How are epilepsy and epileptiform EEG abnormalities related to language and cognitive disorders in LKS?

Reflection of brain pathology

The relationship between epilepsy and epileptiform EEG abnormalities and the language and cognitive deficits in classic Landau-Kleffner syndrome (LKS) continues to be debated. Some investigators consider the epileptiform abnormalities an epiphenomenon reflecting underlying brain pathology rather than the direct cause of the language, cognitive, or behavioral disorder.4,68,69 They cite the lack of clear correlation between the status of the epilepsy and EEG abnormalities and the status of the language, cognitive, or behavioral disorder, as well as the lack of consistent response to medication. Although structural lesions are uncommon,70 metabolic abnormalities consistent with primary dysfunctional cortex are described more frequently as technology advances.

Direct cause of disorders

Other researchers believe that the language, cognitive, or behavioral disorder is a direct consequence of the epileptiform activity.3,20,71–73 In essence, LKS and its variants are a form of epileptic encephalopathy. Studies documenting transient cognitive impairment during epileptiform discharge lend support to this position,24,74–78 but electrical status epilepticus can occur without cognitive correlates.79 The anatomic specificity between the particular clinical deficit and the focus of epileptiform abnormalities also supports this position. That is, LKS and its variants each seem to reflect different areas of maximal epileptiform activity:

• In classic LKS, the intrasylvian cortex appears to be the pacemaker of epileptiform discharges.44,45
• Autistic epileptiform regression has both sylvian and extrasylvian pacemakers.44
• Occipital spike fields extend to posterior temporal and parietal areas.
• Centrotemporal spikes interfere with simple oromotor functions or complex movements including speech production.

Consistent with the argument that the epileptiform activity per se has a specific, negative effect on language processing, Seri et al.80 found that left hemisphere spike-triggered auditory evoked responses are associated with a greater reduction in amplitude and increase in latency of responses than are right-triggered auditory evoked responses. Morrell’s group81 demonstrated that intracarotid amobarbital (Amytal) injection into the hemisphere having the primary epileptiform focus causes the disappearance of discharges over both hemispheres, whereas contralateral Amytal injection suppresses spikes on only the injected side. Patients with significant focal seizure diathesis have shown dramatic improvement of language and cognitive function when hemispherectomy eliminates seizures.38,39

Theoretically, epileptiform activity could disrupt the development of language and cognitive function during a critical period.71 Neurons and axons affected by abnormal electrical discharge may not develop or perform normally.8 Epileptiform activity could interfere with the establishment of normal cortical circuitry.7,11,67,71,82–85 Synaptic contacts that should have degenerated by apoptosis could instead be strengthened.2

From a clinical perspective, the time of onset of epileptiform discharges may further obscure the boundaries of LKS and its variants. For example, LKS might start early in the course of language development, making it difficult to distinguish it from a developmental language disorder.86 Verbal auditory agnosia is a well-described developmental language disorder subtype.87 Epileptiform activity is relatively frequent in developmental language disorder cohorts.88–91

Does the epilepsy parallel the aphasia?

Controversy also exists as to the extent of the parallel between the presence and severity of the epilepsy and EEG abnormalities and the aphasic disorder (which must be distinguished from ictal aphasia). Many investigators have demonstrated a parallel between the status of the aphasia and the EEG.37 Several have noted that children who received early treatment with anticonvulsants demonstrated a remarkable clinical improvement paralleled by normalization of their EEG.92–94 Another report95 told of a patient with an arachnoid cyst whose language and EEG improved after the cyst was shunted.

The status of continuous spikes and waves during slow sleep (CSWS) correlates with aphasia in some cases. Because the disappearance of CSWS may harbinger an improvement in aphasia (although not coinciding with it), some investigators suggest that long-term expectant treatment with anticonvulsants, corticosteroids, or both is worthwhile if the EEG is improved significantly.96 Most long-term prospective case studies generally fail to demonstrate a parallel between the EEG and clinical status, however.97–104

Adapted from: Nass R and Gross A. Landau-Kleffner syndrome and its variants. In: Devinsky O and Westbrook LE, eds. Epilepsy and Developmental Disabilities. Boston: Butterworth-Heinemann; 2001;79–92.
With permission from Elsevier (www.elsevier.com).
Reviewed and revised May 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.

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