Search Results (148)

Epilepsy is a neurological disorder characterized by recurrent, unprovoked seizures, affecting millions worldwide. While anti-seizure medications serve as first-line treatment, approximately one-third of patients develop drug-resistant epilepsy (DRE), necessitating alternative interventions. Deep brain stimulation (DBS) has emerged as a promising therapy for DRE, particularly for patients who are ineligible for resective surgery. DBS involves stereotactic implantation of electrodes into target brain regions, such as the anterior nucleus of the thalamus (ANT), centromedian nucleus (CMT), and hippocampus (HC), to modulate aberrant neural activity and to reduce seizure frequency. Anesthesia plays a critical role in DBS implantation, influencing both patient safety and procedural success. The choice of anesthetic technique must balance patient comfort with the preservation of neurophysiological signals used for intraoperative electrode localization. A well-chosen anesthetic strategy can enhance the efficacy of electrode placement by minimizing patient movement and preserving critical neurophysiological signals for real-time monitoring. This precise targeting enhances safety via a reduction in perioperative risks and an improvement in long-term seizure control. Anesthetic considerations in epilepsy patients differ from those in movement disorders due to variations in their nuclei targets during DBS. Despite the increasing use of DBS for epilepsy following its FDA approval in 2018, research on anesthetic effects specific to this population remains limited. This narrative review, therefore, examines anesthetic approaches, pharmacological implications, potential complications, and evolving methods for DBS implantation in epilepsy patients, highlighting new insights and unique considerations in this population. Understanding these factors is essential for optimizing surgical outcomes and improving the safety and efficacy of DBS in epilepsy treatment. Full article

Background: Developmental epileptic encephalopathies (DEEs) are often associated with variably severe cognitive and motor impairment and frequent refractory epilepsy, with many children not achieving adequate seizure control via standard antiepileptic medications. The classic ketogenic diet (KD) has proven effective in reducing seizure frequency and/or severity in a category of DEEs and in certain refractory epilepsies of infancy. However, its multifaceted mechanisms, e.g., epigenetic modulation, anti-inflammatory and antioxidative effects, and direct neuronal excitability changes, are balanced by a high burden and low long-term adherence. Medium-chain triglycerides (MCTs), particularly decanoic acid (C10:0), have gained attention in recent years for their potential direct inhibitory action on AMPA receptors, contributing to seizure reduction. Methods: A systematic review was conducted, including articles from January 2000 to January 2025, to explore the potential role of medium-chain triglyceride (MCT) add-on to classic KD and as MCT supplementation in free diets in the management of pediatric drug-resistant epilepsy (DRE). Results: Selected studies show how the action of MCTs, and decanoic acid in particular, is via negative modulation of AMPA receptors, with a positive impact on epileptic seizures. Conclusions: This review discusses the complexities of implementing and sustaining KD in children and presents recent pre-clinical and clinical evidence, including trials where MCTs (often enriched in decanoic acid) serve as an add-on therapy in both ketogenic and free/unrestricted diets. The summarized findings reinforce the therapeutic potential of MCTs, highlighting both the beneficial seizure outcomes and the hurdles that remain to be addressed through future research. Full article

Background: It has been demonstrated that levetiracetam can decrease absence epileptic activity in both human patients and different types of animal models of absence epilepsy, such as the genetically absence epileptic Wistar Albino Glaxo/Rijswijk (WAG/Rij) rat. It was also suggested previously that exogenous ketone supplements (EKSs)-evoked ketosis not only decreases the number of spike-wave discharges (SWDs) but also enhances the anti-absence epileptic effect of pyrimidine nucleoside uridine in WAG/Rij rats. These findings suggest that EKSs may enhance the efficacy of clinically used anti-epileptic drugs, such as levetiracetam. Methods: We investigated the effect of not only levetiracetam (intraperitoneal/i.p. 200 mg/kg) alone and KEKS supplemented food (containing 10% ketone ester/KE and 10% ketone salt/KS in a normal rat chow) alone, but also the combination of levetiracetam and KEKS supplemented food on SWD number and SWD time for 5 days in WAG/Rij rats. For evaluation of SWDs, electroencephalographic (EEG) recordings were performed every day. Moreover, for the measurement of blood glucose and R-beta-hydroxybutyrate (R-βHB) levels, the blood was taken from the tail vein of rats after EEG registration. Results: It was demonstrated that the administration of both levetiracetam alone and KEKS food alone decreased the SWD number and time spent in SWD, compared to control. Moreover, after combined administration of levetiracetam with KEKS food, enhanced anti-absence epileptic effect was observed, compared to levetiracetam alone. Blood R-βHB level significantly increased after administration of both KEKS food alone and KEKS food in combination with levetiracetam. Nevertheless, these treatments did not significantly change the blood glucose levels. Conclusions: We can conclude that EKSs may be able to enhance the anti-epileptic effect of different drugs, and this combined treatment method may represent a promising new approach and effective therapy against epileptic seizures, especially in treatment-resistant patients. Full article

Background and Objectives: Epilepsy is a common neurological disrupt that involves recurring seizures. α-Synuclein (α-Syn), one of the most abundant proteins in the nervous system, is implicated in both neurodegenerative conditions and epilepsy. This study aimed to assess serum α-Syn levels in children with drug-resistant epilepsy (DRE) and explore the relationship with diagnosis and clinical severity. Materials and Methods: This cross-sectional study was carried out at the Pediatric Neurology Outpatient Clinic of Beni-Suef University Hospital. It involved 30 children with DRE, 30 with drug-responsive epilepsy, and 30 age- and sex-matched healthy controls. Serum α-Syn levels were evaluated using enzyme-linked immunosorbent assay (ELISA). Results: Serum α-Syn levels were significantly higher in children with epilepsy compared to healthy controls (p < 0.001), with significantly high levels observed in drug-resistant cases versus drug-responsive ones (p < 0.001). Receiver operating characteristic (ROC) investigation confirmed that α-Syn effectively distinguished epilepsy patients from healthy controls, yielding an area under the curve (AUC) of 0.773. It also successfully differentiated between drug-responsive and drug-resistant epilepsy, with an AUC of 0.858. Further analysis revealed significant positive correlations between serum α-Syn levels and the frequency of hospitalizations due to seizures, the number of anti-epileptic drugs (AEDs) prescribed, and monthly seizure frequency (p = 0.018, 0.009, and <0.001, respectively). In contrast, α-Syn levels were negatively associated with the time since the last seizure and the age at seizure onset (p = 0.001 and 0.016, respectively). Conclusions: Serum α-Syn levels are elevated in epilepsy patients, particularly those with drug-resistant epilepsy, suggesting its potential role as a biomarker for disease severity and treatment resistance. Full article

Background/Objectives: Approximately 1% of people worldwide suffer from epilepsy. The development of safer and more effective antiepileptic medications (AEDs) is still urgently needed because all AEDs have some unwanted side effects and roughly 30% of epileptic patients cannot stop having seizures when taking current AEDs. It should be noted that the derivatives of pyrazolo[3,4-b]pyridine are important core structures in many drug substances. The aim of this study is to synthesize new derivatives of piperazino-substituted pyrazolo[3,4-c]-2,7-naphthyridines and 9,11-dimethylpyrimido[1′,2′:1,5]pyrazolo[3,4-c]-2,7-naphthyridines for the evaluation of their neurotropic activity. Methods: The synthesis of the target compounds was performed starting from 1-amino-3-chloro-2,7-naphthyridines and using well-known methods. The structures of all the synthesized compounds were confirmed by spectroscopic data. Compounds were studied for their potential neurotropic activities (anticonvulsant, sedative, anti-anxiety, and antidepressive), as well as side effects, in 450 white mice of both sexes and 50 male Wistar rats. The anticonvulsant effect of the newly synthesized compounds was investigated by using the following tests: pentylenetetrazole, thiosemicarbazide-induced convulsions, and maximal electroshock. The psychotropic properties of the selected compounds were evaluated by using the following tests: the Open Field test, the Elevated Plus Maze (EPM), the Forced Swimming test, and Rotating Rod Test to study muscle relaxation. For the docking studies, AutoDock 4 (version 4.2.6) was used, as well as the structures of the GABA_A receptor (PDB ID: 4COF), the SERT transporter (PDB ID: 3F3A), and the 5-HT_1A receptor (PDB ID: 3NYA) obtained from the Protein Data Bank. Results: A series of piperazino-substituted pyrazolo[3,4-c]-2,7-naphthyridines (3a–j) and 9,11-dimethylpyrimido[1′,2′:1,5]pyrazolo[3,4-c]-2,7-naphthyridines (4a–j), as well as new heterocyclic systems, i.e., isoxazolo[5,4-c]-2,7-naphthyridines 6a–d, were synthesized and evaluated for their neurotropic activity. The investigation showed that some of these compounds (3a,b,d,f–i and 4a,d,f,i) display high anticonvulsant activity, especially in the test of antagonism with pentylenetetrazol, surpassing the well-known antiepileptic drug ethosuximide. Thus, the most active compounds in the pentylenpotetrazole test are 3h, 3i, and 4i; the ED50 of compound 4i is 23.8, and the therapeutic index is more than 33.6, which is the highest among these three active compounds. On the other hand, they simultaneously exhibit psychotropic (anxiolytic, antidepressant, or sedative) or behavioral depressant) effects. The effective compounds do not cause myorelaxation at the tested doses and have high therapeutic indices. Docking on the most active compounds, i.e., 3h, 3i, and 4i, is in agreement with the experimental results. Conclusions: The studies reveled that some of these compounds (3i, 4a, and 4i) display high anticonvulsant and psychotropic activities. The most active compounds contained methyl and diphenylmethyl groups in the piperazine ring. The docking studies identified compounds 3i, 4i, and 4a as the most potent anticonvulsants, showing strong affinity for GABA_A, 5-HT_1A receptors, and the SERT transporter. Notably, compound 4i formed two hydrogen bonds with Thr176 and Arg180 on GABA_A and exhibited a binding energy (−8.81 kcal/mol) comparable to that of diazepam (−8.90 kcal/mol). It also showed the strongest binding to SERT (−7.28 kcal/mol), stabilized by interactions with Gly439, Ile441, and Arg11. Furthermore, 4i displayed the best docking score with 5-HT_1A (−9.10 kcal/mol) due to multiple hydrogen bonds and hydrophobic interactions, supporting its potential as a dual-acting agent targeting both SERT and 5-HT_1A. Full article

Objective: Focal epilepsy is the most frequent type of epilepsy in childhood, particularly after the first year of life. This study aims to analyze the clinical aspects, electrophysiological and neuroimaging findings, and genetic predispositions in pediatric focal epilepsy. Specifically, we investigate the association between these parameters and evaluate their impact on therapeutic decisions. Methods: This is a retrospective study, in which we enrolled 39 patients currently receiving follow-up in our unit, 20 male and 19 female. Using the Chi-squared test, we compared them considering several genetic traits, pre/peri/postnatal risk factors, family history, clinical and instrumental features, and treatments. Differences are considered significant with a p value < 0.005. Results: Our findings highlight the multifactorial nature of focal epilepsy, with a combination of genetic and environmental contributions. EEG demonstrated the highest sensitivity among diagnostic tools, being non-significant in only 12.8% of cases, while MRI (p < 0.001), CT (p < 0.04), and brain ultrasound had lower detection rates. MRI findings were significant in 43.6% of patients, predominantly showing vascular malformations (35.8%). MRI-negative findings were more common in temporal and occipital epilepsy, whereas MRI-positive results were observed in 100% of frontal seizures. Importantly, some MRI-negative cases may still be lesional, particularly in temporal lobe epilepsy, where focal cortical dysplasia could be present but undetected with standard imaging. Valproic acid remains the most commonly used anti-seizure medication, and, despite guideline recommendations, it was still prescribed as a first-line treatment in 34.3% of cases and is being used in 23.5% of female patients, raising concerns about its appropriateness. Conclusions: This study highlights the role of genetic and environmental risk factors in pediatric focal epilepsy. EEG showed superior diagnostic sensitivity over MRI, particularly in MRI-negative cases. While high-resolution MRI (3T or 7T) could improve lesion detection, its cost limits accessibility. Valproate was the most prescribed drug, despite its recommended use in generalized epilepsy, emphasizing the need for improved adherence to treatment guidelines. Together with other studies, these findings can contribute to optimizing diagnostic and therapeutic strategies for pediatric focal epilepsy. Full article

Sturge–Weber Syndrome (SWS) is a rare neurocutaneous disorder caused by a somatic nonsynonymous mosaic mutation most commonly in the GNAQ gene (G protein guanine Nucleotide-binding protein Alpha subunit q). SWS is characterized by capillary-venous malformations in the brain and eyes and a characteristic facial port wine (PW) birthmark (previously called port wine stain/PWS) in the head/neck region. Clinical manifestations vary and include epilepsy, stroke-like episodes, migraine headaches, cognitive delays, glaucoma, ocular vascular anomalies, heterochromia of the iris, visual field defects, and endocrine disorders like growth hormone deficiency or central hypothyroidism. The pathognomonic findings seen in neuroimaging with magnetic resonance imaging (MRI) include the presence of unilateral intracranial leptomeningeal angiomatosis, typically ipsilateral to the facial birthmark. SWS does not currently have a definitive cure, and management strategies focus on symptomatic management such as anti-seizure medications, limited surgical resection of the epileptogenic tissue or hemispherectomy for cases of drug-resistant epilepsy (DRE), selective photo-thermolysis of the PWS using a pulsed dye laser, and the medical and/or surgical management of glaucoma. In addition to these symptomatic treatments, the use of preventive, modifying, or stabilizing treatments like low-dose aspirin in reducing the frequency and severity of seizures and stroke-like events and the use of newer therapies like cannabidiols and mTOR inhibitors are being reviewed and have shown promising early results. This comprehensive narrative review summarizes the current literature on clinical management strategies, ongoing research studies, and future directions in the diagnosis and management of SWS. Full article

Drug-resistant epilepsy (DRE) affects 20–30% of patients with epilepsy who fail to achieve seizure control with antiseizure medications, posing a significant therapeutic challenge. In this narrative review, we examine the clinical efficacy and safety of the classic ketogenic diet (cKD) and its variants, including the modified Atkins diet (MAD), medium-chain triglyceride diet (MCTD), and low glycemic index treatment (LGIT), in patients with genetically confirmed drug-resistant epilepsy. These diets induce a metabolic shift from glucose to ketones, enhance mitochondrial function, modulate neurotransmitter balance, and exert anti-inflammatory effects. However, genetic factors strongly influence the efficacy and safety of the cKD, with absolute indications including glucose transporter type 1 deficiency syndrome (GLUT1DS) and pyruvate dehydrogenase complex deficiency (PDCD). Preferred adjunctive applications of the KD include genetic epilepsies, such as SCN1A-related Dravet syndrome, TSC1/TSC2-related tuberous sclerosis complex, and UBE3A-related Angelman syndrome. However, because of the risk of metabolic decompensation, the cKD is contraindicated in patients with pathogenic variants of pyruvate carboxylase and SLC22A5. Recent advancements in precision medicine suggest that genetic and microbiome profiling may refine patient selection and optimize KD-based dietary interventions. Genome-wide association studies and multiomics approaches have identified key metabolic pathways influencing the response to the cKD, and these pave the way for individualized treatment strategies. Future research should integrate genomic, metabolomic, and microbiome data to develop biomarker-driven dietary protocols with improved efficacy and safety. As dietary therapies continue to evolve, a personalized medical approach is essential to maximize their clinical utility for genetic epilepsy and refractory epilepsy syndromes. Full article

Background: Epilepsy is the most common chronic neurological condition in children, with a prevalence of 0.3% in Jordan. It significantly impacts patients’ and their families’ lives, shaped by cultural and socioeconomic factors. This study assessed the perceived impact of epilepsy on children and their families in Jordan. Method: This was a hospital-based, cross-sectional study recruiting 184 children under 18 years with epilepsy using a custom-designed questionnaire. Results: Nearly half of the patients experienced epilepsy onset before age three, and seizures were controlled in 73%. Around 60% of parents were satisfied with their understanding of the disease. Male gender and older age at diagnosis were associated with greater perceived severity, while older age at diagnosis correlated with a negative impact on caregivers’ earning potential. Patients with more anti-epileptic drugs reported more social constraints and older children expressed concerns about medication and seizure-related injuries. Cultural factors, such as family size and history, were associated with higher caregiver burden, emphasizing the importance of culturally sensitive assessment tools. Conclusions: Effective seizure control and quality of life improvements should be priorities in managing epilepsy in children. Cultural factors are strongly linked to caregiver burden, emphasizing the need for culturally sensitive assessment tools for enhancing support and care outcomes across diverse populations. Full article

Background: Combination medication strategies often involve complex interactions, making determining the appropriate pharmacodynamic component ratios challenging. Methods: This study established a time–dose relationship model through the compartment model, deriving the in vivo drug quantity ratios corresponding to the blood concentrations of the pharmacodynamic components. A neural network was then employed to establish a dose–effect relationship model between the blood concentrations of the pharmacodynamic components and the overall body response. Utilizing the feedback adjustment mechanism of neural networks continuously adjusts the network to achieve the desired drug efficacy, thereby deriving the corresponding dose ratio of the pharmacodynamic components. Empirical studies were conducted on combining Cynanchum otophyllum saponins M₁ and M₂ with phenobarbital for epilepsy treatment, as well as the anti-ischemic stroke activity of the prototype and metabolites of Erigeron breviscapus. Results: After adjusting the efficacy, the model recalculated the new ratio proportions for each combination, validated by the reduced Combination Index (CI). Conclusions: This model provides a new approach to combination medication strategies. Full article

Background/Objectives: Despite the availability of antiepileptic drugs (AEDs) that can manage seizures, they often come with cognitive side effects. Furthermore, the role of oxidative stress and neuroinflammatory responses in epilepsy and the limitations of current AEDs necessitate exploring alternative therapeutic options. Medicinal plants, e.g., Lavandula dentata L., are rich in phenolic compounds and may provide neuroprotective and anti-inflammatory benefits. However, limited research evaluates their effectiveness in modulating neuroinflammation and histopathological changes in epilepsy models. Therefore, the current study hypothesized that treating Lavandula dentata L. extract or essential oils may reduce neuroinflammatory responses and mitigate histopathological changes in the brain, providing a natural alternative or adjunct therapy for epilepsy management. Methods: Five groups of male Wistar rats were used: control, pilocarpine-treated epileptic, valproic acid (VPA-treated epileptic), L. dentata extract, and essential oils. Numerous electrolyte levels, monoamine levels, neurotransmitter levels, and the mRNA expression of specific gate channel subtypes were evaluated in homogenate brain tissue. Additionally, histological changes in various brain regions were investigated. Results: The investigation revealed that the extract and essential oils obtained from L. dentata L. exhibited the ability to improve the modulation of electrolytes and ions across voltage- and ligand-gated ion channels. Furthermore, it was revealed that they could decrease neuronal excitability by facilitating repolarization. Moreover, L. dentata’s oil and ethanol extract re-balances T-reg/Th-17 cytokines, restoring the pro/anti-inflammatory cytokines and Treg markers, e.g., FOXP3 and CTLA-4, to their normal level. Conclusions: The present work confirms that the extract and essential oils of L. dentata L. have different activities to ameliorate the progression of histopathological alterations. Therefore, when used in conjunction with other AEDs, the extract and essential oils of L. dentata can slow the progression of epileptogenesis. Full article

Objective: The objective was to develop and validate a multidimensional scale that measures adherence levels to antiseizure medications and detects patients’ reasons for non-adherence. Methods: A new scale was developed, namely the “Adherence Scale for Anti-Seizure Medication(s)-10 items [ASASM-10]”. It consists of ten statements that cover different causes of non-adherence to antiseizure medications. The domain selection was based on a comprehensive literature review. Guidelines for constructing an effective scale were followed to write the statements. Three independent expert judges assessed the content validity of the scale. The reliability of ASASM-10 was tested using three methods: internal consistency measurement (Cronbach’s alpha), Intraclass Correlation Coefficient [ICC] with a 95% Confidence Interval [95% CI], and test–retest reliability. Validity was tested using Principal Component Analysis [PCA] and a correlation coefficient. PCA was applied after measuring sampling adequacy via Kaiser–Meyer–Olkin [KMO] and Bartlett’s sphericity. The Medication Adherence Rating Scale [MARS] was selected as a pre-existing self-report method for validation of this new scale. Results: A total of 162 patients completed the study scales (mean ages ± SD: 34.07 ± 10.406 years). The scale demonstrated a good internal consistency with Cronbach’s alpha coefficient of 0.80 and exceeded the required value (i.e., 0.70) for the reliability of new scales. ASASM-10 showed a satisfactory ICC (95% CI) of 0.799 (0.718–0.857), p-value < 0.001. The test–retest reliability demonstrated a good correlation of ρ = 0.648, p-value < 0.001. The construct validity assessed by PCA retained four components as their eigenvalues exceeded one. The correlation coefficient demonstrated a positive moderate correlation between ASASM-10 and MARS (ρ = 0.283), p-value < 0.001. Conclusions: The present analyses provided evidence that ASASM-10 is a reliable and valid scale for evaluating patients’ adherence to antiseizure medications. It is the first available scale for assessing medication adherence in patients with epilepsy that can be utilized in clinical practice and research settings. Full article

Cannabidiol, the primary non-psychoactive phytocannabinoid found in cannabis, has generated significant research interest due to its potential for biological effects, such as anti-inflammatory, analgesic, immunomodulatory, and anticonvulsant properties. Several studies have demonstrated the potential of CBD to alter inflammatory cytokines; however, data on CBD’s effects on cell viability and pro-inflammatory cytokines in target animals, such as dogs, are limited. Therefore, in this study, we investigated the effects of CBD on the cell viability and modulation of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α), in canine PBMCs stimulated with LPS. To evaluate the effect of CBD on neuroinflammation in epilepsy pathology, an independent study of five refractory epileptic dogs co-treated with CBD for 30 days was conducted. The current findings revealed that CBD concentrations of 16 µg/mL had a statistically significant effect on the viability of canine PBMCs with a calculated IC₅₀ of 15.54 µg/mL. The effect of CBD on inflammatory cytokines in LPS-stimulated PBMCs tended to be dose-dependent, with CBD concentrations of 5–30 μg/mL resulting in decreased production of the tested pro-inflammatory cytokines. Considering the effect of CBD on cytokine production by PBMCs from epileptic dogs, CBD has the potential to modulate immune responses and provide benefits when used in combination with antiepileptic drugs. The findings provided evidence of CBD cytotoxicity and its effect on the alteration of pro-inflammatory cytokines in canine PBMCs. Full article

Pediatric genetic epilepsies, such as CDKL5 Deficiency Disorder (CDD), are severely debilitating, with early-onset seizures occurring more than ten times daily in extreme cases. Existing antiseizure drugs frequently prove ineffective, which significantly impacts child development and diminishes the quality of life for patients and caregivers. The relaxation of cannabis legislation has increased research into potential therapeutic properties of phytocannabinoids such as cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). CBD’s antiseizure properties have shown promise, particularly in treating drug-resistant genetic epilepsies associated with Lennox–Gastaut syndrome (LGS), Dravet syndrome (DS), and Tuberous Sclerosis Complex (TSC). However, specific research on CDD remains limited. Much of the current evidence relies on anecdotal reports of artisanal products lacking accurate data on cannabinoid composition. Utilizing model systems like patient-derived iPSC neurons and brain organoids allows precise dosing and comprehensive exploration of cannabinoids’ pharmacodynamics. This review explores the potential of CBD, THC, and other trace cannabinoids in treating CDD and focusing on clinical trials and preclinical models to elucidate the cannabinoid’s potential mechanisms of action in disrupted CDD pathways and strengthen the case for further research into their potential as anti-epileptic drugs for CDD. This review offers an updated perspective on cannabinoid’s therapeutic potential for CDD. Full article

Background/Objectives: Although the involvement of progressive brain alterations in epilepsy was recently suggested, individual patients’ trajectories of white matter (WM) disruption are not known. Methods: We investigated the disease progression patterns of WM damage and its associations with clinical metrics. We examined the cross-sectional diffusion tensor imaging (DTI) data of 155 patients with unilateral temporal lobe epilepsy (TLE) and 270 age/gender-matched healthy controls, and we then calculated the average fractional anisotropy (FA) values within 20 WM tracts of the whole brain. We used the Subtype and Stage Inference (SuStaIn) program to detect the progression trajectory of FA changes and investigated its association with clinical parameters including onset age, disease duration, drug-responsiveness, and the number of anti-seizure medications (ASMs). Results: The SuStaIn algorithm identified a single subtype model in which the initial damage occurs in the ipsilateral uncinate fasciculus (UF), followed by damage in the forceps, superior longitudinal fasciculus (SLF), and anterior thalamic radiation (ATR). This pattern was replicated when analyzing TLE with hippocampal sclerosis (n = 50) and TLE with no lesions (n = 105) separately. Further-progressed stages were associated with longer disease duration (p < 0.001) and a greater number of ASMs (p = 0.001). Conclusions: the disease progression model based on WM tracts may be useful as a novel individual-level biomarker. Full article