[Risk of epilepsy after a first epileptic seizure with unknown etiology in elderly patients]. / Riesgo de epilepsia tras una primera crisis epiléptica de etiología desconocida en pacientes de edad avanzada.

AIM: Patients whose epilepsy begins with seizures with unknown etiology in old age have been studied to a limited extent. The aim is to clinically characterise these patients, and predict their risk of developing epilepsy in the long term. MATERIALS AND METHODS: This is a retrospective observational study of patients over 55 years old experiencing a first epileptic seizure with unknown etiology. The data were collected from their clinical history, including electroencephalogram (EEG) and brain magnetic resonance imaging (MRI) results. RESULTS: Eighty-seven patients (58.6% male; 71.5 ± 8.1 years) were included. The mean follow-up was 7.3 ± 4.9 years. The most common vascular risk factor was arterial hypertension (77%; n = 67). Focal seizures with altered consciousness were the most frequent type of seizure (44.8%; n = 39), followed by focal seizures evolving to bilateral tonic-clonic seizures (39.1%; n = 34). Brain MRI showed cortical atrophy (50%; n = 42) and signs of small-vessel vascular disease (SVVD) (67.8%; n = 57). Interictal epileptiform EEG abnormalities were observed in 43.7% (n = 38) of the patients, mostly with temporal localisations (94.7%; n = 36). 44.8% (n = 39) had mild cognitive impairment at baseline. Recurrence of seizures, which was observed in 49 patients (56.1%), occurred after a median of 12 months (interquartile range: 4.4-25.9). Finally, 71 patients (81.6%) developed epilepsy. CONCLUSION: The risk of epilepsy in the long term following a single seizure of unknown etiology in elderly patients is greater than 80%. Arterial hypertension and mild cognitive impairment at baseline are the most common clinical features. Cortical atrophy and the presence of SVVD are frequent in MRI, and routine EEGs do not usually show epileptiform alterations.

TITLE: Riesgo de epilepsia tras una primera crisis epiléptica de etiología desconocida en pacientes de edad avanzada.Objetivo. Los pacientes que comienzan con crisis de origen desconocido en la edad avanzada no están bien estudiados. El objetivo es caracterizar clínicamente a estos pacientes y predecir el riesgo de desarrollar epilepsia a largo plazo. Materiales y métodos. Es un estudio observacional retrospectivo en pacientes mayores de 55 años con una primera crisis epiléptica de causa desconocida. Se recogieron los datos desde la historia clínica, incluyendo electroencefalograma (EEG) y resonancia magnética (RM) cerebral. Resultados. Se incluyó a 87 pacientes (58,6% varones; 71,5 ± 8,1 años). El seguimiento medio fue de 7,3 ± 4,9 años. El factor de riesgo vascular más frecuente fue la hipertensión arterial (77%; n = 67). Las crisis focales con alteración de la conciencia fueron el tipo de crisis más frecuente (44,8%; n = 39), seguidas de las crisis focales con evolución a bilaterales tonicoclónicas (39,1%; n = 34). La RM cerebral mostró atrofia cortical (50%; n = 42) y signos de enfermedad vascular de pequeño vaso (EVPV) (67,8%; n = 57). Se observaron anomalías epileptiformes intercríticas en el EEG en un 43,7% (n = 38) de los pacientes, mayoritariamente con localización temporal (94,7%; n = 36). Hasta un 44,8% (n = 39) presentaba deterioro cognitivo leve basalmente. La recurrencia de crisis, observada en 49 pacientes (56,1%), sucedió con una mediana de 12 meses (rango intercuartílico: 4,4-25,9). Finalmente, 71 pacientes (81,6%) desarrollaron epilepsia. Conclusión. El riesgo de epilepsia a largo plazo tras una crisis única de etiología desconocida en pacientes de edad avanzada es superior al 80%. La hipertensión arterial y el deterioro cognitivo leve en el inicio son las características clínicas más frecuentes. En la RM, la atrofia cortical y la presencia de EVPV son frecuentes, y los EEG de rutina no suelen mostrar alteraciones epileptiformes.

Pathophysiology, Diagnosis, Prognosis, and Prevention of Poststroke Epilepsy: Clinical and Research Implications.

Poststroke epilepsy (PSE) is associated with higher mortality and poor functional and cognitive outcomes in patients with stroke. With the remarkable development of acute stroke treatment, there is a growing number of survivors with PSE. Although approximately 10% of patients with stroke develop PSE, given the significant burden of stroke worldwide, PSE is a significant problem in stroke survivors. Therefore, the attention of health policymakers and significant funding are required to promote PSE prevention research. The current PSE definition includes unprovoked seizures occurring more than 7 days after stroke onset, given the high recurrence risks of seizures. However, the pathologic cascade of stroke is not uniform, indicating the need for a tissue-based approach rather than a time-based one to distinguish early seizures from late seizures. EEG is a commonly used tool in the diagnostic work-up of PSE. EEG findings during the acute phase of stroke can potentially stratify the risk of subsequent seizures and predict the development of poststroke epileptogenesis. Recent reports suggest that cortical superficial siderosis, which may be involved in epileptogenesis, is a promising marker for PSE. By incorporating such markers, future risk-scoring models could guide treatment strategies, particularly for the primary prophylaxis of PSE. To date, drugs that prevent poststroke epileptogenesis are lacking. The primary challenge involves the substantial cost burden due to the difficulty of reliably enrolling patients who develop PSE. There is, therefore, a critical need to determine reliable biomarkers for PSE. The goal is to be able to use them for trial enrichment and as a surrogate outcome measure for epileptogenesis. Moreover, seizure prophylaxis is essential to prevent functional and cognitive decline in stroke survivors. Further elucidation of factors that contribute to poststroke epileptogenesis is eagerly awaited. Meanwhile, the regimen of antiseizure medications should be based on individual cardiovascular risk, psychosomatic comorbidities, and concomitant medications. This review summarizes the current understanding of poststroke epileptogenesis, its risks, prognostic models, prophylaxis, and strategies for secondary prevention of seizures and suggests strategies to advance research on PSE.

Review of the spectrum of tuberous sclerosis complex: The Saudi Arabian Experience.

OBJECTIVES: To determine the prevalence of tuberous sclerosis complex (TSC) in the paediatric Saudi population and to characterise the range of clinical symptoms, neurocutaneous findings, neuroimaging results, and complications of the disease. METHODS: A total of 61 genetically confirmed TSC patients from the National Guard Health Affairs (NGHA) in Saudi Arabia were the subject of this retrospective descriptive analysis. The data were presented using descriptive measures. RESULTS: The mean age at diagnosis was found to be 4.9 years. Subependymal nodules (86.9%), numerous cortical tubers and/or radial migration lines (63.9%), and hypomelanotic macules (63.9%) were the 3 most common significant criteria. The vast majority (86.9%) of those diagnosed had epilepsy, of which 50% were considered medically intractable. Nearly half of our subjects underwent genetic testing, which revealed that TSC2 predominated over TSC1. Symptoms of Tuberous Sclerosis Complex-Associated Neuropsychiatric Disorders (TAND) were present in 66.7% of TSC1 patients and 73.9% of TSC2 patients. CONCLUSION: The findings of this study demonstrate that the clinical spectrum of TSC among Saudi children is consistent with the body of existing literature. The TSC2 was more prevalent than TSC1. The most frequent signs were cutaneous and neurological. Monitoring TSC patients regularly is crucial to identify any issues as soon as possible.

[Bilateral Dorsal Fracture-Dislocation of the Proximal Humerus]. / Bilaterálna dorzálna luxacná zlomenina proximálneho humeru.

Fractures of the proximal humerus constitute approximately 5% of all fractures. Shoulder joint injuries without any external mechanical impact during seizures with the occurrence of spasms occur only sporadically. The occurrence rate is reported in approximately 0.4% of patients. Very rarely they occur in the form of epileptic seizure-induced dorsal fracturedislocation impacting both sides. The case report describes a case of a 48-year-old woman with no treatment for epileptic seizures in her medical history. During the first seizure she sustained a bilateral dorsal fracture-dislocation caused by a muscle spasm, without any other mechanical impact. The fractures were classified as a 3-fragment fracture on the right side and a 4-fragment fracture on the left side. After the patient's admission to the inpatient emergency department, reduction under anaesthesia was attempted. Subsequently, after preparation, open reduction and osteosynthesis using an angularly stable plate were performed as a two-stage surgery. No complications were observed postoperatively Currently, at 3 years after surgeries, the female patient has full mobility of her shoulder joints with no subjective difficulties. Key words: epilepsy, seizure, dorsal fracture-dislocation of the proximal humerus.

Incidence and Risk Factors Epilepsy in Patients with Dementia: A Population-Based Study Using Regional Healthcare Databases in Umbria.

Background: Dementia is prevalent among the elderly, also representing a risk for seizures/epilepsy. Estimations of epilepsy risk in dementia patients are not widely available. Objective: Our research aims to ascertain the incidence of epilepsy and its associated risk factors in subjects with dementia in the Umbria region, based on data from healthcare databases. Methods: In this retrospective study based on the healthcare administrative database of Umbria, we identified all patients diagnosed with dementia from 2013 to 2017, based on ICD-9-CM codes. For epilepsy ascertainment, we used a validated algorithm that required an EEG and the prescription of one or more anti-seizure medications post-dementia diagnosis. A case-control analysis was conducted, matching five non-dementia subjects by gender and age to each dementia patient. Cox proportional hazards models were then utilized in the analysis. Results: We identified 7,314 dementia cases, also including 35,280 age- and sex-matched control subjects. Out of patients with dementia, 148 individuals (2.02%) were diagnosed with epilepsy. We observed a progressive increase in the cumulative incidence of seizures over time, registering 1.45% in the first year following the diagnosis, and rising to 1.96% after three years. Analysis using Cox regression revealed a significant association between the development of epilepsy and dementia (HR = 4.58, 95% CI = 3.67-5.72). Additional risk factors were male gender (HR = 1.35, 95% CI = 1.07-1.69) and a younger age at dementia onset (HR = 1.03, 95% CI=1.02-1.04). Conclusions: Dementia increases epilepsy risk, especially with early onset and male gender. Clinicians should have a low threshold to suspect seizures in dementia cases.

Virus-Induced Epilepsy vs. Epilepsy Patients Acquiring Viral Infection: Unravelling the Complex Relationship for Precision Treatment.

The intricate relationship between viruses and epilepsy involves a bidirectional interaction. Certain viruses can induce epilepsy by infecting the brain, leading to inflammation, damage, or abnormal electrical activity. Conversely, epilepsy patients may be more susceptible to viral infections due to factors, such as compromised immune systems, anticonvulsant drugs, or surgical interventions. Neuroinflammation, a common factor in both scenarios, exhibits onset, duration, intensity, and consequence variations. It can modulate epileptogenesis, increase seizure susceptibility, and impact anticonvulsant drug pharmacokinetics, immune system function, and brain physiology. Viral infections significantly impact the clinical management of epilepsy patients, necessitating a multidisciplinary approach encompassing diagnosis, prevention, and treatment of both conditions. We delved into the dual dynamics of viruses inducing epilepsy and epilepsy patients acquiring viruses, examining the unique features of each case. For virus-induced epilepsy, we specify virus types, elucidate mechanisms of epilepsy induction, emphasize neuroinflammation's impact, and analyze its effects on anticonvulsant drug pharmacokinetics. Conversely, in epilepsy patients acquiring viruses, we detail the acquired virus, its interaction with existing epilepsy, neuroinflammation effects, and changes in anticonvulsant drug pharmacokinetics. Understanding this interplay advances precision therapies for epilepsy during viral infections, providing mechanistic insights, identifying biomarkers and therapeutic targets, and supporting optimized dosing regimens. However, further studies are crucial to validate tools, discover new biomarkers and therapeutic targets, and evaluate targeted therapy safety and efficacy in diverse epilepsy and viral infection scenarios.

Microsurgical removal of supratentorial and cerebellar cavernous malformations: what has changed? A single institution experience.

BACKGROUND: Features associated with a safe surgical resection of cerebral cavernous malformations (CMs) are still not clear and what is needed to achieve this target has not been defined yet. METHODS: Clinical presentation, radiological features and anatomical locations were assessed for patients operated on from January 2008 to January 2018 for supratentorial and cerebellar cavernomas. Supratentorial CMs were divided into 3 subgroups (non-critical vs. superficial critical vs. deep critical). The clinical outcome was assessed through modified Rankin Scale (mRS) and was divided into favorable (mRS 0-1) and unfavorable (mRS ≥ 2). Post-operative epilepsy was classified according to the Maraire Scale. RESULTS: A total of 144 were considered eligible for the current study. At 6 months follow-up the clinical outcome was excellent for patients with cerebellar or lobar CMs in non-critical areas (mRS ≤ 1: 91.1 %) and for patients with superficial CMs in critical areas (mRS ≤ 1: 92.3 %). Patients with deep-seated suprantentorial CMs showed a favorable outcome in 76.9 %. As for epilepsy 58.5 % of patients presenting with a history of epilepsy were free from seizures and without therapy (Maraire grade I) at last follow-up (mean 3.9 years) and an additional 41.5 % had complete control of seizures with therapy (Maraire grade II). CONCLUSIONS: Surgery is safe in the management of CMs in non-critical but also in critical supratentorial locations, with a caveat for deep structures such as the insula, the basal ganglia and the thalamus/hypothalamus.

The Role of the Orexin System in Craniocerebral Trauma-Induced Epilepsy in Mice.

BACKGROUND: Following traumatic brain injury (TBI), an imbalance arises in the central nervous system within the hippocampus region, resulting in the proliferation of mossy cell fibers, causing abnormal membrane discharge. Moreover, disruptions in cellular neurotransmitter secretion induce post-traumatic epilepsy. Extensive experimental and clinical data indicate that the orexin system plays a regulatory role in the hippocampal central nervous system, but the specific regulatory effects are unclear. Therefore, further experimental evaluation of its relevance is needed. OBJECTIVE: This study aims to investigate the effects of orexin receptor agonists (OXA) on the seizure threshold and intensity in controlled cortical impact (CCI) mice, and to understand the role of the orexin system in post-traumatic epilepsy (PTE). METHODS: Male C57BL/6 mice weighing 18-22 g were randomly divided into three groups: Sham, CCI, and CCI+OXA. The three groups of mice were sequentially constructed with models, implanted with electrodes, and established drug-delivery cannulas. After a 30-day recovery, the Sham and CCI groups were injected with physiological saline through the administration cannulas, while the CCI+OXA group was injected with OXA. Subsequently, all mice underwent electrical stimulation every 30 minutes for a total of 15 times. Epileptic susceptibility, duration, intensity, and cognitive changes were observed. Concurrently, the expression levels and changes of GABAergic neurons in the hippocampus of each group were examined by immunofluorescence. RESULTS: Injecting OXA into hippocampal CA1 reduces the threshold of post-traumatic seizures, prolongs the post-discharge duration, prolongs seizure duration, reduces cognitive ability, and exacerbates the loss of GABAergic neurons in the hippocampal region. CONCLUSIONS: Based on the results, we can find that injecting OXA antagonists into the CA1 region of the hippocampus can treat or prevent the occurrence and progression of post-traumatic epilepsy.

Potential of focal cortical dysplasia in migraine pathogenesis.

Focal cortical dysplasias are abnormalities of the cerebral cortex associated with an elevated risk of neurological disturbances. Cortical spreading depolarization/depression is a correlate of migraine aura/headache and a trigger of migraine pain mechanisms. However, cortical spreading depolarization/depression is associated with cortical structural changes, which can be classified as transient focal cortical dysplasias. Migraine is reported to be associated with changes in various brain structures, including malformations and lesions in the cortex. Such malformations may be related to focal cortical dysplasias, which may play a role in migraine pathogenesis. Results obtained so far suggest that focal cortical dysplasias may belong to the causes and consequences of migraine. Certain focal cortical dysplasias may lower the threshold of cortical excitability and facilitate the action of migraine triggers. Migraine prevalence in epileptic patients is higher than in the general population, and focal cortical dysplasias are an established element of epilepsy pathogenesis. In this narrative/hypothesis review, we present mainly information on cortical structural changes in migraine, but studies on structural alterations in deep white matter and other brain regions are also presented. We develop the hypothesis that focal cortical dysplasias may be causally associated with migraine and link pathogeneses of migraine and epilepsy.

Epileptic encephalopathies and progressive neurodegeneration.

Developmental encephalopathies (DE), epileptic encephalopathies (EE) and developmental and epileptic encephalopathies (DEE) are overlapping neurodevelopmental disorders characterized by early-onset, often severe epileptic seizures, developmental delay, or regression and have multiple etiologies. Classical nosology in child neurology distinguished progressive and nonprogressive conditions. A progressive course with global cognitive worsening in DEE is usually attributed to severe seizures and electroencephalographic abnormalities whose deleterious effects interfere with developmental processes both in an apparently healthy brain and in an anatomically compromised one. Next generation sequencing and functional studies have helped identifying and characterizing clinical conditions, each with a broad spectrum of clinical and anatomic severity corresponding to a variable level of neurodegeneration, such that both a rapidly progressive course and considerably milder phenotypes with no obvious deterioration can be configured with mutations in the same gene. In this mini review, we present examples of genetic DEE that draw connections between neurodevelopmental and neurodegenerative disorders.

Channelopathies in epilepsy: an overview of clinical presentations, pathogenic mechanisms, and therapeutic insights.

Pathogenic variants in genes encoding ion channels are causal for various pediatric and adult neurological conditions. In particular, several epilepsy syndromes have been identified to be caused by specific channelopathies. These encompass a spectrum from self-limited epilepsies to developmental and epileptic encephalopathies spanning genetic and acquired causes. Several of these channelopathies have exquisite responses to specific antiseizure medications (ASMs), while others ASMs may prove ineffective or even worsen seizures. Some channelopathies demonstrate phenotypic pleiotropy and can cause other neurological conditions outside of epilepsy. This review aims to provide a comprehensive exploration of the pathophysiology of seizure generation, ion channels implicated in epilepsy, and several genetic epilepsies due to ion channel dysfunction. We outline the clinical presentation, pathogenesis, and the current state of basic science and clinical research for these channelopathies. In addition, we briefly look at potential precision therapy approaches emerging for these disorders.

Predictive Model for Estimating the Risk of Epilepsy After Aneurysmal Subarachnoid Hemorrhage: The RISE Score.

BACKGROUND AND OBJECTIVES: The occurrence of seizures after aneurysmal subarachnoid hemorrhage (aSAH) is associated with a poorer functional and cognitive prognosis and less favorable quality of life. It would be of value to promptly identify patients at risk of epilepsy to optimize follow-up protocols and design preventive strategies. Our aim was to develop a predictive score to help stratify epilepsy risk in patients with aSAH. METHODS: This is a retrospective, longitudinal study of all adults with aSAH admitted to our center (2012-2021). We collected demographic data, clinical and radiologic variables, data on early-onset seizures (EOSs), and data on development of epilepsy. Exclusion criteria were previous structural brain lesion, epilepsy, and ≤7 days' follow-up. Multiple Cox regression was used to evaluate factors independently associated with unprovoked remote seizures (i.e., epilepsy). The best fitting regression model was used to develop a predictive score. Performance was evaluated in an external validation cohort of 308 patients using receiver-operating characteristic curve analysis. RESULTS: From an initial database of 743 patients, 419 met the inclusion criteria and were included in the analysis. The mean age was 60 ± 14 years, 269 patients (64%) were women, and 50 (11.9%) developed epilepsy within a median follow-up of 4.2 years. Premorbid modified Rankin Score (mRS) (hazard ratio [HR] 4.74 [1.8-12.4], p = 0.001), VASOGRADE score (HR 2.45 [1.4-4.2], p = 0.001), surgical treatment (HR 2.77 [1.6-4.9], p = 0.001), and presence of EOSs (HR 1.84 [1.0-3.4], p = 0.05) were independently associated with epilepsy. The proposed scale, designated RISE, scores 1 point for premorbid mRS ≥ 2 (R), VASOGRADE-Yellow (I, Ischemia), surgical intervention (S), and history of EOSs (E) and 2 points for VASOGRADE-Red. RISE stratifies patients into 3 groups: low (0-1), moderate (2-3), and high (4-5) risk (2.9%, 20.8%, and 75.7% developed epilepsy, respectively). On validation in a cohort from a different tertiary care center (N = 308), the new scale yielded a similar risk distribution and good predictive power for epilepsy within 5 years after aSAH (area under the curve [AUC] 0.82; 95% CI 0.74-0.90). DISCUSSION: The RISE scale is a robust predictor of post-SAH epilepsy with immediate clinical applicability. In addition to facilitating personalized diagnosis and treatment, RISE may be of value for exploring future antiepileptogenesis strategies.

Impact of annual community-directed treatment with ivermectin on the incidence of epilepsy in Mvolo, a two-year prospective study.

OBJECTIVES: The potential impact of cumulative community-directed treatment with ivermectin (CDTI) on epilepsy epidemiology in Mvolo County, South Sudan, an onchocerciasis-endemic area with high epilepsy prevalence, was investigated. Annual CDTI was introduced in 2002 in Mvolo, with interruptions in 2016 and 2020. METHODS: Comprehensive house-to-house surveys in Mvolo (June 2020 and 2022) identified cases of epilepsy, including probable nodding syndrome (pNS). Community workers screened households in selected sites for suspected epilepsy, and medical doctors confirmed the diagnosis and determined the year of seizure onset. The incidence of epilepsy, including pNS, was analysed using 95% confidence intervals (CIs). Data on ivermectin intake and onchocerciasis-associated manifestations (itching and blindness) were collected. RESULTS: The surveys covered 15,755 (2020) and 15,092 (2022) individuals, identifying 809 (5.2%, 95% CI: 4.8-5.5%) and 672 (4.5%, 95% CI: 4.1-4.8%) epilepsy cases, respectively. Each survey reported that a third of the surveyed population experienced skin itching, and 3% were blind. Epilepsy incidence per 100,000 person-years gradually declined, from 326.5 (95% CI: 266.8-399.1) in 2013-2015 to 96.6 (95% CI: 65.5-141.7) in 2019-2021. Similarly, pNS incidence per 100,000 person-years decreased from 151.7 (95% CI: 112.7-203.4) to 27.0 (95% CI: 12.5-55.5). Coverage of CDTI was suboptimal, reaching only 64.0% of participants in 2019 and falling to 24.1% in 2021 following an interruption in 2020 due to COVID-19 restrictions. Additionally, while 99.4% of cases had active epilepsy in 2022, less than a quarter of these had access to antiseizure medication. CONCLUSIONS: The observed decrease in epilepsy incidence despite suboptimal CDTI coverage highlights the potential impact of onchocerciasis control efforts and underscores the need to strengthen these efforts in Mvolo County and across South Sudan. As a proactive measure, Mvolo and neighbouring counties are transitioning to biannual CDTI. Furthermore, the substantial epilepsy treatment gap in Mvolo should be addressed.

Seizures in inflammatory demyelinating disorders of the central nervous system.

BACKGROUND: Multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) may be associated with acute symptomatic seizures and chronic epilepsy as well. The clinical features of the seizures and/or accompanying epilepsy seen in each disease group may vary. In this study, we aimed to contribute to the existing literature by describing the clinical features of seizures and epilepsy in our demyelinating patient population. METHODS: We retrospectively analyzed patients who were followed up in our tertiary referral center neurology demyelinating diseases outpatient clinic between 2019 and 2024. Patients who had at least one seizure before, simultaneously, or after the diagnosis of demyelinating disease were included in the study. RESULTS: Among 1735 patients with MS, 40 had experienced at least one epileptic seizure (2.3 %). Thirty patients (1.7 %) had seizures that could not be explained by another factor than MS. When secondary progressive MS (SPMS) and relapsing-remitting MS (RRMS) were compared, the interval between MS-epilepsy diagnosis was longer and seizure recurrence was more in SPMS. However, the prognosis of epilepsy was good in both subtypes. There were 21 patients followed up with antibody-positive neuromyelitis optica spectrum disorder. No patient had a seizure during the follow-up. We identified 56 patients who fulfilled the criteria for MOGAD with high antibody titers. Seizures were observed in three of them (5.4 %). All of them had status epilepticus either at the onset or during the course of the disease. CONCLUSION: Even rare, seizures constitute one of the important clinical features of the inflammatory demyelinating disorders of the central nervous system. The pathophysiologic mechanism underlying seizures in MS is still not clear. Seizures may occur through different mechanisms in patients where seizures are the initial symptom or a sign of relapse and those that occur spontaneously during the progressive course of the disease. Prevalence of status epilepticus was common in MOGAD patients. Given the rarity of the seizures in CNS demyelinating disorders, it is difficult the define clinical and pathophysiological characteristics of accompanying seizures and epilepsy. Future studies conducted on large patient groups will contribute to the existing literature.

PAEDIATRIC SYMPTOMATIC SEIZURES IN INDIA: UNRAVELLING VARIED ETIOLOGIES AND NEUROIMAGING PATTERNS - A MULTICENTRIC STUDY.

Pediatric neuroimaging presents a unique set of challenges, primarily stemming from the intricacies of normal myelination processes occurring within the initial two years of life. This complexity is particularly pronounced in the context of pediatric epilepsy, where a substantial proportion of neuroimaging cases appears normal, especially in instances of idiopathic or provoked seizures. Nevertheless, abnormalities in neuroimaging tend to manifest in cases of acute or remote symptomatic seizures. Notably, the etiological landscape of seizures in children diverges significantly from that observed in adults, with neurodevelopmental, neurometabolic, and neuro-infectious factors emerging as predominant contributors. This multicentric study, conducted between November 2021 and November 2023, spanned diverse hospitals across various states in India. Encompassing children from birth to 12 years of age experiencing acute and remote symptomatic seizures, the study meticulously documented clinical and demographic profiles. Exclusion criteria were applied, excluding typical febrile seizures and idiopathic epilepsy syndromes to ensure a focused analysis. The study encompassed a total of 109 cases, revealing a spectrum of neuroimaging findings. Noteworthy among these were cortical malformations, including focal cortical dysplasia (12 cases), tuberous sclerosis (6 cases), polymicrogyria (3 cases), hemimegalencephaly (1 case), lissencephaly (1 case), schizencephaly (2 cases), heterotopias (3 cases), cavernous hemangioma (1 case), and AV malformation (1 case). Additionally, neoplastic lesions (6 cases), neurocysticercosis (5 cases), tuberculoma (4 cases), hippocampal sclerosis (3 cases), post-hypoxic and cerebrovascular accident gliosis (3 cases), leukodystrophies (2 cases), and non-lesional cases (58 cases) were documented. Pediatric neuroimaging in symptomatic seizures may present with normal findings, influenced by interpreter bias and the non-uniform availability of 3T MRI across different medical centers. The diverse causative factors for symptomatic seizures underscore the impact of demographic features, including the endemicity of specific infections and birth injuries, on the observed variability across medical centers. These findings underscore the imperative for a comprehensive understanding and standardization in pediatric neuroimaging practices.

Tuberous sclerosis complex in adulthood: focus on epilepsy prognosis.

OBJECTIVE: Typically diagnosed in early childhood or adolescence, TSC is a chronic, multisystemic disorder with age-dependent manifestations posing a challenge for transition and for specific surveillance throughout the lifetime. Data on the clinical features and severity of TSC in adults and on the prognosis of epilepsy are scarce. We analyzed the clinical and genetic features of a cohort of adult patients with TSC, to identify the prognostic predictors of seizure remission after a long follow-up. METHOD: We conducted a retrospective analysis of patients diagnosed with TSC according to the updated international diagnostic criteria. Pearson's chi-square or Fisher's exact test and Mann Whitney U test were used to compare variables among the Remission (R) and Non-Remission (NR) group. Univariate and multivariate logistic regression analyses were performed. RESULTS: We selected 43 patients with TSC and neurological involvement in terms of epilepsy and/or brain lesions, attending the Epilepsy Center of our Institute: of them, 16 (37.2%) were transitioning from the pediatric care and 6 (13.9%) were referred by other specialists. Multiorgan involvement includes cutaneous (86.0%), nephrological (70.7%), hepatic (40.0%), ocular (34.3%), pneumological (28.6%) and cardiac (26.3%) manifestations. Thirty-nine patients (90.7 %) had epilepsy. The mean age at seizure onset was 4 ± 7.3 years: most patients (29, 76.3 %) presented with focal seizures or spasms by age 3 years; only 2 (5.3 %) had seizure onset in adulthood. Twenty-seven patients (69.2 %) experienced multiple seizure types overtime, 23 (59.0 %) had intellectual disability (ID). At last assessment, 14 (35.9 %) were seizure free (R group) and 25 (64.1 %) had drug-resistant seizures (NR group). At logistic regression univariate analysis, ID (OR 7.9, 95 % CI 1.8--34.7), multiple seizure types lifelong (OR 13.2, 95 % CI 2.6- 67.2), spasms/tonic seizures at presentation (OR 6.5, 95 % CI 1.2--35.2), a higher seizure frequency at onset (OR 5.4, 95 % CI 1.2--24.3), abnormal neurological examination (OR 9.8, 95 % CI 1.1--90.6) and pathogenic variants in TSC2 (OR 5.4, 95 % CI 1.2--24.5) were significantly associated with non-remission. In the multivariate analysis, both ID and multiple seizure types lifelong were confirmed as independent predictors of poor seizure outcome. CONCLUSIONS: In our cohort of adult patients with TSC, epilepsy remains one of the main neurological challenges with only 5.3% of cases manifesting in adulthood. Approximately 64% of these patients failed to achieve seizure remission. ID and multiple seizure types were the main predictors of poor outcome. Nephrological manifestations require continuous specific follow-up in adults.