The FGF2 Improves VEPs in Dyslexic Children (DCh).
Recent Advances in Human Neurophysiology.
March 1998. Okazaki, Japan.
L. C. AGUILAR, P. ROSIQUE, F. ALFARO, R. MARTIN, S. CRUZ, A. ISLAS, AND J. M. CANTU.
IINEDEC, a.p. 3920, Guadalajara, Jal, Mexico. IFC. CUCBA. U.de G. Div. de Genetica, CIBO.IMSS.
INTRODUCTION
The FGF 2, is a neurotrophic factor, with effect on CNS neurons (cortex, hippocampus (HP), striatum (ST), thalamus, etc.( Eckenstein et. al., 1990, Weise et. al., 1993, Walike et. al., 1986, Deloulme, et. al., 1991) showing in vitro increase of survival and neurite outgrowth (Walicke, 1988); in vivo increases CAT activity in HP and ST and dopamine levels in ST (Aguilar et.al., 1994a). FGF 2 reverses morphological deficits in dopaminergic neurons after MPTP (Otto and Unsicker, et.al. 1990), and ameliorates learning deficits in basal-forebrain lesioned mice (Ishihara, et.al., 1992). In mentally retarded patients FGF 2 improves mental development (Aguilar et al., 1993). Also improves language disabilities and visomotor deficits in children with these pathologies (Aguilar, et.al. 1994b).
We report here, the effect of FGF 2 therapy in children with dyslexia in whom phonological, semantic and visual-spatial deficits were observed. 41 patients of both sexes, in ages between 8 and 12 years of age, separated in two groups were examined. Topographic flash VEPs were recorded from a treated group (TG) n=26 and from untreated group (n= 15), both sexes, between 8 and 12 years. The stimulation was performed using a white stroboscopic xenon flash (Grass PS22). All stimuli were presented binocularly with a variable repetition rate during awake state, 16 electrodes were placed according to 10-20 international system, amplifier bandpass was 1-35 Hz, 200 epochs were averaged and obtained twice. Symmetry analysis of each area was performed using Pearson coefficient (PC) to know the linear correlation and energy ratio (ER) to know the symmetry in energy (comparison of the area below the curve of one region respect to contra lateral), for 50-200 and 200-400 milliseconds (ms) segments, the result of each area in a specific segment of time of every dyslexic child was compared with a control group (n=25, age matched) using Z transform (p<0.025) in order to know the significant deviations.
FGF2 was administered at dosage of 0.2 mg/kg of body weight every 2 weeks during 12 months to TG, the UG received only neurophsycological therapy.
RESULTS
The VEPs showed in the initial study that the PC was significantly (p<0.025) reduced in 58 % of dyslexic respect to normal controls in at least one segment and the 48 % in the 200-400 ms segment. In ER 48% of patients showed asymmetries at least in one segment, a great reduction of voltage and area of N100 component on left occipital and temporal regions was observed in 28 % of dyslexic children (Fig. 1 a and 2 a ), causing the mentioned asymmetries in ER and PC, in occipital regions only the 26 % showed asymmetries.
After 12 months of treatment with FGF2, a significant (p<0.01) improvement in PC was observed in T5-T6 (Fig. 3) in 200-400 ms segment, the ER improved significantly (p<0.01) in both segments of T5-T6 (Fig. 3 ),. The UG did not show significant changes.
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Fig. 1 a.- Case one, before treatment. Observe the reduction in voltage and area below the curve in O1 and T5 respect to contralaterals, in dyslexic child (male, 7 years old).
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Fig. 2 a.- Case two, before treatment. Observe the reduction of area below the curve in O1 and T5 respect to contralaterals in dyslexic child (male 9 years old). |
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Fig. 3.- Notice the significant increase in Pearson coefficient (p<0.01) in 200-400 ms. and energy ratio in 50-200 and 200-400 ms segments (p<0.01) of T5-T6 after 12 months of FGF2 therapy |
DISCUSSION AND CONCLUSIONS
The improvement in ER was associated with the increase of voltage (area below the curve) on the regions in which previously was reduced ( Fig. 1 b and 2 b), this occurs more frequently on left occipital and temporal regions. This correlates with neurophsycological studies in which several authors demonstrate anatomical deficits on these regions of dyslexic children (Greenblat, 1973, Ajax et al.1977, Staller et al. 1978).. The above mentioned suggests an increase on the number of the responding neurons of these regions, probably due to new pathways formation between geniculate lateral nucleus and area IV of occipital cortex as well as between occipital and temporal cortex, there was also an increase in the activity of neurons of the mentioned areas.
The VEPs improvement in PC suggest a better synchrony and organisation.
We conclude that the flash VEPs are useful for detecting the neurophysiological abnormalities in dyslexic patients and for monitoring the effects of treatments like the one with FGF2, in which a significant improvement of dyslexic children was observed in neuropsychological and neurophysiological parameters.
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Fig. 1 b.- Case one, after 12 months treatment. Notice the recovery in area below the curve, Pearson coefficient and energy ratio in O1 and T5. |
Fig. 2 b.- Case two, after treatment. Observe the improvement in energy ratio of T5-T6 and O1-O2 in 50-200 ms. segment. |
REFERENCES
Aguilar_LC; Islas_A; Rosique_P; Hernandez_B; Portillo_E; Herrera_JM; Cortes_R; Cruz_S; Alfaro_F; Martin_R; et_al Psychometric analysis in children with mental retardation due to perinatal hypoxia treated with fibroblast growth factor (FGF) and showing improvement in mental development. J Intellect Disabil Res, 1993 Dec, 37 ( Pt 6):, 507-20
Aguilar, L.C., Islas, A., Morales, A., Alfaro, F., Cruz, S., Martin, R., and Cantu, J.M. 1994a. Estudios preclinicos de la administración del Factor de Crecimiento Fibroblástico en daño cerebral. Capitulo VI. 83-94. En Avances en la Restauración del Sistema Nervioso. Aguilar-Rebolledo, F. Ed. Vicova Editores.
Aguilar, L.C., Rosique, P., Cruz, S., Martin, M., Alfaro, F., Islas, A., and Cantu, J.M. 1994b. Administración del factor Fibroblástico de Crecimiento en disfunciones neurológicas consecutivas a hipóxia-isquemia perinatal. Capitulo VII. 95-106. En Avances en la Restauración del Sistema Nervioso. Aguilar-Rebolledo, F. Ed. Vicova Editores.
Ajax, E.T., Schenkenberg, T., & Kasteljanetz, M. (1997). Alexia without agraphia. Archives of Neurology (Chicago), 17, 645-652.
Deloulme_JC; Baudier_J; Sensenbrenner_M Establishment of pure neuronal cultures from fetal rat spinal cord and proliferation of the neuronal precursor cells in the presence of fibroblast growth factor. J Neurosci Res, 1991 Aug, 29:4, 499-509.
Eckenstein_FP; Esch_F; Holbert_T; Blacher_RW; Nishi_R Purification and characterisation of a trophic factor for embryonic peripheral neurons: comparison with fibroblast growth factors.
Neuron, 1990 Apr, 4:4, 623-31 .
Greenblatt, S.H. (1973). Alexia without agraphia or hemianopia; anatomical analysis of autopsied case, Brain, 96, 307-316.
Ishihara, A., Saito, H., and Nishiyama, N. 1992. Basic Fibroblast Growth Factor ameliorates learning deficits in basal forebrain lesioned mice. Jpn. J. Pharmacol. 59: 7-13.
Otto, D. and Unsicker, K. 1990. Basic FGF reverses chemical and morphological deficits in the nigrostriatal system of MPTP-treated mice. J. Neurosci. 10:1912-1921.
Staller, J., Buchanan, D., Singer, M., Lappin, J., & webb, W. (1978), Alexia without agraphia: An experimental case study, Brain and Language, 5, 378-387.
Walicke, P., Cowan, W.M., Ueno, N., Baird, A. and Guillemin R. 1986. Fibroblast growth factor promotes survival of dissociated hippocampal neurons and enhances neurite extension. Proc. Natl. Acad. Sci. USA. 83:3012-3016.
Walicke, P.A. 1988. Basic and acidic fibroblast growth factors have trophic effects on neurons from multiple CNS regions. J. Neurosci. 8:2618-2627.
Weise_B; Janet_T; Grothe_C Localization of bFGF and FGF-receptor in the developing nervous system of the embryonic and newborn rat. J Neurosci Res, 1993 Mar 1, 34:4, 442-53
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