A number of patients diagnosed with COVID-19 infection also had headaches caused by underlying cerebral venous thrombosis (CVT), researchers reported during the American Headache Society virtual annual scientific meeting.
Four of the 20 cases identified by an international consortium died and one patient was transferred to a hospital for rehabilitation, said the lead researcher, Mohammed Wasay, MD, professor of neurology at Aga Khan University in Karachi, Pakistan.
However, Dr. Wasay said that the other patients recovered well, with an average discharge score of 1.3 on the modified Rankin Scale.
“COVID-19 increases the propensity for systemic hypercoagulability and thromboembolism," he said. “An association with cerebrovascular diseases, especially cerebral venous thrombosis, has been reported among these patients."
“Cerebral venous thrombosis should be suspected in COVID-19 patients presenting with headache or seizures," Dr. Wasay said. “Mortality is high, but the functional neurological outcome is good among survivors."
The patients in the study were identified from 10 centers in Pakistan, Egypt, Singapore, and the United Arab Emirates. Dr. Wasay said 14 of the patients were men, and the average age of the group as a whole was 42.4 years.
He and his colleagues attempted to determine if there were identifiable risk factors for patients who developed cerebral venous thrombosis in connection with exposure to COVID-19.
Eighty-five percent of the patients in the study reported a headache, and 65 percent had seizures upon presentation, with a mean admission Glasgow Coma Scale score of 13. CVT was the presenting feature in 13 cases, while seven patients developed cerebral venous thrombosis while being treated for COVID-19 infection.
Dr. Wasay said respiratory symptoms were absent in 45 percent of the patients. The most common imaging finding was infarction in 13 patients; hemorrhage occurred in four patients. The superior sagittal sinus was the most common site of thrombosis in 13 patients. Acute inflammatory markers were raised, including elevated serum D-dimer in 17 of the patients, erythrocyte sedimentation rate and C-reactive protein levels. Homocysteine was elevated in half of the tested cases.
He suggested that the mechanism of CVT is likely associated with the known ability of SARS-CoV-2 to bind to angiotensin-converting enzyme-2 receptors, which are variably present in the arterial and venous vascular endothelium.
“COVID-19 not only causes direct vascular damage but may also create an intense inflammatory reaction affecting hemostasis and the coagulation cascade," he said. “COVID-19-associated arterial stroke predominantly affects younger males with vascular risk factors and mostly presents as large vessel stroke. These findings may suggest a common pathway for both COVID-19-associated CVT and arterial stroke."
Dr. Wasay acknowledged that the study was limited by selection bias, the absence of a control sample and a prothrombotic workup, limited neurological examination, and the inability to examine the influence of confounding variables on outcomes.
“The current number of CVT cases is probably an underestimation," he suggested. “COVID-19 testing may be included as standard workup among all CVT patients, including those who have no throat or respiratory symptoms. All COVID-19-positive patients with headache and neurologic symptoms should be evaluated for cerebral venous thrombosis. Early diagnosis by MRI and anticoagulation for high-risk populations may lead to improved outcomes."
In commenting on the study, Noah Rosen, MD, director of Northwell Health's Headache Center in Great Neck, NY, said the findings—although from a small sample and preliminary— should alert clinicians to be aware of the connection between COVID-19 and headaches that may be caused by CVT in this younger age population.
Dr. Rosen noted that as a case series the study has limitations. “It doesn't really tell us the frequency of these cases and whether it is greater than in the general population," he told Neurology Today At the Meetings. “This is more a descriptor of what these researchers saw across all these cases."
He said that headache specialists often see CVT among patients who have hypercoagulative states. “It is relatively infrequent when compared with other headache conditions but it is well-described as a cause of headaches," Dr. Rosen said.
“This is not a definitive study, but it does raise the question of whether we should be looking for more of these cases in the year of COVID-19," he said.
Dr. Wasay disclosed no industry relationships. Dr. Rosen disclosed relationships with Alder, AbbVie, Amgen, Biohaven, Eli Lilly, Lundbeck, and Teva.
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AHS Abstract P-55: Shaikh S, Wasay M. Cerebral venous thrombosis (CVT) associated with COVID-19 infection: A multi-center study.