Genetic testing advised in alleged vaccine-induced encephalopathy

Cases of alleged vaccine-induced encephalopathy should be carefully assessed clinically for characteristics of severe myoclonic epilepsy of infancy, and genetic testing for SCN1A mutations should be considered, according to Larry K. Pickering, MD.

“Correct diagnosis will reassure the family as to the true cause of their child’s condition,” said Pickering, who serves as senior adviser to the director of the CDC and also is an Infectious Diseases in Children Editorial Board member. “Establishing the correct diagnosis also will remove any guilt of having immunized the child; it will direct appropriate treatment and permit realistic planning for the prognosis.”

Severe myoclonic epilepsy (SMEI), also known as Dravet syndrome, is thought to be caused by SCN1A gene mutations.

To make his case, Pickering cited an August report by the Institute of Medicine, in which it concluded that inadequate evidence exists to “accept or reject a causal relationship between diphtheria toxoid-, tetanus toxoid- and acellular pertussis-containing vaccine and encephalopathy.”

He also highlighted two studies that have investigated a potential link between vaccines and Dravet syndrome.

SMEI caused by spontaneous mutations

In the first study, which appeared in Lancet Neurology in 2006, researchers evaluated 96 children with unexplained encephalopathy and seizures identified at 1 year of age or younger. Fourteen of these children who had symptom onset within 72 hours of receipt of the diphtheria-(whole-cell) pertussis-tetanus (DPT) vaccine were further evaluated. Eleven who met the criteria for post-vaccine encephalopathy corresponded to the phenotype for severe myoclonic epilepsy of infancy (SMEI), or Dravet syndrome, and 10 of these 11 children had mutations in the gene, Pickering said.

The researchers further found no family history of severe epilepsy, nor did they find the mutation among parents from whom they collected blood — a finding that the researchers said provided “a compelling explanation of the cause of the encephalopathy.”

“The results show that alleged vaccine encephalopathy appears to be a genetically determined epileptic encephalopathy that arose de novo,” Pickering said. “This article reported that SMEI is caused by severe and often spontaneous mutations in SCN1A gene (neuronal sodium channel subunit).”

Testing recommended at any age

In a second article, which appeared this year in the electronic version of Pediatrics, researchers reported a case series of five children from three institutions who presented for epilepsy care with a parental diagnosis of alleged vaccine encephalopathy caused by pertussis vaccinations. Seizure onset occurred at 2 to 7 months of age, with three of the children experiencing seizure less than 12 hours after vaccination and two at 24 hours after vaccination. Genetic testing revealed that all five children, who were aged 2, 3, 4, 14 and 20 years at the time of diagnosis, had Dravet syndrome.

The researchers of the case series said patients of any age with unexplained chronic encephalopathy and suggestive clinical history should be considered for genetic testing for SCN1A mutation, which recently has become more available.

“Medical and societal energies directed at the alleged association with vaccines need to be redirected to the care of these children and to novel treatment and prevention approaches,” Pickering said.

Origins of controversy

A documentary film released in 1982 is partially to blame for these misdirected energies, according to Paul A. Offit, MD, who said the film claimed that whole-cell pertussis vaccine caused epilepsy and severe developmental delays.

“Thirty years ago, a documentary film, titled Vaccine Roulette, made national headlines. For parents, the case was clear. Their children were fine. They got vaccinated, and then they weren’t fine anymore. The vaccine must have been the cause,” said Offit, who is chief of the Division of Infectious Diseases and director of the Vaccine Education Center at The Children’s Hospital of Philadelphia, and an Infectious Diseases in Children Editorial Board member. “At the time, we didn’t have the tools available to determine whether these children had an underlying genetic defect that explained their neurological symptoms. Now we do.”

Samuel F. Berkovic, MD, of the University of Melbourne, and colleagues have reviewed those cases of children with alleged vaccine-induced encephalopathy and found that many had an SCN1A mutation, which causes a neuronal sodium channel transport defect, according to Offit, who is also the Maurice R. Hilleman Professor of Vaccinology and professor of pediatrics at the University of Pennsylvania School of Medicine, Philadelphia.

“In many ways, Vaccine Roulette launched the modern American antivaccine movement. The Berkovic study clearly demonstrates that the origin of that movement was built on a false belief,” Offit said. “Is it too late for the filmmakers to issue a retraction?” – by Tina DiMarcantonio-Brown and Cassandra R. Richards

For more information:

• Berkovic SF. Lancet Neurol. 2006;5:488-492.
• Pickering LK. #120. Presented at: IDSA 49th Annual Meeting; Oct. 20-23, 2011; Boston.
• Reyes IS. Pediatrics. 2011;doi:10.1542/peds.2010-0887.
• von Spiczak S. Epilepsia. 2011;52:1506-1512.

Disclosures: Drs. Pickering and Offit report no relevant financial disclosures.

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