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Hippocampal Malrotation Is Associated With Prolonged Febrile Seizures: Results of the FEBSTAT Study
Stephen Chan1, Jacqueline A Bello2, Shlomo Shinnar3
11 Department of Radiology, Harlem Hospital Center, 506 Lenox Ave, New York, NY 10037.
Insights
Hippocampal malrotation, a developmental brain malformation, is more common in children with prolonged febrile seizures. This condition predominantly affects the left hippocampus in boys, suggesting a pathologic origin.
Area of Science:
- Neuroscience
- Developmental Biology
- Pediatric Neurology
Background:
- Hippocampal malrotation is a condition characterized by incomplete inversion, resulting in a rounded shape and blurred internal architecture.
- The pathological significance of hippocampal malrotation remains debated.
- The Consequences of Prolonged Febrile Seizures in Childhood (FEBSTAT) study investigated its frequency and risk factors.
Purpose of the Study:
- To determine the frequency of hippocampal malrotation in children with febrile status epilepticus.
- To identify risk factors associated with hippocampal malrotation.
- To evaluate whether hippocampal malrotation represents a pathological developmental error.
Main Methods:
- Prospective, multicenter study (FEBSTAT) analyzing MRI scans of 226 children with febrile status epilepticus.
- Comparison with MRI scans of 96 children with first simple febrile seizure.
- Visual analysis by blinded neuroradiologists and quantitative volumetric MRI analysis.
Main Results:
- Hippocampal malrotation was observed in 8.8% of febrile status epilepticus patients versus 2.1% of controls (OR, 4.56).
- Malrotation was predominantly left-sided (81.8%) and more common in boys (OR, 6.1).
- Patients with malrotation showed smaller left hippocampal volumes and altered right-to-left hippocampal volume ratios.
Conclusions:
- Hippocampal malrotation is a developmental malformation, more prevalent in prolonged febrile status epilepticus, particularly in boys and affecting the left hippocampus.
- Findings suggest hippocampal malrotation is a pathological brain development error, not a normal variant.
- This malformation is associated with altered hippocampal volumes.
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.
Subjects And 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).
Conclusion:
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.
