A quantitative study on changes of the myelinated fibers in the cerebral cortex of cortical dysplasia rats

An animal model of cortical dysplasia was established through X-ray irradiation induced subcortical heterotopic nodules in rats. Transmission electron microscopy detection of the ultrastructure and the stereology examination showed that there was a significant decrease in cerebral white matter and hippocampal volume, the total volume, volume density, length density and total length of the myelinated fibers in the white matter of cortical dysplasia rats. Subcortical heterotopic nodules of the hippocampal CA1 region and synaptic number density in the CA3 region were reduced compared with normal rats. Our experimental findings indicate that erosed subcortical heterotopic nodules, decreased total length of myelinated nerve fibers and demyelination directly lead to a reduction of white matter volume.

Pathological Networks Involving Dysmorphic Neurons in Type ⅡFocal Cortical Dysplasia

Focal cortical dysplasia(FCD)is one of the most common causes of drug-resistant epilepsy.Dysmorphic neurons are the major histopathological feature of typeⅡFCD,but their role in seizure genesis in FCD is unclear.Here we performed whole-cell patch-clamp recording and morphological reconstruction of cortical principal neurons in postsurgical brain tissue from drug-resistant epilepsy patients.Quantitative analyses revealed distinct morphological and electrophysiological characteristics of the upper layer dysmorphic neurons in typeⅡFCD,including an enlarged soma,aberrant dendritic arbors,increased current injection for rheobase action potential firing,and reduced action potential firing frequency.Intriguingly,the upper layer dysmorphic neurons received decreased glutamatergic and increased GABAergic synaptic inputs that were coupled with upregulation of the Na^(+)-K^(+)-Cl^(−)cotransporter.In addition,we found a depolarizing shift of the GABA reversal potential in the CamKⅡ-cre::PTENflox/flox mouse model of drug-resistant epilepsy,suggesting that enhanced GABAergic inputs might depolarize dysmorphic neurons.Thus,imbalance of synaptic excitation and inhibition of dysmorphic neurons may contribute to seizure genesis in typeⅡFCD.

Non-specific histological variant of dysembryoplastic neuroepithelial tumor:a diagnostic challenge

Objective The accurate diagnosis of the non-specific variant of dysembryoplastic neuroepithelial tumor （DNT） is very difficult because it is characterized by absence of the histological hallmark of the ＂specific glioneuronal element＂ in lesions. We herein present two cases of the non-specific form of DNT to analyze the clinical, radiological, and histological features of this unusual subtype of DNT. Methods A 16-year-old and a 23-year-old patient had been treated for pharmacoresistant epilepsy for several years before undergoing referral to the hospital for further examination and treatment. Magnetic resonance imaging （MRI） revealed that both patients had a small, well-demarcated cystic lesion within the cortex of the brain without obvious contrast enhancement or peritumoral edema. The lesions were totally resected and routinely examined using histological and immunohistochemical analysis. Results Both lesions exhibited similar histological appearances with cyst formation and mural nodule architecture. The glial nodules were mainly composed of oligodendrocyte-like components, and partly of pi^oid cells resembling pilocytic astrocytoma. The cortex adjacent to the lesion in both cases was found to have the histological features of focal cortical dysplasia （FCD） Type I. Immunohistochemically, the oligoden- drocyte-like components were diffusely positive for Syn and Olig-2, but staining for CD34, p53, and IDH1 R132H was negative. The Ki-67 （MIB-1） labeling index was low, approximately 1%. There was no 1p/19q co-deletion in either lesion by fluorescence in situ hybridization （FISH） assay. Neither patient received postoperative adjuvant treatment, and both underwent regular follow-up for at least 24 months. No signs of recurrence or epileptic attacks were observed during the follow-up period. Conclusion The non-specific variant of DNT is a diagnostic challenge for pathologists in clinical practice, and differentiation from some low-grade gliomas needs to be considered. The careful inspection of radio- logic and histopathologic findings, accompanied by analysis of patients＇ clinical manifestations, may be helpful in making an accurate diagnosis.

Neuropathology of Schizophrenia

The paper is to study the structural changes in cortex and cerebellum of autopsies of subjects with schizophrenia. In the Pathology Department of the Psychiatric Hospital ＂Fray Bernardino ,Avarez＂, there are 410 autopsy cases with diagnosis of mental disease, from which 52 match schizophrenia. The aim of this work is to describe structural changes in the autopsy material and make markers in order to confirm neurodevelopment alterations. The tissues were preserved in formol, paraffin-embedded; cut into 5-7 μm slices; stained with H-E （Hematoxilin and Eosin）, Bielschowsky, crystal fast of violet. The observed changes were brain asymmetry, cortical dysplasia, neuronal distortion, axon bifurcation, neuronophagia and generalized demyelination. Schizophrenia is the result of several happenings, it is important to devise new treatment strategies for prevention and genetic counseling for population.

Predictors of outcome in the surgical treatment for epilepsy

Background Knowledge about factors influencing the prognosis of resective epilepsy surgery can be used to identify which patients are most suitable for surgical treatment. The aim of this study was to identify preoperative prognostic factors associated with the chance of achieving long-term seizure freedom. Methods We retrospectively reviewed seizure outcomes and clinical, electroencephalography （EEG）, magnetic resonance imaging （MRI）, histopathology, and surgical variables from 99 epilepsy surgery patients with at least one year of postoperative follow-up. Seizure outcomes were categorized based on the modified classification by the International League Against Epilepsy. Results We found that the seizure-free rate was 27.9% after one year, and that it stabilized at about 20.0% between two and six years after surgery. Univariate analysis showed that medial temporal lobe epilepsy with hippocampal sclerosis, MRI with visible focal lesions concordant with EEG, and regional ictal EEG and electrocorticography patterns were associated with a favorable surgical outcome. On the other hand, seizure recurrence within six months, incomplete focus resection, and surgical complications were associated with a poor outcome. Multivariate analysis showed that medial temporal lobe epilepsy with hippocampal sclerosis and MRI with visible focal lesions were independent presurgical predictors of a favorable outcome （P 〈0.01）. Seizure recurrence within six months was the only significant independent predictor associated with a poor outcome （P〈0.01）. Conclusion Hippocampal sclerosis and abnormal MRI findings are strongly associated with a favorable surgical outcome, whereas seizure recurrence within six months is associated with a poor outcome.

Early surgical intervention for structural infantile spasms in two patients under 6 months old:a case report

Background:Infantile spasms(IS)are the most common childhood epileptic encephalopathy.Focal cortical dysplasia(FCD)and gray matter heterotopias(GH)are common structural causes of IS.The recommended first-line treatment for IS patients with structural causes is surgical intervention,according to the International League Against Epilepsy(ILAE)commission guidelines.However,there is currently no consensus on appropriate timings of surgery.Case presentations:Two structural IS cases are presented here:one was caused by FCD,and the other by GH.Both patients exhibited recurrent seizures at the age of 2 months,had poor responses to various antiepileptic drugs(AEDs)and displayed severe mental and motor developmental retardation.Seizure types included focal seizures and spasms.Brain magnetic resonance imaging showed abnormal gray signal or suspicious FCD lesions that coincided with the origin of the focal seizures.The patients underwent lesion resection before the age of 6 months.Follow-up observation showed that seizures of both patients were completely controlled several days after the surgery.All AEDs were gradually reduced in dosage within 1 year,and the mental and motor development almost returned to normal.Conclusion:Early resection of lesions in structural IS patients has benefits of effectively controlling convulsions and improving developmental retardation.Infants at several months of age can well tolerate craniotomy,and their cognitive development is more likely to return to normal after early surgery.