Refractory focal epilepsy: findings by MRI. Doctors Nicolás Sgarbi, Osmar Telis Clinical Radiology Department Hospital de Clínicas Montevideo- Uruguay ABSTRACT Epilepsy is one of the most frequent neurological diseases, being one of the most common reasons MRIs are requested in our environment. Although an adequate control of the disease is achieved with most patients, close to 30 % do not achieve an adequate therapeutic response, developing so called refractory epilepsy. The possibility of finding a focal lesion responsible for the clinical picture increases significantly in patients with refractory epilepsy, which gives great importance to this imaging study. In this article we show findings in a group of patients with refractory epilepsy studied within the epilepsy program in our center, highlighting the contributions of MRI and the importance of an adequate study protocol. Key words: refractory epilepsy, temporomesial sclerosis, cortical malformations, MRI. INTRODUCTION Epilepsy is the second most frequent neurological disease and MRI is the chosen diagnostic method for this pathology. It is estimated that approximately 8% of the population will suffer at least one critical episode during its life with the health impact this entails (1). Correct classifying of the crisis and the clinical picture is crucial to establish the etiological diagnosis precisely and the according treatment which substantially impacts the patient s prognosis (1). Although most patients are able to control the disease with medical treatment, approximately 30% do not respond to the same with the resulting increase in morbimortality and with the ORIGINAL ARTICLE E II/Vol. XV/Num. 2/ Jun 2012
Refractory focal epilepsy: findings by MRI. high costs this represents for the health system (2, 3). Diagnostic and therapeutic algorithms in this group of patients differ substantially, the contributions of MRI being essential due to greater probabilities of identifying an anatomical substrate (3). The objective of our work is to carry out an iconographic trial with the findings by MRI in a group of patients with refractory epilepsy, systematizing and organizing hierarchically the most frequent alterations. The main signs in conventional and high resolution are highlighted and in some cases the usefulness and contributions of spectroscopy are highlighted. MATERIALS AND METHOD A series of patients with refractory epilepsy were analyzed retrospectively. These patients were sent to our Service for assessment within the Epilepsy Program. The total of patients studied in one year (June 2010 till July 2011) due to epilepsy was of 375 and of them 43 (11,5%) with the clinical reference data of refractory epilepsy, all with partial epilepsy. In all of them the institutional protocol of imaging assessment by MRI was performed using closed field unit, 1,5 T potency which includes as routine: a high resolution volumetric 3D sequence T1- weighted (MPRAGE), at Figure 1: left temporo mesial sclerosis. Patient with a history of temporal epilepsy. Using coronal FLAIR sequence (A), an increase in the intensity of the signal is observed in the temporo mesial region on the left side, with conserved anatomic structure (B) also visualized in the corresponding IR high resolution sequence. In FSE T2 coronal sequence (C) in a more posterior position, one of the secondary signs is observed, namely, less development of the posterior pillar of the trigone of the same side.
least one sequence T2- weighted, preferably in the coronal plane, FLAIR sequences and diffusion in the axial plane and specific sequences to study FLAIR and STIR hyppocampus with fine cuts 2mm in maximum thickness. In some patients we also counted with sequences with paramagnetic i.v. contrast based on gadolinium salts and in specific cases spectroscopic sequence with PRESS and CSI technique, TE 40 and 135 ms in the area of interest. In patients with vascular malformations, as we will later see we included and analyzed the contributions of gradient echo sequences (GRE T2*) or magnetic susceptibility (SWI) and of arterial or venous MRA with time of flight protocol TOF. RESULTS Of the selected 43 patients, 23 are of feminine sex and 20 of masculine sex, all over 14 years of age, their ages ranging from 14 to 47 years. In this group of patients the MRI performed in our Service was to control lesions or images already known and the study was part of the routine protocol for structural evaluation with the aim of including it or not in the epilepsy surgery program. All patients were catalogued as bearers of refractory partial epilepsy according to the criteria established by ILAE (2). Within the structural anomalies found we should highlight that in 27 of the 43 patients studied the topography of the lesions was temporal, concordant in every case with the clinical profile of the crisis. Figure 2: cortical focal dysplasia. Patient with partial simple motor crisis of right hemibody which presents in high resolution T2 sequence (A) a pathological cortical frontal left area, with increased signal I FLAIR (B), drawing a tract which is directed towards the lateral ventricle, located in depth. ORIGINAL ARTICLE E II/Vol. XV/Num. 2/ Jun 2012
Refractory focal epilepsy: findings by MRI. For didactic and illustrative purposes we will systematize the patients in the following groups (Table 1): patients without TMS 2 had a history of temporal epilepsy, both with a final diagnosis of cortical dysplasia. Alterations in development and congenital disorders (23). b.- Vascular malformations. Vascular malformations (8). Tumoral lesions (6). Miscellaneous (6). a.- Alterations in development and congenital disorders. This group is formed by different entities. The main group was formed by 13 patients bearing temporal epilepsy who were diagnosed as having temporomesial sclerosis (STM). (Figure 1). The remaining patients had different alterations in development: cortical dysplasias (Figure 2) (4 patients), grey matter heterotopias (3 cases), schizencephaly (1 case) and 2 patients with polymicrogyria. All these patients had a history of epilepsy since childhood. Of the Within this group 3 types of pathologies were found: aneurisms (1 case), cavernous angiomas ( 4 cases) and arterio- venous (3 cases). Within this group it was found one patient bearing an aneurism, in 2 patients with cavernous angiomas and in one of the patients an arterio- venous malformation localization of the lesion coincided with the clinic (temporal epilepsy). In all cases diagnosis was established by MRI which was confirmed in the cases of the aneurism and MAV by direct angiographic methods. In the case of patients with cavernous angiomas diagnosis was confirmed after surgery by pathologic anatomic study of the piece. (Figure 3). In patients with aneurisms or MAV conventional sequences showed typical findings added to the contributions of the sequences of the MRA. C.- Tumoral lesions. In this group of patients the lesions found were all primary neoplasias of the nervous system and low grade of the OMS. In all cases an MRI established the correct diagnosis of neoplasia, confirmed by the metabolic findings of the spectroscopy performed.
The tumor grade was also established, which coincided in every case with the final anatomo- pathological study. Of the 6 patients with tumoral lesions 2 corresponded to fibrillary astrocytomas (OMS grade II ), 1 case was a pilocytic astrocytoma ( OMS grade I), 1 neuro epithelial dysembrioplastic tumor (DNET) and in 2 cases it was gangliogliomas. Of the total lesions in this group, 4 were of temporal localization. (Figure 4). perinatal background related to the lesion found. In 3 of these patients localization of the sequelae area was temporal. One patient presented a lesion of the hypophiseal stem with diagnosis of probable hypothalamic hamartoma by stereotactic biopsy. The remaining patient presented epilepsy which had started recently and 6 months of evolution, refractory to all established medical treatment and which showed a large pathological area Figure 3: anterior right cavernous temporo mesial angioma. Typical image with high signal in T1 ( A ) areas due to the presence of hemoglobin in different stages, with artifice of magnetic susceptibility in GRE T2* (B) and classic popcorn aspect as seen in high resolution sequence IR (C). d.- Miscellaneous. In this group of patients, 6 in total, 4 patients were found with sequelae areas and gliosis, 3 of which were epileptic since infancy and with which the biopsy study showed to correspond to sub acute encephalitis. (Figure 5). DISCUSSION Epilepsy is a highly frequent neurological disease, MRI is the ORIGINAL ARTICLE E II/Vol. XV/Num. 2/ Jun 2012
Refractory focal epilepsy: findings by MRI. Figure 4: Ganglioglioma. Patient who presents a tumoral lesion located in the posterior sector of the temporo mesial region on the left side, heterogeneous with high signal cystic sectors in T2 (A), low signal in T1 (B) and without evidence of significant edema nor enhancement in sequence with i.v. contrast ( C ). method of reference to evaluate affected patients. The ways it manifests are very varied and there is a consensus on the definition and way of classifying the different syndromes it may present (1). Focal forms are the ones which most frequently present an anatomic structural substrate, which can be identified with different study techniques. This group of patients may be refractory to medical treatment and the structural study of the nervous system is of particular interest in order to identify an epileptogenic focus and evaluate the possibility of surgical treatment. When performing an MRI study on these patients it is vital to count with the largest array of clinical and physiological information possible, which definitely increases the sensitivity of the method to identify structural anomalies or lesions which are the cause of the disease. This has been particularly proven in the case of patients with focal and temporal epilepsy, in which the percentage of pathological studies increases notably when the patients are referred with the clinical categorization of temporal epilepsy and lateralization of focus. Using high resolution sequences is indispensable since they significantly increase global performance of the method. That is why generic protocols, not destined to the study of deep regions, such as the temporal lobule, pass by a significant percentage of lesions.
CONCLUSIONS In our series, all patients were bearers of focal epilepsy and most of them (62,7%) of temporal localization, which coincided in all cases with localization of the anomaly or lesion found. Furthermore, 41 out of 43 patients presented the alterations most frequently found in adult patients as being responsible for refractory focal epilepsy according to the consulted literature. A point to highlight in this small series is that all the patients referred as bearers of refractory epilepsy presented anomalies diagnosed by MRI, there weren t no cases of negative MRI and other methods which established the diagnosis. It is vital to know the wide spectrum of alterations, which can be the cause of functional alterations in the patient with refractory focal epilepsy, correct anatomic and structural analysis of the encephalus and its different areas is of great importance. MRI protocols used must be directed towards clinical suspicion, type of epilepsy and performed with all the available physiological information, which allows carrying out a detailed analysis of the encephalic region, probably pathological. Taking into account the multiple diagnostic possibilities and carrying out a detailed analysis of the signs found, a positive diagnosis may be established in most cases with good levels of sensitivity and specificity. A B C Figure 5: sub acute encephalitis. Patient with final diagnosis of sub acute encephalitis by surgical biopsy of temporal lobule on the left side. In FLAIR (A) a large area with edema is observed, with effect of mass with high signal in diffusion ( B ) and without enhancement with i.v. contrast (C). ORIGINAL ARTICLE E II/Vol. XV/Num. 2/ Jun 2012
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