ObjectiveTo summarize the clinical characteristics of epilepsy comorbid with tic disorders in children, and discuss its diagnosis, treatment and management. MethodsThe clinical data of 12 epileptic children comorbid with tic disorders treated in Wuhan children's Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology from December, 2018 to June, 2021 was collected retrospectively. The clinical characteristics, EEG, MRI, treatment, prognosis of epileptic children comorbid with tic disorders were analyzed and summarized. ResultsThere were 12 epileptic children comorbid with tic disorders in total, 11 males, 1 female, average (10.0±2.9) years old. The onset age of epilepsy was ranged from 0.6 to 11 years old, average (6.5±3.3) years old. The onset age of tic disorders ranged from 3.5 to 11 years old, average (7.2±2.0) years old. The epileptic seizure types included focal seisures (Focal, 8 cases), atypical absence seizures(AAS, 2 cases), myoclonic seizure (MS, 1 case), generalized tonic-clonic seisures (GTCS, 3 cases). The epileptic syndromes included benign epilepsy with centrotemporal spikes (BECT, 2 cases), Dravet syndrome (1 case), juvenile myoclonic epilepsy(JME, 1 case), temporal lobe epilepsy (TLE, 1 case).The average oral antiepileptic seizure drug was 1, including lamotrigine(LTG), valproic acid(VPA), oxcarbazepine(OXC), levetiracetam(LEV), topiramate(TPM) and Perampanel. The clinical course of tic disorders ranged from 0.5 to 3.0 years, average (1.5±0.9) years. The clinical types included provisional tic disorder (PTD, 4 cases), chronic tic disorder (CTD, 5 cases, all of which were motor tics) and Tourette syndrome (TS, 3 cases). The severity of tic disorders was mild up to the last follow-up. In addition to tic disorders, other comorbidities included attention deficit and hyperactivity disorder (ADHD, 2 cases), 1 children was mixed type, 1 children was hyperactive impulse dominated type, psychomotor development disorder(3 cases), enuresis (1 case) and emotional disorder (1 case). There were interictal epileptiform discharges in 12 children with EEG, including focal discharges(7 cases, 1 EEG showed that focal discharges originated from the right temporal region), multiple discharges (5 cases, 1 EEG showed that multiple discharges originated from the right centro-temporal region), and clinical seizures were monitored in 6 cases (3 cases of focal seizures, 2 cases of atypical absence seizures, and 1 case of myoclonic seizure). Magnetic resonance imaging (MRI) of head showed no obvious abnormalities. The follow-up time was ranged from 0.5 to 3.0 years. Up to the last follow-up (2022.01.01), 8 cases of epilepsy had been controlled and 4 cases of tic disorders were cured. The prognosis of epilepsy comorbid with tic disorders in most children was good. ConclusionsThe prognosis of epilepsy comorbid with tic disorders in most children is good, the types of epileptic seizures and epileptic syndromes are various. Prognosis of these chidren mainly depends on the control of epileptic seizures, the severity of tics and existence of other neuropsychiatric comorbidities. Therefore, drug treatment mainly focuses on controlling the epileptic seizures, and the impact of comorbidities on children can not be ignored. The clinical management needs regular follow-up, timely evaluation and corresponding interventions.
Objective To analyze the causal relationship between cerebrospinal fluid (CSF) metabolites and tic disorder (TD) based on two-sample Mendelian randomization (MR). Methods CSF metabolites data from humans were downloaded from genome-wide association study databases, and CSF metabolites were selected as exposure factors. single nucleotide polymorphisms (SNPs) strongly associated with the exposure factors and independent of each other were selected as instrumental variables. The TD dataset from the Finngen database was downloaded, including 365 cases of TD and 411 816 controls. Analysis was conducted using inverse variance weighting, MR-Egger, weighted median, weighted mode, and simple mode. Sensitivity analysis was conducted using leave-one-out, and multiple-effects testing was conducted using MR-Egger and MR-PRESSO. Heterogeneity was detected using Cochran’s Q. Results A total of 9 CSF metabolites were found to have a causal relationship with the occurrence and development of TD (P<0.05), with a total of 394 SNPs included in the analysis. Inverse variance weighting results showed that N-acetylneuraminic acid [odds ratio (OR)=2.715, 95% confidence interval (CI) (1.102, 6.961), P=0.030], γ-glutamylglutamine [OR=1.402, 95%CI (1.053, 1.868), P=0.021], lysine [OR=2.816, 95%CI (1.084, 7.319), P=0.034] could increase the risk of TD. Cysteinylglycine disulfide [OR=0.437, 95%CI (0.216, 0.885), P=0.021], propionylcarnitine [OR=0.762, 95%CI (0.616, 0.941), P=0.012], pantothenate [OR=0.706, 95%CI (0.523, 0.952), P=0.023], gulareic acid [OR=0.758, 95%CI (0.579, 0.992), P=0.044], and cysteine-glycine [OR=0.799, 95%CI (0.684, 0.934), P=0.005] could reduce the risk of TD. The results of leave-one-out sensitivity analysis were stable, and no horizontal pleiotropy or heterogeneity was observed. Conclusions N-acetylneuraminic acid, γ-glutamylglutamine, and lysine can increase the risk of TD, but cysteinylglycine disulfide, propionylcarnitine, pantothenate, gulagic acid and cysteine-glycine can reduce the risk of TD. However, the mechanism of their effects on TD still needs to be further explored.