Remarkable increase in the detection and molecular characterization of adenovirus F41 in children with acute gastroenteritis in Japan, 2017-2023.

Human adenovirus (HAdV) is one of the causative viruses of acute gastroenteritis (AGE) in children worldwide. Species F is known to be enteric adenovirus (genotypes 40 and 41) detected in stool samples. In Japan, we conducted an epidemiological study and molecular characterization of HAdV before and after the COVID-19 pandemic from 2017 to 2023. Among 821 patients, HAdV was detected in 118 AGE cases (14.4%). During a period of 6 years, the HAdV detection rates for each year were relatively low at 3.7% and 0%, in 2017-2018, and 2020-2021, respectively. However, the detection rate increased to remarkably high rates, ranging from 13.3% to 27.3% in the other 4-year periods. Of these HAdV-positive strains, 83.1% were F41 genotypes and 16.9% were other genotypes (A31, B3, C1, C2/C6, and C5). Phylogenetic analyses of the nucleotide and deduced amino acid sequences of the full-length hexon gene demonstrated that HAdV-F41 strains were comprised of three clades, and each clade was distributed across the study period from 2017 to 2023. Analysis of deduced amino acid sequences of the hexon gene of the representative HAdV-F41 strains from each clade revealed numerous amino acid substitutions across hypervariable regions (HVRs) from HVR-1 to HVR-7, two insertions in HVR-1 and HVR-7, and two deletions in HVR-1 and HVR-2 of the hexon gene compared to those of the prototype strain, particularly, those of clade 3 HAdV-F41 strains. The findings suggested that the HAdV-F41 of each clade was stable, conserved, and co-circulated for over two decades in Japan.

Whole genome sequencing and genomic characterization of a DS-1-like G2P[4] group A rotavirus in Japan.

After rotavirus was discovered in 1973, it became the leading pathogen in causing acute gastroenteritis in humans worldwide. In this study, we performed whole genome sequencing and genomic characterization of a DS-1-like G2P[4] group A rotavirus in feces of a Japanese child with acute gastroenteritis who was fully Rotarix® vaccinated. The genomic investigation determined a genomic constellation G2-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2 of this rotavirus strain. Its antigenic epitopes of the VP7 and VP4 proteins had significant mismatches compared with the vaccine strains. Our study is the latest attempt to investigate the evolution of the VP7 and VP4 genes of emerging G2P[4] rotavirus in Japan.

A Comparative Study of Acute Gastroenteritis Symptoms in Single- versus Multiple-Virus Infections.

Many different enteric viruses can cause acute gastroenteritis in humans worldwide. While a single virus can indeed cause disease, multiple-virus infections are commonly reported. However, data regarding a comparison between single- and multiple-virus infections upon clinical manifestations of acute gastroenteritis are relatively limited. In this study, a total of 2383 fecal specimens were collected from children with acute gastroenteritis during June 2014-July 2017 in a pediatric clinic in Japan and tested for 11 viruses by multiplex RT-PCR. At least 1 virus was found in 1706 (71.6%) specimens and norovirus GII was the most frequent agent, followed by rotavirus A and other viruses. Multiple-virus infections were identified in 565 cases (33.1%). While major clinical symptoms were found to be significantly different in some single- vs. multiple-virus infections, the disease severity was statistically non-significant. Our study highlights the burden of multiple-virus infections for acute gastroenteritis and the clinical features of patients with multiple-virus infections.

Molecular Epidemiology of Classic, MLB, and VA Astroviruses in Children with Acute Gastroenteritis, 2014-2021: Emergence of MLB3 Strain in Japan.

Human astroviruses (HAstVs) are important causative pathogens of acute gastroenteritis (AGE) in children worldwide. MLB and VA HAstVs, which are genetically distinct from the previously known classic HAstVs, have been detected since 2008. To investigate the role of HAstVs in AGE, we conducted molecular detection and characterization of HAstVs circulating in children with AGE in Japan from 2014 to 2021. Out of 2,841 stool samples, HAstVs were detected in 130 (4.6%). MLB1 was the predominant genotype detected (45.4%), followed by HAstV1 (39.2%), MLB2 (7.4%), VA2 (3.1%), HAstV3 (2.3%), HAstV4, HAstV5, and MLB3 (0.8% each). The results demonstrated that HAstV infection in pediatric patients in Japan was dominated by the two major genotypes MLB1 and HAstV1, with a small proportion of other genotypes. The overall infection rates of MLB and VA HAstVs were higher than those of classic HAstVs. The HAstV1 strains detected in this study belonged solely to lineage 1a. The rare MLB3 genotype was detected for the first time in Japan. All three HAstV3 strains belonged to lineage 3c based on the ORF2 nucleotide sequence and were shown to be recombinant strains. IMPORTANCE HAstVs are one of the pathogens of viral AGE and are considered the third most common viral agents of AGE after rotavirus and norovirus. HAstVs are also suspected to be the causative agents of encephalitis or meningitis in immunocompromised patients and elderly persons. However, little is known about the epidemiology of HAstVs in Japan, especially that of MLBs and VA HAstVs. This study demonstrated epidemiological features and molecular characterization of human astroviruses encompassing a 7-year study period in Japan. This study highlights the genetic diversity of HAstV circulating in pediatric patients with acute AGE in Japan.

Caffeine consumption as a risk factor for childhood and adolescence migraine.

BACKGROUND: Caffeine consumption is a risk factor for chronic daily headache but few studies have addressed relationships between pediatric patient caffeine levels and headache severity. We examined associations between serum and urine caffeine levels and headache severity in childhood and adolescent migraine cases. METHODS: Levels of caffeine and caffeine metabolites in serum and urine samples were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The Wilcoxon rank-sum test was used for comparisons of age, sleep time, headache severity, caffeine consumption, and caffeine detection. Spearman's rank correlation coefficient (ρ) was calculated for associations. Correlations where ρ ≥ 0.3 and differences where p < 0.05 were considered statistically significant. RESULTS: Of the 40 patients studied, 34 declared caffeine consumption and six declared no caffeine consumption. These two groups did not differ significantly in any of the above clinical parameters. Liquid chromatography-tandem mass spectrometry analysis of both serum and urine samples revealed nine caffeine-negative (level <0.0625 µM) and 31 caffeine-positive cases. The Headache Impact Test-6 (HIT-6) score was higher (p = 0.033) for the caffeine-positive group versus the caffeine-negative group. Caffeine was detected by LC-MS/MS in the serum and/or urine of three of the six patients who declared no caffeine consumption. No significant correlations were observed among age, sleep times, headache severity score, or levels of caffeine and caffeine metabolites. CONCLUSION: Thirty one of 40 (77.5%) cases of childhood/ adolescence migraine showed serum and urine caffeine positivity based on LC-MS/MS. The HIT-6 score, a measure of headache severity, was significantly higher for caffeine-positive versus caffeine-negative cases. Symptoms of childhood/adolescence migraine were exacerbated by caffeine consumption.

Prevalence and incidence of cyclic vomiting syndrome in Japan: A study using Japanese claims data.

Cyclic vomiting syndrome (CVS) is a gastrointestinal disorder that is characterized by recurrent episodes of vomiting. Previous studies have provided reliable data on the prevalence of CVS among children in Japan; however, neither prevalence data nor incidence of CVS is available for adults. Hence, we obtained detailed prevalence and incidence data for CVS and estimated the total number of CVS cases in Japan. This retrospective cross-sectional study was conducted using the JMDC (JMDC, Inc.; formerly known as Japan Medical Data Center Co., Ltd.,) database, which is a de-identified Japanese claims database. Individuals enrolled between January 2017 and December 2017 were included in this study. Longitudinal data for eligible populations were used to identify patients who displayed CVS symptoms throughout the follow-up period. Due to the lack of a specific diagnosis code for CVS in 2017, the Rome IV criteria were applied to identify CVS cases in the pediatric and adult populations. The prevalence was standardized to the 2017 Japanese census and extrapolated to estimate the number of CVS cases. A total of 2,093 patients with CVS were identified from 3,506,144 individuals. The overall age-and-sex-standardized prevalence was 0.32 per 1,000 population (95% confidence interval [CI]: 0.30-0.34), projected to approximately 49,000 patients with CVS across Japan. The pediatric age-and-sex-standardized prevalence was 2.10 per 1,000 population (95% CI: 2.01-2.19), and the adult prevalence was 0.05 per 1,000 population (95% CI: 0.04-0.06). Marked sex differences were observed before and after 12 years of age. Thus our study provides the first large-population-based estimates of CVS prevalence and incidence in Japan, and currently, the only estimates for adult CVS in Japan.

Changing distribution of rotavirus A genotypes circulating in Japanese children with acute gastroenteritis in outpatient clinic, 2014-2020.

BACKGROUND: Rotavirus A (RVA) is a major cause of severe acute gastroenteritis (AGE) in infants and children worldwide. In Japan, two kinds of rotavirus vaccines have been introduced as voluntary vaccines in 2011 and 2012, respectively, and launched into the national vaccine program in October 2020. METHODS: In this study, we investigated prevalence of RVA and their molecular characterization in the stool samples collected from infants and children with AGE who visited one outpatient clinic in Japan, from July 2014 to June 2020, during voluntary vaccination with two kinds of rotavirus vaccines. RESULTS: The RVA detection rates decreased from 44.7 % in 2014-2015 to 35.4 % in 2018-2019, whereas in 2019-2020 the numbers of samples collected were dramatically decreased and none of RVA was detected. During this study period, rotavirus vaccination rates in this area increased from 32.4 % to 62.2 %. Distribution of RVA VP7 (G), VP4 (P), and VP6 (I) genotypes in this area had changed year by year; the major genotype combinations were G1P[8]I1 and G1P[8]I2 in 2014-2015, G2P[4]I2 and G9P[8]I1 in 2015-2016, G1P[8]I1 and G8P[8]I2 in 2017-2018, and G8P[8]I2 in 2018-2019. Phylogenetic analysis demonstrated that VP7 nucleotide sequences of G1 were genetically diverse compared with those of other G genotypes in this study. Meanwhile, predominance of unusual G2P[8]I1, G2P[8]I2 and mixed P genotypes were observed only in 2016-2017, but did not carry on in 2017-2019. The equine-like G3 was detected only in 2016-2017. CONCLUSIONS: The results revealed diversity of RVA genotypes and the genotype combinations have changed year by year in Japan, during the study period of 2016-2020.

The Detection of Rotavirus Antigenemia by Immunochromatographic Kits: a Case Series.

BACKGROUND: Acute gastroenteritis is the most common cause of illness and death in infants and young children worldwide. Rotaviruses (RVs) are the major viruses that cause acute gastroenteritis in young children, especially in developing countries in Asia and Africa. METHODS: The presence of rotavirus antigens in sera of four unvaccinated pediatric patients, aged between 4 and 6 years with severe diarrhea and dehydration, were detected by using three immunochromatographic (IC) kits. In addition, the presence of anti-rotavirus IgG, IgA, and IgM antibodies and their concentrations in patient sera were also determined by enzyme immunoassay (EIA). RESULTS: All three kits could detect rotavirus antigen in patient sera with different intensity of the test lines. When patient sera were pretreated with anti-VP6 rotavirus mouse monoclonal antibody prior to testing, the rotavirus positive test lines disappeared, suggesting that all patient sera contained VP6 protein antigen of rotavirus. Assessment of antibody concentration in these patient sera revealed that all patient sera contained IgG, IgA, and IgM antibodies against rotavirus antigen at different concentrations. CONCLUSIONS: The sensitivity of rotavirus protein detection in the patient sera of one IC kit brand was comparable to those of the EIA, suggesting this IC kit could be an alternative screening method for rapid diagnosis of rotavirus infection.

Diversity of human sapovirus genotypes detected in Japanese pediatric patients with acute gastroenteritis, 2014-2017.

Sapovirus (SaV) is one of the pathogens related to acute gastroenteritis (AGE) in adults and children worldwide. This study reported the diversity of SaV genotypes in children with AGE in Japan from July 2014 to June 2017. Of a total of 2259 stool samples tested by using reverse transcription-PCR method and further analyzed by nucleotide sequencing, 114 (5.0%) were positive for SaV and GI.1 (83.3%) was the most predominant genotype, followed by GII.1, GIV.1, GI.2, GI.3, and GII.3 genotypes. Monthly distribution analysis demonstrated two epidemic peaks from July to December 2015 and February to May 2017. However, no detection peak was observed in 2014 and 2016. Phylogenetic analysis of the complete VP1 nucleotide sequences of these GI.1 strains revealed two major clusters of GI.1 and each of which contained GI.1 strains of both 2015 and 2017. This study suggests that the continuous surveillance of SaV is needed to monitor high genetic diversity in Japanese children with AGE.

Diagnosis of Acute Gastroenteritis with Immunochromatography and Effectiveness of Rotavirus Vaccine in a Japanese Clinic.

Despite the well known effectiveness of two licensed live attenuated oral rotavirus (RV)-vaccines, Rotarix and RotaTeq, constant monitoring of vaccine effectiveness (VE) is essential considering the evolving power and reassortment capability of RVs. In this study, we detected RV, norovirus (NV) and adenovirus (AV) infections using immunochromatography (IC)-based kits in children with acute gastroenteritis (AGE) who attended a pediatric clinic in Kiryu city, Gunma, Japan during June, 2014-September, 2018. VEs were determined using a test-negative study design. Among 1658 AGE-children, RV, NV and AV were detected in 96 (5.8 %), 146 (8.8 %) and 46 (2.8 %) children, respectively. Interestingly, the distributions of infections were found to be associated with age and sex. Namely, RV infections were significantly higher in female (P=0.02) and in the 19-30 month age group children, while NV and AV infections predominated in the 13-24 month and 7-18 month age groups, respectively. The disease severity for RV and NV infections remained similar and significantly higher than that of AV infections. The VE of RV-vaccines was 49.8 % (95 % CI: 22.7 to 67.3 %) against all RV infections, which was increased up to 67.2 % (95 % CI: 35.3 to 83.4 %) against severe RV infections. RV-vaccinated children experienced less severe symptoms in RV-infections while non-RV AGE remained less serious for both RV-vaccinated and unvaccinated children. Finally, the prevalence of RV infection remained minimized (≤5.4 %) in this population since 2015. Thus, this study provided important information on distribution of major AGEs in young children and exhibited the effective role of RV vaccines in post-vaccine era.

Detection and molecular characterization of two rare G8P[14] and G3P[3] rotavirus strains collected from children with acute gastroenteritis in Japan.

This study describes the detection and molecular characterization of two rare G8P[14] and G3P[3] rotavirus strains, which were collected from children with acute gastroenteritis in 2014 in Japan. Among 247 rotaviruses, one G8P[14] (strain 12,597) and one G3P[3] (strain 12,638) rotaviruses were detected. The genotypes of 11 gene segments of these two rotavirus strains (RVA/Human-wt/JPN/12597/2014/G8P[14] and RVA/Human-wt/JPN/12638/2014/G3P[3]) were characterized. The genotype constellation of strain 12,597 was assigned to G8-P[14]-I2-R2-C2-M2-A3-N2-T9-E2-H3, and this strain possessed a rare T9 genotype of NSP3 gene which has never been reported previously in combination with G8 genotype of VP7 gene. Molecular characterization and phylogenetic analysis suggested that the strain 12,597 had the consensus G8P[14] backbone that originated from the rotaviruses of animal origins such as cows, deer, dogs, and cats. The genotype constellation of strain 12,638 was identified as G3-P[3]-I3-R3-C3-M3-A9-N2-T3-E3-H6. The VP7 and VP4 genotypes of strain 12,638 was similar to those of the Cat97-like strains, but the VP1, VP2, and VP3 were closely related to those of the AU-1-like strain. Interestingly, the NSP1 to NSP3 genes shared highest identities with those of a bat rotavirus (RVA/Bat-wt/ZMB/LUS12-14/2012/G3P[3] strain). These findings indicated that the strain 12,638 was an intra-genotype reassortant strain among the AU-1-like strains, the Cat97-like strains and the bat strain. Interestingly, the strains 12,597 and 12,638 possessed the same N2 genotype of NSP2 gene. The results of this study support the possible roles of interspecies transmission and multiple reassortment events for generating the genetic diversity of rotavirus in human.

Immunochromatography test for rapid diagnosis of Mycoplasma pneumoniae infection.

The sensitivity and specificity of a new rapid Mycoplasma pneumoniae antigen immunochromatography (IC) test, DK-MP-001, were determined using particle agglutination (PA) antibody response and loop-mediated isothermal amplification (LAMP) gene detection as the gold standard. Of 165 patients, 59 were diagnosed with M. pneumoniae infection based on a ≥fourfold rise of serum PA antibody during the course of the illness. Of the first visit swabs, 60 were positive for M. pneumoniae on LAMP, and 49 were positive for M. pneumoniae antigen on IC test. Compared with PA antibody and LAMP, the sensitivity/specificity of the IC test were 81.4% (48/59) and 99.1% (105/106); and 81.7% (49/60) and 100% (105/105), respectively. IC test detected antigen in pharyngeal swabs more sensitively than in nasal swabs for the same subjects (P < 0.05). The IC test performs well enough to be used with pharyngeal swabs at the first examination.

Prevalence of abdominal migraine and recurrent abdominal pain in a Japanese clinic.

Prevalence of abdominal migraine (AM) and recurrent abdominal pain (RAP) was evaluated in patients who visited Hikita Pediatric Clinic between May 2010 and April 2015. Patient data were collected prospectively using a questionnaire. Out of a total of 3611 cases, observed prevalence was 2.44% for repeated abdominal pain over a period of ≥3 months, 1.47% for RAP, and 0.19% for AM. Duration of abdominal pain was longer for AM than for non-AM RAP. Certain clinical features were significantly different between AM and non-AM RAP. No correlations were found among age at onset, frequency of attack, and duration of attack for various types of RAP. It was difficult to determine useful diagnostic criteria for distinguishing between AM and non-AM RAP. They did not appear to be separate disease entities but, instead, lie on a disease spectrum. The present prevalence of AM (0.19%) was lower than that in many previous studies from countries other than Japan.

Cyclic Vomiting Syndrome in Infants and Children: A Clinical Follow-Up Study.

BACKGROUND: Cyclic vomiting syndrome is characterized by recurrent vomiting that is associated with increased adrenocorticotropic hormone and antidiuretic hormone levels during cyclic vomiting syndrome attacks. However, both prognosis and treatment remain unclear. We therefore evaluated the clinical features, prognosis, and effectiveness of the prophylaxis of cyclic vomiting syndrome as well as the relationship between symptoms and adrenocorticotropic hormone/antidiuretic hormone levels. METHODS: We included 31 patients with cyclic vomiting syndrome who were admitted to Teikyo University between 1996 and 2008. All patients were diagnosed with cyclic vomiting syndrome based on the criteria of the second edition of the International Headache Classification. The patients (25 of 31) were followed until 2013. RESULTS: The median overall duration of the disorder was 66 (3-179) months. Follow-up was completed for 25 patients with cyclic vomiting syndrome, of whom 44% (n = 11) developed migraine. Valproic acid, valproic acid with phenobarbital, phenobarbital, and amitriptyline were effective in nine, four, three, and one patients, respectively. Abnormally high adrenocorticotropic hormone (n = 17) and antidiuretic hormone (n = 18) levels were found among the 25 patients for whom follow-up data were available. The following correlations were significant: attack duration and adrenocorticotropic hormone levels (correlation coefficient: 0.5153, P = 0.0084) and attack duration and antidiuretic hormone levels (correlation coefficient: 0.5666, P = 0.0031). Antidiuretic hormone levels in patients with bilious vomiting were higher than in those without bilious vomiting (P = 0.048). CONCLUSIONS: Most patients with cyclic vomiting syndrome recovered completely and benefited from prophylactic therapy, although half of them developed migraines.

Domain composition of rhamnose-binding lectin from shishamo smelt eggs and its carbohydrate-binding profiles.

Osmerus (Spirinchus) lanceolatus egg lectin (OLL) is a member of the rhamnose-binding lectin (RBL) family which is mainly found in aqueous beings. cDNA of OLL was cloned, and its genomic architecture was revealed. The deduced amino acid (aa) sequence indicated that OLL was composed of 213 aa including 95 aa of domain N and 97 aa of domain C. N and C showed 73 % sequence identity and contained both -ANYGR- and -DPC-KYL-peptide motifs which are conserved in most of the RBL carbohydrate recognition domains. The calculated molecular mass of mature OLL was 20,852, consistent with the result, and 20,677.716, from mass spectrometry. OLL was encoded by eight exons: exons 1 and 2 for a signal peptide; exons 3-5 and 6-8 for N- and C-domains, respectively. Surface plasmon resonance spectrometric analyses revealed that OLL showed comparable affinity for Galα- and ß-linkages, whereas Silurus asotus lectin (SAL), a catfish RBL, bound preferentially to α-linkages of neoglycoproteins. The Kd values of OLL and SAL against globotriaosylceramide (Gb3) were 1.69 × 10⁻5 M for and 2.81 × 10⁻6 M, respectively. Thus, the carbohydrate recognition property of OLL is slightly different from that of SAL. On the other hand, frontal affinity chromatography revealed that both OLL and SAL interacted with only glycolipid-type oligosaccharides such as Gb3 trisaccharides, not with N-linked oligosaccharides. The domain composition of these RBLs and an analytical environment such as the "cluster effect" of a ligand might influence the binding between RBL and sugar chains.

Clinical effectiveness of peramivir in comparison with other neuraminidase inhibitors in pediatric influenza patients.

The currently used antivirals in the treatment of influenza in Japan include amantadine, oseltamivir, zanamivir, laninamivir, and peramivir. We compared the efficacy of intravenous peramivir with that of other neuraminidase inhibitors for treating pediatric influenza. The present study included 223 influenza patients (≤18 years) who presented at the Hikita Pediatric Clinic between February and April 2011. We compared fever duration after starting treatment with antiviral drugs. Because inhalation drugs are difficult to use in <5-year-old patients and because of the potential adverse effects of oseltamivir in teenagers, we created two different age groups (<10-year-old group and 5-18-year-old group) to evaluate treatment results. In influenza A patients between 5 and 18 years old, the median fever duration after treatment with zanamivir was 2 days, compared with 1 day for peramivir (P = 0.0242). In influenza B patients between 5 and 18 years old, the median fever duration after treatment with laninamivir was 3 days, compared with 1 day for peramivir (P = 0.0097). We found no significant difference for any of the other combinations of drug/disease type/age groups. No adverse effects were observed with the antiviral drugs used. The results suggest that peramivir is very useful in pediatric influenza patients.

Regional cerebral blood flow abnormalities in patients with kawasaki disease.

PURPOSE: Kawasaki disease (KD) is an acute febrile disorder of unknown etiology. Brain single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) help in detecting regional cerebral blood flow abnormalities and brain damage. The usefulness of SPECT and MRI in patients with KD was evaluated. MATERIALS AND METHODS: All 22 patients with KD underwent brain SPECT using Tc-99m-hexamethyl propylene amine oxime from 6 days to 3 years after onset, and 8 patients underwent brain MRI. Of the 22 patients, 4 had neurologic symptoms. Case 1 showed prolonged apnea; case 2, prolonged disturbance of consciousness; and cases 3 and 4 generalized tonic-clonic seizures. Initial brain SPECT showed localized hypoperfusion in 4 and 13 patients with and without neurologic symptoms, respectively. RESULTS: All patients with neurologic symptoms underwent follow-up SPECT; localized hypoperfusion was detected between 1- and 6-month follow-up in 3 of these patients. Six patients without neurologic symptoms underwent follow-up SPECT. Localized hypoperfusion was detected at approximately 1- to 11-month follow-up in 4 of these patients. Diffusion-weighted imaging revealed abnormal high-intensity areas in the corpus callosum in case 1. Case 2 showed a bilateral chronic subdural hematoma with decreased size and ischemic changes, and case 3 showed bilateral hippocampal atrophy and left hippocampal sclerosis. CONCLUSIONS: Because the occurrence of localized hypoperfusion is possibly not restricted to only the acute phase in KD, brain SPECT and MRI should also be performed in KD patients with neurologic symptoms.

Sumatriptan as a treatment for cyclic vomiting syndrome: a clinical trial.

BACKGROUND AND OBJECTIVE: Cyclic vomiting syndrome (CVS) is associated with migraine. This study aimed to evaluate the efficacy of sumatriptan in treating CVS. METHODS: Twelve patients were enrolled in this trial. Sumatriptan was administered either subcutaneously [(age x 4 + 20)/100 x 3 mg] or by nasal spray (NS; 20 mg). Response to the treatment was classified as complete, effective, or noneffective. RESULTS: Eleven patients, who presented with 35 attacks, were treated by subcutaneous injection of sumatriptan. The treatment was responsive in 19 attacks. The efficacy of sumatriptan was high in attacks that occurred in cases with a family history of migraine compared to those without (p = .0482). Five patients were treated with sumatriptan NS for six attacks. The treatment was completely responsive in two of six attacks. We observed no adverse effects associated with sumatriptan treatment in this trial. CONCLUSION: We conclude that sumatriptan has potential efficacy in treating of patients with CVS.