Commentary

Brain Structure and Epilepsy: The Impact of Modern Imaging

Frederick Andermann, Professor of Neurology and Paediatrics, Department of Neurology and Neurosurgery, McGill University, , ,

After the pioneering work of Hans Berger in Then came the era of magnetic resonance the 1930s (1), electroencephalography (EEG) (MR), which led to important insights into the opened a new window on epilepsy. This led to structural basis of temporal epilepsy, the most its general acceptance and now widespread common form of the intractable disease, and use. It provided an invaluable new dimension to recognition of a wide range of structural cortical the ability to locate epileptogenic abnormalities abnormalities, often developmental, leading to in patients with focal or partial epilepsy. The seizures which were often difficult or impossible presence of structural lesions in patients with to control. The introduction of MR coincided partial epilepsy had, of course, been long real- with a period of renewed and widespread inter- ized but there evolved a widely held concept est in the surgical treatment of epilepsy. Ad- that the lesion was not nearly as important as vances in epileptology made it very clear that in the electrographically defined epileptogenic ab- as many as 20% of epileptic patients medical normalities. control of seizures was not possible with the In the early days of neuroradiology, the available pharmacologic armamentarium (2, founding fathers, like Arthur Childe and Donald 3). Advances in surgical technique and, above McCrae, soon realized that asymmetries in skull all, in preoperative electrographic studies and growth and identification of lesions by pneumo- neuropsychological investigation held out the encephalography and arteriography contrib- promise of improved results of surgical treat- uted to our study of patients with intractable ment. There was, in North America, a prolifer- epilepsy. Nevertheless, imaging continued to ation of centers hoping to embark on surgical labor in the shadow of the EEG until the advent treatment (2, 3). We now see an improved bal- of computed tomography, which ushered in the ance between the enthusiasm of the physicians era of modern imaging in patients with epilepsy and surgeons and the recognition of the essen- (2–8). First came the recognition of disorders or tialness of searching imaging, EEG, and neuro- cortical organization such a polymicrogyria and psychological investigations. Functional imag- pachygyria (4–7) and the beginning of the ing is also increasingly used (10). explosion of diagnosis by imaging of small MR imaging is now the standard of reference inert lesions, some calcified, like the cavernous in the investigation of patients with epilepsy, angiomata (8). It was at that time that we fi- particularly those with intractable seizures (4). nally realized that electrographic localization, Computed tomography retains a role in recog- whether from the surface or from intracranial nition of calcifications. It is not a sufficient recording, might not provide as reliable an an- screening procedure because of the difficulty of swer as one had anticipated (2, 3). Patients with recognizing temporal lobe abnormalities and posterior temporal or temporal occipital lesions parenchymatous changes. and anterior and inferomesial temporal epilep- Neurologists and neurosurgeons are now be- togenic foci had disappointing results after re- ginning to recognize that referring patients for section of the electrically defined epileptogenic routine MR imaging is inappropriate. To obtain area (9), and it became progressively clearer maximal usefulness, the problem should be dis- that the lesion and its immediate surround was cussed in advance with the neuroradiologists much more important in epileptogenesis than and the procedures tailored to the specific clin- we had suspected (8–10). ical problem.

Address correspondence to Frederick Andermann, MD, Montreal Neurological Institute and Hospital, 3801, rue University, Montreal, Quebec, Canada H3A 2B4. Index terms: Magnetic resonance, surface coils; Seizures; Commentaries AJNR 18:302–3006, Feb 1997 0195-6108/97/1802–0302 © American Society of Neuroradiology 302 AJNR: 18, February 1997 COMMENTARY 303

In patients with a clinical history of temporal Taylor, Falconer, and the pathologists Bruton lobe epilepsy, evaluation of the size and mea- and Corsellis (20, 21) were based on pathologic surement of the volume of the amygdala and findings in surgical specimens. They referred to hippocampus greatly outweighs the radiolo- small areas of dysplasia totally included in the gist’s ability to assess these structures visually resected tissue. (11–13). The technique has been well validated. Dysplastic lesions of varying configuration When the mesial temporal structures are unilat- and pathologic severity have now been increas- erally small (below 2 standard deviations in our ingly recognized. The ones containing balloon center), there is a very high correlation with an cells were previously considered to represent excellent surgical outcome (14). When electro- the “forme fruste” of tuberous sclerosis. The graphic and volumetric studies appear to be molecular relationship of these lesions to the contradictory, recordings with depth electrodes genetic form of tuberous sclerosis is not yet have shown that the small volume is clinically clarified, though the affected patients do not more significant than the surface EEG findings have the multiple lesions or involvement of (15, 16), which may result from lower ampli- other systems or a family history of tuberous tude and rapid contralateral spread from a sclerosis. Dysplastic lesions usually, though not shrunken hippocampus. always, produce extremely active epileptogenic When there is bilateral atrophy, the trend is EEG abnormalities with a characteristic burst- for greater likelihood of the clinically significant ing pattern (22, 23). It has become clear that for seizures to originate in the smaller hippocam- surgical treatment of intractable epilepsy, the pus and amygdala. There are, however, a num- areas of brain generating this bursting pattern ber of patients who have seizures originating in had to be resected in addition to the visible both temporal lobes, and it appears that in ex- lesion in order to obtain a good result. Dysplas- ceptional cases the majority of seizures can tic lesions are somewhat like the tip of an ice- arise in the less atrophic mesial structures (15, berg. Lesser pathologic changes, invisible by 16). This is obviously an area that requires fur- modern imaging (24), may extend beyond the ther clarification; some of these patients present visible lesion and likely account for some of the the most difficult temporal epileptic problems. less successful outcomes after surgical treat- Patients with temporal lobe epilepsy and with ment. Recording with invasive techniques may normal volume of hippocampus and amygdala not necessarily solve this problem, because are a minority and they, like the ones with bi- some of these abnormalities may involve areas lateral atrophy and bilateral seizures, do not do that cannot be resected. The challenge is to find as well after surgical resection than those pa- such areas of lesser but still significant patho- tients who have good evidence of mesial tem- logic abnormality. poral sclerosis (14–16). Mild pathologic Looking for smaller lesions with the help of changes may be found in patients without atro- surface coils has led Grant et al (25), in this phy. Some of these patients have abnormalities issue of AJNR, to be able to see small but im- on MR spectroscopy, a technology that is rap- portant areas of structural abnormality. Cur- idly gaining clinical acceptance and that can rently, patients with intractable partial epilepsy contribute to the lateralization of temporal epi- and completely normal MR images represent a leptogenic processes (4, 17–19). Abnormalities major challenge, particularly when seizures of signal and disturbed organization of the inter- seem to arise in extratemporal areas. Thus in nal structure of the hippocampus have also such patients, even when invasive EEG record- been recognized (4). In their preoperative inves- ings seem to show an epileptogenic area, there tigation, different centers emphasize different is often a poor outcome when this region is groups of imaging studies. This is similar to the resected. The recently recognized familial fron- variation in the electrographic investigations tal epilepsy with predominantly nocturnal sei- and especially in the perceived need for inva- zures (26) may account for some, but by no sive recording and neuropsychological studies. means all, of these poor results. The important Another major area of progress has been the lesson from the paper by Grant et al is that one recognition of lesions. Before modern imaging, would not accept a normal study using a head about a third of patients with intractable epi- coil as sufficient evidence of structural normal- lepsy were found to have lesions at surgery. The ity. The identification of even small structural original descriptions of cortical dysplasia by lesions could influence a decision regarding sur- 304 ANDERMANN AJNR: 18, February 1997 gical treatment with all that this implies for the least one patient. The more anterior and in- patient’s future. One may, with some justifica- feromesial temporal epileptogenic abnormali- tion, wonder what the clinical significance of ties may be attributable to secondary epilepto- such small lesions is. This must be assessed by genesis or abnormality of the cortex overlying the congruence of the imaging findings with all the nodule. other available information: clinical, electro- An analogous syndrome, with what one graphic, neuropsychological, and that derived might call pseudotemporal epileptic discharges, from functional imaging. is found in patients with hypothalamic hamar- There is currently a great deal of discussion tomata (29). These patients sometimes have about the effect of resection of the epileptogenic temporal and, more rarely, frontal EEG abnor- lesion. Some forms of cortical dysplasia are in malities. When these areas were resected after themselves epileptogenic, whereas other le- studies with depth recording or other invasive sions, such as glial tumors, are probably not (4, techniques, there was no improvement. The sit- 8, 27). In that case, the epileptogenic abnor- uation was further clarified when the hamar- mality arises in surrounding brain. Other le- tomata were shown to be in themselves epilep- sions, such as cavernous hemangiomata, are togenic by recording directly from them. This surrounded by a rim of hemosiderin-impreg- also explained the secondary generalized epi- nated tissue, which is epileptogenic. It is likely, leptic pattern with deterioration and drop at- though not conclusively proved, that when both tacks that often develops late in the first decade. the cavernous angioma and the rim are com- This is yet another example suggesting second- pletely resected, patients become seizure free ary epileptogenesis caused by a lesion whose irrespective of the presence of more widespread tendency to cause laughing attacks was never epileptogenic EEG abnormalities. understood until recently. The surgical results of lesionectomy for the Another group of lesions diagnosed with MR treatment of intractable epilepsy have improved are the micropolygyrias (7). These are unilat- progressively. The need for invasive recording eral or bilateral; patient 25 in the paper by Grant and wide resection is increasingly questioned. et al illustrates that these lesions may be very Some of the inadequate results of lesionectomy, asymmetric and that a small abnormality con- however, can be explained by the presence of tralateral to the major one may be present. The dual pathology (8, 27). This term is used to lesions are often perisylvian but are at times describe the association of mesial temporal bilateral mesial occipital. Others, again often sclerosis or atrophy in association with a lesion bilateral, extend from the perisylvian region not directly impinging on these mesial temporal along the sylvian fissure into the parietooccipi- structures. When both the mesial temporal tal region (5, 7, 30). structures and the lesion are resected, the re- Bilateral perisylvian polymicrogyria might be sults are optimal. Resection of the mesial struc- genetically determined; there are several sibling tures alone is generally inadequate, whereas pairs reported (31). In the majority of cases, a resection of the lesion alone in the presence of prenatal watershed vascular abnormality is sus- mesial temporal atrophy may also not be suffi- pected to cause the micropolygyria. There has cient. Obviously, greater experience is needed been some reluctance to consider surgical re- to clarify further the optimal treatment of pa- section in patients with very widespread areas tients with such dual pathology. of micropolygyria, because the whole area Imaging has brought to light a number of cannot be removed. Evidence is beginning to epileptic syndromes. Thus, patients with poste- appear that in some patients, depending on ac- rior periventricular nodular heterotopia and curate clinical and EEG location, improvement more anterior temporal mesial epileptogenic can be obtained by resection of the area of foci have a specific natural course and response maximal epileptic discharge. In the majority of to mesial temporal resection. In a series of 10 patients with bilateral perisylvian polymicro- such patients similar to patient 17 reported by gyria, however, there is no evidence of such a Grant et al, only one has become seizure free focal process. These patients can show a bilat- and that after only a 6-month follow-up (28). All eral or generalized epileptic process with drop others continued or again developed attacks, attacks that respond to callosotomy. suggesting that these lesions may be in them- Imaging has recently brought to light at least selves epileptogenic. This has been shown in at two autosomal sex-linked migration abnormal- AJNR: 18, February 1997 COMMENTARY 305 ities: band heterotopia and periventricular nod- lepsy. The clinical significance of these findings ular heterotopia (7, 31, 32). has allowed identification of new syndromes Most of the patients with band heterotopia are and the development of new strategies for sur- female (31). Some have affected daughters gical treatment. With the aid of surface coils, the whose lesions are similar to those of the mother, identification of progressively smaller and and sons with lissencephaly (33). Contiguous smaller lesions has been well illustrated in the periventricular nodular heterotopia can also be paper of Grant et al. It is an important contribu- found in several generations of female patients. tion because it has led to recognition of yet In these families, the abnormalities are probably another group of lesions, which previously de- lethal for the male. 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