Tonic-clonic Research Articles

Canine distemper with myoclonus and tonic-clonic seizures in a domestic cat (Felis catus) in Kerala, India

Canine distemper with myoclonus and tonic-clonic seizures in a domestic cat (Felis catus) in Kerala, India

Ultradian rhythms in accelerometric and autonomic data vary based on seizure occurrence in paediatric epilepsy patients.

Ultradian rhythms are physiological oscillations that resonate with period lengths shorter than 24 hours. This study examined the expression of ultradian rhythms in patients with epilepsy, a disease defined by an enduring seizure risk that may vary cyclically. Using a wearable device, we recorded heart rate, body temperature, electrodermal activity and limb accelerometry in patients admitted to the paediatric epilepsy monitoring unit. In our case-control design, we included recordings from 29 patients with tonic-clonic seizures and 29 non-seizing controls. We spectrally decomposed each signal to identify cycle lengths of interest and compared average spectral power- and period-related markers between groups. Additionally, we related seizure occurrence to the phase of ultradian rhythm in patients with recorded seizures. We observed prominent 2- and 4-hour-long ultradian rhythms of accelerometry, as well as 4-hour-long oscillations in heart rate. Patients with seizures displayed a higher peak power in the 2-hour accelerometry rhythm (U = 287, P = 0.038) and a period-lengthened 4-hour heart rate rhythm (U = 291.5, P = 0.037). Those that seized also displayed greater mean rhythmic electrodermal activity (U = 261; P = 0.013). Most seizures occurred during the falling-to-trough quarter phase of accelerometric rhythms (13 out of 27, χ2 = 8.41, P = 0.038). Fluctuations in seizure risk or the occurrence of seizures may interrelate with ultradian rhythms of movement and autonomic function. Longitudinal assessments of ultradian patterns in larger patient samples may enable us to understand how such rhythms may improve the temporal precision of seizure forecasting models.

Clinical features and genetic analysis of five children with epilepsies due to variants of SCN8A gene

To explore the clinical and genetic characteristics of five children with epilepsies due to variants of SCN8A gene. Clinical data of five children (four males and one female) admitted to Linyi People's Hospital due to hereditary epilepsies between August 2015 and August 2022 were collected. Whole exome sequencing was carried out for these children, and candidate variants were verified by Sanger sequencing. All of the five children were found to harbor variants of the SCN8A gene. Case 1, who had benign familial infantile epilepsy, inherited a known pathogenic c.4840A>G variant from his father with similar symptoms. Cases 2 to 4 had presented with intermediate epilepsy. Among these, case 2 has harbored a de novo c.3967G>A variant which was rated as pathogenic (PS1+PS2+PM1+PM2_Supporting+PP3) based on the guidelines from the American College of Medical Genetics and Genomics. Cases 3 and 4 were found to respectively harbor a de novo c.415A>T and a c.4697C>T variant, which were both rated as likely pathogenic (PS2+PM1+PM2_Supporting+PP3). Case 5, who had early-onset infantile epileptic encephalopathy transformed into Lennox Gastaut-like syndrome, has harbored a de novo c.5615G>A variant, which was known to be pathogenic. The children had their age of onset ranging from 2 to 14 months, and all had focal seizures and generalized tonic clonic seizures. Four children (cases 1, 2, 3 and 5) had cluster seizures, four (cases 1 to 4) had become seizure-free after single or dual treatment and showed normal growth and development, whilst case 5 was drug-resistant and showed severe developmental retardation. The five children had new features such as cluster seizures, occasional benign seizures in adulthood, and intermediate epilepsy which are prone to relapse after discontinuation of medication, which may be attributed to the pathogenic variants of the SCN8A gene.

Von der Fallsucht zur modernen Epilepsiechirurgie – Entwicklung der Epilepsieversorgung in Norwegen

AbstractThroughout history, epilepsy has been considered a mysterious and unexplained illness. People with tonic–clonic seizures were believed to be possessed by evil spirits, and in Norway, as in many other countries, these people were stigmatized, discriminated against, and often excluded from society. Only in the second part of the 19th century did a shift take place from a magical to a scientific view of the disease. Nevertheless, until the middle of the 20th century epilepsy was confused with psychiatric illness in Norway. Although people with epilepsy today are not stigmatized to the same degree as before, we still have some way to go.

Epilepsy care and outcome in low- and middle-income countries: A scoping review.

Epilepsy is a common neurological condition in low- and middle-income countries (LMICs). This study aims to systematically review, analyze, evaluate, and synthesize information on the current state of medical and surgical management and outcomes of epilepsy in LMICs. Systematic searches were conducted on MEDLINE, EMBASE, World Health Organization Global Index Medicus, African Journals Online, WOS, and Scopus, covering the period from the inception of the databases to August 18th, 2021, focusing on studies reporting management and outcomes of epilepsy in LMICs. A total of 2298 unique studies were identified, of which, 48 were included (38035 cases). The mean age was 20.1 ± 19.26 years with a male predominance in 60.92% of cases. The type of seizure commonly reported in most of the studies was absence seizures (n = 8302, 21.82%); partial focal seizure (n = 3891, 10.23%); and generalized tonic-clonic seizures (n = 3545, 9.32%) which were the next most common types of seizures. Mesiotemporal epilepsy was less frequently reported (n = 87, 0.22%). Electroencephalogram was commonly used (n = 2516, 6.61%), followed by computed tomography scan (n = 1028, 2.70%), magnetic resonance imaging (n = 638, 1.67%), and video telemetry (n = 484, 1.27%) in the care of patients with seizures. Primary epilepsy was recorded in 582 patients (1.53%) whereas secondary epilepsy was present in 333 patients (0.87%). Carbamazepine was the most used anti-epileptic drug (n = 2121, 5.57%). Surgical treatment was required for 465 (1.22%) patients. In LMICs, epilepsy is underreported. There is still a lack of adequate tools for the diagnosis of primary or secondary epilepsy as well as adequate access to medical management of those reported.

Primary hypoaldosteronism in a dog with concurrent suspected chronic hepatitis

A 3-year-old female spayed English Cocker Spaniel presented with a 2-month history of lethargy. The owner reported a single tonic-clonic seizure 7 months before presentation and intermittent mild gastrointestinal signs for the past 18 months. Initial investigations revealed hyponatraemia, hyperkalaemia and increased levels of liver enzymes. An adrenocorticotropic hormone stimulation test excluded hypocortisolism. The gastrointestinal signs resolved following a dietary change, suggesting that chronic enteropathy and most primary and secondary causes of hepatic disease were excluded, leaving idiopathic chronic hepatitis as the most likely cause of increased levels of liver enzymes. Liver parameters reduced to levels just above reference range after immunosuppressive doses of prednisolone. Aldosterone levels pre- and post-adrenocorticotrophic hormone stimulation were <20 pmol/litre, consistent with mineralocorticoid deficiency. The mineralocorticoid deficiency was treated with desoxycorticosterone pivalate at 1–1.3 mg/kg subcutaneously every 48–87 days, which resulted in immediate and complete resolution of the clinical signs and electrolyte imbalance. Given the dog's signalment and results from clinical investigations, the isolated hypoaldosteronism is speculated to be caused by immune-mediated adrenal gland destruction. Isolated hypoaldosteronism should be considered a differential diagnosis for hyponatraemia in dogs, when an adrenocorticotrophic hormone stimulation test excludes hypocortisolism.

Diagnostic role of serum prolactin level in different kinds of seizure and seizure-like episode in children: A hospital-based study

Background: Serum prolactin level has been previously used in distinguishing epileptic seizure from non-epileptic seizure, as prolactin level usually rises following an epileptic seizure in children. Aims and Objectives: We conducted this study to determine the role of serum prolactin as a surrogate marker of seizure disorder and whether serum prolactin level varies between different types of seizure, febrile seizure, and seizure mimics. Materials and Methods: This cross-sectional comparative study was conducted for 1 year among 113 children between 6 months and 16 years of age of either sex. They were divided into 3 groups (1) epileptic seizure, (2) febrile seizure, and (3) seizure mimics. The blood sample was collected within 1 h of the occurrence of seizure for estimation of serum prolactin level. Each child was investigated and treated according to the protocol. Results: Mean post-ictal prolactin level was found significantly higher in epileptic seizure (29.94±7.97 ng/mL) compared to febrile seizure (10.21±0.94 ng/mL), and seizure mimics (8.73±0.67 ng/mL). Among group 1, serum prolactin levels significantly elevated in children with generalized tonic-clonic seizure (GTCS) (34.18±2.76 ng/mL) and complex partial seizure (CPS) (31.38±1.59 ng/mL) compared to simple partial seizure (SPS) (14.36±2.33 ng/mL). Post-ictal serum prolactin levels remain elevated for a longer duration in GTCS (54.26±5.19 min) and CPS (45.19±1.73 min) compared to children with SPS (26.76±2.33 min). Conclusion: Estimation of serum prolactin level within 1 h after a seizure can be used for screening purposes to distinguish between epileptic and non-epileptic seizures. A high prolactin level is suggestive of GTCS or CPS whereas a low level is indicative of SPS, febrile convulsion, or seizure mimics with a prolactin cutoff taken 24 ng/mL in our study.

Macroscale intrinsic dynamics are associated with microcircuit function in focal and generalized epilepsies

Epilepsies are a group of neurological disorders characterized by abnormal spontaneous brain activity, involving multiscale changes in brain functional organizations. However, it is not clear to what extent the epilepsy-related perturbations of spontaneous brain activity affect macroscale intrinsic dynamics and microcircuit organizations, that supports their pathological relevance. We collect a sample of patients with temporal lobe epilepsy (TLE) and genetic generalized epilepsy with tonic-clonic seizure (GTCS), as well as healthy controls. We extract massive temporal features of fMRI BOLD time-series to characterize macroscale intrinsic dynamics, and simulate microcircuit neuronal dynamics used a large-scale biological model. Here we show whether macroscale intrinsic dynamics and microcircuit dysfunction are differed in epilepsies, and how these changes are linked. Differences in macroscale gradient of time-series features are prominent in the primary network and default mode network in TLE and GTCS. Biophysical simulations indicate reduced recurrent connection within somatomotor microcircuits in both subtypes, and even more reduced in GTCS. We further demonstrate strong spatial correlations between differences in the gradient of macroscale intrinsic dynamics and microcircuit dysfunction in epilepsies. These results emphasize the impact of abnormal neuronal activity on primary network and high-order networks, suggesting a systematic abnormality of brain hierarchical organization.

Rare case in Somalia: Fahr’s syndrome

Introduction and importance: Fahr’s syndrome is primarily familial, autosomal dominant, and genetically diverse. Basal ganglia calcification that is bilaterally symmetrical is a hallmark of this illness. Although the specific origins of this illness are unknown, it may be brought on by problems with calcium metabolism, infections, toxins, hereditary factors, hypoparathyroidism, and pseudohypoparathyroidism. The prevalence of this syndrome is less than 0.5%. Case presentation: An 11-year-old female comes to the Emergency Department with her parents complaining of high-grade fever and convulsions for 1 week. Convulsion, which is a generalized tonic–clonic seizure, duration was ~5 min and associated with urinary incontinence and biting tongue. On examination, the patient was confused and irritable. Vital signs were normal; there is weakness in the right arm and right leg, associated with irregular movement. There was alternation in her level of consciousness, slurring of speech, and psychiatric symptoms. Another aspect of the neurological examination and systems was normal, and there was no meningeal irritation. Clinical discussion: The pathogenesis of Fahr’s syndrome is not completely known. The calcification is caused by flaws in the transport of radioactive particles and tissue damage caused by free radicals. Bilateral calcification found on a computed tomography (CT) scan of the brain, autosomal dominant inheritance, the absence of any infection, drugs, or toxins, the absence of mitochondrial dysfunction, and the presence of progressive neurological dysfunction is the clinical criteria for diagnosing Fahr’s syndrome. Conclusion: Basal ganglia calcification that is bilaterally symmetrical is a hallmark of Fahr’s syndrome. CT scans are the gold standard for conclusively diagnosing Fahr’s syndrome.

Temporary atrial fibrillation associated with generalized tonic clonic seizures in a not known epileptic Caucasian male: two unrelated episodes or a temporary autonomic neurocardiac dysfunction caused by the seizure? A case report and a review of literature

Temporary atrial fibrillation associated with generalized tonic clonic seizures in a not known epileptic Caucasian male: two unrelated episodes or a temporary autonomic neurocardiac dysfunction caused by the seizure? A case report and a review of literature

A PROSPECTIVE OBSERVATIONAL STUDY ON PRESCRIPTION ANALYSIS OF ANTIEPILEPTIC DRUGS AT TERTIARY CARE HOSPITAL

The present study was aimed to analyze the prescription patterns of various uses of antiepileptic drugs (AEDs)in the strategic treatment of different types of epilepsy in a tertiary care hospital in the northern Telangana of India. A total of 157 patients were included in this study and patients with epilepsy of specific group are included. The demographic data shows a greater number of males 99 (63%) and female 58 (37%). The majority of patients were 44 (28%) belonged to 20-30 years of age group, 43 (27%) patients belonged to 30-40 years of age group. Generalized tonic clonic seizures (GTCS) were the most commonly diagnosed epilepsy (46%) and monotherapy (75%) were prescribed. Levetiracetam was the most common monotherapy (54%). Levetiracetam with clobazam was commonly prescribed two drug combinations (6%). Among polytherapy levetiracetam with sodium valproate and clobazam (2%). Levetiracetam was commonest prescribed AED as monotherapy and in combinational as well as polytherapy. The study concluded that educating patients regarding the antiepileptic drugs is necessary to avoid the medications related problems which helps in improving patient for better care.

Focal electroclinical features in generalized tonic-clonic seizures: Decision flowchart for a diagnostic challenge.

Bilateral tonic-clonic seizures with focal semiology or focal interictal electroencephalography (EEG) can occur in both focal and generalized epilepsy types, leading to diagnostic errors and inappropriate therapy. We investigated the prevalence and prognostic values of focal features in patients with idiopathic generalized epilepsy (IGE), and we propose a decision flowchart to distinguish between focal and generalized epilepsy in patients with bilateral tonic-clonic seizures and focal EEG or semiology. We retrospectively analyzed video-EEG recordings of 101 bilateral tonic-clonic seizures from 60 patients (18 with IGE, 42 with focal epilepsy). Diagnosis and therapeutic response were extracted after ≥1-year follow-up. The decision flowchart was based on previous observations and assessed concordance between interictal and ictal EEG. Focal semiology in IGE was observed in 75% of seizures and 77.8% of patients, most often corresponding to forced head version (66.7%). In patients with multiple seizures, direction of head version was consistent across seizures. Focal interictal epileptiform discharges (IEDs) were observed in 61.1% of patients with IGE, whereas focal ictal EEG onset only occurred in 13% of seizures and 16.7% of patients. However, later during the seizures, a reproducible pattern of 7-Hz lateralized ictal rhythm was observed in 56% of seizures, associated with contralateral head version. We did not find correlation between presence of focal features and therapeutic response in IGE patients. Our decision flowchart distinguished between focal and generalized epilepsy in patients with bilateral tonic-clonic seizures and focal features with an accuracy of 96.6%. Focal semiology associated with bilateral tonic-clonic seizures and focal IEDs are common features in patients with IGE, but focal ictal EEG onset is rare. None of these focal findings appears to influence therapeutic response. By assessing the concordance between interictal and ictal EEG findings, one can accurately distinguish between focal and generalized epilepsies.

Unverricht-Lundborg Disease: Tackling the Challenges of a Complex Clinical Picture


 Unverricht-Lundborg disease (ULD), also called progressive myoclonic epilepsy type 1, is characterized by stimulus-induced myoclonus and seizures without major progressive cognitive deficit, usually presenting during late childhood and early adolescence. It is an autosomal recessive disease, and, so far, only pathogenic variants in the gene encoding cystatin B (CSTB) have been described. We report the case of a 9-year-old boy who presented with generalized tonic-clonic seizures and developed paroxysmal myoclonic events over several years. The patient was started on antiseizure medication, but disease progression resulted in several changes to the therapeutic scheme, with highly variable clinical responses. The genetic study detected the pathogenic variant c.67-1G>C p.(?) in heterozygosity in the CSTB gene, after having identified the typical dodecameric expansion in the other allele, confirming the diagnosis of ULD.

Hypophosphatemia as Potential Biomarker of Tonic-Clonic Seizures in the Emergency Room


 Transient alteration of consciousness is common in the emergency department. Tonic-clonic seizures (TCS) are a frequent presumptive diagnosis, but there is no reliable postictal biological marker. We report the case of a 19-year-old man with two episodes of generalized TCS, four months apart. Both were associated with moderate-to-severe hypophosphatemia (0.9 mg/dL, reference range 3.0-4.5 mg/dL). The investigation of phospho-calcium metabolism was negative, and phosphorus levels normalized between the two episodes and after the second TCS. The diagnosis of epilepsy was made based on the occurrence of two unprovoked TCS 24 hours apart.
 The patient started antiseizure medication after the second TCS and has remained free of seizures (20 months of follow-up). Routine EEG with sleep showed slow temporal activity without epileptiform activity, and the brain magnetic resonance imaging was normal. Changes in serum phosphorus are not usually associated with acute symptomatic seizures. In this case, hypophosphatemia might have been a marker of TC.

Demographic and clinical characteristics, seizure disorders, and antiepileptic drug usage in different types of corpus callosum disorders: a comparative study in children

BackgroundThis study aimed to investigate the demographic and clinical characteristics, types of seizure disorders, and antiepileptic drug usage among individuals with different types of corpus callosum disorders.MethodsA total of 73 individuals were included in the study and divided into three groups based on the type of corpus callosum abnormality: hypoplasia (H), agenesis (A), and dysgenesis (D). Demographic data, including gender and preterm birth, as well as clinical characteristics such as seizure disorders, attention deficit hyperactivity disorder (ADHD), severe developmental delay/intellectual disability, and other brain malformations, were analyzed. The types of seizure disorders and antiepileptic drugs used were also examined.ResultsThe H group had the highest number of participants (n = 47), followed by the A group (n = 11) and the D group (n = 15). The A group had the highest percentage of males and preterm births, while the D group had the highest percentage of seizure disorders, other brain malformations, and severe developmental delay/intellectual disability. The A group also had the highest percentage of ADHD. Focal seizures were observed in all three groups, with the highest proportion in the A group. Focal impaired awareness seizures (FIAS) were present in all groups, with the highest proportion in the D group. Generalized tonic-clonic seizures (GTCS) were observed in all groups, with the highest proportion in the H group. Different types of antiepileptic drugs were used among the groups, with variations in usage rates for each drug.ConclusionThis study provided insights into the demographic and clinical characteristics, seizure disorders, and antiepileptic drug usage among individuals with different types of corpus callosum disorders. Significant differences were found between the groups, indicating the need for tailored management approaches. However, the study has limitations, including a small sample size and a cross-sectional design. Further research with larger sample sizes and longitudinal designs is warranted to validate these findings and explore the relationship between corpus callosum abnormality severity and clinical outcomes.

Molecular and Phenotypic Characterization of the RORB-Related Disorder.

Heterozygous variants in RAR-related orphan receptor B (RORB) have recently been associated with susceptibility to idiopathic generalized epilepsy. However, few reports have been published so far describing pathogenic variants of this gene in patients with epilepsy and intellectual disability (ID). In this study, we aimed to delineate the epilepsy phenotype associated with RORB pathogenic variants and to provide arguments in favor of the pathogenicity of variants. Through an international collaboration, we analyzed seizure characteristics, EEG data, and genotypes of a cohort of patients with heterozygous variants in RORB. To gain insight into disease mechanisms, we performed ex vivo cortical electroporation in mouse embryos of 5 selected variants, 2 truncating and 3 missense, and evaluated on expression and quantified changes in axonal morphology. We identified 35 patients (17 male, median age 10 years, range 2.5-23 years) carrying 32 different heterozygous variants in RORB, including 28 single-nucleotide variants or small insertions/deletions (12 missense, 12 frameshift or nonsense, 2 splice-site variants, and 2 in-frame deletions), and 4 microdeletions; de novo in 18 patients and inherited in 10. Seizures were reported in 31/35 (89%) patients, with a median age at onset of 3 years (range 4 months-12 years). Absence seizures occurred in 25 patients with epilepsy (81%). Nineteen patients experienced a single seizure type: absences, myoclonic absences, or absences with eyelid myoclonia and focal seizures. Nine patients had absence seizures combined with other generalized seizure types. One patient had presented with absences associated with photosensitive occipital seizures. Three other patients had generalized tonic-clonic seizures without absences. ID of variable degree was observed in 85% of the patients. Expression studies in cultured neurons showed shorter axons for the 5 tested variants, both truncating and missense variants, supporting an impaired protein function. In most patients, the phenotype of the RORB-related disorder associates absence seizures with mild-to-moderate ID. In silico and in vitro evaluation of the variants in our cohort, including axonal morphogenetic experiments in cultured neurons, supports their pathogenicity, showing a hypomorphic effect.

Incidence of sudden death in epilepsy (SUDEP): update and limitations

Sudden unexpected death in epilepsy (SUDEP) is in most cases probably due to afatal complication of tonic-clonic seizures and plays asignificant role in the premature mortality of individuals with epilepsy. The reported risks of SUDEP vary considerably depending on the study population, so that an up-dated systematic review of SUDEP incidence including most recent studies is required to improve the estimated SUDEP risk and the counseling of individuals with epilepsy. To provide an overview of the current research landscape concerning SUDEP incidence across different patient populations and discuss potential conclusions and existing limitations. Asystematic literature review on SUDEP incidence was conducted in MEDLINE and EMBASE, supplemented by amanual search in June 2023. Out of atotal of 3324 publications, 50were reviewed for this study. The analyzed studies showed significant heterogeneity concerning cohorts, study design and data sources. Studies conducted without specific criteria and relying on comprehensive registers indicated an incidence of 0.78-1.2 per 1000 patient-years. Research providing incidences across various age groups predominantly show an increase with age, peaking in middle age. Due to varying methods of data collection and incidence calculation, comparing between studies is challenging. The association with age might be due to an underrepresentation of children, adolescents and patients over 60years. Considering all age groups and types of epilepsy it is estimated that about 1 in 1000 individuals with epilepsy dies of SUDEP annually. With an assumed epilepsy prevalence of 0.6% in Germany, this could lead to more than one SUDEP case daily. Standardization of research methods is essential to gain more profound insights.

Posterior Reversible Encephalopathy Syndrome in an Elderly Patient with Acute Myeloid Leukemia

Posterior Reversible Encephalopathy Syndrome (PRES) is a neurological condition presenting with encephalopathy, seizures and headache with concurrent edema in the posterior cerebral circulation. While hypertension is the most common associated, PRES has been reported in patients receiving chemotherapy for various cancers such as AML. We report a 61-year-old female with history of hypertension who presented with sepsis and a new diagnosis of Acute Myeloid Leukemia (AML). She was started on broad spectrum antibiotics for her sepsis concurrently with Azacitidine and Venetoclax for treatment of sepsis and AML, respectively. Shortly after initiation of her AML treatment, patient became encephalopathic and experienced tonic clonic seizures. She had clinical and imaging features consistent with PRES. PRES has been reported as rare complication of chemotherapy of various cancer generally, and AML specifically. It is important to recognize it in a timely manner to prevent further damage. This case report highlights this important complication of the chemotherapy initiation in AML especially in elderly patient who presented with sepsis.

Effect of alpelisib, a selective phosphatidylinositol-3-kinase inhibitor, on seizure development in a rat pentylenetetrazole model

Epilepsy is a neurological disease that results from an abnormality in the brain's activity. Phosphatidylinositol-3-kinase (PI3K) signaling pathway has played a crucial role in epilepsy pathogenesis. Alpelisib (ALP) is a selective inhibitor of PI3K. We examined the ability of ALP to treat pentylenetetrazole (PTZ)-induced convulsions in a rat model. Male Wistar rats (200-250 g, 8 weeks old) were injected intraperitoneally (IP) with ALP at different doses of 15 and 30 mg/kg, or vehicle 30 min prior to PTZ (70 mg/kg, IP) treatment. Racine's scale was used to assess behavioral seizures. The results showed that pretreatment with ALP decreased the seizure stages according to the Racine scale, significantly prolonged the duration of general tonic-clonic seizure (GTCS) and reduced the number of myoclonic jerks (P < 0.05). In conclusion, based on results it was shown that PI3K antagonist ALP inhibited PTZ-induced seizure by inhibiting the PI3K signaling pathway via ALP.

Mapping progressive damage epicenters in epilepsy with generalized tonic-clonic seizures by causal structural covariance network density (CaSCNd)

AimsMapping progressive patterns of structural damage in epilepsies with idiopathic and secondarily generalized tonic-clonic seizures with causal structural covariance networks and multiple analysis strategies. MethodsPatients with idiopathic generalized tonic-clonic seizures (IGTCS) (n = 114) and secondarily generalized tonic-clonic seizures (SGTCS) (n = 125) were recruited. Morphometric parameter of gray matter volume was analyzed on structural MRI. Structural covariance network based on granger causality analysis (CaSCN) was performed on the cross-sectional morphometric data sorted by disease durations of patients. Seed-based CaSCN analysis was firstly carried out to map the progressive and influential patterns of damage to thalamus-related structures. A novel technique for voxel-based CaSCN density (CaSCNd) analysis was further proposed, enabling for identifying the epicenter of structural brain damage during the disease process. ResultsThe thalamus-associated CaSCNs demonstrated different patterns of progressive damage in two types of generalized tonic-clonic seizures. In IGTCS, the structural damage was predominantly driven from the thalamus, and expanded to the cortex, while in SGTCS, the damage was predominantly driven from the cortex, and expanded to the thalamus through the basal ganglia. CaSCNd analysis revealed that the IGTCS had an out-effect epicenter in the thalamus, whereas the SGTCS had equipotent in- and out-effects in the thalamus, cortex, and basal ganglia. ConclusionCaSCN revealed distinct damage patterns in the two types of GTCS, featuring with measurement of structural brain damage from the accumulating effect over a relatively long time period. Our work provided evidence for understanding network impairment mechanism underlying different GTCSs.