Hippocampal Malrotation Is Associated With Prolonged Febrile Seizures: Results of the FEBSTAT Study.
OBJECTIVE
Hippocampal malrotation is characterized by incomplete hippocampal inversion with a rounded shape and blurred internal architecture. There is still debate about whether hippocampal malrotation has pathologic significance. We present findings from the Consequences of Prolonged Febrile Seizures in Childhood (FEBSTAT) study on the frequency of and risk factors for hippocampal malrotation.


METHODS
FEBSTAT is a prospective multicenter study investigating the consequences of febrile status epilepticus in childhood. MRI studies of 226 patients with febrile status epilepticus were analyzed visually by two board-certified neuroradiologists blinded to clinical details and were compared with MRI studies of 96 subjects with first simple febrile seizure. Quantitative analysis of hippocampal volume was performed by two independent observers.


RESULTS
Hippocampal malrotation was present in 20 of 226 (8.8%) patients with febrile status epilepticus compared with two of 96 (2.1%) control subjects (odds ratio [OR], 4.56; 95% CI, 1.05-19.92). Hippocampal malrotation was exclusively left-sided in 18 of 22 (81.8%) patients and bilateral in the remaining four patients (18.2%). There was no case of exclusively right-sided hippocampal malrotation. Hippocampal malrotation was more common in boys than in girls (OR, 6.1; 95% CI, 1.7-21.5). On quantitative volumetric MRI analysis, the left hippocampal volume was smaller in patients with hippocampal malrotation than in control subjects with simple febrile seizure (p = 0.004), and the right-to-left hippocampal volume ratio was higher in the hippocampal malrotation group than in the simple febrile seizure group (p < 0.001).


CONCLUSIONS
Hippocampal malrotation is a developmental malformation that predominantly affects the left hippocampus in male patients and is more frequently found in children with prolonged febrile status epilepticus than in control subjects. These data provide further evidence that hippocampal malrotation represents a pathologic error in brain development rather than a normal variant.
1 Department of Radiology, Harlem Hospital Center, 506 Lenox Ave, New York, NY 10037.
Stephen
S
Chan
2 Department of Radiology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.
Jacqueline A
JA
Bello
3 Department of Neurology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.
Shlomo
S
Shinnar
4 Gertrude Sergievsky Center, Columbia University, New York, NY.
Dale C
DC
Hesdorffer
5 Department of Pediatrics, Division of Neurology, Duke University Medical Center, Durham, NC.
Darrell V
DV
Lewis
6 Department of Radiology, Duke University Medical Center, Durham, NC.
James
J
MacFall
3 Department of Neurology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.
Ruth C
RC
Shinnar
2 Department of Radiology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.
William
W
Gomes
4 Gertrude Sergievsky Center, Columbia University, New York, NY.
Claire
C
Litherland
5 Department of Pediatrics, Division of Neurology, Duke University Medical Center, Durham, NC.
Yuan
Y
Xu
7 Department of Neurology, Lurie Children's Hospital, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Douglas R
DR
Nordli
8 Department of Neurology, Virginia Commonwealth University, Richmond, VA.
John M
JM
Pellock
9 Department of Neurology, Eastern Virginia Medical School, Norfolk, VA.
L Matthew
LM
Frank
3 Department of Neurology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.
Solomon L
SL
Moshé
10 International Epilepsy Consortium, Virginia Commonwealth University, Richmond, VA.
Shumei
S
Sun
D002675:Child, Preschool; D005260:Female; D006624:Hippocampus / Q000002:abnormalities*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007223:Infant; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D003294:Seizures, Febrile / Q000209:etiology*; D013226:Status Epilepticus / Q000209:etiology*; D014102:Torsion Abnormality / Q000175:diagnosis*
MRI; febrile seizures; hippocampal malrotation; status epilepticus