*5.3.1 Background*

*Epilepsy - Advances in Diagnosis and Therapy*

appropriate therapeutic intervention.

recommended [54].

**5.1 Overview**

sporadic EIMFS [64–66].

**5.2 Seizures: symptoms and semiology**

even with the long duration of seizures.

increase in frequency within the first 2 years of life.

warm baths or exercising on warm days, and avoiding photosensitivity triggers are

ine, and phenytoin should also be avoided because they can aggravate seizures.

**5. Epilepsy of infancy with migrating focal seizures (EIMFS)**

with athetotic movements may appear; about 18% of the patients died [65].

Sodium channel-blocking drugs such as carbamazepine, oxcarbazepine, lamotrig-

Valproic acid, clobazam, topiramate, levetiracetam, and stiripentol are the drugs of choice. Stiripentol combined with valproic acid and clobazam, as well as topiramate, give promising results [54, 57, 58]. The ketogenic diet is an alternative with good results for several patients, achieving a reduction of the seizures by 50% or more [59, 60]. The prognosis for children with DS is poor; the complete cessation of epileptic seizures is not achievable in these patients. Since the onset of disease, the neurological status worsens, and about 10–20% of afflicted children will die prematurely [61, 62]. Early mortality, sometimes due SUDEP, occurs in about 10% of patients. However, the outcome, in at least some children, improves with early diagnosis and

EIMFS, previously called malignant migrating partial seizures of infancy, is a rare and severe condition describe in 1995 [63]. EIMFS is characterized by focal "migrating" or "random" seizures beginning within the first 6 months of life, severe global developmental delay, and acquired microcephaly. Epilepsy is highly pharmacoresistant. At onset brain MRI is typically normal, but later it may show delayed myelination, thin corpus callosum, and cerebral atrophy [64]. Patients with intractable seizures have a progressive deterioration with major axial and limb hypotonia, loss of visual contact, and loss of other motor and social skills. Pyramidal and/or extrapyramidal features

De novo KCNT1 mutations have been reported in about 50% of patients with

It is accepted that the natural history of the EIMFS goes through three distinct phases [63]. The first phase starts in the first 6 months of life and lasts a few weeks or months; patients have sporadic seizures with frequency every few weeks or months. Seizures used to be focal motor with quick generalization or associated with autonomic features like apnea, flushing, or cyanosis [63, 67]. The second phase, called "stormy phase," arises between 1 and 12 months; seizures become more frequent, occurring in clusters several times a day or being practically continuous for several days. Seizure consists of lateral deviation of the head and eyes, twitches of the eyelids, unilateral clonic or tonic jerks of one or both limbs, apnea, flushing and/or cyanosis of the face, chewing movements, and secondary tonicclonic seizures [68]. Additionally, clinical manifestations may be "subtle" or absent

The age at onset of the third phase is variable, from the end of the first year to the fifth year of age. This phase is typically seizure-free, even if interposing illnesses can trigger recurrent seizures or SS. Some patients can evolve to a WS [63, 65].

Migrating focal seizures (MFS) are seizures which occur usually in clusters that last for a few days and are then followed by a few weeks or months of recovery. Within a cluster, seizures are very frequent and may even extend to SS. Clusters

**88**

EEG is usually normal during the first months apart from slowing for many hours after long-lasting seizures. As the disease progresses, background activities become gradually diffusely slower with decline of physiological features. Activity may show alternating asymmetries, with slow activity that change from one hemisphere to another [63]. In seizure-free periods, sleep and wakefulness are obviously differentiated; nevertheless sleep spindles are rare, asynchronous, and asymmetric.
