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Lesion lateralization in patients with epilepsy and precocious destructive insults
Epilepsy & Behavior 5 (2004) 1014–1016 www.elsevier.com/locate/yebeh
Brief Communication
Lesion lateralization in patients with epilepsy and precocious destructive insults Ricardo A. Teixeira, Li M. Li, Fernando Cendes* Department of Neurology, University of Campinas (UNICAMP), Campinas, Brazil Received 10 July 2004; revised 7 September 2004; accepted 7 September 2004
Abstract Destructive brain lesions that occur early in development are often unilateral or asymmetric. We analyzed the lateralization of lesions among a previously reported series of 51 patients with three kinds of destructive lesions based on their topography: specific arterial territory (AT), arterial borderzone territory (Bdz), hemispheric (H). Five patients (all from group Bdz) had bilateral nonlateralizing lesions. The distributions of left- and right-sided lesions were distinct among the groups (P = 0.014): in group H, all patients except one presented with right-sided lesions (89%); in group Bdz, left-sided lesions (53%) were more frequent than right-sided lesions (17.7%); in group AT, left- and right-sided lesions were more equally distributed (56 and 44%). Our study suggests that there is a trend toward lesion lateralization among patients with different patterns of precocious destructive lesions. Differences in cerebral maturation and vulnerability between the hemispheres is a possible factor explaining lesion lateralization in early life insults. Ó 2004 Elsevier Inc. All rights reserved. Keywords: Magnetic resonance; Lateralization; Hemiatrophy; Infarct; Borderzone; Epilepsy
1. Introduction Precocious destructive brain lesions comprise a wide variety of congenital, perinatal, and postnatally acquired neuropathologic conditions that have in common tissue necrosis of a previously normally formed brain, and constitute a significant cause of epilepsy [1]. There is good evidence that unilateral or asymmetrical destructive lesions are caused in many instances by presumed diffuse brain insults (e.g., hypoxia, hypotension, status epilepticus) [2,3]. Few studies investigated a possible differential vulnerability between hemispheres in different periods of brain maturation [4]. Furthermore, the nature of the ‘‘diffuse’’ insult must also play some role on the development of lesional asymmetry [5]. We performed this study in an attempt to identify the pattern of lesion *
Corresponding author. Fax: +55 19 3289 1818. E-mail address: [email protected] (F. Cendes).
1525-5050/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2004.09.006
lateralization among patients with distinct types of precocious destructive brain lesions. Clinical and other neuroimaging features of these patients were already published by our group [6].
2. Methods Fifty-one consecutive adult patients (22 women) were evaluated at the Epilepsy Clinic of UNICAMP from March 1999 to April 2001 with the diagnosis of epilepsy secondary to nontraumatic and nonprogressive destructive brain lesion of early development (disease onset before the fifth year of age). We excluded patients with foreign tissue lesions detected on MRI (e.g., tumors, dysplasias) as well as those with a history of major traumatic brain injury or with signs of progressive disease. MRI was performed in a 2.0-T scanner (Elscint Prestige, Haifa, Israel). Sequences performed were sagittal
Brief Communication / Epilepsy & Behavior 5 (2004) 1014–1016
1015
Fig. 1. Axial T1-weighted images illustrating the three groups. Left: Hemispheric (H): diffuse atrophy of the whole right cerebral hemisphere without loss of tissue continuity. Middle: Border zone (Bdz): bilateral atrophy on the border zone between the three main arterial territories. Right: Main arterial territory (AT): large cavity on the territory of the right MCA. R, right; L, left.
T1, coronal T1 and T2, axial T1 and T2, and volumetric T1–gradient echo for multiplanar reconstruction. We divided these patients into three different groups according to the topographical distribution of the lesions (Fig. 1). 2.1. Hemispheric lesions (H) Patients in this group had homogeneous atrophy of an entire hemisphere without loss of tissue continuity. 2.2. Arterial territory lesions (AT) In this group lesions were limited to a main arterial territory and were cavitations or localized retractions of the cerebral tissue with a substantial gliotic scar.
trast, antecedent perinatal complications were more frequent in group Bdz (60%) as compared with the other groups: H (11%), AT (33.3%) (v2, P = 0.043). In five patients (all from group Bdz), the lesions were bilateral and symmetrical. In 22 patients, the main lesion was on the right hemisphere, and in 24 on the left. However, the distributions of left- and right-sided lesions were distinct among the groups (P = 0.014): in group H all patients except one presented with right-sided lesions (89%); in group Bdz, left-sided lesions (53%) were more frequent than right-sided lesions (17.7%); in group AT, left- and right-sided lesions were more equally distributed (56 and 44%).
4. Discussion 2.3. Arterial borderzone lesions (Bdz) These patients had atrophic-gliotic lesions between one or more of the main cerebral arterial territories with an ulegyric aspect [6]. We used PearsonÕs v2 or FisherÕs exact test for comparing proportions among groups. We considered a significance level of 0.05.
3. Results There were 9 patients in group H, 25 in group AT, and 17 in group Bdz. The mean age of the patients was 31.8 years (range, 15–55 years). Status epilepticus (SE) was more frequent in patients from group H (89%) than in the other groups: Bdz (6.6%), AT (4%) (v2(4) = 30.39, P < 0.001). Patients from group H developed a permanent motor deficit after SE, corresponding to the diagnosis of hemiconvulsion– hemiplegia–epilepsy syndrome (HHE syndrome) [7]. Twenty-two (88%) patients from group AT had congenital hemiparesis. Significant prenatal events (e.g., abortion attempt) were described in only 6 (25%) patients from group AT (FisherÕs exact test, P = 0.036). By con-
We studied a population of patients with epilepsy and heterogeneous neuropathologic entities unified by the finding of precocious brain tissue destruction. The clinical and MRI data on patients with arterial territory lesions (group AT) suggest that these individuals had a pre- or perinatal stroke [6]. A trend toward left-sided lesion lateralization among this group of patients was shown by Volpe [8]: 104 infants with congenital focal cerebral necrosis from eight different studies showed a left right ratio of 2.75. A possible explanation for this left-sided preponderance is that most pre- and perinatal strokes must have an embolic source, and the direct route from the subclavian artery via the left common carotid artery makes left-sided strokes more common. Even though our study also showed arterial territory lesions with a left-side preponderance, it was in fact very discrete (left right ratio of 1.27). Lesion lateralization among patients from groups H and Bdz may theoretically be analyzed under the light that both lesion patterns were caused by diffuse insults (hypoxia/ischemia, status epilepticus), quite distinct from the presumed focal (vascular) pathogenesis of group AT. We found that patients with hemiatrophy
1016
Brief Communication / Epilepsy & Behavior 5 (2004) 1014–1016
had their lesions almost exclusively in the right hemisphere, whereas among those with arterial borderzone lesions, lateralization to the left was more common. Because the groups also tended to reflect the timing of injury (Bdz: pre- or perinatal, H: postnatal), it could be hypothesized that there is a difference in cerebral maturation and vulnerability between the hemispheres. Taylor [4] analyzed a series of patients with temporal lobe epilepsy with first seizure before the age of 10 and observed that patients with left-sided lesions tended to present with their first seizure in the first year of life, whereas those with right-sided lesions had their first seizure during the first 4 years of life. The proposed explanation relies on interhemispheric differential maturation, and it is speculated that the less functionally active hemisphere would be the one to react most. Thus, the left hemisphere would be more vulnerable until the acquisition of speech (first year of life), whereas the right hemisphere becomes more vulnerable by the time of verbal skill acquisition. Indeed, it has recently been demonstrated that human infants have greater functional brain activity in the right hemisphere, shifting to left-side predominance during the fourth year of life [9]. TaylorÕs hypothesis would explain in some way how a diffuse cerebral insult can produce predominantly unilateral damage. Our data are not discrepant with this hypothesis: right-sided hemiatrophic lesions were associated with insults after the second year of life and leftsided arterial borderzone lesions were associated with perinatal insults. Brann and Myers [2] experimentally produced asymmetrical arterial borderzone lesions with left-sided predominance in fetal monkey brain after maternal hypotension. A small number of neuropathologic studies demonstrated a predominance of right-sided lesions among patients with hemiatrophy who had status epilepticus in the first years of life [5,10]. In one of these studies [5], it was hypothesized that the nondominant hemisphere has a less efficient desynchronizing drive exerted on the cortex in the first years of life, making it more vulnerable to epileptic damage. In agreement with that, a recent publication [11] showed that antecedent febrile seizures (especially complex febrile seizures) are more frequent among patients with right-sided hippocampal sclerosis. Our study is limited by the fact that most data regarding significant events in early life were obtained by interviews with the patientsÕ mothers. All our patients were adults at the time of the study, and few of them were followed in our institution since the first years of life. The attribution of a cause–effect relationship between the
events described by the family and the lesions on MRI is quite imprecise. However, except for the patients who presented with status epilepticus, patients had no evidence of postnatal events that could be related to their lesions on MRI. Therefore, it does not seem unreasonable to consider patients from groups Bdz and AT as having pre- or perinatal lesions. In conclusion, our study suggests that the lateralization of cerebral lesions occurring early in life differs for different pathologies; hemispheric lesions are predominantly right-sided, those within the territory of a single cerebral artery show a trend toward the left, and watershed lesions may be symmetrical but otherwise show a bias to the left. Further prospective studies will be helpful in determining if the hemispheres are differently prone to distinct kinds of insults in different periods of life.
Acknowledgment Financial support: Dr. Teixeira was supported by a grant from FAPESP.
References [1] Friede RL. Developmental neuropathology. New York: Springer-Verlag; 1989. [2] Brann AW, Myers RE. Central nervous system findings in the newborn monkey following severe in utero partial asphyxia. Neurology 1975;25:327–38. [3] Meldrum BS, Vigouroux RA, Brierley JB. Systemic factors and epileptic brain damage. Arch Neurol 1973;29:82–7. [4] Taylor DC. Differential rates of cerebral maturation between sexes and between hemispheres: evidence from epilepsy. Lancet 1969;2:140–2. [5] Mori Y. Anatomopathology and pathogeny of the hemiconvulsion–hemiplegia–epilepsy syndrome. Part II. J Neurosurg Sci 1978;23:1–22. [6] Teixeira RA, Li LM, Santos SL, et al. Early developmental destructive brain lesions and their relationship to epilepsy and hippocampal damage. Brain Dev 2003;25:560–70. [7] Gastaut H, Poirier F, Payan H, et al. H.H.E. syndrome: hemiconvulsions, hemiplegia, epilepsy. Epilepsia 1959/1960; 1:418–46. [8] Volpe JJ. Neurology of the newborn. Philadelphia: Saunders; 1995. pp. 314–69. [9] Chiron C, Jambaque I, Nabbout R, Lounes R, Syrota A, Dulac O. The right brain hemisphere is dominant in human infants. Brain 1997;120:1057–65. [10] Tan N, Urich H. Postictal cerebral hemiatrophy: with a contribution to the problem of crossed cerebellar atrophy. Acta Neuropathol 1984;62:332–9. [11] Janszki J, Woermann FG, Barsi P, et al. Right hippocampal sclerosis is more common than left after febrile seizures. Neurology 2003;60:1209–10.
Brief Communication
Lesion lateralization in patients with epilepsy and precocious destructive insults Ricardo A. Teixeira, Li M. Li, Fernando Cendes* Department of Neurology, University of Campinas (UNICAMP), Campinas, Brazil Received 10 July 2004; revised 7 September 2004; accepted 7 September 2004
Abstract Destructive brain lesions that occur early in development are often unilateral or asymmetric. We analyzed the lateralization of lesions among a previously reported series of 51 patients with three kinds of destructive lesions based on their topography: specific arterial territory (AT), arterial borderzone territory (Bdz), hemispheric (H). Five patients (all from group Bdz) had bilateral nonlateralizing lesions. The distributions of left- and right-sided lesions were distinct among the groups (P = 0.014): in group H, all patients except one presented with right-sided lesions (89%); in group Bdz, left-sided lesions (53%) were more frequent than right-sided lesions (17.7%); in group AT, left- and right-sided lesions were more equally distributed (56 and 44%). Our study suggests that there is a trend toward lesion lateralization among patients with different patterns of precocious destructive lesions. Differences in cerebral maturation and vulnerability between the hemispheres is a possible factor explaining lesion lateralization in early life insults. Ó 2004 Elsevier Inc. All rights reserved. Keywords: Magnetic resonance; Lateralization; Hemiatrophy; Infarct; Borderzone; Epilepsy
1. Introduction Precocious destructive brain lesions comprise a wide variety of congenital, perinatal, and postnatally acquired neuropathologic conditions that have in common tissue necrosis of a previously normally formed brain, and constitute a significant cause of epilepsy [1]. There is good evidence that unilateral or asymmetrical destructive lesions are caused in many instances by presumed diffuse brain insults (e.g., hypoxia, hypotension, status epilepticus) [2,3]. Few studies investigated a possible differential vulnerability between hemispheres in different periods of brain maturation [4]. Furthermore, the nature of the ‘‘diffuse’’ insult must also play some role on the development of lesional asymmetry [5]. We performed this study in an attempt to identify the pattern of lesion *
Corresponding author. Fax: +55 19 3289 1818. E-mail address: [email protected] (F. Cendes).
1525-5050/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2004.09.006
lateralization among patients with distinct types of precocious destructive brain lesions. Clinical and other neuroimaging features of these patients were already published by our group [6].
2. Methods Fifty-one consecutive adult patients (22 women) were evaluated at the Epilepsy Clinic of UNICAMP from March 1999 to April 2001 with the diagnosis of epilepsy secondary to nontraumatic and nonprogressive destructive brain lesion of early development (disease onset before the fifth year of age). We excluded patients with foreign tissue lesions detected on MRI (e.g., tumors, dysplasias) as well as those with a history of major traumatic brain injury or with signs of progressive disease. MRI was performed in a 2.0-T scanner (Elscint Prestige, Haifa, Israel). Sequences performed were sagittal
Brief Communication / Epilepsy & Behavior 5 (2004) 1014–1016
1015
Fig. 1. Axial T1-weighted images illustrating the three groups. Left: Hemispheric (H): diffuse atrophy of the whole right cerebral hemisphere without loss of tissue continuity. Middle: Border zone (Bdz): bilateral atrophy on the border zone between the three main arterial territories. Right: Main arterial territory (AT): large cavity on the territory of the right MCA. R, right; L, left.
T1, coronal T1 and T2, axial T1 and T2, and volumetric T1–gradient echo for multiplanar reconstruction. We divided these patients into three different groups according to the topographical distribution of the lesions (Fig. 1). 2.1. Hemispheric lesions (H) Patients in this group had homogeneous atrophy of an entire hemisphere without loss of tissue continuity. 2.2. Arterial territory lesions (AT) In this group lesions were limited to a main arterial territory and were cavitations or localized retractions of the cerebral tissue with a substantial gliotic scar.
trast, antecedent perinatal complications were more frequent in group Bdz (60%) as compared with the other groups: H (11%), AT (33.3%) (v2, P = 0.043). In five patients (all from group Bdz), the lesions were bilateral and symmetrical. In 22 patients, the main lesion was on the right hemisphere, and in 24 on the left. However, the distributions of left- and right-sided lesions were distinct among the groups (P = 0.014): in group H all patients except one presented with right-sided lesions (89%); in group Bdz, left-sided lesions (53%) were more frequent than right-sided lesions (17.7%); in group AT, left- and right-sided lesions were more equally distributed (56 and 44%).
4. Discussion 2.3. Arterial borderzone lesions (Bdz) These patients had atrophic-gliotic lesions between one or more of the main cerebral arterial territories with an ulegyric aspect [6]. We used PearsonÕs v2 or FisherÕs exact test for comparing proportions among groups. We considered a significance level of 0.05.
3. Results There were 9 patients in group H, 25 in group AT, and 17 in group Bdz. The mean age of the patients was 31.8 years (range, 15–55 years). Status epilepticus (SE) was more frequent in patients from group H (89%) than in the other groups: Bdz (6.6%), AT (4%) (v2(4) = 30.39, P < 0.001). Patients from group H developed a permanent motor deficit after SE, corresponding to the diagnosis of hemiconvulsion– hemiplegia–epilepsy syndrome (HHE syndrome) [7]. Twenty-two (88%) patients from group AT had congenital hemiparesis. Significant prenatal events (e.g., abortion attempt) were described in only 6 (25%) patients from group AT (FisherÕs exact test, P = 0.036). By con-
We studied a population of patients with epilepsy and heterogeneous neuropathologic entities unified by the finding of precocious brain tissue destruction. The clinical and MRI data on patients with arterial territory lesions (group AT) suggest that these individuals had a pre- or perinatal stroke [6]. A trend toward left-sided lesion lateralization among this group of patients was shown by Volpe [8]: 104 infants with congenital focal cerebral necrosis from eight different studies showed a left right ratio of 2.75. A possible explanation for this left-sided preponderance is that most pre- and perinatal strokes must have an embolic source, and the direct route from the subclavian artery via the left common carotid artery makes left-sided strokes more common. Even though our study also showed arterial territory lesions with a left-side preponderance, it was in fact very discrete (left right ratio of 1.27). Lesion lateralization among patients from groups H and Bdz may theoretically be analyzed under the light that both lesion patterns were caused by diffuse insults (hypoxia/ischemia, status epilepticus), quite distinct from the presumed focal (vascular) pathogenesis of group AT. We found that patients with hemiatrophy
1016
Brief Communication / Epilepsy & Behavior 5 (2004) 1014–1016
had their lesions almost exclusively in the right hemisphere, whereas among those with arterial borderzone lesions, lateralization to the left was more common. Because the groups also tended to reflect the timing of injury (Bdz: pre- or perinatal, H: postnatal), it could be hypothesized that there is a difference in cerebral maturation and vulnerability between the hemispheres. Taylor [4] analyzed a series of patients with temporal lobe epilepsy with first seizure before the age of 10 and observed that patients with left-sided lesions tended to present with their first seizure in the first year of life, whereas those with right-sided lesions had their first seizure during the first 4 years of life. The proposed explanation relies on interhemispheric differential maturation, and it is speculated that the less functionally active hemisphere would be the one to react most. Thus, the left hemisphere would be more vulnerable until the acquisition of speech (first year of life), whereas the right hemisphere becomes more vulnerable by the time of verbal skill acquisition. Indeed, it has recently been demonstrated that human infants have greater functional brain activity in the right hemisphere, shifting to left-side predominance during the fourth year of life [9]. TaylorÕs hypothesis would explain in some way how a diffuse cerebral insult can produce predominantly unilateral damage. Our data are not discrepant with this hypothesis: right-sided hemiatrophic lesions were associated with insults after the second year of life and leftsided arterial borderzone lesions were associated with perinatal insults. Brann and Myers [2] experimentally produced asymmetrical arterial borderzone lesions with left-sided predominance in fetal monkey brain after maternal hypotension. A small number of neuropathologic studies demonstrated a predominance of right-sided lesions among patients with hemiatrophy who had status epilepticus in the first years of life [5,10]. In one of these studies [5], it was hypothesized that the nondominant hemisphere has a less efficient desynchronizing drive exerted on the cortex in the first years of life, making it more vulnerable to epileptic damage. In agreement with that, a recent publication [11] showed that antecedent febrile seizures (especially complex febrile seizures) are more frequent among patients with right-sided hippocampal sclerosis. Our study is limited by the fact that most data regarding significant events in early life were obtained by interviews with the patientsÕ mothers. All our patients were adults at the time of the study, and few of them were followed in our institution since the first years of life. The attribution of a cause–effect relationship between the
events described by the family and the lesions on MRI is quite imprecise. However, except for the patients who presented with status epilepticus, patients had no evidence of postnatal events that could be related to their lesions on MRI. Therefore, it does not seem unreasonable to consider patients from groups Bdz and AT as having pre- or perinatal lesions. In conclusion, our study suggests that the lateralization of cerebral lesions occurring early in life differs for different pathologies; hemispheric lesions are predominantly right-sided, those within the territory of a single cerebral artery show a trend toward the left, and watershed lesions may be symmetrical but otherwise show a bias to the left. Further prospective studies will be helpful in determining if the hemispheres are differently prone to distinct kinds of insults in different periods of life.
Acknowledgment Financial support: Dr. Teixeira was supported by a grant from FAPESP.
References [1] Friede RL. Developmental neuropathology. New York: Springer-Verlag; 1989. [2] Brann AW, Myers RE. Central nervous system findings in the newborn monkey following severe in utero partial asphyxia. Neurology 1975;25:327–38. [3] Meldrum BS, Vigouroux RA, Brierley JB. Systemic factors and epileptic brain damage. Arch Neurol 1973;29:82–7. [4] Taylor DC. Differential rates of cerebral maturation between sexes and between hemispheres: evidence from epilepsy. Lancet 1969;2:140–2. [5] Mori Y. Anatomopathology and pathogeny of the hemiconvulsion–hemiplegia–epilepsy syndrome. Part II. J Neurosurg Sci 1978;23:1–22. [6] Teixeira RA, Li LM, Santos SL, et al. Early developmental destructive brain lesions and their relationship to epilepsy and hippocampal damage. Brain Dev 2003;25:560–70. [7] Gastaut H, Poirier F, Payan H, et al. H.H.E. syndrome: hemiconvulsions, hemiplegia, epilepsy. Epilepsia 1959/1960; 1:418–46. [8] Volpe JJ. Neurology of the newborn. Philadelphia: Saunders; 1995. pp. 314–69. [9] Chiron C, Jambaque I, Nabbout R, Lounes R, Syrota A, Dulac O. The right brain hemisphere is dominant in human infants. Brain 1997;120:1057–65. [10] Tan N, Urich H. Postictal cerebral hemiatrophy: with a contribution to the problem of crossed cerebellar atrophy. Acta Neuropathol 1984;62:332–9. [11] Janszki J, Woermann FG, Barsi P, et al. Right hippocampal sclerosis is more common than left after febrile seizures. Neurology 2003;60:1209–10.