Landau-Kleffner syndrome is a rare disorder of early childhood, characterized by sudden regression of language skills, with primary features of aphasia, epilepsy, and electroencephalographic (EEG) abnormalities. Landau-Kleffner syndrome was first described in a series of cases described in 1957 by William Landau, a neurologist at Washington University, and Frank Kleffner, a speech pathologist at St Louis Central Institute for the Deaf.1

In this case report, we describe the anesthetic management of a child with a diagnosis of Landau-Kleffner syndrome.

CASE REPORT

A 9-year-old male child with no significant past medical history except for the presence of Landau-Kleffner syndrome was scheduled for multiple dental extractions and restorations under general anesthesia at our hospital.

According to the history obtained from the parents and from the neurology consultation, the child had normal motor, sensory, and psychosocial development until his sixth birthday. At that point, he lost his auditory comprehension and verbal communication skills and became completely aphasic over a period of 2 weeks. A neurologist, a speech pathologist, and an occupational therapist had evaluated the child, and a diagnosis of Landau-Kleffner syndrome was made. The child had been managed by these specialists in collaboration with his primary care physician.

The patient had several episodes of partial seizures before initiation of antiepileptic medications but has been seizure-free since he started taking the medication. His current medications include quetiapine fumarate (Seroquel), sodium valproate (Depakote), trazodone, and lamotrigine (Lamictal).

Since the onset of this disease, the child has regained very little verbal comprehension or expression. He is able to express needs with sign language, and his articulation is limited to grunts and groans.

The child has undergone craniotomy twice in the past, at the ages of 7 and 8 years, for subpial transection, a treatment for this disorder. Both were performed with the patient under general anesthesia with no complications.

On examination, the child was moderately cooperative. He was not disruptive or violent but was slightly withdrawn from the surroundings. His height (134 cm) and weight (42 kg) were at 25th and 90th percentiles, respectively, for his age and gender. No obvious abnormality in general appearance was noted. Size and shape of the chin, thyromental distance, and range of motion (ROM) of his neck were within normal limits; his airway was Mallampati class II. Examination of the organ systems, including the nervous system, revealed no obvious abnormality. As expected, no organic features, no motor abnormalities, and no evidence of sensory deficits were noted; reflexes were normal.

The patient had a normal complete blood count (CBC). Plasma levels of valproic acid (93.7 mcg/mL) and lamotrigine (3.1 mcg/mL) were within therapeutic limits.

The child was premedicated with 10 mg of midazolam oral syrup. Standard ASA monitors were placed and mask induction was uneventfully completed with O₂ (4 L/min), N₂O (6 L/min), and sevoflurane (8%). A 22-gauge angiocatheter was placed in the dorsum of the left hand. Glycopyrrolate 0.2 mg was administered as an antisialogogue and to prevent bradycardia. Both nostrils were prepared with phenylephrine nasal drops (0.25%) to achieve vasoconstriction of the nasal mucosa, thus facilitating nasal intubation and minimizing nasal bleeding. Rocuronium 0.6 mg/kg was administered by IV to facilitate intubation. A 6-mm uncuffed, lubricated nasal RAE tube was passed through the left nostril without difficulty and was negotiated into the patient's trachea through the vocal cords under direct vision with the aid of Magill forceps. The throat pack was placed by the surgeon.

The patient was maintained with N₂O ∶ O₂ (50 ∶ 50) and sevoflurane 1.5% end-tidal concentration. Analgesia was provided by injection of 2% lidocaine with 1 ∶ 100,000 epinephrine by the surgeon. IV ketorolac 20 mg was administered before the end of the procedure for postoperative pain. Use of narcotics was deemed unnecessary because of the nature of the procedure, the use of nitrous oxide, the use of local anesthetic intraoperatively, and the desire for early extubation. Dexamethasone 4 mg was administered at 65 minutes before the end of the procedure and 4 mg of ondansetron was administered at 33 minutes before the end of the procedure for prophylaxis against postoperative nausea and vomiting.

To exploit the anticonvulsant properties of propofol, sevoflurane was discontinued and infusion of propofol started 90 minutes before the end of the procedure at a rate of 100 mcg/kg/min. It was titrated down to 40 mcg/kg/min 30 minutes before the procedure ended, then was terminated 10 minutes before completion.

Total duration of the procedure was 2 hours 40 minutes. The trachea was extubated once criteria were met. The patient did well, maintaining adequate tidal volume, respiration rate, and oxygen saturation first with 100% oxygen via mask and then on room air. The patient was transported to the postanesthesia care unit (PACU) while breathing spontaneously and sleeping comfortably.

Recovery was uneventful and the patient was discharged from the PACU after 1 hour 30 minutes.

Routine follow-up by telephone at 24 hours and at the surgeon's office at 7 days disclosed no surgical or anesthetic complication.

DISCUSSION

Landau-Kleffner syndrome is characterized by gradual or rapid onset of aphasia in a previously normal child and is associated with abnormal epileptic activity on EEG, with or without clinical seizure activity. The usual age of onset is 2 to 8 years,1 but the disorder may present at a later age.

The affected child loses the ability to comprehend spoken language. Auditory verbal agnosia, leading to complete loss of speech (aphasia), is often misdiagnosed as acquired deafness early in the course of the disease. Some may have other variations of linguistic dysfunction such as neologism and paraphasia.2 Affected children develop behavioral abnormalities such as outbursts of anger and aggressiveness, as well as hyperactivity, secondary to the sudden loss of ability to communicate.2 Males are affected at twice the rate of females.3

Although only 70% of affected children show clinical seizures,2 EEG abnormalities are present in 100% of cases in the form of generalized or focal spike waves.3 Nearly 85% of cases involve the temporal lobes. The seizure associated with Landau-Kleffner syndrome is usually partial in nature. Generalized tonic-clonic seizure has rarely been described with this disorder.

Imaging studies, including computed tomography and magnetic resonance imaging of the brain, do not show structural abnormalities.2 In some affected children, positron emission tomography and single-photon emission computed tomography have revealed some abnormal findings in focal cerebral metabolism and blood flow that are nonspecific to be correlated with this disorder.

The etiopathogenesis of this disorder is obscure. Infection (slow viral infection, Toxoplasma gondii, or neurocysticercosis), cerebral arteritis, and inflammatory demyelinating illness all have been postulated as possible causes.2 A favorable response to corticosteroid and intravenous gamma globulin suggests an autoimmune pathogenesis.3

The natural course of the illness shows spontaneous improvement of seizure and EEG abnormalities in early adolescence, with a variable degree of recovery of linguistic function. In a follow-up of 7 patients over a period of 3 to 16 years, Duran et al found that “epilepsy and EEG abnormality does not always disappear and language disturbances tend to persist in most patients.”4

Treatment is directed toward control of seizures, which is easily achieved with antiepileptic drugs (AEDs). Valproate, carbamazepine, phenytoin, lamotrigine, topiramate, clonazepam, and clobazam all have been used successfully. Unfortunately, the anticonvulsants fail to improve the language deficit. Most of these children need speech and language therapy, as well as some kind of rehabilitation therapy. The quality of life of most of these patients is poor, primarily because of language difficulties.

The role of surgery (ie, multiple subpial transection [MST]) is still “experimental and controversial” in Landau-Kleffner syndrome.3 With this procedure, the transverse fibers of certain eloquent areas of brain that cannot be removed are transected, leaving the longitudinal fibers intact.5

Eloquent areas of the brain are involved in communication, including speech and comprehension of speech.

While providing anesthesia to our patient with Landau-Kleffner syndrome, we had no guidelines regarding anesthetic management. After reviewing the literature, we focused on avoiding medications that reduce the seizure threshold, such as ketamine,6 as well as medications that are known to cause myoclonus, such as etomidate.6 Specific instruction was given to ensure continuation of the antiseizure medication on the day of surgery, and the therapeutic level of the pertinent AED used was documented. Oral syrup of midazolam was administered as an additional precaution to suppress seizure activity during the perioperative period, and for its anxiolytic action. We meticulously avoided hypoxia and hypercarbia that might trigger seizure activity.

We do not know whether exposure to general anesthetic has any short-term or long-term effect on the disease process, especially on language and cognitive function. No clinical information is available regarding the susceptibility of these patients to malignant hyperthermia.

We believe that drugs that have metabolites known to induce seizure activity (eg, laudanosine with cisatracurium,7 normeperidine with meperidine8) should be avoided. Whether the induction drugs (ie, propofol vs thiopental) or inhalational agents have comparative advantages remains to be determined. Based on the information that has been gathered from the literature, regional anesthesia should present no additional risk for these patients.

A child with a rare syndrome and the anesthesiologist are at a predictable disadvantage. We expect that this report will encourage communication among anesthesia professionals and will help in sharing short-term and long-term anesthetic outcomes for this group of patients, thus improving anesthetic management.