English

Infantile Epileptic Spasms Syndrome, IESS

IESS is a term proposed to encompass both West syndrome as well as infants presenting with epileptic spasms who do not fulfil all the criteria for West syndrome (West syndrome classically referred to the triad of epileptic spasms, hypsarrhythmia, and developmental stagnation or regression. However, IESS can lack one of these three criteria. For example, the developmental impact may not be apparent or typical hypsarrhythmia may not be present) [36].

Note: the previous West Syndrome often used as a synonym for infantile spasms (IS), but it is more appropriate to describe infantile spasms only as a seizure type (it is more reasonable to replace it with epileptic spasm, which often appears but not unique in West syndrome) [21]

Etiologies: Perinatal or postnatal injury, infection of central nervous system, abnormality of brain structure, Chromosomal abnormalities (such as Down syndrome, Miller-Dieker syndrom) or gene mutations (such as ARX, ADSL, CALN1, CASK, CD99L2, CDKL5, CLCN6, CYFIP1, CYFIP2, HUWE1, KMT2D, SPTAN1, STXBP1, TSC1, TSC2, TBC1D24, TCF4, SCN1A, SCN2A, SETBP1, SIK1, ST3GAL3, KCNQ2, GABRA1, GNAO1, KCNB1, FOXG1, FGF12, FGF13, GABRB1, GABRB2, GABRB3, GRIN1, GRIN2A, GRIN2B, GLYCTK, GNB1, GPT2, IARS2, MAG12, MEF2, MTOR, MYO18A, ALG13, IQSEC2, WDR45, SCA2, SLC1A4, SLC25A22, SLC35A2, UBA5, ATP2A2, ATP6V1A, GNB1, RARS2, DOCK7, DNM1, NEDD4L, NDP, NOS3, NRXN1, NSD1, PHACTR1, PIGA, PLCB1, PTEN, PURA, WWOX, DYNC1H1, DCX, PAFAH1B1, RYR1, RYR2, RYR3, TAF1, TECTA, TUBA1A, etc.), metabolic abnormalities (such as phenylketonuria, pyridoxine dependent epilepsy, Menkes disease, etc.), and there may be cross overlap among various causes, such as mutations in TSC1 and TSC2 genes, which can also cause abnormalities in brain structure [1-20, 23-35].

Age of onset: Most of them occur within 3-12 months after birth (the peak is around 5 months after birth). Some infants can evolve from Ohtahara Syndrome (OS)or other early onset epilepsies (typically with focal seizures), and some infants can develop Lennox-Gastaut Syndrome (LGS) around the age of 2-4 years.

Seizure characteristics: Epileptic spasms are a mandatory seizure type (most of which occur in wakefulness (more common after waking up or before falling asleep). Of course, it can also occur in sleep. Sudden sound or tactile stimulation is easy to induce, but light stimulation is often not). It can be manifested as flexion type (common, classic performance is nodding and hugging), or only extension type (rare), or flexion extension mixed type (common, neck, trunk, and upper limbs are usually flexed, but lower limbs are straight). Sometimes the seizures is often accompanied by crying or laughter. The manifestation of a series of spasms is a very important feature. Sometimes some mild spasms can only be manifested as repeated and brief eye deflection, mouth curling, eye squeezing, slight nod and limb "tightening" or instant gaze. Sometimes even ultra-high definition videos are difficult to see clearly, but some families can often feel it. It is important to paste the EMG of the corresponding position when doing video EEG. In addition, some epileptic spasms can also show bilateral asymmetry, or only involve one limb or a limited part, which often suggests that there may be local epileptic lesions in the brain. In addition, especially in the later stage of the course of disease, some patients can also have isolated spasm (this kind of spasm is difficult to be distinguished from myoclonus and transient tonic attack clinically, which needs to be comprehensively judged in combination with synchronous EEG, EMG and clinical manifestations) [22].

EEG: Interictal: EEG shows hypsarrhythmia (often highly disorganized with high voltage irregular slow waves intermixed with multifocal spikes and polyspikes and more obvious during sleep and may appear intermittently). Ictal: the typical EEG performance of epileptic spasms can be divided into 3 phases: 1. Short-term and extensive low-medium amplitude fast wave activity (sometimes it may be absent or compounded in the slow wave of the next phase); 2. Widespread high-amplitude multi-phase slow wave, sometimes the descending branch of slow wave can have a very deep positive deflection (corresponding to the symptoms of spastic contraction); 3. Diffuse voltage depression (sometimes not obvious). After 1-2 years of age, some children’s EEG can evolve into a broadly synchronized spike slow comprehensive wave, and there are often rapid rhythmic bursts during sleep, suggesting that it may transform into Lennox-Gastaut syndrome (LGS), and some children left the localized spike slow complex wave in the occipital region after the hypsarrhythmia subsided, and some of them could also be transformed into focal discharges in other parts in the later stage, and some of them may returned to normal [22].

Brain MRI: There may be abnormal brain structures, and some may be normal.

Developmental progress: Mostly development is backward (there are certain differences between individuals, which are mainly closely related to their own etiology, and occasionally development may be normal and developmental trajectory continues as expected when controlled).

Treatment:

National Institute for health and Clinical Excellence (NICE) epilepsy guidelines 2022:

First-line treatment: combination therapy with high-dose oral prednisolone (dosage calculation) and vigabatrin (vigabatrin monotherapy in children at high risk of steroid-related side effects or for infantile spasms due to tuberous sclerosis) (In 2012 NICE guideline it refer to offer a steroid (prednisolone or tetracosactide (analogues of ACTH)) or vigabatrin as first-line treatment to infants with infantile spasms).

Second-line treatment: If first-line treatment for infantile spasms is unsuccessful, one of the following treatment can be added: ketogenic diet, levetiracetam, nitrazepam, valproate sodium, topiramate (If the first choice is unsuccessful, consider the other second-line options).

 

Chinese clinical diagnosis and treatment guidelines epilepsy volume 2015:

First line drugs: Steroids (including ACTH (dosage calculation) and prednisone (dosage calculation)), vigabatrin.

Drugs that can be added: topiramate, valproate sodium, clonazepam, Iamotrigine.

2022 International League Against Epilepsy (ILAE) diagnostic criteria [36]:

Mandatory: Flexor, extensor or mixed epileptic spasms which often occur in clusters; EEG Interictal:Hypsarrhythmia, multifocal or focal epileptiform discharges (that might be seen quickly after the spasms onset); age of seizure onset within 1–24 months (while epileptic spasms may begin later, this would not be ISS); Developmental slowing after spasms onset but may be absent early in the course (difficult to determine in a child with existing significant developmental disorders).

Alerts: EEG Interictal: Normal EEG or Suppression-burst pattern; age of seizure onset within 1–2 months.

Exclusionary: EEG Ictal: Normal EEG during recorded clinical events of suspected spasms.

 

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