheath, and patients are at higher risk of severe infection with the SARS­CoV­2. A comprehensive literature search was performed using relevant terms and inclusion­exclusion criteria. Recent articles, subjects older than 50 years, and articles written in the English language were included, whereas letters to the editor and articles related to pregnant women were excluded from the review study. COVID­19 appears to damage angiotensin­II receptors which cause natural killer cells to lose the ability to clear virus­infected cells, owing to worse outcomes in patients with NDD. COVID­19 can worsen the symptoms of Alzheimer's disease. In addition, COVID­19 worsens drug­responsive motor symptoms in Parkinson's disease (PD) and other symptoms like fatigue and urinary complaints. Vitamin D is essential in decreasing pro­inflammatory and increasing anti­inflammatory cytokines in ongoing COVID­19 infections and reducing angiotensin receptors and, hence, decreasing COVID­19 infection severity. Telemedicine shows promise for patients with NDD but is yet to overcome legal issues and personal barriers. COVID­19 has a significant effect on neurodegenerative conditions, which appears partly to the nature of the NDD and the neuro­invasive capabilities of the SARS­CoV­2. The protective role of vitamin D in patients with NDD further supports this hypothesis. Modifications in current health care, like the telemedicine platform, are required to address the increased risk of serious infection in this population. Further studies will be required to clarify conflicting reports in many fields.

When brain devices go wrong: a patient with a malfunctioning deep brain stimulator (DBS) presents to the emergency department.

A man in his 50s attended the emergency department with an acute deterioration in his Parkinson's symptoms, presenting with limb rigidity, widespread tremor, choreiform dyskinesia, dysarthria, intense sadness and a severe occipital headache. After excluding common differentials for sudden-onset parkinsonism (eg, infection, medication change), an error on the patient's deep brain stimulator was noted. The patient's symptoms only resolved once he was transferred to the specialist centre so that the programmer could reset the device settings. Due to COVID-19-related bed pressures on the ward, there was a delay in the patient receiving specialist attention-highlighting the need for non-specialist training in the emergency management of device errors.

A pilot study of a 12-week community-based boxing program for Parkinson's disease.

INTRODUCTION: Community-based exercise programs for Parkinson's disease (PD) have gained popularity. Our understanding of such programs on non-motor features is limited. We characterized the effect of a 12-week community-based boxing exercise program on motor and non-motor symptoms in people with Parkinson's disease (PwPD). METHODS: In this prospective observational study, PwPD underwent a 12-week community-based boxing program (2 sessions per week, for a total of 24 sessions). The following assessments were performed by a movement disorders neurologist at baseline and after completion of the program: MDS-Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) in a modified version since assessments were performed virtually due to COVID-19 pandemic, MDS Non-Motor Rating Scale (MDS-NMS), Hamilton Depression Rating Scale (HDRS), Lilli Apathy Rating Scale (LARS), Parkinson's Disease Questionaire-39 (PDQ-39), and Schwab and England Activities of Daily Living scale (SE-ADL). Pre- and post-assessments were compared using Wilcoxon signed rank test; only participants who completed the program and both assessments were analyzed. RESULTS: A total of 14 PwPD agreed to be a part of the study and completed assessments. All participants were ambulatory and functionally independent at baseline. Total non-motor feature severity (MDS-NMS, p = 0.0031), depression (HDRS, p = 0.015), and motor features (MDS-UPDRS PART 3 modified, p = 0.023) all improved significantly after the intervention. Scales on apathy (LARS, p = 0.29), Parkinson's disease-specific health related quality (PDQ-39, p = 0.093), and activities of daily living (SE-ADL, p = 0.32) did not demonstrate significant change. CONCLUSION: PwPD who participated in a community-based, pilot boxing program showed improvements in motor exam and non-motor symptoms.

Exploring the relationship between novel Coronavirus pneumonia and Parkinson's disease.

The hypothesis is that there is 0a relationship between Parkinson's disease and coronavirus disease 2019 (COVID-19). By summarizing the pathogenesis of Parkinson's disease and COVID-19 and the impact of COVID-19 on the central nervous system, the relationship between Parkinson's disease and COVID-19 was analyzed, including whether Parkinson's disease is a predisposition factor for COVID-19 and whether COVID-19 causes the occurrence of Parkinson's disease. Discuss the impact of COVID-19 on patients with Parkinson's disease, including symptoms and life impact. To summarize the principles, goals and methods of home rehabilitation for Parkinson's disease patients during COVID-19. Through the analysis of this paper, it is believed that COVID-19 may cause Parkinson's disease. Parkinson's disease has the condition of susceptibility to COVID-19, but this conclusion is still controversial.

Cognitive Digital Intervention for Older Patients with Parkinson's Disease during COVID-19: A Mixed-Method Pilot Study.

Mild cognitive impairment is frequent among people with Parkinson's disease. Cognitive training seems effective for cognitive status and for mitigating anxiety and depression. With the COVID-19 outbreak, such therapeutic interventions were delivered online. This longitudinal mixed-method study was aimed at evaluating the effectiveness of an online cognitive treatment, carried out during COVID times and based on Parkinson's-Adapted Cognitive Stimulation Therapy, on cognitive domains and mood of 18 older people with Parkinson's disease. After screening, the cognitive status and mood were assessed three times by Addenbrooke's Cognitive Examination-Revised scale and the Geriatric Depression Scale-Short Form. At the follow-up, patients were also interviewed for understanding their experience with the technology. Such treatment was effective on the participants' cognitive functions, but not on their mood. Despite some initial problems with the technology, the online intervention was experienced as a way of not being 'left behind', staying in contact with others, and being safe during the lockdown. This suggests that online cognitive treatment can be adopted to integrate face-to-face interventions by increasing their efficacy, accessibility, and long-term outcomes. Suggestions for future research are given.

Acute Worsening of Atypical Parkinson's Syndrome After Receiving Second Dose of Moderna COVID-19 Vaccine.

INTRODUCTION: Atypical Parkinson's syndromes are a rare set of neurodegenerative conditions in which a patient experiences the typical symptoms of Parkinson's disease, in addition to various other unrelated issues. CASE PRESENTATION: We present the case of a 71-year-old White man with a 1-year history of weakness and upper extremity tremors that, per patient report, rapidly worsened after receiving the second dose of the Moderna COVID-19 vaccine. His symptoms were consistent with an asymmetric atypical Parkinson's disease, with electromyogram results indicating chronic motor neuron involvement. DISCUSSION: There have been multiple reports of deterioration in patients with Parkinson's disease and atypical Parkinson's syndromes in response to contracting COVID-19. However, there are few, if any, case reports that describe an acute change in Parkinson-related symptoms in association with the COVID-19 vaccines. CONCLUSIONS: As the pandemic continues, we must continue to remain vigilant as we learn more about the long-lasting effects of the virus and vaccines.

Covid-19 and Parkinson's disease: Acute clinical implications, long-COVID and post-COVID-19 parkinsonism.

The Coronavirus Disease 2019 (Covid-19), caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has led to unprecedented challenges for the delivery of healthcare and has had a clear impact on people with chronic neurological conditions such as Parkinson's disease (PD). Acute worsening of motor and non-motor symptoms and long-term sequalae have been described during and after SARS-CoV-2 infections in people with Parkinson's (PwP), which are likely to be multifactorial in their origin. On the one hand, it is likely that worsening of symptoms has been related to the viral infection itself, whereas social restrictions imposed over the course of the Covid-19 pandemic might also have had such an effect. Twenty cases of post-Covid-19 para-infectious or post-infectious parkinsonism have been described so far where a variety of pathophysiological mechanisms seem to be involved; however, a Covid-19-induced wave of post-viral parkinsonism seems rather unlikely at the moment. Here, we describe the interaction between SARS-CoV-2 and PD in the short- and long-term and summarize the clinical features of post-Covid-19 cases of parkinsonism observed so far.

Exploring the Paradox of COVID-19 in Neurological Complications with Emphasis on Parkinson's and Alzheimer's Disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a human coronavirus (HCoV) that has created a pandemic situation worldwide as COVID-19. This virus can invade human cells via angiotensin-converting enzyme 2 (ACE2) receptor-based mechanisms, affecting the human respiratory tract. However, several reports of neurological symptoms suggest a neuroinvasive development of coronavirus. SARS-CoV-2 can damage the brain via several routes, along with direct neural cell infection with the coronavirus. The chronic inflammatory reactions surge the brain with proinflammatory elements, damaging the neural cells, causing brain ischemia associated with other health issues. SARS-CoV-2 exhibited neuropsychiatric and neurological manifestations, including cognitive impairment, depression, dizziness, delirium, and disturbed sleep. These symptoms show nervous tissue damage that enhances the occurrence of neurodegenerative disorders and aids dementia. SARS-CoV-2 has been seen in brain necropsy and isolated from the cerebrospinal fluid of COVID-19 patients. The associated inflammatory reaction in some COVID-19 patients has increased proinflammatory cytokines, which have been investigated as a prognostic factor. Therefore, the immunogenic changes observed in Parkinson's and Alzheimer's patients include their pathogenetic role. Inflammatory events have been an important pathophysiological feature of neurodegenerative diseases (NDs) such as Parkinson's and Alzheimer's. The neuroinflammation observed in AD has exacerbated the Aß burden and tau hyperphosphorylation. The resident microglia and other immune cells are responsible for the enhanced burden of Aß and subsequently mediate tau phosphorylation and ultimately disease progression. Similarly, neuroinflammation also plays a key role in the progression of PD. Several studies have demonstrated an interplay between neuroinflammation and pathogenic mechanisms of PD. The dynamic proinflammation stage guides the accumulation of α-synuclein and neurodegenerative progression. Besides, few viruses may have a role as stimulators and generate a cross-autoimmune response for α-synuclein. Hence, neurological complications in patients suffering from COVID-19 cannot be ruled out. In this review article, our primary focus is on discussing the neuroinvasive effect of the SARS-CoV-2 virus, its impact on the blood-brain barrier, and ultimately its impact on the people affected with neurodegenerative disorders such as Parkinson's and Alzheimer's.

Impact of COVID-19 pandemic on patients with Parkinson's disease: A meta-analysis of 13,878 patients.

BACKGROUND: The clinical, neuropsychological, and socioeconomic factors affecting Parkinson's disease (PD) during COVID-19 pandemic across different populations have not been systematically studied. To address this, we conducted a meta-analysis of factors that impact the well-being of PD patients during the pandemic. METHODS: Medline and Embase were searched for articles published between 2020 and 2022. We conducted random-effects pooling of estimates and meta-regression. RESULTS: Twenty-seven studies involving 13,878 patients from America, Europe, Asia, and Africa were included. There is a high prevalence of decreased physical activity and exercise, and worsening motor and neuropsychiatric symptoms (17-56%). Patients in lower-income countries more frequently reported worsening anxiety (adjusted OR [aOR] 8.94, 95% confidence interval [CI] 1.62-49.28, p = 0.012), sleep (aOR 5.16, 95% CI 1.15-23.17, p = 0.032), and PD symptoms (aOR 3.57, 95% CI 0.96-13.34, p = 0.058). Lockdown was associated with decreased exercise levels (aOR 0.13, 95% CI 0.02-0.78, p = 0.025) and worsening mood (aOR 0.48, 95% CI 0.24-0.95, p = 0.035). Younger age correlated with decreased physical activity (ß -0.30, 95% CI -0.53 to -0.07, p = 0.012), exercise (ß -0.11, 95% CI -0.15 to -0.07, p < 0.001), worsening PD symptoms (ß -0.08, 95% CI -0.15 to -0.01, p = 0.018), and sleep (ß -0.14, 95% CI -0.27 to 0, p = 0.044). Female PD patients reported a greater decrease in physical activity (ß 11.94, 95% CI 2.17-21.71, p = 0.017) and worse sleep (ß 10.76, 95% CI 2.81-18.70, p = 0.008). CONCLUSION: This large meta-analysis of PD patients in diverse populations identified a high prevalence of physical and mental worsening during the COVID-19 pandemic, with patients in lower-income countries being exceptionally vulnerable.

Research on depression in Parkinson disease: A bibliometric and visual analysis of studies published during 2012-2021.

BACKGROUND: The diagnosis and treatment rate of Parkinson disease (PD) with depression has a low diagnostic rate, and there is no consensus on the choice of treatment mode. This study evaluates the global research trends of scientific outputs related to depression in PD from multiple perspectives, using a bibliometric analysis and visualization tool to scientifically analyze the knowledge from the literature. METHODS: Literature related to depression in PD published from 2012 to 2021 was included and selected from the Web of Science Core Collection database in October 2021. CiteSpace software was used to visualize and analyze co-occurrence analyses for countries, institutions, authors, and keywords. RESULTS: A total of 4533 articles from the Web of Science database were included. The United States made the largest contribution with the majority of publications (1215; 29.40%). Toronto University was the most productive institution. PD, depression, quality of life, dementia, nonmotor symptom, prevalence, anxiety, Alzheimer disease, symptom, and disorder would be significantly correlated with depression in PD. The current hot spots in this field focus on the following: risk factors for depression in PD, assessment scale of depression in PD, and rehabilitation of depression in PD. CONCLUSIONS: This analysis not only reveals the current research trends and hotspots but also provides some instructive suggestions on the development of depression in PD.

Smell deficits in COVID-19 and possible links with Parkinson's disease.

Olfactory impairment is a common symptom in Coronavirus Disease 2019 (COVID-19), the disease caused by Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) infection. While other viruses, such as influenza viruses, may affect the ability to smell, loss of olfactory function is often smoother and associated to various degrees of nasal symptoms. In COVID-19, smell loss may appear also in absence of other symptoms, frequently with a sudden onset. However, despite great clinical interest in COVID-19 olfactory alterations, very little is known concerning the mechanisms underlying these phenomena. Moreover, olfactory dysfunction is observed in neurological conditions like Parkinson's disease (PD) and can precede motor onset by many years, suggesting that viral infections, like COVID-19, and regional inflammatory responses may trigger defective protein aggregation and subsequent neurodegeneration, potentially linking COVID-19 olfactory impairment to neurodegeneration. In the following chapter, we report the neurobiological and neuropathological underpinnings of olfactory impairments encountered in COVID-19 and discuss the implications of these findings in the context of neurodegenerative disorders, with particular regard to PD and alpha-synuclein pathology.

D2/D3 Receptor Agonism: Paving the Way for a New Therapeutic Target for Taste Disorders in Parkinson's Disease and Other Conditions?

Chemosensory (i.e., olfaction and taste) dysfunction is common in neurodegenerative (e.g., Parkinson's disease, Alzheimer's disease, and dementia), psychiatric (e.g., depression, bipolar disorders, other conditions), and postinfectious (i.e., long COVID) diseases and in the elderly. Despite its impact on patients' quality of life, no established treatment for taste disorders exists so far. A recent report on the effect of pramipexole, a D2/D3 agonist, on taste performance in healthy participants provides support for a new potential therapeutic target for taste dysfunction to be tested in future randomized, placebo-controlled, clinical trials across several populations reporting gustatory symptoms.

Total esophageal food impaction in the era of the COVID-19 pandemic: a delayed presentation in a patient with Parkinson's disease.

Total esophageal food impaction is extremely rare. We report a patient with Parkinsonism who presented with total dysphagia to solids and liquids and with inability to swallow her saliva of 3 days duration. She did not present sooner as she was afraid of contracting COVID-19 during hospitalization. Chest CT scan revealed total esophageal food impaction. Awake fiberoptic endotracheal intubation followed by EGD and clearance of the impacted food were performed. This patient illustrates esophageal involvement in Parkinson's disease, delayed presentation with an emergency in the COVID-19 era, and the multidisciplinary approach to minimize the risk of aspiration during endoscopy.

COVID-19 and Parkinsonism: A Critical Appraisal.

A few cases of parkinsonism linked to COVID-19 infection have been reported so far, raising the possibility of a post-viral parkinsonian syndrome. The objective of this review is to summarize the clinical, biological, and neuroimaging features of published cases describing COVID-19-related parkinsonism and to discuss the possible pathophysiological mechanisms. A comprehensive literature search was performed using NCBI's PubMed database and standardized search terms. Thirteen cases of COVID-19-related parkinsonism were included (7 males; mean age: 51 years ± 14.51, range 31-73). Patients were classified based on the possible mechanisms of post-COVID-19 parkinsonism: extensive inflammation or hypoxic brain injury within the context of encephalopathy (n = 5); unmasking of underlying still non-symptomatic Parkinson's Disease (PD) (n = 5), and structural and functional basal ganglia damage (n = 3). The various clinical scenarios show different outcomes and responses to dopaminergic treatment. Different mechanisms may play a role, including vascular damage, neuroinflammation, SARS-CoV-2 neuroinvasive potential, and the impact of SARS-CoV-2 on α-synuclein. Our results confirm that the appearance of parkinsonism during or immediately after COVID-19 infection represents a very rare event. Future long-term observational studies are needed to evaluate the possible role of SARS-CoV-2 infection as a trigger for the development of PD in the long term.

The BioVisualSpeech Serious Game with Voice Exercises for People with Parkinson's Disease with Hypokinetic Dysarthria.

People with Parkinson's disease (PD) can have dysarthria, a voice disorder that affects speech intelligibility. To fight this disorder people may resort to speech and language therapy. Unfortunately, weekly speech therapy sessions may not be enough, because to achieve and maintain good voice quality, intensive training is required. Additionally, the COVID-19 pandemic brought attention to the need for alternative speech therapy treatments that complement face-to-face appointments. Here, we propose a serious therapy game to improve voice loudness that can be used for intensive therapy or when face-to-face appointments are not possible. The game integrates three voice exercises used in speech therapy sessions for people with PD and aims to provide motivation for patients to perform the exercises on a daily basis. This application evaluates the vocal intensity, vocal frequency and maximum phonation time, offering real-time visual feedback. It also allows pathologists to customize the exercises difficulty to the needs of each patient.

COVID-19 and Parkinson's Disease: Possible Links in Pathology and Therapeutics.

The outbreak of SARs-CoV-2 with emerging new variants is leading to global health crisis and has brought a major concern for patients with comorbidities. Parkinson's disease (PD) is a motor neurodegenerative disease involving various metabolic and psychological ailments along with the common occurrence of hyposmia as observed in COVID-19 patients. In addition, the observed surplus inflammatory responses in both diseases are also alarming. Alongside, angiotensin-converting enzyme 2 (ACE2) receptor, essentially required by SARS-CoV-2 to enter the cell and dopamine decarboxylase (DDC), required for dopamine synthesis is known to co-regulate in the non-neuronal cells. Taken together, these conditions suggested the probable reciprocal pathological relation between COVID-19 and PD and also suggested that during comorbidities, the disease diagnosis and therapeutics are critical and may engender severe health complications. In this review, we discuss various events and mechanisms which may have implications for the exacerbation of PD conditions and must be taken into account during the treatment of patients.