Slight Association Identified Between Cerebral Microbleeds and Acute Symptomatic Seizures


Stroke of an undetermined cause was associated with acute symptomatic seizures, an effect that was marginally mediated by cerebral microbleeds.

Alain Z. Looti, MD, MS, assistant professor, Penn State Neuroscience Institute

Alain Z. Looti, MD, MS

Findings from a retrospective study of hospitalized patients with anterior circulation ischemic stroke showed an association between cerebral microbleeds (CMBs) and acute symptomatic seizures (ASS); however, this connection was attenuated after accounting for multiple different covariates.1

Among a cohort of 381 participants, 17 (4.4%) patients had seizures during hospitalization after the index stroke. On an univariable analysis, the presence of 4 or more CMB (OR, 3.84 95% CI, 1.16-12.71) and stroke etiologies were associated with ASS. After adjusting for cofounders such as stroke severity, cortical infarct location, and hemorrhagic transformation, the association between CMBs and ASS was reduced (adjusted OR, 3.11; 95% CI, 0.74-11.03; P = .09).

"The presence of CMB alone would be insufficient to explain the onset of seizures after stroke as this is a gradual process, reflecting the prolonged effects of stroke risk factors on cerebral small vessels," lead author Alain Z. Looti, MD, MS, assistant professor, Penn State Neuroscience Institute, and colleagues, wrote. "The presence of cerebral microbleeds may thus indicate a patient with greater risk factors for stroke and thus more likely to have a more severe stroke. Stroke severity, which is associated with an increased risk of seizures, could therefore potentially mediate the relationship between CMB and seizures."

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In this single center study, multivariable logistic regression analysis showed that patients with a stroke of undetermined cause were found to be more likely to have ASS (adjusted OR, 5.09; 95% CI, 1.17-35.25; P = .05). A summary of ASS characteristics revealed that time to seizure after stroke was less than 1 day in 71% of the cases, 47% of the ASS were focal, status epilepticus was observed in 6%, and most patients had started on levetiracetam. In casual mediation analysis, findings showed that the effect of CMB on ASS was not mediated by stroke severity.

In terms of the association between cryptogenic strokes and ASS, investigators noted that “establishing causality would be hazardous in the absence of solid biological plausibility and confirmation by other studies.” They continued that confirmatory evidence should come from prospective analyses accounting for the association between cryptogenic strokes, cortical infarcts, and their characteristics.

The study had several limitations, including the fact that seizures were reported by clinicians, with 94% of patients having diagnosis supported by an electroencephalography. In addition, the cohort was limited to patients with anterior circulation stroke, precluding the generalizability of the results to all patients with stroke. Furthermore, there was no information about the localization of CMB relative to seizure onset, as this would have required that all seizures be captured during a continuous EEG monitoring, which was beyond the scope of the analysis.

1. Lekoubou A, Ssentongo P, Maffie J, et al. Associations of small vessel disease and acute symptomatic seizures in ischemic stroke patients. Epileps & Behav. 2023;145:109233. doi:10.1016/j.yebeh.2023.109233
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