**2.4 Etiology**

The etiologies of OS are diverse, including specific genetic mutations, cortical brain malformations, mitochondrial disorders, nonketotic hyperglycinemia, and severe perinatal hypoxic-ischemic injury. On the other hand, EE vitamin-responsive disorders need to be ruled out as a potential underlying etiology; in certain cases the cause is unknown.

The most frequent genetic abnormalities linked with OS are aristaless-related homeobox (ARX) gene mutations at Xp22.13, cyclin-dependent kinase-like 5 (CLDK5) (STK9) gene at Xp22, solute carrier family 25 [mt carrier, glutamate carrier-1/GC-1] member 22 (SLC25A22) gene at 11p15.5, STXBP1 (MUNC18-1) gene microdeletion at 9 q33.3-q34.11, KCNQ2 gene mutations, SCN2A gene mutations, and GABRA1 gene mutations [14].

EME is usually associated with inherited metabolic disorders, such as nonketotic hyperglycinemia, organic acidemias, Zellweger syndrome, and molybdenum cofactor deficiency [15]. Until the report of Cohen in 2014, in two siblings with early myoclonic encephalopathy, born to consanguineous parents of Arab Muslim origin, a potential mutation of SLC25A22 should be considered in infants presenting as EME, severe microcephaly, and autosomal recessive inheritance with negative metabolic workup [16].

Several of the genes may manifest as phenotypes that overlap not only with OS and EME but also with other EEs such as West syndrome [14].

**Box 1** shows differences between early epileptic encephalopaties [17].


*OS, Ohtahara syndrome; EME, early myoclonic encephalopathy; S-B, suppression-burst; ARX, aristalessrelated homeobox*

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*Epileptic Encephalopathies in Infants and Children DOI: http://dx.doi.org/10.5772/intechopen.85378*

There is no specific treatment efficacious for these epileptic syndromes. For OS, adrenocorticotropic hormone (ACTH)/corticosteroids, vigabatrin, levetiracetam, zonisamide, phenobarbitone, rufinamide, and ketogenic diet should be tried. Resective surgery may be useful in cases of focal cortical dysplasia or hemimegalencephaly. Patients diagnosed as EME should receive a trial of pyridoxine. In cases with nonketotic hyperglycinemia, oral administration of ketamine, tryptophan, and dextromethorphan, in combination with benzoate, may improve the neurological symptoms [18]. Vigabatrin and sodium channel blocker AEDs should be avoided

Prognosis in both syndromes is very poor, and the response to treatment is very disappointing. About half of patients die within weeks or months from onset, and the others progress with severe neurological impairments. Two-thirds of the survived OS patients develop infantile spasms, around 3–7 months, and numerous advances to LGS after 1 year of age [18]. In EME, the erratic myoclonus will improve spontaneously with time, and then they will carry on having focal seizures, despite

West syndrome (WS) was first described by Dr. WJ West of Tunbridge, United Kingdom, in 1841, in a letter addressed to the editor of *The Lancet*. West reports the characteristic clinical features in his own son. In 1952, Gibbs and Gibbs describe hypsarrhythmia, the characteristic electroencephalographic feature of WS [1]. WS is an age-dependent epilepsy that usually starts in the first year of life, most frequently between the first 3 and 9 months of life; however spasms can also affect older children but rarely beyond the age of 2 years. Even though the triad of epileptic spasms in cluster, developmental regression, and hypsarrhythmia on the EEG defines WS, it is not always associated with the classical hypsarrhythmic EEG pattern, and patients do not always have developmental regression at the beginning of the disease [19]. The recent ILAE classification included the term "epileptic spasms" (ES), rather than "infantile spasms," when this seizure type is observed at other ages. Hypsarrhythmia can also be incidentally recorded in the absence of spasms.

ES are a seizure type, characterized by short-term muscle contractions that affect predominate proximal and truncal muscles which lead to abrupt flexion, extension, or mixed movements. According to EEG-EMG polygraphy records, an epileptic spasm reaches the full contraction more slowly than myoclonia but faster than a tonic seizure [20]. Usually, ES occurs in clusters but may be isolated. Clusters of ES increase progressively in frequency and intensity, reach a peak, and then

Some ES are limited to making only grimaces, deviation of the eye, and nodding; they can also be subclinical; it's called "subtle" ES. On the other hand, ES may be asymmetric, or asynchronous, concomitant with various focal manifestations that may implicate the limbs, head, or eyes; sometimes ES may express with compartmental and vegetative features. If ES is preceded or followed by, or interspersed

**3. Infantile spasms (IS) and West syndrome (WS)**

**3.2 Seizures: symptoms and semiology**

gradually decline before they stop.

with, focal seizures, it suggests a focal lesion [21].

**2.5 Treatment and prognosis.**

in the myoclonic phase of EME.

its treatment.

**3.1 Overview**

### **Box 1.**

*Differences between early infantile epileptic encephalopathy (EME) and Ohtahara syndrome (OS).*
