Aphasia, broadly defined as abnormal language function, can be the sole expression of a focal seizure or focal status epilepticus. Ictal aphasia is often mixed (with deficits in comprehension, fluency, and repetition) or may impair individual language functions specifically, such as naming, syntax, or grammar, and in subtle cases may be reflected as intermittent paraphasic errors only. These may be either semantic paraphasias (where the intended word is replaced by a word of a similar meaning, such as blouse instead of shirt) or phonemic paraphasias (where a word is replaced by another with a similar sound, such as duck instead of truck). Ictal impairment of language function may spare verbal fluency and comprehension entirely and may selectively impair reading (alexia), writing (agraphia), or both.

Reductions in speech quantity or verbal output are often the first clue to the presence of an aphasia, but it is important to recognize that not every patient with diminished speech has an underlying language disorder. Examples include failures of speech production due to primary impairment in consciousness (e.g., coma or obtundation), or severe speech apraxia or impairment in buccofacial muscle activity, due to central or peripheral etiologies. Reductions in arousal and attention that are central features of toxic and metabolic encephalopathies may produce reductions in verbal output in association with other clinical features such as abulia and intermittent agitation and are seen commonly in hospitalized patients with metabolic derangements. Nevertheless, true paroxysmal aphasia does occur in the setting of encephalopathic states and may represent an epileptic phenomenon or the clinical recrudescence of the effects of a known structural lesion (e.g., old infarction) which led previously to transient aphasia.

Many reports of ictal aphasia do not provide the results of detailed language testing, and thus do not provide a comprehensive assessment of clinical phenomenology. Ictal aphasia may be an uncommon entity, but in many instances, underreporting occurs for various reasons. For example, if the subject is asleep or obtunded and no effort is made to prompt speech, reading, or writing during a seizure arising from the relevant brain region, there may be no overt manifestations of aphasia. A related difficulty that may lead to under-recognition of ictal aphasia is the presence of more striking coincident motor activity, such that no effort is made to speak or to formally evaluate language function during the seizure. These concerns have implications for any attempt to determine the incidence or frequency of ictal aphasia.

Table 21.2 [20–38] summarizes a series of select cases of ictal aphasia. Where possible, details of language testing have been designated as Broca’s, Wernicke’s, mixed, or transcortical. Where the features suggest a Broca’s or Wernicke’s aphasia but the ability to repeat is not tested, the designations “anterior” and “posterior” have been used. In several of these cases, aphasia was due to underlying status epilepticus. A few conclusions may be drawn from these case reports. First, virtually every type of aphasia may occur as a clinical manifestation of seizures or status epilepticus. Second, various electrographic correlates can be seen, ranging from lateralized periodic discharges (LPDs) to high voltage rhythmic slowing. Third, there does not appear to be a characteristic feature of ictal aphasia that can be used to distinguish it from aphasia due to other causes. In a minority of cases, other paroxysmal seizure symptoms were seen (e.g., clonic limb movements, olfactory hallucinations, post-ictal impaired consciousness, etc.) that suggested an underlying epileptic origin. Fourth, a correlation between the spatial location of ictal activity and the nature of the aphasia is not straightforward. For example, there is no clear tendency for Wernicke type aphasias to result from more posteriorly located ictal discharges. Finally, underlying structural pathology may or may not be seen on conventional neuroimaging.

Documenting the presence and degree of post-ictal aphasia can provide tremendous lateralizing value in the evaluation of patients with medically refractory temporal lobe epilepsy, particularly in those patients in whom (i) interictal epileptiform discharges are bilateral, or (ii) complex partial seizures, presumably emanating from temporal regions, have a very limited scalp representation. In a prospective study of 105 seizures recorded from 26 patients, all of whom progressed to have identification of the seizure focus confirmed by successful temporal lobectomies, all 62 seizures originating from the dominant temporal lobe were associated with a significant post–ictal language delay (PILD). This was assessed by presenting promptly a phrase from the Boston Diagnostic Aphasia Test (“They heard him speak on the radio last night”) on a placard in large bold print. Following left (i.e., language dominant) temporal seizures, patients required more than 68 s to read the phrase correctly, in contrast to under 54 s for seizures arising from nondominant temporal regions, with similar findings observed when post-ictal paraphasias were assessed quantitatively [39]. These results have been replicated [40], and follow-up studies have demonstrated the value of simple but systematic post-ictal language testing in identifying frontal lobe complex partial seizures that spread to the adjacent temporal lobe [41]. Interestingly, a majority of patients with psychogenic nonepileptic seizures reported that they either “couldn’t read” the phrase or that the words were “blurry,” a finding not seen in patients with true temporal lobe seizures [42]. These results confirm the importance of systematic post-ictal language testing in patients with complex partial seizures.

A chapter dealing with ictal aphasia would be incomplete without reference to the Landau–Kleffner syndrome, defined originally as “a syndrome of acquired aphasia with convulsive disorder in children” [43]. In this syndrome, a language disorder is thought to be caused directly by epileptic discharges in regions of the brain critical for normal language function. The anatomic boundaries of the syndrome are not well defined. The classic history is that of a child with normal early language development, who shows signs of regression of already-acquired linguistic skills between the ages of 3 and 7 years [44]. The onset may be abrupt or insidious, and the degree of language impairment may fluctuate. Initially, comprehension is more severely affected, but with time there is a gradual decline in verbal output. Clinically overt seizures are uncommon. The waking EEG is often normal, and a key finding in this syndrome is the presence of very frequent spike and wave discharges during sleep. The topography, abundance, and persistence of spike and wave discharges vary among patients and at different stages of the syndrome. Additionally, during the course of the illness, patients inevitably display continuous spike/wave discharges (bilateral or generalized) during slow wave sleep (CSWS). While traditional antiseizure drugs remain first line therapy, the use of corticosteroids tends to produce more longlasting benefits [45]. In certain extreme cases, surgical treatments (such as multiple subpial transection) have been undertaken, though often without clear benefit [46]. This syndrome serves as a model for the relationship between epilepsy and language and exemplifies the concept that prolonged language dysfunction may result from persistent epileptic activity in relevant brain regions.

Ictal and post-ictal aphasia can vary in phenomenology and severity, ranging from subtle paraphasic errors to global aphasia with mutism. In cases of new onset aphasia, continuous EEG (C-EEG) monitoring is necessary to identify electrographic correlates, which may themselves be quite subtle (e.g., rare discharges) and may not unambiguously differentiate between ictal and post-ictal states (e.g., rhythmic or hemispheric slowing). Together with a comprehensive neurologic examination and C-EEG video monitoring, neuroimaging studies (which include measures of perfusion) may help distinguish between aphasia related to transient ischemia and an underlying epileptic etiology.

The relationship between seizures and memory dysfunction is complex. Memory impairments are common in patients with epilepsy and are likely mediated by a variety of factors, including the long-term disruptive effects of seizures on memory circuits, the cognitive dulling effects of most ASDs, poor sleep, and in some cases, the underlying epileptogenic lesion itself [47, 48]. Aside from these interictal deficits, many focal seizures with “dyscognitive” features are themselves associated with some degree of amnesia for the events that transpire during the seizure. Whether this transient amnesia is a result of impairment in arousal, attention, or perception, however, is difficult to ascertain. Can seizures result in an isolated deficit in memory function without a more diffuse impairment in cognition?

Before answering this question, some terminology should be clarified. Working memory, also known as short-term memory, describes the active “on-line” holding and manipulation of information, and is largely subserved by frontal and prefrontal circuits. Long–term memory, on the other hand, refers to information that is stored “off-line” for periods varying from minutes to years. Long-term memory can be further subdivided into explicit (also termed declarative memory, for events, facts, meanings, and concepts of the external world) and implicit (also termed nondeclarative or procedural memory, for actions, skills, and habits). The formation of stable long-term declarative memory is facilitated primarily by the hippocampus, receiving input from an array of cortical and subcortical regions through entorhinal, perirhinal, and parahippocampal cortical regions [49]. Accordingly, selective bilateral hippocampal lesions (such as those following limbic status epilepticus [50, 51]) result in persistent anterograde amnesia, occasionally associated with hyperphagia and hypersexuality (the Kluver–Bucy syndrome, [52]). Procedural memory formation is encoded by extrahippocampal circuits, including the striatum, motor cortex and the cerebellum, and is often spared in bilateral temporal lesions [49]. In contrast, retrograde amnesia refers to the inability to recall previous memories that have already been established. As can be expected, testing objectively for retrograde amnesia is difficult to standardize (as patients may vary in their knowledge of previous events). Retrograde amnesia is classically seen following traumatic brain injuries and is often temporally graded, such that larger or more severe lesions to mesial temporal structures result in more chronologically extensive retrograde amnesia (i.e., with patients unable to recall events covering a greater number of past years [53]). Ictal memory disturbances may affect anterograde memory, retrograde memory, or a combination of the two. Anterograde amnesia may result from a disturbance of any number of cognitive processes involved in the formation of new stable long-term memories, including encoding, consolidation, storage, and retrieval. Finally, the combination of anterograde and retrograde amnesia has been termed global amnesia.

Vuilleumier and colleagues provided the most unequivocal description of an isolated memory disturbance resulting from nonconvulsive status epilepticus (NCSE) [54]. A 41-year-old, previously healthy woman was found trying to enter her former house where she had not lived for three years. She was brought to the hospital, where she appeared calm and cooperative although a little perplexed. She answered questions appropriately and executed complex commands quickly and accurately. She did not engage in repetitive questioning. She was fully awake and alert but was disoriented for time, and globally amnestic. She knew her name, but not her address, phone number, or the contact details for a friend or relative. She was unable to give an account of her activities over the preceding few days. Her forward digit span was 6, and from a 10-word list she recalled four words on the first two attempts and six words on the third attempt. She recalled only one word after a 3-minute delay. The only other finding on examination was occasional rhythmic eye blinking. An EEG showed continuous generalized epileptic activity with rhythmic spikes at 3.5–4 Hz. Within 4 min of the administration of an intravenous bolus of 1 mg clonazepam, this epileptiform pattern ceased and the patient said, “Now I can tell you … I recall everything … I can see all that happened …”. She was able to provide an account of the events that had transpired over the preceding few hours. The episode appeared to last about 10 h in total. It subsequently emerged that she had experienced a number of similar episodes since her teenage years and that these either occurred upon awakening in the morning or were preceded by an epigastric sensation. Treatment with carbamazepine was initiated, and no recurrences were noted over the following 6 months of follow-up.

Lee and colleagues described the case of a young otherwise healthy woman who presented with the acute onset of amnesia [55]. She had limited recollection of the events of the preceding four months (retrograde amnesia), and examination showed normal working memory but with failure to recall any of three words or three hidden objects after a five-minute delay (anterograde amnesia, involving both verbal and visual modalities). EEG with nasophargyngeal electrodes showed frequent electrographic seizures arising from the left medial temporal lobe. Treatment with ASDs led to the complete cessation of epileptiform discharges and was followed by complete recovery of her memory, except for the events that transpired during the course of her illness. The duration of her amnestic episode was 12 days. While seizures were not ongoing, they occurred frequently during this period. It is not possible, therefore, to discern whether the memory dysfunction was an ictal or post-ictal phenomenon. In the sense, however, in which she had recurrent electrographic seizures without complete recovery of memory function in between, it is reasonable to ascribe her prolonged amnestic period as due to status epilepticus.

A similar case of fluctuating memory loss was described by Dong and colleagues, where repeated scalp EEGs identified “nonspecific intermingled slow activity” only. An FDG-PET (fluorodeoxyglucose positron emission tomography) imaging identified hypermetabolic foci in temporal regions bilaterally (right > left), prompting an ASD trial, which improved both memory function and the PET findings [56]. These case reports are of interest as they establish the possibility that an isolated memory disturbance may (rarely) be the sole manifestation of NCSE, which may, as in the first case above, be associated with widespread electroencephalographic changes.

There are many case reports and case series that describe patients with episodes of transient amnesia that are likely related to seizures. For the most part, these are reports of patients with recurrent, short-lived episodes of amnesia who had unequivocal seizures at other times (with other semiologies, typically temporal lobe seizures), who had other symptoms suggestive of focal seizure activity preceding or during the amnestic attack and who responded to treatment with ASDs. For example, in the study by Zeman and colleagues [57], a rather strict definition of transient epileptic amnesia (TEA) was adopted (and consistently applied to subsequent studies), requiring (1) a history of recurrent witnessed episodes of transient amnesia, during which (2) cognitive functions other than memory were judged to be intact by a reliable witness, and (3) evidence for a diagnosis of epilepsy (based on epileptiform features on an interictal EEG, the co-occurrence of other seizure types or a clear-cut response to ASDs). The data from these reports are summarized in Table 21.3 [58–72], which includes representative data from 34 patients with TEA (see also Palmini and colleagues [73] and Mosbah and colleagues [74] for other case series). Anterograde amnesia was present in all but one patient, and most patients displayed a combination of anterograde and retrograde amnesia. Attacks were recurrent in all but two patients and varied from 2–3 per week to 1 per year. The duration of attacks varied widely, and in the vast majority of patients, attack frequently either markedly reduced or ceased completely following the initiation of ASD therapy.