The Effect of Smartphone Video on Lead Time to Diagnosis of Infantile Spasms.

OBJECTIVE: To assess whether access to smartphone video capture of infantile spasms at initial presentation is associated with improved time to diagnosis and treatment. METHODS: We conducted a collaborative retrospective cohort study of 80 consecutive infants with confirmed infantile epileptic spasms syndrome initially presenting from 2015 to 2021 at 2 US pediatric centers. Statistical methods used included Mann-Whitney U test to assess the difference in lead times to electroencephalogram (EEG), diagnosis, and treatment between groups with and without video capture. A χ2 analysis was used to assess differences in demographics, clinical characteristics, and treatment outcomes between groups. Multivariate regression analysis was used to account for etiology types and infantile spasms capture on EEG. RESULTS: Patients with smartphone video infantile spasms capture initially presented a median of 9 days earlier (P = .02), had their first EEG 16 days earlier (P = .007), and were diagnosed and started treatment 17 days earlier (P = .006 and P = .008, respectively) compared with the nonvideo group. The video group had a 25% greater response to initial standard treatment (P = .02) and a 21% greater freedom from infantile spasms at long-term follow-up (P = .03), although this long-term outcome lost statistical significance after adjustment for etiology type (P = .07) and EEG capture of infantile spasms (P = .059). CONCLUSION: Our findings suggest a benefit of smartphone video capture of infantile spasms in reduced time to diagnosis and initial standard treatment, which are associated with improved treatment response rates. Substantial differences in lead times and treatment response highlight the clinical importance of pediatricians recommending caregivers to obtain smartphone video of events concerning for infantile spasms.

EEG Findings Enhance the Yield of Epilepsy Gene Panel Testing in Children.

BACKGROUND: Epilepsies with encephalopathy are important to promptly and thoroughly evaluate because of their associated refractory nature and potential for neurologic regression. METHODS: The results of epilepsy gene panel testing were obtained for 109 pediatric patients at Nemours Children's Center in Jacksonville, Florida, from 04/2019 to 02/2021. Results were obtained from Invitae TM via the offered epilepsy gene panel test and Behind the Seizure program. The EEGs for each patient were independently analyzed and categorized based on the presence or absence of features consistent with an epileptogenic encephalopathy. RESULTS: EEG characterization and identification of patients with epileptogenic encephalopathy in our study was helpful in identifying patients, with an 80% yield on epilepsy gene panel testing. CONCLUSIONS: EEG characterization can be incorporated into the evaluation of patients with epilepsy in order to optimize the selection of patients who are likely to benefit from an epilepsy gene panel test.

Advances in Epilepsy Surgery.

BACKGROUND: A large number of patients have epilepsy that is intractable and adversely affects a child's lifelong experience with addition societal burden that is disabling and expensive. The last two decades have seen a major explosion of new antiseizure medication options. Despite these advances, children with epilepsy continue to have intractable seizures. An option that has been long available but little used is epilepsy surgery to control intractable epilepsy. METHODS: This article is a review of the literature as well as published opinions. RESULTS: Epilepsy surgery in pediatrics is an underused modality to effectively treat children with epilepsy. Adverse effects of medication should be weighed against risks of surgery as well as risks of nonefficacy. CONCLUSIONS: We discuss an approach to selecting the appropriate pediatric patient for consideration, a detailed evaluation including necessary evaluation, and the creation of an algorithm to approach patients with both generalized and focal epilepsy. We then discuss surgical options available including outcome data. New modalities are also addressed including high-frequency ultrasound and co-registration techniques including magnetic resonance imaging-guided laser therapy.

Patterns Specific to Pediatric EEG.

Misinterpretations of the EEG can result in erroneous diagnosis of epilepsy, causing considerable family anxiety, over protectiveness of children, and delays in normal development and developmental exploration. The burden of a chronic disease can result in expensive and unnecessary medical treatment. The misdiagnosis of epilepsy has been well documented in adults, but misdiagnosis in normal children can have a long-lasting impact on their health. Furthermore, the EEG has a wider range of morphology and hence a greater opportunity for the missed diagnosis of epilepsy. Lack of familiarity of normal sleep patterns and age-related changes from the premature neonate to the young child make children particularly susceptible to misdiagnosis of epilepsy.

Time course of reversal of valproate-mediated inhibition of lamotrigine.

PURPOSE: Conversion to lamotrigine (LTG) monotherapy from sodium valproate (VPA) is complicated by the robust pharmacokinetic interaction between the two AEDs. This study examined changes in LTG serum concentrations immediately following VPA discontinuation. METHODS: Ten healthy female and male adult subjects were initiated on LTG (Lamictal) 10 mg orally every morning for 30 days and VPA (Depakote ER) 500 mg orally every morning for 14 days. Morning trough (pre-dose) venous blood samples were obtained for determination of LTG and VPA concentrations on study days 14, 15, 16, 18, 20, 22, 24, 26, 28, and 30. Following the collection of the blood sample on day 15, VPA was discontinued. RESULTS: Despite stable LTG dosage serum concentrations on study day 20, 22, 24, 26, and 28, all were significantly lower compared to baseline (p < 0.05). CONCLUSIONS: These observations demonstrate that the pharmacokinetic interaction between LTG and VPA is reversible, and that de-inhibition appears to follow a predictable time course. Complete offset, or reversal of this interaction takes place 10-14 days after VPA discontinuation. Our data also confirms the observation that LTG oral clearance may be inhibited by very low concentrations of VPA. These data support the conversion algorithm suggested by the manufacturer, and provide guidance to the clinician. These data provide clinically useful information in developing a dosing algorithm for converting patients to LTG monotherapy.

Early Diagnosis and Treatment of Lennox-Gastaut Syndrome.

Lennox-Gastaut syndrome (LGS) is a severe form of childhood-onset epilepsy associated with high morbidity and mortality. The peak period for manifestations of Lennox-Gastaut syndrome is between ages 3 and 5 years, a time of critical brain development and corresponding vulnerability to the electroclinical dysfunction arising from Lennox-Gastaut syndrome. Diagnosis is based on a triad of symptoms: multiple seizure types, cognitive impairment, and slow spike-and-wave pattern on electroencephalography. In practice, Lennox-Gastaut syndrome presentation is diverse, and there may be a delay between initial symptoms and emergence of the full triad of clinical features. Additionally, differential diagnosis is complicated by the resemblance of Lennox-Gastaut syndrome to other forms of epilepsy and by the need for varied diagnostic techniques requiring specific clinical skills. Because diagnosis is complex and early intervention may lead to improved outcomes, clinicians should consider treatment when Lennox-Gastaut syndrome symptoms are present, even in the absence of a formal diagnosis.

Brain-responsive neurostimulation in patients with medically intractable seizures arising from eloquent and other neocortical areas.

OBJECTIVE: Evaluate the seizure-reduction response and safety of brain-responsive stimulation in adults with medically intractable partial-onset seizures of neocortical origin. METHODS: Patients with partial seizures of neocortical origin were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. Additional analyses considered safety and seizure reduction according to lobe and functional area (e.g., eloquent cortex) of seizure onset. RESULTS: There were 126 patients with seizures of neocortical onset. The average follow-up was 6.1 implant years. The median percent seizure reduction was 70% in patients with frontal and parietal seizure onsets, 58% in those with temporal neocortical onsets, and 51% in those with multilobar onsets (last observation carried forward [LOCF] analysis). Twenty-six percent of patients experienced at least one seizure-free period of 6 months or longer and 14% experienced at least one seizure-free period of 1 year or longer. Patients with lesions on magnetic resonance imaging (MRI; 77% reduction, LOCF) and those with normal MRI findings (45% reduction, LOCF) benefitted, although the treatment response was more robust in patients with an MRI lesion (p = 0.02, generalized estimating equation [GEE]). There were no differences in the seizure reduction in patients with and without prior epilepsy surgery or vagus nerve stimulation. Stimulation parameters used for treatment did not cause acute or chronic neurologic deficits, even in eloquent cortical areas. The rates of infection (0.017 per patient implant year) and perioperative hemorrhage (0.8%) were not greater than with other neurostimulation devices. SIGNIFICANCE: Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including adults with seizures of neocortical onset, and those with onsets from eloquent cortex.

Brain-responsive neurostimulation in patients with medically intractable mesial temporal lobe epilepsy.

OBJECTIVE: Evaluate the seizure-reduction response and safety of mesial temporal lobe (MTL) brain-responsive stimulation in adults with medically intractable partial-onset seizures of mesial temporal lobe origin. METHODS: Subjects with mesial temporal lobe epilepsy (MTLE) were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. RESULTS: There were 111 subjects with MTLE; 72% of subjects had bilateral MTL onsets and 28% had unilateral onsets. Subjects had one to four leads placed; only two leads could be connected to the device. Seventy-six subjects had depth leads only, 29 had both depth and strip leads, and 6 had only strip leads. The mean follow-up was 6.1 ± (standard deviation) 2.2 years. The median percent seizure reduction was 70% (last observation carried forward). Twenty-nine percent of subjects experienced at least one seizure-free period of 6 months or longer, and 15% experienced at least one seizure-free period of 1 year or longer. There was no difference in seizure reduction in subjects with and without mesial temporal sclerosis (MTS), bilateral MTL onsets, prior resection, prior intracranial monitoring, and prior vagus nerve stimulation. In addition, seizure reduction was not dependent on the location of depth leads relative to the hippocampus. The most frequent serious device-related adverse event was soft tissue implant-site infection (overall rate, including events categorized as device-related, uncertain, or not device-related: 0.03 per implant year, which is not greater than with other neurostimulation devices). SIGNIFICANCE: Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including patients with unilateral or bilateral MTLE who are not candidates for temporal lobectomy or who have failed a prior MTL resection.

Survival following decompressive hemicraniectomy for hemiconvulsion-hemiplegia-epilepsy syndrome: case report.

Hemiconvulsion-hemiplegia-epilepsy (HHE) is an uncommon epileptic syndrome that affects young children. Typical management includes early initiation of benzodiazepines to abate the initial seizure activity quickly. Patients in whom epilepsy develops require prolonged use of antiepileptic agents. Herniation due to diffuse cerebral edema from HHE is rare; however, decompressive craniectomy has been described as a lifesaving measure. The authors present the case of a patient in whom a decompressive craniectomy was performed. They advocate a proactive approach in the detection and management of cerebral edema in HHE causing intracranial hypertension. In HHE cases that exhibit radiographic evidence of malignant cerebral edema (although not previously described in this disease, but similar to the setting of stroke and trauma), the authors advocate early neurosurgical consultation and evaluation for insertion of an intracranial pressure monitor for those patients who do not have a reliable neurological examination (i.e., Glasgow Coma Scale score ≤ 8).

Factors Influencing Patient Experience in Pediatric Neurology.

INTRODUCTION: Hospitals have begun to shift toward patient-centered care because of the pay-for-performance system that was established by the Patient Protection and Affordable Care Act. In pediatrics, the needs of both the caregiver and the pediatric patient have to be taken into account. Pediatric practices have been shifting toward a family-centered approach, although the primary drivers have not been well defined. Identifying the key patient experiences that lead to higher patient satisfaction would enable a more meaningful clinical encounter. To better understand patient experience, we examined waiting time and the elements of the physician-patient interaction in pediatric neurology. We predict that the determining factor in patient satisfaction is the physician-patient interaction. METHODS AND MATERIAL: Patient satisfaction surveys were sent to families via mail or e-mail after their ambulatory pediatric neurology visit. The visits took place between January 1, 2012, and December 31, 2014, at one of multiple locations in a children's health system spanning four states. A Likert scale was used for these surveys, and a top-box method (measuring percent of survey questions were rated 5 out of 5) was used to filter data from this database. Statistical analysis using a Pearson correlation was used for data analysis, with likelihood to recommend practice as the dependent variable. RESULTS: The five survey questions that correlated most with overall likelihood to recommend the practice were cheerfulness of practice (r = 0.79); staff working together (r = 0.76); cleanliness of practice (r = 0.70); wait time at clinic, from entering to leaving (r = 0.66); and likelihood of recommending care provider (r = 0.65). CONCLUSION: Pediatric neurologists striving to enhance overall patient satisfaction in their practices should work toward providing an atmosphere that supports office staff cheerfulness, teamwork, and visit efficiency provided in a clean and friendly environment.

Anti-NMDA-receptor antibody encephalitis in infants.

PURPOSE: Anti-N-methyl-d-aspartate (NMDA) receptor antibody encephalitis is an autoimmune disorder manifesting subacutely with prominent aberrant movements and psychiatric symptoms. The clinical course is one of progressive clinical deterioration that can be halted and often reversed by early diagnosis and treatment. Patterns of presentation and etiology of anti-NMDA-receptor antibody encephalitis are dependent on age and can be challenging to recognize in very young children. REPORTS: Sequential clinical case observations of anti-NMDA-receptor antibody encephalitis presenting in very young children were examined over a year at a single tertiary pediatric institution. Cerebrospinal fluid confirmed anti-NMDA-receptor antibodies in two cases (a 21-month-old boy and a 29-month-old girl) that demonstrated either bizarre behavioral patterns or status epilepticus both associated with progressive deterioration. Once recognized, the clinical course was arrested and reversed by aggressive treatment with plasma exchange, immunoglobulin, and high dose IV steroids. CONCLUSION: Infants with anti-NMDA-receptor antibody encephalitis can present with frank seizures or seizure mimics. Regardless, prompt recognition and aggressive treatment of anti-NMDA-receptor antibody encephalitis, while challenging, can quickly arrest deterioration and hasten recovery, thereby, limiting neurological morbidity.

Pediatric anti-NMDA (N-methyl D-aspartate) receptor encephalitis.

BACKGROUND: We report the clinical features and course of pediatric patients presenting with anti-N-methyl D-aspartate receptor (NMDA-R) encephalitis. METHODS: Single-center 4-year observational study of pediatric encephalitis associated with NMDA-R antibodies in the serum and/or the cerebrospinal fluid. RESULTS: Three girls with anti-NMDA-R encephalitis were identified. All presented with an acute hyperkinetic movement disorder and seizures, expressive aphasia, and emotional lability requiring inpatient treatment for 1-3 months. Imaging and electroencephalogram findings were nondiagnostic. None had an underlying tumor or ovarian teratoma. All received immune-modulatory therapy, including one or more of the following: high-dose methyl-prednisolone, plasma exchange, intravenous immunoglobulin or mycophenolate mofetil. Two of the three patients relapsed within 6 months of presentation and required retreatment with plasma exchange. All have remained in subsequent remission, with two of the three requiring second-line immunotherapy with rituximab. CONCLUSIONS: Hyperkinetic movements in pediatric patients presenting with acute encephalopathy and prominent psychiatric symptoms should elicit a search for NMDA-R antibodies early in the evaluation. Relapses require aggressive immunomodulatory treatment for remission. This series highlights a unique positron emission tomography scan finding of hypermetabolism in one of the patients that correlated with her clinical symptoms. Recovery and rehabilitation can be prolonged, often taking years after the initial diagnosis. Early identification and treatment is likely to reduce relapses and limit morbidity associated with this potentially devastating but treatable encephalitis.

Seizures from valproate-carbapenem interaction.

BACKGROUND: Antiepileptic medication interactions can complicate the management of epilepsy, by either increasing or reducing the effective serum concentrations thereby causing adverse effects or loss of seizure control. RESULTS: A 14-year-old girl with well-controlled juvenile absence epilepsy lost control of her seizures acutely following the administration of carbapenem for pneumonia. Serum valproate concentrations fell by 90% within 48 hours following carbapenem and returned to baseline following its discontinuation. CONCLUSIONS: Awareness of this clinically significant interaction alters clinical practice by avoiding carbapenem or temporary use of adjunctive medication to prevent the clinical consequences of this significant drug interaction.

Is lower IQ in children with epilepsy due to lower parental IQ? A controlled comparison study.

AIM: The aim of this study was to determine the relationship between parent and child Full-scale IQ (FSIQ) in children with epilepsy and in typically developing comparison children and to examine parent-child IQ differences by epilepsy characteristics. METHOD: The study participants were 97 children (50 males, 47 females; age range 8-18y; mean age 12y 3mo, SD 3y1mo) with recent-onset epilepsy including idiopathic generalized (n=43) and idiopathic localization-related epilepsies (n=54); 69 healthy comparison children (38 females, 31 males; age range 8-18y; mean age 12y 8mo, SD 3y 2mo), and one biological parent per child. All participants were administered the Wechsler Abbreviated Scale of Intelligence (WASI). FSIQ was compared in children with epilepsy and typically developing children; FSIQ was compared in the parents of typically developing children and the parents of participants with epilepsy; parent-child FSIQ differences were compared between the groups. RESULTS: FSIQ was lower in children with epilepsy than in comparison children (p<0.001). FSIQ of parents of children with epilepsy did not differ from the FSIQ of the parents of typically developing children. Children with epilepsy had significantly lower FSIQ than their parents (p<0.001), whereas comparison children did not. The parent-child IQ difference was significantly higher in the group with epilepsy than the comparison group (p=0.043). Epilepsy characteristics were not related to parent-child IQ difference. INTERPRETATION: Parent-child IQ difference appears to be a marker of epilepsy impact independent of familial IQ, epilepsy syndrome, and clinical seizure features. This marker is evident early in the course of idiopathic epilepsies and can be tracked over time.

Pediatric epileptology.

Challenges facing children with epilepsy are understanding the neurobiology of pharmacoresistance of epileptic encephalopathies and the development of effective surgical treatment options for those with "non-lesional" epilepsy. Although, understanding the genetics of childhood epilepsy has advanced, an effective treatment intervention has not occurred. Recently, understanding the neurobiology of hamartin and tuberin in the development of epilepsy and cognitive impairment associated with tuberous sclerosis complex allowed the development of sirolimus and everolimus to be used in human clinical trials. In spite of these breakthroughs a large number of children are likely to be outside the scope of interventional therapies. For such patients the burden of seizures is onerous and psycho-social consequences debilitating. Surgical resective options are often limited by the lack of a well defined epileptic lesion. Co-registered synthesis of advanced functional, structural and electrographic seizure onset allows identification of a focus in patients thought to have "non-lesional" epilepsy. Developments of a Pipeline for prospective data sharing are likely to increase understanding and validation of the epileptogenic zone and offer the hope of seizure freedom. Two outstanding young investigators provide a review of their exciting research and its implications in pediatric epilepsy.

Absence epilepsy with focal clinical and electrographic seizures.

Primary generalized seizures occur in half of all children with epilepsy. Correct classification carries important diagnostic, therapeutic, and prognostic information. Approximately half of all patients with generalized juvenile myoclonic epilepsy may have a partial semiology or focal electroencephalographic features although similar findings have not been described in absence epilepsy. Two examples, one with semiology characteristic of focal seizures and the other with a video-electroencephalogram documented partial seizure emanating after the completion of typical 3-Hz generalized spike-wave absence epilepsy, are discussed.

Adolescent and caregiver experiences with epilepsy.

Epilepsy during adolescence can impede the development of psychosocial independence and typical biological maturational processes. We examined in parallel the experiences and perceptions of adolescent patients with epilepsy and their caregivers. Specifically, we focused on frequency and type of seizures, comorbid conditions, adherence to therapies, productivity, clinical and quality of life consequences of seizures, estimated use and content of seizure emergency plans, and the patient-physician relationship. Two cross-sectional online surveys were conducted among 153 adolescent patients with epilepsy and their respective caregivers. A total of 35% of adolescents indicated that they had been nonadherent to antiepileptic medications in the prior month. Adolescents scored significantly lower compared with their peers on quality-of-life measures. Adolescents and caregivers reported similarly on nearly all domains. An adolescent-centered epilepsy management program may help alleviate concerns and also help the adolescent independently manage their epilepsy as they transition into adulthood.

Thalamofrontal circuitry and executive dysfunction in recent-onset juvenile myoclonic epilepsy.

PURPOSE: Thalamofrontal abnormalities have been identified in chronic primary generalized epilepsy, specifically in juvenile myoclonic epilepsy (JME). These regions also underlie executive functioning, although their relationship has yet to be examined in JME. This study examined the relationship between thalamic and frontal volumes and executive function in recent-onset JME compared to healthy control subjects and recent-onset benign childhood epilepsy with centrotemporal spikes (BCECTS), a syndrome not typically associated with thalamocortical or executive dysfunction. METHODS: Twenty children with recent-onset JME were compared to 51 healthy controls and 12 children with BCECTS using quantitative magnetic resonance imaging (MRI) and measures of executive abilities. Quantitative thalamic and frontal volumes were obtained through semi-automated software. Subtests from the Delis-Kaplan Executive Function System (D-KEFS) and the Behavior Rating Inventory of Executive Function (BRIEF) were used to measure executive function. RESULTS: Executive functions were impaired in JME subjects compared to control and BCECTS subjects. Subjects with JME had significantly smaller thalamic volumes and more frontal cerebrospinal fluid (CSF) than control and BCECTS subjects. Thalamic and frontal volumes were significantly related to executive functioning in the JME group, but not in the other two groups. DISCUSSION: Children with JME have significant executive dysfunction associated with significantly smaller thalami and more frontal CSF. Children with recent-onset BCECTS do not display the same pattern. Frontal and thalamic volumes appear to mediate the relationship between executive functioning and brain structure in JME.