Developmental epileptic encephalopathy in DLG4-related synaptopathy.

OBJECTIVE: The postsynaptic density protein of excitatory neurons PSD-95 is encoded by discs large MAGUK scaffold protein 4 (DLG4), de novo pathogenic variants of which lead to DLG4-related synaptopathy. The major clinical features are developmental delay, intellectual disability (ID), hypotonia, sleep disturbances, movement disorders, and epilepsy. Even though epilepsy is present in 50% of the individuals, it has not been investigated in detail. We describe here the phenotypic spectrum of epilepsy and associated comorbidities in patients with DLG4-related synaptopathy. METHODS: We included 35 individuals with a DLG4 variant and epilepsy as part of a multicenter study. The DLG4 variants were detected by the referring laboratories. The degree of ID, hypotonia, developmental delay, and motor disturbances were evaluated by the referring clinician. Data on awake and sleep electroencephalography (EEG) and/or video-polygraphy and brain magnetic resonance imaging were collected. Antiseizure medication response was retrospectively assessed by the referring clinician. RESULTS: A large variety of seizure types was reported, although focal seizures were the most common. Encephalopathy related to status epilepticus during slow-wave sleep (ESES)/developmental epileptic encephalopathy with spike-wave activation during sleep (DEE-SWAS) was diagnosed in >25% of the individuals. All but one individual presented with neurodevelopmental delay. Regression in verbal and/or motor domains was observed in all individuals who suffered from ESES/DEE-SWAS, as well as some who did not. We could not identify a clear genotype-phenotype relationship even between individuals with the same DLG4 variants. SIGNIFICANCE: Our study shows that a subgroup of individuals with DLG4-related synaptopathy have DEE, and approximately one fourth of them have ESES/DEE-SWAS. Our study confirms DEE as part of the DLG4-related phenotypic spectrum. Occurrence of ESES/DEE-SWAS in DLG4-related synaptopathy requires proper investigation with sleep EEG.

Safety & feasibility of responsive neurostimulation in children with refractory epilepsy: A single-center experience.

OBJECTIVES: Responsive neurostimulation (RNS) is a relatively recent addition to the epilepsy surgery armory, gaining FDA approval in 2013 for use in adults with intractable focal epilepsy. Data for the use of RNS system in patients less than 18 years of age is limited. We aim to determine the safety and feasibility of RNS in children with refractory epilepsy. METHODS: A retrospective chart review was conducted for all patients who underwent RNS implantation at an urban tertiary children's hospital. Demographics of the patients were obtained, including age at the time of implant, MRI findings, seizure onset zone identification, and RNS targets. RESULTS: Out of a fourteen patient cohort, one patient had a post-operative complication of infection at surgical site requiring explantation. Thirteen out of 14 patients had immediate post-operative head imaging that was negative for hemorrhage, infarction, or skull fracture; one patient did not undergo head imaging. No patients reported a worsening clinical seizure frequency at a 6-month follow up visit. In the subset of patients who were implanted with RNS and did not undergo concurrent resections, there was a statistically significant reduction in the average number of long episodes at the most recent visit when compared to the 1-month post-operative visit (p = 0.0268). CONCLUSIONS: RNS is a feasible and safe option for children as young as six years with refractory epilepsy when appropriate seizure focus identification has been performed with stereo CT and stereo EEG evaluations, and can be used in conjunction with other surgical epilepsy treatment modalities. Two canister RNS placement is achievable for patients with a broad epileptogenic network or multifocal seizure onset zones.

Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice.

Importance: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes. Objective: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes. Design, Setting, and Participants: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals. Exposures: Genetic test results. Main Outcomes and Measures: Clinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-linked diseases; 2 P/LP variants in autosomal recessive diseases) and subsequent patient outcomes as reported by health care professionals on case report forms. Results: Among 418 patients, median (IQR) age at the time of testing was 4 (1-10) years, with an age range of 0 to 52 years, and 53.8% (n = 225) were female individuals. The mean (SD) time from a genetic test order to case report form completion was 595 (368) days (range, 27-1673 days). A genetic diagnosis was associated with changes in clinical management for 208 patients (49.8%) and usually (81.7% of the time) within 3 months of receiving the result. The most common clinical management changes were the addition of a new medication (78 [21.7%]), the initiation of medication (51 [14.2%]), the referral of a patient to a specialist (48 [13.4%]), vigilance for subclinical or extraneurological disease features (46 [12.8%]), and the cessation of a medication (42 [11.7%]). Among 167 patients with follow-up clinical information available (mean [SD] time, 584 [365] days), 125 (74.9%) reported positive outcomes, 108 (64.7%) reported reduction or elimination of seizures, 37 (22.2%) had decreases in the severity of other clinical signs, and 11 (6.6%) had reduced medication adverse effects. A few patients reported worsening of outcomes, including a decline in their condition (20 [12.0%]), increased seizure frequency (6 [3.6%]), and adverse medication effects (3 [1.8%]). No clinical management changes were reported for 178 patients (42.6%). Conclusions and Relevance: Results of this cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcomes.

Child Neurology: Initial Presentation of PCDH19-Related Epilepsy With New-Onset Refractory Status Epilepticus and Treatment With Anakinra.

PCDH19-related epilepsy is a developmental and epileptic encephalopathy typically presenting with epilepsy and varying degrees of intellectual disability. Seizures typically present in clusters of focal or generalized seizures, sometimes in the setting of fever. We present the case of a 7-month-old girl presenting with new-onset refractory status epilepticus that followed routine vaccine administration and ensuing cytokine storm. She was diagnosed with a pathogenic variant in PCDH19 The patient required 5 antiseizure medications and pentobarbital-induced burst suppression for control of seizures. She was noted to have elevated serum cytokine levels (interleukin [IL]-2, IL-4, IL-10, IL-13, IL-17, IL-1, IL-1ß, and IL-8) and CSF cytokine levels (IL-6 and IL-13). Anakinra was initiated and titrated based on serial cytokine levels, with doses ranging from 5 to 20 mg/kg/d resulting in reduction in cytokine levels and seizure reduction. By age 14 months, she was able to be maintained on 3 active antiseizure medications and ketogenic diet for seizure control.

Adjunctive use of cenobamate for pediatric refractory focal-onset epilepsy: A single-center retrospective study.

OBJECTIVE: We explored the efficacy and safety profile of cenobamate as an adjunctive therapy in patients with refractory focal-onset epilepsy in the pediatric population. METHODS: This was a retrospective, single-center study of cenobamate used as an adjunctive medication in pediatric patients with refractory focal-onset epilepsy . We measured seizure reduction, median reduction in seizure frequency, median dose, responder rate, and treatment-emergent adverse events. RESULTS: We studied the efficacy and safety profile of cenobamate in 21 pediatric patients (mean age 15.9). Cenobamate was up titrated using the prescribed starter pack with final doses ranging from 100 mg to 400 mg daily. The mean and median dose of cenobamate was 209.8 mg (±98.87 mg) and 200 mg (175-275), respectively. For patients weighing less than 50 kg, mean and median dose was 4.0 mg/kg/day (3.20-4.63) and 4.32 mg/kg/day, respectively. Mean and median baseline seizure frequency per month in this cohort was 15.38 and 16, respectively, prior to the introduction of cenobamate. After the adjunctive use of cenobamate, mean and median seizure frequency per month reduced to 7.29 and 1, respectively; median reduction in seizure frequency was 93.7%. Seizure reduction of at least 50% (responder rate) was noted in 13 (62.5%) patients and a seizure reduction of at least 75% noted in 11 (52.4%) patients, similar to that seen in adults. Four patients (19%) achieved seizure freedom. Of the 21 pediatric patients, 9 (42.8%) patients had treatment-emergent adverse events (TEAE) with the most commonly reported symptom being ataxia (5, 23.8%) and sedation (2, 9.5%). Three (14.3%) patients discontinued early due to these side effects. No children developed drug rash with eosinophilia and systemic symptoms (DRESS). CONCLUSION: Cenobamate demonstrates similar efficacy rates and safety profile within the pediatric population when compared to the published adult data, making it an effective, safe, and tolerable adjunctive medication for children with refractory focal-onset epilepsy, even at the maximum daily dose.

Evaluating vagus nerve stimulation treatment with heart rate monitoring in pediatric patients with intractable epilepsy.

PURPOSE: Vagus nerve stimulators (VNS) have emerged as an effective treatment modality for pediatric patients suffering from intractable, drug-resistant epilepsy. Newer devices, AspireSR™ Model 106 and the SenTiva™ Model 1000 (VNS TherapyⓇ, LivaNova™), contain an "auto-stimulation" feature that detects ictal tachycardia and transmits pulsations to attenuate seizures. However, the exact benefits of auto-stimulation compared to its risks still merit further exploration. This study evaluates the utility of these specific devices in a heterogeneous population of pediatric and young adult patients with intractable epilepsy. METHODS: This is a retrospective chart review of 55 patients who underwent either VNS insertion with or without an auto-stimulation-enabled VNS device at a single level four epilepsy center. Seizure frequency, seizure subtype, side effects, and change in anti-seizure medication load both before and after VNS implantations were collected from patient self-reporting at the time of VNS insertion and 12 months following implantation. Information regarding output current, auto-stimulation current, duty cycling, and auto-stimulation threshold of the device was obtained from documented VNS interrogation for patients with auto-stimulation-enabled VNS devices. RESULTS: Patients with auto-stimulation-enabled VNS devices had a mean 56.0% (SD = 0.414) seizure frequency reduction 12 months post-VNS insertion, while patients without auto-stimulation-enabled VNS devices had a mean 41.6% (SD = 0.456) seizure frequency reduction during the same interval. The mean seizure frequency reduction 12 months post-VNS insertion for patients with a SenTiva™ 1000 model was 66.0% (SD = 0.426). For patients with auto-stimulation-enabled VNS devices, post-treatment seizure reduction was significantly correlated with daily auto-stimulation activation (R = 0.432, p = 0.025). CONCLUSION: This study supports the clinical safety and utility of auto-stimulation-enabled VNS models, specifically the SenTiva™ 1000, in treating pediatric patients with intractable epilepsy of various subtypes and etiologies. Further research is needed to evaluate the sustained impact of auto-stimulation on long-term outcomes (≥ 2 years follow-up post-VNS).

A Role for Electroconvulsive Therapy in the Management of New Onset Refractory Status Epilepticus (NORSE) in a Young Child.

New-onset refractory status epilepticus (NORSE) describes prolonged or recurring new onset seizures which fail to respond to antiseizure medications. NORSE poses a challenge in diagnosis and treatment, and limited high-quality evidence exists to guide management. The efficacy of Electroconvulsive therapy (ECT) in aborting refractory status epilepticus has been described in case reports, but its application remains uncommon, particularly in young children. We describe a case of NORSE in a 3-year old child in which ECT played an important role in aborting status epilepticus, facilitating the diagnosis and surgical excision of an underlying focal cortical dysplasia. Although further research is needed, our case suggests that ECT can be a valuable tool in the treatment of refractory status epilepticus in children.

Robot-assisted stereoelectroencephalography electrode placement in twenty-three pediatric patients: a high-resolution analysis of individual lead placement time and accuracy at a single institution.

PURPOSE: We describe a detailed evaluation of predictors associated with individual lead placement efficiency and accuracy for 261 stereoelectroencephalography (sEEG) electrodes placed for epilepsy monitoring in twenty-three children at our institution. METHODS: Intra- and post-operative data was used to generate a linear mixed model to investigate predictors associated with three outcomes (lead placement time, lead entry error, lead target error) while accounting for correlated observations from the same patients. Lead placement time was measured using electronic time-stamp records stored by the ROSA software for each individual electrode; entry and target site accuracy was measured using postoperative stereotactic CT images fused with preoperative electrode trajectory planning images on the ROSA computer software. Predictors were selected from a list of variables that included patient demographics, laterality of leads, anatomic location of lead, skull thickness, bolt cap device used, and lead sequence number. RESULTS: Twenty-three patients (11 female, 48%) of mean age 11.7 (± 6.1) years underwent placement of intracranial sEEG electrodes (median 11 electrodes) at our institution over a period of 1 year. There were no associated infections, hemorrhages, or other adverse events, and successful seizure capture was obtained in all monitored patients. The mean placement time for individual electrodes across all patients was 6.56 (± 3.5) min; mean target accuracy was 4.5 (± 3.5) mm. Lesional electrodes were associated with 25.7% (95% CI: 6.7-40.9%, p = 0.02) smaller target point errors. Larger skull thickness was associated with larger error: for every 1-mm increase in skull thickness, there was a 4.3% (95% CI: 1.2-7.5%, p = 0.007) increase in target error. Bilateral lead placement was associated with 26.0% (95% CI: 9.9-44.5%, p = 0.002) longer lead placement time. The relationship between placement time and lead sequence number was nonlinear: it decreased consistently for the first 4 electrodes, and became less pronounced thereafter. CONCLUSIONS: Variation in sEEG electrode placement efficiency and accuracy can be explained by phenomena both within and outside of operator control. It is important to keep in mind the factors that can lead to better or worse lead placement efficiency and/or accuracy in order to maximize patient safety while maintaining the standard of care.

Clinical features of paediatric and adult autoimmune encephalitis: A multicenter sample.

BACKGROUND: Autoimmune encephalitis (AE) is a heterogeneous class of inflammatory diseases of the brain that can present with a wide spectrum of neuropsychiatric symptoms. Patients may be negative for CSF anti-neuronal antibodies, which can make the diagnosis of AE challenging. Distinguishing features between paediatric and adult patients with AE are not well characterized. OBJECTIVE: Describe the clinical presentation, seizure type, EEG and sleep patterns in paediatric and adult patients with AE. METHODS/DESIGN: Retrospective review of clinical data from paediatric and adult patients diagnosed with AE from three medical centers between 1/2008-12/2019. RESULTS: We included 100 patients with AE, including 65 children. Median age at presentation was 14 years (1-88years). Fifty-five patients had positive CSF autoantibody results (NMDAR 36%, VGKC Ab 10%, anti-GAD65 4%, miscellaneous 3%), and 47 patients were autoantibody-negative. Paediatric patients were more likely to present with psychiatric symptoms, focal seizures and/or status epilepticus, and sleep disturbances compared to adult patients (p < 0.05). There was a higher incidence of NMDA-R encephalitis in children compared to adults. CONCLUSION: Paediatric patients with AE were more likely to present with psychiatric symptoms, sleep disturbances, focal seizures, and/or status epilepticus compared to adults (p < 0.05). Insomnia and hypersomnia are common sleep problems associated with AE that should be screened early in the diagnostic evaluation. Further studies can be performed to explore the relationship between sleep disturbances and long-term cognitive effects and the incidence of chronic epilepsy in this subset of patients.

Improved seizure burden and cognitive performance in a child treated with responsive neurostimulation (RNS) following febrile infection related epilepsy syndrome (FIRES).

Responsive neurostimulation (RNS) is an emerging therapy for patients with refractory focal epilepsy who are not candidates for surgical resection, with limited published experience in the pediatric population. We report a case of refractory multifocal epilepsy following febrile infection related epilepsy syndrome (FIRES) in which surgical resection was not feasible due to multifocal independent seizures and risk of cognitive deficit, and RNS was pursued. Relevant RNS data and neuropsychological testing results were reviewed. By eight months after implantation, decreased frequency and severity of clinical seizures were noted, and RNS data revealed decreased "long episodes," reduced spread of electrographic seizures, and fewer detections. Neuropsychological assessment, though potentially confounded by stimulant medication, revealed significant improvement in multiple cognitive domains, particularly working memory and processing speed, at six months. These findings illustrate success in detecting and aborting seizures, and additionally suggest a neuromodulatory effect of RNS stimulation. Our case demonstrates feasibility, efficacy and safety of RNS in a pediatric patient with FIRES, with evidence to also suggest cognitive improvement.

Quality improvement strategies improve pediatric neurology inpatient discharges before noon.

BACKGROUND: Early hospital discharge is an important quality improvement (QI) measure that has not been well studied in pediatric neurology. The objective of our study was to implement strategies to improve hospital discharge times for patients admitted to the pediatric neurology service. METHODS: This was a pilot QI study of hospital discharge before noon (DBN) in pediatric neurology patients admitted to a tertiary care children's hospital. The study duration was 6 months (12/2017-05/2018)-first 3 months preintervention and next 3 months postintervention. Strategies focusing on preidentifying MRI candidates and those needing home care services, identifying pharmacy preference, reviewing overnight video EEGs first thing in the morning, and implementing morning huddles, etc., were implemented. Demographic and clinical data were collected, including age, sex, race, and reasons for delay in discharge. Chi-square, t test, and survival analysis (log-rank test) were performed to determine differences between baseline and post-QI implementation. RESULTS: One hundred ninety-one patients were included in the study. There were 76 participants before the implementation of the study and 115 participants during the study. DBN percentage increased in the intervention period, from a baseline of 40.7% to 60.8%. Survival analysis showed that the discharge time after QI implementation improved significantly (p = 0.043). CONCLUSIONS: Our study successfully identified the factors associated with late discharge and developed effective strategies to improve DBN in an inpatient pediatric neurology setting.

Comparison of artifacts between paste and collodion method of electrode application in pediatric EEG.

OBJECTIVES: Children pose challenges to obtain quality EEG data due to excessive artifact. Collodion is used in EEG electrodes due to its water resistance and strong adhesive qualities. This study was done to evaluate differences in artifacts between the collodion and paste method. METHODS: 115 subjects (children age >3 years) were randomized into paste and collodion groups and artifacts evaluated at baseline and every hour over 30 s increments. Age, sleep state, and number of electrodes with artifact were also documented. T-test was performed to determine differences in the various parameters between the two groups. RESULTS: 61 subjects were in the paste group and 54 in the collodion group. Mean of total seconds of artifact from 0 to 24 h were 41.8 s in paste group versus 30.3 s in collodion group (P = 0.02). Children >11 years old had less artifact than younger children from 0 to 24 h (24.3 versus 41.2 s, P = 0.03), and from 24 to 48 h (33.1 versus 43.1 s, P = 0.03). There was a significant effect of sleep vs. awake state recordings on artifact from 0 to 24 h (30.3 versus 50.2 s, P = 0.01). CONCLUSION: Electrode problems are common with both collodion and paste in prolonged AEEG monitoring. However, for studies less than 24 h, collodion may be a better alternative. SIGNIFICANCE: Our study provides evidence that in some cases collodion may be a better alternative to paste in terms of decreased artifacts.

Characteristics and predictors of 7- and 30-day hospital readmissions to pediatric neurology.

OBJECTIVE: Hospital readmission is an important quality improvement measure that has not been well-studied in pediatric neurology. We examined predictors of 7-day and 30-day readmissions for pediatric patients hospitalized with a neurologic diagnosis. METHODS: This was a retrospective study of hospital readmission rates in pediatric neurology patients admitted to a tertiary children's hospital from January 2017 to December 2017. Inclusion criteria were age ≤18 years and a primary neurologic diagnosis on admission, with an unplanned readmission within 7 or 30 days. Demographic and clinical data were collected, including age, sex, income, insurance type, discharge occurring on a weekend, admission to the pediatric intensive care unit (PICU), use of multiple antiepileptic drugs (AEDs), and involvement of multiple subspecialties. RESULTS: There were 923 neurology admissions, and 64 readmissions within 30 days. Total unplanned readmission rate was 6.9%, with 56% (36/64) readmitted within 30 days, 44% (28/64) readmitted within 7 days, and 11% (7/64) admitted multiple times within 30 days. The most common readmission diagnosis was seizure (62%), followed by other neurologic diagnosis (21%), headache (8%), encephalitis/meningitis (7%), stroke (1%), and ataxia (1%). Readmission was significantly associated with multiple AED, PICU admission, seizure with major complication or comorbidity, and presence of a major complication or comorbidity irrespective of diagnosis (p < 0.05). CONCLUSIONS: This study identifies factors associated with higher rates of readmission for pediatric neurology patients. Patients with epilepsy and chronic neurologic conditions should be targeted for future discharge-related interventions to reduce hospital readmission and ensure safe transitions from the inpatient to the outpatient setting.

Anti-N-Methyl-D-Aspartate Receptor Encephalitis and Rasmussen-like Syndrome: An Association?

BACKGROUND: N-methyl-D-aspartate (NMDA) receptor encephalitis is an immune-mediated condition that has a broad spectrum of manifestations, including seizures, coma, psychosis, and focal neurological deficits. Although usually a diffuse process, unihemispheric involvement mimicking early stages of Rasmussen encephalitis can occur. Rasmussen's encephalitis is a unique syndrome characterized by progressive hemiplegia, drug-resistant focal epilepsy, cognitive decline, and hemispheric brain atrophy contralateral to the hemiplegia. PATIENT DESCRIPTION: We describe a two-year-old girl with progressive right weakness and epilepsia partialis continua, concerning for early Rasmussen's encephalitis, who tested positive for anti-NMDA receptor antibodies. She experienced complete clinical recovery after immunotherapy. Anti-NMDA receptor antibodies were absent at three weeks and again at one year after the first treatment of intravenous immunoglobulin. CONCLUSIONS: There are few reports of Rasmussen-like encephalitis in individuals with anti-NMDA receptor antibody positivity. Thus the clinical significance of this association is yet to be determined. In addition, several other antibodies have been documented in individuals with Rasmussen encephalitis. The lack of a consistently reported antibody in Rasmussen encephalitis patients and the temporary nature of the anti-NMDA receptor antibody in our patient raise the following question: Is the presence of anti-NMDA receptor antibodies the cause of the symptoms or secondary to the pathogenic process?

Seizure control after subtotal lesional resection.

Reports on seizure outcomes following surgery for lesional epilepsy consistently cite extent of resection as a significant predictor of outcome. Unfortunately, gross-total resection is not technically feasible in all cases of medically refractory tumor-associated epilepsy. Here, the authors present the case of a 4-year-old girl whose epilepsy was medically controlled after 1-stage electrocorticography-guided subtotal resection (STR) of a large diffuse protoplasmic astrocytoma. They also review the modern literature on epilepsy associated with brain tumors. Outcomes are compared with those following surgical treatment of focal cortical dysplasia and vascular lesions. Gross-total lesional resection shows significant superiority across pathologies and anatomical regions. Despite a considerable number of STRs yielding seizure freedom, other favorable treatment factors have not been defined. Although gross-total lesional resection, if possible, is clearly superior, tailored surgery may still offer patients a significant opportunity for a good outcome. Treatment factors yielding successful seizure control following STR remain to be fully elucidated.

Case report of subacute cerebellar ataxia of adolescence with long-term sequelae.

Acute ataxia is not an uncommon childhood complaint. It most commonly occurs in young patients secondary to a postinfectious cerebellitis, which is typically associated with a very good prognosis and recovery. In adolescence, acute cerebellar ataxia is more often the product of an etiology likely to progress into a chronic disorder without recovery to preillness baseline. In the present case, the authors describe a 15-year-old girl with subacute cerebellar ataxia of presumed immune-mediated etiology that advanced into a chronic cerebellar ataxia. Due to a family history, celiac disease was suspected as the origin of the ataxia; biopsy ruled out enteropathy, and the severe, abrupt radiological changes to the patient's cerebellum are inconsistent with the reported sequelae of gluten ataxia. This case serves as a discussion for diagnostic challenges in adolescent patients with acute cerebellar ataxia with long-term sequelae as well as providing an adjunct discussion on the neurological complications of celiac disease.

MELAS with A3243G mutation presenting with occipital status epilepticus.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a mitochondrial disorder commonly caused by the A3243G mutation. We report a patient who initially presented with visual hallucinations, headaches, and nonconvulsive status epilepticus originating in left occipital lobe who subsequently progressed to have multifocal seizures. His magnetic resonance imaging (MRI) showed subtle T2 hyperintensity at first presentation that subsequently fully resolved. He then had more typical diffusion restriction not conforming to vascular territories. Evolution of his neuroimaging and electroencephalogram (EEG) is discussed with a brief review of literature. Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes should be suspected early with occipital lobe seizures.