Epileptic spasms

Overview

  • "Epileptic spasms" (also known as West Syndrome) is an age related epilepsy syndrome characterized by epileptic spasms, and chaotic EEG abnormalities, associated with modification of behaviour and cognitive decline.
  • ILAE Commission on Classification and Terminology (2010) classified this group as Epileptic Spasms because spasms may continue past or even occur de novo after infancy.
  • Epileptic spasms may be classified as focal, generalized or unknown.
  • It is the prototype of an epileptic encephalopathy - a condition in which epileptic abnormalities themselves contribute to the progressive disturbance in cerebral function.
  • There can be a profound impact on neurological development, particularly cognition and behaviour.

According to the NICE Guideline: The Epilepsies:

  • The seizure type(s) and epilepsy syndrome, aetiology, and co-morbidity, should be determined.
  • If there is diagnostic uncertainty, individuals should be referred to tertiary services soon (within 4 weeks) for further assessment.

Demographics

  • Prevalance: 0.25-0.4 / 1000
  • Age of onset: Peak age: 3-7 months, 90% present in first year, rare after 18 months of age
  • Genetics: There are rare single gene epilepsies. Genetic consultation is required to explore this aetiology.
  • Aetiology: The etiologies in about 50% of cases are prenatal (malformations, intrauterine insults, neurocutaneous syndromes - including Tuberous Sclerosis, metabolic and genetic disorders)

Most common causes/associations are:

Hypoxic ischaemic encephalopathy (10%), genetic (8%), Tuberous Sclerosis (7%), other cerebral malformation (8%), stroke, including porencephaly (8%), periventricular leukomalacia (5%).

  • Tuberous Sclerosis: Epilepsy is the most common neurological symptom of Tuberous Sclerosis (80-90%), with frequent presentation of Infantile Spasms in first year of life (33%).
  • Hypoxic Ischemic Encephalopathy (HIE): Prolonged depression of EEG over 21 days of age in term or near-term infants with HIE is a valuable predictor of later development of Infantile Spasms.
  • Mitochondrial disorders: Spasms are the most common presenting seizure type in children with probable and definite mitochondrial disease. In unexplained Infantile Spasms, particularly with developmental delay, investigate for mitochondrial disease.

Signs | Symptoms

Seizure semiology

  • Epileptic spasm: Sudden, bilateral and symmetric contraction of muscles of neck, trunk, and extremities. The type of seizure depends on muscles (flexor or extensor) affected and on extent of contraction. The intensity of contractions and number of muscle groups involved vary considerably.
  • The episodes are grouped in series or clusters, 5-30 secs apart, mainly on awakening or during transition from NREM to REM sleep.
  • Asymmetric spasms may occur.

Differential Diagnosis

 - Other non epileptic events eg: shudders.

 - Benign myoclonus of early infancy:

  • Spells begin in less than 1 year, self-limited
  • Clusters of head, trunk or extremity spasms, eye-blinking, brief jerking of upper extremity or trunk, and head nodding episodes
  • EEG invariably normal, neurologic development is not affected
  • Complete resolution 2 weeks to 8 months after onset.

Investigations

Tailor investigations depending on the clinical phenotype.

EEG

  • Classic hypsarrhythmia: Very high voltage asynchronous, random and independent spike and sharp wave discharges with periods of electro-decrements. Discharges are worse in NREM sleep.
  • Modified hypsarrhythmia: Focal or asymmetric discharges, episodes of voltage attenuation and some inter-hemispheric synchronization.
  • There is no difference in prognosis or treatment with these EEG patterns.

Neuroimaging

  • MRI/MRS

Genetic

  • chromosomes, CGH array, and when indicated, gene panel and next generation sequencing.

Ophthalmological evaluation

  • recommended

Hearing assessment

  • recommended

TORCH screen

  • recommended

Metabolic

  • It is important to treat treatable conditions (B12, copper, UMS, CSF glucose)
  • First line investigations include Urine metabolic screen, biotinidase, Vitamine B12, Lactate, ammonia, LFTs.
  • Second line investigations (often in consultation with a Paediatric Neurologist) include copper, transferrins, CSF analysis including glucose, aminoacids, lactate, neurotransmitters (if clinically indicated), urine metabolic screen (including P6C), plasma amino acids
  • Glucose transporter disorder has been reported as a cause of epileptic spasms.

Prognosis

A population based, 10-yr follow-up observational study of 18 infants (Trevathan et al., 1999), found:

  • 80% of 10 year olds had developmental delay, often severe
  • 40% - cerebral palsy
  • 94% - active epilepsy, with 50% Lennox Gastaut (other series 15-20%)
  • 15% - died before 11 years

In addition, others have shown:

  • There is a very high incidence of neuropsychiatric difficulties, and
  • There is significant increase in Autistic Spectrum Disorder.

Poor prognostic factors

  • Adverse neonatal history
  • Symptomatic aetiology
  • Partial seizures
  • Asymmetric EEGs
  • Age of onset <4months
  • Seizures preceding spasms (outside neonatal period)
  • Delayed development prior to onset of spasms
  • Time delay in treating > 1 month

Management

Aim for:

  • Cessation of seizures
  • Resolution of hypsarrhythmia on EEG
  • Preserved development
  • Short lag time to treatment leads to better long-term developmental outcome

Treatment options

  • Hormone (ACTH / prednisolone)
  • Vigabatrin: Considered by many as preferred treatment  in Tuberous Sclerosis group. Monitor for visual field defects – Electro retinography (ERG) at base line and every 3 months
  • If patient fails one option, try other (e.g. if patient fails Vigabatrin try steroids and vice versa)

UK Infantile Spasm Study (UKISS) (2004)

  • Multi centre study compared the treatment effects of Vigabatrin with hormonal treatment (prednisolone and tetracosactide) in infantile spasms
  • Cessation of spasms by 2 weeks was more likely with hormonal treatment than vigabatrin
  • Generally, development and epilepsy outcomes were not significantly different between the two treatment groups at 4 years of follow up
  • Better development was seen at 14 months and 4 year follow up in those with no identified aetiology allocated hormonal treatment.
  • Patient may respond to one or other. If above fails – there is no data to suggest one drug is superior.

ICISS: Follow-up to UKISS (2017)

Hormonal treatment with vigabatrin is significantly more effective in stopping infantile spasms and resolving EEG than hormonal treatment alone.

Other options include:

  • Ketogenic Diet - >50% improvement of spasms at 1-2 years
  • Consider surgical options in appropriate candidates with intractable spasms
  • Other suitable antiepileptics (many other drugs have been tried but are not first line treatment and are used when other options fail). 

References

  • Arce-Portillo E, Rufo-Campos M, Munoz-Cabello B, Blanco-Martinez B, Madruga-Garrido M, Ruiz-Del Portal L, et al. West syndrome: Aetiology, therapeutic options, clinical course and prognostic factors. Rev Neurol 2011;52(2):81-9.
  • Darke K, Edwards SW, Hancock E, Johnson AL, Kennedy CR, Lux AL, et al. Developmental and epilepsy outcomes at age 4 years in the UKISS trial comparing hormonal treatments to vigabatrin for infantile spasms: A multi-centre randomised trial. Arch Dis Child 2010;95(5):382-6.
  • Go CY, Mackay MT, Weiss SK, Stephens D, Adams-Webber T, Ashwal S, et al. Evidence-based guideline update: Medical treatment of infantile spasms. Report of the Guideline Development Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology 2012;78(24):1974-80.
  • Hancock E, Osborne JP. Vigabatrin in the treatment of infantile spasms in tuberous sclerosis: Literature review. J Child Neurol 1999;14(2):71-4.
  • Kosoff EH. Infantile spasms. The Neurologist 2010;16(2):69-75.
  • Lux AL, Edwards SW, Hancock E, Johnson AL, Kennedy CR, Newton RW, et al. The United Kingdom Infantile Spasms Study (UKISS) comparing hormone treatment with vigabatrin on developmental and epilepsy outcomes to age 14 months: A multicentre randomised trial. Lancet Neurol 2005;4(11):712-7.
  • Maydell BV, Berenson F, Rothner AD, Wyllie E, Kotagal P, et al. Benign myoclonus of early infancy: An imitator of West's syndrome. J Child Neurol 2001;16(2):109-12.
  • Roger J, Bureau M, Dravet C, Genton P, Tassinari CA, Wolf P, editors. Epileptic syndromes in infancy, childhood and adolescence (5th ed). Montrouge, France: John Libbey Eurotext Ltd; 2012.
  • Trevathan E, Murphy CC, Yeargin-Allsopp M. The descriptive epidemiology of infantile spasms among Atlanta children. Epilepsia 1999;40(6):748-51.
  • O’Callaghan FJK, Edwards SW, Alber FD, Hancock E, Johnson AL, Kennedy CR et al. Safety and effectiveness of hormonal treatment versus hormonal treatment with vigabatrin for infantile spasms (ICISS): a randomised, multicentre, open-label trial. The Lancet Neurology  2017;16(1):33-42.