Contribution of the MP2RAGE 7T Sequence in MS Lesions of the Cervical Spinal Cord.

BACKGROUND AND PURPOSE: The detection of spinal cord lesions in patients with MS is challenging. Recently, the 3D MP2RAGE sequence demonstrated its usefulness at 3T. Benefiting from the high spatial resolution provided by ultra-high-field MR imaging systems, we aimed to evaluate the contribution of the 3D MP2RAGE sequence acquired at 7T for the detection of MS lesions in the cervical spine. MATERIALS AND METHODS: Seventeen patients with MS participated in this study. They were examined at both 3T and 7T. The MR imaging examination included a Magnetic Imaging in MS (MAGNIMS) protocol with an axial T2*-WI gradient recalled-echo sequence ("optimized MAGNIMS protocol") and a 0.9-mm isotropic 3D MP2RAGE sequence at 3T, as well as a 0.7-mm isotropic and 0.3-mm in-plane-resolution anisotropic 3D MP2RAGE sequences at 7T. Each data set was read by a consensus of radiologists, neurologists, and neuroscientists. The number of lesions and their topography, as well as the visibility of the lesions from one set to another, were carefully analyzed. RESULTS: A total of 55 lesions were detected. The absolute number of visible lesions differed among the 4 sequences (linear mixed effect ANOVA, P = .020). The highest detection was observed for the two 7T sequences with 51 lesions each (92.7% of the total). The optimized 3T MAGNIMS protocol and the 3T MP2RAGE isotropic sequence detected 41 (74.5%) and 35 lesions (63.6%), respectively. CONCLUSIONS: The 7T MP2RAGE sequences detected more lesions than the 3T sets. Isotropic and anisotropic acquisitions performed comparably. Ultra-high-resolution sequences obtained at 7T improve the identification and delineation of lesions of the cervical spinal cord in MS.

Alterations of Microstructure and Sodium Homeostasis in Fast Amyotrophic Lateral Sclerosis Progressors: A Brain DTI and Sodium MRI Study.

BACKGROUND AND PURPOSE: While conventional MR imaging has limited value in amyotrophic lateral sclerosis, nonconventional MR imaging has shown alterations of microstructure using diffusion MR imaging and recently sodium homeostasis with sodium MR imaging. We aimed to investigate the topography of brain regions showing combined microstructural and sodium homeostasis alterations in amyotrophic lateral sclerosis subgroups according to their disease-progression rates. MATERIALS AND METHODS: Twenty-nine patients with amyotrophic lateral sclerosis and 24 age-matched healthy controls were recruited. Clinical assessments included disease duration and the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale. Patients were clinically differentiated into fast (n = 13) and slow (n = 16) progressors according to the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale progression rate. 3T MR imaging brain protocol included 1H T1-weighted and diffusion sequences and a 23Na density-adapted radial sequence. Quantitative maps of diffusion with fractional anisotropy, mean diffusivity, and total sodium concentration were measured. The topography of diffusion and sodium abnormalities was assessed by voxelwise analyses. RESULTS: Patients with amyotrophic lateral sclerosis showed significantly higher sodium concentrations and lower fractional anisotropy, along with higher sodium concentrations and higher mean diffusivity compared with healthy controls, primarily within the corticospinal tracts, corona radiata, and body and genu of the corpus callosum. Fast progressors showed wider-spread abnormalities mainly in the frontal areas. In slow progressors, only fractional anisotropy measures showed abnormalities compared with healthy controls, localized in focal regions of the corticospinal tracts, the body of corpus callosum, corona radiata, and thalamic radiation. CONCLUSIONS: The present study evidenced widespread combined microstructural and sodium homeostasis brain alterations in fast amyotrophic lateral sclerosis progressors.

The Sylvia Lawry Centre for Multiple Sclerosis Research (SLCMSR)--Critical review facing the 20 anniversary.

The SLCMSR was formed as an international Multiple Sclerosis Trials, Research and Resource Center to identify clinical MRI and other predictors of the course of multiple sclerosis (MS) based on a large database of natural history and clinical trial data. Using an elaborate validation concept several key findings were published, challenging established outcome parameters and their assessment in MS such as disability ratings with Expanded Disability Status Scale (EDSS), relapses and MRI endpoints. Sustained increase of EDSS appeared to be an invalid outcome for 2-3 year clinical trials at least in patients with relapsing-remitting MS. The number of gadolinium-enhancing lesions and T2-lesion load on MRI were shown not to have a meaningful additional predictive value for the disease course. These issues risen some 15 years ago had triggered controversial discussions which have also been noticed by regulatory authorities and they all have not been resolved. In addition the SLCMSR contributed to the development of new outcomes such as real-world walking speed as an attractive, ecologically valid tool based on a wearable device. A so-called evidence-based-decision-support tool was constructed to provide individual prognostic estimates based on a matching algorithm to a given database. This paper condensates the findings of 20 years of critical MS research.

Perfusion-weighted techniques in MRI grading of pediatric cerebral tumors: efficiency of dynamic susceptibility contrast and arterial spin labeling.

PURPOSE: Dynamic susceptibility contrast (DSC) and arterial spin labeling (ASL) perfusion MRI are applied in pediatric brain tumor grading, but their value for clinical daily practice remains unclear. We explored the ability of ASL and DSC to distinguish low- and high-grade lesions, in an unselected cohort of pediatric cerebral tumors. METHODS: We retrospectively compared standard perfusion outcomes including blood volume, blood flow, and time parameters from DSC and ASL at 1.5T or 3T MRI scanners of 46 treatment-naive patients by drawing ROI via consensus by two neuroradiologists on the solid portions of every tumor. The discriminant abilities of perfusion parameters were evaluated by receiver operating characteristic (ROC) over the entire cohort and depending on the tumor location and the magnetic field. RESULTS: ASL and DSC parameters showed overall low to moderate performances to distinguish low- and high-grade tumors (area under the curve: between 0.548 and 0.697). Discriminant abilities were better for tumors located supratentorially (AUC between 0.777 and 0.810) than infratentorially, where none of the metrics reached significance. We observed a better differentiation between low- and high-grade cancers at 3T than at 1.5-T. For infratentorial tumors, time parameters from DSC performed better than the commonly used metrics (AUC ≥ 0.8). CONCLUSION: DSC and ASL show moderate abilities to distinguish low- and high-grade brain tumors in an unselected cohort. Absolute value of K2, TMAX, tMIP, and normalized value of TMAX of the DSC appear as an alternative to conventional parameters for infratentorial tumors. Three Tesla evaluation should be favored over 1.5-Tesla.

MOG-IgG in primary and secondary chronic progressive multiple sclerosis: a multicenter study of 200 patients and review of the literature.

BACKGROUND: Antibodies to human full-length myelin oligodendrocyte glycoprotein (MOG-IgG) as detected by new-generation cell-based assays have recently been described in patients presenting with acute demyelinating disease of the central nervous system, including patients previously diagnosed with multiple sclerosis (MS). However, only limited data are available on the relevance of MOG-IgG testing in patients with chronic progressive demyelinating disease. It is unclear if patients with primary progressive MS (PPMS) or secondary progressive MS (SPMS) should routinely be tested for MOG-IgG. OBJECTIVE: To evaluate the frequency of MOG-IgG among patients classified as having PPMS or SPMS based on current diagnostic criteria. METHODS: For this purpose, we retrospectively tested serum samples of 200 patients with PPMS or SPMS for MOG-IgG using cell-based assays. In addition, we performed a review of the entire English language literature on MOG-IgG published between 2011 and 2017. RESULTS: None of 139 PPMS and 61 SPMS patients tested was positive for MOG-IgG. Based on a review of the literature, we identified 35 further MOG-IgG tests in patients with PPMS and 55 in patients with SPMS; the only reportedly positive sample was positive just at threshold level and was tested in a non-IgG-specific assay. In total, a single borderline positive result was observed among 290 tests. CONCLUSION: Our data suggest that MOG-IgG is absent or extremely rare among patients with PPMS or SPMS. Routine screening of patients with typical PPMS/SPMS for MOG-IgG seems not to be justified.

Perceptions on the value of bodily functions in multiple sclerosis.

BACKGROUND: In neurological diseases presenting with a plethora of symptoms, the value of bodily functions for a given patient might be a guide for clinical management. Multiple sclerosis (MS) is paradigmatic in this respect, and little is known about the value of different bodily functions of patients and their physicians' perceptions. METHODS: In a multicenter study, 171 patients with relapsing-remitting multiple sclerosis (RRMS), 61% with a clinically active disease within the last 2 years were followed over up to 3 years and yearly patients and their study physician rated on the perceived value of 13 bodily functions via a priority list. Differences between patients and physicians as well as modulating disease demographic factors were analyzed. RESULTS: Patients with RRMS rated visual function followed by thinking and memory and walking highest while physicians stressed mobility, followed by thinking and memory and alertness most. Ratings were independent from disease duration or disability. Strongest value judgment differences were seen in swallowing regarded more relevant by patients and hand function regarded more relevant by physicians. In general, patients' and physicians' ratings through time were quite stable. Collapsing physical items into a physical functioning scale and mental items in a mental function scale, both dimensions were regarded equally important by patients while physicians underscored physical functioning (P = .016). CONCLUSION: There are differences between patients and physicians in value statements of bodily functions in MS. In particular, visual functioning is under-recognized by physicians.

Low clinical conversion rate in clinically isolated syndrome patients - diagnostic benefit of McDonald 2010 criteria?

BACKGROUND AND PURPOSE: New diagnostic criteria of multiple sclerosis (MS) increase the number of patients being diagnosed with MS whilst a substantial part might not convert to clinically definite MS (CDMS). The diagnostic accuracy of the McDonald 2005 and 2010 criteria for conversion to CDMS was evaluated in an unselected cohort of patients in whom an MS diagnostic work-up was decided. METHODS: Clinical, magnetic resonance imaging and cerebrospinal fluid data were analysed for all patients who presented with symptoms suspicious for MS at the university based MS outpatient clinic between 2006 and 2010 (n = 165). RESULTS: Follow-up was available for 131 patients. During the mean follow-up period of 2 years, 19% of patients developed CDMS whereas 64% of the patients fulfilling McDonald 2010 criteria did not convert to CDMS. CONCLUSION: The low clinical conversion rate indicates that the new diagnostic criteria may increase the incidence of MS cases with a less active disease course.

No relevant impact of ambient temperature on disability measurements in a large cohort of patients with multiple sclerosis.

BACKGROUND AND PURPOSE: Many patients with multiple sclerosis (MS) report a worsening of symptoms due to high ambient temperatures, but objective data about this association are rare and contradictory. The aim of this study was to investigate the influence of ambient temperature on standard clinical tests. METHODS: We extracted the Symbol Digit Modality Test, Nine Hole Peg Test, Timed 25 Foot Walk (T25FW), Timed Tandem Walk, Expanded Disability Status Scale (EDSS) and quality-of-life items on cognition, fatigue and depression from our clinical database and matched them to historical temperatures. We used linear mixed-effect models to investigate the association between temperature and outcomes. RESULTS: A total of 1254 patients with MS (mean age, 42.7 years; 69.9% females; 52.1% relapsing-remitting MS, mean EDSS, 3.8) had 5751 assessments between 1996 and 2012. We observed a worsening in the T25FW with higher ambient temperatures in moderately disabled patients (EDSS ≥ 4) but not in less disabled patients. However, an increase of 10°C prolonged the T25FW by just 0.4 s. Other outcomes were not associated with ambient temperatures. CONCLUSIONS: Higher ambient temperature might compromise walking capabilities in patients with MS with a manifest walking impairment. However, effects are small and not detectable in mildly disabled patients. Hand function, cognition, mood and fatigue do not appear to be correlated with ambient temperature.

T1 Recovery Is Predominantly Found in Black Holes and Is Associated with Clinical Improvement in Patients with Multiple Sclerosis.

BACKGROUND AND PURPOSE: Quantitative MR imaging parameters help to evaluate disease progression in multiple sclerosis and increase correlation with clinical disability. We therefore hypothesized that T1 values might be a marker for ongoing tissue damage or even remyelination and may help increase clinical correlation. MATERIALS AND METHODS: MR imaging was performed in 17 patients with relapsing-remitting MS at baseline and after 12 months of starting immunotherapy with dimethyl fumarate. On baseline images, lesion segmentation was performed for normal-appearing white matter, T2 hyperintense (FLAIR lesions), T1 hypointense (black holes), and contrast-enhancing lesions, and T1 relaxation times were obtained at baseline and after 12 months. Changes in clinical status were assessed by using the Expanded Disability Status Scale and Symbol Digit Modalities Test at both dates (Expanded Disability Status Scale-difference/Symbol Digit Modalities Test-diff). RESULTS: The highest T1 relaxation time at baseline was measured in black holes (1460.2 ± 209.46 ms) followed by FLAIR lesions (1400.38 ± 189.1 ms), pure FLAIR lesions (1327.5 ± 210.04 ms), contrast-enhancing lesions (1205.59 ± 199.95 ms), and normal-appearing white matter (851.34 ± 30.61 ms). After 12 months, T1 values had decreased significantly in black holes (1369.4 ± 267.81 ms), contrast-enhancing lesions (1079.57 ± 183.36 ms) (both P < .001), and normal-appearing white matter (841.98 ± 36.1 ms, P = .006). With the Jonckheere-Terpstra Test, better clinical scores were associated with decreasing T1 relaxation times in black holes (P < .05). CONCLUSIONS: T1 relaxation time is a useful quantitative MR imaging technique, which helps detect changes in MS lesions with time. We assume that these changes are associated with the degree of myelination within the lesions themselves and are pronounced in black holes. Additionally, decreasing T1 values in black holes were associated with clinical improvement.

Improved Lesion Detection by Using Axial T2-Weighted MRI with Full Spinal Cord Coverage in Multiple Sclerosis.

BACKGROUND AND PURPOSE: Identification of lesions in specific locations gains importance in multiple sclerosis imaging diagnostic criteria. In clinical routine, axial scans are usually exclusively obtained to depict the cervical spinal cord or used to confirm suspected lesions on sagittal scans. We sought to evaluate the detection rate for MS lesions on axial T2WI scans with full spinal cord coverage in comparison with sagittal scans. MATERIALS AND METHODS: One hundred fifteen patients with definite or suspected MS underwent an MR imaging examination including 3-mm sagittal and 3.5-mm axial T2-weighted images with full spinal cord coverage. T2WI lesions were identified on axial and sagittal scans independently by 2 raters. Axial diameter, craniocaudal extension, lesion intensity, and location were analyzed. RESULTS: Four hundred forty-nine of 509 (88.2%) lesions were detected on axial and 337/509 (66.2%) on sagittal scans. Only 277/449 (61.7%) axial lesions were also detected on sagittal images. The number of lesions visible on sagittal and axial images was dependent on the axial lesion diameter (P < .001). CONCLUSIONS: Axial T2WI scans with full spinal cord coverage showed 22% more lesions in patients with MS in comparison with sagittal scans, especially for lesions with small axial diameters. We suggest including biplanar spinal MR imaging with full spinal cord coverage for lesion detection in MS in clinical routine and for clinical studies.

Chronic T2 Lesions in Multiple Sclerosis are Heterogeneous Regarding Phase MR Imaging.

PURPOSE: Phase imaging provides additional information on multiple sclerosis (MS) lesions and may in combination with mean diffusivity (MD) and magnetization transfer ratio (MTR) help differentiating heterogeneity of MS lesion pathology. METHODS: Magnetic resonance imaging (MRI) was performed in 23 MS patients including diffusion tensor imaging (DTI), magnetization transfer imaging (MTI), and SWI. Mean values (MTR, MD, and homodyne filtered phase) from 138 chronic MS lesions and normal appearing white matter (NAWM) were obtained and correlations examined. For explorative analysis, a divisive hierarchical clustering algorithm was applied. RESULTS: Phase characteristics were an independent characteristic of chronic T2 lesions, as MTR and MD were not correlated with phase values (R = - 0.23, R = - 0.18). Dependent on MTR, MD, and phase, cluster analysis led to five lesion groups. Of the two groups with phase values close to NAWM, one presented with highest MD and most severe MTR decrease (p = 0.01), the other with slight MD increase and MTR decrease. Two lesion groups with highest phase values (p = 0.01) displayed slightly increased MD and moderate decrease in MTR. Clinical data including EDSS, disease duration, and age did not differ significantly between groups. CONCLUSIONS: Increased phase is predominantly detectable in lesions with clear MTR decrease but only moderate MD increase. Phase images seem to represent an independent parameter for MS lesion characterization and may provide additional information on MS lesion heterogeneity.

[Stem cell transplantation for multiple sclerosis. Hamburg experiences and state of international research]. / Stammzelltransplantation bei Multipler Sklerose. Hamburger Erfahrungen und internationaler Forschungsstand.

BACKGROUND: Autologous hematopoietic stem cell transplantation (aHSCT) is still not the standard treatment for highly inflammatory multiple sclerosis (MS). Even though randomized controlled trials are lacking, predictors for treatment response have been established. Since 2007, ten patients have received aHSCT in Hamburg. OBJECTIVE: To present observational data from patients treated in Hamburg and a review of the literature. METHODS: Descriptive statistics were used for evaluating the course of the expanded disability status scale (EDSS) as a measure for clinical outcome, magnetic resonance imaging (MRI) and neuropsychology. New gadolinium and T2-MRI uptake lesions per scan were compared. In addition, a systematic review of the currently available literature was performed. RESULTS: The Hamburg series can be divided in two groups, one group including four patients with chronic progressive MS with low inflammatory activity (median EDSS = 6.25, 0.5 relapses per year, no gadolinium-enhancing lesions) and the other group including six patients with mild to moderate disability, relapses and inflammatory activity (median EDSS = 4.25, 1 relapse per year, 2 gadolinium-enhancing lesions). The median follow-up was 2.4 years. While the first group did not seem to benefit from aHSCT, an improvement in five out of six patients was observed in the second group. New T2 lesions occurred within the first 6 months but gadolinium-enhancing lesions were not observed (p < 0.05). A systematic literature search identified a higher efficacy of aHSCT in younger, less disabled MS patients with inflammatory activity, similar to the findings from Hamburg. CONCLUSION: Cohort reports describe aHSCT as a safe and efficient treatment option in highly inflammatory MS. Based on these data aHSCT seems to be a reasonable option in selected patients with highly inflammatory MS but a randomized controlled trial is warranted.

Ecological validity of walking capacity tests in multiple sclerosis.

BACKGROUND: Ecological validity implicates in how far clinical assessments refer to real life. Short clinical gait tests up to ten meters and 2- or 6-Minutes Walking Tests (2MWT/6MWT) are used as performance-based outcomes in Multiple Sclerosis (MS) studies and considered as moderately associated with real life mobility. OBJECTIVE: To investigate the ecological validity of 10 Meter Walking Test (10mWT), 2MWT and 6MWT. METHODS: Persons with MS performed 10mWT, 6MWT including 2MWT and 7 recorded days by accelerometry. Ecological validity was assumed if walking tests represented a typical walking sequence in real-life and correlations with accelerometry parameters were strong. RESULTS: In this cohort (n=28, medians: age=45, EDSS=3.2, disease duration=9 years), uninterrupted walking of 2 or 6 minutes occurred not frequent in real life (2.61 and 0.35 sequences/day). 10mWT correlated only with slow walking speed quantiles in real life. 2MWT and 6MWT correlated moderately with most real life walking parameters. CONCLUSION: Clinical gait tests over a few meters have a poor ecological validity while validity is moderate for 2MWT and 6MWT. Mobile accelerometry offers the opportunity to control and improve the ecological validity of MS mobility outcomes.

Introducing a new method to assess vision: Computer-adaptive contrast-sensitivity testing predicts visual functioning better than charts in multiple sclerosis patients.

BACKGROUND: Impaired low-contrast visual acuity (LCVA) is common in multiple sclerosis (MS) and other neurological diseases. Its assessment is often limited to selected contrasts, for example, 2.5% or 1.25%. Computerized adaptive testing with the quick contrast-sensitivity function (qCSF) method allows assessment across expanded contrast and spatial frequency ranges. OBJECTIVE: The objective of this article is to compare qCSF with high- and low-contrast charts and patient-reported visual function. METHODS: We enrolled 131 consecutive MS patients (mean age 39.6 years) to assess high-contrast visual acuity (HCVA) at 30 cm and 5 m, low-contrast vision with Sloan charts at 2.5% and 1.25%, qCSF and the National Eye Institute Visual Functioning Questionnaire (NEIVFQ). Associations between the different measures were estimated with linear regression models corrected for age, gender and multiple testing. RESULTS: The association between qCSF and Sloan charts (R2 = 0.68) was higher than with HCVA (5 m: R2 = 0.5; 30 cm: R2 = 0.41). The highest association with NEIVFQ subscales was observed for qCSF (R2 0.20-0.57), while Sloan charts were not associated with any NEIVFQ subscale after correction for multiple testing. CONCLUSION: The qCSF is a promising new outcome for low-contrast vision in MS and other neurological diseases. Here we show a closer link to patient-reported visual function than standard low- and high-contrast charts.

A 3meter Timed Tandem Walk is an early marker of motor and cerebellar impairment in fully ambulatory MS patients.

BACKGROUND: Mobility assessment in Multiple Sclerosis (MS) is crucial for trials and individual patient counseling. Up to now, standard tests as the Timed 25-Foot Walk (T25FW) are restricted by floor effects in mildly disabled patients. The 3-meter Timed Tandem Walk (TTW) as a possibly more sensitive measure has not been investigated yet. OBJECTIVE: To investigate sensitivity and specificity of the TTW and T25FW to detect mild clinical impairment in a large cohort of MS patients. METHODS: We extracted T25FW, TTW and EDSS from our UMC patient database (2009-2012). After randomization into an explorative (n = 497) and validation (n = 228) cohort, we calculated change rates and performed ROC analyses of gait tests and EDSS including Functional System Scores. RESULTS: Between disability stages of EDSS 0-2.5 and EDSS 3.0-4.0, the mean TTW difference was 4s (T25FW = 0.9s). The accuracy to separate between EDSS groups was moderate but identical for both tests (ROC-AUC T25FW = 0.79, TTW = 0.80, p = 0.4). TTW had a higher sensitivity and specificity to differentiate between asymptomatic and symptomatic patients concerning FS motor/cerebellar scores (ROC-AUC T25FW = 0.71, TTW = 0.75, p < 0.05). All hypotheses could be validated in the second cohort. CONCLUSION: A 3-m Timed Tandem Walk is a standardized test that is easy to implement to detect impairment of the motor or cerebellar system in fully ambulatory MS patients. Based on the complex-task character, TTW is a potential new outcome measure for MS mobility in mildly disabled patients and can act as easily accessible and significant additional information in patient counseling.

Comparison of patient-reported outcome measures in multiple sclerosis.

BACKGROUND: Patient-reported outcome measurements (PROMS) have been proposed sensitive outcome parameters in multiple sclerosis (MS). In this study, we assessed a German version of the Multiple Sclerosis Impact Scale (MSIS-29) and a revised version of the Hamburg Quality of Life Questionnaire in Multiple Sclerosis (HAQUAMS) in comparison with rater- and physician-based tools. METHODS: Consecutive MS patients (n = 117) of the MS outpatient unit were included. In addition to MSIS-29 and HAQUAMS, the following parameters were obtained: Expanded Disability Status Scale (EDSS) and modified Multiple Sclerosis Functional Composite (MSFC) [9-hole peg test (9HPT), 25-foot walk test and symbol digit modalities test]. We investigated validity, internal consistency and test-retest reliability as well as correlation between these measures. RESULTS: Internal consistency (Cronbach's α ≤ 0.96) and test-retest coefficients (ICC ≤ 0.87) of both scales were high and satisfied psychometric standards. Convergent and discriminant validity was supported by direction, magnitude and pattern of correlation with other rater-based measures depending on the functional subdomain. Both MSIS-29 and HAQUAMS correlated with EDSS (ρ = 0.55 vs 0.62), but stronger correlation was found between MSIS-29 and HAQUAMS total score (ρ = 0.90). Both scales distinguished between patient groups of varied disease severity and cognitive impairment. CONCLUSION: Patient-reported outcome measurements as MSIS-29 and HAQUAMS seem to be valid instruments to detect different impairment levels in comparison with traditional rater-based instruments like EDSS or MSFC.

Long-term treatment risks in multiple sclerosis: risk knowledge and risk perception in a large cohort of mitoxantrone-treated patients.

BACKGROUND: Balancing treatment benefits and risks is part of a shared decision-making process before initiating any treatment in multiple sclerosis (MS). Patients understand, appreciate and profit from evidence-based patient information (EBPI). While these processes are well known, long-term risk awareness and risk processing of patients has not been studied. Mitoxantrone treatment in MS is associated with long-term major potential harms - leukaemia (LK) and cardiotoxicity (CT). The risk knowledge and perception among patients currently or previously treated with mitoxantrone is unknown. OBJECTIVES: The objective of this article is to conduct a retrospective cohort study in greater Hamburg, Germany, to estimate risk awareness and perception in MS patients treated with mitoxantrone. METHODS: MS patients with at least one dose of mitoxantrone between 1991 and 2010 from six major MS centres in greater Hamburg received a questionnaire assessing risk awareness and perception as well as a written EBPI about mitoxantrone-associated LK and CT. RESULTS: Fifty-one per cent in the cohort of n = 575 patients returned the questionnaire. Forty per cent correctly estimated the risk of LK (CT 16%); 56% underestimated the risk (CT 82%). Reading the information increased the accuracy of LK risk estimation, and patients did not report an increase of worries. The EBPI was appreciated and recommended by 85%. CONCLUSION: Risk awareness of mitoxantrone-treated patients is insufficient, but can be increased by EBPI without increasing worries. Continued patient information during and after treatment should be implemented in management algorithms.

[Chronic facial pain due to a brainstem cavernoma]. / Therapieresistenter Gesichtsschmerz durch ein Hirnstammkavernom.

Idiopathic trigeminal neuralgia is almost always associated with pathological nerve/vessel contact. Symptomatic forms of trigeminal neuralgia include cases of multiple sclerosis, infratentorial tumours and postherpetic neuralgia. Vascular malformations causing neuralgia have rarely been reported. We present the case of a 55-year old woman, who suffered from facial pain and ptosis on her left side. Repeated neurological examinations as well as repeated magnetic resonance imaging did not lead to a definite diagnosis or therapy. The pain suddenly stopped three weeks before admission and only a slight left sided facial hypaesthesia persisted. Reevaluating the older MRI we found a small signal alteration of 2 mm in the caudal part of the left trigeminal nucleus. A new MRI showed a subacute haemorrhage into a small brainstem cavernoma, which must have caused the pain and later on the hypaesthesia. Small vascular malformations are a rare cause of neuropathic facial pain.