ABSTRACT
Outcomes following vagus nerve stimulation (VNS) improve over years after implantation in children with drug-resistant epilepsy. The added value of deep brain stimulation (DBS) instead of continued VNS optimization is unknown. In a prospective, non-blinded, randomized patient preference trial of 18 children (aged 8-17 years) who did not respond to VNS after at least 1 year, add-on DBS resulted in greater seizure reduction compared with an additional year of VNS optimization (51.9% vs. 12.3%, p = 0.047). Add-on DBS also resulted in less bothersome seizures (p = 0.03), but no change in quality of life. DBS may be considered earlier for childhood epilepsy after non-response to VNS. ANN NEUROL 2024;96:405-411.
Subject(s)
Deep Brain Stimulation , Drug Resistant Epilepsy , Patient Preference , Vagus Nerve Stimulation , Humans , Child , Vagus Nerve Stimulation/methods , Adolescent , Male , Deep Brain Stimulation/methods , Female , Drug Resistant Epilepsy/therapy , Treatment Outcome , Prospective Studies , Quality of LifeABSTRACT
INTRODUCTION: L-2-hydroxyglutaric aciduria (L2HGA) is a rare neurometabolic disorder marked by progressive and debilitating psychomotor deficits. Here, we report the first patient with L2HGA-related refractory dystonia that was managed with deep brain stimulation to the bilateral globus pallidus internus (GPi-DBS). CASE PRESENTATION: We present a 17-year-old female with progressive decline in cognitive function, motor skills, and language ability which significantly impaired activities of daily living. Neurological exam revealed generalized dystonia, significant choreic movements in the upper extremities, slurred speech, bilateral dysmetria, and a wide-based gait. Brisk deep tendon reflexes, clonus, and bilateral Babinski signs were present. Urine 2-OH-glutaric acid level was significantly elevated. Brain MRI showed extensive supratentorial subcortical white matter signal abnormalities predominantly involving the U fibers and bilateral basal ganglia. Genetic testing identified a homozygous pathogenic mutation in the L-2-hydroxyglutarate dehydrogenase gene c. 164G>A (p. Gly55Asp). Following minimal response to pharmacotherapy, GPi-DBS was performed. Significant increases in mobility and decrease in dystonia were observed at 3 weeks, 6 months, and 12 months postoperatively. CONCLUSION: This is the first utilization of DBS as treatment for L2HGA-related dystonia. The resulting significant improvements indicate that pallidal neuromodulation may be a viable option for pharmaco-resistant cases, and possibly in other secondary metabolic dystonias.
Subject(s)
Deep Brain Stimulation , Dystonia , Globus Pallidus , Humans , Female , Globus Pallidus/diagnostic imaging , Adolescent , Dystonia/therapy , Dystonia/genetics , Brain Diseases, Metabolic, Inborn/therapy , Brain Diseases, Metabolic, Inborn/geneticsABSTRACT
Epilepsy is a common and debilitating neurological disorder, and approximately one-third of affected individuals have ongoing seizures despite appropriate trials of two anti-seizure medications. This population with drug-resistant epilepsy (DRE) may benefit from neurostimulation approaches, such as vagus nerve stimulation (VNS), deep brain stimulation (DBS) and responsive neurostimulation (RNS). In some patient populations, these techniques are FDA-approved for treating DRE. VNS is used as adjuvant therapy for children and adults. Acting via the vagus afferent network, VNS modulates thalamocortical circuits, reducing seizures in approximately 50 â% of patients. RNS uses an adaptive (closed-loop) system that records intracranial EEG patterns to activate the stimulation at the appropriate time, being particularly well-suited to treat seizures arising within eloquent cortex. For DBS, the most promising therapeutic targets are the anterior and centromedian nuclei of the thalamus, with anterior nucleus DBS being used for treating focal and secondarily generalized forms of DRE and centromedian nucleus DBS being applied for treating generalized epilepsies such as Lennox-Gastaut syndrome. Here, we discuss the indications, advantages and limitations of VNS, DBS and RNS in treating DRE and summarize the spatial distribution of neuroimaging observations related to epilepsy and stimulation using NeuroQuery and NeuroSynth.