West syndrome (Infantile Spasms)

West syndrome (aka infantile spasms) is one of the most severe epileptic syndromes of infancy and early childhood. The seizures themselves only last a few seconds and consist of brief jerking movements. The EEG abnormalities are unique – the ictal event (seizure) is dominated by an electrodecremental response (flattening of the EEG). In the interictal event (period between seizures), the brain generates an abnormal EEG pattern called hypsarrhythmia, which is unique to this syndrome. Spasms in some children are responsive to vigabatrin or adrenocorticotrophin (ACTH) hormone but usually not to other anticonvulsants. 

Researchers in the laboratories of Drs. Peter Kellaway, Richard Hrachovy, James Frost, Daniel Glaze, and John Swann at the Baylor College of Medicine and the Gordon and Mary Cain Pediatric Neurology Research Foundation Laboratories at Texas Children’s Hospital have been studying West syndrome for almost 40 years. Here are some of the important findings from their studies that have significantly advanced our understanding of this epileptic syndrome -

• A breakthrough study published in 1979 in Annals of Neurology by Dr. Kellaway and his team characterized spams in infants and described the abnormal EEG pattern of West syndrome for the first time. Read more
   
• In 1983, the same team performed a double-blind, placebo-controlled trial of twenty-four patients with infantile spasms to test and compare the effectiveness of ACTH with another hormone, prednisolone. They found similar reduction in seizure frequency using both hormones in most of the patients, which is one of the studies that led to the current use of ACTH in these patients. Read more
   
• Chronic infusion of a sodium channel blocker, tetrodotoxin (TTX) into the developing neocortex of hippocampus of infant rats recapitulated the pathophysiology of this syndrome. This led to the creation of a new animal model of unprovoked infantile spasms (West syndrome) which has proved to be a very valuable tool in studying this disorder. Read more
   
• High-frequency electroencephalographic (EEG) oscillations (HFOs) accompany seizures in West syndrome patients and is a hallmark of this epileptic syndrome. Earlier, it was thought that HF oscillations and seizures may originate from the same site in the brain. However, in the animal model of infantile spasms where the seizures are induced by the infusion of tetrodotoxin (TTX), HF oscillations did not always originate from the infusion site, instead they were present most intensely in the contralateral brain regions, indicating these may be the sites of seizure generation. Read more
   
• The neural networks in the rat models of West syndrome are abnormally excitable. High-frequency EEG oscillations (HFOs) occurred most frequently during sleep and hypsarrthymia. These HFOs were most prominently present contralateral to the TTX infusion site, which implicated those brain regions in the generation of epileptic spasms. Read more
   
• Vigabatrin, an antiepileptic drug inhibits the breakdown of aminobutyric acid (GABA), the chief inhibitory neurotransmitter in the mammalian nervous system and is used to suppress spasms in children. Cain lab investigators found it has similar effects on the mouse models of West syndrome. It was also found that vigabatrin selectively suppressed abormal HFOs, implicating them as the causative mechanism in the infantile spasms and also, pinpointing them as a potential therapeutic target for West syndrome. Read more