Lennox‐Gastaut syndrome with late‐onset and prominent reflex seizures in trisomy 21 patients

Abstract

Summary Purpose: Lennox‐Gastaut syndrome (LGS) is a severe epileptic condition characterized by multiple seizure types including tonic seizures, slow spike‐and‐wave discharges on electroencephalography (EEG), and cognitive impairment. LGS can occur in apparently healthy subjects or in patients with preexisting brain damage. The onset peaks between 3 and 5 years of age and the prognosis is usually poor. Herein we report 13 subjects with trisomy 21 who developed LGS. Methods: We retrospectively reviewed the clinical and EEG data of consecutive patients with LGS and trisomy 21 referred to five epilepsy centers over the last 30 years. Results: Data for 13 patients (8 male, 5 female) were collected. The mean age at onset was 9.1 years (range 5–16). The mean age at last follow‐up was 23.5 years (range 11–43 years). Seizure onset was after age 8 years in eight (62%) patients and between age 5 and 8 in the other five. In none of the cases did a West syndrome precede the onset of LGS. Nine of 13 patients (69%) had unambiguous reflex seizures, mostly precipitated by sudden unexpected sensory stimulations, usually preceding or accompanying the onset of a full‐blown LGS picture. Interictal and ictal EEG findings were typical for LGS. All patients were drug‐resistant. Discussion: Patients with trisomy 21 may present a peculiar LGS, characterized by late onset and high occurrence of reflex seizures. Mechanisms underlying this particular presentation of LGS may include dendritic rarefaction and decreased interneurons, as well as functional abnormalities leading to overall decreased brain inhibition in these patients.

The pharmacological management of Lennox-Gastaut syndrome and critical literature review

“…LGS is strictly connected to cognitive impairment; in fact, 7% of children with ID have LGS and 55% of patients diagnosed with LGS have a profound ID with an IQ < 20. LGS generally begins between the 2nd and the 8th year of life, with a peak of incidence between the 3rd and the 5th year of age [4]; later onset is rare and often associated with specific conditions, such as Down syndrome [5].…”

“…Other seizure types, including generalised tonic-clonic, generalised clonic, focal, reflex [[8] [5],] and non-epileptic psychogenic seizures [9] have been reported in patients with LGS.…”

Autism spectrum disorder and epilepsy: Disorders with a shared biology

“…Multiple seizure types have been reported in patients with DS, including progressive myoclonic epilepsy associated with dementia [42], infantile spasms [43], and Lennox-Gastaut syndrome with reflex seizures [44]. Reports of developmental outcome of children with a history of infantile spasms and DS has been mixed, with some reporting better than expected outcome [45] and others noting high prevalence of ASDs and less favorable outcome [46].…”

Neurological phenotypes for Down syndrome across the life span

“…When Lennox–Gastaut syndrome occurs in DS, the onset is usually later than seen in the typical population and may be associated with reflex seizures (Ferlazzo et al, 2009). There is a high rate of EEG abnormalities in DS without the recognition of clinical seizures (40%); therefore, EEG findings do not correlate with outcome (Smigielska-Kuzia et al, 2009).…”