Seasonal Influenza Vaccine Is Priority for Patients With Dravet Syndrome

Influenza vaccination is safer than influenza infection in patients with SCN1A-positive Dravet syndrome.

Complications following influenza infection, including persistent neurological impairment and death, are high among individuals with SCN1A-positive (SCN1A) Dravet syndrome. Prioritizing the safe administration of the seasonal influenza vaccine among these patients may be protective of the severe symptoms of influenza infection. These are the findings of a study published in Neurology.

Dravet syndrome is characterized by developmental and epileptic encephalopathy with over 90% of cases caused by pathogenic variants of the SCN1A sodium channel gene.

Any febrile infections, including influenza, increase the risk for seizures and status epilepticus; however, many patients and their caregivers experience vaccine hesitancy due to reports of vaccine-proximate seizures or status epilepticus in between 27-40% of patients with Dravet syndrome.

Researchers in Australia conducted a retrospective cohort study of influenza infection among patients with SCN1A-positive Dravet syndrome at the Royal Children’s Hospital Melbourne and the Austin Hospital Dravet clinic in Melbourne between 2019 and 2020. They studied the frequency and spectrum of neurological complications following influenza A or B infections in this patient population.

The researchers reviewed the medical records of 82 individuals diagnosed with Dravet syndrome between the ages of 0.5-25 years (median age of 4 years). Of these 82 individuals, 21 (26%) had medical documentation of 24 episodes of influenza infection (17 influenza A infections and 7 influenza B infections).

[S]afe administration of the seasonal influenza vaccine should be prioritized in patients with DS.

All 21 patients were admitted to the hospital 24 times for infection-induced exacerbations of seizures (21%), status epilepticus (54%), or gastrointestinal or respiratory complications (25%). Two of the 6 patients with gastrointestinal or respiratory complications also had increased seizures or encephalopathy without seizures. Neurological complications occurred in 88% (21 of 24) of influenza infections.

Most patients experienced prompt recovery within 1-7 days after hospital admission without neurological sequelae following 18 of 24 infections (75%). One patient experienced delayed but complete recovery (4%), while 5 experienced incomplete recovery (21%) from their neurological complications after influenza infection.

Of the 5 with incomplete recoveries, 1 child died from influenza-related pneumonia and 4 individuals experienced long-term neurological sequelae following infection. Imaging revealed cerebral edema in 2 patients with 1 patient also showing laminar necrosis.

Compared with baseline measurements, all 4 patients with incomplete recovery from influenza-related neurological exacerbations of Dravet syndrome present with persistent neurological deficits, one of which demonstrates profound global impairment.

Only 1 of the 6 patients who experienced transient or persistent neurological sequelae had received the previous season’s influenza vaccine, whereas the remaining 5 had not received either the current or previous season’s influenza vaccine. Among the patients without sequelae, 3 of 16 were vaccinated for influenza prior to infection and 2 had missing vaccination data.

Approximately 15 of the 21 patients received 60 influenza vaccines, most of them following the initial infection with 95% (n=57) vaccines being well-tolerated. Only 3 vaccines resulted in complications, including vaccine-proximate seizures (n=1) and vaccine-proximate status epilepticus (n=2). The latter may have been attributed to vaccine provision without antipyretics or additional antiseizure medications.

“[P]atients with SCN1A-DS are highly susceptible to neurologic complications during and severe sequelae following influenza infection, including moderate to severe persistent neurologic impairments and death,” the researchers noted. “[S]afe administration of the seasonal influenza vaccine should be prioritized in patients with DS [Dravet syndrome],” they recommended.

Study limitations included referral bias, underestimation of influenza infection among the patient population (especially among mild cases), and possible overestimation of the proportion of influenza infections associated with neurological complications.

References:

Howell KB, Butcher S, Schneider AL, et al. Complications of influenza A or B virus infection in individuals with SCN1A-positive Dravet syndrome. Neurology. Published online November 2, 2022:10.1212/WNL.0000000000201438. doi:10.1212/WNL.0000000000201438