Ischemic stroke and cerebral vasospasm in a COVID-19 patient

BACKGROUND

• COVID-19 has presented with a plethora of wide-ranging complications
• Neurological complications¹
  • Stroke
  • Cerebral or subarachnoid hemorrhage
  • Central nervous system (CNS) vasculitis
  • Cerebral vasospasm
  • Guillain-Barré Syndrome
  • Ageusia and/or anosmia
• Paramount to anticipate and report complications for better patient outcomes

• Possible mechanisms leading to cerebral vasospasm (CV) in COVID-19 patients have been described
  • Cerebral vasculitis describes endothelial damage and vasoconstriction leading to CV²
  • Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by a reversible, multifocal narrowing of cerebral arteries with or without neurological deficits³
  • Hypothesized that SARS-CoV-2 may induce vasoconstriction due to downregulation of the ACE2 receptor⁴

THE CASE

• A 62-year-old man with a history of hypertension, smoking, and alcohol abuse and noncompliant with medication presented to the hospital after being found unconscious in his car by EMS. 
  • Per family history, the patient had been complaining of headaches for several days
  • Intubated due to low GCS score and vomiting/concern for airway
  • Given levetiracetam, mannitol, and furosemide to be stabilized to transfer from OSH
• The patient was found to be in hypertensive crisis with his BP being 240/140
  • Controlled with clevidipine
• Lab findings: hyperglycemia, hyperlipidemia, polycythemia, normal coagulation studies, blood alcohol test negative, arterial blood gasses within normal limits
• Home 81mg aspirin reversed on arrival with desmopressin
• Neuro exam: intubated, minimal sedation, no eye-opening, pupils 2mm round and reactive, +cough/gag/corneal reflexes, bilateral upper extremity localization right > left, bilateral lower extremity withdrawal, not following commands
• Found to be COVID positive on nasopharyngeal swab RT-PCR assay

• Presenting non-contrast head CT showing an intraventricular hemorrhage.

• Presenting MRI acute lacunar infarct in the left caudate body, with adjacent casted hematoma within the left lateral ventricle. 

HOSPITAL COURSE

• Patient was admitted to the NeuroICU 
  • Right external ventricular drain (EVD) was placed emergently
• Increased FiO2 demands with COVID, started on prednisone 
• Physical exam began to improve however required oxazepam for high CIWA* scores consistent with history of significant alcohol abuse
• Patient became agitated
  • Self-extubated, transition to O2 via nasal cannula
  • Was also pulling at EVD
• Marked improvement – patient was following commands and conversational
• EVD self-removed day 12 
  • Neuro exam: drowsy but arousable, moves all extremities to commands, mild left paresis
  • Patient was saturating well on room air

• Sudden onset decline and somnolence on day 13 requiring intubation
  • Sudden change in mental status, not verbalizing, not following commands with extremely decreased response to deep tactile stimuli, pupils reactive
  • Neuro exam: unequal pupils, left pupil 5mm and irregular, right pupil 2mm and regular; patient nonverbal and gargling
  • Intubated due to unresponsiveness
  • Non-contrast head CT demonstrating stability with mildly enlarged ventricles
  • EVD replaced emergently; normal opening pressure
• Further imaging was obtained due to worsening exam – CT, MRI, MRA

• Non-contrast head CT obtained demonstrating diffuse hypodensities

• Brain MRI DWI with diffuse ischemic changes in multiple vascular territories - bilateral MCA distributions, bilateral ACA distributions, and to a lesser degree PCA distributions and posterior circulation.

   

• MRI ADC map correlating ischemia.

   

• MRA of Head demonstrating diffuse vascular spasm and no evidence of large vessel occlusion or high-grade stenosis.

   

HOSPITAL COURSE

• Day 15 – Family had made decision to pursue palliative care and comfort measures only
  • Family declined autopsy
• Work-up:
  • Venous duplex of bilateral lower extremities on days 1 & 11 showed no deep venous thrombosis
  • No cardiac structural abnormalities on echocardiogram; Ejection Fraction of 55% 
  • Vasculitis panel negative – ANA, ANCA, SS-A/SS-B, RPR, C3, C4

CONCLUSION

• COVID-19 associated with a myriad of neurological complications
• Patient's intracerebral hemorrhage (ICH) solely intraventricular, extremely unusual, and unlikely for ICH to cause cerebral vasospasm
• CNS vasculitis appears to be a rare complication of COVID-19 and could potentially be responsible for this patient's presentation
• RCVS remains another possible explanation

• Vasculitis
  • Symptoms frequently include stroke, encephalopathy, and seizures
  • No known CNS-specific vasculitis markers
  • Possible increased inflammatory markers in CSF
• Reversible cerebral vasoconstriction syndrome (RCVS)
  • RCVS frequently presents with thunderclap headache and neurological deficits after exposure to a trigger
  • RCVS in rare cases can cause massive strokes and severe morbidity
  • Typically develops over the course of weeks to days and not suddenly
• More research needed to compare the correlation between neurological deficits and COVID-19

RESOURCES

• Al-Ramadan A, Rabab'h O, Shah J, Gharaibeh A. Acute and Post-Acute Neurological Complications of COVID-19. Neurol Int. 2021;13(1):102-119. Published 2021 Mar 9. doi:10.3390/neurolint13010010
• Berlit P. Diagnosis and treatment of cerebral vasculitis. Ther Adv Neurol Disord. 2010 3(1):29-42. Doi: 10.1177/1756285609347123
• Chen SP, Fuh JL, Wang SJ. Reversible cerebral vasoconstriction syndrome: an under-recognized clinical emergency. Ther Adv Neurol Disord. 2010;3(3):161-171. doi:10.1177/1756285610361795
• Eleuteri D, Montini L, Cutuli SL, Rossi C, Alcaro F, Antonelli M. Renin-angiotensin system dysregulation in critically ill patients with acute respiratory distress syndrome due to COVID-19: A preliminary report. Crit Care. 2021;25(1):91. Doi: 10.1186/s13054-021-03507-7.
• Singhal A, et al. Reversible cerebral vasoconstriction syndromes: analysis of 139 cases. Arch Neurosci. 2011;68(8):1005-12
• Sommer B, Maurer C, Berlis A, Shiban E. Spontaneous Intracerebral Hemorrhage and Delayed Cerebral Vasospasm in a Patient with COVID-19 Infection. Arch Neurosci. 2021;8(3):e116184.doi: 10.5812/ans.116184
• Spudich S. and Nath A. “Nervous system consequences of COVID-19” Science. January 21, 2022

SOURCES

1. Al-Ramadan A, Rabab'h O, Shah J, Gharaibeh A. Acute and Post-Acute Neurological Complications of COVID-19. Neurol Int. 2021;13(1):102-119. Published 2021 Mar 9. doi:10.3390/neurolint13010010
2. Berlit P. Diagnosis and treatment of cerebral vasculitis. Ther Adv Neurol Disord. 2010 3(1):29-42. Doi: 10.1177/1756285609347123
3. Chen SP, Fuh JL, Wang SJ. Reversible cerebral vasoconstriction syndrome: an under-recognized clinical emergency. Ther Adv Neurol Disord. 2010;3(3):161-171. doi:10.1177/1756285610361795
4. Eleuteri D, Montini L, Cutuli SL, Rossi C, Alcaro F, Antonelli M. Renin-angiotensin system dysregulation in critically ill patients with acute respiratory distress syndrome due to COVID-19: A preliminary report. Crit Care. 2021;25(1):91. Doi: 10.1186/s13054-021-03507-7