Hippocampal malrotation is associated with prolonged febrile seizures

Results of the FEBSTAT study

Stephen Chan, Jacqueline A. Bello, Shlomo Shinnar, Dale C. Hesdorffer, Darrell V. Lewis, James MacFall, Ruth C. Shinnar, William A. Gomes, Claire Litherland, Yuan Xu, Douglas R. Nordli, John M. Pellock, L. Matthew Frank, Solomon L. Moshe, Shumei Sun

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1068-1074
Number of pages7
JournalAmerican Journal of Roentgenology
Volume205
Issue number5
DOIs
StatePublished - Nov 1 2015

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Febrile Seizures
Status Epilepticus
Fever
Odds Ratio
Multicenter Studies
Hippocampus
Prospective Studies
Brain

Keywords

  • Febrile seizures
  • Hippocampal malrotation
  • MRI
  • Status epilepticus

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Hippocampal malrotation is associated with prolonged febrile seizures : Results of the FEBSTAT study. / Chan, Stephen; Bello, Jacqueline A.; Shinnar, Shlomo; Hesdorffer, Dale C.; Lewis, Darrell V.; MacFall, James; Shinnar, Ruth C.; Gomes, William A.; Litherland, Claire; Xu, Yuan; Nordli, Douglas R.; Pellock, John M.; Frank, L. Matthew; Moshe, Solomon L.; Sun, Shumei.

In: American Journal of Roentgenology, Vol. 205, No. 5, 01.11.2015, p. 1068-1074.

Research output: Contribution to journalArticle

Chan, S, Bello, JA, Shinnar, S, Hesdorffer, DC, Lewis, DV, MacFall, J, Shinnar, RC, Gomes, WA, Litherland, C, Xu, Y, Nordli, DR, Pellock, JM, Frank, LM, Moshe, SL & Sun, S 2015, 'Hippocampal malrotation is associated with prolonged febrile seizures: Results of the FEBSTAT study', American Journal of Roentgenology, vol. 205, no. 5, pp. 1068-1074. https://doi.org/10.2214/AJR.14.13330
Chan, Stephen ; Bello, Jacqueline A. ; Shinnar, Shlomo ; Hesdorffer, Dale C. ; Lewis, Darrell V. ; MacFall, James ; Shinnar, Ruth C. ; Gomes, William A. ; Litherland, Claire ; Xu, Yuan ; Nordli, Douglas R. ; Pellock, John M. ; Frank, L. Matthew ; Moshe, Solomon L. ; Sun, Shumei. / Hippocampal malrotation is associated with prolonged febrile seizures : Results of the FEBSTAT study. In: American Journal of Roentgenology. 2015 ; Vol. 205, No. 5. pp. 1068-1074.
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abstract = "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.",
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T2 - Results of the FEBSTAT study

AU - Chan, Stephen

AU - Bello, Jacqueline A.

AU - Shinnar, Shlomo

AU - Hesdorffer, Dale C.

AU - Lewis, Darrell V.

AU - MacFall, James

AU - Shinnar, Ruth C.

AU - Gomes, William A.

AU - Litherland, Claire

AU - Xu, Yuan

AU - Nordli, Douglas R.

AU - Pellock, John M.

AU - Frank, L. Matthew

AU - Moshe, Solomon L.

AU - Sun, Shumei

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N2 - 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.

AB - 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.

KW - Febrile seizures

KW - Hippocampal malrotation

KW - MRI

KW - Status epilepticus

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