Comorbidities in Dravet Syndrome and Lennox–Gastaut Syndrome

Abstract

This study aims to describe the main cognitive and behavioral comorbidities of Dravet syndrome (DS) and Lennox–Gastaut syndrome (LGS), their impact on the health-related quality of life (QOL) of patients and their caregivers, and provide a summary of the neuropsychological tools available for the evaluation of these comorbidities. The cognitive and behavioral comorbidities in patients with DS and LGS have a profound effect on the QOL of affected individuals and their caregivers and, as patients grow, tend to surpass the impact of the seizures. DS is a genetic condition associated with loss-of-function mutations in the SCNA1 sodium channel gene; LGS is an etiologically heterogeneous condition that is often secondary to structural brain abnormalities. The first seizures associated with DS typically present in the first year of life, and developmental delay becomes progressively evident thereafter. LGS usually starts between the ages of 3 and 8 years, with cognitive impairment becoming clinically evident in most patients within 5 years from the onset. In both DS and LGS, cognitive impairment is generally moderate to severe and is often accompanied by behavioral problems such as hyperactivity and inattention. In addition to optimal seizure control, regular assessment and active management of cognitive and behavioral comorbidities are required to meet the complex needs of patients with DS or LGS.

Psychobehavioural and Cognitive Adverse Events of Anti-Seizure Medications for the Treatment of Developmental and Epileptic Encephalopathies

“…Developmental and epileptic encephalopathies are complex syndromes; however, treatment often primarily focuses on seizure control, and there is a need for improvements in the identification and treatment of the developmental, behavioural and psychiatric comorbidities (including treatment-related exacerbations) [ 12 , 15 , 324 , 325 ]. The management of DEEs requires a rational, holistic and multi-disciplinary approach tailored to the unique circumstances of the individual patient and their evolving symptoms throughout all stages of childhood, adolescence and adulthood, including a smooth transition from paediatric to adult care [ 12 , 15 , 324 , 325 ]. Indeed, the comorbidities can be the predominant burden in older children and adults when seizures decrease [ 320 , 326 , 327 ].…”

“…Sleep problems may also cause neuroinflammation and neurodegeneration, further intensifying seizures [8]. These comorbidities can have profound effects on the quality of life (QoL) of patients and their families [9][10][11][12][13], and therefore their importance has been growing in recent decades, with more recent clinical trials and observational studies including specific evaluations of these outcomes.…”

Assessment of aggressive behavior in Dravet syndrome: a critical look

“…As mentioned earlier, in DEE, especially in Dravet syndrome, the connection between AEDs and behavioral problems has also been reported (Strzelczyk and Schubert-Bast, 2022 ). DEEs are complex syndromes where the therapeutic approach often focuses on seizure control, neglecting the need to improve the identification and treatment of developmental, behavioral, and psychiatric comorbidities (including exacerbations related to treatment) (Kerr et al, 2011 ; Marchese et al, 2021 ; Samanta, 2021 ; Cardenal-Muñoz et al, 2022 ). Furthermore, a significant proportion of these patients undergo long-term polytherapy treatment with multiple AEDs instead of monotherapy, which may have a detrimental impact on higher cortical functions and exacerbate the behavioral problems.…”

Real‐world use of the updated refractory epilepsy screening tool for Lennox–Gastaut syndrome

“…Third, patients may no longer tolerate EEG testing 12,13 . Finally, comorbid conditions, such as behavioral difficulties, cognitive impairment, and sleep disturbances, can develop in adolescence and adulthood, further complicating diagnosis and delaying treatment 11,14 . For these reasons, LGS frequently remains undiagnosed in adulthood, and without appropriate diagnosis, these patients may not receive timely and optimal care.…”

“… 12 , 13 Finally, comorbid conditions, such as behavioral difficulties, cognitive impairment, and sleep disturbances, can develop in adolescence and adulthood, further complicating diagnosis and delaying treatment. 11 , 14 For these reasons, LGS frequently remains undiagnosed in adulthood, and without appropriate diagnosis, these patients may not receive timely and optimal care. Early intervention, including treatments specifically tailored for adults, is critically important for patients with LGS and has been shown to significantly improve outcomes in this population.…”