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OBJECTIVE: This study aimed to investigate the prevalence of autism spectrum disorder and its possible correlations with clinical characteristics in patients with infantile epileptic spasms syndrome in a single center in Brazil. METHODS: This retrospective cross-sectional study examined 53 children with the diagnosis of infantile epileptic spasms syndrome prior to an autism spectrum disorder assessment. Participants were divided into two groups based on the presence or absence of autism spectrum disorder. Available variables (sex, medications, median age at onset of infantile epileptic spasms syndrome, and presence of comorbidities) were compared using Mann-Whitney U or chi-square tests. RESULTS: Among the included patients, 12 (23 %) were diagnosed with autism spectrum disorder, corresponding to a relative risk of 0.29 (95 % confidence interval 0.174-0.492). The age at the first seizure ranged from 3 to 15 months, with a mean of 6.65 months. This age significantly differed between participants with autism spectrum disorder (10.58 months) and those without (5.43 months), p

• VGB effectiveness for IESS was evaluated based on etiology excluding TSC. • Overall effectiveness of VGB for IESS with variable etiologies was 39.0 % (16/41 cases). • VGB effectiveness for congenital structural diseases was 9.1 % (1/11 cases). • Alternative treatments should be considered for congenital structural diseases. We aimed to assess the effectiveness of vigabatrin (VGB) in patients diagnosed with infantile epileptic spasm syndrome (IESS) and categorize these patients based on their etiologies. This retrospective study included patients diagnosed with IESS who exhibited epileptic spasms before the age of 2 years between January 1, 2015, and October 31, 2023 at Saitama Children's Medical Center. Patients with tuberous sclerosis as the identified etiology were excluded. The effectiveness of VGB was assessed based on the resolution of ES for three months with the absence of hypsarrhythmia on interictal electroencephalogram. This study analyzed 41 patients (26 boys). The etiologies included genetic, congenital structural, acquired structural, and unknown in 12, 11, 10, and 8 patients, respectively. Patient characteristics did not significantly differ among the four groups. The overall effectiveness of VGB for IESS was 39.0 % (16/41). Categorized based on etiology, VGB was effective in 41.7 % (5/12), 9.1 % (1/11), 50 % (5/10), and 75 % (6/8) in the genetic, congenital structural, acquired structural, and unknown groups, respectively. Statistical analysis revealed a significant difference in effectiveness among the four groups (p = 0.03). Categorized based on diseases, VGB was effective in 28.6 % (2/7) and 50 % (4/8) in trisomy 21 and perinatal brain injury, respectively. The effectiveness of VGB in patients with IESS varied with etiology. Further investigations into the effectiveness of VGB in etiological subtypes of IESS could facilitate the development of tailored treatment algorithms for each etiology, representing valuable guidelines for future medical practice. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the prevalence of autism spectrum disorder and its possible correlations with clinical characteristics in patients with infantile epileptic spasms syndrome in a single center in Brazil. Methods: This retrospective cross-sectional study examined 53 children with the diagnosis of infantile epileptic spasms syndrome prior to an autism spectrum disorder assessment. Participants were divided into two groups based on the presence or absence of autism spectrum disorder. Available variables (sex, medications, median age at onset of infantile epileptic spasms syndrome, and presence of comorbidities) were compared using Mann-Whitney U or chi-square tests. Results: Among the included patients, 12 (23 %) were diagnosed with autism spectrum disorder, corresponding to a relative risk of 0.29 (95 % confidence interval 0.174-0.492). The age at the first seizure ranged from 3 to 15 months, with a mean of 6.65 months. This age significantly differed between participants with autism spectrum disorder (10.58 months) and those without (5.43 months), p<0.001. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the prevalence of autism spectrum disorder and its possible correlations with clinical characteristics in patients with infantile epileptic spasms syndrome in a single center in Brazil. Methods: This retrospective cross-sectional study examined 53 children with the diagnosis of infantile epileptic spasms syndrome prior to an autism spectrum disorder assessment. Participants were divided into two groups based on the presence or absence of autism spectrum disorder. Available variables (sex, medications, median age at onset of infantile epileptic spasms syndrome, and presence of comorbidities) were compared using Mann–Whitney U or chi-square tests. Results: Among the included patients, 12 (23 %) were diagnosed with autism spectrum disorder, corresponding to a relative risk of 0.29 (95 % confidence interval 0.174–0.492). The age at the first seizure ranged from 3 to 15 months, with a mean of 6.65 months. This age significantly differed between participants with autism spectrum disorder (10.58 months) and those without (5.43 months), p

Epileptic spasms are a unique, age-dependent manifestation of epilepsies in infancy and early childhood, commonly occurring as part of infantile epileptic spasms syndrome. Developmental stagnation and subsequent decline may occur in children with epileptic spasms, partly due to the abundant high-amplitude interictal epileptiform and slow wave abnormalities. Early recognition and treatment of epileptic spasms, along with the reversal of the electroencephalography (EEG) findings, are critical for improving outcomes. Recognizing hypsarrhythmia and its variations is key to confirming the diagnosis. The various patterns of hypsarrhythmia are not etiology specific, but could indicate the severity of the disease. Several scoring systems have been proposed to improve the inter-rater reliability of recognizing hypsarrhythmia and to assess EEG progress in response to treatment. Ictal patterns during spasms are brief and composed of slow waves, sharp transients, fast activity, and voltage attenuation, either in isolation or more commonly as a combination of these waveforms. Ictal patterns are commonly diffuse, but may be lateralized to one hemisphere in children with structural etiology. A subset of patients with epileptic spasms has a surgically remediable etiology, with readily identifiable lesions on neuroimaging in most cases. Asymmetry in epileptic spasms, concurrent focal seizures, and asymmetric interictal and ictal EEG findings may be present, but a lack of focality in electrophysiological findings is not uncommon. Intracranial EEG features of epileptic spasms have been described, but the utility of intracranial EEG monitoring in surgical candidates with overt focal epileptogenic lesions on magnetic resonance imaging is questionable, and surgery could be performed using noninvasive data.

• Clinical resolution of epileptic spasms was associated with stronger pre-treatment long-range temporal correlations. • Response was independently characterized by higher entropy and stronger long-range temporal correlations on post-treatment EEG. • On an exploratory basis, low entropy and weaker long-range temporal correlations were linked to early epileptic spasms relapse. We set out to evaluate whether response to treatment for epileptic spasms is associated with specific candidate computational EEG biomarkers, independent of clinical attributes. We identified 50 children with epileptic spasms, with pre- and post-treatment overnight video-EEG. After EEG samples were preprocessed in an automated fashion to remove artifacts, we calculated amplitude, power spectrum, functional connectivity, entropy, and long-range temporal correlations (LRTCs). To evaluate the extent to which each feature is independently associated with response and relapse, we conducted logistic and proportional hazards regression, respectively. After statistical adjustment for the duration of epileptic spasms prior to treatment, we observed an association between response and stronger baseline and post-treatment LRTCs (P = 0.042 and P = 0.004, respectively), and higher post-treatment entropy (P = 0.003). On an exploratory basis, freedom from relapse was associated with stronger post-treatment LRTCs (P = 0.006) and higher post-treatment entropy (P = 0.044). This study suggests that multiple EEG features—especially LRTCs and entropy—may predict response and relapse. This study represents a step toward a more precise approach to measure and predict response to treatment for epileptic spasms. [ABSTRACT FROM AUTHOR]

Epileptic spasms are a unique, age-dependent manifestation of epilepsies in infancy and early childhood, commonly occurring as part of infantile epileptic spasms syndrome. Developmental stagnation and subsequent decline may occur in children with epileptic spasms, partly due to the abundant high-amplitude interictal epileptiform and slow wave abnormalities. Early recognition and treatment of epileptic spasms, along with the reversal of the electroencephalography (EEG) findings, are critical for improving outcomes. Recognizing hypsarrhythmia and its variations is key to confirming the diagnosis. The various patterns of hypsarrhythmia are not etiology specific, but could indicate the severity of the disease. Several scoring systems have been proposed to improve the inter-rater reliability of recognizing hypsarrhythmia and to assess EEG progress in response to treatment. Ictal patterns during spasms are brief and composed of slow waves, sharp transients, fast activity, and voltage attenuation, either in isolation or more commonly as a combination of these waveforms. Ictal patterns are commonly diffuse, but may be lateralized to one hemisphere in children with structural etiology. A subset of patients with epileptic spasms has a surgically remediable etiology, with readily identifiable lesions on neuroimaging in most cases. Asymmetry in epileptic spasms, concurrent focal seizures, and asymmetric interictal and ictal EEG findings may be present, but a lack of focality in electrophysiological findings is not uncommon. Intracranial EEG features of epileptic spasms have been described, but the utility of intracranial EEG monitoring in surgical candidates with overt focal epileptogenic lesions on magnetic resonance imaging is questionable, and surgery could be performed using noninvasive data. [ABSTRACT FROM AUTHOR]

BackgroundWest syndrome (WS) is a devastating epileptic encephalopathy with onset in infancy and early childhood. It is characterized by clustered epileptic spasms, developmental arrest, and interictal hypsarrhythmia on electroencephalogram (EEG). Hypsarrhythmia is considered the hallmark of WS, but its visual assessment is challenging due to its wide variability and lack of a quantifiable definition. This study aims to analyze the EEG patterns in WS and identify computational diagnostic biomarkers of the disease.MethodLinear and non-linear features derived from EEG recordings of 31 WS patients and 20 age-matched controls were compared. Subsequently, the correlation of the identified features with structural and genetic abnormalities was investigated.ResultsWS patients showed significantly elevated alpha-band activity (0.2516 vs. 0.1914, p

Infantile spasms (IS) is a neurological disorder causing mental and/or developmental retardation in many infants. Hypsarrhythmia is a typical symptom in the electroencephalography (EEG) signals with IS. Long-term EEG/video monitoring is most frequently employed in clinical practice for IS diagnosis, from which manual screening of hypsarrhythmia is time consuming and lack of sufficient reliability. This study aims to identify potential biomarkers for automatic IS diagnosis by quantitative analysis of the EEG signals. A large cohort of 101 IS patients and 155 healthy controls (HC) were involved. Typical hypsarrhythmia and non-hypsarrhythmia EEG signals were annotated, and normal EEG were randomly picked from the HC. Root mean square (RMS), teager energy (TE), mean frequency, sample entropy (SamEn), multi-channel SamEn, multi-scale SamEn, and nonlinear correlation coefficient were computed in each sub-band of the three EEG signals, and then compared using either a one-way ANOVA or a Kruskal-Wallis test (based on their distribution) and the receiver operating characteristic (ROC) curves. The effects of infant age on these features were also investigated. For most of the employed features, significant ( ${p} < {0}.{05}$ ) differences were observed between hypsarrhythmia EEG and non-hypsarrhythmia EEG or HC, which seem to increase with increased infant age. RMS and TE produce the best classification in the delta and theta bands, while entropy features yields the best performance in the gamma band. Our study suggests RMS and TE (delta and theta bands) and entropy features (gamma band) to be promising biomarkers for automatic detection of hypsarrhythmia in long-term EEG monitoring. The findings of our study indicate the feasibility of automated IS diagnosis using artificial intelligence.

Early diagnosis and treatment are critical for young children with infantile spasms (IS), as this maximizes the possibility of the best possible child-specific outcome. However, there are major barriers to achieving this, including high rates of misdiagnosis or failure to recognize the seizures, medication failure, and relapse. There are currently no validated tools to aid clinicians in assessing objective diagnostic criteria, predicting or measuring medication response, or predicting the likelihood of relapse. However, the pivotal role of EEG in the clinical management of IS has prompted many recent studies of potential EEG biomarkers of the disease. These include both visual EEG biomarkers based on human visual interpretation of the EEG and computational EEG biomarkers in which computers calculate quantitative features of the EEG. Here, we review the literature on both types of biomarkers, organized based on the application (diagnosis, treatment response, prediction, etc.). Visual biomarkers include the assessment of hypsarrhythmia, epileptiform discharges, fast oscillations, and the Burden of AmplitudeS and Epileptiform Discharges (BASED) score. Computational markers include EEG amplitude and power spectrum, entropy, functional connectivity, high frequency oscillations (HFOs), long-range temporal correlations, and phase-amplitude coupling. We also introduce each of the computational measures and provide representative examples. Finally, we highlight remaining gaps in the literature, describe practical guidelines for future biomarker discovery and validation studies, and discuss remaining roadblocks to clinical implementation, with the goal of facilitating future work in this critical area.

Objective: To compare the efficacy and tolerability of modified Atkins diet (mAD) and ketogenic diet (KD) among children aged 9 mo to 3 y with epileptic spasms refractory to the first line treatment. Methods: An open labelled, randomized controlled trial with parallel group assignment was conducted among children aged 9 mo to 3 y with epileptic spasms refractory to the first line treatment. They were randomized to either receive the mAD along with conventional anti-seizure medications (n = 20) or KD with conventional anti-seizure medications (n = 20). Primary outcome measure was proportion of children who achieved "spasm freedom" at 4 wk and 12 wk. Secondary outcome measures were proportion of children who achieved >50% and >90% reduction in spasms at 4 wk and 12 wk, nature and proportion of the adverse effects as per parental reports. Results: Proportion of children achieving spasm freedom [mAD {4 (20%)} vs. KD {3 (15%)}: OR (95% CI) 1.42 (0.27–7.34); P = 0.67], >50% spasm reduction [mAD {3 (15%)} vs. KD {5 (25%)}: OR (95% CI) 0.53 (0.11–2.59); P = 0.63] and >90% spasm reduction [mAD {4 (20%)} vs. KD {2 (10%)}: OR (95% CI) 2.25 (0.36–13.97); P = 0.41] was comparable between the two groups at 12 wk. The diet was well tolerated in both the groups with vomiting and constipation being the most common reported adverse effect. Conclusions: mAD is an effective alternative to KD in the management of children with epileptic spasms refractory to first line treatment. However, further studies with adequately powered sample size and longer follow-up are required. Trial registration: CTRI/2020/03/023791. [ABSTRACT FROM AUTHOR]

• Nutritional vitamin B12 deficiency (NVBD) has been shown to cause west syndrome. • The prevalence of vitamin B12 deficiency in our cohort was 12.9%. • NVBD group had a lower number of clusters per day(p=0.02) and the number of spasms per cluster at presentation. • NVBD group had a lower BASED score (p=0.03) and cHPI, dHPI at presentation (p <0.001). • All of them remained spasm-free, with normal electroencephalogram at 6-months. Nutritional vitamin B12 deficiency has been shown to cause Infantile epileptic spasms syndrome (IESS) in infants in anecdotal studies. In this retrospective cohort study, we intended to study the clinical presentation, neurophysiological, laboratory abnormalities, treatment, and neurodevelopmental outcome at 6-months in infants presenting with IESS secondary to nutritional vitamin B12 deficiency (NVBD) and to compare these variables from the rest of the infants with IESS without vitamin B12 deficiency. We included only spasm-free cases or those who showed at least a 50% reduction in spasm frequency on D7 after starting oral/parenteral vitamin B12. We used well-validated measurement tools like the Developmental Assessment Scale for Indian Infants (DASII), Child Feeding Index (CFI), Burden of amplitudes and epileptiform discharges (BASED) score, countable Hypsarrhythmia paroxysm index (cHPI), durational Hypsarrhythmia paroxysm index (dHPI), and Early childhood epilepsy severity scale (E-CHESS) score for documenting these variables. Data from 162 infants with IESS (21 caused by NVBD) were included in our study. The NVBD group had more patients residing in the rural region, with lower socioeconomic status, vegetarian mothers and poor complementary feeding index (p <0.001 for all). The NVBD group also had less number of patients requiring antiseizure medications (ASMs) and hormonal therapy(p <0.001), remained seizure free at six months (p=0.008), lower number of clusters per day (p=0.02) and the number of spasms per clusters at presentation (p=0.03), lower BASED score (p=0.03) and cHPI, dHPI at presentation (p <0.001). All of them remained spasm-free, with normal electroencephalogram at 6-months. Development quotient at baseline, at 6-months, and improvement in development quotient between these two-time points were more in the vitamin B12 deficiency group (p <0.001). All of them had clinical features of pre-ITS (infantile tremor syndrome) or ITS and it was found to be the only independent predictor of NVBD in infants with IESS. Mothers of all these infants had low serum vitamin B12 levels (<200 pg/ml). Nutritional vitamin B12 deficiency may cause IESS in infants. Hence, vitamin B12 deficiency needs to be ruled out in patients with IESS without any definite etiology. [ABSTRACT FROM AUTHOR]

Objective: We aimed to assess the treatment response of infantile‐onset epileptic spasms (ES) in CDKL5 deficiency disorder (CDD) vs other etiologies. Methods: We evaluated patients with ES from the CDKL5 Centers of Excellence and the National Infantile Spasms Consortium (NISC), with onset from 2 months to 2 years, treated with adrenocorticotropic hormone (ACTH), oral corticosteroids, vigabatrin, and/or the ketogenic diet. We excluded children with tuberous sclerosis complex, trisomy 21, or unknown etiology with normal development because of known differential treatment responses. We compared the two cohorts for time to treatment and ES remission at 14 days and 3 months. Results: We evaluated 59 individuals with CDD (79% female, median ES onset 6 months) and 232 individuals from the NISC database (46% female, median onset 7 months). In the CDD cohort, seizures prior to ES were common (88%), and hypsarrhythmia and its variants were present at ES onset in 34%. Initial treatment with ACTH, oral corticosteroids, or vigabatrin started within 1 month of ES onset in 27 of 59 (46%) of the CDD cohort and 182 of 232 (78%) of the NISC cohort (p <.0001). Fourteen‐day clinical remission of ES was lower for the CDD group (26%, 7/27) than for the NISC cohort (58%, 106/182, p =.0002). Sustained ES remission at 3 months occurred in 1 of 27 (4%) of CDD patients vs 96 of 182 (53%) of the NISC cohort (p <.0001). Comparable results were observed with longer lead time (≥1 month) or prior treatment. Ketogenic diet, used within 3 months of ES onset, resulted in ES remission at 1 month, sustained at 3 months, in at least 2 of 13 (15%) individuals with CDD. Significance: Compared to the broad group of infants with ES, children with ES in the setting of CDD often experience longer lead time to treatment and respond poorly to standard treatments. Development of alternative treatments for ES in CDD is needed. [ABSTRACT FROM AUTHOR]

• ACTH monotherapy outcomes assessed for infantile epileptic spasm syndrome and PVL. • A positive response was observed in seven of 12 patients (58.3%). • Epileptic discharge in the parieto-occipital region was associated with relapse. • PVL grade III was also associated with relapse. • Our results will help identify patients at risk of relapse post-ACTH therapy. Infantile epileptic spasms syndrome (IESS) with periventricular leukomalacia (PVL) has a poor neurological prognosis. Adrenocorticotropic hormone (ACTH) and vigabatrin therapies are the recommended first-line treatments for IESS. However, ACTH monotherapy for IESS with PVL has not been studied in detail. We analysed long-term outcomes of ACTH monotherapy for IESS with PVL. We retrospectively examined 12 patients with IESS and PVL at Saitama Children's Medical Center between January 1993 and September 2022. We evaluated seizure outcomes 3 months post-ACTH therapy and at the last visit. We also assessed electroencephalography findings and developmental outcomes. A positive response was defined as complete remission of epileptic spasms, no other seizure types, and hypsarrhythmia resolution post-ACTH therapy. The median onset age of epileptic spasms was 7 (range: 3–14) months. The median age at initiation of ACTH therapy was 9 (7–17) months. Seven of 12 patients (58.3%) showed a positive response. The median age at the last visit was 5 years and 6 months (1 year and 5 months–22 years and 2 months). At the last visit, only 2 of 7 initial responders remained seizure-free who demonstrated normal electroencephalography findings within 1-month post-ACTH therapy. Patients with epileptic discharge in the parieto-occipital region within 1-month post-ACTH therapy showed relapse of epileptic spasms or other seizure types. Patients having epileptic discharge in the parietal or occipital regions on electroencephalography within 1-month post-ACTH therapy may be at a high risk of epileptic spasm recurrence or other seizure types in the long term. [ABSTRACT FROM AUTHOR]

Introduction. West Syndrome (WS) is one of the most common causes of epilepsy in infants and young children. It is characterized by symptomatic triad: epileptic spasms, hypsarrhythmia in interictal electroencephalogram (EEG, and mental retardation. WS is a devastating brain disorder thus the prognosis is an unfavourable one for young children with epilepsy. The purpose of the study was to elucidate the pathognomonic electroencephalographic features of WS. Material and methods. We examined 430 patients aged from 3 months to 2 years, who were admitted to PHMI MCI, with convulsive attacks, but 16 (3,7, ES 0,91) had epileptic spasms. The patients were examined by the neurological, encephalographic and neuroimaging methods. Results: Among those 430 patients - 16 (3,7%, ES 0,91) had: sudden movements in upper and lower limbs, which occurred serially on awakening, 14 (87,5%, ES 8,27) presented retardation in neuropsychic development, the electroencephalographic diagnosis of WS was confirmed in 11 (68,75%, ES 11,59) patients. Electroencephalographic results in WS showed the following changes: 9 (81,8%; ES 11,63) patients - typical hypsarrhythmia and 2 (18,2%, ES 11,63) patients - modified hypsarrhythmia. In one patient (9,09%, ES 8,67) MRI imaging confirmed the diagnosis of tuberous sclerosis (MRI results). Despite the treatment in 4 children (36,36%, ES 14,50), the EEG was with changes. Conclusions. The results of the study show that the WS remains one of the most common forms of epilepsy in children, which is characterized by specific clinical features, characteristic electroencephalographic tracks, and various relevant imaging changes such as tuberous sclerosis are often suggestive of developing epileptic encephalopathy risk. [ABSTRACT FROM AUTHOR]

A series of relatively small studies collectively suggest that zonisamide may be effective in the treatment of infantile spasms. Using a large single-center cohort of children with infantile spasms, we set out to evaluate the efficacy and safety of zonisamide. We retrospectively identified all patients with infantile spasms who were treated with zonisamide at our center. For each patient, we recorded dates of birth, infantile spasms onset, response (if any), and most recent follow-up. To quantify zonisamide exposure, we recorded daily dosage and patient weight at each sequential encounter so as to allow calculation of peak and weighted-average weight-based dosage. We identified 87 children who were treated with zonisamide, of whom 78 had previously been treated with hormonal therapy or vigabatrin. Peak and weighted-average zonisamide dosage were 7.1 (interquartile range 3.6, 10.2) and 5.4 (interquartile range 3.0, 8.9) mg/kg/day, respectively. Whereas five (6%) patients exhibited resolution of epileptic spasms, only two (2%) patients exhibited video-EEG confirmed resolution of both epileptic spasms and hypsarrhythmia (electroclinical response). Importantly, both electroclinical responders had not previously been treated with hormonal therapy or vigabatrin; in contrast, none of the 78 children with prior failure of hormonal therapy or vigabatrin subsequently responded to zonisamide. Zonisamide was well tolerated, and there were no deaths. This study suggests that zonisamide exhibits favorable tolerability but very limited efficacy among patients who do not respond to first-line therapy.

Background: Miller–Dieker syndrome (MDS) is a rare genetic disorder, due to contiguous gene deletion on chromosome 17p13.3, characterized by classical type I lissencephaly, severe developmental delay, seizures, cardiac defects, and dysmorphisms. West syndrome is a severe form of epilepsy with epileptic spasms, hypsarrhythmia in electroencephalogram (EEG), and neuropsychomotor delay. Herein, we describe the neurophysiological and neuroimaging findings of a patient with MDS with associated West syndrome. Clinical Description: A 5-month-old boy was brought with new-onset infantile spasms and a history of delay and some regression in milestones. Facial dysmorphism was noted in the form of a prominent forehead, bitemporal hollowing, short nose with upturned nares, thickened upper lip, long philtrum, low-set ears, and hypertelorism. There was hypotonia of all four limbs. Management and Outcome: An EEG showed hypsarrhythmia, and the magnetic resonance imaging brain revealed hypoplastic sulci with pachygyria and smooth cortical surface of supratentorial brain parenchyma – features suggestive of lissencephaly type 1. Echocardiography showed atrial septal defect and minimal pericardial effusion. Whole-exome sequencing showed a contiguous large heterozygous deletion on chromosome 17 which was suggestive of Miller–Dieker lissencephaly syndrome. Parents were counseled, and the spasms were treated with an injection adrenocorticotropic hormone and oral vigabatrin. Conclusion: Structural brain abnormalities are well-known causes of infantile spasms. MDS is a severe malformative condition, lissencephaly being the hallmark of this disorder. This case report will create awareness among pediatricians regarding this rare condition with a characteristic combination of clinical features, which can be confirmed by brain imaging and genetic analysis.

Background: Infantile epileptic spasm syndrome (IESS) is an age-dependent epileptic encephalopathy with a significant risk of developmental regression. This study investigates the association between heart rate variability (HRV) in infants at risk of IESS and the clinical onset of IESS. Methods: Sixty neonates at risk of IESS were prospectively followed from birth to 12 months with simultaneous electroencephalogram (EEG) and electrocardiogram recordings for 60min at every 2-month interval. HRV metrics were calculated from 5min time-epoch during sleep including frequency domain measures, Poincare analysis including cardiac vagal index (CVI) and cardiac sympathetic index (CSI), and detrended fluctuation analysis (DFA a1, DFA a2). To assess the effect of each HRV metric at the 2-month baseline on the time until the first occurrence of either hypsarrhythmia on EEG and/or clinical spasm, univariate cox-proportional hazard models were fitted for each HRV metric. Results: Infantile epileptic spasm syndrome was diagnosed in 20/60 (33%) of the cohort in a 12-month follow-up and 3 (5%) were lost to follow-up. The median age of developing hypsarrhythmia was 25 (7-53) weeks and clinical spasms at 24 (8-40) weeks. Three (5%) patients had clinical spasms without hypsarrhythmia, and 5 (8%) patients had hypsarrhythmia before clinical spasms at the initial presentation. The infants with high CSI (hazard ratio 2.5, 95% CI 1.2-5.2, P = 0.01) and high DFA α1 (hazard ratio 16, 95% CI 1.1-240, P = 0.04) at 2 months were more likely to develop hypsarrhythmia by the first year of age. There was a trend toward decreasing CSI and DFA a1 and increasing CVI in the first 8 months of age. Conclusion: Our data suggest that relative sympathetic predominance at an early age of 2monthsmay be a potential predictor for developing IESS. Hence, early HRV patterns may provide valuable prognostic information in children at risk of IESS allowing early detection and optimization of cognitive outcomes. Whether early intervention to restore sympathovagal balance per se would provide clinical benefit must be addressed by future studies. [ABSTRACT FROM AUTHOR]

Abstract Background Infantile spasm (IS) is an age-specific epileptic disorder of early infancy that typically presents with epileptic spasms occurring in clusters. International League Against Epilepsy (ILAE) also recommends the term “IS syndrome” for clustered spasms occurring during infancy (~ 1 year, rarely after 2 years of age) accompanied by electroencephalography (EEG) hypsarrhythmia. Older clinical studies comparing efficacy of adrenocorticotrophic hormone (ACTH) and corticosteroids preferred ACTH, but recent studies did not observe a significant difference between both nor showed better efficacy of oral prednisolone compared to intramuscular synthetic one. Participants were 53 patients with epileptic spasms divided into two groups: 26 patients treated by intravenous methylprednisolone (group A) and 27 treated by oral prednisolone (group B). Both groups were matched in age, sex, and age of spasm onset. The outcome measures were spasms cessation at 7 and 14 days and recurrence at 6 weeks after tapering, EEG improvement at 2 and 6 weeks, and frequency of side effects. Results We found that both groups had similar results regarding frequency of children achieving spasms cessation at day 7 and day 14 (53.8% vs 51.9% and 38.5% vs 40.7%, p = 1.000 each), respectively. After drug tapering, there was insignificant difference between both groups regarding recurrence of spasm at 6 weeks (14.8% vs 11.5%, p = 1.000) and EEG improvement at 2 weeks (42.3% vs 33.3%, p = 0.577) with nearly similar improvement in both groups at 6 weeks (46.2% vs 48.1%, p = 1.000). With regard to adverse effects of both therapies, no difference observed between both groups. Conclusions No significant difference was found between oral prednisolone and intravenous methylprednisolone in treatment of epileptic spasm regarding short-term outcomes. The only advantage of intravenous therapy is decreased time to get response and the only advantage of oral therapy is its applicability at home without hospitalization. Further studies are warranted to explore the long-term outcomes.

Background: Infantile spasms are an age-specific epileptic disorder. They occur in infancy and early childhood. They can be caused by multiple etiologies. Structural abnormalities represent an important cause of infantile spasms. Brain magnetic resonance imaging (MRI) is one of the integral modalities in the evaluation of this condition. Purpose: The aim of this study is to review and analyze the clinical characteristics and brain MRI findings in a cohort of children diagnosed with infantile spasms. Material and Methods: A cohort of fifty-six children diagnosed with infantile spasms in infancy and early childhood was included. All of them underwent brain MRI for evaluation. The study was conducted in the period from January 2016 to January 2020. Results: Females comprised 57% of the cohort. The mean age for seizure onset was 5.9 months (SD 2.7). Forty-one patients (73%) had active epilepsy, and 51% were diagnosed with global developmental delay. Consanguinity was present in 59% of the cohort. Most of the follow-up MRIs showed structural abnormalities (84%). Hypoxia was reported in 17% of MRIs. Malformations of cortical development were seen in five patients. Brain MRI findings were normal in 16% of patients, and delayed myelination was seen in nineteen patients. Most of the children with active epilepsy (64%) and developmental delay (82%) had an abnormal brain MRI. It was noticed that abnormal second brain MRIs were more likely to be associated with active epilepsy and developmental delay (p = 0.05). Conclusions: Brain MRI is an integral part of infantile spasms’ clinical evaluation. Infantile spasms and abnormal brain MRI can be associated with active epilepsy and global developmental delay.

OBJECTIVE:Epileptic spasms (ES) are associated with pathological neuronal networks, which may underlie characteristic EEG patterns such as hypsarrhythmia. Here we evaluate EEG functional connectivity as a quantitative marker of treatment response, in comparison to classic visual EEG features. METHODS:We retrospectively identified 21 ES patients and 21 healthy controls. EEG data recorded before treatment and after ≥10 days of treatment underwent blinded visual assessment, and functional connectivity was measured using cross-correlation techniques. Short-term treatment response and long-term outcome data were collected. RESULTS:Subjects with ES had stronger, more stable functional networks than controls. After treatment initiation, all responders (defined by cessation of spasms) exhibited decreases in functional connectivity strength, while an increase in connectivity strength occurred only in non-responders. There were six subjects with unusually strong pre-treatment functional connectivity, and all were responders. Visually assessed EEG features were not predictive of treatment response. CONCLUSIONS:Changes in network connectivity and stability correlate to treatment response for ES, and high pre-treatment connectivity may predict favorable short-term treatment response. Quantitative measures outperform visual analysis of the EEG. SIGNIFICANCE:Functional networks may have value as objective markers of treatment response in ES, with potential to facilitate rapid identification of personalized, effective treatments.

BackgroundInfantile epileptic spasm syndrome (IESS) is an age-dependent epileptic encephalopathy with a significant risk of developmental regression. This study investigates the association between heart rate variability (HRV) in infants at risk of IESS and the clinical onset of IESS.MethodsSixty neonates at risk of IESS were prospectively followed from birth to 12 months with simultaneous electroencephalogram (EEG) and electrocardiogram recordings for 60 min at every 2-month interval. HRV metrics were calculated from 5 min time-epoch during sleep including frequency domain measures, Poincare analysis including cardiac vagal index (CVI) and cardiac sympathetic index (CSI), and detrended fluctuation analysis (DFA α1, DFA α2). To assess the effect of each HRV metric at the 2-month baseline on the time until the first occurrence of either hypsarrhythmia on EEG and/or clinical spasm, univariate cox-proportional hazard models were fitted for each HRV metric.ResultsInfantile epileptic spasm syndrome was diagnosed in 20/60 (33%) of the cohort in a 12-month follow-up and 3 (5%) were lost to follow-up. The median age of developing hypsarrhythmia was 25 (7–53) weeks and clinical spasms at 24 (8–40) weeks. Three (5%) patients had clinical spasms without hypsarrhythmia, and 5 (8%) patients had hypsarrhythmia before clinical spasms at the initial presentation. The infants with high CSI (hazard ratio 2.5, 95% CI 1.2–5.2, P = 0.01) and high DFA α1 (hazard ratio 16, 95% CI 1.1–240, P = 0.04) at 2 months were more likely to develop hypsarrhythmia by the first year of age. There was a trend toward decreasing CSI and DFA α1 and increasing CVI in the first 8 months of age.ConclusionOur data suggest that relative sympathetic predominance at an early age of 2 months may be a potential predictor for developing IESS. Hence, early HRV patterns may provide valuable prognostic information in children at risk of IESS allowing early detection and optimization of cognitive outcomes. Whether early intervention to restore sympathovagal balance per se would provide clinical benefit must be addressed by future studies.

Background: There are preliminary reports of the benefit of additional pulse methylprednisolone (MP) to oral prednisolone in the treatment of West syndrome. Aim: To compare the efficacy and safety of intravenous pulse MP followed by low-dose prednisolone versus low-dose prednisolone alone for children with West syndrome. Materials and Methods: This randomized, open-labeled, controlled clinical trial was conducted among children aged two months to 30 months with a diagnosis of West syndrome. They were randomized to either of pulse MP (30 mg/kg for 3 days) followed by low-dose prednisolone (2 mg/kg) [n = 26] or low-dose prednisolone (2 mg/kg) alone [n = 24] for four weeks. Results: The efficacy of pulse MP was comparable with oral prednisolone in terms of spasms cessation (11 [45.8%] vs. 7 [26.9%]; RRR [95% confidence interval [CI]: 0.74 [0.47-1.14]; P = 0.24), more than 50% spasms reduction (16 [66.6%] vs. 11 [42.3%]; RRR [95% CI]: 0.57 [0.31-1.12]; P = 0.09), more than 90% reduction (11 [42.8%] vs. 7 [26.9%]; RRR [95% CI]: 0.74 [0.47-1.14]; P = 0.24), and primary electroclinical remission (5 [20.8%] vs. 2 [7.6%]; RRR [95% CI]: 0.85 [0.68-1.08]; P = 0.21). The adverse effect profile was comparable in the two groups. Conclusion: Pulse MP therapy followed by oral prednisolone in low-dose (2 mg/kg) was as effective as low-dose prednisolone (2 mg/kg) therapy alone in West syndrome. Although pulse MP did not result in any adverse outcome, routine use of the same before initiation of oral prednisolone needs further studies with a larger sample size; longer follow-, up and comparative trial with high dose steroids (4 mg/kg). [ABSTRACT FROM AUTHOR]

Developmental and epileptic encephalopathies (DEEs) are severe forms of epilepsy characterized by seizure onset in infancy or childhood. The seizures are typically drug-resistant and often accompanied by significant alterations in the electroencephalogram (EEG). DEEs are associated with neurodevelopmental impairment, which can arise from both the epileptic activity itself and the underlying etiology, which is most often genetic in origin. We present the clinical and molecular features of two patients with DEE associated with a pathogenic variant in the UGDH gene. This gene encodes a protein that converts uridine diphosphate (UDP)-glucose into UDP-glucuronate, which plays a crucial role in the biosynthesis of glycosaminoglycans, essential components of the connective tissue and extracellular matrix. Both patients started with epileptic spasms associated with a pattern of hypsarrhythmia in the EEG at 4 months of age. Both developed global developmental delay and the physical examination revealed hypotonia and mildly dysmorphic features. In both families, there was another affected sibling with a similar clinical presentation, although genetic studies were not performed in one of these children. A homozygous pathogenic variant in the UGDH gene, NM&#95;003359.4:c.131C>T - p.(Ala44Val), previously reported to be associated with the described phenotype, was identified., (© 2024 International League Against Epilepsy.)

Early diagnosis and treatment are critical for young children with infantile spasms (IS), as this maximizes the possibility of the best possible child-specific outcome. However, there are major barriers to achieving this, including high rates of misdiagnosis or failure to recognize the seizures, medication failure, and relapse. There are currently no validated tools to aid clinicians in assessing objective diagnostic criteria, predicting or measuring medication response, or predicting the likelihood of relapse. However, the pivotal role of EEG in the clinical management of IS has prompted many recent studies of potential EEG biomarkers of the disease. These include both visual EEG biomarkers based on human visual interpretation of the EEG and computational EEG biomarkers in which computers calculate quantitative features of the EEG. Here, we review the literature on both types of biomarkers, organized based on the application (diagnosis, treatment response, prediction, etc.). Visual biomarkers include the assessment of hypsarrhythmia, epileptiform discharges, fast oscillations, and the Burden of AmplitudeS and Epileptiform Discharges (BASED) score. Computationalmarkers include EEG amplitude and power spectrum, entropy, functional connectivity, high frequency oscillations (HFOs), long-range temporal correlations, and phase-amplitude coupling. We also introduce each of the computationalmeasures and provide representative examples. Finally, we highlight remaining gaps in the literature, describe practical guidelines for future biomarker discovery and validation studies, and discuss remaining roadblocks to clinical implementation, with the goal of facilitating future work in this critical area. [ABSTRACT FROM AUTHOR]

Developmental and epileptic encephalopathy 70 (DEE70) is an epileptic encephalopathy associated with multiple neurological abnormalities and global developmental delay, among other characteristics. It has recently been established that it is caused by a heterozygous variant of the PHACTR1 gene, with currently four cases reported in the literature. This article presents a case report of a patient with DEE70 with a heterozygous variant in the PHACTR1 gene, who also presents a hemizygous variant in the AFF2 gene, associated with FRAXE syndrome. A phenotypic comparison is made between this case and the four other previously reported cases with variants in the PHACTR1 gene. In addition, the possible participation of the PHACTR1 and AFF2 genes in the clinical characteristics of the individual is discussed. [ABSTRACT FROM AUTHOR]

Infantile spasms syndrome is an epileptic encephalopathy in which prompt diagnosis and treatment initiation are critical to therapeutic response. Diagnosis of the disease heavily depends on the identification of characteristic electroencephalographic (EEG) patterns, including hypsarrhythmia. However, visual assessment of the presence and characteristics of hypsarrhythmia is challenging because multiple variants of the pattern exist, leading to poor inter-rater reliability. We investigated whether a quantitative measurement of the control of neural synchrony in the EEGs of infantile spasms patients could be used to reliably distinguish the presence of hypsarrhythmia and indicate successful treatment outcomes. We used autocorrelation and Detrended Fluctuation Analysis (DFA) to measure the strength of long-range temporal correlations in 21 infantile spasms patients before and after treatment and 21 control subjects. The strength of long-range temporal correlations was significantly lower in patients with hypsarrhythmia than control patients, indicating decreased control of neural synchrony. There was no difference between patients without hypsarrhythmia and control patients. Further, the presence of hypsarrhythmia could be classified based on the DFA exponent and intercept with 92% accuracy using a support vector machine. Successful treatment was marked by a larger increase in the DFA exponent compared to those in which spasms persisted. These results suggest that the strength of long-range temporal correlations is a marker of pathological cortical activity that correlates with treatment response. Combined with current clinical measures, this quantitative tool has the potential to aid objective identification of hypsarrhythmia and assessment of treatment efficacy to inform clinical decision-making.

West syndrome (WS) is a rare, severe form of epilepsy with onset in infancy and early childhood. It involves clustered epileptic spasm episodes, the aberrant interictal electroencephalogram pattern known as hypsarrhythmia, and neuropsychomotor delay. In this view, we present a case of a 6-year-old female child a known case of west syndrome, global developmental delay, hypothyroidism, and postoperative laparoscopic gastrotomy performed under general anaesthesia on March 31/2022, in view of recurrent aspiration and came with the chief complaints of seizure 6-7 episodes per day, decreased urine output, constipation for two days, straining to pass urine, and three episodes of vomiting. The history included that the baby cried immediately after birth, seizure on day 5 of life, and was shifted to the Neonatal intensive care unit (NICU), admitted there for 5 days because of respiratory distress syndrome and hyperalbuminemia. During their stay in the hospital, the child has been prescribed Lamotrigine 50mg, Levocarnitine 500mg, Levetiracetam 250mg, Clobazam 5mg, Phenobarbital 60mg, Sodium Valproate 100mg, Thyronorm 50mcg. Now the patient is symptomatically better. This case report intends to sensitize physicians in this region toward this rare neurological syndrome. [ABSTRACT FROM AUTHOR]

Early diagnosis and treatment are critical for young children with infantile spasms (IS), as this maximizes the possibility of the best possible child-specific outcome. However, there are major barriers to achieving this, including high rates of misdiagnosis or failure to recognize the seizures, medication failure, and relapse. There are currently no validated tools to aid clinicians in assessing objective diagnostic criteria, predicting or measuring medication response, or predicting the likelihood of relapse. However, the pivotal role of EEG in the clinical management of IS has prompted many recent studies of potential EEG biomarkers of the disease. These include both visual EEG biomarkers based on human visual interpretation of the EEG and computational EEG biomarkers in which computers calculate quantitative features of the EEG. Here, we review the literature on both types of biomarkers, organized based on the application (diagnosis, treatment response, prediction, etc.). Visual biomarkers include the assessment of hypsarrhythmia, epileptiform discharges, fast oscillations, and the Burden of AmplitudeS and Epileptiform Discharges (BASED) score. Computational markers include EEG amplitude and power spectrum, entropy, functional connectivity, high frequency oscillations (HFOs), long-range temporal correlations, and phase-amplitude coupling. We also introduce each of the computational measures and provide representative examples. Finally, we highlight remaining gaps in the literature, describe practical guidelines for future biomarker discovery and validation studies, and discuss remaining roadblocks to clinical implementation, with the goal of facilitating future work in this critical area.

Aim: Early recognition and initiation of standard therapy are crucial for the management of West syndrome. The study aimed to assess the magnitude, potential determinants, and impact of treatment lag impact on short-term therapeutic outcomes. Materials and Methods: The study design was prospective, observational, and data were ascertained through personal interviews with caregivers and reviewing medical records according to a pre-structured questionnaire. We defined shortterm therapeutic response as the cessation of epileptic spasms commencing within 14 days of initiation of hormonal therapy and sustained for ≥28 days. Results: Of 82 consecutively enrolled children with West syndrome, the median treatment lag was 90 days (95% confidence interval [CI]: 110--198 days). The significant determinants of treatment lag in our study were as follows: the preexisting developmental delay, educational status of the parents, and qualification of the first practitioner visited. Our study showed that a shorter treatment lag (<1 month) was associated with a favorable cessation of epileptic spasms (85% vs. 15%; P = 0.011). Conclusion: We observed a significant treatment lag in children with West syndrome. The lead time to treatment emerged as a potentially modifiable risk factor for short-term therapeutic response with hormonal therapy. [ABSTRACT FROM AUTHOR]

Background: Infantile spasm (IS) is an age-specific epileptic disorder of early infancy that typically presents with epileptic spasms occurring in clusters. International League Against Epilepsy (ILAE) also recommends the term "IS syndrome" for clustered spasms occurring during infancy (~ 1 year, rarely after 2 years of age) accompanied by electroencephalography (EEG) hypsarrhythmia. Older clinical studies comparing efficacy of adrenocorticotrophic hormone (ACTH) and corticosteroids preferred ACTH, but recent studies did not observe a significant difference between both nor showed better efficacy of oral prednisolone compared to intramuscular synthetic one. Participants were 53 patients with epileptic spasms divided into two groups: 26 patients treated by intravenous methylprednisolone (group A) and 27 treated by oral prednisolone (group B). Both groups were matched in age, sex, and age of spasm onset. The outcome measures were spasms cessation at 7 and 14 days and recurrence at 6 weeks after tapering, EEG improvement at 2 and 6 weeks, and frequency of side effects. Results: We found that both groups had similar results regarding frequency of children achieving spasms cessation at day 7 and day 14 (53.8% vs 51.9% and 38.5% vs 40.7%, p = 1.000 each), respectively. After drug tapering, there was insignificant difference between both groups regarding recurrence of spasm at 6 weeks (14.8% vs 11.5%, p = 1.000) and EEG improvement at 2 weeks (42.3% vs 33.3%, p = 0.577) with nearly similar improvement in both groups at 6 weeks (46.2% vs 48.1%, p = 1.000). With regard to adverse effects of both therapies, no difference observed between both groups. Conclusions: No significant difference was found between oral prednisolone and intravenous methylprednisolone in treatment of epileptic spasm regarding short-term outcomes. The only advantage of intravenous therapy is decreased time to get response and the only advantage of oral therapy is its applicability at home without hospitalization. Further studies are warranted to explore the long-term outcomes. [ABSTRACT FROM AUTHOR]

Background: Infantile spasms are an age-specific epileptic disorder. They occur in infancy and early childhood. They can be caused by multiple etiologies. Structural abnormalities represent an important cause of infantile spasms. Brain magnetic resonance imaging (MRI) is one of the integral modalities in the evaluation of this condition. Purpose: The aim of this study is to review and analyze the clinical characteristics and brain MRI findings in a cohort of children diagnosed with infantile spasms. Material and Methods: A cohort of fifty-six children diagnosed with infantile spasms in infancy and early childhood was included. All of them underwent brain MRI for evaluation. The study was conducted in the period from January 2016 to January 2020. Results: Females comprised 57% of the cohort. The mean age for seizure onset was 5.9 months (SD 2.7). Forty-one patients (73%) had active epilepsy, and 51% were diagnosed with global developmental delay. Consanguinity was present in 59% of the cohort. Most of the follow-up MRIs showed structural abnormalities (84%). Hypoxia was reported in 17% of MRIs. Malformations of cortical development were seen in five patients. Brain MRI findings were normal in 16% of patients, and delayed myelination was seen in nineteen patients. Most of the children with active epilepsy (64%) and developmental delay (82%) had an abnormal brain MRI. It was noticed that abnormal second brain MRIs were more likely to be associated with active epilepsy and developmental delay (p = 0.05). Conclusions: Brain MRI is an integral part of infantile spasms' clinical evaluation. Infantile spasms and abnormal brain MRI can be associated with active epilepsy and global developmental delay. [ABSTRACT FROM AUTHOR]

Objective: In a randomized trial, we aimed to evaluate the efficacy of cosyntropin injectable suspension, 1 mg/mL, compared to vigabatrin for infantile spasms syndrome. An additional arm was included to assess the efficacy of combination therapy (cosyntropin and vigabatrin) compared with cosyntropin monotherapy. Methods: Children (2 months to 2 years) with new-onset infantile spasms syndrome and hypsarhythmia were randomized into 3 arms: cosyntropin, vigabatrin, and cosyntropin and vigabatrin combined. Daily seizures and adverse events were recorded, and EEG was repeated at day 14 to assess for resolution of hypsarhythmia. The primary outcome measure was the composite of resolution of hypsarhythmia and absence of clinical spasms at day 14. Fisher exact test was used to compare outcomes. Results: 37 children were enrolled and 34 were included in the final efficacy analysis (1 withdrew prior to treatment and 2 did not return seizure diaries). Resolution of both hypsarhythmia and clinical spasms was achieved in in 9 of 12 participants (75%) treated with cosyntropin, 1/9 (11%) vigabatrin, and 5/13 (38%) cosyntropin and vigabatrin combined. The primary comparison of cosyntropin versus vigabatrin was significant (64% [95% confidence interval 21, 82], P <.01). Adverse events were reported in all 3 treatment arms: 31 (86%) had an adverse event, 7 (19%) had a serious adverse event, and 15 (42%) had an adverse event of special interest with no difference between treatment arms. Significance: This randomized trial was underpowered because of incomplete enrollment, yet it demonstrated that cosyntropin was more effective for short-term outcomes than vigabatrin as initial treatment for infantile spasms. [ABSTRACT FROM AUTHOR]

To evaluate whether serum matrix metallopeptidase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels predict response to adrenocorticotropic hormone (ACTH) therapy in patients with infantile spasms. We prospectively evaluated patients with infantile spasms who were referred to Saitama Children's Medical Center from January 2011 to December 2020. We measured Q-albumin and serum MMP-9 and TIMP-1 levels before ACTH therapy. Patients were divided into three groups based on the etiology of their infantile spasms: those with an unknown etiology and normal development (unknown-normal group); those with a structural and acquired etiology (structural-acquired group); and those with a structural and congenital, genetic, metabolic, or unknown etiology with developmental delay (combined-congenital group). Responders were defined as those having complete cessation of spasms for more than 3 months with the resolution of hypsarrhythmia on electroencephalography during ACTH therapy. We collected serum from 36 patients with West syndrome and five patients with infantile spasms without hypsarrhythmia before ACTH therapy. Twenty-three of 41 patients (56.1%) were responders, including 8/8 (100%) in the unknown-normal group, 6/9 (66.7%) in the structural-acquired group, and 9/24 (37.5%) in the combined-congenital group. The serum MMP-9 level and MMP-9/TIMP-1 ratio were significantly higher in responders than in nonresponders (P = 0.001 for both). A therapeutic response to ACTH was associated with a higher serum MMP-9 level and higher MMP-9/TIMP-1 ratio in patients with infantile spasms. Therefore, these biomarkers may predict responses to ACTH therapy in this patient population. [ABSTRACT FROM AUTHOR]

Background: Prediction of outcome of West syndrome (WS) in relation to etiology and electrophysiology remain pertinent challenges. Objective: This study aimed to compare electro-clinical and imaging characteristics between WS of "unknown-etiology"; "symptomatic"WS; to gauge the evolution and impact of electroencephalographic (EEG) patterns on seizure outcomes. Materials and Methods: Electro-clinico-radiological data of 76 children with WS who were followed up for atleast 1 year was collected for reviewing clinical, therapeutic and EEG profiles (sub-typed as typical and modified hypsarrhythmia [HA]). Quantified seizure scores were assessed. Results: Among 76 children included in this retrospective analysis, 31 (40.8%) were of unknown-etiology and 45 (59.2%) were "symptomatic" (structural cause/developmental-encephalopathy). Children with symptomatic WS (p = 0.037), specifically with gliosis on imaging (p = 0.05) and typical HA (including the multifocal subtype; P = 0.023) were more likely to have other seizure types before onset of spasms and exhibit prior delay or regression in milestones (p = 0.017). There was negative correlation between time to diagnosis and reduction in seizure scores (r = -0.32; p = 0.005).Significant reduction was noted in seizure scores with pharmacotherapy, irrespective of etiology (P < 0.001 in unknown-etiology and symptomatic subgroups). Seizure freedom rates did not differ between typical and modified HA groups (p = 0.215) with a higher proportion of children with meaningful reduction in seizure scores in the former sub-group (p = 0.030). Children who failed to achieve seizure remission were more likely to exhibit developmental impairment (p = 0.019). Conclusions: Early diagnosis and initiation of optimal therapy is crucial towards improving outcome, irrespective of etiology (which impacts pre-spasm development) and HA subtypes. [ABSTRACT FROM AUTHOR]

Abstract Objectives Considering the dearth of literature on West syndrome (WS) from South Asian countries, this study aimed to evaluate the management practices in South Asia by an online survey and meta‐analysis. Methods An online questionnaire was sent to 223 pediatric neurologists/pediatricians in India, Pakistan, Myanmar, Sri Lanka, Bhutan, Nepal, and Bangladesh. Their responses were evaluated and supplemented by a meta‐analysis. Results Of 125 responses received (response rate: 56%), around 60% of responders observed male preponderance and an approximate lead‐time‐to‐treatment (LTTT) of 4‐12 weeks. The commonest etiology observed was a static structural insult (88.6% of responders). Most commonly used first‐line drug (country‐wise) was as follows: India—adrenocorticotropin hormone (ACTH, 50%); Pakistan—oral steroids (45.5%); Myanmar, Sri Lanka, and Nepal—oral steroids (94.4%); Bangladesh—ACTH (2/2); Bhutan—vigabatrin (3/5). ACTH and vigabatrin are not available in Myanmar and Nepal. The most commonly used regime for ACTH was maximal‐dose‐at‐initiation‐regime in India, Sri Lanka, and Bangladesh and gradually escalating‐regime in Pakistan. Maximum dose of prednisolone was variable—most common response from India: 3‐4 mg/kg/d; Pakistan, Bhutan, and Bangladesh: 2 mg/kg/d; Sri Lanka, Nepal, and Myanmar: 5‐8 mg/kg/d or 60 mg/d. The total duration of hormonal therapy (including tapering) ranged from 4 to 12 weeks (67/91). Most responders considered cessation of spasms for four weeks as complete response (54/111) and advised electroencephalography (EEG; 104/123) to check for hypsarrhythmia resolution. Difficult access to pediatric EEG in Bhutan and Nepal is concerning. More than 95% of responders felt a need for more awareness. The meta‐analysis supported the preponderance of male gender (68%; confidence interval [CI]: 64%‐73%), structural etiology(80%; CI 73%‐86%), longer LTTT (2.4 months; CI 2.1‐2.6 months), and low response rate to hormonal therapy(18% and 28% for ACTH and oral steroids respectively) in WS in South Asia. Significance This study highlights the practices and challenges in the management of WS in South Asia. These include a preponderance of male gender and structural etiology, a longer LTTT, difficult access to pediatric EEG, nonavailability of ACTH and vigabatrin in some countries, and low effectiveness of hormonal therapy in this region.

Aim: Based on published reports and our own observations, we aimed to assign the graphical elements of EEG into normal and abnormal groups and then identify up to five main graphic elements in each group to facilitate visual analysis and interpretation of EEG in young children.Materials and methods. We searched for the relevant sources in the Medline and Medscape databases using the following keywords: «neonatal EEG», «neonatal seizures», «theta burst», «delta brushes», «trace discontinue», «burst-suppression», hypsarrhythmia», etc. Our own research was conducted using an Encephalan-EEGR-19/26 encephalograph equipped with children size gold cup electrodes with a diameter of 0.6 cm. Encephalograms were recorded from 10 electrodes according to the international “10-20” system.Results and discussion. In early childhood EEGs, two large groups of EEG graphic elements can be discerned: the likely normative graphic elements and patterns of pediatric EEG (normal patterns) and the likely non-normative (abnormal) graphic elements and patterns of pediatric EEG. In the likely normative group, the main features are represented by: theta bursts, delta brushes, the “intermittent EEG curve” pattern, the occipital theta rhythm, and slow-sleep waves. In the likely non-normative group, those are: paroxysmal EEG graphic elements, asynchronous EEG patterns, spike-wave discharges, 3 Hz peak waves, hypsarrhythmia, burst-suppression pattern, rolandic occipital spikes, and a slowing rhythm pattern.Conclusion. Along with the numerous attempts to characterize the age-dependent graphic elements at an early age, there are few reports concerning older children and adults. Here we try to overcome this discrepancy by identifying two large groups of graphic elements in EEG that are similar between infants and children of an older age. Such an approach may contribute to a better understanding of normal and pathological ontogenesis.

Abstract A series of relatively small studies collectively suggest that zonisamide may be effective in the treatment of infantile spasms. Using a large single‐center cohort of children with infantile spasms, we set out to evaluate the efficacy and safety of zonisamide. We retrospectively identified all patients with infantile spasms who were treated with zonisamide at our center. For each patient, we recorded dates of birth, infantile spasms onset, response (if any), and most recent follow‐up. To quantify zonisamide exposure, we recorded daily dosage and patient weight at each sequential encounter so as to allow calculation of peak and weighted‐average weight‐based dosage. We identified 87 children who were treated with zonisamide, of whom 78 had previously been treated with hormonal therapy or vigabatrin. Peak and weighted‐average zonisamide dosage were 7.1 (interquartile range 3.6, 10.2) and 5.4 (interquartile range 3.0, 8.9) mg/kg/day, respectively. Whereas five (6%) patients exhibited resolution of epileptic spasms, only two (2%) patients exhibited video‐EEG confirmed resolution of both epileptic spasms and hypsarrhythmia (electroclinical response). Importantly, both electroclinical responders had not previously been treated with hormonal therapy or vigabatrin; in contrast, none of the 78 children with prior failure of hormonal therapy or vigabatrin subsequently responded to zonisamide. Zonisamide was well tolerated, and there were no deaths. This study suggests that zonisamide exhibits favorable tolerability but very limited efficacy among patients who do not respond to first‐line therapy.

Aim: West syndrome is characterized by a triad of infantile spasms, arrested psychomotor development, and pronounced paroxysmal electroencephalogram (EEG) abnormalities, notably hypsarrhythmia. This case report aims to discuss the various considerations and strategies for the dental management of a child with West syndrome., Method and Result: This report focuses on a case of a 5-year-old girl diagnosed with West Syndrome who presented for her first dental visit with complaints of pain and swelling in the right posterior tooth region for the past three weeks. Due to frequent seizure episodes, neuropsychomotor delay, and multiple dental treatment needs, comprehensive full-mouth rehabilitation was performed under general anesthesia., Conclusion: Awareness of syndromes like West syndrome equips dentists to better manage children with complex conditions. Additionally, parental counselling and early preventive measures can significantly reduce the added burden of dental diseases in these patients., (© 2024 Special Care Dentistry Association and Wiley Periodicals LLC.)

Background: West syndrome (WS) is a devastating epileptic encephalopathy with onset in infancy and early childhood. It is characterized by clustered epileptic spasms, developmental arrest, and interictal hypsarrhythmia on electroencephalogram (EEG). Hypsarrhythmia is considered the hallmark of WS, but its visual assessment is challenging due to its wide variability and lack of a quantifiable definition. This study aims to analyze the EEG patterns in WS and identify computational diagnostic biomarkers of the disease., Method: Linear and non-linear features derived from EEG recordings of 31 WS patients and 20 age-matched controls were compared. Subsequently, the correlation of the identified features with structural and genetic abnormalities was investigated., Results: WS patients showed significantly elevated alpha-band activity (0.2516 vs. 0.1914, p  < 0.001) and decreased delta-band activity (0.5117 vs. 0.5479, p  < 0.001), particularly in the occipital region, as well as globally strengthened theta-band activity (0.2145 vs. 0.1655, p  < 0.001) in power spectrum analysis. Moreover, wavelet-bicoherence analysis revealed significantly attenuated cross-frequency coupling in WS patients. Additionally, bi-channel coherence analysis indicated minor connectivity alterations in WS patients. Among the four non-linear characteristics of the EEG data (i.e., approximate entropy, sample entropy, permutation entropy, and wavelet entropy), permutation entropy showed the most prominent global reduction in the EEG of WS patients compared to controls (1.4411 vs. 1.5544, p  < 0.001). Multivariate regression results suggested that genetic etiologies could influence the EEG profiles of WS, whereas structural factors could not., Significance: A combined global strengthening of theta activity and global reduction of permutation entropy can serve as computational EEG biomarkers for WS. Implementing these biomarkers in clinical practice may expedite diagnosis and treatment in WS, thereby improving long-term outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Li, Ping, Zhou, Su, Li and Xu.)

Objectives: To perform spectral analysis on previously recorded electroencephalograms (EEGs) containing hypsarrhythmia in an initial recording and to assess changes in spectral power (µV 2 ) in a follow-up recording after a period of 10-25 days. Methods: Fifty participants, aged 2-39 months, with hypsarrhythmia in an initial recording (R1), were compared with regard to their spectral findings in a later recording (R2). Typically, anticonvulsant therapy was initiated or modified after R1. Average delta, theta, alpha, and beta power was derived from approximately 3 min of artifact-free EEG data recorded from 19 electrode derivations. Group and individual changes in delta power between R1 and R2 formed the main analyses. Results: Delta accounted for 84% of the total power. In group comparisons, median delta power decreased statistically significantly between R1 and R2 in all 19 derivations, for example, from 3940 µV 2 in R1 to 1722 µV 2 in R2, Cz derivation. When assessing individual participants, delta power decreases in R2 were >50% in 60% of the participants, but <25% in 24% of the participants. Conclusion: Spectral analysis may be used as an additional tool for providing a potential biomarker in the assessment of short-term changes in hypsarrhythmia, including the effects of treatment., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Valproate, levetiracetam, benzodiazepines, and topiramate are antiseizure medications (ASMs) considered to have definite efficacy in reducing the frequency of epileptic spasm frequency, apart from ketogenic dietary therapies. Although zonisamide has also been shown to have efficacy as second-line ASM for epileptic spasms, various studies have conflicting results in literature. This systematic review aims to summarize clinical studies regarding the efficacy of zonisamide for epileptic spasms.Methods: We conducted a systematic literature search collating all available literature. The primary objective was to determine efficacy in terms of proportion with complete spasm resolution, we also intended to determine proportion with at least 50% spasm reduction, hypsarrhythmia resolution, and nature/frequency of adverse effects. All prospective/retrospective, controlled/uncontrolled studies describing the use of zonisamide with epileptic spasms were included in the qualitative review excluding case reports, but for metanalysis pertaining to key outcomes, we included studies with at least 10 participants.Results: A total of nineteen publications were found eligible for inclusion in the qualitative review, out of 101 search items. A total of 401 children with epileptic spasms were tried up to a maximum of 9.9-35 mg/kg/day dose with only mild adverse effects in a few patients. Total 20.8% (95% CI-11.4%-29.2%) and 23.4% (95% CI-17.8%-29.1%) patients had complete cessation of spasms and at least a 50% reduction in total spasm frequency as compared to baseline after starting zonisamide. Similarly, 20.3% (95% CI-10.1%-30.5%) had resolution of hypsarrhythmia in EEG after starting zonisamide.Conclusion: Zonisamide can reduce spasms in 21% of children with epileptic spasms, without major adverse effects. But there are only limited studies on epileptic spasms of sufficient quality to give high confidence in meta-analysis. Large controlled trials are needed in this regard to provide high-quality evidence favoring/disfavoring its use in patients with epileptic spasms. [ABSTRACT FROM AUTHOR]

Objective: To compare intravenous methylprednisolone (IVMP) with oral prednisolone (OP) for the treatment of West syndrome. Methods: In this randomized, open-label trial, children aged 2 to 30 mo presenting with epileptic spasms with hypsarrhythmia or its variants on EEG were randomized to receive either IVMP (30 mg/kg/d for 3 d followed by oral prednisolone taper) or OP (4 mg/kg/d for two weeks followed by taper). The primary outcome measure was spasms cessation on day 14. Secondary outcomes included time to response, electroclinical remission at 2 and 6 wk, and frequency of adverse effects. (ClinicalTrials.gov Identifier: NCT 03876444). Results: Sixty children were enrolled; 31 in the IVMP and 29 in the OP arm. Proportion of children achieving spasms cessation at day 14 was similar in both groups (54.8% versus 68.9%, p = 0.26). Time to achieve remission was lower in the IVMP group (mean 5.4 ± 0.9 versus 9.5 ± 2.6 d, p < 0.0001). Electroclinical remission at 2 wk was similar in both groups (51.6% versus 44.8%, p = 0.59) but lower at 6 wk in the IVMP group (45.2% versus 75.9%, p < 0.015). Adverse effects like sleep disturbance, irritability and hypertension were more common in IVMP group whereas weight gain was more common in the OP group. Conclusions: There was no significant difference in spasms cessation between the groups on day 14 although remission was higher at 6 wk in OP group. Our study suggests that OP was better than IVMP in efficacy and sustained remission with fewer adverse effects. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to evaluate the efficacy of the modified Atkins diet in children with epileptic spasms who had failed hormonal therapy. Methods: Children aged 9 months to 3 years having daily epileptic spasms despite a trial of ACTH or oral prednisolone and 1 additional anticonvulsant medication were enrolled. Children were randomly assigned to receive the modified Atkins diet either immediately or after a delay of 4 weeks. The ongoing anticonvulsant medications were continued unchanged. The primary outcome variable was the proportion of children who achieved spasm freedom as per parental reports at 4 weeks. Secondary outcomes included time to spasm cessation, proportion of children with electroclinical remission, the proportion of children with >50% reduction of spasms at 4 weeks, and adverse effects of the diet. (ClinicalTrials.gov Identifier: NCT03807141). Results: A total of 91 children were enrolled in the study; 46 in the diet group and 45 in the control group. At the end of 4 weeks, 11 children in the diet group were spasm free compared with none in the control group (P ≤.001). The median time to achieve spasm cessation was 10 days (interquartile range 9-20). Nine of these had resolution of hypsarrhythmia on electroencephalography (EEG). Thirty (65.2%) in the diet group had >50% reduction in spasms, compared with none in the control group (P <.001). The most common side effect was constipation, noted in 34.8% of the children. Conclusions: The modified Atkins diet was found to be effective and well tolerated in children with epileptic spasms refractory to hormonal therapy. [ABSTRACT FROM AUTHOR]

PurposeThis study investigated the short-term response to a standardized hormonal therapy protocol for treatment of infantile spasms.MethodsTwenty-seven children with video electroencephalography (EEG)-confirmed infantile spasms received very high dose (8 mg/kg/day, max 60 mg/day) oral prednisolone for 2 weeks. Response (absence of both hypsarrhythmia and spasms) to prednisolone was ascertained by repeat overnight video-EEG. Responders were tapered over 2 weeks and nonresponders were immediately transitioned to high dose (150 IU/m(2)/day) intramuscular adrenocorticotropic hormone (ACTH) for two additional weeks. Response was again determined by overnight video-EEG after ACTH therapy.Key findingsSixty-three percent (17/27) of patients responded completely to prednisolone. Subsequently, 40% (4/10) of prednisolone nonresponders exhibited a complete response after an additional 2-week course with ACTH. Among 27 subjects with median follow-up of 13.5 months (interquartile range [IQR] 4.8-25.9), 12% (2/17) of prednisolone responders and 50% (2/4) of ACTH responders experienced a relapse between 2 and 9 months after initial response.SignificanceVery high dose prednisolone demonstrated significantly higher efficacy than previously reported for lower doses in prior studies. High dose ACTH may be superior to very high dose prednisolone, and in lieu of a definitive clinical trial, the choice between prednisolone and ACTH for initial treatment of infantile spasms remains controversial.

West syndrome is a severe form of childhood epilepsy associated with drug-resistant seizures and intellectual disability. The disease is characterized by specific seizures called infantile spasms, hypsarrhythmia on the electroencephalogram, and delayed psychomotor development. The identification of the disease etiology may affect the prognosis and the choice of therapy. The following prognostic factors have been described so far: etiology, abnormal neurological signs, presence of other epileptic seizures before and after epileptic spasms, response to therapy regardless of the drug type. Difficulties associated with the diagnosis of West syndrome and long-term examination in outpatient settings lead to persistence of hypsarrhythmia and worsen the prognosis. Lack of universal standards for IS therapy results in significant diffe rences in treatment outcomes observed in different regions. Despite significant efforts made towards studying West syndrome, many aspects are still poorly understood. Further studies are needed to help physicians in choosing an optimal treatment strategy and appropriate duration of follow-up as well as to improve the disease prognosis.

Background: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy is a rare autosomal recessive disorder caused by a mutation in the autoimmune regulator gene. Patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy typically exhibit hypoparathyroidism, adrenocortical failure, and chronic mucocutaneous candidiasis. There are only a few case reports of autoimmune encephalitis during autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, but not as an initial manifestation. Furthermore, there are no reports of patients with infantile spasms/West syndrome with autoimmune encephalitis, partly because the median age for paediatric patients with anti-N-methyl-D-aspartate receptor encephalitis, which is the most frequent and best characterised in paediatric autoimmune encephalitides, is 13–14 years. Herein, we present a case of a 3-month-old infant with autoimmune encephalitis as an initial manifestation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy who later developed infantile spasms/West syndrome.Case Presentation: A 3-month-old girl was admitted to our hospital with a fever, involuntary movements in all four limbs, and right-side facial palsy. Acute central nervous system demyelination diseases were suspected from neuroimaging findings and the presence of the cerebrospinal fluid oligoclonal band. She did not respond to multiple methylprednisolone pulse therapies and later developed infantile spasms/West syndrome and diabetes mellitus. Rituximab, a chimeric mouse/human monoclonal antibody directed against human CD20 which depletes B cells, was initially administered as a treatment for autoimmune encephalitis. Unexpectedly, this treatment resulted in complete spasm cessation and resolution of hypsarrhythmia. The patient eventually showed severely delayed developmental milestones, and her electroencephalography findings showed periodic generalised slow spike-and-wave pattern.Conclusions: Despite the limited ability to extrapolate findings from a single case, rituximab's effects may suggest that B cells play a crucial role in infantile spasms/West syndrome mechanisms; use of rituximab as an aetiology-specific treatment for infantile spasms/West syndrome patients with autoimmune encephalitis or its effectiveness for infantile spasms/West syndrome patients with other underlying mechanisms warrants further investigation.