Infantile Spasms Research Articles

The Evolving Landscape of Therapeutics for Epilepsy in Tuberous Sclerosis Complex.

Tuberous sclerosis complex (TSC) is a rare multisystem genetic disorder characterized by benign tumor growth in multiple organs, including the brain, kidneys, heart, eyes, lungs, and skin. Pathogenesis stems from mutations in either the TSC1 or TSC2 gene, which encode the proteins hamartin and tuberin, respectively. These proteins form a complex that inhibits the mTOR pathway, a critical regulator of cell growth and proliferation. Disruption of the tuberin-hamartin complex leads to overactivation of mTOR signaling and uncontrolled cell growth, resulting in hamartoma formation. Neurological manifestations are common in TSC, with epilepsy developing in up to 90% of patients. Seizures tend to be refractory to medical treatment with anti-seizure medications. Infantile spasms and focal seizures are the predominant seizure types, often arising in early childhood. Drug-resistant epilepsy contributes significantly to morbidity and mortality. This review provides a comprehensive overview of the current state of knowledge regarding the pathogenesis, clinical manifestations, and treatment approaches for epilepsy and other neurological features of TSC. While narrative reviews on TSC exist, this review uniquely synthesizes key advancements across the areas of TSC neuropathology, conventional and emerging pharmacological therapies, and targeted treatments. The review is narrative in nature, without any date restrictions, and summarizes the most relevant literature on the neurological aspects and management of TSC. By consolidating the current understanding of TSC neurobiology and evidence-based treatment strategies, this review provides an invaluable reference that highlights progress made while also emphasizing areas requiring further research to optimize care and outcomes for TSC patients.

Distinct manifestations and potential mechanisms of seizures due to cortical versus white matter injury in children

PurposeTo study seizure manifestations and outcomes in children with cortical versus white matter injury, differences potentially explaining variability of epilepsy in children with cerebral palsy. MethodsIn this population-based retrospective cohort study, MRIs of children with cerebral palsy due to ischemia or haemorrhage were classified according to presence or absence of cortical injury. MRI findings were then correlated with history of neonatal seizures, seizures during childhood, epilepsy syndromes, and seizure outcomes. ResultsOf 256 children studied, neonatal seizures occurred in 57 and seizures during childhood occurred in 93. Children with neonatal seizures were more likely to develop seizures during childhood, mostly those with cortical injury. Cortical injury was more strongly associated with (1) developing seizures during childhood, (2) more severe epilepsy syndromes (infantile spasms syndrome, focal epilepsy, Lennox-Gastaut syndrome), and (3) less likelihood of reaching > 2 years without seizures at last follow-up, compared to children without cortical injury. Children without cortical injury, mainly those with white matter injury, were less likely to develop neonatal seizures and seizures during childhood, and when they did, epilepsy syndromes were more commonly febrile seizures and self-limited focal epilepsies of childhood, with most achieving > 2 years without seizures at last follow-up. The presence of cortical injury also influenced seizure occurrence, severity, and outcome within the different predominant injury patterns of the MRI Classification System in cerebral palsy, most notably white matter injury. ConclusionsEpileptogenesis is understood with cortical injury but not well with white matter injury, the latter potentially related to altered postnatal white matter development or myelination leading to apoptosis, abnormal synaptogenesis or altered thalamic connectivity of cortical neurons. These findings, and the potential mechanisms discussed, likely explain the variability of epilepsy in children with cerebral palsy and epilepsy following early-life brain injury in general.

PIGW-related glycosylphosphatidylinositol deficiency: A case report and literature review.

PIGW-related glycosylphosphatidylinositol deficiency is a rare disease that manifests heterogeneous clinical phenotypes. We describe a patient with PIGW deficiency and summarize the clinical characteristics of the case. In addition, we conducted a literature review of previously reported patients with pathogenic variants of PIGW. A Chinese girl presented with refractoryepilepsy, severe intellectual disability, recurrent respiratory infections, and hyperphosphatasia. Seizures worsened during fever and infections, making her more susceptible to epileptic status. She was found to carry a heterozygous variant of PIGW and a deletion of chromosome 17q12 containing PIGW. Only six patients with homozygous or compound heterozygous pathogenic variants of PIGW have been identified in the literature thus far. Epileptic seizures were reported in all patients, and the most common types of seizures were epileptic spasms. Distinctive facial and physical features and recurrent respiratory infections are common in these patients with developmental delays. Serum alkaline phosphatase (ALP) levels were elevated in four of the six patients. PIGW-related glycosylphosphatidylinositol deficiency is characterized by developmental delay, epilepsy, distinctive facial features, and multiple organ anomalies. Genetic testing is an important method for diagnosing this disease, and flow cytometry and serum ALP level detection are crucial complements for genetic testing.

West Syndrome: A Case Report

Infantile spasms (IS), formerly known as West syndrome, are a type of seizure associated with the epileptic disorder known as West syndrome. Infants and children are affected by West syndrome. Mental deficits are associated with infantile spasms. A particular kind of seizure that starts in the first year of life is known as infantile spasms. Loss of developmental milestones or developmental regression. However, an electroencephalogram is required to confirm the diagnosis of west syndrome (EEG). We describe the unusual West syndrome case.

Bioequivalence Study of Two Tablet Formulations of Clonazepam 2mg: A Randomized, Open-Label, Crossover Study in Healthy Mexican Volunteers Under Fasting Conditions.

The prevalence of neurological disorders is high among the Mexican population. Clonazepam is primarily indicated to treat panic disorders, certain kinds of epilepsy such as status epilepticus, childhood motor seizures (petit mal absence, Lennox-Gastaut syndrome, and infantile spasms), anxiety, and muscle spasm. This study was performed to compare bioequivalence between two oral tablet formulations of clonazepam 2mg in healthy Mexican volunteers under fasting conditions. This phaseI, randomized, open-label, two-treatment, crossover study included 30healthy volunteers. Subjects were randomly assigned to either test or reference formulation of clonazepam 2mg. Each study period was separated by 21-day washout period. Blood samples were collected at pre-dose and up to 72h after drug administration. Clonazepam concentrations were determined using a validated ultra-flow liquid chromatography-tandem mass spectrometric method. Pharmacokinetic parameters were determined using a non-compartmental method. Two formulations were considered bioequivalent if geometric mean ratios (test/reference) were between 80% and 125%. Safety was evaluated by recording adverse events. Pharmacokinetic parameters were comparable between test and reference formulations. The mean maximum plasma concentration (Cmax) was ≈ 13ng/mL, area under the plasma concentration-time curve from time0 to last measurable concentration (AUC0-t) was ≈ 360ngh/mL, time to reach maximum plasma concentration (Tmax) was ≈ 3h, and elimination half-life (t1/2) was ≈ 43h. Geometric mean ratios (90% confidence interval) of Cmax (99.2-115.3%), AUC0-t (100.6-110.6%), and AUC0-∞ (98.5-111.6%) were within the bioequivalence range. Seven non-serious adverse events (mostly asymptomatic hypotension) were recorded. The test and reference formulations of clonazepam 2mg were bioequivalent and well tolerated in healthy Mexican volunteers under fasting conditions. 213301410B0051 (Approved on April 13, 2021).

Infantile epileptic spasms syndrome: a cohort study of 88 children

BackgroundThis study aimed to investigate and analyze the risk factors for non-etiology-specific infantile spasms (IS) and unrelieved clinical symptoms after treatment.MethodsEighty-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.ResultsGender, 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.ConclusionThe occurrence of nonetiology-specific IS is associated with gender and metabolic abnormalities in children. After medication, unrelieved IS symptoms are associated with etiologies.

Infant masturbation presented as infantile spasm

Infant masturbation presented as infantile spasm

Clinical features and outcome in infantile epileptic spasms syndrome-results from a multi-ethnic cohort

Clinical features and outcome in infantile epileptic spasms syndrome-results from a multi-ethnic cohort

Delineating clinical and developmental outcomes in STXBP1-related disorders.

STXBP1-related disorders are among the most common genetic epilepsies and neurodevelopmental disorders. However, the longitudinal epilepsy course and developmental end points, have not yet been described in detail, which is a critical prerequisite for clinical trial readiness. Here, we assessed 1281 cumulative patient-years of seizure and developmental histories in 162 individuals with STXBP1-related disorders and established a natural history framework. STXBP1-related disorders are characterized by a dynamic pattern of seizures in the first year of life and high variability in neurodevelopmental trajectories in early childhood. Epilepsy onset differed across seizure types, with 90% cumulative onset for infantile spasms by 6 months and focal-onset seizures by 27 months of life. Epilepsy histories diverged between variant subgroups in the first 2 years of life, when individuals with protein-truncating variants and deletions in STXBP1 (n = 39) were more likely to have infantile spasms between 5 and 6 months followed by seizure remission, while individuals with missense variants (n = 30) had an increased risk for focal seizures and ongoing seizures after the first year. Developmental outcomes were mapped using milestone acquisition data in addition to standardized assessments including the Gross Motor Function Measure-66 Item Set and the Grasping and Visual-Motor Integration subsets of the Peabody Developmental Motor Scales. Quantification of end points revealed high variability during the first 5 years of life, with emerging stratification between clinical subgroups. An earlier epilepsy onset was associated with lower developmental abilities, most prominently when assessing gross motor development and expressive communication. We found that individuals with neonatal seizures or early infantile seizures followed by seizure offset by 12 months of life had more predictable seizure trajectories in early to late childhood compared to individuals with more severe seizure presentations, including individuals with refractory epilepsy throughout the first year. Characterization of anti-seizure medication response revealed age-dependent response over time, with phenobarbital, levetiracetam, topiramate and adrenocorticotropic hormone effective in reducing seizures in the first year of life, while clobazam and the ketogenic diet were effective in long-term seizure management. Virtual clinical trials using seizure frequency as the primary outcome resulted in wide range of trial success probabilities across the age span, with the highest probability in early childhood between 1 year and 3.5 years. In summary, we delineated epilepsy and developmental trajectories in STXBP1-related disorders using standardized measures, providing a foundation to interpret future therapeutic strategies and inform rational trial design.

Infantile epileptic spasm syndrome as a new NR2F1 gene phenotype.

NR2F1 pathogenetic variants are associated with the Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS). Recent studies indicate that BBSOAS patients not only have visual impairments but may also have developmental delays, hypotonia, thin corpus callosum and epileptic seizures. However, reports of BBSOAS occurrence along with infantile epileptic spasm syndrome (IESS) are rare. Here, we report three cases involving children with IESS and BBSOAS caused by de novo NR2F1 pathogenetic variants and summarize the genotype, clinical characteristics, diagnosis and treatment of them. All three children experienced epileptic spasms and global developmental delays, with brain Magnetic Resonance Imaging (MRI) suggesting abnormalities (thinning of the corpus callosum or widened extracerebral spaces) and two of the children exhibiting abnormal visual evoked potentials. Our findings indicate that new missense NR2F1 pathogenetic variants may lead to IESS with abnormal visual evoked potentials. Thus, clinicians should be aware of the Bosch-Boonstra-Schaaf optic atrophy syndrome and regular monitoring of the fundus, and the optic nerve is necessary during follow-up.

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

AimsThe 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. MethodsWe 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). ResultsThe 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). InterpretationReal-life data confirm the interest of combination therapy as a first-line treatment for IESS.

Efficacy of Combined Therapy of ACTH plus Vigabatrin Compared to ACTH Alone for Treatment of Infantile Spasm-A RCT

Background: Infantile spasms (epileptic spasm) is difficult to treat and has a high morbidity. So it’s crucial to initiate an early effective therapy. ACTH, Prednisolone and Vigabatrin have shown better efficacy on cessation of spasms.&#x0D; Objective: To compare the efficacy and tolerability of combined ACTH and Vigabatrin with ACTH alone in treatment of infantile spasms.&#x0D; Materials &amp; Methods: This randomized controlled trial was conducted from June, 2017 to June, 2018 at outdoor and indoor, department of Paediatric Neurology of National Institute of Neurosciences and Hospital, Dhaka. Fifty (50) patients aged 2 months to 24 months who had a clinical diagnosis of infantile spasms and hypsarrhythmia (classical or modified hypsarrhythmia) in EEG were enrolled. With parent’s written informed consent, they were randomized (1:1 by lottery method) into two groups, 25 in each. One group got ACTH only and another group got both ACTH and vigabatrin. At the end of the treatment two groups were compared regarding efficacy and safety of the drugs.&#x0D; Result: The primary outcome was assessed in 50 children at 91st day. The primary outcome was cessation of spasms from 14th day to 42nd day after initiation of therapy. Cessation of spasms (between 14 to 42 days) occurred in 18 children (72%) in combination therapy and 11 children (44%) in hormonal therapy (p=0.045). Treatment response was faster on combination therapy (p=0.001). Treatment was well tolerated in both groups with few adverse effects.&#x0D; Conclusion: Combination therapy of ACTH plus Vigabatrin was found better than ACTH therapy alone in cessation of infantile spasms.&#x0D; BANGLADESH J CHILD HEALTH 2022; VOL 46 (1) : 14-18

A case of infantile spasms with three possibly pathogenic de novo missense variants in NF1 and GABBR1

Neurofibromatosis type 1 (NF1) is one of the most common hereditary neurocutaneous disorders. Here, we report a unique case of a patient with typical NF1 findings and infantile spasms who had three possibly pathogenic de novo variants, c.3586C>T, p.(Leu1196Phe) and c.3590C>T, p.(Ala1197Val) in NF1 located in cis and c.1042G>C, p.(Ala348Pro) in GABBR1. This study contributes to our understanding of the effect of two cis variants on NF1 phenotypes and GABBR1-related neuropsychiatric disorders.

Development of an online calculator for the prediction of seizure freedom following pediatric hemispherectomy using the Hemispherectomy Outcome Prediction Scale (HOPS).

Although hemispheric surgeries are among the most effective procedures for drug-resistant epilepsy (DRE) in the pediatric population, there is a large variability in seizure outcomes at the group level. A recently developed HOPS score provides individualized estimation of likelihood of seizure freedom to complement clinical judgement. The objective of this study was to develop a freely accessible online calculator that accurately predicts the probability of seizure freedom for any patient at 1-, 2-, and 5-years post-hemispherectomy. Retrospective data of all pediatric patients with DRE and seizure outcome data from the original Hemispherectomy Outcome Prediction Scale (HOPS) study were included. The primary outcome of interest was time-to-seizure recurrence. A multivariate Cox proportional-hazards regression model was developed to predict the likelihood of post-hemispheric surgery seizure freedom at three time points (1-, 2- and 5- years) based on a combination of variables identified by clinical judgment and inferential statistics predictive of the primary outcome. The final model from this study was encoded in a publicly accessible online calculator on the International Network for Epilepsy Surgery and Treatment (iNEST) website (https://hops-calculator.com/). The selected variables for inclusion in the final model included the five original HOPS variables (age at seizure onset, etiologic substrate, seizure semiology, prior non-hemispheric resective surgery, and contralateral fluorodeoxyglucose-positron emission tomography [FDG-PET] hypometabolism) and three additional variables (age at surgery, history of infantile spasms, and magnetic resonance imaging [MRI] lesion). Predictors of shorter time-to-seizure recurrence included younger age at seizure onset, prior resective surgery, generalized seizure semiology, FDG-PET hypometabolism contralateral to the side of surgery, contralateral MRI lesion, non-lesional MRI, non-stroke etiologies, and a history of infantile spasms. The area under the curve (AUC) of the final model was 73.0%. Online calculators are useful, cost-free tools that can assist physicians in risk estimation and inform joint decision-making processes with patients and families, potentially leading to greater satisfaction. Although the HOPS data was validated in the original analysis, the authors encourage external validation of this new calculator.

Clinical and electroencephalographic characteristics of 34 infant with onset of epileptic spasms before three months of age

Epileptic spasms (ES) occur mostly between age 3 months and 24 months. ES beginning before 3 months of age were called early-onset ES in previous studies. The aim of this study was to identify clinical and electroencephalographic characteristics of patients with ES onset before 3 months of age. In total, 34 ES patients were retrospectively identified at Children’s Hospital of Chongqing Medical University from January 1, 2020 to October 1, 2022. Our patients had diverse etiologies, including genetic (32.3 %), genetic-structural (11.8 %), structural-acquired (11.8 %), structural-congenital (8.8 %), and metabolic (5.9 %), with 29.4 % of patients having unknown etiology. Some patients experienced ES in clusters (either symmetrical or flexional) that occurred most often during awakening after sleep, and a minority of ES were characterized as isolated or asymmetrical, occurred during sleep, and could also manifest as relatively subtle. Approximately 35.3 % of patients also experienced other seizure types concurrently, including 10 focal seizures and 2 generalized seizures, and only half of the focal seizures had structural causes. The other seizure types occurred alone or sequentially with ES. Interictal electroencephalography revealed hypsarrhythmia or its variants, multifocal discharge, or burst suppression. 18 patients had no seizures lasting for more than 2 months, however, at the last follow-up visit, 5 of them had relapsed. All patients had different degrees of psychomotor retardation.

A single-center observational study on long-term neurodevelopmental outcomes in children with tuberous sclerosis complex

BackgroundTuberous sclerosis complex (TSC) is a rare multisystem disorder caused by mutations in the TSC1 or TSC2 gene. More than 90% of patients with TSC develop neurological and/or neuropsychiatric manifestations. The aim of the present study was to determine the developmental and cognitive long-term outcomes of pediatric TSC patients.MethodsThis cross-sectional, monocenter study included pediatric TSC patients who received multidisciplinary long-term care with a last visit between 2005 and 2019. Neurological manifestations and cognitive development (BSID, K-ABC) were analyzed in relation to age and type of mutation.ResultsThirty-five patients aged 13.5 ± 7.8 years were included in the study. Diagnosis was confirmed genetically in 65.7% of patients (TSC1, 26.1%; TSC2, 65.2%; NMI, 8.7%). Mean age at diagnosis was 1.3 ± 3.5 years; 74.3% of the patients had been diagnosed within the first year of life due to seizures (62.9%) or/and cardiac rhabdomyomas (28.6%). The most common TSC manifestations included structural brain lesions (cortical tubers, 91.4%; subependymal nodules, 82.9%), epilepsy (85.7%), and cardiac rhabdomyomas (62.9%). Mean age at seizure onset was 1.5 ± 2.3 years, with onset in 80.0% of patients within the first two years of life. Infantile spasms, which were the first seizure type in 23.3% of the patients, developed earlier (0.6 ± 0.4 years) than focal seizures (1.8 ± 2.5 years). Refractory epilepsy was present in 21 (70.0%) patients, mild or severe intellectual impairment in 66.6%, and autism spectrum disorders in 11.4%. Severe cognitive impairment (33.3%) was significantly associated with epilepsy type and age at seizure onset (p < 0.05).ConclusionsThe results emphasized the phenotypic variability of pediatric-onset TSC and the high rate of neurological and neuropsychiatric morbidity. Early-onset refractory epilepsy was associated with impaired cognitive development. Children of all ages with TSC require multidisciplinary long-term care and individual early-intervention programs.

Developmental and epileptic encephalopathy 82 (DEE82) with novel compound heterozygous mutations of GOT2 gene

PurposeDevelopmental and Epileptic Encephalopathies (DEEs) are rare neurological disorders characterized by early-onset medically resistant epileptic seizures, structural brain malformations, and severe developmental delays. These disorders can arise from mutations in genes involved in vital metabolic pathways, including those within the brain. Recent studies have implicated defects in the mitochondrial malate aspartate shuttle (MAS) as potential contributors to the clinical manifestation of infantile epileptic encephalopathy. Although rare, mutations in MDH1, MDH2, AGC1, or GOT2 genes have been reported in patients exhibiting neurological symptoms such as global developmental delay, epilepsy, and progressive microcephaly. MethodIn this study, we employed exome data analysis of a patient diagnosed with DEE, focusing on the screening of 1896 epilepsy-related genes listed in the HPO and ClinVar databases. Sanger sequencing was subsequently conducted to validate and assess the inheritance pattern of the identified variants within the family. The evolutionary conservation scores of the mutated residues were evaluated using the ConSurf Database. Furthermore, the impacts of the causative variations on protein stability were analyzed through I-Mutant and MuPro bioinformatic tools. Structural comparisons between wild-type and mutant proteins were performed using PyMOL, and the physicochemical effects of the mutations were assessed using Project Hope. ResultsExome data analysis unveiled the presence of novel compound heterozygous mutations in the GOT2 gene coding for mitochondrial glutamate aspartate transaminase. Sanger sequencing confirmed the paternal inheritance of the p.Asp257Asn mutation and the maternal inheritance of the p.Arg262Cys mutation. The affected individual exhibited plasma metabolic disturbances, including hyperhomocysteinemia, hyperlactatemia, and reduced levels of methionine and arginine. Detailed bioinformatic analysis indicated that the mutations were located within evolutionarily conserved domains of the enzyme, resulting in disruptions to protein stability and structure. ConclusionHerein, we describe a case with DEE82 (MIM: # 618721) with pathologic novel biallelic mutations in the GOT2 gene. Early genetic diagnosis of metabolic epilepsies is crucial for long-term neurodevelopmental improvements and seizure control as targeted treatments can be administered based on the affected metabolic pathways.

EEG-based spatiotemporal dynamics of fast ripple networks and hubs in infantile epileptic spasms.

Infantile epileptic spasms (IS) are epileptic seizures that are associated with increased risk for developmental impairments, adult epilepsies, and mortality. Here, we investigated coherence-based network dynamics in scalp EEG of infants with IS to identify frequency-dependent networks associated with spasms. We hypothesized that there is a network of increased fast ripple connectivity during the electrographic onset of clinical spasms, which is distinct from controls. We retrospectively analyzed peri-ictal and interictal EEG recordings of 14 IS patients. The data was compared with 9 age-matched controls. Wavelet phase coherence (WPC) was computed between 0.2 and 400 Hz. Frequency- and time-dependent brain networks were constructed using this coherence as the strength of connection between two EEG channels, based on graph theory principles. Connectivity was evaluated through global efficiency (GE) and channel-based closeness centrality (CC), over frequency and time. GE in the fast ripple band (251-400 Hz) was significantly greater following the onset of spasms in all patients (P < 0.05). Fast ripple networks during the first 10s from spasm onset show enhanced anteroposterior gradient in connectivity (posterior > central > anterior, Kruskal-Wallis P < 0.001), with maximum CC over the centroparietal channels in 10/14 patients. Additionally, this anteroposterior gradient in CC connectivity is observed during spasms but not during the interictal awake or asleep states of infants with IS. In controls, anteroposterior gradient in fast ripple CC was noted during arousals and wakefulness but not during sleep. There was also a simultaneous decrease in GE in the 5-8 Hz range after the onset of spasms (P < 0.05), of unclear biological significance. We identified an anteroposterior gradient in the CC connectivity of fast ripple hubs during spasms. This anteroposterior gradient observed during spasms is similar to the anteroposterior gradient in the CC connectivity observed in wakefulness or arousals in controls, suggesting that this state change is related to arousal networks.

Proteomic analysis of salivary inflammatory biomarkers of developmental gingival enlargements in patients with West and Noonan syndromes: a preliminary pilot single-center retrospective study.

The aim of the preliminary pilot single-center retrospective cross-sectional study was to analyze and compare the presence of non-secretory salivary inflammatory biomarkers in pediatric patients with West syndrome, Noonan syndrome, and a healthy control group. A total of 60 saliva samples were collected during dental check-ups. The saliva samples collected were analyzed by liquid chromatography. The results were analyzed with a t-test, and the statistical significance was given by a p-value lower than 0.05. We found statistical significance for defensin α1 (p=0.006) and thymosin β4 (p=0.025) in the Noonan syndrome. In the West syndrome, only the defensin α1 had a statistically significant difference with the other groups (p=0.022). Proteomic analysis revealed an overexpression of peptides related to the innate (thymosin β4) and acquired (defensin α1, α3) immunity. West and Noonan's syndromes showed the overexpression of molecular biomarkers involved in the pathogenesis of chronic periodontitis. The inflammatory status is triggered and amplified by the abnormal overgrowth of gingival tissues, the amplified release of proinflammatory cytokines from the immune cells, and the poor cooperation in maintaining adequate oral hygiene.

39 Neurodevelopmental Complexity of a Patient with Perinatal Right Middle Cerebral Artery Stroke and Infantile Spasms

Objective:A rich literature exists on cognitive changes related to focal injury in the adult brain. In contrast, the developing brains of children are less understood. In contrast to adult cases, 20% to 25% of perinatal strokes result in language disorder regardless of lesion lateralization. Existing literature suggests children with perinatal stroke may present with a range of executive functioning and visuospatial processing difficulties. Gross and fine motor challenges are also likely to occur. Furthermore, these children have an increased prevalence of autism spectrum disorder (ASD) and carry the highest risk for epilepsy. Despite growing research on neurodevelopmental profiles in patients with perinatal stroke, published literature is limited.Participants and Methods:Our study examines neurodevelopment of a 2-year-old, right-handed male with a history of perinatal ischemic right middle cerebral artery (MCA) stroke, infantile spasms, and left hemiparesis following right hemispherectomy for seizure management who underwent two neurodevelopmental evaluations at our medical center over approximately 3 years.Results:Findings from the patient’s evaluation with the Mullen Scales of Early Learning revealed overall cognitive ability in the low average range (SS = 89, 23rd percentile); however, notable variability was seen in his performance. His receptive language was average (SS = 98, 45th %tile) and consistent with previous evaluation results, and he has made gains in visual reception (from SS = 75, 5th %tile to SS = 91, 27th %tile) and expressive language (from SS = 55, 0.1st %tile to SS = 70, 2nd %tile). In addition, his gross motor was exceptionally low (SS = 55, 0.1st %tile) and consistent with previous evaluation results. Fine motor was low average (SS = 84, 14th %tile).Conclusions:Our patient showed cognitive gains in language and visual reception since his prior evaluation despite history of right MCA stroke and right hemispherectomy. Improvements are likely due to a combination of early brain plasticity and intensive therapies he has received. Consistent with published findings in this population, he experienced seizures associated with his stroke. Our results add to the limited literature on neurodevelopmental challenges associated with perinatal stroke and progress that can be made when appropriate supports are provided early and consistently.