Case Report of Succesful Multidisiplinary Treatment for Patient with Metastatic Lung Cancer and Relapsed/Refractory Chronic Lymphatic Leukemia/Small Lymphocytic Lymphoma

Introduction: Croatian National Cancer Registry of Croatian Institute for Public Health reported that in year 2020 lung cancer was the second most common cancer site diagnosed in men with 16% and the third most common in women with 10% incidence among all cancer sites. Unfortunatelly lung cancer has the highest mortality in both men and women. Haematological malignancies had 7% share in all malignancies in both male and female cances cases. In 2020 190 newly diagnosed cases of lymphatic leukemia in men and 128 cases in women were reporeted, meaning 1.5 and 1.2% of all malignancies, respectively. Chronic lymphatic leukemia (CLL) is an advanced age disease and incidence increases with age. Impaired immunity, T and B cell dysfunction in CLL, chromosomal aberations, long-term immunosuppressive therapy and genetic factors can all cause secondary malignancies. Co- occurence of solid tumors and CLL is very rare. Although patiens with CLL have an increased risk of developing second primary malignancies including lung carcinoma, the data about their clinical outcomes are lacking. Parekh et al. retrospectively analyzed patients with simultaneous CLL and lung carcinoma over a 20-year period, and they found that ~2% of patients with CLL actually developed lung carcinoma. The authors claimed that up to 38% of patients will also develop a third neoplasm more likely of the skin (melanoma and basal cell carcinoma), larynx (laryngeal carcinoma) or colon. Currently there are no specific guidelines for concurrent CLL and non-small cell lung carcinoma (NSCLC) treatment. Usually, when the tumors are diagnosed simultaneously, treatment is based to target the most aggressive malignancy, as the clinical outcomes depend on the response of the tumor with the poorest prognosis. For this reason, a multidisciplinary approach is mandatory. Case report: A patient with history of coronary heart disease, myocardial infarction and paroxysmal atrial fibrillation was diagnosed in 2019 (at the age of 71) with B chronic lymphocytic leukemia with bulky tumor (inguinal lymph nodes 8x5 cm), stage B according to Binet, intermediate risk. He was treated with 6 cycles of chemoimmunotherapy (rituximab/cyclofosfamid/fludarabine). In 10/2019 remission was confirmed, but MSCT described tumor in the posterior segment of upper right lung lobe measuring 20x17 mm and bilateral metastases up to 11 mm. Bronchoscopy and biopsy were performed, and EGFR neg, ALK neg, ROS 1 neg, PD-L1>50% adenocarcinoma was confirmed. He was referred to Clinical Hospital Center Osijek where monotherapy with pembrolizumab in a standard dose of 200 mg intravenously was started in 01/2020. Partial remission was confirmed in October 2020. Immunotherapy was discontinued due to development of pneumonitis, dysphagia and severe weight loss (20kg), but without radiologically confirmed disease progression. At that time he was referred to our hospital for further treatment. Gastroscopy has shown erosive gastritis with active duodenal ulcus, Forrest III. Supportive therapy and proton pump inhibitor were introduced. After complete regression of pneumonitis, improvement of general condition and resolution of dysphagia, no signs of lung cancer progression were found and pembrolizumab was reintroduced in 12/2021. Hypothyroidism was diagnosed in 01/2021 and levothyroxine replacement ther apy was started. In 03/2021 he underwent surgical removal of basal cell carcinoma of skin on the right temporal region with lobe reconstruction. From 02/2021, when pembrolizumab was reintroduced, regression in tumor size was continously confirmed with complete recovery of general condition. He was hospitalized for COVID 19 infection in 09/2021, and due to complications pembrolizumab was discontinued till 11/2021. Lung cancer immunotherapy proceeded till 11/2022, when Multidisciplinary team decided to finish pembrolizumab because of CLL relapse. CLL was in remission till August 2022 when due to B symptoms, lymphcytosis, anemia and generalized lymphadenopathy, hematological workup including biopsy of cervical lymph node was performed and CLL/SLL relapse was confirmed. Initially chlorambucil was introduced, but disease was refractory. Based on cytogenetic test results (IGHV unmutated, negative TP53) and due to cardiovascular comorbidity (contraindication for BTK inhibitors) venetoclax and rituximab were started in 01/2023. After just 1 cycle of treatment normal blood count as well as regression of B symptoms and peripheral lymphadenopathy occured, indicating the probability of complete disease remission. In our patient with metastatic lung adenocarcinoma excellent disease control is achieved during 41 month of treatment in first line setting. Furthermore, relapsed/refractory CLL/SLL is currently in confirmed remission. Conclusion(s): Successful treatment of patients with multiple primary malignancies is based on multidisciplinarity, early recognition and management of side effects, treatment of comorbidities with the aim of prolonging life, controlling symptoms of disease and preserving quality of life.

Demographic profile and outcome in primary pediatric brain tumors. A single tertiary institute experience in India

Introduction: Pediatric brain tumors are the most common tumor in children after hematological malignancies. There is very few data about the epidemiology of pediatric brain tumors in India. Methods - This was a prospective and retrospective study in pediatric patients who had undergone surgery in our institute (JIPMER,Pondicherry). 80 cases were recruited and followed up for minimum follow up period of 1 year. The demographic profile was analysed and IHC markers were done for embroyonal tumors and glioma. Result(s): Pediatric brain tumors was equally distributed among male and females. (1:1) .Mean age of presentation was 10 years . 27.5 % of our cases were embryonal tumors,low grade glioma (16.25 % ) ,high grade glioma ( 12.5 % ) ,ependymoma and craniopharyngioma comprised 15 % of our cases each. Medulloblastoma comprised 23.75 % of cases Out of which 31.5 % had craniospinal metastasis at time of diagnosis. The most common location of SHH pathway medulloblastoma was cerebellar hemisphere and non WNT/non SHH was fourth ventricle. 45.45 % of patients with high grade glioma had recurrence .50 % of ependymoma cases were infratentorial. we had 2 cases of ganglioglioma ,one in the midbrain and other in temporal lobe .Gross total resection was achieved in 30 % ,Subtotal resection in 46.25 % and partial resection in 20 % of our cases. Outcome of patients at the end of 1 year for low and high grade glioma, ependymoma and craniopharyngioma were similar to western literature. Two patients acquired COVID 19 and died while undergoing treatment. Molecular markers like INI1, LIN28 A was highly sensitive and specific for diagnosing atypical teratoid rhabdoid tumor (ATRT) and embryonal tumor with multilayered rosettes (ETMR )respectively. Conclusion(s): Our study emphasizes the need of standardized and systemic cancer registries in India. (Figure Presented).

Novel Framework for Neurocognitive Covid-19 Assessment

Background The neurotrophic effects of Covid-19 are becoming increasingly recognized, with altered mental state now being the second most common presenting complaint insert numbers. A key question is whether this has long term consequences. Cognitive problems are commonly reported in patients 3 months after acute infection as part of the so called Long-Covid syndrome. However, the underlying cause is not well understood. Candidate explanations include legacy from encephalitis and stroke;however, other complications such as the sequelae, delirium, remain underexplored. Furthermore, little consideration has been given to functional cognitive disorders and the cognitive consequences of depression, anxiety and fatigue. Aims We propose a structured approach to clinical assessment for clinicians reviewing late cognitive complaints after COVID 19. Methods We created our own unique framework for neurocognitive Covid assessment based upon a review of the literature. Results Covid status- Any positive test. If not review of core symptoms such as breathlessness, headache, anosmia, nasal obstruction, cough, myalgia, or gustatory dysfunction;duration, extent of exposure to Covid confirmed cases. Consider rapid antibody testing. Neuropsychiatric history- Part 1 symptoms at onset- in particular disruptions of consciousness and altered mental state. Acute memory impairment, anterograde/retrograde and with/ without a temporal gradient. neurocognitive function. ITU admission and oxygen requirements. Part 2 Current cognitive and mental state- in addition to standard history seek evidence of internal inconsistency of memory symptoms and attentional dysregulation. Has social cognition and meta-cognition been affected. Note attribution bias i.e. no Im not depressed, I cant enjoy anything because of my symptoms Background history- subtle suggestion of neurodegeneration and depression, anxiety and functional symptoms should be explored. MRI findings- signal changes in the medial temporal lobe, nonconfluent multifocal white matter hyperintense lesions, and isolated white matter microhemorrhages. Novel biomarkers IL-6, MCP-1, and IP-10. Conclusion Cognitive symptoms are common after confirmed and assumed COVID exposure. We propose a framework for neuropsychiatric assessment and the use of adjuvant imaging and potential biomarkers.

FDG-PET Brain Imaging in the Evaluation and Follow-up of COVID-19

Aim/Introduction: The novel coronavirus disease (COVID-19) is caused by the respiratory infection of SARS-CoV-2 virus and is characterized by a multisystemic inflammation, presenting with a wide spectrum of symptoms. 18F-fluoro-deoxy-glucose positron emission tomography/computed tomography (FDG-PET/CT) is a promising imaging method in the evaluation of acute-phase and late changes in the central nervous system. Material(s) and Method(s): A single-centre, prospective clinical study (COMPOSIT study) was initiated where FDG-PET/CT was performed in adult COVID-19 patients during acute, infective state and 3 months later. Brain FDG-PET images were evaluated with a software utilizing a built-in, age-matched normal database and the degree of the differences (Z-scores) were investigated at the two imaging timepoints. Result(s): We present the data of 36 patients (14 women, 22 men), with a mean age of 52 years (42-75 years). In the acute, infective state, the majority of the patients presented with diffuse, significant cortical hypometabolism whereas at 3 months followup, the involved regions showed a marked and often complete metabolic normalization. The most common regions with residual hypometabolism at 3 monts were the medial prefrontal and medial temporal regions and the anterior cingulate. Also, these regions showed the proportionally lowest rates of normalization. Hypometabolism was the least frequent in the cerebellum at the acute, infective state and its FDG-uptake showed a nomalization in all but one case. Conclusion(s): Residual hypometabolism is common in the areas encompassing the orbitofrontal cortex and the limbic system while the cerebellar cortex was relatively spared. However, our study is limited by the corticosteroid-effect in the scans performed at the acute, infective state and furthermore, the fact that no metabolic data is available of the patients before SARS-CoV-2 infection.

Stroke in patients with COVID associated Mucormycosis: A Report of Two Cases

Mucormycosis is a rare and invasive fungal disease with potentially fatal outcome. It most commonly affects patients with compromised immunity, especiallly those with poorly controlled diabetes. The incidence of mucormycosis has increased after the COVID-19 pandemic and both COVID-19 and mucormycosis are associated with an increased incidence of stroke. We present a report of two cases of COVID associated mucormycosis who had stroke. A 50-year-old patient with uncontrolled diabetes developed swelling of left eye and face ultimately leading to complete ophthalmoplegia of left eye. Imaging studies of brain revealed infarcts. MRI/MRA brain showed left internal carotid artery thrombosis, cavernous sinus thrombosis and a brain abscess in left temporal lobe. A second patient was a 65-year-old diabetic and hypertensive male who had COVID and then developed right MCA territory infarct and right sided cavernous sinus thrombosis. Diagnostic nasal endoscopy and biopsy was suggestive of mucormycosis in both the cases. Both these cases were managed with combination of tight glycemic control, antifungal therapy, and surgery. Clinicians should be aware of the association of stroke with COVID and COVID associated mucormycosis (CAM). Copyright © 2022 International Medical Sciences Academy. All rights reserved.

Endogenous miRNA-Based Innate-Immunity against SARS-CoV-2 Invasion of the Brain.

The severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19, possesses an unusually large positive-sense, single-stranded viral RNA (ssvRNA) genome of about ~29,903 nucleotides (nt). In many respects, this ssvRNA resembles a very large, polycistronic messenger RNA (mRNA) possessing a 5'-methyl cap (m7GpppN), a 3'- and 5'-untranslated region (3'-UTR, 5'-UTR), and a poly-adenylated (poly-A+) tail. As such, the SARS-CoV-2 ssvRNA is susceptible to targeting by small non-coding RNA (sncRNA) and/or microRNA (miRNA), as well as neutralization and/or inhibition of its infectivity via the human body's natural complement of about ~2650 miRNA species. Depending on host cell and tissue type, in silico analysis, RNA sequencing, and molecular-genetic investigations indicate that, remarkably, almost every single human miRNA has the potential to interact with the primary sequence of SARS-CoV-2 ssvRNA. Individual human variation in host miRNA abundance, speciation, and complexity among different human populations and additional variability in the cell and tissue distribution of the SARS-CoV-2 angiotensin converting enzyme-2 (ACE2) receptor (ACE2R) appear to further contribute to the molecular-genetic basis for the wide variation in individual host cell and tissue susceptibility to COVID-19 infection. In this paper, we review recently described aspects of the miRNA and ssvRNA ribonucleotide sequence structure in this highly evolved miRNA-ssvRNA recognition and signaling system and, for the first time, report the most abundant miRNAs in the control superior temporal lobe neocortex (STLN), an anatomical area involved in cognition and targeted by both SARS-CoV-2 invasion and Alzheimer's disease (AD). We further evaluate important factors involving the neurotropic nature of SARS-CoV-2 and miRNAs and ACE2R distribution in the STLN that modulate significant functional deficits in the brain and CNS associated with SARS-CoV-2 infection and COVID-19's long-term neurological effects.

Immediate and 6-month seizure outcomes following first and second SARS-CoV2 mRNA vaccinations: A multicenter study with a nationwide survey.

OBJECTIVE: This study aimed to identify seizure outcomes in people with epilepsy (PWE) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) messenger RNA vaccination. METHODS: We examined PWE (n = 332, age ≥ 14 years) treated in four tertiary hospitals between 2021 and 2022 to assess the incidence of seizure worsening following vaccination using closed questions. We identified the clinical factors associated with worsening and 6-month vaccination outcomes. We also conducted a nationwide survey on self-reported seizure worsening using open questions, to which 261 general practitioners from 99 institutes contributed. RESULTS: Of the 282 PWE vaccinated in the four hospitals, 16 (5.7%) exhibited seizure worsening; most of them emerged within 48 h of vaccination and were not sustained. Thus, all PWE were at baseline condition 6 months after their vaccination. PWE with seizure worsening were more significantly associated with focal impaired awareness seizures (p < 0.001), high seizure frequency (p = 0.025), and drug-resistant epilepsy (p = 0.007) at baseline compared to PWE without worsening. Multivariate logistic regression analysis revealed that focal impaired awareness seizures were independently associated with worsening (odds ratio, 7.0; 95% confidence interval, 1.50-32.77). A nationwide survey of 5156 PWE data (real-world data) confirmed an extremely low incidence rate of self-reported seizure worsening (0.43%). SIGNIFICANCE: Some PWE, particularly refractory focal epilepsy, exhibit seizure worsening. However, the worsening events were infrequent, non-sustainable, and probably under-reported by PWE, suggesting that there is little evidence that worsening seizures discourage current and future vaccinations.

SUPERIOR SAGITTAL SINUS THROMBOSIS PRESENTING AS DETERIORATING RESIDUAL WEAKNESS

SESSION TITLE: Imaging, ECMO, and other Procedures in the ICU Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Superior sagittal sinus (SSS) thrombosis is a rare cause of stroke that is difficult to identify due to various clinical presentations. It is the most common form of dural sinus thrombosis, and common risk factors include hypercoagulable state, traumatic head injury, pregnancy/postpartum, and malignancy. More than 85 percent of adult patients have at least one risk factor for cerebral venous thrombosis. Some patients with SSS thrombosis do not have clearly identifiable risk factors, and this case highlights one such patient. CASE PRESENTATION: A 60-year-old Caucasian male with hypertension, hyperlipidemia, and a recent intracranial hemorrhage with residual left-sided weakness, presented to the emergency department with worsening left-sided weakness. Upon admission, his physical exam was notable for 4/5 strength in the left upper extremity and 2/5 strength in the left lower extremity. This was a reduction in strength from a baseline of 4/5 in the left upper and lower extremities. Labs on admission were normal except for high-sensitivity troponin of 86 and WBC of 14.5. UA with a small amount of blood. An initial CT brain without contrast showed no acute changes, evolutionary changes in the right frontal temporal lobe, and subtle curvilinear hyperdensity near a site of the intracranial hemorrhage identified in the prior month. This curvilinear hyperdensity was thought to reflect early parenchymal calcification. MRI brain without contrast showed new and evolving areas of abnormal signaling and an evolving hematoma with surrounding vasogenic edema, all of which are in the right lobe. There was no apparent diffusion coefficient correlate. Thus, MRI with contrast and MRV was recommended. EEG showed no evidence of epileptiform activity. Additionally, transthoracic echo demonstrated new non-ischemic cardiomyopathy with an EF of 35-40%. The diagnosis was ultimately made after the patient had a Magnetic Resonance Venography (MRV) which showed evidence of the SSS thrombosis and an indication that the previously visualized curvilinear hyperdensity is suspected to represent slowed flow within a surface vein. Heparin was started to recanalize the sinus and prevent thrombus propagation. After the appropriate treatment was started, the patient's weakness improved dramatically. DISCUSSION: Typically, patients with SSS thrombosis have identifiable risk factors like hypercoagulable states, traumatic head injuries, pregnancy/postpartum, malignancy, and more recently association with COVID-19 infection. In this case, since the patient lacked identifiable risk factors, the MRV played a key role in the diagnosis. CONCLUSIONS: Like our patient, 30-40 percent of patients present with an intracerebral hemorrhage. Differentials of SSS thrombosis should be considered in etiologies for intracerebral hemorrhage, especially when an identifiable cause is lacking, in order to avoid delays in treatment and resolution. Reference #1: Abdalkader M, Shaikh SP, Siegler JE, Cervantes-Arslanian AM, Tiu C, Radu RA, Tiu VE, Jillella DV, Mansour OY, Vera V, Chamorro Á, Blasco J, López A, Farooqui M, Thau L, Smith A, Gutierrez SO, Nguyen TN, Jovin TG. Cerebral Venous Sinus Thrombosis in COVID-19 Patients: A Multicenter Study and Review of Literature. J Stroke Cerebrovasc Dis. 2021 Jun;30(6):105733. doi: 10.1016/j.jstrokecerebrovasdis.2021.105733. Epub 2021 Mar 4. PMID: 33743411;PMCID: PMC7931726. Reference #2: Rehman A, Husnain MG, Mushtaq K, Eledrisi MS. Cerebral venous sinus thrombosis precipitated by Graves’ disease. BMJ Case Rep. 2018 Jun 4;2018:bcr2017224143. doi: 10.1136/bcr-2017-224143. PMID: 29866676;PMCID: PMC5990097. Reference #3: Nakase H, Takeshima T, Sakaki T, Heimann A, Kempski O. Superior sagittal sinus thrombosis: a clinical and experimental study. Skull Base Surg. 1998;8(4):169-74. doi: 10.1055/s-2008-1058178. PMID: 17171061;PMCID: PMC1656696. DISCLOSURES: No relevant rel tionships by Ken Johnson No relevant relationships by Nina Le No relevant relationships by Riaz Mahmood No relevant relationships by Ngoc Phan

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

COMMON PRESENTATION WITH AN UNCOMMON ETIOLOGY: THYMOMA-ASSOCIATED AUTOIMMUNE ENCEPHALITIS INDUCED BY COVID-19 BOOSTER VACCINE

SESSION TITLE: Issues After COVID-19 Vaccination Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Thymoma-associated autoimmune encephalitis (TAAE) is an understudied and overlooked diagnosis in patients presenting with abrupt altered mental status. Described as inflammation of brain tissue, autoimmune encephalitis is seen in 5-10 cases per 100,000 across all age groups per year. A rare subtype involves neuronal surface antibodies to alpha-amino-3-hydroxyl-5-methyl-4isoxazolepropionic acid receptors (AMPA-R) encephalitis is seen even less commonly. Given the "unicorn” nature of presenting cases and difficulty of diagnosis, prompt identification and treatment are critical as prolonged courses without treatment are irreversible and deadly. CASE PRESENTATION: A 47-year-old male with no past medical history presented 3 days after a Johnson & Johnson coronavirus-2019 (COVID-19) booster vaccine due to worsening acute altered mental status over the past week. He complained of episodes of fever & chills prior to this. The patient's wife reported abrupt changes in memory and personality. Upon admission, the patient had a Glasgow Coma Scale of 4. The patient was intubated and transferred to the intensive care unit. Intravenous (IV) vancomycin, ceftriaxone and acyclovir was initiated for meningitis. Computed tomography (CT) scan of the head without contrast was unremarkable. Magnetic resonance imaging (MRI) showed enhancements of the right anterior and medial temporal lobe suggesting encephalitis. Cerebrospinal fluid analysis (CSF) revealed lymphocytic pleocytosis. A CT scan of the chest, abdomen and pelvis showed an anterior mediastinal mass measured 1.8 x 2.3 cm (Figure 1). FilmArray Meningitis polymerase chain reaction was negative as well as Herpes Simplex Virus (HSV) 1 and 2. Autoimmune encephalitis antibody was positive for Anti-AMPAR. Pulse dose steroids and intravenous immunoglobulin were initiated but failed. Rituximab was initiated and cardiothoracic surgery completed a thymectomy. DISCUSSION: TAAE is a rare disease, permanently debilitating, and deadly if unrecognized or treatment is delayed. Autoimmune encephalitis is an umbrella disease process seen in 0.00005% of patients per year. AMPA-R positive encephalitis is even less commonly seen with only 22 cases reported between the years 2009 and 2014 [1]. A rapidly progressive cognitive decline or psychiatric disorders are early features of this disease.Our patient had prodromal symptoms of fever and cognitive decline days after receiving his COVID-19 booster vaccine. CONCLUSIONS: Post-vaccine encephalomyelitis has been described in other settings[2]. This patient was free of symptoms prior to the COVID-19 vaccine booster, and demonstrated altered mental status hours after receiving it. This furthers the possibility of an association of the COVID-19 booster vaccine, development of encephalitis, and in this case a thymoma. Despite this, conclusions can not be made on the account of one report, but introduces a new area of focus to study. Reference #1: Höftberger, R., van Sonderen, A., Leypoldt, F., Houghton, D., Geschwind, M., Gelfand, J., Paredes, M., Sabater, L., Saiz, A., Titulaer, M. J., Graus, F., & Dalmau, J. (2015). Encephalitis and AMPA receptor antibodies: Novel findings in a case series of 22 patients. Neurology, 84(24), 2403–2412. https://doi.org/10.1212/WNL.0000000000001682 Reference #2: Huynh, W., Cordato, D. J., Kehdi, E., Masters, L. T., & Dedousis, C. (2008). Post-vaccination encephalomyelitis: literature review and illustrative case. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, 15(12), 1315–1322. https://doi.org/10.1016/j.jocn.2008.05.002 DISCLOSURES: No relevant relationships by Matthew Frank No relevant relationships by Justin Ilagan No relevant relationships by Danielle Mahon No relevant relationships by Danielle Mahon No relevant relationships by Harshini Sahani No relevant relationships by Kameron Tavakolian No relevant relationship by Ndausung Udongwo

Documented growth of a de novo intracranial capillary hemangioma: a case report

Background: Intracranial capillary hemangiomas are rare, particularly in adults, and diagnosis can be challenging. The literature lacks visualization of intracranial capillary hemangioma growth over time. Here we document growth of a de novo intracranial capillary hemangioma, initially interpreted radiologically as a glioma. Methods: We report a case of a 64 year old male with history of HIV, recent Lyme disease and unconfirmed prior COVID-19 infection, who presented with exhaustion and confusion. Imaging demonstrated an intra-axial high T2/FLAIR signal lesion centred in the subcortical white matter of the posterior right temporal lobe. There was faint enhancement, and a few mildly prominent vessels were seen along its anterior aspect. Imaging 2 years prior had not shown the lesion. Stereotactic biopsy was nondiagnostic. Craniotomy and resection was carried out. Results: Pathological examination and immunohistochemistry returned the diagnosis of capillary hemangioma. We review how this case adds to proposed theories of de novo intracranial capillary hemangioma growth. Our patient's co-morbidities support possible inflammation related triggers for symptomatic progression of these uncommon lesions. Conclusions: This unusual case documents the radiological appearance and progression of a de novo intracranial capillary hemangioma. It represents the first time such growth has been visualized in an adult male.

CLIPPERS and lymphoma: a unified syndrome

Background and aims: Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS) is a defined inflammatory central nervous system disorder characterized by established lesions, predominantly on the cerebellum and pons, with punctate gadolinium enhancement on the MRI and responsiveness to glucocorticosteroid-based immunosuppression. Its pathogenesis is unknown. Methods: A 54-year-old man, with history of obesity and alcoholism, was admitted to our emergency ward due to fever, disorientation, and behavior disorder for 3 days. The neurological examination manifested left eye ptosis and unceasing left gaze torsional nystagmus. He tested positive for SARS-CoV2. A lumbar puncture revealed 41 leucocytes/ mm3, with negative antibody determinations. MRI depicted hyperintense lesions on cerebellum, brain stem, left temporal lobe and right parieto-occipital cortex, with punctate gadolinium enhancement. There was a radiological and clinical response to glucocorticosteroid treatment. He was diagnosed of possible CLIPPERS. Results: Several months following the discharge, after the patient voluntarily abandoned the treatment, the symptoms reappeared. A new MRI showed extensive lesions suitable with primary lymphoma. A biopsy confirmed the diagnosis. In situ hybridization detected Epstein-Barr virus (EBV). Conclusion: Reports describing the development of lymphoma on patients previously diagnosed with CLIPPERS, and the fact that both conditions share anatomopathological findings such as infiltrating CD4+ lymphocytes, support the theory of a syndrome with various prestages encompassing both entities. Furthermore, a nexus between B-cell lymphoma and EBV has already been established, but recent studies dwell on the possibility of this same infection being one of the main triggers of CLIPPERS and its progression into lymphoma.

“Long-hauler ” impact of COVID-19 on brain microstructure: a 3-month follow-up study

Objective: This study investigates the chronic effects of COVID-19 on brain microstructure. Background: Microstructural differences have previously been detected in comparisons of COVID-19 patients with controls, particularly in the insula, cuneus, inferior temporal and anterior cingulate regions. Design/Methods: Here we report diffusion magnetic resonance imaging (3 T Siemens MRI) findings from 20 participants (mean age: 45.3, 55% female), both immediately after recovery and at a 3-month follow-up. Fractional anisotropy (FA), mean diffusivity (MD), mode of diffusivity (MO), free water fraction (F), tissue-specific FA (FAt) and tissue-specific MD (MDt) were obtained using DTI data with b=700 and 1400 (DIPY free-water model). Regions of interest in the grey matter and white matter were delineated using FreeSurfer. To assess differences between baseline and follow-up, a paired t-test, the Wilcoxon Test and Friedman Test were performed, corrected for false-discovery rate of 0.05. Effect size (Cohen's d) was also computed (d>0.45 deemed large effect). Results: All three tests revealed decreased F in the hippocampus and decreased MD in the parahippocampal region of the WM at follow-up. In the GM, F was increased in the medial orbitofrontal region. In the WM, MD was increased in the paracentral region and MDt was increased in the parahippocampal and lateral orbitofrontal regions. Conclusions: These results suggest that microstructural abnormalities persist following recovery. Increased extracellular fluid (i.e. F and MD) in the frontal lobe suggest spreading of COVID-19 impact, while decreased F and MD in the hippocampal region suggest debris accumulation as part of the inflammatory process. None of the regions affected in sub-acute COVID-19 appear to fully recover within three months.

Two Rare Cases of Glioma in Total Spine with Metastasesto Brain

Objective: NA Background: Glioma classification evolved over the years but remains a diagnostic challenge. Primary spinal cord (PSC) glioblastoma is extremely rare and represents fewer than 1.5% of all spine tumors in adults. Presentation may mimic demyelinating or inflammatory disorders, but prognosis is significantly worse. We present two aggressive cases of extensive, total spinal cord gliomas with early metastases to brain. Design/Methods: NA Case #1: A 44-year-old woman with a diagnosis of demyelinating disorder with paraplegia, bladder and bowel incontinence presented with new appendicular ataxia. Previous MRI revealed unremarkable brain and hyperintensity in T7-10 concerning for multiple sclerosis. Empiric methylprednisolone and cyclophosphamide showed no improvement. Repeat MRI showed extensive intramedullary cystic lesions throughout cervical, thoracic, and lumbar spine, hyperintensities in the brainstem, and enhancing lesions in the corpus callosum and R frontal lobe. Biopsy revealed brain Glioblastoma, WHO grade IV, IDH wildtype. H3K27M test was not performed. Patient expired 13 months after initial symptom onset. Case #2: A 49-year-old man with a recent COVID-19 infection presented with 2 weeks of bilateral lower extremity numbness and weakness. MRI brain was unremarkable, and spine revealed intra-dural, extra-medullary nodular enhancing lesions throughout cervical and thoracic spine, and the cauda equina. Infectious, inflammatory, and rheumatologic causes were investigated until repeat imaging in 1 week (after a course of empiric methylprednisolone) demonstrated the rapid development of a non-enhancing expansile mass in the R temporal lobe. Biopsy revealed spinal Glioblastoma, WHO grade IV, IDH wildtype, negative for H3K27M mutation, and brain low grade glioma. The patient remains on palliative radiation with concurrent temozolomide and adjuvant temozolomide. Conclusions: Primary spinal cord glioblastomas are rare and devastating. Timely diagnosis remains a challenge since clinical and radiographic findings mimic demyelinating or inflammatory disorders. Our cases highlight the diagnostic challenge and importance of early suspicion in the diagnosis of malignant spinal glioma.

A Systematic Review Of Clinical Profile Of Cerebral Abscess In Post Covid Rhino Orbital Cerebral Mucormycosis

Objective: To analyse demographic data, provide an overview of the diverse clinico-radiological presentations of cerebral abscess in post covid ROCM. Background: The vulnerability of COVID-19 patients to ROCM, a spectrum of limited sinonasal, rhino-orbital and rhino-orbital-cerebral disease, often has underlying uncontrolled diabetes, immunosuppressive therapy in moderate to severe cases Design/Methods: We systematically reviewed 65 patients diagnosed with post covid ROCM with cerebral abscess admitted to the hospital during MAY 2021 to AUGUST 2021.Data pertaining to demographic variables, clinico-radiological features were analysed using percentage of total cases Results: Of 65 patients, incidence is more in the age group of 40-60yrs, males are more affected than females. Risk factors - inadvertent steroid use [ 89%], diabetes mellitus [ 81%], CKD [0.07%], HIV[ 0.03%].clinical profile include headache [97%], seizure [80%], vomitings [60%], focal neurologic deficit [18%], encephalopathy [3%]. Radiological profile showed abscess in temporal lobe [49%], frontal lobe [28%], occipital [14%], parietal [6%], optic nerve[ 3%]. Conclusions: Caution needs to be exercised with regard to Glycemic control, widespread usage of corticosteroids to reduce super infections. Expedient commencement of antifungal therapy together with surgical debridement help to improve the survival of these patients. In a country with prevalence of high risk factors and relatively poor resources, covid vaccination programmes should be the topmost priority to avoid massive outbreaks, complications and mortality.

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.

New onset limbic encephalitis and COVID-19 vaccine: a case report

Background: Autoimmune limbic encephalitis (ALE) is an inflammatory disease involving the medial temporal lobes. It is characterized by subacute onset of short-term memory deficits, seizures and psychiatric disorders. Few new cases of ALE associated both with SARS-CoV2 infection and COVID-19 vaccine have recently been described. Case presentation: A 56-year-old woman was admitted to emergency department for persistent fever and acute onset of confusion few days apart the first dose of BNT162b2 COVID-19 vaccine. Neurological examination revealed confusion and short-term memory loss. Blood test showed only leukopenia and mild increase of the PCR. The patient underwent brain CT-scan which excluded organic lesion for the cognitive deficit. During the hospitalization the patient presented tonic clonic seizures and postictal state therefore an EEG was performed and revealed epileptiform abnormalities in the temporal lobes. Since the hypothesis of encephalitis brain MRI and lombar puncture for cerebral spinal fluid (CSF) analysis were performed with evidence of T2 hyperintensity in temporal lobes and normal values of CSF. Despite steroid and antiepileptic therapy with Carbamazepine, Valproate and Perampanel, several epileptic relapses occurred and there was no improvement of neurological manifestation. The patient was finally discharged with need of home care Conclusions: New onset ALE following COVID-19 vaccine or infection has rarely been described. Clinicians should monitor neurological symptoms to ensure appropriate therapy to maximize the likelihood of good outcome.

EVIDENCE of BRAIN HYPOXIA in NEUROPATHOLOGY of SARS-CoV-2-INFECTED NONHUMAN PRIMATES

Background: Neurological manifestations are a major complication of sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and likely contribute to symptoms of "long COVID". Elucidating the mechanisms that underlie neuropathogenesis in infection is critical for identifying or developing viable therapeutic strategies. While neurological injury in infection is varied, cerebrovascular disease is seen at a high frequency among patients over 50 years of age. Additionally, microhemorrhages and hypoxic-ischemic injury are often described in brain autopsy series of human subjects who died from COVID-19. Here, we report neuropathology in aged SARS-CoV-2 infected non-human primates (NHPs) is consistent with that observed in aged human subjects and provide insight into the underlying cause. Methods: Four adult Rhesus macaques and four African green monkeys were inoculated with the 2019-nCoV/USA-WA1/2020strain of SARS-CoV-2 via a multi-route mucosal or aerosol challenge. Two of each species were included as age-matched controls. Frontal, parietal, occipital, and temporal lobes, basal ganglia, cerebellum, and brainstem were interrogated through histopathological and immunohistochemical techniques to identify and characterize the observed pathology. Results: Like humans, pathology was variable but included wide-spread inflammation with nodular lesions, neuronal injury, and microhemorrhages. Neuronal degeneration and apoptosis were confirmed with FluoroJade C and cleaved caspase 3 IHC, which showed foci of positivity, particularly among cerebellar Purkinje cells. This was seen even among infected animals that did not develop severe respiratory disease but was not seen in age-matched controls. Significant upregulation of the alpha subunit of hypoxia inducible factor 1 (HIF1-α), indicative of tissue hypoxia, was observed in brain of all infected animals, regardless of disease severity. Sparse virus was detected in brain endothelial cells but did not associate with the severity of CNS injury. Conclusion: SARS-CoV-2 infected NHPs are a viable animal model for advancing our current understanding of infection-associated neuropathogenesis. Upregulation of HIF1-α in brain of infected animals suggests cerebral hypoxia may underlie or contribute to neuroinflammation and neuronal injury/death and may provide some insight into neurological manifestations observed among asymptomatic patients or those only suffering mild disease.