Bilateral frontal polymicrogyria is a recently recognized syndrome characterized by symmetric polymicrogyria of both frontal lobes that presents with delayed motor and language development, spastic quadriparesis, and variable mental retardation. However, the postmortem findings of this syndrome are not fully elaborated. Here we describe an autopsy case of bilateral frontal polymicrogyria in a male fetus delivered at 22 weeks gestation due to extensive chorioamnionitis. The microscopic findings included a thinned cortical plate with fair neuronal maturation. There were no signs of neuronal damage and the white matter was unremarkable.
Autopsy ; Chorioamnionitis ; European Continental Ancestry Group ; Female ; Fetus ; Frontal Lobe ; Humans ; Intellectual Disability ; Language Development ; Male ; Malformations of Cortical Development ; Muscle Spasticity ; Neuronal Migration Disorders ; Neurons ; Pregnancy ; Quadriplegia

Cortical malformation-associated epileptic seizures are resistant to conventional anticonvulsant drugs. Relatively little research has been conducted on the effects of antiepileptic drugs (AEDs) on seizure activity in a rat model of dysplasia. We have used rats exposed to methylazoxymethanol acetate (MAM) in utero, an animal model featuring nodular heterotopia, to investigate the effects of ethosuximide (ETX) in the dysplastic brain. Pilocarpine was used to induce acute seizure in MAM-exposed and age-matched vehicle-injected control animals. Field potential recordings were used to monitor the amplitude and number of population spikes, and paired pulse inhibition in response to stimulation of the commissural pathway. Pharmaco-resistance was tested by measuring seizure latencies after pilocarpine administration (320 mg/kg, i.p.) with and without pre-treatment with ETX. Pre-treatment with 300 mg of ETX significantly prolonged the latency to the status epilepticus (SE) in both control and MAM-treated groups. Pre-treatment with ETX 100mg and ETX 200 mg had little effect in MAM-exposed rats. However, ETX 200 mg prolonged the latency to the SE in control groups. Spontaneous field potential and secondary after-discharges were higher for MAM-treated rat in comparison with control rats injects with ETX. The main findings of this study are that acute seizures initiated in MAM-exposed rats are relatively resistant to standard ETX assessed in vivo. These data suggest that ETX do not prolong seizure latencies in MAM-rats exposed to pilocarpine.
Animals ; Anticonvulsants ; Brain ; Epilepsy ; Ethosuximide* ; Methylazoxymethanol Acetate ; Models, Animal* ; Neuronal Migration Disorders* ; Neurons* ; Pilocarpine* ; Rats* ; Seizures* ; Status Epilepticus

OBJECTIVE: Congenital bilateral perisylvian syndrome (CBPS) has been defined as a characteristic malformative perisylvian polymicrogyria (PMG) in patients with clinical symptoms of pseudobulbar palsy and epileptic seizures. For the present study, we investigate clinicopathologic features of CBPS associated with timing of lesion formation. METHODS: Clinicopathologic features of CBPS from 6 patients with surgical resection of the cerebral lesions due to medically intractable seizures were studied. RESULTS: Seizure onset ranged from 1 to 10years (average 6.7years) of age, and average duration of seizure was 23years. All had complex partial seizures, and two patients had additional tonic clonic seizures. Magnetic resonance (MR) images showed polymicrogyria, atropic gyri with gliosis. In the histopathologic examination, the cortical lesions revealed features of ulegyria ; atrophic and sclerotic gyri, laminar loss of neurons, extensive lobular gliosis throughout the gray and white matter, neuronoglial nodule formation, and many amyloid bodies. Unlayered or four-layered PMG was not identified. CONCLUSION: Above data suggest that CBPS might be caused by ulegyria resulting from developmental cortical defect during early fetal stage or acquired hypoxic/ischemic injury in prenatal or postnatal life.
Amyloid ; Epilepsy ; Gliosis ; Humans ; Malformations of Cortical Development ; Neuronal Migration Disorders ; Neurons ; Pseudobulbar Palsy ; Seizures

OBJECTIVE: The authors study a relationship between the presence of cavum septum pellucidum(CSP) and the development of epilepsy by comparing the presence of CSP, which has been known to be a normal variation, in normal control group and epilepsy patients. METHODS: This study included 377 patients with epilepsy and 252 controls without epilepsy. Of epilepsy patients, 168 patients underwent surgery due to intractability and 209 patients was on medication of antiepileptic drugs. Control group had only headache and no visible lesion in MRI. Of 168 surgical patients, 102 patients had temporal lobe epilepsy and 66 patients had extratemporal lobe epilepsy. Ninty five patients showed a neuronal migration disorder in histopathologic findings. Definition of "CSP" and "partial CSP" was followed by Pauling's classification. RESULTS: CSP was present 8.2% of epilepsy patients and 1.6% of control group(p<0.01). CSP was detected in 11.3% of patients with surgical treatment and in 5.7% of patients with medical treatment. CSP was noticed in 8.9% of temporal lobe epilepsy, in 15.2% of extratemporal lobe epilepsy, in 13.7% of patients with neuronal migration disorder, and in 8.2% of patients with no neuronal migration disorder. CONCLUSION: Presence of CSP is statistically higher in epilepsy patients than in control group. This results indicates that the presence of CSP may not be a simple normal variation, and it can be considered a developmental anomaly that may contribute to epileptogenesis.
Anticonvulsants ; Classification ; Epilepsy* ; Epilepsy, Temporal Lobe ; Headache ; Humans ; Magnetic Resonance Imaging ; Neuronal Migration Disorders ; Septum Pellucidum*

BACKGROUND: Neuronal migration disorder (NMD) is one of the causes of medically intractable epilepsy. As neurosurgical treatments for medically intractable epilepsy have expanded recently, precise histopathologic diagnosis is required. Histopathologic grading of NMD is important due to its association with neocortical development and expectation of prognosis. Many studies revealed abnormalities of neuronal cytoskeletal protein in abnormal neuronal cells of NMD. METHODS: We performed immunohistochemical staining for neurofilament protein (NF) subtypes, one of the neuronal cytoskeletal proteins, and investigated the staining pattern of specific cells in each grade of NMD. RESULTS: NF-L was more intensely labeled in perikarya, dendrites, and axons of normal or small sized dysplastic neurons, cytomegalic neurons, and balloon cells than of normal-looking neurons. Furthermore, positive reaction was more intense in high-grade lesion. NF-H and NF-M were mainly positive in the axons of gray and white matter and weakly positive in a few cytomegalic neurons and some balloon cells. CONCLUSION: NF-L is a better marker than NF-H and NF-M for the detection of normal or small sized dysplastic neurons, cytomegalic neurons, and balloon cells and for grading of NMD.
Axons ; Cerebral Cortex ; Cytoskeletal Proteins ; Dendrites ; Diagnosis ; Epilepsy ; Nervous System Malformations ; Neurofilament Proteins ; Neuronal Migration Disorders* ; Neurons* ; Prognosis

OBJECTIVE: To estimate the probable cause and the time of cerebral insult in cerebral palsy (CP) based on MRI findings and risk factors. METHOD: The subjects comprised all sixty-seven patients with CP showing abnormal MRI findings between March 1999 and September 2001 at the Catholic University of Korea, St. Mary's Hospital. A detailed medical history was available for all patients including those not born in our hospital. They ranged in age from two months to five years. We analyzed the brain magnetic resonance (MR) findings of patients with CP to correlate the probable cause and the time of cerebral insult through the consideration of medical histories including prenatal, perinatal and postnatal histories. RESULTS: Of the 67 MRIs, abnormalities were the followings; periventricular leukomalacias (PVLs) in 49 cases, cortical or subcortical infarction in 4 cases, brain atrophy in 7 cases, neuronal migration disorder in 4 cases, and delayed myelination in 3 cases. Among the patients with PVL, perinatal risk factors were responsible for cerebral insult in preterm, but pre- and perinatal contribution were similar in patients born at full term. Among the patients with cerebral infarction, only one case with meningitis at 11 months was suspected for cerebral insult. These patients had no risk factor as a peri- or post-natal etiology. Four patients with neuronal migration disorder had no risk factor for peri- or postnatal etiology except for the one who was a twin. CONCLUSION: Review of brain MRI findings such as PVL, infarct, neuronal migration disorder and a detailed medical history including prenatal and perinatal etiology would be a useful method to estimate the probable cause and the time of cerebral insult in CP.
Atrophy ; Brain ; Cerebral Infarction ; Cerebral Palsy* ; Humans ; Infant, Newborn ; Korea ; Leukomalacia, Periventricular ; Magnetic Resonance Imaging ; Meningitis ; Myelin Sheath ; Neuronal Migration Disorders ; Risk Factors ; Twins

PURPOSE: The objective of this study is to investige the clinical features, natural histories, and results of medical and surgical treatment of NMD in patients who were diagnosed during childhood. METHODS: We performed a retrospective analysis of medical records of 57 patients with NMD who were newly diagnosed by MRI or pathologically in epilepsy children since March 1993 to June 2000. RESULTS: These 57 patients with NMD consisted of 26 with cortical dysplasia, 9 with lissencephaly, 7 with polymicrogyria, 6 with schizencephaly, 4 with hemimegalencephaly, 3 with heterotopias, and 2 with double cortex. Clinically, 94.7% of these patients showed seizures, 33.3% with developmental delay, 21.1% mental retardation, 15.8% cerebral palsy, and 7.0% attention deficit hyperactivity disorder. Their response to antiepileptic drugs was good to 31 patients (75.6%), moderate to 3 (7.3%), and poor to 7 (17.1%). Twelve patients were completely seizure-free after receiving medication for at least 15 months. Seventeen patients tolerated with monotherapy with antiepileptic drugs. Fourteen patients underwent surgical resection. The results of operation were highly correlated with the complete removal of epileptic focus. Six patients who underwent complete resection were seizure-free after operation. On the other hand, Eight patients who had incomplete resection of the epileptic focus showed poor outcome. CONCLUSION: Most of previous reports suggested that NMD is associated with refractory to medical treatments, and early surgical operation has been recommended. Our study demonstrates remarkably good responses of NMD patients with medical treatment only.
Anticonvulsants ; Attention Deficit Disorder with Hyperactivity ; Cerebral Palsy ; Child* ; Epilepsy ; Hand ; Humans ; Intellectual Disability ; Lissencephaly ; Magnetic Resonance Imaging ; Malformations of Cortical Development ; Medical Records ; Neuronal Migration Disorders* ; Neurons* ; Retrospective Studies ; Seizures

PURPOSE: A majority of patients with neuronal migration disorders(NMDs) in cortical structures suffer from medically intractable epilepsy. The role of NMDs on seizure susceptibility or epileptogenecity has not been well documented. In the present study, we established an experimental model of NMDs in Sprague-Dawley rats by exposing fetal rats to external irradiation in order to demonstrate epileptogenic effect of NMDs lesions. METHODS: Pregnant rats were exposed to 240cGy of external X-irradiation delivered by a linear accelerator source on gestational day 16 and 17 to produce NMDs lesions in rat brain. RESULTS: Microcephaly was evident on gross examination of the affected brains. Seizure susceptibility was tested by a small dose of kainate(0.1mg/kg) injected intraperitoneally, and the irradiated animals showed increased susceptibility to kainate. Histopathologic examination revealed cortical dysplasia consisting of dyslamination of cerebral cortex and appearance of cytomegalic neurons, neuronal heterotopia in periventricular white matter, dispersion of pyramidal layer and hippocampal dentate gyrus, and agenesis of corpus callosum. Histopathologic change of the cerebral cortex and hippocampus was closely correlated with seizure activity. Quantitative autoradiography of [H]muscimol binding to GABAA receptors was significantly reduced in NMDs lesions(P=0.02). CONCLUSION: In utero irradiation of fetal rats resulted in histopathologic abnormalities that mi- miced several characteristic features of human neuronal migration disorders, and hyperexcitability appears to be associated with reduction in density of GABAp receptors in the brain, particularly in hippocampus and neocortex.
Agenesis of Corpus Callosum ; Animals* ; Autoradiography ; Brain ; Cerebral Cortex ; Dentate Gyrus ; Epilepsy ; Hippocampus ; Humans ; Kainic Acid ; Kinetics* ; Malformations of Cortical Development ; Mice ; Microcephaly ; Models, Animal* ; Models, Theoretical ; Neocortex ; Neuronal Migration Disorders* ; Neurons* ; Particle Accelerators ; Rats ; Rats, Sprague-Dawley ; Seizures

Cortical dysplasia(CD) is recently known as a cause of intractable partial epilepsies that are amenable to surgical treatment. The development of new neuroimaging has facilitated the recognition of these neuronal migration disorders. Here we examine some clinical features that permit early suspicion of focal cortical dysplasia and better surgical results. From a consecutive surgical series of 239 patients with intractable epilepsy since 1992, pathologically verified 31 CD including 6 CD with dysembryoplastic neuroepithelial tumor(DNT) were selected for this study. The location and extent of resection were determined by both epileptogenic zones and the structural lesion, according to presurgical evaluation(neuroimaging, EEG, intracranial recording), intraoperative electrocorticography(ECoG) and functional brain mapping. The series consisted of 21 men and 10 women with ages at seizure onset ranging from 1 to 26 years(mean 11.1year). The duration of the epilepsy prior to surgery ranged from 3 to 30 years(mean 14.3). The CD was verified in 17(11.1%) of 153 cases with temporal lobe epilepsy and 8(16.6%) of 48 cases with extratemporal epilepsy, mainly peri-Rolandic area. The lesion location of CD with DNT were temporal(4 cases) and extratemporal(2 cases). The histology of the surgical specimens showed cortical dyslamination in 26 patients, additional dysplastic neurons in 2 patients, and additional balloon cells in 3 patients. Excellent and good clinical results were achieved in 29 cases. CD should be suspected when intractable partial epilepsy occur in children. Careful investigation of neuroimaging techniques with high resolution MRI and sophisticated presurgical and intraoperative tailoring is essential for better outcome with identification of CD.
Brain Mapping ; Child ; Electroencephalography ; Epilepsies, Partial ; Epilepsy* ; Epilepsy, Temporal Lobe ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Malformations of Cortical Development* ; Neuroimaging ; Neuronal Migration Disorders ; Neurons ; Seizures

Band heterotopia is a rare neuronal migration disorder, resulting in epilepsy and mental retardation. Epilepsy in band heteropopia, of which Lennox-Gastaut syndrome constituted about 20%, varied in nature and degree of severity. Band heterotopia can be diagnosed by brain magnetic resonance imaging (MRI), showing another diffuse layer of gray matter underlying the normal-looking cortex with intervening thin rim of white matter. While positron emission tomography (PET) with [18F]-fluorodeoxyglucose revealed glucose uptake similar to the overlying cortex, single photon emission computerized tomography (SPECT) findings of band heterotopia have not been reported. We report a 8-year-old girl who presented with variable types of generalized seizures and mild mental retardation. She was diagnosed as having band heterotopia with Lennox-Gastaut syndrome by MRI and interictal electroencephalogram (EEG) showing immature background and generalized 2 Hz slow spike and wave complexes. Interictal SPECT, using Tc 99m hexamethyl propylenamine oxime (Tc 99m-HMPAO), revealed the same degree of perfusion in both the areas of band heterotopia and the overlying cortex. By using valproate and lamotrigine, she is now in stable condition with a significant decrease in seizure frequency.
Brain ; Child ; Electroencephalography ; Epilepsy ; Female ; Glucose ; Humans ; Intellectual Disability ; Magnetic Resonance Imaging ; Neuronal Migration Disorders ; Perfusion ; Positron-Emission Tomography ; Seizures ; Tomography, Emission-Computed, Single-Photon ; Valproic Acid