Acute encephalitis following COVID-19 vaccines: A case series

Case report Background: Neurological adverse effects (NAE) as headache and dizziness are commonly reported with COVID-19 vaccines but are transient and self-limited. However, few serious NAE have been recently described which can be fatal. Here we report two rare cases of encephalitis related to COVID-19vaccination BNT162b2 (Pfizer) and mRNA-1273 (Moderna) and the inherent challenges in their diagnosis. Method(s): We report two cases of acute encephalitis notified to the department of pharmacovigilance in the University Hospital of Monastir Results: Case n'1: Three weeks after receiving her first dose of mRNA-1273, a 35-year- old female, with a medical history of hypothyroidism and eczema was admitted to the intensive care unit as she had confusion and a febrile tonic-clonic seizure complicated with a status epilepticus and dysautonomia. CSF investigations were nonspecific, and the MRI head did not detect any abnormality. Common causes were excluded by an extensive workup (neoplastic, neuro-vascular, autoimmune and infectious causes). She received cefotaxime and acyclovir without any recovery. However, a spectacular recovery was noticed when receiving methylprednisolone. Case n'2: Three days after receiving her first dose of BNT162b2, a-40- year- old female, with a medical history of rheumatoid arthritis was admitted to the medical care unit as she had experienced a three-day history of headache, memory disturbance, severe cognitive disorders and 4 febrile tonic-clonic seizures. MRI head showed signs of bitemporal encephalitis and CSF investigations was with no findings. Extensive laboratory studies ran out alternative causes as neoplastic, autoimmune and infectious diseases. A twenty-one- day acyclovir regimen was administrated with no recovery. As the cognitive deficit is getting more severe, she got intravenous immunoglobulin therapy with a spectacular improvement. Conclusion(s): Based on the Naranjo Algorithm, this adverse NAR can be possibly (score = 6) induced by COVID-19 vaccines. The dramatic improvement after receiving either corticoids or immunoglobulin therapy supports an immune-mediated mechanism behind this acute presentation. Cases of acute encephalitis secondary to H1N1 influenza and poliomyelitis vaccines have been previously reported but those related to COVID-19 vaccines are still not yet elucidated due to the unproven causality. Further prospective studies are needed to evaluate the causal association between vaccine and NAE occurring vaccination.

Neuropsychiatric Manifestations of COVID-19 in Hospitalized Pediatrics: A Multicenter Cross-sectional Study

Background: The large proportion of coronavirus disease 2019 (COVID-19) patients has been associated with a large number of neu-ropsychiatric manifestations. Despite the high prevalence of COVID-19, few studies have examined such manifestations, especially in children and adolescents. Objective(s): This study investigated neuropsychiatric manifestations in hospitalized children and adolescents admitted for COVID-19 infection in Iran. Method(s): This prospective observational study included admitted children and adolescents (4-18 years old) diagnosed with COVID-19 infection, pediatric neurologists, child and adolescent psychiatrists, and infectious disease specialists, and assessed 375 infected patients during August and December 2021. Result(s): Of the 375 patients, 176 (47%) were female, with a mean age of 9.0 +/- 3.39 years. Psychiatric and neurological manifestations were reported in 58 (15.5%) and 58 (15.5%) patients, respectively. The most prevalent psychiatric disorders were separation anxiety disorder (SAD) (5.1%), major depressive disorder (MDD) (3.5%), generalized anxiety disorder (GAD) (2.7%), insomnia (2.4%), and op-positional defiant disorder (ODD) (2.4%). Regarding neurological complications, seizures were the most prevalent (13.1%), followed by encephalitis (1.9%), transverse myelitis (0.3%), acute ischemic stroke (0.3%), and Guillain-Barre syndrome (0.3%). There was no significant relationship between the duration of COVID-19 infection (P = 0.54) and ICU admission (P = 0.44) with the emergence of psychiatric symptoms. Conclusion(s): The most prevalent neurologic and psychiatric complications among children and adolescents with COVID-19 infection were seizures and the symptoms of anxiety/mood disorders, respectively.Copyright © 2023, Author(s).

A rare case of managing near sudden unexpected death in status epilepticus with COVID-19 infection in rural area: what is the possible cause?

COVID-19, a pandemic caused by the SARS-CoV-2 infection, has many fatal complications related to neurological and cardiovascular events such as seizures and arrhythmia leading to cardiac arrest. The direct and indirect mechanisms of SARS-CoV-2 played a significant role to generate its clinical manifestation. Near-sudden unexpected death in epilepsy (SUDEP) is a reversal of cardiopulmonary arrest in an epileptic patient which is very dangerous if not treated well. Here we present a 27-year-old man with VF and near sudden unexpected death due to status epilepticus (SE) and COVID-19 infection that was successfully managed in a rural area emergency setting. Prompt treatment in the emergency room followed by supportive management is important for patient survival. This rare and complex case possibly happened and should be differentiated whether the cause is COVID-19 or SUDEP to establish definitive management though the supportive management is still the same. Prevention of COVID-19 complications and SUDEP should also be done to reduce morbimortality. Copyright © 2022, Amaltea Medical Publishing House. All rights reserved.

Sedation Practices in Covid-19 Versus Non-Covid-19 Acute Respiratory Distress Syndrome Patients

INTRODUCTION: Coronavirus disease 2019-associated acute respiratory distress syndrome (CARDS) has been associated with high opioid and sedative requirements in patients requiring mechanical ventilation (MV). The purpose of this study was to characterize opioid and sedative use in patients with CARDS compared to those with non-CARDS. METHOD(S): A retrospective cohort study compared adult patients admitted to an intensive care unit (ICU) on MV with CARDS or non-CARDS between January 2018 and May 2020. Patients receiving at least one opioid or sedative infusion for at least 48 hrs were included. Patients were excluded if they were transferred from an outside hospital while on MV, deemed comfort care, admitted for status epilepticus, ischemic, or hemorrhagic stroke and/ or cardiac arrest, admitted with a tracheostomy, or received extracorporeal membrane oxygenation. Statistical analysis was conducted using descriptive statistics with the appropriate statistical tests depending on the distribution type. The primary objective was to compare the use of opioid and sedative agents administered to patients with CARDS and non-CARDS. Secondary objectives included neuromuscular blocking agent (NMBA) use, time on mechanical ventilation (MV), in-hospital and ICU length of stay (LOS). RESULT(S): A total of 59 CARDS and 19 non-CARDS patients were included. Opioid infusions were used in 100% of non-CARDS patients and 98% of CARDS patients during the first 10 days of MV (p=0.57). There was significantly higher use of propofol in CARDS patients compared to non- CARDS patients (100% vs 89%, p=0.01) and higher median daily dose (3847mg vs 2992mg;p=0.018). No difference in median cumulative dose of BZD was observed in the CARDS group vs non-CARDS group (50mg vs 9mg;p=0.131). Time on mechanical ventilation was significantly longer in the CARDS group compared to the non-CARDS group (17 days vs 11 days, p=0.003). Comparably, 73% of CARDS received NMBA vs 53% in non-CARDS, p=0.05. There was significantly higher in-hospital LOS (36 days vs 48 days, p=0.005) and ICU LOS (15 days vs 31 days, p=0.002) in the CARDS group compared to the non- CARDS group. CONCLUSION(S): Patients with CARDS were more likely to receive NMBA and required higher dosages of propofol. CARDS patients were on MV longer and had longer hospital and ICU LOS.

MeRIT Project: Scoping review of rational polytherapy in patients with drug resistant epilepsy

Introduction: There is a paucity of literature regarding the optimal selection of combination anti-seizure medications (ASMs) for drug resistant epilepsy (DRE). The aim of this scoping review is to evaluate current evidence related to "rational polytherapy" among adults with DRE. Research Question or Hypothesis: What is the current evidence of clinical and health-related humanistic and economic outcomes of rational polytherapy with ASMs in DRE? If DRE is mentioned, is the appropriate definition applied? What are the current gaps? Study Design: Scoping review Methods: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-SCr) guidelines, PubMed, ProQuest, CINAHL, and Cochrane databases were searched using DRE- and polytherapy-related keywords. The exclusion criteria applied included: non-English;non-human studies;non-research studies;participants less than 18 years;status epilepticus;ASM monotherapy;and certain ASMs. In Covidence, two researchers independently reviewed articles for inclusion at each phase, with a third resolving conflicts. Data were extracted, with quality appraisal using the Mixed Methods Appraisal Tool (MMAT). Result(s): Of the 6477 studies imported for screening, 33 studies were included. Clinical, humanistic, and economic outcomes were reported by 26, 12, and one study, respectively. Common efficacyrelated clinical outcomes included >=50% reduction in seizure frequency (n=14), seizure freedom (n=13), and percent reduction in seizure frequency (n=8). Common humanistic outcomes included quality of life (n=4), medication adherence (n=2), sleep-related outcomes (n=2), and physician and patient global assessments (n=2). The economic study reported quality-adjusted life years. Two studies referenced the standard definition of DRE. Five studies did not specifically define DRE. Gaps in the literature include limited generalizability, minimal reports in pregnancy, and lack of optimal ASM combinations. Conclusion(s): Strengths of the evidence include addressing a variety of outcomes. Inconsistent definitions of DRE, small sizes, and heterogeneity among studies limit the ability to draw meaningful conclusions. Optimal combinations of ASMs for rational polytherapy for DRE is unclear.

POSTINFECTIOUS COVID-19 ENCEPHALITIS RESPONSIVE TO PULSE-DOSE STEROIDS AND IV IMMUNOGLOBULINS

SESSION TITLE: Post-COVID-19 Infection Complications SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is the causative agent of coronavirus disease-2019 (COVID-19). Post-infectious encephalitis secondary to SARS-CoV-2 may present with delirium, seizures, or transient comatose state. The mechanism of encephalitis in patients with COVID-19 is multifactorial. Cytokine release syndrome, a systemic hyperinflammatory condition, might have an integral part in the pathophysiology of this manifestation. Beneficial effects of pulse dose glucocorticoid therapy, with and without plasma exchange or IVIG, have been described. (1, 2) In this case report, we disclose a case of a young healthy male that presented with acute encephalopathy after 10 days of contracting SARS-CoV-2 and aim to discuss the potential role of IVIG and pulse dose steroid. CASE PRESENTATION: A 37-year-old previously healthy Caucasian man initially presented to urgent care with fatigue and generalized weakness and was diagnosed with acute COVID-19 infection through positive PCR. Four days later, he developed shortness of breath, syncope and vomiting. He was taken to the ER, where he had a witnessed seizure complicated by status epilepticus requiring endotracheal intubation for airway protection. He was then airlifted to our University Hospital. Upon arrival, labs were notable for elevated troponin, leukocytosis, and mildly elevated liver enzymes. An echocardiogram revealed stress induced (Takotsubo) cardiomyopathy. CT head was normal and continuous EEG showed focal electrographic seizures of left temporal onset. MRI of brain with/without contrast showed subtle areas of cortical diffusion hyperintensity involving left cerebral hemisphere including left posterior temporal lobe, lateral occipital lobe, posterior lateral frontal lobe and posterior lateral parietal lobe with subtle patchy areas of cortical enhancement on postcontrast T1-weighted images. CSF analysis was benign and CSF PCR for SARS-CoV-2 was negative. One gram daily IV methylprednisolone and IVIG therapy was given for total 5 days. On Day 2 of therapy, seizures subsided, and patient was successfully extubated after. Repeat MRI brain with/without contrast done after day of therapy showed improvement in previously demonstrated findings. He improved clinically and was discharged home on hospitalization day. DISCUSSION: Post-infectious COVID-19 encephalitis falls under the spectrum of disease described under neurological syndromes related to SARS-CoV-2 infection.(3) Diagnosis is based on Clinical presentation, positive COVID PCR on nasopharyngeal swab and Imaging demonstrating cortical enhancement on post contrast T1-weighted imaging. Out of various treatment options described in literature (1,2), our patient responded well to pulse dose steroids and IVIG therapy for 5 days. CONCLUSIONS: Careful selection of patients and therapies should be considered when post-infectious COVID-19 encephalitis is suspected. Reference #1: Cao A, Rohaut B, Le Guennec L, et al. Severe COVID-19-related encephalitis can respond to immunotherapy. Brain. 2020;143(12):e102. doi:10.1093/brain/awaa337 Reference #2: Pugin D, Vargas MI, Thieffry C, et al. COVID-19-related encephalopathy responsive to high-dose glucocorticoids. Neurology. 2020;95(12):543-546. doi:10.1212/WNL.0000000000010354 Reference #3: Al-Ramadan A, Rabab'h O, Shah J, Gharaibeh A. Acute and Post-Acute Neurological Complications of COVID-19. Neurol Int. 2021;13(1):102-119. Published 2021 Mar 9. doi:10.3390/neurolint13010010 DISCLOSURES: No relevant relationships by Ali Ahmad No relevant relationships by Varun Halani No relevant relationships by Michael Lasky No relevant relationships by Posan Limbu

A RARE CASE OF POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES)

SESSION TITLE: COVID-19 Case Report Posters 3 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: We are presenting a rare case of Posterior Reversible Encephalopathy Syndrome (PRES) without traditional risk factors in a patient with Covid 19. CASE PRESENTATION: Patient is a 41 y/o F with a past medical history of obesity, seizure disorder, epilepsy, hyperlipidemia and asthma who was admitted for Covid 19 pneumonia. Patient was transferred to the ICU on day #5 and intubated on day #8. Patient was given remdesivir, dexamethasone and baricitinib. Patient required intermittent vasopressors as her blood pressure varied between hypotensive and normotensive. Rarely her blood pressure increased to a hypertensive range. Patient had a thrombotic event on day #19 in her right upper extremity secondary to continuous renal replacement to manage acute renal failure. On Day #24, patient became unresponsive without sedation with an EEG showing moderate to severe slowing. On day #26 patient had a decreased response to stimuli leading to an MRI to evaluate for Posterior Reversible Encephalopathy Syndrome (PRES). MRI highlighted abnormal signal in the brain parenchyma concentrated mainly in the posterior brain consistent with PRES. On day #31 patient exhibited seizure like diffuse tremor. Blood pressure ranged from 90/72 to 137/84 hospital days #20-31. Status epilepticus was evaluated by an long term monitoring EEG showed diffuse slowing and occasional sharp wave activity in the right posterior cerebellum and occipital region without active seizures. On day #39 patient was found to have an acute hemorrhagic stroke of the left temporal region which resolved on day #43. On day #47 patient was transferred to a tertiary care center for tracheostomy placement and discharged on day #55 to a LTACH for rehab. DISCUSSION: PRES is a rare but severe complication of Covid 19 infection. Previous cases showed variability in underlying causes. Our patient showed significant endothelial dysfunction leading to multiple thrombotic events[1]. While our patient had rare hypertensive episodes, they were not persistent nor severe, nor were they present at the time of her seizure activity[1][2]. In comparison to previous cases, our patient had overlapping risk factors such as renal failure, obesity and dyslipidemia[1]. Our patient showed common clinical manifestations of PRES such as seizures, focal neurological deficits, and altered mental status with previous cases[1]. Our patient was not given tocilizumab in contrast with previous cases, however was given corticosteroids[1][2]. CONCLUSIONS: The above is a rare case of PRES without traditional risk factors. Providers must keep a wide differential diagnosis in patients with Covid 19. Reference #1: Lallana, S., Siegler, J. E., Chen, A., Requena, M., Rubiera, M., & Sanchez, A. (2021). Response to correspondence concerning "posterior reversible encephalopathy syndrome (PRES) associated with covid-19.” Journal of Clinical Neuroscience, 92, 189–190. https://doi.org/10.1016/j.jocn.2021.08.006 Reference #2: Kishfy, L., Casasola, M., Banankhah, P., Parvez, A., Jan, Y. J., Shenoy, A. M., Thomson, C., & AbdelRazek, M. A. (2020). Posterior reversible encephalopathy syndrome (PRES) as a neurological association in severe covid-19. Journal of the Neurological Sciences, 414, 116943. https://doi.org/10.1016/j.jns.2020.116943 DISCLOSURES: No relevant relationships by Arka Bhattacharya No relevant relationships by Benjamin Silverman

New-onset refractory status epilepticus due to autoimmune encephalitis after vaccination against SARS-CoV-2: First case report.

Background: Vaccination against SARS-CoV-2 has been conducted frequently to limit the pandemic but may rarely be associated with postvaccinal autoimmune reactions or disorders. Case presentation: We present a 35-year-old woman who developed fever, skin rash, and headache 2 days after the second SARS-CoV-2 vaccination with BNT162b2 (Pfizer/Biontech). Eight days later, she developed behavioral changes and severe recurrent seizures that led to sedation and intubation. Cerebral magnetic resonance imaging showed swelling in the (para-) hippocampal region predominantly on the left hemisphere and bilateral subcortical subinsular FLAIR hyperintensities. Cerebrospinal fluid analysis revealed a lymphocytic pleocytosis of 7 cells/µl and normal protein and immunoglobulin parameters. Common causes of encephalitis or encephalopathy such as viral infections, autoimmune encephalitis with well-characterized autoantibodies, paraneoplastic diseases, and intoxications were ruled out. We made a diagnosis of new-onset refractory status epilepticus (NORSE) due to seronegative autoimmune encephalitis. The neurological deficits improved after combined antiepileptic therapy and immunomodulatory treatment including high-dose methylprednisolone and plasma exchange. Conclusions: Although a causal relationship cannot be established, the onset of symptoms shortly after receiving the SARS-CoV-2 vaccine suggests a potential association between the vaccination and NORSE due to antibody-negative autoimmune encephalitis. After ruling out other etiologies, early immunomodulatory treatment may be considered in such cases.

Coronavirus-2019 Disease with Pancytopenia with Leptospirosis and Herpes Simplex Virus Co-infection

Aim and background: COVID-19 pandemic has affected the whole world. Besides COVID, many infections may emerge during the course of the disease. Lymphopenia, use of immunosuppressants underlying comorbidities, and immune dysregulation secondary to SARS-CoV-2 could be the likely cause of the emergence such infections. We hereby describe a case of COVID-19 disease which presented with pancytopenia and was found to have Leptospirosis and Herpes Simplex Virus co-infection. Case summary: A 23-yearold postpartum female with no comorbidities and uneventful obstetric history was referred to our hospital 2 weeks after a full-term normal vaginal delivery. She developed generalized convulsive status epilepticus on the 10th day of her delivery, which was managed elsewhere with anti-epileptic drugs (AEDs). During her hospital stay, RTPCR for COVID-19 turned out to be positive but she remained asymptomatic throughout the course of her illness and seizures remained well-controlled on AEDs. On admission to our hospital, she was fully conscious, alert with no focal neurological deficits. Notable findings on evaluation were pancytopenia with megaloblastic features, bilateral pedal edema, and hepatosplenomegaly. NCCT brain was done which was suggestive of subarachnoid hemorrhage (SAH) along bilateral parietooccipital region for which conservative management was planned. 2D echocardiography was normal. Ultrasonography of abdomen revealed gross splenomegaly and mild hepatomegaly with mesenteric lymphadenopathy. NCCT thorax and abdomen were unremarkable apart from hepatosplenomegaly. In the panel sent for pancytopenia workup, IgM anti-HSV 1 antibodies turned out to be positive in blood. In addition, tropical workup was suggestive of Leptospirosis (IgM antibodies were positive). Workup for tuberculosis was negative. Bone marrow workup revealed features of trilineage hematopoiesis with micronormoblastic maturation consistent with iron deficiency anemia with no evidence of hemophagocytosis. Subsequently, IV acyclovir, IV doxycycline, and iron replacement were added. She improved clinically after these therapies and was subsequently discharged in a stable condition. MRI brain with MR angiography and venography done before discharge showed T1 sulcal hyperintensities along bilateral parietooccipital regions suggestive of SAH which was not progressing (as compared to NCCT brain scan done at admission). On day 60 of telephonic follow-up, patient was doing well and leading normal life without any persistence or emergence of symptoms.

A Case Report of Coronavirus (COVID-19) Disease and Herpesviridae Viral Co-Infections: A Lethal Combination? ABS0138)

Introduction: COVID-19 pandemic has affected the whole world. Besides COVID, other viral infections may emerge during the course of the disease owing to lymphopenia, use of immunosuppressants, underlying comorbidities, and immune dysregulation, which may pose additional threats.1 We hereby describe two cases of COVID- 19 with viral co-infections belonging to the Herpesviridae family with undulating clinical course. Case 1: Cytomegalovirus (CMV) Co-infection: A 55-year-old male, COVID unvaccinated, chronic smoker, overweight and hypertensive was admitted to our ICU with a 1-week history of fever, cough, and breathlessness. SARSCoV- 2 reverse transcriptase-polymerase chain reaction (RT-PCR) test was positive. At admission, he had hypoxaemia (SpO2 86%on room air), respiratory rate 35-40/minute, and ground-glass opacities in chest X-ray involving 50% of bilateral lung parenchyma suggestive of severe COVID-19 pneumonia. He was managed with lung-protective invasive mechanical ventilation, restrictive fluid strategy, 16-18 hour/day proning sessions (4-5), intravenous (IV) remdesivir, IV dexamethasone 6 mg 12 hourly, and enoxaparin thromboprophylaxis. After 2 weeks of ICU stay, weaning was attempted but the weaning attempts failed due to underlying neuromuscular weakness. On examination, bilateral (B/L) cranial nerve palsies, areflexia, and motor power 0/5 in bilateral upper and lower limbs were noticed. possibility of Guillain-Barre syndrome (GBS) was kept and IV immunoglobulin therapy was empirically administered for 5 days with some improvement in power up to 1/5 in upper limbs. On day 35 of hospitalization, he developed pancytopenia along with features of deranged liver function and gut dysfunction. In evaluation, PCR for CMV turned out to be positive in blood. Bone marrow aspiration and biopsy showed hemopoiesis with viral inclusion bodies and hemophagocytosis (HLH) [Figs 1 and 2]. A diagnosis of secondary HLH related to CMV was contemplated and IV ganciclovir was initiated along with steroids. Histological evidence of CMV co-infection was present and moreover, the quantitative viral load of CMV showed a decreasing trend after initiating IV gancyclovir. However, the patient continued to deteriorate and succumbed to his illness in the 8th week of the ICU stay. Case 2: Herpes Simplex Virus (HSV) Co-infection: Twenty-three years postpartum female with no comorbidities and uneventful obstetric history was referred to our hospital two weeks after a full-term normal vaginal delivery. She developed generalized status epilepticus on the 10th day of delivery, which was managed with anti-epileptic drugs (AEDs). During the hospital stay, RTPCR for COVID-19 turned out to be positive but she remained asymptomatic and seizures were well-controlled on AEDs. On admission to our hospital, she was fully conscious and alert with no neurological deficits. Notable findings were pancytopenia with megaloblastic features, B/L pedal edema, and hepatosplenomegaly. NCCT brain revealed mild subarachnoid hemorrhage (SAH) along the bilateral parietooccipital region for which conservative management was planned. 2D echocardiography was normal. Ultrasonography of the abdomen showed gross splenomegaly and mild hepatomegaly with mesenteric lymphadenopathy. NCCT thorax and abdomen were unremarkable apart from hepatosplenomegaly. In pancytopenia workup, IgM anti-HSV-1 antibodies turned out to be positive in blood. In addition, tropical workup was suggestive of Leptospirosis (IgM antibodies positive). Serological evidence was suggestive of acute HSV-1 infection (based on antibody titers). Bone marrow workup had features of trilineage hematopoiesis with micronormoblastic maturation consistent with iron deficiency anemia without any evidence of hemophagocytosis. IV acyclovir, IV doxycycline, and iron replacement were added, after which she improved clinically and was discharged in stable condition. Tables 1 and 2 show a detailed description of these cases. Discussion: Herpesviridae family is the most important group of viruses responsible for persistent vi al infections in humans, of which CMV contributes to 60-90% of infections in adults, especially in developing countries.2 In healthy individuals, these viruses are kept dormant by the body's immune mechanisms but in an immunocompromised population, reactivation from the latent state can occur. SARS-CoV-2 infection predisposes patients to concomitant viral co-infections, owing to T-cell lymphopenia, decreased NK cell number, and use of immunosuppressive medications.3,4 The first case of CMV co-infection was first reported by D'Ardes and co-workers in 2020.5 Since then, many studies have been emerging in this area. In an observational study from France, 38 COVID-19 patients on >7 days of MV were studied for HSV and CMV pulmonary co-infections (by quantitative real-time PCR in tracheal samples) out of which 47% of patients had one of these infections (24% HSV, 5% CMV, 18% both).6 Another study looking for HSV-1 in patients on invasive MV found HSV-1 reactivation between days 11 and 40, which correlated with immunological markers of decreased innate immunity.7 A case series looking for CMV infection (by PCR in plasma or BAL) in COVID-19, also found CMV reactivation between day 7 and 45 of illness. Most of these patients were above 60 years of age and immunosuppressed (HIV, diabetes mellitus, medications).8 Although immunocompromised individuals are more vulnerable, healthy immunocompetent adults who are critically ill or on prolonged MV may also be susceptible to these infections.9-12 This may be explained by a state of immunoparalysis inherent to prolonged critical illness. In case 1, an ICU stay of around 9 weeks complicated with recurrent nosocomial infections, multiple blood product transfusions, and steroid usage could have the likely triggers. Whether viral co-infections are merely bystanders or truly pathogenic is difficult to comment but timely management is essential to avoid end-organ damage (EOD) which may occur directly (by enhanced viral load secondary to compromised host immunity) or indirectly (by inflammatory changes consequent to prolonged cell-mediated immunity required to maintain viral dormancy).2-4,13 It also seems imperative to study if a viral co-infection has a proclivity to develop more severe hematological anomalies (besides the inherent risk of HLH with COVID) as was seen in case 1, in which the patient had a downward spiral of illness with multiorgan dysfunction.14-15 Limitations: Dynamics of PCR trends and virology studies of samples from trachea, gut, and urine could not be analysed in our patients. Conclusion: Viral co-infections can occur in COVID-19 disease as these patients are often immunocompromised and critically ill. A high index of suspicion and prompt management is needed to improve the outcome of patients. Patients with organ dysfunctions especially hematologic abnormalities with bone marrow involvement should be worked up in detail to look for concomitant viral co-infections. In the future, large-scale research is needed to better elucidate the relationship between SARS-CoV-2 and other viral co-infections.

Status epilepticus due to COVID-19;a cases series and literature review

Complications are increasingly recognized with SARS-CoV-2, the causative pathogen for COVID-19. Various mechanisms have been proposed to justify the cause of seizures in Covid-19 patients. To our knowledge, 13 cases of status epilepticus (SE) associated with COVID-19 have been reported so far. Here, we present a single-center case series, including the clinical, laboratory, and imaging characteristics, and the EEG and the outcome of SE in 5 Iranian patients with laboratory-confirmed SARS-CoV-2 virus. SE was para-infectious in four patients and post-infectious in one other patient. In Three patients, the causes of seizure were included severe hyponatremia, acute ischemic stroke, and meningoencephalitis. However, in two other patients, no specific reason for seizure was found, but there are possibilities for lesser-known mechanisms of Covid-19 that play roles in developing SE. Two of the patients recovered, and three patients, older and with higher comorbidities, failed to recover and died.

Frequency of New Onset Seizures Amongst Adult Hospitalized Patients with COVID-19;A Systematic Review and Meta-Analysis

Objective: The objective of this study is to determine the frequency of seizures in adult hospitalized patients with COVID-19 without a prior history of epilepsy. Background: Infection with COVID-19 has been associated with neurological complications such as headache, dizziness, peripheral neuropathy, and acute vascular events. Acute onset seizures have been reported as a rare neurological complication in patients with COVID-19 infection. Design/Methods: PUBMED and EMBASE were searched from 12/01/2019 - 3/31/2021 in accordance with PRISMA guidelines, using the MESH terms ((Seizure) OR (Electroencephalography) OR (Status Epilepticus)) AND (COVID-19). The primary outcome was frequency of new onset seizure in hospitalized COVID-19 patients. Secondary outcomes were frequency of seizure in patients who had Electroencephalography (EEG) completed, risk of abnormal CerebroSpinal Fluid (CSF) results, and risk of abnormal imaging in patients with COVID-19. An inverse variance meta-analysis of single proportions was performed using the double arcsine method. A random effects model was used due to high inconsistency within the studies. Results: Ninety-four studies identifying 333 patients with COVID-19 and new onset seizures were included. Frequency of new onset seizures in adult hospitalized patients with COVID-19 was 0.71% ([95% confidential interval]: [0.16-1.65], I2=89%, 147/28242 patients). Frequency of seizures in hospitalized COVID-19 patients who had EEG completed was 8.49% ([95% confidential interval]: [0.62-24.07], I2=14%, 44/535 patients). The risk of abnormal imaging by either CT head, MRI or vessel imaging was 43.85% ([95% confidential interval]: [17.47-72.27%], I2=58%, 58/128 patients). The risk of abnormal CSF results was 43.03% ([95% confidential interval]: [4.28-88.35], I2=41%, 28/58 patients). Conclusions: The frequency of new onset seizures in patients with COVID-19 was 0.71% ([95% confidential interval]: [0.16-1.65], I2=89%, 147/28242 patients). Slightly less than half of COVID-19 patients with seizures had evidence of structural abnormalities on head imaging as a complication from infection. A small percentage of patients with COVID-19 and seizures were diagnosed with acute viral encephalitis.

Severe Multifocal Cortical Encephalopathy Following COVID-19 Vaccination: A Case Report

Objective: This clinical case history details a woman who received the COVID-19 vaccine BNT162b2 and developed an acute, severe encephalopathy associated with new onset seizures within days of her first vaccination. Background: BNT162b2, an mRNA-LNP-vaccine, has been strategically purified and modified to suppress immunogenicity. It still possesses powerful intrinsic immune-stimulatory features that induce type-I INF production, which has been associated with both inflammation and potentially autoimmunity in several mRNA-vaccine phase-I/II clinical trials (HIVNCT02413645, influenza-NCT03076385, rabies-NCT02241135 and Zika virus-NCT03014089). Design/Methods: A 69-year-old woman who received her first dose of BNT162b2 five days prior, was found unresponsive. Within twenty-four hours of arrival, she developed focal seizures with secondary generalized, and remained in non-convulsive status epilepticus on longterm EEG monitoring until day 5 of admission despite three anti-seizure medications and a propofol drip. Brain MRI on day 3 of admission showed gyriform-pattern diffusion restriction in the right hemisphere and left frontoparietal region without features suggestive of an acute vascular event. Vascular imaging was normal. Cerebrospinal fluid examination revealed an elevated protein level (135 mg/dl), with negative findings for infections from bacteria, fungi, mycobacteria, HIV, syphilis, and viruses, including COVID-19 PCR, as well as paraneoplastic and autoimmune encephalitis panels. Serum COVID-19 IgG antibody was negative on post-immunization day 8. Results: There was no significant improvement following empiric methylprednisolone and meningitis antibiotic/antiviral treatment. She was discharged in a deeply comatose status on day 30 of hospital admission. Repeat MRI brain on day 14 showed similar findings to her previous scan with the addition of Wallerian degeneration in the right cerebral peduncle. Conclusions: In a patient who develops an acute encephalopathy with new onset of seizure within days of BNT162b2 vaccine, do consider mRNA-vaccine related encephalopathy in the differential diagnosis.

Meta-analysis of175 Patients with COVID-19 and Seizures, Status Epilepticus, or Cortical Myoclonus: An Individual Patient Data Analysis

Objective: To characterize management and outcomes of seizures, status epilepticus, and cortical myoclonus in COVID-19, with individual patient data analysis of published literature. Background: Seizure disorders in COVID-19 have been sparingly reported. Lack of large-scale studies create challenges in identifying clinically relevant associated factors. Design/Methods: Systematic literature review was conducted in accordance with PRISMA guidelines. Criteria included new-onset seizures, status epilepticus, and/or cortical myoclonus developing prior to or during hospitalization, with concomitant COVID-19. COVID-19 severity was dichotomized into mild and severe cases, based on severity of respiratory symptoms. Good outcome was defined as discharge without severe deficits, and/or return to near baseline. Results: A total of 105 studies reporting 175 patients (male 56.6%;mean age 47.9, SD 25.7) were included. Status epilepticus occurred in 44 patients (25.1%) and myoclonus in 38 (21.7%). Any seizure-like activity on electroencephalography (EEG) was noted in 53/102 patients (52.0%). Abnormal cerebrospinal fluid analysis was reported in 32/83 patients (38.6%). Most common underlying diagnosis was encephalitis (autoimmune or infectious) in 42/175 patients (24.0%), followed by infarct (15/175;8.6%) and intracerebral hemorrhage (ICH) (13/175;7.4%). The most common treatment was levetiracetam (92/130;70.8%). Overall, 106/160 patients (66.3%) had good outcomes while 24/156 died (15.4%). Encephalitis was associated with good outcomes (p=0.005). Severe COVID-19 was associated with more myoclonus, poor outcome, and mortality (all p<0.001), with a trend towards more EEG abnormalities (p=0.066). In multivariate regression, only severe COVID-19 was associated with reduced odds of good outcome (OR=0.095;p=0.006), and higher odds of mortality (OR=4.60, p=0.040). Conclusions: Encephalitis, infarct, and ICH are common underlying etiologies in COVID-19 patients with seizure disorders. Overall, most patients achieved good outcome, thus highlighting the necessity of aggressively treating seizures, and identifying any treatable underlying etiology. Future research should investigate long-term neurocognitive outcomes in COVID-19 patients with seizure disorders.

Hemiconvulsion-Hemiplegia-Epilepsy Syndrome in the Setting of COVID-19 Infection and Multisystem Inflammatory Syndrome in Children

Objective: To present a case of Hemiconvulsion-Hemplegia-Epilepsy (HHE) Syndrome in a child with COVID-19 infection and Multisystem Inflammatory Syndrome in Children (MIS-C). Background: HHE Syndrome is a rare pediatric epilepsy syndrome that presents with prolonged unilateral convulsive status epilepticus in the setting of fever, followed by hemiparesis, unilateral hemispheric swelling and atrophy, and the development of epilepsy. Though it was first described over six decades ago, the pathophysiology is still poorly understood with multiple factors contributing, including hyperthermia, inflammation, and cytotoxic edema from prolonged ictal activity. Prognosis is variable, from the resolution of hemiplegia and seizures to permanent hemiparesis and refractory epilepsy. Design/Methods: This is a case report based on a chart review. Results: The patient is a 2-year-old boy with a history of one prior complex febrile seizure who presented with greater than one hour of convulsive status epilepticus in the setting of fever. The patient had a generalized tonic-clonic seizure with more prominent convulsions on the right side. The patient required intubation and was initially given multiple anti-seizure loads though continued to have persistent electrographic and electroclinical seizures. EEG showed lefthemispheric high amplitude spike/polyspike and wave discharges. The patient required continuous midazolam infusion with eventual control of seizures on levetiracetam, phenobarbital, and clobazam. The examination was notable for persistent right-sided hemiparesis with gradual improvement. MRI brain without contrast revealed T2 signal abnormality and restricted diffusion diffusely throughout the left cerebral hemisphere. Infectious workup was significant for positive COVID-19 PCR and elevated inflammatory markers, consistent with MIS-C. Conclusions: Our patient had prolonged focal convulsive status epilepticus in the setting of acute febrile illness secondary to COVID-19 and MIS-C leading to hemiparesis and diffuse left cerebral hemisphere edema on MRI brain consistent with HHE syndrome. More research is needed to elucidate further HHE syndrome's pathophysiology and assess long-term outcomes in patients with HHE syndrome.

Atypical Presentation of Lance Adams Syndrome in the setting of Clonazepam overdose and SARS-CoV-2 pneumonia

Objective: To report an atypical presentation of Lance-Adams Syndrome presenting from severe respiratory depression rather than cardiac arrest and to highlight the importance of distinguishing it from post hypoxic myoclonic variants. Background: Clinicians often face difficulty distinguishing Lance-Adams Syndrome (LAS) from Myoclonic Status Epilepticus (MSE). Similarities between the two conditions frequently result in confusion when diagnosing, managing and prognosticating for post-hypoxic myoclonus patients. Design/Methods: A 23-year-old male with a history pertinent for Hemophilia B, depression, opiate and alcohol abuse and chronic pain was found down in his home next to an empty bottle of clonazepam. He was hypoxic with oxygen saturation in the 40s and intubated in the field. Upon arrival to the Emergency room, neurological examination revealed intact corneal reflexes but no gag reflex, cough, or purposeful movements of the extremities. The patient exhibited stimulus induced myoclonic jerking which lasted >30 minutes despite being loaded on valproic acid and levetiracetam. Jerking subsequently ceased with propofol drip. Chest X-ray confirmed interstitial opacities and tested positive for SARS-CoV-2. On attempting to wean sedation, patient exhibited full-body myoclonus including face and palate with inability to follow commands and lack of spontaneous movements. As the EEG showed BIPEDS greater than 2.5 HZ, we decided to burst suppress him and treat with targeted temperature management. After 10 days, the patient was successfully weaned from sedation and extubated, but remained on multiple anti-seizure medications. Results: Patient responded well despite his diffuse cerebral anoxic injury. He regained the ability to follow commands upon discharge but had residual moderate expressive aphasia and post-hypoxic action-induced myoclonus, consistent with LAS. Conclusions: The atypical presentation of this case emphasizes the importance of distinguishing LAS from MSE to guide neurologists to aggressively treat LAS to improve outcome, particularly since MSE historically results with a 90-100% mortality rate.

New-Onset Refractory Status Epilepticus After Pfizer-BioNTech COVID-19 Vaccination

Objective: NA Background: Previous case reports have described 3 cases of autoimmune encephalitis and 1 case of new-onset refractory status epilepticus (NORSE) following COVID-19 viral vector vaccinations. However, no cases have been documented in association with COVID-19 mRNA vaccinations. We describe a case of NORSE after vaccination with Pfizer-BioNTech COVID-19 vaccine. Design/Methods: Case report. Results: A 56 year old healthy man presented with three days of fever, fatigue, and aphasia beginning 2 weeks after he received his first dose of the Pfizer-BioNTech COVID-19 vaccine. Video EEG showed temporally predominant seizures occurring independently bilaterally (right greater than left). Clinical seizures were characterized by head turn to the left and right hand movements. He then developed sustained right frontotemporal spike and slow wave activity consistent with non-convulsive status epilepticus. CSF demonstrated mild lymphocytic pleocytosis with WBC 16 cells/mm3, protein 24, glucose 76, and an opening pressure of 47. CSF bacterial and viral encephalitis panels, HSV, lyme, West Nile virus, and VDRL were all negative. Oligoclonal bands, paraneoplastic panel, and encephalopathy panel were negative. Systemic malignancy workup was negative. Initial MRI brain was unremarkable, but 1 week after symptom onset he developed bilateral hippocampal edema. The patient was empirically treated with broad spectrum antibiotics and antivirals which were later discontinued. Due to presumed diagnosis of autoimmune encephalitis, he was treated with high dose steroids, plasmapheresis, IVIG, and rituximab. He was treated with progressively escalating anti-seizure medications including midazolam, propofol, and ketamine continuous infusions and eventually stabilized on levetiracetam, lacosamide, phenobarbital, clobazam, zonisamide, oxcarbazepine, and perampanel. At the time of discharge, mental status had improved and aphasia resolved. Conclusions: To our knowledge, this is the first case of NORSE reported after Pfizer COVID-19 vaccination. While no test exists to definitively establish causality, these findings warrant further investigation of the possible association between COVID-19 vaccination and autoimmune encephalitis.

An Autoimmune Epilepsy Case Series: Atypical Presentations with Atypical Autoimmune Antibodies

Objective: We present three patients with insidious onset of high-frequency atypical seizures, in association with atypical autoantibodies, with significant improvement with immunotherapy. Background: Autoimmune epilepsy (AE) is a relatively newly discovered epilepsy etiology. Although, It was described to present as New-Onset Refractory Status Epilepticus (NORSE). Our understanding of the clinical presentations and autoantibodies linked to AE is still sparse. Design/Methods: Case Series Case 1: A 44-year-old man presented with more than 10 years of recurrent episodes of mild confusion. Patient presented to our ER during one of these episodes where EEG revealed right temporal lobe status epilepticus. He had suboptimal response to multiple Antiepileptic Drugs (AEDs). MRI brain showed T2/FLAIR hyperintensities in the right frontal, parietal, and temporal lobes consistent with postictal effect. CSF was positive Neuronal Intermediate Filament (NIF) heavy chain antibodies Treatment with plasmapheresis (PLEX) and intravenous immunoglobulin (IVIG) with a good response. Case 2: A 73-year-old woman presented with daily episodes of mild confusion and falls over few months. EEG was consistent with frontal lobe seizures. MRI brain and CSF were unremarkable. She was treated with multiple AEDs, without adequate control. Serum paraneoplastic panel was positive for voltage-gated potassium channel antibodies. Seizures were controlled with PLEX. Case 3: A 22-year-old woman presented with daily episodes of behavioral arrest and confusion few weeks after COVID-19 vaccination. EEG showed bitemporal seizures, refractory to AEDs, requiring pentobarbital induced coma. CSF and MRI brain were unremarkable. Thyroid peroxidase and anti-thyrotropin antibodies were highly elevated. Treatment with IVIG and PLEX for AE, with a prolonged recovery. Conclusions: Seizures associated with AE appear to be trivial;however, it can have an aggressive course. Among antibodies have been reported in AE, NIF antibodies has not been reported. AE should be considered in patients with High-frequency of atypical seizures. Early initiation of immunotherapy is the key for disease control.

Neurocysticercosis, Epilepsy, COVID-19 and a Novel Hypothesis: Cases Series and Systematic Review

Background: There have been many patients with neurological manifestations reported in medical literature following a COVID-19 infection. We conducted a literature review to identify patients with coronavirus disease (COVID-19) who presented with Neurocysticercosis (NCC) and associated seizure disorders/ epilepsy. Currently, there is a new variant of the COVID-19 virus strain invading South Africa and no indication when this pandemic will end and what kind of tardive sequelae may occur going forward. Case: We searched the medical literature looking for all publications regarding NCC, Status Epilepticus (SE), Epileptic Seizures (ES), and Epilepsy (Ep), in patients infected by COVID-19. Based on the therapeutic response of our series, we propose a novel approach for patients presenting NCC, epilepsy and associated with COVID-19. We have hypothesized on the pathogenesis of ES and SE from the NCC/Cytokine Release Syndrome (CRS), SARS-CoV-2/CRS, including the role played by gut microbiota from the enteric nervous system (gut hormones, gut metabolites, inflammatory factors, neuroactive substances, and microbiota-derived products) to the medulla oblongata/hypothalamus-pituitary-adrenal axis via microbiota gut brain axis in ES, Ep and associated depression, plus the mechanism of hyperferritinemia on the overall process. This article is the first publication approaching this comorbidity as far as we know.