ACOX1 Gain-of-Function Variant in Two German Pediatric Patients, in One Case Mimicking Autoimmune Inflammatory Disease.

Mitchell syndrome is a very rare genetic disorder due to a specific de novo gain-of-function variant in acyl-CoA oxidase 1 (ACOX1). So far, only five patients with this disease have been described worldwide. We present here two additional unrelated German patients found to carry the same heterozygous ACOX1 N237S variant through exome sequencing (ES). Both patients showed neurodegenerative clinical features starting from ∼4 to 5 years of age including progressive hearing loss, ataxia, ichthyosis, as well as progressive visual impairment leading to amaurosis, and died at the ages of 16 and 8 years, respectively. The first patient was clinically suspected to have anti-myelin oligodendrocyte glycoprotein-antibody-associated myelitis, but the disease course overall deteriorated despite extensive immunomodulatory therapy. The second patient was originally suspected to have a mitochondrial disorder due to intermittent elevated blood lactate. Since Mitchell syndrome has only been identified in 2020, the diagnosis in this second patient was only established through re-evaluation of ES data years after the original analysis. Comparison of all seven reported patients suggests that Mitchell syndrome often (but not always) clinically mimics autoimmune-inflammatory disease. Therefore, in patients with autoimmune central nervous system disease who do not respond adequately to standard therapies, re-evaluation of this diagnosis is needed and genetic analyses such as trio ES should be considered.

Prognostic value of single-subject grey matter networks in early multiple sclerosis.

The identification of prognostic markers in early multiple sclerosis (MS) is challenging and requires reliable measures that robustly predict future disease trajectories. Ideally, such measures should make inferences at the individual level to inform clinical decisions. This study investigated the prognostic value of longitudinal structural networks to predict 5-year Expanded Disability Status Scale (EDSS) progression in patients with relapsing-remitting MS (RRMS). We hypothesized that network measures, derived from MRI, outperform conventional MRI measurements at identifying patients at risk of developing disability progression. This longitudinal, multicentre study within the Magnetic Resonance Imaging in MS (MAGNIMS) network included 406 patients with RRMS (mean age = 35.7 ± 9.1 years) followed up for 5 years (mean follow-up = 5.0 ± 0.6 years). EDSS was determined to track disability accumulation. A group of 153 healthy subjects (mean age = 35.0 ± 10.1 years) with longitudinal MRI served as controls. All subjects underwent MRI at baseline and again 1 year after baseline. Grey matter atrophy over 1 year and white matter lesion load were determined. A single-subject brain network was reconstructed from T1-weighted scans based on grey matter atrophy measures derived from a statistical parameter mapping-based segmentation pipeline. Key topological measures, including network degree, global efficiency and transitivity, were calculated at single-subject level to quantify network properties related to EDSS progression. Areas under receiver operator characteristic (ROC) curves were constructed for grey matter atrophy and white matter lesion load, and the network measures and comparisons between ROC curves were conducted. The applied network analyses differentiated patients with RRMS who experience EDSS progression over 5 years through lower values for network degree [H(2) = 30.0, P < 0.001] and global efficiency [H(2) = 31.3, P < 0.001] from healthy controls but also from patients without progression. For transitivity, the comparisons showed no difference between the groups [H(2) = 1.5, P = 0.474]. Most notably, changes in network degree and global efficiency were detected independent of disease activity in the first year. The described network reorganization in patients experiencing EDSS progression was evident in the absence of grey matter atrophy. Network degree and global efficiency measurements demonstrated superiority of network measures in the ROC analyses over grey matter atrophy and white matter lesion load in predicting EDSS worsening (all P-values < 0.05). Our findings provide evidence that grey matter network reorganization over 1 year discloses relevant information about subsequent clinical worsening in RRMS. Early grey matter restructuring towards lower network efficiency predicts disability accumulation and outperforms conventional MRI predictors.

Automatic estimation of brain parenchymal fraction in patients with multple sclerosis: a comparison between synthetic MRI and an established automated brain segmentation software based on FSL.

PURPOSE: We aimed to validate the estimation of the brain parenchymal fraction (BPF) in patients with multiple sclerosis (MS) using synthetic magnetic resonance imaging (SyMRI) by comparison with software tools of the FMRIB Software Library (FSL). In addition to a cross-sectional method comparison, longitudinal volume changes were assessed to further elucidate the suitability of SyMRI for quantification of disease-specific changes. METHODS: MRI data from 216 patients with MS and 28 control participants were included for volume estimation by SyMRI and FSL-SIENAX. Moreover, longitudinal data from 35 patients with MS were used to compare registration-based percentage brain volume changes estimated using FSL-SIENA to difference-based calculations of volume changes using SyMRI. RESULTS: We observed strong correlations of estimated brain volumes between the two methods. While SyMRI overestimated grey matter and BPF compared to FSL-SIENAX, indicating a systematic bias, there was excellent agreement according to intra-class correlation coefficients for grey matter and good agreement for BPF and white matter. Bland-Altman plots suggested that the inter-method differences in BPF were smaller in patients with brain atrophy compared to those without atrophy. Longitudinal analyses revealed a tendency for higher atrophy rates for SyMRI than for SIENA, but SyMRI had a robust correlation and a good agreement with SIENA. CONCLUSION: In summary, BPF based on data from SyMRI and FSL-SIENAX is not directly transferable because an overestimation and higher variability of SyMRI values were observed. However, the consistency and correlations between the two methods were satisfactory, and SyMRI was suitable to quantify disease-specific atrophy in MS.

Factors associated with depressive mood at the onset of multiple sclerosis - an analysis of 781 patients of the German NationMS cohort.

Background: Depression has a major impact on the disease burden of multiple sclerosis (MS). Analyses of overlapping MS and depression risk factors [smoking, vitamin D (25-OH-VD) and Epstein-Barr virus (EBV) infection] and sex, age, disease characteristics and neuroimaging features associated with depressive symptoms in early MS are scarce. Objectives: To assess an association of MS risk factors with depressive symptoms within the German NationMS cohort. Design: Cross-sectional analysis within a multicenter observational study. Methods: Baseline data of n = 781 adults with newly diagnosed clinically isolated syndrome or relapsing-remitting MS qualified for analysis. Global and region-specific magnetic resonance imaging (MRI)-volumetry parameters were available for n = 327 patients. Association of demographic factors, MS characteristics and risk factors [sex, age, smoking, disease course, presence of current relapse, expanded disability status scale (EDSS) score, fatigue (fatigue scale motor cognition), 25-OH-VD serum concentration, EBV nuclear antigen-1 IgG (EBNA1-IgG) serum levels] and depressive symptoms (Beck Depression Inventory-II, BDI-II) was tested as a primary outcome by multivariable linear regression. Non-parametric correlation and group comparison were performed for associations of MRI parameters and depressive symptoms. Results: Mean age was 34.3 years (95% confidence interval: 33.6-35.0). The female-to-male ratio was 2.3:1. At least minimal depressive symptoms (BDI-II > 8) were present in n = 256 (32.8%), 25-OH-VD deficiency (<20 ng/ml) in n = 398 (51.0%), n = 246 (31.5%) participants were smokers. Presence of current relapse [coefficient (c) = 1.48, p = 0.016], more severe fatigue (c = 0.26, p < 0.0001), lower 25-OH-VD (c = -0.03, p = 0.034) and smoking (c = 0.35, p = 0.008) were associated with higher BDI-II scores. Sex, age, disease course, EDSS, month of visit, EBNA1-IgG levels and brain volumes at baseline were not. Conclusion: Depressive symptoms need to be assessed in early MS. Patients during relapse seem especially vulnerable to depressive symptoms. Contributing factors such as fatigue, vitamin D deficiency and smoking, could specifically be targeted in future interventions and should be investigated in prospective studies.

Diffusion-based structural connectivity patterns of multiple sclerosis phenotypes.

BACKGROUND: We aimed to describe the severity of the changes in brain diffusion-based connectivity as multiple sclerosis (MS) progresses and the microstructural characteristics of these networks that are associated with distinct MS phenotypes. METHODS: Clinical information and brain MRIs were collected from 221 healthy individuals and 823 people with MS at 8 MAGNIMS centres. The patients were divided into four clinical phenotypes: clinically isolated syndrome, relapsing-remitting, secondary progressive and primary progressive. Advanced tractography methods were used to obtain connectivity matrices. Then, differences in whole-brain and nodal graph-derived measures, and in the fractional anisotropy of connections between groups were analysed. Support vector machine algorithms were used to classify groups. RESULTS: Clinically isolated syndrome and relapsing-remitting patients shared similar network changes relative to controls. However, most global and local network properties differed in secondary progressive patients compared with the other groups, with lower fractional anisotropy in most connections. Primary progressive participants had fewer differences in global and local graph measures compared with clinically isolated syndrome and relapsing-remitting patients, and reductions in fractional anisotropy were only evident for a few connections. The accuracy of support vector machine to discriminate patients from healthy controls based on connection was 81%, and ranged between 64% and 74% in distinguishing among the clinical phenotypes. CONCLUSIONS: In conclusion, brain connectivity is disrupted in MS and has differential patterns according to the phenotype. Secondary progressive is associated with more widespread changes in connectivity. Additionally, classification tasks can distinguish between MS types, with subcortical connections being the most important factor.

Diagnosis behind the mask: A rare case of infected Charcot's spine.

Charcot's spine is a very uncommon long-term complication of spinal cord injury. Infection of the spine is a common pathology, but infection of a Charcot's spine is rare and is challenging to diagnose, especially in differentiating between the Charcot defect and the osteomyelitis defect. Surgical reconstruction has to be extremely individualized. A 65-year-old man with a history of thoracic spinal cord injury with paraplegia 49 years ago was admitted to our hospital with high fever and aphasia. After a thorough diagnostic process, destructive Charcot's spine and secondary infection were diagnosed. This report additionally reviews the surgical management of secondary infected destructive lumbar Charcot's spine and follows the patient's recovery and postoperative quality of life.

Cortical blindness as a sign of delayed post-hypoxic encephalopathy: a case report.

We present a case of a 67-year-old female patient, who presented with acute cortical blindness five days after a successful resuscitation from cardiac arrest. The magnetic resonance tomography revealed a mild FLAIR signal increase of the bilateral occipital cortex. A lumbar puncture revealed considerably elevated tau protein levels, in the presence of normal phospho-tau, as a marker of brain injury, whilst neuron-specific enolase levels were normal. The diagnosis of delayed post-hypoxic encephalopathy was set. We hereby describe a rare clinical manifestation after initially successful resuscitation and encourage the studying of tau protein as a potential marker of this disease entity.

Clinical and MRI measures to identify non-acute MOG-antibody disease in adults.

MRI and clinical features of myelin oligodendrocyte glycoprotein (MOG)-antibody disease may overlap with those of other inflammatory demyelinating conditions posing diagnostic challenges, especially in non-acute phases and when serologic testing for MOG antibodies is unavailable or shows uncertain results. We aimed to identify MRI and clinical markers that differentiate non-acute MOG-antibody disease from aquaporin 4 (AQP4)-antibody neuromyelitis optica spectrum disorder and relapsing remitting multiple sclerosis, guiding in the identification of patients with MOG-antibody disease in clinical practice. In this cross-sectional retrospective study, data from 16 MAGNIMS centres were included. Data collection and analyses were conducted from 2019 to 2021. Inclusion criteria were: diagnosis of MOG-antibody disease; AQP4-neuromyelitis optica spectrum disorder and multiple sclerosis; brain and cord MRI at least 6 months from relapse; and Expanded Disability Status Scale (EDSS) score on the day of MRI. Brain white matter T2 lesions, T1-hypointense lesions, cortical and cord lesions were identified. Random forest models were constructed to classify patients as MOG-antibody disease/AQP4-neuromyelitis optica spectrum disorder/multiple sclerosis; a leave one out cross-validation procedure assessed the performance of the models. Based on the best discriminators between diseases, we proposed a guide to target investigations for MOG-antibody disease. One hundred and sixty-two patients with MOG-antibody disease [99 females, mean age: 41 (±14) years, median EDSS: 2 (0-7.5)], 162 with AQP4-neuromyelitis optica spectrum disorder [132 females, mean age: 51 (±14) years, median EDSS: 3.5 (0-8)], 189 with multiple sclerosis (132 females, mean age: 40 (±10) years, median EDSS: 2 (0-8)] and 152 healthy controls (91 females) were studied. In young patients (<34 years), with low disability (EDSS < 3), the absence of Dawson's fingers, temporal lobe lesions and longitudinally extensive lesions in the cervical cord pointed towards a diagnosis of MOG-antibody disease instead of the other two diseases (accuracy: 76%, sensitivity: 81%, specificity: 84%, P < 0.001). In these non-acute patients, the number of brain lesions < 6 predicted MOG-antibody disease versus multiple sclerosis (accuracy: 83%, sensitivity: 82%, specificity: 83%, P < 0.001). An EDSS < 3 and the absence of longitudinally extensive lesions in the cervical cord predicted MOG-antibody disease versus AQP4-neuromyelitis optica spectrum disorder (accuracy: 76%, sensitivity: 89%, specificity: 62%, P < 0.001). A workflow with sequential tests and supporting features is proposed to guide better identification of patients with MOG-antibody disease. Adult patients with non-acute MOG-antibody disease showed distinctive clinical and MRI features when compared to AQP4-neuromyelitis optica spectrum disorder and multiple sclerosis. A careful inspection of the morphology of brain and cord lesions together with clinical information can guide further analyses towards the diagnosis of MOG-antibody disease in clinical practice.

Early spinal cord pseudoatrophy in interferon-beta-treated multiple sclerosis.

BACKGROUND AND PURPOSE: Brain pseudoatrophy has been shown to play a pivotal role in the interpretation of brain atrophy measures during the first year of disease-modifying therapy in multiple sclerosis. Whether pseudoatrophy also affects the spinal cord remains unclear. The aim of this study was to analyze the extent of pseudoatrophy in the upper spinal cord during the first 2 years after therapy initiation and compare this to the brain. METHODS: A total of 129 patients from a prospective longitudinal multicentric national cohort study for whom magnetic resonance imaging scans at baseline, 12 months, and 24 months were available were selected for brain and spinal cord volume quantification. Annual percentage brain volume and cord area change were calculated using SIENA (Structural Image Evaluation of Normalized Atrophy) and NeuroQLab, respectively. Linear mixed model analyses were performed to compare patients on interferon-beta therapy (n = 84) and untreated patients (n = 45). RESULTS: Patients treated with interferon-beta demonstrated accelerated annual percentage brain volume and cervical cord area change in the first year after treatment initiation, whereas atrophy rates stabilized to a similar and not significantly different level compared to untreated patients during the second year. CONCLUSIONS: These results suggest that pseudoatrophy occurs not only in the brain, but also in the spinal cord during the first year of interferon-beta treatment.

Spinal cord lesions and brain grey matter atrophy independently predict clinical worsening in definite multiple sclerosis: a 5-year, multicentre study.

OBJECTIVES: To evaluate the combined contribution of brain and cervical cord damage in predicting 5-year clinical worsening in a multicentre cohort of definite multiple sclerosis (MS) patients. METHODS: Baseline 3.0T brain and cervical cord T2-weighted and three-dimensional T1-weighted MRI was acquired in 367 patients with MS (326 relapse-onset and 41 progressive-onset) and 179 healthy controls. Expanded Disability Status Scale (EDSS) score was obtained at baseline and after a median follow-up of 5.1 years (IQR=4.8-5.2). At follow-up, patients were classified as clinically stable/worsened according to EDSS changes. Generalised linear mixed models identified predictors of clinical worsening, evolution to secondary progressive (SP) MS and reaching EDSS=3.0, 4.0 and 6.0 milestones at 5 years. RESULTS: At follow-up, 120/367 (33%) patients with MS worsened clinically; 36/256 (14%) patients with relapsing-remitting evolved to SPMS. Baseline predictors of EDSS worsening were progressive-onset versus relapse-onset MS (standardised beta (ß)=0.97), higher EDSS (ß=0.41), higher cord lesion number (ß=0.41), lower normalised cortical volume (ß=-0.15) and lower cord area (ß=-0.28) (C-index=0.81). Older age (ß=0.86), higher EDSS (ß=1.40) and cord lesion number (ß=0.87) independently predicted SPMS conversion (C-index=0.91). Predictors of reaching EDSS=3.0 after 5 years were higher baseline EDSS (ß=1.49), cord lesion number (ß=1.02) and lower normalised cortical volume (ß=-0.56) (C-index=0.88). Baseline age (ß=0.30), higher EDSS (ß=2.03), higher cord lesion number (ß=0.66) and lower cord area (ß=-0.41) predicted EDSS=4.0 (C-index=0.92). Finally, higher baseline EDSS (ß=1.87) and cord lesion number (ß=0.54) predicted EDSS=6.0 (C-index=0.91). CONCLUSIONS: Spinal cord damage and, to a lesser extent, cortical volume loss helped predicting worse 5-year clinical outcomes in MS.

Computed tomography hypoperfusion-hypodensity mismatch vs. automated perfusion mismatch to identify stroke patients eligible for thrombolysis.

Background and purpose: Automated perfusion imaging can detect stroke patients with unknown time of symptom onset who are eligible for thrombolysis. However, the availability of this technique is limited. We, therefore, established the novel concept of computed tomography (CT) hypoperfusion-hypodensity mismatch, i.e., an ischemic core lesion visible on cerebral perfusion CT without visible hypodensity in the corresponding native cerebral CT. We compared both methods regarding their accuracy in identifying patients suitable for thrombolysis. Methods: In a retrospective analysis of the MissPerfeCT observational cohort study, patients were classified as suitable or not for thrombolysis based on established time window and imaging criteria. We calculated predictive values for hypoperfusion-hypodensity mismatch and automated perfusion imaging to compare accuracy in the identification of patients suitable for thrombolysis. Results: Of 247 patients, 219 (88.7%) were eligible for thrombolysis and 28 (11.3%) were not eligible for thrombolysis. Of 197 patients who were within 4.5 h of symptom onset, 190 (96.4%) were identified by hypoperfusion-hypodensity mismatch and 88 (44.7%) by automated perfusion mismatch (p < 0.001). Of 22 patients who were beyond 4.5 h of symptom onset but were eligible for thrombolysis, 5 patients (22.7%) were identified by hypoperfusion-hypodensity mismatch. Predictive values for the hypoperfusion-hypodensity mismatch vs. automated perfusion mismatch were as follows: sensitivity, 89.0% vs. 50.2%; specificity, 71.4% vs. 100.0%; positive predictive value, 96.1% vs. 100.0%; and negative predictive value, 45.5% vs. 20.4%. Conclusion: The novel method of hypoperfusion-hypodensity mismatch can identify patients suitable for thrombolysis with higher sensitivity and lower specificity than established techniques. Using this simple method might therefore increase the proportion of patients treated with thrombolysis without the use of special automated software.The MissPerfeCT study is a retrospective observational multicenter cohort study and is registered with clinicaltrials.gov (NCT04277728).

Relaxometry and brain myelin quantification with synthetic MRI in MS subtypes and their associations with spinal cord atrophy.

Immune-mediated demyelination and neurodegeneration are pathophysiological hallmarks of Multiple Sclerosis (MS) and main drivers of disease related disability. The principal method for evaluating qualitatively demyelinating events in the clinical context is contrast-weighted magnetic resonance imaging (MRI). Moreover, advanced MRI sequences provide reliable quantification of brain myelin offering new opportunities to study tissue pathology in vivo. Towards neurodegenerative aspects of the disease, spinal cord atrophy - besides brain atrophy - is a powerful and validated predictor of disease progression. The etiology of spinal cord volume loss is still a matter of research, as it remains unclear whether the impact of local lesion pathology or the interaction with supra- and infratentorial axonal degeneration and demyelination of the long descending and ascending fiber tracts are the determining factors. Quantitative synthetic MR using a multiecho acquisition of saturation recovery pulse sequence provides fast automatic brain tissue and myelin volumetry based on R1 and R2 relaxation rates and proton density quantification, making it a promising modality for application in the clinical routine. In this cross sectional study a total of 91 MS patients and 31 control subjects were included to investigate group differences of global and regional measures of brain myelin and relaxation rates, in different MS subtypes, using QRAPMASTER sequence and SyMRI postprocessing software. Furthermore, we examined associations between these quantitative brain parameters and spinal cord atrophy to draw conclusions about possible pathophysiological relationships. Intracranial myelin volume fraction of the global brain exhibited statistically significant differences between control subjects (10.4%) and MS patients (RRMS 9.4%, PMS 8.1%). In a LASSO regression analysis with total brain lesion load, intracranial myelin volume fraction and brain parenchymal fraction, the intracranial myelin volume fraction was the variable with the highest impact on spinal cord atrophy (standardized coefficient 4.52). Regional supratentorial MRI metrics showed altered average myelin volume fraction, R1, R2 and proton density in MS patients compared to controls most pronounced in PMS. Interestingly, quantitative MRI parameters in supratentorial regions showed strong associations with upper cord atrophy, suggesting an important role of brain diffuse demyelination on spinal cord pathology possibly in the context of global disease activity. R1, R2 or proton density of the thalamus, cerebellum and brainstem correlated with upper cervical cord atrophy, probably reflecting the direct functional connection between these brain structures and the spinal cord as well as the effects of retrograde and anterograde axonal degeneration. By using Synthetic MR-derived myelin volume fraction, we were able to effectively detect significant differences of myelination in relapsing and progressive MS subtypes. Total intracranial brain myelin volume fraction seemed to predict spinal cord volume loss better than brain atrophy or total lesion load. Furthermore, demyelination in highly myelinated supratentorial regions, as an indicator of diffuse disease activity, as well as alterations of relaxation parameters in adjacent infratentorial and midbrain areas were strongly associated with upper cervical cord atrophy.

Quantification of individual remyelination during short-term disease course by synthetic magnetic resonance imaging.

MRI is an important diagnostic tool for evaluation of myelin content in multiple sclerosis and other CNS diseases, being especially relevant for studies investigating remyelinating pharmacotherapies. In this study, we evaluated a new synthetic MRI-based myelin estimation in methylenetetrahydrofolate reductase deficiency as a treatable primary demyelinating disorder and compared this method with established diffusion tensor imaging in both methylenetetrahydrofolate reductase deficiency patients and healthy controls. This is the first synthetic MRI-based in vivo evaluation of treatment-associated remyelination. 1.5 T synthetic MRI and 3 T diffusion MRI were obtained from three methylenetetrahydrofolate reductase deficiency patients at baseline and 6 months after therapy initiation, as well as from age-matched healthy controls (diffusion tensor imaging: n = 14, synthetic MRI: n = 9). Global and regional synthetic MRI parameters (myelin volume fraction, proton density, and relaxation rates) were compared with diffusion metrics (fractional anisotropy, mean/radial/axial diffusivity) and related to healthy controls by calculating z-scores and z-deviation maps. Whole-brain myelin (% of intracranial volume) of the index patient was reduced to 6 versus 10% in healthy controls, which recovered to a nonetheless subnormal level of 6.6% following initiation of high-dosage betaine. Radial diffusivity was higher at baseline compared with healthy controls (1.34 versus 0.79 × 10-3 mm2/s), recovering at follow-up (1.19 × 10-3 mm2/s). The index patient's lesion volume diminished by 58% under treatment. Regional analysis within lesion area and atlas-based regions revealed lower mean myelin volume fraction (12.7Baseline/14.71Follow-up%) and relaxation rates, higher proton density, as well as lower fractional anisotropy and higher radial diffusivity (1.08 × 10-3 Baseline/0.94 × 10-3 Follow-up) compared with healthy controls. The highest z-scores were observed for myelin volume fraction in the posterior thalamic radiation, with greater deviation from controls at baseline and reduced deviation at follow-up. Z-deviations of diffusion metrics were less pronounced for radial and mean diffusivity than for myelin volume fraction. Z-maps for myelin volume fraction of the index patient demonstrated high deviation within and beyond lesion areas, among others in the precentral and postcentral gyrus, as well as in the cerebellum, and partial remission of these alterations at follow-up, while radial diffusivity demonstrated more widespread deviations in supra- and infratentorial regions. Concordant changes of myelin volume fraction and radial diffusivity after treatment initiation, accompanied by dramatic clinical and paraclinical improvement, indicate the consistency of the methods, while myelin volume fraction seems to characterize remyelinated regions more specifically. Synthetic MRI-based myelin volume fraction provides myelin estimation consistent with changes of diffusion metrics to monitor short-term myelin changes on individual patient level.

Mechanical Thrombectomy for Acute Ischemic Stroke in Patients with Malignancy: A Systematic Review.

BACKGROUND: Ischemic stroke is a common occurrence in patients with concomitant malignancy. Systemic thrombolysis is often contraindicated in these patients, and mechanical thrombectomy (MT) is the preferred method of intervention. This review aims to collect the available data on the safety and efficacy of MT in cancer patients (CPs). METHODS: The PubMed/MEDLINE and SCOPUS databases were systematically searched for studies assessing safety (mortality, intracranial hemorrhage) and efficacy (reperfusion, functional outcome) indices in CPs receiving MT. Potentially relevant parameters examined in solitary studies were also extracted (e.g., stroke recurrence, brain malignancy). RESULTS: A total of 18 retrospective studies of various methodologies and objectives were identified. Rates of in-hospital mortality, intracranial hemorrhage of any kind, reperfusion rates, and discharge condition did not seem to present any considerable differences between CPs and patients without cancer. On the contrary, 90-day mortality was higher and 90-day functional independence was lower in CPs. Three studies on cancer-related stroke (no other identifiable etiology and high D-dimer levels in the presence of active cancer) showed constant tendencies towards unfavorable conditions. CONCLUSIONS: Per the available evidence, MT appears to be a safe treatment option for CPs. It is still unclear whether the 90-day mortality and outcome rates are more heavily influenced by the malignancy and not the intervention itself, so MT can be considered in CPs with prospects of a good functional recovery, undertaking an individualized approach.

No optical coherence tomography changes in premanifest Huntington's disease mutation carriers far from disease onset.

BACKGROUND: Spectral-domain optical coherence tomography (OCT) may detect retinal changes as a biomarker in neurodegenerative diseases like manifest Huntington's disease (HD). We investigate macular retinal layer thicknesses in a premanifest HD (pre-HD) cohort and healthy controls (HC). METHODS: Pre-HD mutation carriers underwent standardized ratings and a preset macular OCT scan. Thickness values were determined for each sector of all macular retinal layers, the mean of all sectors and the mean of the inner ring (IR, 3 mm) after segmentation (Heyex segmentation batch). HC were retrospectively included from an existing database. The IR thickness of the ganglion cell layer (GCL), retinal nerve fiber layer (RNFL), GCL + inner plexiform layer (GCIPL), and total retina were included in the exploratory correlation analyses with paraclinical ratings and compared to HC. RESULTS: The analyses comprised n = 24 pre-HD participants (n = 10 male, n = 14 female) and n = 38 HC (n = 14 male, n = 24 female). Retinal layer parameters did not correlate with paraclinical ratings. Expected correlations between established HD biomarkers were robust. The IR thicknesses of the GCL, GCIPL, and total retina did not differ between pre-HD and HC. The IR thickness of the RNFL was significantly higher in pre-HD participants (pre-HD: 23.22 µm (standard deviation 2.91), HC: 21.26 µm (1.90), p = .002). DISCUSSION: In this cross-sectional cohort of genetically determined pre-HD participants, neurodegenerative features were not detected with retinal layer segmentation. Since our pre-HD collective was more than 16 years before disease onset, OCT may not be sensitive enough to detect early changes.

Understanding Magnetic Resonance Imaging in Multiple Sclerosis (UMIMS): Development and Piloting of an Online Education Program About Magnetic Resonance Imaging for People With Multiple Sclerosis.

Background: People with multiple sclerosis (pwMS) lack sufficient magnetic resonance imaging (MRI) knowledge to truly participate in frequently occurring MRI-related therapy decisions. An evidence-based patient information (EBPI) about MRI is currently lacking. Objective: The aim of this study was to develop an evidence-based online education program about limitations and benefits of MRI for pwMS. Ultimately, our goal was to improve MRI risk-knowledge, empower pwMS, and promote shared decision-making. Methods: The program's contents were based on literature research and a previous pilot study. It was revised following 2 evaluation rounds with pwMS, MRI experts and expert patients. In a pilot study, n = 92 pwMS received access to the program for 4 weeks. User experiences and acceptance, MRI knowledge (MRI-RIKNO 2.0 questionnaire) and emotions and attitudes toward MRI (MRI-EMA questionnaire) were assessed. Results were compared to a previous survey population of n = 508 pwMS without access to the program. Results: Participants rated the program as easy to understand, interesting, relevant, recommendable, and encouraging. In comparison to pwMS without access to the program, MRI risk-knowledge and perceived MRI competence were higher. Conclusion: Satisfaction with the program and good MRI-risk knowledge after usage demonstrates the need and applicability of EBPI about MRI in MS.

Preservation of aberrant right hepatic arteries does not affect safety and oncological radicality of pancreaticoduodenectomy-own results and a systematic review of the literature.

Background: Aberrant right hepatic arteries (aRHA) are frequently encountered during pancreaticoduodenectomy (PD). Their effects on surgical morbidity and resection margin are still debated. This study aimed to compare the short term and long term outcomes in patients with and without aRHA. Methods: A single-center retrospective analysis of 353 consecutive PD during a 5-year period was done. The type of arterial supply was determined preoperatively by CT and confirmed at surgery. Hiatt types III-VI included some type of aRHA and comprised the study group. Hiatt types I and II were considered irrelevant for PD and used as controls. Primary endpoints were the rates of major postoperative complications and the rate of R0-resection in cases of malignant disease. Secondary endpoints included duration of surgery, postoperative stay, number of harvested lymph nodes and survival in patients with pancreatic cancer. Own results were compared to existent data using a systematic review of the literature. Results: No aRHA had to be sacrificed or reconstructed. Surgical morbidity and specific complications such as post-pancreatectomy hemorrhage (PPH), pancreatic fistula and bile leak were the same in patients with and without aRHA. There was no significant difference in operative time, blood loss, length of ICU- and hospital stay. Patients with malignancy had similar high rates of R0-resection and identical number of harvested lymph nodes. Survival of patients with pancreatic cancer was not affected by aRHA. Conclusions: aRHA may be preserved in virtually all cases of PD for resectable pancreatic head lesions without increasing surgical morbidity and without compromising oncological radicality in patients with cancer, provided the variant anatomy is being recognised on preoperative CT and a meticulous surgical technique is used.