Las pruebas arqueológicas

T2 relaxometry and 'H MRS as described above provide information from different anatomical regions; T2 relaxometry specifically about the hippocampus and 'H MRS a wider area of the mesial temporal lobe. Fourteen children with nonlesional TLE

underwent T2 relaxometry as well as ’H MRS of the mesial temporal regions ; seven had bilaterally abnormal NAA/(Cho+Cr) ratios, four had unilaterally abnormal ratios and three were normal (see Table 5.7). O f the seven who had bilaterally abnormal values, three had unilaterally high T2 values, three bilateral abnormalities (with none o f these six showing discordant latéralisation) and one bilaterally normal T2 values. O f the four who had unilaterally low NAA/(Cho+Cr), three had unilaterally high T2 of the hippocampus and one bilaterally abnormal T2. O f the three with bilaterally normal 'H MRS, two had unilaterally abnormal T2 relaxometry of the hippocampus (110ms and 111ms) and one bilaterally normal T2 values. Therefore only in a very small number of children was

T îbïe 5.7: Comparison o f H MRS and T2 relaxometry in temporal lobe epilepsy H MRS Bilaterally normal Unilaterally abnormal Bilaterally abnormal Total Bilaterally normal 1 0 1 2 T2 relaxometry Unilaterally abnormal 2 3 3 8 Bilaterally abnormal 0 1 3 4 Total 3 4 7 14 5.7.2 Extratemporal epilepsy H M RS Bilaterally normal Unilaterally abnormal Bilaterally abnormal Total Bilaterally normal 4 0 0 4 T2 relaxometry Unilaterally abnormal 0 2 0 2 Bilaterally abnormal 1 1 0 2 Total 5 3 0 8

Table 5.8: Comparison of H MRS and T2 relaxometry in extratemporal epilepsy

Eight children with extratemporal epilepsy underwent both T2 relaxometry o f the hippocampi and *H MRS of the mesial temporal regions (Table 5.8). ’H MRS was

bilaterally normal in five children, and unilaterally abnormal in three. T2 relaxometry was normal in four and abnormal in four (two bilateral, two unilateral). Of the five with bilaterally normal MRS, four had bilaterally normal T2 of the hippocampi and one bilaterally abnormal values. O f the three with unilateral abnormalities of 'H MRS, two

had unilaterally abnormal T2 on the same side as the abnormal MRS, and one bilaterally abnormal T2, lateralising to the same side as the ^ H MRS abnormality.

5,8 Discussion

In the 20 children with temporal lobe epilepsy, abnormalities were seen in the absolute intensities of the NAA, Cho and Cr signals, as well as in the signal intensity ratio

NAA/(Cho+Cr). There was a 19% reduction in the NAA signal intensity ipsilateral to the seizure focus compared to normal data, with no significant reduction on the contralateral side. Animal and cell culture studies suggest that N-acetylaspartate is present

predominantly in neurons (Roller et a l, 1984; Urenjak et al., 1992). Therefore these results suggest neuronal loss or dysfunction, particularly on the ipsilateral side.

The NAA/(Cho+Cr) ratio was chosen as a simple index of spectral abnormality and of latéralisation. This ratio showed abnormalities in 15/20 (75%) children with temporal lobe epilepsy with correct latéralisation of the seizure focus in 55% of the children and incorrect latéralisation in none. This suggests that 'H MRS could provide additional information about mesial temporal abnormality to that obtained from visual inspection of images and T2 relaxometry. One child in this study had abnormal MRS ratios that were lateralising in the absence of any imaging abnormality. Furthermore, comparison of

MRS and T2 relaxometry in children who underwent both studies revealed only two children where the abnormality was localised to the hippocampus alone. The hippo­ campus occupies only a small proportion of the 8ml region of interest used in this study (see Fig 5.2), which includes a substantial proportion of neocortex and white matter.

the focal lesions demonstrated on MRI. The term ‘mesial temporal sclerosis’ was originally employed as it was recognised that changes were consistently seen in nonlesional TLE of mesial temporal structures outside the hippocampus, and this has been confirmed by this study. In addition, this suggests evidence of the so-called ‘dual pathology’ advocated to be common in children (Jay et a l, 1993).

Bilateral abnormalities were shown in 45% o f the children with TLE. This is a similar percentage to that found in adult studies (40%, (Connelly et a l, 1994); 42%, (Ng et a l,

1994)) and emphasises the early presence of such abnormalities. The rate was also higher than that found on T2 relaxometry (26%), suggesting changes to the temporal neocortex and white matter rather than to the hippocampus. As a group a significant increase was seen in both Cho and Cr bilaterally, whereas a decrease in NAA was only seen ipsilateral to the seizure focus. The concentrations of creatine + phosphocreatine and of choline- containing compounds are higher in astrocyte and oligodendrocyte cell preparations than in cerebellar granule neurons (Urenjak et a l, 1993). It is therefore possible that any increase in Cho and Cr may reflect reactive astrocytosis. The relationship o f contralateral pathology to postoperative outcome is not clear. However, a group of 34 adults who had undergone temporal resection demonstrated an incidence of abnormality on *H MRS on the unoperated side (50%) (Incisa della Rocchetta et a l, 1995) similar to that (40-45%) of bilateral pathology shown both here and in adult MRS studies performed

preoperatively (Connelly et a l, 1994; Ng et a l, 1994). In the post-operative study (Incisa della Rocchetta et a l, 1995) no relationship was seen between the abnormalities on the unoperated side and seizure outcome, although there was a relationship to cognitive outcome. The high rate of bilateral abnormalities and the good seizure outcome in many

such patients following surgery suggest that spectral abnormalities occur frequently in nonepileptogenic mesial temporal structures; their exact relationship to epileptogenesis remains unclear. This emphasises the importance of obtaining some form of functional ictal information, as will be discussed in later sections.

A small number o f children underwent repeat ’H MRS of the mesial temporal regions; eleven underwent MRS of the temporal lobe contralateral to the seizure focus following ipsilateral temporal lobe surgery, and three had MRS of both temporal lobes two years following the first examination. Although numbers are small, the data from the three children with repeat bilateral studies showed change over time. Furthermore, although the group data a short time after surgery do not show a significant change, review of

individual signal intensities suggest that there may be a ‘recovery’, most likely in NAA. Hugg et al (Hugg et a l, 1996) repeated spectroscopic imaging in five patients o f the contralateral hippocampus 12 months following surgery and concluded that two showed ‘recovery’. The lack of correlation of spectroscopic abnormalities with volume loss of the hippocampus (and therefore atrophy) in some studies (Ende et a l, 1997) would suggest that NAA may be a marker of neuronal dysfimction rather than neuronal loss, and that such a ‘recovery’may be possible. Within our own study, the numbers are small, and the length o f time between surgery and repeat examination short, with inadequate time to make comment about outcome with regard to seizures. Foliowup studies with clinical review at least two years following surgery should be performed to make further

comment about this. Furthermore, comparison with neuropsychological data would also be invaluable.

The data from children with extratemporal epilepsy suggest a low rate o f abnormality of the mesial temporal regions; two o f the three children showing abnormalities had a progressive inflammatory condition as the underlying aetiology. Of the seven children who underwent both examinations, both 'H MRS and T2 relaxometry were bilaterally normal in three, and unilaterally abnormal ipsilateral to the seizure focus in two. In two children however, T2 values were bilaterally abnormal but MRS normal on at least one side (unilateral in one and bilateral in one).The numbers are extremely small and therefore it is difficult to draw specific conclusions. However, these data suggest that any temporal lobe damage in extratemporal epilepsy may be more localised to the hippocampus than a wider area of the temporal lobe.

The well defined anatomical boundaries of the mesial temporal lobe enable

reproducibility of reliable localisation of a region of interest. Other areas of the brain, eg frontal and parietal lobe do not provide such boundaries and therefore reliable placement of a consistent region of interest, small enough to consider in surgery would be more difficult. The development of chemical shift imaging (CSI) has enabled wider review of other areas of the brain. Other centres have reported on CSI in adults in TLE (Hugg et al.,

1993; Cendes et al., 1994; Ng et al., 1994; Ende et al., 1997), and also in frontal lobe epilepsy (Garcia et a l, 1995). This technique theoretically has an advantage over single voxel techniques as it enables collection of individual spectra from many single voxels over a slice of tissue. Such studies have demonstrated a correlation between abnormal signal intensity ratios and the side of the seizure focus in TLE in adults (Cendes et a l ,

1995; Ende et a l, 1997; Hugg et a l, 1993), and have also demonstrated bilateral

(Connelly et a l, 1994). However, there remain limitations to the technique at present. In the case o f TLE studies, field inhomogeneities generally limit the aquisition of

hippocampal data to the mid and posterior portions of the hippocampus. Some studies also summate the data from each hippocampus to provide average signal intensity data (Cendes et a l, 1995). In addition, signal bleeding between voxels can lead to

contamination of individual spectra. This is particularly true of the high signal intensities obtained from the cerebellar vermis. Single voxel spectroscopy therefore provides a reliable method of producing consistent information in TLE, although CSI techniques may well play an increasingly important role in the evaluation of extratemporal epilepsy.

In conclusion, single voxel ’H MRS of the mesial temporal lobes has demonstrated abnormalities in children with TLE that have proved reliable in the latéralisation of brain abnormality for use in the presurgical evaluation. Such data appear to complement quantitative hippocampal measures of abnormality such as T2 relaxometry. The consequence of abnormalities seen contralateral to the seizure focus remains to be evaluated.

Publication arising from this work:

Cross JH, Connelly A, Jackson GD, Johnson CL, Neville BGR, Gadian DG (1996)

Proton magnetic resonance spectroscopy in children with temporal lobe epilepsy

APPENDIX

Table A5.1: H MRS in relation to clinical, EEG, MRI and pathology data in children with TLE.

P A T IE N T AG E C L IN IC A L IN T E R IC T A L EEG IC T A L EEG M RI (V isual analysis) IrM R S (N A A /(C ho+C r) Ipsi C ontra T 2 relaxom etry (m s) Ipsi C ontra P A T H O L O G Y (if surgery)

T1 14y4m LTLE N o abnormality L temporal LHS 0.48 0.63 120 105 A m m on’s Horn sclerosis

T2 7 y l l m LTLE L frontotemporal L temporal LHA 0.48 0.92 125 106 Rasmussens encephalitis

T3 9y9m LTLE L mid temporal L temporal LHS+L temporal signal

change

0.59 0.65 121 116 A m m on’s Horn sclerosis

T4 lly 8 m LTLE Bilateral L temporal LHS+L temporal signal

change

0.6 0.77 123 111 A m m on’s Horn Sclerosis

T5 13y4m LTLE L temporal L temporal LHS+L temporal signal

change

0.82 0.72 111 99 Am m on’s Horn sclerosis

T6 17y9m LTLE Bitemporal L anterior temporal LHS 0.62 0.89 128 106 A m m on’s Horn sclerosis

T7 16y TLE R temporal N /A Normal 0.82 0.86 108 108

T8 lOy TLE Bitemporal L temporal Normal 0.84 0.92 110 107 End plate gliosis

TIO 14y RTLE N o abnormality R centrotemporal RHS 0.64 0.69 130 106 A m m on’s Horn sclerosis

T i l 9 y l0 m LTLE L centrotemporal L centrotemporal LHS+L temporal signal

change

0.47 0.76 128 108

T12 10y7m LTLE Bitemporal L anterior temporal LHS 0.56 0.66 125 102 A m m on’s Horn sclerosis

T16 9y3m RTLE N o abnormality N /A RHS+R hemiatrophy 0.48 0.49 129 110

T17 9y IM TLE L temporal N /A LHS+L temporal lobe

atrophy

0.71 0.68 118 117

T18 5y8m TLE R posterior temporal R temporal Normal 0.54 0.68 101 101

T20 13y LTLE L temporal N /A LHS 0.73 0.8

T21 lly 9 m LTLE N o abnormality N /A LHS 0.77 0.92

T22 lOy RTLE R temporal N /A RHS 0.66 0.85 Am m on’s Horn sclerosis

T23 8y RTLE Bilateral N /A RHS 0.62 0.77

T24 5y RTLE R temporal R temporal RHS 0.44 0.52

T25 1 6 y llm TLE R temporal N /A RHS 0.62 0.59

w

CHAPTER 6

REGIONAL CEREBRAL BLOOD FLOW IN LOCALISATION OF THE