Intractable Seizures Research Articles

Quantitative summary on the human pharmacokinetic properties of cannabidiol to accelerate scientific clinical application of cannabis.

Cannabidiol (CBD) is a non-psychoactive substance that exerts numerous pharmacological benefits, including anti-inflammatory and antioxidant properties. It has received attention as a useful substance for the treatment of intractable pain, seizures, and anxiety, and related clinical trials have continued. However, the CBD pharmacokinetic results between reports are highly variable, making it difficult to clearly identify the pharmacokinetic properties of CBD. The main purpose of this study was to identify CBD clinical pharmacokinetic properties through meta-analysis. In particular, we sought to derive valid, interpretable independent variables and interpret their pharmacokinetic parameter correlations in relation to the large inter-individual and inter-study variability in CBD pharmacokinetics. For this study, CBD-related clinical trial reports were extensively screened and intercomparisons were performed between internal data sets through systematic classification and extraction of pharmacokinetic parameter values. The candidate independent variables associated with interpretation of CBD pharmacokinetic diversity established and explored in this study were as follows: diet, tetrahydrocannabinol (THC) combination, sample matrix type, liver and renal function, exposure route, dosage form, CBD exposure dose, cannabis smoking frequency, multiple exposure. The results of this study showed that CBD pharmacokinetics were influenced (increased plasma exposure by approximately 2-5 times) by diet immediately before or during CBD exposure, and that THC was not expected to have an antagonistic effect on the CBD absorption. The influence of changes in liver function would be significant in CBD pharmacokinetic diversity. Due to decreased liver function, the plasma exposure of CBD increased 2.57-5.15 times compared to healthy adults, and the half-life and clearance showed a 2.58-fold increase and a 5.15-fold decrease, respectively. CBD can be rapidly absorbed into the body (time to reach maximum concentration within 3.18h) by oral, transdermal, and inhalation exposures, and lipid emulsification and nanoformulation of CBD will greatly improve CBD bioavailability (up to approximately 2 times). The pharmacokinetics of CBD generally follow linear kinetic characteristics. The importance of this study is that it suggests key factors that should be considered in terms of pharmacokinetics in further clinical trials and formulations of CBD in the future.

Corticosteroid Treatment for Intractable Seizures Associated with Post-radiosurgical Peritumoral Edema in Intracranial Meningioma

Corticosteroid Treatment for Intractable Seizures Associated with Post-radiosurgical Peritumoral Edema in Intracranial Meningioma

Seizure solver- pyridoxine dependent seizures

Pyridoxine dependency is a rare cause of seizures. Pyridoxine dependent seizures (PDS) occur despite normal vitamin B6 levels and is due to defective binding of pyridoxine to its apoenzyme, glutamate decarboxylase, which converts glutamic acid to gamma aminobutyric acid (GABA). Pyridoxine-dependent seizure is a rare autosomal recessive disorder that usually presents with neonatal intractable seizures. Parenteral pyridoxine injection test is a highly effective and reproducible test in confirming the diagnosis. Hunt, et al.(l) described the first case of PDS with autosomal recessive inheritance. Since then, several cases have been reported with onset of seizures after neonatal period (2-6). Pyridoxine-dependent epilepsy – ALDH7A1 (PDE-ALDH7A1) is characterized by seizures not well controlled with anti-seizure medication that are responsive clinically and electrographically to large daily supplements of pyridoxine (vitamin B6). This is true across a phenotypic spectrum that ranges from classic to atypical PDE-ALDH7A1. Intellectual disability is common, particularly in classic PDE-ALDH7A1.(7)

6791 Pituitary Apoplexy as Presentation of Atypical Teratoid/Rhabdoid Tumor

Abstract Disclosure: S.I. Babli: None. H. Alkubedan: None. N.M. Ali: None. R. Alqawahmed: None. M.M. Elhassan: None. Introduction: Pituitary apoplexy occurs in a pituitary adenoma; it migh occur in other less common types of tumors. The atypical teratoid/rhabdoid tumor (ATRT) is a very aggressive malignant tumor of the central nervous system and has a poor prognosis. It is rare to occur in adult and in the sellar region. Clinical Case: 32 years old male presented to ER with 4 days history of fever, headache and vomiting. He was conscious but confused. Vital signs Temperature 39 C, BP 120/80, HR 110 beats/min and Saturation of 95 %, Possibility of meningoencephalitis was raised, patient Brain CT showed Sellar and suprasellar mass with compression over the optic chiasma and invasion to the left cavernous sinus. Patient suddenly developed Generalize tonic-clonic convulsion and hypotension. He received IV midazolam, intubated and was started on noradrenaline and hydrocortisone, he was admitted to ICU as a case of meningoencephalitis and started on Ceftriaxone, Vancomycin and Acyclovir. Cerebrospinal fluid analysis showed RBC 175/cumm, WBC 20/cumm with 20% polymorph and 80% mononuclear cells, Protein 1.38 g/l (0.24-0.49) glucose 7.9 mmol/l with plasma glucose of 10 mmol/l. Repeated Brain CT showed Sellar and suprasellar mass with compression over the optic chiasma and invasion to the left cavernous sinus and with minimal heterogenicity and increased density suggestive of hemorrhagic components. Endocrine history revealed weight gain but no history to suggest acromegaly, Cushing’s syndrome or hypogonadism . Examinations: Patient was intubated and sedated BP 90/60 on Maximum inotropic support. Left oculomotor nerve palsy, Bilateral papilledema, he was having acanthosis nigricans with no signs of acromegaly, CS or hypogonadism. Laboratory finding: WBC17 with neutrophilia, Hgb 14.7 g/dl plt 360 Na 140 mmol/l, creatnin 180 mmol/, FT4 6.2 pmol/l, TSH 0.015, PROLACTINE 22, IGF1 29 ng/ml (41-246) Free testosterone index 2.13 (33-106), LH 0.5, FSH 0.3 .Patient had TTS and histopathology showed: SMARCB1 deficient malignant neoplasm, consistent with sellar atypical teratoid rhabdoid tumor. Post OP, patient had Ventilator associated pneumonia and recurrent attacks of seizures despite multiple antiepileptic medications. Patient was evaluated by medical and radiation oncologists but due to his general condition the treatment was postpone. One month after TSS, he developed intractable seizure new Brain CT showed interventricular haemorrhage with hydrocephalus and marked enlargement of hyperdense pituitary lesion which suggests haemorrhage. External ventricular drain was inserted but patient arrested and died. Conclusions: ATRT of the CNS usually affects young children. In the literature review performed in adults, only nine cases have occurred in the sellar or suprasellar region. Survival is variable in the different cases reported in the literature, with a mean of 26 months. Presentation: 6/2/2024

Dyke-Davidoff-Masson Syndrome in a Tanzanian patient: a case report

BackgroundDyke-Davidoff-Masson Syndrome (DDMS) is a rare neurological disorder resulting from an insult to the developing brain in utero or during early life which is characterized by refractory seizures and a wide variety of deficits. Due to its rarity, the condition is often overlooked although a detailed history and imaging can help distinguish it from other similar conditions and provide early diagnosis.Case presentationA 30-year-old African female presented with a history of recurrent seizures and intellectual disability. She was born via vaginal delivery, and her post-natal history was unremarkable. Her developmental milestones were normal until the age of three, when she was hospitalized for two weeks due to a febrile illness accompanied by generalized seizures, from which she fully recovered. On cognitive assessment, she scored 14 out of 60 on the Ravens Standard Progressive Matrices (RSPM), indicating an intellectual disability. Neurological examination revealed constructional apraxia, an upper motor neuron lesion (UMNL) affecting the facial nerve, and left-sided spastic paresis. Additionally, a slow, sinuous writhing movement involving all the fingers of her left hand was observed. A computed tomography (CT) scan of her head confirmed a diagnosis of Dyke-Davidoff-Masson syndrome (DDMS). The scan showed significant volume loss in the right cerebral hemisphere, gross dilation of the right lateral ventricle with ex-vacuo dilatation, right calvarial thickening, and hyperpneumatization of the right frontal sinus. She was managed conservatively with anticonvulsants, which effectively controlled her seizures.ConclusionIn the setting of recurrent seizures, intellectual disability, hemiparesis, or facial asymmetry, a clinician should have a high index of suspicion for DDMS. Late diagnosis is often related to intractable seizures to anticonvulsants, necessitating hemispherectomy, which is not a readily available option in limited resource settings.

New Surgical Approach to Carpus Callosum Agenesis with Intractable Seizure: Subdural Peritoneal Shunt

New Surgical Approach to Carpus Callosum Agenesis with Intractable Seizure: Subdural Peritoneal Shunt

Elucidating the clinical and genetic spectrum of inositol polyphosphate phosphatase INPP4A-related neurodevelopmental disorder

PurposeBiallelic INPP4A variants have recently been associated with severe neurodevelopmental disease in single-case reports. Here, we expand and elucidate the clinical-genetic spectrum and provide a pathomechanistic explanation for genotype-phenotype correlations. MethodsClinical and genomic investigations of 30 individuals were undertaken alongside molecular and in silico modelling and translation reinitiation studies. ResultsWe characterize a clinically variable disorder with cardinal features, including global developmental delay, severe-profound intellectual disability, microcephaly, limb weakness, cerebellar signs, and short stature. A more severe presentation associated with biallelic INPP4A variants downstream of exon 4 has additional features of (ponto)cerebellar hypoplasia, reduced cerebral volume, peripheral spasticity, contractures, intractable seizures, and cortical visual impairment. Our studies identify the likely pathomechanism of this genotype-phenotype correlation entailing translational reinitiation in exon 4 resulting in an N-terminal truncated INPP4A protein retaining partial functionality, associated with less severe disease. We also identified identical reinitiation site conservation in Inpp4a−/− mouse models displaying similar genotype-phenotype correlation. Additionally, we show fibroblasts from a single affected individual exhibit disrupted endocytic trafficking pathways, indicating the potential biological basis of the condition. ConclusionOur studies comprehensively characterize INPP4A-related neurodevelopmental disorder and suggest genotype-specific clinical assessment guidelines. We propose that the potential mechanistic basis of observed genotype-phenotype correlations entails exon 4 translation reinitiation.

Clinical and genetic delineation of autosomal recessive and dominant ACTL6B-related developmental brain disorders

PurposeThis study aims to comprehensively delineate the phenotypic spectrum of ACTL6B-related disorders, previously associated with both autosomal recessive and autosomal dominant neurodevelopmental disorders. Molecularly, the role of the nucleolar protein ACTL6B in contributing to the disease has remained unclear. MethodsWe identified 105 affected individuals, including 39 previously reported cases, and systematically analyzed detailed clinical and genetic data for all individuals. Additionally, we conducted knockdown experiments in neuronal cells to investigate the role of ACTL6B in ribosome biogenesis. ResultsBiallelic variants in ACTL6B are associated with severe-to-profound global developmental delay/intellectual disability, infantile intractable seizures, absent speech, autistic features, dystonia, and increased lethality. De novo monoallelic variants result in moderate-to-severe global developmental delay/intellectual disability, absent speech, and autistic features, whereas seizures and dystonia were less frequently observed. Dysmorphic facial features and brain abnormalities, including hypoplastic corpus callosum, and parenchymal volume loss/atrophy, are common findings in both groups. We reveal that in the nucleolus, ACTL6B plays a crucial role in ribosome biogenesis, particularly in pre-rRNA processing. ConclusionThis study provides a comprehensive characterization of the clinical spectrum of both autosomal recessive and dominant forms of ACTL6B-associated disorders. It offers a comparative analysis of their respective phenotypes provides a plausible molecular explanation and suggests their inclusion within the expanding category of “ribosomopathies.”

Gnao1 is a molecular switch that regulates the Rho signaling pathway in differentiating neurons

GNAO1 encodes G protein subunit alpha O1 (Gαo). Pathogenic variations in GNAO1 cause developmental delay, intractable seizures, and progressive involuntary movements from early infancy. Because the functional role of GNAO1 in the developing brain remains unclear, therapeutic strategies are still unestablished for patients presenting with GNAO1-associated encephalopathy. We herein report that siRNA-mediated depletion of Gnao1 perturbs the expression of transcripts associated with Rho GTPase signaling in Neuro2a cells. Consistently, siRNA treatment hampered neurite outgrowth and extension. Growth cone formation was markedly disrupted in monolayer neurons differentiated from iPSCs from a patient with a pathogenic variant of Gαo (p.G203R). This variant disabled neuro-spherical assembly, acquisition of the organized structure, and polarized signals of phospho-MLC2 in cortical organoids from the patient’s iPSCs. We confirmed that the Rho kinase inhibitor Y27632 restored these morphological phenotypes. Thus, Gαo determines the self-organizing process of the developing brain by regulating the Rho-associated pathway. These data suggest that Rho GTPase pathway might be an alternative target of therapy for patients with GNAO1-associated encephalopathy.

Stereotactic Radiosurgery in the Management of Intractable Seizure Due to Hypothalamic Hamartoma

Stereotactic Radiosurgery in the Management of Intractable Seizure Due to Hypothalamic Hamartoma

The anesthetic management of a child with ohtahara syndrome and severe stridor: a case report

BackgroundOhtahara syndrome is a progressive developmental and epileptic encephalopathy that manifests in the early infantile period. This rare condition is characterized by intractable seizures, psychomotor retardation, and poor prognosis. To date, there are a handful of case reports regarding the anesthetic management of children with Ohtahara syndrome. However, limited reports exist of patients with Ohtahara syndrome who present with difficult airways. This report describes our airway findings and general anesthetic management of a pediatric patient with Ohtahara syndrome undergoing diagnostic bronchoscopy for severe inspiratory stridor.Case presentationA 14-month-old, 9 kg, male patient with Ohtahara syndrome presented with a year-long history of severe inspiratory stridor and was scheduled for bronchoscopy with lavage. On exam, the patient had noisy breathing, was non-verbal with developmental delay, and had poor head control with significant central hypotonia. The patient was induced with ketamine and general anesthesia was maintained with propofol. Bronchoscopic evaluation was completed uneventfully and revealed a diagnosis of laryngotracheomalacia. The patient’s breathing was maintained spontaneously throughout the procedure and no seizures were noted. In the post anesthesia care unit, the patient’s respiratory and cardiovascular function were stable.ConclusionsThis report documents the unusual finding of severe inspiratory stridor in a 14-month-old child diagnosed with Ohtahara syndrome and our anesthetic management during their diagnostic bronchoscopy. Currently, documentation of complex airway pathology present in patients with Ohtahara syndrome is limited and should be further evaluated. This will assist pediatric anesthesiologists as these patients may require careful preoperative assessment, thoughtful airway management, and surgical alternatives on standby.

Vagus Nerve Stimulation for Intractable Focal Epilepsy

Abstract Background Epilepsy is a common neurological condition affecting 0.5-1% of the population. Despite the advances in the medical management of epilepsy 25-35% of patients have poor control of their seizures or have unacceptable side effects from the medication. Aim and Objectives To make up-to-date recommendations for the value of vagus nerve stimulation (VNS) in patients suffering from intractable focal epilepsy and not candidates for surgical resection. Subjects and Methods Eight studies were included in the present meta-analysis. The flow diagram of the study selection processes. The total number of patients in the eight included studies was 266. The follow-up periods ranged from 12–124 months. Because of significant heterogeneity (I2 = 94 %) among the included studies, a sensitivity analysis was performed. Result 59.4% of all the included patients showed a 50% or greater reduction in seizure frequency after VNS. The patients with > 50% reduction in seizure frequency ranged from 25–66% among the eight included studies. Non-significant improvement in seizure frequency after VNS. Conclusion After VNS, the frequency of seizures was reduced by 50% in about 59.4% of the patients with intractable focal seizures. The present study's random effects forest plot, however, indicated that the reduction in seizure frequency following VNS was not statistically significant. The effectiveness of VNS in reducing seizure frequency in the population under study is therefore still unknown,.

Endoscopic trans-orbital approach for the tumor-related epilepsy at the temporal tip.

Minimally invasive surgery is gaining increasing interest in epilepsy surgery. In this video, the authors present the endoscopic transorbital approach for an epileptogenic lesion located at the temporal tip. The patient was a man in his 40s who has had intractable focal impaired awareness seizures and focal to bilateral tonic-clonic seizures since he was 31 years of age. According to the preoperative examination, including stereotactic electroencephalography, a cavernous angioma located at the tip of the right temporal lobe was diagnosed as an epileptogenic lesion. Lesionectomy for this lesion was performed using the endoscopic transorbital approach as minimally invasive surgery and a favorable outcome was achieved. The video can be found here: https://stream.cadmore.media/r10.3171/2024.4.FOCVID2414.

Use of En-Bloc Multiple Monitored Electroconvulsive Therapy in Benzodiazepine Refractory Malignant Catatonia.

We report a case of an adolescent female experiencing benzodiazepine and single-stimulation electroconvulsive (ECT)-refractory malignant catatonia, who improved with the use multiple monitored ECT (mmECT). Per the 2001 American Psychiatric Association guidelines, mmECT should be considered only in cases of intractable seizures or neuroleptic malignant syndrome. Since 2001, neuroleptic malignant syndrome and malignant catatonia have been described as occurring along the same spectrum of illness. Therefore, given the life-threatening nature of her condition, as well as the brief seizure duration she experienced from single-stimulation ECT, the patient was treated with en-bloc and 2-stimulation mmECT. The patient demonstrated a significant improvement in response to this treatment, with her Bush-Francis Catatonia Rating Scale score decreasing by 89%. At 2-year follow-up in an outpatient neurodevelopmental catatonia clinic, the patient has been able to return to school in her previous advanced placement classes and has not required maintenance ECT.

Vagal Nerve Stimulation in the Pediatric Population and Correlation Between Family and Treatment Team Perspectives: Single-center Experience.

Vagal nerve stimulation (VNS) is an adjunctive therapy to pharmacological treatment in patients with drug-resistant epilepsy. This study aimed to assess the efficacy of VNS therapy for seizure frequency reduction and improving quality of life (QOL) measures in children with refractory epilepsy and to evaluate the correlation between the perspectives of families and those of the treating team. This was a prospective cohort study conducted at Abha Maternity and Children's Hospital, Saudi Arabia, from 2018 to 2022. A total of 21 pediatric patients who completed one year of follow-up after VNS implantation were included. Patients were aged between 2 and 14 years, with a mean age of 8.14 ± 3.92; 11 (52.4%) patients were female. Family and physician assessments were collected blinded to each other using Clinical Global Impression of Improvement (CGI-I) scores and QOL assessments to evaluate the correlation between the families' and treating team's perspectives on VNS outcomes. In this study involving 21 patients with intractable epilepsy, VNS showed significant efficacy in reducing the frequency of seizures. VNS significantly reduced the number of seizures per week from a baseline median of 35 to a median of 0.25 at the end of the follow-up period, representing a dramatic reduction of 99.3% (p < 0.001). The number of emergency department visits per year decreased from a baseline median of 12 to a median of 2, a reduction of 83.3% (p < 0.001), whereas the number of hospital admissions per year decreased from a baseline median of 3 to a median of 1, a 66.7% decrease (p < 0.001). The number of antiepileptic medications taken decreased from a median of 4 to 3 (p < 0.001). Notably, 28.57% of the patients achieved complete seizure freedom, and 38% exhibited significant improvement, with at least 50% reduction in seizure frequency. Importantly, none of the patients experienced an escalation in seizure frequency following VNS treatment. The family and physician assessments showed varying degrees of alignment in perceptions, with "concentration" exhibiting a significant positive correlation (r = 0.498, p = 0.022), indicating noteworthy agreement, whereas verbal communication did not show a substantial correlation (r = -0.062, p = 0.791), indicating a divergence of views. VNS is a promising and well-tolerated therapy for individuals with intractable seizures, offering clinical benefits and potential enhancements in various aspects of QOL. The varying perceptions between family and physician assessments highlight the importance of considering multiple perspectives when evaluating treatment outcomes.

Fine mapping and candidate gene analysis of Dravet syndrome modifier loci on mouse chromosomes 7 and 8

Dravet syndrome is a developmental and epileptic encephalopathy (DEE) characterized by intractable seizures, comorbidities related to developmental, cognitive, and motor delays, and a high mortality burden due to sudden unexpected death in epilepsy (SUDEP). Most Dravet syndrome cases are attributed to SCN1A haploinsufficiency, with genetic modifiers and environmental factors influencing disease severity. Mouse models with heterozygous deletion of Scn1a recapitulate key features of Dravet syndrome, including seizures and premature mortality; however, severity varies depending on genetic background. Here, we refined two Dravet survival modifier (Dsm) loci, Dsm2 on chromosome 7 and Dsm3 on chromosome 8, using interval-specific congenic (ISC) mapping. Dsm2 was complex and encompassed at least two separate loci, while Dsm3 was refined to a single locus. Candidate modifier genes within these refined loci were prioritized based on brain expression, strain-dependent differences, and biological relevance to seizures or epilepsy. High priority candidate genes for Dsm2 include Nav2, Ptpn5, Ldha, Dbx1, Prmt3 and Slc6a5, while Dsm3 has a single high priority candidate, Psd3. This study underscores the complex genetic architecture underlying Dravet syndrome and provides insights into potential modifier genes that could influence disease severity and serve as novel therapeutic targets.

Late-Onset Molybdenum Cofactor Deficiency Type A: A Treatable Cause of Developmental Delay.

Molybdenum cofactor deficiency classically presents in neonates with intractable seizures; however, milder cases generally present before age 2 years with developmental delays and may go undiagnosed. Early diagnosis, and safe, US Food and Drug Administration-approved substrate replacement are critical to preserve neurologic function. This article discusses 2 children who presented with late-onset molybdenum cofactor deficiency type A.

Generation of a human induced pluripotent stem cell line from a patient with GM3 synthase deficiency using self-replicating RNA vector

GM3 synthase deficiency (GM3SD) is caused by biallelic variants in the ST3GAL5 gene. Early clinical features of GM3SD include infantile onset of severe irritability and feeding difficulties, early intractable seizures, growth failure, hypotonia, sensorineural hearing impairment. We describe the generation and characterization the human induced pluripotent stem cell (hiPSC) line derived from fibroblasts of a 13-year-old girl with GM3 synthase deficiency resulted compound heterozygous for two new variants in the ST3GAL5 gene, c.1166A > G (p.His389Arg) and the c.1024G > A (p.Gly342Ser). The generated hiPSC line shows a normal karyotype, expresses pluripotency markers, and is able to differentiate into the three germ layers.

Ketogenic Diet in the Treatment of Epilepsy.

Epilepsy is one of the most disabling neurological diseases. Despite proper pharmacotherapy and the availability of 2nd and 3rd generation antiepileptic drugs, deep brain stimulation, and surgery, up to 30-40% of epilepsy patients remain drug-resistant. Consequences of this phenomenon include not only decreased a quality of life, and cognitive, behavioral, and personal disorders, but also an increased risk of death, i.e., in the mechanism of sudden unexpected death in epilepsy patients (SUDEP). The main goals of epilepsy treatment include three basic issues: achieving the best possible seizure control, avoiding the undesired effects of treatment, and maintaining/improving the quality of patients' lives. Therefore, numerous attempts are made to offer alternative treatments for drug-resistant seizures, an example of which is the ketogenic diet. It is a long-known but rarely used dietary therapy for intractable seizures. One of the reasons for this is the unpalatability of the classic ketogenic diet, which reduces patient compliance and adherence rates. However, its antiseizure effects are often considered to be worth the effort. Until recently, the diet was considered the last-resort treatment. Currently, it is believed that a ketogenic diet should be used much earlier in patients with well-defined indications. In correctly qualified patients, seizure activity may be reduced by over 90% or even abolished for long periods after the diet is stopped. A ketogenic diet can be used in all age groups, although most of the available literature addresses pediatric epilepsy. In this article, we focus on the mechanisms of action, effectiveness, and adverse effects of different variants of the ketogenic diet, including its classic version, a medium-chain triglyceride diet, a modified Atkins diet, and a low glycemic index treatment.

Genetic exploration of Dravet syndrome: two case report

BackgroundDravet syndrome is an infantile-onset developmental and epileptic encephalopathy (DEE) characterized by drug resistance, intractable seizures, and developmental comorbidities. This article focuses on manifestations in two Indonesian children with Javanese ethnicity who experienced Dravet syndrome with an SCN1A gene mutation, presenting genetic analysis findings using next-generation sequencing.Case presentationWe present a case series involving two Indonesian children with Javanese ethnicity whom had their first febrile seizure at the age of 3 months, triggered after immunization. Both patients had global developmental delay and intractable seizures. We observed distinct genetic findings in both our cases. The first patient revealed heterozygous deletion mutation in three genes (TTC21B, SCN1A, and SCN9A). In our second patient, previously unreported mutation was discovered at canonical splice site upstream of exon 24 of the SCN1A gene. Our patient’s outcomes improved after therapeutic evaluation based on mutation findings When comparing clinical manifestations in our first and second patients, we found that the more severe the genetic mutation discovered, the more severe the patient’s clinical manifestations.ConclusionThese findings emphasize the importance of comprehensive genetic testing beyond SCN1A, providing valuable insights for personalized management and tailored therapeutic interventions in patients with Dravet syndrome. Our study underscores the potential of next-generation sequencing in advancing genotype–phenotype correlations and enhancing diagnostic precision for effective disease management.