Conventional MR imaging has limitations in detecting focal cortical dysplasia. We assessed the added value of 7T in patients with histologically proved focal cortical dysplasia to highlight ...correlations between neuropathology and ultra-high-field imaging.
Between 2013 and 2019, we performed a standardized 7T MR imaging protocol in patients with drug-resistant focal epilepsy. We focused on 12 patients in whom postsurgical histopathology revealed focal cortical dysplasia and explored the diagnostic yield of preoperative 7T versus 1.5/3T MR imaging and the correlations of imaging findings with histopathology. We also assessed the relationship between epilepsy surgery outcome and the completeness of surgical removal of the MR imaging-visible structural abnormality.
We observed clear abnormalities in 10/12 patients using 7T versus 9/12 revealed by 1.5/3T MR imaging. In patients with focal cortical dysplasia I, 7T MR imaging did not disclose morphologic abnormalities (
= 0/2). In patients with focal cortical dysplasia II, 7T uncovered morphologic signs that were not visible on clinical imaging in 1 patient with focal cortical dysplasia IIa (
= 1/4) and in all those with focal cortical dysplasia IIb (
= 6/6). T2*WI provided the highest added value, disclosing a peculiar intracortical hypointense band (black line) in 5/6 patients with focal cortical dysplasia IIb. The complete removal of the black line was associated with good postsurgical outcome (
= 4/5), while its incomplete removal yielded unsatisfactory results (
= 1/5).
The high sensitivity of 7T T2*-weighted images provides an additional tool in defining potential morphologic markers of high epileptogenicity within the dysplastic tissue of focal cortical dysplasia IIb and will likely help to more precisely plan epilepsy surgery and explain surgical failures.
In the context of lung transplant (LT), because of diagnostic difficulties, antibody‐mediated rejection (AMR) remains a matter of debate. We retrospectively analyzed an LT cohort at Foch Hospital to ...demonstrate the impact of AMR on LT prognosis. AMR diagnosis requires association of clinical symptoms, donor‐specific antibodies (DSAs), and C4d+ staining and/or histological patterns consistent with AMR. Prospective categorization split patients into four groups: (i) DSA positive, AMR positive (DSAposAMRpos); (ii) DSA positive, AMR negative (DSAposAMRneg); (iii) DSA limited, AMR negative (DSALim; equal to one specificity, with mean fluorescence intensity of 500–1000 once); and (iv) DSA negative, AMR negative (DSAneg). AMR treatment consisted of a combination of plasmapheresis, intravenous immunoglobulin and rituximab. Among 206 transplanted patients, 10.7% were DSAposAMRpos (n = 22), 40.3% were DSAposAMRneg (n = 84), 6% were DSALim (n = 13) and 43% were DSAneg (n = 88). Analysis of acute cellular rejection at month 12 showed higher cumulative numbers (mean plus or minus standard deviation) in the DSAposAMRpos group (2.1 ± 1.7) compared with DSAposAMRneg (1 ± 1.2), DSALim (0.75 ± 1), and DSAneg (0.7 ± 1.23) groups. Multivariate analysis demonstrated AMR as a risk factor for chronic lung allograft dysfunction (hazard ratio HR 8.7) and graft loss (HR 7.56) for DSAposAMRpos patients. Our results show a negative impact of AMR on LT clinical course and advocate for an early active diagnostic approach and evaluation of therapeutic strategies to improve prognosis.
The authors find an association between antibody‐mediated rejection in lung transplantation and chronic lung allograft dysfunction and graft loss.
There have been difficulties in achieving a uniform terminology in the literature regarding issues of classification with respect to focal cortical dysplasias (FCDs) associated with epilepsy.
S: To ...review and refine the current terminology and classification issues of potential clinical relevance to epileptologists, neuroradiologists, and neuropathologists dealing with FCD.
A panel discussion of epileptologists, neuropathologists, and neuroradiologists with special expertise in FCD was held.
The panel proposed 1) a specific terminology for the different types of abnormal cells encountered in the cerebral cortex of patients with FCD; 2) a reappraisal of the different histopathologic abnormalities usually subsumed under the term "microdysgenesis," and suggested that this terminology be abandoned; and 3) a more detailed yet straightforward classification of the various histopathologic features that usually are included under the heterogeneous term of "focal cortical dysplasia."
The panel hopes that these proposals will stimulate the debate toward more specific clinical, imaging, histopathologic, and prognostic correlations in patients with FCD associated with epilepsy.
Since the original description by Taylor, the term focal cortical dysplasia has been used to refer to a wide range of alterations of the cortical mantle. More recently, these conditions have been ...described from neuroimaging, neuropathological and genetic standpoints, generating several classifications. It is widely recognized that these classifications are unsatisfactory. We propose a simplified classification of focal cortical dysplasias based on easily recognized neuropathological characteristics. We retrospectively re‐examined histological sections of cortex from 52 of 224 (23%) patients operated on for drug‐resistant partial epilepsy in which cortical dysplasia was present but not associated with other brain pathologies except hippocampal sclerosis. Three subgroups were identified: (i) architectural dysplasia (31 patients) characterized by abnormal cortical lamination and ectopic neurones in white matter; (ii) cytoarchitectural dysplasia (six patients) characterized by giant neurofilament‐enriched neurones in addition to altered cortical lamination; and (iii) Taylor‐type cortical dysplasia (15 patients) with giant dysmorphic neurones and balloon cells (all but two patients) associated with cortical laminar disruption. The patients with architectural dysplasia had lower seizure frequency than those with cytoarchitectural and Taylor‐type dysplasia, and the epileptogenic zone was mainly in the temporal lobe. In patients with Taylor‐type dysplasia, the epileptogenic zone was mainly extratemporal, and interictal stereo‐EEG was distinctive. MRI was unrevealing in 34% of patients, but distinctive signal alterations characterized most patients with Taylor‐type dysplasia, while focal hypoplasia with MRI abnormalities was found in architectural dysplasia. Patients with Taylor‐type dysplasia had the best outcome, with 75% seizure‐free (Engel class Ia) after at least a year of follow‐up compared with 50% of cytoarchitectural dysplasia and 43% of architectural dysplasia patients seizure‐free. This three‐category classification is based on easily recognized histopathological characteristics and avoids complicated terminology, while the distinctive ensemble of other characteristics defines clinically homogeneous groups.
Gap junctions are specialized channels composed of several connexins, membrane proteins that mediate electrical and metabolic coupling between cells. Previous data have suggested that changes in the ...expression of Cx43, the main astrocytic Cx isoform, may be involved in seizure activity in human epileptic tissue. However, Cx43 has never been examined in focal cortical dysplasia (FCD) and in other human refractory epilepsies.
We analyzed Cx43 protein localization and Cx43 mRNA levels in surgical specimens of cortex from a cohort of patients with intractable epilepsy vs control nonepileptic tissue. Samples had neuropathologically defined diagnosis of cryptogenic epilepsy or epilepsy secondary to FCD.
Cx43 immunoreactivity, which labeled punctate elements, did not reveal distinctive features in cryptogenic epilepsy and FCD type IA and IIA. A peculiar pattern of immunolabeling was instead observed in FCD type IIB, in which large aggregates of Cx43-immunopositive puncta were clustered around subsets of balloon cells and astrocytes. Further characterization revealed that these balloon cells do not express markers of precursor cells, such as CD34. Quantitative real-time reverse transcriptase PCR showed elevated levels of Cx43 transcript in a subgroup (25%) of cryptogenic epilepsy specimens compared to control and FCD ones.
Our study points out that a rearrangement of Cx43-positive elements is part of abnormal tissue organization in FCD type IIB, and that cryptogenic epilepsies include forms with increased Cx43 mRNA expression. The data implicate functional consequences of altered Cx43 expression, and therefore of altered gap junctional coupling, in abnormal network properties of subtypes of human refractory epilepsies.
Rasmussen encephalitis (RE) is a rare but severe immune-mediated brain disorder leading to unilateral hemispheric atrophy, associated progressive neurological dysfunction and intractable seizures. ...Recent data on the pathogenesis of the disease, its clinical and paraclinical presentation, and therapeutic approaches are summarized. Based on these data, we propose formal diagnostic criteria and a therapeutic pathway for the management of RE patients.
We present the results of a retrospective study on 10 patients operated on for intractable epilepsy associated with nodular heterotopia as identified by high resolution MRI. Seven patients had ...unilateral heterotopia, one patient had symmetric bilateral heterotopia and two patients had asymmetric bilateral heterotopia. By stereo-electroencephalogram (SEEG) (nine patients) interictal activity within nodules was similar in all cases, and ictal activity never started from nodules alone but from the overlying cortex or simultaneously in nodules and cortex. Excellent outcomes (Engel class Ia, 1987) were achieved in the seven patients with unilateral heterotopia, showing that surgery can be highly beneficial in such cases when the epileptogenic zone is carefully located prior to surgery by MRI and particularly SEEG. For the bilateral cases surgical outcomes were Engel IIa (one patient) or Engel IIIa (two patients). Histological/immunohistochemical studies of resected specimens showed that all nodules had similar microscopic organization, even though their extent and location varied markedly. The overlying cortex was dysplastic in nine patients, but of normal thickness. We suggest that nodule formation may be the result of a dual mechanism: (i) failure of a stop signal in the germinal periventricular region leading to cell overproduction; and (ii) early transformation of radial glial cells into astrocytes resulting in defective neuronal migration. The intrinsic interictal epileptiform activity of nodules may be due to an impaired intranodular GABAergic system.
This paper discusses the implications of Brexit for both the UK and its regions, as the latter depends on the former. We concentrate on the forecasts by Her Majesty's Treasury (HMT), the Cambridge ...Centre for Business Research and the Economists for Brexit. It is argued that the estimates of HMT of the loss of GDP are likely to be overstated, but, nevertheless, there will probably be a fall in output. Given this, the effect on the UK regions is analysed using the regional balance‐of‐payments constrained growth model. This suggests that Brexit will cause regional disparities to widen.
Resumen
Este artículo discute las implicaciones de Brexit para el Reino Unido y sus regiones, ya que estas últimas dependen del Reino Unido. El artículo se concentra en los pronósticos del Tesoro de Su Majestad (HMT, por sus siglas en inglés), del Cambridge Center for Business Research y de Economists for Brexit. Aunque se argumenta que es probable que las estimaciones de HMT de la pérdida del PIB sean exageradas, en cualquier caso es probable que haya una caída en la producción. Debido a esto, se analizó el efecto sobre las regiones del Reino Unido mediante el modelo de crecimiento restringido de la balanza regional de pagos. Esto sugiere que Brexit causará una ampliación de las disparidades regionales.
抄録
本稿では、地域が国に依存しているものとして、イギリスとその地域の双方にとってのブレグジッド(Brexit:イギリスのEU離脱)の意義を考察する。本稿では、女王陛下の大蔵省(Her Majesty's Treasury:HMT)、ケンブリッジ大学ビジネスリサーチセンター、Economists for Brexitの予測結果に絞って注目する。HMTが推算したGDPの損失額は過大であると言われているが、それでもやはり、ほぼ間違いなく生産が減少すると考えられる。これを踏まえて、地域のbalance‐of‐payments constrained growth model(国際収支制約成長モデル)を用いてイギリスの地域に対する影響を分析する。結果からブレグジッドは地域格差を更に拡大することが示唆される。
In patients with temporal lobe epilepsy (TLE), assessment of language lateralization is important as anterior temporal lobectomy may lead to language impairments. Despite the widespread use of fMRI, ...evidence of its usefulness in predicting postsurgical language performance is scant. We investigated whether preoperative functional lateralization is related to the preoperative language performance, peri-ictal aphasia, and can predict language outcome one year post-surgery. We studied a total of 72 TLE patients (42 left, 30 right), by using three fMRI tasks: Naming, Verb Generation and Fluency. Functional lateralization indices were analyzed with neuropsychological scores and presence of peri-ictal aphasia. The key findings are:1)Both left and right TLE patients show decreased left lateralization compared to controls.2)Lateralization correlates with language performance before surgery. In left TLE, decreased left lateralization correlates with better fluency performance. In right TLE, increased left lateralization during the Naming task correlates with better naming.3)Left lateralization correlates with peri-ictal aphasia in left TLE patients.4)Lateralization correlates with language performance after surgery. In a subgroup of left TLE who underwent surgery (17 left), decreased left lateralization is predictive of better naming performance at 6 and 12 months after surgery. The present study highlights the clinical relevance of fMRI language lateralization in TLE, especially to predict language outcome one year post-surgery. We also underline the importance of using fMRI tasks eliciting frontal and anterior temporal activations, when studying left and right TLE patients.