Abstracts

Rationale: Pallister Hall syndrome (PHS) is a rare genetic syndrome characterized by polydactyly, hypothalamic hamartoma (HH), bifid epiglottis, imperforate anus, hypogonadotropic hypogonadism, hypoglycemia, electrolyte dysfunction, and metabolic acidosis. It has autosomal dominant inheritance, but many cases are due to spontaneous mutations. It is associated with frameshift mutation of GLI3 gene in short arm of chromosome 7 that functions in the sonic hedgehog pathway. Most patients with PHS and hamartoma do not have seizures and the gelastic seizures reported in literature responded well to medications. This is the first report of a patient with PHS HH associated drug resistant epilepsy treated successfully with MRI-guided laser interstitial thermotherapy (MRI-LITT). Methods: We report a case of drug resistant epilepsy successfully treated with MRI-LITT of hypothalamic hamartoma in a patient with PHS. Results: 67 year-old male, with childhood diagnosis of PHS (with polydactyly, hypogonadotropic hypogonadism, imperforate anus) had giggling spells early in his life. He was found to be positive for frameshift GLI3 mutation with a sequence variant (c.2387-2390 del TTCT) which has not been previously described resulting in premature stop codon and is predicted to be pathologic. Seizure semiology was characterized by rising epigastric sensation followed by an urge to laugh and shiver without loss of awareness, lasting 1-minute and postictal fatigue. His seizure frequency increased up to one seizure every 15 minutes. He was treated with levetiracetam and lacosamide with minimal improvement in seizures. Brain 3T-MRI showed a non-enhancing 2.0X1.6X1.4 cm left hypothalamic mass consistent with left HH. Video-EEG over 3 days captured 121 gelastic seizures without electrographic correlation and no epileptiform discharges.  He underwent laser ablation of the HH with MRI-LITT. MRI brain 2-week post-resection showed subacute blood and overall decrease in size of lesion. Unfortunately, his seizures continued every 2 hours despite addition of clonazepam. At 3 week interval, he underwent re-ablation of HH, which resulted in seizure freedom (ENGEL 1 at 1.5-year). Conclusions: Gelastic seizures secondary to HH in patients with PHS are rare and controlled with anti-seizure medications. In contrary, this case report highlights an unusual intractable epilepsy in the absence of secondary epileptogenesis and seizure freedom after 2 sessions of laser ablation.  Funding: None