BRAIN AND BEHAVIOR PREDICTORS OF SARS-CoV-2 INFECTION AMONG PEOPLE WITH HIV

Background: Recent findings from the UK Biobank revealed that healthy adults who later became infected with SARS-CoV-2 had lower brain volumes in regions involved in risk-taking behavior and olfaction compared to individuals who did not become infected. We examined if similar pre-existing differences in brain regions correspond to SARS-CoV-2 infection among people with HIV (PWH) receiving suppressive ART. Method(s): Participants included adult Thai MSM enrolled in the acute HIV (AHI) cohort (RV254/SEARCH010) in Bangkok, Thailand. Participants underwent 3T MRI and clinical assessments (i.e., HIV disease metrics, cognitive testing, and self-reported mood and substance use). ART initiation occurred within 5 days of the MRI (median=same day). Regional brain volumes were summed across hemispheres and corrected for head size. Brain volumes and clinical indices were compared between participants with laboratory confirmed SARS-CoV-2 and those without a diagnosis of SARS-CoV-2 following ART initiation. Machine learning was utilized to identify variables at the time of enrollment into the cohort that predicted subsequent SARS-CoV-2 infection status. Result(s): 112 participants were included in the analysis. All study participants achieved viral suppression after ART and received SARS-CoV-2 vaccinations. Fifty-four participants became infected with SARS-CoV-2 during the observation period (median=79 weeks from ART initiation). Study participants who became infected with SARS-CoV-2 after ART had lower volumes at the time of enrollment in several subcortical brain regions with the most pronounced effect in the pallidum (p=.025). There were no associations between brain volumes and ratings of mood, demographics, or HIV disease indices. SARS-CoV-2 infection was two-fold higher among individuals who reported use of amyl nitrites (i.e., poppers) during chemsex. Machine learning with repeated cross validation revealed that lower orbital and medial frontal lobe, anterior cingulate, pallidum, vermis, and olfactory volumes, worse motor function, and higher education collectively predicted co-infection status (average AUC of 85%). Conclusion(s): Study findings point toward a risk phenotype for SARS-CoV-2 infection among PWH defined by pre-existing differences in brain volumes relevant to risk-taking behavior, emotion, and neuroHIV as well as behavioral factors such as inhalant use and lack of social distancing during chemsex. (Table Presented).

Comorbidity of purulent meningitis with COVID‐19: A case report

To date, only a few cases of intracranial infection related to severe acute respiratory syndrome‐coronavirus‐2 (SARS‐CoV‐2) were reported. Here we describe a case of coronavirus disease 2019 (COVID‐19) that was comorbid with purulent meningitis. A 62‐year‐old male patient was diagnosed with moderate COVID‐19 and had no fever or cough after treatment. However, he suffered from a head injury and experienced headache and fever immediately after the accident. Computed tomography (CT) of the brain showed bilateral frontal lobe contusion, subdural hematoma, and subarachnoid hemorrhage. In the following days, the patient suffered from recurrent fever, although chest CT did not show evidence of worsening of infection. Several lumbar punctures were made, confirming increased cerebrospinal fluid (CSF) pressure and karyocyte count. SARS‐CoV‐2 nucleic acid was not detected in CSF but revealed the presence of Escherichia coli. Thus, the patient was diagnosed with purulent meningitis, presumably caused by brain trauma or the immunologic dysfunction caused by COVID‐19, which was supported by the significant reduction of all kinds of immune cells. Since immunologic dysfunction is commonly presented in COVID‐19 patients, comorbidity with meningitis should be considered when a COVID‐19 patient presents with headache and fever. Lumbar punctures and CSF cultures may help in the diagnosis.

The Role of Monoclonal Antibodies in Contrasting Cases of Norse

1. A 42-year-old female developed status ten days following admission for alcohol-related liver disease. MRI brain showed symmetrical medial temporal high signal. No cause was identified. Though the convulsive seizures settled, focal seizures persisted. A second MRI showed extensive multi-lobar signal change, presumed inflammatory in nature. Pulsed methylprednisolone and plasma exchange were ineffective. Tocilizumab was administered ten weeks following onset of seizures. Sequential MRIs showed resolution of inflammatory changes. The patient was discharged to rehabilitation-Modified Rankin Score 3. 2. A 79-year-old female presented with convulsive NORSE, 24hours after first dose of Pfizer COVID vaccine. She had a background of vascular dementia. The patient never recovered her GCS. Convulsive seizures were replaced by epilepsy partialis continua. Sequential MRIs showed diffuse left parietal cortical high signal. An inflammatory aetiology was presumed, pulsed methylprednisolone and the ketogenic diet (3 months) were ineffective. Anakinra was administered on week twelve. Subsequent MRIs showed progression of confluent white matter disease, now bi-hemispheric. She remains symptomatic, a year post presentation. We hypothesise that both patients had NORSE arising from an unidentified inflammatory aetiology. Age and premorbid function are known to influence recovery. Early use of monoclonal antibodies may be beneficial, including in those with systemic disease.

Progressive multifocal leukoencephalopathy, neuroradiology-neuropathology

Introduction: Progressive multifocal leukoencepha-lopathy (PmL) is an unfavorable demyelinating disease of the CNS caused by reactivation of JC virus (JCV). JCV is a double-stranded DNA human polyomavirus predominatingly acquired in childhood. Blood samples taken from healthy persons indicate that 50-90% of adults have been exposed to this virus. JCV is an opportunistic pathogen, with PmL manifesting primarily in patients with immunodefciency or taking immunomodulatory treatments or with lymphoproliferative diseases. We report a patient who developed PmL shortly after diagnosis of follicular lymphomma. Case presentation: A 70-year-old-woman admitted to the neurological departament with hemiparesis, psy-chomotor slowing down, balance problems, dizziness and in depressed mood. the patient underwent aorto-femoral transplant 12 years ago and for 10 years was under constant observation of a hematologist due to enlarged lymph nodes. Five years ago, the patient had planoepithelial cell carcinoma removed. the patient also sufered from COViD-19 infection and sufered from depression. elevated leukocytosis and D dimers, were the only abnormal results obtained in laboratory tests. However, pulmonary embolism was excluded in Ct angio. Cytometry of blood showed follicular lymphoma. Radiological fndings: mRi and Ct scans showed multiple asymmetrical pathological areas of hyperin-tense signal in t2-dependent images, hypointense in t1-dependent ones and Ct-hypodense regions which extended continuously in control examinations. they were located in the white matter of multiple lobes of both brain hemispheres subcortically and periventric-ullary. the subcortical U-fbers were involed. they did not show contrast enhancement and mass efect. they showed peripheral ring and patchy difusion restriction particularly at their leading edge. in spite of the used steroid therapy the patient's health deteriorated rapidly. the patient died of symptoms of cardio-respiratory failure 1 month after admission to hospital. Neuropathological features: the neuropathological examination revealed numerous foci of demyelination in the white matter of the frontal lobe, the parietal lobe in the pons and in the cerebellum. myelin losses were accompanied by damage to oligodendrocytes and proliferation of macrophages. the nuclei of the damaged oligodendrocytes were enlarged and hyperchromatic, and some had a "ground-glass" appearance typical of viral infection. the astrocytes were bizarre with lobulat-ed, hiperchromatic or hypochromatic nuclei and damage of cytoplasmic procesesses (clasmatodendrosis). Conclusion(s): the triad of neuropathological injuries: destruction of oligodendrocytes with intranuclear viral inclusions ("ground-glass" appearance), multifocal demyelination and bizarre astrocytes allowed for the diagnosis of late form of classical progressive multifo-cal leukoencephalopathy (cPmL), despite the short time since diagnosis of follicular lymphoma, but with many years of enlargement of the lymph nodes.

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)

Maternal COVID-19 Infection: A Cause of Neonatal Stroke?

Perinatal arterial ischemic stroke (PAIS) is a rare cause of neonatal seizures, with an incidence of 1 in 2500 to 4000 live births, globally. This is a case of a neonate with PAIS due to transpla-cental passage of COVID-19 IgG antibodies from the mother. A term, male neonate, born to a primigravida with an unevent-ful antenatal history was presented on the second day of life with multiple episodes of focal clonic seizures involving the right upper and lower limbs. Magnetic resonance imaging revealed an acute infarct in the left frontal lobe, extending into the parietal region, anterior limb, and genu of internal capsule suggestive of arterial ischemic stroke. The known causes of PAIS were evaluated and ruled out. The result of reverse transcription polymerase chain reaction analysis for SARS-CoV-2 antigen was negative for both the mother and the neonate. COVID-19 IgG antibodies in the mother and neonate were elevated. Seizures were controlled with antiepileptics. The neonate had no further seizure episodes and was discharged on oral levetiracetam. The infant was developmentally and neurologically normal at 3 months of age. PAIS is a rare cause of neonatal seizures, and maternal COVID-19 infection may be associated with neonatal stroke.Copyright © 2022, Himalaya Wellness Company. All rights reserved.

Encephalitis as a post-COVID-19 complication: causation or association?

Case Report: Although the coronavirus disease 2019 (COVID-19) affects the respiratory system, neurological complications in children have been reported. Neurological manifestations in children with acute COVID-19 infection are rare and range from headaches, transverse myelitis, strokes, and encephalitis which presents as a part of Multisystem Inflammatory Syndrome in Children (MIS-C). However, encephalitis presenting post-COVID-19 in the absence of MIS-C in children has not been described. Case presentation: A 9-year-old Hispanic female with no past medical history presented with altered mental status and seizures. Associated symptoms prior to seizures included worsening headaches and vomiting. Initial labs were significant for an elevated erythrocyte sedimentation rate of 32 mm/hr, C-reactive protein of 2 mg/dL, and white blood cell (WBC) count of 28 000 cells/mcl with neutrophilia. Comprehensive metabolic panel was normal. Computed tomography of the head and urine drug screen were normal. Magnetic resonance imaging of the brain demonstrated diffusion restriction in the left frontal lobe as well as mild leptomeningeal enhancement concerning for meningoencephalitis. Lumbar puncture (LP) showed pleocytosis (WBC 169 cells/mcl, 76% neutrophils), elevated glucose 77 mg/dl, normal protein 56 mg/dl, and elevated myelin basic protein indicative of a demyelinating disease. Infectious workup was significant for a positive COVID-19 immunoglobulin (Ig) G (19.66), positive Mycoplasma pneumoniae (M. pneumoniae) IgM (0.87 units/L), with an equivocal IgG (0.11 units/L). Autoimmune workup was negative. She received dexamethasone 0.15 mg/kg/dose for 1 day, followed by methylprednisolone (10 mg/kg/dose) for 3 days and oral prednisone for 5 days resulting in significant improvement. Although CSF cultures returned negative, she received a 7-day course of doxycycline for a possible coexisting M. pneumoniae infection. Repeat LP showed improving pleocytosis, and lymphocytic predominance. Discussion: In this case report, rapid neurological recovery after administration of corticosteroids in the presence of positive COVID-19 IgG and demyelinating disease was suggestive of encephalitis presenting post- COVID-19 infection. Although M. pneumoniae can present with neurological symptoms (e.g., encephalitis), repeat titers at follow-up after recovery did not show the expected 4-fold increase in IgG, making it less likely the cause of this presentation. The proposed pathophysiology of COVID-19-mediated encephalitis includes direct invasion of the nervous system, immune-mediated cytokine response, and molecular mimicry between coronaviruses and neuronal proteins causing demyelination. The mainstay treatment includes immunomodulators such as corticosteroids, Intravenous Immunoglobulin, monoclonal antibodies (eg., rituximab), or plasma exchange. Conclusion: COVID-19 infection should be considered when evaluating a patient with meningoencephalitis or post-infectious encephalitis.

A Case of SARS-CoV-19-Associated Encephalitis in a Neonate

Objective: To describe a case of SARS-CoV-19-associated encephalitis in a neonate. Method(s): Case report. Report: A 9-day-old term neonate presented with two focal motor seizures (right upper limb jerking and facial twitching). He had a 1-day history of coryzal illness with reduced feeding, but was afebrile. Antenatal course was uneventful. He was born at term via vaginal delivery. He did not require resuscitation or admission to SCBU. Maternal history was notable for symptomatic SARS-CoV-19 infection at time of delivery. Two siblings subsequently tested positive for SARS-CoV-19. He had further seizures in the emergency department and was loaded with phenobarbitone. The infant was stabilised locally and transferred to a tertiary paediatric hospital for the management of neonatal sepsis. He never required respiratory support. However, he was diffusely hypotonic with poor suck, necessitating nasogastric feeding. Nasopharyngeal PCR was positive for SARS-CoV-19. Lumbar puncture microscopy was negative (WCC 6). All CSF bacterial and viral investigations were negative. CSF testing of SARS-CoV-19 was not available. Brain MRI revealed bilateral asymmetric areas of reduced diffusivity involving the subcortical white matter, medulla and the corpus callosum with frontal lobe predominance. He made a full neurologic recovery with supportive therapies and was discharged following a 9-day admission. He had no further clinical seizures and phenobarbitone was successfully weaned pre-discharge. Conclusion(s): In the absence of another aetiology or antenatal risk factor, SARS-CoV-19 infection was presumed causative in this case of focal seizures and white matter changes in this term neonate. White matter abnormalities on MRI imaging are reported in neonates with seizures in the context of other viral infections. Single case reports have been published of SARS-CoV-19 infection with associated abnormal MRI brain findings, particularly diffusion abnormalities of the corpus callosum, as seen in our case.

EEG Characteristics in Hospitalized Patients With Acute COVID-19 Symptoms

Objective Our objective was to evaluate the incidence of seizures, pattern of EEG abnormalities, and localization of abnormal discharges in hospitalized patients with COVID-19. Background The COVID-19 epidemic has revealed significant neurological manifestations including de novo seizures in patients who do not have a prior history of epilepsy or clear epilepsy risk factors. Our center is located in Arizona, which in the early part of January 2021 had more cases per capita than any other place in the world. Design/Methods We performed a retrospective review to observe the electroencephalogram (EEG) patterns of hospitalized adult patients with COVID-19 between March 2020 and February 2021. Results We identified 99 patients who were COVID-19 positive and had EEG testing during the same hospitalization. The most common EEG abnormality was diffuse background slowing, which was seen in 63.6% of patients (n = 63/99), compare to 15.1% of focal background slowing. Epileptiform discharges were seen in 11.1% of patients and seizures were found in 5.1% of patients, as newly diagnosed seizures. When combining all focal abnormalities, the most common location for these abnormalities was in the frontal regions 36.4% (n = 8/22). Even though 21 patients had acute focal neuroradiologic findings, only 5 had correlated EEG abnormalities within the same region. When EEG was obtained with suspected seizures (n = 33), 4 cases (12.1%, n = 4/33) indeed showed ictal pattern compared to 1.6% when seizures was not suspected (p = 0.087). Conclusions Abnormal EEG findings are most commonly found in the frontal lobe among hospitalized patients with acute COVID-19 symptoms. De novo seizures may be seen with COVID-19 infection. Suspicion of seizures should be raised in patients with COVID-19 encephalopathy. The utility of an EEG may help allow us better insight into how and where the COVID infection affects our central nervous system.

Anatomical barriers against SARS-CoV-2 neuroinvasion at vulnerable interfaces visualized in deceased COVID-19 patients.

Can SARS-CoV-2 hitchhike on the olfactory projection and take a direct and short route from the nose into the brain? We reasoned that the neurotropic or neuroinvasive capacity of the virus, if it exists, should be most easily detectable in individuals who died in an acute phase of the infection. Here, we applied a postmortem bedside surgical procedure for the rapid procurement of tissue, blood, and cerebrospinal fluid samples from deceased COVID-19 patients infected with the Delta, Omicron BA.1, or Omicron BA.2 variants. Confocal imaging of sections stained with fluorescence RNAscope and immunohistochemistry afforded the light-microscopic visualization of extracellular SARS-CoV-2 virions in tissues. We failed to find evidence for viral invasion of the parenchyma of the olfactory bulb and the frontal lobe of the brain. Instead, we identified anatomical barriers at vulnerable interfaces, exemplified by perineurial olfactory nerve fibroblasts enwrapping olfactory axon fascicles in the lamina propria of the olfactory mucosa.

MULTIPLE SCLEROSIS AFTER COVID-19: A SIGN OF THINGS TO COME?

SESSION TITLE: Unique Inflammatory and Autoimmune Complications of COVID-19 Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: We present a patient with left-sided eye pain and headache developing 3 weeks after hospitalization for COVID-19. MRI showed inflammation of the left optic nerve and other demyelinating lesions in the brain and cervical spinal cord consistent with multiple sclerosis. CASE PRESENTATION: Our patient is a 36-year-old female with a history of migraines who presented to the emergency department (ED) with complaints of right-sided eye pain and throbbing intractable headache for the past week. The pain was worse on eye movement and the patient reported color changes in her vision. She had been hospitalized for coronavirus disease 2019 (COVID-19) 3 weeks previously. Her workup in the ED revealed white matter changes in the right frontal lobe on computer tomography (CT) scan of the head. She subsequently had a Magnetic resonance imaging (MRI) scan of her brain, cervical and thoracic spine showing left optic peri-neuritis, and scattered foci in the periventricular white matter, corpus callosum, and cervical spine. She was diagnosed with multiple sclerosis (MS) and treatment started with high-dose corticosteroids. The patient had a good response, with a resolution of her symptoms, and was discharged, on a tapering course of steroids, to follow up with neurology in the clinic. DISCUSSION: There is a well-known association between MS and viral infections capable of causing a neuroinflammatory response. COVID-19 includes several neurological manifestations both in the acute and chronic phase (Long COVID). It seems possible that an immune mechanism induced by COVID-19, which can activate lymphocytes and an inflammatory response, can induce the clinical onset of the disease. Other authors have reported an association between recent COVID and MS symptoms onset as well as exacerbations in MS symptoms in patients with established disease. CONCLUSIONS: In patients presenting with neurological symptoms after a recent COVID 19 infection, we should consider demyelinating disease as a possible diagnosis. Reference #1: Palao, M., Fernández-Díaz, E., Gracia-Gil, J., Romero-Sánchez, C. M., Díaz-Maroto, I., & Segura, T. (2020). Multiple sclerosis following SARS-CoV-2 infection. Multiple sclerosis and related disorders, 45, 102377. Reference #2: Bellucci, G., Rinaldi, V., Buscarinu, M. C., Reniè, R., Bigi, R., Pellicciari, G., … & Ristori, G. (2021). Multiple Sclerosis and SARS-CoV-2: Has the Interplay Started?. Frontiers in Immunology, 3850. Reference #3: Garjani A, Middleton RM, Hunter R, Tuite-Dalton KA, Coles A, Dobson R, Duddy M, Hughes S, Pearson OR, Rog D, Tallantyre EC, das Nair R, Nicholas R, Evangelou N. COVID-19 is associated with new symptoms of multiple sclerosis that are prevented by disease modifying therapies. Mult Scler Relat Disord. 2021 Jul;52:102939. doi: 10.1016/j.msard.2021.102939. Epub 2021 May 5. PMID: 34010764. DISCLOSURES: No relevant relationships by Adrian Estepa No relevant relationships by Neelima Manda No relevant relationships by Rehan Saeed

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

ANOTHER COMPLICATION OF COVID-19?: A CASE OF RHINOORBITAL-CEREBRAL MUCORMYCOSIS

CASE: A 44-year-old male with past medical history of type II insulindependent diabetes mellitus (DM) and end stage liver disease (ESLD) due to alcohol use and nonalcoholic fatty liver disease (NAFLD) presented with one week of left-sided retroorbital headache and diplopia. Two weeks prior, the patient tested positive for COVID-19 and initially his severe headache was attributed to this diagnosis. On hospital presentation the patient was found to have ophthalmoplegia, ptosis and diminished sensation in the CN V1 distribution on the left. The patient was in diabetic ketoacidosis (DKA) with glucose of 686, venous blood gas of 7.32/29/15 and serum anion gap of 17. Contrasted orbital and maxillofacial CT showed complete opacification of the left sphenoid sinus and CT angiography/venography of the head were negative for venous sinus thrombosis. MRI of the brain showed left optic nerve ischemia and left frontal lobe cerebritis without abscess. Bedside nasal endoscopy with ENT showed purulent, fuzzy white debris bilaterally concerning for fungal sinusitis. He was taken urgently to the operating room and was found to have angioinvasive fungal sinusitis with cultures growing Lichthemia corymbifera, a fungus in the Mucor family. In addition to treatment with IV insulin and fluids for DKA, the patient was given amphotericin B and posaconazole;however, surgical intervention was deemed too high risk and futile in the setting of patient's comorbidities. IMPACT/DISCUSSION: Mucormycosis is a fungal infection that typically involves the sinuses, orbits and the central nervous system (CNS). Infection of the sinuses manifests with fever, sinus congestion/pain and headache, but can rapidly progress to involve the orbits, leading to vision changes, and the CNS, leading to encephalopathy. Other structures that can be involved include the cavernous sinus, leading to palsies of cranial nerves III-VI. Known risk factors for mucormycosis include DM, especially in patients with DKA, glucocorticoid treatment, immunosuppression and deferoxamine use. Urgent histopathologic diagnosis, initiation of intravenous antifungal agents (amphotericin B) and surgical intervention with ENT, ideally prior to extension beyond the sinuses, are fundamental to decreasing mortality, which is as high as 62%. There have been numerous case reports of mucormycosis in patients with COVID-19, particularly from India. Many of these patients were prescribed glucocorticoids as part of the COVID-19 treatment pathway or had underlying DM. Additional research is needed into the association between COVID-19 and invasive mucormycosis. CONCLUSION: In patients with poorly controlled DM or immunosuppression presenting with severe headache, sinus pain, and/or neurologic changes, mucormycosis must be considered, as it is a fatal entity requiring urgent surgical intervention and initiation of antifungal agents. Patients with COVID-19 infection may be at increased risk for mucormycosis, especially in those with underlying DM or on glucocorticoids.

Cerebellar Symptoms: An Uncommon Presentation of Legionnaires' Disease

A 27- year-old previously healthy man presented to the emergency department with a 3-day history of confusion, urinary retention, cough, slurred speech, intermittent vertigo, and unsteady gait after being started on outpatient abx for diagnosis of community acquired pneumonia at an outside facility. On presentation, his vital signs were significant for a Temp. of 102.4 F, a HR of 118 bpm, a RR of 22 bpm, a BP of 135/75 mmHg, O2 sats down to the 80s% with a new oxygen requirement of 3 L/min. His neurological exam was remarkable for dysarthria, a wide based and unsteady gait, forward drift on standing, bilateral dysmetria and was otherwise non-focal. Bilateral basilar rales were noted on lung exam. Initial workup was significant for a sodium level of 129, potassium 3.1, AST 178, ALT 31. His urine legionella antigen test was positive and COVID-19 PCR test was negative. CT of the chest demonstrated multifocal pneumonia. The predominant neurological picture on presentation warranted a lumbar puncture as well as an MRI of the brain, both of which came back negative. HIV test was negative as well. The spectrum of neurological manifestations of legionnaire's disease is quite wide ranging from simple headaches to acute disseminated encephalomyelitis (ADEM). While up to 40% of patients may present with headaches and some confusion, the specific cerebellar presentation is quite rare and has been described in case reports. According to Shelburne(1), there has been instances where the neurological manifestations have lasted up to 3 years after resolution of the pulmonary disease. In a review article detailing 29 cases of cerebellar dysfunction in Legionnaire's disease, a lumbar puncture performed in 16 of the cases showed that the majority had no abnormalities in CSF studies. The propensity for Legionella to specifically manifest as cerebellar Sx remains to be studied. Interestingly, another case report of two patients with neurological symptoms, showed hypoperfusion of the cerebellar and frontal lobes on single photon emission while CT and MRI imaging of the brain were normal. We add to the literature another 'cerebellar' presentation of Legionnaire's disease.

A Fatal Case of Intraparenchymal Hemorrhage Masquerading as Central Diabetes Insipidus

This is 32-year-old women presented to us on postpartum day 10 with severe covid-19 pneumonia. Hercomplaints were dyspnea and headache which she described as, frontally located, 8/10 in intensity, non-radiating and not associated with any posture. She had no prior history of migraines. She was afebrile, tachycardiac and hypoxic on exam. Physical examination was unremarkable. Patient failed trial of non-invasive ventilation following which she was intubated. CT head on admission was unremarkable.For COVID 19 ARDS, she was started on dexamethasone, tocilizumab, paralysis was achieved withcisatracurium and prone protocol was followed for refractory hypoxia. Patient was placed on DVTprophylaxis with heparin. Her pneumonia and oxygenation improved. However, on hospital day 8, herlab results were suspicious of Diabetes insipidus (DI). Her serum sodium was 152mEq/L with serumosmolarity of 360 and polyuria (more than 2L of urine in one hour). A full neurological examinationcould not be obtained as she was paralyzed, however, pupils were equal in size and reactive to light. With high clinical suspicions of diabetes insipidus she received a one-time dose of 16mcg of DDAVP andMRI of pituitary gland was ordered to delineate etiology. Subsequent improvement in polyuria wasnoted. Despite DDAVP her serum sodium continued to worsen. We continued to monitor serumsodium levels every four hours. Her serum sodium levels remained labile with a precipitous drop notedfrom 174mEq/L to 152mEq/L. Review of Pituitary MRI revealed multiple intraparenchymal hemorrhageson bilateral frontal lobes along with trans tentorial and cerebellar tonsillar herniation. Subsequently, patient underwent a brain death exam and declared brain dead. We suspect the development of intracranial hemorrhage in our patient was secondary to covid-19. Onliterature review, an incidence of 0.2% in covid-19 patients with a mortality of 48% is reported. In ourpatient, inability to perform a full neurological exam due to paralysis limited early recognition andintervention. This case highlights the need for increased awareness in patients with features of central diabetesinsipidus and the urgency to obtain CT head immediately after a diagnosis has been established. Promptconsideration of neuroimaging should be made when features of central diabetes mellitus are noted with limited neurological exam.

“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.