Dravet Seizure Frequency Linked to Worse Severity of Other Symptoms

Longer seizure remission leads to better functioning for patients

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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There are close statistical associations between seizure frequency and the severity of other disease symptoms, such as language problems, in people with Dravet syndrome, a new study reports.

“The significant relationships found between seizure measures and composite scores suggest that extended periods of seizure remission (whether expressed in terms of seizure frequency or periods free of seizures) are associated with overall better physical and psychosocial functioning in [Dravet syndrome],” the researchers wrote.

The team added that these findings suggest “that it may be possible to use evidence on seizure experience as a proxy for a broad set of impacts which can be summarised on a single scale.”

For patients, creating such a composite score could potentially help in developing personalized treatments, according to researchers.

“These results … may be useful in developing a clinical understanding of the severity of [Dravet syndrome] for an individual patient and establishing their treatment goals,” the team wrote.

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The study, “Exploring the relationships between composite scores of disease severity, seizure-freedom and quality of life in Dravet syndrome,” was published in Neurological Research and Practice.

The work was sponsored by Zogenix, the developer of a medication used for Dravet syndrome called Fintepla (fenfluramine). Zogenix was recently acquired by UCB.

The impact of seizure frequency

Dravet syndrome is a form of epilepsy that, in addition to seizures, commonly causes a number of other symptoms. Indeed, patients typically experience challenges with cognition, language, and communication.

Clinical trials that test the effect of potential Dravet therapies commonly focus on their impact on seizures, with less attention paid to other disease manifestations. This, in part, is due to logistical constraints.

“Clinical trials may be able to demonstrate short-term effects in terms of seizure reduction but may lack the sample size or the duration of follow-up to assess the broader and mid to longer-term impacts of treatment,” the researchers wrote.

Too often, they noted, trials “may not fully capture the impact of a treatment on … patients’ health-related quality of life.”

To address this knowledge gap, a team of scientists in Germany analyzed data from people with Dravet syndrome that was collected during a German clinical trial (DRKS00011894). The analysis included caregiver-reported findings for 75 Dravet patients, most of whom were children.

Using available data, the researchers constructed simple scores assessing disease impact across three domains: a physical domain, which included measures of muscle tone and spasticity; a psychosocial domain, encompassing difficulties with cognition and communication; and a care domain, reflecting how much patients were dependent on caregivers in their day-to-day life.

From these simple scores, the researchers calculated composite scores for each patient: one score including only the physical and psychosocial domains, a second score with all three domains, and a third score with all three domains in which the care domain was mathematically weighted to have a more pronounced effect.

“[Dravet syndrome] is a complex disease with multiple clinical manifestations. Therefore, single symptoms, including seizure frequency, can provide information about individual aspects of the underlying disease, but the development of a true picture of disease severity relies on an understanding of all the clinical effects,” the scientists wrote.

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Using a composite score paints a fuller picture, the team noted.

More than just seizures

“The advantage of a composite score is that it can allow for heterogeneity in [Dravet syndrome] patients’ symptomatology whereby the severity of the disease’s effects can vary between patients on the different individual manifestations of [Dravet syndrome],” they wrote.

Using seizure frequency data obtained from diaries, the researchers looked for statistical associations between these composite scores and measures of seizure frequency. Generally, the results showed highly significant associations. In other words, patients with more seizures tended to also experience more substantial non-seizure-related impairment.

“Those who experienced the more severe seizure symptoms of [Dravet syndrome] were also likely to experience more severe non-seizure manifestations,” the researchers wrote. “This highlights the potential contribution that earlier and more effective use of interventions to prevent seizures may make, not only in reducing an acute hazard to health from injury or death, but also in its impact on the broader multidimensional aspects of [Dravet syndrome].”

While most measures showed strong associations with seizure frequency, the team noted that “we failed to find a consistent relationship between seizure measures and speech and language problems.”

Additional analyses showed some connections between non-seizure symptoms and measures of health-related quality of life (HRQoL), though associations were generally only statistically significant in younger patients.

The researchers noted that the small number of patients in the study was “only one of several challenges with collecting and reporting HRQoL data in this context.” This type of data is difficult to reliably collect for young children at the best of times, the team noted. Thus, it’s likely to be even harder in children with Dravet who have difficulties with communication.

Overall, the team concluded that this study “represents the continuation of a body of literature in [Dravet syndrome] investigating the relationships between seizure experience, the broader manifestations of [Dravet syndrome] and patient HRQoL, as well as its impact on carers.”