Combination Treatment of High‐Dose Pyridoxal Phosphate and Low‐Dose ACTH in Children with West Syndrome and Related Disorders

Abstract

Combination therapy of high-dose pyridoxal phosphate (PAL-P, 40-50 mg/kg/day) and low-dose ACTH beta 1-24-Z (tetracosactide acetate-Zn, Cortrosyn Z, 0.01 mg/kg/day) was instituted in 26 children suffering from West syndrome and related disorders--pretreated without success with high-dose PAL-P alone; 18 with West syndrome (14 with symptomatic and 4 with cryptogenic types), 2 with symptomatic Lennox-Gastaut syndrome, 5 with cerebral palsy with hypsarhythmia or diffuse slow spike-waves and one with myoclonic seizures (secondary generalized epilepsy). Clinical, electroencephalographic and neurochemical investigations were carried out. The results were summarized as follows. 1) Only one of 27 children with West syndrome and related disorders pretreated using high-dose PAL-P alone before ACTH showed a clinically excellent response. 2) Clinical seizures were completely suppressed in 19 of 21 children who initially had seizures (90%) after this combination therapy. 3) Twenty-one of the total 26 children (80%) had disappearance of hypsarhythmia or diffuse slow spike-waves in EEG after this therapy. 4) During PAL-P treatment alone transient increases in liver enzymes occurred in 37 percent. The brain shrinkage of CT and the significant rise in CSF NSE were seen in 95% and 78% after ACTH, respectively. 5) Twenty-three children have been followed for one to 29 months after tapering off of ACTH. No relapses were experienced in 11 of 18 who initially had seizures (61%) and 13 of 23 with hypsarhythmia or diffuse slow spike-waves (57%). 6) Postictal PRL elevations were suppressed during high-dose PAL-P. 7) No significant changes in the CSF levels of HVA and 5-HIAA were seen during this combination therapy. The CSF levels of HVA were significantly lower than the controls. 8) Daily ACTH therapy transiently suppressed the secretion of anterior pituitary hormones (GH, TSH, PRL, LH and FSH) and thyroid hormones (T3 free T3, T4 and free T4). It is recommended that the combination therapy of high-dose PAL-P and low-dose ACTH is a promising new method and should be tried in children with West syndrome and related disorders. The mechanism of action of this combination therapy remains obscure although some information has been obtained from our investigations.