Figure 9. The effect of VPA correlates with the pre-treatment frequency of spreading seizures.

A–D) Correlations of the effect of VPA on the frequency of G1 seizures during week 5 or 6 vs week 4 with the pre-treatment frequency of G1 and G2 seizures. The pre-treatment frequency of non-spreading G1 seizures is not correlated with the effect of VPA at week 5 (A) and after cessation of VPA treatment at week 6 (B). The crossed circle indicates the one animal critical for the lack of correlation. C) The pre-treatment frequency of G2 events is significantly correlated with the effect of VPA at wk 5. D) The pre-treatment frequency of G2 events is significantly correlated with the effect of VPA at week 6. Straight lines in B and D represent linear least-square fits to the experimental points. E–F) Lack of correlation of the effect of VPA on the frequency of all seizure types during week 5 or 6 vs week 4 with plasma levels. Plasma [VPA] at week 5 is not significantly correlated with the effect of VPA assessed either during (E) or after cessation (F) of VPA administration. G) Proportions of G1 (non-spreading), and G2 and G3 (spreading) seizures assessed prior to treatment in rats that became seizure-free with VPA treatment (responders) and in those that did not (non-responders). The non-responders exhibited a larger proportion of spreading seizures than the responders. H) VPA does not affect the frequency of G1 events in non-responders (hollow circles), but abolishes G1 seizures in responders (filled squares). Data are displayed for each 24h observation period (3 recordings per week). The value −1.45 represents the logarithm of the floor seizure-frequency value assigned to observations of no seizures in each 24h recordings. Note that the responders exhibit a slow, steady decline in seizure frequency during VPA administration, and no seizures in the last recording during treatment and in the week after treatment.