Seizure frequency reduction after posteromedial hypothalamus deep brain stimulation in drug‐resistant epilepsy associated with intractable aggressive behavior

Abstract

Summary Objectives The aim of this study was to analyze the impact of deep brain stimulation (DBS) of the posteromedial hypothalamus (pHyp) on seizure frequency in patients with drug‐resistant epilepsy (DRE) associated with intractable aggressive behavior (IAB). Methods Data were collected retrospectively from nine patients, who received bilateral stereotactic pHyp‐DBS for the treatment of medically intractable aggressive behavior, focusing on five patients who also had DRE. All patients were treated at the Colombian Center and Foundation of Epilepsy and Neurological Diseases—FIRE (Chapter of the International Bureau for Epilepsy), in Cartagena de Indias, Colombia from 2010 to 2014. Each case was evaluated previously by the institutional ethical committee, assessing the impact of aggressive behavior on the patient's family and social life, the humanitarian aspects of preserving the safety and physical integrity of caregivers, and the need to prevent self‐harm. Epilepsy improvement was measured by a monthly seizure reduction percentage, comparing preoperative state and outcome. Additional response to epilepsy was defined by reduction of the antiepileptic drugs (AEDs). Aggressive behavior response was measured using the Overt Aggression Scale (OAS). Results All the patients with DRE associated with IAB presented a significant decrease of the rate of epileptic seizures after up to 4 years follow‐up, achieving a general 89.6% average seizure reduction from the state before the surgery. Aggressiveness was significantly controlled, with evident improvement in the OAS, enhancing the quality of life of patients and families. Significance In well‐selected patients, DBS of the pHyp seems to be a safe and effective procedure for treatment of DRE associated with refractory aggressive behavior. Larger and prospective series are needed to define the pHyp as a target for DRE in different contexts.

Exploring the brain through posterior hypothalamus surgery for aggressive behavior

“…Seizure outcomes also were impressive. 15 In all these series, adverse neurovegetative effects were encountered when the stimulation amplitude was higher than 3 V, which confirms what Sano found in the 1970s and might limit the therapeutic window of DBS. A summary of the aforementioned experiences is listed in Table 2.…”

“…For these reasons, it has been used successfully as a palliative therapy in some rare cases in which pharmacological therapy and social measures were not enough to control aggressive behavior. 15,23 Both the lesional and DBS experiences have enabled us to understand the role of specific brain structures and to formulate reliable hypotheses on the physiology of the brain and the pathophysiology of aggressive behavior. These data are of paramount relevance, together with those coming from clinical and animal laboratory studies.…”

“…For example, surgery of the posterior hypothalamic region has been reported to be an effective treatment in severe cases of aggressive behavior in patients with intellectual disability (ID), 15,23,35,38,66 which enables us to formulate a hypothesis on disease pathogenesis and brain functioning. 51 …”

Deep Brain Stimulation for the Treatment of Aggressive Behaviour: Considerations on Pathophysiology and Target Choice

“…Bilateral pHyp DBS has been extensively used with efficacy [6,7,8,9,10,11,12]. Some disputations about the fact that the pHyp target of Sano et al [13] be at the level of the diencephalon-mesencephalic junction (the “posterior hypothalamic region”) [14] or definitely in the ventral tegmental area (VTA) have to be considered [15,16] in order to better understand the anatomical substrate of the disorder.…”

“…The pHyp target was reported to be effective in the palliative treatment of drug refractory seizures in different series [8,10]. The mechanism of action probably relies on the modulation of the mammillothalamic tract of Vicq d'Azir, which lies just anterior to the pHyp target.…”