key: cord-0783650-2jx91bxj authors: Ray, Somdattaa; Kamath, Vikram V; Raju P, Arjun; K.N, Rajesh; N, Shalini title: Fulminant reversible cerebral vasoconstriction syndrome in breakthrough COVID 19 infection date: 2021-11-26 journal: J Stroke Cerebrovasc Dis DOI: 10.1016/j.jstrokecerebrovasdis.2021.106238 sha: 71a57ab477392d3346baa551fdf04cc659fb6bee doc_id: 783650 cord_uid: 2jx91bxj COVID 19 infection continues to afflict people worldwide. Neurological complications of COVID infection are common. We report a case of fulminant reversible cerebrovascular constriction syndrome (RCVS) in a patient with breakthrough COVID 19 infection who was fully vaccinated. A 64 year old lady, fully vaccinated 2 months back, presented with headache, drowsiness, partial seizures, visual impairment and quadriplegia. Her nasopharyngeal swab was tested positive for SARS COV2 on real time PCR assay. MRI brain showed multifocal hyperintensities in MRI brain FLAIR images with MR angiogram showing arterial vasoconstriction suggestive of RCVS. Despite initiation of nimodipine, patient's symptoms worsened and she succumbed to sepsis. RCVS following COVID infection has been reported to have a benign outcome. However, despite vaccination, fulminant RCVS following a breakthrough COVID infection was observed in our patient. CSF analysis was normal. Although patient was diagnosed with COVID 19, patient did not complain of cough, breathlessness or fever. Oxygen saturation in room air was 92% and CT chest showed mild basal ground glass opacities. Hence, no steroids were administered and patient was started on low molecular weight heparin in view of high D dimer levels and given oxygen supplementation as treatment for COVID infection. Patient was also initiated on oral nimodipine 60 mg Q4 hours and telmisartan and intravenous levetiracetam and admitted to intensive care unit. She went on to develop status epilepticus that was controlled with a combination of antiepileptics (levetiracetam, clobazam and valproate). Patient's sensorium however deteriorated further. Repeat MRI brain showed increase in size of lesions with hemorrhagic transformation and significant edema. The MRI intracranial angiogram revealed persisting vasospasm in all vessels. Patient succumbed to aspiration pneumonia and sepsis ten days after admission. Discussion-RCVS is considered as a monophasic illness and is traditionally associated with a benign prognosis with 90-95% of the patients demonstrating near complete recovery within weeks and mortality has been seldom reported (4) . A fulminant course of RCVS has been reported in 5-10% of the patients (5). In one study describing a cohort of 191 patients with RCVS, 3 patients died following progression of RCVS (6) . The pathophysiology of RCVS in COVID is probably due to effect of SARS COV2 mediated downregulation of ACE receptors. The downregulation of ACE-2 receptors by SARS COV2 leads to sympathetic and/or renin angiotensin overactivity leading to vasoconstriction (7) triggering blood pressure spikes that subsequently impairs cerebral autoregulation (3) . RCVS in the background of COVID infection has responded favourably to nimodipine and aspirin (2) . However, fulminant RCVS shows poor response to nimodipine (8) . Fulminant RCVS has not been previously published in the setting of COVID-19 infection. This patient developed RCVS after developing COVID following completion of vaccination. Breakthrough infection following Covid vaccination have been associated rarely with severe symptoms requiring hospitalisation with most of the patients developing asymptomatic or mild illness (9) . This patient presented with symptoms during the surge of second wave wherein the infections were predominantly mediated by the delta variant (10) . The delta variant has been associated with higher likelihood of hospitalisation (11) although vaccination (both COVISHIELD and COVAXIN) has been effective in decreasing the disease mortality and morbidity in delta variant breakthrough infections (10) . Despite vaccination, severe complications in breakthrough COVID infection such as fulminant RCVS in our patient, are prevalent. Further reports from larger cohorts providing pathological insights will be required to strengthen the association between COVID infection and RCVS and confirm the hypothesis of COVID infection as a definite cause of RCVS in these patients. Neurological associations of COVID-19. The Lancet Neurology Associated Reversible Cerebral Vasoconstriction Syndrome Successfully Treated with Nimodipine and Aspirin Reversible cerebral vasoconstriction syndrome and dissection in the setting of COVID-19 infection Reversible cerebral vasoconstriction syndromes: analysis of 139 cases Reversible cerebral vasoconstriction syndrome Long-term outcomes after reversible cerebral vasoconstriction syndrome Downregulation of Membrane-bound Angiotensin Converting Enzyme 2 (ACE2) Receptor has a Pivotal Role Case Report and Review of the Literature: Fatal Reversible Cerebral Vasoconstriction Syndrome Breakthrough COVID19 infections after vaccinations in healthcare and other workers in a chronic care medical facility Clinical outcomes in vaccinated individuals hospitalized with Delta variant of SARS-CoV-2. medRxiv Legends to figure-Figure 1-MRI brain (A) and (B) FLAIR sequences show grey and white matter hyperintensities in parieto occipital, fronto parietal region. (C) Susceptibility weighted image sequence shows haemorrhagic transformation of the lesions. (D) and (E) Diffusion weighted image sequences show diffusion restriction of bilateral occipital