Voxel-based morphometry reveals gray matter network atrophy in refractory medial temporal lobe epilepsy.

BACKGROUND Conventional volumetric studies have shown that brain structures functionally and anatomically related to the hippocampus are smaller in patients with drug-refractory medial temporal lobe epilepsy (MTLE). OBJECTIVES To determine the extent of gray matter atrophy in the brains of patients with MTLE and to examine the pattern of atrophy. DESIGN We performed a voxel-based morphometric study of 43 consecutive patients with unilateral drug-refractory MTLE (21 patients with right-sided MTLE and 22 patients with left-sided MTLE) whose magnetic resonance images showed signs of unilateral hippocampal atrophy. The data from the patients with MTLE were compared with the data from 49 healthy control subjects to identify differences between groups in gray matter concentration (GMC). SETTING Academic hospital's epilepsy clinic. RESULTS We observed that patients with left- and right-sided MTLE exhibited GMC reduction in the hippocampus ipsilateral to the seizure origin. In addition, we found GMC reduction in the ipsilateral parahippocampal and isocortical temporal regions. Patients with MTLE also showed GMC reduction in subcortical nuclei such as the thalamus and caudate, in the cerebellum, in the midbrain, and in parieto-occipital regions. CONCLUSIONS Patients with MTLE exhibit a reduction in GMC in regions outside the temporal lobe, specifically in areas that are connected to the hippocampus and parahippocampal region, suggesting an anatomical route for atrophy.

[1]  Neda Bernasconi,et al.  MRI volumetry of the thalamus in temporal, extratemporal, and idiopathic generalized epilepsy , 2003, Neurology.

[2]  E. Kobayashi,et al.  Hippocampal atrophy and T2-weighted signal changes in familial mesial temporal lobe epilepsy , 2003, Neurology.

[3]  D. Arnold,et al.  Mesial temporal damage in temporal lobe epilepsy: a volumetric MRI study of the hippocampus, amygdala and parahippocampal region. , 2003, Brain : a journal of neurology.

[4]  Richard Wennberg,et al.  Preeminence of Extrahippocampal Structures in the Generation of Mesial Temporal Seizures: Evidence from Human Depth Electrode Recordings , 2002, Epilepsia.

[5]  Neil Roberts,et al.  Voxel-Based Morphometric Comparison of Hippocampal and Extrahippocampal Abnormalities in Patients with Left and Right Hippocampal Atrophy , 2002, NeuroImage.

[6]  E. Bertram,et al.  Midline Thalamic Region: Widespread Excitatory Input to the Entorhinal Cortex and Amygdala , 2002, The Journal of Neuroscience.

[7]  Thomas E. Nichols,et al.  Thresholding of Statistical Maps in Functional Neuroimaging Using the False Discovery Rate , 2002, NeuroImage.

[8]  S. Spencer.  Neural Networks in Human Epilepsy: Evidence of and Implications for Treatment , 2002, Epilepsia.

[9]  L. Spinelli,et al.  Volumetric measurements of subcortical nuclei in patients with temporal lobe epilepsy , 2001, Neurology.

[10]  M Vapalahti,et al.  MR volumetry of the entorhinal, perirhinal, and temporopolar cortices in drug-refractory temporal lobe epilepsy. , 2001, AJNR. American journal of neuroradiology.

[11]  J. Baron,et al.  In Vivo Mapping of Gray Matter Loss with Voxel-Based Morphometry in Mild Alzheimer's Disease , 2001, NeuroImage.

[12]  P. Mangan,et al.  The Midline Thalamus: Alterations and a Potential Role in Limbic Epilepsy , 2001, Epilepsia.

[13]  Karl J. Friston,et al.  A Voxel-Based Morphometric Study of Ageing in 465 Normal Adult Human Brains , 2001, NeuroImage.

[14]  F Andermann,et al.  Entorhinal cortex atrophy in epilepsy patients exhibiting normal hippocampal volumes , 2001, Neurology.

[15]  E. Kobayashi,et al.  Seizure outcome and hippocampal atrophy in familial mesial temporal lobe epilepsy , 2001, Neurology.

[16]  Asla Pitkänen,et al.  MRI volumetry of the hippocampus, amygdala, entorhinal cortex, and perirhinal cortex after status epilepticus , 2000, Epilepsy Research.

[17]  D. Mcintyre,et al.  The Parahippocampal Cortices and Kindling , 2000, Annals of the New York Academy of Sciences.

[18]  E. Bertram,et al.  The Pathological Substrate of Limbic Epilepsy: Neuronal Loss in the Medial Dorsal Thalamic Nucleus as the Consistent Change , 2000, Epilepsia.

[19]  Karl J. Friston,et al.  Voxel-Based Morphometry—The Methods , 2000, NeuroImage.

[20]  F Andermann,et al.  Morphometric MRI Analysis of the Parahippocampal Region in Temporal Lobe Epilepsy , 2000, Annals of the New York Academy of Sciences.

[21]  Richard S. J. Frackowiak,et al.  Navigation-related structural change in the hippocampi of taxi drivers. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[22]  Asla Pitkänen,et al.  Quantitative MRI volumetry of the entorhinal cortex in temporal lobe epilepsy , 2000, Seizure.

[23]  J. Ashburner,et al.  Voxel-by-Voxel Comparison of Automatically Segmented Cerebral Gray Matter—A Rater-Independent Comparison of Structural MRI in Patients with Epilepsy , 1999, NeuroImage.

[24]  W. Feindel,et al.  Entorhinal cortex in temporal lobe epilepsy , 1999, Neurology.

[25]  E. Bertram.  Functional Anatomy of Spontaneous Seizures in a Rat Model of Limbic Epilepsy , 1997, Epilepsia.

[26]  D. Mcintyre,et al.  Perirhinal cortex involvement in limbic kindled seizures , 1996, Epilepsy Research.

[27]  P. Gloor,et al.  MRI volumetric measurement of amygdala and hippocampus in temporal lobe epilepsy , 1993, Neurology.

[28]  Gregory McCarthy,et al.  Quantitative magnetic resonance imaging in temporal lobe epilepsy: Relationship to neuropathology and neuropsychological function , 1992, Annals of neurology.

[29]  J. L. Stringer,et al.  Functional anatomy of hippocampal seizures , 1991, Progress in Neurobiology.

[30]  L. Squire,et al.  The medial temporal lobe memory system , 1991, Science.

[31]  C R Jack,et al.  Temporal lobe seizures: lateralization with MR volume measurements of the hippocampal formation. , 1990, Radiology.

[32]  T. Kurashige,et al.  Proposal for Revised Classification of Epilepsies and Epileptic Syndromes , 1989, No to hattatsu = Brain and development.

[33]  J H Margerison,et al.  Epilepsy and the temporal lobes. A clinical, electroencephalographic and neuropathological study of the brain in epilepsy, with particular reference to the temporal lobes. , 1966, Brain : a journal of neurology.

[34]  J. Zentner,et al.  Surgical treatment of epilepsies. , 2002, Acta neurochirurgica. Supplement.

[35]  C. Rorden,et al.  Stereotaxic display of brain lesions. , 2000, Behavioural neurology.

[36]  Karl J. Friston,et al.  Statistical parametric maps in functional imaging: A general linear approach , 1994 .