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Focal cortical dysplasias (FCDs) are malformations of cortical development and one of the most common pathologies causing pharmacoresistant focal epilepsy. Resective neurosurgery yields high success rates, especially if the full extent of the lesion is correctly identified and completely removed. The visual assessment of magnetic resonance imaging does not pinpoint the FCD in 30%-50% of cases, and half of all patients with FCD are not amenable to epilepsy surgery, partly because the FCD could not be sufficiently localized. Computational approaches to FCD detection are an active area of research, benefitting from advancements in computer vision. Automatic FCD detection is a significant challenge and one of the first clinical grounds where the application of artificial intelligence may translate into an advance for patients' health. The emergence of new methods from the combination of health and computer sciences creates novel challenges. Imaging data need to be organized into structured, well-annotated datasets and combined with other clinical information, such as histopathological subtypes or neuroimaging characteristics. Algorithmic output, that is, model prediction, requires a technically correct evaluation with adequate metrics that are understandable and usable for clinicians. Publication of code and data is necessary to make research accessible and reproducible. This critical review introduces the field of automatic FCD detection, explaining underlying medical and technical concepts, highlighting its challenges and current limitations, and providing a perspective for a novel research environment.

Pathogenic variants in 5 genes (GCH1, TH, PTS, SPR, and QDPR), involved in dopamine/tetrahydrobiopterin biosynthesis or recycling, have been linked to Dopa-responsive dystonia (DRD). Diagnosis and treatment are often delayed due to high between- and within-group variability.Comprehensively analyzed individual genotype, phenotype, treatment response, and biochemistry information.734 DRD patients and 151 asymptomatic GCH1 mutation carriers were included using an MDSGene systematic literature review and an automated classification approach to distinguish between different forms of monogenic DRDs.Whereas dystonia, L-Dopa responsiveness, early age at onset, and diurnal fluctuations were identified as red flags, parkinsonism without dystonia was rarely reported (11%) and combined with dystonia in only 18% of patients. While sex was equally distributed in autosomal recessive DRD, there was female predominance in autosomal dominant DYT/PARK-GCH1 patients accompanied by a lower median age at onset and more dystonia in females compared to males. Accordingly, the majority of asymptomatic heterozygous GCH1 mutation carriers (8 years of age) were males. Multiple other subgroup-specific characteristics were identified, showing high accuracy in the automated classification approach: Seizures and microcephaly were mostly seen in DYT/PARK-PTS, autonomic symptoms appeared commonly in DYT/PARK-TH and DYT/PARK-PTS, and sleep disorders and oculogyric crises in DYT/PARK-SPR. Biochemically, homovanillic acid and 5-hydroxyindoleacetic acid in CSF were reduced in most DRDs, but neopterin and biopterin were increased only in DYT/PARK-PTS and DYT/PARK-SPR. Hyperphenylalaninemia was seen in DYT/PARK-PTS, DYT/PARK-QDPR, and rarely reported in autosomal recessive DYT/PARK-GCH1.Our indicators will help to specify diagnosis and accelerate start of treatment. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

OBJECTIVE: Focal cortical dysplasias (FCDs) are a common cause of drug-resistant focal epilepsy but frequently remain undetected by conventional magnetic resonance imaging (MRI) assessment. The visual detection can be facilitated by morphometric analysis of T1-weighted images, for example, using the Morphometric Analysis Program (v2018; MAP18), which was introduced in 2005, independently validated for its clinical benefits, and successfully integrated in standard presurgical workflows of numerous epilepsy centers worldwide. Here we aimed to develop an artificial neural network (ANN) classifier for robust automated detection of FCDs based on these morphometric maps and probe its generalization performance in a large, independent data set. METHODS: In this retrospective study, we created a feed-forward ANN for FCD detection based on the morphometric output maps of MAP18. The ANN was trained and cross-validated on 113 patients (62 female, mean age ± SD =29.5 ± 13.6 years) with manually segmented FCDs and 362 healthy controls (161 female, mean age ± SD =30.2 ± 9.6 years) acquired on 13 different scanners. In addition, we validated the performance of the trained ANN on an independent, unseen data set of 60 FCD patients (28 female, mean age ± SD =30 ± 15.26 years) and 70 healthy controls (42 females, mean age ± SD = 40.0 ± 12.54 years). RESULTS: In the cross-validation, the ANN achieved a sensitivity of 87.4% at a specificity of 85.4% on the training data set. On the independent validation data set, our method still reached a sensitivity of 81.0% at a comparably high specificity of 84.3%. SIGNIFICANCE: Our method shows a robust automated detection of FCDs and performance generalizability, largely independent of scanning site or MR-sequence parameters. Taken together with the minimal input requirements of a standard T1 image, our approach constitutes a clinically viable and useful tool in the presurgical diagnostic routine for drug-resistant focal epilepsy. ispartof: EPILEPSIA vol:62 issue:4 pages:1005-1021 ispartof: location:United States status: published

Here, we report a consanguineous family harboring a novel homozygous frame-shift mutation in ASPM leading to a truncation of the ASPM protein after amino acid position 1830. The phenotype of the patients was associated with microcephaly, epilepsy, and behavioral and cognitive deficits. Despite the obvious genetic similarity, the affected patients show a considerable phenotypic heterogeneity regarding the degree of mental retardation, presence of epilepsy and MRI findings. Interestingly, the degree of mental retardation and the presence of epilepsy correlates well with the severity of abnormalities detected in brain MRI. On the other hand, we detected no evidence for substantial nonsense-mediated ASPM transcript decay in blood samples. This indicates that other factors than ASPM expression levels are relevant for the variability of structural changes in brain morphology seen in patients with primary hereditary microcephaly caused by ASPM mutations.

Die Ursache der Epilepsie bleibt auch heute noch bei vielen Patienten unklar, trotz groser Fortschritte der Magnetresonanztomographie (MRT) in den letzten 3 Jahrzehnten. Unterstutzung der qualitativ-visuellen MRT-Auswertung durch computergestutzte digitale Analyse von strukturellen MRT-Daten. Die morphometrische MRT-Auswertung vergleicht die individuelle Hirnanatomie mit einer MRT-Normdatenbank und hebt mittels spezieller Filter Abweichungen bezuglich Gyrierung, Kortexdicke und Mark-Rinden-Differenzierung hervor. Die volumetrische MRT-Auswertung quantifiziert die Atrophie oder Volumenzunahme des Gehirns und seiner Substrukturen und vergleicht die Resultate mit den Ergebnissen von altersgematchten gesunden Probanden bzw. von Patienten mit unterschiedlichen Pathologien. In diversen Studien wurde nachgewiesen, dass die morphometrische MRT-Auswertung die Erkennung und Visualisierung fokaler kortikaler Dysplasien, aber auch anderer subtiler Formen von kortikaler Malformation verbessert. Der diagnostische Mehrwert im Vergleich zur visuellen Auswertung liegt im Bereich von ca. 5–40 % je nach Selektion der Patientenkohorte, der Qualitat der Ausgangsdaten und der vorherigen visuellen Befundung. Die volumetrische MRT-Auswertung erleichtert die Diagnose und Verlaufsbeurteilung von verschiedenen, mit epileptischen Anfallen einhergehenden entzundlichen, metabolischen oder neurodegenerativen Erkrankungen. Insbesondere bei bislang kryptogenen Epilepsien stellen die beiden hier vorgestellten MRT-Auswerteverfahren eine wertvolle Erganzung des diagnostischen Repertoires dar.

Introduction. The diagnosis of progressive supranuclear palsy (PSP) involves head MRI, including detection of atrophy patterns of the mesencephalon and frontoparietal regions. In this study, MRI-based alterations of the texture in the corpus callosum (CC) in PSP patients compared with Parkinson's disease (PD) patients and healthy controls were investigated. Methods. In sagittal T1-weighted MRI scans of 66 PSP patients, 66 PD patients and 44 healthy controls the corpus callosum was segmented by atlas-based volumetry and TIFT [1] in areas I-V based on the Hofer & Frahm scheme [2]. The texture parameters entropy and homogeneity were calculated separately for areas I-V and results were compared for PSP patients (including phenotypes Richardson-syndrome and PSP-parkinsonism) vs. PD patients vs. healthy controls. Results. A significant increase of parameters entropy and homogeneity compared to controls was detected for PSP as well as for PD for areas I, II, and III of the CC; here PSP patients showed a higher increase compared to PD patients. Highest alterations were detected in area II where the increase of (in)homogeneity of PSP compared with PD was significant. Differences between the phenotypes Richardson-syndrome und PSP-parkinsonism could not be shown. Discussion. Texture analysis of the CC could contribute to diagnosis, screening and differentiation between PSP and PD. References [1] Muller HP, et al. Neuroimage Clin. 2020; 26:102223. [2] Hofer S, Frahm J. Neuroimage. 2006; 32,989-994.

Purpose Focal cortical dysplasias (FCD) type IIb and cortical tubers in tuberous sclerosis complex (TSC) are histopathologically similar and are both epileptogenic lesions frequently causing pharmacoresistant epilepsies. Morphometric analysis of T1- and T2-weighted MRI volume data sets can enhance visualization of FCD. Here, we retrospectively investigated whether morphometric MRI analysis is of equal benefit for visualizing cortical tubers. Materials and methods Morphometric analysis was applied to T1- and partly also T2-weighted 1.5T or 3T MRI volume data sets of 15 TSC patients using a fully automated MATLAB ® script (i.e. MAP07) commonly used for FCD detection. In this study, focus was on the most sensitive of the resulting morphometric feature maps (i.e. the ‘junction image') which highlights blurring of the gray–white matter junction in comparison to a normal database. The visualization of tubers in these ‘junction images' was quantitatively compared with that in conventional MR sequences. Results In all patients, morphometric analysis visualized almost all tubers detected in the normal MRI, and additionally highlighted on average 23% (range 3–50%) more tubers which were not detected by visual analysis of the conventional MR sequences. When T2 volume data sets from a 3T scanner were available for postprocessing, the rate of additionally detected tubers increased to 29% on average. These formerly overlooked tubers were usually smaller than the tubers already found in the conventional MRI. Conclusion Morphometric analysis of MRIs in TSC can highlight cortical tubers which are likely to be overlooked in conventional MRI sequences alone. Additionally detected tubers may be of potential importance for both presurgical evaluation and initial diagnosis of TSC.

We report on a female patient presenting with primary progressive aphasia (PPA) and her brother presenting with psychosis. Both siblings had an R5H-mutation in exon 1 of the MAPT-gene. The PPA patient presented for the first time at the age of 72 years with a 4-year-history of language impairment. After a progressive course the patient died at the age of 76 years. The R5H-MAPT-gene mutation detected in the siblings has been described only once in 2002 by Hayashi et al. [1]. In this previous case from Japan, a 75-year-old patient initially displayed amnesia and disorientation. He became bedridden, with progressive mutism and rigidity of the upper extremities. Noteworthy are the manifold signs and symptoms in R5H-mutations and the late age of onset. For future trials, the detection of biomarkers for frontotemporal lobar degeneration in presymptomatic cohorts like the genetic frontotemporal dementia initiative (GENFI) is of help for stratifying subjects at risk.

The purpose of this study is to relate hippocampal volume and FLAIR signal intensity to Wyler grading of hippocampal sclerosis (HS). Of 100 consecutive patients with temporal lobe epilepsy and HS as histopathological diagnosis, 32 had high-resolution 3 Tesla MRI and anatomically well-preserved hippocampi following amygdalo-hippocampectomy. Hippocampal volume on 3D T1-weighted gradient echo and signal intensity on coronal FLAIR sequences were determined using FreeSurfer and SPM tools and related to Wyler grading. Seizure outcome was determined after 1 year. Histopathology showed four Wyler II, 19 Wyler III, and 9 Wyler IV HS. Hippocampal volumes were 3.08 ml for Wyler II (Wyler II/contralateral side: p > 0.05), 2.19 ml for Wyler III (p

In patients with pharmacorefractory epilepsy, preoperative epilepsy evaluation and subsequent epilepsy surgery lead to a significant improvement of seizure control, proportion of seizure-free patients, quality of life and social participation. The aims of preoperative epilepsy evaluation are to define the chance of complete seizure freedom and the likelihood of inducing new neurological deficits in a given patient. As epilepsy surgery is an elective procedure quality standards are particularly high. As detailed in the first edition of these practice guidelines, quality control relates to seven different domains: (1) establishing centres with a sufficient number of sufficiently and specifically trained personnel, (2) minimum technical standards and equipment, (3) continuing medical education of employees, (4) surveillance by trained personnel during the video electroencephalography (EEG) monitoring (VEM), (5) systematic acquisition of clinical and outcome data, (6) the minimum number of preoperative evaluations and epilepsy surgery procedures and (7) cooperation of epilepsy centres. In the first edition of these practice guidelines published in 2000 it was defined which standards were desirable and that their implementation should be aimed for. These standards related especially to the certification required for different groups of medical doctors involved and to the minimum numbers of procedures required. In the subsequent decade quite a number of colleagues have been certified by the trinational Working Group (Arbeitsgemeinschaft, AG) for Presurgical Epilepsy Diagnosis and Operative Epilepsy Treatment (http://www.ag-epilepsiechirurgie.de) and therefore, on 8 May 2013 the executive board of the AG decided to now make these standards obligatory.

It is believed that glycogen synthase kinase-3 hyperphosphorylates tau protein in progressive supranuclear palsy (PSP). The Tau Restoration on PSP (TAUROS) trial assessed the glycogen synthase kinase-3 inhibitor tideglusib as potential treatment. For the magnetic resonance imaging (MRI) substudy reported here, we assessed the progression of brain atrophy. TAUROS was a multinational, phase 2, double-blind, placebo-controlled trial in patients with mild-to-moderate PSP who were treated with oral tideglusib (600 mg or 800 mg daily) or with placebo for 1 year. A subset of patients underwent baseline and 52-week MRI. Automated, observer-independent, atlas-based, and mask-based volumetry was done on high-resolution, T1-weighted, three-dimensional data. For primary outcomes, progression of atrophy was compared both globally (brain, cerebrum) and regionally (third ventricle, midbrain, pons) between the active and placebo groups (Bonferroni correction). For secondary outcomes, 15 additional brain structures were explored (Benjamini & Yekutieli correction). In total, MRIs from 37 patient were studied (placebo group, N = 9; tideglusib 600 mg group, N = 19; tideglusib 800 mg group, N = 9). The groups compared well in their demographic characteristics. Clinical results showed no effect of tideglusib over placebo. Progression of atrophy was significantly lower in the active group than in the placebo group for the brain (mean ± standard error of the mean: -1.3% ± 1.4% vs. -3.1% ± 2.3%, respectively), cerebrum (-1.3% ± 1.5% vs. -3.2% ± 2.1%, respectively), parietal lobe (-1.6% ± 1.9% vs. -4.1% ± 3.0%, respectively), and occipital lobe (-0.3% ± 1.8% vs. -2.7% ± 3.2%, respectively). A trend toward reduced atrophy also was observed in the frontal lobe, hippocampus, caudate nucleus, midbrain, and brainstem. In patients with PSP, tideglusib reduced the progression of atrophy in the whole brain, particularly in the parietal and occipital lobes.

Summary Purpose: To describe a novel magnetic resonance imaging (MRI) postprocessing technique for the detection of periventricular nodular heterotopia (PNH) and to evaluate its diagnostic value. The method is a further development of voxel-based morphometric analysis with focus on a region of interest around the lateral ventricles to increase the sensitivity and specificity for automated detection of abnormally located gray matter in this area. Methods: T1-weighted MRI volume data sets were normalized and segmented in statistical parametric mapping (SPM 5 software), and the distribution of gray matter was compared to a normal database. As a new approach, individual masks derived from segmentation of the lateral ventricles were used to restrict the search for ectopic gray matter to the periventricular area. PNH were automatically detected by localizing the maximum deviation from the normal database in this area, provided that the z-score exceeded a certain threshold. The optimal z-score threshold for maximum sensitivity and specificity was determined by a receiver operating characteristic (ROC) curve analysis. The method was applied in 40 patients with PNH and 400 controls. Key Findings: PNH were detected in 37 of 40 patients, and false positives were found in 34 of 400 controls, amounting to 92.5% sensitivity and 91.5% specificity. In 17 of the patients in whom PNH could be identified, these lesions had been overlooked in the past, and in 8 patients even in the high-resolution MRI subsequently used for postprocessing. Significance: The results suggest that automated morphometric MRI analysis with focus on ectopic gray matter in the periventricular areas facilitates the evaluation of MRI data and increases the sensitivity for the detection of PNH.

Summary Purpose To describe and evaluate a novel MRI post-processing technique for automated quantitative hippocampal FLAIR analysis in patients with hippocampal sclerosis (HS). Patients and methods Based on a method for FLAIR analysis presented by Focke et al. (2009) , T1 and coregistered FLAIR scans of individual subjects were processed together in SPM5 to conduct both a spatial and an intensity normalization of the FLAIR scans. In a further development described here, the resulting normalized FLAIR images were thresholded and weighted by a probabilistic hippocampal mask to determine the average FLAIR intensities of left and right hippocampus. The method was applied to the MRI data of 103 HS patients and 131 controls. Using a 95% confidence region calculated from the FLAIR intensities of controls as threshold, the performance in discriminating both groups was assessed. Results One hundred of 103 patients and among those all 23 patients with histologically confirmed HS fell outside the 95% confidence region, amounting to 97.1% sensitivity. All but 6 controls (=95.4%) were found within the confidence region, corresponding to the expected specificity. The method could also distinguish bilateral HS and visualize signal changes after status epilepticus. Conclusion Automated FLAIR analysis is a promising tool to quantify hippocampal signal alterations, to support the detection of HS, and to monitor the temporal evolution of the disease.

This study describes the existence and the clinical and electrophysiological features of multi-focal cortical dysplasia in epilepsy patients. Five patients with intractable focal epilepsy are reported. All patients underwent invasive presurgical video-electroencephalography monitoring. Localization of dysplastic areas was based on high-resolution magnetic resonance scanning, surface and intracranial electroencephalography. Four patients underwent epilepsy surgery. Histological findings in focal cortical dysplasia (FCD) were classified according to Palmini. In addition, genetic examinations were performed in order to assess possible mutations in the genes for tuberous sclerosis complex. In four patients, FCDs were located in the same hemisphere. One case presented with bilateral FCDs. In three patients seizures arose from two separate dysplastic areas and in one patient, one lesion showed only interictal activity. In one further patient, seizures started exclusively from the hippocampus. In two of three patients with removal of the FCDs, the histological subtype was identical (Palmini type 2) and in one patient, histology differed between the lesions. All operated patients became seizure-free. In patients with FCD type 2, germ-line mutations in the tuberous sclerosis complex genes were not detectable. Dysplastic brain regions may not be restricted to a single brain region. Areas of FCD can have different degrees of epileptogenicity, ranging from electrographic silence to interictal epileptic discharges and initial involvement in seizure generation. Based on genetic analysis and clinical features, multi-FCD in this patient series was not likely to be related to tuberous sclerosis.

Refractory mesial temporal lobe epilepsy (MTLE) is the most frequent focal epilepsy and is often accompanied by deficits in social cognition including emotion recognition, theory of mind, and empathy. Consistent with the neuronal networks that are crucial for normal social-cognitive processing, these impairments have been associated with functional changes in fronto-temporal regions. However, although atrophy in unilateral MTLE also affects regions of the temporal and frontal lobes that underlie social cognition, little is known about the structural correlates of social-cognitive deficits in refractory MTLE. In the present study, a psychometrically validated empathy questionnaire was combined with whole-brain voxel-based morphometry (VBM) to investigate the relationship between self-reported affective and cognitive empathy and gray matter volume in 55 subjects (13 patients with right MTLE, 9 patients with left MTLE, and 33 healthy controls). Consistent with the brain regions underlying social cognition, our results show that lower affective and cognitive empathy was associated with smaller volume in predominantly right fronto-limbic regions, including the right hippocampus, parahippocampal gyrus, thalamus, fusiform gyrus, inferior temporal gyrus, dorsomedial and dorsolateral prefrontal cortices, and in the bilateral midbrain. The only region that was associated with both affective and cognitive empathy was the right mesial temporal lobe. These findings indicate that patients with right MTLE are at increased risk for reduced empathy towards others' internal states and they shed new light on the structural correlates of impaired social cognition frequently accompanying refractory MTLE. In line with previous evidence from patients with neurodegenerative disease and stroke, the present study suggests that empathy depends upon the integrity of right fronto-limbic and brainstem regions and highlights the importance of the right mesial temporal lobe and midbrain structures for human empathy.

We investigated whether alterations in glutamate metabolising glutamine synthetase activity occur in human epileptic neocortex, as shown previously for human epileptic hippocampus [Eid, T., Thomas, M.J., Spencer, D.D., Runden-Pran, E., Lai, J.C.K., Malthankar, G.V., Kim, J.H., Danbolt, N.C., Ottersen, O.P., de Lanerolle, N.C., 2004. Loss of glutamine synthetase in the human epileptic hippocampus: possible mechanism for raised extracellular glutamate in mesial temporal lobe epilepsy. Lancet 363, 28-37]. Glutamine synthetase activity was equivalent in both non-epileptic and epileptic human neocortex. Epileptic tissue, however, was characterised by a 37% increase in the density of synaptosomal NMDA receptor sites compared to non-epileptic tissue, as revealed by a radioligand binding assay (B max(non-epileptic) 1.45 pmol/mg protein and B max(epileptic) 1.99 pmol/mg protein, P < 0.05). Our findings shed some doubts on a role of glutamine synthetase in the pathophysiology of epilepsy in the neocortex. However, the detection of a significantly reduced enzymatic activity in the epileptic amygdala supports the assumption that the enzyme defect is localized to the epileptic mesial temporal lobe of corresponding patients.

In ALS, advanced magnetic resonance imaging (MRI) techniques are increasingly used to investigate the underlying pathology. In this study, the technique of voxel-based morphometry (VBM) was applied to 3-D MRI data in ALS patients to localize regional grey and white matter changes. Twenty-two ALS patients (mean age 58+/-9 years) with clinically definite ALS by revised El Escorial criteria were studied. None of the patients had any signs of associated frontotemporal dementia. High-resolution 3-D MRI data sets of the whole brain, collected on a 1.5 T scanner, were analysed by statistical parametric mapping (SPM) and VBM in comparison to an age-matched normal data base consisting of 22 healthy volunteers (mean age 59+/-11 years), for grey matter and white matter segments separately. Global brain atrophy was assessed by calculation of brain parenchymal fractions (BPF). In ALS patients, BPF were significantly reduced compared to controls (p = 0.0003), indicating global brain atrophy. Regional decreases of grey matter density were found in the ALS patients at corrected p

Background Characteristically impaired oculomotor functions are recognized in Parkinsonian syndromes including idiopathic Parkinson disease (PD), Multiple System Atrophy (MSA), Progressive Supranuclear Palsy (PSP) ( Pinkhardt and Kassubek, 2011 ). Atrophy of specific brain structures has been reported in Parkinsonian syndromes ( Brenneis et al., 2007 , Focke et al., 2011 ). The aim of this study was to investigate possible relationships between oculomotor alterations and volumetric alterations in PD, PSP and MSA. Methods Forty-two PD, 18 MSA, and 32 PSP patients together with 26 healthy controls underwent standardized video-oculographic testing and MRI at a clinical 1.5T scanner. Whole-brain based T1-weighted MRI-images were analyzed using atlas-based volumetry ( Kassubek et al., 2011 ). Data of 5 brain structures (forebrain, brainstem, cerebellum, midbrain, pons) and 5 oculomotor parameters (smooth pursuit gain, peak eye velocity, rate of saccadic intrusions, anti-saccade errors) were used for group comparisons in PD, MSA and PSP with healthy controls. Oculomotor parameters were correlated with regional brain volumes in the patients. Results PD patients compared with control showed a significantly increased rate of saccadic intrusions (p). Conclusions The worse the oculomotor performance the lower the regional brain volume, suggesting a relationship between regional brain atrophy and cerebral oculomotor network disturbances. Deficits in eye movement control in PD appear to be characterized by executive abnormalities, whereas oculomotor dysfunctions in MSA and PSP were associated with impaired pontine and midbrain pathways.

Malformations of cortical development (MCD) are a recognized cause of epilepsy. Their special significance lies in the fact that, once detected and delineated, they are amenable to surgical removal. However, diagnosis from high-resolution MRI is still difficult, time-consuming, and highly dependent on individual expertise. We have recently proposed a simple procedure to detect cortical dysplasias, using automated procedures available within SPM99 (Wellcome Department, University College London, UK). Here, we aimed to systematically determine the best combination of processing parameters, using an optimized voxel-based morphometry approach. We included 20 patients with a known MCD and compared them to a normal database of 53 healthy, age- and gender-matched controls. The approaches taken during spatial normalization and a number of other parameters were systematically altered in order to find the best combination of parameters. Overall, 99 different approaches were evaluated in different ways. As far as possible, automatic processing and evaluation steps were used. With the number of candidate regions for MCD limited to five per patient, the best approaches resulted in the correct identification of up to 16 of 20 malformations. However, a number of approaches failed to perform well. The reasons for these failures and the implications this has for other studies are discussed. We conclude that voxel-based morphometry is able to detect cortical malformations with a high degree of accuracy. However, specific problems seem to arise when using an optimized protocol for voxel-based morphometry, indicating that this protocol may not be optimal for all voxel-based studies on brain morphology. Our approach, involving systematic alterations of parameters and evaluation, may be useful for other studies.

Subtle prefrontal and limbic structural abnormalities have been reported in borderline personality disorder (BPD). In order to further validate the previously reported findings and to more precisely describe the nature of the structural change we performed a voxel-based morphometric (VBM) study in patients with BPD. Twenty female patients with BPD and 21 female healthy controls were investigated. High-resolution 3-D datasets were acquired and analyzed following an optimized protocol of VBM in the framework of statistical parametric mapping (SPM99). Gray matter volume loss was found in the left amygdala. No other differences in gray or white matter volume or density were found anywhere else in the brain. Our findings support the hypothesis that temporolimbic abnormalities play a role in the pathophysiology of BPD. Prefrontal structural alterations in BPD were not observed in this study.

In three patients with acute occlusion of the basilar artery intra-arterial fibrinolysis resulted in only partial recanalization and revealed severe stenosis as the underlying cause. Application of micro-stents without previous dilatation resulted in vessel re-opening. Two patients had an excellent clinical outcome. One patient died 10 days after the stroke due to brainstem infarction. Emergency primary stent application may improve the outcome in acute basilar artery occlusion, if intra-arterial thrombolysis fails to re-establish a sufficient flow.

Impaired energy expenditure parallels ongoing motor neuron degeneration in patients with amyotrophic lateral sclerosis (ALS). Translational animals provide evidence that energy metabolism is associated with impaired hypothalamic function. We aimed at analyzing the hypothalamic volumes in ALS patients compared with controls. Hypothalamic volume of 281 ALS patients and 116 healthy matched controls were manually delineated based on high-resolution anatomic T1-weighted MRI images using a dedicated segmentation technique.The volume of the hypothalamus, was normalized to the intracranial volume and adjusted with age.The total hypothalmic volume was significantly decreased in ALS patients compared with controls ( p 0.0001 ); morespecifically the posterior part of the hypothalamus was more severely atrophied compared with the anterior part. The volume loss didnotcorrelate significantly with clinical and metabolic parameters which suggests an early affection of hypothalamic function possibly preceding motor symptom onset in ALS. Volumetric alterations of the hypothalamus could be an early feature of ALS.

Background Assessment of eye movement control in Parkinson’s disease (PD), multisystematrophy (MSA), and progressive supranuclear palsy (PSP) shows disease-related oculomotor alterations ( Pinkhardt and Kassubek, 2011 ). Volumetric 3D MRI analysisis a tool of growing relevance inthe differential diagnosis in neurodegenerative Parkinsonism ( Huppertz et al., 2016 ). Objective To investigate the association between impaired eye movement control and regional volume loss in PD, MSA, and PSP patients. Methods Video-oculographic data (EyeLink®) and high resolution 3-dimensional T1-weighted MRI images from 39 PD, 32 PSP, 18 MSA patients, and 24 matched healthy control subjects wereincluded in the analysis. Atlas based volumetry (ABV) was used to investigate for regional volumetric alterations ( Huppertz et al., 2016 ). Results In PD, saccadic intrusions were commonly observed as a measure for executive control (pppp). Conclusions The worse the characteristically impaired eye movement parameter in PD, MSA and PSP, the more severe was the disease-specific regional volume loss.

To describe a novel magnetic resonance imaging (MRI) postprocessing technique for the detection of periventricular nodular heterotopia (PNH) and to evaluate its diagnostic value. The method is a further development of voxel-based morphometric analysis with focus on a region of interest around the lateral ventricles to increase the sensitivity and specificity for automated detection of abnormally located gray matter in this area.T(1) -weighted MRI volume data sets were normalized and segmented in statistical parametric mapping (SPM 5 software), and the distribution of gray matter was compared to a normal database. As a new approach, individual masks derived from segmentation of the lateral ventricles were used to restrict the search for ectopic gray matter to the periventricular area. PNH were automatically detected by localizing the maximum deviation from the normal database in this area, provided that the z-score exceeded a certain threshold. The optimal z-score threshold for maximum sensitivity and specificity was determined by a receiver operating characteristic (ROC) curve analysis. The method was applied in 40 patients with PNH and 400 controls.PNH were detected in 37 of 40 patients, and false positives were found in 34 of 400 controls, amounting to 92.5% sensitivity and 91.5% specificity. In 17 of the patients in whom PNH could be identified, these lesions had been overlooked in the past, and in 8 patients even in the high-resolution MRI subsequently used for postprocessing.The results suggest that automated morphometric MRI analysis with focus on ectopic gray matter in the periventricular areas facilitates the evaluation of MRI data and increases the sensitivity for the detection of PNH.