Abnormal spindle-like microcephaly-associated (ASPM) mutations strongly disrupt neocortical structure but spare the hippocampus and long-term memory

Sandrine Passemard; Alain Verloes; Thierry Billette de Villemeur; Odile Boespflug-Tanguy; Karen Hernandez; Marion Laurent; Bertrand Isidor; Corinne Alberti; Nathalie Pouvreau; Séverine Drunat; Bénédicte Gérard; Vincent El Ghouzzi; Jorge Gallego; Monique Elmaleh-Bergès; Wieland B Huttner; Stephan Eliez; Pierre Gressens; Marie Schaer

doi:10.1016/j.cortex.2015.10.010

Abnormal spindle-like microcephaly-associated (ASPM) mutations strongly disrupt neocortical structure but spare the hippocampus and long-term memory

Sandrine Passemard, Alain Verloes, Thierry Billette de Villemeur, Odile Boespflug-Tanguy, Karen Hernandez, Marion Laurent, Bertrand Isidor, Corinne Alberti, Nathalie Pouvreau, Séverine Drunat, Bénédicte Gérard, Vincent El Ghouzzi, Jorge Gallego, Monique Elmaleh-Bergès, Wieland B Huttner, Stephan Eliez, Pierre Gressens, Marie Schaer

Research output: Contribution to journal › Article › peer-review

27 Citations (Scopus)

Abstract

Autosomal recessive primary microcephaly results from abnormal brain development linked to proliferation defects in neural progenitors. The most frequent form, caused by ASPM mutations, is usually defined by a reduced brain volume and is associated with intellectual disability. Although many ASPM cases have now been reported, structural brain abnormalities and their link with cognitive disabilities have rarely been investigated. In this study, we used high resolution T1-weighted magnetic resonance imaging in seven patients with ASPM mutations and 39 healthy age-matched controls to quantify regional volumes, thickness, surface area, gyrification index and white matter volumes of 30 cortical regions. We observed a consistent reduction of 50% or more in the volume and surface area of all cortical regions except for the hippocampus and surrounding medial temporal structures, which were significantly less reduced. Neuropsychologic assessment indicated significant impairments of cognitive abilities. However, these impairments were associated with normal mnesic abilities, in keeping with the relative preservation of the hippocampus and medial temporal structures. These results show that, contrary to current opinion, the cortical volume and surface area of patients with ASPM mutations is reduced depending on a regionally specific fashion and their cognitive profile reflects this heterogeneity. The precise characterization of the cortical map and cognitive abilities of patients with ASPM mutations should allow developing more focused reeducative interventions well-suited to their real abilities.

Original language	English
Pages (from-to)	158-76
Number of pages	19
Journal	Cortex; a journal devoted to the study of the nervous system and behavior
Volume	74
Early online date	31 Oct 2015
DOIs	https://doi.org/10.1016/j.cortex.2015.10.010
Publication status	Published - Jan 2016

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Passemard, S., Verloes, A., Billette de Villemeur, T., Boespflug-Tanguy, O., Hernandez, K., Laurent, M., Isidor, B., Alberti, C., Pouvreau, N., Drunat, S., Gérard, B., El Ghouzzi, V., Gallego, J., Elmaleh-Bergès, M., Huttner, W. B., Eliez, S., Gressens, P., & Schaer, M. (2016). Abnormal spindle-like microcephaly-associated (ASPM) mutations strongly disrupt neocortical structure but spare the hippocampus and long-term memory. Cortex; a journal devoted to the study of the nervous system and behavior, 74, 158-76. https://doi.org/10.1016/j.cortex.2015.10.010

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title = "Abnormal spindle-like microcephaly-associated (ASPM) mutations strongly disrupt neocortical structure but spare the hippocampus and long-term memory",

abstract = "Autosomal recessive primary microcephaly results from abnormal brain development linked to proliferation defects in neural progenitors. The most frequent form, caused by ASPM mutations, is usually defined by a reduced brain volume and is associated with intellectual disability. Although many ASPM cases have now been reported, structural brain abnormalities and their link with cognitive disabilities have rarely been investigated. In this study, we used high resolution T1-weighted magnetic resonance imaging in seven patients with ASPM mutations and 39 healthy age-matched controls to quantify regional volumes, thickness, surface area, gyrification index and white matter volumes of 30 cortical regions. We observed a consistent reduction of 50% or more in the volume and surface area of all cortical regions except for the hippocampus and surrounding medial temporal structures, which were significantly less reduced. Neuropsychologic assessment indicated significant impairments of cognitive abilities. However, these impairments were associated with normal mnesic abilities, in keeping with the relative preservation of the hippocampus and medial temporal structures. These results show that, contrary to current opinion, the cortical volume and surface area of patients with ASPM mutations is reduced depending on a regionally specific fashion and their cognitive profile reflects this heterogeneity. The precise characterization of the cortical map and cognitive abilities of patients with ASPM mutations should allow developing more focused reeducative interventions well-suited to their real abilities.",

author = "Sandrine Passemard and Alain Verloes and {Billette de Villemeur}, Thierry and Odile Boespflug-Tanguy and Karen Hernandez and Marion Laurent and Bertrand Isidor and Corinne Alberti and Nathalie Pouvreau and S{\'e}verine Drunat and B{\'e}n{\'e}dicte G{\'e}rard and {El Ghouzzi}, Vincent and Jorge Gallego and Monique Elmaleh-Berg{\`e}s and Huttner, {Wieland B} and Stephan Eliez and Pierre Gressens and Marie Schaer",

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Passemard, S, Verloes, A, Billette de Villemeur, T, Boespflug-Tanguy, O, Hernandez, K, Laurent, M, Isidor, B, Alberti, C, Pouvreau, N, Drunat, S, Gérard, B, El Ghouzzi, V, Gallego, J, Elmaleh-Bergès, M, Huttner, WB, Eliez, S, Gressens, P & Schaer, M 2016, 'Abnormal spindle-like microcephaly-associated (ASPM) mutations strongly disrupt neocortical structure but spare the hippocampus and long-term memory', Cortex; a journal devoted to the study of the nervous system and behavior, vol. 74, pp. 158-76. https://doi.org/10.1016/j.cortex.2015.10.010

Abnormal spindle-like microcephaly-associated (ASPM) mutations strongly disrupt neocortical structure but spare the hippocampus and long-term memory. / Passemard, Sandrine; Verloes, Alain; Billette de Villemeur, Thierry et al.
In: Cortex; a journal devoted to the study of the nervous system and behavior, Vol. 74, 01.2016, p. 158-76.

Research output: Contribution to journal › Article › peer-review

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AU - Passemard, Sandrine

AU - Verloes, Alain

AU - Billette de Villemeur, Thierry

AU - Boespflug-Tanguy, Odile

AU - Hernandez, Karen

AU - Laurent, Marion

AU - Isidor, Bertrand

AU - Alberti, Corinne

AU - Pouvreau, Nathalie

AU - Drunat, Séverine

AU - Gérard, Bénédicte

AU - El Ghouzzi, Vincent

AU - Gallego, Jorge

AU - Elmaleh-Bergès, Monique

AU - Huttner, Wieland B

AU - Eliez, Stephan

AU - Gressens, Pierre

AU - Schaer, Marie

PY - 2016/1

Y1 - 2016/1

N2 - Autosomal recessive primary microcephaly results from abnormal brain development linked to proliferation defects in neural progenitors. The most frequent form, caused by ASPM mutations, is usually defined by a reduced brain volume and is associated with intellectual disability. Although many ASPM cases have now been reported, structural brain abnormalities and their link with cognitive disabilities have rarely been investigated. In this study, we used high resolution T1-weighted magnetic resonance imaging in seven patients with ASPM mutations and 39 healthy age-matched controls to quantify regional volumes, thickness, surface area, gyrification index and white matter volumes of 30 cortical regions. We observed a consistent reduction of 50% or more in the volume and surface area of all cortical regions except for the hippocampus and surrounding medial temporal structures, which were significantly less reduced. Neuropsychologic assessment indicated significant impairments of cognitive abilities. However, these impairments were associated with normal mnesic abilities, in keeping with the relative preservation of the hippocampus and medial temporal structures. These results show that, contrary to current opinion, the cortical volume and surface area of patients with ASPM mutations is reduced depending on a regionally specific fashion and their cognitive profile reflects this heterogeneity. The precise characterization of the cortical map and cognitive abilities of patients with ASPM mutations should allow developing more focused reeducative interventions well-suited to their real abilities.

AB - Autosomal recessive primary microcephaly results from abnormal brain development linked to proliferation defects in neural progenitors. The most frequent form, caused by ASPM mutations, is usually defined by a reduced brain volume and is associated with intellectual disability. Although many ASPM cases have now been reported, structural brain abnormalities and their link with cognitive disabilities have rarely been investigated. In this study, we used high resolution T1-weighted magnetic resonance imaging in seven patients with ASPM mutations and 39 healthy age-matched controls to quantify regional volumes, thickness, surface area, gyrification index and white matter volumes of 30 cortical regions. We observed a consistent reduction of 50% or more in the volume and surface area of all cortical regions except for the hippocampus and surrounding medial temporal structures, which were significantly less reduced. Neuropsychologic assessment indicated significant impairments of cognitive abilities. However, these impairments were associated with normal mnesic abilities, in keeping with the relative preservation of the hippocampus and medial temporal structures. These results show that, contrary to current opinion, the cortical volume and surface area of patients with ASPM mutations is reduced depending on a regionally specific fashion and their cognitive profile reflects this heterogeneity. The precise characterization of the cortical map and cognitive abilities of patients with ASPM mutations should allow developing more focused reeducative interventions well-suited to their real abilities.

U2 - 10.1016/j.cortex.2015.10.010

DO - 10.1016/j.cortex.2015.10.010

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JO - Cortex; a journal devoted to the study of the nervous system and behavior

JF - Cortex; a journal devoted to the study of the nervous system and behavior

ER -

Passemard S, Verloes A, Billette de Villemeur T, Boespflug-Tanguy O, Hernandez K, Laurent M et al. Abnormal spindle-like microcephaly-associated (ASPM) mutations strongly disrupt neocortical structure but spare the hippocampus and long-term memory. Cortex; a journal devoted to the study of the nervous system and behavior. 2016 Jan;74:158-76. Epub 2015 Oct 31. doi: 10.1016/j.cortex.2015.10.010

Abnormal spindle-like microcephaly-associated (ASPM) mutations strongly disrupt neocortical structure but spare the hippocampus and long-term memory

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