Cortical Specimens Research Articles

Adenosine kinase expression in cortical dysplasia with balloon cells: analysis of developmental lineage of cell types.

Focal cortical dysplasia type IIB (FCDIIB) is a developmental malformation of the cerebral cortex that is associated with pharmacoresistant epilepsy. Overexpression of adenosine kinase (ADK) has been regarded as a pathologic hallmark of epilepsy. We hypothesized that the epileptogenic mechanisms underlying FCDIIB are related to abnormal ADK expression. We used immunohistochemistry to examine the expression of ADK and of heterogeneous cell population markers of astrocytes (glial fibrillary acidic protein), immature glia (vimentin), immature neurons (neuronal class III beta-tubulin, TUJ1), multipotential progenitor cells (nestin), mature neurons (microtubule-associated protein 2), and antiapoptotic gene products (Bcl-2) in surgically resected human epileptic cortical specimens from FCDIIB patients (n = 20). Expression patterns were compared with those in normal autopsy (n = 6) and surgical control (n = 6) brain samples. Balloon cells in FCDII lesions were immunoreactive for ADK (77%) and balloon cells expressing the different cell markers expressing different degrees of ADK. Adenosine kinase expression assessed by Western blot and enzymatic activity were also greater in FCD versus control samples. These results suggest that upregulation of ADK is a common pathologic component of FCDIIB. Adenosine kinase might, therefore, be a target in the treatment of epilepsy associated with FCD.

Quantitative study of white matter neurons in human temporal lobe resection with mild malformation of cortical development (MCD) type II

Quantitative study of white matter neurons in human temporal lobe resection with mild malformation of cortical development (MCD) type II

Probing region-specific microstructure of human cortical areas using high angular and spatial resolution diffusion MRI

Regional heterogeneity in cortical cyto- and myeloarchitecture forms the structural basis of mapping of cortical areas in the human brain. In this study, we investigate the potential of diffusion MRI to probe the microstructure of cortical gray matter and its region-specific heterogeneity across cortical areas in the fixed human brain. High angular resolution diffusion imaging (HARDI) data at an isotropic resolution of 92-μm and 30 diffusion-encoding directions were acquired using a 3D diffusion-weighted gradient-and-spin-echo sequence, from prefrontal (Brodmann area 9), primary motor (area 4), primary somatosensory (area 3b), and primary visual (area 17) cortical specimens (n=3 each) from three human subjects. Further, the diffusion MR findings in these cortical areas were compared with histological silver impregnation of the same specimens, in order to investigate the underlying architectonic features that constitute the microstructural basis of diffusion-driven contrasts in cortical gray matter. Our data reveal distinct and region-specific diffusion MR contrasts across the studied areas, allowing delineation of intracortical bands of tangential fibers in specific layers—layer I, layer VI, and the inner and outer bands of Baillarger. The findings of this work demonstrate unique sensitivity of diffusion MRI to differentiate region-specific cortical microstructure in the human brain, and will be useful for myeloarchitectonic mapping of cortical areas as well as to achieve an understanding of the basis of diffusion NMR contrasts in cortical gray matter.

Preparation and Characterization of Injectable Brushite Filled-Poly (Methyl Methacrylate) Bone Cement.

Powder-liquid poly (methyl methacrylate) (PMMA) bone cements are widely utilized for augmentation of bone fractures and fixation of orthopedic implants. These cements typically have an abundance of beneficial qualities, however their lack of bioactivity allows for continued development. To enhance osseointegration and bioactivity, calcium phosphate cements prepared with hydroxyapatite, brushite or tricalcium phosphates have been introduced with rather unsuccessful results due to increased cement viscosity, poor handling and reduced mechanical performance. This has limited the use of such cements in applications requiring delivery through small cannulas and in load bearing. The goal of this study is to design an alternative cement system that can better accommodate calcium-phosphate additives while preserving cement rheological properties and performance. In the present work, a number of brushite-filled two-solution bone cements were prepared and characterized by studying their complex viscosity-versus-test frequency, extrusion stress, clumping tendency during injection through a syringe, extent of fill of a machined void in cortical bone analog specimens, and compressive strength. The addition of brushite into the two-solution cement formulations investigated did not affect the pseudoplastic behavior and handling properties of the materials as demonstrated by rheological experiments. Extrusion stress was observed to vary with brushite concentration with values lower or in the range of control PMMA-based cements. The materials were observed to completely fill pre-formed voids in bone analog specimens. Cement compressive strength was observed to decrease with increasing concentration of fillers; however, the materials exhibited high enough strength for consideration in load bearing applications. The results indicated that partially substituting the PMMA phase of the two-solution cement with brushite at a 40% by mass concentration provided the best combination of the properties investigated. This alternative material may find applications in systems requiring highly injectable and viscous cements such as in the treatment of spinal fractures and bone defects.

Identification of anisotropic tensile strength of cortical bone using Brazilian test

For a proper analysis of cortical bone behaviour, it is essential to take into account both the elastic stiffness and the failure criteria. While ultrasound methods allow complete identification of the elastic orthotropic coefficients, tests used to characterise the various failure mechanisms and to identify the brittle tensile strength in all directions are currently inadequate. In the present work we propose the Brazilian test as a complement to conventional tensile tests. In fact, this experimental technique, rarely employed in the biomechanics field, has the potential to provide an accurate description of the anisotropic strength of cortical bone. Additionally, it allows us to assess the scale influence on failure behaviour which may be attributed to an intrinsic length in correlation with the cortical bone microstructure. In order to correctly set up the Brazilian test, several aspects such as the machining, the geometrical parameters of the specimen and the loading conditions were determined. The finite element method was used to evaluate the maximal tensile stress at the centre of a 2D anisotropic elastic specimen as a simple function of the loading. To validate the protocol, the Brazilian test was carried out on 29 cortical bovine cylindrical specimens with diameters ranging from 10mm to 4mm.

Growth-associated protein 43 and progressive epilepsy in cortical dysplasia.

ObjectiveTo investigate growth-associated protein 43 (GAP-43), a marker for axonal growth and synaptic plasticity, as potential substrate for progressive epilepsy and potential predictor of postsurgical seizure outcome in patients with focal cortical dysplasia (FCD).MethodsGAP-43 immunohistochemistry was performed on cortical specimens from 21 patients with FCD: 12 with FCD type II (IIA or IIB) and nine with FCD type IA. Twenty normal anterior temporal lobe specimens from patients with mesial temporal lobe epilepsy due to hippocampal sclerosis (mTLE/HS) were used as controls. Semiquantitative analysis of GAP-43 staining patterns was performed. Additionally, GAP-43 immunoblotting was performed on resected tissue from three patients with FCD type IIA/B; GAP-43 protein levels in electroencephalography-verified epileptic, and distal nonepileptic, areas were compared within each patient. Two outcome categories were used: completely seizure free (Engel IA) versus not seizure free. We examined the relationship of GAP-43 scores with epilepsy duration and seizure-free outcome for each of the three pathologies.ResultsWithin-patient GAP-43 expression is selectively increased in the epileptic as compared to nonepileptic cortex. GAP-43 immunoreactivity (IRs) patterns were seen on the cell surface and tubular punctate structures intercellularly only in FCD cortex. Higher GAP-43 scores were correlated (P < 0.0001) with longer epilepsy duration only in FCD IIA/B. Lower GAP-43 scores were associated with better surgical outcome in the same group. No such relationship was observed in FCD IA.InterpretationGAP-43 proteins are not only associated with intrinsic epileptogenicity but may be markers of progressive epilepsy and predictors of postoperative seizure outcome in patients with pharmacoresistant epilepsy due to FCD IIA/B.

A peridynamic material model for the analysis of dynamic crack propagation in orthotropic media

A new material model for the dynamic fracture analysis of anisotropic materials has been proposed within the framework of the bond-based peridynamic theory. This model enables predicting complex fracture phenomena such as spontaneous crack nucleation and crack branching, curving and arrest, a capability inherited from the bond-based peridynamic theory. An important feature of the model is that the bond properties, i.e. the stiffness constant and critical stretch, are continuous functions of bond orientation in the principal material axes. This facilitates fracture analysis of anisotropic materials with random orientations, such as polycrystalline microstructures. Elastic and fracture behaviour of the model has been verified through simulating uniaxial tension of a composite plate and fracture of a cortical bone compact tension specimen, and making quantitative comparisons to analytical and experimental data. To further demonstrate the capabilities of the proposed model, dynamic fracture of a polycrystalline microstructure (alumina ceramic) has been simulated. The influence of the grain boundary and grain interior fracture energies on the interacting and competing fracture modes of polycrystalline materials, i.e. intergranular and transgranular fracture, has been studied.

Dysembryoplastic neuroepithelial tumors: Where are we now?

Dysembryoplastic neuroepithelial tumors (DNTs) belong to the surgically treatable long-term epilepsy-associated group of tumors. Based on cortical specimens provided through epilepsy surgery at Sainte-Anne hospital, three histologic subtypes (simple, complex, and nonspecific) have been described. Electroclinical data, imaging, intralesional recordings (stereo-electroencephalography [EEG]) and histologic correlations have been recently reviewed in order to assess the relationship between the epileptogenic zone (EZ), the tumor, and associated focal cortical dysplasia (FCD), and to determine optimal strategy for curing epilepsy. Based on a large series (78 patients, 50 male, aged 3-54 years, temporal location 73%, nonspecific forms 68%), we found similar electroclinical data in all DNT subtypes, and demonstrated that magnetic resonance imaging (MRI) features allow differentiation of histologic subtypes. Type 1 (cystic/polycystic-like) always corresponded to complex or simple forms, whereas type 2 (nodular-like) and type 3 (dysplastic-like) corresponded to nonspecific forms. It is notable that we demonstrated intrinsic epileptogenicity in all cases, but found that the EZ differed significantly according to MRI subtype, colocalizing with the tumor in type 1 MRI, including perilesional cortex in type 2 MRI, and involving extensive areas in type 3 MRI. The main prognostic factors for favorable outcome (83% of seizure-free patients) were complete tumor and EZ removal, short epilepsy duration, and lack of cortico-subcortical damage. According to these findings, surgical resection may be restricted to the tumor in type 1 MRI but should be more extensive in other MRI subtypes, especially in type 3 MRI. This MRI-based scheme may be helpful for optimal resection in epilepsy due to DNTs. In addition, we emphasize that early surgery is crucial in curing epilepsy.

Upregulation of Adenosine Kinase in Rasmussen Encephalitis

Rasmussen encephalitis (RE) is a rare neurologic disorder of childhood characterized by unihemispheric inflammation, progressive neurologic deficits, and intractable focal epilepsy. The pathogenesis of RE is still enigmatic. Adenosine is a key endogenous signaling molecule with anticonvulsive and anti-inflammatory effects, and our previous work demonstrated that dysfunction of the adenosine kinase (ADK)–adenosine system and astrogliosis are the hallmarks of epilepsy. We hypothesized that the epileptogenic mechanisms underlying RE are related to changes in ADK expression and that those changes might be associated with the development of epilepsy in RE patients. Immunohistochemistry was used to examine the expression of ADK and glial fibrillary acidic protein in surgically resected human epileptic cortical specimens from RE patients (n = 12) and compared with control cortical tissues (n = 6). Adenosine kinase expression using Western blot and enzymatic activity for ADK were assessed in RE versus control samples. Focal astrogliosis and marked expression of ADK were observed in the lesions of RE. Significantly greater ADK expression in RE versus controls was demonstrated by Western blot, and greater enzymatic activity for ADK was demonstrated using an enzyme-coupled bioluminescent assay. These results suggest that upregulation of ADK is a common pathologic hallmark of RE and that ADK might be a target in the treatment of epilepsy associated with RE.

Effect of gamma sterilization on microhardness of the cortical bone tissue of bovine femur in presence of N-Acetyl-L-Cysteine free radical scavenger

Gamma sterilization is usually used to minimize the risk of infection transmission through bone allografts. However, it is believed that gamma irradiation affects the mechanical properties of allografts and free radical scavengers can be used to alleviate the radiation-induced degradation of these properties. The aim of this study was to investigate the radioprotective effects of N-Acetyl-L-Cysteine (NAC) free radical scavenger on the material properties of sterilized bovine cortical bone at microstructure level. Forty-two cortical tissue specimens were excised from three bovine femurs and irradiated to 35 and 70 kGy gamma rays in the presence of 5, 50, and 100 mM concentrations of NAC. The localized variations in microhardness were evaluated via indentation in the radial and longitudinal directions to examine different regions of the microstructures of the specimens, including the osteonal and interstitial tissues. A significant increase was observed in the hardness of osteonal, interstitial, and longitudinal combined microstructures exposed to 35 and 70 kGy radiations (P < 0.05), whereas a relative reduction of the hardness was observed in the radial direction. Furthermore, it was found that the application of 50 and 100 mM NAC during gamma irradiation significantly subsided the hardening in longitudinal combined microstructure. Moreover, the reduction of hardness in radial direction was suppressed in the presence of 100 mM of NAC. In conclusion, the results indicated that NAC free radical scavenger can protect the cortical bone against deteriorative effects of ionizing radiation and can be used to improve the material properties of sterilized allografts.

The effects of vagal nerve stimulation in focal cerebral ischemia and reperfusion model

This study aimed to investigate the effects of VNS in transient middle cerebral artery occlusion and reperfusion (MCAO/R) rat model of ischemia based on behavioral, morphological, and molecular approaches. Wistar albino rats were divided into 3 groups: ischemia-reperfusion (I/R), I/R+VNS, and sham (for I/R). Each group was further divided into two subgroups for the assessment of neurological deficits and infarct area, or biochemical parameters related to oxidative stress. The infarct area and neurological scores were significantly lower in I/R+VNS group compared with the I/R group. MDA levels were significantly higher in I/R group compared to control and I/R+VNS groups in the cortical and subcortical specimens. There were also betweengroup differences in terms of GSH levels. GSH levels were higher in sham group compared with and I/R and I/R+VNS groups in cortical specimens whereas these levels for lower in I/R group compared to control and I/R+VNS groups in the subcortical specimens. SOD activity was higher in control group compared to I/R and I/R+VNS groups both in the cortical and subcortical specimens. There was no difference between I/R and I/R+VNS groups in neither cortical nor subcortical specimens. The neuroprotective and antioxidant properties of VNS suggest its efficacy as a potential anti-ischemic treatment.

Biomechanical Measurements of Surgical Drilling Force and Torque in Human Versus Artificial Femurs

Few experimental studies have examined surgical drilling in human bone, and no studies have inquired into this aspect for a popular commercially-available artificial bone used in biomechanical studies. Sixteen fresh-frozen human femurs and five artificial femurs were obtained. Cortical specimens were mounted into a clamping system equipped with a thrust force and torque transducer. Using a CNC machine, unicortical holes were drilled in each specimen at 1000 rpm, 1250 rpm, and 1500 rpm with a 3.2 mm diameter surgical drill bit. Feed rate was 120 mm/min. Statistical significance was set at p < 0.05. Force at increasing spindle speed (1000 rpm, 1250 rpm, and 1500 rpm), respectively, showed a range for human femurs (198.4 ± 14.2 N, 180.6 ± 14.0 N, and 176.3 ± 11.2 N) and artificial femurs (87.2 ± 19.3 N, 82.2 ± 11.2 N, and 75.7 ± 8.8 N). For human femurs, force at 1000 rpm was greater than at other speeds (p ≤ 0.018). For artificial femurs, there was no speed effect on force (p ≥ 0.991). Torque at increasing spindle speed (1000 rpm, 1250 rpm, and 1500 rpm), respectively, showed a range for human femurs (186.3 ± 16.9 N·mm, 157.8 ± 16.1 N·mm, and 140.2 ± 16.4 N·mm) and artificial femurs (67.2 ± 8.4 N·mm, 61.0 ± 2.9 N·mm, and 53.3 ± 2.9 N·mm). For human femurs, torque at 1000 rpm was greater than at other speeds (p < 0.001). For artificial femurs, there was no difference in torque for 1000 rpm versus higher speeds (p ≥ 0.228), and there was only a borderline difference between the higher speeds (p = 0.046). Concerning human versus artificial femurs, their behavior was different at every speed (force, p ≤ 0.001; torque, p < 0.001). For human specimens at 1500 rpm, force and torque were linearly correlated with standardized bone mineral density (sBMD) and the T-score used to clinically categorize bone quality (R ≥ 0.56), but there was poor correlation with age at all speeds (R ≤ 0.37). These artificial bones fail to replicate force and torque in human cortical bone during surgical drilling. To date, this is the largest series of human long bones biomechanically tested for surgical drilling.

Significance of horizontal propagation of synchronized activities in human epileptic neocortex investigated by optical imaging and immunohistological study

To characterize the physiological condition of human epileptic neocortex, we employed flavoprotein fluorescence imaging (FFI), an optical imaging method which detects intrinsic signals accompanying neural activation, and immunohistologically studied human cortical specimens. The experimented materials were cortical tissues surrounding various intracerebral lesions obtained from 5 patients with epilepsy (epileptic patients: EPs) and 5 without epilepsy (non-epileptic patients: NEPs). These tissues were immersed in oxygenated artificial cerebrospinal fluid immediately after removal in the operating room. Signal changes of FFI in the cortical layers subjected to electrical stimulation were observed under bicuculline methiodide perfusion. Immunohistological staining for parvalbumin (PV), calbindin, and calretinin were performed on the same specimens to evaluate expressions of calcium-binding protein positive cells. The FFI study showed the characteristic cortical propagation pattern of elicited activities horizontally along the cortical layers in EPs but not in NEPs. The propagated area with more than 0.5% signal changes was significantly larger in EPs than in NEPs (p=0.008). Only the expression of PV positive neurons was significantly lower in EPs than in NEPs (p=0.006). The propagated area on FFI and the decrease in PV positive neurons correlated significantly (R=-0.78, p=0.04). The present study visualized the unique horizontal propagation of signal changes on FFI and demonstrated a correlation of this propagation with immunohistological decreases in PV positive neurons in human epileptic cortex. Further investigations may elucidate the mechanism of hyper-excitability and hyper-synchronization in epileptic cortical tissue itself.

Design and validation of bending test method for characterization of miniature pediatric cortical bone specimens

Osteogenesis imperfecta is a genetic disorder of bone fragility; however, the effects of this disorder on bone material properties are not well understood. No study has yet measured bone material strength in humans with osteogenesis imperfecta. Small bone specimens are often extracted during routine fracture surgeries in children with osteogenesis imperfecta. These specimens could provide valuable insight into the effects of osteogenesis imperfecta on bone material strength; however, their small size poses a challenge to their mechanical characterization. In this study, a validated miniature three-point bending test is described that enables measurement of the flexural material properties of pediatric cortical osteotomy specimens as small as 5 mm in length. This method was validated extensively using bovine bone, and the effect of span/depth aspect ratio (5 vs 6) on the measured flexural properties was examined. The method provided reasonable results for both Young's modulus and flexural strength in bovine bone. With a span/depth ratio of 6, the median longitudinal modulus and flexural strength results were 16.1 (range: 14.4-19.3)GPa and 251 (range: 219-293)MPa, respectively. Finally, the pilot results from two osteotomy specimens from children with osteogenesis imperfecta are presented. These results provide the first measures of bone material strength in this patient population.

Depth of penetration of methylene blue in mandibular cortical bone

Surgeons treating keratinizing odontogenic tumors (KOT) and other intrabony lesions frequently use methylene blue as an adjunct in peripheral ostectomy in estimating the depth of bone that has been removed. Depth of methylene blue penetration in cortical bone has not been evaluated. Specimens of mandible harvested from 9 fresh unembalmed cadaveric mandibles were stained with methylene blue. A microcaliper was used to measure total thickness of the cortical specimen along with the amount of dye penetration within the cortical block to the nearest 0.1 mm. Average depth of dye penetration was 0.48 mm in the symphysis. Average dye penetration was 0.53 mm in the body. Average depth of penetration of 0.42 mm in the angle. The use of methylene blue as a depth gauge to ensure adequate ostectomy with a single application of the dye may be inadequate to ensure complete removal of lesion from bony wall.

Variability and Anisotropy of Fracture Toughness of Cortical Bone Tissue

Bones form protective and load-bearing framework of the body. Therefore, their structural integrity is vital for the quality of life. Unfortunately, bones can only sustain a load until a certain limit, beyond which they fail. Therefore, it is essential to study their mechanical and fracture behaviours in order to get an in-depth understanding of the origins of its fracture resistance that, in turn, can assist diagnosis and prevention of bone's trauma. This can be achieved by studying mechanical properties of bone, such as its fracture toughness. Generally, most of bone fractures occur for long bones that consist mostly of cortical bone. Therefore, in this study, only a cortical bone tissue was studied. Since this tissue has an anisotropic behaviour and possesses hierarchical and complex structure, in this paper, an experimental analysis for the fracture toughness of cortical bone tissue is presented in terms of J-integral. The data was obtained using single-edge-notch bending (SENB) cortical specimens of bone tested in a three-point bending setup. Variability of values of fracture toughness was investigated by testing specimens cut from different cortex positions of bovine femur called anterior, posterior, medial, and lateral. In addition, anisotropy ratios of fracture toughness were considered by examining specimens cut from three different orientations: longitudinal, transverse and radial. Moreover, in order to link cortical bone fracture mechanisms with its underlying microstructure, fracture surfaces of specimens from different cortices and along different orientations were studied. Experimental results of this study provide a clear understanding of both variability and anisotropy of cortical bone tissue with regard to its fracture toughness.

No evidence for disturbed COL1A1 and A2 expression in otosclerosis

Otosclerosis is a complex bone remodeling disorder of the human otic capsule that might be associated with various mutations of A1 and A2 alleles of type-I collagen. The study herein presented, investigates the possibilty of the genetic involvement of type-I collagen in the pathogenesis of histologically confirmed otosclerosis. A total of 55 ankylotic stapes footplates were analyzed. Cortical bone fragments (n = 30), incus (n = 3) and malleus (n = 2) specimens were employed as negative controls. Specimens were divided into two groups. The first group was processed using conventional H.E. hematoxylin-eosin (H.E.) staining and type-I collagen-specific immunofluorescent assay (IFA), while the second group was examined by COL1A1 and A2-specific RT-PCR. Otosclerotic- (n = 31) and non-otosclerotic stapes footplates (n = 9) as well as cortical bones (n = 20), incus (n = 2) and malleus specimens (n = 1) showed normal and quite similar A1 and A2 allele expression confirmed by IFA. RT-PCR analysis revealed normal and consistent mRNA expression of both alleles in each specimen. Expression levels and patterns of COL1A1/A2 alleles did not show significant correlation with the histological diagnosis of otosclerosis. Type-I collagen is a highly conserved structure protein, which plays a fundamental role in the integritiy of various connective tissues. Mutations of A1 and A2 alleles result in serious systemic disorders of the skeleton, tendons and skin. Since otosclerosis is an organ-specific disease, it is difficult to explain its genetic association with type-I collagen. In conclusion, we found no evidence supporting the putative link of COL1A1 and COL1A2 alleles with otosclerosis.

α-methyl-L-tryptophan: mechanisms for tracer localization of epileptogenic brain regions.

The purpose of this paper is to discuss the mechanisms of α-[(11)C]methyl-L-tryptophan (AMT) PET as an in vivo biomarker for detection of epileptogenic cortex. AMT was originally designed as a tracer to measure the serotonin synthesis rate. This tracer was first applied in patients with medically refractory epilepsy in an attempt to detect changes in serotonin synthesis based upon reports of increased serotonergic innervation in cortical specimens obtained following epilepsy surgery. The first group of epilepsy patients undergoing AMT PET scans were patients with tuberous sclerosis complex. Studies of brain tissue subsequent to epilepsy surgery in these patients with tuberous sclerosis complex implicated the kynurenine pathway of tryptophan metabolism as a primary mechanism of increased brain tissue retention of AMT in epileptogenic brain regions, rather than alterations in serotonin synthesis. Kinetic analyses of AMT in brain tumors indicate changes in tryptophan transport and tissue retention in other pools as well. These studies indicate that AMT PET may be a biomarker of immune activation in the epileptogenic process.

Altered layer-specific gene expression in cortical samples from patients with temporal lobe epilepsy

Neuropathologic investigations frequently reveal the presence of architectural cortical dysplasia in patients with temporal lobe epilepsy (TLE), sometimes as an isolated finding but more commonly associated with hippocampal sclerosis (HS) and white matter abnormalities. The histologic pattern and the developmental origin of these alterations are not clear, and their diagnostic criteria are poorly defined. The aim of this study was to investigate the expression patterns of layer-specific genes in cortical specimens from patients with TLE presenting different subtypes of cortical malformations in order to elucidate the disorganization of the laminar architecture of such epileptogenic abnormalities and provide evidence to enable a more objective neuropathologic diagnosis. We analyzed the expression patterns of CUX2, RORBETA, ER81, NURR1, and CTGF genes, respectively specific markers of layers II-III, IV, V, VI, and VIb, in surgical samples by means of in situ hybridization and compared them with those observed in control cortices. The pathologic samples included typical architectural dysplasia (group 1); temporal lobe sclerosis, a variant of architectural dysplasia (group 2); and white matter heterotopic neuronal aggregates, namely small lentiform nodules (group 3). These abnormalities may have been associated or not with HS. All of the genes had a laminar expression pattern in normal cortices, whereas groups 1 and 2 showed alterations mainly involving layers V and VI, and highlighted by the altered distribution of ER81- and NURR1-positive cells. The expression of ER81 and NURR1 genes was different among the groups, and atypical coexpression of NURR1 and CUX2 mRNA was detected in the neurons making up the small lentiform nodules. These findings indicate that defects in cortical organization involving the deeper cortical neurons may be a common etiopathogenic mechanism in group 1 and 2 cortical dysplasia, whether isolated or associated with HS, and that developmental disorders may also be present in the white matter (group 3). They also provide evidence that the layer-specific genes can be usefully used to investigate the neuropathology of human cortical dysplasia.

Association Between In Vivo Fluorine 18–Labeled Flutemetamol Amyloid Positron Emission Tomography Imaging and In Vivo Cerebral Cortical Histopathology

To determine the correspondence of in vivo quantitative estimates of brain uptake of fluorine 18-labeled flutemetamol with immunohistochemical estimates of amyloid levels in patients who underwent previous biopsy. Cross-sectional study of ¹⁸F-flutemetamol positron emission tomography (PET) findings in patients with prior cortical biopsy specimen stained for the presence or absence of amyloid plaques. University hospital. Patients Seven patients who previously had a prior right frontal cortical biopsy at the site of ventriculoperitoneal placement for presumed normal pressure hydrocephalus were recruited. Inclusion criteria included an adequate biopsy specimen for detection and quantification of β-amyloid pathology and age older than 50 years. Intervention All patients underwent an ¹⁸F-flutemetamol PET scan. Quantitative measures of ¹⁸F-flutemetamol uptake (standardized uptake value ratio, a ratio of mean target cortex activity divided by that in a cerebellar reference region) were made at a location contralateral to the biopsy site and compared with estimates of amyloid load based on immunohistochemical and histological staining. There was complete agreement between visual reads of ¹⁸F-flutemetamol PET scans (3 blinded readers with majority rule) and histology. A regression model, including time from biopsy as a covariate, demonstrated a significant relationship (P = .01) between ¹⁸F-flutemetamol uptake and percentage of area of amyloid measured by a monoclonal antibody raised against amyloid (NAB228). Similar results were found with the amyloid-specific monoclonal antibody 4G8 and Thioflavin S. To our knowledge, these data are the first to demonstrate the concordance of ¹⁸F-flutemetamol PET imaging with histopathology, supporting its sensitivity to detect amyloid and potential use in the study and detection of Alzheimer disease.