Onset Of Spasms Research Articles

Association of Time to Clinical Remission With Sustained Resolution in Children With New-Onset Infantile Spasms.

Standard therapies (adrenocorticotropic hormone [ACTH], oral steroids, or vigabatrin) fail to control infantile spasms in almost half of children. Early identification of nonresponders could enable rapid initiation of sequential therapy. We aimed to determine the time to clinical remission after appropriate infantile spasms treatment initiation and identify predictors of the time to infantile spasms treatment response. The National Infantile Spasms Consortium prospectively followed children aged 2-24 months with new-onset infantile spasms at 23 US centers (2012-2018). We included children treated with standard therapy (ACTH, oral steroids, or vigabatrin). Sustained treatment response was defined as having the last clinically recognized infantile spasms on or before treatment day 14, absence of hypsarrhythmia on EEG 2-4 weeks after treatment, and persistence of remission to day 30. We analyzed the time to treatment response and assessed clinical characteristics to predict sustained treatment response. Among 395 infants, clinical infantile spasms remission occurred in 43% (n = 171) within the first 2 weeks of treatment, of which 81% (138/171) responded within the first week of treatment. There was no difference in the median time to response across standard therapies (ACTH: median 4 days, interquartile range [IQR] 3-7; oral steroids: median 3 days, IQR 2-5; vigabatrin: median 3 days, IQR 1-6). Individuals without hypsarrhythmia on the pretreatment EEG (i.e., abnormal but not hypsarrhythmia) were more likely to have early treatment response than infants with hypsarrhythmia at infantile spasms onset (hazard ratio 2.23, 95% CI 1.39-3.57). No other clinical factors predicted early responders to therapy. Remission after first infantile spasms treatment can be identified by treatment day 7 in most children. Given the importance of early and effective treatment, these data suggest that children who do not respond to standard infantile spasms therapy within 1 week should be reassessed immediately for additional standard treatment. This approach could optimize outcomes by facilitating early sequential therapy for children with infantile spasms.

Early-onset spontaneously relieved spasms of infancy in sleep: Electroclinical characteristics and differential diagnoses

PurposeInfantile spasm-like paroxysms are often difficult to classify as epileptic or non-epileptic. We aimed to study spontaneously relieved (non-epileptic) spasms of infancy in sleep. Elucidation of the electroclinical characteristics and differential diagnoses of such spasms could facilitate accurate diagnosis in the future. MethodsWe retrospectively analyzed the clinical data, video-EEG recordings, and other laboratory test results of patients with spontaneously relieved spasms of infancy during sleep. All the enrolled patients were followed up for at least 5 months. ResultsSeven infants were included in this study. The median age at spasm onset was 0.5 months (range: 0.1–2 months). The episodes were characterized by clusters of non-epileptic spasms of the head, trunk, or extremities lasting approximately 0.5–2 s, and were validated by ictal electromyography (EMG)/video EEG. Episodes occurred several times daily in clusters, particularly during sleep; two patients also experienced episodes while awake. Additionally, non-epileptic jerks were recorded in 3 patients. All non-epileptic spasms were completely resolved 2 weeks to 3 months after onset. Moreover, neuropsychomotor development in all patients was normal at the last follow-up (5 to 12 months). ConclusionsSpontaneously relieved spasms of infancy in sleep is a self-limiting movement disorder characterized by onset between 0.1 and 2 months of age, and by clusters of spasms occurring in sleep. Correct differential diagnosis relies on familiar clinical and electrophysiological features.

COVID-19 in Children with West Syndrome: An Ambispective Study.

ObjectivesTo study the course of West syndrome (WS) and coronavirus disease-19 (COVID-19) in children with WS who contracted SARS-CoV-2 infection.MethodsThis ambispective study was conducted at a tertiary-care center in North India between December 2020 and August 2021 after approval from the Institute Ethics Committee. Five children with WS, positive for COVID-19 based on RT-PCR, fulfilled the inclusion criteria.ResultsOne child with COVID-19 during the first wave was retrospectively included while four children (of the 70 children screened) were prospectively enrolled. The median age at onset of epileptic spasms was 7 mo (2 boys), and that at presentation with COVID-19 was 18.5 mo. Three had underlying acquired structural etiology. Three were in remission following standard therapy, while two had ongoing spasms at the time of COVID-19 illness. During the illness, two of those in remission continued to be in remission while one child had a relapse. The children with ongoing epileptic spasms had variable course [one had persistent spasms and other had transient cessation lasting 3 wk from day 2 of COVID-19 illness, but electroencephalography (on day 8 of COVID-19 illness) continued to show hypsarrhythmia]. Fever was the most typical symptom (and sometimes the only symptom) of COVID-19, with a duration ranging from 1–8 d. Two children had moderate COVID-19 illness requiring hospitalization, while the rest had a mild illness. All the affected children had complete recovery from COVID-19.ConclusionThe severity of COVID-19 illness in children with WS is often mild, while the subsequent course of WS is variable.

A Combination of Curcuma longa and Diazepam Attenuates Seizures and Subsequent Hippocampal Neurodegeneration.

Epilepsy is one of the most common neurological disorders, which occurs due to the instability in the inhibitory and excitatory synaptic transmissions in the brain. However, many patients develop resistance to the available drugs, which results in cell degeneration caused due to inadequate control of the seizures. Curcumin, Curcuma longa, is known to be effective for the treatment of organic disorders and may prevent seizures, reduce oxidative stress, and decrease brain damage. Given this, the present study evaluated the antiepileptic effects of C. longa in comparison with both the diazepam and the combined application of these two substances, in terms of their effects on the brain activity and the potential histopathological changes in the hippocampus. This study used male Wistar rats (age: 10–12 weeks; weight: 260 ± 20 g), which were pretreated for 4 days with either saline, C. longa, diazepam, or C. longa + diazepam; and on the fifth day, pentylenetetrazol (PTZ) was administered to induce the seizure. In the C. longa group, a significant increase was observed in the latency of the onset of seizure-related behavior. Surprisingly, however, the combined treatment resulted in the best control of the seizure-related behavior, with the greatest latency of the onset of spasms and isolated clonic seizures. This group also obtained the best results in the electroencephalographic trace and seizure control, with a reduction in the frequency and amplitude of the spike-waves. In the saline group, PTZ significantly reduced the number of cells present in the CA1 and CA3 regions of the hippocampus, while the combined treatment obtained the best results in terms of the preservation of the neuron-like cells. These findings indicate that C. longa may contribute to the control of both seizures and the cell damage induced by PTZ, and that its association with diazepam may be a potentially effective option for the treatment of epilepsy in the future.

Anticonvulsant Activity of trans-Anethole in Mice.

Epilepsy is a chronic neurological disorder affecting 1-2% of world population, and one-third of patients are refractory to pharmacological treatment. This fact has stimulated research for new antiepileptic drugs and natural products have been an important source. trans-Anethole (TAN) is a phenylpropanoid, component of some essential oils, extracted from plants, and its effects have been little studied. Therefore, this study is aimed at investigating the TAN effect in classic seizure models and evaluate the electroencephalographic (EEG) profile of animals treated with this substance. For this, Swiss male mice (Mus musculus) were used, and the lethal dose was evaluated and subsequently submitted to the test maximal electroshock (MES), the pentylenetetrazole- (PTZ) induced seizure test, and the EEG profile. Initially, the LD50 for TAN was estimated in 1000 mg/kg (i.p.) dose and there was no sign of acute toxicity or death. In the MES test, TAN 300, i.p. (12.00 ± 2.9 s) and 400 mg/kg, i.p. (9.00 ± 4.4 s) doses was able to decrease tonic seizures duration induced by electric discharge (0.5 mA, 150 pulses/s, for 0.5 s). In the PTZ test (75 mg/kg, i.p.), TAN 400 mg/kg, i.p. increased the latency to myoclonic jerks (80.0 (56.0–134.0)), the latency totonic-clonic seizures (900.0 (861.0–900.0) and decrease seizure duration (0.0 (0.0–10.0)). No deaths were found in this groups compared to vehicle. EEG analysis showed an amplitude decrease of waves (ratio of baseline) in TAN 300 (1.82 ± 0.23) and 400 mg/kg (1.06 ± 0.16) groups. In this way, TAN at 400 mg/kg was able to inhibit and/or attenuate seizures by increasing the time for the onset of spasms and convulsions, as reducing the duration of seizures. The EEG profile corroborate with this results showing a reduction in the amplitude of waves compared to the PTZ group. Thus, TAN showed an anticonvulsant effect in all experimental models performed, behavioral and electroencephalographic.

The Clinical Features and Long-Term Follow-Up of Vitamin B6-Responsive Infantile Spasms in a Chinese Cohort.

ObjectiveTo analyze the clinical features, treatment, and prognosis of patients with vitamin B6-responsive infantile spasms (IS).MethodsThe clinical features, genetics, and follow-up data of 30 patients were collected and analyzed.ResultsThe age of epileptic spasms (ES) onset was from 3 months to 12 months. They all received high doses of vitamin B6 at different times after the onset of ES, ranging from 1 day to 5 months. ES were controlled within 11 days in 93% (28/30) patients, and as late as 1 month and 2 months in the other two patients. In the course of treatment, 28 patients were seizure-free all the time, and seizures of other two patients recurred due to withdrawal of vitamin B6. The available follow-up EEG results of 28 patients were normal in 26 cases, and 81% (21/26) had suppressed epileptic discharges within 6 months. Of the 26 cases with normal follow up EEG, 4 had developmental delay and 22 had normal development. The time for EEG to return to normal in 22 patients with normal development ranged from 14 days to 2 years (mean = 111.5 days; median = 52.5 days). The time for EEG to return to normal in the other 4 patients with development delay ranged from 4 months to 2 years (mean = 375 days; median = 330 days). To the last follow-up, seizures were controlled well in 29 surviving patients, and 21 patients were able to deactivate from all medications without seizures recurrence. Sixteen patients showed varying degrees of developmental delay after onset. After seizure control, the psychomotor development was delayed in 7 patients (one died) until the last follow-up. Genetic analysis did not show any meaningful results.ConclusionAn observation period of 1–2 weeks is essential to identify patients with vitamin B6-responsive IS. The treatment time could be extended according to the treatment response and EEG changes. It might take a longer time for EEG to return to normal and to stop taking drugs in patients with persistent or unimproved developmental delay. Neurodevelopmental outcomes and prognosis of vitamin B6-responsive IS were relatively favorable.

Predictors of outcome among 31 children with infantile spasms syndrome.

Infantile spasms syndrome is a severe epileptic encephalopathy. Management of infantile spasms remains challenging because of pharmacoresistant forms and relapsing seizures. A high number of patients with this syndrome have neurodevelopmental delay. The main objective of our study was to determine predictors to measure the neurodevelopmental outcome of patients with infantile spasms. We prospectively evaluated 31 patients with infantile spasms from 2014 to 2017 at three hospitals in Tbilisi, Georgia. Various demographic data were evaluated at the first visit; video-EEG, brain MRI and neurodevelopmental evaluation were performed upon admission. A diary to record spasms was provided and completed by all parents/caregivers. Seizures were recorded on video and the phenomenology of infantile spasms was studied. Children were followed for one and two years after the first assessment. Neurodevelopmental deterioration was revealed in 61.1% on the second and 53% on the third evaluation in patients with onset of spasms before seven months of age. The mean score on the ASQ communication domain was low among structural cases. Eleven patients with pre-existing delay had developmental regression based on the second evaluation (Fisher's exact test: 7.2; df 1; p=0.01). Our study reveals that age at onset of infantile spasms at less than seven months, pre-existing developmental delay, low ASQ scores and structural abnormalities on MRI are predictors of poor developmental outcome. Our data suggest that clinicians should inform parents at the first clinical evaluation about prognosis, and intervention should be started as early as possible in order to improve development.

Short-term outcome of intravenous methylprednisolone pulse therapy versus oral prednisolone in patients with epileptic spasms

BackgroundInfantile 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.ResultsWe 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.ConclusionsNo 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.

Infantile spasms: Assessing the diagnostic yield of an institutional guideline and the impact of etiology on long-term treatment response.

Neuroimaging and genetic testing have been proposed for diagnostic evaluation of infantile spasms (IS), establishing etiology in ~60% of multicenter IS cohorts. A retrospective analysis of the yield of diagnostic etiology following an institutionally established guideline for investigation/treatment of IS was conducted, and the association between etiological subgroups and sustained response to standard treatment was evaluated. Etiology of IS, neuroimaging, and genetic results were extracted from clinical records. Etiology was categorized as acquired or nonacquired, the latter including syndromic patients, nonsyndromic patients with confirmed etiology, and unknown cases. Regression analyses, using clinical variables including subtypes of etiology, were conducted to determine which factors correlated with favorable (spasm freedom at last follow-up after two or fewerstandard treatments) versus unfavorable treatment outcome (refractory spasms despite two standard treatments or relapse). We included 127 IS patients (60% males) with a follow-up of 2.4years (range = .6-5years). All patients had neuroimaging, and 95% of patients in the nonacquired category (103 of 108 patients) had genetic testing. Etiology was identified in 103 of 127 (81%, 95% confidence interval = .73-.86). At last follow-up, 42 (33%) patients had favorable treatment outcome. No difference in treatment response was observed between acquired and nonacquired etiologies. Among patients with nonacquired etiologies, developmental delay prior to spasms onset increased the odds of unfavorable treatment outcome (p=.014), whereas a clearly recognizable dysmorphic/syndromic etiology was associated with a lower risk for treatment failure (p=.034). In nonacquired etiology without a recognizable dysmorphic/syndrome but with a genetic etiology, unfavorable treatment outcome was more likely (p=.043). Rigorous evaluation with neuroimaging and genetic testing yields an etiological diagnosis in most patients with IS. Among patients with a nonacquired etiology, those with recognizable dysmorphic/syndromic diagnosis had a higher likelihood of a favorable treatment outcome, whereas the absence of such a finding, when associated with an identifiable genetic diagnosis, was associated with unfavorable treatment outcomes.

A tale of two cohorts: Differing outcomes in infantile-onset focal epilepsy.

Infants with focal-onset epilepsy are an understudied population, requiring additional evaluation for clinical assessment and prognostication. Our goal was to characterize the etiology and natural history of infantile-onset focal epilepsy. We retrospectively identified all infants (0-24months) with onset of focal epilepsy while resident in Olmsted County, Minnesota, between 1980 and 2018, using the Rochester Epidemiology Project Database. We assessed the impact of etiology on both seizure and neurodevelopmental outcome, and mortality. Of 686 children with epilepsy onset <18years, 125 (18.2%) presented with focal-onset seizures in infancy. Median follow-up for this group was 10.9years (interquartile range [IQR] 6.2, 19.3). Etiology was identified in 65.6% (structural N=62, genetic N=13, both structural and genetic N=3, metabolic N=4). Of 107 patients followed >2years, 38 (35.5%) developed drug-resistant epilepsy (DRE). DRE was more likely with younger age at onset, known etiology, and presence of epileptic spasms. Sixty-eight (63.0% of those with follow-up) were developmentally delayed at last follow-up, and known etiology, DRE, and presence of epileptic spasms were significantly associated with delay (p<.001 for all). Fifteen patients (12.0%) died at a median age of 7.1years (IQR 1.7, 21.7), but only one death was seizure related (suspected sudden unexpected death in epilepsy [SUDEP]). Of 20 infants with normal development at onset and no known etiology with >2years follow-up, none developed DRE, all were seizure-free at last follow-up (95% off antiseizure medications [ASMs]), and all remained developmentally normal. Infantile-onset focal epilepsy accounts for 18% of all epilepsy in childhood, is frequently due to known etiologies, and has a high rate of DRE. However, developmentally normal infants without a known cause appear to have a very favorable course.

Response to treatment and outcomes of infantile spasms in Downsyndrome.

AimTo estimate the prevalence, and evaluate presentation, treatment response, treatment side effects, and long‐term seizure outcomes in all known cases of children with Down syndrome and infantile spasms on the island of Ireland.MethodThis was a 10‐year retrospective multicentre review of clinical records and investigations, focusing on treatment response, side effects, and long‐term outcomes.ResultsThe prevalence of infantile spasms in Down syndrome was 3.0% during the study period. Fifty‐four infants were identified with median age of spasm onset at 201 days (interquartile range [IQR] 156–242). Spasm cessation was achieved in 88% (n=46) at a median of 110 days (IQR 5–66). The most common first‐line medications were prednisolone (n=20, 37%), vigabatrin (n=18, 33.3%), and sodium valproate (n=9, 16.7%). At follow‐up (median age 23.7mo; IQR 13.4–40.6), 25% had ongoing seizures and 85% had developmental concerns. Treatment within 60 days did not correlate with spasm cessation. Seventeen children (31%) experienced medication side effects, with vigabatrin accounting for 52%.InterpretationPrednisolone is an effective and well‐tolerated medication for treating infantile spasms in Down syndrome. Despite the high percentage of spasm cessation, developmental concerns and ongoing seizures were common.

Comparative Antiseizure Activities of Some Branded and Generic Antiepileptic Drugs in a Nigerian City

Branded antiepileptic drugs (AEDs) are expensive, and in developing countries, cheaper generic equivalents may be used interchangeably. Therefore, this study aimed to compare the antiseizure activities of some available branded and generic AEDs in mice. The physicochemical properties of four generic and branded AEDs (carbamazepine, CAB; sodium valproate, SVP; phenytoin, PHY, and phenobarbitone, PHB) were determined according to pharmacopoeial methods. The organoleptic proper-ties, tablet hardness and thickness of the samples were also assessed. The anticonvulsant effect of AEDs was determined using maximal electroshock (MES) and pentylenetetrazole (PTZ) induced seizure. The samples of AEDs showed uniformly comparable organoleptic properties. The active moiety content for all the samples fell within the acceptable ranges stipulated in the official compendia. A significant statistical difference (p≤0.05) in disintegration time existed between two generic formulations of PHB, PHB01 (4.62±1.17 min), and PHB02 (1.40±0.26 min). Similarly, a significant statistical difference (p≤0.05) in hardness (10.40±0.15 kgF vs 5.61±0.03 kgF) and disintegration time (4.65±0.49 min vs 0.64±0.30 min) was observed between the two brands of CAB (CAB02 and CAB03 respectively). No significant statistical difference exists in mean recovery time between control (5.70±0.72 min) and treatment groups (CAB01, 6.50±0.65 min) in the MEST. In the PTZ test, there was a significant (p≤0.001) difference in the mean onset of clonic spasm between control (10.03±0.75 min) and PHB, PHB01 (17.50±0.99 min) 30 min post-treatment. In conclusion, no significant variation in the physicochemical and antiseizure activity of branded and generic formulations of AEDs was observed

Does Etiology and Hypsarrhythmia Subtype Influence Outcome in West Syndrome? Challenges Encountered from a Referral Center Perspective.

Prediction of outcome of West syndrome (WS) in relation to etiology and electrophysiology remain pertinent challenges. 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. 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. 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). Early diagnosis and initiation of optimal therapy is crucial towards improving outcome, irrespective of etiology (which impacts pre-spasm development) and HA subtypes.

A Retrospective Cohort Study of Combined Therapy in West Syndrome associated with Trisomy 21.

Background: West syndrome (WS) is a frequent epileptic encephalopathy associated with Down syndrome (DS). This study evaluated an outpatient protocol for WS in patients with DS who received vigabatrin (VGB) or VGB plus adrenocorticotrophic hormone. Methods: We analyzed infants treated in two neuropediatric centers from 2001–2021. We reviewed perinatal and familial history of epilepsy, spasm onset, treatment lag, electroencephalogram, neuroimaging, progression to epilepsy, and other neurological conditions. The outcomes were electroclinical resolution (ECR), relapses, and epilepsy progression. Results: Nineteen infants were included; 57.8% were male. The average spasm onset, follow-up, and treatment lag were 6.4 months, 8.15 years, and 2.33 months, respectively. Almost 74% had ECR after protocol intervention and minor epilepsy progression. Relapses occurred during combined therapy. Conclusions: The treatment protocol, especially combined therapy, was effective for WS in DS, impacting epilepsy progression and indicating the effectiveness of combined therapy to treat WS in patients with trisomy 21.

Adjunctive perampanel therapy for patients with epileptic spasms

Perampanel is an antiepileptic drug. Some studies have documented the efficacy of perampanel in epileptic spasms. We aimed to evaluate the efficacy and safety of adjunctive perampanel therapy (PT) in patients with epileptic spasms. We retrospectively surveyed the efficacy and safety of adjunctive PT in 14 patients with epileptic spasms at the Saitama Children's Medical Center between June 2016 and September 2021. Seizure outcomes and safety were evaluated 12months after commencing PT. Response to perampanel was defined as complete remission of epileptic spasms for more than 3 months. The median age at onset of epileptic spasms was 0.4 years (range, 0.1-1.3 years). The etiology was structural in 11 patients, genetic in two, and unknown in one. The median age at the commencement of PT was 3.2 years (1.5-10.3 years). The initial and maintenance doses of perampanel were administered at 0.04 (range, 0.02-0.05) mg/kg/day and 0.12 (range, 0.03-0.24) mg/kg/day, respectively. Five of the 14 patients (35.7%) showed remission of epileptic spasms for more than 3 months at 12months after PT; these patients had a structural etiology. The median duration between commencement of perampanel and spasm remission was 2 months (range, 1-6 months). No serious adverse effects occurred. This is the first case series evaluating adjunctive PT for epileptic spasms. PT is worth investigating to treat epileptic spasms in patients with structural etiologies. As our study population primarily comprised children aged 2 years and older, PT may be useful for epileptic spasms beyond infancy.

P.109 Diagnostic Yield of Targeted Exome Sequencing in West Syndrome

Background: West syndrome (WS) is characterized by the onset of epileptic spasms usually within the first year of life. Global developmental delay with/without regression is common. Advances in high-throughput sequencing have supported the genetic heterogeneity of this condition. To better understand the genetic causes of this disorder, we investigated the results of targeted exome sequencing in 29 patients with WS. Methods: Whole exome sequencing (WES) was performed on an Ion ProtonTM and variant reporting was restricted to sequences of 620 known epilepsy genes. Diagnostic yield and treatment impact are described for 29 patients with WS. Results: A definitely/likely diagnosis was made in 10 patients (34%), which included 10 different genes (ALG13, PAFAH1B1, SLC35A2, DYNC1H1, ADSL, DEPDC5, ARX, CDKL5, SCN8A, STXBP1) known to be associated with epilepsy or WS. Most variants were de novo dominant (X-linked/autosomal) except for ARX (X-linked recessive) and ADSL (autosomal recessive). 4 out of 10 (40%) had a genetic diagnosis with potential treatment implications. Conclusions: These results emphasize the genetic heterogeneity of WS. The high diagnostic yield, along with the significant genetic variability, and the potential for treatment impact, supports the early use of this testing in patients with unexplained WS.

Clinical characteristics of patients with young-onset hemifacial spasm: a retrospective analysis of 151 cases

Objective The average age of hemifacial spasm (HFS) onset is mostly between the fifth and sixth decades of life, with a relatively low incidence in younger age groups. The objective of this study was to analyze the characteristics and clinical outcomes of young-onset hemifacial spasm (YOHFS). Methods Between April 1997 and March 2021, 151 HFS patients aged 30 years or younger at the time of microvascular decompression (MVD) were selected. We analyzed their epidemiological characteristics, intraoperative findings, improvements, and postoperative complications by reviewing medical records. Results This study included 151 patients who underwent MVD. The average age of the patients was 26 years. The mean symptom duration was 36.5 months. The male-to-female sex ratio was 1:1.5. The most common offending vessel was the anterior inferior cerebellar artery, and the most common compression type was the arachnoid type. Improvements in spasm after MVD were seen in 96.7% of patients. No permanent facial palsy was noted after MVD. Changes in brainstem auditory-evoked potentials were recorded in 11 patients; however, no permanent hearing loss was observed. Conclusion The characteristics and clinical outcomes of YOHFS in this study were similar to those of patients with HFS in the general population. Based on the clinical outcomes, MVD for YOHFS is effective and safe. Therefore, MVD should be considered in patients with YOHFS. KEY WORDS: Hemifacial spasm, Microvascular decompression surgery, Prevalence

Effectiveness and Safety of Nitrazepam in Children with Resistant West Syndrome.

To study the effectiveness, tolerability, and safety of oral nitrazepam in children with resistant West syndrome (WS). This prospective observational study was conducted at a tertiary care hospital in North India from January 2019 to October 2020. Children with WS resistant to standard therapy were enrolled within 7 d of initiation of nitrazepam and prospectively followed-up for cessation of spasms and adverse events. Forty-one children with resistant WS initiated on nitrazepam therapy were evaluated. The median age at onset of spasms was 6 mo (Q1, Q3: 4, 8). There was a preponderance of male gender (71%) and structural causes (78%). More than half of the enrolled children had failed four or more antiseizure medications (ASM) for epileptic spasms. The study participants had a long lead-time-to-treatment (LTTT) for the initial standard therapy (median: 2 mo; Q1, Q3: 1, 5) and nitrazepam (median: 11 mo; Q1, Q3: 8, 16). Nitrazepam was instituted as monotherapy in 7 (17%) children and as an adjunct in the rest. Twenty-one (51%) children achieved persistent cessation of epileptic spasms. However, the electroclinical response was observed in 17 (42%) children. Drowsiness, sialorrhea, and decreased appetite were the most commonly observed adverse events. Most adverse events were mild to moderate in severity and did not require dose reduction or change of medication. There was no significant difference between the responders and nonresponders in terms of LTTT, age at onset, or etiology. Nitrazepam is a safe and feasible treatment alternative in children with resistant WS resulting in persistent cessation of spasms and electroclinical response in nearly half of patients.

Financial Burden in Families of Children with West Syndrome.

ObjectiveTo evaluate the illness-related expenditure by families of children with West syndrome (WS) during the first year of illness and to explore the potential determinants of the financial drain.MethodsThis cross-sectional study was conducted at a tertiary care hospital between July 2018 and June 2020. Eighty-five children with WS who presented within one year from the onset of epileptic spasms were included. The details of the treatment costs (direct medical and nonmedical) incurred during the first year from the onset of epileptic spasms were noted from a parental interview and case record review. Unit cost was fixed for drugs and specific services. Total cost was estimated by multiplying the unit cost by the number of times a drug or service was availed. The determinants of the financial burden were also explored.ResultsThe median monthly per-capita income of the enrolled families (n = 85) was INR 3000 (Q1, Q3, 2000, 6000). The median cost of treatment over one year was INR 27035 (Q1, Q3, 17,894, 39,591). Median direct medical and nonmedical expenses amounted to INR 18802 (Q1, Q3, 12,179, 25,580) and INR 6550 (Q1, Q3, 3500, 15,000), respectively. Seven families had catastrophic healthcare expenditure. Parental education and choice of first-line treatment were important determinants driving healthcare expenses. The age at onset of epileptic spasms, etiology, treatment lag, the initial response to treatment, and relapse following initial response did not significantly influence the illness-related expenditure by the families.ConclusionWS imposes a substantial financial burden on the families and indirectly on the healthcare system.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12098-021-03761-1.

Long-term epilepsy control, motor function, cognition, sleep and quality of life in children with West syndrome

PurposeTo assess epilepsy, motor function, cognitive, sleep, and quality of life outcomes and their predictors in a follow-up cohort with West syndrome (WS) at ≥5 years of age. MethodsCross-sectional evaluation in a follow-up cohort of WS (aged 5–14 years), between July 2018 and December 2019, was performed at a tertiary-care referral center in Northern India. 164 children were assessed in-person for epilepsy severity, functional status (gross motor and hand function), social quotient, behavioral comorbidities, sleep problems, and quality of life (QoL) using Early Childhood Epilepsy Severity Scale, Gross Motor Function Classification System, Manual Ability Classification System, Vineland Social Maturity Scale, Diagnostic and Statistical Manual of Mental disorders-5 criteria, Children’s Sleep Habits Questionnaire, and PedsQL-Epilepsy module respectively. Furthermore, 238 children with the inability to visit the hospital were assessed through telephonic interview along with retrospective case record review for epilepsy control, gross and fine motor measures. Results402 children with WS (75 % boys) with regular follow-up were studied and the majority (80 %) had underlying structural etiology. The median age (interquartile range) of the cohort was 92 (78–107) months. Of these, 60 % had evolved to Lennox-Gastaut syndrome (LGS). The following long-term outcomes were observed: ongoing epilepsy (261/402), unfavorable motor status (130/402), moderate to profound intellectual disability (111/164), autistic spectrum disorder (42/164), attention-deficit hyperactivity disorder (18/164), poor sleep (135/164), and impaired QoL (115/164). Non-structural etiology (odds ratio [OR] = 3.8, 95 % confidence interval [CI]: 2.1−5.5, p=<0·0001) and older age (>5 months) at the onset of epileptic spasms (OR = 2·9, 95 % CI: 1.5−5.0, p=<0·0001) were associated with enduring seizure freedom for more than two years. ConclusionThe present study revealed a preponderance of structural etiology and a high rate of transition to LGS. Early age at onset of spasms (before five months) and structural etiology were the predictors of unfavorable long-term epilepsy outcome. QoL was impaired in more than two-thirds of patients and it correlated significantly with cognitive, sleep, motor, and behavioral outcomes. However, the results of our study should be interpreted in the context of significant attrition of the original cohort.