Epilepsiu , 3 1I Suppl. 3):SSS-S66, 1990 Raven Press, Ltd.. New York Q 1990 International League Against Epilepsy
Mesial Temporal Sclerosis: Pathogenesis, Diagnosis, and Management John R. Gates and Raul Cruz-Rodriguez Department of Neurology and Neurosurgery, University of Minnesota Medical School, and MINCEP Epilepsy Care. P . A . , Minneapolis, Minnesota, U.S.A.
Summary: Mesial temporal sclerosis (MTS) is probably the most common symptomatic pathologic entity-alone or mixed with other pathologic features-for seizures of temporal lobe origin. The pathophysiology of MTS, including any genetic influence, needs clarification. A characteristic ictal expression for seizures of MTS origin appears not to exist. The majority of patients (78%) with postresection MTS who are seizure-free have tightly localized interictal abnormalities restricted to F7/F8, Spl/Sp2, T3/T4, and T5/T6 more than %% of the time.
MRI abnormalities may be seen in 55% of patients with MTS if both “hard” and “soft” criteria are used or in 20% when only “hard” criteria are used. The neuropsychologic evaluation of patients with MTS, which includes intracarotid amobarbital test (IAT), may prove to be increasingly useful in identifying patterns of cognitive deficit that correlate with enhancement of both lateralizing and localizing preoperative information. Key Words: Epilepsy-Partial seizures-Neurosurgery-Pathology-Hippocampus-Mesial temporal sclerosis.
In 1825, Bouchet and Cazauvieilh first described hippocampal sclerosis as visible or probable changes in 8 of 14 hippocampi of autopsied epileptic patients who had suffered from “mental alienation” seizures. Heger (1 880) postulated nutritional deficiencies in circulating blood as a mechanism during seizures. Sommer (1880) described maximal destruction within a band of pyramidal cells adjacent to the extreme base of the temporal horn, especially in the more anterior hippocampus. The band corresponds to the prosubiculum in the terminology of Ramon y Cajal (1968), the H I field of Rose (1927) or-as it is called in deference to Sommer-the Sommer’s sector. Sommer reported that loss of pyramidal cells, especially in CA4 (the end folium) and granular cells at the fascia dentata, was not as great as that of CAI through CA3. Sommer concluded that atrophy of the hippocampus may easily result and that the associated sclerosis would cause seizures. As reviewed by Babb and Brown (1987). Bratz (1899) reported 50 autopsies of seizure patients and found hippocampal atrophy in 25 cases. Figure 1,
from an epilepsy patient, shows a nQrmal and a contralateral atrophied hippocampus with CA2 preserved, the presubiculum relatively intact, and the subiculum damaged. Of importance, Bratz ( 1 8 9 ) opposed the conclusion that all hippocampal atrophy is secondary to seizures, because atrophy is not always found in the brains of epilepsy patients. Bratz concluded that because hippocampal atrophy was not always present in epilepsy patients with focal cerebral tumors, hippocampal atrophy was not always a consequence of seizures in patients with hereditary or infectious seizures. Thus, he argued that hippocampal sclerosis is the cause, not the consequence, of seizures. Stauder (1936) was the first to relate the presence of complex partial seizures with auras to the presence of hippocampal sclerosis. In 29 of 36 patients with proven temporal lobe epilepsy, damage to Ammon’s horn was present, a finding that led Stauder to conclude that the symptoms, especially the unique auras, of temporal lobe seizures resulted from the hippocampal injury. Margerison and Corsellis (1966) verified Stauder’s findings when they found hippocampal sclerosis in 85% of their temporal lobe epilepsy patients. Despite the excellent pathological studies delineating an association of mesial temporal sclerosis
Address correspondence and reprint requests to Dr. J. R. Gates at MINCEP Epilepsy Care, P.A., 5775 Wayzata Boulevard, Suite 255, Minneapolis, MN 55416, U.S.A.
s55
S56
J . R . GATES AND R . CRUZ-RODRIGUEZ uncus and the hippocampus in the surgical removal of temporal lobe specimens was apparently not popular. Penfield and Jasper (1954) also advised removal of the deeper structures at surgery. PATHOPHYSIOLOGY
FIG. 1. Wood-cawed plate by Bratz (1899) of cells in normal (top) and atrophied epileptic (bottom) hippocampus. Although the numbers of pyramidal cells are overrepresented at the top, the Ammon’s horn (CA), fascia dentata (FD), and subicular complex are identifiable in both normal and sclerotic hippocampus. We have labeled the important subfield, and one can note large CA3 pyramids, properly oriented pyramids around Ammon’s horn to the presubiculum (PRE), smaller granule cells of the FD, and the white matter of the fimbria fornix (F) in the normal hippocampus. In the epileptic hippocampus, granule cells (FD) and CA4 pyramids are less damaged than CA3, CAI, and prosubiculum (PRO). Most notable is the preservation of CA2 and the relatively intact presubiculum (PRE)adjacent to the damaged subiculum (SUB). This epileptic pattern is found presently in temporal lobe resections and autopsies of patients having suffered from temporal lobe epilepsy. [Reprinted from Babb and Brown (1987) with permission.]
(MTS) to epilepsy, clinicians involved in the care of patients with epilepsy ignored or decried the views originally set forth by Sommer and Bratz. As summarized by Falconer (1974), “Hughlings Jackson, who was the first to correlate the ‘dreamy state’ or uncinate epilepsy with lesions of the temporal lobe, never mentioned this [MTS] lesion.” In 1881, Gowers, in his well-known textbook on epilepsy (reprint, 1964), denied that Ammon’s horn sclerosis had any relationship to epilepsy. Penfield in 1929 (as quoted by Malamud, 1966) declared that the hippocampus and cerebellum were “the two areas which are perhaps the farthest removed from the attention of those who are interested in the epileptic mechanism.” Therefore, until the 1950s, the concept championed by Falconer (1953) of including the Epilepsia. Vol. 31, Suppl. 3, 1990
The German pathologists Spielmeyer (1930) and Scholz (1933) postulated that MTS was due to an anoxic lesion and hence was the result, and not the cause, of epilepsy. Penfield and Jasper (1954) speculated that MTS was the consequence of parturitional brain injury, perhaps the result of excessive molding of the newborn head, resulting in compression of intracarotid and posterior cerebral artery branches at the incisural edge, leading to localized anoxic infarction within the territories of these vessels. In due course, these damaged areas matured into epileptogenic lesions. Earle et al. (1953) coined the term incisural sclerosis. Falconer et al. (1964) obtained histories of birth injury in patients who were shown at surgery to have MTS and concluded that such damage was not likely to occur more frequently in these patients than in other newborns. As summarized by Babb and Brown (1987), kernicterus and Hodgkin’s disease can result in a destruction of the hippocampus; the pattern of cell loss is not similar to that in complex partial epilepsy patients. Several studies have suggested that hippocampal sclerosis is produced primarily in infancy, presumably during a time of increased metabolic demands. Febrile seizures during infancy have been suggested as a cause of hippocampal sclerosis. However, a study of 846 children showed that the incidence of complex partial seizures in a febrile convulsion cohort did not differ from that in a random population of epileptic patients (Falconer and Taylor, 1968). A signifcant correlation was suggested, however, between serious childhood illness and hippocampal sclerosis in adults with complex partial seizures (Falconer and Taylor, 1969). Cavanaugh and Meyer (1956) also emphasized that MTS was seen more commonly in adults whose seizures started before age 4 years. They also found that a first seizure experience of status epilepticus was more strongly associated with MTS, especially when such a seizure occurred in early infancy. Consequently, it is possible that repeated, severe seizures at an early age can cause neuronal damage and reactive gliosis, as concluded by Babb and Brown (1987), “in a pattern typical of hippocampal sclerosis in psychomotor epilepsy.” However, the “chicken and egg theory” becomes complicated when we ask why these children have initial seizures at this earlier age. Consequently, we may conclude that a clear pathophy-
MESIAL TEMPORAL SCLEROSIS
siologic mechanism for MTS has not been established. INCIDENCE
Hippocampal sclerosis as the sole pathologic feature has been reported in several studies of temporal lobe epilepsy. As reviewed by Babb and Brown (1987), the average percentage of postsurgical specimens showing hippocampal sclerosis is 64.9%. the modal percentage is 64.5%, and the overall incidence is 64.7%. An important point is emphasized here, in that extrahippocampal pathologies from a variety of other sources, such as hamartoma, glioma, and heterotopia, also can cause complex partial epilepsy. Babb and Brown (1987) have concluded: “It is now well established that psychomotor seizures may originate from sclerotic hippocampal formation or from a variety of lesions in the temporal lobe.” In their review of the incidence of bilateral hippocampal sclerosis,the incidenceof asymmetrical bilateral damage was high (-8O%), the incidence of symmetric dainage was low (
Mesial Temporal Sclerosis: Pathogenesis, Diagnosis, and Management John R. Gates and Raul Cruz-Rodriguez Department of Neurology and Neurosurgery, University of Minnesota Medical School, and MINCEP Epilepsy Care. P . A . , Minneapolis, Minnesota, U.S.A.
Summary: Mesial temporal sclerosis (MTS) is probably the most common symptomatic pathologic entity-alone or mixed with other pathologic features-for seizures of temporal lobe origin. The pathophysiology of MTS, including any genetic influence, needs clarification. A characteristic ictal expression for seizures of MTS origin appears not to exist. The majority of patients (78%) with postresection MTS who are seizure-free have tightly localized interictal abnormalities restricted to F7/F8, Spl/Sp2, T3/T4, and T5/T6 more than %% of the time.
MRI abnormalities may be seen in 55% of patients with MTS if both “hard” and “soft” criteria are used or in 20% when only “hard” criteria are used. The neuropsychologic evaluation of patients with MTS, which includes intracarotid amobarbital test (IAT), may prove to be increasingly useful in identifying patterns of cognitive deficit that correlate with enhancement of both lateralizing and localizing preoperative information. Key Words: Epilepsy-Partial seizures-Neurosurgery-Pathology-Hippocampus-Mesial temporal sclerosis.
In 1825, Bouchet and Cazauvieilh first described hippocampal sclerosis as visible or probable changes in 8 of 14 hippocampi of autopsied epileptic patients who had suffered from “mental alienation” seizures. Heger (1 880) postulated nutritional deficiencies in circulating blood as a mechanism during seizures. Sommer (1880) described maximal destruction within a band of pyramidal cells adjacent to the extreme base of the temporal horn, especially in the more anterior hippocampus. The band corresponds to the prosubiculum in the terminology of Ramon y Cajal (1968), the H I field of Rose (1927) or-as it is called in deference to Sommer-the Sommer’s sector. Sommer reported that loss of pyramidal cells, especially in CA4 (the end folium) and granular cells at the fascia dentata, was not as great as that of CAI through CA3. Sommer concluded that atrophy of the hippocampus may easily result and that the associated sclerosis would cause seizures. As reviewed by Babb and Brown (1987). Bratz (1899) reported 50 autopsies of seizure patients and found hippocampal atrophy in 25 cases. Figure 1,
from an epilepsy patient, shows a nQrmal and a contralateral atrophied hippocampus with CA2 preserved, the presubiculum relatively intact, and the subiculum damaged. Of importance, Bratz ( 1 8 9 ) opposed the conclusion that all hippocampal atrophy is secondary to seizures, because atrophy is not always found in the brains of epilepsy patients. Bratz concluded that because hippocampal atrophy was not always present in epilepsy patients with focal cerebral tumors, hippocampal atrophy was not always a consequence of seizures in patients with hereditary or infectious seizures. Thus, he argued that hippocampal sclerosis is the cause, not the consequence, of seizures. Stauder (1936) was the first to relate the presence of complex partial seizures with auras to the presence of hippocampal sclerosis. In 29 of 36 patients with proven temporal lobe epilepsy, damage to Ammon’s horn was present, a finding that led Stauder to conclude that the symptoms, especially the unique auras, of temporal lobe seizures resulted from the hippocampal injury. Margerison and Corsellis (1966) verified Stauder’s findings when they found hippocampal sclerosis in 85% of their temporal lobe epilepsy patients. Despite the excellent pathological studies delineating an association of mesial temporal sclerosis
Address correspondence and reprint requests to Dr. J. R. Gates at MINCEP Epilepsy Care, P.A., 5775 Wayzata Boulevard, Suite 255, Minneapolis, MN 55416, U.S.A.
s55
S56
J . R . GATES AND R . CRUZ-RODRIGUEZ uncus and the hippocampus in the surgical removal of temporal lobe specimens was apparently not popular. Penfield and Jasper (1954) also advised removal of the deeper structures at surgery. PATHOPHYSIOLOGY
FIG. 1. Wood-cawed plate by Bratz (1899) of cells in normal (top) and atrophied epileptic (bottom) hippocampus. Although the numbers of pyramidal cells are overrepresented at the top, the Ammon’s horn (CA), fascia dentata (FD), and subicular complex are identifiable in both normal and sclerotic hippocampus. We have labeled the important subfield, and one can note large CA3 pyramids, properly oriented pyramids around Ammon’s horn to the presubiculum (PRE), smaller granule cells of the FD, and the white matter of the fimbria fornix (F) in the normal hippocampus. In the epileptic hippocampus, granule cells (FD) and CA4 pyramids are less damaged than CA3, CAI, and prosubiculum (PRO). Most notable is the preservation of CA2 and the relatively intact presubiculum (PRE)adjacent to the damaged subiculum (SUB). This epileptic pattern is found presently in temporal lobe resections and autopsies of patients having suffered from temporal lobe epilepsy. [Reprinted from Babb and Brown (1987) with permission.]
(MTS) to epilepsy, clinicians involved in the care of patients with epilepsy ignored or decried the views originally set forth by Sommer and Bratz. As summarized by Falconer (1974), “Hughlings Jackson, who was the first to correlate the ‘dreamy state’ or uncinate epilepsy with lesions of the temporal lobe, never mentioned this [MTS] lesion.” In 1881, Gowers, in his well-known textbook on epilepsy (reprint, 1964), denied that Ammon’s horn sclerosis had any relationship to epilepsy. Penfield in 1929 (as quoted by Malamud, 1966) declared that the hippocampus and cerebellum were “the two areas which are perhaps the farthest removed from the attention of those who are interested in the epileptic mechanism.” Therefore, until the 1950s, the concept championed by Falconer (1953) of including the Epilepsia. Vol. 31, Suppl. 3, 1990
The German pathologists Spielmeyer (1930) and Scholz (1933) postulated that MTS was due to an anoxic lesion and hence was the result, and not the cause, of epilepsy. Penfield and Jasper (1954) speculated that MTS was the consequence of parturitional brain injury, perhaps the result of excessive molding of the newborn head, resulting in compression of intracarotid and posterior cerebral artery branches at the incisural edge, leading to localized anoxic infarction within the territories of these vessels. In due course, these damaged areas matured into epileptogenic lesions. Earle et al. (1953) coined the term incisural sclerosis. Falconer et al. (1964) obtained histories of birth injury in patients who were shown at surgery to have MTS and concluded that such damage was not likely to occur more frequently in these patients than in other newborns. As summarized by Babb and Brown (1987), kernicterus and Hodgkin’s disease can result in a destruction of the hippocampus; the pattern of cell loss is not similar to that in complex partial epilepsy patients. Several studies have suggested that hippocampal sclerosis is produced primarily in infancy, presumably during a time of increased metabolic demands. Febrile seizures during infancy have been suggested as a cause of hippocampal sclerosis. However, a study of 846 children showed that the incidence of complex partial seizures in a febrile convulsion cohort did not differ from that in a random population of epileptic patients (Falconer and Taylor, 1968). A signifcant correlation was suggested, however, between serious childhood illness and hippocampal sclerosis in adults with complex partial seizures (Falconer and Taylor, 1969). Cavanaugh and Meyer (1956) also emphasized that MTS was seen more commonly in adults whose seizures started before age 4 years. They also found that a first seizure experience of status epilepticus was more strongly associated with MTS, especially when such a seizure occurred in early infancy. Consequently, it is possible that repeated, severe seizures at an early age can cause neuronal damage and reactive gliosis, as concluded by Babb and Brown (1987), “in a pattern typical of hippocampal sclerosis in psychomotor epilepsy.” However, the “chicken and egg theory” becomes complicated when we ask why these children have initial seizures at this earlier age. Consequently, we may conclude that a clear pathophy-
MESIAL TEMPORAL SCLEROSIS
siologic mechanism for MTS has not been established. INCIDENCE
Hippocampal sclerosis as the sole pathologic feature has been reported in several studies of temporal lobe epilepsy. As reviewed by Babb and Brown (1987), the average percentage of postsurgical specimens showing hippocampal sclerosis is 64.9%. the modal percentage is 64.5%, and the overall incidence is 64.7%. An important point is emphasized here, in that extrahippocampal pathologies from a variety of other sources, such as hamartoma, glioma, and heterotopia, also can cause complex partial epilepsy. Babb and Brown (1987) have concluded: “It is now well established that psychomotor seizures may originate from sclerotic hippocampal formation or from a variety of lesions in the temporal lobe.” In their review of the incidence of bilateral hippocampal sclerosis,the incidenceof asymmetrical bilateral damage was high (-8O%), the incidence of symmetric dainage was low (
