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Neuropathology and Applied Neurobiology Apr 2022The pathological processes leading to synapse loss, neuronal loss, brain atrophy and gliosis in Alzheimer's disease (AD) and their relation to vascular disease and... (Review)
Review
The pathological processes leading to synapse loss, neuronal loss, brain atrophy and gliosis in Alzheimer's disease (AD) and their relation to vascular disease and immunological changes are yet to be fully explored. Amyloid-β (Aβ) aggregation, vascular damage and altered immune response interact at the blood-brain barrier (BBB), affecting the brain endothelium and fuelling neurodegeneration. The aim of the present systematic literature review was to critically appraise and to summarise the published evidence on the clinical correlations and pathophysiological concepts of BBB damage in AD, focusing on human data. The PubMed, Cochrane, Medline and Embase databases were searched for original research articles, systematic reviews and meta-analyses, published in English language from 01/2000 to 07/2021, using the keywords Alzheimer*, amyloid-β or β-amyloid or abeta and BBB. This review shows that specific changes of intercellular structures, reduced expression of transendothelial carriers, induction of vasoactive mediators and activation of both astroglia and monocytes/macrophages characterise BBB damage in human AD and AD models. BBB dysfunction on magnetic resonance imaging takes place early in the disease course in AD-specific brain regions. The toxic effects of Aβ and apolipoprotein E (ApoE) are likely to induce a non-cerebral-amyloid-angiopathy-related degeneration of endothelial cells, independently of cerebrovascular disease; however, some of the observed structural changes may just arise with age. Small vessel disease, ApoE, loss of pericytes, proinflammatory signalling and cerebral amyloid angiopathy enhance BBB damage. Novel therapeutic approaches for AD, including magnetic resonance-guided focused ultrasound, aim to open the BBB, potentially leading to an improved drainage of Aβ along perivascular channels and increased elimination from the brain. In vitro treatments with ApoE-modifying agents yielded promising effects on modulating BBB function. Reducing cardiovascular risk factors represents one of the most promising interventions for dementia prevention at present. However, further research is needed to elucidate the connection of BBB damage and tau pathology, the role of proinflammatory mediators in draining macromolecules and cells from the cerebral parenchyma, including their contribution to cerebral amyloid angiopathy. Improved insight into these pathomechanisms may allow to shed light on the role of Aβ deposition as a primary versus a secondary event in the complex pathogenesis of AD.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Blood-Brain Barrier; Brain; Cerebral Amyloid Angiopathy; Endothelial Cells; Humans
PubMed: 34823269
DOI: 10.1111/nan.12782 -
Alzheimer's & Dementia : the Journal of... Jan 2022Reported prevalence estimates of sporadic cerebral amyloid angiopathy (CAA) vary widely. CAA is associated with cognitive dysfunction and intracerebral hemorrhage, and... (Meta-Analysis)
Meta-Analysis
Reported prevalence estimates of sporadic cerebral amyloid angiopathy (CAA) vary widely. CAA is associated with cognitive dysfunction and intracerebral hemorrhage, and linked to immunotherapy-related side-effects in Alzheimer's disease (AD). Given ongoing efforts to develop AD immunotherapy, accurate estimates of CAA prevalence are important. CAA can be diagnosed neuropathologically or during life using MRI markers including strictly lobar microbleeds. In this meta-analysis of 170 studies including over 73,000 subjects, we show that in patients with AD, CAA prevalence based on pathology (48%) is twice that based on presence of strictly lobar cerebral microbleeds (22%); in the general population this difference is three-fold (23% vs 7%). Both methods yield similar estimated prevalences of CAA in cognitively normal elderly (5% to 7%), in patients with intracerebral hemorrhage (19% to 24%), and in patients with lobar intracerebral hemorrhage (50% to 57%). However, we observed large heterogeneity among neuropathology and MRI protocols, which calls for standardized assessment and reporting of CAA.
Topics: Alzheimer Disease; Cerebral Amyloid Angiopathy; Cerebral Hemorrhage; Cognitive Dysfunction; Humans; Immunotherapy; Magnetic Resonance Imaging; Neuropathology; Prevalence
PubMed: 34057813
DOI: 10.1002/alz.12366 -
Stroke Jan 2023There are limited data regarding the prevalence of distinct clinical, neuroimaging and genetic markers among patients diagnosed with cerebral amyloid angiopathy-related... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There are limited data regarding the prevalence of distinct clinical, neuroimaging and genetic markers among patients diagnosed with cerebral amyloid angiopathy-related inflammation (CAA-ri). We sought to determine the prevalence of clinical, radiological, genetic and cerebrospinal fluid biomarker findings in patients with CAA-ri.
METHODS
A systematic review and meta-analysis of published studies including patients with CAA-ri was conducted to determine the prevalence of clinical, neuroimaging, genetic and cerebrospinal fluid biomarker findings. Subgroup analyses were performed based on (1) prospective or retrospective study design and (2) CAA-ri diagnosis with or without available biopsy. We pooled the prevalence rates using random-effects models and assessed the heterogeneity using Cochran-Q and I-statistics.
RESULTS
We identified 4 prospective and 17 retrospective cohort studies comprising 378 patients with CAA-ri (mean age, 71.5 years; women, 52%). The pooled prevalence rates were as follows: cognitive decline at presentation 70% ([95% CI, 54%-84%]; I=82%), focal neurological deficits 55% ([95% CI, 40%-70%]; I=82%), encephalopathy 54% ([95% CI, 39%-68%]; I=43%), seizures 37% ([95% CI, 27%-49%]; I=65%), headache 31% ([95% CI, 22%-42%]; I=58%), T2/fluid-attenuated inversion recovery-hyperintense white matter lesions 98% ([95% CI, 93%-100%]; I=44%), lobar cerebral microbleeds 96% ([95% CI, 92%-99%]; I=25%), gadolinium enhancing lesions 54% ([95% CI, 42%-66%]; I=62%), cortical superficial siderosis 51% ([95% CI, 34%-68%]; I=77%) and lobar macrohemorrhage 40% ([95% CI, 11%-73%]; I=88%). The prevalence rate of the ApoE (Apolipoprotein E) ε4/ε4 genotype was 34% ([95% CI, 17%-53%]; I=76%). Subgroup analyses demonstrated no differences in these prevalence rates based on study design and diagnostic strategy.
CONCLUSIONS
Cognitive decline was the most common clinical feature. Hyperintense T2/fluid-attenuated inversion recovery white matter lesions and lobar cerebral microbleeds were by far the most prevalent neuroimaging findings. Thirty-four percent of patients with CAA-ri have homozygous ApoE ε4/ε4 genotype and scarce data exist regarding the cerebrospinal fluid biomarkers and its significance in these patients.
Topics: Humans; Female; Aged; Retrospective Studies; Genetic Markers; Prospective Studies; Cerebral Hemorrhage; Cerebral Amyloid Angiopathy; Neuroimaging; Inflammation; Magnetic Resonance Imaging
PubMed: 36453271
DOI: 10.1161/STROKEAHA.122.040671 -
American Journal of Otolaryngology 2022The larynx is the most common site of localized head and neck amyloidosis. Our study aimed to review the clinical features, treatments, and outcomes associated with... (Review)
Review
OBJECTIVE
The larynx is the most common site of localized head and neck amyloidosis. Our study aimed to review the clinical features, treatments, and outcomes associated with localized laryngeal amyloidosis (LA). We also compared these features between two different time periods to evaluate the evolution of LA management.
METHODS
A literature search using PubMed, CINAHL, Embase, and Cochrane Library identified cases of LA published between 1891 and 2021. Biopsy-proven cases of localized LA were included. Non-English studies, animal studies, and reviews were excluded.
RESULTS
282 patients (1891-1999: 142 patients, 2000-2021: 140 patients) from 129 studies were included. Results are reported as 1891-2000 vs. 2000-2021: Mean age was 48.5 years (range, 8-90 years) vs. 46.0 years (range, 9-84 years). The most common presenting symptoms were dysphonia (n = 30, 95 % vs. n = 127, 96 %) and difficulty breathing (n = 37, 27 % vs. n = 35, 27 %). A total of 62 (44 %) vs. 46 (33 %) lesions were found in the true vocal folds and 35 (25 %) vs. 59 (42 %) were found in the false vocal folds. 133 (94 %) vs. 137 (98 %) patients underwent surgical interventions to investigate and/or treat LA. Recurrent LA was reported in 27 (19 %) vs. 33 (24 %) patients with a mean time to recurrence of 25.4 months (range, 0.3-132 months) vs. 34.5 months (range, 0.8-144 months). Of cases reporting survival rate, 104 (97 %) vs. 107 (99 %) were alive at source study endpoints.
CONCLUSION
LA typically exhibits an indolent course; therefore, early intervention may address longstanding symptoms. Recurrent disease poses a clinical challenge in patients with LA.
Topics: Amyloidosis; Hoarseness; Humans; Laryngeal Diseases; Larynx; Vocal Cords
PubMed: 35917657
DOI: 10.1016/j.amjoto.2022.103550 -
Medicina Oral, Patologia Oral Y Cirugia... Jul 2023Amyloidosis is a disease characterized by the progressive deposition of abnormal proteins that can occur in any organ. In the oral cavity, the tongue is the most common...
BACKGROUND
Amyloidosis is a disease characterized by the progressive deposition of abnormal proteins that can occur in any organ. In the oral cavity, the tongue is the most common affected site, usually causing macroglossia. Biopsy is essential for the diagnosis and the occurrence of its systemic form is mandatory to be investigated. This systematic review evaluated the existing information in the literature on Amyloidosis in the oral cavity to allow a more comprehensive and updated analysis of its clinicopathological characteristics, as well as to explore the main forms of treatment and prognostic factors.
MATERIAL AND METHODS
Electronic searches were undertaken in five databases supplemented by manual scrutiny.
RESULTS
A total of 111 studies were included with 158 individuals.
CONCLUSIONS
The disease had a higher prevalence in women, the tongue was the most affected site, as well as the systemic form of the disease. The worst prognosis was for cases of systemic amyloidosis associated with multiple myeloma.
Topics: Humans; Female; Amyloidosis; Macroglossia; Multiple Myeloma; Tongue Diseases; Tongue
PubMed: 37330968
DOI: 10.4317/medoral.25761 -
European Archives of... Jul 2023The aim of this review was to study the surgical management of laryngeal amyloidosis and estimate the rate of recurrence after surgery. (Review)
Review
PURPOSE
The aim of this review was to study the surgical management of laryngeal amyloidosis and estimate the rate of recurrence after surgery.
METHODS
A systematic review searching PubMed and EMBASE was performed. A qualitative synthesis of data regarding the surgical management of LA and a quantitative analysis of the recurrence rate after surgery was conducted.
RESULTS
This systematic review included 14 retrospective studies, one of whom is retrospective controlled. A total of 515 subjects were included, the mean age ranged from 43.3 to 58 years with a male-to-female ratio of 1:1.3. All cases had a localized laryngeal amyloidosis. The supraglottic region was the most affected laryngeal site and multiple sites were commonly involved. Surgical treatment consists of endoscopic excision using laser, cold or powered instruments. Open surgery is required for severe primary case or revision surgery. Surgical complications such as granulomatosis scar tissue formation, tracheostomy, laryngotracheal stenosis, pneumothorax and concomitant malignancy were developed in 17.5% of patients. The time onset to diagnosis varied from 1 months to 15 years and the duration of follow-up from 3 months to 25 years. The rate of recurrence was 28.4% (95% CI 24.5-32.6) and the timing of recurrences ranged from 3 months to 10 years.
CONCLUSION
The recurrence rate after primary surgery for laryngeal amyloidosis is high. A tailored surgical treatment based on the disease extension and a long-term follow up are recommended.
Topics: Humans; Male; Female; Adult; Middle Aged; Retrospective Studies; Laryngeal Diseases; Larynx; Laryngostenosis; Amyloidosis
PubMed: 36790723
DOI: 10.1007/s00405-023-07881-6 -
Current Cardiology Reviews 2020There is a growing interest in the observed significant incidence of transthyretin cardiac amyloidosis in elderly patients with aortic stenosis. Approximately, 16% of...
BACKGROUND
There is a growing interest in the observed significant incidence of transthyretin cardiac amyloidosis in elderly patients with aortic stenosis. Approximately, 16% of patients with severe aortic stenosis undergoing aortic valve replacement have transthyretin cardiac amyloidosis. Outcomes after aortic valve replacement appear to be worst in patients with concomitant transthyretin cardiac amyloidosis.
METHODS
Publications in PubMed, Cochrane Library, and Embase databases were systematically searched from January 2012 to September 2018 using the keywords transthyretin, amyloidosis, and aortic stenosis. All studies published in English that reported the prevalence, association and outcomes of transthyretin cardiac amyloidosis in patients with aortic stenosis undergoing were included.
RESULTS/CONCLUSION
The relationship between aortic stenosis and transthyretin cardiac amyloidosis is not well understood. A few studies have proven successful surgical management when both conditions coexist. This systematic review suggests that transthyretin cardiac amyloidosis is common in elderly patients with aortic stenosis and tend to have high mortality rates after AVR. The significant incidence of the two diseases occurring simultaneously warrants further investigation to improve management strategies in the future.
Topics: Amyloid Neuropathies, Familial; Aortic Valve Stenosis; Female; Humans; Male; Treatment Outcome
PubMed: 31544701
DOI: 10.2174/1573403X15666190722154152 -
Stroke Jun 2022Limited data exist regarding the prevalence of clinical and neuroimaging manifestations among patients diagnosed with cerebral amyloid angiopathy (CAA). We sought to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Limited data exist regarding the prevalence of clinical and neuroimaging manifestations among patients diagnosed with cerebral amyloid angiopathy (CAA). We sought to determine the prevalence of clinical phenotypes and radiological markers in patients with CAA.
METHODS
Systematic review and meta-analysis of studies including patients with CAA was conducted to primarily assess the prevalence of clinical phenotypes and neuroimaging markers as available in the included studies. Sensitivity analyses were performed based on the (1) retrospective or prospective study design and (2) probable or unspecified CAA status. We pooled the prevalence rates using random-effects models and assessed the heterogeneity using the Cochran and statistics.
RESULTS
We identified 12 prospective and 34 retrospective studies including 7159 patients with CAA. The pooled prevalence rates were cerebral microbleeds (52% [95% CI, 43%-60%]; I=93%), cortical superficial siderosis (49% [95% CI, 38%-59%]; I=95%), dementia or mild cognitive impairment (50% [95% CI, 35%-65%]; I=97%), intracerebral hemorrhage (ICH; 44% [95% CI, 27%-61%]; I=98%), transient focal neurological episodes (48%; 10 studies [95% CI, 29%-67%]; I=97%), lacunar infarcts (30% [95% CI, 25%-36%]; I=78%), high grades of perivascular spaces located in centrum semiovale (56% [95% CI, 44%-67%]; I=88%) and basal ganglia (21% [95% CI, 2%-51%]; I=98%), and white matter hyperintensities with moderate or severe Fazekas score (53% [95% CI, 40%-65%]; I=91%). The only neuroimaging marker that was associated with higher odds of recurrent ICH was cortical superficial siderosis (odds ratio, 1.57 [95% CI, 1.01-2.46]; I=47%). Sensitivity analyses demonstrated a higher prevalence of ICH (53% versus 16%; =0.03) and transient focal neurological episodes (57% versus 17%; =0.03) among retrospective studies compared with prospective studies. No difference was documented between the prevalence rates based on the CAA status.
CONCLUSIONS
Approximately one-half of hospital-based cohort of CAA patients was observed to have cerebral microbleeds, cortical superficial siderosis, mild cognitive impairment, dementia, ICH, or transient focal neurological episodes. Cortical superficial siderosis was the only neuroimaging marker that was associated with higher odds of ICH recurrence. Future population-based studies among well-defined CAA cohorts are warranted to corroborate our findings.
Topics: Cerebral Amyloid Angiopathy; Cerebral Hemorrhage; Dementia; Humans; Magnetic Resonance Imaging; Neuroimaging; Prevalence; Prospective Studies; Retrospective Studies; Siderosis
PubMed: 35264008
DOI: 10.1161/STROKEAHA.121.035836 -
Journal of Lower Genital Tract Disease Jul 2019The aim of the study was to review uncommon foreskin dermatopathology conditions clinically and pathologically.
OBJECTIVES
The aim of the study was to review uncommon foreskin dermatopathology conditions clinically and pathologically.
METHODS
A database search of PubMed and Google Scholar were extracted between March 1, 2009, and March 1, 2019, using the search terms "foreskin," "prepuce," "penis," "pathology," "dermatology," and "rare." The search was limited to "humans" and "dermatopathology." Full article texts were reviewed. Reference lists were screened for additional articles. Patient details (diagnosis, dermatopathology, treatment, and follow-up if available) were extracted. We excluded articles written in the non-English language, unusual variants of common conditions, and cases of common dermatologic conditions.
RESULTS
A list of 369 articles was identified and another screening identified 30 articles for rare foreskin pathologies. Those are divided into categories based on the following etiologies: (a) benign, including congenital (e.g., aposthia), infectious (graft versus host disease and histoplasma), autoimmune (Crohn's disease and pyoderma gangrenosum), and benign neoplasms (neurofibroma, apocrine hidrocystoma, verruciform xanthoma, porokeratosis, penile cutaneous horn, localized amyloidosis) and (b) malignancies, including primary (myeloid sarcoma, basal cell carcinoma, Kaposi's sarcoma, mucosal-associated lymphoid tissue lymphoma), and metastasis.
CONCLUSIONS
We reviewed and discussed unusual benign and malignant dermatopathology conditions that can affect the foreskin.
Topics: Adult; Aged; Autoimmune Diseases; Child; Child, Preschool; Dermatitis; Foreskin; Humans; Male; Middle Aged; Neoplasms; Penile Neoplasms
PubMed: 31149956
DOI: 10.1097/LGT.0000000000000478 -
ESC Heart Failure Jun 2022Wild-type transthyretin amyloid cardiomyopathy (ATTRwt CM) is a more common disease than previously thought. Awareness of ATTRwt CM and its diagnosis has been challenged... (Review)
Review
Wild-type transthyretin amyloid cardiomyopathy (ATTRwt CM) is a more common disease than previously thought. Awareness of ATTRwt CM and its diagnosis has been challenged by its unspecific and widely distributed clinical manifestations and traditionally invasive diagnostic tools. Recent advances in echocardiography and cardiac magnetic resonance (CMR), non-invasive diagnosis by bone scintigraphy, and the development of disease-modifying treatments have resulted in an increased interest, reflected in multiple publications especially during the last decade. To get an overview of the scientific knowledge and gaps related to patient entry, suspicion, diagnosis, and systematic screening of ATTRwt CM, we developed a framework to systematically map the available evidence of (i) when to suspect ATTRwt CM in a patient, (ii) how to diagnose the disease, and (iii) which at-risk populations to screen for ATTRwt CM. Articles published between 2010 and August 2021 containing part of or a full diagnostic pathway for ATTRwt CM were included. From these articles, data for patient entry, suspicion, diagnosis, and screening were extracted, as were key study design and results from the original studies referred to. A total of 50 articles met the inclusion criteria. Of these, five were position statements from academic societies, while one was a clinical guideline. Three articles discussed the importance of primary care providers in terms of patient entry, while the remaining articles had the cardiovascular setting as point of departure. The most frequently mentioned suspicion criteria were ventricular wall thickening (44/50), carpal tunnel syndrome (42/50), and late gadolinium enhancement on CMR (43/50). Diagnostic pathways varied slightly, but most included bone scintigraphy, exclusion of light-chain amyloidosis, and the possibility of doing a biopsy. Systematic screening was mentioned in 16 articles, 10 of which suggested specific at-risk populations for screening. The European Society of Cardiology recommends to screen patients with a wall thickness ≥12 mm and heart failure, aortic stenosis, or red flag symptoms, especially if they are >65 years. The underlying evidence was generally good for diagnosis, while significant gaps were identified for the relevance and mutual ranking of the different suspicion criteria and for systematic screening. Conclusively, patient entry was neglected in the reviewed literature. While multiple red flags were described, high-quality prospective studies designed to evaluate their suitability as suspicion criteria were lacking. An upcoming task lies in defining and evaluating at-risk populations for screening. All are steps needed to promote early detection and diagnosis of ATTRwt CM, a prerequisite for timely treatment.
Topics: Amyloid Neuropathies, Familial; Cardiomyopathies; Contrast Media; Gadolinium; Humans; Prealbumin; Prospective Studies
PubMed: 35343098
DOI: 10.1002/ehf2.13884