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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.

Detailed pathophysiological mechanisms causing migraine are still elusive, however, there is evidence that iron metabolization might play a role. Studies using R2 (=1/T2) or R2* (=1/T2*) relaxometry, a common magnetic resonance imaging (MRI) based iron mapping technique, reported increased R2 and R2* values in various brain structures of patients with migraine, indicating an iron accumulation compared to healthy controls. The aim of this first-of-its-kind study was to investigate if there are alterations in R2* in the brain caused by the migraine cycle. Therefore, quantitative MRI, including R2* relaxometry and diffusion tensor imaging (DTI) of a patient with migraine was acquired on 21 consecutive days, comprising headache free days and days with a migraine attack. Combining R2* with DTI, allowed to separate isotropic and anisotropic R2* contributions in white matter. A significant difference in R2* between left and right hemisphere was found in the nucleus accumbens (p = 0.02), the amygdala (p < 0.001) and the pallidum (p < 0.001). During a migraine attack, R2* decreased in the amygdala of the left hemisphere by 13.9% (p = 0.01) and in the nucleus accumbens of the right hemisphere by 7.8% (p = 0.01). In contrast, R2* increased in the caudate of the left hemisphere by 5.3% (p = 0.01). In white matter, isotropic R2* increased by approximately 1.9% (p = 0.04) and anisotropic R2* decreased by approximately 30% (p = 0.02) during a migraine attack. Our study revealed a decrease and increase in iron content in various brain regions during the migraine cycle. Furthermore, white mater iron content increased accompanied by a decrease in anisotropic tissue components during a migraine attack. The observed alterations in R2* indicate that the iron content fluctuates over time depending on the migraine phase. However, the altered iron content reaches normal levels after the migraine attack resolved.

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.

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.

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.

ObjectiveTo 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.MethodsA 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.ResultsAt 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, pConclusionsOur 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.

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.

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., Haider et al. followed a cohort of individuals for 30 years after their initial presentation with symptoms suggestive of multiple sclerosis. Cortical involvement was the main correlate of progressive disease and disability and therefore might provide a promising diagnostic and therapeutic target.

Background: 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.Methods: 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.Results: 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 (pConclusions: 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.

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 3rdV width makes P/M2.0 and MRPI2.0 more accurate in diagnosing early stage PSP patients than the P/M and MRPI.

Funder: University of Innsbruck and Medical University of Innsbruck, 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.

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.

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, Quantitative 7 Tesla MRI (susceptibility, relaxation, fractional anisotropy) found differences between ten Friedreich's ataxia patients and matched healthy controls in eight structures of brainstem and cerebellum which correlated with disease characteristics. Voxel‐based morphometry revealed white matter atrophy in partially overlapping volumes of interest (VOI) used for the VOI‐based evaluation. *Statistically significant differences between patients and controls; middle cerebellar peduncle (MCP), pontine crossing tract (PCT), corticospinal tract (CS), medial lemniscus (ML), inferior cerebellar peduncle (ICP), superior cerebellar peduncle (SCP), cerebral peduncle (CP), posterior thalamic radiation (PTR), sagittal stratum (SS), dentate nuclei (DN), red nuclei (RN), substantia nigra (SN).

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.

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.

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.

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.

Simple Summary Gliobastoma is one of the deadliest tumors overall, yet the most common malignant brain tumor. The new World Health Organization Classification of Brain Tumors brought changes in how we look at this type of malignancy. Now we know that glioblastoma is rather a spectrum of similar tumors, but with some distinct characteristics that include molecular footprint, response to therapy and with that overall survival, among others. We hypothesised that by employing phosphorous magnetic resonance we will be able to show differences in cellular energy metabolism in these various subtypes of glioblastoma. For example, we found indices of faster cell reproduction and tumor growth in MGMT-methylated and EGFR-amplified tumors. These tumors also could have reduced energetic state or tissue oxygenation due to the increased necrosis. Tumors with EGFR-amplification could have increased apoptotic activity regardless of their MGMT status. Our study indicated various differences in energetic metabolism in tumors with different molecular characteristics, which could potentially be important in future therapeutic strategies. Abstract 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.

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.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.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.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.

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.

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 (Pd/Md) 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.

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 naive 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.

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.

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.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.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.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.

To evaluate the efficacy of a combined protocol of mifepristone and misoprostol in the management of early pregnancy failure (EPF) and the average time to expulsion of tissue and rate of side effects.Retrospective chart review of all consecutive women treated with primary medical management for EPF at our institution from 2006 to 2012.168 patients were included in the present study. The overall success rate, defined as the absence of the need for surgical intervention, was 61 % and did not differ by calendar year. There was no difference in success rate grouped by diagnosis [intrauterine embryonic/fetal demise (IUED/IUFD) vs. anembryonic gestation; p = 0.30] or gestational age (9 or ≥9 weeks; p = 0.48). The success rate varied significantly according to the required dose of misoprostol, ≤800 or800 μg (68 vs. 50 %, p = 0.029). Of the possible predictive factors of success, only the dose of misoprostol required was a significant independent negative predictor. Mean and median time to tissue expulsion after the first dose of misoprostol were 8.4 and 5.5 h, respectively. The incidence of side effects was low with no blood transfusions required.The success rate in this study is markedly below published data. This can possibly be attributed to retrospective study design, allowing for physician subjectivity and patients' wishes in the absence of strict study requirements. The protocol was well tolerated with a paucity of side effects. We make suggestions for enhancing success rates in the clinical setting by optimizing medication protocols, establishing precise treatment guidelines and training physicians in the accurate interpretation of treatment outcomes.

Background and objective There is limited evidence about the efficacy and safety of cannabinoids in the treatment of patients with Huntington’s disease (HD). Five patients with HD were treated with nabilone, a synthetic cannabinoid, in order to alleviate therapy-resistant symptoms. Methods All patients and caregivers were informed about the off-label use of nabilone and gave written informed consent. A Clinical Global Impression Scale (CGI) and the Unified Huntington9s Disease Rating Scale (UHDRS) were applied prior, after one and four weeks to decide on the continuation of nabilone treatment. Case reports Patient 1 is a 20-year-old male who presented with disabling tics, generalised chorea and increased irritability. He developed severe parkinsonism during therapy with amisulpiride and olanzapine. Amisulpiride was stopped and he was treated with nabilone 1 mg/d. Patient 2 is a 48-year-old female with 10 years history of HD and chronic pain. Multiple treatment trials were ineffective. Nabilone 2 mg/d was introduced. Patient 3 is a 62-year-old female with disabling chorea and increased irritability. She developed severe akathisia as a side effect of several antidopaminergic therapies. Treatment with nabilone 1.5 mg/d was commenced. Patient 4 is a 46-year-old female who had parkinsonism and depression under therapy with tetrabenazine. Treatment with nabilone 3 mg/d was introduced as monotherapy. Patient 5 is a 67-year-old female with disabling chorea and increased irritability. She developed parkinsonism during therapy with tetrabenazine. Medication was changed to 2 mg/d nabilone. Results Transient mild sedation during titration occurred in patients 3, 4 and 5, mild non-disturbing xerostomia in patient 3. All patients reported improved symptoms as assessed by the CGI. UHDRS and Chorea-scores improved in all patients. A reduction of tics without worsening of parkinsonism with nabilone was seen in patient 1. Patient 2 reported that her pain completely subsided. Irritability substantially improved with nabilone in patients 1, 3 and 5. Moreover, tetrabenazine could be stopped in patients 3, 4 and 5. This resulted in a remission of akathisia in patient 3, in improved parkinsonism in patients 4 and 5 as well as in ameliorated mood in patient 4. Conclusions These case series suggest that nabilone may be an effective and well tolerated adjunct to the drug treatment of HD. However, larger controlled trials are needed to confirm these preliminary open-label observations.