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INVITED REVIEW |
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| Year : 2008 | Volume
: 3
| Issue : 1 | Page : 2-6 |
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Temporal lobe epilepsy in children
Jayanti Mani
Department of Neurology, Bombay Hospital Institute of Medical Sciences and Medical Research Centre and Wockhardt Hospitals, Mumbai, Maharashtra, India
Correspondence Address:
Jayanti Mani
R. No. 209, New Wing IInd floor, MRC Building, Bombay Hospital, 12, New Marine Lines, Mumbai - 400 020, Maharashtra
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/1817-1745.40584
 Abstract | | |
Temporal lobe epilepsy is a fairly homogenous syndrome in adults, with hippocampal sclerosis being the commonest etiology. In children, temporal lobe epilepsy is more commonly due to cortical dysplasia or tumors. The semiology and electrophysiology of temporal lobe seizures in children are distinct from adults and have age-dependent variations. The first-line treatment option in children includes antiepileptic drugs. Ketogenic diet and surgery are therapeutic options in refractory pediatric temporal lobe epilepsy.
Keywords: Epilepsy, pediatric, temporal
How to cite this article:
Mani J. Temporal lobe epilepsy in children. J Pediatr Neurosci 2008;3:2-6 |
| Introduction | |  |
Temporal lobe epilepsy (TLE) in adults and adolescents is a fairly homogeneous syndrome, both in terms of seizure semiology and in terms of its pathology; and it has been studied extensively. Temporal lobe epilepsy in infants and young children has a different clinico-pathological picture. Clinically, the concept of complex partial seizures, which may be useful in adults, is difficult to apply to infants, since it is often not possible to assess impairment of consciousness in this age group. In contrast to adult and adolescent patients, mesial temporal sclerosis is a rare finding in infants, in whom the pathological abnormalities associated with seizures of temporal lobe origin consist mostly of dysplasias, migrational disorders, hamartomas and low-grade tumors such as gangliogliomas.
| Mesial Temporal Lobe Epilepsy Syndrome in Adults | | |
The temporal lobe plays an extremely important role in the refractory partial epilepsies in adolescents and adults. TLE in adults is a rather homogenous syndrome, and mesial temporal sclerosis (MTS) is its most common pathologic substrate. This constitutes the mesial temporal lobe epilepsy (MTLE) syndrome. It is defined not only by the topography of the pathology but also on clinical, EEG and evolutive features. [1]
Clinical and evolutive features
It is associated with febrile seizures in at least 40% of cases, [2] which is often considered the first phase of the syndrome. Patients may report other preceding insults like head trauma, birth injury or infection and prolonged nonfebrile convulsions in childhood - a second quiescent phase of variable latency.
A third phase of chronic epilepsy begins in the second half of the first decade of life with refractory habitual complex partial seizures.
Seizure description
Typical mesial temporal seizures start with an epigastric aura associated with fear, followed by behavioral arrest, oroalimentary and ipsilateral hand automatisms, contralateral limb dystonic posturing. Secondarily generalized seizures are rare.
Associated problems
Memory disturbances are common with left hemisphere involvement.
EEG features
Interictal: Anterior temporal, subtemporal and sphenoidal spikes.
Ictal: The typical pattern is a theta frequency rhythm that is best appreciated over the sphenoidal or basal temporal electrode array.
Neuroimaging
High-resolution MR images of the temporal lobes reveal [Figure - 1]:
- Increased signal in the hippocampus on FLAIR and T2 W images
- Loss of hippocampal volume on T1 images
- Loss of gray-white differentiation of the hippocampus
Pathology
MTS is the commonest substrate for mesial temporal epilepsy in adults. This includes neuronal loss in the cornu ammonis CA1 region of the hippocampus, moderate loss in CA3/CA4 with relative sparing of the CA2 region. The subiculum, entorhinal cortex are resistant to cell loss
| Etiology of TLE in Children | | |
Critical differences exist between TLE in adults and children.
Unlike in adults, isolated MTS is reported in very few childhood cases. Low-grade neoplasms and cortical dysplasia are common causes of TLE in children. These may involve the mesial temporal structures or the lateral neocortex or both. Even in children with MTS, it is rarely isolated, but rather coexists with cortical dysplasia. Temporal lobe epilepsies due to lesions other than MTS are likely to present first at an earlier age than isolated MTS.
Semiology of TLE children
Semiology of TLE in children older than six years resembles adult semiology, but younger children exhibited features reminiscent of frontal lobe seizures, with symmetric motor phenomena of the limbs and head dropping. [3] Prominent and early motor features in the form of tonic, myoclonic or infantile spasms are common in children younger than three years and progressively decrease with age. [4] Complexity of mouth and hand automatisms increases with age. Ictal semiology has been demonstrated to have poor localizing value in TLE in very young children. [5] Case series have also documented the occurrence of epileptic spasms in patients with focal temporal lesions. [6]
The main distinctive features of complex partial seizures of temporal lobe origin in infants are (1) a predominance of behavioral arrest with possible impairment of consciousness, (2) no identifiable aura, (3) automatisms that are discrete and mostly orofacial, (4) more prominent convulsive activity and (5) a longer duration (more than one minute). In addition, seizures of temporal lobe origin in infants may appear clinically generalized, such as infantile spasms or generalized tonic seizures
EEG patterns in TLE in children
Older children with TLE due to MTS demonstrate interictal and ictal EEG patterns similar to those in adults, which are of good localizing value. However, infants and younger children with temporal lobe neoplasms often have unusual EEG features including bilateral, multifocal or contralateral interictal discharges and poorly localized ictal onsets. [3],[5] Despite these EEG features, seizure outcomes have been good after surgery. Thus the main value of video EEG in very young children with neocortical temporal epilepsy is to establish that the reported ictal behavior is indeed epileptic with temporal lobe semiology and not to localize ictal EEG patterns.
Imaging in pediatric TLE
As discussed above, seizure semiology and EEG may not clearly localize partial seizures in infants and very small children. Neuroimaging, both structural and functional, may be crucial in clarifying the diagnosis and proceeding with presurgical evaluation. Relatively recent advances in MRI technology have revolutionized the field and resulted in a paradigm shift in the management of refractory lesional pediatric epilepsy. While the role of MRI in the identification of tumors is unquestionable [Figure - 2], the major impact has been in the identification of small focal cortical dysplasias and other subtle focal lesions.
Functional imaging studies like PET (positron emission tomography) and ictal and interictal SPECT (single photon emission computed tomography) may provide additional information in a few patients and thus aid in clinical decision making. Chugani et al. have demonstrated the value of PET scans to identify focal lesions in infants with epileptic spasms. [7] They believe that PET studies are particularly useful in infants in whom incomplete myelination may limit the value of the MRI.
| Treatment | | |
Medical therapy for TLE
A variety of conventional and newer anti-epileptic drugs AEDs are available for medical therapy of recurrent seizures. Benefits of AED therapy outweigh risks in patients who have had more than two unprovoked seizures. Most drugs are approved for pediatric use and are available in pediatric formulations. Large trials have established similar efficacy of conventional AEDs in children with focal epilepsy. [8],[9] The role of newer AEDs in pediatric epilepsy has not been clearly defined yet, especially with respect to side-effect profiles. The current guidelines for the use of AEDs in refractory epilepsies have been outlined by the practice parameters published by the American Academy of Neurology and American Epilepsy Society (AANAES). [10]
Surgical therapy for TLE
About 10-20% of epilepsy is refractory to medical therapy. Failure of the first AED trial in children predicts refractoriness to medical therapy at two years. [11] Failure of the first AED has a positive predictive value of 0.89 and a negative predictive value of 0.95. The chances of seizure freedom in children who failed one AED are about 11% with additional AEDs. These results are similar to trials in adults. [12] Hence most experts opine that patients who fail adequate trials of two AEDs should be considered for a presurgical evaluation.
While newer antiepileptic drugs have widened drug choice and have better tolerability, none of the existing drugs are likely to cure epilepsy. While a third of newly diagnosed pediatric TLE remits spontaneously, presence of a lesion on MRI is a predictor of intractability. [13] Surgical resection of a focal lesion offers the best chances of seizure freedom. Presurgical evaluation is required to confirm the relationship of the lesion to the ictal onset zone and to eloquent areas in the cortex. The surgical strategy may range from a limited lesionectomy to selective amygdalohippocampectomy (SAH), anterior mesial temporal resection and finally a standard mesial temporal plus neocortical resection. The limited data available comparing various surgical techniques reports worse seizure outcomes after selective surgery in children. [14] Significantly better seizure outcome (95%) was achieved after standard temporal lobectomy compared with more limited surgery like SAH (75%) or lesionectomy plus hippocampectomy (77%). Larger resections are potentially likely to worsen neuropsychological outcome after TLE surgery, especially of the dominant temporal lobe. Systematic studies comparing the neuropsychological outcomes after the various surgical strategies are lacking.
The other unique situation that is encountered in children with TLE is dual pathology. Mohammed et al. report coexistent cortical dysplasia on histopathology in nearly 80% of children and adolescents who had temporal lobectomy for MTS. [15] Interestingly the presence of dual pathology did not portend worse surgical outcome in their study group, with 90% being seizure free after standard temporal lobectomy. The existence of dual pathology is also likely to influence the choice of the surgical technique.
| Outcome Measures | | |
Seizure freedom
Much evidence is now available regarding the effectiveness of surgery for refractory TLE. Based on a single randomized trial [16] and an analysis of retrospective data from several centers globally, the AANAES established that approximately two-thirds of patients with refractory TLE were free of disabling seizures after standard anterior temporal lobectomy. Exclusively pediatric studies are few, but Clusmann et al. report good outcome in 86.5% children with a mean follow-up of 48 months. [14] Wyllie and colleagues report seizure-free outcomes in 74% children (<12 years of age) and 80% adolescents (13-20 years) after temporal resections. [17] The outcome is found to be slightly better with low-grade neoplasms and restricted lesions (86%) than with cortical (56%) or hippocampal sclerosis (75%) or nonlesional cases in short-term analysis. [14] Long-term outcome data is significantly lacking in children. In adults it has been established that seizure freedom rates after TLE may not be sustained in the longer term. Seizure freedom rates decline from 66% at one- or two-year follow-up to 45-55% at 10 years. [18],[19] In adults the one-year outcome is predictive of the long-term durability of seizure outcome [18] (Salanova) but such an association has not been reported in children. Long-term data in children from pooled data (444 patients) suggest seizure freedom rate of 62%.
Predictors of seizure outcome
In adults, a previous history of febrile seizures, unilateral interictal discharges, concordant unilateral temporal ictal onsets, type I seizure pattern, concordant and unilateral focal MRI lesion, absence of interictal discharges on postoperative EEG and infrequent and disabling seizures in the first operative year have been predictors of good seizure outcome post-surgery.
In the outcome studies performed in children, however, the validity of these variables in predicting good postoperative outcome was questionable. In a study on 33 children with TLE, younger age at surgery, shorter duration of epilepsy, unilateral temporal lesion on MRI and right-sided surgery showed trends toward a better seizure outcome after surgery. [20]
These confusing and counter-intuitive results suggest that the predictors of outcome after surgery may be different in the pediatric and adult populations.
Neuropsychological outcome
The evidence for neuropsychological impact of TLE surgery comes from small studies and is conflicting. Some report unchanged or improved verbal memory scores, [21] and others document verbal memory declines after dominant temporal lobectomy (Adams, Williams). [22],[23] However, the functional significance of the decline in memory scores is not clear.
Complete freedom from seizures has been identified as crucial for postoperative improvement in quality of life in adults with refractory epilepsy, but quality of life (QOL) issues remain to be studied in children.
Timing of surgery
The other major issue that needs to be evaluated in children is the timing of surgery. In their study of 22 patients with childhood-onset TLE who had surgery in adulthood, Mizrahi et al. suggest that patients with surgery later in life had problems with adjusting to a seizure-free existence despite good outcome with respect to seizure freedom. [24] The ongoing Early randomized surgical epilepsy trial (ERSET) to evaluate early surgery versus medical therapy in adult TLE began enrollment in 2003 and results are still awaited.
Other treatment options
Ketogenic diet
This high-fat low-carbohydrate and low-protein diet is another therapeutic option in drug-resistant epilepsy. Although it was initially introduced for resistant epilepsy due to some metabolic deficiencies, it is now widely prescribed for other medically resistant generalized epilepsies as well.
The evidence for the effectiveness of ketogenic diet in drug-resistant partial epilepsies is conflicting, but no systematic studies have compared the ketogenic diet in partial versus generalized epilepsies. The diet may be considered in drug-resistant TLE patients who are not good candidates for surgery. Problems with the diet include poor compliance due to poor tolerability and metabolic derangements, reduced bone density, hemolytic anemia, renal stones.
Vagal nerve stimulation
The vagal nerve stimulator was first implanted in humans in 1989. It involves continuous pulsed stimulation of the vagus nerve through an implanted pacemaker and is approved for use in refractory partial and generalized epilepsies. Its efficacy is modest; and in the largest trial that included 198 patients, a 50% reduction in seizures was reported in 23% versus 16% in controls at three months. [25] A review of vagal nerve stimulation (VNS) therapy in the pediatric population suggests that it is at least as effective in children as in adults. [26] Costs prohibit its routine use, and it is reserved for drug-resistant epilepsies if surgery is not an option.
| Future Therapies | | |
In the current scenario, respective surgery offers the best chances of cure for resistant focal lesional epilepsy in carefully selected patients.
Future areas of research include newer AED development, better imaging techniques to map brain structure and function and brain stimulation techniques.
Recommendations for lesional epilepsy in older children and adolescents
Cortical dysplasia, tumors, mesial temporal sclerosis, remote symptomatic epilepsy due to perinatal or childhood brain injury are common causes of refractory lesional epilepsies in late childhood and adolescence. Rasmussen's encephalitis is a rare cause for refractory epilepsy that manifests at this age.
Treatment options in epilepsy are based on various medical, social and economic considerations and may vary with the social context. In the context of the current evidence,
- Medical therapy with AEDs will be the first treatment option in lesional epilepsies in children.
- The choice of the AED would be driven by issues of tolerance and cost rather than efficacy.
- A trial of at least two AEDs in adequate therapeutic doses for a period of one to two years is recommended.
- In view of the excellent results offered by surgery for lesional TLE, it would appropriate to evaluate surgical candidacy after a trial of two AEDs.
- Presurgical evaluation establishes the location of the epileptogenic zone based on concordance of clinical EEG and imaging data. Additionally the seizure frequency and its impact on cognitive development; the pathology of the lesion, its anatomical location with regard to eloquent cortex and easy resectability will be factors that influence decision making.
- If surgery is not an option, other alternatives, viz., ketogenic diet or vagal nerve stimulation, may be considered.
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[Figure - 1], [Figure - 2]
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