Directional Deep Brain Stimulation of the Posteromedial Hypothalamus for Refractory Intermittent Explosive Disorder: A Case Series Using a Novel Neurostimulation Device and Intraoperative Microdialysis.

BACKGROUND: Intermittent explosive disorder (IED) is a psychiatric disorder characterized by recurrent outbursts of aggressive behavior. Deep brain stimulation (DBS) in the posteromedial nucleus of the hypothalamus (pHyp) is an alternative therapy for extreme cases and shows promising results. Intraoperative microdialysis can help elucidate the neurobiological mechanism of pHyp-DBS. We sought to evaluate efficacy and safety of pHyp-DBS using 8-contact directional leads in patients with refractory IED (rIED) and the accompanying changes in neurotransmitters. METHODS: This was a prospective study in which patients with a diagnosis of rIED were treated with pHyp-DBS for symptom alleviation. Bilateral pHyp-DBS was performed with 8-contact directional electrodes. Follow-up was performed at 3, 6, and 12 months after surgery. RESULTS: Four patients (3 men, mean age 27 ± 2.8 years) were included. All patients were diagnosed with rIED and severe intellectual disability. Two patients had congenital rubella, one had a co-diagnosis of infantile autism, and the fourth presented with drug-resistant epilepsy. There was a marked increase in the levels of gamma-aminobutyric acid and glycine during intraoperative stimulation. The average improvement in aggressive behavior in the last follow-up was 6 points (Δ: 50%, P = 0.003) while also documenting an important improvement of the Short Form Health Survey in all domains except bodily pain. No adverse events associated with pHyp-DBS were observed. CONCLUSIONS: This is the first study to show the safety and beneficial effect of directional lead pHyp-DBS in patients with rIED and to demonstrate the corresponding mechanism of action through increases in gamma-aminobutyric acid and glycine concentration in the pHyp.

Patient Evaluation and Selection for Movement Disorders Surgery: The Changing Spectrum of Indications.

This report summarizes the state-of-the-art and controversies around patient selection for deep brain stimulation (DBS) for various conditions. Parkinson's disease (PD): several class I studies have shown superiority of DBS over best medical treatment for advanced PD with fluctuations and further inclusion criteria. One class I study suggests that PD patients with early motor complications might gain more quality of life if operated within 3 years after the onset of fluctuations. The subthalamic nucleus (STN) is still the standard target. STN DBS has an impact on impulse control disorders though the exact mechanism is unclear. Tremor: essential tremor (ET) patients found to be eligible for DBS surgery should first be treated with primidone, propranolol, and with a combined therapy preoperatively. Second-line drugs (i.e., topiramate and gabapentin) may be useful. No class I studies exist for DBS treatment of ET. The optimal target of DBS in ET might be the posterior subthalamic area. Dystonia: there is class I evidence for primary generalized and segmental dystonia and for some botulinum-resistant focal dystonias. The impact of age, symptom duration, and DYT-mutation status in primary dystonia on the outcome of DBS surgery clearly demands more studies. DBS has a role in SCGE-mutation positive myoclonus dystonia and tardive dystonia. Finally, neurostimulation in secondary dystonia might be considered in selected patients based on an individual patient's approach.

Deep Brain Stimulation of the Anterior Limb of the Internal Capsule May Be Efficacious for Explosive Aggressive Behaviour.

BACKGROUND: Intermittent explosive disease (IED) is a psychiatric disorder characterized by intermittent attacks of rage and violence frequently resistant to pharmacological therapy. Deep brain stimulation (DBS) of the posteromedial hypothalamus has been applied with fair results and clinical improvement with some surgical morbidity due to neurovegetative side effects. The anterior limb of the internal capsule/ventral capsule/ventral striatum (VC/VS) has never been used alone as a target for this disease. OBJECTIVES: The aim of this study is to evaluate the efficacy of bilateral DBS of the VC/VS for the treatment of IED. METHODS: We performed bilateral DBS of the VC/VS in a 21-year-old patient with IED. This young man had a traumatic birth complicated by hypoxia, and he showed a mild mental impairment. Different pharmacological treatments were carried out with no results before DBS was proposed to the patient's relatives after multidisciplinary approval. RESULTS: After 22 months of high-frequency monopolar bilateral DBS of the VC/VS, the patient showed a significant improvement. Postoperative 18F-FDG PET-CT studies ruled out a reduction of the hypermetabolic areas located in the limbic system previously detected in pre-operative investigations. CONCLUSIONS: Bilateral DBS of the VC/VS may be considered for the treatment of IED without the risk of neurovegetative side effects.

Single Case Study: Neuropsychological Functioning in a Patient Diagnosed with Intermittent Explosive Disorder Pre and Post Neurosurgery.

Intermittent explosive disorder (IED) is characterized by a difficulty to resist the urge to carry out a recognized harmful behavior. The central symptom is aggressiveness, expressed in isolated episodes. Executive function impairments are habitually found in impulse control disorders. Neuropsychology of impulsivity is related to dysfunctions in the orbito-frontal cortex, dorsolateral cortex and anterior-cingulated regions, being consequently involved in cognitive mechanisms of inhibition. Lesions in those areas are common in IED. In the most severe cases of IED, surgical procedures are required for treatment. In this study, we examined JML; a patient suffering from a severe case of IED. He experienced frequent episodes of auto and heteroaggression and multiple psychiatric admissions, and thus stereotactic surgery was the recommended treatment. The procedure consisted of an electrode situated lateral to the lateral ventricle, targeting the projections between frontal and subcortical affected regions. We aimed to study the neuropsychological functioning of JML, before and after electrode implantation. Our results suggested that surgery in IED improves cognitive performance at some levels. JML significantly improved his cognitive flexibility, measured with WCST, and alternate attention assessed with CPT and TMT-B tests, after electrode implantation. Cognitive flexibility deficits may be also related to increased aggressiveness. Therefore, improvements at this level may involve a reduction of impulsivity and aggressive behavior.

Cognitive development from two to ten years after pediatric epilepsy surgery.

The development of cognitive functions and the sustainability of seizure control between two and ten years after epilepsy surgery were prospectively investigated in 17 children and adolescents. Intelligence quotient remained stable. Learning capacity improved. Verbal memory improved in half of the subjects and declined in half, whereas figurative memory declined in most patients. Working memory improved as did attention regarding sustained attention and impulse control. In contrast, reaction times were longer, and the auditory attention span was shorter. Executive functions were not affected. Six subjects (35%) were seizure free at the 10-year follow-up, and a seizure reduction of more than 75% had been achieved in 13 (76%). Seizure control improved in five and seizures recurred in two subjects between the two- and the 10-year follow-up.

Deep brain stimulation of the orbitofrontal projections for the treatment of intermittent explosive disorder.

Intermittent explosive disorder (IED) is characterized by a dysfunction in the greater limbic system leading an individual to experience sudden aggressive behavior with little or no environmental perturbation. This report describes a procedure for the treatment of IED in a 19-year-old woman with a history of IED, having had episodes of severe violent attacks against family, dating to early childhood. Due to the severity and intractability of the illness, deep brain stimulation was performed, targeting the orbitofrontal projections to the hypothalamus. The patient's history and the procedure, management, and rationale are described in detail.