In June 2006, a 9-month-old male presented to the Emergency Department at the Royal Hospital for Kids and Young People in Edinburgh, Scotland, with seizures, nausea and vomiting, tachycardia, and bulging fontanelles (Fig. 1). His past medical history included pseudo-squint, gastro-oesophageal reflux disease (GORD), and a recent episode of gastroenteritis. At the time of admission, his only regular medication was omeprazole, while his family history was unremarkable. Physical examination revealed good neurodevelopmental progress, with no neurological deficits or cerebellar signs. The fontanelles were soft and enlarged, measuring 2.5 by 2.5cm. The CT scan showed significant intracranial bleed and increased intracranial pressure, likely secondary to multiple intracranial angiomatous formations.
Given the patient’s presentation and investigation findings, a working diagnosis of intracranial bleeding into cavernoma, seizure disorder, and acute hydrocephalus was established. A surgical procedure for left frontal bleeding of frontal giant cavernoma was carried out. Pharmacological therapy with carbamazepine 80mg twice daily was started to address recurrent seizures, along with a “rescue” therapy of buccal midazolam 0.24ml and paraldehyde 3ml in 3ml of olive oil. Following the eventually discharge from the hospital, the patient’s seizures significantly reduced in frequency while a battery of genetic tests relieved a KRIT1 mutation in him and his father.
In March 2008, a brain MRI was arranged to re-assess the size and number of cavernomas identified at the initial presentation. The imaging showed an increase in the size of left frontal cavernoma with multiple cystic lesions within. These cystic lesions were likely to represent minor interval bleeds into the lesion over the last two years. Eventually, in January 2010, a left frontal craniotomy for the excision of cavernoma was performed and a ventriculoperitoneal shunt in situ was inserted. The surgical procedure was uneventful, and the patient made a good postoperative recovery.
In June 2011, a brain MRI showed an increase in the size of the cavernoma within the left cerebellar hemisphere. This was initially observed and monitored with regular MRI scans. In September 2015, a left-sided retro-sigmoid craniotomy was performed for the excision of this cavernous malformation. Due to the patient’s persistent growth of cavernomas and recurrent prophylactic surgeries, he fulfilled the criteria to be a candidate for “Propranolol for Intracranial Cavernoma” (PICC) clinical trial at our institution.
A baseline MRI scan was obtained in February 2017 and the patient commenced on the propranolol 20mg TDS. A regular ECG, blood pressure measurement, and blood sugar monitoring were arranged. On a three-month follow-up, the MRI scan showed no increase in the size of the angiomatous formations. Propranolol was well tolerated by the patient, with the only side-effect being mildly cold hands. A subsequent MRI scan in March 2018 showed no change in the size of cavernomas, with a possible reduction in the size of left frontal cavernoma. As the patient reported no side effects at this visit, it was decided to increase the propranolol dose to 40mg TDS.
The most recent MRI scan, performed in March 2022, showed very minor enlargement in the largest cavernoma cantered within the left parasagittal frontal lobe with other numerous supra and infratentorial cavernomas remaining unchanged (Fig. 2).