Headache in Pediatric Moyamoya Disease after Revascularization Surgery.

INTRODUCTION: Patients with moyamoya disease (MMD) often have headaches after successful revascularization surgery. We aimed to characterize headache in surgically treated MMD patients and elucidate its clinical meaning and pathophysiology. METHODS: Headache and related symptoms were surveyed using structured questionnaires in pediatric MMD patients with follow-up for 6 months or longer after indirect revascularization surgery. Clinical information including initial presentation, surgical method, and outcome was collected from medical records. Surgical outcomes were assessed clinically and by perfusion imaging. We defined "headache associated with MMD" as the headache accompanied by a transient ischemic attack or provoked by hyperventilation. Other headaches were further classified based on the diagnostic criteria of the International Headache Society-3. We analyzed the characteristics of "headache associated with MMD" and newly developed headache after surgery. RESULTS: Among 90 participants, 65 (72.2%) had headaches within the last year before survey, including 28 (43.1%) with "headaches associated with MMD," 10 (15.3%) with probable migraines, 2 (3.1%) with infrequent episodic tension-type headaches, and 4 (6.2%) with probable tension-type headaches. Headache quality was pulsatile in 27 (41.5%) patients and pressing or tightening in 27 (41.5%) patients. Nausea or vomiting was accompanied in 30 (46.2%) patients. Headache upon awakening was reported in 37 (57.8%) patients. Headache disturbed daily life in 12 (18.5%) patients. Among the 32 (35.6%) patients who suffered headache during both the pre- and postoperative period, the headache quality was similar in 27 (84.4%) patients, and its severity decreased in 24 (75.0%) and did not change in 8 (25.0%) patients. Twelve (13.3%) patients experienced newly developed headaches after surgery. Among them, six (50.0%) were classified as having "headaches associated with MMD." They were predominantly electric shock-like or stabbing in 5 (45.6%) patients and nondisturbing in all patients. All 90 patients achieved improvement of ischemic symptoms after surgery. CONCLUSION: Headaches often persist or newly develop after revascularization surgery in MMD patients. Accompanying nausea or vomiting and occurrence upon awakening are characteristic features. Postoperative headache does not necessarily imply insufficient disease control.

Prevalence and clinical characteristics of primary headaches among school children in South Korea: a nationwide survey.

OBJECTIVES: To determine the 1-year prevalence of headache and clinical characteristics of primary headaches among school children in South Korea. BACKGROUND: Many population-based studies have estimated the 1-year prevalence of headache, migraine, and tension-type headache (TTH). The results of those studies vary in terms of race and region. There have been few epidemiological population-based studies of headache in children and adolescents in Korea. METHODS: We conducted a cross-sectional school-based study of a randomized and proportional sample of 5360 boys and girls. All 180 sampled schools participated in this study. The questionnaires collected demographic data in addition to specific questions about headache according to the International Classification of Headache Disorder criteria, 2nd Edition. Valid questionnaires were returned by 94.1% of the sample population. Modified criteria changed the "duration" of migraine (>1 hour instead of 4 hours). RESULTS: The prevalence of headache among school children was 29.1% (1465/5039) in South Korea. The prevalence of headache in girls (33.4%) was significantly higher than in boys (24.4%) (P<.001). The mean age of students with headaches (14.02±3.03) was significantly higher than students without headaches (12.73±3.36) (P <.001). The prevalence of headache according to region was 30.7% among students in urban, 31.2% in suburban, and 21.6% in rural areas. The prevalence of headache according to age was 20.8% among students ∼6-12 years, 32.0% ∼13-15 years, and 38.2% ∼16-18 years. The prevalence according to headache types was 8.7% (boys 7.0%, girls 10.3%) in migraine, 13.7% (boys 10.7%, girls 16.3%) in TTH, and 6.7% in others. The mean frequency, severity of headache, and duration of symptoms were significantly higher in girls than in boys (P<.001). CONCLUSIONS: Recurrent primary headaches are quite prevalent among school-aged children and adolescents in South Korea, and the prevalence rates are similar to those reported elsewhere. TTH was more common than migraine. The prevalence of migraine headache increased with age. The prevalence rate of headache in students in urban and suburban areas was significantly higher than the rate of students in rural areas.

The role of neuroimaging in children and adolescents with recurrent headaches--multicenter study.

OBJECTIVES: To evaluate the role of neuroimaging and to estimate the prevalence of significant and treatable intracranial lesions in children and adolescents with recurrent headaches. BACKGROUND: Neuroimaging studies are commonly performed in children and adolescent patients with headache because of increasing demands by parents and physicians, although objective data and studies to support this widespread practice are minimal. METHODS: We retrospectively reviewed the medical records of all 1562 (male 724, female 838) new patients presenting with recurrent headaches to 9 Pediatric Neurology Clinics of tertiary Hospitals. Data regarding age of onset, duration of symptoms before presentation, frequency, duration of each episode, intensity, location and quality of headache, associated neurologic symptoms and a comprehensive neurological examination were obtained for each patient. The International Classification of Headache Disorders, second edition, was used to classify headache types. RESULTS: Neuroimaging procedures were performed in 77.1% of the patients. Overall, 9.3% (112/1204) of the patients had abnormal findings from neuroimaging. The highest yield was in patients with an abnormal neurological examination wherein abnormal findings on neuroimaging were seen in 50.0% (9/18) of patients (P < .001). The yield was low when imaging was carried out in view of changes in the type of headache (12.9% [26/201]), neurologic dysfunction (10.8% [9/83]), recent onset of severe headaches (7.0% [12/171]), and demands of parent and physicians (10.1% [21/208]). Eleven patients underwent surgery based on neuroimaging results. There was no significant relation between abnormality on neuroimaging and age, sex, headache type, age of onset of headache, duration of symptoms before presentation, duration, frequency, location and intensity of headache (P > .05). CONCLUSIONS: Neuroimaging procedures in children and adolescents with headaches, although not always required, are very commonly performed. We suggest that more strict guidelines for rational use of neuroimaging are needed for pediatric headache patients.

Factors contributing to Korean teachers' attitudes toward students with epilepsy.

We investigated factors contributing to teachers' attitudes toward students with epilepsy. Data were collected from 604 teachers in Korea. The questionnaire included the Scale of Attitudes Toward Persons with Epilepsy (ATPE) and a demographic and teaching experience survey. In stepwise linear regression analysis, ATPE Knowledge scores (P<0.001) and prior experience teaching a student with epilepsy (P=0.001) were identified as significant factors for ATPE Attitude scores. The ATPE Knowledge scores accounted for 50.1% of the variance in the Attitude scores, and experience teaching a student with epilepsy accounted only for 1.0%. Our finding that teachers' knowledge is the most important factor influencing teacher's attitudes toward epilepsy indicates that teachers should be provided with information about epilepsy universally, across geographic settings, educational levels, and experience levels.

Factors contributing to Korean adolescents' perceptions of stigma with respect to epilepsy.

We assessed knowledge and perceptions of epilepsy held by Korean adolescents in the general population, and investigated factors important in adolescents' perceptions of stigma with respect to epilepsy. Surveys were distributed to students at 22 schools. A total of 1377 students participated. Fewer than half of all students (45.1%) reported hearing or reading about epilepsy. Overall, students showed a general lack of familiarity with and knowledge of epilepsy. Stigma perception scores were significantly higher in boys than in girls (P<0.05) and in middle school than in high school (P<0.05) students. We also found that stigma perception scores were significantly correlated with both younger age (r=-0.074, P=0.006) and lower knowledge scores (r=-0.404, P=0.000). Linear regression analysis showed that stigma-related perception was associated with lower knowledge scores (P<0.001) and middle school (P<0.05). These results indicate a need for public education of adolescents in the general population to decrease the stigma associated with epilepsy.

EEG Characteristics and Diagnostic Implications in Childhood Headache: A Multi-Center Study.

Introduction: Epilepsy and migraines are frequently observed as comorbidities, with the occurrence of one disorder increasing the probability of the other. The aim of our study was to evaluate the EEG characteristics by the type of headache and the implications of EEGs in headache patients, comparing the clinical characteristics and treatments between the headache patients with normal and abnormal EEGs. Methods: We conducted a retrospective analysis reviewing the medical records of 259 patients with headaches who visited the pediatrics departments of five university hospitals and underwent EEGs over a period of 3 years. Based on the data entered, analyses of the following items were conducted: (1) comparison of the EEG abnormalities by the type of headache and the characteristics of the EEG findings and (2) comparison of the clinical characteristics between patients with normal and abnormal EEGs. Results: Of the 259 patients, 31 showed abnormal EEGs, while 228 had normal EEGs. Of the 31 patients with abnormal EEGs, 17 showed epileptiform discharges, and 11 showed rhythmic slowing. The frequency of EEG abnormalities was significantly high in patients with migraines with auras than other types of headache. The Pediatric Migraine Disability Assessment (PedMIDAS) score was significantly higher in the abnormal EEG group compared with the normal EEG group (p = 0.001). Conclusion: The results of this study suggest that the abnormal EEG group had more significant disruptions in their daily lives due to headaches than the normal EEG group and that patients with migraines with aura may need EEGs and they might also have overlapping pathophysiologic mechanisms with epilepsy.

Decreases of ganglioside GM3 in streptozotocin-induced diabetic glomeruli of rats.

Ganglioside GM(3) (NeuAcalpha3Galbeta4Glcbeta1Cer) is known to regulate the proliferation of many cell types and to maintain the charge-selective filtration barrier of glomeruli. Based on these, this study examined whether altered expression of ganglioside GM(3) was pathologically related with glomerular hypertrophy and proteinuria occurring in diabetic human and rat kidneys. Diabetic rats were produced by intraperitoneal injection of streptozotocin (80 mg/kg, I.P.). At 15 days after the induction of diabetes, glomerular volume and fibrotic matrix were dramatically elevated, whereas glomerular sialic acid contents were significantly reduced compared with control. Based upon mobility on high-performance thin-layer chromatography (HPTLC) and reactivity to anti-GM(3) monoclonal antibody, normal glomeruli showed a complex ganglioside pattern that consisted of six different components of gangliosides, mainly GM(3), and diabetes caused a severe reduction of these gangliosides with apparent changes in the composition of major ganglioside GM(3). Semi-quantitative analysis by HPTLC showed that ganglioside GM(3) was reduced to 57% of control in diabetic glomeruli. A prominent immunofluorescence microscopy showed a dramatic disappearance of GM(3) expression in diabetic glomeruli. These results indicate that diabetic glomeruli can be characterized by decreases of glomerular sialic acid content and ganglioside GM(3) expression, which may cause loss of charge-selective filtration barrier in renal glomeruli. These changes may be account, at least in part, for the development of glomerular hypertrophy and proteinuria seen in the early stage of diabetic glomerulopathy.

Mechanism for the negative regulation of cell proliferation by ganglioside GM3 in high glucose-treated glomerular mesangial cells.

We recently identified ganglioside GM3 as a modulator of glomerular hypertrophy in streptozotocin-induced diabetic rats (Life Sci., 72: 1997-2006, 2003). This study examined whether alteration of ganglioside GM3 expression could modulate the high glucose-induced proliferation of glomerular mesangial cells (GMCs). GMCs isolated from rat kidneys were cultured under normal (5.6 mM) or high (25 mM) glucose condition for 24-72 hrs. Cell proliferation was predominantly stimulated when GMCs were cultured with high glucose as well as 20 microM of d-threo-PDMP, an inhibitor of ganglioside biosynthesis, for 24 hrs, whereas raising ambient glucose significantly reduced the mesangial sialic acid contents. Based upon mobility on high-performance thin-layer chromatography (HPTLC), GMCs showed a complex pattern of ganglioside expression that consisted of three major components of gangliosides, mainly GM3. High glucose induced a significant reduction of ganglioside expression with apparent changes in the composition of major ganglioside GM3, and semi-quantitative analysis by HPTLC showed that ganglioside GM3 was reduced to 62% of GMCs cultured under normal glucose condition. A prominent immunofluorescence microscopy using anti-GM3 monoclonal antibody also showed a dramatic disappearance of immunoreactivity in high glucose-treated GMCs. Moreover, high glucose significantly lowered the Km values of GM3 synthase (16 microM vs. 49 microM), but did not change the Vmax. These results provide the pathophysiological relationship between the high glucose-induced proliferation of GMCs and the decreased expression of ganglioside GM3, indicating a mechanism for the negative regulation of mesangial proliferation by ganglioside GM3. This mechanism may play an important role in the development of diabetic glomerulopathy.

Anti-angiogenic activities of Cnidium officinale Makino and Tabanus bovinus.

This study investigated the anti-angiogenic activities of Cnidium officinale Makino and Tabanus bovinus by using cultured glomerular capillary endothelial cells (GECs), chorioallantoic membrane (CAM) and rat cornea. Treatment of GECs with several concentrations (5-50 microg/ml) of C. officinale Makino and T. bovinus extracts for 24 h inhibited angiotensin II (10(-8) M)-induced increases of [3H]thymidine uptake and cell numbers in a concentration-dependent manner. The extent of inhibitory rate of [3H]thymidine incorporation by C. officinale Makino and T. bovinus at 50 microg/ml was a similar to that by 10(-5) M of retinoic acid. Herbal extracts also conspicuously inhibited the neovascularization. In contrast to the normal branching of vascular vessels, blood vessel patterns in CAMs treated with extracts (50 microg per egg) of C. officinale Makino and T. bovinus were ran parallel to each other without much branching. Moreover, oral administration of herbal extracts (20 mg/kg per day) for 4 weeks significantly inhibited the rat corneal neovascularization induced by suture, and the length of blood vessels in herbal medicine-treated rat cornea was conspicuously lower than that in control animals. A similar inhibitory effect to these was also observed in the rat cornea treated with thalidomide (200 mg/kg per day). These findings indicate that the anti-angiogenic properties of C. officinale Makino and T. bovinus may be one of the pharmacological mechanisms underlying the anti-tumor and anti-metastatic activities of herbal extracts tested in this study.

Overlapping Guillain-Barré syndrome and Bickerstaff's brainstem encephalitis associated with Epstein Barr virus.

A flaccid tetraparesis in Bickerstaff's brainstem encephalitis (BBE) is presumed to be a sign of overlapping Guillain-Barré syndrome (GBS). In addition, BBE and Fisher syndrome, which are clinically similar and are both associated with the presence of the immunoglobulin G anti-GQ1b antibody, represent a specific autoimmune disease with a wide spectrum of symptoms that include ophthalmoplegia and ataxia. A 2-year-old boy presented with rapidly progressive ophthalmoplegia, ataxia, hyporeflexia, weakness of the lower extremities, and, subsequently, disturbance of consciousness. He experienced bronchitis with watery diarrhea and had laboratory evidence of recent infection with Epstein-Barr virus (EBV). He was diagnosed as having overlapping GBS and BBE associated with EBV and received treatment with a combination of immunoglobulin and methylprednisolone, as well as acyclovir, and had recovered completely after 3 months. In addition, he has not experienced any relapse over the past year. We suggest that combinations of symptoms and signs of central lesions (disturbance of consciousness) and peripheral lesions (ophthalmoplegia, facial weakness, limb weakness, and areflexia) are supportive of a diagnosis of overlapping GBS and BBE and can be helpful in achieving an early diagnosis, as well as for the administration of appropriate treatments.

Early clinical characteristics according to developmental stage in children with definite moyamoya disease.

The objective is to clarify the early clinical characteristics in childhood moyamoya disease (MD). Epidemiologic characteristics, symptoms and diagnostic rates were assessed in 64 children (0-18 years) with definite MD according to developmental stage: infancy (5; 0-1 years); toddlerhood/preschool age (22; 2-5 years); school age (29; 6-10 years); and adolescence (8; 11-18 years). The median ages at onset was 6.25 years and the female to male ratio was 1.9 (~2.5 in toddlerhood/preschool age and in adolescence, P=0.71). Previous headache was observed in 23% (14/64): frequently in school age (38%, P=0.02) and within 6 months before main symptoms (6/11). As an initial symptom, weakness was observed in 78% (50/64) mainly as transient ischemic attack (TIA, 61%) in limbs (90%) and unilaterally (82%). TIA was less frequent in infancy (40%, P=0.04). Seizure was observed in 27% (17/64): frequently in infancy (100%, P<0.01), as the focal type (71%), and in the right extremity (3:1). Isolated seizures without other symptoms was frequent in children ~5 years (P<0.01). Severe headache associated with MD was observed in 14% (9/64). Provoking events were positive in 42% (27/64): in school age, frequently during eating (28%); and in toddlerhood/preschool age, during crying (27%). The diagnostic rates at 3 and 12 months from symptom-onset were 39% (80% during infancy vs. 28% in school age, P=0.14) and 67%, respectively. Symptomatic progression at diagnosis was observed in 38% (24/64). Initial clinical characteristics in childhood definite MD differed according to developmental stage and from at diagnosis.

Mutation Screening of the γ-Aminobutyric Acid Type-A Receptor Subunit γ2 Gene in Korean Patients with Childhood Absence Epilepsy.

BACKGROUND AND PURPOSE: Since the γ-aminobutyric acid type-A receptor subunit γ2 gene (GABRG2) mutation was discovered in an Australian family with childhood absence epilepsy (CAE) and febrile convulsions, a few screening studies for the GABRG2 mutation have been conducted in sporadic individuals with CAE from other ethnic groups. The aim of this study was to determine whether or not the previously reported genetic mutations and single-nucleotide polymorphisms (SNPs) of GABRG2 can be reproduced in sporadic Korean individuals with CAE, compared to healthy Korean individuals. METHODS: Thirty-five children with CAE in Chonnam National University Hospital and healthy controls (n=207) were enrolled, and the medical records of patients with CAE were reviewed. CAE was diagnosed according to the Classification and Terminology of the International League Against Epilepsy. All nine exons of GABRG2 were directly sequenced. In addition, the two SNPs found in our CAE patients were analyzed: C315T in exon 3 (E3) and C588T in exon 5 (E5). The frequencies of the two SNPs in the CAE patients were compared with data from healthy controls (for E3 and E5) and from previously reported Korean population data (only for E3). RESULTS: No mutation of GABRG2 was found in our CAE patients. In addition, the allele and genotype frequencies of the two polymorphisms did not differ significantly between CAE patients, healthy controls, and the Korean general population (p>0.05). CONCLUSIONS: Our study of sporadic Korean individuals with CAE found no evidence that GABRG2 contributes to the genetic basis of CAE.