Treatment-resistant psychosis in familial cerebral cavernous malformation: A case series

• Familial Cerebral Cavernous Malformations (FCCMs) rarely have psychotic symptoms. • Two siblings with FCCM had psychosis with hallucinations, delusions and aggression • They were resistant to multiple antipsychotics and required clozapine. • Electroconvulsive therapy conducted was safe and effective. Familial Cerebral Cavernous Malformations (FCCMs) are associated with symptomatic clinical findings, including neurological deficits and seizures, a positive family history, and supportive gene mutations. Current evidence on neuropsychiatric manifestations is limited to case reports, primarily describing mood and anxiety symptoms. The use of Electroconvulsive Therapy (ECT) has been limited, largely due to concerns about precipitating cavernoma bleeding. Notably, there are no documented cases of psychotic manifestations in cavernomas that are not actively haemorrhagic. We report on two siblings with FCCMs, diagnosed based on brain imaging and family history, who presented with rare neuropsychiatric symptoms of psychosis. A 15-year-old female presented with auditory hallucinations, delusions of erotomania and passivity, affective symptoms including overfamiliarity and disinhibition, and significant aggression toward herself and others. She demonstrated resistance to multiple trials of antipsychotics and lithium. Treatment with clozapine and ECT was required, alongside propranolol to manage blood pressure and mitigate the risk of cavernoma bleeding during ECT. A 21-year-old male presented with auditory hallucinations, delusions of guilt, and aggression. He also exhibited treatment resistance and required clozapine for symptom management. Patients with FCCMs may exhibit genetic and clinical overlaps, posing significant medical challenges when managing psychotic symptoms. Their psychosis may demonstrate resistance to conventional treatments. ECT appears to be a novel, potentially safe, and effective therapeutic option when precautions are taken to minimize the risk of cavernoma bleeding.