Infantile epileptic spasms syndrome

Epileptic spasms Epileptic spasms are a seizure type characteristic for the first year of life. The spasms are typically resistant to conventional pharmacotherapy. There are many episodes per day. Episode duration, intensity, and muscle groups affected are variable. Mild spasms may involve mere nodding, muscle twitching or eye movements, whereas powerful spasms may result in the infant's body violently bending over (the so-called "salaam" or "jackknife" movements). Individual spasms typically last only seconds, but episodes may last over 20 minutes. An episode is typically followed by exhaustion; episodes are typically followed by over a minute of motionlessness and diminished responsiveness. The spasms present as episodes of brisk (0.2-2s) neck flexions-extensions and upper limp abductions-adductions, lower limb extension, and trunk musculature contractions, accompanied by upward deviation of the eyes. Nevertheless, individual muscle groups (abdominal, shoulder, neck) may be involved. Most often, there is simultaneous contraction of both flexors and extensors, followed by flexor spasms, and the least frequent extensor spasms. Spasms are usually symmetrical, but up to 30% of cases may exhibit varying degrees of lateralisation. Unilateral brain lesions often (but not always) result in asymmetric spasms; unilateral spasms may progress to generalised spasms. Drop attacks may be the initial presentation of West syndrome of later onset. Altered or absent breathing is common during episodes. When spontaneous remissions occurs, it is typically gradual. Remission by the age of three is 50%, rising to 90% by the age of five. Developmental The onset of epileptic spasms is often associated with developmental regression: autistic withdrawal, and loss of social smiling and of visual attention. A majority of individuals with West syndrome exhibit regression of psychomotor skills. However, developmental delay is noted in up to about two-thirds of infants with West syndrome already before the onset of spasms, whereas only about a third had exhibited normal development prior to spasm onset. ==Causes==

Based on etiology, cases of IESS are commonly classified as either symptomatic or cryptogenic - although these terms have not been used consistently. Symptomatic cases are most often defined as those in which a clear cause can be identified, though some investigators also use the designation in cases in which there was previous clinical or imaging evidence of brain lesions and/or abnormal development was noted prior to the onset of the syndrome. Cryptogenic cases are thus contrastingly defined as those in which no specific cause can be identified, or where no such lesions or abnormalities were noted prior to syndrome onset. Genetic Mutations in several genes have been associated with IESS. These include the Aristaless related homeobox (ARX) and cyclin dependent kinase like 5 (CDKL5) genes. The ARX gene in particular seems to be responsible for at least some of the X linked cases. Variants in genes associated with channelopathies, such as KCNT1 and SCN2A, can also, in rare cases, result in West syndrome. ==Diagnosis==

Infantile spasms can be misdiagnosed as non-epileptic, non-pathological movements such as infantile colic, startle response, or Moro reflex. ==Treatment==

Pharmacotherapy There is limited evidence as to which pharmacotherapy approach is optimal. ACTH therapy produces improvement in spasms within days whereas neurodevelopmental improvements take weeks. ACTH therapy is associated with increased risk of infections (which account for the majority of deaths). Small epileptic foci augur a favourable outcome, however, in most cases, resection of extensive multilobar cortical dysplasias is called for, resulting in limited cognitive improvement. Dietary interventions There is some evidence for the use of the ketogenic diet or modified Atkins diet in cases which have failed to respond to pharmacotherapy, though ketogenic diet was more effective. ==Prognosis==

Prognosis of epileptic spasms and IESS depends predominately upon aetiology, and less so on treatment. Unfavourable prognostic factors include: symptomatic aetiology, early onset (prior to 3 months), presence of other seizure types prior to onset of infantile spasms, poor treatment response, electroencephalogram asymmetry, absence of typical hypsarrhythmia, and (prolongued) developmental regression. ==Epidemiology==

Incidence is around 1:3200 to 1:3500 of live births. Statistically, boys are more likely to be affected than girls at a ratio of around 3:2. ==See also==