Christoph Stippich

Magnetic resonance imaging correlates of physical disability in relapse onset multiple sclerosis of long disease duration.

Background: Understanding long-term disability in multiple sclerosis (MS) is a key goal of research; it is relevant to how we monitor and treat the disease. Objectives: The Magnetic Imaging in MS (MAGNIMS) collaborative group sought to determine the relationship of brain lesion load, and brain and spinal cord atrophy, with physical disability in patients with long-established MS. Methods: Patients had a magnetic resonance imaging (MRI) scan of their brain and spinal cord, from which we determined brain grey (GMF) and white matter (WMF) fractional volumes, upper cervical spinal cord cross-sectional area (UCCA) and brain T2-lesion volume (T2LV). We assessed patient disability using the Expanded Disability Status Scale (EDSS). We analysed associations between EDSS and MRI measures, using two regression models (dividing cohort by EDSS into two and four sub-groups). Results: In the binary model, UCCA (p < 0.01) and T2LV (p = 0.02) were independently associated with the requirement of a walking aid. In the four-category model UCCA (p < 0.01), T2LV (p = 0.02) and GMF (p = 0.04) were independently associated with disability. Conclusions: Long-term physical disability was independently linked with atrophy of the spinal cord and brain T2 lesion load, and less consistently, with brain grey matter atrophy. Combinations of spinal cord and brain MRI measures may be required to capture clinically-relevant information in people with MS of long disease duration.

Increased Volume and Function of Right Auditory Cortex as a Marker for Absolute Pitch

Absolute pitch (AP) perception is the auditory ability to effortlessly recognize the pitch of any given tone without external reference. To study the neural substrates of this rare phenomenon, we developed a novel behavioral test, which excludes memory-based interval recognition and permits quantification of AP proficiency independently of relative pitch cues. AP- and non-AP-possessing musicians were studied with morphological and functional magnetic resonance imaging (fMRI) and magnetoencephalography. Gray matter volume of the right Heschls gyrus (HG) was highly correlated with AP proficiency. Right-hemispheric auditory evoked fields were increased in the AP group. fMRI revealed an AP-dependent network of right planum temporale, secondary somatosensory, and premotor cortices, as well as left-hemispheric Brocas area. We propose the right HG as an anatomical marker of AP and suggest that a right-hemispheric network mediates AP perception, whereas pitch labeling takes place in the left hemisphere.

Evaluation of a new approach for semi-automatic segmentation of the cerebellum in patients with multiple sclerosis

Cerebellar dysfunction is an important contributor to disability in patients with multiple sclerosis (MS), however, few in vivo studies focused on cerebellar volume loss so far. This relates to technical challenges regarding the segmentation of the cerebellum. In this study, we evaluated the semi-automatic ECCET software for performing cerebellar volumetry using high-resolution 3D T1-MR scans in patients with MS and healthy volunteers. We performed test–retest as well as inter-observer reliability testing of cerebellar segmentation and compared the ECCET results with a fully automatic cerebellar segmentation using the FreeSurfer software pipeline in 15 MS patients. In a pilot matched-pair analysis with another data set from 15 relapsing–remitting MS patients and 15 age- and sex-matched healthy controls (HC), we assessed the feasibility of the ECCET approach to detect MS-related cerebellar volume differences. For total normalized cerebellar volume as well as grey and white matter volumes, intrarater (intraclass correlation coefficient (ICC)xa0=xa00.99, 95xa0% CIxa0=xa00.98–0.99) and interobserver agreement (ICCxa0=xa00.98, 95xa0% CIxa0=xa00.74–0.99) were strong. Comparison between ECCET and FreeSurfer results likewise yielded a good intraclass correlation (ICCxa0=xa00.86, 95xa0% CIxa0=xa00.58–0.95). Compared to HC, MS patients had significantly reduced normalized total brain, total cerebellar, and grey matter volumes (pxa0≤xa00.05). ECCET is a suitable tool for cerebellar segmentation showing excellent test–retest and inter-observer reliability. Our matched-pair analysis between MS patients and healthy volunteers suggests that the method is sensitive and reliable in detecting cerebellar atrophy in MS.

Exercise might bias skeletal-muscle fat fraction calculation from Dixon images

We examined the influence of a single exercise session on quantitative muscle fat fraction MRI measurements. Ten healthy volunteers were scanned on a 3T body scanner before and after a session of bilateral squats until muscular fatigue. Axial in- and opposed phase images were acquired at a fixed distance from the knee joint and fat fractions were calculated using a 2-point Dixon technique as well as muscle cross sectional area at the same position. After the squat session, calculated fat fraction in the quadriceps bilaterally appeared to be significantly decreased, while all but one non-exercised muscles showed no change. In conclusion exercise might modify the measured apparent fat fraction. Trials using quantitative MRI should consider the timing of scanning sessions and physical examinations to avoid bias caused by the influence of exercise on measurements.

Cortical thinning of parahippocampal subregions in very early Alzheimer's disease.

The stereotypical pattern of neurofibrillary tangle spreading in the earliest stages of typical Alzheimers dementia (AD) predicts that medial perirhinal cortex (mPRC) atrophy precedes entorhinal cortex (ERC) atrophy, whereas the status of the parahippocampal cortex (PHC) remains unclear. Atrophy studies have focused on more advanced rather than early AD patients, and usually segment the entire PRC as opposed to the mPRC versus lateral PRC (lPRC). The present study therefore determined the extent of ERC, mPRC, lPRC, and PHC atrophy in very early AD (mean Mini-Mental State Examination scorexa0= 26) patients and its presumed prodrome amnestic mild cognitive impairment (mean Mini-Mental State Examination scorexa0= 28) compared to demographically matched controls. PHG structures were manually segmented (blinded rater) and cortical thicknesses extracted. ERC and mPRC were similarly atrophied in both patient groups. The lPRC was atrophied in the AD group only. Thus, atrophic changes in very early AD broadly map onto the pattern of neurofibrillary tangle spreading and suggest that mPRC, ERC, and lPRC, but not PHC-associated functional impairments, characterize very early-stage AD.

Endovascular treatment of cervical artery dissection: ten case reports and review of the literature.

Purpose: The role of endovascular treatment in cases of cervical artery dissection (CeAD) is debatable. With an increasing number of endovascular therapies such as endovascular recanalization and embolization the number of complications such as iatrogenic dissection is also rising. We report our experience with endovascular stenting in the treatment of patients presenting with CeAD. Methods: We included all consecutive patients with CeAD (n = 168) treated in our hospital between 2001 and 2010 for our retrospective study. Patients with CeAD were considered eligible for stenting: (1) in iatrogenic dissections and (2) in noniatrogenic dissections if they suffered from recurrent ischemic events despite antithrombotic treatment. Results: During our observation period 10 out of 168 patients presenting with CeAD were selected for stenting. Several types of stents were used. Stenting was technically successful in 8 but unsuccessful in 2 patients with complete arterial occlusion. Stent-related clinically apparent complications occurred in 3 of the 10 patients. All were transient. During a mean follow-up of 47 (±24.8) months none of the patients had new cerebrovascular ischemic events. Conclusion: In our patient sample stenting due to dissection is a rare procedure performed in less than 10% of CAD patients. It should be considered as a feasible rescue treatment in cases of impending stroke despite optimal antithrombotic therapy.

Vascular Anatomy Predicts the Risk of Cerebral Ischemia in Patients Randomized to Carotid Stenting Versus Endarterectomy.

Background and Purpose— Complex vascular anatomy might increase the risk of procedural stroke during carotid artery stenting (CAS). Randomized controlled trial evidence that vascular anatomy should inform the choice between CAS and carotid endarterectomy (CEA) has been lacking. Methods— One-hundred eighty-four patients with symptomatic internal carotid artery stenosis who were randomly assigned to CAS or CEA in the ICSS (International Carotid Stenting Study) underwent magnetic resonance (n=126) or computed tomographic angiography (n=58) at baseline and brain magnetic resonance imaging before and after treatment. We investigated the association between aortic arch configuration, angles of supra-aortic arteries, degree, length of stenosis, and plaque ulceration with the presence of ≥1 new ischemic brain lesion on diffusion-weighted magnetic resonance imaging (DWI+) after treatment. Results— Forty-nine of 97 patients in the CAS group (51%) and 14 of 87 in the CEA group (16%) were DWI+ (odds ratio [OR], 6.0; 95% confidence interval [CI], 2.9–12.4; P<0.001). In the CAS group, aortic arch configuration type 2/3 (OR, 2.8; 95% CI, 1.1–7.1; P=0.027) and the degree of the largest internal carotid artery angle (≥60° versus <60°; OR, 4.1; 95% CI, 1.7–10.1; P=0.002) were both associated with DWI+, also after correction for age. No predictors for DWI+ were identified in the CEA group. The DWI+ risk in CAS increased further over CEA if the largest internal carotid artery angle was ≥60° (OR, 11.8; 95% CI, 4.1–34.1) than if it was <60° (OR, 3.4; 95% CI, 1.2–9.8; interaction P=0.035). Conclusions— Complex configuration of the aortic arch and internal carotid artery tortuosity increase the risk of cerebral ischemia during CAS, but not during CEA. Vascular anatomy should be taken into account when selecting patients for stenting. Clinical Trial Registration— URL: http://www.isrctn.com/ISRCTN25337470. Unique identifier: ISRCTN25337470.

Intravenous Thrombolysis in Patients with Stroke Taking Rivaroxaban Using Drug Specific Plasma Levels: Experience with a Standard Operation Procedure in Clinical Practice

Background and Purpose Standard operating procedures (SOP) incorporating plasma levels of rivaroxaban might be helpful in selecting patients with acute ischemic stroke taking rivaroxaban suitable for IVthrombolysis (IVT) or endovascular treatment (EVT). Methods This was a single-center explorative analysis using data from the Novel-Oral-Anticoagulants-in-Stroke-Patients-registry (clinicaltrials.gov:NCT02353585) including acute stroke patients taking rivaroxaban (September 2012 to November 2016). The SOP included recommendation, consideration, and avoidance of IVT if rivaroxaban plasma levels were <20 ng/mL, 20‒100 ng/mL, and >100 ng/mL, respectively, measured with a calibrated anti-factor Xa assay. Patients with intracranial artery occlusion were recommended IVT+EVT or EVT alone if plasma levels were ≤100 ng/mL or >100 ng/mL, respectively. We evaluated the frequency of IVT/EVT, door-to-needle-time (DNT), and symptomatic intracranial or major extracranial hemorrhage. Results Among 114 acute stroke patients taking rivaroxaban, 68 were otherwise eligible for IVT/EVT of whom 63 had plasma levels measured (median age 81 years, median baseline National Institutes of Health Stroke Scale 6). Median rivaroxaban plasma level was 96 ng/mL (inter quartile range [IQR] 18‒259 ng/mL) and time since last intake 11 hours (IQR 4.5‒18.5 hours). Twenty-two patients (35%) received IVT/EVT (IVT n=15, IVT+EVT n=3, EVT n=4) based on SOP. Median DNT was 37 (IQR 30‒60) minutes. None of the 31 patients with plasma levels >100 ng/mL received IVT. Among 14 patients with plasma levels ≤100 ng/mL, the main reason to withhold IVT was minor stroke (n=10). No symptomatic intracranial or major extracranial bleeding occurred after treatment. Conclusions Determination of rivaroxaban plasma levels enabled IVT or EVT in one-third of patients taking rivaroxaban who would otherwise be ineligible for acute treatment. The absence of major bleeding in our pilot series justifies future studies of this approach.

Imaging of Primary Brain Tumors and Metastases with Fast Quantitative 3-Dimensional Magnetization Transfer.

This study assesses whether magnetization transfer (MT) imaging provides additive information to conventional MRI in brain tumors.

New ischaemic brain lesions in cervical artery dissection stratified to antiplatelets or anticoagulants

To determine the frequency of new ischaemic or hemorrhagic brain lesions on early follow‐up magnetic resonance imaging (MRI) in patients with cervical artery dissection (CAD) and to investigate the relationship with antithrombotic treatment.