Introduction: Hypothalamic hamartomas (HH) are congenital benign tumors known to cause gelastic or dacrystic seizures. In 95% of cases they occur sporadically without further abnormalities. Only 5% are associated with Pallister-Hall syndrome (PHS)[1]. PHS is a very rare autosomal dominant genetic disorder due to mutation in GLI3 gene on the short arm of chromosome 7 with variable penetrance and expressivity [2]. There are two subtypes of HH depending on the anatomical location: The first type is the intrahypothalamic lesion that is usually associated with gelastic seizures. The second type is the parahypothalamic lesion, which typically develops multiple seizure types, cognitive decline and psychiatric symptoms [1].

We report on a patient (11y) with PHS, associated Panhypopituitarism and HH. She has a developmental delay and cognitive disability. At the age of 9 years she developed anxiety disorder, panic attacks and severe aggressive behaviour towards others as well as disinhibited behaviour. EEG was normal and HH ws stable on MRI. She was in child psychiatric treatment and received atypical neuroleptics, without symptom reduction.

Objective: Is this a primary psychiatric case due to cognitive impairment and psychosocial factors on PHS or secondarily induced by the HH?

Methods: Diagnostic testing included neurological examination, routine blood test, Electrocardiogramm, Echocardiography, Electroencephalography (EEG), cerebrospinal fluid analysis, including neuronal antibodies and metabolism parameters and cMRI.

Results: cMRI showed HH in constant size and all the other examinations- especially repeated EEG- were within normal range. There was no evidence for autoimmune encephalitis. After four month our patient developed her first focal status epilepticus, presenting with myoclonus, crying and anxiety. EEG showed left frontocentral epileptiform discharges and Lacosamid was started. Seizures with clonus stopped and anxiety states were reduced. However aggressive and disinhibited behaviour only became less frequent after increasing Risperidone dose. Freedom of psychiatric symptoms could not be reached so far.

Conclusion: Our patient developed psychiatric symptoms and multiple seizure types including psychiatric semiology due to HH. EEG appears normal during gelastic seizures, so the presence of other seizure types , showing focal, multifocal, or general spikes are helpful in attributing psychiatric symptoms to seizure semiology [1]. Epilepsies and severe psychiatric symptoms associated with HH are frequently drug resistant [3, 4]. The gold-standard treatment is surgical resection of the hamartoma via an open technique or by thermoablation [1, 4]. Our patient will proceed to epilepsy monitoring and surgery in an epilepsy surgery center.

Our case demonstrates the difficulties of treatment of psychiatric symptoms in patients with PHS, especially if clear seizures are absent and EEG is normal.

[1] Carballo Cuello et al, 2024: Hypothalamic Hamartoma, StatPearls, PMID: 32809498

[2] Chandra et al, 2017: Pallister-Hall Syndrome, J Pediatr Neurosci. 12(3):276-279

[3] Killeen et al, 2017: Psychiatric comorbidity with hypothalamic hamartoma: Systematic review for predictive clinical features. Epilepsy Behav. 73:126-130

[4] Régis et al, 2017: Safety and efficacy of Gamma Knife radiosurgery in hypothalamic hamartomas with severe epilepsies: A prospective trial in 48 patients and review of the literature. Epilepsia.58 Suppl 2:60-71