Objective:To analyze the clinical features of anti-neurofascin-155 (NF155) antibody positive autoimmune nodopathy in children.Methods:This was a case series study. A total of 6 children who were diagnosed accurately as anti-NF155 antibody positive autoimmune nodopathy by cell immunofluorescence assay at the Children′s Hospital of Fudan University from January 2020 to December 2023 were collected. This study retrospectively analyzed 6 pediatric children′s clinical manifestations, laboratory and electrophysiological examination results, and treatment outcomes.Results:Among 6 children with anti-NF155 antibody positive autoimmune nodopathy, there were 4 boys and 2 girls. The onset age of 6 children ranged from 3 years and 8 months to 12 years. All 6 children had extremity weakness (more severe in the distal and the lower extremities than in the upper extremities), 5 children had sensory deficits such as numbness or pain in the extremities, 4 children had tremors and ataxia, 3 children had cranial nerve involvement. Among the 6 children, 4 children had protein-cell separation in cerebrospinal fluid examinations. Among the 6 children, 1 child had central nervous system demyelination, the brain magnetic resonance imaging showed multiple abnormal signals in the bilateral cerebral hemispheres. Four children showed motor and sensory nerve damage in electrophysiological examination, and 2 children only showed motor nerve damage. Three children showed myelin and axonal damage, and 3 children only showed axonal damage. Among the 6 children, 5 children were treated with intravenous immunoglobulin and steroids. Among them, 2 children underwent plasma exchange due to poor efficacy, and subsequently, rituximab was added. There was 1 child changed the treatment with olfatomumab since the symptoms did not significantly improve after using rituximab. After treatment for 4-15 months, 2 children had no clinical symptoms, 1 child had improvement in clinical symptoms, 2 children had no significant improvement in clinical symptoms, and 1 child who did not receive the immunotherapy had no significant change in clinical symptoms.Conclusions:Anti-NF155 antibody positive autoimmune nodopathy in children presents with varying degrees of clinical manifestations. It is mainly characterized by extremity weakness, numbness and pain, often accompanied bytremorsand ataxia. Some pediatric patients may also have central nervous system demyelination. Cerebrospinal fluid and electrophysiological examination are important auxiliary examination methods. If steroid therapy is not effective, plasma exchange and rituximab treatment should be used as soon as possible.

Anti-seizure medications (ASMs) are the main therapy for epilepsy.There are many kinds of ASMs with complex mechanism of action, so it is difficult for pharmacists to examine prescriptions.This paper put forward some suggestions on the indications, dosage forms/routes of administration, appropriateness of usage and dosage, combined medication and drug interaction, long-term prescription review, individual differences in pathophysiology of children, and drug selection when complicated with common epilepsy, for the reference of doctors and pharmacists.

Objective:To explore the clinical phenotype characteristics of early-onset epileptic encephalopathy (EOEE) caused by sodium channel mutations.Methods:A retrospective study was used.A total of 52 EOEE patients treated in the Department of Neurology, Children′s Hospital of Fudan University and Department of Neurology, Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science & Technology from June 2016 to June 2019 were recruited.Peripheral blood samples of 52 patients and their parents were collected for analyzing pathogenic mutations by the next generation sequencing and copy number variations of whole exons in family. Chi- square test was used to compare seizure control data among different voltage-gated sodium channel α1 subunit ( SCN1A) mutation types. Results:A total of 35/52 cases (67.3%) were diagnosed as Dravet syndrome, 3/52 cases (5.8%) were West syndrome, and 14/52 cases (26.9%) were non-symptomatic EOEE.The electroencephalogram (EEG) findings showed a large number of multifocal spikes, spike-slow waves, sharp waves, and sharp-slow waves.A total of 45/52 cases (86.5%) showed normal brain magnetic resonance imaging(MRI), 1 case had slightly widened bilateral frontal sulcus, 1 case had widened bilateral temporal pole and frontal top subarachnoid space, and the remaining 5 cases had widened extracerebral space and slightly larger ventricles.Thirteen cases were re-examined with brain MRI, and 3 cases had mild brain atrophy.A total of 43/52 cases (82.7%) were examined with SCN1A gene mutations, of which 28/52 cases (53.8%) were missense mutations, 5/52 cases (9.6%) were nonsense mutations, 7/52 cases (13.5%) were frameshift mutations and 3/52 cases (5.8%) were splice site mutations.A total of 3/52 cases (5.8%) had SCN2A mutations, of which 2/52 cases (3.8%) were missense mutations, and 1/52 case (1.9%) was a frameshift mutation, 1/52 cases (1.9%) carrying the missense mutation of the SCN3A gene.A total of 5/52 cases (9.6%) had missense mutations of the SCN8A gene.After an average of 1-year follow-up, a total of 13/52 cases (25.0%) had more than 1-year control of seizure, of which 6/52 cases (11.5%) with seizure control for more than 2 years, and 4/52 cases (7.7%) with more than 3-year control.Children carrying SCN1A missense mutations were relatively easier to be controlled for seizures than those carrying SCN1A truncation mutations (nonsense mutations+ frameshift mutations) ( P<0.05). In 5 children carrying SCN8A mutations, 2 cases of them had seizures control for more than 1 year after adding Oxcarbazepine, but the improvement of mental motor function was not obvious. Conclusions:In children with EOEE associated with sodium channel gene mutations, SCN1A, SCN2A, SCN3A, and SCN8A mutations were pathogenic factors.Among them, SCN1A was the most common pathogenic gene for EOEE, with the mutation rate of 82.7%.Dravet syndrome was the most common clinical phenotype of EOEE associated with sodium channel gene mutations.Epileptic seizures in children carrying SCN1A missense mutations were easier to be controlled than those with truncated mutation (nonsense mutations + frameshift mutations), suggesting that the gene mutation type was related to the degree of seizures control.Oxcarbazepine was effective in the treatment of EOEE with SCN8A gene mutations, indicating that the combination therapy using anti-epilepsy drugs can be applied to EOEE patients according to the type of gene function.

Objective:To summarize the clinical features of childhood opsoclonus-myoclonus syndrome (OMS), evaluate severity degree and prognosis using OMS Symptom Severity Standard Rating Scale.Methods:The clinical features,diagnosis, therapeutic regimen and follow-up of 9 children with OMS in Department of Neurology and Oncology Department of Children's Hospital of Fudan University between 2011 and 2019 were retrospectively reviewed. Severity degree and prognosis were evaluated using OMS Symptom Severity Standard Rating Scale.Results:Among the 9 children with OMS, 4 were males and 5 were females. The onset age ranged from 14 months to 5 years, with a median of 17 months. Main symptoms were opsoclonus, myoclonus, ataxia, motor function regression, behavior and mood changes and sleep disorders. Eghit patients were combined with tumor. Seven of them with neuroblastoma were confirmed by surgical pathology, the other one showed spontaneous regression and symptom remission without treatment. Eight patients received hormone combined with intravenous immunoglobulin, of which 3 cases received adrenocorticotropic hormone, while 5 cases received methylprednisolone pulse therapy, with prednisone sequential therapy, decreasing dose gradually. Rituximab was administrated in 3 patients whose annual recurrent time was≥2. Nine patients were divided into 3 groups according to OMS Symptom Severity Standard Rating Scale, 1 of mild degree, 3 of moderate degree, 5 of severe degree. There was no recurrence and sequelae in the mild-degree patient after 3 years follow-up. There was no recurrence and sequelae in 2 of the moderate-degree patients after 1-2 years follow-up. Different degrees of motor, cognitive sequelae were found in 1 of moderate-degree patients and all of severe-degree patients after 1-8 years follow-up.Conclusions:Childhood OMS patients have early onset age. Bad symptom severity before treatment and multiphase course are associated with poor prognosis. OMS Symptom Severity Standard Rating Scale is suitable for estimations of long-term prognosis.

Background & Objective: Nonsense mutations in SMC1A have been reported only in females with cluster seizures, all of whom have been described as drug-resistant epilepsy. Here, we aim to explore the use of ketogenic diet treatment. Methods: The clinical data of female patients with de novo nonsense mutations in SMC1A were collected and analyzed. The clinical data was recruited and analyzed. The peripheral blood of children and their parents was collected. The next generation sequencing was used to find suspected pathogenic mutations and all the confirmed mutations were verified by Sanger sequencing. Results: Three patients with heterozygous de novo mutations in SMC1A gene were reviewed. All patients were females, presenting with seizure onset at age between 2.5 to 11 months old. One patient had mild developmental delay. One had moderate developmental delay. Another had severe developmental retardation. None of the patients had a clinical diagnosis of Cornelia de Lange syndrome. All three patients had prominent clinical features of cluster seizures. All the nonsense mutations were predicted damaging SMC1A protein by PolyPhen-2 HVAR. All the patients were treated with multiple antiepileptic drugs but their seizures remained refractory. When initiated with ketogenic diet, they became seizure free within 3 to 4 weeks. Conclusion: SMC1A nonsense mutations can cause early onset epilepsy only in females with cluster seizures. These patients are characterized by drug-resistant epilepsy, but all our three patients have good effect on ketogenic diet add-on therapy.

Objective:To investigate the status of monotherapy for newly diagnosed tic disorders and its comorbidity in children, so as to provide a reference for clinical medication.Methods:A questionnaire survey was conducted to collect the application experience of monotherapy for newly diagnosed tic disorders and comorbidities in 110 pediatric neurologists and psychiatrists from Chinese Tic Disorders Study Consortium from February to August in 2019. Doctors were asked to rate treatment options based on a rank 5-point scale with "1" least appropriate and "5" most appropriate. The drug evaluation index was based on the comparison of the median score of a single drug with the overall scores of all drugs in this disease ( M( Q1, Q3)), single drug M≥ overall Q3 was recommended as preferred drugs; overall Q1≤ single drug M< overall Q3 was considered as secondary drugs; single drug M< overall Q1 was considered as unsuitable drugs. Results:Among 110 electronic questionnaires, 94 (86%) were availably responded, responding doctors included 37 (39%) males and 57 (61%) females, the age of responding doctors was (48±10) years, and their working year was (17±10) years. In the investigation of the first and second monotherapy for newly diagnosed tic disorders in children without comorbidities, there were no preferred drugs for mild transient tic disorders. The scores of clonidine, aripiprazole and tiapride were 4 (3, 4), 4 (3, 4), 4 (4, 5) scores respectively, and were greater than overall scores (3 (2, 4) scores), so they could be recommended as the preferred drugs for moderate chronic tic disorders, the recommendation for initial mild Tourette syndrome (TS) treatment was the same as preferred drugs for moderate chronic tic disorders. Similarly, clonidine, aripiprazole, tiapride and haloperidol could be recommended as the preferred drugs for other kinds of tic disorders. As for the second monotherapy, the preferred drugs for moderate transient tic disorders, mild chronic tic disorders and severe TS were all aripiprazole, tiapride, haloperidol, sulpiride, clonidine and topiramate. While clonidine, aripiprazole, tiapride could be considered as preferred drugs for severe transient tic disorders, moderate to severe chronic tic disorders and mild to moderate tic disorders. In the investigation of monotherapy for newly diagnosed tic disorders in children with comorbidities, for moderate chronic tic disorders and TS comorbid with obsessive-compulsive disorder, aripiprazole (4 (3, 5) scores) and sertraline (4 (3, 4) scores) were preferred drugs,the median scores of which were all greater than overall scores (3 (3, 4) scores), they were also the preferred treatment for severe transient tic disorders and mild chronic tic disorders. For mild and moderate transient tic disorders, severe chronic tic disorders and TS comorbid with obsessive-compulsive disorder, aripiprazole, fluvoxamine, fluoxetine, haloperidol and sertraline were preferred drugs. When comorbid with attention deficit hyperactivity disorder (ADHD), severe transient tic disorders, moderate chronic tic disorders and TS, tomoxetine and clonidine were recommended as preferred drugs (both 4 (4, 5) scores), and tomoxetine and clonidine were also the preferred treatment for severe TS. For severe chronic tic disorders comorbid with ADHD, clonidine (5(4, 5) scores) was preferred drug, greater than overall scores (4 (3, 5) scores), while for mild and moderate transient tic disorders clonidine, tomoxetine, guanidine and methylphenidate were recommended as preferred drugs. For mild chronic tic disorders and TS comorbid with ADHD tomoxetine was preferred drug. When comorbid with sleep disorders, there were no preferred drugs for mild transient tic disorders; estazolam (3 (2, 3) scores) was the preferred drug for mild chronic tic disorders and TS comorbid with sleep disorders. For othe kind of tic disorders comorbid with sleep disorders, estazolam, melatonin and clonazepam were preferred drugs. When comorbid with anxiety and depressive disorders, for all kinds of tic disorders sertraline was recommended as preferred drugs, the median scores of sertraline were all (4 (3, 5) scores) in severe transient tic disorders, moderate to severe chronic tic disorders and moderate TS, and greater than overall scores (3 (3, 4) scores). While severe chronic tic disorders comorbid with anxiety and depressive disorders, fluvoxamine could also be chosen as preferred drugs.Conclusions:Drug therapy is not recommended for mild transient tic disorders, while tiapride, aripiprazole, clonidine, and haloperidol are mainly preferred drugs for the other kinds of tic disorders. Corresponding drugs should be selected when tic disorders are combined with obsessive-compulsive disorder, ADHD, sleep disorders, anxiety, depression, etc.

Objective: To summarize the clinical and genetic features of β-propeller protein-associated neurodegeneration (BPAN). Methods: The clinical data of 17 patients with BPAN with WDR45 gene variants were retrospectively collected at Children’s Hospital of Fudan University, Peking University First Hospital, Capital Institute of Pediatrics, Shengjing Hospital of China Medical University and Shanghai Children's Hospital from June 2016 to December 2018, and their clinical manifestations, electroencephalogram, neuroimaging and genetics were analyzed. Results: Seventeen cases (13 females, 4 males), aged 1.1-8.8 years, were included. The median age of seizure onset was 14.5 months, from 3 months to 24 months of age, manifested with epileptic spasm in 6 cases and focal seizures in 5 cases. Eight patients had only one seizure type and 8 patients had two or more seizure types. Nine patients had complete remission of seizures. All 16 patients with seizures had developmental delay before the seizure onset, of whom 13 patients had moderate to severe seizures. The brain magnetic resonance imaging (MRI) was abnormal in 13 patients, including cerebral atrophy (10 cases) and thinning of the corpus callosum (9 cases). The brain magnetic susceptibility weighted imaging (SWI) in preschool stage showed prominent T2 hypointense signals in bilateral globus pallidus and brainstem ventral in two cases. Five seizure types (spasm, focal, absence, myodonic and generalized tonic clonic seizures)were found on ictal electroencephalogram(EEG) recordings. Compared to female patients(17(6-24) months of ege), male cases had earlier seizure onset (3, 4, 5, 18 months of age) . All patients had de novo variations in WDR45(6 nonsense, 4 frameshift, 3 missense and 4 splicing variations), with hemizygous variants in 3 males, mosaic variants in a male and heterozygous variants in 13 females, within which 5 variations had not been reported (c.977-1C>T,c.976+1G>C,c.10C>T,c.806del and c.110T>C). Conclusions The patients with BPAN have profound developmental delay and are vulnerable to seizures. The male patients with BPAN tend to have more severer clinical phenotype than females. Early brain SWI could facilitate the timely diagnosis of this disease.

To summarize the clinical and genetic features of β?propeller protein?associated neurodegeneration (BPAN). Methods The clinical data of 17 patients with BPAN with WDR45 gene variants were retrospectively collected at Children's Hospital of Fudan University, Peking University First Hospital, Capital Institute of Pediatrics, Shengjing Hospital of China Medical University and Shanghai Children's Hospital from June 2016 to December 2018, and their clinical manifestations, electroencephalogram, neuroimaging and genetics were analyzed. Results Seventeen cases (13 females, 4 males), aged 1.1-8.8 years, were included. The median age of seizure onset was 14.5 months, from 3 months to 24 months of age, manifested with epileptic spasm in 6 cases and focal seizures in 5 cases. Eight patients had only one seizure type and 8 patients had two or more seizure types. Nine patients had complete remission of seizures. All 16 patients with seizures had developmental delay before the seizure onset, of whom 13 patients had moderate to severe seizures. The brain magnetic resonance imaging (MRI) was abnormal in 13 patients, including cerebral atrophy (10 cases) and thinning of the corpus callosum (9 cases). The brain magnetic susceptibility weighted imaging (SWI) in preschool stage showed prominent T2 hypointense signals in bilateral globus pallidus and brainstem ventral in two cases. Five seizure types (spasm, focal, absence, myodonic and generalized tonic clonic seizures) were found on ictal electroencephalogram(EEG)recordings. Compared to female patients(17(6-24) months of ege), male cases had earlier seizure onset (3, 4, 5, 18 months of age). All patients had de novo variations in WDR45 (6 nonsense, 4 frameshift, 3 missense and 4 splicing variations), with hemizygous variants in 3 males, mosaic variants in a male and heterozygous variants in 13 females, within which 5 variations had not been reported (c.977?1C>T,c.976+1G>C,c.10C>T,c.806del and c.110T>C). Conclusions The patients with BPAN have profound developmental delay and are vulnerable to seizures. The male patients with BPAN tend to have more severer clinical phenotype than females. Early brain SWI could facilitate the timely diagnosis of this disease.

Objective: To investigate the clinical features and genetic characteristics of patients with TBC1D24 gene mutations. Method: The clinical data of a patient with novel TBC1D24 compound heterozygous mutations from Children′s Hospital of Fudan University were collected, the related literature was searched from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, National Center from Biotechnology Information and Pubmed (up to April 2016) by using search terms "TBC1D24" "epilepsy" . The clinical features, electroencephalogram (EEG) and prognosis of the patients with TBC1D24 gene mutations were studied. Result: The patient was a boy with non-consanguineous healthy parents.He had an acute episode of focal continuous myoclonus lasting a few hours with consciousness preserved at the age of 3 months.Myoclonic jerks alternatively affected the eyelids, either the right or left limbs, sometimes triggered by fever or fatigue.The frequency was once 3-7 days.At the age of 6 months he was found to have myoclonus seizures with onset from a unilateral eyes lid and limb lasting 10 more minutes and subsequently affected four extremities or the trunk.They occurred once 3-4 months with perserved consciousness and lasted from several hours to up to ten more hours.They mostly disappeared during sleep.He had ataxia and mild mental retarding.Paroxysmal anomalies were not found on ictal traces.A novel compound heterozygous mutation of TBC1D24 gene, c. 730G>A, p.A244T and c. 1571G>C, p.R524P were found in the patient.Further study showed that c. 730G>A mutation was inherited from his father and c. 1571G>C from his mother. These two were not reported in public databases and predicted deleterious by Mutation Taster and polyphen-2.Literature relevant to TBC1D24 published all around the world was reviewed, no Chinese cases with TBC1D24 gene mutations had been reported. The total of 24 cases including the present case with TBC1D24 gene mutation were reported.Among them, 11 cases had compound heterozygous mutations and 13 cases had homozygous mutations.Ten mutations were identified, including 1 termination mutation, 1 frameshift mutation and 8 missense mutations. Conclusion TBC1D24 gene mutational analysis should be performed on patients with early-onset focal continuous myoclonus, if the etiology was unclear.