MRI volumetry of the hippocampus, amygdala, entorhinal cortex, and perirhinal cortex after status epilepticus
Introduction
Most histologic analyses of post mortem tissue from patients with status epilepticus demonstrate neuronal loss in the medial temporal lobe. Both generalized convulsive and nonconvulsive status epilepticus may result in hippocampal damage (Norman, 1964, Corsellis and Bruton, 1983, DeGiorgio et al., 1992, Wasterlain et al., 1993). The amygdala and surrounding cortical areas are also often damaged in patients who died from status epilepticus (Meyer et al., 1955, Cavanagh and Meyer, 1956, Fowler, 1957, Gastaut et al., 1959, Falconer et al., 1964, Fujikawa and Itabashi, 1994). Although the structural changes observed in human pathological studies may be related to the underlying disease or systemic complications of the insult, experimental animal studies have shown that repetitive cell firing alone results in neuronal damage (Meldrum et al., 1973). Hippocampal and extrahippocampal damage, including neuronal loss in the amygdala and entorhinal and perirhinal cortices, is a typical finding in various animal models of status epilepticus (Schwob et al., 1980, Turski et al., 1983, Du et al., 1995, Tuunanen et al., 1996, Pitkänen et al., 1997, Du et al., 1998). Experimental studies in rats demonstrate signs of ongoing neuronal damage even after the cessation of status epilepticus (Mathern et al., 1992, Fujikawa, 1996, Tuunanen et al., 1996). In humans, however, little histologic data are available regarding the time course of the development of the pathologic changes.
Serial magnetic resonance imaging (MRI) provides a modern tool for monitoring the temporal progression of cerebral damage following status epilepticus over a lifetime. In several case reports, acute increases of T2 signal intensity after status epilepticus were followed by progressive hippocampal atrophy (Nohria et al., 1994, Tien and Felsberg, 1995). For example, Wieshmann et al. (1997) described one patient in whom the progression of hippocampal atrophy continued for up to 58 months after generalized status epilepticus. In another patient with extratemporal focal status epilepticus, progressive MRI changes were confined to the epileptogenic region of the superior frontal gyrus, which appeared normal in a scan taken prior to status epilepticus (Meierkord et al., 1997). Moreover, VanLadingham et al. (1998) recently provided quantitative MRI evidence suggesting that prolonged complex febrile seizures produce hippocampal damage. In a follow-up study of two of the four patients with an acute increase of the hippocampal volume and signal intensity, they demonstrated the development of hippocampal atrophy within 8–10 months. Some researchers, however, claim that T2 changes associated with status epilepticus are transient (Riela et al., 1991, Callahan and Noetzel, 1992, Henry et al., 1994).
The MRI case studies available suggest that in some patients with status epilepticus, prolonged seizure activity causes progressive atrophy in the hippocampus, long after the end of an acute episode. In the present study, we used quantitative MRI to systematically and prospectively follow status epilepticus patients who were treated in hospital with a predetermined protocol. The study was designed to address the following questions. First, is there damage in the medial temporal lobe in patients with status epilepticus when assessed soon after the insult? Second, do the changes progress after the insult? We analyzed the volumes of the hippocampus and the adjacent connectionally-related structures, the amygdala, the entorhinal cortex, and the perirhinal cortex. To our knowledge, no previous studies evaluating volumetric changes in the perirhinal cortex of patients with seizure activity exist, and there have been few attempts to evaluate the entorhinal cortex with MRI.
Section snippets
Patients and controls
Adult patients with status epilepticus requiring intravenous antiepileptic medication and treated at the emergency unit of the Kuopio University Hospital (KUH) between January 1, 1996 and December 31, 1997, were enrolled in the MRI follow-up study. The evaluation of patients for the study was performed by one of the investigators (T.S.) during the initial treatment period at KUH. Status epilepticus was defined as more than 30 min of continuous seizure activity or two or more sequential seizures
Patients
Nine patients with status epilepticus requiring intravenous antiepileptic medication and treated initially at the KUH during the 24-months study period were examined using MRI 3 weeks, 6 and 12 months after the insult. The patient group consisted of four males and five females (age 40±19, range 18–74 years).
Epilepsy
Seven of the nine patients had partial secondarily generalized epilepsy prior to the status epilepticus. The etiology and duration of epilepsy, seizure type, and antiepileptic medication of
Discussion
The major finding of this quantitative MRI study was that status epilepticus did not lead to progressive volume reduction in the medial temporal lobe structures of adult patients treated in the hospital with a predetermined protocol. Even the patient with a s-NSE elevation had no clear volume reduction. In the first MRI volumetry taken 3 weeks after status epilepticus, hippocampal damage was found in five of the nine patients (56%). Atrophy in the amygdala was observed in two (25%) and atrophy
Conclusion
This is the first prospective quantitative MRI study that systematically follows the volumes of hippocampus, amygdala, entorhinal and perirhinal cortices in adult status epilepticus patients treated in hospital. We provide evidence that status epilepticus does not invariably lead to progressive damage in the medial temporal lobe structures. Although the present study does not exclude the possibility that the status epilepticus episodes observed may have caused damage to some other brain
Acknowledgements
This study was financially supported by the Academy of Finland, the Vaajasalo Foundation, and the Sigrid Juselius Foundation.
References (52)
- et al.
Hippocampal formation
- et al.
Transfer of epileptogenesis between perirhinal cortex and amygdala induced by electrical kindling
Brain Res.
(1997) The temporal evolution of neuronal damage from pilocarpine-induced status epilepticus
Brain Res.
(1996)- et al.
MRI volumetry and T2 relaxometry of the amygdala in newly diagnosed and chronic temporal lobe epilepsy
Epilepsy Res.
(1997) - et al.
Amygdala damage in experimental and human temporal lobe epilepsy
Epilepsy Res.
(1998) - et al.
Widespread patterns of neuronal damage following systemic or intracerebral injections of kainic acid: a histological study
Neuroscience
(1980) - et al.
Limbic seizures produced by pilocarpine in rats: behavioural, electroencephalographic and neuropathological study
Behav. Brain Res.
(1983) - Brodmann, K., 1909. Vergleichende Lokalisationslehre der Grosshirnrinde in ihren Prinzipien dargestellet auf Grund des...
- et al.
Prolonged absence status epilepticus associated with carbamazepine therapy, increased intracranial pressure and transient MRI abnormalities
Neurology
(1992) - et al.
Aetiological aspects of Ammon’s horn sclerosis associated with temporal lobe epilepsy
Br. Med. J.
(1956)