Epileptic seizures or TFNEs: the diagnostic dilemma in CAA

A review published online on 13 October 2026 in Seizure: European Journal of Epilepsy addresses one of the most persistent diagnostic dilemmas in cerebral amyloid angiopathy (CAA, a small-vessel disease defined by amyloid deposition in cortical and leptomeningeal vessels): whether a patient's transient focal neurological episodes are epileptic seizures or so-called TFNEs, transient focal neurological episodes without an epileptic mechanism.

Authors Giulia Negro and Jacopo C. DiFrancesco structured the paper around the clinical overlap between the two phenomena. Both present with abrupt, transient focal deficits in patients who often already carry imaging evidence of CAA, such as cortical superficial siderosis or convexity subarachnoid hemorrhage. The distinction matters directly for treatment: antiseizure medication is indicated for epileptic events, whereas TFNEs may instead point to recurrent transient ischemic-like mechanisms that require a different management pathway.

Why the EEG question comes first

For electroencephalographers, the core practical issue is that scalp EEG, the standard non-invasive recording of cortical electrical activity with electrodes placed on the scalp, frequently fails to separate the two entities at the time of the event. Episodes are brief, patients are often not monitored when they occur, and interictal findings in CAA can be nonspecific. The review by Negro and DiFrancesco therefore examines how clinical semiology, timing, and ancillary investigations should be weighted when the recording is unrevealing.

The authors also address the broader context: CAA is increasingly recognized as a cause of both intracerebral hemorrhage and, separately, epilepsy in the aging population. Patients presenting with transient focal symptoms and CAA-compatible imaging therefore arrive regularly in monitoring units and reading rooms, where the question of ictal versus non-ictal must be answered with limited electrophysiological evidence.

What does this change for clinical practice?

The practical takeaway for neurologists and clinical neurophysiologists is procedural rather than technological. When a CAA patient reports recurrent stereotyped transient episodes, the review argues for a structured comparison of the episode's semiology against the published characteristics of TFNEs and focal seizures, combined with MRI findings and, where available, ictal or interictal EEG. Prolonged monitoring should be considered when the episodes are frequent enough to capture, since a definitive ictal recording remains the only way to confirm an epileptic mechanism.

No new device, drug trial, or cohort data appear in the paper. It is a synthesis and analysis of existing knowledge rather than an interventional study, and readers should treat its conclusions as guidance for diagnostic reasoning, not as evidence from a new clinical trial.

Looking ahead

The review signals growing recognition that the seizure-versus-TFNE question will become more common as populations age and CAA detection improves. Future work will need to define how prolonged scalp EEG monitoring, and potentially intracranial approaches in selected patients, can sharpen the differential diagnosis before treatment decisions are made.