Metabolic etiologies in children with infantile epileptic spasm syndrome: Experience at a tertiary pediatric neurology center.

OBJECTIVE: Infantile epileptic spasm syndrome (IESS), including West syndrome (WS) and infantile spasm (IS), causes a challenging prognosis, particularly when associated with metabolic etiologies. METHODS: This study, conducted at a tertiary pediatric neurology center, explored the prevalence and clinical features of inborn errors of metabolism in 112 children with IESS over 10 years. RESULTS: Most patients presented with seizures, primarily flexor spasms, and the median age at onset was 5 months. Comprehensive clinical evaluation and neuroimaging revealed structural-acquired causes as the most common etiology. Notably, inborn errors of metabolism were identified in 5.4 % of cases, with six distinct diagnoses including nonketotic hyperglycinemia, pyridoxine-dependent epilepsy, primary coenzyme Q10 deficiency 7, congenital disorder of glycosylation type IIM, 6-pyruvoyl tetrahydrobiopterin synthase deficiency, and argininosuccinate lyase deficiency. The prevalence of inborn errors of metabolism in this cohort was consistent with global variations reported in the literature. Genetic testing, including karyotype analysis and whole exome sequencing, was performed in a subset of cases with no clear diagnosis, revealing abnormalities in approximately 50 % of cases. Adrenocorticotropic hormone emerged as the most frequently prescribed antiseizure medication. CONCLUSION: This study provides insight into the diagnostic challenges associated with IESS and highlights the importance of metabolic investigations, especially in cases without a clear etiology. The findings emphasize the need for further genetic and metabolic studies to enhance prognostic accuracy and guide potential treatment options for children with IESS, particularly in populations with high rates of consanguinity.

Real-life data comparing the efficacy of vigabatrin and oral steroids given sequentially or combined for infantile epileptic spasms syndrome.

AIMS: The prognosis of Infantile epileptic spasm syndrome (IESS), relates to the underlying etiology and delay in controlling epileptic spasms. Based on the spasm-free rate, a randomized controlled trial has demonstrated the superiority of combining oral steroids and vigabatrin over oral steroids alone but confirmation in real-life conditions is mandatory. METHODS: We compared two real-life IESS cohorts: a multicenter, retrospective cohort of 40 infants treated with vigabatrin followed by a sequential (ST) addition of steroids, and a prospective, single-center cohort of 58 infants treated with an immediate combination of vigabatrin and steroids (CT). RESULTS: The two cohorts were similar. When the rate of spasm-free infants in the two cohorts was compared on day 14, a significant difference was observed between the ST (27,5 %) and CT cohorts (64 %) (p < 0.0004). This difference remained significant on day 30, with 55 % spasm-free patients in the ST cohort compared to 76 % in the CT cohort (p = 0.03). After the infants had received both vigabatrin and steroids, without taking into account the time point after treatment initiation, no significant difference was observed in the spasm-free rate between the two cohorts (p = 0.38). INTERPRETATION: Real-life data confirm the interest of combination therapy as a first-line treatment for IESS.

Predicting Antiseizure Medication Treatment in Children with Rare Tuberous Sclerosis Complex-Related Epilepsy Using Deep Learning.

BACKGROUND AND PURPOSE: Tuberous sclerosis complex disease is a rare, multisystem genetic disease, but appropriate drug treatment allows many pediatric patients to have positive outcomes. The purpose of this study was to predict the effectiveness of antiseizure medication treatment in children with tuberous sclerosis complex-related epilepsy. MATERIALS AND METHODS: We conducted a retrospective study involving 300 children with tuberous sclerosis complex-related epilepsy. The study included the analysis of clinical data and T2WI and FLAIR images. The clinical data consisted of sex, age of onset, age at imaging, infantile spasms, and antiseizure medication numbers. To forecast antiseizure medication treatment, we developed a multitechnique deep learning method called WAE-Net. This method used multicontrast MR imaging and clinical data. The T2WI and FLAIR images were combined as FLAIR3 to enhance the contrast between tuberous sclerosis complex lesions and normal brain tissues. We trained a clinical data-based model using a fully connected network with the above-mentioned variables. After that, a weighted-average ensemble network built from the ResNet3D architecture was created as the final model. RESULTS: The experiments had shown that age of onset, age at imaging, infantile spasms, and antiseizure medication numbers were significantly different between the 2 drug-treatment outcomes (P < .05). The hybrid technique of FLAIR3 could accurately localize tuberous sclerosis complex lesions, and the proposed method achieved the best performance (area under the curve = 0.908 and accuracy of 0.847) in the testing cohort among the compared methods. CONCLUSIONS: The proposed method could predict antiseizure medication treatment of children with rare tuberous sclerosis complex-related epilepsy and could be a strong baseline for future studies.

Infantile epileptic spasms syndrome: a cohort study of 88 children.

BACKGROUND: This study aimed to investigate and analyze the risk factors for non-etiology-specific infantile spasms (IS) and unrelieved clinical symptoms after treatment. METHODS: Eighty-eight children with IS who were treated at our hospital from March 2018 to December 2021 were included in the study. The children were divided into etiology-specific (n = 46) and nonetiology-specific (n = 42) groups, based on the diagnostic results, and remission (n = 45) and nonremission (n = 43) groups, based on clinical outcomes after treatment. The clinical data from patients in the etiology-specific and nonetiology-specific groups and the remission and nonremission groups were compared. Risk factors for non-etiology-specific IS were identified using logistic regression analysis. RESULTS: Gender, family history, birth status, and metabolic abnormalities were significantly different between the etiology-specific and non-etiology-specific groups. Gender and metabolic abnormalities were risk factors for nonetiology-specific IS. Family history, birth status, metabolic abnormalities, and brain magnetic resonance imaging were significantly different between the remission and nonremission groups, and different etiologies were risk factors for unrelieved symptoms after treatment. CONCLUSION: The occurrence of nonetiology-specific IS is associated with gender and metabolic abnormalities in children. After medication, unrelieved IS symptoms are associated with etiologies.

Epileptic Spasms During Recovery From Nutritional Infantile Vitamin B12 Deficiency.

Development of epileptic spasms in infants with vitamin B12 deficiency is uncommon. In some cases, infants presenting with epileptic spasms have been found to have concurrent vitamin B12 deficiency. Treatment with vitamin B12 and adrenocorticotropic hormone (ACTH) resulted in resolution of epileptic spasms. In others, epileptic spasms have developed during recovery from vitamin B12 deficiency. Treatment with ACTH or other seizure medications resulted in resolution of epileptic spasms, although response has been less predictable. We describe three infants who initially presented with clinical and laboratory features of vitamin B12 deficiency. Treatment with vitamin B12 resulted in rapid resolution of symptoms. However, recovery was interrupted by the development of epileptic spasms. All infants showed hypsarrhythmia on electroencephalography. Treatment with prednisolone, with or without other antiseizure medications, resulted in slow resolution of spasms. Cognitive and language delays were noted in two infants. Epileptic spasms may supervene during recovery from vitamin B12 deficiency affecting outcomes.

Nutritional vitamin B12 deficiency-associated Infantile epileptic spasms syndrome: Clinico-neurophysiological presentation, response to treatment, and neurodevelopmental outcome.

INTRODUCTION: Nutritional vitamin B12 deficiency has been shown to cause Infantile epileptic spasms syndrome (IESS) in infants in anecdotal studies. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Clinical seizure semiology is subtle and identification of seizures by parents is unreliable in infants with tuberous sclerosis complex.

OBJECTIVE: The objectives of this study were to assess the accuracy of parental seizure detection in infants with antenatally diagnosed tuberous sclerosis complex (TSC), and to document the total seizure burden (clinical and subclinical) in those patients who met criteria for prolonged electroencephalography (EEG) recording. METHODS: Consecutive infants at a single institution with antenatally diagnosed TSC who met criteria for prolonged video-EEG (vEEG) were recruited to this study. The vEEG data were reviewed and when a seizure was identified on EEG, the video and audio recording was assessed for evidence of clinical seizure and, if present, whether there was evidence of parent seizure identification. RESULTS: Nine infants were enrolled, for whom 674 focal seizures were identified in eight of nine patients across 24 prolonged vEEG recordings, with vEEG total duration of 634 h 49 min (average seizure frequency of 1 focal seizure/h). Only 220 of 674 (32.6%) were clinical seizures, 395 of 674 (58.6%) were subclinical seizures, and 59 of 674 seizures could not be classified. Only 63 of 220 clinical seizures (28.6%) were identified by parents, with 157 of 220 (71.4%) not identified. Thirty clusters of epileptic spasms were detected in one patient. At least one clinical epileptic spasm occurred in 2 of 30 clusters (6.7%), 24 of 30 clusters of epileptic spasms (80%) were electrographic only, and classification was uncertain for 4 of 30 clusters (13.3%). No clinical epileptic spasms were detected by parents. Clinical seizure frequency was significantly underestimated by parents for all patients. SIGNIFICANCE: This study demonstrates that in infants with TSC who met criteria for prolonged vEEG, (1) parents significantly under recognize total clinical seizure count, (2) parents fail to identify epileptic spasms, and (3) seizure frequency is high. This highlights that epilepsy treatment decisions should not be based solely on parental clinical seizure identification. Prolonged vEEG monitoring may have an important role in the routine epilepsy care of infants with TSC, as demonstrating undetected high clinical seizure frequency may allow improved epilepsy management decisions.

[Epileptic encephalopathies of onset in neonates and infants]. / Encefalopatías epilépticas de inicio en recién nacidos y lactantes.

The International League Against Epilepsy (ILAE) recently socialized the proposed classification for epileptic syndromes of neonatal onset and up to the first 2 years of age, dividing them into self-limited epileptic syndromes and epileptic and developmental encephalopathies (DEEs). In this review we will focus on DEEs, defined as disorders in which there is developmental impairment related to both the underlying aetiology independent of epileptiform activity and epileptic encephalopathy. These include early infantile epileptic encephalopathy or Ohtahara syndrome and early myoclonic encephalopathy in the neonatal period, now grouped under the name of epileptic and early childhood developmental encephalopathies (EIDEE). Infantile epileptic spasms syndrome, childhood epilepsy with migratory crises and Dravet syndrome are part of the infant-onset encephalopathies. The importance of early recognition of epileptic encephalopathies lies not only in the control of epileptic seizures, but also in stopping deterioration by trying to change the course of the disease. It is essential to know the etiology, avoiding medications that can exacerbate seizures and worsen the course, applying precision m edicine as well as identifying candidate patients for early epilepsy surgery.

Recientemente la Liga Internacional contra la Epilepsia (ILAE) socializó la clasificación propuesta para síndromes epilépticos de inicio neonatal y hasta los primeros 2 años de edad, dividiéndolos en síndromes epilépticos autolimitados y las encefalopatías epilépticas y del desarrollo (DEEs). En esta revisión nos dedicaremos a las DEEs, definidas como trastornos donde existe deterioro del desarrollo relacionado tanto con la etiología subyacente independiente de la actividad epileptiforme como con la encefalopatía epiléptica. Estas incluyen en el período neonatal la encefalopatía epiléptica infantil temprana o síndrome de Ohtahara y la encefalopatía mioclónica temprana, ahora agrupadas bajo la denominación de encefalopatías epilépticas y del desarrollo infantil temprano (EIDEE). El síndrome de espamos epilépticos infantiles, la epilepsia de la infancia con crisis migratorias y el síndrome de Dravet forman parte de las encefalopatías de inicio en el lactante. La importancia del reconocimiento temprano de las encefalopatías epilépticas radica no solo en el control de las crisis epilépticas, sino en detener el deterioro intentando cambiar el curso de la enfermedad. Es fundamental conocer la etiología evitando medicamentos que puedan exacerbar las crisis y empeorar el curso, aplicando medicina de precisión así como identificando pacientes candidatos a cirugía temprana de epilepsia.

Cohort study of infantile epileptic spasms syndrome: etiological analysis and treatment of corticosteroids.

BACKGROUND: Infantile epileptic spasms syndrome (IESS) is the most common type of severe epilepsy in infants. However, etiological frequency and optimized therapy, particularly corticosteroid regimen and dose, remain unknown. METHODS: An ambispective study of an IESS-diagnosed cohort was conducted. Etiologies were evaluated based on the 2017 International League Against Epilepsy classification system. Patients received intravenous dexamethasone or methylprednisolone for 3-5 consecutive days, followed by usual-dose (2 mg/kg/d) oral prednisone for 60-90 days with tapering doses for 1-2 months or high-dose (4 mg/kg/d) oral prednisone for 9-11 days with tapering doses for 2-4 weeks. Treatment responses were compared between the usual and high-dose prednisone groups after propensity score matching. Correlation analysis between treatment responses and underlying etiology was performed. RESULTS: Of the 441 included participants, 218 (49.4%) cases had proven etiologies. The most common etiology of IESS was acquired-structural (23.6%), followed by genetic (15.4%) and congenital-structural (7.0%). Hypoxic-ischemic encephalopathy (55, 52.8%) was the most common acquired-structural etiology. Among the 242 patients administered corticosteroids, 95 received usual-dose oral prednisone and 147 received high-dose oral prednisone. After propensity score matching, 54 patients were included in the usual-dose and high-dose groups, respectively, and treatment effectiveness was compared. There were no significant differences in seizure freedom at days 13-14 (55.6% vs. 51.9%, p = 0.700) and continued seizure freedom between days 14-42 (29.6% vs. 38.9%, p = 0.311) post corticosteroid administration between the usual- and high-dose prednisone groups. The proportion of children achieving seizure cessation at days 13-14 (χ2 = 1.470, p = 0.698) and days 14-42 (χ2 = 0.928, p = 0.836) was similar in the different etiological subgroups. Unknown etiological group showed significantly higher resolution of hypsarrhythmia than other etiological groups (χ2 = 10.761, p = 0.009). Both usual-dose and high-dose group showed tolerance to full-dose corticosteroids and similar adverse events over the observation period. CONCLUSION: IESS etiology was primarily related to structural causes. Clinical response in short-term follow-up was independent of prednisone dosage and underlying etiology. Better EEG responses may occur in patients with unknown etiology.

Long-term outcome of developmental and epileptic encephalopathies.

Developmental and epileptic encephalopathies are conditions where there is developmental impairment related to both the underlying etiology independent of epileptiform activity and the epileptic encephalopathy. Usually they have multiple etiologies. Therefore, long-term outcome is related to both etiology-related factors and epilepsy-related factors-age at onset of epilepsy, type(s) of seizure(s), type of electroencephalographic abnormalities, duration of the epileptic disorder. This paper focuses on long-term outcome of six developmental and epileptic encephalopathies with onset from the neonatal period to childhood: early epileptic encephalopathy with suppression bursts, West syndrome, Dravet syndrome, Lennox-Gastaut syndrome, epilepsy with myoclonic atonic seizures and epileptic encephalopathy with continuous spike and waves during slow-wave sleep including Landau-Kleffner syndrome. For each syndrome, definition, main etiologies if multiple, and long-term outcome are discussed.

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

OBJECTIVE: 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. METHODS: 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 fewer standard treatments) versus unfavorable treatment outcome (refractory spasms despite two standard treatments or relapse). RESULTS: We included 127 IS patients (60% males) with a follow-up of 2.4 years (range = .6-5 years). 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). SIGNIFICANCE: 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.

OBJECTIVE: 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. METHODS: We retrospectively identified all infants (0-24 months) 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. RESULTS: Of 686 children with epilepsy onset <18 years, 125 (18.2%) presented with focal-onset seizures in infancy. Median follow-up for this group was 10.9 years (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 >2 years, 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 7.1 years (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 >2 years follow-up, none developed DRE, all were seizure-free at last follow-up (95% off antiseizure medications [ASMs]), and all remained developmentally normal. SIGNIFICANCE: 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.

Comparison of Cosyntropin, Vigabatrin, and Combination Therapy in New-Onset Infantile Spasms in a Prospective Randomized Trial.

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.

Epilepsy and Neurodevelopmental Outcomes in a Cohort of West Syndrome Beyond Two Years of Age.

OBJECTIVE: To determine epilepsy and neurodevelopmental outcomes beyond 2 y of age and their putative prognostic factors in children with West syndrome (WS). METHODS: This cross-sectional study was initiated after approval from Institutional Ethics Committee. A follow-up cohort of 114 children (aged ≥ 2 y) diagnosed and treated for WS at the authors' center were assessed in-person for epilepsy and neurodevelopmental outcomes using Vineland Social Maturity Scale - Malin's adaptation for Indian children. Subsequently, age at onset, lead-time-to-treatment, etiology, and response to any of the standard therapies were analyzed as possible predictors of these outcomes. RESULTS: Of 114 children (mean age: 55 ± 32 mo, 91 boys), structural etiology was the predominant underlying etiology (79.8%) for WS. At 2 y of age, 64% had ongoing seizures. At the last follow-up, 76% had social quotient < 55, and 39% had cerebral palsy (spastic quadriparesis in 21%). An underlying structural etiology was associated with ongoing seizures [OR (95% CI) 3.5 (1.4-9); p = 0.008] at 2 y of age and poor developmental outcomes [OR (95% CI): 3.3 (1.3-8.9); p = 0.016]. Complete cessation of spasms with the standard therapy was significantly associated with better seizure control [OR (95% CI): 5.4 (2.3-13); p < 0.001] and neurodevelopmental outcome [OR (95% CI): 5.2 (1.8-14.9); p < 0.001]. CONCLUSION: The majority of children with WS have a poor neurodevelopmental outcome and epilepsy control on follow-up. The underlying etiology and response to initial standard therapy for epileptic spasms have a prognostic role in predicting the neurological outcome in these patients on follow-up.

Flashing lights and epileptic spasms: should we be routinely performing intermittent photic stimulation in infants?

Abnormal cortical excitation in response to photic stimulation (photosensitivity) has historically been associated with generalized epilepsies, in patients outside of infancy. At our tertiary centre, we encountered a patient with infantile spasms secondary to a mutation in ALG13 (c320A>G) who had photic stimulation-induced epileptic spasms over a broad range of frequencies on multiple EEGs, which were worse without treatment and decreased as treatment was escalated. This is the first reported case of epileptic spasms triggered by photic stimulation and it is unclear whether the phenomenon is unique to this patient, to those with this mutation or whether it is present in a broader group of patients with infantile spasms.

Predictors of outcome among 31 children with infantile spasms syndrome.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). SIGNIFICANCE: 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.

Prevention of infantile spasms in tuberous sclerosis complex.

Since the ground-breaking work of Gomez in the 1970s and the later epidemiological studies of Webb and Osborne [1], the link between early onset epilepsy, especially infantile spasms (IS), and intellectual disability in tuberous sclerosis complex (TSC) has been accepted. This association raises the question of whether prevention of epilepsy in early life in TSC patients may improve the longer-term cognitive outcome.

Could prevention of infantile spasms have been possible in a historical cohort of 31 tuberous sclerosis patients?

Efforts to prevent epilepsy in infants with tuberous sclerosis complex (TSC) has been the focus of EPISTOP. PURPOSE: The present study was carried out to evaluate whether prevention could have been realistic. METHODS: A retrospective analysis by hospital chart review of 31 patients with TSC and infantile spasms (practically all patients) admitted to two tertiary hospitals, Children's Hospital, University of Helsinki and Kuopio in 1980-2000. Clinical history, early cognitive development, early clinical signs of TSC, clinical signs of suspicious seizures, first seizures and EEG, response to adrenocorticotropic hormone (ACTH) therapy, EEG and brain imaging were evaluated. RESULTS: Early development prior the spasms was apparently normal in 25 (80%). The first EEG ever performed for a child showed hypsarrhythmia in 16 (51%) or modified hypsarrhythmia in 10 (32%). Treatment lag was short (0-4, mean 2 weeks) and the primary response to ACTH favorable in 19 (64%). Etiological diagnostic workup of IS revealed TSC. In one single case (3%) the diagnosis of TSC could be made at birth due to a congenital cardiac rhabdomyoma. Three other rhabomyomas were diagnosed later. In brain imaging, subependymal periventricular calcifications or hypodense areas were seen in every patient at onset of IS. Other organ manifestations of TSC were retinal phakomas (6), polycystic kidneys (2), and renal angiolipomatosis (1). CONCLUSIONS: Preventive treatment of epileptic discharges could have been possible in a single case of neonatal rhabdomyoma suggesting that preventive treatment is challenging in everyday practice. The main obstacle is the delay of TSC diagnosis.