CHOP Study Suggests New Method for Measuring Quality of Life in Children with Severe Epilepsies

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Researchers from the Epilepsy Neurogenetics Initiative (ENGIN) at Children’s Hospital of Philadelphia (CHOP) found that assessing the days children are minimally impacted by seizures may be a more appropriate method of evaluating severe childhood epilepsies than measuring seizure frequency alone when determining a patient’s quality of life. The findings were published online by the journal Developmental Medicine and Child Neurology.

Developmental and epileptic encephalopathies (DEEs) are a group of severe epilepsies that frequently begin in childhood and significantly impact health and wellbeing. Many of these result in therapy-resistant seizures in addition to other neurological symptoms and medical problems. A significant proportion of severe DEE have a genetic basis.

In genetic epilepsies, understanding how various medical issues impact quality of life is complex. However, finding a good way to measure the severity of a disease is important in many clinical situations, such as assessing whether a drug benefits a given patient in a clinical trial. For genetic epilepsies in particular, many new therapies that target specific genetic changes are on the horizon, a field of neurology referred to as precision medicine.

Stacey R. Cohen, MS, LCGC Stacey R. Cohen, MS, LCGC Such studies rely on outcome measures that can be precisely quantified to determine the severity of the disease. For epilepsies, seizure frequency and seizure severity are generally considered to be the main outcome measure. However, given that genetic epilepsies result in additional symptoms indirectly related to seizures, there may be factors other than seizure frequency that impact a patient’s quality of life. Measuring the impact of these features in genetic epilepsies is therefore important, and novel measurements of quality of life are needed to assess whether therapeutic interventions are truly benefitting the patient.

“In our ENGIN clinic, we see more than 1,000 new patients with known or presumed genetic epilepsies each year. Seizure frequency alone does not capture the full burden of disease that our families are experiencing, even though seizures are an important factor for quality of life,” said the study’s first author Stacey Cohen, MS, LCGC, a genetic counselor in ENGIN at CHOP. “Therefore, we tried to understand how we can better measure quality of life in individuals with genetic epilepsies.”

For this study, CHOP researchers worked with patient advocacy organizations and developed a novel questionnaire that was distributed to primary caregivers of patients with genetic epilepsies. The questionnaire addressed 89 items including demographic characteristics, genetic diagnosis, clinical features and quality of life. A total of 176 responses were received and covered a variety of genetic diagnoses such as mutations of the SCN1A, KCNQ2, and SLC6A1 genes, which result in some of the most common genetic epilepsies in children.

The researchers found that quality of life scores were strongly associated with the number of days minimally disrupted by seizures rather than seizure frequency alone. Cohen and collaborators also found associations with medication side effects, genetic diagnosis, and whether the patients lived in rural or urban communities. Individuals in this study had significantly lower quality of life scores than those with Rett syndrome, cerebral palsy, autism spectrum disorder, and Down syndrome, highlighting the more severe impact of genetic epilepsies on quality of life compared to other neurodevelopmental disorders.

Ultimately, the researchers found that there was a lack of association between quality of life and reported seizure frequency, which suggests the need to re-evaluate how disease severity is measured in DEEs and genetic epilepsies in a way that is more useful in both present day patient care and future precision medicine clinical trials.

This study was supported by the National Society of Genetic Counselors Neurogenetics Special Interest Group.

Cohen et al, “Caregiver assessment of quality of life in individuals with genetic developmental and epileptic encephalopathies.” Dev Med Child Neurol. Online February 28, 2022. DOI: 10.1111/dmcn.15187.