Pensadores que sustentan el marco teórico

The hippocampal ADC^^ was elevated (>mean + 2SD of control subjects) in eight patients (bilaterally in five and unilaterally in three)(fig.3.8). Hippocampal

Figure 3.8 - Coronal maps of the ADC,y of the mesiotemporal region. A: patient with temporal lobe epilepsy, B: normal control. The signal is higher in the right hippocampus than in the left hippocampus in the patient, measurements revealed an elevated ADC,^ on the right.

T2-relaxation time and hippocampal ADC^^ and were positively correlated (r=0.76, p<0.001) (fig. 3.9). Hippocampal volume and hippocampal ADC^^ were negatively correlated (r=-0.61, p<0.001) (fig. 3.10). There was also a weak

correlation between hippocampal T2-relaxation time and hippocampal AI (r=-0.39, p=0.01) and hippocanpal volume and hippocampal AI (r=0.37, p=0.02). Group comparisons ADC and AI in HS, HS negative hippocampi and controls. Fourteen hippocampi of 11 patients fiilfiUed the MR criteria for HS (8 had unilateral, three had bilateral HS). Fourteen hippocampi of patients did not fiilfiU MR criteria for HS ("HS negative"). In 12 hippocampi the T2-relaxation time and volume were both within normal limits, in two the T2-relaxation time was prolonged but the volume normal. All values of T2-relaxation time and volumes of control hippocampi were within the normal range.

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Figure 4.9 - Correlation of hippocampal T2-relaxation time and ADC^. The triangles represent hippocampi of control subjects, the squares represent hippocampi of patients.

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G 1000 2000 3000 4000

HV [mm3]

Figure 3.10 -Correlation of hippocampal volume and ADC^ The triangles represent hippocampi of control subjects, the squares represent hippocampi of patients.

The ADCav was significantly increased in the HS group compared to the HS negative and the control group (p=0.0004, posthoc comparison with least mean square (LSD) and Bonferoni test). The mean ADC^v in the HS group was 1.13 x 10‘^mmVs (SD 0.17 x lO’^mmVs), in the HS negative group was 0.94 x lO'^mmVs (SD 0.13 X lO'^mmVs), and in the control group was 0.91 x lO’^mmVs (SD 0.03

X 10‘^mmVs) (p=0.0004). (fig. 3.10).

The AI was significantly reduced in the HS group compared to the HS negative and the control group (p=0.04, posthoc comparison LSD). The mean AI in HS was 0.05 (SD 0.02), in HS negative hippocampi was 0.09 (SD 0.06), and in hippocampi of control subjects 0.09 (SD 0.04) (p=0.04) (fig. 3.12).

3.3.3.2.2 Outliers

In the HS negative group two hippocanpi had outlying ADC^v values indicated as points in fig 4.11 Both had a normal hippocampal volume but a prolonged T2

relaxation time (patient 12 and patient 8). The AI in these patients was 0.06 and 0.16 respectively.

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no HS

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Figure 4.11 - Boxplot showing ADC^ in sclerotic hippocampi (HS), HS negative hippocampi of patients (no HS) and control hippocampi. Boxes contain the 50% of values falling between the 25th and 75th percentiles, and the ^whiskers^ lines that extend from the box to the highest and lowest values, outliers are indicated by dots. The line across the box is the median.

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HS

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Figure 3.12 - Boxplot showing AI in sclerotic hippocampi (HS), HS negative hippocampi of patients (no HS) and control hippocampi. (For explanation see fig. 4.11)

3.3.4 Discussion

Our measurements showed that water difftisicn is frequently abnormal in hippocampi of patients with epilepsy. We found a positive correlation of hippocampal T2-relaxation time and ADC^v and a negative correlation of hippocampal volume and ADC • This is in keeping with the observed trend of Zhong et al.^®’ We also found a negative correlation of T2-relaxation time and AI and a positive correlation of hippocampal volume and AI. However, correlations for AI were weak and the coefiScient of variation in control subjects of AI measurements was higher than the coefiBcient of variation of ADC^y measurements. AI measurements may be less robust than ADC^y measurements because they propagate noise differently. Both ADC^v and AI are not rotationally invariant."*® Variation occurs if brains are not scanned in the same position, a condition which is in practice unlikely to be satisfied because of the interindividual

anatomical differences and variations of head position in the scanner. The measurements used here are therefore a relatively crude estimates. Other methods to quantify anisotropy which provide rotationally invariant measures. Despite the limitations, we found significant differences between normal and abnormal hippocampi for both ADC^y and AI. In hippocampi with reduced volume and prolonged T2-relaxation time difiusivity was significantly increased and anisotropy significantly reduced. The combination of reduced volume and prolonged T2-relaxation time in the context of epilepsy is predictive of 104,105,106 Therefore it seems to be reasonable to assunfe that difiusivity is increased and anisotropy reduced in HS.

Our findings imply that the tissue texture in the sclerotic hippocampus must be conç)romised in a way that allows increased water mobility rather than restriction. Measurements using in vitro models have shown that both the expansion of the extracellular space and the increased permeability of membranes can cause an elevation of the ADC (see tab. 3.1). However, changes in membrane permeability only occur in severe and acute disturbance of cellular function, and the major factor for the increased difiusion in a chronic lesion like HS seems to be an expansion of the extracellular space. We interpret our findings as showing that the cells are not as densely packed and not as asymmetrically organized as in normal hippocanpL This information could not be derived fi*om T2-measurements which are relatively nonspecific.^®^ Our findings are likely to reflect neuronal loss and reduction of dendritic branching, microstructural changes believed to be the associated with epüeptogenesis. For practical reasons the visual inspection of standard MR images including fast FLAIR will probably remain the method of choice to detect HS in a clinical setup.*®* However, quantitative measurements of diffusion may help to clarify cases where visual inspection, measurements of volumes and measurements of T2-relaxation time are not concordant. Interestingly in our study the ADC^y was elevated in two hippocampi with normal volume but prolonged T2-relaxation time which may suggest damage on the microstructural level in these hippocampi. Further studies correlating pathological (and clinical) parameters with T2-relaxation time and ADQy are necessary to determine if

ADCav or T2-measurements are more sensitive.

3.3.5 Conclusion

In summary we showed that hippocampal difiiision is frequently abnormal in patients with epilepsy. Our findings are compatible with an expansion of the extracellular space in HS.

3.4 Diffusion-weighted MRl Demonstrates Abnormal Pyramidal Tract in