Epileptologists from Children's Hospital, Boston, and UCLA, California, discuss approaches to the differential diagnosis of Lennox Gastaut syndrome (LGS) and identification of a possible underlying etiology. The classic diagnostic criteria for LGS consist of a triad of features: multiple seizure types, abnormal EEG, and cognitive impairment. Onset is commonly between 3 and 5 years of age, with slight male preponderance, and is sometimes preceded by West syndrome. Tonic seizures during sleep are the classic feature used for diagnosis but in fact LGS has multiple concurrent seizure types: tonic, atypical absence, atonic, and myoclonic jerks. Nonconvulsive status epilepticus, lasting days to weeks, occurs in 50% patients, and sudden tonic or atonic falls, or “drop attacks,” occur with the same frequency. The abnormal EEG shows slow spike-wave complexes (known originally as petit mal variant) at 2-2.5 Hz during wakefulness, and paroxysmal fast rhythms (10-20 Hz) during REM sleep. The MRI is abnormal in two thirds or more of patients with LGS. The IQ deteriorates over time, with 99% having cognitive delay by adolescence. Nonconvulsive status epilepticus is the most significant risk factor for severe cognitive impairment. Behavioral problems such as hyperactivity, aggression, and autistic traits occur in 50% cases.

The epileptic syndromes listed in differential diagnosis of LGS are Doose (myoclonic astatic epilepsy), Dravet (severe infantile myoclonic epilepsy), West (infantile spasms), and pseudo Lennox (atypical benign partial epilepsy). If diagnosis is not readily apparent from clinical history and exam, EEG, MRI, cardiac and eye exams, further tests suggested include DNA microarray, SLC2A1 (glucose transporter defect), CLN2 (late infantile neuronal ceroid lipofuscinosis), and TSC 1,2 (tuberous sclerosis). Diagnosis is important in determining prognosis and in treatment. [1]

COMMENTARY. A Working Group of experts chaired by Drs John M Pellock of Virginia Commonwealth University, Richmond, VA, and Dr James W Wheless of Le Bonheur Children's Hospital, Memphis, TN, met in Chicago, June 2012, and discussed diagnostic criteria and the management of LGS [2]. Investigators from Boston University; Tennessee, and Cincinnati, list FDA approved treatment options for LGS, including felbamate, lamotrigine, topiramate, rufinamide, and clobazam, and several others used off-label [3]. Investigators from Boston University and Kennedy Krieger Institute, Baltimore, outline surgical options that include lesionectomy and lobar resection, corpus callosotomy (effective in control of drop attacks), and vagus nerve stimulation [4]. Investigators from Johns Hopkins University and UCLA report a 50% response to treatment with the ketogenic diet and a similar response to vagus nerve stimulation [5]. The Director of Epilepsy Information Service at Wake Forest University, Winston-Salem, NC, lists resources for caregivers and families of patients with LGS. They include the LGS Foundation, Epilepsy Foundation, Child Neurology Foundation and CNS, Charlie Foundation, and TS Alliance [6].