The responsive neurostimulation (RNS) system, an adjunctive treatment for pharmacoresistant partial-onset seizures with 1 or 2 foci, has been available to patients aged 18 years or older since the device’s FDA approval in 2013. Herein, the authors describe their off-label application of this technology in 2 pediatric patients and the consequent therapeutic benefit without surgical complications or treatment side effects. A 14-year-old nonambulatory, nonverbal male with severe developmental delay was considered for RNS therapy for medically and surgically refractory epilepsy with bilateral seizure onsets in the setting of a normal radiological examination and a known neuropathological diagnosis of type I cortical dysplasia. The RNS system was implanted with strip electrodes placed on the left lateral frontal and right lateral temporal neocortex. At 19 months’ follow-up, cortical stimulation resulted in sustained reduction in both seizure frequency—3 seizures per day down from 15 to 30 per day—and seizure severity. The patient subsequently underwent a trial of corticothalamic stimulation with a right temporal cortical strip and a left thalamic depth electrode, which resulted in a further 50% reduction in seizure frequency. In a second case, a 9-year-old right-handed female with radiological evidence of a small watershed infarct on the left and medically refractory seizures was referred for presurgical evaluation. Invasive monitoring revealed an unresectable seizure focus in the eloquent cortex of the left posterior frontal and parietal lobes. The RNS device was implanted with cortical leads placed at the putative seizure focus. At 21 months after surgery, the patient had been seizure free for 4 months, following a 17-month period in which the seizure frequency had decreased from 12 per month to 2 per month, with associated functional and behavioral improvement. The authors’ results suggest that RNS may be a palliative option for children with intractable seizures whose condition warrants off-label use of the surgical device. The improved therapeutic effect noted with time and sustained RNS treatment points to a possible neuromodulatory effect.

Object The risk of developing epilepsy after perinatal stroke, hypoxic/ischemic injury, and intracerebral hemorrhage is significant, and seizures may become medically refractory in approximately 25% of these patients. Surgical management can be difficult due to multilobar or bilateral cortical injury, nonfocal or poorly lateralizing video electroencephalography (EEG) findings, and limited functional reserve. In this study the authors describe the surgical approaches, seizure outcomes, and complications in patients with epilepsy due to vascular etiologies in the perinatal period and early infancy. Methods The records were analyzed of 19 consecutive children and adults with medically refractory epilepsy and evidence of perinatal arterial branch occlusions, hypoxic/ischemic insult, or hemorrhagic strokes, who underwent surgery at the Comprehensive Epilepsy Center of Beth Israel Medical Center and St. Luke's-Roosevelt Hospital Center. Preoperative findings including MRI, video EEG, functional MRI, and neuropsychological testing were analyzed. The majority of patients underwent staged operations with invasive mapping, and all patients had either extra- or intraoperative functional mapping. Results In 7 patients with large porencephalic cysts due to major arterial branch occlusions, periinsular functional hemispherotomy was performed in 4 children, and in 3 patients, multilobar resections/disconnections were performed, with 1 patient undergoing additional resections 3 years after initial surgery due to recurrence of seizures. All of these patients have been seizure free (Engel Class IA) after a mean 4.5-year follow-up (range 15–77 months). Another 8 patients had intervascular border-zone ischemic infarcts and encephalomalacia, and in this cohort 2 hemispherotomies, 5 multilobar resections/disconnections, and 1 focal cortical resection were performed. Seven of these patients remain seizure free (Engel Class IA) after a mean 4.5-year follow-up (range 9–94 months), and 1 patient suffered a single seizure after 2.5 years of seizure freedom (Engel Class IB, 33-month follow-up). In the final 4 patients with vascular malformation-associated hemorrhagic or ischemic infarction in the perinatal period, a hemispherotomy was performed in 1 case, multilobar resections in 2 cases, and in 1 patient a partial temporal lobectomy was performed, followed 6 months later by a complete temporal and occipital lobectomy due to ongoing seizures. All of these patients have had seizure freedom (Engel Class IA) with a mean follow-up of 4.5 years (range 10–80 months). Complications included transient monoparesis or hemiparesis in 3 patients, transient mutism in 1 patient, infection in 1 patient, and a single case of permanent distal lower-extremity weakness. Transient mood disorders (depression and anxiety) were observed in 2 patients and required medical/therapeutic intervention. Conclusions Epilepsy surgery is effective in controlling medically intractable seizures after perinatal vascular insults. Seizure foci tend to be widespread and rarely limited to the area of injury identified through neuroimaging, with invasive monitoring directing multilobar resections in many cases. Long-term functional outcomes have been good in these patients, with significant improvements in independence, quality of life, cognitive development, and motor skills, despite transient postoperative monoparesis or hemiparesis and occasional mood disorders.

OBJECTIVE The purpose of this study was to report outcomes of epilepsy surgery in 56 consecutive patients with autism spectrum disorder. METHODS Medical records of 56 consecutive patients with autism who underwent epilepsy surgery were reviewed with regard to clinical characteristics, surgical management, postoperative seizure control, and behavioral changes. RESULTS Of the 56 patients with autism, 39 were male, 45 were severely autistic, 27 had a history of clinically significant levels of aggression and other disruptive behaviors, and 30 were considered nonverbal at baseline. Etiology of the epilepsy was known in 32 cases, and included structural lesions, medical history, and developmental and genetic factors. Twenty-nine patients underwent resective treatments (in 8 cases combined with palliative procedures), 24 patients had only palliative treatments, and 3 patients had only subdural electroencephalography. Eighteen of the 56 patients had more than one operation. The mean age at surgery was 11 ± 6.5 years (range 1.5–35 years). At a mean follow-up of 47 ± 30 months (range 2–117 months), seizure outcomes included 20 Engel Class I, 12 Engel Class II, 18 Engel Class III, and 3 Engel Class IV cases. The age and follow-up times are stated as the mean ± SD. Three patients were able to discontinue all antiepileptic drugs (AEDs). Aggression and other aberrant behaviors observed in the clinical setting improved in 24 patients. According to caregivers, most patients also experienced some degree of improvement in daily social and cognitive function. Three patients had no functional or behavioral changes associated with seizure reduction, and 2 patients experienced worsening of seizures and behavioral symptoms. CONCLUSIONS Epilepsy surgery in patients with autism is feasible, with no indication that the comorbidity of autism should preclude a good outcome. Resective and palliative treatments brought seizure freedom or seizure reduction to the majority of patients, although one-third of the patients in this study required more than one procedure to achieve worthwhile improvement in the long term, and few patients were able to discontinue all AEDs. The number of palliative procedures performed, the need for multiple interventions, and continued use of AEDs highlight the complex etiology of epilepsy in patients with autism spectrum disorder. These considerations underscore the need for continued analysis, review, and reporting of surgical outcomes in patients with autism, which may aid in better identification and management of surgical candidates. The reduction in aberrant behaviors observed in this series suggests that some behaviors previously attributed to autism may be associated with intractable epilepsy, and further highlights the need for systematic evaluation of the relationship between the symptoms of autism and refractory seizures.

Two individuals with intractable generalized dystonia secondary to glutaric aciduria type 1 (GA1) were treated with continuous intraventricular baclofen (IVB) infusion. On IVB of 220 lg/day, one 10-year-old girl had an 85% reduction in dystonia, from Barry-Albright Dystonia Scale (BADS) score 30.7 to 4.5 (maximum score: 32) at 30 postoperative months. Her enteral dystonia medications were reduced >60%, and she discontinued medications for pain, anxiety, and depression. A second GA1 patient, age 23, experienced a more modest 18% reduction in dystonia (BADS decrease from 29.7 to 24.3) on IVB of 1,665 lg/day at 14 postoperative months. He substantially reduced his enteral dystonia medications and reported meaningful pain relief. These cases demonstrate that IVB may be a palliative option in the intractable dystonia of GA1. Our provisional observations suggest that IVB may be more beneficial in younger GA1 patients.Glutaryl-CoA dehydrogenase deficiency (glutaric aciduria type 1; GA1, MIM 231670) is a rare hereditary metabolic disorder that can result in striatal degeneration during early brain development, either precipitated by an infectious illness or presenting as insidious motor delay subsequent to perinatal brain injury. In recent years, advances in dietary therapy have allowed effective prevention of brain injury in more than 90% of asymptomatic children diagnosed by newborn screening. Nevertheless, a large number of adolescent and adult GA1 patients worldwide have irreversible striatal lesions and consequently suffer from chronic, medically intractable dystonia.Pallidotomy and internal pallidal DBS have been attempted in GA1 patients, but compared to their utility in treating primary dystonias have proven minimally effective for relieving the secondary dystonia of GA1 (Table 1). [1][2][3][4] We successfully treated 2 GA1 patients with severe dystonia using intraventricular baclofen (IVB). We based this approach on the work of Albright and Ferson, who pioneered the use of IVB and demonstrated that it is more effective for treating secondary dystonias in children than the intrathecal route of baclofen delivery.5 Importantly, 2 of their study subjects with neurogenetic disorders that share pathophysiological similarities to GA1 (pantothenate kinase deficiency and methylmalonic acidemia) responded well to IVB, with Barry-Albright Dystonia Scale (BADS) scores decreasing by 83% and 100%, respectively. 5 Based on these observations, we implanted IVB catheters in 2 GA1 patients and here report favorable postoperative outcomes. Patient 1A 10-year-old girl presented with generalized dystonia of 8 years' duration. After an uneventful gestation and term delivery, she made good developmental progress until 17 months of age, when she suffered acute striatal lesions during a febrile illness, prompting the diagnosis of GA1. She subsequently

No abstract