Lennox-Gastaut syndrome (LGS) is a pharmacoresistant epileptic encephalopathy. Herein reported is a case of LGS that combination therapy with levetiracetam, lamotrigine and valproate culminated in control of all seizure types and resolution of epileptic discharges in electroencephalography. This case indicates that logical combination therapy may provide seizure control and improvement of electroencephalographic pattern in patients with LGS even in cases at which epileptic surgery fails.
Lennox-Gastaut syndrome (LGS) is an electroclinical entity that is characterized by severe epileptic and developmental encephalopathy, which is associated with a high rate of morbidity and mortality and usually refractory to pharmacological treatment. Patients generally continue with seizures despite treatment with multiple antiseizure medicines (ASMs). Choosing suitable ASMs to maintain better seizure control, avoiding side effects and providing synergistic effects between drugs are crucial in management of LGS patients.
A 9-year-old boy was brought for evaluation of seizures occurring since the age of 5 years. The patient was born at 38 weeks of gestation via normal vaginal delivery and had an uneventful course of birth. He had no history of perinatal distress, infection, encephalitis or exanthems. His first seizure at 5 years old was generalized tonic-clonic seizure (GTCS) and had been treated with phenobarbital 3 mg/kg/d at that time, and then was seizure free up to 1 year until parents noticed that the patient drops things from his hands. During the visit by a pediatric neurologist, carbamazepine 10 mg/kg/d was added to phenobarbital and the symptom disappeared and has not recurred up to 8 years old when other seizure types including many episodes of staring and occasional fallings started to emerge, and thereafter multiple ASMs had been tried to control patient’s seizures.
At the time of my visit, the patient had multiple seizure types including repetitive episodes of absence, GTCS, atonic and myoclonic seizures and was under treatment with vigabatrin 50 mg/kg/d, acetazolamide 20 mg/kg/d, and primidone 25 mg/kg/d. The patient also had learning disability and parents said that these drugs had been ineffective in control of seizures and spells continue to occur frequently each day. The patient was noted to suffer from many episodes of GTCS and to be resistant to ASMs had tried in the past. Atonic seizures were particularly troublesome and drop attacks had been causing repetitive facial and scalp lacerations and nasal fractures, but protective helmets had not been tolerated. His vitals were normal and laboratory data including complete blood count, basic metabolic panel, liver, and renal panel were within normal limits. Electroencephalography (EEG) revealed frequent bursts of generalized slow spike and wave discharges (1–2 Hz, 200–300 μV) with generalized paroxysmal fast activity plus to disorganized background consistent with EEG findings of LGS (
The patient’s medications were revised and topiramate was added to patient’s regimen, and he was sent home and advised of regular follow-up visits. Topiramate gradually increased up to 7 mg/kg/d, but there was little or no benefit, so clobazam 1.0 mg/kg/d was added again without remarkable benefit. Vigabatrin was slowly tapered due to lack of evidence in favor of tuberous sclerosis. Considering lack of response to these measures, the patient was referred to a tertiary center and his drugs changed to levetiracetam 50 mg/kg/d, primidone 25 mg/kg/d, and lamotrigine 3 mg/kg/d, but again seizures continued and finally a ketogenic diet was started for the patient. After starting the ketogenic diet, seizures frequency reduced, but after 2-month, patient was not compliant to the diet. As a measure of last resort, epileptic surgery was considered, and based on non lesional MRI, the patient underwent corpus callosotomy (
Based on previous studies, lamotrigine combined with sodium valproate has evidence for synergies,
LGS is the most common form of epileptic encephalopathy. Most definitions of LGS require
Lamotrigine is approved in Europe and the USA for the treatment of seizures associated with LGS. Motte et al. showed that lamotrigine is effective and well tolerated in the treatment of LGS.
The author declares that there is no conflict of interest.
Electroencephalography showing a burst of slow spike wave (2 Hz, 200–300 μV) followed by slowing of background. FP, frontopolar; F, frontal; T, temporal; O, occipital; P, parietal; Fz, midline frontal; Cz, vertex; Pz, midline parietal; ECG, electrocardiogram; REF, reference.
Brain magnetic resonance imaging of patient showing no remarkable or resectable lesion.
Brain magnetic resonance imaging obtained after corpus callosotomy.
Electroencephalography after successful pharmacotherapy shows a well-formed alpha frequency posterior dominant rhythm. FP, frontopolar; F, frontal; T, temporal; O, occipital; P, parietal; T, temporal; Fz, midline frontal; Cz, vertex; Pz, midline parietal; ECG, electrocardiogram; REF, reference.