Benign infantile convulsions associated with mild gastroenteritis: a retrospective study of 39 cases including virological tests and efficacy of anticonvulsants

Benign convulsions associated with mild gastroenteritis (CwG) are a commonly observed disorder in Asia, especially in infants and seniors. Here, we describe a retrospective study about the clinical features of CwG in 62 children hospitalized at St. Mary’s Hospital (Kurume City, Japan) between January 1, 2000 and March 31, 2006, and further evaluate the efficacies of various anticonvulsant treatments for patients with CwG due to either rotavirus or norovirus. Causative diarrheal viruses were detected in 71% of the fecal specimens tested; 30 patients were positive for rotavirus, nine patients were positive for norovirus, two patients were positive for sapovirus, two patients were positive for adenovirus, and one patient was positive for coxackievirus A4. The age of onset for patients with norovirus-positive CwG (16.7 ± 2.7 months) was significantly lower than that of patients with rotavirus-positive CwG (23.0 ± 8.7 months). The duration of the seizures due to norovirus infection (11.8 ± 12.0 h) was significantly longer than that due to rotavirus infection (4.9 ± 5.7 h). There were no significant differences between the two groups with regard to the results of blood chemistry analysis, including the concentrations of serum electrolytes, blood glucose levels, and liver function tests. In this preliminary study, the duration of seizures in patients with CwG due to norovirus that was treated with carbamazepine was significantly shorter than the duration of seizures in the patients treated with another anticonvulsant (phenobarbital). Further randomized controlled studies are required to clarify the efficacies of the various anticonvulsants for patients with CwG.     

A comparative study of febrile and afebrile seizures associated with mild gastroenteritis

Purpose: Seizures associated with mild gastroenteritis have been increasingly reported. We analyzed the clinical characteristics of febrile and afebrile seizures associated with mild gastroenteritis, and attempted to determine the influence of fever in these two groups. Methods: We reviewed the medical records of 59 children presenting with seizures during a mild gastroenteritis episode. They were classified into an afebrile group (n = 27) and a febrile group (n = 32). We compared the age of onset, sex, seizure semiology, frequency, duration, family history, and prior history of seizures between the two groups. Results: The mean age, family history, seizure semiology, and frequency of seizures were not significantly different between the two groups. However, more patients in the afebrile group experienced ?2 seizures/day than in the febrile group (63% vs. 38%, p = 0.051). The febrile patients had a tendency of experiencing prolonged seizures lasting ?5 min compared with the afebrile group (34% vs. 11%, p = 0.063). Prior febrile seizures were noted in 5 of the 32 patients (15.6%) in the febrile group, while none of the 27 patients in the afebrile group had a history of prior seizures (p = 0.056). Conclusions: It seems that the presence of fever may influence the clinical characteristics of seizures associated with mild gastroenteritis. We suggest that afebrile seizures associated with gastroenteritis may be regarded as a distinct condition from those associated with fever, and it needs to be clarified by a further large sample study.     

Infantile convulsions with mild gastroenteritis: a retrospective study of 25 patients

Background:  The aim of this study was to analyze the epidemiologic, clinical, and evolutional characteristics in patients who presented convulsions with mild gastroenteritis (CwG) to facilitate the diagnosis in daily clinical practice. Methods:  Twenty‐five medical records of patients diagnosed with CwG were reviewed, and the epidemiological and clinical features, results of complementary studies, and evolutional data were collected. Results:  Age of onset ranged between 12 and 24 months in 76% of patients. Female/male ratio was 2.6 (18 women and seven men). Seizures were mostly brief (<5 min) and apparently generalized, and often repetitive occurring in cluster (2.2 seizures per episode). One patient with status epilepticus was recorded. The average interval between the onset of gastroenteritis and seizures was 3.8 days, even though seizure preceded diarrhea in three cases. Mean rectal temperature at the moment of seizure was 37.1°C. Rotavirus antigen was positive in stool in 17 episodes (55.8%). There were no abnormalities in serum biochemistry tests and cerebrospinal fluid studies. Four patients showed anomalies in the interictal electroencephalogram. The period of follow‐up was 4.2 years. Five patients (20%) experienced recurrences when suffering a new gastroenteritis episode. One patient developed epilepsy during the follow‐up period. Conclusions:  CwG would constitute a well‐differentiated convulsive syndrome. Prognosis is excellent, but a relatively important percentage of patients relapse when suffering a new diarrhea episode.     

Single-dose chloral hydrate for benign convulsions with mild gastroenteritis

PURPOSE: To reveal the efficacy of single-dose treatment with chloral hydrate (CH) for clustering seizures in benign convulsions with mild gastroenteritis. METHODS: We retrospectively studied the details of treatment in 33 patients with ages ranging from 7 to 39 months. The time-series records of seizures and processes of drug administrations were investigated. RESULTS: A single-dose therapy with CH was effective in 19 of 22 patients (86%), and diazepam in two of 16 (13%). The doses of CH in patients having a successful treatment with single-dose therapy ranged from 41.7 to 62.5 mg/kg (mean 50.2). In two patients, seizures were resistant to single-dose CH therapy, and their doses of CH were 33.8 and 35.1 mg/kg. CONCLUSIONS: An advantage of the single-dose therapy with CH was shown. We recommend treatment with a sufficient dose of not less than 40 mg/kg of CH.     

Genetic analysis of PRRT2 for benign infantile epilepsy,infantile convulsions with choreoathetosis syndrome,and benign convulsions with mild gastroenteritis

Purpose: PRRT2 mutations were recently identified in benign familial infantile epilepsy (BFIE) and infantile convulsions with paroxysmal choreoathetosis (ICCA) but no abnormalities have so far been identified in their phenotypically similar seizure disorder of benign convulsions with mild gastroenteritis (CwG), while mutations in KCNQ2 and KCNQ3 have been recognized in benign familial neonatal epilepsy (BFNE). The aim of this study was to identify PRRT2 mutations in infantile convulsions in Asian families with BFIE and ICCA, CwG and BFNE. Methods: We recruited 26 unrelated Japanese affected with either BFIE or non-familial benign infantile seizures and their families, including three families with ICCA. A total of 17 Japanese and Taiwanese with CwG, 50 Japanese with BFNE and 96 healthy volunteers were also recruited. Mutations of PRRT2 were sought using direct sequencing. Results: Heterozygous truncation mutation (c.649dupC) was identified in 15 of 26 individuals with benign infantile epilepsy (52.1%). All three families of ICCA harbored the same mutation (100%). Another novel mutation (c.1012+2dupT) was found in the proband of a family with BFIE. However, no PRRT2 mutation was found in either CwG or BFNE. Conclusions: The results confirm that c.649dupC, a truncating mutation of PRRT2, is a hotspot mutation resulting in BFIE or ICCA regardless of the ethnic background. In contrast, PRRT2 mutations do not seem to be associated with CwG or BFNE. Screening for PRRT2 mutation might be useful in early-stage differentiation of BFIE from CwG.     

Benign familial infantile convulsions: linkage to chromosome 16p12-q12 in 14 families

PURPOSE: Benign familial infantile convulsions (BFIC) is a form of idiopathic epilepsy. It is characterized by clusters of afebrile seizures occurring around the sixth month of life. The disease has a benign course with a normal development and rare seizures in adulthood. Previous linkage analyses defined three susceptibility loci on chromosomes 19q12-q13.11, 16p12-q12, and 2q23-31. However, a responsible gene has not been identified. We studied linkage in 16 further BFIC families. METHODS: We collected 16 BFIC families, without an additional paroxysmal movement disorder, of German, Turkish, or Japanese origin with two to eight affected individuals. Standard two-point linkage analysis was performed. RESULTS: The clinical picture included a large variety of seizure semiologies ranging from paleness and cyanosis with altered consciousness to generalized tonic-clonic seizures. Interictal EEGs showed focal epileptiform discharges in six patients, and three ictal EEGs in three distinct patients revealed a focal seizure onset in different brain regions. In all analyzed families, we found no evidence for linkage to the BFIC loci on chromosomes 19q and 2q, as well as to the known loci for benign familial neonatal convulsions on chromosomes 8q and 20q. In 14 of the families, the chromosome 16 locus could be confirmed with a cumulative maximum two-point lod score of 6.1 at marker D16S411, and the known region for BFIC could be narrowed to 22.5 Mbp between markers D16S690 and D16S3136. CONCLUSIONS: Our data confirm the importance of the chromosome 16 locus for BFIC and may narrow the relevant interval.     

Incidence and characteristics of norovirus-associated benign convulsions with mild gastroenteritis,in comparison with rotavirus ones

Background and purpose

Rotavirus was detected in 40–50% of patients with benign convulsions with mild gastroenteritis (CwG) before the rotavirus vaccine was introduced in late 2000. However, the rate of rotavirus positivity has decreased since 2010 while the prevalence of norovirus has gradually increased. We investigated the incidence of norovirus-associated CwG during a recent 3-year period and additionally compared the characteristics of norovirus-associated CwG with those of rotavirus-associated CwG.

A trial of lacosamide for benign convulsions with gastroenteritis

Benign convulsions with gastroenteritis are characterized by a cluster of seizures. Sodium channel blockers are efficacious. We prescribed lacosamide, a new channel blocker, for five patients. Patient age ranged from 17 to 33 months; all five experienced 1–4 generalized convulsions persisting for 30–120 s. One patient exhibited a transient splenial lesion on head magnetic resonance imaging. All received one dose (2 mg/kg) of lacosamide. The convulsions ceased, and no adverse drug effect was noted. A single dose of lacosamide was effective and well-tolerated in five patients with benign convulsions with gastroenteritis.     

Benign familial neonatal convulsions: A family with a rare disorder

The authors report a family from Punjab (India) with 10 members having benign familial neonatal convulsions (also known as benign familial neonatal seizures) in two generations. This disorder is quite rare. The clinical presentation of index case along with the findings of computed tomography of the brain and electroencephalograph is described. Important features of all the family members along with a brief review of the literature are also given.     

Benign infantile seizures with mild gastroenteritis: Study of 22 patients

PurposeTo analyze the electroclinical features, aetiology and outcome in patients with normal neurological examination and psychomotor development who presented seizures during a mild gastroenteritis (MG).Patients and methodsEvaluation of the clinical charts of 22 patients who were assessed in the Neurology Department, Hospital Nacional de Pediatría Prof. Dr. JP Garrahan between 1999 and 2007.ResultsTwelve patients were boys and 10 were girls, the age of onset ranged from 5 to 26 months, and the median age was 10 months. Rotavirus antigen test in stool was positive in 9 of 18 studied patients. The seizures were brief, focal with secondary generalization in 15 patients (68.5%), apparently generalized in 5 (22.5%) and focal in two (9%). Seven of the patients (35%) had more than one seizure in 24 h. The interictal EEG was normal in all patients. Neuroradiological studies were performed in 19 patients with a normal result. No patient was put on long-term treatment with antiepileptic drugs. Four patients had subsequent mild gastroenteritis and two of them presented convulsions during the disease. After between 12 and 67 months of follow-up, all patients had normal psychomotor development and neurological examination.ConclusionsIn this study we confirmed the association of benign infantile seizures (BIS) and MG with or without rotavirus. The identification of this entity allows avoiding unnecessary complementary studies and treatment with antiepileptic drugs.     

轻度胃肠炎伴良性婴幼儿惊厥的临床研究

回顾性分析65例急性胃肠炎合并惊厥发作患儿(轻度胃肠炎伴良性婴幼儿惊厥18例、热性惊厥15例、癫13例、病毒性脑炎6例、低钠性脑病6例、高钠性脑病3例、中毒性脑病2例和低钙惊厥2例)临床资料。主要表现为全面性强直或强直-阵挛发作,持续时间短暂,多发生在病程前2 d内,轮状病毒阳性检出率高达83.33%(15/18)。首次惊厥发作患儿肌肉注射苯巴比妥[5~10 mg(/kg·次)],住院过程中再次发作者静脉注射地西泮[0.10~0.30 mg(/kg·次)]。轻度胃肠炎伴良性婴幼儿惊厥为婴幼儿常见惊厥发作疾病,治疗以控制反复发作为原则,预后良好。     

轮状病毒感染与轻度胃肠炎并良性婴幼儿惊厥的相关性历史队列研究

目的 研究轮状病毒(RV)感染与轻度胃肠炎并良性婴幼儿惊厥的相关性.方法 将我院既往3年内收住院的轮状病毒肠炎(大便轮状病毒抗原阳性)321例设为暴露组,而非轮状病毒肠炎(大便轮状病毒抗原阴性)350例为非暴露组.观察胃肠炎症状后1周时间,统计发生惊厥的病例数,计算相对危险度(RR值)及95%可信区间并进行统计学分析.结果 暴露组中37例出现惊厥,发生率为11.53%;而非暴露组11例发生惊厥,发生率为3.14%,RR= 3.67,95%可信区间为2.0 ～ 6.72 ,χ2=17.71,P＜0.01.结论 轮状病毒感染与轻度胃肠炎并良性婴幼儿惊厥之间存在相关性.     

Efficacy of phenobarbital for benign convulsions with mild gastroenteritis: A randomized,placebo-controlled trial

ObjectiveThis study was performed to evaluate the efficacy and safety of intravenous phenobarbital (PB) for benign convulsions with mild gastroenteritis (CwG).MethodsA randomized, single-blind, placebo-controlled trial involving patients with CwG was conducted at the Japanese Red Cross Society Himeji Hospital. Patients with CwG who had experienced two or more seizures were eligible. Patients were excluded if any anticonvulsant was used before enrollment. Patients who were allocated to the PB group were administered 10 mg/kg of PB intravenously. Patients who were allocated to the placebo group were administered 20 ml of normal saline.ResultsFrom April 2016 to October 2018, 13 of 24 patients with CwG were randomized (PB group, n = 7; placebo group, n = 6; age, 1–3 years). Five of six patients in the placebo group had seizures after administration of placebo. However, patients in the PB group had no seizures after administration of PB, with a significant difference in efficacy between the two groups (P = 0.005). Five patients who had seizures after administration of normal saline were administered 10 mg/kg of PB, and no patients had a seizure thereafter. No significant differences were found in heart rate, blood pressure, or saturation of percutaneous oxygen between the two groups.ConclusionThis is the first randomized controlled trial to evaluate the efficacy of an anticonvulsant for CwG. Intravenous PB at 10 mg/kg is effective and well tolerated for CwG.     

Benign convulsion with mild gastroenteritis and benign familial infantile seizure

The authors present Japanese siblings of a 6-year-old girl and a 4-year-old boy, who concurrently experienced convulsions with mild gastroenteritis. These siblings, their father and paternal grandfather had afebrile seizures that intermittently occurred without symptoms of gastroenteritis and terminated within a few days at their infancy. An underlying genetic factor might not only cause benign familial infantile seizures but it might also confer the susceptibility to the convulsions with mild gastroenteritis in these siblings.     

Ictal EEG in patients with convulsions with mild gastroenteritis

The aim of this study is to reveal detailed clinical manifestations and an evolution of ictal EEG discharges of convulsions with mild gastroenteritis (CwG). We recorded ictal EEGs of six patients with CwG. Clinical manifestations included loss of responsiveness, motion arrest, cyanosis, lateral eye deviation, and hemifacial convulsion. Automatism was not observed in any patients. A generalized tonic-clonic convulsion was observed in five of six patients. Ictal EEGs demonstrated that all seizures were of focal onset that evolved into a secondarily generalized seizure. The region of the onset of ictal discharge was the occipital area in three patients, parietal in one, central in one, and frontal in one, respectively. The seizure of patients with CwG is likely to be a partial seizure with secondary generalization.     

Low-dose therapy with carbamazepine for convulsions associated with mild gastroenteritis

We investigated the effect of carbamazepine on convulsions associated with mild gastroenteritis. Sixteen infants and young children (aged 9 months to 3 years) who experienced repetitive convulsions associated with mild gastroenteritis were admitted to our hospital. We treated the sixteen affected patients with 5 mg/kg of carbamazepine once per day until the diarrhea had stopped. Thirteen of the sixteen patients were subjected to intravenous and/or suppository administration of diazepam (0.3-0.5 mg/kg/time), and one patient suppository administration of 0.5 mg/kg diazepam and 5.7 mg/kg phenobarbital before the administration of carbamazepine. In all patients who were given diazepam and/or phenobarbital, the convulsions recurred after the administration of these medicines. The convulsions occurred 2 to 8 times (mean, 4.1 times) before the administration of carbamazepine. Fifteen of the sixteen patients had no seizures after the administration of carbamazepine. One patient had one convulsion 15 min after the administration of carbamazepine. All patients were treated with 5 mg/kg of carbamazepine once per day until the diarrhea had stopped, i.e. for 2 to 9 days (mean, 6.4 days). Low dose therapy with carbamazepine once per day is thus effective for convulsions associated with mild gastroenteritis.     

Comparison between febrile and afebrile seizures associated with mild rotavirus gastroenteritis

PurposeWe aimed on identifying the differences of febrile and afebrile seizures associated with mild rotavirus gastroenteritis (RVGE) in the pediatric population.MethodMedical charts of pediatric patients who had been admitted between July 1999 and June 2011 due to RVGE were retrospectively reviewed. Subjects were ultimately divided into three groups; ‘no seizure’ (NS: patients without seizure), ‘febrile seizure’ (FS: patients with fever during seizure), ‘afebrile seizure’ (AFS: patients without fever during seizure). Comparisons between groups were carried out on demographic and clinical characteristics, laboratory test results, electroencephalogram findings, brain magnetic resonance imaging findings, antiepileptic treatment, and prognosis.ResultsAmong the 755 subjects who had been admitted due to mild rotavirus enteritis, 696 (90.3%) did not have any seizures, 17 (2.2%) had febrile seizures, 42 (5.5%) had afebrile seizures. The duration of gastrointestinal symptoms before the onset of seizures were significantly shorter in the FS group compared to the AFS group (1.3 ± 0.8 vs. 2.8 ± 1.0 days; p < 0.0001). A single seizure attack was significantly higher in the AFS group (3.0 ± 1.6 vs. 1.7 ± 1.0 episodes; p = 0.0003), and the frequency of seizures that were of focal type with or without secondary generalization were significantly higher in the AFS group (33.3% vs. 6.0%; p = 0.0139). All patients among the FS and AFS group had not received further antiepileptic treatment after discharge, and none developed epilepsy during follow up period.ConclusionDespite some differences in seizure characteristics, both febrile and afebrile seizures associated with mild RVGE were mostly benign with a favorable prognosis.     

Benign convulsions with mild gastroenteritis: a report of 10 recent cases detailing clinical varieties

To better define the characteristic clinical features of benign convulsions with mild gastroenteritis, recently recognized as a new entity in Japan, we reviewed all the 10 patients we have seen from 1992 to 1994. The clinical features have been previously reported in the literature to be afebrile generalized tonic-clonic seizures occurring between the first and the fifth sick day of mild gastroenteritis. In our series, four of 10 patients had convulsions before the onset of gastroenteritis. Overall, seizures were mostly brief and often repetitive occurring in cluster (19 seizures/10 episodes). Among these, a prolonged or partial seizure was frequently observed. In six of the 10 patients, the seizure type changed during an episode: from generalized to partial seizures (n = 2), from partial to generalized seizures (n = 2), or from partial to another type of partial seizures (n = 2). None in our series experienced a recurrence episode of afebrile convulsion during follow-up. These findings suggest that benign convulsions with mild gastroenteritis exhibit some variations in their clinical manifestation.     

轮状病毒肠炎伴良性婴幼儿惊厥23例临床分析

目的分析轮状病毒肠炎伴良性婴幼儿惊厥的临床特点。方法对我院收治的23例轮状病毒肠炎伴惊厥患儿进行临床观察和随访。结果23例患儿发病年龄(13．8±6．4)个月,3 d内发生惊厥者19例,均为全身性发作,持续时间短,不超过5 min,一次病程中平均发作次数1．7次。多数病例不复发,部分可复发,病程＜1年。惊厥停止后未行抗癫痫治疗。发作间期脑电图正常,血生化、脑脊液、脑CT等检查正常。全部病例无癫痫和热性惊厥家族史,精神运动发育正常。结论本组病例具有以下特点：(1)1～2岁高发,冬春季多见,婴幼儿既往体健,无家族史；(2)惊厥于病程1～5 d发作,1～3 d多见,惊厥多发生于玩耍过程中,全身性发作为主,无脱水及酸中毒；(3)血生化、脑脊液、脑CT和发作间期脑电图均正常；(4)多数病例不复发,部分可复发,病程＜1年,预后好。