Fatal Post COVID mRNA-Vaccine Associated Cerebral Ischemia (2024)

Abstract

Keywords: COVID-19, Moderna vaccine, cerebral edema, neurology, stroke

Consent

Family consent to publish this case was obtained both verbally and written. Theconversation was documented in our institutions electronic medical record.

Case Presentation

A 30-year-old woman with prior asymptomatic COVID-19 infection three months earlierdeveloped severe, throbbing bi-frontal headache 24-hours after first dose of themRNA COVID-19 vaccine (Moderna). The headaches were atypical, prompting evaluationby her primary care provider and three emergency department visits where vital signsand neurologic examinations were normal. She had a history of class I obesity, butno prior headaches. Symptomatic management for presumed migraine did not alleviatethe headaches. Three weeks after vaccination, she developed blurred vision andconfusion, prompting further emergency evaluation. At this time, imaging of her headwas first obtained. Computed tomography (CT) of her head was normal, and lumbarpuncture revealed an opening pressure of 27cmH20 with lymphocytosis (Table 1). A brain MRIwith contrast showed multiple punctate areas of diffusion restriction in occipitalregions but no evidence of large arterial or venous occlusion. There was no evidenceof abnormal enhancement (Figure1A). Upon transfer to this hospital, the patient endorsed a bifrontalheadache with photophobia. Complete blood count was without leukocytosis, extendedchemistry panel, and toxicology screening were normal. Repeat lumbar puncturerevealed an opening pressure of 50mmH20 and rising lymphocytic pleocytosis (Table 1). Broad spectrumantimicrobial coverage was started. Her mental status acutely worsened later thatevening, and she was noted to have a new left hemiparesis. Vitals were notable forfever and tachycardia. CT/CT angiography with perfusion were without major vesselocclusion and no evidence for low pressure/post-LP herniation. Labs were notable formild thrombocytopenia (119 K/u) and elevated D-dimer (3457) with a negative plateletfactor 4 antibody (PF4). Given elevated ICP, hyperosmolar therapy was given and anexternal ventricular drain (EVD) was placed. Studies to evaluate for infectiousetiology, primary angiitis of the CNS, secondary CNS vasculitis, or one of itsmimics were sent (Table1). CSF cultures and PCR testing returned negative (Table 1), and she wasstarted on high dose intravenous methylprednisolone followed by intravenous immuneglobulin. Intracranial pressure remained refractory to maximal medical managementincluding deep sedation, paralysis and hypothermia, prompting a right decompressivehemicraniectomy. Subsequent brain MRI showed extensive bilateral subacute infarctswithout evidence of infection or cerebral venous sinus thrombosis (CVST) (Figure 1B). Upper extremityand bilateral lower extremity ultrasounds to evaluate for systemic thromboses werenegative for deep vein thrombosis. The patient expired from refractory cerebraledema. Brain autopsy showed leptomeningeal, perivascular and focal intraparenchymalinfiltrates of CD8 and CD4-positive T-cells in association with intravascularthrombi (Figure 1C and D).There was no CVST or demyelination. Fungal and bacterial stains werenegative.

Discussion

The diffuse endothelial damage and vessel wall inflammation seen on pathologysuggested an underlying pro-thrombotic state and T cell inflammatory response. Anumber of case reports have demonstrated cerebral venous sinus thrombosis andsystemic thromboses post-COVID-19 vaccination.^1-3 While this patient did not haveCVST, CVST has been previously associated with COVID-19 vaccination^1-3 where thrombocytopenia isfrequent and termed ‘vaccine-induced prothrombotic immune thrombocytopenia’ (VIPIT).VIPIT is similar to heparin-induced thrombocytopenia (HIT) with antibodies directedagainst platelet factor 4 (PF4).^1,4,5 Mild thrombocytopenia occurredin this case, but PF4 antibodies were negative. The arterial infarct in this case islikely related to a pro-thrombotic state but with a different underlying mechanismto that seen in venous thrombosis. Due to the large volume of infarction, thepatient was not started on anticoagulation after extensive discussion of the risksvs potential benefit.

In summary, administration of COVID-19 vaccine was considered a possible cause of theextensive multifocal arterial thromboses with associated inflammatory response andelevated intracranial pressure given the temporal association. The mechanism forinitial elevation in intracranial pressure is not known but may relate to cerebralautoregulatory changes in the setting of cortical microvascular thrombosis. Reviewof the medical literature and vaccine adverse event reporting system (VAERS)produced no similar cases, suggesting the condition is extremely rare, but apotentially fatal vaccine-associated event.

Footnotes

ORCID iDs

Nadia McMillan https://orcid.org/0000-0003-0423-0471

Corey R. Fehnel https://orcid.org/0000-0003-1726-5809

References