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Background: The pathogenesis of spontaneous cervical artery dissection remains unclear, and no established predictors of recurrence exist. Our goal was to investigate the potential association between cervical artery tortuosity, a characteristic of patients with connective tissue disorder, and spontaneous cervical artery dissection., Methods: The ReSect study (Risk Factors for Recurrent Cervical Artery Dissection) is an observational study that invited all spontaneous cervical artery dissection patients treated at the Innsbruck University Hospital between 1996 and 2018 for clinical and radiological follow-up. Internal carotid and vertebral artery tortuosity was assessed on magnetic resonance angiography using a validated 3-dimensional algorithm. Differences between patients and healthy controls as well as dependent on recurrence status were assessed by applying χ 2 , Mann-Whitney U test, and Kruskal-Wallis test where applicable, and confounders were established by bivariable Pearson correlation. Logistic regression was used to address the impact of tortuosity on dissection occurrence and recurrence as well as its association to extracellular matrix proteome data derived from skin biopsies in a subset of patients., Results: Magnetic resonance angiography was performed a median of 6.5 years after dissection in the included dissection patients. Patients with dissection (n=125) had significantly increased values of internal carotid artery tortuosity compared with healthy controls (n=24; odds ratio, 2.65 [95% CI, 1.68-3.86], 1 SD increase; P <0.01). This was also true for patients with long-term dissection recurrence (n=7) when compared with those with single time-point dissection (n=118; odds ratio, 2.00 [95% CI, 1.47-3.99], 1 SD increase; P <0.01). In patients with dissection and available extracellular matrix protein data (n=37), 6 of 13 (46.2%) proteins previously found linked with dissection recurrence were also associated with increased tortuosity. All 3 proteins associated with both anterior and posterior circulation tortuosity belonged to the desmosome-related cluster., Conclusions: Internal carotid artery tortuosity is elevated in spontaneous cervical artery dissection patients compared with healthy controls, and this difference is most pronounced if individuals suffer from long-term dissection recurrence. Additionally, an association between tortuosity, being a readily measurable biomarker in routine magnetic resonance angiography, and proteomic markers of dissection recurrence exists, further enhancing the prospect of underlying subclinical connective tissue disease in dissection patients.

Introduction: The increasing prevalence of Alzheimer's disease (AD) has created an urgent need for rapid and cost-effective methods to diagnose and monitor people at all stages of the disease. Progressive memory impairment and hippocampal atrophy are key features of the most common so-called typical variant of AD. However, studies evaluating detailed cognitive measures combined with region of interest (ROI)-based imaging markers of progression over the long term in the AD dementia (ADD) stage are rare., Method: We conducted a retrospective longitudinal follow-up study in patients with mild to moderate ADD (aged 60-92 years). They underwent magnetic resonance imaging (MRI; 3 Tesla, MPRAGE) as well as clinical and neuropsychological examination (Consortium to Establish a Registry for Alzheimer's Disease [CERAD] -Plus test battery) at baseline and at least one follow-up visit. ROI-based brain structural analysis of baseline MRIs was performed using the Computational Anatomy Toolbox (CAT) 12. Clinical dementia progression (progression index [PI]) was measured by the annual decline in the Mini Mental State Examination (MMSE) scores. MRI, demographic, and neuropsychological data were included in univariate and multiple linear regression models to predict the PI., Results: 104 ADD patients (age 63 to 90 years, 73% female, mean MMSE score 22.63 ± 3.77, mean follow-up 4.27 ± 2.15 years) and 32 age- and gender-matched cognitively intact controls were included. The pattern of gray matter (GM) atrophy and the cognitive profile were consistent with the amnestic/typical variant of ADD in all patients. Deficits in word list learning together with temporal lobe GM atrophy had the highest predictive value for rapid cognitive decline in the multiple linear regression model, accounting for 25.4% of the PI variance., Discussion: Our results show that temporal atrophy together with deficits in the encoding of verbal material, rather than in immediate or delayed recall, is highly predictive for rapid cognitive decline in patients with mild to moderate amnestic/typical ADD. These findings point to the relevance of combining detailed cognitive and automated structural imaging analyses to predict clinical progression in patients with ADD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Doganyigit, Defrancesco, Schurr, Steiger, Gizewski, Mangesius, Galijasevic, Hofer and Tuovinen.)

Background: Pharmacological treatment options for patients with dementia owing to Alzheimer's disease are limited to symptomatic therapy. Recently, the US Food and Drug Administration approved the monoclonal antibody lecanemab for the treatment of amyloid-positive patients with mild cognitive impairment (MCI) and early Alzheimer´s dementia. European approval is expected in 2024. Data on the applicability and eligibility for treatment with anti-amyloid monoclonal antibodies outside of a study population are lacking., Aims: This study examined eligibility criteria for lecanemab in a real-world memory clinic population between 1 January 2022 and 31 July 2023., Method: We conducted a retrospective, single-centre study applying the clinical trial eligibility criteria for lecanemab to out-patients of a specialised psychiatric memory clinic. Eligibility for anti-amyloid treatment was assessed following the phase 3 inclusion and exclusion criteria and the published recommendations for lecanemab., Results: The study population consisted of 587 out-patients. Two-thirds were diagnosed with Alzheimer's disease (probable or possible Alzheimer's disease dementia in 43.6% of cases, n = 256) or MCI (23%, n = 135), and 33.4% ( n = 196) were diagnosed with dementia or neurocognitive disorder owing to another aetiology. Applying all lecanemab eligibility criteria, 11 (4.3%) patients with dementia and two (1.5%) patients with MCI would have been eligible for treatment with this compound, whereas 13 dementia (5.1%) and 14 (10.4%) MCI patients met clinical inclusion criteria, but had no available amyloid status., Conclusions: Even in a memory clinic with a good infrastructure and sufficient facilities for dementia diagnostics, most patients do not meet the eligibility criteria for treatment with lecanemab.

Introduction: Aneurysmal wall enhancement (AWE) of non-ruptured sacular intracranial aneurysms (IA) after endovascular treatment (ET) is a frequently observed imaging finding using AWE-sequences in brain magnetic resonance imaging (MRI). So far, its value remains unclear. We aimed to investigate the effect of AWE on aneurysm reperfusion rates in a longitudinal cohort., Methods: This is a retrospective MRI study over the timespan of up to 5 years, assessing the correlation of increased AWE of non-ruptured IAs and events of aneurysm reperfusion and retreatment, PHASES Score and grade of AWE. T1 SPACE fat saturation (FS) and T1 SE FS blood suppression sequences after contrast administration were used for visual interpretation of increased AWE. The IAs' sizes were assessed via the biggest diameter. The grade of enhancement was defined in a grading system from grade 1 to grade 3., Results: 127 consecutive non ruptured IA-patients (58.9 ± 9.0 years, 94 female, 33 male) who underwent elective aneurysm occlusion were included. AWE was observed in 40.2% of patients (51/127) after ET, 6 patients already showed AWE before treatment. In large IAs (which were defined as a single maximum diameter of over 7.5 mm), AWE was significantly associated with aneurysm reperfusion in contrast to large aneurysm without AWE). All grades of AWE were significantly associated with reperfusion., Conclusions: Our data suggests that in patients with initially large IAs, AWE is correlated with aneurysm reperfusion.

One of the main causes of the dismal prognosis in patients who survive the initial bleeding after aneurysmal subarachnoidal hemorrhage is the delayed cerebral ischaemia caused by vasospasm. Studies suggest that cerebral magnesium and pH may potentially play a role in the pathophysiology of this adverse event. Using phosphorous magnetic resonance spectrocopy (31P-MRS), we calculated the cerebral magnesium (Mg) and pH levels in 13 patients who suffered from aSAH. The values between the group that developed clinically significant vasospasm ( n = 7) and the group that did not ( n = 6) were compared. The results of this study show significantly lower cerebral Mg levels ( p = 0.019) and higher pH levels ( p < 0.001) in the cumulative group (all brain voxels together) in patients who developed clinically significant vasospasm. Further clinical studies on a larger group of carefully selected patients are needed in order to predict clinically significant vasospasm.

This study aims to evaluate the clinical outcome of stereotactic radiosurgery as the sole treatment for brain metastases and to assess prognostic factors influencing survival. A total of 108 consecutive patients with 213 metastases were retrospectively analyzed. Treatment was determined with close-meshed MRI follow-up. Various prognostic factors were assessed, and several prognostic indices were compared regarding their reliability to estimate overall survival. Median overall survival was 15 months; one-year overall survival was 50.5%. Both one- and two-year local controls were 90.9%. The rate of new metastases after SRS was 49.1%. Multivariate analysis of prognostic factors revealed that the presence of extracranial metastases, male sex, lower KPI, and progressive extracranial disease were significant risk factors for decreased survival. Of all evaluated prognostic indices, the Basic Score for Brain Metastases (BSBMs) showed the best correlation with overall survival. A substantial survival advantage was found for female patients after SRS when compared to male patients (18 versus 9 months, p = 0.003). SRS of brain metastasis is a safe and effective treatment option when frequent monitoring for new metastases with MRI is performed. Common prognostic scores lack reliable estimation of survival times. Female sex should be considered as an additional independent positive prognostic factor influencing survival.

Background: Assessments of subclinical connective tissue disorders depend on complex approaches, emphasizing the need for more accessible methods applicable to clinical routine. Therefore, we aimed to establish a reliable approach assessing cervical vessel tortuosity, which is known to be associated with such disorders., Methods: Magnetic resonance angiography (MRA) images of ReSect study participants [single-center prospective cohort of spontaneous cervical artery dissection (sCeAD) patients] were used. Each patient underwent the same magnetic resonance imaging (MRI) protocol. The segmentation procedure was done using MATrix LABoratory 9.4 [up-sampling of raw MRA images, distance metric (DM) calculation], ITK-SNAP [region of interest (ROI) determination, vessel segmentation] and Vascular Modelling ToolKit (centerline determination). To assess inter-user variability and validity, we (I) had two blinded independent users segment all arteries and we (II) compared the results of our method to visual appraisal of vessel tortuosity done by two blinded expert neuro-radiologists., Results: A total of 526 extracranial cervical arteries were available for analysis. The inter-user variability of our method users was below 0.5% throughout. Overall, our method outperformed the visual tortuosity appraisal, as the visual grading underestimated the DM in 38.8% subjects when tasked to assess overall cervical artery tortuosity (both vertebral and internal carotid arteries) and in 16.6% and 33.3% respectively if tasked to grade anterior or posterior circulation separately., Conclusions: We present a reliable method to assess cervical artery tortuosity derived from MRA images applicable in clinical routine and future research investigating the potential correlation of sCeAD and connective tissue disorder., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-1057/coif). All authors report that this study was supported by VASCage-Research Centre on Clinical Stroke Research. VASCage is a COMET Centre within the Competence Centers for Excellent Technologies (COMET) program and funded by the Federal Ministry for Climate Action, Environment, Energy, Mobility, Innovation and Technology, the Federal Ministry of Labour and Economy, and the federal states of Tyrol, Salzburg and Vienna. COMET is managed by the Austrian Research Promotion Agency (Österreichische Forschungsförderungsgesellschaft), FFG Project number: 898252. S.P. Jr reports the support from the Austrian Science Fund (FWF): project P 29514-N32. The authors have no other conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Introduction: Recent advances in the radiation therapy of prostate cancer have brought a shift toward moderate- and ultra-hypofractionated treatment schedules. Reducing safety margins can broaden the therapeutic window in stereotactic treatments and alleviate concerns for toxicity in high dose-per-fraction treatment schedules. Management of intrafractional motion is a necessity for stereotactic body radiation therapy (SBRT). It can be achieved by performing intrafractional image guidance and position corrections. We evaluate the suitability of such a novel prostate motion management system and its potential benefit for treatment accuracy., Methods: Intrafractional IGRT was performed for 22 patients during 149 treatment sessions using repeated orthogonal kV-XR imaging of implanted fiducial markers with the ExacTrac Dynamic (EXTD) system. Position measurements were taken four times during each arc of the applied volumetric modulated arc therapy (VMAT). Position correction was performed if translational deviation exceeded 2 mm in any direction., Results: Of 677 single EXTD measurements, 20.6% exceeded the predefined threshold of 2 mm 3D deviation. Without intrafractional corrections, 39.4% of all individual measurements would exceed the threshold. The 3D accuracy could thus significantly be improved, reducing mean 3D shifts from 1.97 (± 1.44) mm to 1.39 (± 1.01) mm by performing intrafractional IGRT. In total, 34% of all treatment sessions required correction of intrafractional position shifts., Conclusion: Monitoring of prostate motion using repeated intrafractional orthogonal kV-X-ray-based position measurements of implanted fiducial markers proved to be a reliable method to improve precision of stereotactic irradiations of the prostate. It can prevent unacceptable translation deviations in one third of all sessions., (© 2023. The Author(s).)

Aim of the Study: There is no consensus on the most suitable non-surgical treatment of chronic lateral elbow tendinopathy. The aim of this pilot randomized controlled trial was to evaluate the size of effect of ultrasound-guided percutaneous needle tenotomy., Material and Methods: Three intervention arms were formed: 1) percutaneous needle tenotomy, hydrodissection, and physiotherapy; 2) hydrodissection and physiotherapy; and 3) physiotherapy alone. Patients with chronic lateral elbow tendinopathy were randomized. Clinical endpoints included multiple questionnaires after three months: Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH), Numeric Rating Scale (NRS) pain at rest and during activity, and EuroQol 5D-5L (EQ-5D-5L)., Results: Thirty patients were included of 128 screened. The QuickDASH score improved in the percutaneous needle tenotomy and physiotherapy group, but not in the hydrodissection group. The NRS pain at rest and during activity improved more in the percutaneous needle tenotomy (resp. -2 and -2) and hydrodissection (resp. -3 and -3) groups than in the physiotherapy (resp. +1 and -1) group. The EQ-5D-5L improved similarly in all groups., Conclusions: Patients receiving percutaneous needle tenotomy and/or hydrodissection may show better results in terms of pain but not in their functional outcomes compared to those who received physiotherapy alone. The size of effect, however, is small, so a large sample size is needed for a future randomized controlled trial to further investigate these results., Competing Interests: Conflict of interest The authors do not report any financial or personal connections with other persons or organizations which might negatively affect the contents of this publication and/or claim authorship rights to this publication., (© 2023 Laurens Koonen et al., published by Sciendo.)

Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) frequently require primary radiochemotherapy (RCT). Despite intensity modulation, the desired radiation-induced effects observed in HNSCC may also be observed as side effects in healthy tissue, e.g., the sternocleidomastoid muscle (SCM). These side effects (e.g., tissue fibrosis) depend on the interval between the completion of RCT and restaging CT. For salvage surgery, the optimal time window for surgery is currently clinically postulated at between 6 and 12 weeks after completion of RCT. Thus, no extensive tissue fibrosis is to be expected. This interval is based on clinical studies exploring surgical complications. Studies directly exploring radiation-induced changes of the SCM in HNSCC patients are sparse. The present study quantified tissue alterations in the SCM and paravertebral musculature (PVM) after RCT, applying radiomics to determine the optimal time window for salvage surgery. Three radiomic key parameters, (1) volume, (2) mean positivity of pixels (MPP), and (3) uniformity, were extracted with mint Lesion TM in the staging CTs and restaging CTs of 98 HNSCC patients. Of these, 25 were female, the mean age was 62 (±9.6) years, and 80.9% were UICC Stage IV. The mean restaging interval was 55 (±28; range 29-229) days. Only the mean volume significantly decreased after RCT, from 9.0 to 8.4 and 96.5 to 91.9 mL for the SCM and PVM, respectively (both p = 0.007, both Cohen's d = 0.28). In addition, the mean body mass index (BMI) decreased from 23.9 (±4.2) to 21.0 (±3.6) kg/m² ( p < 0.001; Cohen's d = 0.9). The mean BMI decreased significantly and was correlated with the volume decrease for the SCM (r = 0.27; p = 0.007) and PVM (r = 0.41; p < 0.001). If t -test p -values were adjusted for the BMI decrease, no significant change in volumes for the SCM and PVM was observed (both p > 0.05). The present data support the clinically postulated optimal interval for salvage surgery of 6 to 12 weeks.

Background: The relation of sarcopenia and disability in MS is unknown., Objective: To investigate the relation of temporal muscle thickness (TMT) and disability., Methods: A cohort of 132 people who presented with a clinically isolated syndrome (CIS) suggestive of MS at a mean age of 30.0 years, were prospectively followed clinically and with MRI over 30-years. TMT and expanded disability status scale (EDSS) were assessed at baseline, one- five- ten- fourteen- twenty- and thirty-year follow-up., Results: At 30-years, 27 participants remained classified as having had a CIS, 34 converted to relapsing remitting MS, 26 to secondary progressive MS, and 16 had died due to MS. Using linear mixed effect models with subject nested in time, greater annualized TMT-thinning was seen in individuals who developed MS (-0.04 mm/a, 95%CI: -0.07 to -0.01, p = 0.023). In those who converted to MS, a thinner TMT was reached at 14- (p = 0.008), 20- (p = 0.002) and 30-years (p< 0.001). TMT was negatively correlated with EDSS at 20-years (R=-0.18, p = 0.032) and 30-years (R-0.244, p = 0.005). Longitudinally, TMT at earlier timepoints was not predictive for 30-year clinical outcomes., Conclusion: TMT thinning is accelerated in MS and correlated with disability in later disease stages, but is not predictive of future disability., Competing Interests: Declaration of Competing Interest LH has no conflicts of interest relevant to this study. KC has received honoraria for speaking at meetings, advisory work or support to attend meetings from Merck, Biogen Idec, Sanofi Genzyme and Roche. SM has no conflicts of interest relevant to this study. JF has no conflicts of interest relevant to this study. OC has served as a consultant for Novartis and has received a speaker honorarium from Merck. She has obtained funding from NIHR, UCLH NIHR BRC, National and UK MS Society, PMSA, and MRC. DC is a consultant Hoffmann-La Roche. In the last three years he has been a consultant for Biogen, has received research funding from Hoffmann-La Roche, the International Progressive MS Alliance, the MS Society, and the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre, and a speaker's honorarium from Novartis. He co-supervises a clinical fellowship at the National Hospital for Neurology and Neurosurgery, London, which is supported by Merck. FB is a consultant for Biogen, Bayer, Merck, Roche, Novartis, IXICO and Combinostics; has received funding from European Commission Horizon (2020), UK MS Society, National Institute for Health Research University College London Hospitals Biomedical Research Centre and GE healthcare; and serves on the editorial boards of Radiology, Brain, Neuroradiology, Multiple Sclerosis Journal, and Neurology., (Copyright © 2023. Published by Elsevier B.V.)

In the present study, we explore the role of attachment for microstructural white matter (WM) changes in adolescents with anorexia nervosa (AN) before and after exposure to short-term and nutritional treatment. The case sample consisted of 22 female adolescent inpatients with AN (mean age: 15.2 ± 1.2 years) and the control sample were 18 gender-matched healthy adolescents (mean age: 16.8 ± 0.9 years). We performed a 3T MRI in the patient group during the acute state of AN and after weight restoration (duration: 2.6 ± 1 months) and compared the data to a healthy control group. To classify attachment patterns, we used the Adult Attachment Projective Picture System. In the patient sample, over 50% were classified with an attachment trauma/unresolved attachment status. Prior to treatment exposure, fractional anisotropy (FA) reductions and concordant mean diffusivity (MD) increases were evident in the fornix, the corpus callosum and WM regions of the thalamus, which normalized in the corpus callosum and the fornix post-therapy in the total patient sample ( p < 0.002). In the acute state, patients with an attachment trauma demonstrated significant FA decreases compared to healthy controls, but no MD increases, in the corpus callosum and cingulum bilaterally, which remained decreased after therapy. Attachment patterns seem to be associated with region-specific changes of WM alterations in AN.

Different results have been reported concerning the relationship of the apparent diffusion coefficient (ADC) values and the status of methylation as the promoter gene for the enzyme methylguanine-DNA methyltransferase (MGMT) in patients with glioblastomas (GBs). The aim of this study was to investigate if there were correlations between the ADC values of the enhancing tumor and peritumoral areas of GBs and the MGMT methylation status. In this retrospective study, we included 42 patients with newly diagnosed unilocular GB with one MRI study prior to any treatment and histopathological data. After co-registration of ADC maps with T1-weighted sequences after contrast administration and dynamic susceptibility contrast (DSC) perfusion, we manually selected one region-of-interest (ROI) in the enhancing and perfused tumor and one ROI in the peritumoral white matter. Both ROIs were mirrored in the healthy hemisphere for normalization. In the peritumoral white matter, absolute and normalized ADC values were significantly higher in patients with MGMT-unmethylated tumors, as compared to patients with MGMT-methylated tumors (absolute values p = 0.002, normalized p = 0.0007). There were no significant differences in the enhancing tumor parts. The ADC values in the peritumoral region correlated with MGMT methylation status, confirmed by normalized ADC values. In contrast to other studies, we could not find a correlation between the ADC values or the normalized ADC values and the MGMT methylation status in the enhancing tumor parts.

Radiation necrosis represents a potentially devastating complication after radiation therapy in brain tumors. The establishment of the diagnosis and especially the differentiation from progression and pseudoprogression with its therapeutic implications requires interdisciplinary consent and monitoring. Herein, we want to provide an overview of the diagnostic modalities, therapeutic possibilities and an outlook on future developments to tackle this challenging topic. The aim of this report is to provide an overview of the current morphological, functional, metabolic and evolving imaging tools described in the literature in order to (I) identify the best criteria to distinguish radionecrosis from tumor recurrence after the radio-oncological treatment of malignant gliomas and cerebral metastases, (II) analyze the therapeutic possibilities and (III) give an outlook on future developments to tackle this challenging topic. Additionally, we provide the experience of a tertiary tumor center with this important issue in neuro-oncology and provide an institutional pathway dealing with this problem.

Locally-advanced head and neck squamous cell carcinoma (HNSCC) is mainly defined by the presence of pathologic cervical lymph nodes (LNs) with or without extracapsular spread (ECS). Current radiologic criteria to classify LNs as non-pathologic, pathologic, or pathologic with ECS are primarily shape-based. However, significantly more quantitative information is contained within imaging modalities. This quantitative information could be exploited for classification of LNs in patients with locally-advanced HNSCC by means of artificial intelligence (AI). Currently, various reviews exploring the role of AI in HNSCC are available. However, reviews specifically addressing the current role of AI to classify LN in HNSCC-patients are sparse. The present work systematically reviews original articles that specifically explore the role of AI to classify LNs in locally-advanced HNSCC applying Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines and the Study Quality Assessment Tool of National Institute of Health (NIH). Between 2001 and 2022, out of 69 studies a total of 13 retrospective, mainly monocentric, studies were identified. The majority of the studies included patients with oropharyngeal and oral cavity (9 and 7 of 13 studies, respectively) HNSCC. Histopathologic findings were defined as reference in 9 of 13 studies. Machine learning was applied in 13 studies, 9 of them applying deep learning. The mean number of included patients was 75 (SD ± 72; range 10-258) and of LNs was 340 (SD ± 268; range 21-791). The mean diagnostic accuracy for the training sets was 86% (SD ± 14%; range: 43-99%) and for testing sets 86% (SD ± 5%; range 76-92%). Consequently, all of the identified studies concluded AI to be a potentially promising diagnostic support tool for LN-classification in HNSCC. However, adequately powered, prospective, and randomized control trials are urgently required to further assess AI's role in LN-classification in locally-advanced HNSCC.

Background and Purpose: Phosphorous magnetic resonance spectroscopy (31P-MRS) allows a non-invasive analysis of phosphorus-containing compounds in vivo. The present study investigated the influence of brain region, hemisphere, age, sex and brain volume on 31P-MRS metabolites in healthy adults., Materials and Methods: Supratentorial brain 31P-MRS spectra of 125 prospectively recruited healthy volunteers (64 female, 61 male) aged 20 to 85 years (mean: 49.4 ± 16.9 years) were examined with a 3D-31P-MRS sequence at 3T, and the compounds phosphocreatine (PCr), inorganic phosphate (Pi) and adenosine triphosphate (ATP) were measured. From this data, the metabolite ratios PCr/ATP, Pi/ATP and PCr/Pi were calculated for different brain regions. In addition, volumes of gray matter, white matter and cerebrospinal fluid were determined., Results: For all metabolite ratios significant regional differences and in several regions sex differences were found. In some brain regions and for some metabolites hemispheric differences were detected. In addition, changes with aging were found, which differed between women and men., Conclusions: The present results indicate that 31P-MRS metabolism varies throughout the brain, with age and between sexes, and therefore have important practical implications for the design and the interpretation of future 31P-MRS studies under physiological conditions and in patients with various cerebral diseases., Competing Interests: Conflict of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Language impairments, hallmarks of speech/language variant progressive supranuclear palsy, also occur in Richardson's syndrome (PSP-RS). Impaired communication may interfere with daily activities. Therefore, assessment of language functions is crucial. It is uncertain whether the Aachen Aphasia Test (AAT) is practicable in PSP-RS, behavioral variant frontotemporal dementia (bvFTD) and Alzheimer's dementia (AD) and language deficits differ in these disorders. 28 PSP-RS, 24 AD, and 24 bvFTD patients were investigated using the AAT and the CERAD-Plus battery. 16-25% of all patients failed in AAT subtests for various reasons. The AAT syndrome algorithm diagnosed amnestic aphasia in 5 (23%) PSP-RS, 7 (36%) bvFTD and 6 (30%) AD patients, Broca aphasia in 1 PSP-RS and 1 bvFTD patient, Wernicke aphasia in 1 bvFTD and 3 (15%) AD patients. However, aphasic symptoms resembled non-fluent primary progressive aphasia in 14 PSP-RS patients. In up to 46% of PSP-RS patients, 61% of bvFTD and 64% of AD patients significant impairments were found in the AAT subtests spontaneous speech, written language, naming, language repetition, language comprehension and the Token subtest. The CERAD-Plus subtest semantic fluency revealed significant impairment in 81% of PSP-RS, 61% of bvFTD, 44% of AD patients, the phonemic fluency subtest in 31, 40 and 31%, respectively. In contrast to bvFTD and AD, severity of language impairment did not correlate with cognitive decline in PSP-RS. In summary, the patterns of aphasia differ between the diagnoses. Local frontal language networks might be impaired in PSP-RS, whereas in AD and bvFTD, more widespread neuropathology might underly language impairment., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The purpose of our study is to quantify the extent to which Virchow-Robin spaces (VRS) detected on in vivo MRI are reproducible by post-mortem MRI.Double Echo Steady State 3T MRIs were acquired post-mortem in 49 double- and 32 single-hemispheric formalin-fixed brain sections from 12 patients, who underwent conventional diagnostic 1.5 or 3T MRI in median 22 days prior to death (25% to 75%: 12 to 134 days). The overlap of in vivo and post-mortem VRS segmentations was determined accounting for potential confounding factors.The reproducibility of VRS found on in vivo MRI by post-mortem MRI, in the supratentorial white matter was in median 80% (25% to 75%: 60 to 100). A lower reproducibility was present in the basal ganglia, with a median of 47% (25% to 75%: 30 to 50).VRS segmentations were histologically confirmed in one double hemispheric section.Overall, the majority of VRS found on in vivo MRI was stable throughout death and formalin fixation, emphasizing the translational potential of post-mortem VRS studies.

Preoperative grade prediction is important in diagnostics of glioma. Even more important can be follow-up after chemotherapy and radiotherapy of high grade gliomas. In this review we provide an overview of MR-spectroscopy (MRS), technical aspects, and different clinical scenarios in the diagnostics and follow-up of gliomas in pediatric and adult populations. Furthermore, we provide a recap of the current research utility and possible future strategies regarding proton- and phosphorous-MRS in glioma research.

Introduction: In this post hoc analysis we compared various response-assessment criteria in newly diagnosed glioblastoma (GB) patients treated with tumor lysate-charged autologous dendritic cells (Audencel) and determined the differences in prediction of progression-free survival (PFS) and overall survival (OS). Methods: 76 patients enrolled in a multicenter phase II trial receiving standard of care (SOC, n = 40) or SOC + Audencel vaccine (n = 36) were included. MRI scans were evaluated using MacDonald, RANO, Vol-RANO, mRANO, Vol-mRANO and iRANO criteria. Tumor volumes (T1 contrast-enhancing as well as T2/FLAIR volumes) were calculated by semiautomatic segmentation. The Kruskal-Wallis-test was used to detect differences in PFS among the assessment criteria; for correlation analysis the Spearman test was used. Results: There was a significant difference in median PFS between mRANO (8.6 months) and Vol-mRANO (8.6 months) compared to MacDonald (4.0 months), RANO (4.2 months) and Vol-RANO (5.4 months). For the vaccination arm, median PFS by iRANO was 6.2 months. There was no difference in PFS between SOC and SOC + Audencel. The best correlation between PFS/OS was detected for mRANO (r = 0.65) and Vol-mRANO (r = 0.69, each p < 0.001). A total of 16/76 patients developed a pure T2/FLAIR progressing disease, and 4/36 patients treated with Audencel developed pseudoprogression. Conclusion: When comparing different response-assessment criteria in GB patients treated with dendritic cell-based immunotherapy, the best correlation between PFS and OS was observed for mRANO and Vol-mRANO. Interestingly, iRANO was not superior for predicting OS in patients treated with Audencel.

The aim of the present study was to investigate whether grey matter (GM) reductions in acute anorexia nervosa (AN) are (i) valid for adolescents (age 14-18 years), (ii) reversible following short-term psychotherapeutic and nutritional therapy and (iii) depend on psychological components like attachment trauma. 3T MRI including a high-resolution T1 MPRAGE was performed in 22 female adolescents in the acute state of AN (age: 15.2 ± 1.2 years) and after weight restoration (duration: 2.6 ± 1 months, n = 18) and compared with 18 gender-matched healthy controls. The Adult Attachment Projective Picture System was used to classify resolved and unresolved attachment patterns. GM decreases were localized in extensive cortical areas including the insula, prefrontal and cingulate cortices as well as subcortical regions during acute AN, which partially increased after therapy with a relative sparing of the hippocampus and parahippocampal gyrus. The resolved group showed more GM recovery in regions of the left hippocampus and parahippocampal gyrus, bilateral cerebellar regions, right precuneus and adjacent cingulate cortices relative to the unresolved pattern. Structural anomalies in adolescent AN that recovered after treatment may be primarily the consequence of malnutrition, whereas several regions did not display significant recovery. Attachment status seems to influence region-specific GM recovery., (© 2022 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Brain volumetric software is increasingly suggested for clinical routine. The present study quantifies the agreement across different software applications. Ten cases with and ten gender- and age-adjusted healthy controls without hippocampal atrophy (median age: 70; 25-75% range: 64-77 years and 74; 66-78 years) were retrospectively selected from a previously published cohort of Alzheimer's dementia patients and normal ageing controls. Hippocampal volumes were computed based on 3 Tesla T1-MPRAGE-sequences with FreeSurfer (FS), Statistical-Parametric-Mapping (SPM; Neuromorphometrics and Hammers atlases), Geodesic-Information-Flows (GIF), Similarity-and-Truth-Estimation-for-Propagated-Segmentations (STEPS), and Quantib™. MTA (medial temporal lobe atrophy) scores were manually rated. Volumetric measures of each individual were compared against the mean of all applications with intraclass correlation coefficients (ICC) and Bland-Altman plots. Comparing against the mean of all methods, moderate to low agreement was present considering categorization of hippocampal volumes into quartiles. ICCs ranged noticeably between applications (left hippocampus (LH): from 0.42 (STEPS) to 0.88 (FS); right hippocampus (RH): from 0.36 (Quantib™) to 0.86 (FS). Mean differences between individual methods and the mean of all methods [mm 3 ] were considerable (LH: FS -209, SPM-Neuromorphometrics -820; SPM-Hammers -1474; Quantib™ -680; GIF 891; STEPS 2218; RH: FS -232, SPM-Neuromorphometrics -745; SPM-Hammers -1547; Quantib™ -723; GIF 982; STEPS 2188). In this clinically relevant sample size with large spread in data ranging from normal aging to severe atrophy, hippocampal volumes derived by well-accepted applications were quantitatively different. Thus, interchangeable use is not recommended.

In head and neck squamous cell carcinoma (HNSCC) pathologic cervical lymph nodes (LN) remain important negative predictors. Current criteria for LN-classification in contrast-enhanced computed-tomography scans (contrast-CT) are shape-based; contrast-CT imagery allows extraction of additional quantitative data ("features"). The data-driven technique to extract, process, and analyze features from contrast-CTs is termed "radiomics". Extracted features from contrast-CTs at various levels are typically redundant and correlated. Current sets of features for LN-classification are too complex for clinical application. Effective eliminative feature selection (EFS) is a crucial preprocessing step to reduce the complexity of sets identified. We aimed at exploring EFS-algorithms for their potential to identify sets of features, which were as small as feasible and yet retained as much accuracy as possible for LN-classification. In this retrospective cohort-study, which adhered to the STROBE guidelines, in total 252 LNs were classified as "non-pathologic" ( n = 70), "pathologic" ( n = 182) or "pathologic with extracapsular spread" ( n = 52) by two experienced head-and-neck radiologists based on established criteria which served as a reference. The combination of sparse discriminant analysis and genetic optimization retained up to 90% of the classification accuracy with only 10% of the original numbers of features. From a clinical perspective, the selected features appeared plausible and potentially capable of correctly classifying LNs. Both the identified EFS-algorithm and the identified features need further exploration to assess their potential to prospectively classify LNs in HNSCC.

Brain parenchyma infiltration with glioblastoma (GB) cannot be entirely visualized by conventional magnetic resonance imaging (MRI). The aim of this study was to investigate changes in the energy and membrane metabolism measured with phosphorous MR spectroscopy (31P-MRS) in the presumably "normal-appearing" brain following chemoradiation therapy (CRT) in GB patients in comparison to healthy controls. Twenty (seven female, thirteen male) GB patients underwent a 31P-MRS scan prior to surgery (baseline) and after three months of standard CRT (follow-up examination. The regions of interest "contrast-enhancing (CE) tumor" (if present), "adjacent to the (former) tumor", "ipsilateral distant" hemisphere, and "contralateral" hemisphere were compared, differentiating between patients with stable (SD) and progressive disease (PD). Metabolite ratios PCr/ATP, Pi/ATP, PCr/Pi, PME/PDE, PME/PCr, and PDE/ATP were investigated. In PD, energy and membrane metabolism in CE tumor areas have a tendency to "normalize" under therapy. In different "normal-appearing" brain areas of GB patients, the energy and membrane metabolism either "normalized" or were "disturbed", in comparison to baseline or controls. Differences were also detected between patients with SD and PD. 31P-MRS might contribute as an additional imaging biomarker for outcome measurement, which remains to be investigated in a larger cohort.

The COVID-19 pandemic has an unprecedented impact on cancer treatment worldwide. We aimed to evaluate the effects of the pandemic on the radiation treatment of patients in order to provide data for future management of such crises. We compared the number of performed radiotherapy sessions of the pandemic period from February 2020 until May 2021 with those of 2018 and 2019 for reference. At our department, no referred patients had to be rejected or postponed, nor any significant changes in fractionation schedules implemented. Nevertheless, there was a substantial drop in overall radiotherapy sessions in 2020 following the first incidence wave of up to -25% (in June) in comparison to previous years. For breast cancer, a maximum decline of sessions of -45% (July) was recorded. Only a short drop of prostate cancer sessions (max -35%, May) followed by a rebound (+42%, July) was observed. Over the investigated period, a loss of 4.4% of expected patients never recovered. The severe impact of COVID-19 on cancer treatment, likely caused by retarded diagnosis and delayed interdisciplinary co-treatment, is reflected in a lower count of radiotherapy sessions. Radiation oncology is a crucial cornerstone in upholding both curative treatment options and treatment capacity during a pandemic.

Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) progress relentlessly and lead to a need for care. Caregiving is often burdensome. Little is known about the course of caregiver burden (CB) in PSP and CBS patients. Longitudinal analysis of CB in family members caring for PSP and CBS patients. Single-center longitudinal pilot study in 68 newly diagnosed patients with probable PSP and CBS (52 Richardson's syndrome; 1 progressive gait freezing of PSP; 15 CBS). Demographic, educational, occupational parameters, family status, motor functions (UPDRSIII, Hoehn and Yahr Score, Tinetti) and neuropsychological performance (CERAD Plus, Frontal Assessment Battery) were assessed, as well as behavioral and neuropsychiatric impairments (Frontal Behavioral Inventory, Neuropsychiatric Inventory), activities of daily living (ADL) and caregiver burden using the Caregiver Strain Index (CSI), in most patients also the Zarit Burden Interview (ZBI). Patients were followed up every 6 months for up to 2 years. Caregivers reported mild to moderate CB at baseline, which increased by 25-30% in 2 years and was significantly greater in PSP than in CBS. Risk for mental health problems increased over time, especially in female caregivers (depression). Important patient-related factors were apathy, aspontaneity, depression, irritability, disorganization, poor judgment, impairment of language, impairments in ADL, a high educational level of the patient and close family relationship. Behavioral symptoms and impaired ADL are the main patient-related factors of CB in PSP and CBS. CB can be severe and needs to be assessed repeatedly from the time of diagnosis to provide comprehensive support., (© 2021. The Author(s).)

Primary CNS lymphoma (PCNSL) is a highly aggressive malignant disease with a high recurrence rate and a poor prognosis. We present the case of a 71-year-old woman diagnosed with PCNSL in June 2010. After 3 relapses and intensive treatment with multiple chemotherapy regimens and whole-brain radiotherapy, she received off-label treatment with the Bruton tyrosine kinase inhibitor ibrutinib, responded well, achieved a complete remission, and is progression-free for now >3 years., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 by S. Karger AG, Basel.)

The World Health Organisation's (WHO) classification of brain tumors requires consideration of both histological appearance and molecular characteristics. Possible differences in brain energy metabolism could be important in designing future therapeutic strategies. Forty-three patients with primary, isocitrate dehydrogenase 1 (IDH1) wild type glioblastomas (GBMs) were included in this study. Pre-operative standard MRI was obtained with additional phosphorous magnetic resonance spectroscopy (31-P-MRS) imaging. Following microsurgical resection of the tumors, biopsy specimens underwent neuropathological diagnostics including standard molecular diagnosis. The spectroscopy results were correlated with epidermal growth factor (EGFR) and O6-Methylguanine-DNA methyltransferase (MGMT) status. EGFR amplified tumors had significantly lower phosphocreatine (PCr) to adenosine triphosphate (ATP)-PCr/ATP and PCr to inorganic phosphate (Pi)-PCr/Pi ratios, and higher Pi/ATP and phosphomonoesters (PME) to phosphodiesters (PDE)-PME/PDE ratio than those without the amplification. Patients with MGMT-methylated tumors had significantly higher cerebral magnesium (Mg) values and PME/PDE ratio, while their PCr/ATP and PCr/Pi ratios were lower than in patients without the methylation. In survival analysis, not-EGFR-amplified, MGMT-methylated GBMs showed the longest survival. This group had lower PCr/Pi ratio when compared to MGMT-methylated, EGFR-amplified group. PCr/Pi ratio was lower also when compared to the MGMT-unmethylated, EGFR not-amplified group, while PCr/ATP ratio was lower than all other examined groups. Differences in energy metabolism in various molecular subtypes of wild-type-GBMs could be important information in future precision medicine approach.

Many studies report an overlap of MRI and clinical findings between patients with relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS), which in part is reflective of inclusion of subjects with variable disease duration and short periods of follow-up. To overcome these limitations, we examined the differences between RRMS and SPMS and the relationship between MRI measures and clinical outcomes 30 years after first presentation with clinically isolated syndrome suggestive of multiple sclerosis. Sixty-three patients were studied 30 years after their initial presentation with a clinically isolated syndrome; only 14% received a disease modifying treatment at any time point. Twenty-seven patients developed RRMS, 15 SPMS and 21 experienced no further neurological events; these groups were comparable in terms of age and disease duration. Clinical assessment included the Expanded Disability Status Scale, 9-Hole Peg Test and Timed 25-Foot Walk and the Brief International Cognitive Assessment For Multiple Sclerosis. All subjects underwent a comprehensive MRI protocol at 3 T measuring brain white and grey matter (lesions, volumes and magnetization transfer ratio) and cervical cord involvement. Linear regression models were used to estimate age- and gender-adjusted group differences between clinical phenotypes after 30 years, and stepwise selection to determine associations between a large sets of MRI predictor variables and physical and cognitive outcome measures. At the 30-year follow-up, the greatest differences in MRI measures between SPMS and RRMS were the number of cortical lesions, which were higher in SPMS (the presence of cortical lesions had 100% sensitivity and 88% specificity), and grey matter volume, which was lower in SPMS. Across all subjects, cortical lesions, grey matter volume and cervical cord volume explained 60% of the variance of the Expanded Disability Status Scale; cortical lesions alone explained 43%. Grey matter volume, cortical lesions and gender explained 43% of the variance of Timed 25-Foot Walk. Reduced cortical magnetization transfer ratios emerged as the only significant explanatory variable for the symbol digit modality test and explained 52% of its variance. Cortical involvement, both in terms of lesions and atrophy, appears to be the main correlate of progressive disease and disability in a cohort of individuals with very long follow-up and homogeneous disease duration, indicating that this should be the target of therapeutic interventions., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Dual-energy computed tomography (DECT) allows distinguishing between tissues with similar X-ray attenuation but different atomic numbers. Recent studies demonstrated that this technique has several areas of application in patients with ischemic stroke and a potential impact on patient management. After endovascular stroke therapy (EST), hyperdense areas can represent either hemorrhage or contrast staining due to blood-brain barrier disruption, which can be differentiated reliably by DECT. Further applications are improved visualization of early infarctions, compared to single-energy computed tomography, and prediction of transformation into infarction or hemorrhage in contrast-enhancing areas. In addition, DECT allows detection and evaluation of the material composition of intra-arterial clots after EST. This review summarizes the clinical state-of-the-art of DECT in patients with stroke, and features some prospects for future developments. KEY POINTS: • Dual-energy computed tomography (DECT) allows differentiation between tissues with similar X-ray attenuation but differentatomic numbers. • DECT has several areas of application in patients with ischemic stroke and a potential impact on patient management. • Prospects for future developments in DECT may improve treatment decision-making.

Overall survival (OS) of patients with brain metastases treated with hypofractionated (HFSRT) or single-fraction (SRS) radiosurgery depends on several prognostic factors. The aim of this study was to investigate the potential of sex as an independent predictor of OS and evaluate the predictive accuracy of common prognostic scores. Retrospective analysis of 281 consecutive patients receiving radiosurgery of brain metastases was performed. Kaplan-Meier survival curves and Cox proportional hazards models were used to compare OS between SRS and HFSRT and by sex, before and after propensity-score matching (PSM) on key baseline prognostic covariates. Prognostic scores were evaluated using Harrell's concordance index. Median OS was 11 months after both SRS and HFSRT. After PSM, median OS was 12 months after SRS (95% CI: 7.5-16.5) and 9 months after HFSRT (95% CI: 5.0-13.0; p = 0.77). Independent prognostic factors were sex, primary tumor, KPI, and systemic disease status. Median OS was 16 months for women and 7 months for male patients (p < 0.001). After excluding sex specific tumors, PSM revealed a median OS of 16 months for women and 8 months for male patients (p < 0.01). Evaluation of prognostic indices showed BSBM to be the most accurate (Harrell's C = 0.68), followed by SIR (0.61), GPA (0.60), RPA (0.58), and Rades et al. (0.57). OS after HFSRT and SRS did not differ, although PSM revealed a non-significant advantage for SRS. Female sex was found to be a major independent positive prognostic factor for survival, and thus should be considered in the personalized decision-making of brain metastases treatment.

Objective: To determine 30-year brain atrophy rates following clinically isolated syndromes and the relationship of atrophy in the first 5 years and clinical outcomes 25 years later., Methods: A cohort of 132 people who presented with a clinically isolated syndrome suggestive of multiple sclerosis (MS) were recruited between 1984-1987. Clinical and MRI data were collected prospectively over 30 years. Widths of the third ventricle and the medulla oblongata were used as linear atrophy measures., Results: At 30 years, 27 participants remained classified as having had a clinically isolated syndrome, 34 converted to relapsing remitting MS, 26 to secondary progressive MS and 16 had died due to MS. The mean age at baseline was 31.7 years (SD 7.5) and the mean disease duration was 30.8 years (SD 0.9). Change in medullary and third ventricular width within the first 5 years, allowing for white matter lesion accrual and Expanded Disability Status Scale increases over the same period, predicted clinical outcome measures at 30 years. 1 mm of medullary atrophy within the first 5 years increased the risk for secondary progressive MS or MS related death by 30 years by 583% (OR 5.83, 95% CI 1.74 to 19.61, p<0.005), using logistic regression., Conclusions: Our findings show that brain regional atrophy within 5 years of a clinically isolated syndrome predicts progressive MS or a related death, and disability 25 years later., Competing Interests: Competing interests: LH has nothing to declare. KC has received honoraria for speaking at meetings, advisory work or support to attend meetings from Biogen, Sanofi-Genzyme and Roche. GB, AE, SM, FP and CT have nothing to declare. OC serves as a consultant for Novartis, Roche, Teva and Merck, and receives personal fees from Neurology and Multiple Sclerosis Journal. Outside the submitted work, she has received research grants from Spinal Cord Research Foundation, Rosetrees trust, Progressive MS Alliance, Bioclinica & GE Neuro, and EU-H2020. FB serves as a consultant for Bayer Schering Pharma, Sanofi-Genzyme, Biogen Idec, Teva, Merck Serono, Novartis, Roche, IXICO, GeNeuro, Apitope and Jansen Research. DC is a consultant for Biogen and Roche., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Immunotherapies targeting α-synuclein aim to limit its extracellular spread in the brain and prevent progression of pathology in Parkinson's disease (PD). PD03A is a specific active immunotherapy (SAIT) involving immunization with a short peptide formulation., Objective: This phase 1 study characterized the safety and tolerability of PD03A in patients with early PD. A key secondary objective was to evaluate immunological activity following immunization., Methods: This was a phase 1 study of two different doses of PD03A versus placebo in PD patients. Patients were randomized (1:1:1) to receive four priming plus one booster vaccination of PD03A 15μg, PD03A 75μg or placebo and were followed for 52 weeks., Results: Overall, 36 patients were randomized, of which 35 received five immunizations and completed the study. All patients experienced at least one adverse event. Transient local injection site reactions affected all but two patients; otherwise most AEs were considered unrelated to study treatment. A substantial IgG antibody response against PD03 was observed with a maximum titer achieved at Week-12. Differences in titers between both active groups versus placebo were statistically significant from the second immunization at Week-8 until Week-52., Conclusion: The safety profile and positive antibody response of PD03A supports the further development of active immunotherapeutic approaches for the treatment of PD.

Introduction: Quantitative MR planimetric measurements were reported to discriminate between progressive supranuclear palsy (PSP) and non-PSP parkinsonism, yet few data exist on the usefulness of these markers in early disease stages., Methods: The pons-to-midbrain area ratio (P/M) and the Magnetic Resonance Parkinsonism Index (MRPI) as well as new indices, termed P/M2.0 and MRPI2.0, multiplying the former by a ratio of the third ventricle (3rdV) width/frontal horns (FH) width, were calculated on T1-weighted images in 84 patients with clinically unclassifiable neurodegenerative parkinsonism (CUP) at the time of imaging. Areas under the curve (AUCs) of these markers for predicting future PSP was determined. The final clinical diagnosis was made after at least 24 months of follow-up., Results: Final diagnosis was Parkinson's disease in 55 patients, multiple system atrophy in 12 cases, and PSP in 17. At baseline imaging, patients with a final PSP diagnosis had significantly higher MRPI, P/M, MRPI2.0 and P/M2.0 values compared to the other groups. AUCs in discriminating between future PSP and non-PSP parkinsonism were 0.91 for both the P/M and the MRPI and 0.98 for the P/M2.0 and the MRPI2.0., Conclusions: Brainstem-derived MR planimetric measures yield high diagnostic accuracy for separating PSP from non-PSP parkinsonism in early disease stages when clinical criteria are not yet fully met. Consistent with the underlying pathology in PSP, our study suggests that inclusion of 3 rd V width makes P/M2.0 and MRPI2.0 more accurate in diagnosing early stage PSP patients than the P/M and MRPI., (Copyright © 2020. Published by Elsevier Ltd.)

Friedreich's ataxia (FRDA) is a rare genetic disorder leading to degenerative processes. So far, no effective treatment has been found. Therefore, it is important to assist the development of medication with imaging biomarkers reflecting disease status and progress. Ten FRDA patients (mean age 37 ± 14 years; four female) and 10 age- and sex-matched controls were included. Acquisition of magnetic resonance imaging (MRI) data for quantitative susceptibility mapping, R 1 , R 2 relaxometry and diffusion imaging was performed at 7 Tesla. Results of volume of interest (VOI)-based analyses of the quantitative data were compared with a voxel-based morphometry (VBM) evaluation. Differences between patients and controls were assessed using the analysis of covariance (ANCOVA; p < 0.01) with age and sex as covariates, effect size of group differences, and correlations with disease characteristics with Spearman correlation coefficient. For the VBM analysis, a statistical threshold of 0.001 for uncorrected and 0.05 for corrected p-values was used. Statistically significant differences between FRDA patients and controls were found in five out of twelve investigated structures, and statistically significant correlations with disease characteristics were revealed. Moreover, VBM revealed significant white matter atrophy within regions of the brainstem, and the cerebellum. These regions overlapped partially with brain regions for which significant differences between healthy controls and patients were found in the VOI-based quantitative MRI evaluation. It was shown that two independent analyses provided overlapping results. Moreover, positive results on correlations with disease characteristics were found, indicating that these quantitative MRI parameters could provide more detailed information and assist the search for effective treatments., (© 2020 The Authors. Journal of Neuroscience Research published by Wiley Periodicals LLC.)

Background: Based on the evidence that meditation is associated with numerous beneficial effects on well-being and reduced stress-related symptoms, mindfulness-based techniques were increasingly implemented into psychotherapeutic programs. However, different meditation styles and the cross-sectional nature of most previous analyses resulted in a great variety of morphometric findings. The present study aims to elucidate cortical reorganization processes and altered axonal integrity caused by short-term meditation training, and benefits from solely using focused attention meditation (FAM)., Methods: 3 T MRI, including T1-MPRAGE and diffusion-weighted sequences, was performed in 27 healthy, meditation naïve participants (age: 43 ± 12.4 years) pre and post FAM meditation training (duration: 7.3 ± 0.4 weeks). Voxel-based morphometry was applied to assess brain changes in gray and white matter. Questionnaires were filled out by the individuals at both time-points to evaluate quality of life and self-awareness deficits., Results: The major findings comprised (i) gray matter increases in the insula, the caudate nucleus and frontal cortices, (ii) decreases in extended parietotemporal regions, the right medial prefrontal cortex and the parahippocampal gyrus, as well as (iii) fractional anisotropy increases of the right hippocampus, the basal ganglia and adjacent regions. Regression analysis revealed an association of specific alterations with reduced levels of state anxiety., Conclusions: FAM training induced a broad range of dynamic brain alterations even within few weeks of training. Interestingly, this cohort revealed more, and partially different patterns of structural gray matter change compared to prior studies. The broad impact on neuronal organization processes may reflect more general outcomes related to health and well-being., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: To determine an exploratory multimodal approach including serum NFL and MR planimetric measures to discriminate Parkinson's disease (PD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP)., Methods: MR planimetric measurements and NFL serum levels, with a mean time interval of 60 months relative to symptom onset, were assessed in a retrospective cohort of 11 progressive supranuclear palsy (PSP), 22 Parkinson's disease (PD), 16 multiple system atrophy (MSA) patients and 42 healthy controls (HC). A decision tree model to discriminate PD, PSP, and MSA was constructed using receiver operating characteristic curve analysis and Classification and Regression Trees algorithm., Results: Our multimodal decision tree provided accurate differentiation of PD versus MSA and PSP patients using a serum NFL cut-off of 14.66 ng/L. The pontine-to-midbrain-diameter-ratio (P d /M d ) discriminated MSA from PSP at a cut-off value of 2.06. The combined overall diagnostic yield was an accuracy of 83.7% (95% CI 69.8-90.8%)., Conclusion: We provide a clinically feasible decision algorithm which combines serum NFL levels and a planimetric MRI marker to differentiate PD, MSA and PSP with high diagnostic accuracy., Classification of Evidence: This study provides Class III evidence that the combination of serum NFL levels und MR planimetric measurements discriminates between PD, PSP and MSA., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: MR planimetry of brainstem structures can be helpful for the discrimination of Parkinsonian syndromes. It has been suggested that ageing might influence brainstem MR measurements assessed by MR planimetry, while effects of gender and total intracranial volume (TIV) have not been assessed so far. The aim of this study was to evaluate age, gender and TIV effects on brainstem MR planimetric measures., Methods: Brainstem MR planimetric measures of diameters (midbrain, pons, middle and superior cerebellar peduncle) and areas (pons and midbrain), the derived ratios, and the magnetic resonance Parkinsonism index (MRPI) were assessed on 1.5-T MR images in a large cohort of 97 healthy controls and analysed for the influence of age, gender and TIV with univariate and multivariate linear models., Results: Neither gender nor age effects on planimetric measurements were observed in the population relevant for the differential diagnosis of neurodegenerative Parkinsonism, aged 50 to 80 years, except for single area-derived measurements, with gender effects on pontine area (p = 0.013) and age effects on midbrain area (p = 0.037). Results were similar upon inclusion of the TIV in the analyses., Conclusions: There is no need to correct for age, gender or TIV when using brainstem-derived MR planimetric measurements in the differential diagnosis of neurodegenerative Parkinsonism., Key Points: • There were no gender effects on single or combined imaging measurements of the brainstem in the population aged 50 to 80 years, the age range relevant for the differential diagnosis of neurodegenerative Parkinsonism (except for pontine area). • There were no age effects on single or combined imaging measurements of the brainstem in the population aged 50 to 80 years, the age range relevant for the differential diagnosis of neurodegenerative Parkinsonism (except for midbrain area). • There is no need for age- or gender-specific cut-offs for the relevant age group.

Introduction: Intracranial neoplasms are an uncommon cause of symptomatic parkinsonism. We here report a patient with an extensive middle and posterior fossa arachnoid cyst presenting with parkinsonism that was treated by neurosurgical intervention., Methods: Retrospective chart review and clinical examination of the patient., Case Report: This 55-year-old male patient with hemiparkinsonism and recurrent bouts of headaches was first diagnosed in 1988. CT scans revealed multiple cystic lesions compressing brainstem and basal ganglia, which were partially resected. Subsequently, the patient was free of complaints for 20 years. In 2009 the patient presented once more with severe unilateral tremor and thalamic pain affecting the right arm. Despite symptomatic treatment with L-Dopa and pramipexole symptoms worsened over time. In 2014 there was further progression with increasing hemiparkinsonism, hemidystonia, unilateral thalamic pain and pyramidal signs. Repeat CT scanning revealed a progression of the cysts as well as secondary hydrocephalus. Following repeat decompression of the brainstem and fenestration of all cystic membranes parkinsonism improved with a MDS- UPDRS III score reduction from 39 to 21. Histology revealed arachnoid cystic material., Conclusion: We report on a rare case of recurrent symptomatic hemiparkinsonism resulting from arachnoid cysts.

Background: The overall frequency of cranial nerve pathology, including cranial nerves other than the trigeminal nerve, as well as its relation to brainstem lesion formation on magnetic resonance imaging (MRI) and clinical correlates in multiple sclerosis (MS) is unknown. Objective: We aimed to determine the frequency of cranial nerve enhancement on MRI, and its association with brainstem lesion formation and clinical outcomes. Methods: We retrospectively analyzed, in 183 patients, (RRMS: 156, SPMS: 15, PPMS: 6, CIS: 6) 651 MRIs (76.5% on the identical scanner Siemens Trio Tim, 3T with identical MRI protocols). Frequencies of cranial nerve enhancement on post contrast T1-weighted MRIs were compared to lesion counts and the MS-severity-score. Results: Cranial nerve enhancement was present in 8.2% of the analyzed MS patients (oculomotor-nerve: 1.1%, trigeminal-nerve: 2.7%, abducens-nerve: 2.2%, facial-/vestibulocochlear nerve: 1.6%, vagal-nerve: 0.5%). Of those, 13% suffered from repeated episodes and 27% exhibited a cranial nerve enhancement duration of >12 months. Age at MS onset was lower in patients with cranial nerve enhancement, 23 vs. 28 years, p = 0.049. The MS-severity-score, 5.15 vs. 0.88 ( p = 0.019), the T2 brainstem-, 1 vs. 0 ( p = 0.041), and the total intracranial contrast-enhancing lesion counts, 2 vs. 0 ( p = 0.000), were higher in patients with cranial nerve enhancement, compared to age-, disease duration-, and gender- matched MS patients. Conclusions: Cranial nerve enhancement, present in 8.2% of our patients, was associated with a younger age at MS onset, brainstem lesions, and a more severe disease course., (Copyright © 2019 Haider, Chan, Olbert, Mangesius, Dal-Bianco, Leutmezer, Prayer and Thurnher.)

Introduction: Several previous studies examined different brainstem-derived MR planimetric measures with regards to their diagnostic accuracy in separating patients with neurodegenerative parkinsonian disorders and reported conflicting results. The current study aimed to compare their performance in a well-characterized sample of patients with neurodegenerative parkinsonian disorders., Methods: MR planimetric measurements were assessed in a large retrospective cohort of 55 progressive supranuclear palsy (PSP), 194 Parkinson's disease (PD) and 63 multiple system atrophy (MSA) patients. This cohort served as a training set used to build C4.5 decision tree models to discriminate PSP, PD and MSA. The models were validated in two independent test sets. The first test set comprised 84 patients with early, clinically unclassifiable parkinsonism (CUP). A prospective cohort of patients with PSP (n = 23), PD (n = 40) and MSA (n = 22) was exploited as a second test-set., Results: The pons-to-midbrain diameter ratio, the midbrain diameter, the middle cerebellar peduncle width and the pons area were identified as the most predictive parameters to separate PSP, MSA and PD in C4.5 decision tree models derived from the training set. Using these decision models, AUCs in discriminating PSP, MSA and PD were 0.90, 0.57 and 0.73 in the CUP-cohort and 0.95, 0.61 and 0.87 in the prospective cohort, respectively., Conclusion: We were able to demonstrate that brainstem-derived MR planimetric measures yield high diagnostic accuracy for the discrimination of PSP from related disorders when decision tree algorithms are applied, even at early, clinically uncertain stages. However, their diagnostic accuracy in discriminating PD and MSA was suboptimal., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Objective: CIC gene is frequently mutated in oligodendroglial tumors with 1p19q codeletion. However, clinical and biological impact remain poorly understood., Methods: We sequenced the CIC gene on 127 oligodendroglial tumors (109 with the 1p19q codeletion) and analyzed patients' outcome. We compared magnetic resonance imaging, transcriptomic profile, and CIC protein expression of CIC wild-type (WT) and mutant gliomas. We compared the level of expression of CIC target genes on Hs683-IDH1(R132H) cells transfected with lentivirus encoding mutant and WT CIC., Results: We found 63 mutations affecting 60 of 127 patients, virtually all 1p19q codeleted and IDH mutated (59 of 60). In the 1p19q codeleted gliomas, CIC mutations were associated with a poorer outcome by uni- (p = 0.001) and multivariate analysis (p < 0.016). CIC mutation prognostic impact was validated on the TCGA cohort. CIC mutant grade II codeleted gliomas spontaneously grew faster than WTs. Transcriptomic analysis revealed an enrichment of proliferative pathways and oligodendrocyte precursor cell gene expression profile in CIC mutant gliomas, with upregulation of normally CIC repressed genes ETV1, ETV4, ETV5, and CCND1. Various missense mutations resulted in CIC protein expression loss. Moreover, a truncating CIC mutation resulted in a defect of nuclear targeting of CIC protein to the nucleus in a human glioma cell line expressing IDH1(R132H) and overexpression of CCND1 and other new target genes of CIC, such as DUSP4 and SPRED1., Interpretation: CIC mutations result in protein inactivation with upregulation of CIC target genes, activation of proliferative pathways, inhibition of differentiation, and poorer outcome in patients with a 1p19q codeleted glioma., (© 2015 American Neurological Association.)

Background: The role of telomerase reverse transcriptase (TERT) in gliomagenesis has been recently further strengthened by the frequent occurrence of TERT promoter mutations (TERTp-mut) in gliomas and evidence that the TERT SNP genetic rs2736100 influences glioma risk. TERTp-mut creates a binding site for Ets/TCF transcription factors, whereas the common rs2853669 polymorphism disrupts another Ets/TCF site on TERT promoter., Methods: We sequenced for TERTp-mut in 807 glioma DNAs and in 235 blood DNAs and analysed TERT expression by RT-PCR in 151 samples. TERTp-mut status and TERTp polymorphism rs2853669 were correlated with histology, genomic profile, TERT mRNA expression, clinical outcome and rs2736100 genotype., Results: TERTp-mut identified in 60.8% of gliomas (491 out of 807) was globally associated with poorer outcome (Hazard ratio (HR)=1.50). We defined, based on TERTp-mut and IDH mutation status, four prognostic groups: (1) TERTp-mut and IDH-mut associated with 1p19q codeletion, overall survival (OS)>17 years; (2) TERTp-wt and IDH-mut, associated with TP53 mutation, OS=97.5 months; (3) TERTp-wt and IDH-wt, with no specific association, OS=31.6 months; (4) TERTp-mut and IDH-wt, associated with EGFR amplification, OS=15.4 months. TERTp-mut was associated with higher TERT mRNA expression, whereas the rs2853669 variant was associated with lower TERT mRNA expression. The mutation of CIC (a repressor of ETV1-5 belonging to the Ets/TCF family) was also associated with TERT mRNA upregulation., Conclusions: In addition to IDH mutation status, defining the TERTp-mut status of glial tumours should afford enhanced prognostic stratification of patients with glioma. We also show that TERTp-mut, rs2853669 variant and CIC mutation influence Tert expression. This effect could be mediated by Ets/TCF transcription factors.