Decision-making in stereotactic epilepsy surgery.

Surgery can cure or significantly improve both the frequency and the intensity of seizures in patients with medication-refractory epilepsy. The set of diagnostic and therapeutic interventions involved in the path from initial consultation to definitive surgery is complex and includes a multidisciplinary team of neurologists, neurosurgeons, neuroradiologists, and neuropsychologists, supported by a very large epilepsy-dedicated clinical architecture. In recent years, new practices and technologies have emerged that dramatically expand the scope of interventions performed. Stereoelectroencephalography has become widely adopted for seizure localization; stereotactic laser ablation has enabled more focal, less invasive, and less destructive interventions; and new brain stimulation devices have unlocked treatment of eloquent foci and multifocal onset etiologies. This article articulates and illustrates the full framework for how epilepsy patients are considered for surgical intervention, with particular attention given to stereotactic approaches.

Utilization of skin biopsy for diagnosis in a case of Lafora disease.

Lafora disease is a rare inherited neurodegenerative disease with onset in adolescence. Patients present with progressive myoclonic seizures and cognitive decline. The disease is linked to mutations in either of the two genes encoding malin and laforin, and it is associated with the accumulation of polyglucosan inclusions (Lafora bodies [LBs]) in various tissues, such as brain, liver, muscle, and skin, with the skin being particularly accessible for biopsy. Histopathologic examination of affected tissue with demonstration of LBs, together with the presence of pathologic mutation in EPM2A or NHLRC1 genes, is sufficient for diagnosis of this neurologic disorder when clinically suspected. Here, we report the case of a 16-year-old female with progressive neurologic symptoms and homozygous mutation in the NHLRC1 gene encoding malin. The skin biopsy was instrumental in reaching the final diagnosis by showing LBs in sweat glands by histopathologic and electron microscopic examination.

Masking for School-Age Children With Epilepsy: We Do Have Consensus!

INTRODUCTION: This study was designed to assess current recommendations from child neurologists and epileptologists on masking for school-age children with epilepsy. METHODS: A 7-item survey was created and sent out to members of the Child Neurology Society and Pediatric Epilepsy Research Consortium in August of 2021 to assess current practice and provider recommendations on masking. RESULTS: One hundred four individuals participated with representation from all regions of the United States. Masking was recommended by 95.1%, with 63.4% (n = 66) noting exception of those with severe intellectual disability, autism, and behavioral problems. Of those who write exemption letters, 54% write these <5% of the time. Only 3% reported potential adverse events associated with masking. CONCLUSION: Nearly all respondents recommended masking for school-age children with epilepsy. Potential risks of masking and adverse events were low. Improved guidance on masking is needed to ensure academic success of our patients with epilepsy.

Seizure Semiology, EEG, and Imaging Findings in Epilepsy Secondary to Mitochondrial Disease.

Background: Identification of an underlying mitochondrial disorder can be challenging due to the significant phenotypic variability between and within specific disorders. Epilepsy can be a presenting symptom with several mitochondrial disorders. In this study, we evaluated clinical, electrophysiologic, and imaging features in patients with epilepsy and mitochondrial disorders to identify common features, which could aid in earlier identification of a mitochondrial etiology. Methods: This is a retrospective case series from January 2011 to December 2019 at a tertiary referral center of patients with epilepsy and a genetically confirmed diagnosis of a mitochondrial disorder. A total of 164 patients were reviewed with 20 patients fulfilling inclusion criteria. Results: A total of 20 patients (14 females, 6 males) aged 0.5-61 years with epilepsy and genetically confirmed mitochondrial disorders were identified. Status epilepticus occurred in 15 patients, with focal status epilepticus in 13 patients, including 9 patients with visual features. Abnormalities over the posterior cerebral regions were seen in 66% of ictal recordings and 44% of imaging studies. All the patients were on nutraceutical supplementation with no significant change in disease progression seen. At last follow-up, eight patients were deceased and the remainder had moderate-to-severe disability. Discussion: In this series of patients with epilepsy and mitochondrial disorders, we found increased propensity for seizures arising from the posterior cerebral regions. Over time, electroencephalogram (EEG) and imaging abnormalities increasingly occurred over the posterior cerebral regions. Focal seizures and focal status epilepticus with visual symptoms were common. Additional study is needed on nutraceutical supplementation in mitochondrial disorders.

Treatment Practices and Outcomes in Continuous Spike and Wave during Slow Wave Sleep: A Multicenter Collaboration.

OBJECTIVES: To determine how continuous spike and wave during slow wave sleep (CSWS) is currently managed and to compare the effectiveness of current treatment strategies using a database from 11 pediatric epilepsy centers in the US. STUDY DESIGN: This retrospective study gathered information on baseline clinical characteristics, CSWS etiology, and treatment(s) in consecutive patients seen between 2014 and 2016 at 11 epilepsy referral centers. Treatments were categorized as benzodiazepines, steroids, other antiseizure medications (ASMs), or other therapies. Two measures of treatment response (clinical improvement as noted by the treating physician; and electroencephalography improvement) were compared across therapies, controlling for baseline variables. RESULTS: Eighty-one children underwent 153 treatment trials during the study period (68 trials of benzodiazepines, 25 of steroids, 45 of ASMs, 14 of other therapies). Children most frequently received benzodiazepines (62%) or ASMs (27%) as first line therapy. Treatment choice did not differ based on baseline clinical variables, nor did these variables correlate with outcome. After adjusting for baseline variables, children had a greater odds of clinical improvement with benzodiazepines (OR 3.32, 95%CI 1.57-7.04, P = .002) or steroids (OR 4.04, 95%CI 1.41-11.59, P = .01) than with ASMs and a greater odds of electroencephalography improvement after steroids (OR 3.36, 95% CI 1.09-10.33, P = .03) than after ASMs. CONCLUSIONS: Benzodiazepines and ASMs are the most frequent initial therapy prescribed for CSWS in the US. Our data suggests that ASMs are inferior to benzodiazepines and steroids and support earlier use of these therapies. Multicenter prospective studies that rigorously assess treatment protocols and outcomes are needed.

A Novel Phenotype in a Previously Described Epilepsy-Aphasia Disorder.

The clinical presentation of patients with epileptic encephalopathies can be heterogenous. When attempting to classify a patient's epilepsy syndrome, challenges can arise due to the phenotypic overlap of various epilepsies as well as the different presentations of mutations within the same gene. Genetic testing can be most helpful in evaluation of children with features spanning several epilepsy phenotypes. In this case, we report on a boy with an epileptic encephalopathy found to have a previously unreported mutation in a recently described gene.

De Novo DNM1L Variant in a Teenager With Progressive Paroxysmal Dystonia and Lethal Super-refractory Myoclonic Status Epilepticus.

BACKGROUND: The dynamin 1-like gene ( DNM1L) encodes a GTPase that mediates mitochondrial and peroxisomal fission and fusion. We report a new clinical presentation associated with a DNM1L pathogenic variant and review the literature. RESULTS: A 13-year-old boy with mild developmental delays and paroxysmal dystonia presented acutely with multifocal myoclonic super-refractory status epilepticus. Despite sustained and aggressive treatment, seizures persisted and care was ultimately withdrawn in the context of extensive global cortical atrophy. Rapid trio-whole exome sequencing revealed a de novo heterozygous c.1207C>T (p.R403C) pathogenic variant in DNM1L. Immunofluorescence staining of fibroblast mitochondria revealed abnormally elongated and tubular morphology. CONCLUSIONS: This case highlights the diagnostic importance of rapid whole exome sequencing within a critical care setting and reveals the expanding phenotypic spectrum associated with DNM1L variants. This now includes progressive paroxysmal dystonia and adolescent-onset super-refractory myoclonic status epilepticus contributing to strikingly rapid and progressive cortical atrophy and death.

Cost-Effectiveness of Evaluation of Children With Epilepsy in the Emergency Department: Need for Investment in Patient Education.

We aimed to study cost-effectiveness of seizure evaluation of children with epilepsy in the emergency department (ED). We reviewed epilepsy patients seen at our ED for 1 year. Age, laboratory and neuroimaging results, treatment, disposition, and usefulness of the visit (need for hospitalization, clinical improvement) were analyzed. We identified 330 patients, aged 23 days-21 years, 190 (57.5%) had blood tests, 45 (13.6%) urinalysis, 2 (0.6%) cerebrospinal fluid testing, and 44 neuroimaging studies (13.3%). Tests' positive yield were 41%, 11%, 0%, and 4.5%, respectively. One-third of patients (n = 122) were treated with antiepileptic drugs. Other treatments were administered to 44 (13.3%). One hundred eighteen patients (35.7%) were admitted to our hospital, 208 (63%) discharged to home. Two hundred eight visits were useful (63%). One-third of visits did not provide useful patient care. Their visits were expensive and not very cost-effective. Investment in patient education could decrease unnecessary ED visits.

Propylene Glycol Toxicity in Adolescent with Refractory Myoclonic Status Epilepticus.

Propylene glycol (PG) is a solvent commonly used in medications that, while benign at low doses, may cause toxicity in adults and children at high doses. We describe a case and the physiologic sequelae of propylene glycol toxicity manifested in a critically ill adolescent male with refractory myoclonic status epilepticus aggressively treated with multiple PG-containing medications (lorazepam, phenobarbital, and pentobarbital)-all within accepted dosing guidelines and a total daily PG exposure previously recognized to be safe. Hemodynamic measurements by bedside echocardiography during clinical toxicity are also reported. Clinicians should have a high index of suspicion for propylene glycol toxicity in patients treated with PG-containing medications even when the total PG exposure is lower than currently accepted limits.

Acetazolamide for electrical status epilepticus in slow-wave sleep.

Electrical status epilepticus in slow-wave sleep (ESES) is characterized by nearly continuous spike-wave discharges during non-rapid eye movement (REM) sleep. ESES is present in Landau-Kleffner syndrome (LKS) and continuous spike and wave in slow-wave sleep (CSWS). Sulthiame has demonstrated reduction in spike-wave index (SWI) in ESES, but is not available in the United States. Acetazolamide (AZM) is readily available and has similar pharmacologic properties. Our aims were to assess the effect of AZM on SWI and clinical response in children with LKS and CSWS. Children with LKS or CSWS treated with AZM at our institution were identified retrospectively. Pre- and posttherapy electroencephalography (EEG) studies were evaluated for SWI. Parental and teacher report of clinical improvement was recorded. Six children met criteria for inclusion. Three children (50%) demonstrated complete resolution or SWI <5% after AZM. All children had improvement in clinical seizures and subjective improvement in communication skills and school performance. Five of six children had subjective improvement in hyperactivity and attention. AZM is a potentially effective therapy for children with LKS and CSWS. This study lends to the knowledge of potential therapies that can be used for these disorders, which can be challenging for families and providers.

A patient with myelomeningocele: is untethering necessary prior to scoliosis correction?

OBJECT: Tethering of the spinal cord is thought to increase the chance of neurological injury when scoliosis correction is undertaken. All patients with myelomeningocele (MM) are radiographically tethered, and untethering procedures carry significant morbidity risks including worsening neurological function and wound complications. No guidelines exist as regards untethering in patients with MM prior to scoliosis correction surgery. The authors' aim in this study was to evaluate their experience in patients with MM who were not untethered before scoliosis correction. METHODS: Seventeen patients with MM were retrospectively identified and 1) had no evidence of a clinically symptomatic tethered cord, 2) had undergone spinal fusion for scoliosis correction, and 3) had not been untethered for at least 1 year prior to surgery. The minimum follow-up after fusion was 2 years. Charts and radiographs were reviewed for neurological or shunt complications in the perioperative period. RESULTS: The average age of the patients was 12.4 years, and the following neurological levels were affected: T-12 and above, 7 patients; L-1/L-2, 6 patients; L-3, 2 patients; and L-4, 2 patients. All were radiographically tethered as confirmed on MR imaging. Fourteen of the patients (82%) had a ventriculoperitoneal shunt. The mean Cobb angle was corrected from 82 degrees to 35 degrees , for a 57% correction. All patients underwent neuromonitoring of their upper extremities, and some underwent lower extremity monitoring as well. Postoperatively, no patient experienced a new cranial nerve palsy, shunt malfunction, change in urological function, or upper extremity weakness/sensory loss. One patient had transient lower extremity weakness, which returned to baseline within 1 month of surgery. CONCLUSIONS: The study results suggested that spinal cord untethering may be unnecessary in patients with MM who are undergoing scoliosis corrective surgery and do not present with clinical symptoms of a tethered cord, even though tethering is radiographically demonstrated.