Idiopathic West Syndrome Research Articles

The Association Between Serum Levels of Glial Biomarkers, Clinical Severity and Electro-encephalography Features in Idiopathic West and Lennox-Gastaut Syndromes.

Although the contribution of enhanced glial activity in seizure induction is increasingly recognized, the role of glia-induced neuroinflammation in the physiopathology of epileptic encephalopathy (EE) has been scarcely investigated. To delineate the contribution of glial activity in EE, we measured levels of glia-derived mediators with previously described biomarker value, including glial fibrillary acidic protein (GFAP), high mobility group box 1 (HMGB1), chitinase-3-like protein 1 (CHI3L1), soluble CD163 (sCD163) and triggering receptor expressed on myeloid cells 2 (TREM2) by ELISA in sera of patients with idiopathic West syndrome (WS, n=18), idiopathic Lennox-Gastaut syndrome (LGS, n=13) and healthy controls (n=31). Patients with EE showed significantly higher CHI3L1 levels compared to healthy controls. Levels of HMGB1, CHI3L1, sCD163 and TREM2 were higher in LGS patients than WS patients and/or healthy controls. One or more of the investigated mediators were associated with treatment responsiveness, disease severity and presence of pathological features on electroencephalography (EEG). To our knowledge, our findings provide the initial patient-based evidence that astrocyte- and microglia-mediated neuroinflammation might be involved in the pathogenesis of LGS and WS. Moreover, glial mediators may serve as prognostic biomarkers in patients with idiopathic EE.

Altered serum levels of platelet-derived growth factor receptor β and cluster of differentiation 13 suggest a role for pericytes in West syndrome

BackgroundPericytes play a role in the maintenance of the blood–brain barrier and neuroinflammation, attracting attention as to whether they are also involved in the pathogenesis of epilepsy.This study aimed to explore the relationship between West syndrome and pericytes. MethodsEighteen Japanese pediatric West syndrome patients and nine controls aged 2 years or younger were retrospectively enrolled in this study. We assessed theserumlevels of pericyte markers, serum PDGFRβ (platelet-derived growth factor receptorβ),CD13 (aminopeptidase N), and 27 cytokines in 17 pediatric patients with West syndrome and the control group. ResultsPatients with West syndrome exhibited significantly increased CD13 and decreased PDGFRβ levels, compared with controls but not serum cytokine levels. These values did not differ significantly between symptomatic and idiopathic West syndrome. ConclusionPericytes might be implicated in the pathogenesis of West syndrome.

Immunoglobulin use in childhood epilepsy

Background: Epilepsy's aetiology is well-known to include an immune component. Several clinical and laboratory research have discovered abnormalities in epileptic patients' immune system branches when compared to the general population. Such anomalies include immunoglobulin deficiencies (mainly immunoglobulin A and immunoglobulin G2), an increased prevalence of specific human leukocyte antigen types, and alterations in cytokine and interleukin profiles. In people with epilepsy, autoantibodies were discovered against glutamic acid decarboxylase, components of the voltage-gated potassium channel complex, and the N-methyl-D-aspartate, gamma-aminobutyric acid, a-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid, and glutamate receptor three receptors. Immune modulating drugs like corticosteroids and corticotrophin have also been demonstrated to help with seizures. In view of these findings, immunosuppressive medicine has potential as an add-on therapy for refractory epilepsy. Aim: We aimed to evaluate the efficacy of immunoglobulin in childhood epilepsy. Conclusion: Despite the fact that new medications are constantly being developed to treat intractable infantile epilepsy, the refractory rate remains high. Despite several investigations on the subject, predictive variables for a good intravenous immunoglobulin response have yet to be identified. In some epileptic disorders, such as idiopathic West syndrome and electrical status epilepticus during sleep, intravenous immunoglobulin appears to be beneficial.

West syndrome: A study of 26 patients receiving short-term therapy

ObjectiveWe describe the electroclinical characteristics of a series of 26 patients with idiopathic West syndrome (WS), who had an excellent response to treatment with vigabatrin (VGB) and corticosteroids alone or in combination. MethodsEvaluating the records of 178 patients with WS studied at Garrahan Hospital, Niño Jesús Hospital, and Clínica San Lucas between January 2005 and June 2017, we selected 26 patients that met the inclusion criteria of idiopathic WS.The inclusion criteria for idiopathic WS were (1) no personal history of disease, (2) normal neurological examination and neurodevelopment, (3) symmetric spasms in clusters not preceded by any other type of seizure, (d) symmetric hypsarrhythmia, (e) normal electroencephalogram (EEG) background, e.g., normal sleep EEG pattern, (f) normal magnetic resonance imaging (MRI) recording, (g) normal neurometabolic and genetic studies, and (h) at least 2 years of follow-up. ResultsFifteen boys and 11 girls met the inclusion criteria of idiopathic WS. The current age of the children ranges between 2 years 10 months and 12 years 10 months. Age at first epileptic spasms (ES) ranged from 4 to 11 months, with a mean age of 7 and a median of 7.5 months, respectively; ES were in clusters, bilateral and symmetrical in all cases. Spasms were flexor in nine (34.7%), mixed flexor-extensor in 15 (57.7%), and extensor in three (7.6%). In all patients the EEG showed typical pattern of hypsarrhythmia. ConclusionThese patients with idiopathic WS who have an excellent response to initial treatment should be treated for a short period of time with adrenocorticotropic hormone (ACTH) and VGB alone or in combination.

F18. EEG and neuroimaging findings in pediatric patients with down syndrome and epilepsy: A single center experience

Down syndrome occurs in 1 in 650–1000 births. Epilepsy has been reported in 1–13% of patients with Down syndrome (Stafstrom et al., 1991) compared to 1.5–5 % in general population (Forsgren et al., 2005). This was a single center retrospective medical record review of patients of less than 18 years of age with Down syndrome and epilepsy from January 2005 to December 2015. Sixteen patients were identified. Patients were grouped by seizure types and data was collected on EEG, MRI and outcome at last follow up. Children with Down syndrome and epilepsy can be grouped in four categories of seizures. Group 1: Infantile spasms – Seven out of sixteen patients in our cohort had infantile spasms with findings of hypsarrhythmia on the EEG. Five patients had MRI’s available for review and were normal. Five patients (70%) were seizure free, three of whom had a normal EEG and were off antiepileptic medications at their last follow up. The two remaining patients had refractory seizures and abnormal EEG findings which included regional sharp waves and hypsarrhythmia with multiregional sharp waves. Group 2: Generalized seizures – Six patients had generalized seizures (GTC, myoclonic, atonic) and regional/multiregional sharp waves on the EEG. Five off these patients had abnormal MRI findings: Two with MCA distribution infarcts and three with more diffuse abnormalities secondary to periventricular leukomalacia, traumatic brain injury and diffuse volume loss. Fifty percent of the patients were seizure free including one following a functional hemispherectomy. All patients continued to have abnormal EEGs at their last follow up. Group 3: Partial seizures – Two patients in our cohort had partial seizures (focal neonatal seizures and benign rolandic epilepsy with centrotemporal spikes) and both were seizure free at their last follow up. Group 4: Partial and Generalized seizures – One patient had partial and generalized seizures with multiregional sharp waves on EEG at diagnosis. This patient continues to have refractory seizures on medications and hypsarrhythmia on the last follow up EEG. Neuroimaging: Thirteen MRI’s were available for review, of which seven were abnormal. 50–55% of patients with normal or abnormal MRI’s became seizure free. All patients except for one (background slowing only) had abnormal EEG’s with epileptiform discharges at diagnosis. Infantile spasms was the most common seizure type in our patient cohort with electro-clinical features resembling those of idiopathic West syndrome. Classic hypsarrhythmia was present in all patients at diagnosis. Patients with infantile spasms had a higher percentage of becoming seizure free with normalization of EEG on long term follow up compared to patients with generalized or partial seizures. Abnormal MRI does not appear to be helpful for predicting seizure outcome.

Electroclinical Features and Long-Term Outcome of Cryptogenic Epilepsy in Children with Down Syndrome

To describe the electroclinical features and the long-term outcomes of epilepsy in a large cohort of males and females with Down syndrome who developed epilepsy in childhood. Subjects with Down syndrome and cryptogenic epilepsy with onset in childhood were identified retrospectively from the databases of 16 Italian epilepsy centers over a 40-year period. For each subject, age at onset of seizures, seizure semiology and frequency, electroencephalography characteristics, treatment with antiepileptic drugs, and long-term clinical and electroencephalography outcomes were analyzed. A total of 104 subjects (64 males [61.5%], 40 females [38.5%]) were identified. Seizure onset occurred within 1 year of birth in 54 subjects (51.9%), between 1 and 12 years in 42 subjects (40.4%), and after 12 years in 8 subjects (7.7%). Males had a younger age of seizure onset than females. Of the 104 subjects, 51 (49.0%) had infantile spasms (IS), 35 (33.7%) had partial seizures (PS), and 18 (17.3%) had generalized seizures (GS). Febrile seizures were recorded in 5 (4.8%) subjects. Intractable seizures were observed in 23 (22.1%) subjects, including 5 (9.8%) with IS, 8 (44.4%) with PS, and 10 (31.3%) with GS. Cryptogenic epilepsy in Down syndrome may develop during the first year of life in the form of IS or, successively, as PS or GS. Electroclinical features of IS resemble those of idiopathic West syndrome, with a favorable response to treatment with adrenocorticotropic hormone seen. Patients experiencing PS and GS may be resistant to therapy with antiepileptic drugs.

De novo 15q13.3 microdeletion with cryptogenic west syndrome

West syndrome is a well-recognized form of epilepsy, defined by a triad of infantile spasms, hypsarrhythmia and developmental arrest. West syndrome is heterogenous, caused by mutations of genes ARX, STXBP1, KCNT1 among others; 16p13.11 and 17q21.31 microdeletions are less frequent, usually associated with intellectual disability and facial dysmorphism. So-called "idiopathic" West syndrome is of better prognostic, without prior intellectual deficiency and usually responsive to anti-epileptic treatment. We report on a boy falling within the scope of idiopathic West syndrome, with no dysmorphic features and normal development before the beginning of West syndrome, with a good resolution after treatment, bearing a de novo 15q13.3 microdeletion. Six genes are located in the deleted region, including CHRNA7, which encodes a subunit of a nicotinic acetylcholine receptor, and is frequently associated with epilepsy. Exploration of the 15q13.3 region should be proposed in idiopathic West syndrome.

Immunoglobulin Treatment for Severe Childhood Epilepsy

We have used intravenous immunoglobulin to treat pediatric patients with various severe epileptic conditions. This retrospective, multicenter study comprised 64 consecutive patients treated with immunoglobulins for either epileptic encephalopathy or refractory epilepsy. The rate of full or partial improvement according to specific syndrome involved three of four patients with idiopathic West syndrome, six of 12 patients with electrical status epilepticus in sleep, eight of 19 patients with an undefined syndrome, one of three patients with Landau-Kleffner syndrome, and one of two patients with Rasmussen encephalitis. Intravenous immunoglobulins were ineffective in 10 patients with symptomatic West syndrome, nine with febrile infection-related status epilepticus, three with myoclonic astatic epilepsy, and two with Lennox-Gastaut syndrome. Nine patients (14%) demonstrated complete resolution, and 10 (15.6%) exhibited partial improvement. Of these 19 responders (29.7%), eight relapsed. Although intravenous immunoglobulin is not suitable for all cases of epilepsy, it may prove efficacious for specific epileptic syndromes, mainly idiopathic West syndrome and electrical status epilepticus during sleep.

Idiopathic West Syndrome followed by childhood absence epilepsy

West Syndrome (WS) is a severe epileptic encephalopathy occurring in the first year of life. According the ILAE classification of epileptic seizures and epilepsy the etiology could be symptomatic or cryptogenic. Some authors identified a small group of patients (5%) with a particular good outcome, a complete recovery from seizures and a normal cognitive development within the cryptogenic group that they suggested to be idiopathic. Between 1996 and 2007, at the Neurology Division of the Bambino Gesù Children's Hospital in Rome, we collected 241 patients with WS. Sixteen (6.6%) were considered with idiopathic aetiology. All clinical notes of these patients were reviewed in order to evaluate the prevalence of other epileptic syndrome after WS. Two of them had at the age of 8 and 3 months idiopathic WS, and at the age of 6 and 4 years respectively, they presented with childhood absence epilepsy (CAE) successfully treated with valproate. The favorable evolution of the WS and the later occurrence of an idiopathic form of epilepsy, such as CAE, confirm the possibility of an idiopathic aetiology for WS that, although rare, can represent one of the etiologies of otherwise severe syndrome. Even if a common physiophatogenetic role, probably related to a genetic predisposition, could be hypothesized and appears to be intriguing, no data are available and more studies are needed to confirm this hypothesis.

Two female siblings with West syndrome: Familial idiopathic West syndrome with genetic susceptibility and variable phenotypic expression

The West syndrome (WS) is a characteristic form of epilepsy which usually begins in the first year of life. We describe two female siblings, aged 4 and 2 years, respectively, born from third degree consanguineous parents, with infantile spasms and developmental delay. Epileptic spasms had not a good outcome under antiepileptic drug treatment. Clinical and imaging features were of different severity in both siblings. Routine biochemical tests, metabolic investigations, and chromosomal analysis were normal. We analyzed CDKL5 gene by direct sequences and denaturing high-performance liquid chromatography using Transgenomic WAVE system. Analysis of the CDKL5 gene, which is responsible for female patient with WS, did not show any disease-causing mutation. WS has heterogeneous backgrounds, and may be more than one gene is responsible for its familial forms. In this family, consanguinity is observed in parents, which usually suggests that autosomal recessive inheritance is likely.

Early infantile epileptic encephalopathy with unusual favourable outcome

The authors report the case of an infant suffered from early infantile epileptic encephalopathy with suppression–burst, or Ohtahara syndrome, a severe form of epilepsy in early childhood. The patient was treated with vigabatrin causing a favourable response. This unusual outcome may be related with the normality of neuroimaging and metabolic studies, as happens with idiopathic West syndrome cases.

Multicenter long-term follow-up of children with idiopathic West syndrome: ACTH versus vigabatrin - CME questions

Multicenter long-term follow-up of children with idiopathic West syndrome: ACTH versus vigabatrin - CME questions

Multicenter long‐term follow‐up of children with idiopathic West syndrome: ACTH versus vigabatrin

Long-term follow-up of children with idiopathic West syndrome (WS) treated with adrenocorticotropic hormone (ACTH) or vigabatrin. Records of 28 normal magnetic resonance imaging (MRI) WS cases were reviewed for seizure development and cognitive outcome in relation to treatment type and lag. Average age at disease onset was 5.5 months, and average lag time to treatment was 25 days. Fourteen patients were treated with ACTH (eight early and six late), and 14 with vigabatrin (without delay). Response rates were 88% for ACTH and 80% for vigabatrin. Short-term outcomes for seizure cessation and electroencephalography normalization were identical between the groups. In the long-term, early ACTH treatment was better than the rest combined. Average follow-up time was 9 years. A normal cognitive outcome was achieved in 100% of the early-ACTH group, 67% of the late-ACTH group and 54% of the vigabatrin group (P = 0.03). Seizures subsequently developed in 54% of the vigabatrin group, in 33% of the late ACTH group, and 0% of the early ACTH group (P < 0.05). Idiopathic WS with normal MRI is associated with a good cognitive outcome. Early ACTH treatment, administered within 1 month, yields a better cognitive and seizure outcome than vigabatrin or late ACTH.

Add-on treatment with pyridoxine and sulthiame in 12 infants with West syndrome: an open clinical study

To investigate the effect of sulthiame (STM) in West syndrome (WS) an open, uncontrolled add-on study was undertaken during initial pyridoxine (PDX) therapy in 12 infants, two with idiopathic and ten with symptomatic WS. All patients were initially treated with PDX (150–300 mg kg −1body weight day−1 ). In seven patients (58%) seizures and hypsarrhythmia stopped during the week after introduction of STM (10 mg kg −1body weight day −1). In one the positive effect was temporary. Five of the responders (42%) remained seizure-free and without hypsarrhythmia under STM monotherapy, while one developed complex partial seizures after 25 months. STM was most effective in idiopathic WS (2 /2). During treatment with STM medication no patient suffered side effects attributable to the substance. Further controlled studies are necessary to evaluate the benefit of this potentially effective treatment.

Epidemiology of West syndrome in Singapore

The incidence of West syndrome (WS) was determined by a search of reports of electroencephalograms (EEG) recorded in 1998 and 1999 in all public hospitals in Singapore. Amongst records of patients born in 1998, nine were found with EEG features of hypsarrhythmia or modified hypsarrhythmia with onset of seizures between January 1,1998 and December 31, 1999. The medical records of these patients were reviewed. The population of children born in 1998 was 43,664. In 1998 and 1999, 67% of all hospital admissions for patients 2 years or younger in Singapore were in public hospitals. The cumulative incidence of WS in Singapore corrected for the percentage of hospital admissions to public hospitals was 3.1/10,000 live births. The corrected cumulative incidences in Chinese, Malays and Indians were 2.7, 3.1 and 3.3 per 10,000, respectively. Three cases were idiopathic; three were due to congenital structural lesions of the brain; one each had periventricular leucomalacia, intracranial hemorrhage and severe intrauterine growth retardation. None of the patients were normal at follow up. The three patients with idiopathic WS had mild global developmental delay and the other six cases had cerebral palsy and severe mental retardation. With the best modern medical treatment, possibly only two of the nine cases of WS may have been prevented.

Familial idiopathic West syndrome.

Two families, each with occurrence of West syndrome in two siblings, are presented. Monozygotic twins in family 1 developed infantile spasms at the age of 4 months. Two female siblings in family 2 started to have seizures at the age of 6 months, but 2 years apart. The family history; development prior to West syndrome; clinical, electroencephalographic, and neuroradiologic findings; diagnostic work-up; and treatment are described. The outcome in family 1 (follow-up after 2 years) showed no conspicuous findings on physical and neurologic examination, and psychomotor development appropriate to cognitive, motor, and language developmental age in both twins. In family 2 (follow-up after 3 and 5 years), the older sister only was one standard deviation below mean in intellectual developmental age. Simultaneous occurrence of infantile spasms in both siblings from these two families but with variable clinical expression suggests there is a genetic susceptibility and variable phenotypic expression. Long-term follow-up will demonstrate whether these cases may be classified as "familial idiopathic West syndrome."

Vigabatrin as a first-choice drug in the treatment of West syndrome.

This is a prospective study designed to evaluate the efficacy and safety of vigabatrin as first-choice monotherapy in infants with West syndrome. One hundred sixteen patients with newly diagnosed West syndrome were studied in Argentina, from June 1994 to April 1998. The follow-up ranged from 17 to 40 months (mean, 23 months). Vigabatrin was administered upon diagnosis, starting with a 50-mg/kg/day dose and increasing 50 mg/kg every 48 hours to reach a maximum dose of 200 mg/kg/day. Twenty-nine percent of cases were considered to be cryptogenic or idiopathic West syndrome, while 70.7% were symptomatic. Response to vigabatrin treatment was measured according to five categories: (1) seizures free: 61.8% of cases for cryptogenic and 29.3% for symptomatic West syndrome, (2) more than 75% reduction in the number of infantile spasms: 14.7% for cryptogenic and 26.8% for symptomatic West syndrome, (3) from 50% to 74% reduction in the number of infantile spasms: 11.8% for cryptogenic and 24.4% for symptomatic West syndrome, (4) poor or null response: 11.8% for cryptogenic and 18.3% for symptomatic West syndrome, and (5) increase in the number of infantile spasms: one symptomatic case (1.2%). All seizure-free cryptogenic cases showed normal neuropsychic development. The most effective dose of vigabatrin was 150 mg/kg of body weight per day. The most frequent adverse events were somnolence in 19 cases and irritability in 15 cases, but none required treatment interruption.

Early clinical and EEG features of infantile spasms in Down syndrome.

The combination of West syndrome (WS) and Down syndrome appears not to be coincidental. Fourteen patients free of cardiac malformation or history of perinatal hypoxia were referred and investigated before they had received any treatment and were followed to the mean age of 4.5 years (range 19 months to 14 years). Spasms had onset at the mean age of 8 months (range 4-18 months) in cluster and were symmetrical. Hypsarrhythmia was symmetrical and, after intravenous diazepam (4 patients, 0.5 mg/kg) it disappeared, without any remaining focus. Recorded spasms during a cluster were "independent," with recurrence of hypsarrhythmia between successive spasms, and thus had the ictal and interictal EEG characteristics of idiopathic WS. Seven patients exhibited other types of seizures after WS, consisting of myoclonic jerks, atonic, tonic-clonic or absence seizures, which proved quite easy to control with valproate and/or ethosuximide.

Transient focal cortical hypometabolism in idiopathic West syndrome

Positron emission tomography (PET) using 18F-labeled 2-deoxy- d-glucose was performed serially in 5 infants with idiopathic West syndrome. While tonic spasms persisted, 2 infants had hypometabolism in the bilateral temporo-parieto-occipital regions, which disappeared after cessation of spasms. In 2 other infants, PET revealed focal hypometabolism in the temporal region a few months after the disappearance of tonic spasms, but subsequent PET studies were normal. PET can detect transient metabolic abnormalities of the cerebral cortex which may be associated with the pathophysiology of West syndrome.

Predicting favorable outcome in idiopathic West syndrome.

Among 45 patients with cryptogenic West Syndrome (WS) we report 30 with a favorable outcome consisting of normal psychomotor development and cessation of epilepsy with at least 2 years follow-up (mean 4 years 7 months). These favorable patients could be recognized from onset by (a) absence of significant mental regression with a preserved visual function; (b) absence of focal interictal EEG abnormalities after intravenous diazepam; and (c) reappearance of hypsarrhythmia between consecutive spasms of a cluster. The latter criterion requires EEG recording of a series of spasms. The favorable outcome in these patients suggests that they had no cortical brain lesions. This new type of idiopathic epilepsy referred to as idiopathic West syndrome has important prognostic, therapeutic, and etiologic implications.