Estimating the active and lifetime prevalence and incidence of epilepsy in Asian Countries: A systematic review and meta-analysis.

OBJECTIVE: In the current era of the World Health Organization's Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders 2022-2031 (IGAP), precise and updated estimates of epilepsy burden are vital in formulating policies to improve the care of persons with epilepsy, especially in Asian countries with significant treatment gap. Hence, we aimed to consolidate the available data and quantify epilepsy prevalence and incidence estimates in Asian countries. METHODS: We systematically searched PubMed, Embase, Ovid, and Scopus databases from inception until March 2023 for studies reporting epilepsy prevalence and incidence in Asian countries. We applied random effects meta-analysis to generate the pooled prevalence and incidence using the Meta package in R. Additionally, we performed a subgroup meta-analysis to explore the potential sources of heterogeneity. A meta-regression analysis was conducted to examine the trend of epilepsy over time. RESULTS: A total of 99 studies with 100,654,124 participants were included in the meta-analysis. The pooled prevalence was 5.6 per 1000 (95 % confidence interval (CI) 4.4-6.8) for active epilepsy and 6.7 per 1000 (95 % CI 5.7-7.9) for lifetime epilepsy. The pooled incidence rate of epilepsy was 52.5 per 100,000 person-years (95 % CI 42.7-79.4). The subgroup analysis revealed a higher prevalence of active epilepsy (6.7/1000) and lifetime epilepsy (8.6/1000) in West Asia than in other regions. The funnel plot and Egger's test (p-value =<0.0001) revealed publication bias for active epilepsy. CONCLUSION: Our findings highlight a high prevalence of active and lifetime epilepsy in West Asia and emphasize the necessity of implementing and formulating specific strategies to tackle the epilepsy burden in this region. Furthermore, high-quality epidemiological studies incorporating economic burdens and comorbidities associated with epilepsy in Asia are still needed.

Bifurcation dissecting aneurysm: tips and tricks to differentiate from saccular aneurysm.

Bifurcations are a common site for saccular aneurysms, but rarely can be a site for dissecting aneurysms. Identification of these aneurysms is extremely important because the management plan depends on it. We describe a rare case of a ruptured dissecting aneurysm at the right ICA bifurcation in a pre-teen child which posed a diagnostic dilemma but ultimately was successfully managed with flow diversion.

PPP2R5D-Related Neurodevelopmental Disorder or Developmental and Epileptic Encephalopathy?: A Novel Phenotypic Description and Review of Published Cases.

BACKGROUND: Protein phosphatase 2 regulatory subunit B' delta (PPP2R5D)-related neurodevelopmental disorder is caused by pathogenic variations in the PPP2R5D gene, product of which is involved in dephosphorylation. This is a rare disorder with description limited to case reports. Its phenotypic spectrum has expanded over the last decade. METHODS: We report a child with a developmental and epileptic encephalopathy phenotype with a pathogenic PPP2R5D variant. This phenotype has not been previously reported. We also reviewed the previously published reports of patients with this disorder. RESULTS: Including the index child, 28 cases (15 girls) were identified from nine relevant research items for analysis. All patients had developmental delay. History of seizures was observed in seven patients while macrocephaly was seen in nearly 80% of patients. Nonneurological manifestations were observed in 13 patients with the most common one being ophthalmological manifestations. The most common genetic variation was c.G592A (p.E198K). The common phenotypic associations of this variation were developmental delay, macrocephaly (11/15), and epilepsy (6/15). CONCLUSION: PPP2R5D gene variations should be suspected in children with developmental delay, autistic features, macrocephaly with or without epilepsy in the absence of any clear etiology. Dysmorphic features might provide a diagnostic clue. DEE phenotype may also be the presenting feature and might be an underreported entity.

Seroprevalence of MOG and AQP4 Antibodies and Outcomes in an Indian Cohort of Pediatric Acquired Demyelinating Syndromes.

This study aimed to determine the seropositivity of myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) and aquaporin-4 antibodies (AQP4-Ab) and outcomes in children with acquired demyelinating syndromes (ADSs). Children (6 months-15 years) with suspected ADS were enrolled and tested for MOG-Ab and AQP4-Ab prospectively over 18 months at a tertiary care hospital in North India. Children with proven nonimmune-mediated neurological disorders were enrolled as controls. Of 79 children with suspected ADS, 66 were enrolled. Among the enrolled children with ADS, acute demyelinating encephalomyelitis (ADEM) (25) was the most common first clinical event followed by optic neuritis (ON) (20) and transverse myelitis (TM) (19; one child had ON and TM simultaneously [neuromyelitis optica spectrum disorders [NMOSDs]]), while two children had clinically isolated syndrome (CIS) apart from ON and TM. Fourteen (21.2%, confidence interval [CI] 11.3-31.1) tested positive for one antibody (12 [18.1%; 95% CI 10.5-25.5%] for MOG-Ab and 2 [3%; 95% CI 0-7.2%] for AQP4-Ab). None of the 62 controls tested positive for any antibody. The final diagnosis in those with the monophasic ADS was ADEM (21), ON (13), TM (16), and other CIS (1) while that in children with recurrent events was multiphasic disseminated encephalomyelitis (MDEM) (2), NMOSD (3), ADEM-ON (4), recurrent ON (4), and MS (2). Among those with the first event, 4/51 (7.8%; 95% CI 0.5-15.2%) were MOG-Ab positive and 2 AQP4-Ab positive, whereas 8/15 (53.3% [95% CI 28.1-78.6%]) with recurrent events (MDEM [2], ADEM-ON [4], recurrent ON [1], and recurrent TM [1]) were MOG-Ab positive. Hence, MOG-Abs are the most common antibodies detected in one in five children with pediatric ADS, especially in relapsing disease. AQP4-Abs are rare in children with ADS.

Neurobehavioral deterioration associated with sleep-augmented epileptiform abnormalities: A steroid responsive state in children.

OBJECTIVE: Retrospective case record analysis of children with Neurobehavioral Deterioration associated with Sleep-augmented Epileptiform abnormalities (NDSE). METHODS: Hospital records of children with NDSE (July, 2015 through December, 2016) were analyzed. Children were categorized as: Encephalopathy with electrical status epilepticus in sleep (ESES) if sleep EEG Spike-wave-Index (SWI) was ≥50% and sleep-induced epileptiform activity (SIEA)-related cognitive dysfunction if SWI ≥25% but <50%. Demography, neurobehavior profile (IQ/SQ and behavior using validated psychometric tools), etiology, investigations and treatment details were documented. Outcome assessment was based on three-month follow-up records. RESULTS: Eighteen children with NDSE {12 boys; median age at diagnosis: 7.5 years (IQR: 6-10 years); SIEA (7); ESES (11)} were included. Etiology was structural (23%) and presumed genetic (77%). All children received intravenous-methylprednisolone pulse followed by oral steroids for eight weeks. Electroencephalography of children with SIEA was partly organized with median SWI of 40% (IQR 35, 42), with anterior-predominant epileptiform abnormalities and less apparent secondary synchronization. Children with ESES had a disorganized EEG background with median SWI of 80% (IQR 66, 95). Both SIEA and ESES groups had a similar neurobehavior profile. Behavior scores improved in 6/8 children with ESES and 5/7 in SIEA post steroids. In both the groups, median SWI improved (to <5% in SIEA, 45% in ESES). Mild improvement in IQ/SQ was also noted {SIEA [Median (IQR): 3 (1.6, 4.3)]; ESES [Median (IQR): 3.8 (2.8, 7)]}. CONCLUSION: The study supports the fact that SWI >50% in the nap EEG is not mandatory for the diagnosis of ESES, thus it should not be a constraint for steroid treatment.

Horizontal Gaze Palsy, Scoliosis, and Split Pons Sign in a 6-Year-Old Girl.

ABSTRACT: A 6-year-old girl presented with complaints of absent horizontal eye movements since birth. There was also associated progressive scoliosis for past 1 year. Neuroimaging revealed split pons sign, butterfly-shaped medulla, and prominent inferior olivary nuclei. The presence of congenital horizontal gaze palsy, childhood onset progressive scoliosis, and abnormal neuroimaging findings confirmed the diagnosis of horizontal gaze palsy with progressive scoliosis. This case highlights the importance of neuroimaging in a child presenting with horizontal gaze palsy and scoliosis that helped for starting early rehabilitation of the child, prevention of permanent vision loss, and parental counseling for future pregnancies.

Psychological and Behavioral Impact of Lockdown and Quarantine Measures for COVID-19 Pandemic on Children, Adolescents and Caregivers: A Systematic Review and Meta-Analysis.

BACKGROUND: During the current ongoing COVID-19 pandemic, psychological problems like anxiety, depression, irritability, mood swings, inattention and sleep disturbance are fairly common among quarantined children in several studies. A systematic review of these publications to provide an accurate burden of these psychiatric/behavioral problems is needed for planning mitigating measures by the health authorities. METHODS: Different electronic databases (MEDLINE, EMBASE, Web of Science, CENTRAL, medRxiv and bioRxiv) were searched for articles describing psychological/behavioral complications in children/adolescents with/without pre-existing behavioral abnormalities and their caregivers related to the COVID-19 pandemic. Only original articles with/without comparator arms and a minimum sample size of 50 were included in the analysis. The pooled estimate of various psychological/behavioral problems was calculated using a random-effect meta-analysis. RESULTS: Fifteen studies describing 22 996 children/adolescents fulfilled the eligibility criteria from a total of 219 records. Overall, 34.5%, 41.7%, 42.3% and 30.8% of children were found to be suffering from anxiety, depression, irritability and inattention. Although the behavior/psychological state of a total of 79.4% of children was affected negatively by the pandemic and quarantine, at least 22.5% of children had a significant fear of COVID-19, and 35.2% and 21.3% of children had boredom and sleep disturbance. Similarly, 52.3% and 27.4% of caregivers developed anxiety and depression, respectively, while being in isolation with children. CONCLUSION: Anxiety, depression, irritability, boredom, inattention and fear of COVID-19 are predominant new-onset psychological problems in children during the COVID-19 pandemic. Children with pre-existing behavioral problems like autism and attention deficit hyperactivity disorder have a high probability of worsening of their behavioral symptoms.

KCNT1-related epilepsy: An international multicenter cohort of 27 pediatric cases.

OBJECTIVE: Through international collaboration, we evaluated the phenotypic aspects of a multiethnic cohort of KCNT1-related epilepsy and explored genotype-phenotype correlations associated with frequently encountered variants. METHODS: A cross-sectional analysis of children harboring pathogenic or likely pathogenic KCNT1 variants was completed. Children with one of the two more common recurrent KCNT1 variants were compared with the rest of the cohort for the presence of particular characteristics. RESULTS: Twenty-seven children (15 males, mean age = 40.8 months) were included. Seizure onset ranged from 1 day to 6 months, and half (48.1%) exhibited developmental plateauing upon onset. Two-thirds had epilepsy of infancy with migrating focal seizures (EIMFS), and focal tonic seizures were common (48.1%). The most frequent recurrent KCNT1 variants were c.2800G>A; p.Ala934Thr (n = 5) and c.862G>A; p.Gly288Ser (n = 4). De novo variants were found in 96% of tested parents (23/24). Sixty percent had abnormal magnetic resonance imaging (MRI) findings. Delayed myelination, thin corpus callosum, and brain atrophy were the most common. One child had gray-white matter interface indistinctness, suggesting a malformation of cortical development. Several antiepileptic drugs (mean = 7.4/patient) were tried, with no consistent response to any one agent. Eleven tried quinidine; 45% had marked (>50% seizure reduction) or some improvement (25%-50% seizure reduction). Seven used cannabidiol; 71% experienced marked or some improvement. Fourteen tried diet therapies; 57% had marked or some improvement. When comparing the recurrent variants to the rest of the cohort with respect to developmental trajectory, presence of EIMFS, >500 seizures/mo, abnormal MRI, and treatment response, there were no statistically significant differences. Four patients died (15%), none of sudden unexpected death in epilepsy. SIGNIFICANCE: Our cohort reinforces common aspects of this highly pleiotropic entity. EIMFS manifesting with refractory tonic seizures was the most common. Cannabidiol, diet therapy, and quinidine seem to offer the best chances of seizure reduction, although evidence-based practice is still unavailable.

Saposin B-Deficient Metachromatic Leukodystrophy Mimicking Acute Flaccid Paralysis.

Metachromatic leukodystrophy (MLD) is a rare sphingolipid storage disorder caused by arylsulfatase A (ARSA) deficiency, resulting in central and peripheral demyelination. However, an uncommon form of MLD caused by saposin B deficiency is also described (around 10 mutations reported till date). MLD is a systemic disorder affecting the central and peripheral nervous system, gall bladder, and kidneys. Acute flaccid paralysis as the initial clinical presentation is previously known in ARSA-deficient MLD. Hereby, we report a child with acute flaccid paralysis with brain magnetic resonance imaging showing nonspecific periventricular leukodystrophy. He had progressive cognitive decline with gall bladder polyposis. ARSA levels were within normal limits. Leukodystrophy gene panel revealed a homozygous pathogenic deletion (Lys227del variant) in prosaposin (PSAP) gene. Hence, a final diagnosis of saposin B-deficient MLD was established. The index case highlights the importance of clinical and electrophysiological clues in the diagnosis of such atypical presentations of MLD.

Predictive Ability of Amplitude Integrated Electroencephalography for Adverse Outcomes in Neonates with Sepsis-Associated Encephalopathy: A Cohort Study.

The authors examined the prevalence of abnormal amplitude integrated electroencephalography (aEEG) patterns in neonates diagnosed with sepsis-associated encephalopathy (SAE). They recorded 36626 min of aEEG in 75 study neonates. Encephalopathy was defined by the Brighton Collaboration Neonatal Encephalopathy criteria. Neonates with primary outcome [either non-survivors or survivors with abnormal neurological examination at discharge using Amiel-Tison assessment tool, n = 58, (77%)] were compared with 17 survivors having normal neurological examination at discharge. Severely abnormal aEEG patterns (isoelectric voltage, continuous low voltage, burst suppression) collectively represented 31% of total 36626 min aEEG tracings. Neonates experiencing primary outcome had significantly higher Burdjalov scores than survivors with normal neurological exam (p value 0.01). After adjusting for gestational age, birth weight, and invasive ventilation, severely abnormal aEEG (aOR 5.8, 95% CI 1.7-19.5, p value 0.005) and Burdjalov score (aOR 0.77, 95% CI 0.63-0.95, p value 0.01) were independently associated with death or abnormal neurological examination at discharge.

Electroclinical Landscape of Infantile Epileptic Spasms Syndrome.

OBJECTIVES: To elucidate the electroclinical characteristics of infantile epileptic spasms syndrome (IESS) and to determine any potential association among these with underlying etiologies and response to therapy. METHODS: Sixty-eight, treatment-naive children with IESS underwent long-term video electroencephalogram (EEG) recording, which was used to characterize the semiology, ictal, and inter-ictal EEG patterns. Children were further followed up to assess electroclinical predictors of etiologies and short-term therapeutic response. RESULTS: Of 68 children enrolled (69% boys), the median age at enrollment was 10.5 mo (IQR-8). Eighty-eight percent of children had flexor spasms, followed by mixed (7%) and extensor (4.4%). Asymmetrical spasms were noted in 17.6% children, and all of them had underlying structural etiology. Two children had the status of epileptic spasms. In the present cohort, authors recognized five distinct ictal EEG correlates of epileptic spasms; the frontocentral dominant slow wave was the most prevalent (32%), followed by the generalized slow-wave complex with superimposed fast rhythm in 29.4%. The occipital dominant slow wave complex was a peculiar pattern in 16%. The major underlying etiologies were hypoxic-ischemic brain injuries (36.7%) and neonatal hypoglycemic brain injuries (22%). Besides asymmetric spasms, authors could not identify any significant association among electroclinical characteristics, underlying etiologies and response to therapy in this study. CONCLUSIONS: The electroclinical landscape of IESS is peculiar and diverse in developing countries. The presence of asymmetrical spasms indicated underlying structural etiology.