Elke R. Gizewski

Embolization of Intracranial Arteriovenous Malformations with Ethylene-Vinyl Alcohol Copolymer (Onyx)

BACKGROUND AND PURPOSE: Endovascular therapy of intracranial arteriovenous malformations (AVMs) is increasingly used. However, it is still under discussion which embolic material is optimal. We report our experience in the treatment of AVMs with ethylene-vinyl alcohol copolymer (Onyx). MATERIALS AND METHODS: Between July 2002 and January 2008, brain AVMs were embolized with Onyx in 82 consecutive patients in our department. There were 41 females and 41 males with a mean age of 44.2 years (range, 15–85 years). Clinical presentation included symptoms due to intracerebral hemorrhage (n = 37), seizures (n = 18), nonhemorrhagic neurologic deficits (n = 8), headaches (n = 9), or incidental symptoms (n = 10). According to the Spetzler-Martin scale, 59 AVMs were grades I–II, 16 were grade III, and 7 were grades IV–V. RESULTS: Complete obliteration at the end of all endovascular procedures was achieved in 20/82 patients (24.4%), with an average of 75% (range, 30%–100%) volume reduction. A mean of 2.9 (range, 1–10) feeding pedicles was embolized per patient, whereas an average of 2.6-mL Onyx was used per patient. Procedure-related permanent disabling morbidity was 3.8%, whereas mortality was 2.4%. CONCLUSIONS: The overall initial complete obliteration rate of intracranial AVMs with Onyx embolization is relatively high, compared with other embolic agents, with evidence of stability with time. Morbidomortality rates due to AVM embolization as a single treatment method or as a part of a multimodality treatment should be further assessed regarding the natural course of the disease.

Affective disturbances modulate the neural processing of visceral pain stimuli in irritable bowel syndrome: an fMRI study

Objective To address the role of anxiety and depression symptoms in altered pain processing in irritable bowel syndrome (IBS). Design In this functional magnetic resonance imaging study, the blood oxygen level-dependent (BOLD) response to rectal distensions delivered at previously determined individual discomfort thresholds was assessed. Patients 15 female patients with irritable bowel syndrome (IBS) and with normal rectal pain thresholds, and 12 healthy women. Measures The correlation of anxiety and depression symptoms, measured with the Hospital Anxiety and Depression Scale (HADS), with subjective pain ratings and the BOLD response during distension-induced brain activation were analysed within IBS. Group differences in pain-induced brain activation with and without controlling for HADS scores were evaluated. Results Patients with IBS experienced significantly more pain and discomfort upon rectal distensions in the scanner, despite unaltered rectal sensory thresholds. Anxiety and depression scores were associated with these subjective stimulus ratings, but not with rectal sensory thresholds. Anxiety symptoms in IBS were significantly associated with pain-induced activation of the anterior midcingulate cortex and pregenual anterior cingulate cortex. Depression scores correlated with activation of the prefrontal cortex (PFC) and cerebellar areas within IBS. Group comparisons with the two-sample t test revealed significant activation in the IBS versus controls contrast in the anterior insular cortex and PFC. Inclusion of anxiety and depression scores, respectively, as confounding variables led to a loss of significant group differences. Conclusions Altered central processing of visceral stimuli in IBS is at least in part mediated by symptoms of anxiety and depression, which may modulate the affective–motivational aspects of the pain response.

Imaging the deep cerebellar nuclei: a probabilistic atlas and normalization procedure.

The deep cerebellar nuclei (DCN) are a key element of the cortico-cerebellar loop. Because of their small size and functional diversity, it is difficult to study them using magnetic resonance imaging (MRI). To overcome these difficulties, we present here three related methodological advances. First, we used susceptibility-weighted imaging (SWI) at a high-field strength (7T) to identify the dentate, globose, emboliform and fastigial nucleus in 23 human participants. Due to their high iron content, the DCN are visible as hypo-intensities. Secondly, we generated probabilistic maps of the deep cerebellar nuclei in MNI space using a number of common normalization techniques. These maps can serve as a guide to the average location of the DCN, and are integrated into an existing probabilistic atlas of the human cerebellum (Diedrichsen et al., 2009). The maps also quantify the variability of the anatomical location of the deep cerebellar nuclei after normalization. Our results indicate that existing normalization techniques do not provide satisfactory overlap to analyze the functional specialization within the DCN. We therefore thirdly propose a ROI-driven normalization technique that utilizes both information from a T1-weighted image and the hypo-intensity from a T2*-weighted or SWI image to ensure overlap of the nuclei. These techniques will promote the study of the functional specialization of subregions of the DCN using MRI.

Adaptation to Visuomotor Rotation and Force Field Perturbation Is Correlated to Different Brain Areas in Patients With Cerebellar Degeneration

Although it is widely agreed that the cerebellum is necessary for learning and consolidation of new motor tasks, it is not known whether adaptation to kinematic and dynamic errors is processed by the same cerebellar areas or whether different parts play a decisive role. We investigated arm movements in a visuomotor (VM) rotation and a force field (FF) perturbation task in 14 participants with cerebellar degeneration and 14 age- and gender-matched controls. Magnetic resonance images were used to calculate the volume of cerebellar areas (medial, intermediate, and lateral zones of the anterior and posterior lobes) and to identify cerebellar structure important for the two tasks. Corroborating previous studies, cerebellar participants showed deficits in adaptation to both tasks compared with controls (P < 0.001). However, it was not possible to draw conclusions from the performance in one task on the performance in the other task because an individual participant could show severe impairment in one task and perform relatively well in the other (rho = 0.1; P = 0.73). We found that atrophy of distinct cerebellar areas correlated with impairment in different tasks. Whereas atrophy of the intermediate and lateral zone of the anterior lobe correlated with impairment in the FF task (rho = 0.72, 0.70; P = 0.003, 0.005, respectively), atrophy of the intermediate zone of the posterior lobe correlated with adaptation deficits in the VM task (rho = 0.64; P = 0.015). Our results suggest that adaptation to the different tasks is processed independently and relies on different cerebellar structures.

Patients With Irritable Bowel Syndrome Have Altered Emotional Modulation of Neural Responses to Visceral Stimuli

BACKGROUND & AIMS In patients with irritable bowel syndrome (IBS), pain amplification and hypervigilance might result from altered affective-motivational modulation of the pain response. We investigated the effects of emotional context on the behavioral and neural response to visceral stimuli in IBS patients. METHODS We used functional magnetic resonance imaging (fMRI) to assess the blood oxygen level-dependent response to nonpainful and painful rectal distensions in 15 female IBS patients and 12 healthy women. Distensions were delivered during psychologic stress or relaxation; data were compared with those in a neutral condition (control). Group and context-dependent differences in the processing of visceral stimulation were assessed at behavioral and the neuronal levels. Secondary analyses of group differences were performed using anxiety scores as a covariate because of higher anxiety symptoms among patients with IBS. RESULTS During rectal stimulation, IBS patients demonstrated more pronounced stress-induced modulation of neural activation in multiple brain regions, including the insula, midcingulate cortex, and ventrolateral prefrontal cortex. In response to relaxation, IBS patients demonstrated reduced modulation of distension-induced activation in the insula. During relaxation, the difference observed between groups could be accounted for by higher anxiety symptoms in patients with IBS; differential effects of stress in the insula and prefrontal regions were not attributable to anxiety. CONCLUSIONS IBS patients appear to have disrupted emotional modulation of neural responses to visceral stimuli, possibly reflecting the neural basis for altered visceral interoception by stress and negative emotions.

There are differences in cerebral activation between females in distinct menstrual phases during viewing of erotic stimuli : a fMRI study

There is evidence that men experience more sexual arousal than women but also that women in mid-luteal phase experience more sexual arousal than women outside this phase. Recently, a few functional brain imaging studies have tackled the issue of gender differences as pertaining to reactions to erotica. The question of whether or not gender differences in reactions to erotica are maintained with women in different phases has not yet been answered from a functional brain imaging perspective. In order to examine this issue, functional MRI was performed in 22 male and 22 female volunteers. Subjects viewed erotic film excerpts alternating with emotionally neutral excerpts in a standard block-design paradigm. Arousal to erotic stimuli was evaluated using standard rating scales after scanning. Two-sample t-test with uncorrected P<0.001 values for a priori determined region of interests involved in processing of erotic stimuli and with corrected P<0.05 revealed gender differences: Comparing women in mid-luteal phase and during their menses, superior activation was revealed for women in mid-luteal phase in the anterior cingulate, left insula, and orbitofrontal cortex. A superior activation for men was found in the left thalamus, the bilateral amygdala, the anterior cingulate, the bilateral orbitofrontal, bilateral parahippocampal, and insular regions, which were maintained at a corrected P in the amygdala, the insula, and thalamus. There were no areas of significant superior activation for women neither in mid-luteal phase nor during their menses. Our results indicate that there are differences between women in the two cycle times in cerebral activity during viewing of erotic stimuli. Furthermore, gender differences with women in mid-luteal phases are similar to those in females outside the mid-luteal phase.

Morphometric changes of sensorimotor structures in focal dystonia

Idiopathic cervical dystonia (CD) and benign essential blepharospasm (BEB) are the most common forms of focal dystonia. Previous autopsy and imaging studies suggested that these disorders are not accompanied by structural brain abnormalities. However, recent brain voxel‐based morphometry (VBM) studies of these conditions suggest that there actually may be changes in gray matter. The objective of this stdy was to detect possible gray matter abnormalities in patients with CD and BEB using VBM and to compare the results between the two conditions and with age‐ and gender‐matched controls. High‐resolution MRI was employed to evaluate healthy controls and individuals with BEB and CD. Eleven BEB, 9 CD, and 14 healthy control subjects were imaged. VBM revealed alterations of gray matter structures involved in sensorimotor processing in the individuals with focal dystonia. In CD subjects there was increased gray matter in the thalamus, caudate head bilaterally, superior temporal lobe, and left cerebellum, while gray matter was decreased in the putamen bilaterally. BEB subjects had increased gray matter in the caudate head and cerebellum bilaterally as well as decrease in the putamen and thalamus bilaterally. These findings strongly underline the recent notion that idiopathic focal dystonias might have a detectable structural correlate. They also demonstrate structural similarities of the investigated focal dystonias, possibly reflecting a shared common pathophysiological origin.

Functional localization in the human cerebellum based on voxelwise statistical analysis: a study of 90 patients.

The aim of the present study was to examine somatotopy in the cerebellar cortex and a possible differential role of the cerebellar cortex and nuclei in functional outcome. Clinical findings and 3D MRI-based cerebellar lesions site were compared in a group of 90 patients with focal cerebellar lesion using International Cooperative Ataxia Rating Scale (ICARS) and voxel-based lesion-symptom mapping (VLSM). Separate analysis was performed in patients with acute and chronic ischemic lesions (n=43) and patients with acute and chronic surgical lesions (n=47). Thirty-eight patients were included after resection of a cerebellar tumor in childhood or adolescence. The most significant lesion symptom correlations were observed in the subgroup with acute ischemic lesions. Limb ataxia was significantly correlated with lesions of the interposed (NI) and part of the dentate nuclei (ND), ataxia of posture and gait with lesions of the fastigial nuclei (NF) including NI. Correlations with cortical lesions were less significant and present in the superior cerebellum only. Upper limb ataxia was correlated with lesions of vermal, paravermal and hemispheral lobules IV-V and VI, lower limb ataxia with lesions of vermal, paravermal and hemispheral lobules III and VI, dysarthria with lesions of paravermal and hemispheral lobules V and VI and ataxia of posture and gait with lesions of vermal and paravermal lobules II, III and IV. In the subgroups with chronic focal lesions, similar correlations were observed with lesions of the cerebellar nuclei, but significantly less correlations with lesions of the cerebellar cortex. Functional localization based on VLSM backs findings in previous animal and functional brain images studies in healthy human subjects. The lesion site appears to be critical for motor recovery. Lesions affecting the cerebellar nuclei are not fully compensated at any age and independent of the pathology in humans.

Dose-Dependent Effects of Endotoxin on Neurobehavioral Functions in Humans

Clinical and experimental evidence document that inflammation and increased peripheral cytokine levels are associated with depression-like symptoms and neuropsychological disturbances in humans. However, it remains unclear whether and to what extent cognitive functions like memory and attention are affected by and related to the dose of the inflammatory stimulus. Thus, in a cross-over, double-blind, experimental approach, healthy male volunteers were administered with either placebo or bacterial lipopolysaccharide (LPS) at doses of 0.4 (n = 18) or 0.8 ng/kg of body weight (n = 16). Pro- and anti-inflammatory cytokines, norephinephrine and cortisol concentrations were analyzed before and 1, 1.75, 3, 4, 6, and 24 h after injection. In addition, changes in mood and anxiety levels were determined together with working memory (n-back task) and long term memory performance (recall of emotional and neutral pictures of the International Affective Picture System). Endotoxin administration caused a profound transient physiological response with dose-related elevations in body temperature and heart rate, increases in plasma interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α and IL-1 receptor antagonist (IL-1ra), salivary and plasma cortisol, and plasma norepinephrine. These changes were accompanied by dose-related decreased mood and increased anxiety levels. LPS administration did not affect accuracy in working memory performance but improved reaction time in the high-dose LPS condition compared to the control conditon. In contrast, long-term memory performance was impaired selectively for emotional stimuli after administration of the lower but not of the higher dose of LPS. These data suggest the existence of at least two counter-acting mechanisms, one promoting and one inhibiting cognitive performance during acute systemic inflammation.

The influence of focal cerebellar lesions on the control and adaptation of gait

Cerebellar ataxic gait is influenced greatly by balance disorders, most likely caused by lesions of the medial zone of the cerebellum. The contributions of the intermediate and lateral zone to the control of limb dynamics for gait and the adaptation of locomotor patterns are less well understood. In this study, we analysed locomotion and goal-directed leg movements in 12 patients with chronic focal lesions after resection of benign cerebellar tumours. The extent of the cortical lesion and possible involvement of the cerebellar nuclei was determined by 3D-MR imaging. The subjects (age range 13-39 years, mean 20.3; seven female; ICARS score: mean 5.7, SD 6.3) performed three tasks: goal-directed leg placement, walking and walking with additional weights on the shanks. Based on the performance on the first two tasks, patients were categorized as impaired or unimpaired for leg placement and for dynamic balance control in gait. The subgroup with impaired leg placement but not the subgroup with impaired balance showed abnormalities in the adaptation of locomotion to additional loads. A detailed analysis revealed specific abnormalities in the temporal aspects of intra-limb coordination for leg placement and adaptive locomotion. These findings indicate that common neural substrates could be responsible for intra-limb coordination in both tasks. Lesion-based MRI subtraction analysis revealed that the interposed and the adjacent dentate nuclei were more frequently affected in patients with impaired compared to unimpaired leg placement, whereas the fastigial nuclei (and to a lesser degree the interposed nuclei) were more frequently affected in patients with impaired compared with unimpaired dynamic balance control. The intermediate zone appears thus to be of particular importance for multi-joint limb control in both goal-directed leg movements and in locomotion. For locomotion, our results indicate an influence of the intermediate zone on dynamic balance control as well as on the adaptation to changes in limb dynamics.