Jan Kassubek

Magnetic source imaging combined with image-guided frameless stereotaxy: A new method in surgery around the motor strip

OBJECTIVE In this study, information about the localization of the central sulcus obtained by magnetic source imaging (MSI) was intraoperatively translated to the brain, using frameless image-guided stereotaxy. In the past, the MSI results could be translated to the surgical space only by indirect methods (e.g., the comparison of the MSI results, displayed in surface renderings, with bony landmarks or blood vessels on the exposed brain surface). METHODS Somatosensory evoked fields were recorded with a MAGNES II biomagnetometer (Biomagnetic Technologies Inc., San Diego, CA). Using the single equivalent current dipole model, the localization of the somatosensory cortex was superimposed on magnetic resonance imaging with a self-developed contour fit program. The magnetic resonance image set containing the magnetoencephalographic dipole was then transferred to a frameless image-guided stereotactic system. Intraoperatively, the gyrus containing the dipole was identified as the postcentral gyrus, using neuronavigation, and the next anterior sulcus was regarded as the central sulcus. With intraoperative cortical recording of somatosensory evoked potentials, this assumption was verified in each case. RESULTS In all cases, the preoperatively assumed localization of the central sulcus and motor cortex with MSI agreed with the intraoperative identification of the central sulcus using the phase reversal technique. CONCLUSION The combined use of MSI and a frameless stereotactic system allows a fast orientation of eloquent brain areas during surgery. This may contribute to a safer and more radical surgery in lesions adjacent to the motor cortex.

Motor, somatosensory and auditory cortex localization by fMRI and MEG

FUNCTIONAL magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) were performed in six subjects during self-paced finger movement performance, tactile somatosensory stimulation and binaural auditory stimulation using identical stimulation paradigms. Both functional imaging modalities localized brain activity in adjacent areas of anatomically correct cortex. The mean distances measured between fMRI activity and the corresponding MEG dipoles were 10.1 mm (motor), 10.7 mm (somatosensory), 13.5 mm (auditory right hemisphere) and 14.3 mm (auditory left hemisphere). The distances found may reflect the correlation between electrophysiological and hemodynamic responses due to the different underlying substrates of neurophysiology measured by fMRI and MEG: BOLD contrast vs neuronal biomagnetic activity.

Global cerebral atrophy in early stages of Huntington's disease: quantitative MRI study

Global brain atrophy was determined in 70 patients suffering from Huntingtons disease (HD) and 70 healthy controls, using brain parenchymal fractions calculated from 3D MRI data in a standardized procedure. In HD patients, brain parenchymal fractions were significantly reduced compared to controls in all age groups; the physiological decline with age was less pronounced in HD. However, brain parenchymal fraction values did not allow the prediction of clinical impairment (as assessed by clinical scores). Global brain parenchyma reduction seems to be an early or even constitutional feature of HD, but clinical symptoms appear to reflect regional rather than global atrophy. Overall, MRI-based brain volume quantification correlated with clinical scores clarifies the functional impact of morphological brain alterations.

Localization analysis of neuronal activities in benign rolandic epilepsy using magnetoencephalography

Benign epilepsy of childhood with rolandic spikes (BECRS) is an electroclinical syndrome characterized by partial sensorimotor seizures with centrotemporal spikes. We report a detailed localization analysis of spontaneous magnetic brain activities in seven BECRS patients using magnetoencephalography (MEG). All patients had BECRS diagnosis with typical seizures and electroencephalographic findings and five patients had minor psychomotor deficits. MEG was recorded over both parieto-temporal regions using a 2x37-channel biomagnetic system. The collected data were digitally bandpass-filtered (2-6, 14-30, or 1-70 Hz) to analyze slow- and fast-wave magnetic activities and rolandic spikes. Slow-wave activity was increased in four hemispheres of three patients. Increased fast-wave activity was found in all five patients with minor neuropsychological deficits. The presence of increased fast-wave magnetic brain activity appeared to cause functional anomalies in the higher brain function processes. In the spike analysis, the dipoles of rolandic spikes which constantly manifested anterior positivity in direction were concentrated in the superior rolandic region in four cases and the inferior rolandic region in three cases. The localizations of increased slow- and fast-wave activities were identical with those of the spikes. The seizure profiles were frequently characterized by the spike locations. Source localizations of the focal brain activities and rolandic spikes by MEG will contribute to the different diagnosis and pathophysiological elucidation of BECRS.

Cortical plasticity in amyotrophic lateral sclerosis: motor imagery and function.

Background. Cortical networks underlying motor imagery are functionally close to motor performance networks and can be activated by patients with severe motor disabilities. Objective. The aim of the study was to examine the longitudinal effect of progressive motoneuron degeneration on cortical representation of motor imagery and function in amyotrophic lateral sclerosis. Methods. The authors studied 14 amyotrophic lateral sclerosis patients and 15 healthy controls and a subgroup of 11 patients and 14 controls after 6 months with a grip force paradigm comprising imagery and execution tasks using functional magnetic resonance imaging. Results. Motor imagery activated similar neural networks as motor execution in amyotrophic lateral sclerosis patients and healthy subjects in the primary motor (BA 4), premotor, and supplementary motor (BA 6) cortex. Amyotrophic lateral sclerosis patients presented a stronger response within premotor and primary motor areas for imagery and execution compared to controls. After 6 months, these differences persisted with additional activity in the precentral gyrus in patients as well as in a frontoparietal network for motor imagery, in which activity increased with impairment. Conclusion. The findings suggest an ongoing compensatory process within the higher order motor-processing system of amyotrophic lateral sclerosis patients, probably to overcome loss of function in primary motor and motor imagery-specific networks. The increased activity in precentral and frontoparietal networks in motor imagery might be used to control brain-computer interfaces to drive communication and limb prosthetic devices in patients with loss of motor control such as severely disabled amyotrophic lateral sclerosis patients in a locked-in-like state.

Laryngospasm: An underdiagnosed symptom of X-linked spinobulbar muscular atrophy

The authors reviewed the occurrence and concomitant factors of laryngospasm in X-linked spinobulbar muscular atrophy (Kennedy disease [KD]). Recurrent laryngospasm was observed in 47% of 49 patients with KD, but in only 2% of a control group of patients with early-stage ALS.

Body Fat Distribution as a Risk Factor for Cerebrovascular Disease: An MRI-Based Body Fat Quantification Study

Background: While adiposity is a well-established risk factor for cardiovascular disease, the association between adiposity and cerebrovascular disease is not entirely understood. For example, common methods to quantify body fat volume such as body mass index, waist circumference and waist-to-hip ratio are not suitable to identify the complex distribution patterns of body fat and its relation to cerebrovascular pathology. In view of a better understanding of the association between fat distribution and cerebrovascular disorders, the aim of the study was to perform measurements of body fat distribution patterns and body fat volumes in correlation to arteriosclerosis of the brain-feeding arteries and white matter lesion load (WMLL). Methods: In this study we performed a magnetic resonance imaging (MRI)-based volumetric differential analysis of subcutaneous and visceral body fat distribution in 25 patients with MRI-proven hyperacute ischemic stroke. For the measurement of adipose tissue volume and tissue distribution automatic labeling analysis software was used. A correlation analysis of MRI volumetric measurements of subcutaneous and visceral body fat, atherosclerotic plaque load of the brain-feeding arteries measured by computed tomography angiography, and WMLL measured by MRI volumetry of the whole brain was performed. Results: The normalized total abdominal adipose tissue and the normalized subcutaneous abdominal adipose tissue showed no significant correlation with either WMLL or total plaque volume. In contrast, the normalized visceral adipose tissue showed a significant correlation with WMLL volume. Visceral adipose tissue as a percentage of total adipose tissue showed a significant correlation with WMLL. In particular, the percentage of visceral adipose tissue rather than total body fat volume strongly correlated with atherosclerosis and ischemic cerebral lesions. Furthermore, the volume of both soft and calcified plaques correlated significantly with WMLL. Conclusions: Our results contribute to existing studies about the association of different patterns of fat distribution with atherosclerosis of the brain-feeding arteries, in particular highlighting the importance of visceral adiposity as a risk factor for cerebrovascular disease. The percentage of visceral adipose tissue in total adipose tissue has the potential of a sensitive parameter and might become a relevant new epidemiological marker, showing highly significant correlations with well-established markers of cerebrovascular disease. In conclusion, the percentage of visceral adipose tissue by itself has to be regarded as a risk factor for both small vessel cerebrovascular disease and cerebral atherosclerosis of the large-to-medium-sized arteries.

Widespread white matter changes in Kennedy Disease: a voxel-based morphometry study

Objective: X linked spinobulbar muscular atrophy (Kennedy disease (KD)), which is clinically characterised mainly by neuromuscular and endocrine symptoms, has to be considered as a multisystem disorder. Based on clinical evidence of central nervous system involvement, potential KD associated cerebral volume alterations were analysed in vivo. Methods: Whole brain based analysis of optimised voxel based morphometry (VBM) was applied to three dimensional MRI data from 18 genetically confirmed KD patients and compared with age matched controls. Results: Subtle decreases in grey matter volume, mainly localised in frontal areas, were found, but extensive white matter atrophy was observed, particularly in frontal areas, but also involving multiple additional subcortical areas, the cerebellar white matter and the dorsal brainstem from the midbrain to the medulla oblongata. Conclusion: The VBM results demonstrated a morphological correlate of central nervous system involvement in KD, in agreement with aspects of the clinical phenotype (behavioural abnormalities, central–peripheral axonopathy) and with pathohistological findings.

Alterations of Eye Movement Control in Neurodegenerative Movement Disorders

The evolution of the fovea centralis, the most central part of the retina and the area of the highest visual accuracy, requires humans to shift their gaze rapidly (saccades) to bring some object of interest within the visual field onto the fovea. In addition, humans are equipped with the ability to rotate the eye ball continuously in a highly predicting manner (smooth pursuit) to hold a moving target steadily upon the retina. The functional deficits in neurodegenerative movement disorders (e.g., Parkinsonian syndromes) involve the basal ganglia that are critical in all aspects of movement control. Moreover, neocortical structures, the cerebellum, and the midbrain may become affected by the pathological process. A broad spectrum of eye movement alterations may result, comprising smooth pursuit disturbance (e.g., interrupting saccades), saccadic dysfunction (e.g., hypometric saccades), and abnormal attempted fixation (e.g., pathological nystagmus and square wave jerks). On clinical grounds, videooculography is a sensitive noninvasive in vivo technique to classify oculomotion function alterations. Eye movements are a valuable window into the integrity of central nervous system structures and their changes in defined neurodegenerative conditions, that is, the oculomotor nuclei in the brainstem together with their directly activating supranuclear centers and the basal ganglia as well as cortical areas of higher cognitive control of attention.

Functional connectivity changes resemble patterns of pTDP-43 pathology in amyotrophic lateral sclerosis

‘Resting-state’ fMRI allows investigation of alterations in functional brain organization that are associated with an underlying pathological process. We determine whether abnormal connectivity in amyotrophic lateral sclerosis (ALS) in a priori-defined intrinsic functional connectivity networks, according to a neuropathological staging scheme and its DTI-based tract correlates, permits recognition of a sequential involvement of functional networks. ‘Resting-state’ fMRI data from 135 ALS patients and 56 matched healthy controls were investigated for the motor network (corresponding to neuropathological stage 1), brainstem (stage 2), ventral attention (stage 3), default mode/hippocampal network (stage 4), and primary visual network (as the control network) in a cross-sectional analysis and longitudinally in a subgroup of 27 patients after 6 months. Group comparison from cross-sectional and longitudinal data revealed significantly increased functional connectivity (p < 0.05, corrected) in all four investigated networks (but not in the control network), presenting as a network expansion that was correlated with physical disability. Increased connectivity of functional networks, as investigated in a hypothesis-driven approach, is characterized by network expansions and resembled the pattern of pTDP-43 pathology in ALS. However, our data did not allow for the recognition of a sequential involvement of functional connectivity networks at the individual level.