Investigating Compensatory Brain Activity in Older Adults with Subjective Cognitive Decline.

BACKGROUND: Preclinical Alzheimer's disease (AD) is one possible cause of subjective cognitive decline (SCD). Normal task performance despite ongoing neurodegeneration is typically considered as neuronal compensation, which is reflected by greater neuronal activity. Compensatory brain activity has been observed in frontal as well as parietal regions in SCD, but data are scarce, especially outside the memory domain. OBJECTIVE: To investigate potential compensatory activity in SCD. Such compensatory activity is particularly expected in participants where blood-based biomarkers indicated amyloid positivity as this implies preclinical AD. METHODS: 52 participants with SCD (mean age: 71.00±5.70) underwent structural and functional neuroimaging (fMRI), targeting episodic memory and spatial abilities, and a neuropsychological assessment. The estimation of amyloid positivity was based on plasma amyloid-ß and phosphorylated tau (pTau181) measures. RESULTS: Our fMRI analyses of the spatial abilities task did not indicate compensation, with only three voxels exceeding an uncorrected threshold at p < 0.001. This finding was not replicated in a subset of 23 biomarker positive individuals. CONCLUSION: Our results do not provide conclusive evidence for compensatory brain activity in SCD. It is possible that neuronal compensation does not manifest at such an early stage as SCD. Alternatively, it is possible that our sample size was too small or that compensatory activity may be too heterogeneous to be detected by group-level statistics. Interventions based on the individual fMRI signal should therefore be explored.

Imaging Neurovascular Uncoupling in Acute Migraine with Aura with Susceptibility Weighted Imaging.

PURPOSE: Migraine with aura (MwA) in the emergency setting is common and sometimes difficult to distinguish from mimicking conditions. Susceptibility weighted imaging (SWI), a magnet resonance (MR) technique is sensitive to deoxygenated hemoglobin in cerebral veins and depicts these according to their level of oxygenation. Our study aimed at evaluating the frequency of regions of prominent focal veins (PFV) on SWI in the acute phase. METHODS: Between 2011 and 2018 we evaluated symptoms and MR imaging of adult patients with acute MwA attacks (< 5 days after onset of symptoms). Abnormal imaging was visually scored in 12 ROIs on both hemispheres distributed on 3 slices. The score ranged from 0 to 3. RESULTS: In all, 638 patients (436 female) mean age 37.39 years (18-89 ±â€¯14.13) were included. Susceptibility weighted imaging was abnormal in 18.8% of patients. The inferior and posterior medial temporal lobe and the occipital lobe were most often affected. Susceptibility weighted imaging was more likely abnormal when MR was performed within 24 hours with an average around 5 hours after symptom onset. The side of aura symptoms and hemispheric imaging alteration in patients with abnormal SWI was highly significant (p < 0.001). CONCLUSION: In the acute episode of MwA, SWI imaging can show a combination of increased deoxygenation. The results may indicate linking PFV to MwA.

Findings in susceptibility weighted imaging in pediatric patients with migraine with aura.

BACKGROUND: Migraine with aura (MwA) in pediatric patients is clinically frequent. Clinically complex symptoms need to be differentiated to exclude mimicking conditions. PURPOSE: We hypothesize that MwA in children induces abnormalities readily visible in perfusion time to peak (TTP) maps as well as non-enhanced susceptibility weighted magnetic resonance imaging (SWI). MATERIALS AND METHODS: Between 2010 and 2018, we retrospectively evaluated symptoms and imaging of consecutive pediatric patients <18 years with MwA. We visually scored abnormalities on SWI and TTP maps in 12 regions of interest on both hemispheres on three axial slices, as normal, slightly, distinctly or severely abnormal. RESULTS: 99 patients (69.7% female), mean age 14.07 y (±2.8) were included. Focally increased deoxygenation (FID) in SWI was present in 61.6%. FID on SWI was dominant for the left hemisphere (60.7% vs. 31.1%, (p < .001)), and in 8.2% symmetric. Side of aura symptoms and contralateral hemispheric imaging alterations in patients with FID correlated significantly (p = .002.). 61 of 99 patients had perfusion MR and 59% of these patients showed focal increase of TTP. Age correlated significantly with FID in SWI (r = -.248, p = .013) and increase of TTP in perfusion (r = -.252, p = .05). Focal abnormalities correlated significantly between SWI and TTP maps. Brain regions most often abnormal were the temporal superior, occipital and fronto-parietal regions. CONCLUSIONS: This study provides confidence in recognizing FID, and linking FID in SWI to acute MwA in pediatric patients. FID phenomenon had a left hemispheric significant dominance, and can be found bilaterally.

Quantification of cerebral veins in patients with acute migraine with aura: A fully automated quantification algorithm using susceptibility-weighted imaging.

INTRODUCTION: Susceptibility weighted imaging (SWI) is a very sensitive technique that often depicts prominent focal veins (PFV) in patients with acute migraine with aura (MwA). Interpretation of visual venous asymmetry (VVA) between brain hemispheres on SWI may help support the clinical diagnosis of MwA. Our goal was to develop an automated algorithm for segmentation and quantification of cerebral veins using SWI. MATERIALS AND METHODS: Expert readers visually evaluated SWI of patients with acute MwA for VVA. Subsequently a fully automated algorithm based on 3D normalization and 2D imaging processing using SPM and MATLAB image processing software including top-hat transform was used to quantify cerebral veins and to calculate volumetric differences between hemispheres. RESULTS: Fifty patients with MwA were examined with SWI. VVA was present in 20 of 50 patients (40%). In 95% of patients with VVA, the fully automated calculation agreed with the side that visually harboured more PFV. Our algorithm showed a sensitivity of 95%, specificity of 90% and accuracy of 92% for detecting VVA. Patients with VVA had significantly larger vein volume on the hemisphere with more PFV compared to patients without (15.90 ± 5.38 ml vs 11.93 ± 5.31 ml; p = 0.013). The mean difference in venous volume between hemispheres in patients with VVA was larger compared to patients without VVA (16.34 ± 7.76% vs 4.31 ± 3.26% p < 1E-10). The average time between aura onset and SWI correlated negatively with venous volume of the dominant brain hemisphere (r = -0.348; p = 0.038). CONCLUSION: A fully automated algorithm can accurately identify and quantify cerebral venous distribution on SWI. Absolute quantification may be useful for the future assessment of patients with suspected diseases, which may be associated with a unilateral abnormal degree of venous oxygenation.

The index vein pointing to the origin of the migraine aura symptom: A case series.

OBJECTIVE: This case series describes and discusses the potential clinical utility of a prominent vein (index vein) found on susceptibility-weighted MRI during migraine aura that drains the cortical area responsible for patients' symptoms. METHODS: Six patients with acute migraine aura had a prominent draining sulcal vein on emergency MRI done initially for suspected stroke. The location of the prominent vein was correlated to patients' symptoms, and the diameter was compared to the corresponding contralateral vein. RESULTS: In our patients with typical migraine aura, an accentuated sulcal vein pointed towards the cortical area correlating with the clinical presentation. Such an index vein outstands the ipsilateral area of hypoperfusion and exceeds the corresponding contralateral vessel in diameter by a factor 2.0 ± 1.6 (mean ± SD). CONCLUSION: This case series provides a definition of an index vein in MRI pointing to the area where the patients' symptoms originate. Although confirmation in a larger systematic study is necessary, the presence of such an index vein might support that, in patients with an acute neurologic deficit, migraine aura is the underlying etiology.

Symptomatic and asymptomatic intracranial atherosclerotic stenosis: 3 years' prospective study.

BACKGROUND: Intracranial stenoses can cause TIA/ischaemic stroke. The purpose of this study was to assess vascular risk factors, clinical and imaging findings and outcome in Caucasians with intracranial stenosis under best prevention management. METHODS: In this prospective observational study (from 05/2012, to last follow-up 06/2017) we compared vascular risk factors, imaging findings and long-term outcome in Swiss patients with symptomatic versus asymptomatic intracranial atherosclerotic stenoses on best prevention management. RESULTS: 62 patients were included [35.5% women, median age 68.3 years], 33 (53.2%) with symptomatic intracranial stenoses. Vascular risk factors (p = 0.635) and frequency of anterior circulation stenoses (66.7% vs. 55.2%; p = 0.354) did not differ between symptomatic and asymptomatic patients, but CT/MR-perfusion deficits in the territory of the stenosis (81.8% vs. 51.7%; p = 0.011) were more common in symptomatic patients. Outcome in symptomatic and asymptomatic patients at last follow-up was similar (mRS 0-1:66.7% vs. 75%;adjp = 0.937, mRS adjp-shift = 0.354, survival:100% vs. 96.4%;adjp = 0.979). However, during 59,417 patient follow-up days, symptomatic patients experienced more cerebrovascular events (ischaemic stroke or TIA) [37.5% vs. 7.1%;adjHR 7.58;adjp = 0.012], mainly in the territory of the stenosis [31.3% vs. 3.6%;adjHR 12.69;adjp = 0.019], more vascular events (i.e. ischaemic stroke/TIA/TNA and acute coronary/peripheral vascular events) [62.5% vs. 14.3%;adjHR 6.37;adjp = 0.001]) and more multiple vascular events (p-trend = 0.006; ≥ 2:37.5% vs. 10.7%;adj OR 5.37;adjp = 0.022) than asymptomatic patients. CONCLUSIONS: Despite best prevention management, one in three patients with a symptomatic intracranial stenosis suffered a cerebrovascular event, three in five a vascular event and two in five ≥ 2 vascular events. There is an unmet need for more rigorous and effective preventive strategies in patients with symptomatic intracranial stenoses.

Comparison of perioperative automated versus manual two-dimensional tumor analysis in glioblastoma patients.

OBJECTIVES: Current recommendations for the measurement of tumor size in glioblastoma continue to employ manually measured 2D product diameters of enhancing tumor. To overcome the rater dependent variability, this study aimed to evaluate the potential of automated 2D tumor analysis (ATA) compared to highly experienced rater teams in the workup of pre- and postoperative image interpretation in a routine clinical setting. MATERIALS AND METHODS: From 92 patients with newly diagnosed GB and performed surgery, manual rating of the sum product diameter (SPD) of enhancing tumor on magnetic resonance imaging (MRI) contrast enhanced T1w was compared to automated machine learning-based tumor analysis using FLAIR, T1w, T2w and contrast enhanced T1w. RESULTS: Preoperative correlation of SPD between two rater teams (1 and 2) was r=0.921 (p<0.0001). Difference among the rater teams and ATA (p=0.567) was not statistically significant. Correlation between team 1 vs. automated tumor analysis and team 2 vs. automated tumor analysis was r=0.922 and r=0.897, respectively (p<0.0001 for both). For postoperative evaluation interrater agreement between team 1 and 2 was moderate (Kappa 0.53). Manual consensus classified 46 patients as completely resected enhancing tumor. Automated tumor analysis agreed in 13/46 (28%) due to overestimation caused by hemorrhage and choroid plexus enhancement. CONCLUSIONS: Automated 2D measurements can be promisingly translated into clinical trials in the preoperative evaluation. Immediate postoperative SPD evaluation for extent of resection is mainly influenced by postoperative blood depositions and poses challenges for human raters and ATA alike.

Differentiating enhancing multiple sclerosis lesions, glioblastoma, and lymphoma with dynamic texture parameters analysis (DTPA): A feasibility study.

PURPOSE: MR-imaging hallmarks of glioblastoma (GB), cerebral lymphoma (CL), and demyelinating lesions are gadolinium (Gd) uptake due to blood-brain barrier disruption. Thus, initial diagnosis may be difficult based on conventional Gd-enhanced MRI alone. Here, the added value of a dynamic texture parameter analysis (DTPA) in the differentiation between these three entities is examined. DTPA is an in-house software tool that incorporates the analysis of quantitative texture parameters extracted from dynamic susceptibility contrast-enhanced (DSCE) images. METHODS: Twelve patients with multiple sclerosis (MS), 15 patients with GB, and five patients with CL were included. The image analysis method focuses on the DSCE image time series during bolus passage. Three time intervals were examined: inflow, outflow, and reperfusion time interval. Texture maps were computed. From the DSCE image series, mean, difference, standard deviation, and variance texture parameters were calculated and statistically analyzed and compared between the pathologies. RESULTS: The texture parameters of the original DSCE image series for mean, standard deviation, and variance showed the most significant differences (P-value between <0.00 and 0.05) between pathologies. Further, the texture parameters related to the standard deviation or variance (both associated with tissue heterogeneity) revealed the strongest discriminations between the pathologies. CONCLUSION: We conclude that dynamic perfusion texture parameters as assessed by the DTPA method allow discriminating MS, GB, and CL lesions during the first passage of contrast. DTPA used in combination with classification algorithms has the potential to find the most likely diagnosis given a postulated differential diagnosis.

Cluster headache and macroprolactinoma: Case report of a rare, but potential important causality.

While headache is not an uncommon symptom in patients suffering from pituitary adenomas, cluster headache (CH) has rarely been reported in such cases. Headache associated with hyperprolactinemia has been reported to be responsive to dopamine agonists (DA agonists) in many patients. We report on a patient with refractory CH secondary to a macroprolactinoma who showed immediate and permanent clinical and radiologic recovery following medical treatment with DA agonists. Measurement of prolactin levels in addition to cranial magnetic resonance imaging might be considered in patients with refractory CH, until the significance of this potential causality becomes clearer.

Implication of cerebral circulation time in intracranial stenosis measured by digital subtraction angiography on cerebral blood flow estimation measured by arterial spin labeling.

PURPOSE: Arterial spin labeling (ASL) magnetic resonance imaging to assess cerebral blood flow (CBF) is of increasing interest in basic research and in diagnostic applications, since ASL provides similar information to positron emission tomography about perfusion in vascular territories. However, in patients with steno-occlusive arterial disease (SOAD), CBF as measured by ASL might be underestimated due to delayed bolus arrival, and thus increased spin relaxation. We aimed to estimate the extent to which bolus arrival time (BAT) was delayed in patients with SOAD and whether this resulted in underestimation of CBF. METHODS: BAT was measured using digital subtraction angiography (DSA) in ten patients with high-grade stenosis of the middle carotid artery (MCA). Regional CBF was assessed with pseudocontinuous ASL. RESULTS: BATs were nonsignificantly prolonged in the stenotic hemisphere 4.1±2.0 s compared with the healthy hemisphere 3.3±0.9 s; however, there were substantial individual differences on the stenotic side. CBF in the anterior and posterior MCA territories were significantly reduced on the stenotic hemisphere. Severe stenosis was correlated with longer BAT and lower quantified CBF. CONCLUSION: ASL-based perfusion measurement involves a race between the decay of the spins and the delivery of labeled blood to the region of interest. Special caution is needed when interpreting CBF values quantified in individuals with altered blood flow and delayed circulation times. However, from a clinician's point of view, an accentuation of hypoperfusion (even if caused by underestimation of CBF due to prolonged BATs) might be desirable since it indexes potentially harmful physiologic deficits.

Susac's syndrome: Leptomeningeal enhancement on 3D FLAIR MRI.

BACKGROUND: Contrast-enhanced (ce) fluid-attenuated inversion recovery magnetic resonance imaging (FLAIR MRI) has recently been shown to identify leptomeningeal pathology in multiple sclerosis. OBJECTIVE: To demonstrate leptomeningeal enhancement on three-dimensional (3D) FLAIR in a case of Susac's syndrome. METHODS: Leptomeningeal enhancement was correlated with clinical activity over 20 months and compared to retinal fluorescein angiography. RESULTS: The size, number, and location of leptomeningeal enhancement varied over time and generally correlated with symptom severity. The appearance was remarkably similar to that of retinal vasculopathy. CONCLUSION: Ce 3D FLAIR may aid in diagnosis and understanding of pathophysiology in Susac's syndrome and may serve as a biomarker for disease activity.

Characterization of Enhancing MS Lesions by Dynamic Texture Parameter Analysis of Dynamic Susceptibility Perfusion Imaging.

PURPOSE: The purpose of this study was to investigate statistical differences with MR perfusion imaging features that reflect the dynamics of Gadolinium-uptake in MS lesions using dynamic texture parameter analysis (DTPA). METHODS: We investigated 51 MS lesions (25 enhancing, 26 nonenhancing lesions) of 12 patients. Enhancing lesions (n = 25) were prestratified into enhancing lesions with increased permeability (EL+; n = 11) and enhancing lesions with subtle permeability (EL-; n = 14). Histogram-based feature maps were computed from the raw DSC-image time series and the corresponding texture parameters were analyzed during the inflow, outflow, and reperfusion time intervals. RESULTS: Significant differences (p < 0.05) were found between EL+ and EL- and between EL+ and nonenhancing inactive lesions (NEL). Main effects between EL+ versus EL- and EL+ versus NEL were observed during reperfusion (mainly in mean and standard deviation (SD): EL+ versus EL- and EL+ versus NEL), while EL- and NEL differed only in their SD during outflow. CONCLUSION: DTPA allows grading enhancing MS lesions according to their perfusion characteristics. Texture parameters of EL- were similar to NEL, while EL+ differed significantly from EL- and NEL. Dynamic texture analysis may thus be further investigated as noninvasive endogenous marker of lesion formation and restoration.

Cognitive improvement in patients with carotid stenosis is independent of treatment type.

Treatment of carotid artery stenosis decreases the long-term risk of stroke and may enhance cerebral blood flow. It is therefore expected to have the potential to prevent cognitive decline or even improve cognition over the long-term. However, intervention itself can cause peri-interventional cerebral infarcts, possibly resulting in a decline of cognitive performance, at least for a short time. We investigated the long-term effects of three treatment methods on cognition and the emotional state one year after intervention. In this prospective observational cohort study, 58 patients with extracranial carotid artery stenosis (≥ 70%) underwent magnetic resonance imaging and assessment of cognition, mood and motor speed before carotid endarterectomy (n = 20), carotid stenting (n = 10) or best medical treatment (n = 28) (i.e., time-point 1 [TP1]), and at one-year follow-up (TP2). Gain scores, reflecting cognitive change after treatment, were built according to performance as (TP2 -TP1)/TP1. Independent of the treatment type, significant improvement in frontal lobe functions, visual memory and motor speed was found. Performance level, motor speed and mood at TP1 were negatively correlated with gain scores, with greater improvement in patients with low performance before treatment. Active therapy, whether conservative or interventional, produces significant improvement of frontal lobe functions and memory in patients with carotid artery disease, independent of treatment type. This effect was particularly pronounced in patients with low cognitive performance prior to treatment.

Protected stent retriever thrombectomy prevents iatrogenic emboli in new vascular territories.

INTRODUCTION: Diagnostic tools to show emboli reliably and protection techniques against embolization when employing stent retrievers are necessary to improve endovascular stroke therapy. The aim of the present study was to investigate iatrogenic emboli using susceptibility-weighted imaging (SWI) in an open series of patients who had been treated with stent retriever thrombectomy using emboli protection techniques. METHODS: Patients with anterior circulation stroke examined with MRI before and after stent retriever thrombectomy were assessed for iatrogenic embolic events. Thrombectomy was performed in flow arrest and under aspiration using a balloon-mounted guiding catheter, a distal access catheter, or both. RESULTS: In 13 of 57 patients (22.8%) post-interventional SWI sequences detected 16 microemboli. Three of them were associated with small ischemic lesions on diffusion-weighted imaging (DWI). None of the microemboli were located in a new vascular territory, none showed clinical signs, and all 13 patients have been rated as Thrombolysis in Cerebral Infarction (TICI) 2b (n = 3) or 3 (n = 10). Retrospective reevaluation of the digital subtraction angiography (DSA) detected discrete flow stagnation nearby the iatrogenic microemboli in four patients with a positive persistent collateral sign in one. CONCLUSION: Our study demonstrates two things: First, SWI seems to be more sensitive to detect emboli than DWI and DSA and, second, proximal or distal protected stent retriever thrombectomy seems to prevent iatrogenic embolization into new vascular territories during retraction of the thrombus, but not downstream during mobilization of the thrombus. Both techniques should be investigated and refined further.

In-vivo phase contrast magnetic resonance angiography of the cerebrovascular system: a comparative study with duplex sonography.

PURPOSE: Assessment of the cerebral blood flow (CBF) is crucial in the evaluation of patients with steno-occlusive diseases of the arteries supplying the brain for prediction of stroke risk. Quantitative phase contrast magnetic resonance angiography (PC-MRA) can be utilised for noninvasive quantification of CBF. The aim of this study was to validate in-vivo PC-MRA data by comparing them with colour-coded duplex (CCD) sonography in patients with cerebrovascular disease. METHODS AND MATERIALS: We examined 24 consecutive patients (mean age 63 years) with stenosis of arteries supplying the brain using PC-MRA and CCD. Velocities were measured in a total of 209 stenotic and healthy arterial segments (110 extra- and 99 intracranial). RESULTS: Moderate to good correlation of velocity measurements between both techniques was observed in all six extracranial and five out of seven intracranial segments (p <0.05). Velocities measured with CCD sonography were generally higher than those obtained by PC-MRA. Reversal of flow direction was detected consistently with both methods. CONCLUSION: PC-MRA represents a robust, standardised magnetic resonance imaging technique for blood flow measurements within a reasonable acquisition time, potentially evolving as valuable work-up tool for more precise patient stratification for revascularisation therapy. PC-MRA overcomes relevant weaknesses of CCD in being not operator-dependent and not relying on a bone window to assess the intracranial arteries.

Suprasellar chordoid neoplasm with expression of thyroid transcription factor 1: evidence that chordoid glioma of the third ventricle and pituicytoma may form part of a spectrum of lineage-related tumors of the basal forebrain.

Chordoid glioma of the third ventricle is a rare neuroepithelial tumor characterized by a unique histomorphology and exclusive association with the suprasellar/third ventricular compartment. Variously interpreted as either astrocytic- or ependymal-like, and speculatively ascribed to the lamina terminalis/subcommissural organ, its histogenesis remains, nevertheless, unsettled. Here, we report on a suprasellar chordoid glioma occurring in a 52-year-old man. Although displaying otherwise typical morphological features, the tumor was notable for expression of thyroid transcription factor 1, a marker of tumors of pituicytic origin in the context of the sellar region. We furthermore found overlapping immunoprofiles of this example of chordoid glioma and pituicytic tumors (pituicytoma and spindle cell oncocytoma), respectively. Specifically, phosphorylated ribosomal protein S6, a marker of mTOR pathway activation, was expressed in both groups. Based on these findings, we suggest that chordoid glioma and pituicytic tumors may form part of a spectrum of lineage-related neoplasms of the basal forebrain.

Multimodal 3 Tesla MRI confirms intact arterial wall in acute stroke patients after stent-retriever thrombectomy.

BACKGROUND AND PURPOSE: The aim of this prospective study was to assess vascular integrity after stent-retriever thrombectomy. METHODS: Dissection, contrast medium extravasation, and vasospasm were evaluated in 23 patients after thrombectomy with biplane or 3D-digital subtraction angiography and 3-Tesla vessel wall MRI. RESULTS: Vasospasm was detected angiographically in 10 patients, necessitating intra-arterial nimodipine in 2 of them. Contrast extravasation, intramural hemorrhage, or iatrogenic dissection were not detected on multimodal MRI in any patient even after Y-double stent-retriever technique. CONCLUSIONS: Our findings suggest that clinically relevant vessel wall injuries occur rarely after stent-retriever thrombectomy.

Cognitive and emotional effects of carotid stenosis.

PRINCIPLES: Patients with carotid artery stenosis (CAS) are at risk of ipsilateral stroke and chronic compromise of cerebral blood flow. It is under debate whether the hypo-perfusion or embolism in CAS is directly related to cognitive impairment. Alternatively, CAS may be a marker for underlying risk factors, which themselves influence cognition. We aimed to determine cognitive performance level and the emotional state of patients with CAS. We hypothesised that patients with high grade stenosis, bilateral stenosis, symptomatic patients and/or those with relevant risk factors would suffer impairment of their cognitive performance and emotional state. METHODS: A total of 68 patients with CAS of ≥70% were included in a prospective exploratory study design. All patients underwent structured assessment of executive functions, language, verbal and visual memory, motor speed, anxiety and depression. RESULTS: Significantly more patients with CAS showed cognitive impairments (executive functions, word production, verbal and visual memory, motor speed) and anxiety than expected in a normative sample. Bilateral and symptomatic stenosis was associated with slower processing speed. Cognitive performance and anxiety level were not influenced by the side and the degree of stenosis or the presence of collaterals. Factors associated with less cognitive impairment included higher education level, female gender, ambidexterity and treated hypercholesterolemia. CONCLUSIONS: Cognitive impairment and increased level of anxiety are frequent in patients with carotid stenosis. The lack of a correlation between cognitive functioning and degree of stenosis or the presence of collaterals, challenges the view that CAS per se leads to cognitive impairment.