The Fibroblast Growth Factor 2 (FGF2) Improves VEPs in Autistic Children.
Recent Advances in Human Neurophysiology.
March 1998. Okazaki, Japan.
AGUILAR L. C., CRUZ S., MARTIN R., ROSIQUE P., ALFARO F., ISLAS A., AND CANTU J.M.
Instituto de Investigaciones en Neuroplasticidad y Desarrollo Celular . Departamento de Biologia Celular y Molecular de la Universidad de Guadalajara. CIBO, IMSS. Guadalajara, Jalisco, MEXICO A.P. 3920.
INTRODUCTION
FGF2 is a protein that has shown neurotrophic effect in many areas of the embryonic (Eckenstein et.al., 1990. Weise et. al., 1993), foetal (Walicke et. al., 1986. Morrison et. al., 1986. . Deloulme, et. al., 1991) and adult brain( Matsuda et al. 1990). Its in vitro effects include survival, neurite extension (Peulve P. Et. al., 1994), increase in choline acetyltransferase (CAT) activity, dopamine levels (Aguilar et. al. 1994a).
In several animal models of brain damage as trauma (Mocchetti et. al. 1995, Anderson et. al., 1988), hypoxia/ischemia (Aguilar et. al., 1994ª, Nakata et. al., 1993), kainic acid (Rudge et. al., 1995), and pathway sections (Koshinaga et. al., 1993), etc.) have shown that the FGF2 is capable of diminishing the degree of lesion. Studies in which FGF2 was administered after damage (Anderson et. al., 1988), showed a significant improvement in morphological, neurochemical (Otto, D. and Unsicker, K. 1990.) and neurophysiological (Aguilar et. al. 1994a) parameters. Previous clinical studies in intellectual disabilities showed a significant improvement in mental retardation (Aguilar et. al., 1993) and language disabilities (Aguilar et. al.,1994b).
Symmetry analysis of Flash VEPs, in previous studies carried out by our group, demonstrates to be a reliable and objective procedure for quantifying abnormalities in autistic children, when using Pearson Coefficient (PC) to analyse interhemispheric linear correlation and Energy Ratio (ER) to compare the voltage generated in a specific segment of time(area below the curve) in both hemispheres.
METHODS
With the purpose of improving the impairment of autistic children, FGF2 was used, applied subcutaneously at dosage of 0.2 mg/kg, every two weeks during 12 months. The autistic group (n=29, both sexes between 3 and 8 years of age), was studied using flash VEPs, with 16 electrodes placed according to 10-20 international system. VEPs were analysed in 2 segments, 50-200 and 200-400 ms through PC and ER, PC was expressed as a value between 1 and –1, the values lower than 0.7, were considered as significant deviations (p<0.025) when compared to control healthy group (CHG) and ER was expressed as a ratio in which the higher value of one area ( any side) was normalised to 1 and the contra lateral as a ratio, the values lower 0.4 were significant deviated (p<0.025) of a CHG indicating asymmetry. The areas that in the initial study showed significant deviations (P<0.025) respect to normal group were totalled and compared before vs. after 12 month of treatment, trough t-test.
RESULTS
The symmetry of area below the curve or ER in P3-P4 and O1-O2 showed significant increase (p<0.004) in segment 50-200 ms (Fig. 1) and in 200-400 ms segment, P3-P4 and T5-T6 (P<0.004) increase after 12 months of treatment (Fig. 1). P3-P4 and T5-T6 showed in the initial study the grater number of asymmetries in PC mainly in 200-400 ms segment and after FGF2 treatment a significant reduction (p<0.01) was observed in all areas in both segments (Fig. 2).
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Fig. 1. Energy Radio (ER) before and after FGF2 Therapy in Autistic Children. Observe the significant increase
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Fig. 2. Deviations in Pearson Coefficient (PC) before and after 12 months of FGF2 Therapy in Autistic Children. Observe the significant reduction (P<0.01) |
DISCUSSION AND CONCLUSIONS
The parietals (P3-P4) improved significantly in ER and less in PC (p<0.08), this probably due to the fact, that first the number of responding neurones increase and then the functional organisation, in general the improvement was higher in ER that in PC. T5-T6 increase significantly in 200-400 ms in both symmetry analysis (ER and PC) indicating improvement in the late components of this regions, probably related to the fact that the best response in neuropsychological evaluation was in language, function highly related with temporal regions (Head, H. 1926).
TWe conclude that FGF2 improves flash VEPs mainly in parietal, temporal and occipital regions of autistic children after 12 months of treatment (Fig 3 a, 3 b, 4 a and 4 b), this correlated with improving in language, visual motor maturation and social behaviour, areas that showed the best evolution in the neuropsychological evaluation. The most noticeable improvement was the recovery of the area below the curve in many patients in which the initial study showed absence or very low response in parietal, temporal and occipital regions mainly in the right side (Fig. 3 a and 3 b).
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Fig. 3 a. Notice the absence of response in O2 and reduction of voltage in T6 and P4, respect to contra lateral regions in autistic child ( male, 4 years old). |
Fig. 3 b. Notice the recovery in voltage and area below the curve in O2, T6 and P4, also observe that the Pearson coefficient increase in the same autistic patient after 12 months of FGF2 therapy. |
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Fig. 4 a. Observe the low Pearson coefficient and the asymmetries in area below the curve in P3-P4, O1-O2 and T5-T6.
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Fig. 4 b. Notice the increase in Pearson coefficient and reduction of asymmetries in voltage (energy ratio) in P3-P4, O1-O2 and T5-T6 after 12 months of FGF2 treatment. |
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