Prevalence and Trajectories of Post-COVID-19 Neurological Manifestations: A Systematic Review and Meta-Analysis.

INTRODUCTION: The aim of this systematic review and meta-analysis was to evaluate the prevalence of thirteen neurological manifestations in people affected by COVID-19 during the acute phase and at 3, 6, 9 and 12-month follow-up time points. METHODS: The study protocol was registered with PROSPERO (CRD42022325505). MEDLINE (PubMed), Embase, and the Cochrane Library were used as information sources. Eligible studies included original articles of cohort studies, case-control studies, cross-sectional studies, and case series with ≥5 subjects that reported the prevalence and type of neurological manifestations, with a minimum follow-up of 3 months after the acute phase of COVID-19 disease. Two independent reviewers screened studies from January 1, 2020, to June 16, 2022. The following manifestations were assessed: neuromuscular disorders, encephalopathy/altered mental status/delirium, movement disorders, dysautonomia, cerebrovascular disorders, cognitive impairment/dementia, sleep disorders, seizures, syncope/transient loss of consciousness, fatigue, gait disturbances, anosmia/hyposmia, and headache. The pooled prevalence and their 95% confidence intervals were calculated at the six pre-specified times. RESULTS: 126 of 6,565 screened studies fulfilled the eligibility criteria, accounting for 1,542,300 subjects with COVID-19 disease. Of these, four studies only reported data on neurological conditions other than the 13 selected. The neurological disorders with the highest pooled prevalence estimates (per 100 subjects) during the acute phase of COVID-19 were anosmia/hyposmia, fatigue, headache, encephalopathy, cognitive impairment, and cerebrovascular disease. At 3-month follow-up, the pooled prevalence of fatigue, cognitive impairment, and sleep disorders was still 20% and higher. At six- and 9-month follow-up, there was a tendency for fatigue, cognitive impairment, sleep disorders, anosmia/hyposmia, and headache to further increase in prevalence. At 12-month follow-up, prevalence estimates decreased but remained high for some disorders, such as fatigue and anosmia/hyposmia. Other neurological disorders had a more fluctuating occurrence. DISCUSSION: Neurological manifestations were prevalent during the acute phase of COVID-19 and over the 1-year follow-up period, with the highest overall prevalence estimates for fatigue, cognitive impairment, sleep disorders, anosmia/hyposmia, and headache. There was a downward trend over time, suggesting that neurological manifestations in the early post-COVID-19 phase may be long-lasting but not permanent. However, especially for the 12-month follow-up time point, more robust data are needed to confirm this trend.

The World Health Organization Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders and the headache revolution: from headache burden to a global action plan for headache disorders.

The World Health Organization (WHO) Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders was developed by WHO to address the worldwide challenges and gaps in provision of care and services for people with epilepsy and other neurological disorders and to ensure a comprehensive, coordinated response across sectors to the burden of neurologic diseases and to promote brain health across life-course. Headache disorders constitute the second most burdensome of all neurological diseases after stroke, but the first if young and midlife adults are taken into account. Despite the availability of a range of treatments, disability associated with headache disorders, and with migraine, remains very high. In addition, there are inequalities between high-income and low and middle income countries in access to medical care. In line with several brain health initiatives following the WHOiGAP resolution, herein we tailor the main pillars of the action plan to headache disorders: (1) raising policy prioritization and strengthen governance; (2) providing effective, timely and responsive diagnosis, treatment and care; (3) implementing strategies for promotion and prevention; (4) fostering research and innovation and strengthen information systems. Specific targets for future policy actions are proposed. The Global Action Plan triggered a revolution in neurology, not only by increasing public awareness of brain disorders and brain health but also by boosting the number of neurologists in training, raising research funding and making neurology a public health priority for policy makers. Reducing the burden of headache disorders will not only improve the quality of life and wellbeing of people with headache but also reduce the burden of neurological disorders increasing global brain health and, thus, global population health.

Metaphoric language in the differential diagnosis of epilepsy and psychogenic non-epileptic seizures: Time to move forward.

Conversation analysis (CA) to identify metaphoric language (ML) has been proposed as a tool for the differential diagnosis of epileptic (ES) and psychogenic nonepileptic seizures (PNES). However, the clinical relevance of metaphoric conceptualizations is not clearly defined. The current study aims to investigate the ML utilized by individuals with ES and PNES in a pulled multi-country sample. Two blinded researchers examined the transcripts and videos of 54 interviews of individuals (n = 29, Italy; n = 11, USA; n = 14, Russia) with ES and PNES, identifying the patient-seizure relationship representative of the patient's internal experience. The diagnoses were based on video-EEG. Metaphors were classified as "Space/place", "External force", "Voluntary action", and "Other". A total of 175 metaphors were identified. No differences between individuals with ES and PNES were found in metaphoric occurrence (χ2 (1, N = 54) = 0.07; p = 0.74). No differences were identified when comparing the types of metaphors utilized by participants with ES and those with PNES. Patients with PNES and ES did not demonstrate differences in terms of occurrence and categories in ML. Therefore, researchers and clinicians should carefully consider the use of metaphor conceptualizations for diagnostic purposes.

The COVID-19 pandemic and neurology: A survey on previous and continued restrictions for clinical practice, curricular training, and health economics.

BACKGROUND AND PURPOSE: The COVID-19 pandemic has significantly impacted health systems worldwide. Here, we assessed the pandemic's impact on clinical service, curricular training, and financial burden from a neurological viewpoint during the enforced lockdown periods and the assumed recovery by 2023. METHODS: An online 18-item survey was conducted by the European Academy of Neurology (EAN) NeuroCOVID-19 Task Force among the EAN community. The survey was online between February and March 2023. Questions related to general, demographic, clinical, work, education, and economic aspects. RESULTS: We collected 430 responses from 79 countries. Most health care professionals were aged 35-44 years, with >15 years of work experience. The key findings of their observations were as follows. (i) Clinical services were cut back in all neurological subspecialties during the most restrictive COVID-19 lockdown period. The most affected neurological subspecialties were services for patients with dementia, and neuromuscular and movement disorders. The levels of reduction and the pace of recovery were distinct for acute emergencies and in- and outpatient care. Recovery was slow for sleep medicine, autonomic nervous system disorders, neurorehabilitation, and dementia care. (ii) Student and residency rotations and grand rounds were reorganized, and congresses were converted into a virtual format. Conferences are partly maintained in a hybrid format. (iii) Affordability of neurological care and medication shortage are emerging issues. CONCLUSIONS: Recovery of neurological services up to spring 2023 has been incomplete following substantial disruption of neurological care, medical education, and health economics in the wake of the COVID-19 pandemic. The continued limitations for the delivery of neurological care threaten brain health and call for action on a global scale.

Post-stroke epilepsy: From clinical predictors to possible mechanisms.

BACKGROUND: Stroke is the most common cause of newly diagnosed epilepsy in the elderly, ahead of degenerative disorders, brain tumors, and head trauma. Stroke accounts for 30-50% of unprovoked seizures in patients aged ≥ 60 years. This review discusses the current understanding of epidemiology, risk factors, mechanisms, prevention, and treatment opportunities for post-stroke epilepsy (PSE). METHODS: We performed a literature search in the PubMed and Cochrane Library databases. The keywords "stroke, epilepsy", "stroke, seizure", "post-stroke seizure", "post-stroke epilepsy" were used to identify the clinical and experimental articles on PSE. All resulting titles and abstracts were evaluated, and any relevant article was considered. The reference lists of all selected papers and reference lists of selected review papers were manually analyzed to find other potentially eligible articles. RESULTS: PSE occurs in about 6% of stroke patients within several years after the event. The main risk factors are cortical lesion, initial stroke severity, young age and seizures in acute stroke period (early seizures, ES). Other risk factors, such as a cardioembolic mechanism or circulation territory involvement, remain debated. The role of ES as a risk factor of PSE could be underestimated especially in young age. Mechanism of epileptogenesis may involve gliosis scarring, alteration in synaptic plasticity, etc.; and ES may enhance these processes. Statins especially in the acute period of stroke are possible agents for PSE prevention presumably due to their anticonvulsant and neuroprotection effects. Antiepileptic drugs (AED) monotherapy is enough for seizure prevention in most cases of PSE; but no evidence was found for its efficiency against epileptic foci formation. The growing interest in PSE has led to a notable increase in the number of published articles each year. To aid in navigating this expanding body of literature, several tables are included in the manuscript. CONCLUSION: Further studies are needed for better understanding of the pathophysiology of PSE and searching the prevention strategies.

Reduced Levels of Lacrimal Glial Cell Line-Derived Neurotrophic Factor (GDNF) in Patients with Focal Epilepsy and Focal Epilepsy with Comorbid Depression: A Biomarker Candidate.

Our previous studies showed that in patients with brain diseases, neurotrophic factors in lacrimal fluid (LF) may change more prominently than in blood serum (BS). Since glial cell line-derived neurotrophic factor (GDNF) is involved in the control of neuronal networks in an epileptic brain, we aimed to assess the GDNF levels in LF and BS as well as the BDNF and the hypothalamic-pituitary-adrenocortical and inflammation indices in BS of patients with focal epilepsy (FE) and epilepsy and comorbid depression (FE + MDD) and to compare them with those of patients with major depressive disorder (MDD) and healthy controls (HC). GDNF levels in BS were similar in patients and HC and higher in FE taking valproates. GDNF levels in LF were significantly lower in all patient groups compared to controls, and independent of drugs used. GDNF concentrations in LF and BS positively correlated in HC, but not in patient groups. BDNF level was lower in BS of patients compared with HC and higher in FE + MDD taking valproates. A reduction in the GDNF level in LF might be an important biomarker of FE. Logistic regression models demonstrated that the probability of FE can be evaluated using GDNF in LF and BDNF in BS; that of MDD using GDNF in LF and cortisol and TNF-α in BS; and that of epilepsy with MDD using GDNF in LF and TNF-α and BDNF in BS.

Post-stroke seizures, epilepsy, and mortality in a prospective hospital-based study.

Background and objectives: Post-stroke epilepsy (PSE) is a significant concern in the elderly population, with stroke being a leading cause of epilepsy in this demographic. Several factors have shown consistent associations with the risk of developing PSE, including cortical lesions, initial stroke severity, younger age, and the occurrence of early seizures. The primary objectives of this study were two-fold: (1) to determine the incidence of PSE and (2) to identify the risk factors associated with PSE in a prospective cohort of post-stroke patients. Methods: A prospective single-hospital study was conducted, involving patients diagnosed with acute ischemic and hemorrhagic stroke. The patients were followed up for 2 years (or until death) from the time of admission. Data about seizure occurrence and recurrent stroke were collected. Kaplan-Meyer curves were used for the assessment of PSE incidence and mortality. Possible predictors of PSE and mortality were selected from between-group analysis and tested in multivariable regressions. Results: Our study enrolled a total of 424 patients diagnosed with acute stroke. Among them, 97 cases (23%) experienced early post-stroke seizures, and 28 patients (6.6%) developed PSE. The cumulative risks of developing PSE were found to be 15.4% after hemorrhagic stroke and 8.7% after ischemic stroke. In multivariable fine and gray regression with competitive risk of death, significant predictors for developing PSE in the ischemic cohort were watershed infarction (HR 6.01, 95% CI 2.29-15.77, p < 0.001) and low Barthel index at discharge (HR 0.98, CI 0.96-0.99, p = 0.04). Furthermore, patients who eventually developed PSE showed slower recovery and presented a worse neurologic status at the time of discharge. The in-hospital dynamics of the National Institutes of Health Stroke Scale (NIHSS) were significantly worse in the PSE group compared to the non-PSE group (p = 0.01). Discussion: A higher proportion of cases experienced early seizures compared to what has been commonly reported in similar studies. Watershed stroke and low Barthel index at discharge were both identified as independent risk factors of PSE in ischemic strokes, which sheds light on the underlying mechanisms that may predispose individuals to post-stroke epilepsy after experiencing an ischemic stroke.

Early Adverse Family Experiences and Elevated Adrenocorticotropic Hormone Predict Non-Suicidal Self-Injury in Females with Non-Psychotic Mental Disorders and Suicidal Ideation.

Nonsuicidal self-injurious behavior (NSSI), prevalent in patients with non-psychotic mental disorders (NPMD), is associated with numerous adverse outcomes. Despite active research into the clinical and psychological aspects of NSSI, the underlying biological mechanisms remain obscure. Early adverse experiences are believed to induce long-lasting changes in neuroendocrine mechanisms of stress control playing a key role in NSSI development. The aim of the study was to evaluate parameters potentially predicting development of NSSI in female patients with NPMD and suicidal ideation. Eighty female patients over 18 years with NPMD and suicidal ideation (40 with and 40 without NSSI) and 48 age matching women without evidence of mental illness (healthy controls) were enrolled. Diagnostic interviews and self-report measures were used to assess childhood maltreatment, presence, frequency, and characteristics of suicidal and self-injurious thoughts and behaviors, the Beck Depression Inventory scale to assess severity of depression. Hypothalamic-pituitary-adrenal axis markers, hormones, and neurotrophic factors were measured in blood serum. The likelihood of developing NSSI in patients with NPMD and suicidal ideation was associated with early adverse family history and elevated adrenocorticotropic hormone levels. Dysregulation of hypothalamic-pituitary-adrenal axis as a result of early chronic stress experiences may represent critical biological mechanism promoting the development of NSSI behaviors in patients with NPMD.

Pre-existing neurological conditions and COVID-19 co-infection: Data from systematic reviews, meta-analyses, and scoping reviews.

BACKGROUND: Pre-existing neurological diseases have been identified as risk factors for severe COVID-19 infection and death. There is a lack of comprehensive literature review assessing the relationship between pre-existing neurological conditions and COVID-19 outcomes. Identification of high risk groups is critical for optimal treatment and care. METHODS: A literature review was conducted for systematic reviews, meta-analyses, and scoping reviews published between January 1, 2020 and January 1, 2023. Literature assessing individuals with pre-existing neurological diseases and COVID-19 infection was included. Information regarding infection severity was extracted, and potential limitations were identified. RESULTS: Thirty-nine articles met inclusion criteria, with data assessing >3 million patients from 51 countries. 26/51 (50.9%) of countries analyzed were classified as high income, while the remaining represented middle-low income countries (25/51; 49.0%). A majority of evidence focused on the impact of cerebrovascular disease (17/39; 43.5%) and dementia (5/39; 12.8%) on COVID-19 severity and mortality. 92.3% of the articles (36/39) suggested a significant association between neurological conditions and increased risk of severe COVID-19 and mortality. Cerebrovascular disease, dementia, Parkinson's disease, and epilepsy were associated with increased COVID severity and mortality. CONCLUSION: Pre-existing neurological diseases including cerebrovascular disease, Alzheimer's disease and other dementias, epilepsy, and Parkinson's disease are significant risk factors for severity of COVID-19 infection and mortality in the acute infectious period. Given that 61.5% (24/39) of the current evidence only includes data from 2020, further updated literature is crucial to identify the relationship between chronic neurological conditions and clinical characteristics of COVID-19 variants.

Functions of nonsuicidal self-injurious behavior in Russian patients with suicidal ideation.

Introduction: Nonsuicidal self-injurious behavior (NSSI) is an important risk factor for future suicide attempts. Previous research has identified a number of motivations for engaging in NSSI. The aim of the present study was to translate the Inventory of Statements About Self-Injury (ISAS) into Russian and then to evaluate its psychometric properties in a sample of patients with non-psychotic mental disorders and suicidal ideation (SI). Other aims were to determine the prevalence of specific NSSI functions in this population and to assess the relationship between different NSSI functions and clinical and psychological parameters. Participants and methods: The study was conducted at the largest center for non-psychotic mental disorders in Moscow. All admitted patients with both NSSI and SI completed the Russian version of the ISAS-II, underwent the Self-Injurious Thoughts and Behaviors Interview, and completed the Personality Inventory for DSM-5 and ICD-11 Brief Form Plus-Modified, the Beck Depression Inventory, and the State-Trait Anxiety Inventory. Results: A total of 614 patients were included in the study. 543 (88.4%) patients were assigned female at birth with a mean age of 24.86 (7.86) years. Factor analysis supported a two-factor structure (Intrapersonal and Interpersonal) of the Russian version of the ISAS-II, but in contrast to the original study, the "Marking distress" function loaded more strongly on the Interpersonal factor. In people with non-psychotic mental disorders and SI, Interpersonal functions of NSSI are associated with more severe depressive symptoms (r = 0.34), 12 months history of NSSI (r = 0.30), higher number of NSSI methods (r = 0.41), likelihood of future NSSI (r = 0.35) and psychoticism (r = 0.32). Conclusion: The Russian version of the ISAS-II is a valid and reliable instrument for assessing NSSI functions in a population at high risk for suicide attempts. Interpersonal functions are associated with a number of unpleasant clinical and psychological features.

Association of breastfeeding with mental disorders in mother and child: a systematic review and meta-analysis.

BACKGROUND: Breastfeeding has long been associated with numerous benefits for both mothers and infants. While some observational studies have explored the relationship between breastfeeding and mental health outcomes in mothers and children, a systematic review of the available evidence is lacking. The purpose of this study is to systematically evaluate the association between breastfeeding and mental health disorders in mothers and children. METHODS: We systematically searched MEDLINE and EMBASE from inception to June 2, 2023. The inclusion criteria consisted of all studies evaluating links between breastfeeding and development of mental health disorders in children and mothers. Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) while grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess the certainty of evidence. A random-effects meta-analysis was used if possible, to estimate the odds ratio for the association between breastfeeding and mental health outcomes. The Mantel-Haenszel method was utilised for pooling ORs across studies. Study heterogeneity was assessed using the I2 statistic. RESULTS: Our review identified twenty-one original study. Of these, 18 focused on the association between breastfeeding and child health, assessing depressive disorders, schizophrenia, anxiety disorders, eating disorders and borderline personality disorder. Three studies evaluated the associations between breastfeeding and maternal mental health disorders. Three studies looking at outcomes in children showed no significant association between breastfeeding and occurrence of schizophrenia later in life (OR 0.98; 95% CI 0.57-1.71; I2 = 29%). For depressive disorders (5 studies) and anxiety disorders (3 studies), we found conflicting evidence with some studies showing a small protective effect while others found no effect. The GRADE certainty for all these findings was very low due to multiple limitations. Three studies looking at association between breastfeeding and maternal mental health, were too heterogeneous to draw any firm conclusions. CONCLUSIONS: We found limited evidence to support a protective association between breastfeeding and the development of mental health disorders in children later in life. The data regarding the association between breastfeeding and maternal mental health beyond the postnatal period is also limited. The methodological limitations of the published literature prevent definitive conclusions, and further research is needed to better understand the relationship between breastfeeding and mental health in mothers and children.

Evaluation and treatment approaches for neurological post-acute sequelae of COVID-19: A consensus statement and scoping review from the global COVID-19 neuro research coalition.

Post-acute neurological sequelae of COVID-19 affect millions of people worldwide, yet little data is available to guide treatment strategies for the most common symptoms. We conducted a scoping review of PubMed/Medline from 1/1/2020-4/1/2023 to identify studies addressing diagnosis and treatment of the most common post-acute neurological sequelae of COVID-19 including: cognitive impairment, sleep disorders, headache, dizziness/lightheadedness, fatigue, weakness, numbness/pain, anxiety, depression and post-traumatic stress disorder. Utilizing the available literature and international disease-specific society guidelines, we constructed symptom-based differential diagnoses, evaluation and management paradigms. This pragmatic, evidence-based consensus document may serve as a guide for a holistic approach to post-COVID neurological care and will complement future clinical trials by outlining best practices in the evaluation and treatment of post-acute neurological signs/symptoms.

Incidence, severity and outcomes of COVID-19 in age and gender matched adults with and without epilepsy in Moscow: A historical cohort study.

OBJECTIVE: We hypothesized that PWE have an increased risk to acquire COVID-19. This was a historical cohort study to determine COVID-19 incidence, severity, mortality and risk factors in adults with active epilepsy (PWE) compared to residents of Moscow without epilepsy matched by age, gender, and region of residence - Moscow Community Comparisons (MCC). METHODS: Subjects were derived from a cohort of adult PWE and a cohort of age- and gender-matched population-based MCC without epilepsy identified in 2018. Incidence of COVID-19 was compared in each cohort from 01.03.2020 through 28.02.21. Influence of age, gender, comorbidities, and for the PWE cohort, epilepsy type, seizure frequency, and number/class of antiseizure medications was evaluated using Pearson's chi-squared test and logistic regression analysis. RESULTS: We found 887 COVID-19 positive people in the two cohorts: 156 in PWE (51.8 ± 19.7 years) and 731 in MCC (52.0 ± 17.3 years,). COVID-19 incidence was lower in PWE: 13.8 % versus 18.7 % in MCC (p = 0.0002). In PWE no specific epilepsy related variables influenced incidence. Despite no difference in severity distribution in PWE versus MCC, hospitalization rate (37.6 % versus 25.5 %, p = 0.002), disease duration (57.1 % versus 47.1, p = 0.023), and mortality (10.9% versus 4.2 %, p = 0.0009) were significantly higher in PWE. Age and number of comorbidities significantly influenced COVID-19 incidence, severity, duration, and outcomes in both cohorts. SIGNIFICANCE: Incidence of COVID-19 in PWE in Moscow was significantly lower compared to MCC. Age and comorbidities were strongly associated with severity, duration and outcomes of COVID-19 for all infected persons. Higher mortality in PWE may be explained by a higher number of comorbidities.

World Brain Day 2023 - Brain Health and Disability: "Leave no one behind".

Worldwide, the number of persons with disability is assumed to be around 1.3 billion. Although several definitions exist, such as the medical and social models, the social model has more holistic approaches and engulfs more aspects. Historically, many considerations were based on eugenics until the middle of the 20th century when a change of paradigm occurred, and disability has since been subject to many developments in the past decades. Previously dependent on mercy and good will, disability has now become a human right, and the implementation of this change is still ongoing. Neurological diseases contribute worldwide to a large proportion of disability and can be classified as reversible or permanent, by their time course, and by disease specific elements. Addtionally, neurological diseases are often accepted and managed differently across cultures and are exposed to variable degrees of stigma. The World Federation of Neurology (WFN) has initiated and continues to promote the concept of brain health, which has a wide range of inclusion and is best summarized in the World Health Organization paper (World Health Organization, 2022a). This concept is embedded in the Intersectoral Global Action Plan (IGAP) (World Health Organization, 2022b), which created a global tool to promote neurology, and the WFN is using this tool for the 2023 World Brain Day to promote and introduce the concept of disability.

A global survey on the attitudes of neurologists and psychiatrists about functional/psychogenic/dissociative/nonepileptic-seizures/attacks, in the search of its name.

PURPOSE: We conducted an observational study to investigate the opinions of neurologists and psychiatrists all around the world who are taking care of patients with seizures [epilepsy and functional seizures (FS)]. METHODS: Practicing neurologists and psychiatrists from around the world were invited to participate in an online survey. On 29th September 2022, an e-mail including a questionnaire was sent to the members of the International Research in Epilepsy (IR-Epil) Consortium. The study was closed on 1st March 2023. The survey, conducted in English, included questions about physicians' opinions about FS and anonymously collected data. RESULTS: In total, 1003 physicians from different regions of the world participated in the study. Both neurologists and psychiatrists identified "seizures" as their preferred term. Overall, the most preferred modifiers for "seizures" were "psychogenic" followed by "functional" by both groups. Most participants (57.9%) considered FS more difficult to treat compared to epilepsy. Both psychological and biological problems were considered as the underlying cause of FS by 61% of the respondents. Psychotherapy was considered the first treatment option for patients with FS (79.9%). CONCLUSION: Our study represents the first large-scale attempt of investigating physicians attitudes and opinions about a condition that is both frequent and clinically important. It shows that there is a broad spectrum of terms used by physicians to refer to FS. It also suggests that the biopsychosocial model has gained its status as a widely used framework to interpret and inform clinical practice on the management of patients.