Abstract Postoperative epilepsy patients may present with new neurological symptoms that raise concern for autoimmune or infectious etiologies. In this case, a 25-year-old man with intellectual disability and left hippocampal sclerosis underwent left temporal lobectomy and hippocampectomy. After a seizure-free interval of 45 days, he developed multiple generalized tonic–clonic seizures in the setting of a postoperative subdural hematoma. Following hematoma evacuation, he received intravenous antiseizure therapy that was complicated by a medication dosing error. Shortly thereafter, he exhibited prominent involuntary orofacial movements, confusion, and persistent electrographic abnormalities. Neuroimaging showed new, mild bilateral posterior cortical enhancement, and electroencephalography (EEG) revealed lateralized periodic discharges. The constellation of movement disorder, seizures, and EEG changes raised concern for an autoimmune encephalitis, which can occur after epilepsy surgery and requires timely immunotherapy. However, cerebrospinal fluid analysis and a comprehensive autoimmune antibody panel were unremarkable. Over the subsequent 2 weeks, symptoms resolved in parallel with normalization of antiseizure drug levels, without the use of immunotherapy. This case underscores the importance of considering medication toxicity in the differential diagnosis of acute postoperative neurological syndromes. Recognition of drug-induced phenomena can prevent both misdiagnosis of autoimmune encephalitis and unnecessary treatment delays in patients who truly require immunotherapy.
Abstract NEXMIF gene variants are increasingly recognized as a significant cause of X-linked developmental and epileptic encephalopathies, presenting unique sex-related patterns that challenge traditional inheritance expectations. This article systematically analyzes genotype–phenotype correlations in NEXMIF-related epilepsy and provides evidence-based clinical management recommendations. We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, searching PubMed, Scopus, Google Scholar, Web of Science, and Embase (January 2010–December 2024) using terms “NEXMIF” and “KIAA2022” combined with “epilepsy,” “seizures,” and “encephalopathy.” Studies were included if they reported patients with confirmed pathogenic NEXMIF variants and detailed epileptic phenotype data. Fourteen studies (218 patients) were included. Epilepsy occurred in 185/218 patients (85%, 95% confidence interval [CI]: 79.3–89.4%). Null variants caused significantly more severe phenotypes than missense variants: earlier seizure onset (median 14 vs. 126 months; mean difference 112 months, 95% CI: 98–126; p < 0.001), higher developmental epileptic encephalopathy rates (85% vs. 7%; odds ratio [OR] 94.4, 95% CI: 32.1–277.8; p < 0.001), and increased pharmacoresistance (75% vs. 24%; OR 9.6, 95% CI: 4.1–22.4; p < 0.001). Females experienced higher seizure occurrence than males (99% vs. 62%; OR 42.5, 95% CI: 13.7–131.9; p < 0.001), though pharmacoresistance rates were comparable (70% vs. 60%; p = 0.21). NEXMIF variant type strongly predicts epileptic severity, enabling precision medicine approaches. These findings should be interpreted cautiously given the retrospective nature and methodological heterogeneity of included studies.
Abstract Epilepsy is a major public health challenge in India, where nearly 10 million people are affected and access to specialized care remains limited. Routine electroencephalography (EEG), although widely available, often fails to capture infrequent or transient seizures, resulting in missed diagnoses. Ambulatory EEG (AEEG) enables prolonged recording in the patient's natural environment and can increase the likelihood of detecting epileptiform activity, particularly when hospital-based video-EEG monitoring in epilepsy monitoring units (EMUs) is not feasible. This narrative review synthesizes existing literature and expert commentary to assess the current status, challenges, and opportunities for AEEG in India. AEEG occupies a diagnostic niche between routine EEG and EMU-based video-EEG, offering portability, lower cost, and improved convenience, but with limitations including susceptibility to artifacts, reliance on patient diaries, and lack of synchronous video in many systems. In India, widespread use is constrained by shortages of neurologists and trained EEG technologists, absence of standardized certification pathways, limited infrastructure, and low patient awareness. A phased roadmap is proposed: first, strengthening foundational epilepsy care through physician training, reliable drug supply, and public awareness; second, targeted integration of AEEG via hub-and-spoke tele-EEG models supported by tertiary centers; and third, leveraging innovations such as artificial intelligence-assisted review and cloud-based storage to extend reach. While AEEG is not a standalone solution to the treatment gap, it can function as a complementary technology within a tiered, evidence-based care model, expanding diagnostic capacity and promoting more equitable epilepsy services in India.
Abstract Temporal lobe epilepsy (TLE) profoundly affects cognitive functions, psychiatric health, and quality of life (QoL). This cross-sectional observational study examined these aspects in 65 TLE patients treated with either epilepsy surgery (35 patients) or anti-seizure medications (30 patients), with a mean epilepsy duration of 24.6 ± 10.9 years. Long-term differences in cognitive and psychiatric outcomes between the two treatment approaches, as well as the influence of seizure persistence and personality traits on decisions regarding surgery, were also investigated. Patients underwent standardized assessments, including neuropsychological tests, structured psychiatric interviews, and the Quality of Life in Epilepsy Inventory-89 QoL inventory. Results showed that seizure freedom was achieved in 65% of surgically treated patients and 16% of medically treated patients (p <0.001). Postoperative seizure freedom correlated with improved attention and verbal fluency (p <0.050), while cognitive recovery was observed in 17 to 57% of surgical patients across various domains. Long-term memory deficits were present in 86% of the medical group and 74% of the surgical group, with no differences in seizure freedom rates between post-surgical patients with stable versus declining memory functions. Visual memory and attention emerged as predictors of better QoL (p <0.001, p <0.050). Psychiatric comorbidities were comparable between groups (46% medical, 37% surgical). Seizure-free patients had higher QoL scores (p = 0.001). Although surgical patients showed better scores in emotional well-being, seizure worry, and medication effects (p <0.050), overall QoL scores were similar. Depression and anxiety were associated with lower QoL (p ≤0.010). In conclusion, surgery offers superior seizure control in TLE. Postoperative seizure freedom is linked to cognitive improvements and better QoL indicators. Seizure freedom remains a critical determinant of long-term outcomes.
Abstract Progressive myoclonic epilepsy (PME) in childhood suggests an underlying neurodegenerative disorder, particularly when associated with organomegaly and gaze palsy. Niemann–Pick disease type C (NPC) is a rare lysosomal storage disorder that may present with PME, often with nonspecific neuroimaging findings. An 11-year-old boy presented with progressive cognitive decline, multifocal myoclonus, generalized seizures, hepatosplenomegaly, and vertical supranuclear gaze palsy. Magnetic resonance imaging showed mild diffuse cortical atrophy. Bone marrow examination revealed foamy storage histiocytes, and exome sequencing identified compound heterozygous pathogenic variants in the NPC2 gene, confirming NPC type C2. This case emphasizes the importance of clinical recognition and genetic confirmation of NPC in children with PME and systemic involvement, even when neuroimaging findings are nonspecific.
Abstract Epilepsy is one of the most common neurological disorders. Many patients with epilepsy can achieve seizure freedom through optimized antiseizure medication therapy, dietary interventions such as the ketogenic diet, or epilepsy surgery. Not all patients with epilepsy are candidates for epilepsy surgery. Epilepsies that can potentially be cured or well-controlled through surgery are called surgically amenable epilepsy. Surgically amenable epilepsy needs to be recognized early so that the patients can benefit from this potentially curative treatment option. Any patient with drug-resistant epilepsy, especially those with a focal lesion(s) identified on MRI, should be referred for further evaluation and for consideration of epilepsy surgery. Despite robust evidence showing superior seizure freedom rates, and cognitive and quality-of-life outcomes with epilepsy surgery compared with continued medical therapy alone, referral for presurgical evaluation remains unacceptably low worldwide. On an average, patients spend more than a decade with uncontrolled seizures before being considered for surgery, leading to irreversible cognitive decline, psychosocial disability, and increased morbidity and mortality, including sudden unexpected death in epilepsy (SUDEP). One of the common myths among many doctors and patients about epilepsy surgery is that epilepsy surgery is a “palliative procedure” and it is the “last resort option” after all other treatments are exhausted. On the contrary, epilepsy surgery is potentially curative in well-selected patients and is the treatment of choice available to patients with surgically amenable epilepsy. This spotlight narrative review article highlights the current evidence in favor of epilepsy surgery and explores persistent barriers to referral, and provides practical guidance for neurologists and physicians to recognize patients who need timely referral for presurgical evaluation.
Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. While children are commonly affected by MIS-C, reports have described MIS in neonates (MIS-N) following maternal coronavirus disease 2019 (COVID-19) infection. We describe a case of early infantile developmental and epileptic encephalopathy (EIDEE) secondary to MIS-N in a day 18 old neonate secondary to maternal COVID-19. A term-born male neonate with a history of maternal COVID-19 at 35 weeks of gestation presented on day 18 of life with seizures, encephalopathy, pneumonitis, transaminitis, and elevated inflammatory markers. Magnetic resonance imaging (MRI) brain showed extensive cortical laminar necrosis. He was managed for MIS-N with antiseizure medications, antibiotics, and intravenous immunoglobulin. COVID-19 reverse transcriptase-polymerase chain reaction was negative, and anti-COVID immunoglobulin G antibody was positive. Near continuous multifocal myoclonic seizures were associated with a suppression burst pattern in the EEG. Follow-up MRI showed cystic encephalomalacia and loss of periventricular white matter. The EIDEE remained drug refractory with poor neurological outcome in follow-up. Cytotoxin-mediated neuronal injury in MIS-N can lead to a catastrophic complication of EIDEE, resulting in drug-refractory epilepsy, microcephaly, and adverse neurological outcome.
New-onset refractory status epilepticus (NORSE) is defined as a condition, not a specific diagnosis, with NORSE without a clear acute or active structural, toxic, or metabolic cause in a patient without active epilepsy. We herein report four cases of NORSE, of which three patients had preceding history of behavioral changes and psychiatric manifestations and one had history of preceding fever. All patients had abnormal electroencephalogram finding. Cerebrospinal fluid and serum examination was positive for anti-N-methyl D-aspartate receptor antibody. All cases received Intravenous pulse methylprednisolone, followed by plasmapheresis in two cases. In these two-patient seizure stopped, and they improved clinically. Two patients died due to ventilator associated pneumonia and sepsis. Our cases highlight that in patient presenting NORSE, preceding history of behavioral or psychiatric abnormality or confusion points toward autoimmune etiology. Early diagnosis and treatment prevent morbidity and mortality in these patients.
Routine electroencephalography (EEG) with video (rVEEG) is a widely used, noninvasive neurodiagnostic tool that aids in the diagnosis and classification of epilepsy by detecting interictal epileptiform discharges. This study aimed to assess its diagnostic utility and identify key clinical correlates in adult patients at a tertiary care center in North India, where specific data on its yield in this resource-constrained context are valuable. We retrospectively analyzed routine EEGs with simultaneous video recording performed in adults aged ≥18 years. Clinical and demographic data—including seizure type, age at onset, etiology, antiepileptic drug use, seizure timing, and activation procedures—were extracted from EEG records and electronic medical records. EEGs were categorized as normal or abnormal, with abnormalities classified as epileptiform or nonepileptiform. Among 347 patients (mean age 41.6 ± 17.8 years), most were aged 18 to 30 (58.2%), with 41.4% experiencing seizure onset before the age of 18 years. Focal seizures were predominant (76.3%), especially focal impaired awareness seizures (52.7%). Etiology was unclear in 85.3% of cases. Neuroimaging data (computed tomography or magnetic resonance imaging) were available for 74 patients; 40 had normal findings, and 34 showed lesions. rVEEGs were commonly performed within 1 week of the last seizure (83%), often during sleep (57.3%). EEG abnormalities were present in 37.5%, primarily generalized spike-and-wave discharges (25.6%). Most patients were on monotherapy (86.2%). Video recording led to a revision or refinement of the initial clinical diagnosis in 7.5% (26) of patients. No significant clinical predictors of abnormal EEG findings were identified (p > 0.05). The diagnostic yield of rVEEG in this cohort was modest. Optimizing patient selection based on detailed clinical history may improve EEG utility in resource-constrained settings.
Identifying the underlying genetic etiology of epilepsy and neurodevelopmental disorders can greatly inform clinical management from diagnosis to treatment to genetic counseling about prognosis. The aim of the study was to establish the genetic/molecular diagnosis in children presenting to two children hospitals in Baghdad, with infantile-onset epilepsy. Twenty-nine Iraqi children with infantile-onset epilepsy, defined as epilepsy with onset in the first year of life, presenting between April 2018 and June 2021, were included in this prospective study. An overall molecular diagnostic rate of 65.5% (in 19/29 subjects) was achieved. Of the subjects with molecular diagnosis, 74% (14/19 subjects) were diagnosed by clinical exome sequencing and 26% (5/19 subjects) were diagnosed by the epileptic encephalopathy panel. Single nucleotide variants were detected in 95% (18/19 subjects) while copy number variants accounted for 5% of the cohort (1/19 subjects). Thirteen subjects (68%) had known pathogenic or likely pathogenic variants in the following genes: SCN1B, SCN1A, ALG13, STXBP1, TBC1D24, PRUNE1, ALDH7A1, PCDH19, SCN8A, and SLC13A5. Six patients (32%) had novel variants potentially explaining the phenotype in the following known genes: SYNJ1, SLC25A22, SCN2A, KCNT1, CACNA1A, and PLPBP. Half (9/19; 47%) of the molecularly diagnosed cases had therapeutic implications. This is the first study to characterize the genotypic and phenotypic spectrum of infantile-onset drug-resistant epilepsy in children from Iraq. Our study demonstrates a high molecular yield with genetic heterogeneity and predominance of autosomal recessive mode of inheritance.
Developmental and epileptic encephalopathies (DEEs) are a group of complex pediatric epilepsies associated with adverse neurodevelopmental outcomes and multiaxial neurological morbidities. The understanding of DEE has evolved from its initial genetic underpinnings, to a clinically driven term encompassing a broader group of etiologies. Although individually rare, the DEEs constitute a sizeable group of pediatric epilepsies. It is especially important to recognize treatable or modifiable entities in this group. This review attempts to highlight the progress in understanding, along with the evolution of the conceptual framework of DEEs. A summary of the currently well-established DEE syndromes is provided along with available precision therapies, which might help the treating physician in the appropriate evaluation and management of the affected children.
Pyridoxine-dependent epilepsy (PDE) is a rare epileptic encephalopathy characterized by early-onset, drug-resistant seizures. It is predominantly caused by mutations in the ALDH7A1 gene, which leads to accumulation of α-aminoadipic semialdehyde (α-AASA) and piperidine-6-carboxylate (P6C) that inactivate pyridoxal 5′-phosphate, an essential cofactor in neurotransmitter metabolism. Seizures are typically unresponsive to standard antiseizure medications but show marked reduction with pyridoxine therapy. We report a 6-month-old boy, born to parents with third-degree consanguinity, who developed drug-resistant seizures of varying semiology from day 2 of life, which showed complete cessation after addition of pyridoxine. Magnetic resonance imaging revealed hydrocephalus. Genetic testing confirmed a pathogenic ALDH7A1 variant. He remains seizure-free on pyridoxine, arginine, and a lysine-restricted diet. This case highlights the importance of early trial of pyridoxine in neonates with resistant seizures. Hydrocephalus is an important clue toward the diagnosis. Genetic confirmation and lifelong pyridoxine therapy, along with a lysine-restricted diet and parental counselling, can prevent recurrent seizures and neurological deterioration. Prompt recognition of PDE, especially in high-risk settings like consanguinity or atypical imaging, enables targeted treatment and improved neurodevelopmental outcomes.
