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This pilot study investigates the feasibility and assesses the impact of Lactobacillus plantarum PS128 probiotics on the neurological function in Rett syndrome. We conducted a randomized, double-blind, and placebo-controlled trial on Rett syndrome with MECP2 mutation aged between 1 and 50 years in Taiwan. In this pilot study, twice-daily L. plantarum PS128 or placebo was administered for 16 weeks. In addition to feasibility, we also assessed the changes utilizing the Mullen Scales of Early Learning. In total, 36 participants were finally randomized into L. plantarum PS128 (n = 18) or placebo (n = 18) groups. At the end of intervention, the retention rates were 100% for L. plantarum PS128 and 94.44% for placebo, with withdrawal rates of 5.56% for the placebo group. Both groups tolerated well, except for one L. plantarum PS128 participant who reported loose stool. The probiotic group showed a change of 2.19 ± 3.76, while the placebo group had −0.85 ± 5.09 (p = 0.051) in the total age-equivalent scores of Mullen Scales of Early Learning. There was a significant difference in the change of the total score on the Burke–Fahn–Marsden Movement Scale between probiotc group and placebo group (−12.19 ± 12.12 vs −4.59 ± 4.20, p = 0.020). In leg dystonia, the probiotic group exhibited a change of −4.11 ± 5.11 compared with −0.38 ± 1.50 in the placebo group (p = 0.008). Our findings affirm the feasibility of L. plantarum PS128 in Rett syndrome. Future clinical trials are mandatory to further explore its long-term impact on Rett syndrome. Rett syndrome often involves gastrointestinal symptoms and gut microbiota imbalances. We conducted a study to explore the feasibility of probiotic Lactobacillus plantarum PS128 and the impact on neurological functions in Rett syndrome. The results of our investigation demonstrated that the supplementation of probiotic L. plantarum PS128 was feasible and well tolerated, with 100% retention rate and 0% withdrawal rate. In addition, there was only one participant who had loose stool after taking L. plantarum PS128. Further, there was a tendency to enhance overall cognitive developmental level, as assessed using Mullen Scales of Early Learning. In addition, it significantly improved dystonia, as assessed using the Burke–Fahn–Marsden Movement Scale, in comparison with the placebo group. This study provides a strong foundation for future research and clinical trials exploring the potential of L. plantarum PS128 probiotics as a complementary therapy for individuals with Rett syndrome. [ABSTRACT FROM AUTHOR]

Objective: Rett syndrome (RTT) is characterized by neurological regression. This pioneering study investigated the effect of age on brain volume reduction by analyzing magnetic resonance imaging findings in participants with RTT, ranging from toddlers to adults. Methods: Functional evaluation and neuroimaging were performed. All scans were acquired using a Siemens Tim Trio 3 T scanner with a 32-channel head coil. Results: The total intracranial volume and cerebral white matter volume significantly increased with age in the control group compared with that in the RTT group (p < 0.05). Cortical gray matter volume reduction in the RTT group continued to increase in bilateral parietal lobes and left occipital lobes (p < 0.05). The differences in cortical gray matter volume between typically developing brain and RTT-affected brain may tend to continuously increase until adulthood in both temporal lobes although not significant after correction for multiple comparison. Conclusions: A significant reduction in brain volume was observed in the RTT group. Cortical gray matter volume in the RTT group continued to reduce in bilateral parietal lobes and left occipital lobes. These results provide a baseline for future studies on the effect of RTT treatment and related neuroscience research. [ABSTRACT FROM AUTHOR]

Dravet syndrome (DS) is an uncommon epilepsy syndrome that may negatively affect the patients and their caregivers. However, reliable and valid measures of its impact on caregivers and the characteristics of patients with DS in Taiwan are lacking. This study aimed to describe the characteristics of patients with DS and concerns of their caregivers and establish a baseline frequency of disease characteristics using a cross-sectional survey in Taiwan. We assessed the caregivers of patients with DS using an online anonymous questionnaire. The seizure frequency decreased with age, although lacking statistical significance. Vaccines show no influence on the condition of patients with DS. Our findings revealed the highest impact on the domains affecting the caregivers' daily life, including additional household tasks, symptom observation, further medical plan, and financial issues. Caregivers also expressed concerns regarding the lack of independence/constant care, seizure control, speech/communication, and impacts on siblings because of long-term care of the patients in parents' absence. Our findings highlight the significant effects of caring for a child with DS on the lives of their caregivers in Taiwan; these findings will help raise awareness regarding the needs of these families. Furthermore, we discussed the possible pathophysiological mechanisms of associated comorbidities. [ABSTRACT FROM AUTHOR]

Purpose: To examine the association between daily screen time exposure and both sleep patterns (sleep onset, sleep offset, and nighttime, and daily sleep durations) and sleep disturbances among a clinical sample of children with epilepsy. Design: A cross‐sectional actigraphic sleep study. Methods: A convenience sample of 141 children with epilepsy (1.5–6 years of age) was recruited from an outpatient pediatric neurology clinic of a university‐affiliated children's hospital in northern Taiwan. Participating families completed questionnaires and reported children's screen time use, with children wearing an actigraphy monitor for 7 days to assess sleep patterns. Multivariable linear regression analyses were conducted to examine the association of screen time exposure with the child's sleep patterns and sleep disturbance scores. Findings: Mean minutes per day of screen time exposure was 89.79 ± 83.94 min, with 62 parents (44.0%) reporting their child having >1 hr of screen time daily. Mean daily sleep duration was 9.26 ± 1.01 hr, with 106 children (93.0%) sleeping <10 hr in a 24‐hr period. In multivariate regression models, daily screen time exposure of >1 hour was associated with 23.4‐min later sleep onset (b = 0.39, p =.02), 20.4‐min later sleep offset (b = 0.34, p =.04), and more severe sleep disturbances (b = 2.42, p =.04). Conclusions: In toddlers and preschool‐age children with epilepsy, daily screen time exposure is greater and sleep duration is shorter than the recommended amount, with increased screen time exposure associated with disturbed sleep. Clinical Relevance: Parents need to be informed about the possible adverse impact of screen time exposure on children's sleep and health as well as the importance of limiting screen time exposure to <1 hr per day for their toddlers and preschool‐age children with epilepsy. [ABSTRACT FROM AUTHOR]

Background and objective: The epidemiology of pediatric acquired demyelinating disorders remains to be clarified in many parts of Asia. We carry out this study to depict the epidemiology of pediatric multiple sclerosis (MS), neuromyelitis optica (NMO), and optic neuritis (ON) in Taiwan. Methods: We conducted a retrospective nationwide population-based study using data from Taiwan's National Health Insurance Research Database. Prevalent cases of pediatric MS and NMO during 2001–2015, and incident cases of pediatric MS, NMO, and ON during 2003–2015 were identified. The demographic features and comorbidities were investigated. Results: We identified 403 MS, 42 NMO, and 1496 ON incident cases under the age of 20 during 2003–2015. The majority of pediatric MS (86.1%) and NMO (90.5%) patients were 10 years old or above. The incidence of MS and ON was relatively steady, while that of NMO increased prominently later during the study period. The average incidence of pediatric MS and NMO during 2011–2015 was 0.52 and 0.11 per 100,000 person-years, respectively. The female preponderance was evident for pediatric MS and NMO, and less so for pediatric ON. The most common autoimmune comorbidities for pediatric MS were thyrotoxicosis (1.0%) and systemic lupus erythematosus (0.7%). Conclusion: The epidemiology of pediatric MS was largely stationary in Taiwan during 2001–2015, while the prevalence of pediatric NMO rose steeply during this period, probably reflecting better recognition of this clinical entity. Autoimmune comorbidities were uncommon for pediatric MS and NMO in Taiwan. [ABSTRACT FROM AUTHOR]

We conducted a cross‐sectional study to examine sleep in mothers of children with epilepsy and its relation to their children's sleep. A total of 133 dyads of mothers and children with epilepsy aged 1.5–6 years were recruited between 2015 and 2018 from a children's hospital in northern Taiwan. Participating families provided demographic and health information, with children wearing an actigraphy monitor for 7 days and mothers completing sleep and depressive mood questionnaires. We found that 76 (57.1%) of the mothers had poor sleep quality, with 65 (48.9%) mothers having a clinically significant depressive symptom score. Mean actigraphic wake after sleep onset in children was 1.42 (standard deviation = 0.51) hours, with 126 (94.7%) of the children having a clinically significant sleep disturbance score. Multivariate regression analyses showed that higher depressive symptom scores in mothers (β = 0.14; p <.01) and higher sleep disturbance scores in children (β = 0.07; p =.04) were associated with poorer maternal sleep quality, even when maternal demographic characteristics and the child's clinical and epilepsy variables were considered. Findings from our study suggest that sleep disturbances are a shared problem for mothers and their children with epilepsy. Sleep in both mothers and their children with epilepsy should be evaluated in pediatric neurologic practices, with maternal depressive symptoms screened concurrently. Future pediatric epilepsy studies are warranted to examine whether a family‐based intervention program would be effective to improve sleep in mother‐child dyads and to promote better health and functioning of the entire family. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To describe sleep patterns in young children with epilepsy and to examine levels of agreement between measurements derived from actigraphy and diary recordings. Design: Cross‐sectional study. Methods: Eighty‐nine toddlers and preschool‐aged children with epilepsy wore an actigraph on their wrists for 7 consecutive days. Parents and caregivers maintained a concurrent sleep diary while the child was wearing the monitor. Levels of agreement between actigraphy and diary recordings were examined using the Bland and Altman method separately for all recording days, weekdays, and weekends. Findings: Discrepancies between actigraphy‐derived and diary‐documented sleep onset, sleep offset, actual sleep at night, wake after sleep onset, and daytime sleep were ±35, ±15, ±82, ±70, and ±29 min, respectively. Differences between actigraphy and diary‐derived sleep variables were consistently greater for weekends than for weekdays. Discrepancies between actigraphy and diary‐derived actual sleep at night were significantly greater for children who slept alone than for those who co‐slept with a parent. Conclusions: Our study demonstrates an acceptable agreement between actigraphy and diary recordings for sleep onset, sleep offset, and daytime sleep, but insufficient agreement for actual sleep at night and wake after sleep onset, with parents of children sleeping alone more likely to misestimate child sleep behaviors. Deviation of weekend sleep from weekdays further decreased the accuracy of parental sleep estimates and increased the discrepancies between actigraphy and diary. Clinical Relevance: Sleep in children with epilepsy assessed using diary recordings alone could be misleading, and actigraphy should be preferred over diaries when resources are available. [ABSTRACT FROM AUTHOR]

Background: Cyclic vomiting syndrome (CVS) is an episodic nausea and non-bilious vomiting disorder characterized by recurrent stereotypic symptoms with disease-free intervals. CVS in children is associated with a high prevalence of migraine, and is commonly considered a precursor to migraine. This study aimed to investigate the clinical manifestations of pediatric CVS and its prognosis, and to clarify its relationship with the risk of migraine development in children.Methods: The clinical features of children diagnosed with CVS before the age of 18 years at the designated hospital were retrospectively studied over the past 30 years (1976-2006) based on the Rome III or ICHD II criteria. Clinical evaluations, including age of onset, sex, family history, symptoms and duration during attacks, frequency, trigger events, electroencephalogram, treatment and subsequent development of migraine were assessed from chart records and telephone interviews.Results: Thirty-five children (17 males and 18 females) were enrolled. Their age of onset ranged from 2 to 17 years (mean, 6.8 ± 3.1 years) and frequency of attacks ranged from once to 36 times per year (mean, 8.2 ± 7.6 times). Duration of symptoms during each attack ranged from 1 to 45 days (mean, 5.9 ± 7.3 days). Of 20 children assessed for migraine development, seven subsequently developed typical migraine symptoms. There was younger onset age in the migraine-positive subgroup (5 ± 1.7 years) than in the migraine-negative subgroup (8.9 ± 3 years; p = 0.001). Co-morbid headache during CVS attack was also more evident in the migraine-positive subgroup (28.6%vs. 0%).Conclusion: Results of the study show that younger onset age and headache during CVS attacks may have increased risk of migraine development. Large-scale prospective studies are warranted to further clarify the relationship between CVS and migraine. [ABSTRACT FROM AUTHOR]

Spinal muscular atrophy (SMA) is caused by a defect in the survival motor neuron 1 (SMN1) gene. The Cooperative Study of the natural history of SMA Type I in Taiwan is a retrospective, longitudinal, observational study that helps in further understanding SMA disease progression in patients who have not received disease-modifying therapeutic interventions. Case report forms were used to collect demographics; genetic confirmation; SMN2 copy number; treatment patterns; and clinical outcomes including ventilator use, endotracheal tube intubation, tracheostomy, gastrostomy, complications, and survival. A total of 111 patients with SMA Type I were identified over the study period (1979–2015). Mean (median) age of onset and age at confirmed diagnosis were 1.3 (0.8) and 4.9 (4.4) months, respectively. SMN1 deletion/mutation was documented in 70 patients and SMN2 copy number in 32 (2 copies, n = 20; 3 copies, n = 12). At 240 months, survival probability for patients born during 1995–2015 versus 1979–1994 was significantly longer (p = 0.0057). Patients with 3 SMN2 copies showed substantially longer 240-month survival versus patients with 2 SMN2 copies. Over the 36-year period, mean (median) age at death was 31.9 (8.8) months. As of December 2015, 95 patients had died, 13 were alive, and 3 were lost to follow-up. The use of supportive measures (tracheostomy and gastrostomy) was associated with improved survival. These data describe the short survival of patients with SMA Type I in Taiwan in the pretreatment era, emphasizing the positive impact of supportive measures on survival. [ABSTRACT FROM AUTHOR]

Background Both refractory convulsive status epilepticus (SE) and super-refractory SE are medical emergencies. However, there are limited data on super-refractory SE in children. Thus, this study focuses on characterizing the demographics, outcomes, and prognostic factors for super-refractory SE in children. Methods This study was a retrospective analysis of super-refractory SE treated in a tertiary referral center in Taiwan. The functional outcome was evaluated by modified Rankin scale (mRS). Significant functional decline was defined as an mRS difference (before hospital admission and at discharge) of more than 2. The variates and the follow-up mRS values were then analyzed statistically. Results We enrolled 134 patients with 191 episodes of convulsive SE and identified 30 patients with 38 episodes of convulsive super-refractory SE. The incidence of convulsive super-refractory SE in the group with SE was 19.9%, and the age ranged from 2.5 months to 17 years. In-hospital mortality was 13.3%, which was much lower than that of adult cohorts. Newly acquired epilepsy and cognitive deficit occurred in 100% and 88.5%, respectively. Newly acquired epilepsy, as a sequel of super-refractory SE, was observed in all 18 patients (100%) who survived and had no history of epilepsy. Significant functional decline (mRS difference of more than 2) at discharge occurred in 76.7%. Poor functional outcome was associated with acute symptomatic etiology (P < 0.001) and the number of anesthetic agents (P = 0.002). The functional outcome improved after 1 year of follow-up in our population. Conclusions Super-refractory SE is associated with significant morbidity and mortality in children. However, the in-hospital mortality rate is much lower compared with adults. The functional outcome in children is associated with acute symptomatic etiology and the number of anesthetic agents and may improve after long-term follow-up. [ABSTRACT FROM AUTHOR]

• Children had a lower COVID-19 vaccination rate and a higher transmission rate. • Children with COVID-19 had more fever and higher peak fever than adults. • The home rapid antigen test had a suboptimal negative predictive rate in children. • The cycle threshold value of those with false-negative antigen tests was lower in children. The SARS-CoV-2 Omicron variant pandemic struck Taiwan in April 2022. Rapid antigen tests (RATs) play an important role in providing rapid results during a pandemic. However, self-collected samples by the children's caregivers without the supervision of medical personnel raise some concerns. This study was performed to investigate household transmission, clinical characteristics, and antigen performance in a special COVID-19 family clinic in a children's hospital. The performance of at-home RATs was evaluated based on reverse transcription-polymerase chain reaction. We included 627 patients in our study between May 11 and June 10, 2022. The COVID-19 full vaccination rate was significantly higher in adults (98.5%) than in children (5.9%, P <0.001). The transmission rate was significantly higher in children (91.3%) than in adults (76.6%, P <0.001). Infected children had more incidents of fever (82.4% vs 22.4%, P <0.001) and a higher peak fever than adults. Based on the reverse transcription-polymerase chain reaction, the negative predictive rate of the home RAT was only 38.7% (95% confidence interval: 31.9-46.0%) in children. The cycle threshold value of those with false-negative antigen tests was significantly lower in children. Children had a higher transmission rate, more fever, and higher peak fever than adults. Home RAT has a suboptimal negative predictive rate in children. [Display omitted] [ABSTRACT FROM AUTHOR]

Summary: Objective: To investigate the attentional processes and symptoms of attention-deficit hyperactivity disorder (ADHD) in pediatric patients with epilepsy and IQ greater than 70 in Taiwan. Methods: We assessed 61 children (male, 62.3%; full-scale IQ >70) with epilepsy, ages 6–16 years, and 61 sex-, age-, and parental education-matched typically developing children (controls). All participants completed the intelligence (WISC-III) and attention assessments (Conners’ Continuous Performance Test, CPT). The parents reported on the ADHD symptoms of their children. Results: Children with epilepsy had more omission errors and deviant response style (β) and scored lower in the Hit Reaction Time (RT) Block Change, reflecting inattention and slowness. Epileptic children with ADHD symptoms had longer and more variable Hit RT than those without ADHD and controls. Higher full-scale IQ was significantly associated with less change in Hit RT, Hit RT block, standard error, and inter-stimulus intervals. There were no effects from age of onset, duration of having epilepsy, etiology of epilepsy, and brain anomaly on the CPT profiles. Conclusion: The findings suggest that children with epilepsy, despite not mentally retarded, may have attention deficits. Hence, screening for attention problems among patients with epilepsy regardless of intelligence level and ADHD symptoms is recommended to offset possible learning adversities of this population. [Copyright &y& Elsevier]

Both epilepsy and tic disorders may share common mechanisms with the involvement of abnormal cortical-basal ganglion circuit connection and dopaminergic dysfunction. However, the association between epilepsy and tic disorders has never been studied. This study investigated the risks of developing tic disorders among children with epilepsy using databases of a universal health insurance system in Taiwan. The data analyzed in this study were retrieved from the National Health Insurance Research Database in Taiwan. The study cohort included children with epilepsy between 2001 and 2007 (n=2629) and a three-fold age- and gender-matched controls (n=7887). All subjects were followed up for 3 years from the date of cohort entry to identify their admissions due to tic disorders (ICD-9-CM codes 307.2, 307.20-307.23). Cox hazard regression analysis was performed to estimate the effect of epilepsy on the occurrence of tics. The epilepsy cohort had a higher prevalence of tics (1.7% vs. 0.2%), and a 8.70-fold increased risk of developing a tic disorder compared with the controls (adjusted hazard ratio (AHR) 8.70, 95% confidence interval (CI) 4.26-16.37, p<0.001). Male patients were observed to have a higher risk of developing a tic disorder (AHR 1.90, 95% CI=1.04-3.46, p<0.001) compared to female individuals. Patients with multiple antiepileptic drugs treatment also exhibited higher crude OR for developing tic disorders. This nationwide population-based cohort study, for the first time, demonstrated that there is a significantly increased risk for tic disorders among children with epilepsy. We also found males, attention deficit disorder and the use of multiple AEDs to be independent risk factors of tic disorders. Closely evaluating possible tic disorders would be crucial for improving the outcome and life quality in children with epilepsy. [ABSTRACT FROM AUTHOR]

The association between epilepsy and Tourette syndrome has rarely been investigated. In this retrospective cohort study, we analyzed a dataset of 1,000,000 randomly sampled individuals from the Taiwan National Health Insurance Research Database to determine the risk of epilepsy in children with Tourette syndrome. The study cohort consisted of 1062 patients with Tourette syndrome aged ≤ 18 years, and the control group consisted of three times the number of age- and sex-matched patients without Tourette syndrome, who were insurants, from the same database during the same period. The Tourette syndrome group had an 18.38-fold increased risk of epilepsy than the control group [hazard ratio=18.38, 95% confidence interval (CI)=8.26-40.92; P<0.001]. Even after adjusting for the comorbidities, the risk of epilepsy in the Tourette syndrome group with comorbidities remained high (hazard ratio=16.27, 95% CI=6.26-18.46; P<0.001), indicating that the increased risk was not associated with comorbidities. This population-based retrospective cohort study provides the first and strong evidence that Tourette syndrome is associated with a higher risk of epilepsy. A close follow-up of children with Tourette syndrome for the development of epilepsy is warranted. [ABSTRACT FROM AUTHOR]

Preterm infants are at risk for emotional difficulties and behavioral problems. This study was aimed to investigate the effects of a clinic-based intervention program (CBIP) and a home-based intervention program (HBIP) compared with a usual care program (UCP) on emotion regulation to stress in preterm infants with very low birth weight (VLBW, birth weight <1500 g). A total of 178 VLBW preterm infants had been previously randomly assigned to receive one of three interventions (57 in CBIP, 63 in HBIP and 58 in UCP). The CBIP and HBIP contained identical child-, parent- and dyad-focused interventions that were provided to infants during hospitalization and were respectively delivered at clinics and at home at PMA 36-38 and 40 weeks, and 1, 2, 4, 6, 9, 12 months of corrected age. All infants were prospectively observed for behavioral reactivity and regulation in response to experimentally evoke stress evoked by a toy-behind-barrier procedure at 12, 18, and 24 months of corrected age. Their cognitive and language abilities, and mothers' responsiveness were also assessed at 12 months as potential covariates. Compared to the UCP-group infants, the HBIP-group infants exhibited shorter durations of visual orientation to a toy (adjusted difference [95% CI]=-1.60 [-3.07 to -0.13], p=0.03), and the CBIP-group infants exhibited shorter durations of avoidance (adjusted difference [95% CI]=-0.84 [-1.57 to -0.10], p=0.03) from 12 to 24 months of corrected age. The CBIP and HBIP showed no difference in the stress reactivity from the UCP, however. These results suggest that comprehensive interventions incorporating child-, parent- and dyad-focused services enhanced VLBW preterm infants' emotion regulation in response to stress at toddler age. [ABSTRACT FROM AUTHOR]

Highlights: [•] The BSID-II and Bayley-III were concurrently administered in this study. [•] The Bayley-III was reliable and generally contained similar constructs as the BSID-II. [•] The Bayley-III overestimated the developmental performance of Taiwanese infants. [•] Upward adjustments of the Bayley-III scores for definition of developmental delay were suggested. [Copyright &y& Elsevier]

Abstract: Introduction: Intervention studies of developmental care for preterm infants in Western societies have shown early but unsustainable effects on child outcomes, however only a limited of studies have examined if developmental care interventions produce similar effects in Eastern cultural contexts. Aims: To examine the effectiveness of in-hospital developmental care on neonatal morbidity, growth and development of preterm infants with very low birth weight (VLBW; birth weight<1500g) in Taiwan. Methods: One hundred and seventy-eight VLBW preterm infants were randomly assigned to the clinical trial during hospitalization at three hospitals in Taiwan; the control group received five sessions of standard child-focused developmental care and the intervention group received five sessions of child- and parent-focused developmental care. Sixty-two normal term infants were also included as a comparison group. Infants were examined for morbidity, growth and developmental outcomes at term age. Results: At study entry, more infants in the intervention group were twins or multiples than those in the control group (29% vs. 16%, p =0.05). After adjusting for birth set, the intervention group had lower incidences of stage II–III retinopathy (odds ratio [OR]=0.34 [95% confidence interval (CI): 0.15–0.79]; p =0.01) and feeding desaturation (OR=0.32 [95% CI: 0.10–1.00]; p =0.05) and had greater daily weight gains (difference=2.0g/day [95% CI: 0–4.0g/day]; p =0.05) as compared with the control group. However, the intervention and control groups did not differ in any of the neurodevelopmental measures. Conclusions: In-hospital developmental care has short-term benefits for Taiwanese VLBW preterm infants in reducing the risk of retinopathy and feeding desaturation as well as in enhancing weight gains at term age. [Copyright &y& Elsevier]

Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system. However, the clinical features of childhood-onset multiple sclerosis in Asia have been rarely reported. This report presents our experience in 21 patients with multiple sclerosis (15 females, 6 males, mean age 12.4 ± 4.5 years) in Taiwan with the onset age before 18. The most common presenting symptoms were limb weakness (62%) and visual disturbance (43%). Poly-symptomatic presentations were found in 16 (76%) patients. Magnetic resonance imaging demonstrated basal ganglion involvement in 33.3% of the patients. Neuroimaging and neurophysiologic evaluations revealed optic nerve involvement in 13 (62%) patients. Only one child had the optico-spinal form. Eighteen (86%) patients had a relapsing remission course, whereas three (14%) patients had secondary progressive course. Three (14%) patients initially diagnosed with acute disseminated encephalomyelitis developed multiple sclerosis after 4 months, 2 years, and 6 years, respectively. In conclusion, childhood multiple sclerosis in Taiwan is frequently poly-symptomatic, and is characterized by a higher ratio of optic nerve and basal ganglion involvement. However, the optico-spinal form of multiple sclerosis occurs rarely in children in Taiwan. Our experience suggests that the chance of relapsing should not be overlooked in patients presenting with clinical and neuroimaging findings suggestive of acute disseminated encephalomyelitis. [Copyright &y& Elsevier]

Lacosamide (LCM) was initially approved in Taiwan in March 2014 for use as adjunctive therapy for focal impaired awareness seizures and secondarily generalized seizures (SGS) in patients with epilepsy ≥ 16 years of age. The efficacy and tolerability of adjunctive LCM for the treatment of patients with focal seizures have been demonstrated in randomized, placebo-controlled trials. However, the trials do not reflect a flexible dose setting. This study (EP0063) was conducted to assess the safety and tolerability of LCM in real-world clinical practice in Taiwan. Effectiveness of LCM was also assessed as an exploratory objective. EP0063 was a multicenter, prospective, noninterventional study with an expected observation period of 12 months ± 60 days. Eligible patients were ≥ 16 years of age, had focal impaired awareness seizures and/or SGS (in line with approved indication in Taiwan at the time of the study), were taking at least one concomitant antiseizure medication (ASM), and had at least one seizure in the 3 months before baseline. Patients were prescribed LCM by their treating physician in the course of routine clinical practice. The primary safety variable was treatment-emergent adverse events (TEAEs) spontaneously reported to, or observed by, the treating physician. Based on safety data from previous studies of LCM and known side effects of other ASMs, certain TEAEs (including but not limited to cardiac and electrocardiogram, suicidality, and rash related terms) were analyzed separately. Effectiveness variables included Clinical Global Impression of Change (CGIC) and change in 28-day seizure frequency from baseline to 12 months (or final visit), and freedom from focal seizures. A total of 171 patients were treated with LCM, of whom 139 (81.3%) completed the study. The Kaplan–Meier estimated 12-month retention was 82.9%. Patients had a mean (standard deviation [SD], range) age of 38.5 (14.0, 16–77) years, and 96 (56.1%) were male. Patients were taking a mean (SD, range) of 2.8 (1.1, 1–6) ASMs at baseline. Mean (SD, range) duration of LCM treatment was 288.7 (111.9, 2–414) days, and the mean (SD, range) daily dosage of LCM was 205.0 (82.7, 50.0–505.2) mg/day. Overall, 95 (55.6%) patients reported at least one TEAE, most commonly dizziness (33 [19.3%] patients). Drug-related TEAEs were reported in 74 (43.3%) patients, and drug-related TEAEs leading to discontinuation of LCM were reported in 14 (8.2%) patients. Two (1.2%) patients died during LCM treatment, which were considered not related to LCM. Two (1.2%) patients had suicidality-related TEAEs; these TEAEs were considered either not related to LCM or the relationship was not recorded. Rash-related TEAEs were reported in five (2.9%) patients (considered LCM-related in two patients). Based on the CGIC, at 12 months (or final visit), 109 (63.7%) patients were considered to have improved, 54 (31.6%) had no change, and the remaining eight (4.7%) were minimally worse. At 12 months (or final visit), the median percentage change in focal seizure frequency was –50.0. During the first 6 months of the study, 21 (12.3%) patients were free from focal seizures; 37 (21.6%) patients were free from focal seizures in the last 6 months of the study; and 14 (8.2%) were free from focal seizures for the full 12 months of the study. Results of this prospective, noninterventional study suggest that adjunctive LCM was generally safe and well tolerated in this patient group in real-world practice in Taiwan. Effectiveness was also favorable, with more than 60% of patients considered to be improved by their physician at 12 months (or final visit). • One hundred thirty-nine of 171 patients (81.3%) completed this 12-month observational LCM study in Taiwan. • Adjunctive LCM was generally safe and well tolerated in this patient group. • Overall, 55.6% of patients reported at least one TEAE, most commonly dizziness. • Drug-related TEAEs leading to discontinuation occurred in 8.2% of patients. • At 12 months, 63.7% of patients were considered improved by their physician. [ABSTRACT FROM AUTHOR]

Background: The incidence of pediatric hospitalizations has significantly increased since the spread of the omicron variant of COVID-19. Changes of characteristics in respiratory and neurological symptoms have been reported. We performed a retrospective, cross-sectional study to characterize the MRI change in children with an emphasis on the change of cerebral vasculatures., Methods: We retrospectively collected clinical and MRI data of 31 pediatric patients with neurological symptoms during the acute infection and abnormalities on MRI during the outbreak of omicron variant from April 2022 to June 2022 in Taiwan. The clinical manifestations and MRI abnormalities were collected and proportion of patients with vascular abnormalities was calculated., Results: Among 31 pediatric patients with post-COVID-19 neurological symptoms, MRI abnormalities were observed in 15 (48.4%), predominantly encephalitis/encephalopathy (73.3%). Notable MRI findings included focal diffusion-weighted imaging (DWI) hyperintensity in cerebral cortex and thalamus, diffuse cortical T2/DWI hyperintensity, and lesions in the medulla, pons, cerebellum, and splenium of corpus callosum. Vascular abnormalities were seen in 12 (80%) patients with MRI abnormalities, mainly affecting the middle cerebral arteries. The spectrum of neurological manifestations ranged from seizures to Alice in Wonderland syndrome, underscoring the diverse impact of COVID-19 on pediatric patients., Conclusion: A high proportion of vascular abnormalities was observed in pediatric patients with neurological involvements, suggesting that vascular involvement is an important mechanism of neurological manifestations in omicron variant infection., Competing Interests: Declaration of competing interest None of the authors has any potential conflict exists., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: The SARS-CoV-2 virus has been a global public health threat since December 2019. This study aims to investigate the neurological characteristics and risk factors of coronavirus disease 2019 (COVID-19) in Taiwanese children, using data from a collaborative registry., Methods: A retrospective, cross-sectional, multi-center study was done using an online network of pediatric neurological COVID-19 cohort collaborative registry., Results: A total of 11160 COVID-19-associated emergency department (ED) visits and 1079 hospitalizations were analyzed. Seizures were the most common specific neurological symptom, while encephalitis and acute disseminated encephalomyelitis (ADEM) was the most prevalent severe involvement. In ED patients with neurological manifestations, severe neurological diagnosis was associated with visual hallucination, seizure with/without fever, behavior change, decreased GCS, myoclonic jerk, decreased activity/fatigue, and lethargy. In hospitalized patients with neurological manifestations, severe neurological diagnosis was associated with behavior change, visual hallucination, decreased GCS, seizure with/without fever, myoclonic jerk, fatigue, and hypoglycemia at admission. Encephalitis/ADEM was the only risk factor for poor neurological outcomes at discharge in hospitalized patients., Conclusion: Neurological complications are common in pediatric COVID-19. Visual hallucination, seizure, behavior change, myoclonic jerk, decreased GCS, and hypoglycemia at admission are the most important warning signs of severe neurological involvement such as encephalitis/ADEM., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: Since April 2022, a notable increase in COVID-19 cases with the rapid spread of the SARS-CoV-2 Omicron variant has been reported in Taiwan. In the epidemic, children were one of the most vulnerable groups, so we analyzed their clinical presentations and factors associated with severe complications of COVID-19 in children., Methods: We included hospitalized patients under 18 years old with lab-confirmed SARS-CoV-2 infection from March 1, 2022, to July 31, 2022. We collected the demographic and clinical characteristics of the patients. Patients requiring intensive care were defined as severe cases., Results: Among the 339 enrolled patients, the median age was 31 months (interquartile range (IQR), 8-79.0 months); and 96 patients (28.3%) had underlying diseases. Fever was noted in 319 patients (94.1%) with a median duration of two days (IQR 2-3 days). Twenty-two patients (6.5%) were severe cases, including 10 patients (2.9%) with encephalopathy with abnormal neuroimaging and ten patients (2.9%) with shock. Two patients (0.6%) died. Patients with congenital cardiovascular disease (aOR: 21.689), duration of fever up to four days or more (aOR: 6.466), desaturation (aOR: 16.081), seizure (aOR: 20.92), and procalcitonin >0.5 ng/mL (aOR: 7.886) had a higher risk of severe COVID-19., Conclusions: Vital signs need close monitoring, early management and/or intensive care may be applied in COVID-19 patients with congenital cardiovascular diseases, fever lasting ≥4 days, seizures, desaturation and/or elevated procalcition since they are at higher risks of severe diseases., Competing Interests: Conflicts of interest None of the authors declare conflicts of interest associated with this manuscript., (Copyright © 2023. Published by Elsevier B.V.)

Background: Hereditary neuromuscular diseases (NMDs) are a group of rare disorders, and the diagnosis of these diseases is a substantial burden for referral centers. Although next-generation sequencing (NGS) has identified a large number of genes associated with hereditary NMDs, the diagnostic rates still vary across centers., Methods: Patients with a suspected hereditary NMD were referred to neuromuscular specialists at the National Taiwan University Hospital. Molecular diagnoses were performed by employing a capture panel containing 194 genes associated with NMDs., Results: Among the 50 patients referred, 43 had a suspicion of myopathy, and seven had polyneuropathy. The overall diagnostic rate was 58%. Pathogenic variants in 19 genes were observed; the most frequent pathogenic variant found in this cohort (DYSF) was observed in only four patients, and 10 pathogenic variants were observed in one patient each. One case of motor neuron disease was clinically mistaken for myopathy. A positive family history increased the diagnostic rate (positive: 72.7% vs. negative: 56.3%). Fourteen patients with elevated plasma creatine kinase levels remained without a diagnosis., Conclusion: The application of NGS in this single-center study proves the great diversity of hereditary NMDs. A capture panel is essential, but high-quality clinical and laboratory evaluations of patients are also indispensable., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2022 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: The long-term outcome of optic neuritis (ON) is heterogeneous, and it appears to vary among different populations. Identification of determinants of natural history of ON would be helpful in therapeutic planning and prognostication, while relevant investigations in Asian patients were less reported. This study aims to clarify whether comorbidities and treatment in ON patients are associated with differential risks of subsequent development of multiple sclerosis (MS) or neuromyelitis optica (NMO) in Taiwan., Methods: We conducted the nationwide population-based cohort study using data from Taiwan's National Health Insurance Research Database. Incident ON cases during 2003~2014 were followed until the end of 2015. Pediatric and adult sub-cohorts were examined separately. The associations between immune-related comorbidities or treatment and outcomes were analyzed using Cox proportional hazards models., Results: A total of 11,923 adult and 1365 pediatric ON patients were enrolled. The rates of subsequent development of MS were 2.7% for adult and 3.1% for pediatric ON with median follow-up duration of 6.3 and 7.3 years respectively, while 1.2% of pediatric and adult ON evolved to NMO. Comorbid systemic lupus erythematosus was associated with increased risks of subsequent development of MS in adult (adjusted hazard ratio [aHR], 2.80; 95% CI, 1.04-7.49) and pediatric ON patients (aHR, 21.65; 95% CI, 1.29-363.4). Adult ON patients were at increased risks of NMO if comorbid with myasthenia gravis (aHR, 9.13; 95% CI, 1.20-69.45) or Sjogren's syndrome (aHR, 4.71; 95% CI, 1.74-12.76)., Conclusion: ON could be the sentinel event linking several peripheral autoimmune comorbidities to distinct forms of central nervous system demyelination., (Copyright © 2020 Elsevier B.V. All rights reserved.)

About 10-30% of pediatric patients with epilepsy have drug-resistant epilepsy. Genetic panels may be useful in identifying etiology and guiding treatment in pediatric patients with drug-resistant epilepsy. In our tertiary center, we used two epilepsy panels, an initial 24-genes panel followed by a more comprehensive 122-genes panel to screen for genetic cause over recent 2 years. A total of 96 patients with drug-resistant epilepsy were evaluated using the 24-genes panel, which revealed 10 (10.4%) of the patients with pathogenic variants. Another 22 patients without causative genetic variants using first-gene panel were evaluated using the 122-genes panel. Out of the 22 patients, 4 had pathogenic variants, and 6 had variants of unknown significance. The total yield rate for the second panel was 18.2% (4/22). In conclusion, although whole exome sequencing has entered clinical practice, epilepsy gene panels may still play some roles because of lower cost and faster time, especially in those with fever-associated epilepsy., Competing Interests: Declaration of competing interest None of the authors have a conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background/purpose: Little is known about whether Asian children with epilepsy have more attention-deficit hyperactivity disorder (ADHD)-related symptoms, emotional/ behavioral problems, and physical conditions compared with those described in Western studies. The authors investigated the rates of ADHD-related symptoms, emotional/behavioral problems, and physical conditions among pediatric patients with epilepsy., Methods: We recruited 61 patients with epilepsy, aged 6-16 years, and 122 age-, sex-, and parental education-matched school controls. Data on demographics, parental reports on the Child Behavior Checklist (CBCL) and Swanson, Nolan, and Pelham, version IV scale (SNAP-IV), and medical records were collected., Results: The average full-scale intelligence quotient of the case group was 95.8. There were 11 (18.0%), 7 (11.5%), 26 (42.6%), and 26 (42.6%) of children with epilepsy ever clinically diagnosed with developmental delay, overt ADHD symptoms, allergies reported by physicians, and behavior problems measured by the CBCL, respectively. Those children with epilepsy had more severe ADHD-related symptoms and a wider range of emotional/behavioral problems than controls (Cohen's d 0.36-0.80). The rate of potential cases of ADHD among children with epilepsy was 24.6%. A history of developmental delay predicted ADHD- related symptoms and internalizing and externalizing problems. Among children with epilepsy, a longer duration of treatment with antiepileptic drugs predicted externalizing problems, and an earlier onset of epilepsy predicted inattention and hyperactivity/impulsivity., Conclusion: Our findings imply that clinicians should assess physical and emotional/behavioral problems among children with epilepsy in order to provide interventions to offset possible adverse psychiatric outcomes., (Copyright © 2012. Published by Elsevier B.V.)

Mitochondrial DNA (mtDNA) deletion is a rare occurrence that results in defects to oxidative phosphorylation. The common clinical presentations of mtDNA deletion vary but include mitochondrial myopathy, Pearson syndrome, Kearns-Sayre syndrome, and progressive external ophthalmoplegia. Here, we report the case of a 10-year-old boy who presented with progressive deterioration of his clinical status (which included hypoglycemia, short stature, sensorineural hearing loss, retinitis pigmentosa, and chronic gastrointestinal dysmotility) that progressed to acute deterioration with pancreatitis, Fanconi syndrome, lactic acidosis, and acute encephalopathy. Following treatment, the patient was stabilized and his neurological condition improved. Through a combination of histological examinations and biochemical and molecular analyses, mitochondrial disease was confirmed. A novel 3670-base pair deletion (deletion of mtDNA nt 7,628-11,297) was identified in the muscle tissue. A direct repeat of CTACT at the breakpoints was also detected., (Copyright © 2012. Published by Elsevier B.V.)

Congenital insensitivity to pain with anhidrosis (hereditary sensory and autonomic neuropathy type IV) is a rare autosomal recessive disorder caused by a defect in neurotrophic tyrosine kinase receptor and nerve growth factor, as reported in previous studies. This report is of a 6-month-old male infant with typical symptoms and signs of congenital insensitivity to pain with anhidrosis. He had a homozygous insertion mutation with c.2086&#95;2087 ins C of neurotrophic tyrosine kinase receptor type 1 (NTRK1) gene with both parents as heterozygous carriers. This mutation may have a strong relation to hereditary sensory and autonomic neuropathy type IV Taiwanese patients. This is the youngest reported patient in Taiwan and first reported with congenital insensitivity to pain with mutation of NTRK1 gene inherited from the parents. Early diagnosis may provide appropriate medical care and education for these children and their families for better prognosis.

Benign convulsions with mild gastroenteritis were afebrile seizures associated with gastroenteritis in previously healthy infants or young children. It has been thought to be a continual spectrum of benign infantile convulsions because of overlapping clinical pictures. Recently, molecular genetic studies have suggested a channelopathy in benign infantile convulsions. The authors prospectively studied the clinical features of benign convulsions with mild gastroenteritis in Taiwanese children and clarified the relationship between neuronal sodium channel alpha 1 subunit (SCN1A) gene and benign convulsions with mild gastroenteritis. The clinical pictures in their patients were similar to those of previous studies except for the low rate of positive rotavirus antigen in the stool, which may indicate a season-related viral infection. No mutations in the SCN1A gene were identified in all patients. This study suggested that SCN1A mutations are probably not associated with benign convulsions with mild gastroenteritis. Other possible pathogenic mechanisms need to be researched in the future.

To identify clinical, neurophysiological and neuroradiological features in acute encephalitis with predictive value for postencephalitic epilepsy (PEE) in children, a retrospective cohort study by following up 0-17-year-old children with the diagnosis of acute encephalitis was done. Total 330 children were enrolled. Of these, 54 (16.4%) developed epilepsy with a mean follow-up period of 6+/-4.6 years, and 79.6% had the diagnosis of epilepsy within six months after encephalitis. Significant risk factors for PEE include the presence of recurrent seizures, status epilepticus, severe disturbance of consciousness, the existence of focal neurological sign, and the presence of neurological deterioration during hospitalization. Patients with abnormal electroencephalogram, including focal (P<0.05), or profound cerebral dysfunction (P<0.001), and focal cortical abnormalities in neuroimaging (P<0.01), also have higher incidence of epilepsy. Furthermore, children with refractory status epilepticus at presentation also significantly increased the possibility of intractable PEE (P<0.01). We concluded that PEE is not a rare complication of acute encephalitis. Children with refractory status epilepticus or poor control of seizures are more likely to have intractable PEE.

Occipital lobe epilepsy in children can present as an idiopathic form (i.e., childhood epilepsy with occipital paroxysms) or as a symptomatic form. Forty-three children (18 boys, 25 girls) were divided into the idiopathic group or symptomatic group, according to the classification for epileptic seizures of the International League Against Epilepsy. Patients in the idiopathic group were further subdivided into the Panayiotopoulos or Gastaut type, according to clinical presentation. The idiopathic group consisted of 15 children (5 boys, 10 girls), of whom 11 were of the Panayiotopoulos type and 4 of the Gastaut type. The symptomatic group consisted of 28 children (13 boys, 15 girls). The average age of seizure onset in the idiopathic group was younger than in the symptomatic group (6.5 +/- 2.4 vs 8.5 +/- 3.0 years). Ictal vomiting was more common in the idiopathic group, and positive visual symptoms were more common in the symptomatic group. Mean epilepsy duration in the idiopathic group was shorter (5.7 +/- 5.3 vs 20.1 +/- 16.0 months), and the response to treatment was better. The average age of seizure onset was much younger in the Panayiotopoulos than in the Gastaut type (5.4 +/- 1.5 vs 9.5 +/- 1.5 years), and mean epilepsy duration was also shorter (3.9 +/- 4.2 vs 10.5 +/- 4.9 months). Seizure semiology can distinguish between idiopathic occipital lobe epilepsy and the symptomatic form with ictal vomiting and positive visual symptoms. In idiopathic occipital lobe epilepsy, the Panayiotopoulos type has better prognosis than the Gastaut type.

To study the efficacy of adrenocorticotrophic hormone (ACTH) in treating Taiwanese children with West syndrome (WS) and the impact on long-term prognosis, 66 patients with WS (54 symptomatic and 12 cryptogenic) were collected from 1987 to 1998 in a medical center in Taiwan. A total of 53 patients were enrolled in this study and treated with ACTH at the dosage of 2.5IU/kg daily for 2 weeks with gradual tapering in subsequent 6 weeks. Immediate responses, side effects of ACTH and long-term outcomes of the patients including seizure and developmental status were evaluated during the average follow-up period of 35.6 months. The spasm-free percentage after one or two courses of ACTH treatment was 77.4%. Nine (17%) patients encountered severe side effects such as major infections, which prompted us to stop ACTH. At the end of follow-up, 22 (41.5%) patients had intractable seizures but 25 (47.2%) patients remained seizure free with or without anticonvulsants. The ACTH-responders had a better chance of remaining seizure free (P<0.05). Regarding the long-term developmental outcome, 12 (22.6%) patients had normal or borderline development; two thirds of them belonged to the crytpogenic group. Six (11.3%) patients expired and 24 (45.3%) were severely retarded; all but one of them belonged to the symptomatic group. The prognosis of WS heavily relies on whether a patient is cryptogenic or symptomatic (P<0.001). Good response to therapy or short treatment lag did not favorably affect the developmental outcomes of the symptomatic cases. We conclude that the long-term outcomes of WS in Taiwan were generally poor despite of treatment. Only cryptogenic patients had favorable prognosis. For symptomatic patients, ACTH therapy may be used to control the spasms and decrease the incidence of subsequent epilepsy, but it will not improve developmental outcome. Considering a high percentage of severe side effects in our study, a lower dosage of ACTH with adequate therapeutic efficacy but less side effects should be considered for treating Taiwanese children with WS.

This study investigated the clinical manifestations and outcomes of central nervous system (CNS) infection by enteroviruses. Cases with CNS involvement among all enterovirus-culture-positive cases from January 1995 to June 2003 were retrospectively reviewed. Among 1028 enterovirus-culture-positive cases, there were 333 cases involving the CNS. Of these, the ratio of male to female subjects was 1.78, and the mean (+/- standard deviation) age was 6.83 +/- 5.9 years; 21 were premature neonates, and 10 failed to thrive. Disease entities included 282 cases of aseptic meningitis (84.7%), 44 cases of encephalitis (13.2%), and 7 cases of encephalomyelitis/polio-like syndrome (2.1%). Of these cases, 97.9% (326/333) had fever with peak body temperature at 38.9 degrees C, 85% had headache and vomiting, 70% had meningeal signs, 64% had neck stiffness, 16.6% (55/333) had change of consciousness, 5.4% (18/333) had seizures and 5.2% (17/333) had myoclonic jerks. Mannitol was administered in 77.2% of patients (257/333), along with intravenous immunoglobulin in 6.6% (22/333). Twelve cases received ventilator support. One patient died of hand-foot-and-mouth disease, encephalitis plus cardiopulmonary failure, and 2 premature neonates died of hepatic failure, disseminated intravascular coagulation, sepsis-like syndrome and myocarditis. Eighteen had neurologic sequelae, including 7 with limb weakness, 5 with epilepsy, 2 with sixth cranial nerve palsy, 3 with cerebral palsy, 4 with psychomotor retardation, 2 with spasticity, and 1 with hearing loss. Factors associated with unfavorable outcomes (death or sequelae) included younger age (p=0.0003), higher peak white blood cell count (WBC) [p=0.0009] and skin rash (p=0.005). Younger age and higher peak WBC were poor prognostic factors of severe enterovirus CNS infection. Death was related to neonatal enterovirus infection and enterovirus 71 infection in young children.

X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder and identified in many races without apparent predilection for any race. This study was designed to investigate the clinical and therapeutic aspects of X-ALD in Taiwanese children with this disorder. We retrospectively reviewed all children admitted to NTUH from Nov. 1993 to Aug. 2002 with the diagnosis of ALD, defined by increased very long chain fatty acid (VLCFA). The mean age at diagnosis of the patients was 7.4 years (range, 2.8 to 13 years). Seven out of 9 patients had abnormal brain magnetic resonance image (MRI) studies. Three patients received bone marrow transplantation. Of these, two died of severe graft-versus-host disease and the other remained stable. Of the remaining 6 patients, two patients were in vegetative status and the other two patients were neurologically normal. X-ALD in Taiwanese children had similar clinical manifestations as reviewed in western countries. Symmetrical demyelination in parieto-occipital region and the accumulation of contrast material at the edge of the lesion are the typical MRI findings. Proton MR spectroscopy (MRS) can be used to evaluate either the asymptomatic patient or patient with normal brain image. Performance of T-cell depletion bone marrow transplantation or cord blood transplantation is suggested for X-ALD with early cerebral involvement.

We analyze the respective roles of neuro-imaging and EEG in the assessment of 11 children with holoprosencephaly and epilepsy. Seizures were present in seven patients (64%); six were treated with antiepileptic drugs; five had intractable epilepsy. Two of the patients with intractable epilepsy became seizure-free under polytherapy. Fourteen EEG recordings were performed in eight patients. The abnormal EEG findings included slow waves, focal epileptiform discharges, slow spike-and-wave complexes, hypsarrhythmia, frontal fast activity, fronto-occipital gradients of amplitudes (posterior amplitude attenuation), lack of photic driving, periodic discharges, and extremely large amplitudes. A fronto-occipital gradient was found only in alobar and semilobar holoprosencephaly (HPE), while hypsarrhythmia only in lobar HPE. Lack of photic driving was found only in alobar HPE. All EEGs showed diffuse slow waves, and all patients had severe developmental delay. The Deep Gray Score(DGS) in neuroimaging studies, thought to predict clinical outcome, was irrelevant given the presence and intractability of the epilepsies. Patients with higher DGS, nonetheless, tended to have higher mortality rate. In conclusion, EEG evaluation provides additional functional information to neuroimaging studies in the assessment of neurological outcome in patients with HPE. With a more mature and well-formed cerebrum, as found in the lobar and semilobar types, the possibility of hypsarrhythmia and photic driving increased, while that of fronto-occipital gradients decreased.

Enterovirus infection has been rarely reported to cause cerebral infarction in infants. We describe a 2-month-old boy with right focal seizure and right hemiparesis associated with enterovirus infection during an epidemic of enterovirus 71 infection in Taiwan in 1998. Magnetic resonance imaging and angiography showed vasculitis in the left anterior cerebral artery with cerebral infarction. In the unclarified pathogenesis of cerebral disease in enterovirus infection, this case suggests focal vasculitis with subsequent cerebral infarction. Enterovirus-related vasculitis of the central nervous system is thus another consideration when facing a child with focal seizure, acute hemiplegia and cerebral infarction.

Neonatal-type nonketotic hyperglycinemia treatment remains unsatisfactory, even if started early. A review of six patients who underwent treatment for neonatal-type nonketotic hyperglycinemia in our hospital is presented. All patients were treated with a standardized protocol. Medical histories were retrieved from case notes. All six patients had elevated cerebrospinal fluid plasma glycine levels initially. All but one had received sodium benzoate and dextromethorphan from 1 month of age. All suffered from intractable seizures and severe mental retardation, and only two patients remain alive. One patient died at 5 days of age. No resuscitation was attempted in accordance with the family's wish after genetic counseling. The prognosis of neonatal nonketotic hyperglycinemia remains poor with current treatment. Genetic counseling helps parents cope with this devastating genetic disease.