Behavioral issues may also be present and their occurrence might be associated with significantly worse cognitive development. Some evidence suggest that  are impairment is more prominent in verbal rather than non-verbal capacities of children with CAE  or are even limited to few areas of verbal expression as phonological and category fluency. Attention deficit disorder and specific learning disorders are also frequently found in the CAE and can interfere with academic performance as well as with day to day activities of the children. Causes
CAE is considered as a complex polygenic disorder. This fact is supported by the high occurrence (up to 20%) of generalized epilepsies or febrile seizures in family members of children with CAE. In cases with early onset or accompanying features, Glut-1 deficiency (a metabolic disorder responding well to ketogenic diet) could be the cause of the absence seizures. Genetic mutations have been identified in recent years involving mainly GABA receptors and calcium channel modulator genes. Pathophysiology
Pathophysiology of absence seizures has been widely studied in animal models but is not fully decoded to date. There is however solid evidence for the involvement of bilateral cortical and subcortical networks which are part of the default state system. Pathophysiology when genetic mutations are present is further discussed below. Particularly in the Han Chinese population, there is an association between mutations in the calcium channel, voltage-dependent, T type, alpha 1H subunit (CACNA1H), and childhood absence epilepsy. These mutations cause increased channel activity and associated increased neuronal excitability.
People survive owing to low amounts of the SMN protein produced from the SMN2 gene. Nusinersen modulates alternative splicing of the SMN2 gene, functionally converting it into SMN1 gene, thus increasing the level of SMN protein in the CNS.The drug distributes to CNS and peripheral tissues.The half-life is estimated to be 135 to 177 days in cerebrospinal fluid (CSF) and 63 to 87 days in blood plasma. The drug is metabolized via exonuclease (3′- and 5′)-mediated hydrolysis and does not interact with CYP450 enzymes. The primary route of elimination is likely by urinary excretion for nusinersen and its metabolites. Chemistry
Nusinersen is an antisense oligonucleotide in which the 2-hydroxy groups of the ribofuranosyl rings are replaced with 2-O-2-methoxyethyl groups and the phosphate linkages are replaced with phosphorothioate linkages. History
Nusinersen was developed in a collaboration between Adrian Krainer at Cold Spring Harbor Laboratory and Ionis Pharmaceuticals (formerly called Isis Pharmaceuticals). Initial work of target discovery of nusinersen was done by Dr. Ravindra Singh and co-workers at the University of Massachusetts Medical School funded by Cure SMA.Starting in 2012, Ionis partnered with Biogen on development and, in 2015, Biogen acquired an exclusive license to the drug for a US$75 million license fee, milestone payments up to US$150 million, and tiered royalties thereafter; Biogen also paid the costs of development subsequent to taking the license.