What happens to cognitive function following surgery for hypothalamic hamartoma?

Hypothalamic hamartoma (HH) and gelastic epilepsy is a rare but well-recognized drug-resistant epileptic syndrome of early life. Cognitive impairments and behavior disturbance occur commonly in patients with HH and gelastic epilepsy, especially those with progressive seizure and EEG evolution during early childhood. Intellectual disability, autism, and episodic rage are commonly encountered in patients who have evolved a generalized epileptic encephalopathy. Over the last 15 years, a variety of microsurgical, endoscopic, and stereotactic approaches to resect and ablate HH have been reported, with variable efficacy and morbidity. Epilepsy surgery is now accepted as the treatment of choice for drug-resistant seizures associated with HH, the questions being which surgical approaches are more effective for which types of HH, how early should one operate, and whether surgery alters cognitive and behavioral outcomes. In this issue of Neurology®,Wethe et al. from the BarrowNeurological Institute address some of these issues. The authors report cognitive findings before and after transcallosal and endoscopic resection of HH in children (older than 3 years) and adults with uncontrolled gelastic epilepsy. Patients with a large prepontine component of HH undergoing skull base or combined approaches are not included in their series, nor are those with small lesions undergoing stereotactic radiosurgery. The Barrow group has the largest experience with HH epilepsy surgery and is well-positioned to report outcomes. As with most pediatric epilepsy surgery outcome studies, their study was made difficult by relatively small patient numbers, heterogeneity of the patient population (age at surgery, seizures, HH type and size, preoperative cognitive functioning), evolution of treatment approach, incomplete and sometimes short follow-up, and variability in cognitive testing related to patient age, patient ability, and referral source. The important findings from the study were that 1) no patients deteriorated in overall cognitive functioning after surgery, 2) measures and estimates of intellectual functioning improved postoperatively at a group level, and 3) patients with more severe cognitive impairment preoperatively improved the most following surgery. The findings are the most comprehensive reported for a large group of patients undergoing HH epilepsy surgery, and are reassuring given the current popularity and ongoing development of surgical therapies for HH and gelastic epilepsy. The mechanisms by which cognitive and behavioral deficits develop in patients with HH and gelastic epilepsy, and are potentially affected by HH surgery, are not examined or discussed in detail by the authors. Gelastic seizures propagate via mammillothalamic pathways, such that their elimination might well be associated with improved limbic function. In patients whose epilepsy evolves with the development of tonic seizures and generalized spike-wave on EEG, successful epilepsy surgery might reverse the generalized epileptic encephalopathy and result in substantial neurobehavioral improvements. Conversely, surgical injury to the mammillary body or fornix during open or stereotactic procedures, particularly if on the language-dominant side or if bilateral, could lead to devastating impairment of new learning. It is worth highlighting at this point that the expertise and experience of the neurosurgeon performing such third ventricular or skull base surgery on HH are significant determinants of seizure control and postoperative complications, including amnesia, endocrine disturbance, and stroke. The study by Wethe et al. is heavily based on psychometric testing and statistical analyses, assessing trends across the group of patients and looking for correlations with clinical and surgical indices such as seizure freedom, type of HH, and surgical technique. Whereas such an approach is scientifically sound, and performed with appropriate statistical rigor by the authors, it potentially masks changes occurring in specific patient subgroups and potentially ignores changes in day-to-day functioning. For example, patients without a measurable increase in intellect following surgery might still, in the absence of seizures and taking fewer medications, make greater academic and vocational achievements and have fewer interpersonal conflicts. Reversal of a generalized epileptic encephalopathy with cessation of tonic seizures and normalization of the EEG, but with persistence of gelastic seizures, would