Focal structural changes and cognitive dysfunction in juvenile myoclonic epilepsy.
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ABSTRACT: Objective
The aim of this study was to determine if there were focal cortical abnormalities in juvenile myoclonic epilepsy (JME) using neuropsychological investigations and MRI.Methods
Twenty-eight patients with JME and a large sample of healthy controls were assessed using a series of neuropsychological tests as well as structural and diffusion tensor MRI (DTI). DTI measures assessed fractional anisotropy (FA) within a white matter skeleton.Results
Neuropsychological testing indicated subtle dysfunctions in verbal fluency, comprehension, and expression, as well as nonverbal memory and mental flexibility. Utilizing whole-brain voxel-based morphometry for gray matter MRI data and tract-based spatial statistics for white matter diffusion MRI data, we found reductions in gray matter volume (GMV) in the supplementary motor area and posterior cingulate cortex and reductions in FA in underlying white matter of the corpus callosum. Supplementary motor area FA predicted scores in word naming tasks and expression scores. Posterior cingulate cortex GMV and FA predicted cognitive inhibition scores on the mental flexibility task.Conclusions
The neuropsychological, structural, and tractography results implicate mesial frontal cortex, especially the supplementary motor area, and posterior cingulate cortex in JME.
SUBMITTER: O'Muircheartaigh J
PROVIDER: S-EPMC3030222 | biostudies-literature | 2011 Jan
REPOSITORIES: biostudies-literature
Publications
Focal structural changes and cognitive dysfunction in juvenile myoclonic epilepsy.
O'Muircheartaigh J J Vollmar C C Barker G J GJ Kumari V V Symms M R MR Thompson P P Duncan J S JS Koepp M J MJ Richardson M P MP
Neurology 20110101 1
<h4>Objective</h4>The aim of this study was to determine if there were focal cortical abnormalities in juvenile myoclonic epilepsy (JME) using neuropsychological investigations and MRI.<h4>Methods</h4>Twenty-eight patients with JME and a large sample of healthy controls were assessed using a series of neuropsychological tests as well as structural and diffusion tensor MRI (DTI). DTI measures assessed fractional anisotropy (FA) within a white matter skeleton.<h4>Results</h4>Neuropsychological tes ...[more]
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Project description:ObjectiveJuvenile myoclonic epilepsy (JME) is the most common genetic generalized epilepsy syndrome. Myoclonus may relate to motor system hyperexcitability and can be provoked by cognitive activities. To aid genetic mapping in complex neuropsychiatric disorders, recent research has utilized imaging intermediate phenotypes (endophenotypes). Here, we aimed to (a) characterize activation profiles of the motor system during different cognitive tasks in patients with JME and their unaffected siblings, and (b) validate those as endophenotypes of JME.MethodsThis prospective cross-sectional investigation included 32 patients with JME, 12 unaffected siblings, and 26 controls, comparable for age, sex, handedness, language laterality, neuropsychological performance, and anxiety and depression scores. We investigated patterns of motor system activation during episodic memory encoding and verb generation functional magnetic resonance imaging (fMRI) tasks.ResultsDuring both tasks, patients and unaffected siblings showed increased activation of motor system areas compared to controls. Effects were more prominent during memory encoding, which entailed hand motion via joystick responses. Subgroup analyses identified stronger activation of the motor cortex in JME patients with ongoing seizures compared to seizure-free patients. Receiver-operating characteristic curves, based on measures of motor activation, accurately discriminated both patients with JME and their siblings from healthy controls (area under the curve: 0.75 and 0.77, for JME and a combined patient-sibling group against controls, respectively; P < .005).SignificanceMotor system hyperactivation represents a cognitive, domain-independent endophenotype of JME. We propose measures of motor system activation as quantitative traits for future genetic imaging studies in this syndrome.
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