As a group, MR images of the TL of cats suffering from any kind of epileptic seizure did not differ significantly from those of cats without epileptic disorders. However when stratified according to seizure semiology, or occurrence of CS or SE, MR images of the TL of cats with a history of epileptic seizures with OI, or cats with CS or SE, differed significantly from epileptic cats that did not, and from non-epileptic cats.
Previous studies have suggested that alterations in the feline TL visible on MR images were caused by various underlying conditions, including astrogliosis, oedema, hypoxia, idiopathic HN and HS, inflammation, intracranial infection, ischemia, malformation and neoplastic conditions [1–9]. A potential toxin or infectious agent cannot be ruled out, nor can genetic predisposition or febrile seizures early in life, as described in human medicine [14]. The hippocampus is also known to have a very low seizure threshold compared to other parts of the brain and is therefore more susceptible to active participation in a post-discharge evoked by a different part of the brain, or even to become an epileptic focus itself [15]. Since the initial histological description of HS in humans, there has been debate about whether HS is a nonspecific result of a primary epileptogenic lesion restricted to the hippocampus, whether it is caused by damage to the cells due to the spread of epileptic discharges to this area, or even whether it develops due to other causes [11]. There is evidence that HN and HS in children is multi-causal [16]; the same can be reasonably assumed for feline patients. At present it is not possible to distinguish the underlying cause of a TL abnormality by diagnostic imaging alone, even if repeated scans could help to differentiate between reversible and irreversible lesions.
Changes in the TL MR morphology seem to be rare in non-epileptic cats and occur much more frequently in epileptic cats with OI compared to other cats. Therefore, we suspect that OI in epileptic cats is not only a specific epileptic phenomenon for feline temporal lobe epilepsy (TLE), in line with early experimental studies [17], but is also significantly associated with temporal lobe changes detected in MR images.
As expected, the images of cats with a history of CS or SE were given significantly higher MR scores (however not by all three observers) compared to the images of cats that had never suffered CS or SE. These groups also included cats presenting OI, since the majority of the cats with OI also had CS or SE.
SE and CS likely cause more severe damage to neurons compared to infrequent short seizures due to the long period in which neurons are exposed to synchronous electric activity [18]. Previous studies have shown that the hippocampus, in particular, tends to develop irreversible MRI-detectable pathologies after convulsive SE [19]. However, we did not evaluate the time span between the last observed epileptic event and the day of diagnostic imaging. Therefore, it is possible that even if there was acute damage to the neurons of the TL, this damage could have been reversible and there may have been sufficient time for the cells to reorganise before the images were taken. This aspect has never been investigated in cats but should be taken into account in further studies as early postictal MRI abnormalities can also be both causes and consequences of seizure [18].
We expected that signal alterations in the hippocampal area would be detected more frequently in cats that experienced a higher number of seizures prior to MRI. Indeed, there was such a tendency but differences in ratings were only significant between non-epileptic patients and patients with 11–25 or more than 25 seizures prior to MRI. These results may indicate that a certain number of a specific kind of seizure is necessary to cause visible MRI changes. Similarly, recent studies in rats showed that hippocampal volume loss was not correlated with seizure frequency [20]. Since the certain number of seizures our subjects had experienced could only be estimated in some cases, these data must be interpreted with caution. Moreover, because the number of postictal days prior to imaging is unknown, MR abnormalities could also be caused by reversible oedema.
In our study, FLAIR sequences were rated with the highest scores. Because the signal of intraventricular cerebrospinal fluid is suppressed, the FLAIR sequence for periventricular lesions is more conspicuous than T2-weighted sequences. T2-weighted sequences were only slightly inferior to FLAIR sequences in detecting alterations of the TL signal, consistent with earlier results [21, 22]. T1C-weighted images were ranked third, and pre-contrast T1-weighted images were ranked fourth. This leads to the conclusion that only lesions that show contrast enhancement are reasonably detectable on T1-weighted images. In human medicine, the gold standard scan protocol includes high-resolution T2-weighted images, with or without inverting the contrast. MR techniques such as hippocampal volume measurements, T2 relaxometry, MR spectroscopy and diffusion tensor imaging of the hippocampus are sometimes used in human medicine [23]. These dedicated techniques are not yet routinely available in veterinary medicine and MR volumetry and diffusion tensor imaging were only performed on few cats experimentally [24, 25]. The hippocampal volume was significantly reduced unilaterally in one study in familial strain of spontaneous epileptic cats in comparison with a healthy control group [24], but this aspect was not investigated by our study.
In this study, there was moderate-good interobserver agreement among specialists, although the overall agreement was perfect among the three observers in 52.2 % of cases and perfect to moderate in 82.6 % of all cases. There were many factors influencing the assessment of images in this blind study. Because the hippocampal signal was not measured objectively in this study, MRI interpretation was associated with considerable subjectivity, although this aspect has not been explicitly discussed in veterinary medicine. Opinions differ in clinical practice regarding what constitutes a normal TL signal, and this discrepancy may result in markedly different assessments among observers [26]. Because the hippocampus contains more grey matter than surrounding parts of the brain [27], mild T2 hyperintensity should be considered normal, but no standard value can be given. Although all three observers involved in this study were expert in neuroimaging, they had diverse backgrounds and different numbers of years’ experience in this specific field of diagnostic imaging, which could have led to different interpretations of the lesion anatomic location, pattern, mass effect, and contrast medium uptake. This discrepancy may also be explained, at least in part, by the tendency of some practitioners to score as uncertain for equivocal patients, whereas others prefer to commit to a diagnosis. Because of partial volume averaging it also may be difficult to distinguish whether the hyperintense signal arises from the hippocampus or the lateral ventricle and in some cases there were intracranial masses present, which displaced the hippocampal tissue and may have interfered with the MR signal of this region. If this was the case, some observers refused to evaluate the specific images. We conclude that subjectivity of the assessments is also a factor that may lead to discrepant evaluations and thus must not be underestimated.
This study had several limitations. First, it was a descriptive study of the agreement among three observers. Because it did not take the final diagnosis into account (most of the patients are still alive and only few histopathologic examinations have been performed yet), no conclusion could be made to the comparability of the radiographic and pathohistologic assessments. Second, the observers had no knowledge of the patients’ histories or physical and neurological examinations and could not contextualise the images. Third, we can not rule out for sure, that patients presenting with altered mentation or behavioral changes were suffering from non-convulsive status epilepticus and were misclassified as non-epileptics. Fourth, although the images were all taken at the same institution, some variability in positioning and MR sequence availability were noted. Fifth, our observers had little specific training in using the scoring system provided and it is possible that this also had an effect on the scoring. Finally, because there was no follow-up imaging, observers could not differentiate between reversible and irreversible changes of the affected side. However, such differentiation is likely relevant but this issue was investigated in cats only experimentally [28]. Volumetry could be helpful as hippocampal size might increase in oedema and decreases in sclerosis. The recently published recommendation on a veterinary epilepsy-specific MRI protocol by the International Veterinary Epilepsy Task Force also emphasised the importance of the evaluation of the hippocampi. At least visual assessment should be carried out including size, symmetry, atrophy and signal changes, however volumetric measurement may be meaningful in the future [29].
