Morphometric MRI Analysis: Improved Detection of Focal Cortical Dysplasia Using the MP2RAGE Sequence.

BACKGROUND AND PURPOSE: Focal cortical dysplasias are the most common resected epileptogenic lesions in children and the third most common lesion in adults, but they are often subtle and frequently overlooked on MR imaging. The purpose of this study was to evaluate whether MP2RAGE-based morphometric MR imaging analysis is superior to MPRAGE-based analysis in the detection of focal cortical dysplasia. MATERIALS AND METHODS: MPRAGE and MP2RAGE datasets were acquired in a consecutive series of 640 patients with epilepsy. Datasets were postprocessed using the Morphometric Analysis Program to generate morphometric z score maps such as junction, extension, and thickness images based on both MPRAGE and MP2RAGE images. Focal cortical dysplasia lesions were manually segmented in the junction images, and volumes and mean z scores of the lesions were measured. RESULTS: Of 21 focal cortical dysplasias discovered, all were clearly visible on MP2RAGE junction images, whereas 2 were not visible on MPRAGE junction images. In all except 4 patients, the volume of the focal cortical dysplasia was larger and mean lesion z scores were higher on MP2RAGE junction images compared with the MPRAGE-based images (P = .005, P = .013). CONCLUSIONS: In this study, MP2RAGE-based morphometric analysis created clearer output maps with larger lesion volumes and higher z scores than the MPRAGE-based analysis. This new approach may improve the detection of subtle, otherwise overlooked focal cortical dysplasia.

[A Pair of Siblings with a rare R5H-Mutation in Exon 1 of the MAPT-Gene]. / Ein Geschwisterpaar mit einer seltenen Tau-Gen-Mutation (MAPT R5H).

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.

Is the type and extent of hippocampal sclerosis measurable on high-resolution MRI?

INTRODUCTION: The purpose of this study is to relate hippocampal volume and FLAIR signal intensity to Wyler grading of hippocampal sclerosis (HS). METHODS: 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. RESULTS: 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 < 0.01), 2.62 ml for Wyler IV (p = 0.01), and 3.08 ml for the contralateral side. Normalized FLAIR signals were 1,354 (p = 0.0004), 1,408 (p < 0.0001), 1,371 (p < 0.04), and 1,296, respectively. Wyler II hippocampi were visually normal. Two of four (50%) Wyler II, 16/19 (84%) Wyler III, and 6/9 (66%) Wyler IV patients achieved Engel I outcome. CONCLUSIONS: Combined volumetry and quantitative FLAIR signal analysis clearly identifies Wyler III and IV HS. Quantitative FLAIR signal analysis may be helpful to identify Wyler II HS.

[Quality guidelines for presurgical epilepsy diagnosis and operative epilepsy therapy: 1st revised version]. / Qualitätsleitlinien für prächirurgische Epilepsiediagnostik und operative Epilepsietherapie : 1. Neufassung.

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.

Volumetric assessment of optic nerve sheath and hypophysis in idiopathic intracranial hypertension.

BACKGROUND AND PURPOSE: Idiopathic intracranial hypertension is a headache syndrome characterized by increased CSF pressure. Compression of the hypophysis and distension of the optic nerve sheath are reliable imaging signs. The purpose of the study was to validate, in patients with idiopathic intracranial hypertension, MR imaging-based volumetric measurements of the optic nerve sheath and hypophysis as an objective observation method for more accurate diagnosis and posttreatment follow-up. MATERIALS AND METHODS: Twenty-three patients with idiopathic intracranial hypertension as well as age-, sex-, and body mass index-matched controls underwent volumetric measurements of the optic nerve, optic nerve sheath, and hypophysis on high-resolution T2-weighted MR images by using a 7-cm surface coil, followed by correlation with CSF opening pressures and clinical symptom scores of visual disturbances and headache. RESULTS: Mean values of optic nerve sheath (341.86 ± 163.69 mm(3) versus 127.56 ± 53.17 mm(3), P < .001) and hypophysis volumes (554.59 ± 142.82 mm(3) versus 686.60 ± 137.84 mm(3), P < .05) differed significantly between healthy and diseased subjects. No significant differences between mean optic nerve volumes were observed. Receiver operating characteristic analysis showed optic nerve sheath volumes of >201.30 mm(3) (sensitivity, 86.96%; specificity, 91.30%) and hypophysis volumes of <611.21 mm(3) (sensitivity, 78.26%; specificity, 69.57%) to be indicative of idiopathic intracranial hypertension diagnosis. In patients with idiopathic intracranial hypertension, no correlations were found between optic nerve sheath and hypophysis volumes and CSF opening pressures or clinical scores of visual disturbances and headache. CONCLUSIONS: Semiautomated volumetric measurement of optic nerve sheath and hypophysis has the potential to more accurately diagnose and follow patients with idiopathic intracranial hypertension.

Multimodality approach in cryptogenic epilepsy with focus on morphometric 3T MRI.

PURPOSE: This study aimed to investigate the potential contribution of morphometric MRI analysis in comparison to other modalities, such as MEG, SPECT and PET, in identifying the epileptogenic focus in patients with cryptogenic epilepsy. PATIENTS AND METHODS: Study inclusion was limited to epilepsy patients with a monolobar focus hypothesis, as concluded from EEG/seizure semiology and the best individual concordance rate. Feature maps, generated by the MATLAB(®) "morphometric analysis program" (MAP), were evaluated by a neuroradiologist blinded to conventional MRI and the focus hypothesis (MAP(1)). In addition, the feature maps were also interpreted by simultaneous matching conventional MRI but, again, with the reader having no knowledge of the focus hypothesis (MAP(2)). RESULTS: In 12 out of 51 patients, true-positive findings were achieved (MAP(1): sensitivity 24%; specificity 96%). The sensitivity of the MAP(1) results was superior extratemporally. After matching conventional MRI, FCD was traced in six of the 12 patients (MAP(2): sensitivity 12%; specificity 100%). MEG sensitivity was 62%. Sensitivity of interictal and ictal SPECT was 20% and 50%, respectively. PET was not as sensitive extratemporally (19%) as temporally (82%). The greatest correspondence with the best individual concordance rate was noted with PET (14/16; 88%) and MEG (8/10; 80%), followed by interictal (5/8; 63%) and ictal (9/15; 60%) SPECT. Results for MAP(1) were 53% (10/19), and 100% for MAP(2) (6/6). CONCLUSION: Although MAP sensitivity and specificity results are lower in comparison to other modalities, implementation of the technique should be considered first, before arranging any further investigations. The present study results offer guidelines for the implementation, interpretation and concordance of diagnostic procedures.

Fully automated atlas-based MR imaging volumetry in Huntington disease, compared with manual volumetry.

BACKGROUND AND PURPOSE: The atrophy of the caudate is considered the hallmark of HD-associated neurodegeneration and has high potential as a biomarker in structural MR imaging. This study aimed at comparing automated and manual caudate volumetry. MATERIALS AND METHODS: In this cross-sectional volumetric study in 40 patients with HD and 30 healthy controls, a fully automated caudate measurement by ABV was used for the first time in HD and was directly compared with manual delineation as the generally accepted criterion standard of volumetry. RESULTS: It could be shown that both techniques were able to separate patients and controls to a similar degree. The differences between the 2 volumetric measurements ranged within the limits of agreement; the systematically lower values by manual volumetry were caused by the different assessment of the dorsal caudate tail, which is hard to delineate manually. CONCLUSIONS: ABV may be used instead of manual volumetry to quantify caudate volume loss. Additionally, the ABV technique has the advantage of being much faster, is less laborious, and is free of a subjective region-of interest definition. ABV might serve as a tool in potential future clinical trials of disease-modifying treatments in HD.

Overlap of musical and linguistic syntax processing: intracranial ERP evidence.

The present study investigated the co-localization of musical and linguistic syntax processing in the human brain. EEGs were recorded from subdural electrodes placed on the left and right perisylvian cortex. The neural generators of the early potentials elicited by syntactic errors in music and language were localized by means of distributed source modeling and compared within subjects. The combined results indicated a partial overlap of the sources within the bilateral superior temporal gyrus, and, to a lesser extent, in the left inferior frontal gyrus, qualifying these areas as shared anatomic substrates of early syntactic error detection in music and language.

Automatic curvilinear reformatting of three-dimensional MRI data of the cerebral cortex.

Curvilinear reformatting of three-dimensional (3D) MRI data of the cerebral cortex is a well-established tool which improves the display of the gyral structure, permits a precise localization of lesions, and helps to identify subtle abnormalities difficult to detect in planar slices due to the brain's complex convolutional pattern. However, the method is time consuming because it requires interactive manual delineation of the brain surface contour. Therefore, a novel technique for automatic curvilinear reformatting is presented. A T1-weighted MRI volume data set is normalized using SPM2. Due to the normalization to a common stereotactic space, predefined masks can be applied to cover skull and outer brain regions in different depths from the brain surface. Thereby, the outer brain regions are subsequently removed in 2-mm layers parallel to the brain surface like 'peeling an onion'. The serial convex planes enclosing the residual inner part of the brain are presented 3-dimensionally. If necessary (e.g., for intraoperative navigation), the normalized data can be transferred to native space by inverse normalization. Compared to cross-sectional images, curvilinear reformatting offers a markedly superior visualization of topographic relations between lesions and cortical structures, helps to detect subtle cortical malformations and to assess the spatial extent of lesions, thus allowing a better planning of neurosurgical procedures. Compared to alternative methods, it is largely based on freely available software and does not require observer-dependent manual input. In conclusion, we present a simple, easy-to-use and fully automated method for curvilinear reformatting of 3D MRI.

Brain atrophy in pure and complicated hereditary spastic paraparesis: a quantitative 3D MRI study.

Hereditary spastic paraparesis (HSP) is a heterogeneous group of neurodegenerative disorders with progressive lower limb spasticity, categorized into pure (p-HSP) and complicated forms (c-HSP). The purpose of this study was to evaluate if brain volumes in HSP were altered compared with a control population. Brain volumes were determined in patients suffering from HSP, including both p-HSP (n = 21) and c-HSP type (n = 12), and 30 age-matched healthy controls, using brain parenchymal fractions (BPF) calculated from 3D MRI data in an observer-independent procedure. In addition, the tissue segments of grey and white matter were analysed separately. In HSP patients, BPF were significantly reduced compared with controls both for the whole patient group (P < 0.001) and for both subgroups, indicating considerable brain atrophy. In contrast to controls who showed a decline of brain volumes with age, this physiological phenomenon was less pronounced in HSP. Therefore, global brain parenchyma reduction, involving both grey and white matter, seems to be a feature in both subtypes of HSP. Atrophy was more pronounced in c-HSP, consistent with the more severe phenotype including extramotor involvement. Thus, global brain atrophy, detected by MRI-based brain volume quantification, is a biological marker in HSP subtypes.

Effect of interstitial stereotactic radiosurgery on behavior and subjective handicap of epilepsy in patients with gelastic epilepsy.

Patients with symptomatic epilepsy due to hypothalamic hamartomas often are compromised not only by pharmacoresistant epileptic seizures but also by behavioral disturbances and cognitive dysfunction. We report the effect of successful treatment with stereotactic interstitial radiosurgery by intrahypothalamic implantation of 125I seeds on behavior and subjective handicap. In all patients rendered seizure-free or suffering only from auras, improvement of behavior was reported by parents and colleagues or schoolteachers. Parents' ratings according to the Child Behavior Checklist showed improvements with respect to social problems and attention. Self-ratings of quality of life by adult patients showed improvements in activities, working situation, and self-perception. These improvements were not observed in patients in whom clinically manifest seizures and interictal EEG discharges persisted after radiosurgery.

Automated detection of gray matter malformations using optimized voxel-based morphometry: a systematic approach.

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.

A voxel-based morphometric MRI study in female patients with borderline personality disorder.

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.

Cortical current density reconstruction of interictal epileptiform activity in temporal lobe epilepsy.

OBJECTIVE: To investigate the value of cortical current density (CCD) reconstruction in localizing intracranial generators of interictal epileptiform activity in mesial and lateral temporal lobe epilepsy (TLE). METHODS: Non-linear minimum L(1)-norm CCD reconstruction (with current sources restricted to the individual cortical surface and a realistic boundary element method (BEM) head model) was used to localize and to study the propagation of interictal epileptiform EEG activity in 13 pre-surgical patients with TLE. RESULTS: In all but one patient with mesial temporal lesions, an initial activation maximum corresponding to the ascending part of averaged sharp waves was found in the ipsilateral anterior basolateral temporal lobe, mostly extending up to the affected mesial structures whose resection rendered the patients seizure-free. In all 3 patients with lateral temporal lesions, the activation was initially confined to temporal neocortex immediately adjacent to the epileptogenic lesion. Towards the peak of sharp waves, two patients showed a propagation of interictal activity to anterior and posterior and partly contralateral temporal regions. A conventional EEG analysis based on amplitude maxima or phase reversal would have missed the initial onset zone. CONCLUSIONS: The findings demonstrate that CCD reconstruction can be a valuable additional non-invasive component in the multimodal pre-surgical evaluation of epilepsy patients.

Myoclonus in epilepsy patients with anticonvulsive add-on therapy with pregabalin.

PURPOSE: To report on the occurrence of myoclonus in patients receiving pregabalin (PGB) for the treatment of focal epilepsy. METHODS: Clinic records of 19 patients who were consecutively enrolled at a tertial referral epilepsy center in a randomized, double-blind and/or open add-on study with PGB were reviewed. RESULTS: In four patients treated with PGB, focal myoclonus newly developed. The side effect appeared with PGB doses of 50-600 mg/day; the intensity showed some dose dependency. All patients had medically refractory focal epilepsy and received other antiepileptic drugs (AEDs) besides the study medication. One patient showed focal myoclonic jerks of the left arm, whereas the other patients developed multifocal myoclonus. Polygraphic studies including electromyogram (EMG)-triggered back-averaging of the EEG in the patient with the highest frequency of myoclonic jerks showed no visible correlate of the myoclonus. In this patient, frequency and intensity of myoclonic jerks significantly decreased after dose reduction of PGB. In the other cases, myoclonus was only subtle and did not significantly interfere with daily activities, so that a dose reduction of PGB was not considered necessary. CONCLUSIONS: These data indicate a relatively high incidence (four of 19) of myoclonus associated with PGB therapy. The rate seems to be at least as high as reported in patients receiving the structurally similar anticonvulsant gabapentin.

[Cognitive impairments due to add-on therapy with topiramate]. / Kognitive Beeinträchtigungen unter Add-on-Therapie mit Topiramat.

In an open study, 37 epilepsy patients were investigated with regard to cognitive impairments in anticonvulsant add-on therapy with topiramate (TPM). In addition to a preexisting antiepileptic medication, TPM administration was started and increased by 25 mg/week. Cognitive side effects noted by the patient or doctor were assessed by a neuropsychological test battery. In 18/37 patients (49%), cognitive deficits consisting of impaired concentration, psychomotoric slowing, memory deficits, and dysphasia were observed. The adverse effects became apparent at dosages of 50-575 mg TPM/day (average 210 mg). In four patients, they were reversible after reducing the dose of TPM by 25-150 mg/day. In eight patients, the adverse effects led to withdrawal of TPM. In spite of slow titration, the present study showed a higher frequency of cognitive side effects under TPM than was previously reported. In some patients, these side effects led to substantial impairments in daily life and at work. For early recognition of cognitive impairments, neuropsychological baseline and follow-up investigations of verbal fluency, psychomotor processing speed, and verbal memory are recommended.

Localization of interictal delta and epileptiform EEG activity associated with focal epileptogenic brain lesions.

The present study was aimed at investigating the accuracy of electric source reconstruction in the presurgical evaluation of epilepsy patients. Spontaneous EEG activity of 14 patients with focal intracerebral epileptogenic lesions was analyzed by source reconstruction based on high-resolution EEG (64-channel system) and a boundary element method head model accounting for the individual head anatomy. Equivalent dipole modeling was applied to focal delta and interictal epileptiform activity. The localization results were validated quantitatively by comparison with the sites of the structural lesions. In 6 of 9 patients with focal delta activity, the maximum of dipole concentration was closer than 10 mm to the nearest lesion margin and mostly at the border or within pathologically altered cortical tissue. In all 11 patients showing interictal epileptiform activity, the localization results were found in the same lobe as the lesion. In almost half of them, they were closer than 10 mm to the lesion margin. Patients with larger distances (22-36 mm) mostly had hippocampal atrophy or sclerosis. Their dipole locations did not appear in the affected hippocampus, but in the adjacent temporal neocortex. In conclusion, electric source reconstruction applied to both abnormal slow and interictal epileptiform EEG activity seems to be a valuable additional noninvasive component in the multimodal presurgical evaluation of epilepsy patients.

Estimation of the accuracy of a surface matching technique for registration of EEG and MRI data.

OBJECTIVES: We developed a method to register EEG and MRI data used for the source reconstruction of electric brain activity. METHODS: The method is based on matching of the head surfaces as obtained by 3D scanning after the EEG recording, and by segmentation of MRI data. The registration accuracy was estimated by calculating the residual error of the surface matching and its intra-individual and inter-individual variability. In addition, the test-retest reliability concerning the transformation of electrode positions was studied, to estimate how inaccuracies resulting from the 3D scanning of the head surface translate into registration uncertainty. RESULTS: For 61 measurements, performed on 20 subjects, the average root mean square of the Euclidean distances between the 3D-scanned and the MRI-derived head surfaces amounted to 3.4 mm. An inter-individual standard deviation of 0.24 mm, and an intraindividual standard deviation of 0.003-0.31 mm proved a high inter- and intra-subject stability of the surface matching technique. The variation of transformation results when studying the test-retest reliability amounted to 1.6 mm on average. The maximum error of transformation was smaller than the diameter of the electrodes. CONCLUSIONS: The findings suggest that the surface matching technique is a precise method for determination of the transformation of electrode positions and MRI data into a single co-ordinate system and can successfully be used in a routine laboratory setting.