A decade of natalizumab and PML: Has there been a tacit transfer of risk acceptance?

The interplay between each of the stakeholder's responsibilities and desires clearly has resulted in continued widespread use of natalizumab with substantial risks and an ongoing quest for better risk mitigation. In the United States, regulatory actions codified the process of risk acceptance-and risk transfer-by escalating monitoring and information transfer to physicians and patients. Management of medication-related risks is a core function of regulatory agencies such as the Food and Drug Administration (FDA), European Medicines Agency (EMA), and the medical community. The interaction among stakeholders in medicine, pharma, regulatory bodies, physicians, and patients, sometimes has changed without overt review and discussion. Such is the case for natalizumab, an important and widely used disease-modifying therapy for multiple sclerosis. A rather silent but very considerable shift, effectively transferring increased risk for progressive multifocal leukoencephalopathy (PML) to the physicians and patients, has occurred in the past decade. We believe this changed risk should be clearly recognized and considered by all the stakeholders

The impact of the Covid-19 pandemic on adult diagnostic neuroradiology in Europe

PURPOSE: The purpose of this survey was to understand the impact the Covid-19 pandemic has or has had on the work, training, and wellbeing of professionals in the field of diagnostic neuroradiology. METHODS: A survey was emailed to all ESNR members and associates as well as distributed via professional social media channels. The survey was held in the summer of 2020 when the first wave had subsided in most of Europe, while the second wave was not yet widespread. The questionnaire featured a total of 46 questions on general demographics, the various phases of the healthcare crisis, and the numbers of Covid-19 patients. RESULTS: One hundred sixty-seven responses were received from 48 countries mostly from neuroradiologists (72%). Most commonly taken measures during the crisis phase were reduction of outpatient exams (87%), reduction of number of staff present in the department (83%), reporting from home (62%), and shift work (54%). In the exit phase, these measures were less frequently applied, but reporting from home was still frequent (33%). However, only 22% had access to a fully equipped work station at home. While 81% felt safe at work during the crisis, fewer than 50% had sufficient personal protection equipment for the duration of the entire crisis. Mental wellbeing is an area of concern, with 61% feeling (much) worse than usual. Many followed online courses/congresses and considered these a viable alternative for the future. CONCLUSION: The Covid-19 pandemic substantially affected the professional life as well as personal wellbeing of neuroradiologists

Somatotopic organization of corticospinal/corticobulbar motor tracts in controls and patients with tumours: A combined fMRI–DTI study

Objectives: To investigate the relative somatotopic organization of the motor corticospinal/corticobulbar foot, hand, lip and tongue fascicles by combining fMRI with DTI and to examine the influence of subjacent intrinsic tumours on these fascicles. Methods: The study was approved by the local ethics committee. Seven male and three female volunteers (median age: 35 years) and one female and eight male patients with brain tumours (median age: 37 years) were scanned on a 1.5-T MRI scanner. fMRI data, analysed using SPM5, identified the motor task-driven fMRI grey matter activations of the hand, foot, lips and tongue as seed regions for probabilistic tractography. The relationship between the components of the CST was assessed and the distances between them were measured. A statistical comparison was performed comparing these distances in the group of healthy hemispheres with those of the group of non-affected hemispheres and healthy hemispheres. Results: Hand fascicles were identified in all subjects (38/38, 100%), followed by foot (32/38, 84%), lip (31/38, 81%) and tongue fascicles (28/38, 74%). At superior levels, the hand fascicles were anterolateral to the foot fascicles in 77–93% of healthy hemispheres (HH), in 50–71% of non-affected patients' hemispheres (pH) and in 67–89% of affected PH. At inferior levels, the hand fascicles were either anteromedial in 46–45% of HH or anterior in 75% of non-affected PH and in 67–83% of affected PH. Tongue and lip fascicles overlapped in 25–45% of HH, in 10–20% of non-affected PH and in 15–25% of affected PH. No significant difference was found between the group of affected hemispheres and that of healthy and non-affected hemispheres. Conclusion: The somatotopy of the hand fascicles in relation to the foot fascicles was anterolateral in patients and volunteers at superior levels but anteromedial in volunteers and mostly anterior in patients at inferior levels. The lip and tongue fascicles generally overlapped. Intracranial tumours displaced the motor fascicles without affecting their relative somatotopy

Muscle "islands": an MRI signature distinguishing neurogenic from myopathic causes of early onset distal weakness

Muscle MRI has an increasing role in diagnosis of inherited neuromuscular diseases, but no features are known which reliably differentiate myopathic and neurogenic conditions. Using patients presenting with early onset distal weakness, we aimed to identify an MRI signature to distinguish myopathic and neurogenic conditions. We identified lower limb MRI scans from patients with either genetically (n=24) or clinically (n=13) confirmed diagnoses of childhood onset distal myopathy or distal spinal muscular atrophy. An initial exploratory phase reviewed 11 scans from genetically confirmed patients identifying a single potential discriminatory marker concerning the pattern of fat replacement within muscle, coined “islands”. This pattern comprised small areas of muscle tissue with normal signal intensity completely surrounded by areas with similar intensity to subcutaneous fat. In the subsequent validation phase, islands correctly classified scans from all 12 remaining genetically confirmed patients, and 12/13 clinically classified patients. In the genetically confirmed patients MRI classification of neurogenic/myopathic aetiology had 100% accuracy (24/24) compared with 65% accuracy (15/23) for EMG, and 79% accuracy (15/19) for muscle biopsy. Future studies are needed in other clinical contexts, however the presence of islands appears to highly suggestive of a neurogenic aetiology in patients presenting with early onset distal motor weakness

Apparent diffusion coefficient for molecular subtyping of non-gadolinium-enhancing WHO grade II/III glioma: volumetric segmentation versus two-dimensional region of interest analysis

OBJECTIVES: To investigate if quantitative apparent diffusion coefficient (ADC) measurements can predict genetic subtypes of non-gadolinium-enhancing gliomas, comparing whole tumour against single slice analysis. METHODS: Volumetric T2-derived masks of 44 gliomas were co-registered to ADC maps with ADC mean (ADCmean) calculated. For the slice analysis, two observers placed regions of interest in the largest tumour cross-section. The ratio (ADCratio) between ADCmeanin the tumour and normal appearing white matter was calculated for both methods. RESULTS: Isocitrate dehydrogenase (IDH) wild-type gliomas showed the lowest ADC values throughout (p < 0.001). ADCmeanin the IDH-mutant 1p19q intact group was significantly higher than in the IDH-mutant 1p19q co-deleted group (p < 0.01). A volumetric ADCmeanthreshold of 1201 × 10-6mm2/s identified IDH wild-type with a sensitivity of 83% and a specificity of 86%; a volumetric ADCratiocut-off value of 1.65 provided a sensitivity of 80% and a specificity of 92% (area under the curve (AUC) 0.9-0.94). A slice ADCratiothreshold for observer 1 (observer 2) of 1.76 (1.83) provided a sensitivity of 80% (86%), specificity of 91% (100%) and AUC of 0.95 (0.96). The intraclass correlation coefficient was excellent (0.98). CONCLUSIONS: ADC measurements can support the distinction of glioma subtypes. Volumetric and two-dimensional measurements yielded similar results in this study. KEY POINTS: • Diffusion-weighted MRI aids the identification of non-gadolinium-enhancing malignant gliomas • ADC measurements may permit non-gadolinium-enhancing glioma molecular subtyping • IDH wild-type gliomas have lower ADC values than IDH-mutant tumours • Single cross-section and volumetric ADC measurements yielded comparable results in this study

FLAIR-only joint volumetric analysis of brain lesions and atrophy in clinically isolated syndrome (CIS) suggestive of multiple sclerosis

Background: MRI assessment in multiple sclerosis (MS) focuses on the presence of typical white matter (WM) lesions. Neurodegeneration characterised by brain atrophy is recognised in the research field as an important prognostic factor. It is not routinely reported clinically, in part due to difficulty in achieving reproducible measurements. Automated MRI quantification of WM lesions and brain volume could provide important clinical monitoring data. In general, lesion quantification relies on both T1 and FLAIR input images, while tissue volumetry relies on T1. However, T1-weighted scans are not routinely included in the clinical MS protocol, limiting the utility of automated quantification. Objectives: We address an aspect of this important translational challenge by assessing the performance of FLAIR-only lesion and brain segmentation, against a conventional approach requiring multi-contrast acquisition. We explore whether FLAIR-only grey matter (GM) segmentation yields more variability in performance compared with two-channel segmentation; whether this is related to field strength; and whether the results meet a level of clinical acceptability demonstrated by the ability to reproduce established biological associations. Methods: We used a multicentre dataset of subjects with a CIS suggestive of MS scanned at 1.5T and 3T in the same week. WM lesions were manually segmented by two raters, ‘manual 1′ guided by consensus reading of CIS-specific lesions and ‘manual 2′ by any WM hyperintensity. An existing brain segmentation method was adapted for FLAIR-only input. Automated segmentation of WM hyperintensity and brain volumes were performed with conventional (T1/T1 + FLAIR) and FLAIR-only methods. Results: WM lesion volumes were comparable at 1.5T between ‘manual 2′ and FLAIR-only methods and at 3T between ‘manual 2′, T1 + FLAIR and FLAIR-only methods. For cortical GM volume, linear regression measures between conventional and FLAIR-only segmentation were high (1.5T: α = 1.029, R2 = 0.997, standard error (SE) = 0.007; 3T: α = 1.019, R2 = 0.998, SE = 0.006). Age-associated change in cortical GM volume was a significant covariate in both T1 (p = 0.001) and FLAIR-only (p = 0.005) methods, confirming the expected relationship between age and GM volume for FLAIR-only segmentations. Conclusions: FLAIR-only automated segmentation of WM lesions and brain volumes were consistent with results obtained through conventional methods and had the ability to demonstrate biological effects in our study population. Imaging protocol harmonisation and validation with other MS phenotypes could facilitate the integration of automated WM lesion volume and brain atrophy analysis as clinical tools in radiological MS reporting

Reproducibility, and age, body-weight and gender dependency of candidate skeletal muscle MRI outcome measures in healthy volunteers

Quantitative magnetic resonance imaging (MRI) can potentially meet the pressing need for objective, sensitive, reproducible outcome measures in neuromuscular disease trials. We tested, in healthy volunteers, the consistency, reliability and sensitivity to normal inter-subject variation of MRI methods targeted to lower limb muscle pathology to inform the design of practical but comprehensive MRI outcome measure protocols for use in imminent patient studies

MS Cortical Lesions on DIR: Not Quite What They Seem?

Accurate identification and localization of cortical gray matter (CGM) lesions in MS is important when determining their clinical relevance. Double inversion recovery (DIR) scans have been widely used to detect MS CGM lesions. Phase sensitive inversion recovery (PSIR) scans have a higher signal to noise, and can therefore be obtained at a higher resolution within clinically acceptable times. This enables detection of more CGM lesions depicting a clearer cortical and juxtacortical anatomy. In this study, we systematically investigated if the use of high resolution PSIR scans changes the classification of CGM lesions, when compared with standard resolution DIR scans