**2.5 Treatment and prognosis.**

*Epilepsy - Advances in Diagnosis and Therapy*

*2.3.4 EEG differential diagnosis*

of S-B.

**2.4 Etiology**

cause is unknown.

and GABRA1 gene mutations [14].

metabolic workup [16].

*Clinical*

*EEG*

states

*Etiology*

and PNKP

*related homeobox*

and rarely tonic spasms

the duration of the burst and the type of seizure [11]. Focal seizures and subclinical

A discontinuous EEG pattern with resemblances to S-B can be seen in neonatal hypoxic ischemic encephalopathy, but in this condition, the pattern is generally transient and can be reactive. Treatment for neonatal status epilepticus, such as midazolam, sufentanil, and fentanyl infusion, may exhibit a pattern evocative

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

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,

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

Several of the genes may manifest as phenotypes that overlap not only with OS

*Clinical*

*EEG*

is never erratic

during sleep

*Etiology*

Characterized by tonic spasms, focal seizures, and rarely massive myoclonus; this

The S-B pattern is limited or more distinct

Cryptogenic, familial, and metabolic. Genes

found: ErbB4 and SEC25A22

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

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

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

and EME but also with other EEs such as West syndrome [14].

**EME OS**

Early myoclonus progressively becoming erratic, fragmented, and massive, followed by focal seizures

The S-B pattern is continuous in both awake and sleep

Structural brain abnormalities, a few metabolic, non-familial. Genes found: ARX, STXBP1, KCNQ2,

phenomena are associated with focal discharges of spikes or sharp wave [8].

**80**

**Box 1.**

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 in the myoclonic phase of EME.

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 its treatment.
