In the current study, the case group included 50 epileptic patients, 30 males (60%), and 20 females (40%) with mean age of 5 ± 3 years. The control group included 20 patients, 11 males (55%), and 9 females (45%) with mean age of 6 ± 4 years. For most recent studies that reported gender, like the study conducted by Hawley et al. in 2015, gender-specific incidence in children was higher in males, although seldom statistically significant [14].
The case group included 8 patients (16%) with intractable epilepsy and 42 patients (84%) who were controlled with medication. This nearly agreed with the Dutch study by Arts et al. conducted as a 5-year follow-up study of epilepsy in childhood who found that 6–4% of children developed intractable epilepsy [15].
In the current study, the ILAE 2017 classification of seizure types was used. The most frequent type of seizures was generalized tonic-clonic seizures 88% followed by focal seizures with awareness which represented 4%, focal seizures with impaired awareness 4%, and myoclonic seizures which also represented 4%. This went with Farghaly et al., who conducted a study to determine the prevalence and clinical pattern of epilepsy among children and adolescents in upper Egypt. This study demonstrated generalized seizures as the most frequent type in epileptic children and adolescents [16].
In the present study, we used SVS technique, as it offered a good signal to noise and homogenous peaks within relatively short scan time [17]. We did not add a multivoxel technique in this study to avoid unnecessary prolongation of the exam time.
The quality of the signal received from metabolites in proton MRS directly depends on the physical parameters of the impulse sequence used, namely on Echo time (TE). In this study, we used short (30 ms) and long (135 ms) TE. As short TE allowed us to detect more metabolites especially myo-inositol and glutamates, As the change of their levels found to be related to poor outcome in some cases [18]. We also used long TE because the attenuation of the signal from the metabolites with shorter time of relaxation (TR), improves the signal-noise ratio of the main three metabolites (NAA, Cho, and Cr), and allowed better calculation of the ratios [19].
In their review article, Caruso et al. suggested one of two SVS protocols for the examination of the patients with non-lesional epilepsy. One protocol was to survey white matter, deep and cortical grey matter by using 3 voxels—using short TE of 35 ms—over the centrum semiovale, lentiform nuclei, and midline occipito-parietal cortex. Another protocol was using one voxel over the basal ganglia in order to save time [18]. In the present study, we went with Caruso’s first protocol, we placed one voxel in the left centrum semiovale, one in the left lentiform nucleus, and one in the midline parieto-occipital region.
In the current study, the compared NAA/Cho, NAA/Cr, and NAA/Cr+Cho ratios between the cases and control groups (in the different sampled sites) showed no significant difference. These findings denied the value of these ratios in identifying the patients with non-lesional epilepsy. This went with Aitouche et al. who found that the measurement of absolute NAA and NAA/Cr ratio cannot differentiate between non-lesional insular epilepsy, extra insular epilepsy, and control groups [9].
On the other hand, the present results were in disagreement with Azab et al. who compared the NAA/Cr ratio between 40 TLE patients and 20 controls. They found a significant difference between the patients and control groups with a decreased level of the NAA/Cr ratio in the patient’s group [8]. Also, Aun et al. conducted a study to evaluate the role of MRS in non-lesional TLE. They found that low NAA/Cho+Cr ratio allowed for lateralization of the epileptogenic focus in comparing both temporal lobes [7]. We did not go with Cendes et al. in their meta-analysis, as they found that proton MRS studies showed a focal reduction of NAA signal in patients with different forms of TLE, including those with normal magnetic resonance imaging (MRI), as well as extratemporal partial epilepsies [20]. This contradiction may be explained as this study was conducted on non-lesional epilepsy without identification of the epileptogenic focus, while other studies were conducted over epilepsy in which epileptogenic foci were detectable in conventional MRI, EEG, and/or fluoro-deoxyglucose–positron emission tomography (FDG-PET).
In comparing metabolite ratios between groups with intractable and non-intractable epilepsy, the NAA/Cr ratio showed a statistically significant difference in basal ganglia, white matter, and grey matter. We also found a borderline significant difference between NAA/Cr+Cho ratio in basal ganglia. Our results pointed to the value of NAA/Cr and NAA/Cr+Cho ratios as biomarkers that can predict the patient’s response to treatment. This agreed with the study done by Campos et al. who demonstrated a significant reduction of NAA/ Cr ratios in interactable TLE group compared with those who responded to the first antiepileptic drugs (AED) and to controls [21]. Also, this went with Briellmann et al. who found that NAA was significantly lower in refractory TLE patients compared with patients who responded to one anti-epileptic drugs [22].
This can be explained by the fact that NAA is considered a neuronal marker as it is found exclusively in neurons and their processes. In human brain spectra, NAA is reduced in the situations associated with neuronal loss or neuronal dysfunction. In patients with intractable seizures, the high frequency of breakthrough seizures, the more duration of the attacks, and the multiple antiepileptic drugs, all of these contribute to neuronal dysfunction [23].
In the present study, there were statistically significant differences between patients with generalized clonic seizures and those with other seizure semiology in NAA/Cho ratio in basal ganglia and grey matter, NAA/Cr ratio in white matter, and NAA/Cr+Cho ratio in the cortex. However, these ratios showed no significant difference between the patients with generalized seizures and the control group. This disagreed with Kasper et al. who used multi-voxel MRS to study the extent of local metabolic alterations in patients with idiopathic generalized epilepsy. They depended on the absolute values of the metabolites rather than ratios. They found a significant decrease (P < 0.05) of tNAA in the cortical grey matter, thalamus, and basal ganglia, compared with the control group [24].
Limitation
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This study was done using magnetic field strength of 1.5 T. A higher-field strength of 3 T or more would yield a better spatial resolution and high SNR.
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Small sample size may reduce or bias the power of the results. Further studies with a larger sample size are necessary to extend these results.
