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Clínica de Epilepsia | Trabalhos na Íntegra

EXTENDED, ONE-STAGE CALLOSAL SECTION FOR TREATMENT OF REFRACTORY SECONDARY GENERALIZED EPILEPSY IN PATIENTS WITH LENNOX-GASTAUT AND LENNOX-like SYNDROME

Arthur Cukiert
Jose Augusto Burattini
Pedro Paulo Mariani
Ródio Brandão Câmara
Lauro Seda
Cristine Mella Baldauf
Meire Argentoni
Carla Baise-Zung
Cássio Roberto Forster
Valeria Antakli Mello

Department of Neurology and Neurosurgery, Hospital Brigadeiro and
São Paulo Epilepsy Clinic, São Paulo SP, Brazil

INTRODUCTION

Callosal section has been used to treat different epileptic syndromes over the last decades1. The surgical technique also varied among centers, and many of the published series have been obtain before the microsurgical era. More recently, papers reporting on callosal section in epilepsy concentrated in a more homogeneous population, namely patients with secondary generalized epilepsy (Lennox-Gastaut syndrome)2.

The extent of callosal section has varied among the different centers and how far the corpus callosum has to be sectioned to obtain the best results is still under debate. Some authors have performed anterior callosal section only, while others have performed complete callosal sections (as a one or 2-stage procedure)3-7.

This paper describes the results regarding seizure’s outcome obtained after extended callosal section, leaving only the splenium of the callosum intact, in a very homogeneous population of patients with Lennox-Gastaut and Lennox-like syndrome.

METHODS

Seventy-six consecutive patients submitted to callosal section at the Hospital Brigadeiro and Sao Paulo Epilepsy Clinic from 1996 to 2003 have been retrospectively reviewed. Mean age at seizure’s onset was 2.8 years; age at operation ranged from 2 to 28 years (mean = 11,2 years). There were 42 men and follow-up time ranged from 2 to 9 years (mean 4,7 years). All patients had refractory secondary generalized epilepsy and have been categorized as having Lennox-Gastaut (n= 28) or Lennox-like (n=48) syndrome.

All patients had multiple seizures per day and had been unsuccessfully treated with high dose politherapy. Seizure’s pattern included tonic, atonic, tonic-clonic, myoclonic and atypical absence episodes. More then one seizure type was present in all patients; 10 patients had all seizure’s type listed above, 42 had four, 14 had three and 10 had two seizure’s types. All patients had multifocal EEG abnormalities; on the other hand, secondary bilateral synchrony was the main interictal finding. Ictal recordings have been obtained from 52 patients and all seizures had generalized ictal onsets. It was not possible to keep the remaining patients in the video-EEG unit in order to obtain ictal recordings, mainly due to agitation, aggressive behavior and mental retardation. MRI findings included diffuse atrophy (n=54) and non-specific focal or multifocal lesions (such as gliosis, vascular anomaly, cyst, demielinating lesion)(n=22). No patient with a definite etiology (such as cortical dysplasia) was included in this series. All patients were severely mentally retarded and only 8 of them were able to complete formal neuropsychological testing (all within the mental retardation functioning level). Pre- and postoperative seizure counts were obtained from monthly diary annotations performed by the family or caregiver.

All patients have been submitted to a maximized callosal section. This has been performed as a one-stage procedure under general anesthesia. After positioning the head in such a way that the corpus callosum’s body would be perpendicular to the floor (as appreciated from a midsagittal MRI scan), a right frontal craniotomy centered over the coronal suture was carried out. After opening of the duramater, the interhemispheric fissure was dissected and the corpus callosum was exposed. The anterior half of the corpus callosum was then sectioned under direct vision using the surgical microscope. The posterior portion of the corpus callosum was then aspirated using an intracallosal suction technique, leaving only the splenium in place. While performing the aspiration of the posterior portion of the callosum, the surgeon followed the intrinsic anatomy of this structure that usually included thinning of the callosal body at the midparietal topography followed by an increase in its diameter before reaching the splenium (this could also be foreseen from individual midsagittal MR scans). The section was terminated when the posterior cingulate cortex could be identified (Figure 1).

RESULTS

Overall, 74 patients had atonic, 56 myoclonic, 68 atypical absence, 42 tonic-clonic and 42 tonic seizures. Worthwhile decrease (>50%) in generalized seizure frequency has been noted in 69 patients; 7 patients have not been improved by the procedure. Fifty-two patients had at least 90% improvement in generalized seizure frequency. A worthwhile reduction (>50%) in specific seizure frequency has been noted in 92% of the atonic, 82% of the atypical absence, 57% of the tonic-clonic, 51% of the tonic and 27% of the myoclonic seizures. Seven patients became seizure-free.

Post-operative EEG examinations have been available for 56 patients. In 42 patients there has been a complete rupture of secondary bilateral synchrony (Figure 2); in 6, only partial rupture of secondary bilateral synchrony has been noted and in 8 no modification regarding bilateral synchrony has been noted.

Seventy-two patients disclosed signs or symptoms of an acute callosal disconnection syndrome postoperatively: 68 patients had apathy, 54 urinary incontinence, 8 right hemineglect and 6 low-verbal output (1 mutism). The mean duration of the acute disconnection syndrome has been 16 days (8-50 days). There has been no additional surgical morbidity or mortality.

Sixty-five patients disclosed a marked increase in the attention level. Although it has been impossible to formally measure this finding, this has been a very consistent report obtained from the family and caregivers; in many instances, this improvement in attention’s level has been considered as more important in terms of quality of life then the seizure frequency reduction itself.

One patient disclosed a transient increase in focal seizure frequency. Two patients disclosed the classical callosal split syndrome (intermanual conflict) after the disappearance of the acute disconnection syndrome.

DISCUSSION

This paper reported one of the larger series of patients submitted to callosotomy. It is one of the few studies to report on the results of callosal section in such a highly homogeneous patient population with refractory secondary generalized epilepsy of the Lennox-Gastaut and Lennox-like type and the first to report on the effectiveness and safety of performing extended callosal section as a one-stage procedure in this patient’s group.

The better seizure’s outcome reported here is very likely related to the refinement of patient’s selection, more extensive callosal section and better surgical technique. All patients have been operated under general anesthesia and by means of microsurgical technique. Operative complications such as mesial hemisphere infarcts, hemispheric edema and hemiparesis noted in earlier series were not documented in our patients5.

A significant increase in focal seizures immediately after callosal section has been previously reported8,9. In our series, only one patient did so and this was not a relevant postoperative issue. This low prevalence of focal seizure increase might be related to differences in patient selection criteria or intraoperative anesthetic and anticonvulsant policies between the centers.

Most of the symptoms found in the acute postoperative disconnection syndrome might be attributed to frontal lobe disconnection. We have observed a clear transient reduction in verbal output postoperatively in 6 patients (1 mutism.). Urinary incontinence occurred in the majority of the patients and is very likely related to the disconnection of the mesial frontal lobes, resembling those symptoms found in high or normal pressure hydrocephalus. Postoperative apathy was probably related to both mesial and convexity frontal lobe disconnection. The only aspect of the acute disconnection syndrome that could be attributed to the posterior corpus callosum was the right hemineglect found in 8 patients.

Increased attention level has been a very consistent finding, but very difficult to measure. Although callosal section was not performed in this patient population in order to improve attention, this finding was considered by many families as more relevant then seizure frequency reduction regarding improvement in quality of life10,11. This increase in attention level might be related to the rupture of bifrontal secondary bilateral synchrony.

Although we got reasonable results treating this same patient population with vagus nerve stimulation (VNS), so far there is no evidence-based study suggesting that VNS would be better then callosal section12. Moreover, in those patients who got a worthwhile reduction in seizure frequency after vagus nerve implantation we did not notice the attention’s level increase described above and there was no rupture in secondary bilateral synchrony. Although callosal section is an intracranial procedure it can be very safely performed.

Atonic seizures represented the seizure’s pattern with the best response to callosal section while myoclonic seizures got the worse result, which is in agreement with other authors findings13. Almost 10% (7 out of 76) of the patients have been seizure-free after surgery. This finding was unexpected due to the clearly palliative nature of the procedure. Seven patients had no response whatsoever to the surgical procedure. All of them had thin corpora callosum.

There is plenty animal and human clinical data that emphasized the role of the corpus callosum on secondary bilateral synchrony genesis and strongly suggests that complete callosal section would be the best option to disrupt completely secondary bilateral synchrony in patients with secondary generalized epilepsy14. We believe that complete callosal section would be the best treatment option for these patients. In our approach, the splenium was left in place, not aiming to avoid the classical visuo-motor disconnection syndrome, but due to the fact the splenium’s downward curve makes it usually difficult to perform its section in such one-stage procedure. The classical split-brain syndrome (intermanual conflict) was transiently noted in only one patient.

Although callosal section is a palliative (not curative) procedure15, it remains a good surgical option to treat this challenging patient population. Although not a primary objective of surgery, an increase in attention level is as useful as seizure control in improving the quality of life of these patients.

REFERENCE

1- Wilson DH, Reeves A, Gazzaniga M. Division of the corpus callosum for uncontrollable epilepsy. Neurology 1978; 28:649-53.

2- Maehara T, Shimizu H. Surgical outcome of corpus callosotomy in patients with drop attacks. Epilepsia 2001; 42:67-71.

3- Sakas DE, Phillips J. Anterior callosotomy in the management of intractable epileptic seizures: significance of the extent of resection.
Acta Neurochir (Wien) 1996; 138:700-7.

4- Rossi GF, Colicchio G, Marchese E, Pompucci A. Callosotomy for severe epilepsies with generalized seizures: outcome and prognostic factors.
Acta Neurochir (Wien) 1996; 138:221-7.

5- Mamelak AN, Barbaro NM, Walker JA, Laxer KD. Corpus callosotomy: a quantitative study of the extent of resection, seizure control, and neuropsychological outcome. J Neurosurg 1993; 79:688-95.

6- Cendes F, Ragazzo PC, da Costa V, Martins LF. Corpus callosotomy in treatment of medically resistant epilepsy: preliminary results in a pediatric population. Epilepsia 1993; 34:910-7.

7- Oguni H, Olivier A, Andermann F, Comair J. Anterior callosotomy in the treatment of medically intractable epilepsies: a study of 43 patients with a mean follow-up of 39 months. Ann Neurol 1991; 30:357-64.

8- Gates JR, Rosenfeld WE, Maxwell RE, Lyons RE. Response of multiple seizure types to corpus callosum section. Epilepsia 1987; 28:28-34.

9- Spencer SS, Spencer DD, Williamson PD, Sass K, Novelly RA, Mattson RH. Corpus callosotomy for epilepsy. I. Seizure effects. Neurology 1988; 38:19-24.

10- Sassower KC, Rollinson DC, Duchowny M. Outcome of corpus callosotomy and other pediatric epilepsy surgery: parental perceptions. Epileptic Disord 2001; 3:197-202.

11- Lassonde M, Sauerwein C. Neuropsychological outcome of corpus callosotomy in children and adolescents. J Neurosurg Sci 1997; 41:67-73.

12- Karceski S. Vagus nerve stimulation and Lennox-Gastaut syndrome: a review of the literature and data from the VNS patient registry. CNS Spectr 2001; 6:766-70.

13- Nordgren RE, Reeves AG, Viguera AC, Roberts DW. Corpus callosotomy for intractable seizures in the pediatric age group. Arch Neurol 1991; 48:364-72.

14- Cukiert A, Timo-Iaria C. An evoked potential mapping of transcallosal projections in the cat. Arq Neuropsiquiatr 1989; 47:1-7.

15- McInerney J, Siegel AM, Nordgren RE, Williamson PD, Thadani VM, Jobst B, Reeves AG, Roberts DW. Long-term seizure outcome following corpus callosotomy in children. Stereotact Funct Neurosurg 1999; 73:79-83.

LEGENDS

Figure 1: Postoperative T2-weighted midsagittal MR slice showing the extent of callosal section performed in the present series. An extended callosal section was performed leaving only the splenium in place. A more lateral slice would show that the apparently intact portion of the rostrum is actually disconnected.

Figure 2: Left- Preoperative interictal EEG recording showing frequent bilateral and synchronous discharges; Right- Postoperative interictal EEG recording showing that secondary bilateral synchrony has been ruptured, although intense epileptic activity could be seen restricted to each hemisphere.

ABSTRACT

Purpose: This paper reports on the efficacy and safety of extended one-stage callosal section performed in a large and homogeneous series of patients.

Methods: Seventy-six patients with Lennox-Gastaut (n=28) and Lennox-like (n=48) syndrome were studied (42 men; mean age = 11,2 years). All patients had multiple seizures types per day, including atonic, tonic-clonic, atypical absence, myoclonic and tonic seizures. All of them were mentally retarded and EEG showed intense secondary bilateral synchrony in all of them. All patients were submitted to an extended, one-stage, callosal section, leaving only the splenium intact. Mean follow-up time was 4.7 years.

Results: Worthwhile improvement (>50%) was noted in 69 out of 76 patients; 52 patients had at least a 90% reduction in seizure frequency and seven patients has been rendered seizure’s-free after surgery. The seizure’s patterns that proved to be more responsive to surgery were atonic (92%), atypical absences (82%) and tonic-clonic (57%) seizures. All patients presented some degree of a transient acute postoperative disconnection syndrome. A consistent increase in attention’s level was observed postoperatively.

Conclusions: This paper reports one of the larger homogeneous series of patients submitted to callosotomy and is the first to report on the effectiveness and safety of performing extended callosal section in a single stage in this patient’s group. Extended callosal section should be considered a good palliative surgical option in this selected group of patients. The increase in attention’s level was as useful as seizure’s control in improving quality of life of these patients.