Experimentally induced disorders of neuronal migration produce an increased propensity for electrographic seizures in rats

Disorders of neuronal migration in humans are associated with intractable epilepsy and some evidence suggests a causal relationship. This study evaluated electroencephalograms (EEG) of rats with experimentally induced disorders of neuronal migration. Fetal Sprague-Dawley rats were exposed to 196 cGy external irradiation on days 16 and 17 of gestation. This produced adult offspring with diffuse cortical dysplasias, agenesis of the corpus callosum, periventricular heterotopias, and dispersion of the pyramidal cell layer of the hippocampus. Epidural electrodes were implanted in four experimental (irradiated on gestational day 17) and four control rats. EEGs were recorded without anesthesia and in the presence of the anesthetic agents ketamine, acepromazine, and xylazine. In the presence of acepromazine, xylazine, or a combination of the two drugs, two of the four experimental rats had prolonged ictal activity on EEG. In one of the rats the ictal activity progressed to electrographic status epilepticus. Ketamine alone did not produce ictal EEG activity. None of the control rats demonstrated ictal activity under any treatment condition. This study demonstrates that disorders of neuronal migration are associated with an increased propensity for seizures in the presence of certain sedating agents.

[1]  A. Galaburda,et al.  The Development of Induced Cerebrocortical Microgyria in the Rat , 1992, Journal of neuropathology and experimental neurology.

[2]  R. Sidman,et al.  Time of origin of corresponding cell classes in the cerebral cortex of normal and reeler mutant mice: An autoradiographic analysis , 1973, The Journal of comparative neurology.

[3]  F. Andermann,et al.  Diffuse cortical dysplasia, or the 'double cortex' syndrome , 1991, Neurology.

[4]  J. Coyle,et al.  Methylazoxymethanol treatment of fetal rats results in abnormally dense noradrenergic innervation of neocortex. , 1979, Science.

[5]  J. Altman,et al.  The contribution of late‐generated neurons to the callosal projection in the rat: A study with prenatal x‐irradiation , 1982, The Journal of comparative neurology.

[6]  A. Barkovich,et al.  Band heterotopias: a newly recognized neuronal migration anomaly. , 1989, Radiology.

[7]  W. Cowan,et al.  The development of the hippocampus and dentate gyrus in normal and reeler mice , 1979, The Journal of comparative neurology.

[8]  J. Aicardi The agyria-pachygyria complex: A spectrum of cortical malformations , 1991, Brain and Development.

[9]  F. Andermann,et al.  Operative Strategies for Patients with Cortical Dysplastic Lesions and Intractable Epilepsy , 1994, Epilepsia.

[10]  P. Barth,et al.  Disorders of Neuronal Migration , 1987, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[11]  H. Riggs,et al.  MALFORMATION OF THE ADULT BRAIN (ALBINO RAT) RESULTING FROM PRENATAL IRRADIATION*,†‡ , 1956, Journal of neuropathology and experimental neurology.

[12]  J. Altman,et al.  Differential radiosensitivity of stationary and migratory primitive cells in the brains of infant rats. , 1968, Experimental neurology.

[13]  F Andermann,et al.  Focal neuronal migration disorders and intractable partial epilepsy: A study of 30 patients , 1991, Annals of neurology.

[14]  J. Coyle,et al.  Histological and neurochemical effects of fetal treatment with methylazoxymethanol on rat neocortex in adulthood , 1979, Brain Research.

[15]  W. Cowan,et al.  The morphology of the hippocampus and dentate gyrus in normal and reeler mice , 1979, The Journal of comparative neurology.

[16]  H Asanuma,et al.  Recent developments in the study of the columnar arrangement of neurons within the motor cortex. , 1975, Physiological reviews.

[17]  A. Barkovich,et al.  Nonlissencephalic cortical dysplasias: correlation of imaging findings with clinical deficits. , 1992, AJNR. American journal of neuroradiology.

[18]  J. Fleshman,et al.  Effects of cytotoxic deletions of somatic sensory cortex in fetal rats. , 1984, Somatosensory research.

[19]  C D Binnie,et al.  Surgical treatment of epilepsy due to cortical dysplasia: clinical and EEG findings. , 1993, Journal of neurology, neurosurgery, and psychiatry.

[20]  Models of simple partial and absence seizures in freely moving rats: Action of ketamine , 1993, Pharmacology Biochemistry and Behavior.

[21]  M A Falconer,et al.  Focal dysplasia of the cerebral cortex in epilepsy , 1971, Journal of neurology, neurosurgery, and psychiatry.

[22]  D. Hubel,et al.  Receptive fields, binocular interaction and functional architecture in the cat's visual cortex , 1962, The Journal of physiology.

[23]  Purohit Rc,et al.  Electroencephalographic patterns of clinically normal, sedated, and tranquilized newborn foals and adult horses. , 1985 .

[24]  H. Oguni,et al.  A Study of Unilateral Brief Focal Atonia in Childhood Partial Epilepsy , 1992, Epilepsia.

[25]  D. Cowen,et al.  LONG-TERM PATHOLOGICAL EFFECTS OF PRENATAL X-IRRADIATION ON THE CENTRAL NERVOUS SYSTEM OF THE RAT , 1960, Journal of neuropathology and experimental neurology.

[26]  D. Norman,et al.  MR of neuronal migration anomalies. , 1987, AJR. American journal of roentgenology.

[27]  V. Mountcastle Modality and topographic properties of single neurons of cat's somatic sensory cortex. , 1957, Journal of neurophysiology.

[28]  R. Quencer,et al.  Association of heterotopic gray matter with seizures: MR imaging. Work in progress. , 1988, Radiology.

[29]  A. Battaglia,et al.  EPILEPSY AND FOCAL GYRAL ANOMALIES DETECTED BY MRI: ELECTROCLINICO‐MORPHOLOGICAL CORRELATIONS AND FOLLOW‐UP , 1992, Developmental medicine and child neurology.

[30]  M. E. Corcoran,et al.  Infusions of α-2 noradrenergic agonists and antagonists into the amygdala: effects on kindling , 1993, Brain Research.

[31]  C. D'amato,et al.  The development of the mammalian nervous system I. Malformations of the brain, especially the cerebral cortex, induced in rats by radiation II. Some mechanisms of the malformations of the cortex , 1959, The Journal of comparative neurology.

[32]  R. Kuzniecky,et al.  Cortical dysplasia in temporal lobe epilepsy: Magnetic resonance imaging correlations , 1991, Annals of neurology.

[33]  F. Andermann,et al.  Neuronal Migration Disorders: A Contribution of Modern Neuroimaging to the Etiologic Diagnosis of Epilepsy , 1991, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[34]  Raman Sankar,et al.  Infantile spasms: II. Lenticular nuceli and brain stem activation on positron emission tomography , 1992, Annals of neurology.

[35]  N. Barbaro,et al.  Life-threatening focal status epilepticus due to occult cortical dysplasia. , 1993, Archives of neurology.

[36]  L. Rorke A Perspective: The Role of Disordered Genetic Control of Neurogenesis in the Pathogenesis of Migration Disorders , 1994, Journal of neuropathology and experimental neurology.

[37]  H Staunton,et al.  Microdysgenesis in resected temporal neocortex , 1988, Neurology.

[38]  F Andermann,et al.  Focal neuronal migration disorders and intractable partial epilepsy: Results of surgical treatment , 1991, Annals of neurology.

[39]  G. Jonsson,et al.  Effects of prenatal methylazoxymethanol treatment on the development of central monoamine neurons. , 1981, Brain research.

[40]  D. Janz,et al.  The Significance of Microdysgenesia in Primary Generalized Epilepsy: An Answer to the Considerations of Lyon and Gastaut , 1985, Epilepsia.