| 1. |
- Andersson, Elin Möller, et al.
(författare)
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Clinicopathological concordance in cognitive disease diagnostics
- 2020
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Ingår i: Clinical Neuropathology. - 0722-5091. ; 39:3, s. 99-104
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Tidskriftsartikel (refereegranskat)abstract
- Neurocognitive disorder encompasses many separate diagnoses, such as frontotemporal dementia (FTD), Alzheimer's disease (AD), Lewy body dementia (LBD), vascular dementia (VaD), and mixed dementia (MD). Because of the many variations between and within each subtype, it may be a challenge to clinically diagnose each condition. In a previous study on 176 dementia patients in a university hospital cohort between the years 1996 and 2006, a full diagnostic concordance of 49% was demonstrated between clinical diagnoses and pathological morphology [1]. The aims of this study were to do a follow-up on diagnostic concordance from the subsequent 10 years (2007 - 2016) and to compare the results with the previous study from 2009. In all cases of neuropathologically diagnosed dementia disorders (n = 324), the clinical records were searched for information on the clinical diagnosis of dementia, including on subtype. All individuals who had been diagnosed by a specialist were selected (n = 210). In this study, a full concordance between clinical diagnoses and neuropathological morphology was found in 61% of individuals, with marked variations between subgroups, including the lowest (31%) in the group of VaD. Vigilance in clinicopathological concordance is important for quality maintenance as well as the improvement of skills in diagnostic work. In light of the previous study, VaD one decade later remains elusive. The unmasking of this complicated and multifaceted disorder may be beneficial to the overall diagnostic accuracy in cognitive disease investigations.
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| 2. |
- Bocci, Matteo, et al.
(författare)
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Infection of Brain Pericytes Underlying Neuropathology of COVID-19 Patients.
- 2021
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Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067 .- 1661-6596. ; 22:21
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Tidskriftsartikel (refereegranskat)abstract
- A wide range of neurological manifestations have been associated with the development of COVID-19 following SARS-CoV-2 infection. However, the etiology of the neurological symptomatology is still largely unexplored. Here, we used state-of-the-art multiplexed immunostaining of human brains (n = 6 COVID-19, median age = 69.5 years; n = 7 control, median age = 68 years) and demonstrated that expression of the SARS-CoV-2 receptor ACE2 is restricted to a subset of neurovascular pericytes. Strikingly, neurological symptoms were exclusive to, and ubiquitous in, patients that exhibited moderate to high ACE2 expression in perivascular cells. Viral dsRNA was identified in the vascular wall and paralleled by perivascular inflammation, as signified by T cell and macrophage infiltration. Furthermore, fibrinogen leakage indicated compromised integrity of the blood-brain barrier. Notably, cerebrospinal fluid from additional 16 individuals (n = 8 COVID-19, median age = 67 years; n = 8 control, median age = 69.5 years) exhibited significantly lower levels of the pericyte marker PDGFRβ in SARS-CoV-2-infected cases, indicative of disrupted pericyte homeostasis. We conclude that pericyte infection by SARS-CoV-2 underlies virus entry into the privileged central nervous system space, as well as neurological symptomatology due to perivascular inflammation and a locally compromised blood-brain barrier.
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| 3. |
- Brabec, Jan, et al.
(författare)
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Histogram analysis of tensor-valued diffusion MRI in meningiomas : Relation to consistency, histological grade and type
- 2022
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Ingår i: NeuroImage: Clinical. - : Elsevier BV. - 2213-1582. ; 33
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Preoperative radiological assessment of meningioma characteristics is of value for pre- and post-operative patient management, counselling, and surgical approach.PURPOSE: To investigate whether tensor-valued diffusion MRI can add to the preoperative prediction of meningioma consistency, grade and type.MATERIALS AND METHODS: 30 patients with intracranial meningiomas (22 WHO grade I, 8 WHO grade II) underwent MRI prior to surgery. Diffusion MRI was performed with linear and spherical b-tensors with b-values up to 2000 s/mm2. The data were used to estimate mean diffusivity (MD), fractional anisotropy (FA), mean kurtosis (MK) and its components-the anisotropic and isotropic kurtoses (MKA and MKI). Meningioma consistency was estimated for 16 patients during resection based on ultrasonic aspiration intensity, ease of resection with instrumentation or suction. Grade and type were determined by histopathological analysis. The relation between consistency, grade and type and dMRI parameters was analyzed inside the tumor ("whole-tumor") and within brain tissue in the immediate periphery outside the tumor ("rim") by histogram analysis.RESULTS: Lower 10th percentiles of MK and MKA in the whole-tumor were associated with firm consistency compared with pooled soft and variable consistency (n = 7 vs 9; U test, p = 0.02 for MKA 10 and p = 0.04 for MK10) and lower 10th percentile of MD with variable against soft and firm (n = 5 vs 11; U test, p = 0.02). Higher standard deviation of MKI in the rim was associated with lower grade (n = 22 vs 8; U test, p = 0.04) and in the MKI maps we observed elevated rim-like structure that could be associated with grade. Higher median MKA and lower median MKI distinguished psammomatous type from other pooled meningioma types (n = 5 vs 25; U test; p = 0.03 for MKA 50 and p = 0.03 and p = 0.04 for MKI 50).CONCLUSION: Parameters from tensor-valued dMRI can facilitate prediction of consistency, grade and type.
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| 4. |
- Durmo, Faris, et al.
(författare)
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Assessment of Amide proton transfer weighted (APTw) MRI for pre-surgical prediction of final diagnosis in gliomas
- 2020
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:12
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Radiological assessment of primary brain neoplasms, both high (HGG) and low grade tumors (LGG), based on contrast-enhancement alone can be inaccurate. We evaluated the radiological value of amide proton transfer weighted (APTw) MRI as an imaging complement for pre-surgical radiological diagnosis of brain tumors.METHODS: Twenty-six patients were evaluated prospectively; (22 males, 4 females, mean age 55 years, range 26-76 years) underwent MRI at 3T using T1-MPRAGE pre- and post-contrast administration, conventional T2w, FLAIR, and APTw imaging pre-surgically for suspected primary/secondary brain tumor. Assessment of the additional value of APTw imaging compared to conventional MRI for correct pre-surgical brain tumor diagnosis. The initial radiological pre-operative diagnosis was based on the conventional contrast-enhanced MR images. The range, minimum, maximum, and mean APTw signals were evaluated. Conventional normality testing was performed; with boxplots/outliers/skewness/kurtosis and a Shapiro-Wilk's test. Mann-Whitney U for analysis of significance for mean/max/min and range APTw signal. A logistic regression model was constructed for mean, max, range and Receiver Operating Characteristic (ROC) curves calculated for individual and combined APTw signals.RESULTS: Conventional radiological diagnosis prior to surgery/biopsy was HGG (8 patients), LGG (12 patients), and metastasis (6 patients). Using the mean and maximum: APTw signal would have changed the pre-operative evaluation the diagnosis in 8 of 22 patients (two LGGs excluded, two METs excluded). Using a cut off value of >2.0% for mean APTw signal integral, 4 of the 12 radiologically suspected LGG would have been diagnosed as high grade glioma, which was confirmed by histopathological diagnosis. APTw mean of >2.0% and max >2.48% outperformed four separate clinical radiological assessments of tumor type, P-values = .004 and = .002, respectively.CONCLUSIONS: Using APTw-images as part of the daily clinical pre-operative radiological evaluation may improve diagnostic precision in differentiating LGGs from HGGs, with potential improvement of patient management and treatment.
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| 5. |
- Eckermann, Marina, et al.
(författare)
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3d phase-contrast nanotomography of unstained human skin biopsies may identify morphological differences in the dermis and epidermis between subjects
- 2021
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Ingår i: Skin Research and Technology. - : Wiley. - 0909-752X .- 1600-0846. ; 27:3, s. 316-323
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Tidskriftsartikel (refereegranskat)abstract
- Background: Enteric neuropathy is described in most patients with gastrointestinal dysmotility and may be found together with reduced intraepidermal nerve fiber density (IENFD). The aim of this pilot study was to assess whether three-dimensional (3d) imaging of skin biopsies could be used to examine various tissue components in patients with gastrointestinal dysmotility. Material and methods: Four dysmotility patients of different etiology and two healthy volunteers were included. From each subject, two 3-mm punch skin biopsies were stained with antibodies against protein gene product 9.5 or evaluated as a whole with two X-ray phase-contrast computed tomography (CT) setups, a laboratory µCT setup and a dedicated synchrotron radiation nanoCT end-station. Results: Two patients had reduced IENFD, and two normal IENFD, compared with controls. µCT and X-ray phase-contrast holographic nanotomography scanned whole tissue specimens, with optional high-resolution scans revealing delicate structures, without differentiation of various fibers and cells. Irregular architecture of dermal fibers was observed in the patient with Ehlers-Danlos syndrome and the patient with idiopathic dysmotility showed an abundance of mesenchymal ground substance. Conclusions: 3d phase-contrast tomographic imaging may be useful to illustrate traits of connective tissue dysfunction in various organs and to demonstrate whether disorganized dermal fibers could explain organ dysfunction.
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| 6. |
- Ek Olofsson, Henric, et al.
(författare)
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Are cortical microvascular raspberries caused by cerebral hypoperfusion? An exploratory pathological study
- 2021
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Ingår i: Cerebral Circulation - Cognition and Behavior. - : Elsevier BV. - 2666-2450. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: This retrospective study investigated a cortical microvascular formation, termed a ‘raspberry’ due to its appearance under a bright-field microscope. We examined whether there is support for the hypothesis that raspberry formation is an angiogenic process induced by cerebral hypoperfusion. Materials and Methods: Raspberries were manually quantified in haematoxylin and eosin-stained cortical sections from the anterior frontal lobe of deceased individuals who had undergone a diagnostic neuropathological examination at the Department of Pathology, Lund, Sweden, during April 2019–January 2021. Subjects represented consecutively received cases during this 22-month period. The raspberry density was compared between subjects according to variables collected from medical records and autopsy reports: age, sex, hypertension, diabetes mellitus, atrial fibrillation, orthostatic hypotension, chronic heart failure, acute circulatory failure, aortic atherosclerosis, atherosclerosis of the basal cerebral arteries (referred to as ‘cerebral atherosclerosis’), cerebral small vessel disease, cerebral amyloid angiopathy, cerebral infarction, and ischaemic white matter disease. Results: 62 subjects were included. The mean age was 71.9 years (range 46–97 years). 21 subjects (33.9%) were female. Independent-samples t-test showed a higher raspberry density in subjects with cerebral atherosclerosis (p = 0.029; 95% CI 0.7, 11.6 raspberries/cm²). The higher raspberry density in subjects with cerebral atherosclerosis remained in multiple linear regression (p = 0.003; 95% CI 2.3, 11.1 raspberries/cm²). Conclusion: This exploratory study indicates that cortical raspberries could be associated with cerebral atherosclerosis. The remaining results were inconclusive but motivate further examination of variables such as acute circulatory failure.
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| 7. |
- Ekman, Linnéa, et al.
(författare)
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Evaluation of small nerve fiber dysfunction in type 2 diabetes
- 2020
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 141:1, s. 38-46
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To assess potential correlations between intraepidermal nerve fiber densities (IENFD), graded with light microscopy, and clinical measures of peripheral neuropathy in elderly male subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes (T2DM), respectively. Materials and methods: IENFD was assessed in thin sections of skin biopsies from distal leg in 86 men (71-77 years); 24 NGT, 15 IGT, and 47 T2DM. Biopsies were immunohistochemically stained for protein gene product (PGP) 9.5, and intraepidermal nerve fibers (IENF) were quantified manually by light microscopy. IENFD was compared between groups with different glucose tolerance and related to neurophysiological tests, including nerve conduction study (NCS; sural and peroneal nerve), quantitative sensory testing (QST), and clinical examination (Total Neuropathy Score; Neuropathy Symptom Score and Neuropathy Disability Score). Results: Absent IENF was seen in subjects with T2DM (n = 10; 21%) and IGT (n = 1; 7%) but not in NGT. IENFD correlated weakly negatively with HbA1c (r = −.268, P =.013) and Total Neuropathy Score (r = −.219, P =.042). Positive correlations were found between IENFD and sural nerve amplitude (r =.371, P =.001) as well as conduction velocity of both the sural (r =.241, P =.029) and peroneal nerve (r =.258, P =.018). Proportions of abnormal sural nerve amplitude became significantly higher with decreasing IENFD. No correlation was found with QST. Inter-rater reliability of IENFD assessment was good (ICC = 0.887). Conclusions: Signs of neuropathy are becoming more prevalent with decreasing IENFD. IENFD can be meaningfully evaluated in thin histopathological sections using the presented technique to detect neuropathy.
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| 8. |
- Ekman, Linnéa, et al.
(författare)
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Temporal trend of small nerve fibre degeneration in people with and without type 2 diabetes mellitus
- 2022
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Ingår i: Diabetic Medicine. - : John Wiley & Sons. - 0742-3071 .- 1464-5491. ; 39:3
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Tidskriftsartikel (refereegranskat)abstract
- Aims: We investigated the long-term temporal trend of intraepidermal nerve fibre density (IENFD) and the association between changes in IENFD and metabolic factors in individuals with and without type 2 diabetes. Methods: A total of 66 participants were enrolled in this longitudinal population-based study, at baseline consisting of 35 individuals (median 61 years) without diabetes and 31 individuals with type 2 diabetes mellitus. Participants underwent clinical and electrophysiological examinations, as well as a skin biopsy both at baseline and at the follow-up visit (mean 8.1 ± 0.5 years). IENFD was assessed in thin sections of 5 μm, stained with the protein gene product 9.5-antibody and compared between the groups. Results: IENFD decreased during the period in both groups, with a greater decline in the group without diabetes than in type 2 diabetes (−2.3 and −0.6 fibres/mm respectively; p < 0.001). While IENFD at baseline was significantly reduced in type 2 diabetes relative to people without (p < 0.001), no difference in IENFD was found between groups at the follow-up (p = 0.183). Linear mixed model analysis indicated that age, weight and HbA1c were associated with decrease in IENFD in the total population (p < 0.007). IENFD also decreased with increasing age and weight, but not with HbA1c, in the separate groups (p < 0.049). Conclusions: Despite lower IENFD levels at baseline in type 2 diabetes, IENFD was equal between the groups at follow-up. A decrease in IENFD is to a limited extent affected by body weight, and HbA1c, but age seems to be the long-term determinant of IENFD in an elderly population.
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| 9. |
- Endisch, Christian, et al.
(författare)
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Hypoxic-Ischemic Encephalopathy Evaluated by Brain Autopsy and Neuroprognostication after Cardiac Arrest
- 2020
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149. ; 77:11, s. 1430-1439
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Neuroprognostication studies are potentially susceptible to a self-fulfilling prophecy as investigated prognostic parameters may affect withdrawal of life-sustaining therapy. Objective: To compare the results of prognostic parameters after cardiac arrest (CA) with the histopathologically determined severity of hypoxic-ischemic encephalopathy (HIE) obtained from autopsy results. Design, Setting, and Participants: In a retrospective, 3-center cohort study of all patients who died following cardiac arrest during their intensive care unit stay and underwent autopsy between 2003 and 2015, postmortem brain histopathologic findings were compared with post-CA brain computed tomographic imaging, electroencephalographic (EEG) findings, somatosensory-evoked potentials, and serum neuron-specific enolase levels obtained during the intensive care unit stay. Data analysis was conducted from 2015 to 2020. Main Outcomes and Measures: The severity of HIE was evaluated according to the selective eosinophilic neuronal death (SEND) classification and patients were dichotomized into categories of histopathologically severe and no/mild HIE. Results: Of 187 included patients, 117 were men (63%) and median age was 65 (interquartile range, 58-74) years. Severe HIE was found in 114 patients (61%) and no/mild HIE was identified in 73 patients (39%). Severe HIE was found in all 21 patients with bilaterally absent somatosensory-evoked potentials, all 15 patients with gray-white matter ratio less than 1.10 on brain computed tomographic imaging, all 9 patients with suppressed EEG, 15 of 16 patients with burst-suppression EEG, and all 29 patients with neuron-specific enolase levels greater than 67 μg/L more than 48 hours after CA without confounders. Three of 7 patients with generalized periodic discharges on suppressed background and 1 patient with burst-suppression EEG had a SEND 1 score (<30% dead neurons) in the cerebral cortex, but higher SEND scores (>30% dead neurons) in other oxygen-sensitive brain regions. Conclusions and Relevance: In this study, histopathologic findings suggested severe HIE after cardiac arrest in patients with bilaterally absent cortical somatosensory-evoked potentials, gray-white matter ratio less than 1.10, highly malignant EEG, and serum neuron-specific enolase concentration greater than 67 μg/L.
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| 10. |
- Ilinca, Andreea, et al.
(författare)
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MAP3K6 Mutations in a Neurovascular Disease Causing Stroke, Cognitive Impairment, and Tremor
- 2021
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Ingår i: Neurology: Genetics. - 2376-7839. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe a possible novel genetic mechanism for cerebral small vessel disease (cSVD) and stroke.Methods: We studied a Swedish kindred with ischemic stroke and intracerebral hemorrhage, tremor, dysautonomia, and mild cognitive decline. Members were examined clinically, radiologically, and by histopathology. Genetic workup included whole-exome sequencing (WES) and whole-genome sequencing (WGS) and intrafamilial cosegregation analyses.Results: Fifteen family members were examined clinically. Twelve affected individuals had white matter hyperintensities and 1 or more of (1) stroke episodes, (2) clinically silent lacunar ischemic lesions, and (3) cognitive dysfunction. All affected individuals had tremor and/or atactic gait disturbance. Mild symmetric basal ganglia calcifications were seen in 3 affected members. Postmortem examination of 1 affected member showed pathologic alterations in both small and large arteries the brain. Skin biopsies of 3 affected members showed extracellular amorphous deposits within the subepidermal zone, which may represent degenerated arterioles. WES or WGS did not reveal any potentially disease-causing variants in known genes for cSVDs or idiopathic basal ganglia calcification, but identified 1 heterozygous variant, NM_004672.4 MAP3K6 c.322G>A p.(Asp108Asn), that cosegregated with the disease in this large family. MAP3K6 has known functions in angiogenesis and affects vascular endothelial growth factor expression, which may be implicated in cerebrovascular disease.Conclusions: Our data strongly suggest the MAP3K6 variant to be causative for this novel disease phenotype, but the absence of functional data and the present lack of additional families with this disease and MAP3K6 mutations still limit the formal evidence for the variant's pathogenicity.
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