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Orphanet Journal of Rare Diseases Jun 2023CSF1R mutations cause autosomal-dominant CSF1R-related leukoencephalopathy with axonal spheroids and pigmented glia (CSF1R-ALSP) and autosomal-recessive brain... (Review)
Review
CSF1R mutations cause autosomal-dominant CSF1R-related leukoencephalopathy with axonal spheroids and pigmented glia (CSF1R-ALSP) and autosomal-recessive brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS). The former is increasingly recognized, and disease-modifying therapy was introduced; however, literature is scarce on the latter. This review analyzes BANDDOS and discusses similarities and differences with CSF1R-ALSP.We systematically retrieved and analyzed the clinical, genetic, radiological, and pathological data on the previously reported and our cases with BANDDOS. We identified 19 patients with BANDDOS (literature search according to the PRISMA 2020 guidelines: n = 16, our material: n = 3). We found 11 CSF1R mutations, including splicing (n = 3), missense (n = 3), nonsense (n = 2), and intronic (n = 2) variants and one inframe deletion. All mutations disrupted the tyrosine kinase domain or resulted in nonsense-mediated mRNA decay. The material is heterogenous, and the presented information refers to the number of patients with sufficient data on specific symptoms, results, or performed procedures. The first symptoms occurred in the perinatal period (n = 5), infancy (n = 2), childhood (n = 5), and adulthood (n = 1). Dysmorphic features were present in 7/17 cases. Neurological symptoms included speech disturbances (n = 13/15), cognitive decline (n = 12/14), spasticity/rigidity (n = 12/15), hyperactive tendon reflex (n = 11/14), pathological reflexes (n = 8/11), seizures (n = 9/16), dysphagia (n = 9/12), developmental delay (n = 7/14), infantile hypotonia (n = 3/11), and optic nerve atrophy (n = 2/7). Skeletal deformities were observed in 13/17 cases and fell within the dysosteosclerosis - Pyle disease spectrum. Brain abnormalities included white matter changes (n = 19/19), calcifications (n = 15/18), agenesis of corpus callosum (n = 12/16), ventriculomegaly (n = 13/19), Dandy-Walker complex (n = 7/19), and cortical abnormalities (n = 4/10). Three patients died in infancy, two in childhood, and one case at unspecified age. A single brain autopsy evidenced multiple brain anomalies, absence of corpus callosum, absence of microglia, severe white matter atrophy with axonal spheroids, gliosis, and numerous dystrophic calcifications.In conclusion, BANDDOS presents in the perinatal period or infancy and has a devastating course with congenital brain abnormalities, developmental delay, neurological deficits, osteopetrosis, and dysmorphic features. There is a significant overlap in the clinical, radiological, and neuropathological aspects between BANDDOS and CSF1R-ALSP. As both disorders are on the same continuum, there is a window of opportunity to apply available therapy in CSF1R-ALSP to BANDDOS.
Topics: Humans; Neuroglia; Leukoencephalopathies; Brain; Mutation; Nervous System Malformations; Atrophy
PubMed: 37349768
DOI: 10.1186/s13023-023-02772-9 -
Translational Stroke Research Jun 2024In intracerebral hemorrhage (ICH) with pathology-proven etiology, we performed a systematic review and meta-analysis to elucidate the association between cerebral... (Meta-Analysis)
Meta-Analysis
In intracerebral hemorrhage (ICH) with pathology-proven etiology, we performed a systematic review and meta-analysis to elucidate the association between cerebral amyloid angiopathy (CAA) and arteriolosclerosis, and directly compared MRI and pathological changes of markers of cerebral small vessel disease (CSVD). Studies enrolling primary ICH who had received an etiological diagnosis through biopsy or autopsy were searched using Ovid MEDLINE, PubMed, and Web of Science from inception to June 8, 2022. We extracted pathological changes of CSVD for each patient whenever available. Patients were grouped into CAA + arteriolosclerosis, strict CAA, and strict arteriolosclerosis subgroups. Of 4155 studies identified, 28 studies with 456 ICH patients were included. The frequency of lobar ICH (p<0.001) and total microbleed number (p=0.015) differed among patients with CAA + arteriolosclerosis, strict CAA, and strict arteriolosclerosis. Concerning pathology, severe CAA was associated with arteriolosclerosis (OR 6.067, 95% CI 1.107-33.238, p=0.038), although this association was not statistically significant after adjusting for age and sex. Additionally, the total microbleed number (median 15 vs. 0, p=0.006) was higher in ICH patients with CAA evidence than those without CAA. The pathology of CSVD imaging markers was mostly investigated in CAA-ICH. There was inconsistency concerning CAA severity surrounding microbleeds. Small diffusion-weighted imaging lesions could be matched to acute microinfarct histopathologically. Studies that directly correlated MRI and pathology of lacunes, enlarged perivascular spaces, and atrophy were scarce. Arteriolosclerosis might be associated with severe CAA. The pathological changes of CSVD markers by ICH etiology are needed to be investigated further.
Topics: Humans; Cerebral Hemorrhage; Cerebral Small Vessel Diseases; Cerebral Amyloid Angiopathy; Arteriolosclerosis
PubMed: 37280502
DOI: 10.1007/s12975-023-01154-4 -
Frontiers in Molecular Biosciences 2023Dementia with Lewy Bodies (DLB) is the second most common cause of neurodegenerative dementia after Alzheimer's disease (AD), but the field is still lacking a specific... (Review)
Review
Dementia with Lewy Bodies (DLB) is the second most common cause of neurodegenerative dementia after Alzheimer's disease (AD), but the field is still lacking a specific biomarker for its core pathology: alpha synuclein (α-syn). Realtime quaking induced conversion (RT-QuIC) has recently emerged as a strong biomarker candidate to detect misfolded α-syn in DLB. However, the variability in the parameters of the technique and the heterogeneity of DLB patients make the reproducibility of the results difficult. Here, we provide an overview of the state-of-the-art research of α-syn RT-QuIC in DLB focused on: (1) the capacity of α-syn RT-QuIC to discriminate DLB from controls, Parkinson's disease (PD) and AD; (2) the capacity of α-syn RT-QuIC to identify prodromal stages of DLB; and (3) the influence of co-pathologies on α-syn RT-QuIC's performance. We also assessed the influence of different factors, such as technical conditions (e.g., temperature, pH, shaking-rest cycles), sample type, and clinical diagnosis versus autopsy confirmation. We conducted a systematic review following the PRISMA guidelines in August 2022, without any limits in publication dates. Search terms were combinations of "RT-QuIC" and "Lewy Bodies," "DLB" or "LBD". Our meta-analysis shows that α-syn RT-QuIC reaches very high diagnostic performance in discriminating DLB from both controls (pooled sensitivity and specificity of 0.94 and 0.96, respectively) and AD (pooled sensitivity and specificity of 0.95 and 0.88) and is promising for prodromal phases of DLB. However, the performance of α-syn RT-QuIC to discriminate DLB from PD is currently low due to low specificity (pooled sensitivity and specificity of 0.94 and 0.11). Our analysis showed that α-syn RT-QuIC's performance is not substantially influenced by sample type or clinical diagnosis versus autopsy confirmation. Co-pathologies did not influence the performance of α-syn RT-QuIC, but the number of such studies is currently limited. We observed technical variability across published articles. However, we could not find a clear effect of technical variability on the reported results. There is currently enough evidence to test misfolded α-syn by RT-QuIC for clinical use. We anticipate that harmonization of protocols across centres and advances in standardization will facilitate the clinical establishment of misfolded α-syn detection by RT-QuIC.
PubMed: 37266333
DOI: 10.3389/fmolb.2023.1193458 -
International Journal of Legal Medicine Sep 2023Post-mortem interval (PMI) is the cornerstone of the forensic field to investigate. The examination technique by seeing the changes in the body such as algor mortis,... (Review)
Review
BACKGROUND
Post-mortem interval (PMI) is the cornerstone of the forensic field to investigate. The examination technique by seeing the changes in the body such as algor mortis, rigor mortis, and livor mortis is a traditional technique in which accuracy is influenced by many factors. A biomolecular technique that uses microRNA (miRNA) biomarkers is developing because miRNA has good stability than other RNA, so it meets the requirements to be used for PMI estimation.
METHOD
Following the PRISMA guidelines, journals were taken from 5 databases: Scopus, Science Direct, PubMed, Embase, and Springer. The review was carried out by two people. Inclusion criteria in this review are original research, published in the last 10 years, discussing miRNA as a biomarker for PMI estimation, and free full access. While exclusion criteria are not original research and not using English.
RESULT
Eighteen journals were reviewed in this study. The study was conducted using test animals (rats) and human samples with tissue sources taken from the liver, skeletal muscle, blood, bone, heart, skin, saliva, semen, brain, lung, vitreous humor, spleen, and kidney. miRNA expression levels after death showed different results based on miRNA target, tissue source, and others.
DISCUSSION
The results of each study are different due to the use of different types of miRNA targets and tissue sources. miRNA has great potential to estimate PMI in forensic science, but it is necessary to control the influencing factors to obtain an accurate conclusion.
Topics: Humans; Animals; Rats; MicroRNAs; Autopsy; Postmortem Changes; Forensic Medicine; Forensic Sciences; Biomarkers
PubMed: 37253884
DOI: 10.1007/s00414-023-03015-z -
Pathogens (Basel, Switzerland) Apr 2023The COVID-19 pandemic raised concerns about the potential for co-infection or over-infection with other respiratory infections, as they can complicate the diagnosis,... (Review)
Review
The COVID-19 pandemic raised concerns about the potential for co-infection or over-infection with other respiratory infections, as they can complicate the diagnosis, treatment and prognosis of the disease. This is also a challenge for forensic pathologists, who may come across cases where the presence of co-infection or over-infection is suspected or confirmed, and it is important that they take this into account when determining the cause of death. The aim of this systematic review is to analyse the prevalence of each specific pathogen co-infecting or over-infecting patients with SARS-CoV-2 infection. In total, 575 studies were selected from the Scopus and Pub-Med online databases and 8 studies were included in a meta-analysis. Male gender, advanced age and nursing home care are risk factors associated with the development of co-infection, whereas age, tachypnoea, hypoxaemia and bacterial infection are predictors of mortality. Overall, however, having a SARS-CoV-2 infection does not represent a real risk for the development of co-infections/super-infections.
PubMed: 37242315
DOI: 10.3390/pathogens12050646 -
Diagnostics (Basel, Switzerland) May 2023(1) Background: Head trauma represents the first cause of death in abused children, but diagnostic knowledge is still limited. The characteristic findings of abusive... (Review)
Review
(1) Background: Head trauma represents the first cause of death in abused children, but diagnostic knowledge is still limited. The characteristic findings of abusive head trauma (AHT) are retinal hemorrhages (RH) and additional ocular findings, including optic nerve hemorrhages (ONH). However, etiological diagnosis must be cautious. (2) Methods: The Preferred Reporting Items for Systematic Review (PRISMA) standards were employed, and the research focus was the current gold standard in the diagnosis and timing of abusive RH. (3) Results: Sixteen articles were included for qualitative synthesis. The importance of an early instrumental ophthalmological assessment emerged in subjects with a high suspicion of AHT, with attention to the localization, laterality, and morphology of the findings. Sometimes it is possible to observe the fundus even in deceased subjects, but the current techniques of choice consist of Magnetic Resonance Imaging and Computed Tomography, also useful for the timing of the lesion, the autopsy, and the histological investigation, especially if performed with the use of immunohistochemical reactants against erythrocytes, leukocytes, and ischemic nerve cells. (4) Conclusions: The present review has made it possible to build an operational framework for the diagnosis and timing of cases of abusive retinal damage, but further research in the field is needed.
PubMed: 37238204
DOI: 10.3390/diagnostics13101722 -
SAGE Open Medicine 2023Virtual autopsy is a non-invasive/minimally invasive method for conducting an autopsy, with the assistance of imaging techniques. We aim to review the benefits of... (Review)
Review
OBJECTIVE
Virtual autopsy is a non-invasive/minimally invasive method for conducting an autopsy, with the assistance of imaging techniques. We aim to review the benefits of virtual autopsy in detecting pathologies in the paediatric population.
METHOD
The procedure adhered to Institute of Medicine and Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Seven databases including MEDLINE and SCOPUS were searched for articles published 2010-2020 worldwide in English. A narrative synthesis of the findings of included studies was carried out to discuss and summarize the results of the review.
RESULTS
From 686 studies on paediatric deaths, 23 met selection/quality criteria. Virtual autopsy was better than conventional autopsy in detecting skeletal lesions and bullet trajectory, thus a crucial tool in the investigation of traumatic and firearm deaths. Virtual autopsy was superior to conventional autopsy in identifying the point of bleeding in postoperative deaths and objectively quantifying air/fluid in body cavities. Virtual autopsy was a useful adjunct for detecting pulmonary thrombo-embolism, foreign body aspiration, drowning and metastatic malignancies. The use of non-contrast imaging in investigating natural paediatric deaths did not offer more information than conventional autopsy. Misinterpretation of normal post-mortem changes as pathological findings was another disadvantage of virtual autopsy leading to erroneous conclusions. But accuracy may be improved with contrast enhancement and post-mortem magnetic resonance imaging.
CONCLUSION
Virtual autopsy is a crucial tool in the investigation of traumatic and firearm deaths in the paediatric population. Virtual autopsy will be useful as an adjunct to conventional autopsy in asphyxial deaths, stillbirths and decomposed bodies. Virtual autopsy has limited value in differentiating antemortem and post-mortem changes with the added risk of misinterpretations, therefore should be used with caution in natural deaths.
PubMed: 37197019
DOI: 10.1177/20503121231172002 -
Cardiovascular Pathology : the Official... 2023Takotsubo syndrome (TTS) is a cardiac syndrome characterized by transient left ventricular systolic dysfunction in the absence of significant obstructive coronary artery... (Review)
Review
Takotsubo syndrome (TTS) is a cardiac syndrome characterized by transient left ventricular systolic dysfunction in the absence of significant obstructive coronary artery disease. At the autopsy, its diagnosis is often challenging, since it is generally thought that it relates to no characteristic macroscopic or microscopic findings. In order to verify this last statement, we performed a systematic review of the literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA) criteria. To the best of our knowledge, it is the first systematic review addressing this issue. We identified recurring but not pathognomonic (microscopic) features of TTS: contraction band necrosis and non-specific inflammatory changes (e.g., interstitial infiltrates of mononuclear lymphocytes and macrophages) typically in the absence of microscopic findings typical of acute myocardial infarction. In cases of TTS-related sudden death, careful evaluation of anamnesis, autopsy data and post-mortem genetic results (to exclude other causes) should be considered to overcome the complexity of these cases.
Topics: Humans; Takotsubo Cardiomyopathy; Myocardial Infarction; Heart; Coronary Artery Disease; Autopsy
PubMed: 37169210
DOI: 10.1016/j.carpath.2023.107543 -
Clinical & Experimental Metastasis Jun 2023With improved survival of cancer patients, we increasingly encounter infrequent metastatic locations. While for the common metastatic locations both prognostic...
With improved survival of cancer patients, we increasingly encounter infrequent metastatic locations. While for the common metastatic locations both prognostic information as well as evidence-based guidelines are available, for rare locations we have to rely on anecdotal case reports, the value of which is currently unknown. Therefore, we performed a systemic literature review and compare the results with a large national real-life cohort focussed on breast cancer patients with colorectal metastases. We performed a systematic literature search for breast cancer patients with colorectal metastases. Autopsy studies were excluded. Data on stage, histological factors, treatment and outcome were extracted. All identified cases were analysed as individual patients. The real-life cohort was extracted from the nationwide Dutch pathology databank. Linkage with the Netherlands Cancer Registry provided clinical characteristics, treatment and outcome data. Survival analyses and univariate regression were performed to identify relevant features for future treatment decisions. We identified 308 patients from 207 studies in the literature, and 454 patients in the real-life cohort. Colorectal metastases were the first metastatic event in 42.5% and 47.0% respectively. Cohorts were comparable for age, gender, location and hormone status, but differed in tumour type, stage and treatment. The time to colorectal metastases was similar in both cohorts (median of 68 months), and was dependent on presence of other metastases, nodal status, and primary breast surgery. The median overall survival after development of colorectal metastases was 20.6 months (95%CI 18.0-23.1 months). Despite a potential publication bias and lack of complete data for patients in the case report series, we have shown that an extensive systematic review can provide data that are comparable to real-life data, which can be used for decision-making and informing patients. Colorectal metastases are a late event in breast cancer patients, that is not associated with a detrimental survival.
Topics: Humans; Female; Breast Neoplasms; Prognosis; Colorectal Neoplasms; Netherlands
PubMed: 37106226
DOI: 10.1007/s10585-023-10207-9 -
Movement Disorders Clinical Practice Apr 2023Neuropathological studies, based on small samples, suggest that symptoms of Parkinson's disease (PD) emerge when dopamine/nigrostriatal loss is around 50-80%. Functional... (Review)
Review
BACKGROUND
Neuropathological studies, based on small samples, suggest that symptoms of Parkinson's disease (PD) emerge when dopamine/nigrostriatal loss is around 50-80%. Functional neuroimaging can be applied in larger numbers during life, which allows analysis of the extent of dopamine loss more directly.
OBJECTIVE
To quantify dopamine transporter (DaT) activity by neuroimaging in early PD.
METHODS
Systematic review and novel analysis of DaT imaging studies in early PD.
RESULTS
In our systematic review, in 423 unique cases from 27 studies with disease duration of less than 6 years, mean age 58.0 (SD 11.5) years, and mean disease duration 1.8 (SD 1.2) years, striatal loss was 43.5% (95% CI 41.6, 45.4) contralaterally, and 36.0% (95% CI 33.6, 38.3) ipsilaterally. For unilateral PD, in 436 unique cases, mean age 57.5 (SD 10.2) years, and mean disease duration 1.8 (SD 1.4) years, striatal loss was 40.6% (95% CI 38.8, 42.4) contralaterally, and 31.6% (95% CI 29.4, 33.8) ipsilaterally. In our novel analysis of the Parkinson's Progressive Marker Initiative study, 413 cases had 1436 scans performed. For a disease duration of less than 1 year, age was 61.8 (SD 9.8) years, and striatal loss was 51.2% (95% CI 49.1, 53.3) contralaterally and 39.5% (36.9, 42.1) ipsilaterally, giving an overall striatal loss of 45.3% (43.0, 47.6).
CONCLUSIONS
Loss of striatal DaT activity in early PD is less at 35-45%, rather than the 50-80% striatal dopamine loss estimated to be present at the time of symptom onset, based on backwards extrapolation from autopsy studies.
PubMed: 37070042
DOI: 10.1002/mdc3.13687