Dravet patients’ cognitive outcomes worsened over 10 years: Analysis

Children under age 6 at start of study saw worse trajectory than older patients

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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The severity of seizures was reduced among Dravet syndrome patients in the U.K. over 10 years, but developmental outcomes worsened, a recent analysis shows.

Children younger than age 6 generally tended to see a worse trajectory during that period than older patients, including having a higher burden of coexisting conditions, such as autistic features, motor problems, and behavioral disturbances.

Predictors of worse developmental outcomes included more severe epilepsy and worse language skills, and having mutations in the SCN1A gene predicted more profound effects.

“This study reaffirms the poor long-term cognitive outcomes in [Dravet syndrome] and the substantial caregiver burden of illness,” the researchers wrote in “Long-term predictors of developmental outcome and disease burden in SCN1A-positive Dravet syndrome,” which was published in Brain Communications.

In most cases, Dravet syndrome is caused by mutations in the SCN1A gene. This drives recurrent and unprovoked seizures, or epilepsy, the disease’s cardinal symptom, along with a host of comorbidities such as developmental delays, behavioral issues, motor difficulties, sleep disturbances, and autistic features.

Long-term studies are attempting to understand how the clinical picture of Dravet changes as patients move from childhood into adulthood, and recent analyses indicate patients continuously fall behind their neurotypical peers in developmental outcomes.

Between 2005 and 2010, a group of SCN1A-positive Dravet patients were enrolled in an observational study in the U.K., with their caregivers completing questionnaires related to clinical features, disease burden, quality of life, behavior, and sleep between 2009-2010. Some caregivers completed follow-up questionnaires about 10 years later.

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Here, researchers studied how the patients’ clinical presentation changed in that period to identify predictors of a worse developmental trajectory. Their analysis involved 68 patients and their median age at the initial assessment, or baseline, was 7, and 17 at the follow-up 10 years later.

Caregivers reported Dravet patients’ mean epilepsy severity was less severe overall after 10 years than it had been at the baseline.

However, cognitive development worsened during that period with the consideration of adaptive skills across several domains. Specifically, average disability levels went from “moderate” to “profound.” More than half (51%) of the patients were classified as having profound cognitive impairments.

Predictors of worse developmental outcomes included worse language abilities and more severe epilepsy severity at baseline, as well as worse SCN1A genetic score, which is a way of predicting how severe the consequences of a patient’s mutation might be.

The prevalence of several comorbidities also increased over the follow-up, including autistic features, which affected 30% at baseline and 77% at follow-up. Similar patterns were seen for behavioral problems (38% vs. 81%) and motor problems (41% vs. 80%).

The patients who were younger than 6 at the baseline assessment generally had more severe outcomes than those 6 or older.

While the older group saw significant reductions in epilepsy severity, younger patients had no significant change. The younger group also saw steeper developmental declines and accumulated a higher comorbidity burden.

Such findings reflect “the rapid disease progression in the first five years of life, contrasting the relative plateauing of functioning in the older group,” the researchers wrote.

At 10 years, other commonly reported issues included sleep abnormalities (71%), eating problems (55%), dental issues (49%), and bone fractures (40%).

Seven children enrolled at the start died. Four deaths were attributed to Sudden Unexpected Death in Epilepsy, or SUDEP. More than a third of the caregivers (35%) at the follow-up reported they hadn’t discussed SUDEP with a healthcare professional.

About two-thirds of patients (66%) were fully dependent on their caregivers in daily life, and 34% were partially dependent. Nearly all the caregivers (99%) said their own health was negatively affected and 91% said their career was negatively affected.

“Overall, our study corroborates the poor long-term developmental outcomes for individuals with [Dravet],” the researchers wrote. “The negative impact of epilepsy severity at baseline on long-term developmental outcomes suggests the importance of implementing early and focused therapeutic strategies.”

The researchers said more research should be undertaken on the impact of newer anti-seizure medications that the patients didn’t have access to at the start of the analysis.