Reorganization of sensory networks after subcortical vestibular infarcts: A longitudinal symptom-related voxel-based morphometry study.

BACKGROUND AND PURPOSE: We aimed to delineate common principles of reorganization after infarcts of the subcortical vestibular circuitry related to the clinical symptomatology. Our hypothesis was that the recovery of specific symptoms is associated with changes in distinct regions within the core vestibular, somatosensory, and visual cortical and subcortical networks. METHODS: We used voxel- and surface-based morphometry to investigate structural reorganization of subcortical and cortical brain areas in 42 patients with a unilateral, subcortical infarct with vestibular and ocular motor deficits in the acute phase. The patients received structural neuroimaging and clinical monitoring twice (acute phase and after 6 months) to detect within-subject changes over time. RESULTS: In patients with vestibular signs such as tilts of the subjective visual vertical (SVV) and ocular torsion in the acute phase, significant volumetric increases in the superficial white matter around the parieto-opercular (retro-)insular vestibular cortex (PIVC) were found at follow-up. In patients with SVV tilts, spontaneous nystagmus, and rotatory vertigo in the acute phase, gray matter volume decreases were located in the cerebellum and the visual cortex bilaterally at follow-up. Patients with saccade pathology demonstrated volumetric decreases in cerebellar, thalamic, and cortical centers for ocular motor control. CONCLUSIONS: The findings support the role of the PIVC as the key hub for vestibular processing and reorganization. The volumetric decreases represent the reciprocal interaction of the vestibular, visual, and ocular motor systems during self-location and egomotion detection. A modulation in vestibular and ocular motor as well as visual networks was induced independently of the vestibular lesion site.

Expansive arterial remodeling of the carotid arteries and its effect on atherosclerotic plaque composition and vulnerability: an in-vivo black-blood 3T CMR study in symptomatic stroke patients.

BACKGROUND: Based on intravascular ultrasound of the coronary arteries expansive arterial remodeling is supposed to be a feature of the vulnerable atheroslerotic plaque. However, till now little is known regarding the clinical impact of expansive remodeling of carotid lesions. Therefore, we sought to evaluate the correlation of expansive arterial remodeling of the carotid arteries with atherosclerotic plaque composition and vulnerability using in-vivo Cardiovascular Magnetic Resonance (CMR). METHODS: One hundred eleven symptomatic patients (74 male/71.8 ± 10.3y) with acute unilateral ischemic stroke and carotid plaques of at least 2 mm thickness were included. All patients received a dedicated multi-sequence black-blood carotid CMR (3Tesla) of the proximal internal carotid arteries (ICA). Measurements of lumen, wall, outer wall, hemorrhage, calcification and necrotic core were determined. Each vessel-segment was classified according to American Heart Association (AHA) criteria for vulnerable plaque. A modified remodeling index (mRI) was established by dividing the average outer vessel area of the ICA segments by the lumen area measured on TOF images in a not affected reference segment at the distal ipsilateral ICA. Correlations of mRI and clinical symptoms as well as plaque morphology/vessel dimensions were evaluated. RESULTS: Seventy-eight percent (157/202) of all internal carotid arteries showed atherosclerotic disease with AHA Lesion-Type (LT) III or higher. The mRI of the ICA was significantly different in normal artery segments (AHA LT I; mRI 1.9) compared to atherosclerotic segments (AHA LT III-VII; mRI 2.5; p < 0.0001). Between AHA LT III-VII there was no significant difference of mRI. Significant correlations (p < 0.05) of the mRI with lumen-area (LA), wall-area (WA), vessel-area (VA) and wall-thickness (WT), necrotic-core area (NC), and ulcer-area were observed. With respect to clinical presentation (symptomatic/asymptomatic side) and luminal narrowing (stenotic/non-stenotic) no relevant correlations or significant differences regarding the mRI were found. CONCLUSION: Expansive arterial remodeling exists in the ICA. However, no significant association between expansive arterial remodeling, stroke symptoms, complicated AHA VI plaque, and luminal stenosis could be established. Hence, results of our study suggest that expansive arterial remodeling is not a very practical marker for plaque vulnerability in the carotid arteries.

White matter volume loss drives cortical reshaping after thalamic infarcts.

OBJECTIVE: The integration of somatosensory, ocular motor and vestibular signals is necessary for self-location in space and goal-directed action. We aimed to detect remote changes in the cerebral cortex after thalamic infarcts to reveal the thalamo-cortical connections necessary for multisensory processing and ocular motor control. METHODS: Thirteen patients with unilateral ischemic thalamic infarcts presenting with vestibular, somatosensory, and ocular motor symptoms were examined longitudinally in the acute phase and after six months. Voxel- and surface-based morphometry were used to detect changes in vestibular and multisensory cortical areas and known hubs of central ocular motor processing. The results were compared with functional connectivity data in 50 healthy volunteers. RESULTS: Patients with paramedian infarcts showed impaired saccades and vestibular perception, i.e., tilts of the subjective visual vertical (SVV). The most common complaint in these patients was double vision or vertigo / dizziness. Posterolateral thalamic infarcts led to tilts of the SVV and somatosensory deficits without vertigo. Tilts of the SVV were higher in paramedian compared to posterolateral infarcts (median 11.2° vs 3.8°). Vestibular and ocular motor symptoms recovered within six months. Somatosensory deficits persisted. Structural longitudinal imaging showed significant volume reduction in subcortical structures connected to the infarcted thalamic nuclei (vestibular nuclei region, dentate nucleus region, trigeminal root entry zone, medial lemniscus, superior colliculi). Volume loss was evident in connections to the frontal, parietal and cingulate lobes. Changes were larger in the ipsilesional hemisphere but were also detected in homotopical regions contralesionally. The white matter volume reduction led to deformation of the cortical projection zones of the infarcted nuclei. CONCLUSIONS: White matter volume loss after thalamic infarcts reflects sensory input from the brainstem as well the cortical projections of the main affected nuclei for sensory and ocular motor processing. Changes in the cortical geometry seem not to reflect gray matter atrophy but rather reshaping of the cortical surface due to the underlying white matter atrophy.

Vessel wall inflammation in spontaneous cervical artery dissection: a prospective, observational positron emission tomography, computed tomography, and magnetic resonance imaging study.

BACKGROUND AND PURPOSE: Vessel wall inflammation (VWI) may be a pathogenetic factor in cervical artery dissection (CAD). We used contrast-enhanced high-resolution MRI (hrMRI) and positron emission tomography CT (PET-CT) to systematically investigate VWI in spontaneous CAD. METHODS: In this monocentric, prospective, observational study, all consecutive patients with acute, MRI-confirmed, spontaneous CAD admitted to our center between August 2007 and August 2009 were included. VWI was defined as perivascular contrast enhancement in hrMRI and increased perivascular [18F]-fluorodesoxyglucose uptake in PET-CT. VWI was further differentiated between local (restricted to the site of dissection) and generalized (exceeding the site of dissection). RESULTS: A total of 37 patients were included. Multiple dissections were seen in 10 patients (27%). Twenty-five patients received both modalities as planned, 8 received only PET-CT, and 4 received only hrMRI. A subset of patients showed signs of a generalized VWI in hrMRI (4/29 patients, 14%) and PET-CT (8/33 patients, 24%). In patients who received both modalities, all with hrMRI signs of generalized VWI were PET-CT positive (3/3), whereas some PET-CT-positive patients were hrMRI-negative (4/7). If present, generalized VWI in hrMRI completely resolved within 6 months. The presence of >2 simultaneous dissections (seen in 2 patients) was significantly associated with generalized VWI in hrMRI (P=0.015) but marginally not in PET-CT (P=0.053). CONCLUSIONS: A subset of patients with spontaneous CAD showed signs of a generalized transient inflammatory arteriopathy in contrast-enhanced hrMRI and PET-CT. This subset of patients may be more prone to multiple dissections.

Age determination of vessel wall hematoma in spontaneous cervical artery dissection: a multi-sequence 3T cardiovascular magnetic resonance study.

BACKGROUND: Previously proposed classifications for carotid plaque and cerebral parenchymal hemorrhages are used to estimate the age of hematoma according to its signal intensities on T1w and T2w MR images. Using these classifications, we systematically investigated the value of cardiovascular magnetic resonance (CMR) in determining the age of vessel wall hematoma (VWH) in patients with spontaneous cervical artery dissection (sCAD). METHODS: 35 consecutive patients (mean age 43.6 ± 9.8 years) with sCAD received a cervical multi-sequence 3T CMR with fat-saturated black-blood T1w-, T2w- and TOF images. Age of sCAD was defined as time between onset of symptoms (stroke, TIA or Horner's syndrome) and the CMR scan. VWH were categorized into hyperacute, acute, early subacute, late subacute and chronic based on their signal intensities on T1w- and T2w images. RESULTS: The mean age of sCAD was 2.0, 5.8, 15.7 and 58.7 days in patients with acute, early subacute, late subacute and chronic VWH as classified by CMR (p < 0.001 for trend). Agreement was moderate between VWH types in our study and the previously proposed time scheme of signal evolution for cerebral hemorrhage, Cohen's kappa 0.43 (p < 0.001). There was a strong agreement of CMR VWH classification compared to the time scheme which was proposed for carotid intraplaque hematomas with Cohen's kappa of 0.74 (p < 0.001). CONCLUSIONS: Signal intensities of VWH in sCAD vary over time and multi-sequence CMR can help to determine the age of an arterial dissection. Furthermore, findings of this study suggest that the time course of carotid hematomas differs from that of cerebral hematomas.

Structural reorganization of the cerebral cortex after vestibulo-cerebellar stroke.

OBJECTIVE: Structural reorganization following cerebellar infarcts is not yet known. This study aimed to demonstrate structural volumetric changes over time in the cortical vestibular and multisensory areas (i.e., brain plasticity) after acute cerebellar infarcts with vestibular and ocular motor symptoms. Additionally, we evaluated whether structural reorganization in the patients topographically correlates with cerebello-cortical connectivity that can be observed in healthy participants. METHODS: We obtained high-resolution structural imaging in seven patients with midline cerebellar infarcts at two time points. These data were compared to structural imaging of a group of healthy age-matched controls using voxel-based morphometry (2×2 ANOVA approach). The maximum overlap of the infarcts was used as a seed region for a separate resting-state functional connectivity analysis in healthy volunteers. RESULTS: Volumetric changes were detected in the multisensory cortical vestibular areas around the parieto-opercular and (retro-) insular cortex. Furthermore, structural reorganization was evident in parts of the frontal, temporal, parietal, limbic, and occipital lobes and reflected functional connections between the main infarct regions in the cerebellum and the cerebral cortex in healthy individuals. CONCLUSIONS: This study demonstrates structural reorganization in the parieto-opercular insular vestibular cortex after acute vestibulo-cerebellar infarcts. Additionally, the widely distributed structural reorganization after midline cerebellar infarcts provides additional in vivo evidence for the multifaceted contribution of cerebellar processing to cortical functions that extend beyond vestibular or ocular motor function.

Vestibular evoked myogenic potentials in vestibular migraine and Menière's disease: cVEMPs make the difference.

OBJECTIVE: Vestibular evoked myogenic potentials (VEMPs) have been suggested as biomarkers in the differential diagnosis of Menière's disease (MD) and vestibular migraine (VM). The aim of this study was to compare the degree of asymmetry for ocular (o) and cervical (c) VEMPs in large cohorts of patients with MD and VM and to follow up the responses. STUDY DESIGN: Retrospective study in an interdisciplinary tertiary center for vertigo and balance disorders. METHODS: cVEMPs to air-conducted sound and oVEMPs to bone-conducted vibration were recorded in 100 patients with VM and unilateral MD, respectively. Outcome parameters were asymmetry ratios (ARs) of oVEMP n10p15 and cVEMP p13n23 amplitudes, and of the respective latencies (mean ± SD). RESULTS: The AR of cVEMP p13n23 amplitudes was significantly higher for MD (0.43 ± 0.34) than for VM (0.26 ± 0.24; adjusted p = 0.0002). MD-but not VM-patients displayed a higher AR for cVEMP than for oVEMP amplitudes (MD 0.43 ± 0.34 versus 0.23 ± 0.22, p < 0.0001; VM 0.26 ± 0.14 versus 0.19 ± 0.15, p = 0.11). Monitoring of VEMPs in single patients indicated stable or fluctuating amplitude ARs in VM, while ARs in MD appeared to increase or remain stable over time. No differences were observed for latency ARs between MD and VM. CONCLUSIONS: These results are in line with (1) a more common saccular than utricular dysfunction in MD and (2) a more permanent loss of otolith function in MD versus VM. The different patterns of o- and cVEMP responses, in particular their longitudinal assessment, might add to the differential diagnosis between MD and VM.

Primary or secondary chronic functional dizziness: does it make a difference? A DizzyReg study in 356 patients.

In 2017, the term "persistent postural-perceptual dizziness" (PPPD) was coined by the Bárány Society, which provided explicit criteria for diagnosis of functional vertigo and dizziness disorders. PPPD can originate secondarily after an organic disorder (s-PPPD) or primarily on its own, in the absence of somatic triggers (p-PPPD). The aim of this database-driven study in 356 patients from a tertiary vertigo center was to describe typical demographic and clinical features in p-PPPD and s-PPPD patients. Patients underwent detailed vestibular testing with neurological and neuro-orthoptic examinations, video-oculography during water caloric stimulation, video head-impulse test, assessment of the subjective visual vertical, and static posturography. All patients answered standardized questionnaires (Dizziness Handicap Inventory, DHI; Vestibular Activities and Participation, VAP; and Euro-Qol-5D-3L). One hundred and ninety-five patients (55%) were categorized as p-PPPD and 162 (45%) as s-PPPD, with female gender slightly predominating (♀:♂ = 56%:44%), particularly in the s-PPPD subgroup (64%). The most common somatic triggers for s-PPPD were benign paroxysmal positional vertigo (27%), and vestibular migraine (24%). Overall, p-PPPD patients were younger than s-PPPD patients (44 vs. 48 years) and showed a bimodal age distribution with an additional early peak in young adults (about 30 years of age) beside a common peak at the age of 50-55. The most sensitive diagnostic tool was posturography, revealing a phobic sway pattern in 50% of cases. s-PPPD patients showed higher handicap and functional impairment in DHI (47 vs. 42) and VAP (9.7 vs. 8.9). There was no difference between both groups in EQ-5D-3L. In p-PPPD, anxiety (20% vs. 10%) and depressive disorders (25% vs. 9%) were more frequent. This retrospective study in a large cohort showed relevant differences between p- and s-PPPD patients in terms of demographic and clinical features, thereby underlining the need for careful syndrome subdivision for further prospective studies.

Global multisensory reorganization after vestibular brain stem stroke.

OBJECTIVE: Patients with acute central vestibular syndrome suffer from vertigo, spontaneous nystagmus, postural instability with lateral falls, and tilts of visual vertical. Usually, these symptoms compensate within months. The mechanisms of compensation in vestibular infarcts are yet unclear. This study focused on structural changes in gray and white matter volume that accompany clinical compensation. METHODS: We studied patients with acute unilateral brain stem infarcts prospectively over 6 months. Structural changes were compared between the acute phase and follow-up with a group of healthy controls using voxel-based morphometry. RESULTS: Restitution of vestibular function following brain stem infarcts was accompanied by downstream structural changes in multisensory cortical areas. The changes depended on the location of the infarct along the vestibular pathways in patients with pathological tilts of the SVV and on the quality of the vestibular percept (rotatory vs graviceptive) in patients with pontomedullary infarcts. Patients with pontomedullary infarcts with vertigo or spontaneous nystagmus showed volumetric increases in vestibular parietal opercular multisensory and (retro-) insular areas with right-sided preference. Compensation of graviceptive deficits was accompanied by adaptive changes in multiple multisensory vestibular areas in both hemispheres in lower brain stem infarcts and by additional changes in the motor system in upper brain stem infarcts. INTERPRETATION: This study demonstrates multisensory neuroplasticity in both hemispheres along with the clinical compensation of vestibular deficits following unilateral brain stem infarcts. The data further solidify the concept of a right-hemispheric specialization for core vestibular processing. The identification of cortical structures involved in central compensation could serve as a platform to launch novel rehabilitative treatments such as transcranial stimulations.

Direct comparison of activation maps during galvanic vestibular stimulation: A hybrid H2[15 O] PET-BOLD MRI activation study.

Previous unimodal PET and fMRI studies in humans revealed a reproducible vestibular brain activation pattern, but with variations in its weighting and expansiveness. Hybrid studies minimizing methodological variations at baseline conditions are rare and still lacking for task-based designs. Thus, we applied for the first time hybrid 3T PET-MRI scanning (Siemens mMR) in healthy volunteers using galvanic vestibular stimulation (GVS) in healthy volunteers in order to directly compare H215O-PET and BOLD MRI responses. List mode PET acquisition started with the injection of 750 MBq H215O simultaneously to MRI EPI sequences. Group-level statistical parametric maps were generated for GVS vs. rest contrasts of PET, MR-onset (event-related), and MR-block. All contrasts showed a similar bilateral vestibular activation pattern with remarkable proximity of activation foci. Both BOLD contrasts gave more bilateral wide-spread activation clusters than PET; no area showed contradictory signal responses. PET still confirmed the right-hemispheric lateralization of the vestibular system, whereas BOLD-onset revealed only a tendency. The reciprocal inhibitory visual-vestibular interaction concept was confirmed by PET signal decreases in primary and secondary visual cortices, and BOLD-block decreases in secondary visual areas. In conclusion, MRI activation maps contained a mixture of CBF measured using H215O-PET and additional non-CBF effects, and the activation-deactivation pattern of the BOLD-block appears to be more similar to the H215O-PET than the BOLD-onset.

Cortical alterations in phobic postural vertigo - a multimodal imaging approach.

OBJECTIVE: Functional dizziness syndromes are among the most common diagnoses made in patients with chronic dizziness, but their underlying neural characteristics are largely unknown. The aim of this neuroimaging study was to analyze the disease-specific brain changes in patients with phobic postural vertigo (PPV). METHODS: We measured brain morphology, task response, and functional connectivity in 44 patients with PPV and 44 healthy controls. RESULTS: The analyses revealed a relative structural increase in regions of the prefrontal cortex and the associated thalamic projection zones as well as in the primary motor cortex. Morphological increases in the ventrolateral prefrontal cortex positively correlated with disease duration, whereas increases in dorsolateral, medial, and ventromedial prefrontal areas positively correlated with the Beck depression index. Visual motion stimulation caused an increased task-dependent activity in the subgenual anterior cingulum and a significantly longer duration of the motion aftereffect in the patients. Task-based functional connectivity analyses revealed aberrant involvement of interoceptive, fear generalization, and orbitofrontal networks. INTERPRETATION: Our findings agree with some of the typical characteristics of functional dizziness syndromes, for example, excessive self-awareness, anxious appraisal, and obsessive controlling of posture. This first evidence indicates that the disease-specific mechanisms underlying PPV are related to networks involved in mood regulation, fear generalization, interoception, and cognitive control. They do not seem to be the result of aberrant processing in cortical visual, visual motion, or vestibular regions.

Clinical evaluation of the bed cycling test.

OBJECTIVE: Additionally to the forearm rolling test to detect mild unilateral upper limb dysfunction, the bed cycling test (BCT) for detection of mild to moderate lower limb dysfunction was developed, evaluated and compared to the leg holding test. METHODS: In a prospective observer-blinded study, 60 patients with MRI/CT-proven focal cerebral hemisphere lesions and a mild to moderate unilateral paresis of the lower limb (graduated MRC 3-4/5), and 60 control persons with normal imaging were examined and filmed. Nine observers blinded to the diagnosis evaluated these videos. The sensitivity, specificity and the positive and negative predictive values of the clinical tests were analyzed. RESULTS: The observers gave a correct evaluation of BCT in 35.5% of all patients with focal cerebral lesions compared to 26.0% for the leg holding test. On the other hand, observers had false negative results in 29.1% of cases with BCT and 44.7% with leg holding test. In 36.7% of patients, only BCT was pathological while leg holding test was unremarkable. The sensitivity of the combination of both tests was 0.68 (95% CI 0.61-0.75). The BCT is more sensitive (64.3%) than leg holding test (46.2%) while the specificity of leg holding test (85.6%) is higher than of BCT (70.1%) to detect a cerebral lesion affecting the lower limb. The inter-rater variability is high with no differences comparing different types of clinical experience. CONCLUSIONS: The BCT is a useful additional clinical bedside test to detect subtle unilateral cerebral lesions. The BCT is easy to perform and can be added to the routine neurological examination.

Natural history of atherosclerotic disease progression as assessed by (18)F-FDG PET/CT.

The aim of this study was to assess the impact of cardiovascular risk factors and plaque inflammation on the progression of atherosclerosis as assessed by positron emission tomography/computed tomography (PET/CT) imaging with (18)F-radiolabled fluorodeoxyglucose ((18)F-FDG). This study was designed as a retrospective cohort study. Patients who received a (18)F-FDG PET/CT scan and follow-up scan 9-24 months later without systemic inflammation or steroid medication were eligible for the study. (18)F-FDG PET/CT included a full diagnostic contrast enhanced CT scan. Cardiovascular risk factors and medication were documented. Calcified plaque volume, lumen area and (18)F-FDG uptake, quantified by the target-to-background ratio (TBR), were measured in the carotid arteries, aorta and iliac arteries. Influence of cardiovascular risk factors and vessel wall inflammation on atherosclerotic disease progression was analyzed. Ninety-four patients underwent baseline and follow-up whole body (18)F-FDG PET/CT (mean follow-up time 14.5 ± 3.5 months). Annualized calcified plaque volume increased by 15.4 % (p < 0.0001), carotid and aortic lumen area decreased by 10.5 % (p < 0.0001) and 1.7 % (p = 0.045). There was no significant difference in (18)F-FDG uptake at baseline and follow-up (mean TBR 1.44 ± 0.18 vs. 1.42 ± 0.19, p = 0.18). Multiple linear regression analysis identified hypertension as an independent predictor for total, aortic and iliac calcified plaque volume progression (all p < 0.04). Carotid lumen reduction was predicted by hypercholesterolemia (p = 0.008) while aortic lumen reduction was associated with BMI and mean (18)F-FDG uptake (p ≤ 0.005). Furthermore we observed a dose response relationship between the number of cardiovascular risk factors and calcified plaque volume progression in the aorta (p = 0.03). Findings from this study provide data on the natural history of atherosclerotic disease burden in multiple vascular beds and emphasize the value of morphological and physiologic information provided by (18)F-FDG PET/CT imaging.

Chronic subjective dizziness: Fewer symptoms in the early morning--a comparison with bilateral vestibulopathy and downbeat nystagmus syndrome.

OBJECTIVE: Chronic subjective dizziness (CSD) is a form of chronic dizziness. Many patients report fewer symptoms when they get up with an aggravation over of the day. Therefore, the change in the severity of the symptoms during daytime was evaluated and compared with other chronic vestibular diseases: bilateral vestibulopathy (BVP) and downbeat nystagmus (DBN). DESIGN/METHODS: In a prospective study 131 patients with CSD, 108 patients with BVP, and 38 patients with DBN filled out a questionnaire asking about the symptom intensity (0 = no symptoms, 1 = light, 2 = moderate, 3 = strong) at 6 time-points. The influences of duration of the disease and physical activity on the change of symptoms were also investigated. RESULTS: The symptom intensity score in CSD was lower after getting up in comparison to later time points. In BVP a strong sensation of dizziness after getting up with worsening in the evening was observed. In DBN symptoms significantly improved during daytime. In BVP, the symptom intensity scores were significantly higher in patients with symptoms more than six month as less than six month. In the other groups, no association between duration of illness and intensity of perceived dizziness could be seen. CONCLUSION: There are considerable differences in the change in symptoms between the three diseases. Taking the patient history simply asking how the symptoms are when the patient gets up in the morning and how they change during daytime can be helpful in the differential diagnosis. Having less or no symptoms after getting up may be a diagnostic criterion for CSD.

Acute Unilateral Vestibular Failure Does Not Cause Spatial Hemineglect.

OBJECTIVES: Visuo-spatial neglect and vestibular disorders have common clinical findings and involve the same cortical areas. We questioned (1) whether visuo-spatial hemineglect is not only a disorder of spatial attention but may also reflect a disorder of higher cortical vestibular function and (2) whether a vestibular tone imbalance due to an acute peripheral dysfunction can also cause symptoms of neglect or extinction. Therefore, patients with an acute unilateral peripheral vestibular failure (VF) were tested for symptoms of hemineglect. METHODS: Twenty-eight patients with acute VF were assessed for signs of vestibular deficits and spatial neglect using clinical measures and various common standardized paper-pencil tests. Neglect severity was evaluated further with the Center of Cancellation method. Pathological neglect test scores were correlated with the degree of vestibular dysfunction determined by the subjective visual vertical and caloric testing. RESULTS: Three patients showed isolated pathological scores in one or the other neglect test, either ipsilesionally or contralesionally to the VF. None of the patients fulfilled the diagnostic criteria of spatial hemineglect or extinction. CONCLUSIONS: A vestibular tone imbalance due to unilateral failure of the vestibular endorgan does not cause spatial hemineglect, but evidence indicates it causes mild attentional deficits in both visual hemifields.

Effects of acetyl-DL-leucine in patients with cerebellar ataxia: a case series.

No existing medication has yet been shown to convincingly improve cerebellar ataxia. Therefore, the identification of new drugs for its symptomatic treatment is desirable. The objective of this case series was to evaluate the efficacy of treatment of cerebellar ataxia with the amino acid acetyl-DL-leucine (Tanganil). Thirteen patients (eight males, median age 51 years) with degenerative cerebellar ataxia of different etiologies (SCA1/2, ADCA, AOA, SAOA) were treated with acetyl-DL-leucine (5 g/day) without titration for 1 week. Motor function was evaluated by changes in the Scale for the Rating and Assessment of Ataxia (SARA) and in the Spinocerebellar Ataxia Functional Index (SCAFI) during treatment compared to a baseline examination. Quality of life (EuroQol-5D-3L) and side effects were also assessed. Mean total SARA decreased remarkably (p = 0.002) from a baseline of 16.1 ± 7.1 to 12.8 ± 6.8 (mean ± SD) on medication. There were also significant improvements in sub-scores for gait (p = 0.022), speech (p = 0.007), finger-chase (p = 0.042), nose-finger-test (p = 0.035), rapid-alternating-movements (p = 0.002) and heel-to-shin (p = 0.018). Furthermore, patients showed better performance in the SCAFI consisting of the 8-m-walking-time (8 MW, p = 0.003), 9-Hole-Peg-Test of the dominant hand (9HPTD, p = 0.011) and the PATA rate (p = 0.005). Quality of life increased during treatment (p = 0.003). No side effects were reported. In conclusion, acetyl-DL-leucine significantly improved ataxic symptoms without side effects and therefore showed a good risk-benefit profile. These findings need to be confirmed in placebo-controlled trials.

Black blood MRI in suspected large artery primary angiitis of the central nervous system.

OBJECTIVES: Single case reports suggest that black blood MRI (T1-weighted fat and blood suppressed sequences with and without contrast injection; BB-MRI) may visualize intracranial vessel wall contrast enhancement (CE) in primary angiitis of the central nervous system (PACNS). In this single-center observational pilot study we prospectively investigated the value of BB-MRI in the diagnosis of large artery PACNS. METHODS: Patients with suspected large artery PACNS received a standardized diagnostic program including BB-MRI. Vessel wall CE was graded (grade 0-2) by two experienced readers blinded to clinical data and correlated to the final diagnosis. RESULTS: Four of 12 included patients received a final diagnosis of PACNS. All of them showed moderate (grade 1) to strong (grade 2) vessel wall CE at the sites of stenosis. A moderate (grade 1) vessel wall CE grade was also observed in 6 of the remaining 8 patients in whom alternative diagnoses were made: arteriosclerotic disease (n = 4), intracranial dissection (n = 1), and Moyamoya disease (n = 1). CONCLUSIONS: Our pilot study demonstrates that vessel wall CE is a frequent finding in PACNS and its mimics. Larger trials will be necessary to evaluate the utility of BB-MRI in the diagnostic workup of PACNS.

Quantification of supra-aortic arterial wall inflammation in patients with arteritis using high resolution dynamic contrast-enhanced magnetic resonance imaging: initial results in correlation to [18F]-FDG PET/CT.

OBJECTIVES: : To compare [F]- -fluoro-D-glucose (FDG) positron emission tomography (PET)/computed tomography (CT), used in clinical routine to detect inflamed arteries in patients with arteritis, with high resolution dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in its ability to measure inflammation in carotid and vertebral arteries. MATERIALS AND METHODS: : This study was performed with written informed consent, Health Insurance Portability and Accountability Act (HIPAA) compliance, and institutional review board approval. DCE-MRI of the carotid and vertebral arteries of 17 patients with suspected arteritis was acquired at 3T (2D saturation-recovery spoiled gradient echo, in plane resolution 0.625 × 0.625 mm) using a dedicated 4-channel carotid coil. Patients underwent [F] FDG-PET/CT within 1 week of the MRI scan. The blood pool-corrected mean standardized uptake value (mean target-to-background ratio [TBRmean]) was measured on PET/CT images at the identical location as the region-of-interest in the magnetic resonance images. MRI signal intensity data was analyzed to generate estimates of the tissue extraction fraction and interstitial volume using a 2-compartment model. RESULTS: : [F]-FDG PET/CT TBRmean was significantly higher in patients with than without arteritis (1.55 ± 0.34 vs. 1.06 ± 0.14, P = 0.001). Patients diagnosed with arteritis had significantly higher extraction fractions as measured by DCE-MRI than patients without arteritis (8.79% ± 2.19% vs. 5.82% ± 1.13%, P = 0.002). TBRmean correlated significantly with the extraction fraction (r = 0.73, P < 0.001). DCE-MRI and FDG-PET/CT yielded the same sensitivity (86%) and specificity (90%) for the detection of arteritis. Intra- and interreader reproducibility was good with Intraclass Correlation Coefficients of 0.82 and 0.78, respectively. CONCLUSIONS: : DCE-MRI is able to measure arterial inflammation reliably and noninvasively with good correlation to [F]-FDG PET/CT in patients suffering from arteritis of the supraaortic arteries.