PURPOSE:The best possible outcomes in infantile epileptic spasms syndrome require electroclinical remission; however, determining electrographic remission is not straightforward. Although the determination of hypsarrhythmia has inadequate interrater reliability (IRR), the Burden of AmplitudeS and Epileptiform Discharges (BASED) score has shown promise for the reliable interictal assessment of infantile epileptic spasms syndrome. Our aim was to develop a BASED training program and assess the IRR among learners. We hypothesized moderate or better IRR for the final BASED score and the presence or absence of epileptic encephalopathy (+/-EE). METHODS:Using a web-based application, 31 learners assessed 12 unmarked EEGs (length 1-6 hours) from children with infantile epileptic spasms syndrome. RESULTS:For all readers, the IRR was good for the final BASED score (intraclass correlation coefficient 0.86) and +/-EE (Marginal Multirater Kappa 0.63). For all readers, the IRR was fair to good for all individual BASED score elements. CONCLUSIONS:These findings support the use of our training program to quickly learn the BASED scoring method. The BASED score may be a valuable clinical and research tool. Given that the IRR for the determination of epileptic encephalopathy is not perfect, clinical acumen remains paramount. Additional experience with the BASED scoring technique among learners and advances in collaborative EEG evaluation platforms may improve IRR.

OBJECTIVE:To determine the optimal duration of electroencephalography (EEG) recording to detect epileptic spasms (ES) based on inpatient overnight video-EEG monitoring in patients with infantile epileptic spasms syndrome (IESS) at the 2-week follow-up. METHODS:Patients with IESS and overnight EEG monitoring between January 2020 and June 2022 were retrospectively reviewed. Time-to-ES, time-to-sleep and time-to-epileptic encephalopathy (EE) per the Burden of Amplitudes and Epileptiform Discharges (BASED 2021) score. BASED 2021 score were reported. ES and sleep detection sensitivity were calculated with respect to monitoring time. Etiology, treatment, and EEG features were assessed for strength of association with continued ES. Time-to-event analysis was performed with the first ES as the event of interest. RESULTS:Of 90 patients, 39 (43%) continued to have ES; 78.6% with EE continued to have ES, whereas only 27.4% without EE had ES (odds ratio [OR] 12.05). Structural etiologies were also associated with continued ES (OR 5.24). ES detection was 35.9%, 76.9%, and 84.6% at 1, 4, and 6 h, respectively, with corresponding negative likelihood ratios (NLRs) of .64, .23, and .15. ES detection reached >90% and >95% at 14 and 19 h, respectively. Sleep detection was 52.2%, 84.4%, and 95.6% at 1, 4, and 6 h, respectively, and captured in all patients by 11 h. EE was observed by 6 h for all associated patients. SIGNIFICANCE:Typical routine EEG durations (<1 h) were not sufficient to detect ES, EE, or sleep in patients with IESS at the 2-week follow-up. Four hour outpatient EEG will capture ES in 77% and sleep in 84% of the patients. EE, if present, was shortly after sleep onset. Additional monitoring of up to 19 h was needed to capture >95% of patients with ES. Although EE was strongly associated with continued ES, 27.4% of patients without EE demonstrated ES. This study will help guide adequate duration of EEG monitoring at the 2-week follow-up for patients with IESS.

Objective To analyze the clinical and neuroimaging features, risk factors, treatment choices, and long-term clinical outcomes in children with cerebral sinus venous thrombosis (CSVT).Methods This is a retrospective cohort study of children diagnosed with CSVT between 2002 and 2018 at Texas Children’s Hospital.Results A total of 183 children (male:62.3%) with CSVT were included. The average presenting age was 7.7 years (SD:5.6). The mean follow-up duration of 33.7 months (SD:38.6). The most common presenting clinical feature was headache (36.6%). Head and neck infections other than meningitis (36.6%) were the most common risk factors. Prevalent neurological exam findings included motor deficit (21.3%) and altered mental status (AMS, 20.2%). Neuroimaging features included hemorrhagic infarction (19.6%), ischemic infarction (8.2%), intracranial hemorrhage without infarction (5.5%). Most common site of thrombosis was superior sagittal sinus (37.2%), with 78.2% of patients demonstrating involvement of multiple sinuses. Treatment of choice was low molecular weight heparin in 69.4% of patients. Factors associated with worse clinical outcomes included: Head and neck infections, malignancy (other than hematologic), cardiac disease, recent surgery; seizure and dehydration on initial presentation; motor abnormalities and AMS on initial examination; ischemic infarct only and involvement of vein of Trolard on neuroimaging. Thrombus condition on repeat imaging, receiving any anticoagulant/antithrombotic treatment, treatment duration, or follow-up duration was not associated with severity of long-term outcome.Conclusions CSVT may lead to unfavorable long-term outcomes in a remarkable portion of pediatric patients. Thus, a high index of suspicion, and early and appropriate management of pediatric CSVT is imperative.

Precision medicine for Mendelian epilepsy is rapidly developing. We describe an early infant with severely pharmacoresistant multifocal epilepsy. Exome sequencing revealed the de novo variant p.(Leu296Phe) in the gene KCNA1, encoding the voltage-gated K+ channel subunit K(V)1.1. So far, loss-of-function variants in KCNA1 have been associated with episodic ataxia type 1 or epilepsy. Functional studies of the mutated subunit in oocytes revealed a gain-of-function caused by a hyperpolarizing shift of voltage dependence. Leu296Phe channels are sensitive to block by 4-aminopyridine. Clinical use of 4-aminopyridine was associated with reduced seizure burden, enabled simplification of co-medication and prevented rehospitalization.

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 chi(2) 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.

OBJECTIVE:To demonstrate that de novo missense single nucleotide variants (SNVs) in EIF2AK2 cause a neurodevelopmental disorder with leukoencephalopathy resembling Pelizaeus-Merzbacher disease (PMD).METHODS:A retrospective chart review was performed of 2 unrelated males evaluated at a single institution with de novo EIF2AK2 SNVs identified by clinical exome sequencing (ES). Clinical and radiographic data were reviewed and summarized.RESULTS:Both individuals presented in the first year of life with concern for seizures and developmental delay. Common clinical findings included horizontal and/or pendular nystagmus during infancy, axial hypotonia, appendicular hypertonia, spasticity, and episodic neurologic regression with febrile viral illnesses. MRI of the brain demonstrated severely delayed myelination in infancy. A hypomyelinating pattern was confirmed on serial imaging at age 4 years for proband 1. In proband 2, repeat imaging at age 13 months confirmed persistent delayed myelination. These clinical and radiographic features led to a strong suspicion of PMD. However, neither PLP1 copy number variants nor pathogenic SNVs were detected by chromosomal microarray and trio ES, respectively. Reanalysis of trio ES identified heterozygous de novo EIF2AK2 missense variant c.290C>T (p.Ser97Phe) in proband 1 and c.326C>T (p.Ala109Val) in proband 2.CONCLUSIONS:The autosomal dominant EIF2AK2-related leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome should be considered in the differential diagnosis for PMD and other hypomyelinating leukodystrophies (HLDs). A characteristic history of developmental regression with febrile illnesses may help distinguish it from other HLDs.

Glial fibrillary acidic protein (GFAP) astrocytopathy is a novel form of autoimmune meningoencephalitis related to autoantibodies to GFAP. 1 Dubey D. Hinson S.R. Jolliffe E.A. et al. Autoimmune GFAP astrocytopathy: prospective evaluation of 90 patients in 1 year. J Neuroimmunol. 2018; 321: 157-163 Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar , 2 Fang B. McKeon A. Hinson S.R. et al. Autoimmune glial fibrillary acidic protein astrocytopathy: a novel meningoencephalomyelitis. JAMA Neurol. 2016; 73: 1297-1307 Crossref PubMed Scopus (154) Google Scholar A recent report described an adult patient developing GFAP astrocytopathy following herpes simplex encephalitis (HSE). 3 Li J. Xu Y. Ren H. Zhu Y. Peng B. Cui L. Autoimmune GFAP astrocytopathy after viral encephalitis: a case report. Mult Scler Relat Disord. 2018; 21: 84-87 Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar We present the first pediatric patient with history of HSE who developed acute cognitive and psychiatric symptoms and positive GFAP immunoglobulin G in the cerebrospinal fluid (CSF).

Objective: To describe clinical/neuroimaging characteristics, risk factors, presenting clinical features, treatment and long-term neurological outcomes in neonates with cerebral sinus venous thrombosis (CSVT). Background: Neonatal CSVT is an extremely rare neurovascular condition. The clinical and radiological characteristics, and long-term outcome are rarely reported. Design/Methods: This is a retrospective, observational study conducted at a single tertiary referral center in neonates with CSVT between 2000 and 2017. Results: 62 neonates diagnosed with CSVT using computed tomography (CT)/magnetic resonance imaging (MRI) and brain venograms (CTV/MRV) were included. Average follow-up duration was 3.6 years (range 3 days to 16 years). Of the 62 patients, 44 (71%) were male. Cardiac diseases were the most common underlying risk factor (24%) followed by meningitis (16%), systemic febrile illness (16%), hypoxia (16%), and dehydration (11%). Common presenting features included seizure (53%), fever (14%), lethargy (11%) and dehydration (11%). Neuroimaging findings (available in 61 subjects) include ischemic infarction (19%), both infarction and hemorrhage (30%), other intracranial hemorrhage (17%), and no parenchymal lesions (30%). Common sites of thrombosis included left transverse sinus in 56%, followed by right transverse sinus in 53% and superior sagittal sinus (44%). Treatment data was available in 59 patients. Thirty five out of 59 subjects were treated with supportive care only (no anticoagulation or antiplatelet). Other treatment options included low molecular weight heparin (30%), unfractionated heparin (16%) and aspirin (4%). Follow up neurological status (data available in 61 subjects) was normal in 50%, abnormal in 30%, and death was reported in 17%. Conclusions: In our study, the most common presenting clinical feature in neonates with CSVT was seizure. Treatment of neonatal CSVT must be aggressive as it could be associated with significant morbidity and neurological disability on long term follow up. Disclosure: Dr. Karakas has nothing to disclose. Dr. Takacs has nothing to disclose. Dr. Edmondson has nothing to disclose. Dr. Fisher has nothing to disclose. Dr. Shukla has nothing to disclose. Dr. Clark has nothing to disclose. Dr. Pehlivan has nothing to disclose.

Background: Neonatal cerebral sinus venous thrombosis (CSVT) causes high morbidity and mortality. Factors associated with either favorable or unfavorable long-term outcomes have not been clearly established. This study aimed to determine the factors involved in long-term neurological outcomes in patients with neonatal CSVT. Methods: This was a retrospective cohort study of patients with neonatal CSVT at a single institution. Clinical factors associated with long-term neurological outcomes were examined. Results: A total of 67 patients met study inclusion criteria for radiologically confirmed neonatal CSVT. The mean patient follow-up duration was four years (range one week to 16 years, median six years). We observed a favorable neurological outcome defined by a pediatric stroke outcome measures (PSOM) score of 0 to 0.5 in 26 (53%) of osurviving patients at follow-up. An unfavorable neurological outcome as defined by PSOM score >0.5 was observed in 23 survivors (47%). Death was reported in 18 (27%) patients, of which 10 patients died due to direct complications of CSVT. Congential heart disease and genetic disease were associated with significantly increased odds for all-cause death. Cardiorespiratory failure and altered mental status during the initial neurological examination were significantly associated with increased odds of death due to CSVT. Among surviving patients, higher PSOM scores were associated with premature birth (i.e., gestational age < 37 weeks), traumatic birth, site of thrombosis in the straight sinus, site of thrombosis in the internal cerebral veins, and hemorrhagic infarct. In contrast, lower PSOM scores were associated with a normal neurological examination at presentation, thrombosis in only superficial sinuses, and hemorrhage without infarct. There was no statistically significant association between the type and duration of CSVT treatment. Conclusions: The major factors influencing outcome of neonates following CSVT included comorbid medical conditions, abnormal neurological examination at presentation, location of venous thrombosis,

April 25, 2018April 10, 2018Free AccessSub-acute Hemiplegia in a Toddler: A Case Study in Anti-MOG Antibody Positive Tumefactive Demyelinating Encephalitis (P4.345)Jason Gill, Danielle Takacs, and Timothy LotzeAuthors Info & AffiliationsApril 10, 2018 issue90 (15_supplement) Letters to the Editor

To describe a case of isolated ophthalmoplegia as the presenting sign of Wernicke encephalopathy in a teenager with recent history of Roux-en-Y gastric bypass.