Sachi Tokunaga

Background/Objectives: There is limited evidence supporting the use of lomerizine, a calcium channel blocker approved for migraine prophylaxis in Japan, in children. This study evaluated the prophylactic efficacy of lomerizine in a pediatric population with migraine and identified the baseline factors independently associated with treatment response. Methods: This single-center, retrospective cohort study enrolled 83 patients aged ≤18 years prescribed lomerizine for migraine prophylaxis. The primary outcome was headache improvement, defined as a ≥50% reduction in monthly headache days from baseline, assessed at 3–4 and 6–8 months. Multivariable logistic regression included prespecified comorbidity-based covariates: psychosocial factors, neurodevelopmental disorder, and postural orthostatic tachycardia syndrome. Results: Headache improvement was observed in 34 of 80 (42.5%) patients at 3–4 months, and in 36 of 71 (50.7%) patients at 6–8 months. Response rates at 3–4 months and 6–8 months, respectively, were 57.7% and 67.4% among patients without psychosocial factors and 14.3% and 20.0% among those with psychosocial factors. Psychosocial factors were the only variables independently associated with a lower probability of improvement at both time points (3–4 months: adjusted odds ratio, 0.122; 95% confidence interval, 0.036–0.419; p < 0.001; 6–8 months: adjusted odds ratio, 0.137; 95% confidence interval, 0.041–0.456; p = 0.001). Conclusions: Patients receiving lomerizine experienced clinically meaningful improvement in headache frequency, particularly those without psychosocial comorbidity. Psychosocial comorbidity was the only baseline factor independently associated with a poor treatment response, underscoring the potential importance of routine psychosocial screening and a possible benefit from concurrent psychological interventions; these findings require prospective confirmation.

Background: Pediatric daily headaches are refractory and disabling. However, the influence of the interval between daily headache onset and initial specialist consultation on clinical outcomes remains unknown. Methods: This retrospective observational study included 51 children and adolescents presenting with daily headaches. Consultation lag was defined as the interval between the date when the headache first became daily and the initial consultation. The primary outcome was headache improvement (≥50% reduction in monthly headache days) at 3–4 months, and the secondary outcome was improvement at 6–7 months. Multivariate logistic regression and receiver operating characteristic curve analyses were performed. Results: Improvements were observed in 41.2% of patients at 3–4 months and 60.0% at 6–7 months. Each additional week of consultation lag was associated with a 12% decrease in the odds of a 3–4-month improvement (adjusted odds ratio, 0.875; 95% confidence interval [CI], 0.783–0.979; p = 0.020). Receiver operating characteristic curve analysis identified an exploratory 5-week threshold (area under the curve, 0.837; 95% CI, 0.711–0.963), with markedly lower odds of early improvement when exceeding this threshold in this cohort (adjusted odds ratio, 0.040; 95% CI, 0.007–0.238; p < 0.001). Comorbid postural orthostatic tachycardia syndrome was associated with the absence of 3–4-month improvement (p = 0.003), whereas other comorbidities were not. Conclusions: A shorter consultation lag was independently associated with early improvement in pediatric daily headaches regardless of comorbidities. Patients presenting within this exploratory 5-week window were substantially more likely to improve early in this cohort; however, this threshold requires prospective external validation before it can inform clinical decision-making. These findings support consideration of prompt specialist referral following the onset of daily headache in children.

Background/Objectives: Pediatric patients with primary headaches frequently exhibit diverse comorbid conditions, often rendering their headaches intractable. Early identification of and intervention for comorbid conditions are crucial for improving prognosis, yet remain challenging. We hypothesized that headache onset timing can predict the presence of these comorbid conditions. Methods: Headache onset timing of 106 pediatric patients (aged 6–17 [median: 13] years) with migraine or tension-type headache and associated comorbidities, including neurodevelopmental and sleep disorders, orthostatic intolerance (OI), and psychosocial factors, was retrospectively analyzed. Results: Headache onset timing was most frequent upon awakening (33.0%), followed by indeterminate (31.1%) and orthostatic (20.8%) onsets. OI (40.6%) and psychosocial factors (38.7%) were the most prevalent comorbid conditions. Psychosocial factors were most common in the awakening (62.9%) and indeterminate (27.3%) onset groups; OI predominated in the orthostatic group (77.3%). Multivariate analysis revealed that psychosocial factors were a significant risk factor for awakening headache (odds ratio [OR]: 4.59, 95% confidence interval [CI]: 1.80–11.71). OI was a risk factor for orthostatic onset headache (OR: 7.18, 95% CI: 1.92–26.87) and inversely associated with indeterminate headache (OR: 0.15, 95% CI: 0.04–0.54). Conclusions: Our findings suggest that detailed classification of headache onset timing can predict potential risks of specific comorbid conditions in pediatric patients.

Background/Objectives: Migraine affects approximately 10% of school-aged children, and frequently co-occurs with orthostatic intolerance (OI). However, although low serum zinc levels have been linked to migraine in adults, yet evidence in pediatric populations remains scarce. We aimed to investigate the association of serum zinc levels with comorbid OI in pediatric patients with migraine. Methods: We retrospectively analyzed medical records of 57 patients (26 male, 31 female; median age 13 years) newly diagnosed with migraine between December 2017 and March 2022. Diagnosis was made according to the International Classification of Headache Disorders, third edition criteria. Serum zinc, iron, copper, and ferritin concentrations were measured at initial presentation. Zinc deficiency was defined as serum concentration < 80 μg/dL. OI diagnosis required ≥2 characteristic symptoms based on modified Japanese diagnostic criteria. Results: The median serum zinc concentration was 80.7 μg/dL, with 40% of patients exhibiting zinc deficiency. Patients without comorbid OI (54%) demonstrated significantly lower serum zinc levels than those with OI (77.5 vs. 84.7 μg/dL, p < 0.001). Linear mixed model analysis identified comorbid OI as the only clinical factor significantly associated with serum zinc concentrations (p = 0.019). Conclusions: Pediatric patients with migraine without comorbid OI exhibit lower serum zinc levels than those with OI, suggesting differences in the underlying pathophysiology. Further large-scale, prospective studies including healthy control groups are warranted to validate these results.

Objective: Evidence on prophylactic drugs for pediatric migraine is limited, especially when comorbid conditions contribute to treatment resistance. This study evaluated the efficacy of cyproheptadine in children with migraine and explored the impact of comorbid neurodevelopmental disorders and orthostatic intolerance (OI). Methods: We retrospectively analyzed pediatric migraine patients treated with cyproheptadine. Efficacy was assessed based on the reduction in headache frequency, with responders defined as patients experiencing at least a 50% reduction in headache episodes. Fisher’s exact test analyzed the relationship between efficacy and comorbid conditions or treatment sequence. Multiple logistic regression was performed to identify factors associated with adverse events. Results: In total, 155 children (71 males, 84 females) aged 3–15 years were included. Comorbid neurodevelopmental disorders and OI were present in 27 (17.4%) and 22 (14.2%) patients, respectively. Efficacy was evaluated in 148 patients, with 68.9% classified as responders. Patients with comorbid conditions showed lower efficacy. Responders required a lower dose of cyproheptadine (p = 0.039). Multiple logistic regression identified headache frequency, cyproheptadine dose, and comorbid OI and neurodevelopmental disorders as factors influencing treatment efficacy. Conclusions: Cyproheptadine is effective in treating pediatric migraine, though patients with neurodevelopmental disorders and OI demonstrated reduced efficacy.

Juvenile myasthenia gravis (MG) is a rare autoimmune neuromuscular disease, often treated with anticholinesterases, corticosteroids, and immunosuppressants. However, optimal treatment durations remain unclear. This study investigated the clinical characteristics and treatment of juvenile MG, including medication duration. The administration period for all drugs, immunosuppressants, and prednisolone at doses greater than 0.35 mg/kg daily was extracted retrospectively from medical records. Nineteen participants (8 boys, 11 girls) aged 8 months to 14 years (median, 2.5 years) at onset were identified. Fourteen patients (73.7%) had ocular MG and five (26.3%) had generalized MG. Drug treatment was conducted in 18 cases; however, 7 patients did not complete the treatment. Among the patients who completed drug treatment, the duration of treatment ranged from 11 to 100 months (median, 47 months). In the six patients treated with continuous administration of prednisolone or immunosuppressants, the treatment duration ranged from 33 to 99 months (median, 56 months). No severe adverse effects requiring hospitalization were reported. The patients treated with prednisolone or immunosuppressants required at least 33 months of treatment. These results will help develop protocols for juvenile MG treatment.

DLG4-related synaptopathy is a neurodevelopmental disorder caused by a DLG4 variant. We identified a novel de novo heterozygous frameshift variant, NM_001321075.3(DLG4):c.554_563del, in a Japanese girl. Intellectual regression without motor delay was observed at 2 years of age, and she was diagnosed with autism spectrum disorder and attention-deficit/hyperactivity disorder. Recognizing the possibility of DLG4-related synaptopathy in patients with intellectual regression is important for ensuring an accurate diagnosis.

Congenital myasthenic syndrome (CMS) is a clinically and genetically heterogeneous inherited disorder that is treatable. Although the disease usually develops at birth or during infancy, some patients develop the disease in the second to third decades of life. Collagen-like tail subunit of asymmetric acetylcholinesterase (COLQ)-related CMS is CMS with mutations in the COLQ, which results in end-plate acetylcholinesterase deficiency. Diagnostic delay is common in patients with later-onset CMS due to slow progression and fluctuating symptoms. Understanding CMS with atypical and unusual presentations is important to treat this condition effectively. Here, we report a case of COLQ-related CMS. A 10-year-old girl presented with only marked fatigue, which was provoked by exercise but improved after 30–60 min of rest. While motor nerve conduction velocity was normal, a compound muscle action potential (CMAP) with four peaks was recorded. Repetitive stimulation of the accessory nerve exhibited a decrease in CMAP amplitude. Genetic tests revealed compound heterozygous mutations in COLQ (c.1196-1_1197delinsTG and c.1354C>T). Treatment with salbutamol improved fatigue but not the electrophysiological markers. Thus, significant fatigue is a hallmark of COLQ-related CMS; early diagnosis is essential for ensuring appropriate treatment.