Infantile Convulsions Research Articles

Clinical and genetic analysis of 23 Chinese children with epilepsy associated with KCNQ2 gene mutations.

To summarize the clinical features and genetic mutation characteristics of Chinese children with KCNQ2-related epilepsy. A cohort of children with genetically caused epilepsy was evaluated at Linyi People's Hospital from January 2017 to December 2023. After next-generation sequencing and pathogenicity analysis, we summarized the medical records and genetic testing data of the children who had KCNQ2 gene mutations. We identified 23 KCNQ2 gene mutations. 73.9% (n = 17) of the mutation sites were located in S5-S6 segments and the C-terminal region. In addition to the common phenotypes, 2 new phenotypes were identified: infantile convulsion with paroxysmal choreoathetosis (ICCA) and febrile seizure plus (FS+). Of all the cases with abnormal video-electro-encephalography, three cases with self-limited familial infantile epilepsy (SeLNE) exhibited a small number of multifocal discharges. Of the patients who have taken a particular antiepileptic drug, the statistics on the number of patients who have responded to the drug are as follows: oxcarbazepine (8/9, 88.9%), levetiracetam (5/7, 71.4%), phenobarbital (9/16, 56.3%), and topiramate (2/5, 40.0%). However, the efficacy of phenobarbital varied widely in treating SeLNE and KCNQ2-DEE. At the final follow-up, 1 case with SeLNE had a transient developmental regression and 7 cases with KCNQ2-DEE had mild to severe developmental backwardness. Although clinically rare, we report 10 new KCNQ2 mutations and two new phenotypes: ICCA and FS+. This further expands genetic and phenotypic spectrum of KCNQ2-related epilepsy. The gene mutation sites are mostly located in S5-S6 segments and the C-terminal region, and the former is usually associated with KCNQ2-DEE. Sodium channel blockers (including oxcarbazepine and topiramate) and levetiracetam should be prioritized over phenobarbital for KCNQ2-DEE. Some cases with KCNQ2-related epilepsy may have transient developmental regression during periods of frequent seizures. Early treatment and early seizure control may be beneficial for willing outcomes in children with KCNQ2-DEE. This article reports 23 cases of children with KCNQ2-related epilepsy, including 10 new mutation sites and 2 new phenotypes. It further expands the genetic and phenotypic spectrum of KCNQ2-related epilepsy. In addition, the article summarizes the gene mutation characteristics and clinical manifestations of children with KCNQ2-related epilepsy, with the expectation of providing a certain theoretical basis for the diagnosis and treatment of such patients.

Analysis of medication rules and application characteristics of Chinese patent medicine containing borneol based on data mining

BackgroundIn this study, the regularity of drug containing borneol proprietary Chinese medicine was mined, to provide reference for the clinical application and new drug research and development of borneol. MethodsThe database of proprietary Chinese medicines on Pharmaceutical Intelligence Network was searched for internal and external prescriptions that contained borneols and the diseases they treat. Microsoft Office Excel 2019 and SPSS Modeler 18.0 were used to analyze the properties, flavors, meridians tropisms and association rule analysis of the medicines, and Origin 21.0 software was used to draw the association rules diagram. ResultsAmong them, 528 prescriptions of internal Chinese patent medicine containing borneol and 387 prescriptions of external Chinese patent medicine were included. The diseases treated by internal prescription were mainly neurological diseases and heart diseases, among which Chinese medicines with higher frequency of compatibility with borneol were bezoar, licorice, cinnabar, musk and scutellaria. The diseases treated by external prescription were mainly physical disabilities, paralysis diseases, sore and ulcer diseases and so on. Among them, menthol, camphor, frankincense, angelica, and carthami flos and so on are the most frequently combined with borneol. ConclusionThe prescription of Chinese patent medicine containing borneol is composed of cold or warm, pungent or bitter Chinese medicine. Internal prescription primarily targets the meridians of the heart, liver, and lungs, and is often combined with sedative, antipyretic and detoxicating drugs to treat stroke, infantile convulsion and angina pectoris. External prescription mainly acts on liver, heart and spleen meridian, and is often combined with drugs for clearing heat, promoting blood circulation and removing blood stasis to treat rheumatic arthralgia syndrome and sore and ulcer diseases.

A Novel Neuroimaging Phenotype in the Pediatric Paroxysmal Kinesigenic Dyskinesia

AbstractParoxysmal kinesigenic dyskinesia (PKD) is a rare disorder characterized by recurrent attacks of hyperkinetic movements which can be isolated or associated with benign infantile seizures as part of the infantile convulsions with choreoathetosis syndrome. We present a case of hyperkinetic movement disorder in the form of choreoathetosis, ballismus, dystonia triggered by sudden movements with a past history of benign infantile convulsions in a 12-year-old girl. The contrast-enhanced brain and spine magnetic resonance imaging showed bilaterally symmetric superior cerebellar cytotoxic edema sparing the vermis with swollen cerebellar foliae. Whole-exome sequencing identified a homozygous frameshift duplication NM_145239.3(PRRT2):c.649dupC(p.Arg217Profs*8) in the PRRT2 gene. This case report highlights the frameshift duplication in the PRRT2 gene and rare neuroimaging findings which further expand the phenotypic characteristics of PKD in children.

Correlation between serum zinc and brain injury in infants with mild gastroenteritis complicated with benign infantile convulsion and febrile convulsion

To investigate the association between serum zinc levels and convulsive brain injury in infants with mild gastroenteritis complicated with benign infantile seizures (BICE) and febrile seizures (FC). A case-control study method was conducted. 120 children with mild gastroenteritis and convulsion admitted to the First Affiliated Hospital of Hebei North University from January 2020 to January 2022 were enrolled as the research subjects. They were divided into BICE group and FC group according to the type of convulsion. The serum zinc level, the frequency and duration of convulsion, and the occurrence of convulsive brain injury in the two groups were recorded. Multivariate Logistic regression analysis was used to screen the risk factors for convulsive brain injury. The Spearman correlation method was used to analyze the association between serum zinc levels, clinical characteristics of convulsion and convulsive brain injury. A total of 120 children were enrolled, of which 81 developed to BICE and 39 developed to FC during hospitalization. The serum zinc level of children in the FC group was significantly lower than that in the BICE group (μmol/L: 39.24±6.50 vs. 48.65±7.21, P < 0.01). In the BICE group and FC group, the serum zinc level in children with more than 2 convulsions was significantly lower than that in the children with one convulsion (μmol/L: 37.65±6.50 vs. 53.17±7.55 in the BICE group, and 30.27±5.58 vs. 44.16±7.57 in the FC group, both P < 0.01). Serum zinc level in children with convulsion duration ≥ 5 minutes was significantly lower than that in the children with convulsion duration < 5 minutes (μmol/L: 38.75±6.74 vs. 51.21±7.58 in the BICE group, and 31.08±5.46 vs. 45.19±7.25 in the FC group, both P < 0.01). Moreover, the serum zinc level of children with different convulsion frequency and duration in the FC group was significantly lower than that in the BICE group (all P < 0.01). Among the 120 children, 9 cases of convulsive brain injury occurred, and the incidence rate was 7.50%. The incidence of convulsive brain injury in the BICE group was 1.23% (1/81), which was significantly lower than 20.51% in the FC group (8/39, P < 0.01). The serum zinc level of children with convulsive brain injury was significantly lower than that of children with non-brain injury (μmol/L: 28.50±5.00 vs. 60.22±7.31, P < 0.01), and the number of convulsion was significantly higher than that of non-cerebral injury (≥ 2 convulsions: 100.00% vs. 1.80%, P < 0.01), and the duration of convulsion in children with brain injury was significantly longer than that of non-brain-injured children (convulsion duration ≥ 5 minutes: 100.00% vs. 11.71%, P < 0.01). Multivariate Logistic regression analysis showed that decreased serum zinc level [odds ratio (OR) = 2.147, 95% confidence interval (95%CI) was 1.354-3.403], increased number of convulsion (OR = 3.452, 95%CI was 1.266-9.417), and prolonged convulsion duration (OR = 3.117, 95%CI was 1.326-7.327) were independent risk factor for convulsive brain injury in children with mild gastroenteritis and convulsion (all P < 0.05). Spearman correlation analysis showed that serum zinc level, convulsion ≥ 2 times, duration of convulsion ≥ 5 minutes and convulsion ≥ 2 times + convulsion duration ≥ 5 minutes were significantly negatively correlated with the occurrence of convulsive brain injury in FC children (r values were -0.546, -0.517, -0.522, and -0.528, all P < 0.01). There was no significant correlation between serum zinc level, convulsion ≥ 2 times, convulsion duration ≥ 5 minutes and convulsion ≥ 2 times+convulsion duration ≥ 5 minutes and convulsive brain injury in BICE children (r values were -0.281, -0.129, -0.201, -0.243, all P > 0.05). Serum zinc level is related to the characteristics of convulsive symptoms in children with mild gastroenteritis complicated with FC, and has a strong negative correlation with the occurrence of convulsive brain injury. Active targeted intervention and treatment may help reduce the incidence of brain injury in children.

Study of the Impact of Air Pollution on Convulsions in Children: A Hospital-Based Retrospective Study in Hangzhou, China.

To investigate the relationship between the occurrence of convulsions in children and air pollution in Hangzhou. From January 1, 2018, to December 31, 2020, 775 children admitted with convulsion to the pediatric outpatient clinic of The Affiliated Hospital of Hangzhou Normal University (Hangzhou, China) were enrolled in this study. The clinical data and the corresponding weather data of the day in Hangzhou were collected and analyzed. Also, the monthly etiological classification of convulsions and the monthly average air data of Hangzhou were statistically analyzed. The highest incidence of convulsion was observed in children 1 to 2 years old, and higher in boys than in girls. The top three main causes were febrile seizure, benign infantile convulsion with mild gastroenteritis, and epilepsy. Among the meteorological factors, the increase in the level of 2.5 micron particulate matter (PM 2.5) in the air per month led to an increase in the number of patients with febrile seizure, benign infantile convulsion with mild gastroenteritis, and epilepsy, where the increase of ozone in 8 hours (O3-8h) per month led to a decrease in the number of patients with such conditions. PM2.5, PM10, and SO2 are the main meteorological factors affecting the occurrence of convulsions in children in Hangzhou, and PM2.5 and SO2 are risk factors. The increase in the level of PM2.5 in the air per month could increase occurrence of child convulsions, but the increase of O3-8h per month could decrease occurrence of child convulsions.

Effectiveness of gastrodin for migraine: A meta-analysis

BackgroundGastrodia elata Blume (GEB), a traditional Chinese medicine, has been widely used to treat dizziness, numbness of limbs, and infantile convulsion, among other issues. Gastrodin is the main component of GEB. This meta-analysis aimed to evaluate the efficacy and safety of gastrodin in the treatment of migraine.MethodsTen electronic databases, namely the Cochrane Library, Embase, EBSCO, PubMed, Web of Science, CENTRAL, CNKI (China National Knowledge Infrastructure), CBM (Chinese Biomedicine Database), WanFang, and VIP (Chinese Scientific Journals Database), were searched for randomized controlled trials (RCTs) of gastrodin for migraine published before September 2021. The data were analyzed by RevMan 5.3 software and evaluated by GRADEpro.ResultsA total of 1,332 subjects were included in 16 RCTs. The meta-analysis showed that gastrodin was significantly effective in treating migraine (RR = 1.21, 95%CI = [1.17, 1.27]), reducing the pain degree (MD = −1.65, 95% CI = [−2.28, −1.02]), reducing the frequency of migraine attack (SMD = −2.77, 95% CI = [−3.92, −1.62]), shortening the duration of migraine attack (SMD = −1.64, 95% CI = [−2.35, −0.93]), and slowing average arterial cerebral blood flow velocity (SMD = −3.19, 95% CI = [−5.21, −1.17]), as well as being safe.ConclusionsThis systematic review revealed gastrodin is effective and safe in the treatment of migraine.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=197094, identifier: CRD42020197094.

PRRT2 gene mutations associated with infantile convulsions induced by sucking and the genotype-phenotype correlation.

IntroductionPRRT2 is a major causative gene for self-limited familial neonatal-infantile epilepsy, paroxysmal kinesigenic dyskinesia, and paroxysmal kinesigenic dyskinesia with infantile convulsions. Voluntary movement trigger is prominent in adolescence and adulthood, but the triggers are unknown in infants.MethodsA gene panel designed for targeted next-generation sequencing (NGS) was used to screen genetic abnormalities in a cohort of 45 cases with infantile convulsions. The copy number variation was detected by a computational method based on the normalized depth of coverage and validated by a quantitative real-time polymerase chain reaction (RT-qPCR) method. The genotype-phenotype correlation of the PRRT2 mutation gene was analyzed.ResultsA de novo heterozygous PRRT2 deletion was identified in a child who had infantile convulsions induced by vigorous sucking. Seizures happened during the change of feeding behavior from breast to formula, which led to hungry and vigorous sucking. Ictal electroencephalograms recorded seizures with focal origination, which provided direct evidence of epileptic seizures in infants with PRRT2 mutations. Seizures stopped soon after the feeding behavior was changed by reducing feeding interval time and extending feeding duration. Data reanalysis on our previously reported cases with PRRT2 mutations showed that six of 18 (33.3%) patients had infantile convulsions or infantile non-convulsion seizures during feeding. The mutations included two truncating mutations (c.579dupA/p.Glu194Argfs*6, and c.649dupC/p.Arg217Profs*8) that were identified in each of the three affected individuals.ConclusionsThis study suggests that feeding, especially vigorous sucking, is potentially a trigger and highlights the significance of feeding behavior in preventing seizures in infants with PRRT2 mutations. Identification of PRRT2 haploinsufficiency mutations in the patients with infantile convulsions induced by sucking suggested a potential genotype-phenotype correlation.

TMEM151A phenotypic spectrum includes paroxysmal kinesigenic dyskinesia with infantile convulsions.

In a three-generation family, five individuals exhibited the typical phenotype of paroxysmal kinesigenic dyskinesia (PKD). Intriguingly, one of the individuals also showed benign familial infantile convulsions (BFIC) at age 4months and spontaneously resolved at age 18months. At age 12, she developed a typical PKD, and was gradually relieved at age 21. Therefore, the clinical phenotype was consistent with PKD with infantile convulsions (PKD/IC). Whole exome sequence and co-segregation analysis revealed a novel heterozygous variant c.1085A > G in the TMEM151A gene. Our study suggests that the TMEM151A gene may be associated with the disease spectrum of PKD-PKD/IC-BFIC.

Shedding light on the phenotypic\u2013genotypic correlation of rare treatable and potentially treatable pediatric movement disorders

BackgroundAdvances in genetic science have led to the identification of many rare treatable pediatric movements disorders (MDs). We explored the phenotypic–genotypic spectrum of pediatric patients presenting with MDs. By this, we aimed at raising awareness about such rare disorders, especially in our region. Over the past 3 years, we reviewed the demographic data, clinical profile, molecular genetics and other diagnostic workups of pediatric patients presenting with MDs.ResultsTwelve patients were identified; however, only six patients were genetically confirmed. The phenomenology of MDs ranged from paroxysmal kinesigenic choreoathetosis (1 patient), exercise-induced dyskinesia (2 patients), ataxia (2 patients) and dystonia (2 patients). Whole-exome sequencing in addition to the functional studies for some patients revealed a specific genetic diagnosis being responsible for their MDs. The genetic diagnosis of our patients included infantile convulsions and paroxysmal choreoathetosis syndrome and episodic ataxia due to “pathogenic homozygous mutation of PRRT2 gene,” glucose transporter type 1 deficiency-exercise induced dyskinesia due to “De Novo pathogenic heterozygous missense mutation of exon 4 of SLC2A1 gene,” aromatic L amino acid decarboxylase deficiency due to “pathogenic homozygous mutation of the DDC gene,” myopathy with extrapyramidal signs due to “likely pathogenic homozygous mutations of the MICU1 gene,” mitochondrial trifunctional protein deficiency due to “homozygous variant of uncertain significance (VUS) of HADHB gene” and glutaric aciduria II with serine deficiency due to “homozygous VUS for both ETFDH and PHGDH genes.” After receiving the treatment as per recognized treatment protocols, two patients showed complete resolution of symptoms and the rest showed variable responses.ConclusionIdentifying the genetic etiology of our patients guided us to provide either disease-specific treatment or redirected our management plan. Hence, highlighting the value of molecular genetic analysis to avoid the diagnostic odyssey and identify treatable MDs.

INFANTILE CONVULSIONS AND CHOREOATHETOSIS (ICCA) SYNDROME WITH PRRT2 MUTATION-A CASE REPORT

Infantile convulsions and choreoathetosis (ICCA) syndrome is a rare autosomal dominant disorder characterised by convulsions during infancy with paroxysmal choreoathetosis at a later age. Mutations in proline rich transmembrane protein 2 (PRRT2) gene have been identified as a cause for ICCA syndrome. Carbamazepine or phenytoin is effective in preventing seizure recurrence and controlling dyskinesias. Here, we report a child with ICCA syndrome with homozygous mutation in PRRT2 gene.

Characteristics of infantile convulsions and choreoathetosis syndrome caused by PRRT2 mutation.

ABSTRACTImportanceInfantile convulsions and choreoathetosis (ICCA) is a rare neurological disorder. Many affected patients are either misdiagnosed or prescribed multiple antiepileptic drugs.ObjectiveTo explore therapeutic drug treatments and dosages for ICCA in children.MethodsDetailed clinical features (e.g., past medical history and family history), genetic features, and treatment outcomes were collected from the records of six patients with ICCA.ResultsMean age at paroxysmal kinesigenic dyskinesia (PKD) onset was 8 years 8 months (range, 3–12 years); the clinical presentation was characterized by daily short paroxysmal episodes of dystonia/dyskinesia. All patients had infantile convulsions at less than 1 year of age, and the mean onset age was 5.5 months (range, 4–7 months). Two patients had a family history of ICCA, PKD, or benign familial infantile epilepsy. Whole exome sequencing identified the c.649–650insC mutation in PRRT2 in six patients; three mutations were inherited and three were de novo. All patients were prescribed low‐dose carbamazepine and showed dramatic improvement with the complete disappearance of dyskinetic episodes after 3 days. They attended follow‐up for 5–17 months and were attack‐free until the final follow‐up.Interpretation PRRT2 mutations are the primary cause of ICCA. Low‐dose carbamazepine monotherapy is effective and well‐tolerated in children.

Hemiplegic Migraines; A Barrage on the Mind

Hemiplegic migraines (HM) are a rare type of migraine with an aura phase that includes muscle weakness. This form of migraine can either occur sporadically or can be seen in patients with familial hemiplegic migraine which is an autosomal dominant subtype that runs in families. Migraines are classically accompanied by phonophobia, photophobia, neurological symptoms, nausea or vomiting. The subcategory of hemiplegic migraine involves a transient wave of motor weakness and muscle spasms secondary to decreased threshold of excitation in the neurologic system. The etiology of Hemiplegic Migraines is either idiopathic condition or genetic mutation in the CACNA1A, ATP1A2 and SCN1A encoding proteins involved in ion transport. Our case outlines a 72 year old Caucasian female with past medical history of transient ischemic attack (TIA) and paroxysmal atrial fibrillation, presenting to the emergency department with sudden onset of headache, slurred speech and numbness and tingling in the left hand and leg. Tissue plasminogen activor t-PA) was administered within the 45 minute window, and a computed tomography angiography(CTA) of the head and neck was negative. Diagnosis of Hemiplegic Migraine was suggestive given the neurologic signs and symptoms with negative neurologic imaging. The expedited movement of neuronal depolarization down the easily excitable neurons causes a high amplitude wave of energy down the muscle fibers. Other hemiparesis syndrome differentials include MELAS, hereditary hemorrhagic telangiectasia, amyloidosis, and familial infantile convulsions. This case highlights the rarity of hemiplegic migraines and although genetic testing was not performed in our patient, it has been shown that some patients have a genetic predisposition. Strong clinical skills are needed to match the concurrent neurologic symptoms with migraines.

Penetrance estimation of PRRT2 variants in paroxysmal kinesigenic dyskinesia and infantile convulsions.

Proline-rich transmembrane protein 2 (PRRT2) is the leading cause of paroxysmal kinesigenic dyskinesia (PKD), benign familial infantile epilepsy (BFIE), and infantile convulsions with choreoathetosis (ICCA). Reduced penetrance of PRRT2 has been observed in previous studies, whereas the exact penetrance has not been evaluated well. The objective of this study was to estimate the penetrance of PRRT2 and determine its influencing factors. We screened 222 PKD index patients and their available relatives, identified 39 families with pathogenic or likely pathogenic (P/LP) PRRT2 variants via Sanger sequencing, and obtained 184 PKD/BFIE/ICCA families with P/LP PRRT2 variants from the literature. Penetrance was estimated as the proportion of affected variant carriers. PRRT2 penetrance estimate was 77.6% (95% confidence interval (CI) 74.5%-80.7%) in relatives and 74.5% (95% CI 70.2%-78.8%) in obligate carriers. In addition, we first observed that penetrance was higher in truncated than in non-truncated variants (75.8% versus 50.0%, P = 0.01), higher in Asian than in Caucasian carriers (81.5% versus 68.5%, P = 0.004), and exhibited no difference in gender or parental transmission. Our results are meaningful for genetic counseling, implying that approximately three-quarters of PRRT2 variant carriers will develop PRRT2-related disorders, with patients from Asia or carrying truncated variants at a higher risk.

Psychogenic seizures in a child with infantile convulsions and choreoathetosis.

Psychogenic seizures in a child with infantile convulsions and choreoathetosis.

A Comprehensive Review of the Chemistry, Pharmacokinetics, Pharmacology, Clinical Applications, Adverse Events, and Quality Control of Indigo Naturalis.

Indigo naturalis (IN), which is derived from indigo plants such as Strobilanthes cusia (Nees) Kuntze, Persicaria tinctoria (Aiton) Spach, and Isatis tinctoria L., has been traditionally used in the treatment of hemoptysis, epistaxis, chest pain, aphtha, and infantile convulsion in China for thousands of years. Clinical trials have shown that the curative effect of IN for psoriasis and ulcerative colitis (UC) is remarkable. A total of sixty-three compounds, including indole alkaloids, terpenoids, organic acids, steroids, and nucleosides, have been isolated from IN, of which indole alkaloids are the most important. Indirubin, isolated from IN, was used as a new agent to treat leukemia in China in the 1970s. Indirubin is also an active ingredient in the treatment of psoriasis. Pharmacological studies have confirmed that IN has inhibitory effects on inflammation, tumors, bacteria, and psoriasis. Indigo, indirubin, tryptanthrin, isorhamnetin, indigodole A, and indigodole C are responsible for these activities. This review provides up-to-date and comprehensive information on IN with regard to its chemistry, pharmacokinetics, pharmacology, clinical applications, adverse events, and quality control. This review may also serve a reference for further research on IN.

PRRT2 Related Epilepsies: A Gene Review

AbstractPRRT2 encodes for proline-rich transmembrane protein 2 involved in synaptic vesicle fusion and presynaptic neurotransmitter release. Mutations in human PRRT2 have been related to paroxysmal kinesigenic dyskinesia (PKD), infantile convulsions with choreoathetosis, benign familial infantile epilepsies, and hemiplegic migraine. PRRT2 mutations cause neuronal hyperexcitability, which could be related to basal ganglia or cortical circuits dysfunction, leading to paroxysmal disorders. PRRT2 is expressed in the cerebral cortex, basal ganglia, and cerebellum. Approximately, 90% of pathogenic variants are inherited and 10% are de novo. Paroxysmal attacks in PKD are characterized by dystonia, choreoathetosis, and ballismus. In the benign familial infantile epilepsy (BFIE), seizures are usually focal with or without generalization, usually begin between 3 and 12 months of age and remit by 2 years of age. In 30% of cases of PRRT2-associated PKD, there is an association with BFIE, and this entity is referred to as PKD with infantile convulsions (PKD/IC). PRRT2 mutations are the cause of benign family childhood epilepsy and PKD/IC. On the other hand, PRRT2 mutations do not seem to correlate with other types of epilepsy. The increasing incidence of hemiplegic migraine in families with PRRT2-associated PKD or PKD/IC suggests a common disease pathway, and it is possible to assert that BFIE, paroxysmal kinesigenic dyskinesia, and PKD with IC belong to a continuous disease spectrum of PRRT2-associated diseases.

The Genotype and Phenotype of Proline-Rich Transmembrane Protein 2 Associated Disorders in Chinese Children.

Objectives: To study the genetic and clinical characteristics of Chinese children with pathogenic proline-rich transmembrane protein 2 (PRRT2) gene-associated disorders.Methods: Targeted next generation sequencing (NGS) was used to identify pathogenic PRRT2 variations in Chinese children with epilepsy and/or kinesigenic dyskinesia. Patients with confirmed PRRT2-associated disorders were monitored and their clinical data were analyzed.Results: Forty-four patients with pathogenic PRRT2 variants were recruited. Thirty-five of them (79.5%) had heterozygous mutations, including 30 frameshifts, three missenses, one nonsense, and one splice site variant. The c.649dupC was the most common variant (56.8%). Eight patients (18.2%) showed whole gene deletions, and one patient (2.3%) had 16p11.2 microdeletion. Thirty-four cases (97.1%) were inherited and one case (2.9%) was de novo. Forty patients were diagnosed with benign familial infantile epilepsy (BFIE), two patients had paroxysmal kinesigenic dyskinesia (PKD) and two had infantile convulsions and choreoathetosis (ICCA). Patients with whole gene deletions had a later remission than patients with heterozygous mutations (13.9 vs. 7.1 months, P = 0.001). Forty-two patients were treated with antiseizure medications (ASMs). At last follow-up, 35 patients, including one who did not receive therapy, were asymptomatic, and one patient without ASMs died of status epilepticus at 12 months of age. One patient developed autism, and one patient showed mild developmental delay/intellectual disability.Conclusion: Our data suggested that patients with whole gene deletions could have more severe manifestations in PRRT2-associated disorders. Conventional ASMs, especially Oxcarbazepine, showed a good treatment response.

Botany, phytochemistry, pharmacology and Unani traditional uses of Jadwar (Delphinium denudatum Wall.): A Review

Delphinium denudatum Wall (DD), commonly known as Jadwar in India, is an essential plant of the Unani system of medicine. In Unani medicine, Jadwar is considered an antidote to poisons, refrigerant, nerve tonic, cardiotonic, demulcent, lithotriptic, diuretic, and antipyretic. It is beneficial in the treatment of fungal infections, paralysis, facial palsy, epilepsy, infantile convulsions, migraine, mania, hysteria, numbness, tremors, cholera, jaundice, cardiac diseases, arthritis, rheumatism, toothache, aconite poisoning, snake bite, scorpion sting and all kinds of pain. Many bioactive constituents are isolated from DD, including flavonoids, triterpenoids, alkaloids, including delphocurarine, staphisagrine, delphine, condelphine, denudatin, delnudine, delnuline, vilmorri anonymouse, vilmorrianone, a diterpenoid alkaloid. The scientific analysis of Jadwar demonstrates many of the activities mentioned in Unani literature. Nevertheless, further research is needed to identify the mechanism, active constituent, and usefulness of Jadwar in clinical practice. Given the encouraging results against neurological disorders in the prefaces, this aspect should be thoroughly investigated to make it a standard medicine.

Presynaptic PRRT2 Deficiency Causes Cerebellar Dysfunction and Paroxysmal Kinesigenic Dyskinesia

PRRT2 loss-of-function mutations have been associated with familial paroxysmal kinesigenic dyskinesia (PKD), infantile convulsions and choreoathetosis, and benign familial infantile seizures. Dystonia is the foremost involuntary movement disorder manifest by patients with PKD. Using a lacZ reporter and quantitative reverse-transcriptase PCR, we mapped the temporal and spatial distribution of Prrt2 in mouse brain and showed the highest levels of expression in cerebellar cortex. Further investigation into PRRT2 localization within the cerebellar cortex revealed that Prrt2 transcripts reside in granule cells but not Purkinje cells or interneurons within cerebellar cortex, and PRRT2 is presynaptically localized in the molecular layer. Analysis of synapses in the cerebellar molecular layer via electron microscopy showed that Prrt2−/− mice have increased numbers of docked vesicles but decreased vesicle numbers overall. In addition to impaired performance on several motor tasks, approximately 5% of Prrt2−/− mice exhibited overt PKD with clear face validity manifest as dystonia. In Prrt2 mutants, we found reduced parallel fiber facilitation at parallel fiber-Purkinje cell synapses, reduced Purkinje cell excitability, and normal cerebellar nuclear excitability, establishing a potential mechanism by which altered cerebellar activity promotes disinhibition of the cerebellar nuclei, driving motor abnormalities in PKD. Overall, our findings replicate, refine, and expand upon previous work with PRRT2 mouse models, contribute to understanding of paroxysmal disorders of the nervous system, and provide mechanistic insight into the role of cerebellar cortical dysfunction in dystonia.

DENTAL CARE OF PATIENTS WITH AICARDI SYNDROME: A CASE REPORT

Aicardi syndrome does not have an etiology defined, linked to the X chromosome. The triad of infantile convulsions, agenesis of the corpus callosum, and chorioretinal gaps are important for the diagnosis. A patient diagnosed with Aicardi syndrome, female, aged 19, has had controlled convulsions for 6 years and presented with a complaint of teeth sensitivity, anterior open bite, and loss of elements 16 and 46. The molars erupted with brownish pigmentation, and the incisors and canines show signs of enamel hypoplasia. The panoramic radiography showed asymmetry in the heads of the mandible. The tooth 11 presented radicular dilaceration, and the teeth 45 and 35 are rotated. The clinical findings evaluated together favor the hypothesis of molar and incisor hypomineralization, enamel hypoplasia, and congenital syphilis. The patient showed motor coordination and was cooperative, allowing oral hygiene instruction techniques, photographic record, restorative procedures, and exodontia. The clinical follow-up of the patient is being performed every 4 months.