Predictors of etiology and drug resistance in children with new‐onset focal seizures

Background Children with epilepsy with onset above five years encompass distinct epidemiological and clinical characteristics that may have specific risk factors for resistance to antiseizure medications (ASMs). Studies on this age group are limited. Purpose To identify risk factors for drug resistance in children with epilepsy with the age of onset above five years. Methods A case-control study was conducted on children with epilepsy with the age of onset above five years visiting the Pediatric Neurology Clinic of Cipto Mangunkusumo and Mohammad Hoesin Hospital between September 2015 and August 2016. Cases consisted of drug-resistant children while control consisted of drug-responsive children according to 2010 ILAE classification. Risk factors studied include onset, number of seizures, illness duration before treatment, cause, seizure type, status epilepticus, initial and evolution of EEG, brain imaging, and initial treatment response. Results Thirty-two pairs of children were included in the study. After logistic regression analysis, symptomatic etiology and failure to achieve early response to treatment were found to be associated with drug resistance with adjusted OR of 84.71 (95% CI: 5.18-1359.15) and 72.55 (95% CI: 7.08-743.85), respectively. Conclusion Poor initial response to ASM and symptomatic etiology are independent risk factors for drug resistance in children with epilepsy with the age of onset above five years.

The International League Against Epilepsy (ILAE) report lists three well-defined syndromes of idiopathic focal epilepsies in childhood: benign childhood epilepsy with centrotemporal spikes (BCECTS), Panayiotopoulos syndrome (PS), and idiopathic childhood occipital epilepsy of Gastaut (ICOE-G). The concept of idiopathic and benign focal epilepsies in childhood is relevant as the term implies absence of structural brain lesions and genetic predisposition in the presence of age-dependent seizures. BCECTS is the most frequent of the benign focal epilepsies in childhood accounting for 15 to 25% of epilepsy syndromes in children below 15 years of age. It is also the most frequent epilepsy syndrome occurring at school age. The prevalence of PS was around 13% in children aged 3 to 6 years with one or more nonfebrile seizures, and 6% in the age group of 1 to 15 years. These figures may be higher if children who are currently considered to have an atypical clinical presentation are included in the syndrome. PS is the most common specific cause of nonfebrile status epilepticus in childhood. ICOE “Gastaut type” is a rare manifestation of a focal idiopathic epilepsy that has an age-related onset and is often age limited. The seizures of ICOE Gastaut type are always of occipital-lobe onset and primarily manifest with visual seizures, which are the most typical and usually the first ictal symptom, but other types of seizures may be associated. ICOE “Gastaut type” is a rare condition with a probable prevalence of 0.2 to 0.9% of all epilepsies, and accounting for 2 to 7% of benign childhood focal seizures.The recognition of these age-dependent epileptic syndromes is crucial for the adequate management of the children and their family.

Real-world utility of whole exome sequencing with targeted gene analysis for focal epilepsy

Genotypic and phenotypic analysis of epilepsy associated with NPRL2/NPRL3 genes.

To investigate the status of the drug-resistant tuberculosis (DR-TB) among children in Sichuan, and to find out the risk factors and high-risk population related to drug resistance among children. The clinical data of tuberculosis patients ≤14 years old with culture-confirmed tuberculosis hospitalized in Chengdu Public Health Clinical Center from January 2013 through December 2022 were collected. Clinical data such as gender, age, ethnicity, history of anti-TB treatment, history of exposure to tuberculosis, nutritional status, and specific drug resistance of the children were collected and recorded. The drug resistance of children in different age groups (0-4 years old, 5-9 years old, 10-14 years old) and different periods (2013-2017 and 2018-2022) were grouped and compared. Logistic regression analysis was to analyze analysis of risk factors of drug resistance in children. A total of 438 children with culture-confirmed tuberculosis were screened. Among them, 26.19% (11/42) were 0 to 4 years old, 33.33% (22/66) were 5 to 9 years old, and 36.67% (121/330) were 10 to 14 years old among the resistant children. There was no statistically significant difference in the resistance rate among the 3 groups (P = .385). The proportions of DR-TB, monoresistant tuberculosis, polydrug-resistant tuberculosis were decreased during 2019 to 2022 compared with 2013 to 2017 (P < .0001). The resistance rates of drug resistant, monoresistant, polydrug-resistant, isoniazid-resistant, and rifampicin resistant during 2018 to 2022 were decreased compared with those from 2013 to 2017 (P < .05), but the multi-drug resistance rate was not decreased (P = .131, without statistical difference). The results of logistic regression analysis showed that male gender OR = 1.566 (95% CI 1.035-2.369), a history of antituberculosis therapy OR = 4.049 (95% CI 1.442-11.367), and pulmonary and extrapulmonary tuberculosis OR = 7.335 (95% CI 1.401-38.392) were risk factors for the development of drug resistance; but fever OR = 0.581 (95% CI 0.355-0.950) was Protective factor. The total drug resistance rate of children in Sichuan showed a downward trend, but the rate of multi-drug-resistant tuberculosis was still at a high level, and the form of drug resistance was still severe. Absence of fever, male, retreatment, and pulmonary concurrent with extrapulmonary tuberculosis are risk factors for DR-TB in children.

To investigate clinicoradiological features associated with epilepsy, its resolution, and drug resistance in children with cerebral palsy (CP). Data were gathered from the New South Wales/Australian Capital Territory CP Register, encompassing children with CP born between 2003 and 2015 (n = 1916). Clinical features and the severity of impairments were compared among three groups: children with current epilepsy (n = 604), those with resolved epilepsy by age 5 years (n = 109), and those without epilepsy (n = 1203). Additionally, a subset of the registry cohort attending Children's Hospital Westmead (n = 256) was analysed to compare epilepsy and treatment characteristics between drug-responsive (n = 83) and drug-resistant groups (n = 147) using logistic regression and hierarchical cluster analysis. Manual Ability Classification System levels IV and V, intellectual impairment, and vision impairment were found to be associated with epilepsy in children with CP on multivariable analysis (p < 0.01). Moderate to severe intellectual impairment and bilateral spastic CP were independent positive and negative predictors of epilepsy persistence at the age of 5 years respectively (p < 0.05). Microcephaly and multiple seizure types were predictors of drug-resistant epilepsy (area under the receiver operating characteristic curve of 0.83; 95% confidence interval 0.77-0.9). Children with a known genetic cause (14%) and CP epilepsy surgery group (4.3%) formed specific clinical subgroups in CP epilepsy. Our study highlights important clinical associations of epilepsy, its resolution, and treatment response in children with CP, providing valuable knowledge to aid in counselling families and identifying distinct prognostic groups for effective medical surveillance and optimal treatment. Severe motor and non-motor impairments in cerebral palsy (CP) increase epilepsy risk. Epilepsy more likely resolves in bilateral spastic and milder CP impairments. Epilepsy in CP often manifests at an early age with multiple seizure types and high drug resistance. Children with a known genetic cause and CP epilepsy surgery group represent distinct clinical subgroups.

The characteristics of seizures were analysed in a population-based study of active epilepsy in 6- to 13-year-old mentally retarded children. The search procedure included diagnostic registers, EEG registers, and registers of the Education of the Subnormal. Medical files were scrutinized, and clinical examinations and interviews with parents or caretakers or both were performed. The median age of seizure onset was 1.3 years, 3.1 for children with mild retardation and 0.8 for children with severe retardation. Among the 98 children identified, current seizure groups were partial in 20, generalized in 59, and mixed in 19. The prevailing seizure types were tonic-clonic, myoclonic, atypical absences, and partial complex seizures, present in 42, 33, 23, and 23 children, respectively. A total of 46 children had more than one seizure type. Seizures every day/week occurred in 44 children. There was a constancy between seizure type at onset and later seizure type. Neonatal seizures (n = 25), infantile spasms (n = 12), and status epilepticus (n = 37) occurred independent of one another. Prognostic factors for poor neurologic outcome were early onset of epilepsy, infantile spasms as onset type, and prior neonatal seizures. Children with only partial seizures less frequently had severe mental retardation, cerebral palsy, and visual impairment than those with only generalized seizures. Epilepsies in children with mental retardation are characterized by severe seizure manifestations. The brain damage giving rise to mental retardation and epilepsy is probably the main factor in terms of seizure outcome.

Objective: To investigate and analyze the profiles of misdiagnosis and risk factors for drug resistance in patients with idiopathic generalized epilepsy (IGE). Methods: The data of 188 patients with IGE treated at the Epilepsy Center of the Second Affiliated Hospital of Zhejiang University School of Medicine from January 2014 to December 2022, who met the latest diagnostic criteria of the International League Against Epilepsy (ILAE) were retrospectively collected. All the patients were followed up for over 12 months. The rates of misdiagnosis and inappropriate medication use were determined. The differences in demographic, clinical and electroencephalography (EEG) characteristics between the drug-resistant and drug-responsive groups were compared. Multivariate logistic regression analysis was employed to identify risk factors for drug resistance in patients with IGE. Results: Among the 188 patients with IGE, there were 105 males and 83 females, with a median onset age of 14 years (Interquartile range: 12.0-16.0). Thirty-five patients (18.6%) were misdiagnosed with focal epilepsy, and 33 (28.0%) patients with juvenile absence or myoclonic epilepsy had ever received inappropriate medication. With a median follow-up duration of 3.8 years (1.4, 6.8), 25 patients(15.4%) were diagnosed with drug-resistant epilepsy at the end of follow-up. Risk factors associated with drug resistance included catamenial cycle-related epilepsy (OR=26.93, 95%CI: 3.44-211.04), presence of≥2 seizure types (OR=5.20, 95%CI: 1.15-23.46), coexistence of generalized and focal discharges on interictal EEG (OR=39.25, 95%CI: 1.76-873.31), and spike and slow wave complex burden grade ≥3 (OR=6.26, 95%CI: 1.59-24.64). Conclusions: Misdiagnosis and inappropriate medication use in IGE are not uncommon. Approximately 15% of patients develop drug-resistant epilepsy, while catamenial cycle-related epilepsy, multiple seizure types, and interictal epileptiform discharge characteristics may be risk factors for drug resistance.

BackgroundUnderstanding the mechanisms of drug resistance can facilitate better management of antiretroviral therapy, helping to prevent transmission and decrease the morbidity and mortality of people living with HIV/AIDS. However, there is little data about transmitted drug resistance and acquired drug resistance for HIV/AIDS patients in Shanghai.MethodsA retrospective cohort study of HIV-infected patients who visited the Department of Infectious Disease from June 2008 to June 2015 was conducted in Shanghai, China. Logistic regression analysis was performed to analyze risk factors for drug resistance among HIV-infected people with virological failure. The related collected factors included patient age, gender, marital status, infection route, baseline CD4 count, antiretroviral therapy regimens, time between HIV diagnosis and initiating antiretroviral therapy. Factors with p<0.1 in the univariate logistic regression test were analyzed by multivariate logistic regression test.ResultsThere were 575 subjects selected for this study and 369 participated in this research. For the antiretroviral therapy drugs, the rates of transmitted drug resistance and acquired drug resistance were significantly different. The non-nucleoside reverse transcriptase inhibitor (NNRTI) had the highest drug resistance rate (transmitted drug resistance, 10.9%; acquired drug resistance, 53.3%) and protease inhibitors (PIs) had the lowest drug resistance rate (transmitted drug resistance, 1.7%; acquired drug resistance, 2.7%). Logistic regression analysis found no factors that were related to drug resistance except marital status (married status for tenofovir: odds ratio = 6.345, 95% confidence interval = 1.553–25.921, P = 0.010) and the time span between HIV diagnosis and initiating antiretroviral therapy (≤6M for stavudine: odds ratio = 0.271, 95% confidence interval = 0.086–0.850, P = 0.025; ≤6M for didanosine: odds ratio = 0.284, 95% confidence interval = 0.096–0.842, P = 0.023; ≤6M for tenofovir: odds ratio = 0.079, 95% confidence interval = 0.018–0.350,P<0.001).ConclusionNNRTI had a higher DR rate compared with nucleoside reverse transcriptase inhibitor (NRTI) and PIs, consequently, LPV/r was a reasonable choice for patients with NNRTI drugs resistance in China. Only married status and a time span≤6 month between the HIV confirmed date and the time initiating antiretroviral therapy were risk factors for TDF drug resistance. Both baseline HIV-RNA load and resistance test is crucial for TDR diagnosis, and frequent monitoring of HIV-RNA load is crucial for ADR identification and intervention. Treatment adherence still plays a positive role on the outcome of ART.

Self-limited epilepsy of childhood with affective seizures: A well-defined epileptic syndrome?

Failure in the prevention of mother-to-child HIV transmission (PMTCT) and pediatric treatment challenges led to pretreatment drug resistance (PDR) and acquired drug resistance (ADR) in children with HIV (CWHIV). Interventional and observational data published between 2010 and 2024 on PDR and ADR in CWHIV were included and analyzed by random effects models. Overall, 72 studies encompassing 9973 children were included. The prevalence (95% CI) of PDR was 32.48% (26.08-39.21), and high among those who failed PMTCT prophylaxis (43.23% [32.94-53.82]) versus those without PMTCT-intervention (P < .01) and driven by nonnucleoside reverse transcriptase inhibitors (NNRTI) mutations (28.38% [18.74-39.08]; P = .013). The prevalence of ADR was 61.43% (49.82-72.45), driven by NNRTI-mutations (65.17% [53.95-75.63]; P < .001). INSTI-ADR was low (5.53% [2.49-9.53]) but emerging. There are high burdens of PDR and ADR among CWHIV, suggesting the need to phase out pediatric NNRTIs used for either PMTCT or treatment. Emerging INSTI resistance among CWHIV highlights the relevance of drug-resistance surveillance strategies. CRD42023470034.

BackgroundBetter understanding of drug resistance patterns in HIV-infected children on antiretroviral therapy (ART) is required to inform public health policies in high prevalence settings. The aim of this study was to characterise the acquired drug resistance in HIV-infected children failing first-line ART in a decentralised rural HIV programme.MethodsPlasma samples were collected from 101 paediatric patients (≤15 yrs of age) identified as failing ART. RNA was extracted from the plasma, reverse transcribed and a 1.3 kb region of the pol gene was amplified and sequenced using Sanger sequencing protocols. Sequences were edited in Geneious and drug resistance mutations were identified using the RegaDB and the Stanford resistance algorithms. The prevalence and frequency of mutations were analysed together with selected clinical and demographic data in STATA v11.ResultsA total of 101 children were enrolled and 89 (88%) were successfully genotyped; 73 on a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen and 16 on a protease inhibitor (PI)-based regimen at the time of genotyping. The majority of patients on an NNRTI regimen (80%) had both nucleoside reverse-transcriptase inhibitor (NRTI) and NNRTI resistance mutations. M184V and K103N were the most common mutations amongst children on NNRTI-based and M184V among children on PI-based regimens. 30.1% had one or more thymidine analogue mutation (TAM) and 6% had ≥3 TAMs. Only one child on a PI-based regimen harboured a major PI resistance mutation.ConclusionsWhilst the patterns of resistance were largely predictable, the few complex resistance patterns seen with NNRTI-based regimens and the absence of major PI mutations in children failing PI-based regimens suggest the need for wider access to genotypic resistance testing in this setting.

Chromosome abnormalities are often associated with central nervous system (CNS) malformations and with other neurologic dysfunctions. In particular, patients with chromosomal abnormalities can have mental retardation (MR) and have a higher risk for seizures than that found in the general population (1). Genetic tools such as karyotyping, high-resolution chromosome banding, fluorescent in situ hybridization (FISH), and other molecular genetics techniques have increased the number of chromosome abnormalities detected in subjects with MR or seizures. However, the majority of studies and reports published have usually considered sporadic cases or very small groups of patients with chromosome abnormalities. Furthermore, the characteristics of seizures and EEGs have been described in detail on very few occasions, to define the electroclinical phenotype, and eventually to classify the epilepsy. In recent years, a few identified chromosome abnormality syndromes seem to show a particular clinical and EEG picture; some of them are relatively common, such as Angelman’s syndrome, the fragile-X (fra-X) syndrome, the Miller‐Dieker syndrome; and others are more rare, such as trisomy 12p syndrome, the Wolf‐ Hirschhorn syndrome, and ring 20 syndrome. We review some clinical and neurophysiologic aspects of these syndromes that can support the neurologist in choosing the genetic analysis to be carried out, and help to identify specific genes influencing epileptogenesis. ANGELMAN’S SYNDROME

Evaluation of long-term antiepileptic drug use in patients with temporal lobe epilepsy: Assessment of risk factors for drug resistance and polypharmacy

ObjectiveHelicobacter pylori (H. pylori) has attracted much attention since its discovery. This bacterium has had a substantial impact on society, the economy, and public health. In recent years, with the continuous increase in drug resistance in H. pylori and the emergence of multidrug resistant strains, the existing diagnostic and treatment options are no longer able to meet clinical needs, so we need to understand the dynamically changing nature of drug resistance of H. pylori in our region. This study collected stool samples from community residents in Lianyungang to analyse the local H. pylori infection status, resistance to commonly used antibacterial agents, and risk factors to provide a reference for local clinical empirical treatment. Methods: Human stool samples from Lianyungang residents were collected, the DNA of H. pylori in the positive samples was extracted, the sites of mutated genes were determined by PCR and nucleic acid mass spectrometry, and genotypes of cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) were tested. The resistance rates of local H. pylori strains to five antibacterial agents, levofloxacin, clarithromycin, furazolidone, amoxicillin, and tetracycline, were collected, and the risk factors for drug resistance were analysed statistically based on questionnaire results. Results: A total of 221 residents with qualified stool samples were enrolled. The infection rate was 25.3%. DNA was extracted from 56 H. pylori samples. Among them, only 17 H. pylori strains were sensitive to all five antibiotics, and a total of five drug resistance patterns were detected. The main drug resistance patterns were single drug resistance to clarithromycin (30.4%) and double drug resistance to levofloxacin + clarithromycin (21.4%). The levofloxacin resistance mutations were mainly located at N87K and D91Y of the gyrA sequence, and the clarithromycin resistance mutations were mainly located at A2143G in the 23S rRNA sequence. Age, gastrointestinal symptoms, and previous history of H. pylori infection were risk factors for resistant H. pylori. A previous history of H. pylori infection was an independent risk factor for the development of drug resistance in H. pylori. Conclusion: The H. pylori infection rate in the Lianyungang area is lower than the national rate, but the rates of resistance to levofloxacin and clarithromycin are quite high. Drug sensitivity testing is needed to provide more accurate individualized treatment and improve the eradication rate of H. pylori. Continuous monitoring of local antibiotic resistance patterns remains the first choice for empirical treatment.