The primary semiology consists of frequent tonic spasms in isolation or clusters (other seizure types can occur, as well). The onset is in first 3 months of life. Neonates can have hundreds of seizures per day. Structural brain lesions are the most common etiology but the following genes also have been associated with EIEE: STXBP1, CDKL5, ARX, KCNQ2. There is a high mortality rate in infancy. Prognosis is characterized by profound neurodevelopmental deficits in survivors. Seizures are typically resistant to treatment but controlled by school age in half of children. Many neonates later progress to West syndrome (see below).

The onset of EME is very early, typically in first month of life (some cases are familial). The seizure semiology typically is myoclonus in the limbs and face. Focal seizures and tonic spasms are common. In terms of etiology, concurrent metabolic disorders are common (the classic one is glycine encephalopathy but others have been noted, as well—a B6 trial is reasonable but it typically is unsuccessful). The EEG (while awake) shows multifocal spikes on slow background ± periodic activity. Unlike EIEE, suppression-burst is observed primarily during sleep. Conventional treatments are typically used with very limited success. Corticosteroids have only a minimal effect on seizures. Myoclonus usually resolves by weeks to months but focal seizures persist. Mortality is high in the early ages. The prognosis is poor for resolution of seizures and neurodevelopment.

In this syndrome, development is initially normal, and then seizure starts between 1 week and 7 mos (mean = 3 mos). Initially, there are sporadic focal motor seizures but eventually they become prolonged or occur in clusters and may secondarily generalize. The interictal EEG initially shows multifocal slowing, which progresses and later includes a disruption of sleep architecture. The ictal EEG shows multifocal origins of seizures with migration to different regions (morphologically, including rhythmical delta or sharp waves/spikes). There are associated extrapyramidal signs and tone worsens over time. There is early intractability but seizure control may improve with age in survivors. Early deaths may be associated with respiratory difficulties.

Neurodevelopmental prognosis in survivors generally is poor. The list of genetic mutations associated with this syndrome is expanding rapidly.

Clinically, this epilepsy syndrome is characterized by flexor or extensor spasms in clusters. The peak onset is 5 mos (typically 4–8 mos). The eponym West syndrome is defined by the triad of spasms, the EEG appearance of hypsarrhythmia, and developmental delay. The etiologies may be symptomatic (i.e., with an identifiable underlying cause, representing 75–85% of patients) or asymptomatic. Underlying conditions may be genetic (ARX, STXBP1), metabolic, congenital infection, neonatal infection, among many others. Intellectual disability is seen in 75–90% of patients. The differential diagnosis includes benign myoclonus, benign myoclonic epilepsy, and gastroesophageal reflux (EEG easily distinguishes these from one another). Treatment includes steroids (ACTH, prednisolone), vigabatrin, the ketogenic diet, zonisamide, and vitamin B6, noted in different published case series. Animal models are generated by inducing early injury and genetic manipulations.

With an onset of 4 mos–3 yo, this syndrome is eventually outgrown in most patients. Clinically, there are axial or upper extremity myoclonic jerks with head drops; trunk flexion or extension has been noted, and the lower extremities are only involved rarely. The EEG shows generalized spike/polyspikes lasting 1–3 s. This syndrome is associated rarely with antecedent febrile seizures. Reflex myoclonic seizures are a subgroup (induced by auditory, tactile stimuli); some patients are photosensitive. The differential diagnosis includes infantile spasms and benign myoclonus. The EEG and normal development differentiate MEI from infantile spasms (hypsarrhythmia) and benign myoclonus (normal EEG). Neurodevelopment generally is normal but patients may develop other seizures later in life. Treatment typically is with VPA, LEV, or CZP.

The terminology used for this family of disorders is in development as of this writing but both familial and non-familial forms have been noted. The onset is between 3 and 20 mos in a developmentally normal infant. The non-familial form onset can be in the 2nd year of life, with equal sex predominance. In the familial form, onset typically is 4–7 mos, with a female predominance. Seizures are characterized by focal onset (head, face, limbs) clonic seizures, may secondarily generalize, and can occur in clusters with varying lateralization. Medicines usually are prescribed but seizures generally are easy to treat. Structural and metabolic workup is negative. The EEG shows a focal ictal onset (posterior or temporal); interictal EEG typically is normal. In the familial form, mutations in PRRT2 (same gene as paroxysmal kinesigenic dyskinesia), ASC–1 (amino acid transporter), and SCN2A have been noted (there likely are others). The prognosis is good for both seizures and development.