A case report on recurrent alternating Tolosa-Hunt syndrome due to bacterial sphenoid sinusitis: rediscussing the diagnostic terminology and classification.

BACKGROUND: Tolosa-Hunt syndrome (THS) is characterized by painful ophthalmoplegia caused by idiopathic granulomatous inflammation involving the cavernous sinus region. Patients respond well to steroid therapy. THS is included in the differential diagnosis of cavernous sinus syndrome, so it is important to fully exclude other lesions in this area before treatment, otherwise steroid treatment may lead to fatal outcomes. Here we describe a patient who initially presented with symptoms that simulated THS symptoms and developed recurrent alternating painful ophthalmoplegia during follow-up, and the patient was finally diagnosed with cavernous sinusitis caused by bacterial sphenoid sinusitis. CASE PRESENTATION: A 34-year-old woman presented with left painful ophthalmoplegia. Magnetic resonance imaging (MRI) revealed abnormal signals in the left cavernous sinus area, and these abnormal signals were suspected to be THS. After steroid treatment, the patient obtained pain relief and had complete recovery of her ophthalmoplegia. However, right painful ophthalmoplegia appeared during the follow-up period. MRI showed obvious inflammatory signals in the right cavernous sinus and right sphenoid sinus. Then nasal sinus puncture and aspiration culture were performed, and the results showed a coagulase-negative staphylococcus infection. After antibiotic treatment with vancomycin, the painful ophthalmoplegia completely resolved, and the neurological examination and MRI returned to normal. CONCLUSION: Some other causes of painful ophthalmoplegia also fulfill the diagnostic criteria for THS in the International Classification of Headache Disorders third edition (ICHD-3) and respond well to steroid therapy. Early diagnosis of THS may be harmful to patients, and clinicians should exercise great caution when dealing with similar cases without a biopsy. Using "cavernous sinus syndrome" instead of "Tolosa-Hunt syndrome" as a diagnostic category may provide a better clinical thinking for etiological diagnosis.

An overview of third, fourth and sixth cranial nerve palsies in the setting of COVID-19: A case report and systematic review.

BACKGROUND: Covid-19 has serious sequelae that may be poorly understood, underreported, and, as a result, not diagnosed promptly, such as variations in clinical manifestations of hyperinflammation among people infected with SARS-CoV-2. ophthalmoplegia can be one of these manifestations. METHODS: We are reporting a 55-year-old male patient with unilateral diplopia considering it as a case of multisystem inflammatory syndrome in adults. We also reviewed the literature systematically for the previously reported studies/cases with third, fourth and sixth cranial nerve palsies due to or after Covid-19. RESULTS: The literature search yielded 17 studies reporting 29 patients. 71.4% of the patients were males with a mean age of 42.23 years. Ophthalmological symptoms took 9.7 days to appear after the respiratory involvement. All patients had diplopia as part of their visual symptoms. 41.4% of the patients had unilateral sixth nerve palsy, 24% had bilateral sixth nerve involvement, 17% had fourth nerve involvement, and 27.6% had third nerve involvement. CONCLUSION: Ophthalmoplegia is considered presenting symptom of Covid-19. Further research is needed to detect all neuro-ophthalmological manifestations of Covid-19.

Miller-Fisher syndrome after first dose of Oxford/AstraZeneca coronavirus disease 2019 vaccine: a case report.

INTRODUCTION: Miller-Fisher Syndrome (MFS) is a variant of Guillain-Barré syndrome (GBS), an acute immune-mediated neuropathy, which manifests as a rapidly evolving areflex motor paralysis. This syndrome presents as a classic triad: ophthalmoplegia, areflexia, and ataxia. MFS is usually benign and self-limited. CASE REPORT: A Caucasian patient was admitted to our hospital with the flu, loss of bilateral strength in the lower limbs and upper limbs and sudden-onset ataxia 7 days after receiving a first dose of the Oxford/AstraZeneca COVID-19 vaccine. On neurological examination, the patient had Glasgow Coma Scale score of 15, with absence of meningeal signs; negative Babinski sign; grade 2 strength in the lower limbs and grade 4 strength in the upper limbs; axial and appendicular cerebellar ataxia; and peripheral facial diparesis predominantly on the right, without conjugate gaze deviation. Cerebrospinal fluid (CSF) was collected on admission, and analysis revealed albuminocytological dissociation with CSF protein of 148.9 mg/dL; leukocytes, 1; chlorine, 122; glucose, 65 mg/mL; red cells, 2; and non-reactive venereal disease research laboratory test result. The COVID-19 IgG/IgM rapid immunological test was negative. Electroneuromyography revealed a recent moderate-grade and primarily sensory and motor demyelinating polyneuropathy with associated proximal motor block. DISCUSSION AND CONCLUSION: Miller-Fisher Syndrome may be related to events other than infections prior to neuropathy, as in the case reported here. The patient presented strong correlations with findings for MFS reported in the literature, such as the clinical condition, the results of electroneuromyography, and results of the CSF analysis typical for MFS. When treatment was provided as proposed in the literature, the disease evolved with improvement. Ultimately, the diagnosis of incomplete MFS was made, including acute ataxic neuropathy (without ophthalmoplegia).

COVID-19 provoked internuclear ophthalmoplegia in a child with arrested hydrocephalus.

Internuclear ophthalmoplegia (INO) is a neuro-ophthalmic disorder caused by damage in the medial longitudinal fasciculus between the third and sixth cranial nerve nuclei. We present a 4-year-old female diagnosed with INO triggered by coronavirus disease 2019 (COVID-19) infection. The patient had history of neonatal meningitis with hydrocephalus without history of surgical intervention. To the best of our knowledge, this is the first case with combined COVID-19 and chronic hydrocephalus as an etiology for INO in a child. COVID-19 may trigger neurological manifestations as INO in susceptible cases.

Hemolytic Uremic Syndrome: A Covid-19 Vaccine Reaction Case Report (preprint)

Hemolytic uremic syndrome (HUS) is associated with microthrombi ,mainly in the kidneys. It may be classified as typical HUS or atypical HUS (aHUS) .Majority of HUS occur in children (usually at 6 months of age), as a sequela of shigella infection. In aHUS, a genetic or sporadic insult causes dysfunction in the complement cascade, leading to complement deposition on endothelial cells, thickening of arterioles and capillaries, and endothelial swelling and detachment. Consequently, there is formation of obstructive thrombi in the vessel lumina and shearing of red blood cells, creating schistiocytes, that results in the triad of Coombs negative hemolytic anemia, renal impairment, and thrombocytopenia. We report a rare case of a 43-year-old black male who reacted to the 2nd booster dose (some 7 months after the 1st) of Astra Zeneca Covid-19 vaccine with aHUS. He had ophthalmoplegia, occipital headaches and suicidal ideation which all resolved on high dose oral prednisolone. The Astra Zeneca vaccine which uses a chimpanzee platform is the only one reported to have similar reactions and this is important to note and manage such potentially life threatening rare adverse event.

Miller Fisher syndrome following Pfizer COVID-19 vaccine.

INTRODUCTION: Miller Fisher syndrome (MFS) is a rare variant of Guillain-Barre syndrome characterized by ataxia, areflexia, and ophthalmoplegia. We present a case of MFS following Pfizer COVID-19 vaccine. CASE PRESENTATION: A previously healthy 24-year-old female presented with binocular horizontal diplopia 18 days after receiving the first dose of Pfizer COVID-19 vaccine (Comirnaty®). Anti-ganglioside testing revealed positive anti-GQ1b antibodies. Intravenous immunoglobulins were administered, in a dose of 2 g per kg of body weight over 5 days. On a follow-up exam 3 weeks after the treatment, clinical improvement was noted with normal bulbomotor examination. CONCLUSION: Patients with acute ophthalmoplegia occurring after COVID-19 vaccination should be screened for the presence of anti-GQ1b antibody. If the antibody is present, intravenous immunoglobulin should be administered as it may hasten clinical improvement.

Spike Protein Cleavage-Activation Mediated by the SARS-CoV-2 P681R Mutation: A Case-Study From Its First Appearance in Variant of Interest (VOI) A.23.1 Identified in Uganda (preprint)

The African continent like all other parts of the world with high infection/low vaccination rates can, and will, be a source of novel SARS-CoV-2 variants. The A.23 viral lineage, characterized by three spike mutations F157L, V367F and Q613H, was first identified in COVID-19 cases from a Ugandan prison in July 2020, and then was identified in the general population with the additional spike mutation P681R at the S1/S2 cleavage site to comprise lineage A.23.1 by September 2020 with subsequent spread to 26 other countries. The P681R spike substitution of A.23.1 is of note as it increases the number of basic residues in the sub-optimal SARS-CoV-2 spike protein furin cleavage site; as such, this substitution may affect viral replication, transmissibility, or pathogenic properties. The same P681R substitution has also subsequently appeared in B.1.617 variants, including B.1.617.2 (Delta). Here, we performed assays using fluorogenic peptides mimicking the S1/S2 from A.23.1 and B.1.617 and observed significantly increased cleavability with furin, compared to sequences derived from the original Wuhan-Hu1 S1/S2. We performed cell-cell fusion and functional infectivity assays using pseudotyped particles harboring SARS-CoV-2 spike proteins and observed an increase in transduction for A.23.1-pseudotyped particles compared to Wuhan-Hu-1. However, these changes in activity were not reproduced in the original Wuhan-Hu-1 spike bearing only the P681R substitution. Our findings suggest that while A.23.1 has increased furin-mediated cleavage linked to the P681R substitution—which may affect viral infection and transmissibility—this substitution alone needs to occur on the background of other spike protein changes to enable its full functional consequences.Funding: This work was funded in part by the National Institute of Health research grant R01AI35270 (to GW and SD). We thank the global SARS-CoV-2 sequencing groups for their open and rapid sharing of sequence data and GISAID for providing an effective platform to make these data available. DLB, MVTP and MC were funded by the UK Medical Research Council (MRC/UK Research and Innovation) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement (grant agreement no. NC_PC_19060) and Wellcome Trust, UK FCDO—Wellcome Epidemic Preparedness—Coronavirus (grant agreement no. 220977/Z/20/Z). TT was supported by the National Science Foundation Graduate Research Fellowship Program under Grant No. DGE-1650441 and the Samuel C. Fleming Family Graduate Fellowship. Declaration of Interests: The authors manifest no conflict of interest.

Isolated ophthalmoparesis in a COVID-19 patient A case report and literature review (preprint)

We are reporting a COVID-19 positive patient who developed diplopia and was found to have an isolated abducens palsy. We reviewed the available English literature of cranial mononeuropathy as a possible manifestation of COVID-19 infection.It is a rare presentation of COVID-19.

Cavernous Sinus Thrombosis in COVID-19 Associated Rhino-Orbital Mucormycosis: A Retrospective Audit in the First Wave of the Pandemic (preprint)

Purpose: Cavernous sinus thrombosis (CST) is a complication of rhino-orbital-cerebral mucormycosis. The COVID-19 pandemic saw a rapid surge in the cases of acute fungal sinusitis, many of whom also had CST, further contributing to the ophthalmoplegia. This study was a retrospective audit of patients with mucormycosis treated during the first wave of the COVID-19 pandemic. Methods: This study was conducted at a tertiary referral centre, and patients with rhino-orbital mucormycosis were included. Relevant laboratory investigations and CT scans of the paranasal sinuses and the cavernous sinus were analysed. Mortality at discharge was calculated. Results: 61 cases of invasive mucormycosis were seen, of whom 20 were COVID-19 positive, and 21 had radiological evidence of CST. All patients in the study initially presented with clinical suspicion of mucormycosis, and COVID-19 was diagnosed during pre-admission investigations. 93% of patients had diabetes. A majority of patients received Amphotericin B and surgical debridement. The sphenoid sinus was involved in 32(52%) patients and the orbit in 34(56%). Factors affecting CST, such as platelet counts, were studied. Fifteen (25%) patients succumbed during their treatment. Conclusions: 34.4% of patients with mucormycosis developed CST. Being COVID-19 positive led to an increase in mortality; however, there was no significant increase in death due to simultaneous COVID-19 and CST. Sinus involvement was not significant for the development of CST.

COVID-19 triggering mucormycosis in a susceptible patient: a new phenomenon in the developing world?

A middle-aged woman with diabetes presented with left-sided facial pain, complete ptosis and fever of short duration. On presentation, she had hyperglycaemia without ketosis. There was total ophthalmoplegia of the left eye with a visual acuity of 6/36. She incidentally tested positive for COVID-19. CT paranasal sinus and MRI brain revealed left-sided pansinusitis with acute infarct in the left parieto-occipital region without angioinvasion. An emergency functional endoscopic sinus procedure was done, which confirmed mucormycosis on histopathological examination. After 1 week of conventional amphotericin B and antibiotics, repeat CT brain showed improvement in mucosal thickening and sinusitis. This case is a rare presentation of mucormycosis associated with rapid progression to orbital apex syndrome with brain infarction in a patient with non-ketotic diabetes and COVID-19. Early diagnosis and treatment are essential to prevent further end-organ damage. It is also interesting that there was no angioinvasion and transient periarterial inflammation was attributed to brain infarction.

Rhino-orbital mucormycosis during steroid therapy in COVID-19 patients: A case report.

PURPOSE: To report two cases of COVID-19 under treatment with a corticosteroid; in one case rhino-orbitocerebral mucormycosis and in another one rhino-orbital mucormycosis developed. CASE PRESENTATION: A 40-year old woman and a 54-year old man with severe COVID-19 underwent corticosteroid therapy for immune-related lung injuries. The first case presented with a bilateral visual loss and complete ophthalmoplegia of the right eye. The second case presented with vision loss, proptosis, orbital inflammation, and complete ophthalmoplegia on the left side. Histopathologic, nasal endoscopic examinations, and radiologic findings confirmed mucormycosis in both patients. The patients denied orbital exenteration and were managed with systemic amphotericin B and daily endoscopic sinus debridement and irrigation with diluted amphotericin B. Because of the intracranial space involvement, the first case died. The second case was successfully managed surgically and medically. CONCLUSION: Rhino-orbital/cerebral mucormycosis may be developed in COVID-19 patients under treatment with corticosteroid, and requires prompt diagnosis and management.

Bilateral, vertical supranuclear gaze palsy following unilateral midbrain infarct.

A 60-year-old man recently admitted for bipedal oedema, endocarditis and a persistently positive COVID-19 swab with a history of anticoagulation on rivaroxaban for atrial fibrillation, transitional cell carcinoma, cerebral amyloid angiopathy, diabetes and hypertension presented with sudden onset diplopia and vertical gaze palsy. Vestibulo-ocular reflex was preserved. Simultaneously, he developed a scotoma and sudden visual loss, and was found to have a right branch retinal artery occlusion. MRI head demonstrated a unilateral midbrain infarct. This case demonstrates a rare unilateral cause of bilateral supranuclear palsy which spares the posterior commisure. The case also raises a question about the contribution of COVID-19 to the procoagulant status of the patient which already includes atrial fibrillation and endocarditis, and presents a complex treatment dilemma regarding anticoagulation.

Bickerstaff's brainstem encephalitis associated with anti-GM1 and anti-GD1a antibodies.

Bickerstaff's brainstem encephalitis (BBE) is a Guillain-Barré syndrome (GBS) spectrum disorder associated with predominantly central nervous system predilection. Patients exhibit a variable constellation of depressed consciousness, bilateral external ophthalmoplegia, ataxia and long tract signs. Although the pathophysiology is not fully understood, it has been associated with anti-GQ1b antibodies in two-thirds of patients. We present a patient with clinical features consistent with BBE and positive anti-GM1 and anti-GD1a antibodies. A diagnostic approach to the acutely unwell patient with brainstem encephalitis is explored in this clinical context with a literature review of the aforementioned ganglioside antibody significance. Intravenous immunoglobulin therapy is highlighted in BBE using up-to-date evidence-based extrapolation from GBS.

Ocular manifestations of SARS-CoV-2: Literature review. / Manifestaciones oftalmológicas del SARS-CoV-2: Revisión de la literatura.

In this review, a summary is presented of the main reports regarding the potential ocular manifestations of the new coronavirus disease (COVID-19). Scientific evidence is based on letters to the editor, clinical cases and case series, cross-sectional, and a few longitudinal studies. To date, it includes viral conjunctivitis, immune conjunctivitis, and oculomotor palsies (OCP) due to the novel coronavirus. Retinopathy is discussed. A viral conjunctivitis outbreak can be isolated or associated with the systemic picture, mainly pulmonary, before or after the onset of respiratory symptoms. It can be both unilateral and bilateral, follicles are typical, and duration is variable between 5 and 21 days. Immune-mediated conjunctivitis consists of eye redness, together with erythroderma and fever. It appears more frequently in children, and has been associated with a «Kawasaki-like¼ disease and toxic shock syndrome. OCP can present on its own, or as part of Miller-Fisher syndrome, along with ataxia, and hyporeflexia. Ophthalmologists have a considerable risk of developing COVID-19 due to close contact with the patient, exposure to tears and eye secretions, and the use of various pieces of equipment and devices susceptible to contamination.

Complications of COVID-19 , a case with both neurological and dermatological complications. (preprint)

Recently, different complications and clinical manifestations of COVID-19 have been reported such as neurological or dermatological complications, We present a confirmed COVID-19 case of diplopia and ophthalmoplegia presenting skin lesions at the same time .