3 Tesla MRI阴性颞下局灶性癫痫的组织病理学外文文献

Lab resource Histopathology of 3 Tesla MRI negative extratemporal focal epilepsies Evangelos Kogias a Dirk Matthias Altenm llerb Jan Helge Klinglera Barbara Schmeisera Horst Urbach c Soroush Doostkamd aDepartment of Neurosurgery Medical Center University of Freiburg Germany bEpilepsy Center Department of Neurosurgery Medical Center University of Freiburg Germany cDepartment of Neuroradiology Medical Center University of Freiburg Germany dInstitute of Neuropathology Medical Center University of Freiburg Germany a r t i c l ei n f o Article history Received 11 November 2017 Accepted 8 January 2018 Keywords Epilepsy surgery MRI negative Histopathology Focal cortical dysplasia a b s t r a c t Background Information about the histopathology in 3 Tesla MRI negative extratemporal epilepsies is relatively limited Most common histopathological fi ndings in earlier mixed 1 5 or 3 Tesla MRI negative series are focal cortical dysplasia FCD gliosis or normal fi ndings These series mostly use the older Palmini criteria for classifi cation and grading We focus on histopathology of only 3 Tesla MRI negative extratemporal epilepsies according to the current ILAE criteria and investigate potential correlation to seizure outcome 1 year postoperatively Materials and methods Sixteen substrates of 3 Tesla MRI negative extratemporal epilepsies were exam ined in two steps Standard stains and immunohistochemical reactions and Palmini criteria were used prospectively during the initial examination Retrospectively all specimens were re examined and re evaluated Phospho 6 and calretinin stains and ILAE criteria were used during the review examination Results Initial examination revealed 5 FCDs Palmini 1b two 1a fi ve 2a and 4 cases of gliosis The review examination according to ILAE criteria revealed 6 FCDs type IIa 2 FCDs Ib and 7 mild malformations of cortical development mMCD type II None of our cases was labelled as isolated gliosis after the review examination The incidence of FCD after the review examination per ILAE criteria was reduced to 56 versus 75 per Palmini Conclusions In true 3 Tesla MRI negative extratemporal epilepsies incidence of FCD may be lower than in earlier MRI negative series that included weaker MRI fi eld Furthermore consistent review examina tion may confi rm the diagnosis of mMCD type II as substrate in cases diagnosed as gliosis or normal in the past 2018 Elsevier Ltd All rights reserved 1 Introduction Patients with pharmacologically intractable epilepsy and nega tive non lesional magnetic resonance imaging MRI are among the most challenging to treat 1 3 The absence of a delineated lesion on MRI or a specifi c histopathological lesion non lesional epilepsy is associated with worse seizure outcome 3 However in the current literature the term non lesional epilepsy is used to refer to either negative MRI or pathology although MRI is the starting point that determines the further diagnostic and treat ment strategy whereas pathology is the ending point Information about the histopathology in MRI negative extratemporal epilepsy is relative limited The most common histopathological fi ndings in surgical series are focal cortical dysplasia FCD 2 4 6 gliosis 7 8 or even normal fi ndings 9 11 These series use 1 5 or 3 Tesla MRI for the selection of MRI negative cases Recently a consensus for the histopathological classifi cation and grading of FCDs inter nationalleagueagainstepilepsy ILAE hasbeenproposed 12 13 This grading system has not been taken into consideration in case series that had been published earlier Therefore the https doi org 10 1016 j jocn 2018 01 071 0967 5868 2018 Elsevier Ltd All rights reserved Abbreviations MRI magnetic resonance imaging FCD focal cortical dysplasia HS hippocampal sclerosis ILAE international league against epilepsy H NF neurofi lament KB Kl ver Barrera SP synaptophysin Map2 microtubule associated protein 2 CD cluster of differentiation HLA DR human leukocyte antigen D related GFAP glial fi brillary acidic protein PS6 phospho S6 NeuN neuronal nuclear antigen FLAIR fl uid attenuation inversion recovery EEG electroencephalography mMCD mild malformation of cortical development mTOR mechanistic target of rapamycin Corresponding author at Department of Neurosurgery Medical Center Univer sity of Freiburg Breisacherstrasse 64 D 79106 Freiburg im Breisgau Germany E mail address evangelos kogias uniklinik freiburg de E Kogias Journal of Clinical Neuroscience 50 2018 232 236 Contents lists available at ScienceDirect Journal of Clinical Neuroscience journal homepage available information often lacks grading or refers to the older grading system of Palmini 14 Within this study we focus on the histopathological fi ndings of extratemporal resection specimens in epilepsy patients with non lesional 3 Tesla MRI according to an epilepsy specifi c protocol We review all resection specimens from 3 Tesla MRI negative cases according to the up to date neuropathology techniques 15 and use the ILAE classifi cation system Aim of this study is 1 to add knowledge on the pathology of 3 Tesla MRI negative extratemporal epilepsies 2 to clarify the prevalence of FCD according to the ILAE classifi cation system and compare it with the old Palmini classifi cation within this patients subgroup and to 3 prove if there is any association between histopathology and seizure outcome in MRI negative extratempo ral epilepsy 2 Materials and methods The local ethics committee approved the study It is part of the DRKS00010013 study registered at the German Clinical Trials Register We retrospectively searched our patients databases from 2004 after the installation of a 3 Tesla MRI device to 2015 Patients with 1 medically refractory extratemporal or multilobar epilep sies and 2 non lesional 3 Tesla MRI that had undergone 3 resec tive surgery were included into the study 2 1 Patients demographics A total of 16 patients 6 male 10 female mean age at time of surgery 32 13 years range 13 50 years with non lesional 3 Tesla MRI negative focal epilepsy and extratemporal or multilobar n 4 resections were included into the study Surgery included 10 frontal resections one occipital one parietal two temporo occipital and two fronto temporal resections 2 2 Magnetic resonance imaging MRI protocols for patients with focal epilepsies have been reported and slightly modifi ed over the years 16 17 Key sequences include a coronal T2 weighted fast spin echo and FLAIR sequences with thin 2 3 mm slices perpendicular to long axis of the hippocampus 18 Subtle cortical signal abnormalities are best appreciated with FLAIR sequences and for morphometric anal yses a 3D T1 weighted MPRAGE sequence is needed Newer 3 Tesla MRI protocols include a 3D FLAIR sequence with 1 mm3iso tropic voxels enabling multiplanar reformations and thus the detection of small FCDs which could have been overlooked in the past 17 The MRI protocol used in our academic institution is shown in Table 1 The criteria for an MRI to be classifi ed as negative non lesional were the judgment of neuroradiologist specialized in epilepsy H U and the consensus of an interdisciplinary epilepsy conferencewithneuroradiologists epileptologistsand neurosurgeons 2 3 Histopathological examination For the present study all specimens n 16 from 16 MRI negative patients that had been prospectively histopathologically examined initialexamination werere examinedandre evaluated retrospectively review examination In all cases the material was macroscopically evaluated by a physician after its entry into the histopathological laboratory and cut and processed for further histopathological examinations Cor tical tissue were cut orthogonally in approximately 5 10 mm thick slices After formalin fi xation and paraffi n embedding conven tional histological stains for hematoxylin and eosin H B Accumulation of neurofi lament proteins and unoriented cellular processes NF immunohistochemistry 100 C Immunoreactivity of dysmorphic nerve cells for Phospho S6 as a sign of the genetic involvement of the mTOR signaling pathway 100 Fig 2 A mMCD Type II blurred border between gray and white matter with detection of several ectopic immature neurons arrows MAP2 immunohistochemistry 40 B perineural cluster of oligodendrocytes satellitosis arrows H C perivascular and pericapillar oligo like cells arranged in rows H number of seizure free Engel IA versus not seizure free Engel IB IV patients Histopathologi cal diagnoses did not correlate to seizure outcome neither the ini tial nor the review examination fi ndings 4 Discussion Within this study we focus on the histopathology of 3 Tesla MRI negative extratemporal epilepsy It is a small series of patients from a single center due to very strict selection criteria Consistent with a recent large study of 1 5 3 Tesla MRI negative epilepsy including 95 temporal and extratemporal cases 6 FCD was the most common fi nding in our series 56 versus 45 by Wang et al In a series of 24 patients with 1 5 3 Tesla MRI negative epilepsy the incidence of FCD was 42 2 The incidence of FCD was notably higher 72 7 in a 55 patient series with 1 5 Tesla MRI negative epilepsy of eloquent and adjacent areas 5 and in a 41 patients series with 1 1 5 Tesla MRI negative cases 78 4 Interestingly the prevalence of FCD is notably higher in series where weaker MRI fi eld is used for the selection of MRI negative cases In our 3 Tesla MRI negative epilepsies the prevalence of FCD is lower than in previous studies of inhomogeneous 1 1 5 or 3 Tesla MRI negative epilepsies 2 5 6 8 20 Nevertheless followed by mMCD FCD remains the most frequent fi nding in our extratemporal MRI negative epilepsy series Mild malformation of cortical development mMCD was found in 44 of cases in our study Although gliosis was an accompanying fi nding in all these specimens none of our cases was labelled as isolated gliosis after the review examination In the work of Wang et al 35 showed gliosis regarded as negative histology 6 In another small surgical series of 16 patients with extratemporal epi lepsy incidence of gliosis was as high as 62 5 7 The term mMCD appears very rarely in surgical series of MRI negative extratemporal epilepsies The term was introduced in the Palmini classifi cation system 14 to describe ectopic neurons Palmini dif ferentiated between mMCD type I layer I and II in white matter Neuropathologists were discouraged from using this diagnosis because it constitutes a very mild aberrancy from normality and preferred gliosis an accompanying fi nding almost in all these cases 15 21 Nevertheless the term mMCD is proposed to be furthermore included in the new ILAE classifi cation 13 It consti tutes a more accurate diagnosis than gliosis and should not be regarded as negative histology Fig 2 Concerning the correlation of histopathology and seizure out come Wang et al found that the fi nding of positive pathology here gliosis is defi ned as negative was signifi cantly associated with seizure free outcome but only in the 6 month and not in the 12 month follow up In our study no correlation between histology and seizure outcome could be confi rmed at 1 year after surgery Another important aspect is that often the grading of FCD is not specifi cally mentioned 2 5 8 20 FCD ILAE IIa represents a typical example of structural abnormality that may remain MRI occult 22 In contrast FCD ILAE IIb that is typically accompanied by transmantle sign in MRI is less likely to escape detection on MRI In cases where FCD IIb is reported as substrate of MRI negative series question could be raised concerning the diagnosis stains interrater variability and or quality of MRI i e fi eld strength and or protocol Comparing the grades of FCDs in our study with those of Wang et al 6 we noticed that our histopatho logical fi ndings did not include any FCD IIb This may refl ect the difference in MRI fi eld strength between the two series Most FCDs in our series were ILAE IIa n 6 there were also two FCDs ILAE Ib and one ILAE Ia In line with our fi ndings in a 3 Tesla MRI negative case series of 11 epilepsy patients Jung et al report 2 FCDs IIa 1 FCD Ia and 2 mMCDs but none FCD IIb the rest of specimens revealed normal fi ndings 23 5 Conclusions In true 3 Tesla MRI negative extratemporal epilepsies inci dence of FCD may be lower than in earlier MRI negative series that included weaker MRI fi eld Furthermore consistent review exam ination may confi rm the diagnosis of mMCD type II as substrate in cases diagnosed as gliosis or normal in the past Notes All Authors have contributed signifi cantly to the preparation of this manuscript and declare no confl icts of interest Appendix A Supplementary data Supplementary data associated with this article can be found in the online version at https doi org 10 1016 j jocn 2018 01 071 References 1 Alarcon G Valent n A Watt C Selway RP Lacruz ME Elwes RDC et al Is it worth pursuing surgery for epilepsy in patients with normal neuroimaging J 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