Lymphoproliferation- a clue towards an underlying monogenic disorder of immune dysregulation- a retrospective analysis from a single center in India

Background: Lymphoproliferation is the persistent proliferation of lymphoid cells and it's incidence in inborn errors of immunity varies from 0.7 to 18%. Material(s) and Method(s): This is a retrospective analysis of patients referred to the department of Immunology, B. J. Wadia Hospital for Children, Mumbai between March 2017 to December 2022. Inclusion criteria consisted of 3 months duration of significant lymphadenopathy and/or splenomegaly or history of lymphoma. The clinical characteristics, laboratory and molecular findings of the included patients were analyzed. Result(s): A total of 66 patients were included. There was a male preponderance with male:female ratio of 25:8. Median age of onset of lymphoproliferation was 4.75 years(Range 1 year to 60 years). Splenomegaly was seen in 75%. Infections included recurrent pneumonia (14/66), recurrent ear infections(5/66), COVID(4/66), one episode of pneumonia(6/66), herpes zoster(3/66), recurrent subcutaneous abscess (3/66), abdominal koch(3/66), chronic sinusitis(2/66), dermatophytosis(2/66), esophageal candidiasis(2/66), recurrent malaria(1/66), recurrent varicella(1/66), cryptococcal meningitis(1/66), gram negative sepsis(1/66), BCG adenitis(1/66), pseudomonas osteomyelitis(1/66), impetigo (1/66), pseudomonas urinary tract infection (1/66), chicken pox(1/66), herpes keratitis(1/66), dengue(1/66), Other manifestations included Evans plus phenotype(10/66), Evans phenotype(8/66), Autoimmune hemolytic anemia(5/66), bronchiectasis(5/66), Type 1 diabetes(3/66), hyper reactive airway disease(2/66), inflammatory bowel disease(4/66), autoimmune thrombocytopenia(2/66), stroke(3/66), hemophagocytic lymphohistiocytosis(2/66), hypertriglyceridemia(2/66), hypothyroidism(2/66), celiac disease(1/66), Type 2 diabetes(1/66), autoimmune encephalitis(1/66), autoimmune hepatitis(2/66), anti-parietal cell antibody(1/66), arthritis(1/66), autoimmune enteropathy(1/66), systemic lupus erythromatosus(1/66), primary biliary cirrhosis requiring liver transplant(1/66), nephrotic syndrome(1/66), lymphoedema(1/66), hypersplenism(1/66), recurrent oral ulcers(1/66), gout(1/66), dermatitis(1/66), ovarian teratoma(1/66), alopecia areata(1/66). Hodgkin's lymphoma(HL) was the most common malignancy(9/66), followed by non Hodgkin lymphoma(NHL)(6/66), transformation from NHL to HL(1/66), Burkitt to T-cell lymphoma(1/66), HL to DLBCL(1/66), HL to anaplastic T-cell lymphoma(1/66). EBV driven lymphoproliferation was seen in biopsy of21/66. Genetic testing showed mutations in LRBA(11/66), PIK3CD(5/66), CTLA4(3/66), TET2(2/66), IL2RA (1/66), IL12RB1(1/66), BACH2(1/66), PRKCD(1/66), TNFSFR13B(1/66), TNFAIP3(1/66), FAS(2/66), FASL(1/66), Caspase8(1/66), CARD11(1/66), RTEL1(1/66), AICD(1/66), PIK3R1(1/66), IKBKB(1/66). Treatment included IVIG, chemotherapy, rituximab, sirolimus, abatacept, HSCT. Conclusion(s): All children with persistent lymphoproliferation, with or without autoimmunity and/or infections should be worked up for an underlying monogenic disorder of immune dysregulation. Lymphomas presenting at abnormal site and/or age, relapse and EBV driven lymphomas require further evaluation. Presence of monogenic cause helps in providing targeted therapy.Copyright © 2023 Elsevier Inc.

Seronegative acute encephalitis following COVID-19 vaccines: a case series of an overlooked diagnosis with literature review.

PURPOSE: Autoimmune encephalitis is a neurological emergency of new-onset altered mental status, caused by an exaggerated immune-mediated response that targets the central nervous system. Autoimmune encephalitis has become an emerging differential diagnosis, when a classical infection cannot explain neurological symptoms. Displaying overlapping clinical presentations, ranging from the insidious onset of cognitive deficiency to more severe forms of encephalopathy with refractory seizures, autoimmune encephalitis can be challenging for clinicians. When evidence of malignancy is absent and pathogenic autoantibodies are undetected, with typical clinical and imaging features of autoimmune encephalitis, seronegative autoimmune encephalitis may be considered. Recently, vaccination-related autoimmune encephalitis and acute encephalitis after COVID-19 vaccination have attracted attention. METHODS AND RESULTS: We report a case series consisting of three patients with autoimmune encephalitis occurring shortly after COVID-19 vaccination and a current review of all previous reported autoimmune encephalitis related to COVID-19 vaccines. CONCLUSION: We emphasise on the prompt diagnosis of autoimmune encephalitis induced by Covid-19 vaccines and its timely treatment to improve the clinical outcome of this severe neurological condition. Post-licencing vaccine safety surveillance for potential adverse events is essential for vaccine safety and public confidence.

Early autoimmunity and outcome in virus encephalitis: a retrospective study based on tissue-based assay.

To explore the autoimmune response and outcome in the central nervous system (CNS) at the onset of viral infection and correlation between autoantibodies and viruses. METHODS: A retrospective observational study was conducted in 121 patients (2016-2021) with a CNS viral infection confirmed via cerebrospinal fluid (CSF) next-generation sequencing (cohort A). Their clinical information was analysed and CSF samples were screened for autoantibodies against monkey cerebellum by tissue-based assay. In situ hybridisation was used to detect Epstein-Barr virus (EBV) in brain tissue of 8 patients with glial fibrillar acidic protein (GFAP)-IgG and nasopharyngeal carcinoma tissue of 2 patients with GFAP-IgG as control (cohort B). RESULTS: Among cohort A (male:female=79:42; median age: 42 (14-78) years old), 61 (50.4%) participants had detectable autoantibodies in CSF. Compared with other viruses, EBV increased the odds of having GFAP-IgG (OR 18.22, 95% CI 6.54 to 50.77, p<0.001). In cohort B, EBV was found in the brain tissue from two of eight (25.0%) patients with GFAP-IgG. Autoantibody-positive patients had a higher CSF protein level (median: 1126.00 (281.00-5352.00) vs 700.00 (76.70-2899.00), p<0.001), lower CSF chloride level (mean: 119.80±6.24 vs 122.84±5.26, p=0.005), lower ratios of CSF-glucose/serum-glucose (median: 0.50[0.13-0.94] vs 0.60[0.26-1.23], p=0.003), more meningitis (26/61 (42.6%) vs 12/60 (20.0%), p=0.007) and higher follow-up modified Rankin Scale scores (1 (0-6) vs 0 (0-3), p=0.037) compared with antibody-negative patients. A Kaplan-Meier analysis revealed that autoantibody-positive patients experienced significantly worse outcomes (p=0.031). CONCLUSIONS: Autoimmune responses are found at the onset of viral encephalitis. EBV in the CNS increases the risk for autoimmunity to GFAP.

Encephalopathy in a Young Female With COVID-19: A Case Report.

Cases of severe central nervous system (CNS) complications have been reported in relation to coronavirus-19 (COVID-19). Cases of encephalitis have been reported primarily in older patients with multiple comorbidities. We present a case of encephalitis in a young female patient with a history of chronic marijuana use that presented with nausea, vomiting, and acute altered mental status. Extensive testing for infectious and autoimmune causes of encephalitis were negative, except for a positive COVID-19 test. She was treated with steroids and intravenous immune globulin (IVIG) and improved with residual mutism.

Autoantibody-negative but probable pediatric autoimmune encephalitis following COVID-19 vaccination: A case report

Background: Large-scale vaccination against the novel coronavirus (COVID-19) occurred globally at an unprecedented pace. Sporadic cases of autoimmune encephalitis (AE) have been reported following COVID-19 vaccination, mainly in adults. Case report: A 14-year-old girl developed altered mental status and was brought to our emergency department because of a seizure 19 days after receiving the third dose of COVID-19 vaccination. She was treated with steroid pulse therapy and fully recovered. The diagnosis of probable autoantibody-negative AE was finally made. Conclusion(s): This case met the criteria for probable autoantibody-negative AE in children, as well as adults. Because of the temporal association and absence of another identifiable cause, her conditions may have been triggered by the COVID-19 vaccination. To our knowledge, this is the first published pediatric case of autoantibody-negative but probable AE following COVID-19 vaccination.Copyright © 2023 The Authors

Possible autoimmune pediatric encephalitis following COVID-19 infection with focal cerebral dysfunction in a young female: A case report

Introduction: Post-COVID-19 autoimmune encephalitis is a rare manifestation following COVID-19. Most cases have not demonstrated solid evidence regarding their pathogenesis. Some believe it to be an immune process. Case presentation: In this case report, we present a case of a young female who presented to our emergency department with visual, auditory, and olfactory hallucinations after successfully treating COVID-19 two weeks prior to this visit. On examination, her vital signs were stable, but she was agitated, distressed, and hallucinating. Neurological examinations were normal. Laboratory investigations, including autoimmune profiles, were all negative. Magnetic resonance imaging of the brain showed non-specific changes in the bilateral frontal area. Electroencephalography (EEG) showed lateralized rhythmic delta activity (LRDA) arising more from the right occipital lobes. Autoimmune psychosis was suspected due to psychosis, abnormal imaging, and abnormal EEG findings. She was given corticosteroids and antipsychotic medication. Her symptoms improved within ten days. On follow-up, she remained well without any return of psychosis. Conclusion(s): Possible autoimmune pediatric encephalitis following COVID-19 is a rare entity that has scarcely been reported. The majority of the cases were reported to have been related to stress following the infection. To establish the correct diagnosis, an extensive workup, including an autoimmune profile, lumbar puncture, magnetic resonance imaging, and electroencephalography, is recommended.Copyright © 2022 The Author(s)

Translocator protein (TSPO)-PET as diagnostic and monitoring tool in COVID-19 related MRI-negative brainstem encephalitis: a case report.

BACKGROUND: Encephalitis and myelitis have been linked to both COVID-19 vaccination and infection, causing symptoms such as reduced consciousness, mental state alterations and seizures. Remarkably, most cases do not show significant structural alterations on MRI scans, which poses a diagnostic challenge. METHODS: We present the diagnostic workup and clinical course of a patient who developed a progressive brainstem syndrome two weeks after COVID-19 vaccination and subsequent infection. We used translocator protein (TSPO)-PET scans for the first time to investigate COVID-related neuroinflammation. RESULTS: The patient developed oculomotor disorder, dysarthria, paresthesia in all distal limbs and spastic-atactic gait. CSF analysis revealed mild lymphocytic pleocytosis with normal protein levels. Brain and spinal cord MRI scans were negative, but TSPO/PET scans showed increased microglia activity in the brainstem, which correlated with the clinical course. Steroid treatment led to clinical improvement, but relapse occurred during prednisone taper after four weeks. Plasmapheresis had no significant effect; however, complete remission was achieved with cyclophosphamide and methotrexate, with normal TSPO signal ten months after onset. CONCLUSIONS: TSPO-PET can be a valuable tool in the diagnostic and therapeutic monitoring of COVID-19-related encephalitis, particularly in cases where MRI scans are negative. Aggressive immunosuppressive therapy can lead to sustained remission.

COVID-19-associated AMPA-R and CRMP-5 autoimmune encephalitis in a patient with thymoma and myasthenia gravis.

Thymomas are associated with autoimmune disease, most commonly myasthenia gravis, and rarely with autoimmune encephalitis. More recently, viral triggers including COVID-19 have also been implicated in autoimmunity. We present a case of antibody-positive autoimmune encephalitis that developed in the setting of COVID-19 in a patient with thymomatous myasthenia gravis.

Autoimmune Encephalitis Due to COVID-19 in a Young Patient.

Autoimmune encephalitis is an inflammatory condition caused by different factors, including viral infections, diagnosed after ruling out other causes of encephalitis. The current study reported novel autoimmune encephalitis in an 11-year-old girl who presented with seizures, cognitive dysfunction, and neurological impairments. During the admission, the researchers observed high levels of anti-N-methyl-D-aspartate receptor (NMDAR) antibodies in the cerebrospinal fluid (CSF). Besides, she had positive anti-COVID-19IgG. Therefore, the diagnosis of COVID-19-induced autoimmune encephalitis was specific. The patient received anti-epileptic, anti-viral drugs, IVIG, and rituximab and was discharged with remission. The case diagnosis was made by anti-NMDAR antibodies, which highlights the importance of this diagnostic tool. Similar cases have been reported earlier, but the point of this case was her younger age compared to the previous cases and her developing neurological deficit before COVID-19 presentations.

Prevalence of iatrogenic CNS inflammation at a tertiary neuroimmunology clinic.

BACKGROUND: Various vaccines, tumor-necrosis-factor-alpha inhibitors (TNFAIs), immune-checkpoint inhibitors (ICIs), and other immunomodulators have been linked to inflammatory CNS events. The prevalence of iatrogenic events in the neuroimmunology clinic is unknown. OBJECTIVE: To evaluate the prevalence and clinical characteristics of iatrogenic CNS inflammation in a tertiary neuroimmunology clinic. METHODS: We analyzed 422 consecutive patients seen over five years at a tertiary neuroimmunology clinic who were systematically screened for exposure to vaccines, TNFAIs, ICIs, or other immunomodulators. In patients with suspected iatrogenic events, the Naranjo Adverse Drug Reaction Probability Scale was used to score the probability of iatrogenicity. RESULTS: In total, 27 potential iatrogenic events were observed, accounting for 6.4% of all new referrals. The average Naranjo score was 5.78 +/- 1.65 with 74% of the cases scored as probable and 26% scored as possible. The clinical phenotypes included MS relapses (37%); autoimmune encephalitis (30%); NMOSD attacks (15%); transverse myelitis (11%); optic neuritis (4%); and MOGAD attacks (4%). A monophasic course was observed in 44% of cases while 41% had a relapsing course. All patients stopped or interrupted treatment with the offending agent. In addition, 41% of the iatrogenic events were fully responsive to corticosteroids; 22% were partially responsive; and 15% resolved spontaneously. The most common potential triggers were vaccines (37%) followed by TNFAIs (33%) then ICIs (26%). A significantly higher number of probable iatrogenic events were observed among the ICI and vaccine groups compared to a higher number of possible events among the TNFAI group. The latter group also had a significantly longer interval since exposure. The ICI group was more likely to present with monophasic autoimmune encephalitis. CONCLUSION: Iatrogenic CNS inflammation is rare and typically involves steroid-responsive monophasic events. A subset of iatrogenic events can unmask or worsen relapsing disorders. The probability of iatrogenicity was higher in vaccine and ICI-related events compared to TNFAI-related events.

Safety of inactivated COVID-19 vaccines in autoimmune encephalitis: A real-world cross-sectional survey.

OBJECTIVE: To assess safety data of the inactivated COVID-19 vaccines in a real-world sample of people with autoimmune encephalitis (pwAE). METHODS: A cross-sectional study was performed between 1 March and 30 April 2022. We invited pwAE from our previous ONE-WC (Outcome of Autoimmune Encephalitis Study in Western China) registration study database, to attend neurological clinics, at West China Hospital to participate in a face-to-face survey using a custom-designed questionnaire for this study. The ONE-WC study began in October 2011 and prospectively enrolled pwAE from four large comprehensive neurological centers in Sichuan province, China. RESULTS: Of the 387 pwAE, 240 (62.0%) completed the questionnaire. Half the 240 participants (121, 50.4%) reported receiving at least one dose of COVID-19 vaccine, which in all but two patients received inactivated COVID-19 vaccine. Among vaccinated pwAE, the median age was 35 years (range 15-69) and 57.8% of them were women. The most frequent reasons that unvaccinated individuals reported for not receiving the COVID-19 vaccine were concern about vaccine-induced relapse of AE (50.4%) and advice from a physician to delay vaccination (21.0%). Small proportions of vaccinated individuals reported adverse events after the first dose (11.5%) or the second dose (10.2%), and none of the adverse events was serious. Across the entire sample, one individual reported relapsing within 30 days after the first dose and three individuals reported relapsing more than 120 days after the first dose. CONCLUSIONS: This real-world survey indicates an overall favorable safety profile of the inactivated COVID-19 vaccine for pwAE.

A Sharp Rise in Autoimmune Encephalitis in the COVID-19 Era: A Case Series.

BACKGROUND: Autoimmune encephalitis was very rare prior to the current pandemic. A sharp rise in cases has been observed from March to August of 2022 in Los Angeles. Such an increase, especially with certain types of antibodies, may point toward the possibility of post-infectious autoimmune encephalitis. While review articles on autoimmune encephalitis during this pandemic have been published, a sharp rise in one geographic area within a short period of time has not been documented yet. AIMS: To report an alarming increase in autoimmune encephalitis with mostly positive glutamic acid decarboxylase (GAD) and/or voltage-gated potassium channel (VGKC) antibodies over six months during 2022 in Downtown Los Angeles. MATERIAL AND METHODS: This is an observational case series from one neurocritical care practice in Downtown Los Angeles. Autoimmune encephalitis antibody panels were sent to patients with altered mental status or neurologic deficits of unclear etiology from March to August of 2022. RESULTS: Of the 29 patients tested, 12 reports came back positive. Ten had positive GAD and/or VGKC antibodies, one had a positive myelin oligodendrocyte glycoprotein antibody, and one had a positive leucine-rich glioma-inactivated 1 protein antibody; a 41% positive rate. CONCLUSIONS: This observation has important implications: (1) We may be entering an era of heightened autoimmune encephalitis. (2) These occurrences may be post-infectious in nature at this point of the pandemic. (3) Mostly GAD and VGKC antibodies have been identified (10 of them), which may point toward a new direction of research from a molecular mimicry standpoint. (4) To benefit patients, clinicians need to be aware of such disease manifestations and increase testing; resources must be increased to improve test availability and shorten turnaround time; and treatment, which is expansive, must be made widely available for these potentially reversible diseases.

Encephalitis lethargica. What is still wrong?

Encephalitis lethargica developed in epidemic from 1919 to 1926 in Europe and throughout the world. From the clinical point of view, the disturbances of consciousness and alertness and the possible outcomes of a postencephalitic Parkinsonism has attracted much attention. For a long time, it was thought that such a disease may still occur sporadically. In this review, the authors examined historical and current pictures of epidemics that may be related to Encephalitis lethargica. The previous Nona and Russian Influenza exhibited frequent neurological symptoms. The Spanish flu, formerly related to Encephalitis lethargica, would appear an epidemic that had its development in a partially overlapping period. The current pandemic linked to COVID-19 sometimes has aspects that can resemble Encephalitis lethargica. Based on historical analysis and the more recent immunological data, it could be suggested that Encephalitis lethargica was an autoimmune encephalitis that arose in a secondary form to the action of a viral agent. It cannot be ruled out that this agent was a coronavirus. From the nosological point of view, the term Encephalitis lethargica should be abolished in designating autoimmune encephalitis pictures that run sporadically.

Clinical and Paraclinical Features of Non-Paraneoplastic NIF-Mediated Disease Associated With Concurrent SARSCoV- 2 Infection

Objective To describe clinical and paraclinical features of non-paraneoplastic NIFmediated disease associated with concurrent SARS-CoV-2 infection. Background Neurologic syndromes associated with neuronal intermediate filament (NIF) immunoglobulin G (IgG) most often are characterized by encephalopathy, cerebellar ataxia, or myelopathy. NIF-IgG has been strongly correlated with the presence of an underlying malignancy, with neuroendocrine tumors being most prevalent. Despite the intracellular target of this antibody, patients with NIF-IgG mediated disease tend to improve clinically with immunotherapy. While some cases have been described in a parainfectious context, this is the first such case in the context of a SARS-CoV-2 infection. Design/Methods NA. Results We reported a case of non-paraneoplastic NIF-mediated disease in the setting of SARS-CoV-2 infection. The patient presented with first time seizure. He was found to have frequent left temporal lobe spikes then two left temporal lobe seizures on neurotelemetry. Brain MRI displayed abnormal signal throughout the left hippocampus and mesial temporal lobe, without contrast enhancement. LP was subsequently performed. CSF showed elevated protein, 14-3-3, T-tau, interleukin 13, interleukin 2 receptor, and interleukin 6. The meningitis/encephalitis panel, and HSV-1/2 IgG were negative. Serum autoimmune encephalitis panel revealed a high-positive titer for anti-NIF 1:960, with concurrent NIF heavy chain cell-based assay positive. He improved with three days of IV steroids and treatment with levetiracetam and lacosamide. He has since been seizure free. Conclusions NIF-mediated diseases usually present with encephalopathy, cerebellar ataxia, or myelopathy and are generally seen in the setting of malignancy. Our case illustrated an example of NIF-mediated disease presenting as seizure in the setting of infection. This highlights the importance of consideration of parainfectious autoimmunity.

Clinical Improvement Following Delayed Initiation of Immunotherapy in a Case of LGI1 Antibody Encephalitis Presenting with Faciobrachial Dystonic Seizures Following COVID-19 Vaccination

Objective To demonstrate a case of suspected post-vaccine autoimmune encephalitis associated with leucine-rich glioma-inactivated protein (LGI1) antibodies with significant clinical improvement after initiation of immunotherapy nearly a year after symptom onset. Background Although the autoimmune encephalitides have overlap in presentation, some have unique manifestations (such as orofacial dyskinesias seen with NMDA encephalitis). These unique associations can serve as a clinical marker of response to treatment and even allow for earlier initiation of immunotherapy while awaiting results from antibody testing. LGI1 encephalitis characteristically presents with faciobrachial dystonic seizures (FBDS) that are refractory to anti-seizure medications (ASMs) but responsive to immunotherapy. Design/Methods Case report Results A previously healthy and highly independent 89-year-old woman developed what she described as abnormal posturing and spasms of the right shoulder two to three weeks after receiving the J&J COVID-19 vaccine. The abnormal movements progressed to involve the right side of her face and were refractory to multiple ASMs. EEG captured multiple events without epileptiform correlate. Several months later she developed paranoia, delusions, and hallucinations. Autoimmune encephalopathy panel returned positive for the LGI1-antibody around nine months after the onset of FBDS. Upon our initial exam, she had a fluctuating level of arousal, impaired recall of recent events, and was tangential in conversation. There were frequent, brief, repetitive, dystonic movements of the right side of the face consistent with FBDS. Admission was arranged for immunotherapy (intravenous methylprednisolone and intravenous immunoglobulin). Upon follow-up four weeks later, there was significant improvement in arousal and concentration with resolution of FBDS and delusions. Conclusions This case highlights a classic case of LGI1 encephalitis after vaccination presenting with FBDS and progressive cognitive changes. Despite immunotherapy being delayed, there was marked clinical improvement. It is important to recognize this entity and that it typically has a favorable outcome.

An Observational Study on the Humoral and Cellular Immune Response to SARS-CoV-2 mRNA Vaccination in Multiple Sclerosis and Other Autoimmune Neurological Disorders Treated With Anti-CD20 Therapies

Objective To assess adaptive immunity to SARS-CoV-2 in anti-CD20 treated individuals with mRNA vaccination. Background Anti-CD20 therapies attenuate humoral responses to vaccines. However, their effect on T cell responses is less clear. We examined B and T cell responses following COVID-19 vaccination in patients receiving anti-CD20 therapy for multiple sclerosis (MS) and other autoimmune inflammatory neurologic diseases (AINDs, e.g., autoimmune encephalitis, stiff person syndrome, etc.). Design/Methods MS and AIND patients on anti-CD20 therapies were prospectively enrolled for longitudinal analysis of antibody and T cell responses after a 3rd COVID-19 vaccination. Serum antibodies against the receptorbinding domain of the S1 spike protein (RBD-S1 IgG), neutralizing antibodies, and SARS-CoV-2 CD8 T cell responses, using activationinduced markers (AIM) and INF-gamma release assays (EUROIMMUN, Germany), were measured at various time points including prevaccination, post initial vaccination series, and 4 and 12 weeks after 3rd dose. Results Thirty-four MS and AIND participants are enrolled. Results for these patients (mean age 52 years-old, 79% female, 21 Pfizer, 13 Moderna) demonstrated attenuated RBD IgG antibody responses. However, a robust CD8 T cell response was observed, following a two-dose series, compared to non-immunosuppressed, age-matched vaccinated controls or unvaccinated with severe SARS-CoV-2 infection (p = 0.01). T cell response was sustained long-term (>12 weeks post 3rd dose) in all 11 anti-CD20 patients analyzed thus far. Collections are completed for all participants at 12 weeks and analysis to be completed by 05/15/22. Further analysis includes correlation of the INF- gamma release assay compared to RBD-CD8 T cell response detected by AIM assay. Conclusions Results suggest that patients treated with anti-CD20 therapy generate a robust CD8 T cell response to SARS-CoV-2 mRNA after three doses but remain with attenuated humoral immune responses. Our observational study will provide important data to guide vaccine management in patients on or anticipating anti-CD20 therapy.

Transcortical sensory aphasia heralding SARS-Cov-2-induced autoimmune encephalitis with gyral restricted diffusion hyperintensities: a novel case report.

Background: Coronavirus disease 2019 (CoVID-19), primarily thought of as a respiratory system disease is actually a multi-system disease with immunological implications. CNS involvement in COVID has been explained in recent literature mainly for stroke, encephalopathy, encephalitis, acute disseminated encephalomyelitis and myelopathy. There are few studies characterizing clinical spectrum of COVID autoimmune encephalitis. We present a unique case of post-COVID autoimmune encephalitis in a diabetic male presenting with language dysfunction and novel radiologic findings. Case presentation: Patient admitted to inpatient department of a tertiary care hospital of India was evaluated by bedside clinical examination, routine blood tests, CSF study with intrathecal SARS-Cov-2 antibody detection, commercially available tests for autoimmune encephalitis, neuroviral panel with HSV PCR, EEG, 3-Tesla MRI and PET scan. Patient was found to have personality change and transcortical sensory aphasia in the outset of COVID encephalitis. MRI findings like temporal involvement and insular ribboning are also being reported. The patient was treated with IV immunoglobulin and is on an improving course. Conclusions: This case reports dysphasia due to COVID-mediated injury to the language networks, with novel radiologic findings. Role of parainfectious versus immune etiology is also discussed. Further studies are needed to elucidate the mechanism and clinical spectrum of post-COVID autoimmune encephalitis.

TH-207. A particular case of Sturge weber syndrome revealed in adulthood, implications of the COVID-19 era

Sturge weber syndrome (SWS) is a rare angiomatosis described in the pediatric population. There are only few cases with a late revelation in adulthood. We report a particular adult case of SWS revealed after a second dose of mRNA-COVID-19 vaccination. A 61-year-old man with cardiovascular factors presented with a set of escalating neurological symptoms (blurred vision, hemiparesis, headaches, CBH, convulsions, movement disorders) a month after he received his second dose of the Pfizer-BioNTech COVID-19 vaccine. Susceptibility weighted imaging on brain MRI showed enlarged transmedullary veins in the right parieto-occipital lobes as well as contrast enhancement of the same localization after gadolinium injection compatible with the diagnosis of cerebral angiomatosis. Lumbar puncture revealed a slight elevation of protein. Multiple EEGs and a video-monitoring EEG showed alternate, predominantly right hemisphere seizures not always accompanied by clinical manifestations. The evolution was marked by refractory seizures to anti-epileptic drugs and movement disorders only stabilized after 10 g of methylprednisolone. A complete panel of investigations was done to look for autoimmune or infectious encephalitis, metabolic encephalopathy, and systemic malignancy but all were negative. Clinical presentation of SWS includes a wide range of neurological symptoms (stroke-like episodes, migraine, blurred vision, seizures, etc.). Our patient had many of these symptoms and is classified as a type III SWS on the Roach Scale. However, the presence of movement disorders in this condition is not reported. The worsening of the patient under anti-epileptic medication was another red flag to the diagnosis of isolated SWS. Since the patient's recovery was only obtained after immunosuppressive therapy and no biological evidence of any other etiology of encephalopathy was found, the hypothesis of an autoimmune encephalitis on a fragile brain triggered by COVID-19 vaccination was the most probable explanation to this presentation. Throughout this case, we wanted to report another case of late-onset SWS meanwhile highlight the importance of further exploration of the possible connection between COVID-19 vaccination and autoimmune encephalitis. Copyright © 2022

"Delirium and COVID-19": From Symptomatology to Laboratorial and Neuroimaging Findings'

Introduction: The infection caused by the SARS-CoV-2 virus called COVID-19 may affect not only the respiratory system but also the central nervous system (CNS). Delirium is a frequent and serious condition in COVID-19 patients and may be caused by the direct invasion of the CNS or the induction of CNS inflammatory mediators or by indirect effects due to the systemic inflammatory status, other organ failure, prolonged mechanical ventilation time, immobilization but also social isolation. We aim to critically review literature reporting this syndrome in patients infected by the SARSCoV-2 virus with a particular emphasis on reported clinical, laboratorial and neuroimaging findings. Method(s): A state-of-the-art literature review was performed using PubMed, Embase and Web of Knowledge using the following keywords: delirium, COVID-19, SARS-Cov-2, neuroimaging, laboratorial findings. Result(s): More than 50% of patients with COVID-19 may present with delirium and in about 20% of the cases this is the primary presentation of the disorder. Previous data suggests that these patients may show a higher frequency of certain symptoms such as agitation, myoclonus, abulia, and alogia. Some distinct neuroinflammatory syndromes have been identified in patients presenting with delirium associated with the virus, namely, autoimmune encephalitis, Acute Disseminated Encephalomyelitis (ADEM) and stroke showing its potential for CNS involvement. Many of these patients present normal brain imaging, EEG and CSF findings but others have more specific laboratorial changes such as elevated creatinine kinase, elevated D-dimer levels, abnormal coagulation parameters and positive SARS-Cov-2 PCR in CSF or meningeal enhancement, ischemic stroke and perfusion changes in MRI imaging.