PO-37 | Trigeminal autonomic cephalalgia as the initial presentation of a cerebral cavernous malformation: a rare case report

Francesco Maurizio Chianese, Marcello Silvestro, Ilaria Orologio, Lorenzo Tartaglione, Marcella Marziani, Antonio Russo | Headache Centre, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy

Background: We report the case of a patient presenting with trigeminal autonomic cephalalgia (TAC)-like headache as the initial symptom of familial cerebral cavernous malformations (CCMs) associated with a pathogenic microdeletion in the KRIT1 gene. A 49-year-old man with no prior neurological history developed a subacute onset of brief, strictly unilateral, left-sided retro-orbital headaches accompanied by ipsilateral cranial autonomic symptoms—such as conjunctival injection and eyelid ptosis—recurring up to 10–15 times per day.

Methods: Upon evaluation at the Headache Center, a diagnosis of Short-lasting Unilateral Neuralgiform Headache Attacks with Conjunctival Injection and Tearing (SUNCT) was initially considered. However, brain MRI revealed a cavernoma with signs of prior hemorrhage and hemosiderin deposits in the left insular region, along with multiple additional supratentorial and infratentorial cavernous malformations—findings consistent with familial CCM. These findings prompted genetic testing. 

Results: Molecular analysis (MLPA confirmed by NGS) identified a heterozygous microdeletion affecting exons 10–11 of the KRIT1 gene, classified as pathogenic and consistent with autosomal dominant familial CCM. Based on the headache phenotype, lamotrigine was initiated at a dose of 50 mg twice daily, leading to complete resolution of attacks within approximately two weeks. Although CCMs most commonly present with seizures, hemorrhage, or focal neurological deficits, TAC-like headaches may occasionally represent the initial clinical manifestation. This presentation likely reflects activation of trigemino-autonomic pathways. The absence of acute hemorrhage, along with the positive response to lamotrigine, suggest a mechanism of altered neuronal functioning rather than a structural or hemorrhagic cause.

Conclusion: This case underscores the importance of considering secondary etiologies in patients with headache with features consistent with a diagnosis of trigemino-autonomic cephalalgias. Familial CCM due to KRIT1 mutations, though rare, should be included in the differential diagnosis when characteristic clinical features and imaging findings coexist.