DWI after status epilepticus
Postictal DWI studies in animal experiments have so far focused on observations during or after the kainic acid– or pilocarpine-induced status epilepticus in the rat (15,16,28,29). In the kainate-induced status epilepticus in the rat, the ADC decreased by 7–30%, and MR-visible sodium contents increased by 12–90% during a period 5–24 h postictally. Maximal changes were seen in the piriform cortex and the amygdala (16). During the early phase, little evidence for structural damage was detected on T2-weighted MR images. These findings are consistent with the hypothesis that sequential seizures lead to an intracellular influx of sodium ions. Failure of the Na+/K+-ATPase may lead to subsequent cytotoxic edema, thereby reducing water diffusion. Excessive release of excitatory amino acids, such as glutamate (30,31), and increased membrane ion permeability may contribute to edema during status epilepticus, which eventually may evolve into cell necrosis or apoptosis. Affirmatively, swelling of dendrites and astrocytes has been described histologically in animal experimental studies (31). The ADC changes were closely correlated with the assumed epileptogenic brain areas and the tissue damage such as neuronal pyknosis and neuropile vacuolation shown on histopathologic examination (15).
The decrease of the ADC in the hippocampus, amygdala, and piriform cortex after the kainic acid–induced status epilepticus may last 1–3 days and completely resolve after 9 days (16,28,29).
The return of the ADC to baseline values and greater during the days to follow may be explained by subsequent neuronal degeneration, leading to an increase of the extracellular space. Neuronal and glial cell death after status epilepticus has been documented in animal experiments (32–35) and by MR-detected brain atrophy in humans (10).
In contrast to experimental data, evaluations of DWI in humans are based on a few patients, mainly with epileptogenic brain lesions (18–20,36). Furthermore, in most reports, the effects of an underlying neurologic disease such as cortical vein thrombosis (20), intraparenchymal hemorrhages, and infection (11) are difficult to distinguish from seizure activity. Lansberg et al. (11) found a decrease of the cortical ADC in circumscribed areas of the cortex in three patients with focal status epilepticus. Diehl et al. (19) found decreases of the ADC in only one of six patients after a short seizure. However, her scanning DWI scans were only 45–150 min after the seizure, and short-lived effects may have vanished. In a patient with a nonconvulsive status epilepticus, an 18% decrease of the ADC and a 28% increase of regional cerebral blood flow was found within the affected left temporoparietal cortex when compared with the unaffected side (21). All changes normalized within 1 month.
DWI after single seizures
In contrast to DWI measurements after status epilepticus, dynamic ADC changes after single seizures have not been reported. Hypothetically, postictal changes may rely on many factors such as seizure duration, type, and propagation or the underlying lesion. Furthermore, the time lag since seizure termination may be crucial.
In this study, we hypothesized that ADC alterations may be assumed to differ from those after status epilepticus, because single seizure–induced cell membrane changes and ion imbalances are quickly transient, and morphologic damage usually does not occur, or only to a minor degree.
In keeping with this hypothesis, Zhong et al. (37) found an ADC reduction of 4% after a single 10-pulse cortical electrical-stimulation train that lasted 0.1 s. The ADC decrease was marked (–7 to 8%) if shocks were repeated once a minute. Based on this experience in animal experiments, one would expect the ADC to decline postictally and return to baseline within minutes to a few hours in humans. Changes resembling this hypothesis were seen in patients 1 and 6, in whom an ADC decline of maximally 25–31% occurred, and a complete (patient 1) or partial (patient 6) return to baseline was seen in the epileptogenic zone. Additional changes of minor extents were seen in both patients additional changes outside the epileptogenic zones.
Hypothetically, postictal ADC changes may be quickly transient and related to the seizure severity (duration). They may not be detected at all if the seizure was short-lived or if the time lag until the first DWI scan was too long. Affirmatively, no major ADC changes were seen in patients 3, 5, and 8, who had seizures of ≤30-s duration and were scanned 16–75 min after the seizure. From the postictal ECoG via subdural electrodes, we know that no slow focal activity is detectable if a seizure lasted <30 s (2). Moreover, in ictal SPECT, injections of the tracer have to be performed within a short period of ∼2 min to enable depiction of hyperperfusion in the epileptogenic zone.1 These observations point out that changes of the ADC values after a single seizure are possible but not obligatory.
In contrast to purely focal seizure activity, generalized suppression of brain electrical activity is known to occur after generalized seizures and may last for hours and days. However, whereas generalized increases of ADC values were seen in all regions other than WM in patient 4 after a GM seizure and in AH, Cortex, and WM of patient 9 after a prolonged CPS, a generalized decrease of ADC values was seen in patient 7, 60 min after a prolonged CPS. There are two possible explanations for this divergence. The first hypothesis is the cyclic course of the interictal–ictal–postictal–interictal transition. The underlying cyclic changes of brain electrical activity are known to correlate with changes of cellular processes at all levels and vascular supply. In particular, reactive hyperpolarizations and hyperperfusion are known to occur (12,13). In SPECT, an interictal hypoperfusion is followed by an ictal hyperperfusion and a marked postictal hypoperfusion. On the cellular level, interictal epileptiform discharge represents synchronous depolarization in a small neuronal pool. This turns into highly repetitive discharges during the seizure and usually sparse epileptiform discharge postictally. The ictal depolarizations may lead mainly to massive Na+ and Ca2+ influx followed by hydrate water and K+ efflux. This possibly results in a temporary breakdown of the Na+/K+ pump, and K+ overload in the extracellular space and glia (38). Because the intracellular compartment is more restrictive to water motion, the ADC usually decreases. During the postictal recovery period, all changes are usually reversed to the interictal baseline but may be overreactive during a transitory phase. The ADC value measured may hence depend on the exact timing and may possibly correlate with phases of reactive hyperperfusion or reactive hyperpolarization (39).
Alternatively, the epileptogenic process itself may cause differences in diffusion changes. Whereas ADC increases have been observed in the rat hippocampus 24 h after a pilocarpine-induced status epilepticus (17), ADC decreases have been found after kainate-induced status epilepticus (16). Whereas kainic acid is a glutamatergic, excitatory amino acid that has a high affinity to CA1 and CA3 hippocampal pyramidal neurons and causes excitotoxic neuronal loss, pilocarpine is a cholinergic agonist that primarily activates cholinergic afferents to the granule cells of the dentate gyrus. Granule cells are known to act as filters to excitatory activation of the secondary pyramidal cells and die apoptotically rather than necrotically (40,41). Both processes may diminish or protract neuronal loss and so cause differences in seizure-induced ADC changes. The specific pathomechanisms of the underlying epilepsy syndrome may lead to differences in postictal diffusion changes.
Overall, because ofo the heterogeneous ADC changes, the small sample size, and different types of seizures, no characteristic correlations could be observed. In contrast to the generally decreased ADC values after focal status epilepticus, ADC changes after a single seizure appear to be complex.
In this respect, serial DWI scans, starting as early as possible after the seizure, are necessary to depict fully the spatiotemporal pattern of DWI changes in the epileptogenic area and its vicinity.
In conclusion, DWI proved to be a sensitive diagnostic tool for the in vivo depiction of functional postictal brain diffusion alterations after single seizures. The spatiotemporal pattern of ADC changes appears to be complex and may be indicative of the underlying seizure activity. More data from larger DWI series are needed to decide whether DWI may be used for functional delineation of the epileptogenic zone in the course of presurgical evaluation (42–44).