Eye Disorders and Neuro-ophthalmic Manifestations of COVID-19

Growing data are confirming the association between the novel coronavirus disease (COVID-19) and eye disorders, including ocular alterations and neuro-ophthalmic manifestations. The main pathophysiological mechanisms considered included a direct infection through the ocular surface, a post-viremia secretion of the virus from the lacrimal glands, and a viral dissemination through the bloodstream. According to the different ways of contagion, different structures could be involved.The most common ocular symptoms reported in COVID-19 patients were dry eye, redness, tearing, itching and pain. Among symptomatic patients, most of them presented conjunctivitis. Considering the posterior chamber, retinal artery and vein occlusions were described in few clinical reports;moreover, some studies presented cases of paracentral acute middle maculopathy occurring in COVID-19 patients. The involvement of the choroid seems to be rare, and a single case of atypical choroiditis was currently described. Between neuro-ophthalmic manifestations, optic neuritis appear to be relatively frequent and generally not associated with magnetic resonance imaging abnormalities. Some reports showed the involvement of the ocular motor nerves, often presenting with palsy. Miller Fisher syndrome has been showed in rare cases;however, this association could be corroborated by the several reports describing Guillain-Barré syndrome occurrence in COVID-19 patients.In line with well-known previous viral infection, COVID-19 seems to be associated with eye involvement. Thus, ocular and neuro-ophthalmic symptoms and signs should be carefully assessed and monitored in these patients. To reach this purpose, it is critical to implement remote diagnostic techniques. Moreover, the comprehension of the pathogenetic mechanisms is still scarce and no standardized diagnostic protocol was established for these patients, making necessary further studies to improve current understandings. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Type 1 diabetes and environment . . . and other stories

A linked ecological analysis of environmental and demographic variables identified several factors, including poor air quality, outdoor light at night, and higher population density that were negatively associated with the incidence of diabetes (Diabetologia doi:10.1007/s00125-020-05087-7). A case-control study using a database of people known to have autoimmune disease raises anxiety about central nervous system inflammatory events (JAMA Neurol doi:10.1001/jamaneurol.2020.1162). A history of exposure to TNF inhibitors carried a threefold increase in risk both of demyelinating diseases, such as multiple sclerosis and optic neuritis, and of non-demyelinating conditions, such as encephalitis, neurosarcoidosis, and vasculitis.

Ocular Adverse Events after Coronavirus Disease 2019 mRNA Vaccination: Matched Cohort and Self-Controlled Case Series Studies Using a Large Database.

PURPOSE: To investigate the risk of ocular adverse events after Coronavirus Disease 2019 (COVID-19) mRNA vaccination. DESIGN: Matched cohort and self-controlled case series (SCCS) studies. PARTICIPANTS: We used a population-based database of medical claims and vaccination records in a large Japanese city. In the matched cohort study, we identified individuals who received COVID-19 vaccination (BNT162b2) from February 2021 to September 2021. One control was selected from nonvaccinated individuals by matching time, date of birth, sex, Charlson comorbidity index, and the enrollment period for health insurance. In the SCCS study, we analyzed individuals who developed ocular adverse events. METHODS: In the matched cohort study, we applied the Kaplan-Meier estimator to estimate the cumulative incidence of ocular adverse events over 21 days after the first dose and 84 days after the second dose. In the SCCS method, we used conditional Poisson regression to estimate the incidence rate ratio (IRR) of ocular adverse events during the risk periods (0-21 days after the first dose and 0-84 days after the second dose) compared with the remaining periods. MAIN OUTCOME MEASURES: Composite outcome of uveitis, scleritis, retinal vein occlusion (RVO), and optic neuritis. RESULTS: There were 99 718 pairs eligible for the matched cohort study after the first dose (mean age, 69.3 years; male, 44%). The vaccinated and control groups developed 29 and 21 events, respectively, over 21 days after the first dose, and 79 and 28 events, respectively, over 84 days after the second dose. The differences in cumulative incidence (reference, the control group) were 2.9 (95% confidence interval, -14.5 to 19.1) events/100 000 persons and 51.3 (16.2-84.3) events/100 000 persons, respectively, for the first and second doses. The SCCS study showed the IRRs of 0.89 (0.62-1.28) and 0.89 (0.71-1.11) for the first and second doses, respectively. CONCLUSIONS: The matched cohort analysis found an increased risk for the composite outcome after the second dose; however, the SCCS analysis showed no increased risk. Considering that the SCCS can cancel out time-invariant confounders, the current results suggest that COVID-19 vaccination is unlikely to causally increase the risk of ocular adverse events. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

The Implications of SARS-CoV-2 Infection in a Series of Neuro-Ophthalmological Manifestations-Case Series and Literature Review.

The global pandemic impact of the COVID-19 infection included clinical manifestations that affected several organs and systems, with various neuro-ophthalmological manifestations associated with the infection. These are rare and occur either secondary to the presence of the virus or by an autoimmune mechanism secondary to viral antigens. The manifestations are atypical, being present even in the absence of the systemic symptoms typical of a SARS-CoV-2 infection. In this article, we introduce a series of three clinical cases with neuro-ophthalmological manifestations associated with COVID infection that were shown in Ophthalmology Clinic of St. Spiridon Emergency Hospital. Case 1 is that of a 45-year-old male patient with no personal history of general pathology or ophthalmology, with binocular diplopia, painful red eyes, and lacrimal hypersecretion with a sudden onset of about 4 days. Based on the evaluations, a positive diagnosis of orbital cellulitis in both eyes is made. Case 2 is that of a 52-year-old female patient with general PPA (personal pathological antecedents) of SARS-CoV-2 infection 1 month prior to presentation with decreased visual acuity in the right eye and a positive central scotoma, preceded by photopsia and vertigo with balance disorders. The diagnosis is made at the right eye for retrobulbar optic neuritis and post-SARS-CoV-2 infection status. The last clinical case is that of a 55-year-old male patient known to have high blood pressure (HBP) with a sudden, painless decrease in VARE approximately 3 weeks post-SARS-CoV-2 immunization (Pfizer vaccine first dose). The diagnosis is made after consulting all the RE results for central retinal vein thrombosis. Conclusions: Although the cases were quickly and efficiently investigated and the treatment was administered adequately by a multidisciplinary team (cases 1 and 3), the evolution was not favorable in all three situations. Atypical neuro-ophthalmological manifestations can also be present in the absence of systemic symptoms typical of SARS-CoV-2 infection.

Management of Allergic Fungal Rhinosinusitis Associated with Vision Loss During COVID-19 Era.

The ongoing COVID-19 pandemic has given rise to unique challenges related to healthcare management. The problems have arisen due to the direct effect of COVID 19 infection and treatment or as repercussions of administrative efforts being undertaken to check the rapid spread of the epidemic. The management of some of the diseases has been hampered with the implementation of the policies like lockdown and transportation difficulties. This paper presents a series of four patients (6 eyes with vision loss) of an otherwise benign entity, Allergic Fungal Rhinosinusitis (AFRS), causing visual deterioration, managed amid the pandemic. AFRS has been known to cause vision loss by pressure over the optic nerve or its blood supply; however, a timely surgical intervention in the form of functional endoscopic sinus surgery to remove the disease and decompress the optic nerve, results in favourable outcomes in most patients. A delay in diagnosis and treatment may result in irreparable damage with the resulting inability to salvage the vision. In our series, we observed that vision recovery could be achieved in 66.7% of the affected eyes (four out of six eyes), while a poor visual outcome was observed in two (33%). The poor visual outcome was observed for the eyes with a prolonged visual impairment (4-6 months) at the time of presentation. We would appeal to the physicians to be cognizant of the adverse outcomes associated with the delayed surgical intervention of AFRS in the current pandemic scenario.

AAPOS Pediatric Uveitis Committee: COVID-19-infection, inflammation, and challenges in children with noninfectious uveitis

Purpose/Relevance: Pediatric cases of COVID-19 have increased in the setting of the highly transmissible delta variant which has impacted the care of children by ophthalmologists. Inflammatory ocular manifestations of acute COVID-19 infections have been observed and are important to recognize and expeditiously manage. Further, ocular involvement has been recognized in MIS-C. Finally, new challenges in treating and monitoring patients with non-infectious uveitis (NIU) evolved. Guidance is needed regarding immunosuppression, reducing clinic visits/in-hospital exposures while maintaining disease control, and vaccination. Target Audience: Pediatric ophthalmologists, fellows, residents. Current Practice: Ocular inflammatory manifestations are reported in children during or after symptomatic or asymptomatic COVID-19 infection and may go unrecognized. Guidelines for managing children with NIU on immunosuppressive treatment (IMT) continues to evolve, and updated information is needed. Best Practice: Knowledge of ocular manifestations of acute and post-infectious COVID-19 including Multisystemic Inflammatory Syndrome in Children (MIS-C) will improve clinical care of children. Patients may present with conjunctivitis, optic neuritis, transient myasthenia-like syndrome, acute anterior uveitis, keratitis, pan-uveitis and papilledema. Ophthalmic management often involves systemic work-up and coordination of care amongst a multidisciplinary team. Consensus guidelines for monitoring uveitis and preventing COVID-19 infection in children with NIU on IMT may be applied to clinical practice. Expected Outcomes: Clinicians will develop an understanding of (1) Ophthalmic manifestations of acute and post-infectious COVID-19 infection and MIS-C (2) Challenges and strategies to manage NIU during a pandemic (3) Updates on infection risk and vaccination strategies for children on IMT. Format: Didactic, case presentations, rheumatology, ophthalmology panel discussion with audience participation. Summary: COVID-19-related ocular manifestations such as conjunctivitis, uveitis, pan-uveitis and optic neuritis are rare but are important to recognize. Children with NIU on IMT represent a unique patient population balancing ophthalmic follow-up and control of ocular/systemic disease and preventing infection.Copyright © 2022

Bilateral longitudinally extensive optic perineuritis post-COVID-19 presenting as "idiopathic" intracranial hypertension: A case report

Background: Severe acute respiratory syndrome coronavirus 2 (SARSCoV2) has been associated with several neuro-ophthalmic manifestations. We report a case of bilateral longitudinally extensive optic perineuritis suspected due to SARSCoV2. Case Presentation: A 32-year-old woman developed headaches, photophobia, pulsatile tinnitus, and blurred vision 8 d after having a positive SARS-CoV-2 qualitative polymerase chain reaction (PCR) testing for coronavirus disease 2019 (COVID-19). She was diagnosed with and treated for idiopathic intracranial hypertension (IIH) elsewhere. Repeat evaluation at our institution showed a poor visual acuity in both eyes with Frisen grade II papilledema and cotton wool spots on fundoscopic examination. Orbital magnetic resonance imaging (MRI) showed bilateral longitudinally extensive optic nerve sheath enhancement. Repeat lumbar puncture revealed an elevated cerebrospinal fluid (CSF) opening pressure and protein, a finding that is incompatible with the diagnosis of IIH. Myelin oligodendrocyte glycoprotein, aquaporin-4 (AQP4)-IgG antibodies, and other serological tests for optic neuritis were unremarkable. Her visual acuity partially improved after corticosteroids. With the growing association of demyelinating disorders and COVID-19, unremarkable serological workup, and temporal relation of the patient's symptoms to the infection, we believe that her diagnosis is SARS-CoV-2 associated bilateral optic neuritis. Conclusion(s): There is a growing association between demyelinating disorders and COVID-19 and COVID-19 vaccination, and it is essential to recognize CSF abnormalities that are incompatible with a diagnosis of IIH, such as increased protein in our case, and may lead to an incorrect diagnosis.Copyright © 2023 The Authors. Clinical and Experimental Neuroimmunology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society for Neuroimmunology.

Bilateral optic neuritis and myocarditis after the first dose of COVID-19 vaccine

Since the introduction of COVID-19 vaccine, various adverse events have been reported including injection site pain, fatigue, headaches, and myocarditis. Cranial neuropathies and optic neuritis, have been also rarely reported, however, the significance of these autoimmune manifestations after the administration of COVID-19 vaccine remain controversial. In this report we present a case of myocarditis and bilateral optic neuritis that occurred in a young healthy male patient after the administration of first dose of mRNA-1273 vaccine (Moderna).Copyright © 2022 The Author(s)

An Astra-Nomical Headache

Introduction We present a case of myelin-oligodendrocyte glycoprotein antibody disease (MOGAD) requiring long-term immunosuppression triggered by a dose of the AstraZeneca COVID-19 vaccination. Relapsing MOGAD is thus far an unknown complication of COVID-19 vaccination. Case Description: A 58-year-old lady developed headache, nausea, dizziness, facial numbness, ataxia and slurred speech 8 days after the COVID-19 AstraZeneca vaccination. Her imaging showed acute disseminated encephalomyelitis (ADEM) with a white matter lesion in the left cerebellum and bilateral smaller lesions. Her cerebrospinal fluid showed 38 white cells and elevated protein. She initially responded well to steroids, however relapsed with optic neuritis 7 months later, requiring long-term immunosuppres- sion with mycophenolate mofetil. Discussion Although there have been some case reports of MOGAD following COVID-19 infection, to our knowledge this is only the second reported case of MOGAD following vaccination against COVID-19, and the first such case to require long-term immunosuppression. The other reported case also occurred following the COVID-19 AstraZeneca vaccine, and also presented with ADEM. This is in contrast to reported cases of MOGAD following COVID-19 infection, where adults mostly presented with optic neuritis. We wanted to highlight the possibility of this vaccine-related neurological complication occurring, particularly in the context of potentially frequent ongoing COVID-19 booster vaccinations.

Optic neuropathy after COVID-19 vaccination: Case report and systematic review

Purpose:: To report a case of anterior ischemic optic neuropathy (AION) following COVID-19 vaccination and provide a systematic review of all published cases of optic neuropathy following COVID-19 vaccination. Method(s):: A systematic literature search was performed using PubMed and Ovid MEDLINE for cases of optic neuropathy following COVID-19 vaccination. Terms used in the search included "COVID-19 vaccination", "optic neuropathy", "optic neuritis", and "ischemic optic neuropathy". Titles and s were initially screened then full texts of eligible studies were reviewed for data extraction. Only cases published in the English language, peer reviewed, and that included details on optic nerve involvement were included. All study types were eligible for inclusion. Result(s):: Including our patient, a total of 10 patients (8 females) were identified as developing optic neuropathy following COVID-19 vaccination. Five patients (50.0%) were diagnosed with AION, while 4 (40.0%) were diagnosed with optic neuritis. One patient was diagnosed with papillitis and neuroretinitis. Three patients (30.0%) had bilateral involvement. Mean age of patients was 48.5+/-19.7 years. Mean time from vaccination to onset of ophthalmic symptoms was 6.5+/-6.4 days. Median (IQR) presenting visual acuity was logMAR 0.3 (0-1). For the 8 eyes which had both presenting and final follow-up visual acuity, median (IQR) presenting vision was logMAR 0.2 (0-0.7) and at final follow-up was logMAR 0 (0-0.05) (P=0.184). Conclusion(s):: COVID-19 vaccination may result in optic neuropathy in the form of optic neuritis and ischemic optic neuropathy. Further studies are needed to determine the incidence, management, and prognosis of optic neuropathies associated with COVID-19 vaccination.Copyright © 2022

Utility of optical coherence tomography in patients of central immune mediated demyelinating diseases - A prospective study.

Optical coherence tomography (OCT) is a non-invasive tool to measure thickness of various layers of retina. Recently, retinal nerve fibre layer (RNFL) and ganglion cell and inner plexiform layer (GCIP) thinning has been observed in OCT in patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), This study compared OCT profile, along with visual acuity (VA), color vision (CV), contrast saturation (CS) and visual evoked potentials (VEP) in two main cohorts of MS and NMOSD and with controls, during acute episode of optic neuritis (ON), at 3 and 6 months. We found that changes of ON were present in 75% of MS eyes and in 45% of NMOSD patients. Of these, subclinical involvement was present in 56.25% of MS eyes and only in 5% of NMOSD eyes suggesting frequent subclinical involvement in the former. Mean RNFL was 95.23 ± 15.53 in MS and 66.14 ± 43.73 in NMOSD after 6 months of ON episode. Thinning of NQ and IQ was observed in NMOSD eyes in the immediate period after ON attack. At 6 months relative sparing of RNFL in TQ was observed in NMOSD ON eyes and MS ON showed predilection for involvement of TQ.

Neuro-Ophthalmic Complications of COVID-19 Infection and Vaccination.

The COVID-19 pandemic has led to the identification of new disease phenotypes associated with infection by the SARS-CoV-2 virus. This includes multiple neuro-ophthalmological sequelae, which have been associated with COVID-19 infection and administration of COVID-19 vaccines. Some of these associations have a plausible pathophysiological link to the infection or vaccination but true causation has yet to be established. We review the literature for associations reported between COVID-19 infection or vaccination and neuro-ophthalmic sequelae and review the potential pathophysiological processes that may underlie these associations.

New-onset neuromyelitis optica spectrum disorder in a patient with COVID-19 and chronic Hepatitis B co-infection

Background: Neurological autoimmune disorders are often triggered by bacterial and viral infections, with growing evidence supporting coronavirus disease 2019 (COVID-19) infection precipitation of these disorders. COVID-19 is already implicated in causing discrete para-infectious neurological syndromes: acute disseminated encephalomyelitis (ADEM), transverse myelitis, neuromyelitis optica spectrum disorders (NMOSD), Guillain-Barre syndrome (GBS), and is also associated with encephalopathy, acute cerebrovascular disease, neuromuscular disorders, and seizures. Case Presentation: We describe a case of a 43-year-old Asian woman with chronic Hepatitis B (HBV) co-infected acutely with COVID-19, presenting with urinary retention, bilateral blindness, thoracic sensory level, and quadriparesis. Extensive workup narrowed down her diagnosis as seronegative NMOSD. She had complete resolution of symptoms after treatment with concurrent plasma exchange (PLEX), high dose corticosteroids, and emtricitabine-tenofovir. Follow-up visit showed no seroconversion at 6 months and no relapses. Conclusion(s): Our literature review highlights the likely link between COVID-19 infection and the development of neurologic autoimmune diseases. Our literature review supports a virus-triggered immune-mediated process rather than neuro-invasion. Many viral illnesses have been linked to the development of NMOSD and anti-AQP4 antibody-related myelitis. Additionally, there is limited literature linking chronic HBV infection with the development of optic neuritis and speculation thatcross-reactivity between HBsAg and myelin antigens may lead to the development of demyelinating diseases in the CNS and PNS. We observed remarkable clinical improvement after treatment with alternating days of IV methylprednisolone and therapeutic PLEX.Copyright © 2022

Transient optic neuritis and perineuritis associated with anti-MOG antibody after SARS-CoV-2 mRNA vaccination

Backgrounds: To report the first case of left optic neuritis and perineuritis associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BNT162b2 mRNA vaccination. Case presentation: A 39-year-old woman was referred and admitted to our hospital due to transient left visual field abnormality with left ophthalmalgia and headache 12 days after the first vaccination dose of SARS-CoV-2 (BNT162b2). On admission (Day 2), she presented with left ophthalmalgia and headache without any other neurological deficits including the movement of eyeballs, visual field, visual acuity, or nystagmus. MRI on Day 2 suggested slight left optic neural swelling;Gadolinium-enhanced MRI on Day 4 revealed left optic perineuritis. Test for serum anti-aquaporin 4 antibody was negative, whereas anti-myelin oligodendrocyte glycoprotein (MOG) antibody was positive. She was diagnosed with left optic perineuritis after SARS-CoV-2 mRNA vaccination. Her visual disturbance never recurred and her ophthalmalgia and headache subsided only with anti-inflammatory agents. Discussion(s): Many cases of optic neuritis associated with vaccinations have been reported except for SARS-CoV-2 BNT162b2 mRNA. To our knowledge, only one neuromyelitis optica case was associated with anti-MOG antibody. Therefore, we propose that SARS-CoV-2 mRNA vaccination may induce transient optic neuritis and perineuritis, associated with anti-MOG antibody in the present case. Conclusion(s): This is the first case of left optic neuritis and perineuritis associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BNT162b2 mRNA vaccination.Copyright © 2022

Bridging the Gap between Ophthalmology and Emergency Medicine in Community-Based Emergency Departments (EDs): A Neuro-Ophthalmology Guide for ED Practitioners.

Coordination of care for patients with neuro-ophthalmic disorders can be very challenging in the community emergency department (ED) setting. Unlike university- or tertiary hospital-based EDs, the general ophthalmologist is often not as familiar with neuro-ophthalmology and the examination of neuro-ophthalmology patients in the acute ED setting. Embracing image capturing of the fundus, using a non-mydriatic camera, may be a game-changer for communication between ED physicians, ophthalmologists, and tele-neurologists. Patient care decisions can now be made with photographic documentation that is then conveyed through HIPAA-compliant messaging with accurate and useful information with both ease and convenience. Likewise, external photos of the anterior segment and motility are also helpful. Finally, establishing clinical and imaging guidelines for common neuro-ophthalmic disorders can help facilitate complete and appropriate evaluation and treatment.

Acute zonal outer retinopathy (AZOOR) masquerading as optic neuritis in a patient with multiple sclerosis under cladribine treatment

Background: Acute zonal occult outer retinopathy (AZOOR) is a rare, recently introduced sectorial outer retinopathy commonly seen in young females. The presence of AZOOR in multiple sclerosis (MS) patients can sometimes masquerade as optic neuritis. We hereby analyze an infrequent case of such an incident, as well as the comorbidities of this particular patient and the arising differential diagnostic dilemmas. Case Presentation: A 29-year-old female MS patient on cladribine presented in the emergency department (ED) due to left eye (LE) visual disturbances which appeared after Covid-19 infection. As a result of her past medical history, the case was considered to be consistent with optic neuritis. The patient was treated with high doses of intravenous methylprednisolone, but despite the treatment symptoms persisted. Ophthalmological findings were compatible with AZOOR. Conclusion(s): AZOOR can coexist with MS. However, it is unclear whether cladribine treatment or Covid-19 infection triggered AZOOR. Given the potential for ocular adverse effects associated with cladribine use, patients should be encouraged to report visual disturbances promptly. In addition, medical professionals must be vigilant of MS patients on cladribine complaining of visual symptoms, and refer them to an ophthalmologist as soon as possible.Copyright © 2022 The Author(s)

Hyperacute optic neuritis in a patient with COVID-19 infection and vaccination: a case report.

BACKGROUND: As scientific knowledge continues to grow regarding coronavirus disease 2019 (COVID-19) infection, several neuro-ophthalmological manifestations have emerged, including rare reports of optic neuritis. Optic neuritis is an inflammatory demyelinating condition of the optic nerve that typically presents as subacute, unilateral vision loss and pain on eye movement. Several cases of COVID-19 infection and COVID-19 vaccination related cases of optic neuritis have been reported. We present a case of hyperacute, unilateral optic neuritis after both recent COVID-19 infection and subsequent booster vaccination. CASE PRESENTATION: Within two hours after receiving her COVID-19 booster vaccination, a 58-year-old female began experiencing bilateral eye pain, worsened by eye movements. The patient had previously contracted a mild COVID-19 infection three weeks prior to receiving her booster vaccination, confirmed by a rapid antigen test. The pain persisted in her right eye for a week at which time she presented to an ophthalmology clinic. She denied any changes to her visual acuity. Neuroimaging revealed right optic nerve enhancement, and the patient was admitted to the hospital for a course of intravenous steroids, which quickly resolved her eye pain. CONCLUSION: To our knowledge, this is the first reported case of COVID-19 related optic neuritis following both COVID-19 infection and vaccination. High clinical suspicion is needed to make the appropriate diagnosis, as cases of COVID-19 related optic neuritis may exhibit mild presentations, as was the case with our patient.

A rare case of bilateral optic neuritis post-Covishield (ChAdOx1-S [recombinant]) vaccination.

Multiple adverse effects have been reported in people receiving the COVID-19 vaccinations including few reports of optic neuritis. However, there is no report till date, of bilateral optic neuritis post-ChAdOx1-S (recombinant) vaccination. We report here, for the first time, such a case in a previously healthy woman. Although a direct causal relationship cannot be proven, there was a temporal association between the vaccination and the onset of optic neuritis. Some vaccine adjuvants inciting disproportionate systemic inflammation, molecular mimicry, and the hypercoagulable state seen after COVID-19 vaccination could be the possible causes for the development of optic neuritis. Clinicians should be aware of this adverse effect apart from various other adverse effects of COVID-19 vaccination.

Prevalence of iatrogenic CNS inflammation at a tertiary neuroimmunology clinic.

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

Post COVID-19 Vaccination-Associated Neurological Complications.

PURPOSE: Neurological sequelae after COVID-19 vaccination are rare. We investigated the possible pathogenesis behind the development of neurological complications within a short period after Saudi residents received a COVID-19 vaccine. PATIENTS AND METHODS: We evaluated 18 patients who recently received a COVID-19 vaccine (Comirnaty and Vaxzevria vaccines) and presented with neurological complications to the Saudi German Hospitals in Jeddah, Saudi Arabia. Neurologists assessed the patients' clinical presentation, radiological investigations, and laboratory findings. RESULTS: Three patients who received the first dose of the Vaxzevria vaccine experienced severe cerebral venous thrombosis, two of them were complicated by intracranial hemorrhage. Their laboratory investigations showed very high d-dimers and severe thrombocytopenia, which have been linked to higher mortality and poor outcome. Ischemic stroke occurred in eight cases (44.4%) with a predominance in older male patients. Three patients presented with seizures, two had optic neuritis. Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS) occurred in two male patients following vaccination with Comirnaty. CONCLUSION: Neurological complications after COVID-19 vaccinations are very rare, and only a few cases have been reported worldwide. The shared pathophysiological basis between COVID-19 viral infection and COVID-19 vaccines stands behind the very rare neurological complications resulting from the hypercoagulable state triggered by the general inflammatory condition. We suspect some differences in the pathogenesis of ischemic stroke caused by COVID-19 infection and COVID-19 vaccines, which render COVID-19 vaccine-associated ischemic stroke more responsive to treatment. To date, no definitive association between the vaccine and GBS has been proven by any strong evidence, but it has recently been added as a very rare side effect of the Janssen COVID-19 vaccine. No possible links of Miller Fisher syndrome to COVID-19 vaccines have been reported before the one reported in this study.