Febrile Status Epilepticus: Cognitive Development

Children who experience febrile status epilepticus do not show significantly impaired early cognitive development at one year, according to a study published online in Epilepsy & Behavior.

“Overall, while the current performances of our cohort are slightly below normative expectations, these data are consistent with the results of large epidemiological studies evaluating cognition in children with febrile seizures and for febrile status epilepticus, which have, for the most part, established generally intact cognitive functioning following febrile seizures and good prognosis following febrile status epilepticus,” wrote first author Erica Weiss, PhD, of Albert Einstein College of Medicine (Bronx, NY), and colleagues with the Consequences of Prolonged Febrile Seizures in Childhood (FEBSTAT) study.

While past studies have suggested that complex febrile seizures and febrile status epilepticus are not linked to impaired global intellectual function, these studies have not specifically evaluated memory. Febrile status epilepticus has been linked to acute hippocampal injury, hippocampal sclerosis, and mesial temporal lobe epilepsy. The hippocampus plays a role in memory and is thought to be impaired in mesial temporal lobe epilepsy, but whether children who experience febrile status epilepticus develop significant memory problems and long-term cognitive sequelae has been unclear.

The prospective multicenter study included children aged one month to five years who had experienced febrile status epilepticus. Children were recruited between June 2003 and March 2010 from five academic medical centers throughout the US.

Using standardized measures, researchers evaluated cognitive and motor development, receptive language, and memory in 214 children who had experienced febrile status epilepticus. Then they compared scores for these children at one month and one year to children who had experienced simple febrile seizures and were part of the Columbia Study of Febrile Seizures (controls, n=102). Children also received serial neurological evaluation, EEG, MRI, and blood work.

Key results:

• One month: No significant difference in cognitive/motor development and receptive language between the febrile status epilepticus group and controls

• One year: Trend toward weaker motor development (P=0.035) and receptive language (P=0.034) in the febrile status epilepticus group compared to controls

♦ Non-white children had weaker scores on measures of early developmental and early language, compared to Caucasian children

• MRI results: Acute hippocampal T2 findings were linked to weaker receptive language skills at one year (P=0.0009)

• Human herpes virus 6 or 7 (HHV6/7) viremia was linked to better memory performance at one year (P=0.047)

The authors noted that children generally scored in the low average to average range for cognitive and motor development, early memory, and receptive language at one month and one year following febrile status epilepticus. They pointed out that results suggesting weaker scores for motor development in febrile status epileptics compared to controls, although statistically significant, may not be clinically significant because both groups performed in the low average to average range.

Furthermore, results suggesting ethnic/racial differences in receptive language may have been due to the inner city location of the medical centers, where many children come from lower socioeconomic backgrounds in which English may not be the primary language.

They highlighted the results linking HHV6/7 infection to better memory performance at one year for those with febrile status epileptics compared to controls. Though research has linked HHV6/7 infection to growth of the hippocampus, HHV6/7 infection has also been linked to encephalitis and later cognitive decline. However, in the absence of encephalitis, HHV6/7 infection may not be associated with higher levels of cognitive impairment, they suggested.

Limitations include the small number of children who were old enough to complete memory tests at one year. The study is ongoing, and researchers plan to test children at least through five years after febrile status epilepticus, which may provide further information on memory function in these children.  

Take-home Points

• A prospective, multicenter study suggests a good prognosis for early cognitive development one year after febrile status epileptics.

• Febrile status epilepticus was linked to weaker motor development and weaker receptive language abilities at one year.

• HHV6/7 infection and febrile status epilepticus were linked to better memory at one year.

• Acute hippocampal findings on MRI were linked to weaker receptive language at one year.

• The study is ongoing; five-year results will add to knowledge about memory and long-term cognitive function in children after febrile status epilepticus.

One or more authors reports grants, serving on a data safety monitoring board, personal compensation, consulting, royalties, expert testimony in legal cases, advisory board membership, other reimbursements, serving as an associate editor and/or being on the editorial board for one or more of the following: NIH, UCB Pharma, Accorda, AstraZenica, Upsher Smith, Accorda, AstraZenica, Neurelis, Xeris, Elsevier, NINDS, PCORI, CDC, PACE, Epilepsy Foundation, The Epilepsy Study Consortium, the Injury Prevention Center at Mount Sinai Medical Center, Acord, Cyberonics,  International League Against Epilepsy, NIH, CURE, US Department of Defense, the Heffer Family, the Segal Family Foundations, the Abbe Goldstein/Joshua Lurie, Laurie Marsh/Dan Levitz families, Neurobiology of Disease, Epileptic Disorders, Brain and Development, Pediatric Neurology and Physiological Research,  Eisai and/or UCB.

Reference: Weiss EF, et al for the FEBSTAT study team. Cognitive functioning one month and one year following febrile status epilepticus. Epilepsy Behav. 2016 Oct 26;64(Pt A):283-288.