Acquired Epileptic Aphasia Workup

Updated: Oct 19, 2017
  • Author: Eli S Neiman, DO, FACN; Chief Editor: Amy Kao, MD  more...
  • Print
Workup

Approach Considerations

The diagnosis of acquired epileptic aphasia (AEA) should be considered in any patient with language regression. Obtaining brain images in a child with history of loss of language milestones is important, as it allows the clinician to rule out potentially treatable causes of aphasia, such as a brain tumor, before the patient is identified as having acquired epileptic aphasia.

The most precise way of confirming acquired epileptic aphasia is by obtaining overnight sleep electroencephalograms (EEGs), including EEGs during all stages of sleep such slow-wave sleep (stage 3) and rapid eye movement (REM). The clinician should refrain from ruling out acquired epileptic aphasia before an EEG is obtained that includes all stages of sleep, especially slow-wave sleep.

Next:

Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) is essential in patients with suspected acquired epileptic aphasia (AEA). Cerebrovascular thromboembolism, brain tumors, demyelination, neurodegenerative disease, and central nervous system (CNS) infections can easily be ruled out on MRI.

Some cases with a lesion and an electroencephalogram (EEG) suggestive of acquired epileptic aphasia (eg, electrical status epilepticus of sleep [ESES]) may represent a secondary form of acquired epileptic aphasia. This was the case in patients described to have cysticercosis or perisylvian polymicrogyria occurring in a pattern similar to that of acquired epileptic aphasia. Otherwise, MRIs in patients with acquired epileptic aphasia are grossly normal.

Volumetric analysis of acquired epileptic aphasia has shown reduced volumes of the planum temporale and superior temporal gyri.

Previous
Next:

PET and SPECT Scanning

In acquired epileptic aphasia (AEA), fluorodeoxyglucose (FDG) positron emission tomography (PET) scanning reveals decreased metabolism in one or both temporal lobes. Hypometabolism is especially prominent in the middle temporal gyrus. Hypermetabolism can also be seen in patients with acquired epileptic aphasia.

Increased metabolism on FDG PET scans has been associated with scans performed during continuous spike and waves of slow-wave sleep; the findings are often localized to both temporal lobes but may be most prominent on the left side. These apparently contradictory findings possibly represent the difference between interictal (hypometabolism) and ictal (hypermetabolism) patterns on FDG PET scans. During continuous spike and wave of slow-wave sleep, FDG PET reflects the increased metabolism induced by this ictal-like pattern.

In patients with intermittent or episodic aphasia, PET scanning is associated with increased metabolism over the temporal lobes. [28] Oxygen-15 water (H2O15) PET scanning has shown decreased metabolic activity over the posterior part of the superior temporal gyrus in patients with acquired epileptic aphasia who have poor short-term memory skills.

Single-photon emission computed tomography (SPECT) scanning of the brain demonstrates decreased perfusion of the left temporal lobe in patients with acquired epileptic aphasia.

Previous
Next:

Electroencephalography

Although electroencephalographic (EEG) abnormalities are present in acquired epileptic aphasia (AEA) by definition, no consensus exists about what constitutes typical abnormalities. Some authors have stated that, as a rule, the localization of the epileptic foci can vary in time and space (multifocal discharges). Beaumanoir also mentioned that, despite the "preference" of acquired epileptic aphasia for the temporal and parieto-occipital location of the discharges, most patients do not have unilateral left anterior and/or midtemporal predominance of the epileptic foci." [15] Other authors have stated that all patients with acquired epileptic aphasia syndrome have frequent left midtemporal spikes as well as generalized ones.

The meaning of the lateralization of the EEG discharges in relation to language dysfunction must take into consideration the fact that language dominance in young children is not as straightforward as in adults. One study in children aged 18-36 months with unilateral lesions revealed that left hemisphere pathology was correlated with severe deficits in only expressive language and that language dysfunction was most significant with posterior lesions. The severity of receptive language deficits did not differ with respect to side, site, or size of the lesion. Because the processing of language uses relatively widespread circuitry in children than in adults, cortical dysfunction affecting areas outside the left temporal region causing receptive language problems is not inconceivable.

Awake electroencephalography

On awake EEG, the background is usually normal initially. Focal theta slowing over the area of the discharges or even generalized slowing (probably secondary to medications) may be seen. In the awake state, some epileptiform abnormalities may be seen. The discharges are either focal or bilateral with temporal or parietal predominance. According to Beaumanoir, in half of the cases, the discharges had a "preference" for the temporal foci, and in one third the focus was in the parieto-occipital location. [15] No clear-cut hemispheric predominance and variable location of the spikes in the same patient over time has been observed in this syndrome. This finding is somewhat baffling, because the intuitive expectation is that the epileptiform abnormalities would be seen primarily over the dominant hemisphere.

Many well-documented cases of acquired epileptic aphasia developing after well-established language have shown exclusively or predominantly right-sided discharges. Findings from one study suggested a correlation between the spike morphology and etiology of epilepsy, with symptomatic and cryptogenic epilepsies, including acquired epileptic aphasia, having low amplitude, as well as "fast" spikes and the benign syndromes having high amplitude, long duration, and discharges less sharp than those of other conditions; however, further studies are necessary to confirm these findings.

Sleep electroencephalography

Besides the discharges seen during the wake state, sleep tends to promote the appearance of generalized paroxysmal abnormalities. Drowsiness or early sleep increases the frequency and generalization of the discharges, but maximal activation of the EEG abnormalities may not occur until stage 3 or rapid eye movement (REM) sleep.

Generalized spike-and-wave discharges initially have frequencies around 3-4 Hz, but during the course of the disease they may be slower, in the 1.5- to 3-Hz range. In some cases, the EEG may resemble the slow spike-and-wave pattern of the Lennox-Gastaut syndrome. At least in some cases, analysis of these generalized looking spike-and-wave discharges with more precise techniques such as EEG displayed on a high-speed oscilloscope, methohexital suppression test, dipole mapping, and magnetoencephalography (MEG) demonstrate a lead from the dominant temporal region.

Unilateral carotid artery injection of amobarbital in patients with bilateral spikes and waves is effective in suppressing discharges on both sides if injected in the dominant side (termination of secondary bilateral synchrony). Amobarbital injection to the nondominant side abolishes only the ipsilateral part of the generalized discharges. This pattern suggests secondary bilateral synchrony as the cause of the generalized-looking discharges in acquired epileptic aphasia. Sleep activation is common in acquired epileptic aphasia and very prominent in slow-wave sleep (stage 3) when the normal elements of sleep architecture disappear and spikes may become almost continuous.

These findings are reminiscent of the syndrome of continuous spike-and-wave during slow sleep (ie, ESES). These similarities have led to the postulation that acquired epileptic aphasia is a variant of the ESES syndrome. However, in many patients with acquired epileptic aphasia the discharges go unabated through REM sleep, a stage in which the epileptiform abnormalities may become focal in ESES. In one case, the continuous spike-and-wave discharges were initially seen exclusively during REM sleep.

ESES is generally defined as continuous spike and wave discharges taking up 85% or more of the slow wave sleep, but this proportion, named spike-and-wave index (SWI), is a matter of significant debate. The University of California at Los Angeles (UCLA) group has taken a more pragmatic approach to the subject and stated that an SWI greater than 50% was more likely to be associated with global developmental disturbances than an SWI of 50% or less.

Nickels and Wirrel found that the longer the ESES continues, the poorer the outcome, resulting in more significant cognitive and language impairment if not treated aggressively. [29] Early recognition of this diagnosis and treatment of the continuous discharges are required to improve overall neuropsychologic outcomes and prognosis. [29]

Tassinari et al suggested that this epileptic encephalopathy with continuous abnormal epileptiform discharges in sleep may interfere with sleep-related physiologic function. [30] ESES disrupts the neuroplastic process that occurs during sleep, adversely affecting learning and memory function and consolidation. [30]

Beaumanoir reported that many cases of otherwise typical acquired epileptic aphasia do not have continuous spike-and-wave during sleep. [15] Besides that, the ESES may not be stable; it was present on and off during the active phase of the disease in one of the author's patients who underwent several overnight EEGs. Many discharges in ESES have frontal or frontocentral predominance or localization, and sometimes the onset of the EEG seizures is also over the frontocentral region. Both these findings suggest that the generalized discharges in ESES may be due to secondary bilateral synchrony of frontal lobe foci as opposed to the temporal (mostly dominant side) onset in acquired epileptic aphasia. More recently, the UCLA group has confirmed this impression and found that the EEG changes tend to fluctuate over time.

EEG activation with sleep is often not seen or mild in children with developmental dysphasia. Patients with autistic disorder may have centrotemporal spikes during sleep. Those cases may easily be dismissed as comorbidity of benign rolandic epilepsy (benign epilepsy with centrotemporal spikes); however, a history of language regression is significantly more common among autistic patients with epileptiform EEGs than in those without it and no history of seizures. This subgroup of patients with autism, language regression, and epileptiform EEGs has been described as having autistic epileptiform regression.

EEG sleep stages in acquired epileptic aphasia are as follows:

  • Activation and generalization of discharges – Initially with stage 1-2, non-REM (NREM) sleep, maximal in stage 3 non-REM and REM sleep

  • Continuous spike-and-wave discharges during slow-wave sleep – Probably secondary generalized (secondary bilateral synchrony), common but not universal, may persist in REM sleep

Previous
Next:

Magnetoencephalography

Magnetoencephalography (MEG) measures variations in the magnetic field produced by electric currents generated in the brain. MEG patterns are somewhat less confusing than electroencephalographic (EEG) patterns, but most of MEG studies have been done in a select subset of patients with acquired epileptic aphasia (AEA), often with long-standing disease and prominent sleep-related bisynchronous spike-and-wave discharges.

Vertical-tangential dipole

Paetau et al demonstrated that, in patients with acquired epileptic aphasia, MEG shows a vertical dipole located in the superior surface of the temporal lobe that is 2-3 cm deep. [31] The experiences of other authors (including the author of this article) confirmed this finding. At times, sound triggers the MEG spikes in patients with acquired epileptic aphasia.

Both EEG and MEG are necessary for comprehensive spatial and temporal description of perisylvian epileptic networks in the Landau-Kleffner syndrome (LKS). According to Paetau, "MEG studies suggest that the bilateral epileptic discharges are generated in the auditory- and language-related perisylvian cortex in more than 80% of patients with LKS. About 20% of children with LKS have a unilateral perisylvian pacemaker that triggers secondary bilateral synchrony of spikes, and this 20% may regain considerable language skills after multiple subpial transections (MSTs) of the pacemaker area." [32]

MEG analysis of the bisynchronous discharges of patients with acquired epileptic aphasia shows onset of epileptiform activity over the left temporal region. Patients may have other discharges that start in the left temporal region but a time-linked component on the right temporal region.

The depth, orientation, and spread of the epileptic focus in acquired epileptic aphasia seen on MEG may at least partly explain the apparently contradictory EEG data. EEG recordings may miss data from attenuation of the electrical signal as it passes through the bone, dura mater, subcutaneous tissue, and skin, especially important in relatively deep foci, which are seen in acquired epileptic aphasia.

EEG vs MEG detection of vertical-tangential dipole

Regular EEG may not detect a vertical-tangential dipole such as that seen in acquired epileptic aphasia (on the superior surface of the temporal lobe), but this is actually the best type to be recorded on MEG. Vertical-tangential generators (electrical) produce a magnetic field that goes in and out of the scalp, because the magnetic field circulates around the axis of the electrical dipole. Magnetic fields with this orientation penetrate the magnetometers (gradiometers), producing a recordable signal. Most magnetometers/gradiometers currently used can record only magnetic fields circulating in and out of the skull, because they are oriented radially. The main limitations of MEG are that the apparatus is not widely available, because it is expensive to purchase and maintain.

MEG may be help in the pre-presurgical evaluation. In a few select cases, MEG may even obviate invasive (depth and subdural grids and strips) evaluation.

Previous
Next:

BAERs and Behavioral Hearing Tests

Brainstem auditory evoked potentials (BAERs) and behavioral hearing tests (BHTs) should be performed on any child who appears to have language problems.

BHT is performed to check the reaction of a child or toddler to a sound, generally by using positive reinforcement. For example, the child hears a unilateral sound in a semi-dark room, and if he or she turns to it, a bunny toy lights up and plays the drums. BHT can be tuned precisely to pitch and loudness but requires good cooperation from the child or toddler. Patients who have normal cognition can cooperate with BHT by the age of 14-18 months at the earliest.

BAERs are electroencephalographic (EEG) signals generated in the auditory nerve, medulla, and brainstem when one hears a sound. The time-locked potentials are averaged to make readable signals by eliminating the random (ie, non–time-locked) EEG activity. BAER testing requires less cooperation than BHT, but the sound can vary only in loudness, because the pitch used is standard and encompasses only the high frequency of the hearing band.

Sounds can also produce a cortical response, which is more difficult to measure than the one generated in the brainstem. Interest has been focused on cortical potentials. P300 potentials are often abnormal in patients with acquired epileptic aphasia (AEA). Preliminary work with steady-state auditory evoked responses to pulsed frequency modulations of a continuous tone may help in identifying patients with acquired epileptic aphasia. This technique, however, does not help in identifying patients with expressive language dysfunction. Large studies are necessary to confirm the utility of steady-state auditory evoked responses to pulsed frequency modulations.

Previous
Next:

Histology

A few cases of acquired epileptic aphasia (AEA) are secondary to brain tumors, cerebral cysticercosis, demyelination, or head injury. Pascual-Castroviejo et al described 4 cases of acquired epileptic aphasia associated with a cerebral angiographic pattern compatible with arteritis, [33] but their findings have not been reproduced. Moreover, cases of acquired epileptic aphasia without inflammatory changes on the neuropathology have been reported.

Most patients with acquired epileptic aphasia have no clear etiology for the aphasia, abnormal electroencephalography (EEG), and seizures. One autopsy study of patients with developmental dysphasia showed patterns similar to those seen in patients with dyslexia, including symmetry of the planum temporale, dysplasia of the insular cortex, poor lamination, neuronal rarefaction, and gliosis. One patient with congenital aphasia and complex cardiac malformation (transposition of the great vessels, ventricular septal defect with an overriding pulmonary artery) had bilateral old atrophic lesions over the opercula, insulae, and central regions.

Previous