New insights to hypothalamic hamartoma syndrome

Hypothalamic Hamartoma (HH) Syndrome is a rare condition in which benign subcortical lesion attached to the hypothalamus results in a multitude of symptoms including refractory epilepsy, endocrine dysfunction, developmental delay and psychiatric comorbidities. Gelastic "laughing" seizures are the identifying symptom of HH syndrome, but often remain unidentified until other seizure types occur. In this review we summarize typical presentations that lead to diagnosis. The literature suggests that early MRI imaging, detailed assessment of endocrine function and formal neuropsychological testing are most important after diagnosis. EEG tests are usually less valuable than in other epilepsies and gelastic seizures may occur without ictal EEG changes. Experts agree that most patients with seizures are refractory to antiseizure medications. Therefore, early surgical intervention is recommended. Three main minimally invasive techniques are currently used: Laserinterstitial thermal therapy, radiosurgery and radiofrequency thermocoagulation. Three large meta-analysis collecting data from more than 500 patients treated with these techniques have been published. Safety profiles of all three methods are good and superior to micro-surgical approaches used previously. Most common complications are hypothalamic-endocrine dysfunction and mild neurological symptoms. 70-90% of patients are seizure free after the interventions, around 20-30% requiring multiple treatment to archive this outcome. Overall, minimally invasive approaches have revolutionized long-term outcomes in HH. Meanwhile, new genetic methods are being developed to better understand mechanisms that cause HH. Most importantly knowledge is still lacking about how these localized lesions can cause substantial developmental delay and psychiatric comorbidity that persist even after successful surgical removal.