Epilepsia, 45(7):872–876, 2004 Blackwell Publishing, Inc. C 2004 International League Against Epilepsy
Surgical Treatment of Temporoparietooccipital Cortical Dysplasia in Infants: Report of Two Cases ∗ Roy Thomas Daniel, ‡Kathleen Meagher-Villemure, †Eliane Roulet, and ∗ Jean-Guy Villemure Departments of ∗ Neurosurgery, †Pediatric Neurology, and ‡Division of Pediatric Pathology, Centre Hospitalier Universitaire Vauduois, Lausanne, Switzerland
Summary: Purpose: Extensive multilobar cortical dysplasia in infants commonly is first seen with catastrophic epilepsy and poses a therapeutic challenge with respect to control of epilepsy, brain development, and psychosocial outcome. Experience with surgical treatment of these lesions is limited, often not very encouraging, and holds a higher operative risk when compared with that in older children and adults. Methods: Two infants were evaluated for surgical control of catastrophic epilepsy present since birth, along with a significant psychomotor developmental delay. Magnetic resonance imaging showed multilobar cortical dysplasia (temporoparietooccipital) with a good electroclinical correlation. They were treated with a temporal lobectomy and posterior (parietooccipital) disconnection.
Results: Both infants had excellent postoperative recovery and at follow-up (1.5 and 3.5 years) evaluation had total control of seizures with a definite “catch up” in their development, both motor and cognitive. No long-term complications have been detected to date. Conclusions: The incorporation of disconnective techniques in the surgery for extensive multilobar cortical dysplasia in infants has made it possible to achieve excellent seizure results by maximizing the extent of surgical treatment to include the entire epileptogenic zone. These techniques decrease perioperative morbidity, and we believe would decrease the potential for the development of long-term complications associated with large brain excisions. Key Words: Epilepsy—Multilobar resection— Hemispherectomy—Cortical dysplasia.
Cortical dysplasias (CDs) are being increasingly recognized as a cause of intractable epilepsy. Total resection of the lesion has been reported to be the predictor for a good seizure outcome (1). Experience with large multilobar dysplasia in infants is limited, and the results have not been gratifying. The main reasons are in part due to the difficulty at this age to define the exact extent of the lesion and to the surgical strategy applied in multilobar epilepsy.
quency of seizures ranged between 10 and 50 every day. Seizures were intractable to multiple anticonvulsants [carbamazepine (CBZ), phenobarbital (PB), vigabatrin (VGB), and clonazepam (CZP)]. Development was very slow during the first 6 months of life, with almost no progress during the last 3 months preceding the surgery. Neurologic examination (9 months) showed a passive infant with preferential gaze to the right, axial hypotonia, and a mild left-sided brachial hemiparesis. His development was significantly delayed, with a mental developmental quotient (DQ) at 33 corresponding to a level of a 3-month-old child. Magnetic resonance imaging (MRI) showed an increase in the volume of the right temporal lobe when compared with the opposite side. Poor differentiation was seen between gray and white matter in the right temporal, parietal, and occipital lobes. In addition, abnormal gyral patterns were noted in these regions, along with a closed schizencephalic cleft. These findings were indicative of an extensive CD involving the temporal, parietal, and occipital lobes on the right side (Fig. 1A). Interictal positron emission tomography (PET) scan showed hypometabolism in the right temporal and occipital lobes. Interictal single-photon emission computed tomography (SPECT) was suggestive of hypoperfusion in the right
CASE REPORTS Case 1 The patient, a 9-month-old infant, had seizures starting in the first week after birth. The seizures consisted of clonic movements of the left upper and lower limbs followed by deviation of the head and eyes to the left side, vocalization, extension of the right upper limb, followed by clonic movements of all four limbs. The freAccepted March 14, 2004. Address correspondence and reprint requests to Dr. R.T. Daniel at Servive de Neurochirurgie, Centre Hospitalier Universitaire Vaudois, Rue du Bugnon 46, Lausanne 1011, Switzerland. E-mail:
[email protected]
872
MULTILOBAR CORTICAL DYSPLASIA IN INFANTS
873
FIG. 1. Magnetic resonance imaging (MRI) fluid-attenuated inversion recovery (FLAIR) axial scan showing the extensive cortical dysplasia in the right temporooccipital lobes for patient 1 is shown (A). B: Temporooccipital part of the cortical dysplasia in patient 2, as seen on a T1 W sagittal MRI scan.
temporal and occipital lobes. Ictal SPECT showed relative hyperperfusion in the occipital and anterolateral temporal lobes. The interictal EEG showed a relative flattening of the background activity on the right hemisphere with numerous spikes, spikes, and sharp waves mainly over the temporooccipital areas and rarely over the parietal area. The ictal EEG was characterized by rhythmic spike-andwaves over the right temporooccipital region, with spread to the posterior part of the left hemisphere. The aim of the surgery was to eliminate the influence of the large dysplastic epileptogenic zone comprising the temporal, parietal, and occipital lobes. This infant underwent right temporal lobectomy and parietooccipital disconnection with no postoperative complications (Fig. 2). At follow-up evaluation 3.5 years after surgery, he was seizure free with decreasing dosage of CBZ. Neurologic examination showed persistent mild left brachial paresis and slightly spastic gait. He had also made significant developmental progress, with a DQ of 59. Case 2 The patient, a 4-month-old infant, had seizures at age 10 days. Initially the seizures were partial complex, consisting of an arrest of activity, loss of contact, abnormal movements of upper limbs, and blinking of eyelids. At age 1 month, the seizure activity became associated with infantile spasms occurring in clusters. The seizures were intractable to CBZ, PHT, and clobazam (CLB). The frequency of seizures was quite variable, with ≥30 to 40 seizures every day. Neurologic examination at 4 months revealed a lethargic baby with preferential gaze to the left, global hypotonia, and no significant asymmetry in tone and mobility of the limbs. Visual and auditory reactions were intermittently present but observed mental development was less than a 1-month level. MRI showed a large cortical malformation involving the left temporal,
parietal, and occipital lobes with malformed gyri with increased thickness (Fig. 1B). The lesion extended anteriorly up to the postcentral sulcus. The interictal EEG showed bursts of spikes and slow waves interrupted by short periods of flattening of the background activity over the left temporoparietal areas. Sporadic asynchronous spikes also were seen over the left temporal region. Seizures began with a fast recruiting activity of low amplitude in the left parietal region, followed by rhythmic spikes and spike-and-waves, and progressive spread to the right hemisphere. Surgery was decided on the basis of catastrophic epilepsy, in the presence of an extensive malformation. The infant underwent a left temporal lobectomy and posterior disconnection (parietal and occipital lobes), which was not complicated by any intraoperative or postoperative problems. A few staring spells occurred in the first postoperative week, and the child was noted to have slightly reduced spontaneous movements of the right upper and lower limbs. Evaluation at age 1 year showed developmental progress in all fields, with a mental DQ of 62 (Bartez scales), corresponding to the level of a 10month-old child. At the latest follow-up review, 1.5 years after surgery, the child was seizure free, receiving treatment with CBZ. Neurologic examination disclosed right hemianopia and a slight right brachial hemiparesis with preserved finger movements. Operative procedure Electrocorticography is done over the exposed cortices, and the location of the sensorimotor cortex is identified either by known anatomic landmarks in correlation with MRI and/or electrophysiological mapping with evoked potentials and motor cortex stimulation. Standard temporal lobectomy is done, including resection of the amygdala and the anterior hippocampus up to the level of the choroid fissure. From the limit of the temporal cortical resection, Epilepsia, Vol. 45, No. 7, 2004
874
R. T. DANIEL ET AL.
FIG. 2. Diagrammatic representation of the temporal lobectomy and posterior (parietooccipital) disconnection. The structures marked are pericallosal artery (1), falx (2), posterior bank of the intraparietal disconnection (3), septum pellucidum (4) and callosal disconnection, and posterior hippocampotomy (5, curved arrow).
the incision is continued around the sylvian fissure to the parietal operculum and stopping just short of the primary sensory gyrus. This incision is then deepened to reach the ventricle. From its posterior limit, the incision is turned upward posterior to the sensory gyrus along the full thickness of the parietal lobe and along the parasagittal tissue to reach the corpus callosum. The posterior corpus callosum is then sectioned. The callosotomy incision is continued through the medial wall of the ventricle to disconnect the fornix. Pathology In both cases, the resected material obtained from surgery revealed similar findings, with structural abnormalities consistent with CD. The normal architecture of the cerebral cortex was not achieved, with no distinct layering formed. An accumulation of numerous balloon cells was present throughout the whole cerebral cortex, as well as in the underlying white matter, indicative of the Taylor type of cortical dysplasia (Fig. 3A and B). Many enlarged cytomegalic neurons were noted (Fig. 3C). In case 2, rare nodular neuroglial heterotopias also were seen in the very deep white matter region. DISCUSSION Epilepsy in infants is frequently a challenging problem, especially in large CDs seen with catastrophic epilepsy (high seizure frequency) and almost no developmental progress possible because of continuous ictal and postictal states. When compared with adults, this group of patients has many significant differences. The plasticity of the brain and the noxious effects of frequent uncontrolled seizures and antiepileptic medications (at high doses) on the developing brain must be considered. Added to this are the social implications of a debilitating disease and the lost time at schooling due to the disease. Therefore an early surgical intervention is mandatory in these cases. With the adEpilepsia, Vol. 45, No. 7, 2004
vent of MRI with specific protocols to detect epileptogenic lesions, focal cortical dysplasias are now increasingly being recognized. The results of surgery for focal cortical dysplasias (FCDs) reported in literature are not uniformly good (2–7). The less favorable outcomes in some patients with FCDs have been thought to be the result of extension of lesions to outside or remote to the MRI-visible lesion (8). In infants, these lesions may be difficult to image because of incomplete myelination. Many epilepsy surgery groups therefore use intraoperative electrocorticography, prolonged subdural recordings, and PET studies to define these lesions accurately. It also has been shown that the extent of resection of the dysplasia correlates with good seizure outcome (1,5,9). For these reasons, the results of surgery for FCDs have remained suboptimal and are a matter of debate (6,10). In a recent study of 68 children after surgery for CD (included 14 children younger than 2 years; both large and small CDs), Engel’s class I and II outcomes were obtained in 60% of the children (1). In this series, 12 of 23 patients younger than 3 years were seizure free after surgery, and in the group of patients with uni/multilobar posterior dysplasias, 45% of 23 children had either Engel’s class I or II outcomes. The experience with large multilobar dysplasias (subhemispheric) in infants has been limited and not always gratifying. Of five patients with subhemispheric dysplasias, Holthausen (11) reported one patient with Engel’s IIB and four patients with Engel’s IIIA outcomes. Of three patients with similar large FCDs, Engel’s outcomes of I, III, and IV were reported by Duchowny (3). However, in the series reported by Wyllie et al. (12) on epilepsy in infants, two cases had large parietooccipitotemporal dysplastic lesions and were seizure free at intervals of 10 and 17 months after surgery. In a report of three infants after surgery for malformations of cortical development, Engel’s class I outcome was obtained in one patient, whereas the other two patients had postoperative seizures (13).
MULTILOBAR CORTICAL DYSPLASIA IN INFANTS
875
FIG. 3. Histopathologic features in both cases were similar. A: Cortical dysplasia with numerous intracortical balloon cells, H&E ×400. B: On immunohistochemistry, the balloon cells have strong reactivity with glial fibrillary acidic protein (×250). C: With Bielschowsky stain (×400), many cytomegalic and dysmorphic neurons loaded with neurofibrillary material were identified and often seen closely apposed to the balloon cells.
Epilepsy surgery in infants also poses a higher risk of perioperative complications. In the series of 12 patients reported by Wyllie (12), one death occurred, and two postoperative complications (subdural hematoma and loculated temporal horn) were successfully managed. The operative mortality in the series of Duchowny (3) was reported to be 6%. Therefore the benefits of the surgery for these lesions in infants must weighed against these potential complications, and most groups are cautious while evaluating infants for epilepsy surgery. Apart from perioperative complications, in patients with large brain excisions, early or late hydrocephalus is known to develop (1,13–15). Introduction of disconnective techniques has reduced the complications in surgery for hemispheric disease (16). The surgical approach described here is thus the logical evolution
of the concept of an anatomically subtotal but functionally complete resection in subhemispheric dysplasias akin to the development of similar techniques in hemispheric epilepsy (Fig. 4). This procedure minimizes the size of the resection cavity and consequently reduces perioperative morbidity, in addition to prevention of hydrocephalus. As the dysplastic cortex left behind is completely disconnected from all its connections, the seizure outcome would be identical to that of multilobar resection. CONCLUSION Subhemispheric CD in infants is a difficult condition to treat because of the problems in identifying the entire lesion, the higher surgical risk, and the possibility Epilepsia, Vol. 45, No. 7, 2004
876
R. T. DANIEL ET AL.
FIG. 4. Postoperative T1 W sagittal magnetic resonance imaging of patient 2, showing the temporal resection and the site of the parietooccipital disconnection.
of delayed complications. However, the potential benefits of seizure control to brain development, education, and psychosocial adaptation cannot be understated. The introduction of disconnective techniques in multilobar surgery maximizes the extent of the surgical treatment. This surgical strategy provides excellent seizure outcome, reduces perioperative morbidity, and avoids potential long-term complications associated with large brain excisions. Acknowledgment: This work was partly supported by the Swiss National Science Foundation (3200-052991/97 and the Vaud-Geneva surgical epilepsy program).
REFERENCES 1. Kloss S, Pieper T, Pannek H, et al. Epilpesy surgery in children with focal cortical dysplasia (FCD): results of long-term seizure outcome. Neuropediatrics 2002;33:21–6. 2. Chugani HT, Shewmon DA, Shields WD, et al. Surgery for intractable infantile spasms: neuroimaging perspectives. Epilepsia 1993;34:764–71. 3. Duchowny M, Jayakar P, Resnick T, et al. Epilepsy surgery in the first three years of life. Epilepsia 1998;39:737–43. 4. Hirabayashi S, Binnie CD, Janota I, et al. Surgical treatment of epilepsy due to cortical dysplasia: clinical and EEG findings. J Neurol Neurosurg Psychiatry 1993;56:765–70. 5. Palmini A, Andermann F, Olivier A, et al. Focal neuronal migration disorders and intractable partial epilepsy: results of surgical treatment. Ann Neurol 1991;30:750–7.
Epilepsia, Vol. 45, No. 7, 2004
6. Raymond AA, Fish DR, Sisodiya SM, et al. Abnormalities of gyration, heterotopias, tuberous sclerosis, focal cortical dysplasia, microdysgenesis, dysembryoplastic neuroepithelial tumour and dysgenesis of the archicortex in epilepsy: clinical, EEG and neuroimaging features in 100 adult patients. Brain 1995;118:629– 60. 7. Wyllie E, Baumgartner C, Prayson R, et al. The clinical spectrum of focal cortical dysplasia and epilepsy. J Epilepsy 1994;7:303– 12. 8. Sisodiya AM, Free SL, Stevens JM, et al. Widespread cerebral structural changes in patients with cortical dysgenesis and epilepsy. Brain 1995;118:1039–50. 9. Palmini A, Gambardella A, Andermann F, et al. Operative strategies for patients with cortical dysplastic lesions and intractable epilepsy. Epilepsia 1994;35:57–71. 10. Raymond AA, Fish DR. EEG features of focal malformations of cortical development. J Clin Neurophysiol 1996;13:495– 506. 11. Holthausen H, Teixeira VA, Tuxhorn I, et al. Epilepsy surgery in children and adolescents with focal cortical dysplasia, In: Tuxhorn I, Holthausen H, Boenigk H, eds. Paediatric epilepsy syndromes and their surgical treatment. London: John Libbey, 1997:199– 215. 12. Wyllie E, Comair YG, Kotagal P, et al. Epilepsy surgery in infants. Epilepsia 1996;37:625–37. 13. Olavarria G, Petronio JA. Epilepsy surgery in infancy. Pediatr Neurosurg 2003;39:44–9. 14. Daniel RT, Lee GYF, Halcrow SJ. Low pressure hydrocephalic state complicating hemispherectomy: a case report. Epilepsia 2002;43:563–5. 15. Rasmussen TB. Hemispherectomy for seizures revisited. Can J Neurol Sci 1983;10:71–8. 16. Daniel RT, Villemure JG. Hemispherectomy. Epileptologie 2003;20:52–9.
