Neuropathologic findings in cortical resections (including hemispherectomies) performed for the treatment of intractable childhood epilepsy

Ma, Farrell; Mj, DeRosa; Jg, Curran; Dl, Secor; Me, Cornford; Yg, Comair; Wj, Peacock; Wd, Shields; Hv, Vinters

doi:10.1007/bf00296786

Cited by 166 publications

(93 citation statements)

References 67 publications

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“…These children often had catastrophic early-onset seizures with generalized or nonlocalized behavioral features, and the neuropathologic substrate was unilateral or focal areas of CD (49)(50)(51)(52)(53). CD patients were subclassified, based on neuroimaging and pathologic criteria, into those with (a) heminiegalencephaly, (b) multilobar dysplasia, (c) focal dysplasia (i.e., involving one nontemporal lobe or less), and (d) mild cortical maldevelopment.…”

Section: Study Design and Clinicopathologic Classificationmentioning

confidence: 99%

Postoperative Seizure Control and Antiepileptic Drug Use in Pediatric Epilepsy Surgery Patients: The UCLA Experience, 1986–1997

et al. 1999

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Summary:Purpose: Young children with refractory symptomatic epilepsy are at risk for developing neurologic and cognitive disabilities. Stopping the seizures may prevent these disabilities, but it is unclear whether resective surgery is associated with adequate long-term seizure control.Methods: This study determined pre-and postsurgery seizure frequency and antiepileptic drug (AED) use (6 months to 10 years) in children with symptomatic seizures from unilateral cortical dysplasia (CD; n = 64) and non-CD etiologies (i.e., ischemia, infection; n = 71), and compared them with older temporal lobe epilepsy (TLE; n = 31) patients with complex partial seizures.Results: Compared with presurgery, postsurgery seizure frequencies were decreased for CD, non-CD, and TLE patients (p < 0.002), and there were no differences between the three groups from 6 to 24 months after surgery (p > 0.12). At 5 years after surgery, seizure frequencies were greater in CD compared with TLE cases (p = 0.009). Compared with presurgery, the number of AEDs declined after surgery in all three groups (p < 0.002), and positively correlated with seizure frequencies (p = Conclusions: This study indicates that seizure relief and AED use after resective surgery for symptomatic CD and non-CD etiologies was comparable with complex partial TLE cases up to 2 years after surgery. Furthermore, at 5 years after surgery, CD patients had outcomes better than those before surgery, but worse than TLE cases. In young children, these findings support the concept that early removal of symptomatic pathologic substrates is associated with seizure control and reduced AED use, similar to that noted in older TLE cases up to 2 years after surgery. Seizure control may reduce the risk of developing the seizure-related encephalopathy associated with severe symptomatic early-onset childhood epilepsy.

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Section: Study Design and Clinicopathologic Classificationmentioning

confidence: 99%

Postoperative Seizure Control and Antiepileptic Drug Use in Pediatric Epilepsy Surgery Patients: The UCLA Experience, 1986–1997

et al. 1999

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“…In epileptic patients, malformations of the neocortex are rather common (Meencke and Janz, 1984;Mischel et al, 1995). Some form of cortical malformation is observed in at least 14% of all cases of epilepsy (Meencke and Veith, 1992) and in ϳ40% of severe or intractable cases (Hardiman et al, 1988;Farrell et al, 1992). Although the etiologies of cortical malformations are poorly understood, they have been postulated to arise from disturbances in cell proliferation, neuronal migration, and/or programmed cell death (Evrard et al, 1978;Rakic, 1988;Barkovich et al, 1992;Meencke and Veith, 1992;Mouritzen-Dam, 1992;Palmini et al, 1993;Rorke, 1994).…”

Section: Abstract: Cortical Heterotopia; Epilepsy; Neuronal Migratiomentioning

confidence: 99%

A Genetic Animal Model of Human Neocortical Heterotopia Associated with Seizures

et al. 1997

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Malformations of the human neocortex are commonly associated with developmental delays, mental retardation, and epilepsy. This study describes a novel neurologically mutant rat exhibiting a forebrain anomaly resembling the human neuronal migration disorder of double cortex. This mutant displays a telencephalic internal structural heterotopia (tish) that is inherited in an autosomal recessive manner. The bilateral heterotopia is prominent below the frontal and parietal neocortices but is rarely observed in temporal neocortex. Neurons in the heterotopia exhibit neocortical-like morphologies and send typical projections to subcortical sites; however, characteristic lamination and radial orientation are disturbed in the heterotopia. The period of neurogenesis during which cells in the heterotopia are generated is the same as in the normotopic neocortex; however, the cells in the heterotopia exhibit a "rim-to-core" neurogenetic pattern rather than the characteristic "inside-out" pattern observed in normotopic neocortex. Similar to the human syndrome of double cortex, some of the animals with the tish phenotype exhibit spontaneous recurrent electrographic and behavioral seizures.The tish rat is a unique neurological mutant that shares several features with a human cortical malformation associated with epilepsy. On the basis of its regional connectivity, histological composition, and period of neurogenesis, the heterotopic region in the tish rat is neocortical in nature. This neurological mutant represents a novel model system for investigating mechanisms of aberrant neocortical development and is likely to provide insights into the cellular and molecular events contributing to seizure development in dysplastic neocortex.

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“…They are often associated with patients having severe epilepsies or cognitive defects (Mischel et al, 1995;Porter et al, 2003). Thus, cortical malformations are present in Ͻ24% of all epilepsy patients but are found in 40% of cases that are refractory to treatment (Hardiman et al, 1988;Farrell et al, 1992). Anatomical and functional studies in rodents with cortical malformations suggest that ectopic neurons form afferent and efferent connections with adjacent cortex (for review, see Chevassus-Au- , indicating that heterotopias are integrated within cortical networks.…”

Section: Introductionmentioning

confidence: 99%

Abnormal Network Activity in a Targeted Genetic Model of Human Double Cortex

Ackman¹,

Aniksztejn²,

Crépel³

et al. 2009

J. Neurosci.

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In human patients, cortical dysplasia produced by Doublecortin (DCX) mutations lead to mental retardation and intractable infantile epilepsies, but the underlying mechanisms are not known. DCX Ϫ/Ϫ mice have been generated to investigate this issue. However, they display no neocortical abnormality, lessening their impact on the field. In contrast, in utero knockdown of DCX RNA produces a morphologically relevant cortical band heterotopia in rodents. On this preparation we have now compared the neuronal and network properties of ectopic, overlying, and control neurons in an effort to identify how ectopic neurons generate adverse patterns that will impact cortical activity. We combined dynamic calcium imaging and anatomical and electrophysiological techniques and report now that DCX Ϫ/Ϫ EGFP ϩ -labeled ectopic neurons that fail to migrate develop extensive axonal subcortical projections and retain immature properties, and most of them display a delayed maturation of GABA-mediated signaling. Cortical neurons overlying the heterotopia, in contrast, exhibit a massive increase of ongoing glutamatergic synaptic currents reflecting a strong reactive plasticity. Neurons in both experimental fields are more frequently coactive in coherent synchronized oscillations than control cortical neurons. In addition, both fields displayed network-driven oscillations during evoked epileptiform burst. These results show that migration disorders produce major alterations not only in neurons that fail to migrate but also in their programmed target areas. We suggest that this duality play a major role in cortical dysfunction of DCX brains.

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Neuropathologic findings in cortical resections (including hemispherectomies) performed for the treatment of intractable childhood epilepsy

Cited by 166 publications

References 67 publications

Postoperative Seizure Control and Antiepileptic Drug Use in Pediatric Epilepsy Surgery Patients: The UCLA Experience, 1986–1997

Postoperative Seizure Control and Antiepileptic Drug Use in Pediatric Epilepsy Surgery Patients: The UCLA Experience, 1986–1997

A Genetic Animal Model of Human Neocortical Heterotopia Associated with Seizures

Abnormal Network Activity in a Targeted Genetic Model of Human Double Cortex

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