Coronavirus Disease 2019-Associated Neurological Manifestations in Children: A Large Single-Center Experience With Rare Cases.

BACKGROUND: We aimed to analyze pediatric patients with coronavirus disease 2019 (COVID-19) with a diverse spectrum of neurological manifestations in a single center since neurological involvement in children is still poorly understood. METHODS: We performed a retrospective study on 912 children aged between zero and 18 years who had a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test result and symptoms of COVID-19 from March 2020 to March 2021 in a single center. RESULTS: Among 912 patients, 37.5% (n = 342) had neurological symptoms and 62.5% (n = 570) had no neurological symptoms. The mean age of patients with neurological symptoms was significantly higher (14.2 ± 3.7 vs 9.9 ± 5.7; P < 0.001). Three hundred and twenty-two patients had nonspecific symptoms (ageusia, anosmia, parosmia, headache, vertigo, myalgia), whereas 20 patients had specific involvement (seizures/febrile infection-related epilepsy syndrome, cranial nerve palsy, Guillain-Barré syndrome and variants, acute disseminated encephalomyelitis, central nervous system vasculitis). The mean age of the patients with nonspecific neurological symptoms was significantly higher (14.6 ± 3.1 vs 7.7 ± 5.7; P < 0.001). CONCLUSION: This study presents a large number of patients with a diverse spectrum of neurological manifestations. The rare neurological manifestations reported in our study will contribute to better understanding the neurological involvement of SARS-CoV-2 in children. The study also points out the differences of SARS-CoV-2-related neurological manifestations between patients at different ages. Physicians should be alert about recognizing the early neurological manifestations of the SARS-CoV-2 in children.

New-onset refractory status epilepticus and febrile infection-related epilepsy syndrome.

PURPOSE OF REVIEW: The concept and understanding of new-onset refractory status epilepticus (NORSE), and its subtype with prior fever known as febrile infection-related epilepsy syndrome (FIRES) have evolved in the recent past. This review aims to summarize the recent developments in the pathophysiology, diagnosis and management of these challenging conditions. RECENT FINDINGS: NORSE and FIRES can have many different causes. Although the list of possible causes is still growing, they mostly fall in the categories of autoimmune encephalitis and genetic disorders. However, despite extensive investigations, most cases of NORSE and FIRES remain cryptogenic. Recent studies have pointed towards the key role of autoinflammation as a unifying pathophysiological mechanism in these cases. These findings also support the use of immunomodulatory treatment in this setting. Consensus recommendations on the management of NORSE and FIRES have recently been published. SUMMARY: NORSE and FIRES remain challenging conditions to diagnose and treat. Recent findings from clinical and basic research and new recommendations, reviewed in this article, contribute to an emerging framework for management and future research.

Eclampsia with hypothyroidism complicated with posterior reversible encephalopathy syndrome-a case report.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a rare neurological disorder with complex physiopathological mechanisms that have not been fully understood. Early identification is of great prognostic significance, of which the symptoms and radiological abnormalities can be completely reversed. If the diagnosis and treatment are delayed, ischemia and massive infarction may be developed in some patients. Posterior reversible encephalopathy syndrome (PRES) has been reported mainly in association with postpartum eclampsia, which have been rarely reported, while the association with hypothyroidism has not been reported at home or abroad. CASE PRESENTATION: Here we report on a pregnant 29-year-old with multipara and a chief complication of hypothyroidism. She presented in the emergency department with frequent attacks of severe headache symptoms resulting from reversible cerebral vasoconstriction syndrome (RCVS), accompanied with prenatal eclampsia. PRES was determined by radiological examination. CONCLUSION: To the best of our knowledge, this is the first case of PRES complicated by hypothyroidism and prepartum eclampsia.Clinicians should be alert for the co-occurence of eclampsia, PRES, and RCVS when patients have convulsions after a typical throbbing headache. Moreover, regular monitoring of thyroid function during pregnancy should also occupy certain special attention.

Sudden Death Associated With Possible Flare-Ups of Multiple Sclerosis After COVID-19 Vaccination and Infection: A Case Report and Literature Review.

We present an autopsy case of a 19-year-old man with a history of epilepsy whose unwitnessed sudden death occurred unexpectedly in the night. About 4 years before death, he was diagnosed with unilateral optic neuritis (ON). Demyelinating disease was suspected, but he was lost to follow up after the recovery. Six months before death, he received a second dose of mRNA coronavirus disease 2019 (COVID-19) vaccine. Three months before death, he experienced epileptic seizures for the first time. Seventeen days before death, he was infected with COVID-19, which showed self-limited course under home isolation. Several days before death, he complained of seizures again at night. Autopsy revealed multifocal gray-tan discoloration in the cerebrum. Histologically, the lesions consisted of active and inactive demyelinated plaques in the perivenous area of the white matter. Perivascular lymphocytic infiltration and microglial cell proliferation were observed in both white matter and cortex. The other major organs including heart and lung were unremarkable. Based on the antemortem history and postmortem findings, the cause of death was determined to be multiple sclerosis with suspected exacerbation. The direct or indirect involvement of cortex and deep gray matter by exacerbated multiple sclerosis may explain the occurrence of seizures. Considering the absence of other structural abnormalities except the inflammatory demyelination of the cerebrum, fatal arrhythmia or laryngospasm in the terminal epileptic seizure may explain his sudden unexpected death in the benign circumstances. In this case, the onset of seizure was preceded by COVID-19 vaccination, and the exacerbation of seizure was preceded by COVID-19 infection, respectively. Literature reporting first manifestation or relapse of multiple sclerosis temporally associated with COVID-19 vaccination or infection are reviewed.

Neurological complications associated with influenza in hospitalized children.

BACKGROUND: Influenza is a known respiratory and potential neurotropic virus. This study aimed to determine the prevalence and outcomes of influenza-related neurological complications among hospitalized children. METHODS: All medical records of hospitalized children aged <18 years old diagnosed with influenza at a tertiary care hospital in Bangkok were retrospectively reviewed. Influenza infection was confirmed by rapid antigen or reverse transcription polymerase chain reaction tests. Neurological characteristics and clinical outcomes were analyzed using the Pediatric Cerebral Performance Category Scale. RESULTS: From 2013 to 2018, 397 hospitalized children with a median age of 3.7 years (interquartile range [IQR]: 1.6-6.9) were included. The prevalence of neurological complications, including seizure or acute encephalopathy, was 16.9% (95% confidence interval [CI]: 13.3-20.9). Influenza A and B were identified in 73.1% and 26.9% of the patients, respectively. Among 39 (58.2%) acute symptomatic seizure cases, 25 (37.3%) children had simple febrile seizures, 7 (10.4%) had repetitive seizures, and 7 (10.4%) had provoked seizures with pre-existing epilepsy. For 28 (41.8%) encephalopathy cases, the clinical courses were benign in 20 (29.9%) cases and severe in 8 (11.9%) cases. Ten (14.9%) children needed intensive care monitoring, and 62 (93.5%) fully recovered to their baselines at hospital discharge. Predisposing factors to the neurological complications included a history of febrile seizure (adjusted odds ratio [aOR]: 20.3; 95% CI: 6.6-63.0), pre-existing epilepsy (aOR: 3.6; 95% CI: 1.3-10.2), and a history of other neurological disorders (aOR: 3.5; 95% CI: 1.2-10.2). CONCLUSIONS: One fifth of hospitalized children with influenza had neurological complications with a favorable outcome. Children with pre-existing neurological conditions were at higher risk for developing neurological complications.

Neurological symptoms and signs associated with COVID-19 in pediatric patients: a single-center experience.

There is insufficient evidence on SARS-CoV-2 induced neurological effects. Studies on CNS involvement during COVID-19 in children are limited. This study aims to identify and manage the neurological signs and symptoms in COVID-19-infected pediatric patients during follow up and plan future follow-ups. Children diagnosed COVID-19 and hospitalized in the pediatric pandemic services, between March 18, 2020, and June 18, 2021, were included in the study. Children with underlying neurological disease were excluded from the study. Patient data retrieved from hospital files and medical records. Children divided into 2 groups, 1 and 2, based on the presence or absence of neurological findings. A total of 243 children received follow-ups in the pandemic wards, 35 (14.4%) of these patients had neurological findings. Major neurological manifestations were headache (n:17, 7%), seizure (n:4, 1.6%), and anosmia/hyposmia (n:17, 7%). The number of boys (n:13, 37.1%) was smaller than the number of girls (n:22, 62.9%) in Group 1. Group 1 showed higher blood leukocyte, lymphocyte, thrombocyte, AST, LDH, d-dimer values. Anosmia/hyposmia occurred more often in girls, anosmia and headache occurred more often over 9 years of age. Pulmonary and hematologic involvement was more common in children with anosmia and headache. Our study is one of the few studies on neurological involvement in COVID-19 in children. To the best of our knowledge, there is limited data on these subjects in the literature.

Multisystem inflammatory syndrome in a neonate with severe hemophilia - a diagnostic challenge in COVID times: a case report.

BACKGROUND: Multisystem Inflammatory Syndrome in Neonates (MIS-N) can occur following antenatal COVID- 19 infection in the mother. Here we report a rare case of a neonate with Hemophilia A and MIS-N. CASE PRESENTATION: A 2-day-old baby presented with an intramuscular hematoma, neonatal seizures, and isolated activated partial thromboplastin time (APTT) prolongation. The neurosonogram showed a subdural hematoma. A diagnosis of Hemophilia A was made and was confirmed by factor 8 assay and genetic analysis. Supportive measures and Factor 8 replacement was initiated. A rising trend of inflammatory markers and an ongoing need for mechanical ventilation were noted. As there was a history of COVID-19 in the mother in the third trimester, MIS-N was diagnosed. The baby was treated with intravenous immunoglobulin (IVIG) and steroids, and there was an improvement in the clinical and laboratory markers. However, the baby developed seizures on day 16. There was an increase in the subdural hemorrhage and a further rise in inflammatory markers. A craniostomy and hematoma evacuation was done and the baby improved. CONCLUSION: The concurrent occurrence of hemophilia A with intracranial bleed, and MIS-N in a neonate is a diagnostic challenge. It is important to have a high index of suspicion to ensure timely diagnosis and treatment of MIS-N in this pandemic era.

Phantosmia and psychogenic non-epileptic seizures in a patient with burning mouth syndrome suffering from severe depression.

Burning mouth syndrome (BMS) is a rare but serious medical condition with important psychiatric comorbidity and specific psychological correlates. Psychopathology related with BMS represents a real challenge for clinical decision-making. In this case, depression is the leading psychiatric diagnosis associated with patient's BMS somatic pain and is driven by anxiety and a dissociative functioning. Facing a complex psychosomatic symptomatology, we offer new clinical perspectives for the screening of psychological traits of BMS. Moreover, we highlight the need to foster interdisciplinarity to improve differential diagnosis and defining an optimal care path. This case report stimulates a reflection on management challenges for the consultation-liaison psychiatry and shows the importance of a person-centred approach when communicating the diagnosis.

Posterior reversible encephalopathy syndrome - A pathology that should not be overlooked in the era of COVID-19.

BACKGROUND AND OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) that causes Coronavirus Disease 2019 (COVID-19) may determine a series of neurological complications directly, by invasion of the nervous system or indirectly, secondary to systemic organ failure. Posterior reversible encephalopathy syndrome (PRES) represents a clinical and radiological neurological entity involving predominantly the occipital lobes. PRES was observed in patients receiving cytotoxic drugs, patients suffering from infectious diseases and sepsis, hypertensive emergencies and eclampsia, renal or autoimmune diseases. As more infectious SARS-COV-2 variants are now dominant in most of the Europe, an increasing number of patients is presenting to the Emergency Department. MATERIALS AND METHODS: Case report of a 38-year-old patient, with previous exposure to SARS-COV-2 presented to the Emergency Department (ED) with generalized tonic-clonic seizures, dyspnea, cortical blindness and aphasia. The patient had been exhibiting fever, cough and shortness of breath in the previous 10 days. He had no relevant medical history and was receiving antibiotics and corticosteroids as prescribed by his general practitioner. RESULTS: Laboratory findings together with the thoracic computed tomography scan were consistent with the diagnosis of severe SARS-COV-2 pneumonia. The cerebral MRI scans showed bilateral T2-weighted/FLAIR hyperintensities that were suggestive for PRES. The patient was diagnosed with COVID-19 complicated with PRES. He received adequate treatment and the symptoms resolved in 48 h. CONCLUSIONS: This is a rare and interesting case of a patient with PRES and COVID-19 as underlying pathology, in whom rapid diagnosis in the ED and early initiation of appropriate treatment led to full recovery. Immediate extensive work-up in patients with COVID-19 and neurological symptoms proves to be paramount for best outcome. To our knowledge this is the first case of PRES described in a patient with Delta variant of SARS-COV-2.

Longstanding Phenytoin Use as a Cause of Progressive Dyspnea.

CASE PRESENTATION: A 54-year-old South African man with a medical history of type 2 diabetes mellitus, seizure disorder, OSA, and latent TB presented to the ER with gradually progressive dyspnea over months. He also reported occasional dry cough and fatigue at presentation but denied fever, chills, chest pain, leg swelling, palpitations, or lightheadedness. He was treated with a course of levofloxacin for presumed community-acquired pneumonia as an outpatient without improvement and had tested negative for COVID-19. He denied occupational or environmental exposures or sick contacts, though he had traveled back to South Africa 1 year before presentation. He had complex partial seizures for the past 22 years, which had been well controlled on phenytoin (300 mg daily). His other home medications included dulaglutide, sertraline, and atorvastatin and had no recent changes. He quit smoking 30 years ago after smoking one pack per day for 10 years.

Evaluation and Treatment of Seizures and Epilepsy During the COVID-19 Pandemic.

PURPOSE OF REVIEW: Seizures, including status epilepticus, have been reported in association with acute COVID-19 infection. People with epilepsy (PWE) have suffered from seizure exacerbations during the pandemic. This article reviews the data for clinical and electrographic seizures associated with COVID-19, technical EEG considerations for reducing risk of transmission, and factors contributing to seizure exacerbations in PWE as well as strategies to address this issue. RECENT FINDINGS: An increasing number of studies of larger cohorts, accounting for a variety of variables and often utilizing EEG with standardized terminology, are assessing the prevalence of seizures in hospitalized patients with acute COVID-19 infections, and gaining insight into the prevalence of seizures and their effect on outcomes. Additionally, recent studies are evaluating the effect of the pandemic on PWE, barriers faced, and the usefulness of telehealth. Although there is still much to learn regarding COVID-19, current studies help in assessing the risk of seizures, guiding EEG utilization, and optimizing the use of telehealth during the pandemic.

A longitudinal seizure outcome following the COVID-19 pandemic in 2020 and 2021: Transient exacerbation or sustainable mitigation.

OBJECTIVE: To study the longitudinal seizure outcomes of people with epilepsy (PWE) following the acute and chronic phases of the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Consecutive PWE who were treated at the epilepsy center of Hiroshima University Hospital between 2018 and 2021 were enrolled. We evaluated the incidence of seizure frequency increase or decrease following the pandemic during observational periods in 2020 and 2021. Data between 2018 and 2019 were used as a control set. The sustainability of the altered seizure frequency condition was evaluated throughout the study period. We analyzed the clinical, psychological, and social factors associated with PWE with seizure exacerbation or amelioration. RESULTS: Among the 223 PWE who were evaluated (mean age 37.8 ± 16.3 years), seizure frequency increased for 40 (16.8%) and decreased for 34 (15.2%) after the pandemic began. While seizure exacerbation tended to be a transient episode during 2020, seizure amelioration was likely to maintain excellent status over the observation periods; the sustainability of the altered seizure frequency condition was more prominent for amelioration than exacerbation (p < 0.001). Seizure exacerbation was significantly associated with "no housemate" (odds ratio [OR] 3.37; p = 0.045) and "comorbidity of insomnia" (OR 5.80; p = 0.004). Conversely, "structural abnormality of MRI" (OR 2.57; p = 0.039) and "two-generation householding" (OR 3.70; p = 0.004) were independently associated with seizure amelioration. CONCLUSION: This longitudinal observation confirmed that seizure exacerbation and amelioration emerged during the COVID-19 pandemic. The COVID-19 pandemic has shed light on the stark difference that social support systems can make on outcomes for PWE.

Telemedicine in epilepsy management during the coronavirus disease 2019 pandemic.

BACKGROUND: Telemedicine has spread rapidly during the coronavirus disease 2019 (COVID-19) pandemic and shown its usefulness, particularly for patients with epilepsy, compared to face-to-face visits. We sought to evaluate the clinical features of patients with childhood onset epilepsy associated with consultations by telephone call during the COVID-19 pandemic. METHODS: We retrospectively investigated the medical records of patients with childhood onset epilepsy who visited an outpatient clinic in Saitama Children's Medical Center, Saitama, Japan, from 1 March 2020 to 30 September 2020. To find the clinical features of patients who utilized telemedicine consultation (by telephone call), we divided the patients into the telemedicine group and the face-to-face group. We then reviewed the clinical features. Telemedicine consultation was not implemented for new patients. RESULTS: We enrolled 776 outpatients in total, and 294 patients (37.9%) utilized telemedicine consultations. The total number of visits was 2,299 and the total number of telemedicine consultations was 373 (16.2%). No clinical feature was associated with telemedicine consultations except for age at onset of epilepsy. The number of oral antiepileptic drugs prescriptions decreased in 23 of 776 (3.0%) of the patients who did not experience seizure deterioration, including status epilepticus, or who visited the emergency room. CONCLUSION: Telemedicine consultations were successfully utilized for epilepsy treatment at our outpatient clinic, regardless of epilepsy type, etiology, seizure frequency, comorbidities, and patients' residential areas. Thus, telemedicine by telephone call may be a useful resource in the management of patients with childhood onset epilepsy during the pandemic.

Clinical Characteristics and Histopathology of Coronavirus Disease 2019-Related Deaths in African Children.

BACKGROUND: Globally, very few childhood deaths have been attributed to coronavirus disease 2019 (COVID-19). We evaluated clinical, microbiologic and postmortem histopathologic findings in childhood deaths in whom severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified antemortem or postmortem. METHODS: Surveillance of childhood deaths was ongoing during the initial COVID-19 outbreak in South Africa from April 14, 2020, to August 31, 2020. All children hospitalized during this time had a SARS-CoV-2 test done as part of standard of care. Postmortem sampling included minimally invasive tissue sampling (MITS) of lung, liver and heart tissue; blood and lung samples for bacterial culture and molecular detection of viruses (including SARS-CoV-2) and bacteria. The cause of death attribution was undertaken by a multidisciplinary team and reported using World Health Organization framework for cause of death attribution. RESULTS: SARS-CoV-2 was identified on antemortem and/or postmortem sampling in 11.7% (20/171) of deceased children, including 13.2% (12/91) in whom MITS was done. Eighteen (90%) of 20 deaths with SARS-CoV-2 infection were <12 months age. COVID-19 was attributed in the causal pathway to death in 91.7% (11/12) and 87.5% (7/8) cases with and without MITS, respectively. Lung histopathologic features in COVID-19-related deaths included diffuse alveolar damage (n = 6, 54.5%), type 2 pneumocyte proliferation (n = 6, 54.5%) and hyaline membrane formation (n = 5, 36.4%). Culture-confirmed invasive bacterial disease was evident in 54.5% (6/11) of COVID-19 attributed deaths investigated with MITS. CONCLUSIONS: COVID-19 was in the causal pathway of 10.5% (18/171) of all childhood deaths under surveillance. The postmortem histopathologic features in fatal COVID-19 cases in children were consistent with reports on COVID-19 deaths in adults; although there was a high prevalence of invasive bacterial disease in the children.

A follow-up study of patients with COVID-19 presenting with seizures.

OBJECTIVE: We performed a follow-up study of patients with COVID-19 presenting with seizures. METHODS: All consecutive patients with seizures, who were referred to Namazee Hospital, Shiraz, Iran, with a diagnosis of COVID-19, from 10 August 2020 until 20 October 2020 were included in this longitudinal study. The clinical data were collected by the admitting physician. In a follow-up phone call to the discharged patients (after eight weeks or more), we inquired their seizure outcome. RESULTS: In total, 32 patients were studied; 28 patients were followed. Twelve patients (37.5%) presented with a single tonic-clonic seizure and nine (28.1%) had convulsive status epilepticus; one patient had functional (psychogenic) seizures. Ten patients (31.3%) had pre-existing epilepsy, eight others (25%) had pre-existing CNS problems (without epilepsy), one person (3.1%) had pre-existing functional seizures, and 13 individuals (40.1%) neither had epilepsy nor had other CNS problems. Eight patients (28.6%) reported experiencing seizure(s) after being discharged from the hospital; six of these had pre-existing epilepsy and one had pre-existing functional seizures. One patient, who had a newly developed ischemic brain infarction, reported experiencing recurrent seizures. CONCLUSION: Seizures in patients with COVID-19 are either acute symptomatic (in about two-thirds) or an exacerbation of a pre-existing epilepsy/functional seizures (in about one-third). A thorough investigation of the underlying etiology of seizures in patients with COVID-19 is necessary. Seizure outcome in patients, who are hospitalized with COVID-19 and seizures, is generally good.

Effects of the COVID-19 pandemic on characteristics of functional (psychogenic) seizures.

OBJECTIVE: We investigated whether the COVID-19 pandemic has affected the clinical characteristics of patients with functional seizure (FS) (at the time of diagnosis). METHODS: In a retrospective study of a prospectively developed and maintained database, all patients diagnosed with FS before and during the COVID-19 pandemic were studied at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran, from December 2008 until February 2021. RESULTS: Three hundred and eighty-eight patients were studied. Three hundred and sixty-four patients (94%) were diagnosed before and 24 persons (6%) during the pandemic. Patients diagnosed during the COVID-19 pandemic less frequently had generalized motor seizures [odds ratio (OR): 0.30, 95% confidence interval (CI): 0.12-0.77; p = 0.012] and had higher seizure frequencies (OR: 1.00, 95% CI: 1.00-1.01; p = 0.044). Functional seizures were inversely associated with the education level as a trend during the COVID-19 pandemic (OR: 0.36, 95% CI: 0.13-1.01; p = 0.052). CONCLUSION: The COVID-19 pandemic has affected the characteristics of patients with FS (at the time of diagnosis). Larger and multi-center studies are needed to investigate the links and associations between the COVID-19 pandemic and characteristics of FS.

COVID-19-related refractory status epilepticus with the presence of SARS-CoV-2 (RNA) in the CSF: a case report.

Amongst the neurologic complications of COVID-19 disease, very few reports have shown the presence of the virus in the cerebrospinal fluid (CSF). Seizure and rarely status epilepticus can be associated with COVID-19 disease. Here we present a 73-year-old male with prior history of stroke who has never experienced seizure before. He had no systemic presentation of COVID-19 disease. The presenting symptoms were two consecutive generalized tonic-clonic seizures that after initial resolution turned into a nonconvulsive status epilepticus despite antiepileptic treatment (a presentation similar to NORSE (new-onset refractory status epilepticus)). There was no new lesion in the brain magnetic resonance imaging (MRI). The CSF analysis only showed an increased protein levels and positive reverse transcription polymerase chain reaction (RT-PCR) of 2019-nCoV. Patient recovered partially after anesthetic, IVIG, steroid, and remdesivir. To our knowledge, this is the first report of a refractory status epilepticus with the presence of SARS-CoV-2 ribonucleic acid (RNA) in the CSF.

Overview of COVID-19 and neurological complications.

The sudden and storming onset of coronavirus 2 infection (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) was associated by severe acute respiratory syndrome. Recently, corona virus disease 19 (COVID-19) has appeared as a pandemic throughout the world. The mutational nature of the virus, along with the different means of entering and spreading throughout the body has involved different organs. Thus, patients are faced with a wide range of symptoms and signs. Neurological symptoms, such as anosmia, agnosia, stroke, paralysis, cranial nerve deficits, encephalopathy, meningitis, delirium and seizures, are reported as common complications affecting the course of the disease and its treatment. In this review, special attention was paid to reports that addressed the acute or chronic neurological manifestations in COVID-19 patients who may present acute respiratory syndrome or not. Moreover, we discussed the central (CNS) and peripheral nervous system (PNS) complications in SARS-Cov2-infected patients, and also the pathophysiology of neurological abnormalities in COVID-19.

CNS implications of COVID-19: a comprehensive review.

COVID-19 was first reported in December 2019 in the Wuhan city of China, and since then it has spread worldwide taking a heavy toll on human life and economy. COVID-19 infection is commonly associated with symptoms like coughing, fever, and shortness of breath, besides, the reports of muscle pain, anosmia, hyposmia, and loss of taste are becoming evident. Recent reports suggest the pathogenic invasion of the SARS-CoV-2 into the CNS, that could thereby result in devastating long term complications, primarily because some of these complications may go unnoticed for a long time. Evidence suggest that the virus could enter the CNS through angiotensin-converting enzyme-2 (ACE-2) receptor, neuronal transport, haematogenous route, and nasal route via olfactory bulb, cribriform plate, and propagates through trans-synaptic signalling, and shows retrograde movement into the CNS along nerve fiber. COVID-19 induces CNS inflammation and neurological degenerative damage through a diverse mechanism which includes ACE-2 receptor damage, cytokine-associated injury or cytokine storm syndrome, secondary hypoxia, demyelination, blood-brain barrier disruption, neurodegeneration, and neuroinflammation. Viral invasion into the CNS has been reported to show association with complications like Parkinsonism, Alzheimer's disorder, meningitis, encephalopathy, anosmia, hyposmia, anxiety, depression, psychiatric symptoms, seizures, stroke, etc. This review provides a detailed discussion of the CNS pathogenesis of COVID-19. Authors conclude that the COVID-19 cannot just be considered as a disorder of the pulmonary or peripheral system, rather it has a significant CNS involvement. Therefore, CNS aspects of the COVID-19 should be monitored very closely to prevent long term CNS complications, even after the patient has recovered from COVID-19.