Neuroimaging in the characterization of the epileptic syndromes

                                                                                              Fernando Cendes

Abstract

Thin coronal MRI slices, perpendicular to the axis of the hippocampus, give the best images for determining hippocampal sclerosis (HS) and other subtle pathologies and for ascertaining anatomical detail. MRI features of HS, detectable by visual inspection of the images, are: (i) hippocampal smallness (atrophy) which is the most specific and reliable feature, (ii) increased T-2 signal which in isolation may be insufficient to diagnose HS; (iii) loss of internal structure. There may also be asymmetry of the horns of the lateral ventricles, which is variable and may lead to false lateralisation, and atrophy of the anterior temporal lobe, which is non-specific. Most patients with HS undergoing presurgical evaluation have one hippocampus which is clearly smaller than the other and which has increased T-2 signal, along with a normal appearing contralateral hippocampus, so that volume measurement is not necessary for clinical purposes.  The visual binary paradigm breaks down in the presence of symmetric bilateral atrophy or mild unilateral disease.  In these cases volumetric MR analysis of the hippocampus is very sensitive and specific for identifying HS. MRI measurements of hippocampi are a surrogate for histopathological methods of assessing the presence and severity of neuronal loss.  This may give useful prognostic information for postoperative seizure control.  Surgical treatment of unilateral HS should give >90% excellent outcome.  Comparisons with EEG localization and surgical outcome have shown the potential clinical utility of proton magnetic resonance spectros-copy (MRS) in the localization of epileptogenic areas. Proton MRS studies have shown that a reduced signal of the neuronal marker N-acetylaspartate (NAA) can reliably localize and lateralize epileptic foci in patients with partial epilepsies, particularly temporal lobe epilepsy (TLE). In addition, relative NAA signal may normalize after successful surgery for TLE.

 

Thin coronal magnetic resonance imaging (MRI) slices, perpendicular to the axis of the hippocampus, give the best images for determining hippocampal sclerosis (HS) and other subtle pathologies and for ascertaining anatomical detail. MRI features of HS, detectable by visual inspection of the images, are: (i) hippocampal smallness (atrophy) which is the most specific and reliable feature, (ii) increased T-2 signal which in isolation may be insufficient to diagnose HS; (iii) loss of internal structure.

There may also be asymmetry of the horns of the lateral ventricles, which is variable and may lead to false lateralisation, and atrophy of the anterior temporal lobe, which is non-specific.  T-2 mapping is an objective method for measuring abnormal T-2 signal, which may be difficult to detect visually.

Most patients with HS undergoing presurgical evaluation have one hippocampus which is clearly smaller than the other on visual inspection, and which has increased T-2 signal, along with a normal appearing contralateral hippocampus, so that volume measurement is not necessary for clinical purposes.  The visual binary paradigm breaks down in the presence of symmetric bilateral atrophy or mild unilateral disease.  In these cases volumetric MR analysis of the hippocampus and the amygdala are very sensitive and specific for identifying HS. MRI measurements of hippocampal volumes are a surrogate for histopathological methods of assessing the presence and severity of neuronal loss in each hippocampus allowing each to be classed as normal or abnormal.  This may give useful prognostic information concerning postoperative seizure control.  Surgical treatment of strictly unilateral HS should give >90% excellent outcome (Engel et al. 1997; Engel, Jr. 1999; Cascino et al. 1996; Cendes et al. 2000; Arruda et al. 1996; Engel et al. 1997).

 

Comparisons with EEG localization and surgical outcome have shown the potential clinical utility of proton magnetic resonance spectroscopy (MRS) in the localization of epileptogenic areas.  MRS provides chemical information from metabolites that are present in tissues at much lower concentration than water. A number of proton MRS studies have shown that a reduced signal intensity of the neuronal marker N-acetyl aspartate (NAA) can reliably localize and lateralize epileptic foci in patients with partial epilepsies, particularly temporal lobe epilepsy (TLE). In addition, relative NAA concentration may normalize after successful surgery for TLE. NAA may be a dynamic marker of epileptic activity, and not simply reflect neuronal number. The MRS findings may have prognostic value as well. Proton magnetic resonance spectroscopy (MRS) lateralises most cases of temporal lobe epilepsy with normal MRI and detects bilateral abnormalities more often than does volumetric MRI although the greater sensitivity of MRS is not invariable.

 

Partial epilepsy arising from a part of the brain other than the temporal lobe (extra-temporal epilepsy) comprises about 1/3 of refractory partial epilepsies. The number of surgical procedures performed in this group is far less and the outcome much less satisfactory than in patients with TLE because of the: (i) difficulty in distinguishing the clinical manifestations from those of TLE, (ii) failure to precisely localize the seizures, even with prolonged EEG monitoring in 40 to 50% of the patients, and (iii) failure to identify a structural lesion by conventional MRI in ~40% of patients (Williamson et al. 1993; Williamson & Spencer, 1986; Quesney et al. 1995).

In patients with extra-temporal epilepsies without identifiable structural lesions, intensive EEG monitoring with intracranially implanted electrodes is considered necessary in most instances (Williamson et al. 1993; Engel, Jr. & Ojemann, 1993). These invasive diagnostic studies must be focused on a particular region of the brain and cannot be used as a screening test. Thus, this procedure is only performed when the results of noninvasive studies suggest a well-defined target (Engel, Jr. & Ojemann, 1993; Olivier et al. 1987) and the presence of a resectable epileptogenic region (Engel, Jr. & Ojemann, 1993; Olivier et al. 1987; Gumnit, 1991). Mapping of an epileptogenic region with implanted electrodes is technically difficult.  The risk of complications is comparable to the risk of the epilepsy surgery itself, and the cost (including the operative procedure and prolonged hospitalization for monitoring) is considerable.

 

We recently studied 100 consecutive patients followed in our epilepsy clinic with partial epilepsy who underwent MRI investigation (Cendes et al, 2001). The MRI protocol included 6mm sagital T1-weighted, 3-4 mm axial T1 and T2-weighted, 3mm coronal T1 inversion recovery and T2-weighted images that were printed on a radiographic film for routine analysis. In addition, all patients had a volume T1-gradient echo acquisition with isotropic voxels (1-1.5 mm) for multiplanar reconstruction (MPR). The MRIs were examined in two different occasions: first using only the images printed on films and in a second occasion in a computer workstation when all the available images and MPR were analyzed blindly to the clinical information. The most frequent risk factors were family history of seizures (14%), head trauma (12%), peri-natal anoxia (12%) and infection (8%). Antecedent of febrile convulsions was present in 23% of patients. Most patients (90%) never had an optimal seizure control and were potential candidates for surgery. Neurological examination was abnormal in 25% of patients: 18% with focal motor deficit, 3% with visual field defect and 4% with global cognitive-motor impairment. Interictal EEG showed epileptiform abnormalities in 85% of patients: 61% in the temporal regions, 9% extra-temporal and 15% generalized. The clinical-EEG diagnoses were temporal lobe epilepsy (TLE) in 81%, extra-temporal epilepsy in 11% and secondarily generalized epilepsy in 8%. The analysis of MRIs printed on films showed abnormalities in 80% of patients, indicating an etiology of epilepsy in 71%. The MRIs were considered normal in 20% of patients in this first analysis. By contrast, the analysis using a computer workstation including MPR showed abnormalities indicating an etiology of seizures in 94% of patients (p<0.05). The lesions previously undetected were cortical dysgenesis and subtle mesial temporal sclerosis (MTS). The etiologies detected by MRI with MPR were: MTS in 50 patients, reactive gliosis in 18, cortical dysgenesis in 15, porencephaly in 7, cysticercosis in two, cavernoma in one and ganglioglioma in one. Most patients with MTS had a normal neurological exam, while all patients with porencephaly had a motor or visual deficit.   We concluded that high resolution MRI including thin coronal slices, in addition to a “dynamic” analysis in a workstation with MPR allowed a significative improvement in lesion detection compared to the traditional analysis with radiographic films (94% versus 80%). Furthermore, MRI showed abnormalities more frequently than routine interictal EEG. Patients with partial epilepsy and “normal” MRI need to be investigated further with thin slices and post-processing techniques using volume acquisitions that allow adequate multi-planar re-slicing.

 

References

 

Arruda, F., Cendes, F., Andermann, F., Dubeau, F., Villemure, J.G., Jones-Gotman, M., Poulin, N., Arnold, D.A., & Olivier, A. (1996): Mesial atrophy and outcome after amygdalohippocampectomy or temporal lobe removal. Ann Neurol 40, 446-450.

 

Cascino, G.D., Trenerry, M.R., So, E.L., Sharbrough, F.W., Shin, C., Lagerlund, T.D., Zupanc, M.L., & Jack, C.R. (1996): Routine EEG and temporal lobe epilepsy - relation to long-term EEG monitoring, quantitative MRI, and operative outcome. Epilepsia 37, 651-656.

 

Cendes, F., Li, L.M., Watson, C., Andermann, F., Dubeau, F., & Arnold, D.L. (2000): Is ictal recording mandatory in temporal lobe epilepsy? Not when the interictal electroencephalogram and hippocampal atrophy coincide. Arch Neurol 57, 497-500.

 

Cendes F, Ghizoni E, Santos SLM, Li LM, Guerreiro CAM. Dynamic assessment of high resolution MRI with multiplanar reconstruction increases the yeld of lesion detection in patients with partial epilepsy. Neurology 2001; 56(Suppl 3): A388.

 

Engel, J., Jr. (1999): When is imaging enough? Epileptic disorders 1, 249-253.

 

Engel, J., Jr., & Ojemann, G.A. (1993): The Next Step. In: Surgical Treatment of the Epilepsies, J. Engel, Jr. (Ed.), pp. 319-329. New York: Raven Press.

 

Engel, J.J., Cascino, G.D., & Shields, W.D. (1997): Surgically remediable syndromes. In: Epilepsy: A comprehensive textbook, J. Engel, Jr. & T.A. Peddley (Eds.), pp. 1687-1696. Philadelphia: Lippincott-Raven.

 

Gumnit, R.J. (1991): Cost, accessibility, and quality-of-life issues in surgery for epilepsy. In: Epilepsy surgery, H. Luders (Ed.), pp. 47-49. New York: Raven Press.

 

Olivier, A., Marchand, E., Peters, T., & Tyler, J. (1987): Depth electrode implantation at the Montreal Neurological Institute and Hospital. In: Surgical treatment of the epilepsies, J. Engel, Jr. (Ed.), pp. 595-601. New York: Raven Press.

 

Quesney, L.F., Cendes, F., Olivier, A., Dubeau, F., & Andermann, F. (1995): Intracranial electroencephalographic investigation in frontal lobe epilepsy. In: Epilepsy and the functional anatomy of the frontal lobe, H.H. Jasper, S. Riggio, & P.D. Goldman-Rakic (Eds.), pp. 243-260. N. York: Raven Press.

 

Williamson, P., & Spencer, S.S. (1986): Clinical and EEG features of complex partial seizures of extratemporal origin. Epilepsia 27 (suppl), 46-63.

 

Williamson, P.D., Van Ness, P.C., Wieser, H., & Quesney, L.F. (1993): Surgically remediable extratemporal syndromes. In: Surgical Treatment of the Epilepsies, J. Engel, Jr. (Ed.), pp. 65-76. New York: Raven Press.