Arterial Spin Labeling Magnetic Resonance Imaging for Acute Disorders of Consciousness in the Intensive Care Unit.

BACKGROUND: To investigate patients with disorders of consciousness (DoC) for residual awareness, guidelines recommend quantifying glucose brain metabolism using positron emission tomography. However, this is not feasible in the intensive care unit (ICU). Cerebral blood flow (CBF) assessed by arterial spin labeling magnetic resonance imaging (ASL-MRI) could serve as a proxy for brain metabolism and reflect consciousness levels in acute DoC. We hypothesized that ASL-MRI would show compromised CBF in coma and unresponsive wakefulness states (UWS) but relatively preserved CBF in minimally conscious states (MCS) or better. METHODS: We consecutively enrolled ICU patients with acute DoC and categorized them as being clinically unresponsive (i.e., coma or UWS [≤ UWS]) or low responsive (i.e., MCS or better [≥ MCS]). ASL-MRI was then acquired on 1.5 T or 3 T. Healthy controls were investigated with both 1.5 T and 3 T ASL-MRI. RESULTS: We obtained 84 ASL-MRI scans from 59 participants, comprising 36 scans from 35 patients (11 women [31.4%]; median age 56 years, range 18-82 years; 24 ≤ UWS patients, 12 ≥ MCS patients; 32 nontraumatic brain injuries) and 48 scans from 24 healthy controls (12 women [50%]; median age 50 years, range 21-77 years). In linear mixed-effects models of whole-brain cortical CBF, patients had 16.2 mL/100 g/min lower CBF than healthy controls (p = 0.0041). However, ASL-MRI was unable to discriminate between ≤ UWS and ≥ MCS patients (whole-brain cortical CBF: p = 0.33; best hemisphere cortical CBF: p = 0.41). Numerical differences of regional CBF in the thalamus, amygdala, and brainstem in the two patient groups were statistically nonsignificant. CONCLUSIONS: CBF measurement in ICU patients using ASL-MRI is feasible but cannot distinguish between the lower and the upper ends of the acute DoC spectrum. We suggest that pilot testing of diagnostic interventions at the extremes of this spectrum is a time-efficient approach in the continued quest to develop DoC neuroimaging markers in the ICU.

Automated white blood cell counts in cerebrospinal fluid using the body fluid mode on the platform Sysmex XE-5000.

BACKGROUND: The Sysmex XE-5000 offers automated quantification of red blood cells and white blood cells (WBCs) in body fluids, with differentiation of polymorphonuclear cells (PMNs) and mononuclear cells (MNCs). METHODS: We evaluated automated WBC counting in cerebrospinal fluid (CSF) using the body fluid mode on the Sysmex XE-5000, comparing it with flow cytometry as the reference method, and also with manual counting by microscopy. Experimental analysis for linearity and limit of detection was performed by diluting isolated WBCs in cell-free CSF. To study the ability to discriminate between PMNs and MNCs, samples were spiked using MNCs separated from peripheral blood. Comparison of WBC counts between a counting chamber and the XE-5000 was performed for 198 CSF samples. RESULTS: In the experimental set-up, within-run (CV 19%) and between-day imprecision (CV 15.3%) in quantitating total number of WBC on XE-5000 was acceptable for WBC counts ≥ 25 × 10(6)/L. Compared with expected cell counts, mean bias was + 2.6% for flow cytometry, + 5.5% for XE-5000 and - 73.2% for manual counting. Differentiation between PMNs and MNCs was in concordance with flow cytometry. In comparisons of clinical CSF samples, overall agreement between the XE-5000 and manual counting was observed in 81% of the samples, but mean difference in WBC differentiation was higher for PMN (51.1 × 10(6)/L) than for MNC (7.95 × 10(6)/L). CONCLUSION: Despite limited precision at low WBC counts, XE-5000 could be a favourable alternative to the labour-intensive, time-consuming and less reliable manual counting and cuts turnaround times in routine CSF-based diagnosis.

Neurological phenotypes and treatment outcomes in Eagle syndrome: systematic review and meta-analysis.

Background: Eagle syndrome is caused by an elongated styloid process affecting carotid arteries and cranial nerves. Pain, dysphagia, tinnitus, paresthesia (classic subtype), and neurovascular events (vascular subtype) may be triggered by head movements or arise spontaneously. However, Eagle syndrome remains underappreciated in the neurological community. We aimed to determine the most common neurological and non-neurological clinical presentations in patients with Eagle syndrome and to assess the clinical outcome post-surgical resection in comparison to non-surgical therapies. Methodology: We conducted a systematic review of patient-level data on adults with Eagle syndrome, following PRISMA guidelines. We extracted data on demographics, presenting symptoms, neurological deficits, radiological findings, and treatments, including outcomes and complications, from studies in multiple indexing databases published between 2000 and 2023. The study protocol is registered with PROSPERO. Results: In total, 285 studies met inclusion criteria, including 497 patients with Eagle syndrome (mean age 47.3 years; 49.8% female). Classical Eagle (370 patients, 74.5%) was more frequent than vascular Eagle syndrome (117 patients, 23.5%, p < 0.0001). Six patients (1.2%) presented with both variants and the subvariant for four patients (0.8%) was unknown. There was a male preponderance (70.1% male) in the vascular subtype. A history of tonsillectomy was more frequent in classic (48/153 cases) than in vascular (2/33 cases) Eagle syndrome (Odds Ratio 5.2, 95% CI [1.2-22.4]; p = 0.028). By contrast, cervical movements as trigger factors were more prevalent in vascular (12/33 cases) than in classic (7/153 cases) Eagle syndrome (Odds Ratio 7.95, 95% CI [2.9-21.7]; p = 0.0001). Headache and Horner syndrome were more frequent in vascular Eagle syndrome and dysphagia and neck pain more prominent in classic Eagle syndrome (all p < 0.01). Surgically treated patients achieved overall better outcomes than medically treated ones: Eighty-one (65.9%) of 123 medically treated patients experienced improvement or complete resolution, while the same applied to 313 (97.8%) of 320 surgical patients (Odds Ratio 1.49, 95% CI [1.1-2.0]; p = 0.016). Conclusions: Eagle syndrome is underdiagnosed with potentially serious neurovascular complications, including ischemic stroke. Surgical treatment achieves better outcomes than conservative management. Although traditionally the domain of otorhinolaryngologist, neurologist should include this syndrome in differential diagnostic considerations because of the varied neurological presentations that are amenable to effective treatment.

Minimal residual disease assessment in childhood acute lymphoblastic leukaemia: a Swedish multi-centre study comparing real-time polymerase chain reaction and multicolour flow cytometry.

Minimal residual disease (MRD) assessment is a powerful prognostic factor for determining the risk of relapse in childhood acute lymphoblastic leukaemia (ALL). In this Swedish multi-centre study of childhood ALL diagnosed between 2002 and 2006, the MRD levels were analysed in 726 follow-up samples in 228 children using real-time quantitative polymerase chain reaction (RQ-PCR) of rearranged immunoglobulin/T-cell receptor genes and multicolour flow cytometry (FCM). Using an MRD threshold of 0·1%, which was the sensitivity level reached in all analyses, the concordance between RQ-PCR and FCM MRD values at day 29 was 84%. In B-cell precursor ALL, an MRD level of ≥0·1% at day 29 predicted a higher risk of bone marrow relapse (BMR) with both methods, although FCM was a better discriminator. However, considering the higher median MRD values achieved with RQ-PCR, a higher MRD cut-off (≥0·2%) improved the predictive capacity of RQ-PCR. In T-ALL, RQ-PCR was notably superior to FCM in predicting risk of BMR. That notwithstanding, MRD levels of ≥0·1%, detected by either method at day 29, could not predict isolated extramedullary relapse. In conclusion, the concordance between RQ-PCR and FCM was high and hence both methods are valuable clinical tools for identifying childhood ALL cases with increased risk of BMR.

Telomere length in relation to immunological parameters in patients with renal cell carcinoma.

Over the last decade, telomere length (TL) has gained attention as a potential biomarker in cancer disease. We previously reported that long blood TL was associated with a poorer outcome in patients with breast cancer and renal cell carcinoma. Based on these findings, we hypothesized that certain immunological components may have an impact on TL dynamics in cancer patients. One aim of the present study was to investigate a possible association between serum cytokines and TL of peripheral blood cells, tumors and corresponding kidney cortex, in patients with clear cell renal cell carcinoma. For this purpose, a multiplex cytokine assay was used. Correlation analysis revealed significant positive correlations between tumor TL and peripheral levels of three cytokines (IL-7, IL-8 and IL-10). In a parallel patient group with various kidney tumors, TL was investigated in whole blood and in immune cell subsets in relation to peripheral levels of regulatory T cells (Tregs). A significant positive association was found between whole blood TL and Treg levels. However, the strongest correlation was found between Tregs and TL of the T lymphocyte fraction. Thus, patients with higher Treg levels displayed longer T cell telomeres, which might reflect a suppressed immune system with fewer cell divisions and hence less telomere shortening. These results are in line with our earlier observation that long blood TL is an unfavorable prognostic factor for cancer-specific survival. In summary, we here show that immunological components are associated with TL in patients with renal cell carcinoma, providing further insight into the field of telomere biology in cancer.