Post-COVID-19 vaccination Guillain-Barre syndrome with sensory ataxia, gaze-evoked nystagmus, mental-status change and positive pathological reflex

Background: Various neurological disorders have been reported after vaccination against coronavirus disease 2019, one of which is Guillain-Barre Syndrome (GBS). Case Presentation: We report a case of a 73-year-old woman who developed GBS and extra-GBS manifestations 19 days after the second dose of BNT162b2 mRNA vaccine. She presented lower limb predominant muscle weakness and loss of tendon reflexes. Nerve conduction study showed acute motor and sensory axonal neuropathy. In addition, she developed notable deep sensory ataxia, and showed positive pathological reflex, gaze-evoked nystagmus and altered consciousness, which suggested brainstem involvement. Conclusion(s): This is the first coronavirus disease 2019 vaccine-related GBS complicated with such central nervous system manifestations.Copyright © 2023 Japanese Society for Neuroimmunology.

Post-Covid Cognitive Impairment Mri Brain Scan Abnormalities: A Potential Biomarker

Background: Post-acute sequelae of SARS-COV-2 infection (PASC) is associated with cognitive impairment (CI) with unclear pathogenesis though blood brain barrier (BBB) impairment and excitotoxic injury appear significant. Post-acute sequelae of SARS-COV-2 infection (PASC) is associated with cognitive impairment (CI) with unclear pathogenesis though blood brain barrier (BBB) impairment and excitotoxic injury appear significant. We hypothesized that PASC CI patients would have brain inflammation and BBB disruption using advanced MR imaging. Method(s): In this prospective longitudinal study, 14 patients with PASC CI (mild and non-hospitalised) were enrolled (mean age of 45;10 F and 4 M) and 10 sex and age matched healthy controls. 13 had a follow up MR at 9-12 months (mean 10 months). All participants underwent DCE perfusion (an index of BBB integrity with Ktrans as the measurement), Diffusion Tensor Imaging (DTI) and single voxel MR spectroscopy (MRS) of the frontal cortex/white matter and the brainstem in addition to brain anatomical MRI. Between group analyses were used to determine which MRI outcomes were significantly different from controls in patients with PASC CI. Result(s): The PASCI CI group showed significantly increased (ie BBB impairment) Ktrans, and increased region (Frontal white matter and Brain Stem)-specific areas in the brain (p=< 0.005), reduction in NAA (ie neuronal injury) and mild reduction of Glx (ie excitotoxicity) in the frontal white matter and brain stem (p=0.004), and reduction in white matter integrity (increased diffusivity -greater radial and mean diffusivity). Increased Ktrans was correlated with increased both radial and mean diffusivity (r=0.9) in all tested brain regions. Ktrans significantly improved in the follow up MR (p= 002596 Z=-2.794872) with no difference between subjects and controls indicating BBB normalisation (p= 0.442418, z= -0.144841). White matter integrity also improved especially in the fractional anisotropy values in the executive networks (p=< 0.00045). MRS showed significant improvement in the NAA in the frontal white matter but Glx remain high as compared to the controls (p=0.0006). Conclusion(s): PASC CI was characterised by reversible diffuse BBB impairment, neuronal/axonal and excitotoxic injury. BBB impairment was associated with white matter disruption. These are suggestive biomarkers for the presence, severity and prognosis of PASC CI. Such biomarkers could underpin appropriate trial design and timing of intervention.

Cerebellar and brainstem stroke possibly associated with booster dose of BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine.

As COVID-19 vaccination becomes widely available and administered globally, there have been several reports of side effects attributed to the vaccine. This report highlights a patient who developed stroke 2 days following the administration of the COVID-19 vaccine, although its association remains uncertain. A man in his late 30s developed acute neurological symptoms 2 days after receiving the booster dose of the BNT162b2 (Pfizer-BioNTech) mRNA COVID-19 vaccine. History and neurological examination suggested a posterior circulation stroke, which was confirmed by MRI, as a right-sided posterior inferior cerebellar artery stroke. Full workup did not suggest other causes of the stroke. Due to the patient's age and well-controlled risk factors, it was presumed to be a rare adverse effect of the vaccine. Medical management with aspirin, statin therapy and rehabilitation led to the improvement of symptoms and enabled ongoing restoration of function. Further cases of stroke following administration of COVID-19 vaccine have been documented in the literature, but the association is yet to be established.

Effect of the COVID-19 pandemic on young stroke

Background & Objective: Covid-19 infection has diverse effect on human health. We aimed to evaluate the effect of COVID-19 pandemic on the young stroke cases in an emergency services in a tertiary hospital in Istanbul, Turkey. Method: A total of 86 patients younger than 50 years confirmed to have stroke seen between January 1, 2019 and December 31, 2020 were included in the study. The year 2019 was defined as the pre-pandemic period and the year 2020 as the pandemic period. The patients' stroke type, localization, mortality, laboratory and imaging data were evaluated. Results: Eighty-six patients were included in the study. The mean age was 38.69±5.39 years, 49 (57%) were female. Of the patients, 78 (90.7%) were ischemic and 8 (9.3%) were hemorrhagic stroke. In the pandemic group, ischemic stroke was observed in 55 (96.5%) and hemorrhagic stroke in 2 (3.5%) (p=0.010). While the mean age of the patients in the survival group was 39.24±5.70 years, it was 36.61±3.38 years in the mortality group (p=0.008). While the mortality was 18 (20.9%) overall, it was 16 (18.6%) patients during the pandemic period, and 2 (2.3%) patients in the pre-pandemic period, the difference was statistically significant. (p=0.014). Conclusion: COVID-19 infection appear to increase the risk of ischemic stroke and worsens the mortality among the young. More comprehensive and prospective studies are needed to confirm this observation. © 2023, ASEAN Neurological Association. All rights reserved.

Central Nervous System Distribution of the Ataxia-Telangiectasia Mutated Kinase Inhibitor AZD1390: Implications for the Treatment of Brain Tumors

Effective drug delivery to the brain is critical for the treatment of glioblastoma (GBM), an aggressive and invasive primary brain tumor that has a dismal prognosis. Radiation therapy, the mainstay of brain tumor treatment, works by inducing DNA damage. Therefore, inhibiting DNA damage response (DDR) pathways can sensitize tumor cells to radiation and enhance cytotoxicity. AZD1390 is an inhibitor of ataxia-telangiectasia mutated kinase, a critical regulator of DDR. Our in vivo studies in the mouse indicate that delivery of AZD1390 to the central nervous system (CNS) is restricted due to active efflux by P-glycoprotein (P-gp). The free fraction of AZD1390 in brain and spinal cord were found to be low, thereby reducing the partitioning of free drug to these organs. Coadministration of an efflux inhibitor significantly increased CNS exposure of AZD1390. No differences were observed in distribution of AZD1390 within different anatomic regions of CNS, and the functional activity of P-gp and breast cancer resistance protein also remained the same across brain regions. In an intracranial GBM patient-derived xenograft model, AZD1390 accumulation was higher in the tumor core and rim compared with surrounding brain. Despite this heterogenous delivery within tumor-bearing brain, AZD1390 concentrations in normal brain, tumor rim, and tumor core were above in vitro effective radiosensitizing concentrations. These results indicate that despite being a substrate of efflux in the mouse brain, sufficient AZD1390 exposure is anticipated even in regions of normal brain. SIGNIFICANCE STATEMENT Given the invasive nature of glioblastoma (GBM), tumor cells are often protected by an intact blood-brain barrier, requiring the development of brain-penetrant molecules for effective treatment. We show that efflux mediated by P-glycoprotein (P-gp) limits central nervous system (CNS) distribution of AZD1390 and that there are no distributional differences within anatomical regions of CNS. Despite efflux by P-gp, concentrations effective for potent radiosensitization are achieved in GBM tumor-bearing mouse brains, indicating that AZD1390 is an attractive molecule for clinical development of brain tumors.Copyright © 2022 American Society for Pharmacology and Experimental Therapy. All rights reserved.

A Case of Sars-Cov-2 Omicron Variant Associated Acute Encephalomyelitis

With the ongoing pandemic of SARS-CoV-2 many neurological complications in relation to COVID-19 infection as well as immune-mediated and vaccine-associated phenomena have been described. To our knowledge, there has been no publication of a case of SARS-CoV-2 Omicron variant associated acute encephalomyelitis. We present a case of a 73-year-old woman with no relevant Background history who is otherwise fit and well and fully vaccinated. She suffered from mild COVID symptoms and had a positive PCR test with presumptive Omicron variant on day 2. Five days into her respiratory illness she developed in quick suc- cession sensory disturbances of hands and feet, bilateral asymmetric flaccid leg weakness, and mild arm weakness. She had absent deep tendon reflexes in the legs and diminished deep tendon reflexes in the right arm. MRI of brain and spine showed signal changes in the brainstem, cervical and low thoracic cord in keeping with acute encephalomyelitis. Her CSF showed an inflammatory picture with raised protein of 1.27g/L and no cells. At the time of submission, the patient received treatment with five days of intravenous steroids followed by ongoing plasma exchange and no comment on treatment response can be made at this stage.

Post-COVID-19 acute disseminated encephalomyelitis: Case report and review of the literature

Background: Our understanding of the spectrum of neurological manifestations associated with COVID-19 keeps evolving. Reports of life-threatening neurological complications, such as acute disseminated encephalomyelitis (ADEM), are alarmingly growing in number. Case presentation: We report a 42 years old previously healthy man who presented with left visual loss and cognition deterioration, manifesting at least ten days after infection with SARS-CoV-2. Serological work-up for potential immunological markers (i.e., antibodies against aquaporin-4 and myelin oligodendrocyte glycoprotein) were negative. Magnetic resonance imaging revealed multiple bilateral and asymmetrical lesions in the brainstem, cortical, juxtacortical, and periventricular regions, with surrounding edema. Post-contrast sequences demonstrated punctate, ring, and open ring enhancement patterns. Methylprednisolone pulse therapy was initiated for the patient, and he was placed on rituximab. After one month, his clinical symptoms had resolved, and his cognitive function was normal. Conclusion(s): We conducted an extensive literature search, and COVID-19-associated ADEM cases reported thus far were identified and reviewed. ADEM often occurs in a post-infectious fashion;however, it is unclear how SARS-CoV-2 infection can trigger such rapidly progressive episodes of encephalopathy and demyelination. Nevertheless, considering the alarming number of cases of ADEM developing after SARS-CoV-2 infection, neurologists should consider this severe phenotype of COVID-19 neurological complication in mind, enabling prompt therapeutic interventions to be made.Copyright © 2022

Neuro-Behcet's disease in the setting of active COVID-19 infection

Background: Cases of SARS-COV-2 triggering or exacerbating autoimmune responses has been described in the literature, and it has shown that use of steroids in non-severe COVID-19 may potentially increase mortality. Case presentation: A 22 year-old African-American man presented with headache, weight, loss, and oral/scrotal ulcerations. Case report: Neurological exam revealed somnolence and right hemiplegia. MRI was remarkable multiple enhancing lesions involving the brainstem and left hemisphere. He was found to have a positive SARS-CoV-2 test. Work-up was unrevealing, and he was diagnosed with Neuro-Behcet's disease (NBD) based on the International Criteria for Behcet's Disease (ICBD)ackspaceD)BackspaceBackspacep. The patient was treated with systemic steroids, which resulted in both clinical and radiological improvement of his disease without exacerbation of his SAR-CoV-2 infection. Conclusion(s): This case presentation suggests that IV steroids may be safe in the treatment of NBD in adult patients presenting with SARS-CoV-2 infection.Copyright © 2021

Varicella zoster virus cerebellitis without skin manifestations in an immunocompetent adult.

The varicella zoster virus (VZV) is a ubiquitous, neurotropic pathogen capable of reactivation from sensory ganglion cells to cause dermatomal herpes zoster infection, alongside a range of pathologies within the central nervous system. The presence of VZV cerebellitis without skin manifestations, however, is exceedingly rare in immunocompetent adults.We report a case of VZV cerebellitis in an immunocompetent woman in her 70s, in the absence of a rash. The patient presented with a 2-week history of progressive gait ataxia, headache and mild confusion. Serological tests and neuroimaging were unremarkable. Diagnosis was confirmed through cerebrospinal fluid (CSF) analysis which revealed lymphocytosis and the presence of VZV DNA on PCR analysis. The patient showed symptomatic improvement following empirical acyclovir treatment, corroborated by favourable CSF analysis 10 days post-treatment initiation.Infective aetiology, including VZV, should be considered in patients presenting with acute cerebellar ataxia, even in immunocompetent adults with an absence of dermatological signs.

An Unusual Case Presentation of MOG-Positive Acute Disseminated Encephalomyelitis (ADEM) in a Preschool Child

Introduction: An unusual case presentation of MOG-positive Acute Disseminated Encephalomyelitis (ADEM) in a preschool child following meta-pneumo viral infection responded to the combination of immune modulatory treatment with a favourable outcome. Material: Three-year-old female child presented with acute encephalopathy, high fever, vomiting, starring episodes, floppiness, and left abducent nerve palsy with rapid deteriorating GCS necessitating intubation and ventilation. Two weeks earlier, she was treated for suspected CNS infection with 10 days of antibiotics in the PICU with a positive meta-pneumo-virus. On admission, she had a GCS score of 6 with left-sided increased tone, bilateral hyperreflexia, and bilateral extensor response and on Day 14 demonstrated hyperkinetic movements of the upper and lower limbs. Method(s): Serum MOG antibody positive, CSF MOG low positive, metabolic investigations, Mycoplasma, EBV, Influenza, corona PCR, SARS-COV-2 Antibody, viral CSF panel unremarkable. MRI brain demonstrated T2 hyperintense signal in bilateral medial thalami and brain stem with a normal spine. Progressive changes were shown on repeated MRI Brains on day 4 and day 14 suggestive of multifocal changes involving deep cortical and subcortical white matter bilaterally with a new short segment of the spinal lesion at the T8 level. Repeated EEG and ambulatory EEG showed a diffusely slow background with intermittent slow runs of slow waves suggestive of generalized cerebral dysfunction. Result(s): After receiving the combination of high pulse steroids with a taper over 10 weeks, IVIG and 10 cycles of plasmapheresis she demonstrated gradual and remarkable clinical improvement over 10-12 weeks with a minimal focal neurological deficit. Conclusion(s): Initial differentiating CNS infection, metabolic disease and ADEM may be clinically challenging. Her clinical presentation, investigations and imaging were in keeping with the diagnosis of MOG-positive ADEM. Previous CNS infection may be related. MOG-positive ADEM treated with the early combination of immunomodulation may lead to positive clinical outcomes.

Multi-System and Cavernous Sinus Inflammatory Syndrome Presenting with Evolving Multiple Cranial Neuropathies Following Zoledronate Infusion

Case report - Introduction: Bisphosphonates are known to rarely cause multi-system inflammation, including multiple cranial neuropathies. This is possibly via provoking transient cytokine storm. The literature reports bisphosphonate-associated orbital inflammatory syndrome, and one case of retrobulbar optic neuritis following zoledronate. Bisphosphonate manufacturers report conjunctivitis, blurred vision, scleritis, orbital inflammation, uveitis and episcleritis as ocular side effects. Separately, neurological sequalae, including cranial neuropathies, are reported following COVID-19 infection and vaccination. Here, we report the first case of cavernous sinus inflammation temporally related to both zoledronate infusion, and more remotely, to Pfizer- BioNTech COVID-19 vaccination. Case report - Case description: A 76-year-old white man developed fever, bony leg pain - which rendered him unable to walk - and frontal headache, within 8 hours of his first zoledronate infusion for osteoporosis. A few weeks earlier he received his first Pfizer-BioNTech COVID-19 vaccine. His General Practitioner commenced a short course of lowdose oral prednisolone for the episode. One week later, off prednisolone, the headache localised around the left eye. He developed horizontal diplopia associated with abduction deficit. He was diagnosed with left VIth nerve palsy. He was started on high-dose steroids and clopidogrel (with PPI) with neuroimaging to exclude stroke or venous sinus thrombosis. Two weeks later, the diplopia worsened over 4 days, with new left adduction deficit (-2 limitation), left ptosis 1-2mm and anisocoria 0.5-1mm R>L suggestive of partial third nerve palsy and early Horner's syndrome. Ocular and neurological examinations were otherwise normal. He wore varifocals and had migraines, osteoporosis, and asthma, for which he used inhalers. He worked in visual arts and was an ex-smoker (>50 years) with moderate alcohol intake. Blood results revealed CRP 38mg/L, but otherwise normal inflammation/ vasculitis/infection screen;anti-thyroglobulin antibodies were >4000 U/ml;GQ1P, Creatinine Kinase, anti-ganglioside, and Anti- AChR/MuSK antibodies were normal. CT head and Optical Coherence Tomography were unremarkable. An enhanced MRI of the brain and orbits revealed abnormal thickening and T2 hyper-intensity of the left oculomotor nerve, most notably involving the left canalicular portion. The left cavernous sinus also appeared asymmetrically bulky with a rind of abnormal enhancing soft tissue in the left cavernous sinus. Subtle STIR hyper-intensity was also observed in the ipsilateral CN IIIinnervated extra-ocular muscles. After a 6-week course of tapering prednisolone, the vertical diplopia and leg swelling persisted;the horizontal diplopia and headaches had resolved. By 3months, there was resolution with mild residual visual changes. Case report - Discussion: We report a constellation of symptoms relating to multi-system inflammatory syndrome involving the cavernous sinus. There is a lack of epidemiological data on the incidence of this rare presentation in the population. This case has close temporal association to bisphosphonate infusion (<12h) and weaker association to coronavirus vaccination (<3wk). It is difficult to determine whether this is a rare presentation of a known drug reaction, a more delayed presentation of a vaccine reaction or whether these events were coincidental. A further possibility in this case is a combined predisposition resulting from both vaccination and bisphosphonate infusion. This case highlights a wider issue relating to the challenging possibility of ascertainment bias and increased 'Yellow Card' reporting of rare presentations during this historic global coronavirus pandemic, which may or may not have any true causal association to vaccination. There is difficulty in disentangling a true vaccine reaction from an unrelated presentation of a rare condition with an unknown baseline incidence rate. This is especially topical given that the majority of the population are receiving the coronavirus ccination at this time. We also question what a plausible cut-off point would be to propose a temporal relationship for an adverse reaction;in the literature, adverse reactions have been postulated to develop beyond 1 month after the provoking agent. Case report - Key learning points: . This case highlights the need for urgent assessment, investigations including neurological imaging and consultant input in patients with evolving cranial neuropathy. The priority is to rule out thrombotic, compressive, inflammatory and infectious pathology in the cavernous sinus, venous sinus, orbit and orbital apex. . Pathology of the cavernous sinus presents with variable involvement of CN III, IV, V and VI and Horner's syndrome. A differential for this case would be superior orbital fissure syndrome, which also presents with multiple oculomotor cranial neuropathies;it involves these cranial nerves and the ophthalmic branch of CN V. Orbital apex syndrome is SOF with a loss of vision due to additional CNII involvement. . The neuro-radiology differential included inflammatory, infiltrative, granulomatous and neoplastic aetiologies and that there was sufficient existing evidence to exclude brainstem pathology. . Through communication between specialties, the temporal relationship was established, and clinical examination and extensive investigation further honed the differential to either inflammatory or vascular. Since it was temporally related to the zolendronate infusion, it seemed plausible it was related. We demonstrate the need for multi-disciplinary collaboration for these patients between rheumatology, ophthalmology and neuro-radiology.

Unmasking of a Relapsing Encephalomyelitis After SARSCoV- 2 Infection and COVID-19 Vaccination

Objective NA. Background Prior case studies suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its vaccines may unmask neuroinflammatory conditions. We present a case of relapsing steroidresponsive encephalomyelitis after SARS-CoV-2 infection and subsequent COVID-19 vaccination. Design/Methods NA. Results A 47-year-old man with a history COVID-19 presented with subacute lower extremity weakness, erectile dysfunction, and gait instability with falls. His symptoms started several weeks after COVID-19 vaccination which he underwent 3 months afterCOVID-19 infection. His initial exam demonstrated weakness at the knees and ankles and extensor plantar responses. MRI demonstrated innumerable enhancing lesions involving the subcortical white matter, basal ganglia, thalami, brainstem, cerebellum, and the entire spinal cord parenchyma. CSF testing revealed a lymphocytic pleocytosis (10 WBC, 88% lymphocytes), and transient matched serum and CSF oligoclonal bands. Testing was unremarkable for infections, malignancies, primary demyelinating conditions, etc. He responded dramatically to five days of high dose methylprednisolone but had recurrence of symptoms with weaning of oral prednisone, requiring another pulse of IV steroids. After 2 months, his steroids were weaned again, with clinical and radiographic recurrence, requiring another course of IV steroids. He was subsequently transitioned to mycophenolate as a steroidsparing agent. Literature review identified 20 additional cases of CNS neuroinflammatory disease after either SARS-CoV-2 infection or vaccination (11 transverse myelitis, 6 optic neuritis, 3 encephalomyelitis). Conclusions Our patient's steroid-dependency and relapsing course suggests unmasking of an underlying CNS neuroinflammatory condition. Temporal associations of neurological conditions with vaccinations or infections do not prove causality despite previous reports of such sequelae. Vaccines containing SARS-CoV-2 antigens may enhance autoimmunity by mechanisms including polyclonal activation, epitope spreading, or molecularmimicry. This case highlights that the resulting inflammation may be insidious and extensive, though treatable. As COVID-19 constitutes a life-threatening infection in some patients, the benefits of vaccination outweigh the smaller risk of unmasking an immune-related condition.

Cerebral Vasculopathy-Associated Ischemic Stroke in the Setting of Bacterial Meningitis

INTRODUCTION: Bacterial Meningitis is known to have high morbidity and mortality rates. A less recognized complication from this disease includes acute ischemic stroke, which conveys a worse prognosis. DESCRIPTION: A 37-year-old previously healthy woman presented to the hospital with progressive encephalopathy associated with ataxia and dysarthria. Her immediate past travel history revealed a trip to Europe where she endured a COVID19 infection three weeks before her admission. Nevertheless, she recovered without any complications. However, she developed fatigue and headaches, prompting a diagnosis of post-COVID19 syndrome by her primary care physician. Over the course of several days, her ability to carry out her normal daily activities and perform work-related duties deteriorated as she developed severe fatigue accompanied by a painless diffuse skin rash. She presented to the ED once she started having symptoms of dysarthria, abasia, and truncal ataxia. An emergently obtained CSF sample was consistent with bacterial meningitis. Standard empiric antibiotics and steroids were administered. The patient's condition acutely decompensated soon after antibiotics administration. A follow-up head CT showed global cerebral edema and hydrocephalus, triggering an EVD placement for ICP monitoring. An MRI brain showed multiple bilateral acute ischemic strokes in the brainstem and basal ganglia. A head CT angiography showed diffuse narrowing of the cerebral arteries. The patient ultimately completed a course of antibiotics (Neisseria PCR was positive). We used TCD-guided blood pressure augmentation to prevent the progression of cerebral ischemia. The patient was discharged on long-term steroid therapy for presumed post-infectious vasculopathy. A follow-up MRI brain did not reveal a progression of cerebral ischemia. DISCUSSION: Bacterial Meningitis is a severe disease with significant complications. One such complication is ischemic stroke. However, the exact pathophysiology is unknown. Understanding the risks of developing cerebral ischemia and the related pathophysiology could help improve patient outcomes with better treatment modalities. The interplay between COVID19 infection and conventional infectious pathogens is an ongoing area of interest.

Bickerstaff's brainstem encephalitis mimicking herpetic encephalomyelitis in a liver transplant patient with anti-GQ1b antibodies.

A woman in her late 70s with a history of liver transplant presented with ophthalmoplegia, ataxia, areflexia, positive Babinski's sign and reduced consciousness. This followed an antecedent illness in the form of a herpes zoster infection. MRI of the brain/spinal cord, cerebrospinal fluid analysis with viral PCR and routine blood tests were normal, and tacrolimus neurotoxicity was ruled out. Serum anti-GQ1b antibodies were positive. A diagnosis of Bickerstaff's brainstem encephalitis was made, forming part of the continuum that involves Miller-Fisher syndrome, entitled the 'anti-GQ1b syndrome'. Complete recovery ensued without intravenous immunoglobulins or plasma exchange. The role of monitoring anti-ganglioside pattern change to predict or confirm disease recurrence and disease severity is further discussed.

Tocilizumab treatment of MOGAD encephalitis nonresponder to Anti CD-20 therapy: efficacy and safety during SARS-COV-2 infection

Introduction: Myelin oligodendrocyte glycoprotein antibodyassociated disease (MOGAD) is an autoimmune disorder of the central nervous system distinct from multiple sclerosis (MS) and neuromyelitis optica spectrum disorder. Common clinical presentations include a recurrent optic neuritis, transverse myelitis, acute disseminating encephalomyelitis (ADEM) or ADEM-like syndromes, and brainstem encephalitis. Objectives/Aims: To report a case of patient affected by MOGAD encephalitis who experienced SARS-CoV-2 infection during the treatment with Tocilizumab. Methods and Results: We report a case of a 57-year-old Caucasian woman with a 5-year history of a demyelinating disease characterized by bilateral and symmetric fronto-temporoparietal demyelinating lesions and previously diagnosed as MS. The patient had been treated with severaltherapies, including interferon beta-1a, Natalizumab, anti-CD-20 monoclonal antibodies, with no benefits.Her symptoms and brain magnetic resonance imaging (MRI) lesionsload had progressively worsened, resulting in a significantmotor and cognitiveimpairment.In April 2020, the diagnosis was reviewed and classified as MOGAD+ encephalitis.Thepatient started anti-CD-20 monoclonal antibody therapy, stopped due to lack of efficacycharacterized by increasing MRI lesion load and worsening of cognitive impairment. In February 2022, Tocilizumab, an IL-6 receptor inhibitor, was initiated at the dosage of 8 mg/kg via intravenous route. Further administrations were repeated every four weeksin March and April 2022. The treatment was well tolerated and the patient did not report any adverse event. IL-6 levels decreased and the caregiver reported an improvement in patient's cognitive performances. Furtherneurological examinations showed a mild improvement in motor performances, walking ability, and brainstem and cognitive functions. On April25th, the patient, previously vaccinated with three doses of Pfizer-BioNTech vaccine, tested positive to SARS-CoV-2which resulted in symptoms characterized by.fever, cough, joint pain, and shortness of breath. Two days after the symptoms onset, she started therapy with nirmatrelvir/ ritonavirobtaining a dramatic regression of all the symptoms in about24 hourswithout any adverse events. Conclusion(s): In light of the lack of literature on the co-occurrence of COVID-19 in Tocilizumab-treated MOGAD patients, the present report highlights the safety and benefit of the use of antiviral therapy in these patients.

Seasonal distribution of relapses in MOG antibody associated disease (MOGAD)

Introduction: The influence of environmental factors on central nervous system demyelinating conditions have been recently studied. In MOG antibody associated disease (MOGAD), a seasonal distribution of relapses is not yet well-defined. Objective(s):: To investigate the presence of seasonal distribution of MOGAD relapses. Method(s): Prospective data from consented MOGAD patients within the Oxford National NMO Highly Specialised Service were analysed until April 2022. Demographic and clinical characteristics, including relapse date and phenotype, were recorded. All relapses with month-defined dates were used to calculate observed monthly frequencies. Expected frequencies were calculated assuming an uniform distribution throughout the year, adjusting for month's length and patient numbers under follow up. Any deviation from a uniform distribution was analysed, and seasonal peaks were assessed using Friedman's, Edward's, Ratchet circular scan and Hewitt's rank-sum tests. Result(s): Three-hundred-four MOGAD patients were included, 190 (62.5%) females, mean age at onset 31 years (SD 16.9), median disease duration 3.0 (IQR 5.0) years, 77 (25.3%) with paediatric age onset. No significant seasonal pattern was identified when analysing all relapses (n=691), or onset relapses (n=286). Regarding age of disease onset, no seasonal pattern was found in onset under 18 (n=483) or over 18 years old (n=208). Regarding phenotype, no seasonal pattern was found in optic neuritis (n=483), transverse myelitis (n=180) or brain and brainstem relapses (n=125). Analysing all the relapses from the start of the COVID-19 pandemic (March 2020 - February 2022, n=112), a seasonal peak was identified from March to May (V(N)=0.132, p<0.05). Conclusion(s): No seasonal pattern of relapses in MOGAD was noted until the COVID-19 pandemic started in the UK. Seasonal infection peaks during winter and subsequent lockdowns could have influenced MOGAD relapse rates in the past two years.

A Shift in SARS-CoV-2 Omicron Variant's Entry Pathway Might Explain Different Clinical Outcomes.

Globally, SARS CoV-2 omicron variant has led to a notable increase of COVID-19 diagnoses, although with less severe clinical manifestations and decreased hospitalizations. The omicron wave swelled faster than previous waves, completely displacing the delta variant within weeks, and creating worldwide concern about final, successful pandemic control. Some authors contend that symptoms associated to omicron differ from 'traditional' symptoms and more closely resemble those of the common cold. One major COVID-19 symptom frequent with other variants-loss of taste and smell-is rarely present with omicron. This may be of interest, since it has also been suggested that direct SARS-CoV-2 invasion into the brainstem through the olfactory nerves by transsynaptic pathways could provide one explanation for the acute respiratory distress syndrome refractory to treatment. Brainstem infection by SARS-CoV-2 can severely damage the respiratory center, triggering functional deviations that affect involuntary respiration, leading to acute respiratory distress syndrome refractory to treatment, the main cause of death in COVID-19 patients. A shift in the omicron SARS-CoV-2 entry pathway from cell-surface fusion, triggered by TMPRSS2, to cathepsin-dependent fusion within the endosome, may affect transmission, cellular tropism and pathogenesis. Therefore, we can hypothesize that this entrance modification may impact transmission from the olfactory nerve to the brainstem through transsynaptic pathways. A decrement of the virus's direct invasion into the brainstem could diminish respiratory center dysfunction, reducing acute respiratory distress syndrome and the need for mechanical ventilation.

Brain stem encephalitis is a rare complication of COVID-19.

Here, we describe the clinical phenotype of SARS-CoV-2-related CNS disease and evaluate the SARS-CoV-2 antibody index as a tool to differentiate between a direct (viral) and indirect etiology. Out of >4000 hospitalized patients with COVID-19, we included 13 patients with neurological symptoms with suspicion of neuroinflammation. On clinical grounds, eight were classified as having a possible/probable relationship between neurological symptoms and COVID-19. A clinically distinctive phenotype of brainstem and cerebellar symptoms was seen in 6/8 patients. As we found a positive SARS-CoV-2 antibody index in 3/5 patients, indicating specific intrathecal SARS-CoV-2 IgG production, a direct link with SARS-CoV-2 is likely.

Sudden sensorineural hearing loss in coronavirus disease-2019: Our experience

Coronavirus disease-2019 (COVID-19) is an ongoing global pandemic exerting considerable strain on the health-care system. Sudden-onset sensorineural hearing loss (SSNHL) among patients with COVID-19 had been reported sparingly in the literature. Hearing loss can be easily overlooked in intensive care settings and establishing diagnosis can also be challenging. Proposed causes include injury to inner ear structures, cochlear nerve, or auditory brainstem. Prompt diagnosis and treatment is recommended to avoid long-term morbidity. All patients presenting with sudden-onset hearing loss should be screened for COVID-19. Here, we report a case of COVID-19 patient with SSNHL and how the hearing level is determined. Copyright © 2022 Indian Journal of Otology Published by Wolters Kluwer-Medknow.