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Immunology Letters Sep 2023West Syndrome (WS) is an epileptic encephalopathy that typically occurs in infants and is characterized by hypsarrhythmia, infantile spasms, and neurodevelopmental...
BACKGROUND
West Syndrome (WS) is an epileptic encephalopathy that typically occurs in infants and is characterized by hypsarrhythmia, infantile spasms, and neurodevelopmental impairment. Demonstration of autoantibodies and cytokines in some WS patients and favorable response to immunotherapy have implicated inflammation as a putative trigger of epileptiform activity in WS. Our aim was to provide additional support for altered inflammatory responses in WS through peripheral blood immunophenotype analysis.
METHODS
Eight WS cases treated with synacthen and 11 age- and sex-matched healthy volunteers were included. Peripheral blood mononuclear cells (PBMC) were isolated and immunophenotyping was performed in pre-treatment baseline (8 patients) and 3 months post-treatment (6 patients) samples. The analysis included PBMC expressing NFκB transcription and NLRP3 inflammasome factors.
RESULTS
In pre-treatment baseline samples, switched memory B cells (CD19IgDCD27) were significantly reduced, whereas plasma cells (CD19CD38CD138) and cytotoxic T cells (CD3CD8) were significantly increased. Regulatory T and B cell ratios were not significantly altered. Synacthen treatment only marginally reduced helper T cell ratios and did not significantly change other T, B, NK and NKT cell and monocyte ratios.
CONCLUSIONS
Our findings lend further support for the involvement of inflammation-related mechanisms in WS. New-onset WS patients are inclined to display increased plasma cells in the peripheral blood. Synacthen treatment does not show a beneficial effect on most effector acquired and innate immunity subsets.
Topics: Infant; Humans; Spasms, Infantile; B-Lymphocytes; Plasma Cells; Natural Killer T-Cells; Inflammation
PubMed: 37459957
DOI: 10.1016/j.imlet.2023.07.007 -
Brain & Development Nov 2001To provide information on the current status of West syndrome (WS) in the Philippines.
AIM
To provide information on the current status of West syndrome (WS) in the Philippines.
METHODS
This is a retrospective review of WS cases from January 1997 to December 1999 from two largest referral government institutions. A questionnaire interview survey on anticonvulsant usage was also conducted among practicing child neurologists.
RESULTS
Twelve patients diagnosed to have infantile spasms at 2-15 months were included, with a male:female ratio of 1:1. The proportion of WS cases among epileptic children under age 3 was 3.18%. The etiologies were idiopathic/cryptogenic in four (33%) and symptomatic in eight (66%). Symptomatic cases include hypoxic-ischemic encephalopathy, neonatal sepsis, bacterial meningitis, inborn error of metabolism, congenital brain anomaly and intracranial hemorrhage. Phenobarbital was the first line drug in 75% of cases. Other drugs used were valproic acid, clonazepam and pyridoxine. With a follow-up duration of 1-40 months, only three patients became seizure free and most had poor neurodevelopmental outcome. Among practicing child neurologists, the preferred ideal drug was adrenocorticotrophic hormone (ACTH) and valproic acid for idiopathic and symptomatic cases, respectively. However, in actual clinical practice valproic acid or prednisone was the initial drug used. Pyridoxine was usually added on.
CONCLUSIONS
The proportion of WS in our patient population may not reflect the true prevalence in our country since our data came from a biased population, i.e. referral centers. A national statistics is currently not available. ACTH, which was perceived by most child neurologists as the ideal first line drug was not used primarily because it is unavailable and unaffordable. The poor seizure control and developmental outcome may be due to the treatment given or directly related to the etiology of WS.
Topics: Adrenocorticotropic Hormone; Anticonvulsants; Female; Humans; Infant; Male; Philippines; Retrospective Studies; Spasms, Infantile; Surveys and Questionnaires
PubMed: 11701266
DOI: 10.1016/s0387-7604(01)00297-2 -
Epilepsy Research Aug 2021We analyzed the records of 198 patients with West syndrome (WS) seen at a single pediatric neurology center in Argentina between June 2004 and June 2017. Five patients...
OBJECTIVE
We analyzed the records of 198 patients with West syndrome (WS) seen at a single pediatric neurology center in Argentina between June 2004 and June 2017. Five patients with infection-related spontaneous remission of the electroclinical manifestations were identified.
METHODS
The following parameters were investigated: personal and family history, clinical characteristics of the seizures - mainly spasms - and EEG findings, type of treatment, and outcome. The inclusion criteria for WS were epileptic spasms (ES) in clusters, hypsarrhythmia, and mental deterioration. Infants with ES without hypsarrhythmia and other epileptic encephalopathies with ES were excluded.
RESULTS
Five children, four boys and one girl, met the inclusion criteria of WS with spontaneous remission after a viral infection. The etiology of ES was unknown in four patients and one had a structural etiology. All patients had spontaneous remission of the ES and normalization of the EEG following acute upper respiratory infection in four and exanthema subitum in one; all of them had fever between 38.5 and 40 °C.
CONCLUSION
We report five patients with spontaneous remission of WS following acute viral infection, associated with a respiratory virus in four and exanthema subitum in one.
Topics: Child; Electroencephalography; Female; Fever; Humans; Infant; Male; Remission, Spontaneous; Seizures; Spasm; Spasms, Infantile
PubMed: 33989887
DOI: 10.1016/j.eplepsyres.2021.106663 -
Brain & Development Nov 2001Children with infantile epileptic encephalopathies comprising 3.5% of the Pediatric Neurology Clinic registrations in a tertiary care hospital were retrospectively...
Children with infantile epileptic encephalopathies comprising 3.5% of the Pediatric Neurology Clinic registrations in a tertiary care hospital were retrospectively analyzed. Data were retrieved from case records and analyzed for seizure semiology, prenatal and perinatal insults, developmental status and relevant investigations. The various therapeutic modalities and their influence on spasm frequency, long-term development and final seizure status were compared. The two primary outcome variables analyzed included final seizure status and developmental outcome. Of the 94 infantile epileptic encephalopathies, West syndrome was the commonest (55.3%), of which two thirds were symptomatic. Etiological factors were prenatal in 66.6% and perinatal in 33.3%. The initial response to ACTH was good in 54.5% with subsequent relapse in 27.8% and for prednisolone was 52.9 and 44.4%, respectively, compared to 25.3% spasms control with conventional antiepileptic drugs. Disease category of infantile epileptic encephalopathies evolved in 4, i.e. early myoclonic encephalopathy to West syndrome 1, early infantile epileptic encephalopathy to West syndrome 1, West syndrome to Lennox-Gastaut syndrome 2. Psychomotor retardation was seen in 88.2%, with 16.1% having normal development at onset of spasms. Microcephaly was associated with delayed development but did not influence final seizure outcome. Final seizure outcome was poor in children with delayed development at onset (adjusted odds ratio [OR]=4), delay in diagnosis >12 months (OR=2.27) and in children with Lennox-Gastaut syndrome (OR=4.75). ACTH/prednisolone and antiepileptic treatment versus antiepileptics alone showed a good final seizure response in 36.6% versus 20%. Development on follow up was delayed in children with initial psychomotor retardation (OR=23.4) and abnormal electroencephalogram (OR=7.46). Perinatal factors constituted one third of symptomatic West syndrome. The use of ACTH/corticosteroids resulted in good initial spasm control though final seizure outcome and development were unaffected. Prednisolone had similar response to ACTH in spasm control but higher subsequent relapse rate. Vigabatrin was useful though often unaffordable. The identification of a neurometabolic etiology, though uncommon, has significant therapy implications. Delay in diagnosis was common and negatively influenced final seizure outcome.
Topics: Adrenocorticotropic Hormone; Anticonvulsants; Child, Hospitalized; Developmental Disabilities; Electroencephalography; Epilepsies, Myoclonic; Epilepsy, Generalized; Female; Humans; India; Infant; Magnetic Resonance Imaging; Male; Microcephaly; Predictive Value of Tests; Prognosis; Retrospective Studies; Spasms, Infantile; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 11701262
DOI: 10.1016/s0387-7604(01)00288-1 -
Brain & Development Mar 2002Children with infantile epileptic encephalopathies comprising 3.5% of the Pediatric Neurology Clinic registrations in a tertiary care hospital were retrospectively...
Children with infantile epileptic encephalopathies comprising 3.5% of the Pediatric Neurology Clinic registrations in a tertiary care hospital were retrospectively analyzed. Data were retrieved from case records and analyzed for seizure semiology, prenatal and perinatal insults, developmental status and relevant investigations. The various therapeutic modalities and their influence on spasm frequency, long-term development and final seizure status were compared. The two primary outcome variables analyzed included final seizure status and developmental outcome. Of the 94 infantile epileptic encephalopathies, West syndrome was the commonest (55.3%), of which two thirds were symptomatic. Etiological factors were prenatal in 66.6% and perinatal in 33.3%. The initial response to ACTH was good in 54.5% with subsequent relapse in 27.8% and for prednisolone was 52.9 and 44.4%, respectively, compared to 25.3% spasms control with conventional antiepileptic drugs. Disease category of infantile epileptic encephalopathies evolved in 4, i.e. early myoclonic encephalopathy to West syndrome 1, early infantile epileptic encephalopathy to West syndrome 1, West syndrome to Lennox-Gastaut syndrome 2. Psychomotor retardation was seen in 88.2%, with 16.1% having normal development at onset of spasms. Microcephaly was associated with delayed development but did not influence final seizure outcome. Final seizure outcome was poor in children with delayed development at onset (adjusted odds ratio [OR] = 4), delay in diagnosis >12 months (OR = 2.27) and in children with Lennox-Gastaut syndrome (OR = 4.75). ACTH/prednisolone and antiepileptic treatment versus antiepileptics alone showed a good final seizure response in 36.6% versus 20%. Development on follow up was delayed in children with initial psychomotor retardation (OR = 23.4) and abnormal electroencephalogram (OR = 7.46). Perinatal factors constituted one third of symptomatic West syndrome. The use of ACTH/corticosteroids resulted in good initial spasm control though final seizure outcome and development were unaffected. Prednisolone had similar response to ACTH in spasm control but higher subsequent relapse rate. Vigabatrin was useful though often unaffordable. The identification of a neurometabolic etiology, though uncommon, has significant therapy implications. Delay in diagnosis was common and negatively influenced final seizure outcome.
Topics: Anticonvulsants; Child; Child Development; Child, Preschool; Disease Progression; Electroencephalography; Epilepsy; Female; Humans; India; Infant; Infant, Newborn; Magnetic Resonance Imaging; Male; Prognosis; Retrospective Studies; Spasms, Infantile; Tomography; Treatment Outcome
PubMed: 11891107
DOI: 10.1016/s0387-7604(02)00029-3 -
Brain & Development Nov 2001Neuroimaging studies with magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning have contributed significantly to our understanding of West... (Review)
Review
Neuroimaging studies with magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning have contributed significantly to our understanding of West syndrome. Cortical dysplastic lesions are the most common abnormalities seen with MRI in infants with spasms, but other structural lesions are also detected occasionally. An underlying cortical dysplasia may not be apparent until myelination has advanced in the brain and poor gray-white matter differentiation becomes observable. Many cortical dysplastic lesions can only be detected using PET scanning of glucose metabolism or gamma-aminobutyric acid(A) (GABA(A)) receptor binding. The MRI and PET findings, together with neurophysiological observations, strongly suggest that infantile spasms are initiated as cortical epileptic discharges that, during a 'critical' developmental period, may undergo secondary generalization in an age-dependent mechanism to emerge as spasms. The onset of spasms often coincides with the functional maturation of cerebral cortex. Based on data from glucose metabolism PET scanning as well as electrophysiological and neurochemical findings on infants with spasms, we have postulated that the offending lesion is a focal or diffuse cortical abnormality which, at a critical stage of maturation, causes abnormal functional interactions with brainstem raphe nuclei which project widely throughout the brain. Raphe-cortical projections could mediate the hypsarrhythmic changes seen on EEG. The prominent serotonergic raphe-striatal pathway and descending spinal pathways may be responsible for secondary generalization of the cortical discharges to result in the relatively symmetric spasms. It is likely that additional factors (e.g. genetic) play a role in the manifestation of the age-specific electroclinical features of West syndrome. Recently developed PET tracers can be used to detect epileptogenic brain regions and also to investigate developmental abnormalities of serotonergic (using the tracer alpha[(11)C]methyl-L-tryptophan) and GABAergic (using [(11)C]flumazenil) neurotransmitter systems. These systems are implicated in epileptogenesis, and their involvement in the pathophysiology of West syndrome can be further addressed by future functional neuroimaging studies.
Topics: Brain; Humans; Infant; Magnetic Resonance Imaging; Spasms, Infantile; Tomography, Emission-Computed
PubMed: 11701243
DOI: 10.1016/s0387-7604(01)00295-9 -
The Tohoku Journal of Experimental... Mar 2020Abusive head trauma (AHT), commonly known as shaken baby syndrome, is a cranial injury of infants and young children. AHT is an important cause of morbidity and...
Abusive head trauma (AHT), commonly known as shaken baby syndrome, is a cranial injury of infants and young children. AHT is an important cause of morbidity and mortality in young children, particularly those younger than 12 months of age. We describe two patients who developed West syndrome, which is a severe epilepsy syndrome composed of the triad of infantile spasms, hypsarrhythmia on electroencephalography, and developmental arrest or regression, possibly attributable to AHT. Case 1 was a 5-month-old boy presented with generalized convulsive status epilepticus when a babysitter had cared for him. Brain magnetic resonance imaging (MRI) exhibited a subdural hemorrhage with diffuse brain edema and a midline shift highly suggestive of AHT. He developed West syndrome at the age of 10 months. Case 2 was a 6-month-old girl presented infantile spasms and diagnosed with West syndrome. Although she had poor weight gain due to inadequate care by her mother, there were no history of trauma, no cutaneous finding, and no developmental delay. Brain MRI performed when West syndrome was diagnosed revealed contusional tears highly suggestive of AHT. The MRI finding indicated that contusional tears had occurred 1~2 months before the development of West syndrome. There are no reports of West syndrome due to contusional tears. AHT may be an important risk factor for postnatal West syndrome. It is noteworthy that evidence of AHT was found only after West syndrome onset, as in Case 2. The onset of West syndrome may contribute to the finding that AHT had occurred earlier.
Topics: Brain; Child Abuse; Child, Preschool; Craniocerebral Trauma; Electroencephalography; Female; Humans; Infant; Magnetic Resonance Imaging; Male; Neuroimaging; Spasms, Infantile; Tomography, X-Ray Computed
PubMed: 32161214
DOI: 10.1620/tjem.250.167 -
Zhurnal Nevrologii I Psikhiatrii Imeni... 2016West syndrome is one of the most well-known epileptic encephalopathies, a catastrophic epilepsy syndrome with onset in the first year of life. Prognosis of this...
West syndrome is one of the most well-known epileptic encephalopathies, a catastrophic epilepsy syndrome with onset in the first year of life. Prognosis of this condition depends on the etiology and adequate treatment. The authors review the hormonal treatment of West syndrome. Adrenocorticotrophic hormone (ACTH) is used in USA and its synthetic analogue tetracosactide is used in Europe. Both of the drugs are not registered in the Russian Federation. The data on the efficacy of corticosteroids, including prednisolone, are contradictory. Recent results have demonstrated the high efficacy of prednisolone in the treatment of West syndrome. The authors discuss different aspects of hormonal treatment of West syndrome: possible mechanisms, choice of medication, hormone doses, its duration, efficacy ant tolerability.
Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Anticonvulsants; Europe; Humans; Infant; Prognosis; Russia; Spasms, Infantile
PubMed: 28005049
DOI: 10.17116/jnevro20161169261-66 -
Epilepsy Research Jul 2021To develop an improved interictal electroencephalogram (EEG) grading scale for children with infantile spasms founded on elements with adequate inter-rater reliability...
OBJECTIVE
To develop an improved interictal electroencephalogram (EEG) grading scale for children with infantile spasms founded on elements with adequate inter-rater reliability (IRR) to justify its further study for clinical and research purposes.
METHODS
Three blinded reviewers assessed five-minute sleep epochs in 93 EEGs from 62 children (31 consecutive controls, 31 consecutive infantile spasms [pretreatment and posttreatment studies]) using a longitudinal bipolar montage. We determined the IRR of background amplitude, epileptiform discharges, >3 spike foci (including <50 % or >50 %), grouped multifocal spikes, paroxysmal voltage attenuations, and symmetry of sleep spindles. Data were used to finalize the 2021 BASED (Burden of AmplitudeS and Epileptiform Discharges) score.
RESULTS
All elements included in the 2021 BASED score had moderate to near perfect IRR. Among controls, >200 μv background waves occurred commonly in the bilateral posterior temporal (T3-T5, T4-T6) and midline (Fz-Cz, Cz-Pz) regions. Excluding midline and occipital channels (which have normal high amplitude background waves), we designated abnormal high amplitude background waves as >200 μv for most channels, but >300 μv for T3-T5 and T4-T6. The IRR was moderate to near perfect for <50 % >3 spike foci, >50 % >3 spike foci, paroxysmal voltage attenuations, grouped multifocal spikes (GMFS), and symmetric sleep spindles. Paroxysmal voltage attenuations, GMFS, and >50 % >3 spike foci all significantly distinguished pretreatment from posttreatment studies whereas symmetric sleep spindles did not (as planned, the latter was not included in the 2021 BASED score). When the 2021 BASED score was applied to the 22 children with infantile spasms achieving clinical remission with treatment, 19 met criteria for electroclinical remission and three did not.
SIGNIFICANCE
The 2021 BASED score includes elements with high levels of IRR and correlates well with the presence or absence of infantile spasms.
Topics: Child; Electroencephalography; Humans; Infant; Reproducibility of Results; Sleep; Spasm; Spasms, Infantile
PubMed: 33839516
DOI: 10.1016/j.eplepsyres.2021.106631 -
Pediatric Neurology Feb 2019
Topics: Drug Resistant Epilepsy; Female; Humans; Infant; Phospholipase C beta; Point Mutation; Spasms, Infantile
PubMed: 30554916
DOI: 10.1016/j.pediatrneurol.2018.11.007