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  • Title: A plausible explanation for superiority of adreno-cortico-trophic hormone (ACTH) over oral corticosteroids in management of infantile spasms (West syndrome).
    Author: Jaseja H.
    Journal: Med Hypotheses; 2006; 67(4):721-4. PubMed ID: 16781824.
    Abstract:
    West syndrome (WS), an age dependent epileptic encephalopathy is identified as a triad of infantile spasms (IS), psychomotor retardation and a specific EEG pattern known as hypsarrhythmia. The exact pathophysiology still remains unclear, although a majority of cases reveal history of exposure to stress, mainly hypoxic-ischemia. The management remains empirical with a poor prognosis. Adrenocorticotrophic hormone (ACTH) and oral steroids continue to remain gold standard treatment. Vigabatrin (VGB), a newer anti-epileptic drug has emerged as an effective alternative but recent observation of a serious visual defect (constriction of peripheral field of vision that is likely to exaggerate the disability status of the WS patient) associated with its administration is gradually limiting its therapeutic usage and popularity. A number of studies have shown superiority of ACTH over oral steroids in the management of West syndrome, but the explanation for this long-standing observation is missing; however, this clinical observation has led to a wide acceptance of the implication of corticotropin releasing hormone (CRH) in causing spasms and at the same time also explaining the relief in spasms obtained by the inhibition of CRH secretion by ACTH and oral steroids. This hypothesis-article compares the negative feedback influences of ACTH and oral steroids on CRH secretion and shows that ACTH exerts a dual significantly stronger inhibitory influence on CRH secretion that far exceeds the inhibition exerted by oral steroids. Thus, this difference in feedback mechanism may be the major factor responsible for the superior therapeutic efficacy of ACTH over oral steroids in the management of West syndrome.
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