Identification of DAGLA as an autoantibody target in cerebellar ataxia.

BACKGROUND: We aimed to investigate the clinical, imaging and fluid biomarker characteristics in patients with antidiacylglycerol lipase alpha (DAGLA)-autoantibody-associated cerebellitis. METHODS: Serum and cerebrospinal fliud (CSF) samples from four index patients were subjected to comprehensive autoantibody screening by indirect immunofluorescence assay (IIFA). Immunoprecipitation, mass spectrometry and recombinant protein assays were used to identify the autoantigen. Sera from 101 patients with various neurological symptoms and a similar tissue staining pattern as the index patient samples, and 102 healthy donors were analysed in recombinant cell-based IIFA (RC-IIFA) with the identified protein. Epitope characterisation of all positive samples was performed via ELISA, immunoblot, immunoprecipitation and RC-IIFA using different DAGLA fragments. RESULTS: All index patients were relatively young (age: 18-34) and suffered from pronounced gait ataxia, dysarthria and visual impairments. Paraclinical hallmarks in early-stage disease were inflammatory CSF changes and cerebellar cortex hyperintensity in MRI. Severe cerebellar atrophy developed in three of four patients within 6 months. All patient samples showed the same unclassified IgG reactivity with the cerebellar molecular layer. DAGLA was identified as the target antigen and confirmed by competitive inhibition experiments and DAGLA-specific RC-IIFA. In RC-IIFA, serum reactivity against DAGLA was also found in 17/101 disease controls, including patients with different clinical phenotypes than the one of the index patients, and in 1/102 healthy donors. Epitope characterisation revealed that 17/18 anti-DAGLA-positive control sera reacted with a C-terminal intracellular DAGLA 583-1042 fragment, while the CSF samples of the index patients targeted a conformational epitope between amino acid 1 and 157. CONCLUSIONS: We propose that anti-DAGLA autoantibodies detected in CSF, with a characteristic tissue IIFA pattern, represent novel biomarkers for rapidly progressive cerebellitis.

Estimation of Cerebral Blood Flow Using the Pulse Wave Amplitude in Brain MRI.

RATIONALE AND OBJECTIVES: First, to test the feasibility of cerebral blood flow (CBF) estimation using the pulse wave amplitude in flow-related enhancement (FREE) brain MRI in comparison to pseudo-continuous arterial spin labeling (pCASL-MRI). Second, the potential for acceleration was evaluated retrospectively. MATERIALS AND METHODS: 24 healthy study participants between 20 and 61 years had cerebral MRI. Perfusion imaging was performed with a balanced steady-state free precession sequence for FREE-MRI and with pCASL-MRI for comparison. RESULTS: The value distribution of the estimated CBF showed a high overlap in the histogram between 0 and 20 mL/100 g/min. However, disparity of the values occurred with more values between 20 and 60 mL/100 g/min using pCASL-MRI and more high values > 60 mL/100 g/min applying FREE-MRI. A Kolmogorov-Smirnov test confirmed a differing probability distribution (P = 0.62). The approximated CBF from FREE-MRI remained stable until only 50% of the acquired data was used. Values from using 40% of the data increased significantly compared to 90% or more (P ≤ 0.05). Values within the white matter presented no significant change after data reduction. The global and voxel-wise correlation coefficients towards pCASL-MRI presented stability during data reduction of FREE-MRI. CONCLUSION: In conclusion, the proposed technique allows a rough approximation of the CBF compared to pCASL-MRI. Further sequence optimization must be achieved to improve the measurement of relatively lowly perfused tissues. Nevertheless, it offers large potential for imaging speed optimization and enables perfusion-weighted images similarly to the color Doppler mode in ultrasound.

Clinical and paraclinical characteristics of optic neuritis in the context of the McDonald criteria 2017.

Optic neuritis is often an initial symptom in multiple sclerosis (MS) or clinically isolated syndrome (CIS), yet comprehensive studies using the 2017 McDonald criteria for MS are scarce. Patient records from our academic centre (2010-2018) were reviewed. Using the 2017 McDonald criteria, three groups were formed: MS optic neuritis (optic neuritis with confirmed MS), CIS optic neuritis (optic neuritis without confirmed MS) and suspected optic neuritis (sON). We compared clinical and paraclinical findings among the groups to identify predictors for CIS- or MS-optic neuritis. The study included 129 MS, 108 CIS, and 44 sON cases. The combination of visual impairment, dyschromatopsia, and retrobulbar pain was observed in 47% of MS patients, 42% of CIS patients, and 30% of sON patients. Dyschromatopsia was the strongest indicator of MS or CIS diagnosis in the backward regression model. 56% of MS patients had relative afferent pupillary defect, 61% optic nerve anomalies within magnetic resonance imaging, and 81% abnormal visual evoked potentials. Our results emphasize the challenges in diagnosing optic neuritis, as not all patients with objectively diagnosed MS exhibit the triad of typical symptoms. To address potentially missing clinical features, incorporating additional paraclinical findings is proposed.

Prognostic relevance of MRI in early relapsing multiple sclerosis: ready to guide treatment decision making?

Magnetic resonance imaging (MRI) of the brain and spinal cord plays a crucial role in the diagnosis and monitoring of multiple sclerosis (MS). There is conclusive evidence that brain and spinal cord MRI findings in early disease stages also provide relevant insight into individual prognosis. This includes prediction of disease activity and disease progression, the accumulation of long-term disability and the conversion to secondary progressive MS. The extent to which these MRI findings should influence treatment decisions remains a subject of ongoing discussion. The aim of this review is to present and discuss the current knowledge and scientific evidence regarding the utility of MRI at early MS disease stages for prognostic classification of individual patients. In addition, we discuss the current evidence regarding the use of MRI in order to predict treatment response. Finally, we propose a potential approach as to how MRI data may be categorized and integrated into early clinical decision making.

Can MRI help select appropriate therapy for recently diagnosed multiple sclerosis? MS is a chronic autoimmune disease of the brain and spinal cord that causes physical and cognitive disability. Initially, most people with MS (pwMS) experience attacks of new symptoms and periods of partial recovery; this is called relapsing-remitting MS (RRMS). RRMS transitions to secondary progressive MS (SPMS), where there is a gradual worsening of disability. MS medications dampen parts of the immune system. They reduce the risk of relapses and delay transition to SPMS if started early. Once a person has SPMS, treatment can slow but not stop further deterioration. MS medications vary in their effects on the immune system, level of efficacy, and treatment risks. The course of MS is highly individual. When starting therapy, it can therefore be difficult to decide whether a drug with lower or higher efficacy is required. Some of the acute and chronic inflammatory changes in MS are shown as focal lesions ('spots') on MRI of the brain and spinal cord. They are very useful for diagnosing MS and determining disease activity. Even if there are no relapses, new lesions indicate that a MS medication is not fully effective. In addition, MRI provides a snapshot of tissue damage that has accumulated up to the examination. At the time of diagnosis, MRI reflects the natural history of MS in the individual, even before the first attack, and contains prognostic information. We review studies that investigate an association between certain MRI findings obtained early after the initial attack and the later course of MS. We propose that these metrics can be applied to a concept of grading and staging of MS as well as estimating functional reserve. We review thresholds that identify pwMS at risk of disability progression and transition to SPMS, who should be recommended highly effective therapy first line. Leveraging the prognostic capabilities of MRI may support initial treatment decisions.

Diagnostic Performance of Cortical Lesions and the Central Vein Sign in Multiple Sclerosis.

Importance: Multiple sclerosis (MS) misdiagnosis remains an important issue in clinical practice. Objective: To quantify the performance of cortical lesions (CLs) and central vein sign (CVS) in distinguishing MS from other conditions showing brain lesions on magnetic resonance imaging (MRI). Design, Setting, and Participants: This was a retrospective, cross-sectional multicenter study, with clinical and MRI data acquired between January 2010 and May 2020. Centralized MRI analysis was conducted between July 2020 and December 2022 by 2 raters blinded to participants' diagnosis. Participants were recruited from 14 European centers and from a multicenter pan-European cohort. Eligible participants had a diagnosis of MS, clinically isolated syndrome (CIS), or non-MS conditions; availability of a brain 3-T MRI scan with at least 1 sequence suitable for CL and CVS assessment; presence of T2-hyperintense white matter lesions (WMLs). A total of 1051 individuals were included with either MS/CIS (n = 599; 386 [64.4%] female; mean [SD] age, 41.5 [12.3] years) or non-MS conditions (including other neuroinflammatory disorders, cerebrovascular disease, migraine, and incidental WMLs in healthy control individuals; n = 452; 302 [66.8%] female; mean [SD] age, 49.2 [14.5] years). Five individuals were excluded due to missing clinical or demographic information (n = 3) or unclear diagnosis (n = 2). Exposures: MS/CIS vs non-MS conditions. Main Outcomes and Measures: Area under the receiver operating characteristic curves (AUCs) were used to explore the diagnostic performance of CLs and the CVS in isolation and in combination; sensitivity, specificity, and accuracy were calculated for various cutoffs. The diagnostic importance of CLs and CVS compared to conventional MRI features (ie, presence of infratentorial, periventricular, and juxtacortical WMLs) was ranked with a random forest model. Results: The presence of CLs and the previously proposed 40% CVS rule had a sensitivity, specificity, and accuracy for MS of 59.0% (95% CI, 55.1-62.8), 93.6% (95% CI, 91.4-95.6), and 73.9% (95% CI, 71.6-76.3) and 78.7% (95% CI, 75.5-82.0), 86.0% (95% CI, 82.1-89.5), and 81.5% (95% CI, 78.9-83.7), respectively. The diagnostic performance of the CVS (AUC, 0.89 [95% CI, 0.86-0.91]) was superior to that of CLs (AUC, 0.77 [95% CI, 0.75-0.80]; P < .001), and was increased when combining the 2 imaging markers (AUC, 0.92 [95% CI, 0.90-0.94]; P = .04); in the random forest model, both CVS and CLs outperformed the presence of infratentorial, periventricular, and juxtacortical WMLs in supporting MS differential diagnosis. Conclusions and Relevance: The findings in this study suggest that CVS and CLs may be valuable tools to increase the accuracy of MS diagnosis.

Use of gadolinium-based contrast agents in multiple sclerosis: a review by the ESMRMB-GREC and ESNR Multiple Sclerosis Working Group.

Magnetic resonance imaging (MRI) is the most sensitive technique for detecting inflammatory demyelinating lesions in multiple sclerosis (MS) and plays a crucial role in diagnosis and monitoring treatment effectiveness, and for predicting the disease course. In clinical practice, detection of MS lesions is mainly based on T2-weighted and contrast-enhanced T1-weighted sequences. Contrast-enhancing lesions (CEL) on T1-weighted sequences are related to (sub)acute inflammation, while new or enlarging T2 lesions reflect the permanent footprint from a previous acute inflammatory demyelinating event. These two types of MRI features provide redundant information, at least in regular monitoring of the disease. Due to the concern of gadolinium deposition after repetitive injections of gadolinium-based contrast agents (GBCAs), scientific organizations and regulatory agencies in Europe and North America have proposed that these contrast agents should be administered only if clinically necessary. In this article, we provide data on the mode of action of GBCAs in MS, the indications of the use of these agents in clinical practice, their value in MS for diagnostic, prognostic, and monitoring purposes, and their use in specific populations (children, pregnant women, and breast-feeders). We discuss imaging strategies that achieve the highest sensitivity for detecting CELs in compliance with the safety regulations established by different regulatory agencies. Finally, we will briefly discuss some alternatives to the use of GBCA for detecting blood-brain barrier disruption in MS lesions. CLINICAL RELEVANCE STATEMENT: Although use of GBCA at diagnostic workup of suspected MS is highly valuable for diagnostic and prognostic purposes, their use in routine monitoring is not mandatory and must be reduced, as detection of disease activity can be based on the identification of new or enlarging lesions on T2-weighted images. KEY POINTS: • Both the EMA and the FDA state that the use of GBCA in medicine should be restricted to clinical scenarios in which the additional information offered by the contrast agent is required. • The use of GBCA is generally recommended in the diagnostic workup in subjects with suspected MS and is generally not necessary for routine monitoring in clinical practice. • Alternative MRI-based approaches for detecting acute focal inflammatory MS lesions are not yet ready to be used in clinical practice.

Cerebral microcirculatory pulse wave propagation and pulse wave amplitude mapping in retrospectively gated MRI.

To analyze cerebral arteriovenous pulse propagation and to generate phase-resolved pulse amplitude maps from a fast gradient-echo sequence offering flow-related enhancement (FREE). Brain MRI was performed using a balanced steady-state free precession sequence at 3T followed by retrospective k-space gating. The time interval of the pulse wave between anterior-, middle- and posterior cerebral artery territories and the superior sagittal sinus were calculated and compared between and older and younger groups within 24 healthy volunteers. Pulse amplitude maps were generated and compared to pseudo-Continuous Arterial Spin Labeling (pCASL) MRI maps by voxel-wise Pearson correlation, Sørensen-Dice maps and in regards to signal contrast. The arteriovenous delays between all vascular territories and the superior sagittal sinus were significantly shorter in the older age group (11 individuals, ≥ 31 years) ranging between 169 ± 112 and 246 ± 299 ms versus 286 ± 244 to 419 ± 299 ms in the younger age group (13 individuals) (P ≤ 0.04). The voxel-wise pulse wave amplitude values and perfusion-weighted pCASL values correlated significantly (Pearson-r = 0.33, P < 0.01). Mean Dice overlaps of high (gray) and low (white matter) regions were 73 ± 3% and 59 ± 5%. No differences in image contrast were seen in the whole brain and the white matter, but significantly higher mean contrast of 0.73 ± 0.23% in cortical gray matter in FREE-MRI compared to 0.52 ± 0.12% in pCASL-MRI (P = 0.01). The dynamic information of flow-related enhancement allows analysis of the cerebral pulse wave propagation potentially providing information about the (micro)circulation on a regional level. However, the pulse wave amplitude reveals weaknesses in comparison to true perfusion-weighting and could rather be used to calculate a pulsatility index.

Adhesion of vessel wall to stentriever during combined technique for mechanical thrombectomy in acute ischemic stroke: A histomorphological study.

PURPOSE: Detection of vessel wall tissue in thrombus material in patients with ischemic stroke is judged as vascular injury. So far, several studies investigated components of the free clots after mechanical thrombectomy. The aim of this retrospective study was to investigate the involvement and role of the stentriever in vessel wall injury by analysis of the composition of adherent tissue to the stentriever during combined aspiration thrombectomy with stentriever. METHODS: Stentriever with adherent tissue and free clots in aspiration samples from patients undergoing mechanical thrombectomy (aspiration plus stentriever) were separately assessed for the occurrence of parts of vascular tissue together with clinical and interventional data as well as clinical outcome data. Specimens were analyzed histomorphologically and immunohistochemically. Findings, focused on parts of vessel wall were reported together with clinical data. RESULTS: Specimens from 21 identified patients were available. Parts of the vessel wall were detected in 7 out 21 (33%) samples. All specimens revealed fresh thrombus material without signs of organization or atheromatous tissue. In 90% of patients mTICI was greater than 2b without signs of secondary vessel injury. No vascular tissue was found in free clots of the aspiration samples. CONCLUSION: The examination of adherent tissue to the stentriever instead of the examination of free clots may affect the number of detected parts of vessel wall. Further studies in combination with vessel wall imaging may elucidate the origin of remnants of vessel wall.

Automatic covariance pattern analysis outperforms visual reading of 18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in variant progressive supranuclear palsy.

BACKGROUND: To date, studies on positron emission tomography (PET) with 18 F-fluorodeoxyglucose (FDG) in progressive supranuclear palsy (PSP) usually included PSP cohorts overrepresenting patients with Richardson's syndrome (PSP-RS). OBJECTIVES: To evaluate FDG-PET in a patient sample representing the broad phenotypic PSP spectrum typically encountered in routine clinical practice. METHODS: This retrospective, multicenter study included 41 PSP patients, 21 (51%) with RS and 20 (49%) with non-RS variants of PSP (vPSP), and 46 age-matched healthy controls. Two state-of-the art methods for the interpretation of FDG-PET were compared: visual analysis supported by voxel-based statistical testing (five readers) and automatic covariance pattern analysis using a predefined PSP-related pattern. RESULTS: Sensitivity and specificity of the majority visual read for the detection of PSP in the whole cohort were 74% and 72%, respectively. The percentage of false-negative cases was 10% in the PSP-RS subsample and 43% in the vPSP subsample. Automatic covariance pattern analysis provided sensitivity and specificity of 93% and 83% in the whole cohort. The percentage of false-negative cases was 0% in the PSP-RS subsample and 15% in the vPSP subsample. CONCLUSIONS: Visual interpretation of FDG-PET supported by voxel-based testing provides good accuracy for the detection of PSP-RS, but only fair sensitivity for vPSP. Automatic covariance pattern analysis outperforms visual interpretation in the detection of PSP-RS, provides clinically useful sensitivity for vPSP, and reduces the rate of false-positive findings. Thus, pattern expression analysis is clinically useful to complement visual reading and voxel-based testing of FDG-PET in suspected PSP. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

[Consensus recommendations on regional interdisciplinary standardization of MRI diagnostics for multiple sclerosis in the metropolitan area of Essen]. / Konsensusempfehlungen zur regionalen fächerübergreifenden Standardisierung der MRT-Diagnostik bei Multipler Sklerose im Großraum Essen.

Magnetic resonance imaging (MRI) is of exceptional importance in the diagnostics and monitoring of multiple sclerosis (MS); however, a close interdisciplinary cooperation between neurologists in private practice, (neuro)radiological practices, hospitals or specialized MS centers is only rarely established. In particular, there is a lack of standardized MRI protocols for image acquisition as well as established quality parameters, which guarantee the comparability of MRI records; however, this is a fundamental prerequisite for an effective application of MRI in the treatment of MS patients, e.g., for making the diagnosis or treatment monitoring. To address these challenges a group of neurologists and (neuro)radiologists developed a consensus proposal for standardization of image acquisition, interpretation and transmission of results and for improvement in interdisciplinary cooperation. This pilot project in the metropolitan area of Essen used a modified Delphi process and was based on the most up to date scientific knowledge. The recommendation takes the medical, economic, temporal and practical aspects of MRI in MS into consideration. The model of interdisciplinary cooperation between radiologists and neurologists with the aim of a regional standardization of MRI could serve as an example for other regions of Germany in order to optimize MRI for MS.

Brain MRI in Progressive Supranuclear Palsy with Richardson's Syndrome and Variant Phenotypes.

BACKGROUND: Brain magnetic resonance imaging (MRI) is used to support the diagnosis of progressive supranuclear palsy (PSP). However, the value of visual descriptive, manual planimetric, automatic volumetric MRI markers and fully automatic categorization is unclear, particularly regarding PSP predominance types other than Richardson's syndrome (RS). OBJECTIVES: To compare different visual reading strategies and automatic classification of T1-weighted MRI for detection of PSP in a typical clinical cohort including PSP-RS and (non-RS) variant PSP (vPSP) patients. METHODS: Forty-one patients (21 RS, 20 vPSP) and 46 healthy controls were included. Three readers using three strategies performed MRI analysis: exclusively visual reading using descriptive signs (hummingbird, morning-glory, Mickey-Mouse), visual reading supported by manual planimetry measures, and visual reading supported by automatic volumetry. Fully automatic classification was performed using a pre-trained support vector machine (SVM) on the results of atlas-based volumetry. RESULTS: All tested methods achieved higher specificity than sensitivity. Limited sensitivity was driven to large extent by false negative vPSP cases. Support by automatic volumetry resulted in the highest accuracy (75.1% ± 3.5%) among the visual strategies, but performed not better than the midbrain area (75.9%), the best single planimetric measure. Automatic classification by SVM clearly outperformed all other methods (accuracy, 87.4%), representing the only method to provide clinically useful sensitivity also in vPSP (70.0%). CONCLUSIONS: Fully automatic classification of volumetric MRI measures using machine learning methods outperforms visual MRI analysis without and with planimetry or volumetry support, particularly regarding diagnosis of vPSP, suggesting the use in settings with a broad phenotypic PSP spectrum. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Progressive Multifocal Leukoencephalopathy: Pathogenesis, Diagnostic Tools, and Potential Biomarkers of Response to Therapy.

JC polyomavirus (JCV) establishes an asymptomatic latent and/or persistent infection in most of the adult population. However, in immunocompromised individuals, JCV can cause a symptomatic infection of the brain, foremost progressive multifocal leukoencephalopathy (PML). In the past 2 decades, there has been increasing concern among patients and the medical community because PML was observed as an adverse event in individuals treated with modern (selective) immune suppressive treatments for various immune-mediated diseases, especially multiple sclerosis. It became evident that this devastating complication also needs to be considered beyond the patient populations historically at risk, including those with hematologic malignancies or HIV-infected individuals. We review the clinical presentation of PML, its variants, pathogenesis, and current diagnostic approaches. We further discuss the need to validate JCV-directed interventions and highlight current management strategies based on early diagnosis and restoring JCV-specific cellular immunity, which is crucial for viral clearance and survival. Finally, we discuss the importance of biomarkers for diagnosis and response to therapy, instrumental in defining sensitive study end points for successful clinical trials of curative or preventive therapeutics. Advances in understanding PML pathophysiology, host and viral genetics, and diagnostics in conjunction with novel immunotherapeutic approaches indicate that the time is right to design and perform definitive trials to develop preventive options and curative therapy for JCV-associated diseases.

Adoptive Allogeneic T-Cell Therapy Improves the Clinical Outcome of JC Virus Granule Cell Neuronopathy: A Case Report.

OBJECTIVES: JC virus granule cell neuronopathy is a potentially fatal otherwise highly disabling disease without an approved therapeutic option. This case report presents the positive record to T-cell therapy in JC virus granule cell neuronopathy. METHODS: The patient represented with subacute cerebellar symptoms. Diagnosis of JC virus granule cell neuronopathy was made because of infratentorially accentuated brain volume atrophy shown by brain MRI and the detection of JC virus DNA in the CSF. RESULTS: Six doses of virus-specific T cells were administered. Within 12 months after therapy initiation, the patient showed clear clinical benefit with improvement of symptoms, and JC viral DNA load significantly declined. DISCUSSION: We present the case report of a positive response to T-cell therapy in JC virus granule cell neuronopathy, leading to an improvement of symptoms.

Anti-GABA-A Receptor Antibody-Mediated Epilepsia Partialis Continua After Treatment With Alemtuzumab: A Case Report.

BACKGROUND AND OBJECTIVES: Patients with anti-GABA-A receptor encephalitis characteristically experience therapy-refractory epileptic seizures. General anesthesia is often required to terminate refractory status epilepticus. The immunologic mechanisms leading to antibody formation remain to be elucidated. Described triggers of anti-GABA-A autoimmunity are tumors, mainly thymomas, and herpes simplex encephalitis. METHODS: We present a young woman with prediagnosis of relapse remitting multiple sclerosis (MS), treated with interferons, natalizumab, and alemtuzumab. Six months after one and only cycle of alemtuzumab, speech arrest and behavioral changes with aggressive and anxious traits appeared. She showed increasing motor convulsions resulting in focal status epilepticus. RESULTS: Anti-GABA-A receptor antibodies in CSF and serum were confirmed in different external laboratories, in a more extensive analysis after antibodies against NMDAR, CASPR2, LGI1, GABABR, and AMPAR were ruled out during in-house examination. Clinical condition improved temporarily with cortisone therapy, plasmapheresis, and IVIG but deteriorated rapidly after steroid discontinuation, resulting in brain biopsy. On histopathologic confirmation consistent with anti-GABA-A receptor antibody-associated CNS inflammation, completing the first rituximab cycle, continuing oral corticosteroids and supplementing immunosuppression with cyclosporine A led to quick recovery. DISCUSSION: Our case describes a severe autoantibody-induced encephalitis in a young patient with MS, with alemtuzumab as a potential trigger for anti-GABA-A receptor encephalitis.

Magnetic resonance imaging of human variegated squirrel bornavirus 1 (VSBV-1) encephalitis reveals diagnostic pattern indistinguishable from Borna disease virus 1 (BoDV-1) encephalitis but typical for bornaviruses.

Human bornavirus encephalitis is an emerging disease caused by the variegated squirrel bornavirus 1 (VSBV-1) and the Borna disease virus 1 (BoDV-1). While characteristic brain magnetic resonance imaging (MRI) changes have been described for BoDV-1 encephalitis, only scarce diagnostic data in VSBV-1 encephalitis exist. We systematically analysed brain MRI scans from all known VSBV-1 encephalitis patients. Initial and follow-up scans demonstrated characteristic T2 hyperintense lesions in the limbic system and the basal ganglia, followed by the brainstem. No involvement of the cerebellar cortex was seen. Deep white matter affection occurred in a later stage of the disease. Strict symmetry of pathologic changes was seen in 62%. T2 hyperintense areas were often associated with low T1 signal intensity and with mass effect. Sinusitis in three patients on the first MRI and an early involvement of the limbic system suggest an olfactory route of VSBV-1 entry. The viral spread could occur per continuitatem to adjacent anatomical brain regions or along specific neural tracts to more distant brain regions. The number and extent of lesions did not correlate with the length of patients' survivals. The overall pattern closely resembles that described for BoDV-1 encephalitis. The exact bornavirus species can thus not be deduced from imaging results alone, and molecular testing and serology should be performed to confirm the causative bornavirus. As VSBV-1 is likely of tropical origin, and MRI investigations are increasingly available globally, imaging techniques might be helpful to facilitate an early presumptive diagnosis of VSBV-1 encephalitis when molecular and/or serological testing is not available.

[Performance of the revised 2017 McDonald criteria]. / Leistungsfähigkeit der McDonald-Kriterien von 2017.

BACKGROUND: A rapid and reliable diagnosis of multiple sclerosis (MS) is crucial to initiate adapted disease-modifying treatment. The 2017 McDonald criteria were revised with the aim of further improving the diagnostic performance. OBJECTIVE: In this article the published studies comparing the use of the 2017 and 2010 McDonald criteria were reviewed and analyzed in terms of diagnostic performance. MATERIAL AND METHODS: A total of 20 studies and 1 review article with a total of 3006 evaluated patients were identified by means of a literature search in the PubMed database (search term: McDonald criteria 2010 and McDonald criteria 2017). RESULTS: Using the 2017 McDonald criteria, a diagnosis of MS was made in more patients (2277/3006 patients, 76%) and in an earlier stage (3-10 months) compared with the 2010 revision (1562/3006 patients, 52%). Of the additional MS diagnoses, 193/715 were due to the adjustment of the imaging criteria of temporal dissemination and 536/715 were due to the introduction of oligoclonal bands as a diagnostic criterion. CONCLUSION: The revised McDonald criteria of 2017 have achieved their goal and enable the diagnosis of MS in a higher proportion of patients at the first clinical event.

Feasibility of flow-related enhancement brain perfusion MRI.

PURPOSE: Brain perfusion imaging is of enormous importance for various neurological diseases. Fast gradient-echo sequences offering flow-related enhancement (FREE) could present a basis to generate perfusion-weighted maps. In this study, we obtained perfusion-weighted maps without contrast media by a previously described postprocessing algorithm from the field of functional lung MRI. At first, the perfusion signal was analyzed in fast low-angle shot (FLASH) and balanced steady-state free precession (bSSFP) sequences. Secondly, perfusion maps were compared to pseudo-continuous arterial spin labeling (pCASL) MRI in a healthy cohort. Thirdly, the feasibility of the new technique was demonstrated in a small selected group of patients with metastases and acute stroke. METHODS: One participant was examined with bSSFP and FLASH sequences at 1.5T and 3T, different flip angles and slice thicknesses. Twenty-five volunteers had bSSFP imaging and pCASL MRI. Three patients with cerebral metastases and one with acute ischemic stroke had bSSFP imaging and were compared to T1 post-contrast images and CT perfusion. Frequency analyses, SNR and perfusion contrast were compared at different flip angles and slice thicknesses. Regional correlations and Sorensen-Dice overlap were calculated in the healthy cohort. Dice overlap of the pathologies in the patient cohort were calculated. RESULTS: The bSSFP sequence presented detectable perfusion signal within brain vessel and parenchyma together with superior SNR compared to FLASH. Perfusion contrast and its corticomedullary differentiation increased with flip angle. Mean regional correlation was 0.36 and highly significant between FREE maps and pCASL and grey and white matter Dice match were 72% and 60% in the healthy cohort. Pathologies presented good overlap between FREE perfusion-weighted and T1 post-contrast images. CONCLUSION: The feasibility of FREE brain perfusion imaging has been shown in a healthy cohort and selected patient cases with brain metastases and acute stroke. The study demonstrates a new approach for non-contrast brain perfusion imaging.

Long-term management of multiple sclerosis patients treated with cladribine tablets beyond year 4.

INTRODUCTION: Oral cladribine is a highly effective pulsed selective immune reconstitution therapy licensed for relapsing multiple sclerosis (RMS) since 2017. A full treatment course comprises two treatment cycles given 1 year apart, followed by two treatment-free years. The management of cladribine-treated patients beyond year 4 needs to be addressed as patients have now passed the initial 4 years since European Medical Agency approval. AREAS COVERED: A panel of neurologists and a neuroradiologist experienced in MS treatment/monitoring evaluated clinical trial data and real-world evidence and proposed recommendations for the management of cladribine-treated patients beyond year 4. EXPERT OPINION: Continuous monitoring of disease activity during the treatment-free period is important. Subsequent management depends on the presence or absence of inflammatory disease activity, determined in the absence of consistent guidelines via practice-driven neurological decision criteria. Persisting or newly occurring inflammatory disease activity is an indication for further treatment, i.e. either re-initiation of cladribine or switching to another highly effective disease-modifying therapy. The decision to retreat or switch should be based on clinical and radiological evaluation considering disease course, treatment history, and safety aspects. In the absence of disease activity, either retreatment can be offered, or the treatment-free period can be extended under structured monitoring.

Clinical applicability of quantitative atrophy measures on MRI in patients suspected of Alzheimer's disease.

OBJECTIVES: Neurodegeneration in suspected Alzheimer's disease can be determined using visual rating or quantitative volumetric assessments. We examined the feasibility of volumetric measurements of gray matter (GMV) and hippocampal volume (HCV) and compared their diagnostic performance with visual rating scales in academic and non-academic memory clinics. MATERIALS AND METHODS: We included 231 patients attending local memory clinics (LMC) in the Netherlands and 501 of the academic Amsterdam Dementia Cohort (ADC). MRI scans were acquired using local protocols, including a T1-weighted sequence. Quantification of GMV and HCV was performed using FSL and FreeSurfer. Medial temporal atrophy and global atrophy were assessed with visual rating scales. ROC curves were derived to determine which measure discriminated best between cognitively normal (CN), mild cognitive impairment (MCI), and Alzheimer's dementia (AD). RESULTS: Patients attending LMC (age 70.9 ± 8.9 years; 47% females; 19% CN; 34% MCI; 47% AD) were older, had more cerebrovascular pathology, and had lower GMV and HCV compared to those of the ADC (age 64.9 ± 8.2 years; 42% females; 35% CN, 43% MCI, 22% AD). While visual ratings were feasible in > 95% of scans in both cohorts, quantification was achieved in 94-98% of ADC, but only 68-85% of LMC scans, depending on the software. Visual ratings and volumetric outcomes performed similarly in discriminating CN vs AD in both cohorts. CONCLUSION: In clinical settings, quantification of GM and hippocampal atrophy currently fails in up to one-third of scans, probably due to lack of standardized acquisition protocols. Diagnostic accuracy is similar for volumetric measures and visual rating scales, making the latter suited for clinical practice. In a real-life clinical setting, volumetric assessment of MRI scans in dementia patients may require acquisition protocol optimization and does not outperform visual rating scales. KEY POINTS: • In a real-life clinical setting, the diagnostic performance of visual rating scales is similar to that of automatic volumetric quantification and may be sufficient to distinguish Alzheimer's disease groups. • Volumetric assessment of gray matter and hippocampal volumes from MRI scans of patients attending non-academic memory clinics fails in up to 32% of cases. • Clinical MR acquisition protocols should be optimized to improve the output of quantitative software for segmentation of Alzheimer's disease-specific outcomes.