Acquired Epileptic Aphasia Treatment & Management

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.^[31]

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.^[32]

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.^{[33, 34]} In a recent study, Kramer et al found clobazam and levetiracetam to be the most efficacious antiepileptic drugs in the treatment of ESES.^[35]

In a case report, felbamate 45 mg/kg/d was successful in treating seizures and aphasia.^[36] 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.

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.^[37] 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).^[37]

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 (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.^[38] 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.^[38] Sawhney et al reported improvement in all 3 of their patients with acquired epileptic aphasia who underwent this procedure.^[39]

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

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.^[40]

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.^[41] The effects of ketogenic diet on acquired epileptic aphasia and CSWS requires further investigation.

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.