Acquired Epileptic Aphasia 

Updated: Oct 19, 2017
Author: Eli S Neiman, DO, FACN; Chief Editor: Amy Kao, MD 

Overview

Background

Acquired epileptic aphasia (AEA) typically develops in healthy children who acutely or progressively lose receptive and expressive language ability coincident with the appearance of paroxysmal electroencephalographic (EEG) changes. In 1957, Landau and Kleffner initially described acquired epileptic aphasia and subsequently reluctantly agreed to the attachment of their names to the syndrome. In this article, acquired epileptic aphasia is used as a synonym for Landau-Kleffner syndrome (LKS).

In most cases described in detail, a clearly normal period of motor and language development occurs before acquired epileptic aphasia symptoms appear. However, in the last 2-3 decades, several reported cases have been difficult to classify, because the patients' presenting symptoms appear to have been variants of those originally described. In one case, expressive language deteriorated instead of receptive language, whereas in another case, a brief period of normal language development (single words) was followed by language regression with abnormal EEG findings.

Acquired epileptic aphasia must be differentiated from autism with minimal language regression, especially when it is associated with isolated EEG abnormalities. Many current researchers classify acquired epileptic aphasia as part of the syndrome of electrical status epilepticus of sleep (ESES), which is also known as continuous spike and wave of slow-wave sleep (CSWS) as initially described by Patry et al 1971.[1]

See also the following:

  • Benign Neonatal Convulsions

  • Epilepsy and Seizures

  • Epileptic and Epileptiform Encephalopathies

  • Autism

  • PET Scanning in Autism Spectrum Disorders

  • Benign Childhood Epilepsy

  • Epilepsy Surgery

  • Epileptiform Normal Variants on EEG

  • First Pediatric Seizure

  • Neuroimaging Epilepsy

  • Outcome of Epilepsy Surgery

Pathophysiology

Whether seizures and epileptiform discharges cause language dysfunction in acquired epileptic aphasia (AEA) is disputed. Aphasia and electroencephalographic (EEG) abnormalities might have a common cause (eg, a left temporal brain astrocytoma or head injury). Some authors speculate that reinforcement of synaptogenesis mediates the neurologic deficits in acquired epileptic aphasia and that epileptiform discharges during a critical period of synaptic reinforcement or pruning in turn mediate the reinforcement of synaptogenesis.

Concrete substantiation of this hypothesis is the existence of poor speech in patients who are affected early and whose condition does not respond to anticonvulsant measures. Other patients with acquired epileptic aphasia appear to have worsened language skills during periods of increased epileptiform activity. However, some reports describe no correlation between EEG abnormality and language dysfunction.

Most cases of acquired epileptic aphasia are spontaneous, although familial clustering has been reported. Descriptions of monozygotic twins include cases in which acquired epileptic aphasia affects only one sibling, cases in which this condition affects both siblings, and cases in which it affects one twin and developmental dysphasia affects the other.[2] These cases cast serious doubt on the role of epilepsy in speech dysfunction.

Etiology

Most cases of acquired epileptic aphasia (AEA) do not have a well-defined cause. However, a few cases of secondary acquired epileptic aphasia have been described.[3]

Low-grade brain tumors,[4] closed-head injury, neurocysticercosis,[5] and demyelinating disease[6, 7] have been associated with the clinical picture of acquired epileptic aphasia. Central nervous system (CNS) vasculitis may also be associated with this condition. One case of otherwise typical acquired epileptic aphasia has been described in association with mitochondrial respiratory chain complex I deficiency.[8] Bilateral perisylvian polymicrogyria may also present with new onset of speech disturbance after a 2-year period of normal language and electroencephalographic (EEG) findings typical of acquired epileptic aphasia.[9] Other diagnostic considerations might be warranted when evaluated a case of suspected acquired epileptic aphasia.

Epidemiology

Population-based epidemiologic data related to acquired epileptic aphasia (AEA) in the United States are limited. The Children's Hospital and Medical Center (Seattle, Wash) treats 1-2 new cases of acquired epileptic aphasia each year.

Globally, more than 200 cases have been described in the literature. Between 1957 and 1980, 81 cases of acquired epileptic aphasia were reported; more than 100 cases are documented every 10 years. Detailed numbers are difficult to report, because patients may be repeated in various series, as switching professional care is common due to the patient's and family's frustration with aggressive treatment that does not improve the patient's speech. An urban Israeli pediatric neurology clinic reported a 0.2% rate of acquired epileptic aphasia.

The first study of AEA in Japan concluded that the incidence in children aged 5-14 years was about 1 in a million; the prevalence of AEA in children aged 5-19 and under medical care was 1 in about 300,000-410,000.[10]

In affected children, aphasia usually appears at age 4-7 years, and there is a slight male predominance (male-to-female ratio, 1.7:1). However, symptom onset has been described in patients as young as 18 months and in those as old as 13 years. This discussion excludes the congenital cases with typical electroencephalographic (EEG) patterns and little or no language development; in such cases, the precise age of onset can never be determined.

In the early descriptions of the syndrome, language dysfunction was not recognized in the early acquisition phase in the first 18 months of life. In the last 2 decades, scrutiny of the language development has revealed some minor abnormalities. Soprano et al found signs of developmental dysphasia in 9 of 12 cases,[11] and Robinson et al reported language delay in 4 of 18 cases.[12]

Prognosis

Long-term outcome studies of patients with acquired epileptic aphasia (AEA) are limited by the lack of uniformity in diagnostic criteria. About half the patients have some fluctuation in aphasia, and the fluctuations usually occur over several months. On occasion, aphasia may worsen for as long as 7 years after the disease onset.

Worsened outcome has been noted in patients with an onset of language regression before age 5 years. Morrell found that symptoms persisting for longer than 1 year are predictive of poor language recovery,[13] and Robinson et al found that poor language recovery was correlated with electrical status epilepticus of sleep (ESES) for longer than 36 months.[12] Impaired short-term memory was universal on long-term follow-up of all of their patients with acquired epileptic aphasia.[12]

Short-term remissions pose a challenge in evaluating responses to various therapeutic modalities. One should be mindful that fluctuations are not unusual on the course of this disease. Both the clinical course and the electroencephalographic (EEG) changes may get worse, better, and even return to the baseline.[13] In many studies, these fluctuations did not always occur simultaneously (see History under the Clinical section for the explanation).

Lower rates of good outcomes have been reported, ranging from 14% to 50%, with a combined rate of 28.6% (see Table 1, below). Duran et al completed a transversal study of 7 patients (all males, aged 8-27 y) with Landau-Kleffner syndrome (acquired epileptic aphasia).[14] On long-term follow-up, most patients did not experience total epilepsy remission and language disturbances persisted. One patient had a normal quality of life and 6 patients reported agnosia/aphasia to be their biggest difficulty.[14]

Beaumanoir analyzed cases with follow-up of more than 10 years, which included those published in peer-reviewed journals and those from other sources, such as a doctoral thesis reported before 1992.[15]

Table 1. Long-Term Follow-up of Acquired Epileptic Aphasia (Open Table in a new window)

Study

Number of Patients

Mean Follow-up, y

Number of Patients with Normal or Mild Language Problems

Soprano et al[11] (1994)

12

8

3

Mantovani and Landau[16] (1980)

9

22

6

Paquier[17] (1992)

6

8.1

3

Rossi[18] (1999)

11

9.7

2

Robinson et al[12] (2001)

18

5.6

3

Duran et al[14] (2009)

7

9.5

1

Total

63

 

18 (28.6%)

Patient Education

Patients with acquired epileptic aphasia (AEA) have special educational needs. Teaching them sign language when they are aphasic may be helpful in maintaining a useful communication channel. Learning sign language does not prevent or delay the recovery of aphasia. These patients may be able to read and write; therefore, these skills should be used for teaching whenever doing so is possible.

It is important to educate patients and their parents regarding acquired epileptic aphasia and realistic outcomes. A potential cause of litigation in acquired epileptic aphasia is the high parental expectations for a complete and quick recovery of language and speech functions. These unrealistic expectations often come from information in the lay press and from television shows that mention isolated miracle cures in cases of acquired epileptic aphasia after treatment with steroids or other measures. These cases do not represent the usual course of most children with this condition but make up good cases for television or newspaper stories.

 

Presentation

History

In this section, the following aspects of acquired epileptic aphasia (AEA) will be briefly discussed:

  • Language symptoms

  • Seizures

  • Behavioral and neuropsychologic disturbances

  • Controversial features

Language symptoms

The first manifestation of the language problem is often word deafness or auditory verbal agnosia. In many patients, auditory verbal agnosia may include lack of recognition of familiar noises; however, alert responses to sound and tonal audiograms are usually normal. In some patients, even the capability of lateralizing and/or localizing sound may be impaired.

Receptive language is often severely or profoundly impaired as a result of an interference with phonologic decoding. Although the primary problem is in the receptive sphere, this syndrome appears in a critical period of language acquisition; therefore, speech production may be affected just as badly as or even worse than language comprehension. This is often the case as the disease progresses.

In some cases, impairment may be most severe in expressive language. In one study, the aphasia was predominantly expressive in 6 of 77 patients who appeared to have AEA.

Reading and writing may be remarkably preserved in children with little speech or auditory comprehension, and these children can be taught lip reading and writing as well. Speech disturbances may include fluent aphasia, use of jargon and paraphasias, asyntaxia, and verbal stereotypies in children who are not completely mute. Some abnormalities may superficially resemble autism or psychosis, common diagnoses given to children with acquired epileptic aphasia.

The age of onset of aphasia is between 18 months and 13 years, but it is usually after 4 years and before 7 years. A few authors include in the definition of acquired epileptic aphasia patients with limited or no language development associated with paroxysmal electroencephalography (EEG). In such cases, being certain about the true age of onset of symptoms is difficult. Other authors have included cases of developmental dysphasia associated with seizure-related fluctuations in speech performance with acquired epileptic aphasia, whereas other authors have not. Further studies are necessary to determine if the response to treatment really differs to justify this separation.

Language deterioration commonly occurs over weeks or months, but acute onset after a seizure has also been described. Intermittent/episodic aphasia may be seen as well. Regarding the course of language dysfunction and its relationship with paroxysmal EEG abnormalities, no consensus exists concerning the relationship between discharges on the EEG and the presence and intensity of language problems. In many cases, continuous spike and wave during sleep seems to precede language deterioration, and improvement in the paroxysmal EEG pattern during sleep often precedes the clinical language improvement.

Several authors have found that aphasia is correlated with unilateral or bilateral temporal-lobe discharges or with periods of 1 or more years of continuous spike and wave of slow-wave sleep (CSWS) when language appears to worsen.[19] Other investigators found this correlation to be far from reliable. Soprano et al observed persistent EEG abnormalities in patients with poor language recovery, but 6 of 9 with EEG normalization remained aphasic.[11]

The relationship between aphasia and paroxysmal EEG may not be an "on-off" response. Several factors limit the reliability of the EEG data. Neurologic deficits do not closely follow the maximal EEG changes in time. Patients with unilateral motor weakness related to a seizure (Todd paralysis) often remain weak for hours, and in rare cases, days after a partial seizure is gone. Repeated and long seizures are most often associated with long postictal dysfunction, which, at some point, may not recover completely.

The assumptions that paroxysmal EEG may or may not be correlated with the aphasia fluctuation also may be flawed, because if epileptic and/or neurotoxic brain damage is present in acquired epileptic aphasia, recovery from this damage may take time or may never happen. Two findings—that some patients improve with the use of corticosteroids or adrenocorticotropin hormone (ACTH) and that patterns on angiograms resemble those seen in cerebral arteritis—suggest that inflammation and vasospasm may play a role in some cases of acquired epileptic aphasia. This phenomenon is probably not universal, because not all patients show EEG or clinical response to steroids, and 2 neuropathologic specimens from temporal lobectomies revealed no inflammatory changes.

Seizures

The prevalence of clinical seizures in acquired epileptic aphasia is 70-85%. In one third of patients, only a single seizure (or episode of status epilepticus) is recorded. In about one half of affected children, a seizure is the initial manifestation of acquired epileptic aphasia. In some, a few years may pass between the first seizure and the onset of any speech problems, whereas the opposite is true in others. Seizures usually appear between ages 4 and 10 years, and many series show that remission of the seizures before adulthood (often before age 15 y) is the rule.

Clinical seizures are often easy to treat, but normalization of EEG discharges can be challenging. Among patients in whom ictal semiology is well described, 59% had partial seizures, 39% had generalized tonic-clonic seizures, and 16% had atypical absences. Myoclonic seizures involving the face and eyes have been described. About 12% of patients have a family history of epilepsy.

Behavioral and neuropsychologic disturbances

Behavioral disturbances are seen in as many as 78% of the patients. Some children may appear deaf or autistic. The diagnosis of autism is often considered because of the common presence of asyntaxia, parapsias, and verbal stereotypies. Hyperactivity and a decreased attention span are observed in as many as 80% of patients. Aggressive and oppositional behavior, including rage attacks, is not unusual. The aggression and rage may be so prominent that the patients may be admitted to a psychiatric service rather than a neurologic service, either initially or during the course of the disease. Anxiety and avoidant or bizarre behavior may also be seen.

Although behavior patterns are thought to be secondary to the language impairment in acquired epileptic aphasia, some patients may have complex, hard-to-explain, and bizarre behaviors, such as avoidance of interpersonal contact and gestural stereotypies. In some cases, frankly psychotic behavior has been described.

Other aspects of cognition are traditionally said to be preserved, but a discrepancy between nonverbal and verbal skills is sometimes seen. Diffuse neuropsychologic deficits may appear over time. Short-term memory is a debilitating feature seen in long-standing cases of acquired epileptic aphasia.

Controversial features

Some cases initially thought to be benign childhood epilepsy with centrotemporal spikes later develop into a picture of acquired epileptic aphasia. In addition, some patients with early onset benign childhood occipital epilepsy (Panayiotopoulos type) syndrome may have language dysfunction because of the continuous spike-and-wave discharges during slow-wave sleep.[20, 21]

Physical Examination

Mental status examination of patients with acquired epileptic aphasia (AEA) demonstrates language, speech, and behavior problems, as described earlier (see History). A history of a poor understanding of spoken language should be substantiated by performing objective testing of all aspects of the patient's speech and language, such as the child's comprehension, repetition, reading, and writing. Bedside and/or office testing of language skills should be supplemented by formal neuropsychologic testing.

Besides language, speech, and behavior, physical and neurologic examination of patients with acquired epileptic aphasia shows motor clumsiness or, less frequently, apraxia. In some cases, frank abnormalities of tone and motor function are noted, but these findings are the exceptions rather than the rule.

Patients with acquired epileptic aphasia secondary to a tumor, stroke, or head injury commonly have hemiparesis (usually right sided). Signs of increased intracranial pressure, such as papilledema and, in more extreme cases, erratic respirations, bradycardia, and hypertension, should alert the clinician to the possibility of a mass lesion.

Syndromes Related to AEA

This section will discuss the following (see also Diagnostic Considerations in the Differentials section):

  • Oromotor-expressive language deficit associated with a centrotemporal epileptic focus (acquired expressive epileptic aphasia)

  • Developmental dysphasia or developmental expressive language disorder

  • Acquired epileptic aphasia [AEA] and autism

  • AEA and ESES

  • Childhood disintegrative disorder

Oromotor-expressive language deficit associated with a centrotemporal epileptic focus (acquired expressive epileptic aphasia)

A rare syndrome has been described in which patients appear to have a primarily expressive language deficit associated with a centrotemporal epileptic focus. Temporary speech and oromotor disturbances may be seen in this syndrome, and voluntary oromotor functions and speech production may be affected depending on the location and spread of the epileptic discharges (more anterior or posterior in the perisylvian region). Similar to acquired epileptic aphasia, these deficits can occur as initial symptoms of the disorder without visible seizures. The range of symptoms in these patients goes from nonlinguistic deficits, such as intermittent drooling to oromotor apraxia, disfluency, and (in severe cases) full-blown anterior opercular syndrome.

Oromotor apraxia and speech problems may be congenital, or they may develop or worsen with episodes of sustained spike and wave discharges during sleep. Seizures are nocturnal and either orofaciobrachial partial or secondarily generalized. The ages of onset, progression, and recovery of the deficits are variable but depend on the degree and duration of epileptic activity. The electroencephalogram (EEG) in this syndrome shows rolandic (ie, centrotemporal) discharges, which are commonly bilateral.

During sleep, continuous spike and wave discharges may be seen on the EEG, and that pattern may be correlated with clinical deterioration. One family with this syndrome had autosomal dominant transmission with anticipation for the seizure disorder, oral and/or speech dyspraxia, and cognitive dysfunction, raising the possibility of a triplet repeat syndrome.[22] Antiepileptic medication and other agents (see Treatment), may affect the course of the disease in some cases.

Developmental dysphasia or developmental expressive language disorder

Developmental dysphasia is a syndrome in which language acquisition does not occur despite normal intelligence and the lack of brain or hearing pathology. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) refers to this syndrome as developmental expressive language disorder, a more appropriate term than developmental dysphasia, because it considers the poor development or lack of acquisition of expressive language.

Overnight sleep recording in patients with developmental dysphasia may show epileptiform discharges; in one study, as many as 30 of 32 cases studied had these discharges even though half of the patients studied never had a seizure. The EEG abnormalities in developmental dysphasia may be more prominent during sleep, but a study found only minimal or no worsening in the transition from sleep stages 1-2 to 3 (slow-wave sleep).

Other investigators have described patients with developmental expressive language disorder and epileptiform EEGs, which suggests that these cases are "congenital variants of the Landau-Kleffner syndrome (AEA)." As can be concluded from the name of this disorder, the main problem is with expressive language, whereas in classic acquired epileptic aphasia the primary problem is in the receptive sphere. Nonetheless, differentiation between this disorder and acquired epileptic aphasia may be difficult for the following reasons:

  • In acquired epileptic aphasia, the primary problem is in the receptive sphere, but speech production may be affected just as badly or even worse than language comprehension.

  • An expressive-aphasia variant of acquired epileptic aphasia is known.

  • Cases of acquired epileptic aphasia and developmental dysphasia can be seen in the same pedigree, including a report of discordant monozygotic twins, suggesting a similar genetic abnormality with different phenotypes.[2]

  • Many patients with developmental dysphasia also have EEG abnormalities, and 3 cases seemed to respond to adrenocorticotropin hormone (ACTH) therapy.

Because of these arguments, clinicians should be open to the possibility that some patients with developmental expressive language disorder may have abnormal EEGs and that they occasionally respond to treatments used for acquired epileptic aphasia. Differentiation of developmental expressive language disorder (developmental dysphasia) and acquired expressive epileptic aphasia (oromotor-expressive language deficit associated with centrotemporal epileptic focus) with an early onset of symptoms is difficult and may be impossible in many cases.

AEA and autism

Autism is a strong consideration in patients presenting with an acquired epileptic aphasia-like picture. Not all patients with acquired epileptic aphasia have seizures, and some patients with autism may have EEG abnormalities with or without seizures. As mentioned earlier, many families change their perception of the patient's history over time. In these cases, consulting the child's initial medical records to obtain the correct information is helpful. In that sense, retrospective analysis, especially if the initial consultation notes are not accessible, may overestimate the incidence of language regression in these patients.

The diagnosis of autism (autistic disorder) based on criteria of the DSM-IV-TR is divided in 3 subgroups: (1) impairment of reciprocal social interaction, (2) qualitative impairment in verbal and nonverbal communication as well as imaginative activity, and (3) markedly restrictive repertoire of activities and interests. Pervasive developmental disorder (PDD) is diagnosed when qualitative impairment of reciprocal social interaction and verbal and nonverbal communication skills is present without fulfillment of the criteria for autistic disorder, schizophrenia, or schizotypal or schizoid personality disorder.

A history of language regression is not unusual in autism and is obtained retrospectively in as many as 39% of children with autism and prospectively in one third of patients with either autism or PDD. Language regression occurs equally among children with autism or PDD with or without epilepsy. Children with low cognitive function are more likely to have undergone regression (34%) than those with better cognitive skills (20%). The age at which language regression occurs (ie, before or after 2 y) makes no difference in the proportion of children with epileptiform EEGs.

The frequency of overt epilepsy among patients with autism or PDD is 7.6-25%. This range partly depends on the definitions of autism and PDD and on how strictly these criteria are applied. Of these patients, epilepsy is more common among males, and the seizures start in the first year of life in more than 80% of the children. Tuchman and Rapin found that epilepsy was present in 14% of autistic children after they excluded patients with Rett syndrome.[23] Other authors have reported higher frequencies than this among patients with autism.

The relationship between autism, epileptiform EEG, epilepsy, and language regression is complex and only partially understood. In a study in which 60% of an autistic population underwent EEG, about 22% had epileptiform abnormalities. In approximately one half of the children in whom EEG demonstrated epileptiform discharges, the discharges were located over the centrotemporal region, regardless of whether the child was epileptic or had regression. Two explanations for this finding are possible: (1) Patients may have comorbidity of benign (rolandic) epilepsy with centrotemporal spike-EEG trait with autistic symptoms (eg, benign epilepsy with centrotemporal spikes, one of the most prevalent epileptic syndromes) or (2) There may be a cause-effect relationship between the epileptiform abnormalities and the autistic and language regression symptoms.

Tuchman and Rapin prospectively studied language regression in patients with PDD and found that, in nonepileptic autistic children, a history of regression was associated with a 2-fold increase in the incidence of epileptiform EEG compared with those who had not undergone regression and had no seizures.[23] The proportion of children with epilepsy or epileptiform EEGs who had regression before or after age 2 years did not differ.[23]

The types of seizures most commonly associated with autism are infantile spasms, complex partial seizures, and generalized tonic-clonic convulsions. About one third of autistic patients with epilepsy have (or had) infantile spasms or myoclonic seizures. Severe mental retardation and motor deficit appear to be associated with an increased incidence of epilepsy in autistic patients. A high incidence of epilepsy occurs in patients with deficit in oral comprehension or verbal auditory agnosia. This finding is not unexpected, because it is probably due to inclusion of patients with acquired epileptic aphasia and its variants, which all can demonstrate autistic features.

AEA and ESES

One of the main differential diagnoses of acquired epileptic aphasia is the syndrome of continuous spike-wave during slow sleep, or ESES. In fact, some authors consider acquired epileptic aphasia as part of the ESES spectrum. A few features may help differentiate these 2 syndromes, as follows:

  • In ESES, nocturnal spike and wave discharges by definition occupy more than 85% of slow-wave sleep (stages 3 non–rapid eye movement [NREM]), especially during the first sleep cycle, and become focal or disappear during REM sleep.

  • In acquired epileptic aphasia, generalized spike-and-wave discharges may continue to be maximal or may be seen only during REM.

  • The EEG in ESES may show frontal or frontocentral location of focal discharges, but in acquired epileptic aphasia the focal discharges often show temporal or parietal distribution.

The use of the source localization of the focal discharges for the differentiation of acquired epileptic aphasia from ESES has limited value, because well-documented ESES cases may have primary parietal generators for secondary generalized discharges. In many cases, the generalized discharges seen in ESES may represent secondary bilateral synchrony from a consistently unilateral focus, which can be located in either hemisphere. The seizures seen in patients with ESES are similar to the ones of acquired epileptic aphasia, but drop attacks and myoclonic and unilateral clonic seizures may be more common in ESES. The nature of the cognitive deterioration is more diffuse in ESES than in acquired epileptic aphasia.

Besides substantial language problems, patients often have reduced temporal-spatial orientation and memory function during the active phase of ESES. As measured by using the Wechsler intelligence scales for children (WISC), cognition (ie, intelligence quotient [IQ]) severely declines. Verbal scores on the WISC are affected more than performance scores. The term disintegrative epileptiform disorder has been used in reference to patients with normal development in whom deterioration of language, sociability, nonverbal communication, and cognition occurs after age 2 years in association with an epileptiform EEG, often with an ESES pattern.

Genetic factors in epileptic aphasias

Lesca et al found the following: "About 20% of cases of LKS, CSWS, and electroclinically atypical rolandic epilepsy are often associated with speech impairment and can have a genetic origin sustained by de novo or inherited mutation in the GRIN2A gene (encoding the N -methyl-D-aspartate (NMDA) glutamate receptor α2 subunit, GluN2A). The identification of GRIN2A as a major gene for these epileptic encephalopathies may provide crucial insights into the underlying pathophysiology."[24]

Rare pathogenic deletions that include GRIN2A can be implicated in neurodevelopmental disorders. Carvill et al found the following: "[They] sought to delineate the pathogenic role of GRIN2A in 519 probands with epileptic encephalopathies with diverse epilepsy syndromes. They identified 4 probands with GRIN2A variants that segregated with the disorder in their families. Notably, all 4 families presented with epileptic aphasia syndromes and accounted for 9% of epilepsy-aphasia cases. They did not detect pathogenic variants in GRIN2A in other epileptic encephalopathies (n = 475) or in probands with benign childhood epilepsy with centrotemporal spikes (n = 81)." They reported the first monogenic cause for epilepsy-aphasia. " GRIN2A mutations are restricted to this group of cases, which has important ramifications for diagnostic testing and treatment and provides new insights into the pathogenesis of this debilitating group of conditions."[25]

Childhood disintegrative disorder

Regression of language, cognition, and behavior after age 2 years has been classified as disintegrative disorder. The definition of the term is still evolving. Rapin suggested that the term disintegrative disorder should be used for patients with autistic regression with onset after age 2 years.[26, 27]

The DSM-IV-TR defines childhood disintegrative disorder as loss of language, social, adaptive, and play skills between the ages of 2 and 10 years after normal development in these areas before age 2 years. The DSM-IV-TR criteria require abnormal functioning in at least 2 of the following areas:

  • Social interaction

  • Verbal and nonverbal communication and make-believe play

  • Stereotyped behavior, interests, activities, mannerisms, and stereotypies

The DSM-IV-TR diagnostic criteria of childhood disintegrative disorder also require the clinician to rule out any of the other PDDs, schizophrenia, and other dementing medical conditions (eg, adrenoleukodystrophy, metachromatic leukodystrophy); however, the criteria do not specifically mention differentiation on the basis of EEG findings. The term disintegrative epileptiform disorder has been used to describe patients with normal development who present with deterioration of language, verbal and/or nonverbal communication, sociability, and cognition after age 2 years associated with an epileptiform EEG.

The EEG abnormality is often ESES with frontal predominance. The latter may be differentiated by widespread deterioration of cognition, as opposed to the picture of acquired epileptic aphasia, which affects mostly language, at times with secondary behavioral changes. Differentiation between disintegrative epileptiform disorder and ESES may be impossible on clinical and EEG grounds, owing to the variability of the behavioral and cognitive findings in ESES.

Table 2, below, summarizes the numbers of patients with abnormal EEG findings among autism, dysphasia, and epilepsy from studies by Tuchman and colleagues.

Table 2. Epileptiform EEG Findings in Autism, Dysphasia, and Epilepsy (Open Table in a new window)

Source

Diagnosis

Number of Patients

Number of Patients with EEGs

Patients with Abnormal EEGs (%)

Tuchman et al (1991)

Autism with epilepsy

42

40

75

Autism without epilepsy

160

139

8

Dysphasia with epilepsy

19

19

58

Dysphasia without epilepsy

218

66

9

Tuchman and Rapin[23] (1997)

PDD or autism

585

392*

NA

With epilepsy

NA

66

59

Without epilepsy

NA

66

59

Without epilepsy but with history of regression

NA

155

14

Without epilepsy and without history of regression

NA

364

6

EEG(s) = electroencephalogram(s); NA = not applicable; PDD = personality developmental disorder.

* Sleep EEGs.

 

DDx

Diagnostic Considerations

The differential diagnosis of acquired epileptic aphasia (AEA) is extensive, including the conditions shown in Table 3, below. Table 3. Differential Diagnosis of Syndromes of Language and/or Cognitive and Behavioral Regression

Table. (Open Table in a new window)

Diagnosis

Deterioration

EEG Patterns

Autistic epileptiform regression

Expressive language, RL, S, verbal and nonverbal communication

Centrotemporal spikes

Autistic regression

Expressive language, RL, S, verbal and nonverbal communication

Normal

Acquired epileptic aphasia

RL, possibly behavioral

Left or right temporal or parietal spikes, possibly ESES

Acquired expressive epileptic aphasia

Expressive language, oromotor apraxia

Centrotemporal spikes

ESES

Expressive language, RL, possibly behavioral

ESES

Developmental dysphasia (developmental expressive language disease)

No; lack of expressive language acquisition

Temporal or parietal spikes

Disintegrative epileptiform disorder

Expressive language, RL, S, verbal and nonverbal communication, possibly behavioral

ESES

EEG = electroencephalographic; ESES = electrical status epilepticus of sleep; RL = receptive language; S = sociability.

* Continuous spike and wave of slow-wave sleep (>85% of slow-wave sleep).

Acquired aphasia in children may be secondary to head trauma, brain tumors, stroke, or neurocysticercosis. As with acquired epileptic aphasia, head injury, brain neoplasms, and cerebrovascular thromboembolism may be associated with an epileptiform electroencephalogram (EEG) and seizures. Other neurologic deficits, such as hemiparesis or signs of increased intracranial pressure, may be a clue of an underlying structural lesion. Imaging studies, especially magnetic resonance imaging (MRI), can help clarify the diagnosis. Patients with brain tumors may develop an acquired aphasia secondary to seizures and epileptic discharges generated around the neoplasm.

Deaf children may have many of the symptoms of acquired epileptic aphasia. Conversely, patients with acquired epileptic aphasia do not always have convulsions, and, even when present, the seizures may be missed. Some children with acquired epileptic aphasia may initially be thought to be deaf and are referred for audiologic evaluation.

Hyperactivity and decreased attention span are common in acquired epileptic aphasia. Patients in whom attention deficit disorder is suspected should be carefully examined for aphasia. The resemblance of acquired epileptic aphasia and attention deficit disorder is superficial, and differentiation of the 2 should not be difficult. Likewise, patients with aggressive (eg, rage attacks), oppositional, or psychotic behavior should be examined for signs of language impairment, because these symptoms can be present in patients with acquired epileptic aphasia.

Complex and bizarre behaviors, such as interpersonal contact avoidance, gestural stereotypies, and frankly autistic behavior can be seen in acquired epileptic aphasia. A careful history is necessary in patients with autism or pervasive developmental disorders (PDDs). When in doubt, a sleep EEG is required.

Patients who never develop language or have a poor acquisition of language must be differentiated from children with hearing deficits and mental retardation. Acquired epileptic aphasia and mental retardation (congenital without intellectual deterioration) should be differentiated on the basis of information from the history, neuropsychologic testing, and EEG. Patients with acquired epileptic aphasia typically have normal hearing threshold on formal testing.

On occasion, patients with neurodegenerative diseases may present with problems in language comprehension. This is especially true for patients with adrenoleukodystrophy in whom the initial complaint can be difficulty in processing auditory information due to dysmyelination of the white matter in the temporoparietal region. At this stage, patients do not necessarily have corticospinal tract signs; however, over time, spasticity, increased deep tendon reflexes, and upgoing toes become apparent. Seizures are infrequent (about 10%) in adrenoleukodystrophy. The age of onset of the childhood form of adrenoleukodystrophy is similar to that of acquired epileptic aphasia. T2-weighted MRIs of the brain show increased signal intensity in the affected areas.

Other problems to be considered include the following:

  • Acquired expressive epileptic aphasia

  • Adrenoleukodystrophy

  • Childhood disintegrative disorder

  • Developmental dysphasia or developmental expressive language disorder

  • Disintegrative epileptiform disorder

  • Electrical status epilepticus of sleep (ESES)

Differential Diagnoses

 

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.

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.

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.

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

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.

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.

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.

 

Treatment

Approach Considerations

The treatment of acquired epileptic aphasia (AEA) is far from standard, and many therapeutic modalities have been tried with variable success. Among these are anticonvulsant drugs, corticosteroids (eg, adrenocorticotropin hormone [ACTH]), ketogenic diet, and surgical intervention with multiple subpial transections (MSTs).

The calcium channel blocker nicardipine has been used in the treatment of acquired epileptic aphasia. In the initial report in 4 patients that suggested the use of nicardipine for acquired epileptic aphasia, nicardipine was given in association with anticonvulsant medications (carbamazepine, valproic acid) and corticosteroids (3 of 4 cases). However, cessation of nicardipine was associated with acute speech deterioration. The dose of nicardipine was 1 mg/kg/d or 60 mg/d for large patients.

A few case reports have demonstrated that intravenous gammaglobulin may be useful in acquired epileptic aphasia, but repeated doses may be necessary.[34]

Anticonvulsant Drugs

Many commonly used anticonvulsant agents effective against partial or generalized seizures have been used in acquired epileptic aphasia (AEA) with variable success. Phenobarbital, carbamazepine, and phenytoin are often ineffective in halting the electroencephalographic (EEG) discharges, and aphasia and may worsen the electrographic activity. In a few cases, the drugs may actually worsen the picture, especially in patients with drop seizures and atypical absences.

Valproic acid, ethosuximide, and benzodiazepines alone or in combination have been partially or transiently effective in some cases. Benzodiazepines, especially clobazam (in Europe) and midazolam, have been most effective when given intravenously (IV). Both the impracticality of this mode of administration and its short-lived effect have limited its use.

Diazepam 0.5 mg/kg given rectally (PR) at bedtime is sometimes effective. This treatment is used in 4- to 6-week courses on and off to avoid tachyphylaxis. The Boston Children's Hospital Epilepsy Group has used continuous diazepam 0.5-0.3 mg/kg given orally (PO) in acquired epileptic aphasia for periods up to 1 year.[35]

Several studies have shown levetiracetam to be beneficial when used as monotherapy in the treatment of electrical status epilepticus of sleep (ESES), continuous spike wave in slow-wave sleep (CSWS), and benign idiopathic focal epilepsies in childhood.[36, 37, 38] In a recent study, Kramer et al found clobazam and levetiracetam to be the most efficacious antiepileptic drugs in the treatment of ESES.[39]

In a case report, felbamate 45 mg/kg/d was successful in treating seizures and aphasia.[40] However, the high frequency of aplastic anemia and liver dysfunction with this drug limits its use.

Among the drugs that the US Food and Drug Administration (FDA) has not approved, sulthiame and clobazam are effective in some patients with acquired epileptic aphasia.

Go to Antiepileptic Drugs for complete information on this topic.

Corticosteroid and Steroid Agents

In 4 cases Lerman et al described, early corticosteroid or adrenocorticotropin hormone (ACTH) therapy improved symptoms of acquired epileptic aphasia (AEA) and normalized the electroencephalogram (EEG). Prolonged steroid therapy with ACTH 80 IU/d (range 0.2-1 U/kg/d from other sources) has been recommended.

Regarding steroids, prednisone 60 mg/d followed by a 3-month taper is commonly used. Another dosing schedule is 3-5 mg/kg/d of prednisone for 3 months. Pulse intravenous (IV) methylprednisolone therapy has been used to induce remission in acquired epileptic aphasia. A dose of 20-30 mg/kg/d for 3-5 d has been used, intervals followed by prednisone 2 mg/kg, which is then tapered after 1-2 months.

Note that steroid reduction may be associated with recurrence of symptoms; 6 months to several years of treatment may be necessary. Some authors have had the impression that early steroid therapy during the deterioration phase may be associated with increased efficacy and decreased need for prolonged treatment.

Buzatu et al reported that corticosteroids can be safely and effectively used in treating children with continuous spike wave in slow-wave sleep (CSWS) and epilepsy.[41] The investigators administered hydrocortisone (initial dose of 5 mg/kg/d and tapered over 21 mo) to 44 children (25 boys) who had CSWS and evaluated its effects on EEG, behavior, and cognition. Positive response to steroids was found during the first 3 months of treatment in 34 children (77.2%), with normalization of EEG in 21 and relapse in 14. Twenty patients (45.4%) were long-term responders after steroid treatment, with a shorter duration of CSWS and significantly higher intelligent quotient/developmental quotient (IQ/DQ).[41]

Adverse effects and contraindications

Treatment with either corticosteroids or ACTH is associated with many complications, including immunosuppression, weight gain, cushingoid appearance, diabetes, hypertension, steroid myopathy, electrolyte imbalances, mood disorders (depression, mania), aseptic osseous necrosis, pathologic fractures, cataracts, and adrenal failure (during or after taper).

Corticosteroids and ACTH are contraindicated in patients with preexisting immunosuppression, a history of aseptic osseous necrosis, untreated tuberculosis, or hookworm infestation (personal case). Both tuberculosis and hookworm infestation may become widespread with corticosteroid treatment. When in doubt, a purified protein derivative (PPD) test for tuberculosis should be administered before treatment is started. Diabetes, glucose intolerance, hypertension, and obesity are relative contraindications that these drugs may aggravate.

Multiple Subpial Transections

Multiple subpial transections (MSTs) have been used with variable success in acquired epileptic aphasia (AEA). In this procedure, the cortex is sliced in parallel lines in the midtemporal gyrus and perisylvian area to attenuate the spread of the epileptiform activity without causing cortical dysfunction.

Demarcation of the epileptiform discharge-generation area requires complete investigation by using the methohexital suppression test, an intracarotid amobarbital injection to abolish secondary bilateral synchrony, and electrical and magnetic dipole mapping.

Morrell et al reported mixed results in their experience at Rush-Presbyterian hospital with mixed results in 14 patients with acquired epileptic aphasia who underwent multiple subpial transections.[42] Seven of 14 patients recovered age-appropriate speech and no longer needed speech therapy or special education classes. Another 4 (29%) of 14 had marked improvement of speech and understanding of instructions given verbally but still required speech therapy. Eleven patients had language dysfunction for 2 or more years.[42] Sawhney et al reported improvement in all 3 of their patients with acquired epileptic aphasia who underwent this procedure.[43]

Go to Epilepsy Surgery and Outcome of Epilepsy Surgery for complete information on these topics.

Ketogenic Diet

Experience with ketogenic diet in patients with acquired epileptic aphasia (AEA) is limited. Bergqvist et al found improvement in language, behavior, and seizures in 3 patients with acquired epileptic aphasia refractory to corticosteroids and immunoglobulin treated with ketogenic diet. Improvement was seen in the 3 patients studied for 26, 24, and 12 months.[44]

Nikanorova et al evaluated the effect of ketogenic diet in 5 patients with continuous spike wave in slow-wave sleep (CSWS) that was refractory to steroids and anticonvulsant agents. One patient had full CSWS disappearance, and a second patient had only partial and intermittent improvement.[45] The effects of ketogenic diet on acquired epileptic aphasia and CSWS requires further investigation.

One study showed that long-term ketogenic diet treatment can cause liver parenchymal injury, hepatic steatosis, and gallstone formation in children with intractable epilepsy. Therefore, patients should be monitored by screening liver enzymes and abdominal ultrasound in order to detect these possible side effects.[46]

Dichotic Listening Treatment

Although there is a body of evidence to support medical treatment for Landau-Kleffner syndrome (LKS), there is limited information about the clinical management for the language disorder or acquired (central) auditory processing disorder [(C)APD].

Dichotic listening treatment is one type of direct remediation for (C)APD being studied that takes advantage of the brain’s lifelong capacity for plasticity and adaptive reorganization.[47]

Dichotic exercises directly stimulate areas of the cortex, which in turn forces the auditory pathways to these areas to exercise and recruit existing neuronal connections or build new neural connections and pathways. As the integrity of these areas pathways is improved, speech stimuli can reach the language processing temporal lobe more efficiently, resulting in improvement of dichotic skills.[48]

 

Consultations

Neuropsychologic testing is mandatory in all patients with acquired epileptic aphasia (AEA).

All patients with acquired epileptic aphasia should be referred for speech therapy. The speech and language therapist has an essential role in the management of these patients. Learning sign language before the patient's recovery can diminish anxiety and improve socialization in these children. Learning sign language does not appear to delay the recovery of speech in cases of acquired epileptic aphasia.

Patients with acquired epileptic aphasia who do not have a response to anticonvulsant medications and steroids or adrenocorticotropin hormone (ACTH) may be considered for multiple subpial transection (MST) at a qualified epilepsy center.

Psychotherapy and psychiatric consultation may be indicated in selected patients with acquired epileptic aphasia in whom the secondary behavioral problems need pharmacologic intervention.

 

Medication

Medication Summary

No drug of choice is known for acquired epileptic aphasia (AEA), but corticosteroids and adrenocorticotropin hormone (ACTH) have become popular despite a lack of controlled trials. One should not treat based on the following information but should reference the most up-to-date literature.

The data presented below, including dosages, are based on how corticosteroids and ACTH have often been prescribed for patients with acquired epileptic aphasia but may be subject to change.

Corticosteroids

Class Summary

The mechanism of action of immunosuppressant-mediated improvement in acquired epileptic aphasia (AEA) is unknown.

Prednisone

Prednisone is effective in improving aphasia in a few reports. Early treatment may be better than late treatment (data from uncontrolled trials).

Corticotropin (H.P. Acthar)

Corticotropin is effective in improving aphasia (few reports); early treatment may be better than late treatment (data from uncontrolled trials).

Prednisolone (Millipred, Orapred ODT, Veripred, Prelone)

Prednisolone is effective in improving aphasia in a few reports. Early treatment may be better than late treatment (data from uncontrolled trials).

Methylprednisolone (Solu-Medrol)

Pulse intravenous (IV) methylprednisolone therapy has been used to induce remission in acquired epileptic aphasia.