Seizures are believed to originate in the thalamus, where there is an abundance of T-type calcium channels such as those encoded by the CACNA1H gene (12). In a European study CACNA1H associated with CAE, 20 mutations have been identified. These mutations are likely not wholly causative and should instead be thought of as giving susceptibility. This is particularly true since some groups have found no connection between CAE and CACNA1H mutations. Many of the CACNA1H mutations have a measurable effect on channel kinetics on activation time constant and voltage dependence, on deactivation time constant, and on inactivation time constant and voltage dependence. should leading either to neuronal excitability or hypo excitability. However, these predictions result from mathematical modeling and may differ from what occurs in neurons (in vivo) where other proteins, some of which may interact with CACNA1H, are present. Along with mutations in the CACNA1H gene, two mutations in gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2), the gene encoding a GABAA receptor gamma subunit, are also associated with a CAE-like phenotype that also overlaps with generalized epilepsy with febrile seizures plus type-3. The first of these, R43Q, abolishes benzodiazepine potentiation of gamma-aminobutyric acid induced currents. The second associated mutation, C588T, has not been further characterized. Diagnosis
CAE can be diagnosed during an outpatient clinic visit with a careful history, physical exam including hyperventilation, and a routine electroencephalogram.
They involve abrupt impairment of consciousness with loss of awareness and responsiveness, behavioral arrest, and arrest of the activity that may vary from complete arrest to continuing the activity with an altered status. Other seizure features include starring, eyelid movement or eye-opening and pallor. Mild automatisms and mild movements at the beginning of the seizures are frequent, but major motor involvement, as atonic falls, early in the course of the disease excludes this diagnosis.The International League Against Epilepsy commission defined absence seizure as “of sudden onset, interruption of ongoing activities, staring, possible upwards version of eyes with few seconds duration, associated with symmetrical 2–4 Hz, mainly 3 Hz spike-wave complexes, normal background activity. Absence seizure was divided into two subgroups (Penry et al. 1975), first with consciousness impairment, and others were associated with the other clinical component, namely clonic, atonic, tonic, autonomic, and with automatisms. Though CAE usually occurs in children with normal neurodevelopment and are sensitive to antiepileptic treatments children with CAE have a risk of academic failure and high rates of attention deficits. Neuropsychological impairment
Neuropsychological impairment in children with CAE is frequent and includes executive dysfunction, attention problems, learning disabilities, and language problems. These problems even persist after seizures are treated. Monitoring with validated cognition scales should be performed. Many existing data illustrate that children with CAE have an average IQ but present subtle cognitive difficulties. In cases with lower IQ, significant social difficulties can be often seen.