Acquired epileptic aphasia: Landau-Kleffner syndrome

Sir,

The Landau-Kleffner syndrome or the syndrome of acquired epileptic aphasia was first described in 1957.[1] The disorder is characterized by gradual or rapid loss of language in a previously normal child. While this disorder appears to be relatively uncommon, its frequency is questionable due to its unfamiliarity among health professionals, and the likelihood of misdiagnosis. It is imperative that communication specialists become alert to the characteristic symptoms of LKS. All pediatric LKS patients have abnormal EEG that is compatible with the diagnosis of epilepsy; however, only 70% have clinical seizures. We report here a case of this rare disorder and a review of the current literature concerning this disorder.

A 14 year-old female presented to us with the complaint of progressive loss of speech and seizure disorder for the past one year. According to the attendant accompanying the patient, the child was developmentally normal before the onset of the illness. However, after some trauma to the head, although the immediate period was uneventful, one month after the trauma, her speech progressively decreased and she started communicating with signs. Over a period of five to six months, the paucity of speech progressed to complete aphasia and the child also had abnormal behavior in the form of bouts of aggressiveness and hyperactivity. The child also had five episodes of generalized tonic-clonic seizures, which occurred during her sleep since the onset of the illness. Examination revealed that the child displayed abnormal behavior and attention deficit, and was not responding verbally to any command. The results of her general and systemic examination were normal. CNS examination results also were normal except for the abnormal behavior, attention deficit, auditory agnosia, and aphasia (both receptive and expressive). Fundus examination results were normal as were the CBC, LFT, RFT, and CSF. BERA was normal, and the EEG revealed generalized spikes bilaterally over the temporoparital region with background slow waves; the MRI was also normal. On the basis of the presentation, EEG, and the normal MRI, Landau-Kleffner syndrome was diagnosed and the child was started on sodium valproate, prednisolone, and speech therapy; the child is under follow-up.

The Landau-Kleffner syndrome is a rare disorder characterized by an acquired receptive and expressive aphasia and epileptic seizures. It is also known as ‘a syndrome of acquired aphasia with convulsive disorder,’ or ‘acquired aphasia of childhood with epilepsy’.[2,3] It is defined on the basis of specific clinical and electroencephalography (EEG) criteria. It is almost certainly under-recognized and therefore, underdiagnosed. This syndrome was first described in 1957 by Dr. William M. Landau and Dr. Frank R. Kleffner, who identified six children with the disorder. Since then, almost 200 cases have been reported;[1,3] there appears to be a male preponderance in an approximate male: female ratio of 2:1.

Over 50% of the affected children present between the ages of three and eight years with an apparent loss of auditory verbal understanding (agnosia) of speech. Deafness is frequently the initially considered diagnosis (this is the predominant reason why Landau-Kleffner syndrome is diagnosed late). In the vast majority of children with the syndrome, the agnosia/aphasia is acquired, occurring in a previously normal child. The aphasia may be primarily receptive or expressive, and auditory agnosia may be so severe that the child is oblivious to everyday sounds. Hearing is normal, but behavioral problems, including irritability and poor attention span, are particularly common. Formal testing often shows normal performance and visual-spatial skills, despite poor language. Seizures are reported to occur in 70–75% of all patients with Landau-Kleffner syndrome at some point in the evolution of the condition, and are usually complex-partial (with focal motor and atypical absence symptomatology), generalized tonic-clonic and atonic (‘drop’) seizures; tonic and myoclonic seizures are rare. Seizures may be infrequent or repeated (nocturnal) with (rarely) episodes of convulsive and nonconvulsive status epilepticus.[3]

The final clinical manifestation of Landau-Kleffner syndrome is a behavioral disturbance, which may occur in almost 75% of the patients with the syndrome, and is frequently severe. Explanations for the behavioral difficulties may include a primary functional disinhibition at a limbic or diencephalic level, or as a secondary (frustration-induced) effect due to loss of comprehension. Unprovoked outbursts of rage and aggression may also occur; rarely, the child may appear autistic or psychotic” and hence, risk exclusion or suspension from school. It is this aspect that often leads to an initial diagnosis of a primary conduct disorder and referral to a psychiatrist.

The pathogenesis and etiology of Landau-Kleffner syndrome are unknown and probably complex. The agnosia/aphasia may represent an ‘epileptic’ phenomenon caused by a paroxysmal spike and slow-wave activity within the appropriate temporal lobe.[3] However, this may be difficult to accept in the absence of clinically occurring epileptic seizures. An alternative hypothesis is that there is an underlying brain pathology in an area or areas concerned with speech, which may be responsible both for the comprehension/speech difficulties and the abnormal EEG findings and subsequently, for the development of epileptic seizures. What the precise nature of this ‘underlying pathology’ is, is also unclear. Children have developed normally and are usually healthy with no preceding illness/infection before the onset of the syndrome and there is no obvious genetic predisposition. Inflammatory head trauma and postinfectious causes have been implicated, but have not been consistently demonstrated or confirmed by neuroradiological or neuropathological investigations, including cerebrospinal fluid analysis. It remains unclear as to whether the underlying pathology is simply functional or due to a subtle structural lesion. The available evidence and the natural history of Landau-Kleffner syndrome would tend to suggest the former hypothesis, possibly on the basis of an impaired or dysfunctional ‘loop’ within the speech cortex: hearing-verbal integration-spoken language.

EEG reveals a high-amplitude spike, and wave discharges predominate and tend to be bitemporal, but they can be multifocal or generalized. The EEG findings may be normal in the evolutionary stages of the condition. The spike discharges are always more apparent during nonrapid eye movement (REM) sleep; thus, a child suspected of LKS should have an EEG during sleep, particularly if the awake record is normal. If the sleep EEG is normal but a high index of suspicion for the diagnosis of LKS continues, the child should be referred to a tertiary pediatric epilepsy center for prolonged EEG recording and specific neuroimaging studies. CT and MRI studies typically yield normal results, and positron-emission tomography (PET) scans have demonstrated either unilateral or bilateral hypo- or hypermetabolism .[4] Microscopic examination of surgical specimens has shown minimal gliosis, but no evidence of encephalitis.

The diagnosis of Landau-Kleffner syndrome depends largely on being aware that the condition exists, and its usual pattern of presentation. Differential diagnoses include deafness, an acute behavioral or psychiatric disorder (including elective mutism), or epilepsy in which there is a transient postictal dysphasia or aphasia, but without the profound agnosia and behavioral dysfunction.

Valproic acid is the anticonvulsant of choice; however, some children require a combination of valproic acid and clobazam to control their seizures. If the seizures and aphasia persist, a trial of steroids should be considered. One recommended schedule consists of oral prednisone, 2 mg/kg/24 h for 1 month, tapered to 1 mg/kg/24 h for an additional month. With clinical improvement, the prednisone is reduced further to 0.5 mg/kg/24 h for up to 6–12 months. It is imperative to initiate speech therapy and maintain treatment for several years, because improvement in language function occurs only over a prolonged period. Some centers advocate an operative procedure—subpial transection—when medical management fails.[5]

In conclusion, although the Landau-Kleffner syndrome is uncommon, there is a need for an increased awareness of the disorder, particularly among those professionals to whom are commonly referred children with acute or subacute loss of speech and language—hospital and community pediatricians; audiologists; personnel in the ear, nose, and throat department; psychiatrists, and pediatric neurologists. Once considered, the diagnosis may be confirmed by sleeping EEG activity. A short course of corticosteroids would seem reasonable, but the role of the newer antiepileptic drugs requires further evaluation. Speech therapy and educational rehabilitation should be introduced as early as possible and a neurosurgical referral should be considered for those children with persisting aphasia and drug-resistant seizures.