Alexander Geissler

Evaluation of preoperative high magnetic field motor functional MRI (3 Tesla) in glioma patients by navigated electrocortical stimulation and postoperative outcome

Objectives: The validity of 3 Tesla motor functional magnetic resonance imaging (fMRI) in patients with gliomas involving the primary motor cortex was investigated by intraoperative navigated motor cortex stimulation (MCS). Methods: Twenty two patients (10 males, 12 females, mean age 39 years, range 10–65 years) underwent preoperative fMRI studies, performing motor tasks including hand, foot, and mouth movements. A recently developed high field clinical fMRI technique was used to generate pre-surgical maps of functional high risk areas defining a motor focus. Motor foci were tested for validity by intraoperative motor cortex stimulation (MCS) employing image fusion and neuronavigation. Clinical outcome was assessed using the Modified Rankin Scale. Results: FMRI motor foci were successfully detected in all patients preoperatively. In 17 of 22 patients (77.3%), a successful stimulation of the primary motor cortex was possible. All 17 correlated patients showed 100% agreement on MCS and fMRI motor focus within 10 mm. Technical problems during stimulation occurred in three patients (13.6%), no motor response was elicited in two (9.1%), and MCS induced seizures occurred in three (13.6%). Combined fMRI and MCS mapping results allowed large resections in 20 patients (91%) (gross total in nine (41%), subtotal in 11 (50%)) and biopsy in two patients (9%). Pathology revealed seven low grade and 15 high grade gliomas. Mild to moderate transient neurological deterioration occurred in six patients, and a severe hemiparesis in one. All patients recovered within 3 months (31.8% transient, 0% permanent morbidity). Conclusions: The validation of clinically optimised high magnetic field motor fMRI confirms high reliability as a preoperative and intraoperative adjunct in glioma patients selected for surgery within or adjacent to the motor cortex.

Influence of fMRI smoothing procedures on replicability of fine scale motor localization

Recent publications analyzing the influence of spatial smoothing on fMRI brain activation results demonstrated that smoothing may artificially combine activations from adjacent though functionally and anatomically distinct brain regions and that activation from large draining vessels may be smoothed into neighboring neuronal tissue. To investigate whether functional localizations may be artificially shifted by the smoothing procedure we performed replicability measurements. Localization centers of motor hand activations achieved during different conditions (isolated hand movements and simultaneous hand and chin movements) were compared with respect to smoothing effects. The voxel with the highest probability to represent a true positive activation was localized with a non-smoothed and a standard 4 x 4 x 6 mm smoothed correlational data analysis technique. Results show an increase of motor center aberrations between measurements by about 100% due to data smoothing indicating a statistically significant decrease in localization replicability.

Improvement of Clinical Language Localization with an Overt Semantic and Syntactic Language Functional MR Imaging Paradigm

BACKGROUND AND PURPOSE: Functional MR imaging (fMRI) is a promising but, in some aspects, still debated noninvasive tool for functional language mapping. We developed a clinical fMRI overt language design at the sentential level to optimize sensitivity for language-related areas of the brain. To evaluate applicability and sensitivity, we investigated a consecutive series of presurgical patients with epilepsy with minimal morphologic brain abnormalities. MATERIALS AND METHODS: Thirty right-handed patients with temporal lobe epilepsy (TLE) and a control group of 23 right-handed healthy subjects participated in the study. The language design included semantic and syntactic error-detection tasks and was constructed to represent the most relevant aspects of everyday language demands. It was applied during block-designed fMRI runs. We performed image preprocessing and statistical analysis with SPM5 at a group level, applying widely used statistical criteria. The study was approved by the local ethics committee, and all participants gave written informed consent. RESULTS: Given the strict statistical criteria, the sensitivity for inferior frontal and posterior temporal activations (comprising Broca and Wernicke regions) was improved relative to previous findings in the literature. For both language areas, we found 100% sensitivity in healthy subjects (Brodmann areas, BA22 and BA44) and 97% sensitivity in patients (when including BA47). Lateralization results demonstrated the capability to detect atypical language lateralizations in patients, which were more frequent in than those in healthy subjects. CONCLUSIONS: We developed a clinical language fMRI design that integrates various relevant aspects of everyday language demands and provides robust localization of core language areas.

Contrast-to-noise ratio (CNR) as a quality parameter in fMRI

To evaluate the impact of data quality on the localization of brain activation in functional magnetic resonance imaging (fMRI) and to explore whether the temporal contrast‐to‐noise‐ratio (CNR) provides a quantitative parameter to estimate fMRI quality.

How much are clinical fMRI reports influenced by standard postprocessing methods? An investigation of normalization and region of interest effects in the medial temporal lobe

Recent evidence has indicated that standard postprocessing methods such as template‐based region of interest (ROI) definition and normalization of individual brains to a standard template may influence final outcome of functional magnetic resonance imaging investigations. Here, we provide the first comprehensive investigation into whether ROI definition and normalization may also change the clinical interpretation of patient data. A series of medial temporal lobe epilepsy patients were investigated with a clinical memory paradigm and individually delineated as well as template‐based ROIs. Different metrics for activation quantification were applied. Results show that the application of template‐based ROIs can significantly change the clinical interpretation of individual patient data. This relates to sensitivity for brain activation and hemispheric dominance. We conclude that individual ROIs should be defined on nontransformed functional data and that use of more than one metric for activation quantification is beneficial. Hum Brain Mapp, 2010.

The benefits of skull stripping in the normalization of clinical fMRI data.

Establishing a reliable correspondence between lesioned brains and a template is challenging using current normalization techniques. The optimum procedure has not been conclusively established, and a critical dichotomy is whether to use input data sets which contain skull signal, or whether skull signal should be removed. Here we provide a first investigation into whether clinical fMRI benefits from skull stripping, based on data from a presurgical language localization task. Brain activation changes related to deskulled/not-deskulled input data are determined in the context of very recently developed (New Segment, Unified Segmentation) and standard normalization approaches. Analysis of structural and functional data demonstrates that skull stripping improves language localization in MNI space — particularly when used in combination with the New Segment normalization technique.

FMRI reveals functional cortex in a case of inconclusive Wada testing

OBJECTIVES The intracarotid amobarbital test (Wada test) currently represents the gold standard for preoperative lateralization of hemispheric dominance. Here, we report an epileptic patient with a longstanding extended lesion of the left hemisphere showing absence of motor and speech dysfunction with left carotid amobarbital injection, but tetraplegia and speech arrest with right carotid injection interpreted as a neuroplastic shift of motor and language functions to the right hemisphere. In contrast to the Wada results, motor functional magnetic resonance imaging (fMRI) showed a strong left hemispheric activation with right hand movements. METHODS Right and left hand motor fMRI was performed. FMRI results and neurophysiological information obtained by motor and sensory evoked potential measurements were compared with the Wada test results. RESULTS Initial interpretation of neuroplastic shifts of intrinsic left hemisphere functions to the right brain was revised after fMRI results which were confirmed by motor and sensory evoked potentials. CONCLUSION As motor inactivation usually is thought to be the most robust feature of the Wada test, this case demonstrates that fMRI may reveal residual functional cortex in cases of inconclusive Wada results.

Variability of Clinical Functional MR Imaging Results: A Multicenter Study

PURPOSE To investigate intersite variability of clinical functional magnetic resonance (MR) imaging, including influence of task standardization on variability and use of various parameters to inform the clinician whether the reliability of a given functional localization is high or low. MATERIALS AND METHODS Local ethics committees approved the study; all participants gave written informed consent. Eight women and seven men (mean age, 40 years) were prospectively investigated at three experienced functional MR sites with 1.5- (two sites) or 3-T (one site) MR. Nonstandardized motor and highly standardized somatosensory versions of a frequently requested clinical task (localization of the primary sensorimotor cortex) were used. Perirolandic functional MR variability was assessed (peak activation variability, center of mass [COM] variability, intraclass correlation values, overlap ratio [OR], activation size ratio). Data quality measures for functional MR images included percentage signal change (PSC), contrast-to-noise ratio (CNR), and head motion parameters. Data were analyzed with analysis of variance and a correlation analysis. RESULTS Localization of perirolandic functional MR activity differed by 8 mm (peak activity) and 6 mm (COM activity) among sites. Peak activation varied up to 16.5 mm (COM range, 0.4-16.5 mm) and 45.5 mm (peak activity range, 1.8-45.5 mm). Signal strength (PSC, CNR) was significantly lower for the somatosensory task (mean PSC, 1.0% ± 0.5 [standard deviation]; mean CNR, 1.2 ± 0.4) than for the motor task (mean PSC, 2.4% ± 0.8; mean CNR, 2.9 ± 0.9) (P < .001, both). Intersite variability was larger with low signal strength (negative correlations between signal strength and peak activation variability) even if the task was highly standardized (mean OR, 22.0% ± 18.9 [somatosensory task] and 50.1% ± 18.8 [motor task]). CONCLUSION Clinical practice and clinical functional MR biomarker studies should consider that the center of task-specific brain activation may vary up to 16.5 mm, with the investigating site, and should maximize functional MR signal strength and evaluate reliability of local results with PSC and CNR.

Impaired activation of somatosensory cortex as FMRI correlate of reduced dexterity in PD

WCN 2013 No: 1278 Topic: 2 — Movement Disorders Impaired activation of somatosensory cortex as FMRI correlate of reduced dexterity in PD T. Foki, W. Pirker, A. Geissler, D. Haubenberger, M. Hilbert, I. Hoellinger, M. Wurnig, J. Rath, J. Lehrner, S. Trattnig, E. Auff, R. Beisteiner. Department of Neurology, Medical University of Vienna, Vienna, Austria; MR Center of Excellence, Department of Radiology, Medical University of Vienna, Vienna, Austria; Department of Radiology, Medical University of Vienna, Vienna, Austria Background: Previously (1ab), the DOPA-resistant component of decreased dexterity in PD was called limb-kinetic apraxia (LkA). Our recent fMRI pilot study (2) investigating PD patients OFF medication suggested impaired activation of primary somatosensory cortex (SSC) as closely related to LkA. Both in the behavioral (1ab) and FMRI studies (2), coin rotation (CR, LkA task, target condition) was contrasted with simple finger tapping (FT, bradykinesia task, reference condition). FMRI signal changes were hence corrected for basic motor skills and represented activation particularly associated with dexterity. Based on the DOPA resistance of CR performance in (1ab), we hypothesized a reproducibility of impaired activation of the SSC ON medication. Objective: The objective of this study is to confirm dysfunction of SSC as closely related to DOPA-resistant dexterity deficits in PD. Patients and methods: According to the experimental setup (CR vs. FT) mentioned above, 10 PD patients performed the FMRI experiment in the ON as well as the OFF condition. 14 healthy controls performed the same experiment. Patients were compared to controls (SPM8). Results: Confirming our pilot study, we assessed decreased activation of the SSC in patients OFF medication compared to controls. In line with our study hypothesis, this finding was reproducible in patients ON medication compared to controls (p b 0.01, uncorr., k = 25 vox.). Comparing FMRI signals in the SSC between ON and OFF conditions, no differences could be assessed (lowering even to p b 0.05). Conclusions: Dexterity deficits in PD are linked to a dysfunction of the SSC. (1a) Gebhardt-et-al._MovDisord 2008;23 :1701-6. (1b) Quencer-et-al._Neurology 2007;68:150-1. (2) Foki-et-al._ExpNeurol 2010;225:416-22. doi:10.1016/j.jns.2013.07.405 Abstract — WCN 2013 No: 1269 Topic: 2 — Movement Disorders Subjective and objective alcohol responsiveness in different tremor disorders WCN 2013 No: 1269 Topic: 2 — Movement Disorders Subjective and objective alcohol responsiveness in different tremor disorders P. Schwingenschuh, M. Koegl-Wallner, U. Werner, T. Pendl, C. Ghadery, S. Seiler, K. Wenzel, R. Schmidt, P. Katschnig-Winter. Department of Neurology, Medical University of Graz, Graz, Austria Background: A few studies exist on the effect of alcohol in essential tremor (ET) and Parkinson s disease (IPD), but so far no systematic studies have been performed in other tremor syndromes. Nevertheless, a positive response to alcohol – commonly simply inquired by history – is used as supportive diagnostic criterion for ET. Objective: The objective of this study is to investigate if subjective/ objective alcohol responses distinguish a broad range of tremor disorders. Methods: (1) We assessed drinking habits and response of tremor to alcohol intake in 100 consecutive patients with arm tremor. (2) For a double-blind placebo-controlled oral alcohol test we recruited 12 patients with ET, 10 IPD, and 7 dystonic tremor (DT). The effect to alcohol/placebo was assessed at baseline and after 30/ 60/120 min by clinical rating scales and accelerometry. Results: (1) We investigated 44 patients with IPD, 22 ET, 20 DT, and 14 others. Of 77 patients drinking alcohol, 23 had no response, 26 had improvement, and 28 never paid attention. None of the evaluated parameters differed between the groups. (2) ET, IPD, and DT had a significant tremor improvement with placebo and alcohol. There were no significant between group differences. However, in the ET group there was a stronger objective effect of alcohol compared to placebo. Conclusions: Subjective alcohol response inquired by history may not be suitable as supportive diagnostic criterion for ET. Objectively, all investigated patients improved with alcohol. This effect seems to be truly alcohol related in ET only. doi:10.1016/j.jns.2013.07.406 Abstract — WCN 2013 No: 1258 Topic: 2 — Movement Disorders Exome sequencing analysis in familial progressive supranuclear palsy WCN 2013 No: 1258 Topic: 2 — Movement Disorders Exome sequencing analysis in familial progressive supranuclear palsy C. Bettencourt, A. Tucci, R. Ros, J. Lopez-Sendon, J. Hardy, J. Garcia deYebenes,H.Houlden. Department ofMolecularNeuroscience, UCL Institute of Neurology, London, UK; Department of Neurology, Hospital Ramon y Cajal, Madrid, Spain Background: Progressive supranuclear palsy (PSP) is a clinicopathological syndrome characterized by akinesia, supranuclear gaze palsy, Abstracts / Journal of the Neurological Sciences 333 (2013) e109–e151 e121