Neurological and Neuropsychiatric Impacts of COVID-19 Pandemic.

BACKGROUND: Albeit primarily a disease of respiratory tract, the 2019 coronavirus infectious disease (COVID-19) has been found to have causal association with a plethora of neurological, neuropsychiatric and psychological effects. This review aims to analyze them with a discussion of evolving therapeutic recommendations. METHODS: PubMed and Google Scholar were searched from 1 January 2020 to 30 May 2020 with the following key terms: "COVID-19", "SARS-CoV-2", "pandemic", "neuro-COVID", "stroke-COVID", "epilepsy-COVID", "COVID-encephalopathy", "SARS-CoV-2-encephalitis", "SARS-CoV-2-rhabdomyolysis", "COVID-demyelinating disease", "neurological manifestations", "psychosocial manifestations", "treatment recommendations", "COVID-19 and therapeutic changes", "psychiatry", "marginalised", "telemedicine", "mental health", "quarantine", "infodemic" and "social media". A few newspaper reports related to COVID-19 and psychosocial impacts have also been added as per context. RESULTS: Neurological and neuropsychiatric manifestations of COVID-19 are abundant. Clinical features of both central and peripheral nervous system involvement are evident. These have been categorically analyzed briefly with literature support. Most of the psychological effects are secondary to pandemic-associated regulatory, socioeconomic and psychosocial changes. CONCLUSION: Neurological and neuropsychiatric manifestations of this disease are only beginning to unravel. This demands a wide index of suspicion for prompt diagnosis of SARS-CoV-2 to prevent further complications and mortality.

Les impacts neurologiques et neuropsychiatriques d'une infection à la COVID-19. CONTEXTE: Bien qu'il s'agisse principalement d'une maladie des voies respiratoires, la maladie infectieuse à coronavirus apparue en 2019 (COVID-19) s'est avérée avoir un lien de causalité avec une pléthore d'impacts d'ordre neurologique, neuropsychiatrique et psychologique. Cette étude entend donc analyser ces impacts tout en discutant l'évolution des recommandations thérapeutiques se rapportant à cette maladie. MÉTHODES: Les bases de données PubMed et Google Scholar ont été interrogées entre les 1er janvier et 30 mai 2020. Les termes clés suivants ont été utilisés : « COVID-19 ¼, « SRAS ­ CoV-2 ¼, « Pandémie ¼, « Neuro ­ COVID ¼, « AVC ­ COVID ¼, « Épilepsie ­ COVID ¼, « COVID ­ encéphalopathie ¼, « SRAS ­ CoV-2 ­ encéphalite ¼, « SRAS ­ CoV-2 ­ rhabdomyolyse ¼, « COVID ­ maladie démyélinisante ¼, « Manifestations neurologiques ¼, « Manifestations psychosociales ¼, « Recommandations thérapeutiques ¼, « COVID-19 et changement thérapeutiques ¼, « Psychiatrie ¼, « Marginalisés ¼, « Télémédecine ¼, « Santé mentale ¼, « Quarantaine ¼, « Infodémique ¼ et « Médias sociaux ¼. De plus, quelques articles de journaux relatifs à la pandémie de COVID-19 et à ses impacts psychosociaux ont également été ajoutés en fonction du contexte. RÉSULTATS: Il appert que les manifestations neurologiques et neuropsychiatriques des infections à la COVID-19 sont nombreuses. Les caractéristiques cliniques d'une implication des systèmes nerveux central et périphérique sautent désormais aux yeux. Ces caractéristiques ont fait l'objet d'une brève analyse systématique à l'aide de publications scientifiques. En outre, la plupart des impacts d'ordre psychologique de cette pandémie se sont révélés moins apparents que les changements réglementaires, socioéconomiques et psychosociaux. CONCLUSION: Les manifestations neurologiques et neuropsychiatriques de cette maladie ne font que commencer à être élucidées. Cela exige donc une capacité accrue de vigilance en vue d'un diagnostic rapide, et ce, afin de prévenir des complications additionnelles et une mortalité accrue.

The Effects of SARS-CoV-2 Infection on the Cognitive Functioning of Patients with Pre-Existing Dementia.

Background: Cognitive postscripts of COVID-19, codenamed as 'cognitive COVID' or 'brain fog,' characterized by multidomain cognitive impairments, are now being reckoned as the most devastating sequelae of COVID-19. However, the impact on the already demented brain has not been studied. Objective: We aimed to assess the cognitive functioning and neuroimaging following SARS-CoV-2 infection in patients with pre-existing dementia. Methods: Fourteen COVID-19 survivors with pre-existing dementia (four with Alzheimer's disease, five with vascular dementia, three with Parkinson's disease dementia, and two with the behavioral variant of frontotemporal dementia) were recruited. All these patients had detailed cognitive and neuroimaging evaluations within three months before suffering from COVID-19 and one year later. Results: Of the 14 patients, ten required hospitalization. All developed or increased white matter hyperintensities that mimicked multiple sclerosis and small vessel disease. There was a significant increase in fatigue (p = 0.001) and depression (p = 0.016) scores following COVID-19. The mean Frontal Assessment Battery (p < 0.001) and Addenbrooke's Cognitive Examination (p = 0.001) scores also significantly worsened. Conclusion: The rapid progression of dementia, the addition of further impairments/deterioration of cognitive abilities, and the increase or new appearance of white matter lesion burden suggest that previously compromised brains have little defense to withstand a new insult (i.e., 'second hit' like infection/dysregulated immune response, and inflammation). 'Brain fog' is an ambiguous terminology without specific attribution to the spectrum of post-COVID-19 cognitive sequelae. We propose a new codename, i.e. 'FADE-IN MEMORY' (i.e., Fatigue, decreased Fluency, Attention deficit, Depression, Executive dysfunction, slowed INformation processing speed, and subcortical MEMORY impairment).

Cerebral venous sinus thrombosis following Russell's viper (Daboia russelii) envenomation: A case report and review of the literature.

Snakebite is a life-threatening and often-neglected public health hazard with high chronic disability and mortality, mainly faced by rural communities in the tropics/subtropics. Stroke and neuromuscular paralysis are the most severe neurological complications. However, cerebral venous sinus thrombosis has rarely been reported among cerebrovascular complications. We report a previously healthy middle-aged Indian woman who developed cerebral venous sinus thrombosis preceded by features of disseminated bleeding diathesis following Russell's viper bite. The cerebral venous sinus thrombosis was diagnosed by magnetic resonance imaging. The patient responded well to treatment with antivenom and subcutaneous enoxaparin and had no demonstrable neurological deficits at three months of follow-up.

2-deoxy-D-glucose as India's Response to COVID-19: A Commitment or Conceit?

2-deoxy-d-glucose (2-DG) has recently been approved for the treatment of moderate to severe COVID-19 patients in India. Here we discuss whether this is a well-thought-out step towards the long-term management of COVID-19 or a decision taken at the spur of the moment. 2-DG, an anticancer drug, also has immunomodulatory functions. Several studies have shown 2-DG to inhibit viral replication and cytokine storm. However, these findings are mostly on cells and animal models. The clinical trial that has become the basis of the approval of this drug in India is yet to be peer-reviewed and has not explicitly addressed several concerns, nor has it established its claim of faster efficacy with rigorous statistics and safety profile. Even though 2-DG shows much promise in COVID-19 treatment, its approval seems rather premature, which may prove to be more harmful than beneficial in the long run.

The cognitive basis of psychosocial impact in COVID-19 pandemic. Does it encircle the default mode network of the brain? A pragmatic proposal.

Epigenetics, hypothalamic-pituitary axes, environmental and metabolic influences, and transgenerational plasticity govern social behavior. Cognitive research considers the brain's default mode network (DMN) as a central hub that integrates various cognitive and social processing domains responsible for emotion perception, empathy, theory of mind, and morality. Hence, DMN is regarded as the "social brain." Upsurge in social turmoil, social anxiety, panic, depression, post-traumatic stress, hoarding, herd behavior, substance and behavioral addictions, sexual abuse, and violence in the time of the COVID-19 pandemic are intricately related to personality traits resulting in disruptive social cognition and social behavior, conceptualized as the result of unsettling and disruption of the functional nexus of the DMN. Considering overt and conspicuous display of neuroticism during the current pandemic, its impact upon modulation of the DMN functional nexus and the DMN itself, and the potential to presage cognitive impairment in the future, the authors caution that an increase in the global burden of dementia may be one of the long-term ramifications of COVID-19. Social behavior, a functional derivative of the DMN, can strikingly affect the functional nexus of DMN and the DMN itself, in a centripetal way via the phenomenon called "Experience-Dependent Plasticity," with long-term consequences. In this review, we intend to 1) decipher the association between social cognition and social behavior with the DMN, in time of COVID-19; and to 2) discuss the prospective aftermath of disrupted social behavior during the pandemic on modulation/alteration of functional connectomes of DMN or the DMN itself in the time ahead.

Non-Aneurysmal Subarachnoid Hemorrhage in COVID-19: A Case Report and Review of Literature.

BACKGROUND: Hemorrhagic cerebrovascular events, either due to aneurysmal rupture or spontaneous subarachnoid hemorrhage (SAH), are not rare in COVID-19. Several mechanisms such as coagulopathy, cytokine storm, viral endotheliopathy, hypertension, and immune modulation might play a role in the pathogenesis of SAH in COVID-19. This study aimed to report the first case of spontaneous non-aneurysmal SAH associated with SARS-CoV-2 from India. We briefly discussed the possible pathogenetic mechanisms underlying this process and succinctly reviewed the relevant literature. CASE REPORT: We herein report a case of a non-comorbid young woman infected with SARS-CoV-2 presenting with thunderclap headache and eventually non-aneurysmal SAH, who recovered with conservative management. CONCLUSION: Headache, although a very common clinical feature of COVID-19 itself, must be investigated in detail to identify alternate causes that may be life-threatening. This case also incites further enquiry into the possible pathogenic mechanisms of neurovascular complications in COVID-19.

Impact of COVID-19 pandemic in natural course of Moyamoya Angiopathy: an experience from tertiary-care-center in India.

BACKGROUND: COVID-19 mediated immune dysregulation and cytokine storm can precipitate and aggravate Moyamoya angiopathy (MMA), influencing its disease course. This index study was undertaken to prospectively evaluate the status of neurological symptoms of MMA in relation to COVID-19 affection. METHODOLOGY AND RESULTS: Follow-up MMA patients of institute's Stroke-clinic were telephonically interview from 24th March to 30th September, 2020. The first call familiarized them with COVID-19 symptoms and neurological manifestations of MMA, followed by monthly-calls with predesigned questionnaire. Patients with suggestion of COVID-19 underwent nasopharyngeal-swab-testing for COVID-19 Reverse transcription-polymerase chain reaction (RT-PCR) positive cases were subjected to antibody levels for COVID-19 Enzyme-linked immunoassay (ELISA) 8-12 weeks after recovery. During symptomatic phase till 14 days of asymptomatic, they were contacted daily/alternate day. Any new onset/worsening of neurological symptoms were noted. The baseline clinico-radiological details were obtained from stroke-clinic registery. Subsequently, all data were analyzed and compared using descriptive statistics. Seventy four of 104 MMA patients could be contacted and enrolled. The mean age, time since last follow-up and compliance to previously prescribed medication were 23.5 ± 16.1 years, 9.2 ± 1.7 months and 90.5% (n = 67), respectively. Aggravation/new onset neurological symptom were seen in 64.3% (n = 9) of COVID-19 positive MMA (n = 14), of which 8 were seen among the 11 pediatric COVID-19 positive MMA [(Transient ischemic attacks) TIA-4, TIA with headache-1, seizure-2, stroke causing mortality-1]. CONCLUSION: COVID-19 infection can potentiate MMA causing significant morbidity and mortality, especially in children. Providing optimal care for severe diseases (such as MMA) in developing countries during pandemic remains a challenge.

COVID-19 Pandemic, Personality and Geriatric Population: Proposed Pragmatism.

The elderly population is a sensitive and delicate cohort of society who is being compelled to bear the significant smoulders of disruptive social behavior of humankind amidst the COVID-19 pandemic. Our aim for this review was (1) to find out the root of disruption of societal integrity and self-centeredness by analyzing the spokes of HEXACO; (2) to delineate their possible relationships with the formation of Neuroticism and eventually Psychopathy, which have endangered human civilization the most in this pandemic; and (3) to search for the potential ways to get rid of these dark times. The constellation of different negative human behaviors probably originate from the negative deflection of components of the HEXACO model of personality towards the genesis of the dark triad. COVID-19 pandemic and upsurge of the dark triad in the form of Neuroticism, Narcissism and Machiavellianism potentially portend major mental health threats. Cultivation and practice of positive emotions and triumph of honesty, humility and humanity are imperative to save the mankind from the savagery of this pandemic.

Recurrent Facial Focal Seizures With Chronic Striatopathy and Caudate Atrophy-A Double Whammy in an Elderly Woman With Diabetes Mellitus.

Seizures and involuntary movements are relatively rare, but well-known neurological complications of non-ketotic hyperglycemia. While hemichorea-hemiballism secondary to diabetic striatopathy is increasingly being reported, unilateral caudate atrophy resulting from chronic vascular insufficiency/insult in a backdrop of poorly controlled diabetes mellitus is sparsely described in literature. We herein report a 75-year-old woman with poorly controlled diabetes mellitus who presented with concurrent epilepsia partialis continua involving left side of her face and hemichorea on the right side in the context of non-ketotic hyperglycemia. Neuroimaging revealed a space-occupying lesion suggestive of low-grade glioma in the right superior frontal cortex and left-sided caudate atrophy as well. Possibly, space-occupying lesion in motor cortex acted as an inciting factor for seizures and non-ketotic hyperglycemia further lowered the seizures threshold. On the other hand, atrophied left caudate had led to persistent choreiform movements secondary to chronic uncontrolled hyperglycemia. The simultaneous presence of acute and chronic neurological complications of diabetes mellitus makes this case unique. It also highlights the need for strict control of blood glucose and utility of appropriate neuroimaging to rapidly diagnose and prevent further complications.

Cerebral venous thrombosis in COVID-19.

BACKGROUND AND AIMS: Initially, novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) was considered primarily a respiratory pathogen. However, with time it has behaved as a virus with the potential to cause multi-system involvement, including neurological manifestations. Cerebral venous sinus thrombosis (CVT) has increasingly been reported in association with coronavirus infectious disease of 2019 (COVID-19). Here, we have shed light upon CVT and its possible mechanisms in the backdrop of the ongoing COVID-19 pandemic. METHODS: In this review, data were collected from PubMed, EMBASE and Web of Science, until March 30, 2021, using pre-specified searching strategies. The search strategy consisted of a variation of keywords of relevant medical subject headings and keywords, including "COVID-19", "SARS-CoV-2", "coronavirus", and "cerebral venous sinus thrombosis". RESULTS: COVID-19 has a causal association with a plethora of neurological, neuropsychiatric and psychological effects. CVT has gained particular importance in this regard. The known hypercoagulable state in SARS-CoV-2 infection is thought to be the main mechanism in COVID-19 related CVT. Other plausible mechanisms may include vascular endothelial dysfunction and altered flow dynamics. CONCLUSIONS: Although there are no specific clinical characteristics, insidious or acute onset headache, seizures, stroke-like, or encephalopathy symptoms in a patient with, or who has suffered COVID-19, should prompt the attending physician to investigate for CVT. The treatment of COVID-19 associated CVT does not differ radically from the therapy of CVT without the infection, i.e. urgent initiation of parenteral unfractionated heparin or low molecular weight heparin followed by conventional or mostly newer oral anticoagulants.

Complex movement disorders in SARS-CoV-2 infection induced acute disseminated encephalomyelitis.

Movement disorders are extremely rare in acute disseminated encephalomyelitis (ADEM) and in the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. We herein report a 34-years-old previously healthy woman who presented with a febrile illness and a constellation of movement disorders (predominantly myoclonus) followed by encephalopathy. After exclusion of common infectious, autoimmune and paraneoplastic etiologies, she was diagnosed to have COVID-19 induced ADEM, which responded to intravenous methylprednisolone and intravenous immunoglobulin. Our case adds to the tally of cases of post-SARS-CoV-2 infection related movement disorders and to the exceedingly rare list of cases in which movement disorders preceded ADEM.

Using Unsupervised Machine Learning to Identify Age- and Sex-Independent Severity Subgroups Among Patients with COVID-19: Observational Longitudinal Study.

BACKGROUND: Early detection and intervention are the key factors for improving outcomes in patients with COVID-19. OBJECTIVE: The objective of this observational longitudinal study was to identify nonoverlapping severity subgroups (ie, clusters) among patients with COVID-19, based exclusively on clinical data and standard laboratory tests obtained during patient assessment in the emergency department. METHODS: We applied unsupervised machine learning to a data set of 853 patients with COVID-19 from the HM group of hospitals (HM Hospitales) in Madrid, Spain. Age and sex were not considered while building the clusters, as these variables could introduce biases in machine learning algorithms and raise ethical implications or enable discrimination in triage protocols. RESULTS: From 850 clinical and laboratory variables, four tests-the serum levels of aspartate transaminase (AST), lactate dehydrogenase (LDH), C-reactive protein (CRP), and the number of neutrophils-were enough to segregate the entire patient pool into three separate clusters. Further, the percentage of monocytes and lymphocytes and the levels of alanine transaminase (ALT) distinguished cluster 3 patients from the other two clusters. The highest proportion of deceased patients; the highest levels of AST, ALT, LDH, and CRP; the highest number of neutrophils; and the lowest percentages of monocytes and lymphocytes characterized cluster 1. Cluster 2 included a lower proportion of deceased patients and intermediate levels of the previous laboratory tests. The lowest proportion of deceased patients; the lowest levels of AST, ALT, LDH, and CRP; the lowest number of neutrophils; and the highest percentages of monocytes and lymphocytes characterized cluster 3. CONCLUSIONS: A few standard laboratory tests, deemed available in all emergency departments, have shown good discriminative power for the characterization of severity subgroups among patients with COVID-19.

COVID-19 Induced Miller Fisher Syndrome Presenting With Autonomic Dysfunction: A Unique Case Report and Review of Literature.

A plethora of neurological manifestations are associated with the 2019 coronavirus infectious disease (COVID-19). We hereby report the first case of a patient infected with SARS-CoV-2 who acutely presented with autonomic dysfunction preceding the onset of complete clinical picture of Miller Fisher syndrome. She was finally diagnosed to be a case of anti-ganglioside antibody positive post-COVID-19 Miller Fisher syndrome with dysautonomia and treated with intravenous immunoglobulin with an excellent response. We also discuss the plausible pathogenic mechanisms of COVID-19 induced Miller Fisher syndrome and furnish a review of the post-COVID-19 Miller Fisher syndrome cases reported.

De Novo Movement Disorders and COVID-19: Exploring the Interface.

Background: Neurological manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are being widely documented. However, movement disorders in the setting of 2019 coronavirus infectious disease (COVID-19) have been a strikingly less discussed topic. Objectives: To summarize available pieces of evidence documenting de novo movement disorders in COVID-19. Methods: We used the existing PRISMA consensus statement. Data were collected from PubMed, EMBASE, Web of Science, and Scopus databases up to the 29th January, 2021, using pre-specified searching strategies. Results: Twenty-two articles were selected for the qualitative synthesis. Among these, a total of 52 patients with de novo movement disorders were reported. Most of these had myoclonus, ataxia, tremor or a combination of these, while three had parkinsonism and one a functional disorder. In general, they were managed successfully by intravenous immunoglobulin or steroids. Some cases, primarily with myoclonus, could be ascribed to medication exposures, metabolic disturbances or severe hypoxia, meanwhile others to a post-or para-infectious immune-mediated mechanism. SARS-CoV-2 could also invade the central nervous system, through vascular or retrograde axonal pathways, and cause movement disorders by two primary mechanisms. Firstly, through the downregulation of angiotensin-converting enzyme 2 receptors, resulting in the imbalance of dopamine and norepinephrine; and secondly, the virus could cause cellular vacuolation, demyelination and gliosis, leading to encephalitis and associated movement disorders. Conclusion: De novo movement disorders are scantly reported in COVID-19. The links between SARS-CoV-2 and movement disorders are not yet established. However, we should closely monitor COVID-19 survivors for the possibility of post-COVID movement disorders.