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American Journal of Clinical Dermatology Oct 2017Primary localized cutaneous amyloidosis (PLCA) is characterized by extracellular deposition of heterogenic amyloid proteins in the skin without systemic involvement.... (Review)
Review
BACKGROUND
Primary localized cutaneous amyloidosis (PLCA) is characterized by extracellular deposition of heterogenic amyloid proteins in the skin without systemic involvement. Lichen amyloidosis, macular amyloidosis, and (primary localized cutaneous) nodular amyloidosis are different subtypes of PLCA.
OBJECTIVE
The aim of this study was to review the current reported treatment options for PLCA.
METHODS
This systematic review was based on a search in the PubMed database for English and German articles from 1985 to 2016.
RESULTS
Reports on the treatment of PLCA were limited predominantly to case reports or small case series. There were a few clinical trials but these lacked control groups. A variety of treatment options for PLCA were reported including retinoids, corticosteroids, cyclophosphamide, cyclosporine, amitriptyline, colchicine, cepharanthin, tacrolimus, dimethyl sulfoxide, vitamin D analogs, capsaicin, menthol, hydrocolloid dressings, surgical modalities, laser treatment, and phototherapy.
CONCLUSION
No definitive recommendation of preferable treatment procedures can be made based on the analyzed literature. Randomized controlled trials are needed to offer patients an evidence-based therapy with high-quality standardized treatment regimens for PLCA.
Topics: Amyloidosis, Familial; Bandages, Hydrocolloid; Dermatologic Agents; Dermatologic Surgical Procedures; Europe; Humans; Laser Therapy; Phototherapy; Practice Guidelines as Topic; Skin; Skin Diseases, Genetic
PubMed: 28342017
DOI: 10.1007/s40257-017-0278-9 -
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 -
Acta Neurologica Scandinavica Feb 2019Hereditary transthyretin(TTR)-related amyloidosis (ATTRm amyloidosis) is an endemic/non-endemic, autosomal-dominant, early- and late-onset, rare, progressive disorder,...
Hereditary transthyretin(TTR)-related amyloidosis (ATTRm amyloidosis) is an endemic/non-endemic, autosomal-dominant, early- and late-onset, rare, progressive disorder, predominantly manifesting as length-dependent, small fiber dominant, axonal polyneuropathy and frequently associated with cardiac disorders and other multisystem diseases. ATTRm amyloidosis is due to variants in the TTR gene, with the substitution Val30Met as the most frequent mutation. TTR mutations lead to destabilization and dissociation of TTR tetramers into variant TTR monomers, and formation of amyloid fibrils, which are consecutively deposited extracellularly in various tissues, such as nerves, heart, brain, eyes, intestines, kidneys, or the skin. Neuropathy may not only include large nerve fibers but also small fibers, and not only sensory and motor fibers but also autonomic fibers. Types of TTR variants, age at onset, penetrance, and clinical presentation vary between geographical areas. Suggestive of a ATTRm amyloidosis are a sensorimotor polyneuropathy, positive family history, autonomic dysfunction, cardiomyopathy, carpal tunnel syndrome, unexplained weight loss, and resistance to immunotherapy. If only sensory A-delta or C fibers are affected, small fiber neuropathy ensues. Diagnostic tests for small fiber neuropathy include determination of intraepidermal nerve fiber density, laser-evoked potentials, heat- and cold-detection thresholds, and measurement of the electrochemical skin conductance. Therapy currently relies on liver transplantation and TTR-stabilizers (tafamidis, diflunisal).
Topics: Amyloid Neuropathies, Familial; Humans; Mutation; Prealbumin
PubMed: 30295933
DOI: 10.1111/ane.13035 -
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 -
International Journal of Cardiology May 2024Cardiac amyloidosis is increasingly recognized as a significant contributor to cardiovascular morbidity and mortality. With the emergence of novel therapies, there is a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cardiac amyloidosis is increasingly recognized as a significant contributor to cardiovascular morbidity and mortality. With the emergence of novel therapies, there is a growing interest in prognostication of patients with cardiac amyloidosis using cardiac magnetic resonance imaging (CMR). In this systematic review and meta-analysis, we aimed to examine the prognostic significance of myocardial native T1 and T2, and extracellular volume (ECV).
METHODS
Observational cohort studies or single arms of clinical trials were eligible. MEDLINE, EMBASE and CENTRAL were systematically searched from their respective dates of inception to January 2023. No exclusions were made based on date of publication, study outcomes, or study language. The study populations composed of adult patients (≥18 years old) with amyloid cardiomyopathy. All studies included the use of CMR with and without intravenous gadolinium contrast administration to assess myocardial native T1 mapping, T2 mapping, and ECV in association with the pre-specified primary outcome of all-cause mortality. Data were extracted from eligible primary studies by two independent reviewers and pooled via the inverse variance method using random effects models for meta-analysis.
RESULTS
A total of 3852 citations were reviewed. A final nine studies including a total of 955 patients (mean age 65 ± 10 years old, 32% female, mean left ventricular ejection fraction (LVEF) 59 ± 12% and 24% had NYHA class III or IV symptoms) with cardiac amyloidosis [light chain amyloidosis (AL) 50%, transthyretin amyloidosis (ATTR) 49%, other 1%] were eligible for inclusion and suitable for data extraction. All included studies were single centered (seven with 1.5 T MRI scanners, two with 3.0 T MRI scanners) and non-randomized in design, with follow-up spanning from 8 to 64 months (median follow-up = 25 months); 320 patients died during follow-up, rendering a weighted mortality rate of 33% across studies. Compared with patients with AL amyloid, patients with ATTR amyloid had significantly higher mean left ventricular mass index (LVMi) (102 ± 34 g/m vs 127 ± 37 g/m, p = 0.02). N-terminal pro-brain natriuretic peptide (NT-proBNP), troponin T levels, mean native T1 values, ECV and T2 values did not differ between patients with ATTR amyloid and AL amyloid (all p > 0.25). Overall, the hazard ratios for mortality were 1.33 (95% CI = [1.10, 1.60]; p = 0.003; I = 29%) for every 60 ms higher T1 time, 1.16 (95% CI = [1.09, 1.23], p < 0.0001; I = 76%) for every 3% higher ECV, and 5.23 (95% CI = [2.27, 12.02]; p < 0.0001; I = 0%) for myocardial-to-skeletal T2 ratio below the mean (vs above the mean).
CONCLUSION
Higher native T1 time and ECV, and lower myocardial to skeletal T2 ratio, on CMR are associated with worse mortality in patients with cardiac amyloidosis. Therefore, tissue mapping using CMR may offer a useful non-invasive technique to monitor disease progression and determine prognosis in patients with cardiac amyloidosis.
Topics: Adult; Humans; Female; Middle Aged; Aged; Adolescent; Male; Cardiomyopathies; Stroke Volume; Ventricular Function, Left; Magnetic Resonance Imaging; Myocardium; Amyloid Neuropathies, Familial; Disease Progression; Magnetic Resonance Imaging, Cine; Predictive Value of Tests; Contrast Media; Observational Studies as Topic
PubMed: 38382853
DOI: 10.1016/j.ijcard.2024.131892 -
International Journal of Surgery... 2008Amyloidosis refers to a variety of conditions in which amyloid proteins are abnormally deposited in organs and/or tissues. Amyloidosis is a rare occurrence in thyroid... (Review)
Review
BACKGROUND AND AIM
Amyloidosis refers to a variety of conditions in which amyloid proteins are abnormally deposited in organs and/or tissues. Amyloidosis is a rare occurrence in thyroid gland.
METHODS
A systematic review of the published data on amyloid goiter was carried out by searching Medline and other online databases (such as Scopus and Endnote) for the period from 1951 to March 2008. A total of 127 publications (case series, single case reports and reviews) was found, of which 31 were case series published from February 1995 to March 2008. Six articles have been considered for our review because they regard amyloid goiter as a manifestation of both primary and secondary amyloidosis (a total of 30 cases have been analyzed). Exclusion criterion was the presence of primary thyroid cancer.
RESULTS
The preoperative diagnosis of amyloid goiter should be considered in patients with known systemic amyloidosis or with a long-standing predisposing disease who present a rapidly growing thyroid volume in association with a euthyroid state. Fine-needle aspiration biopsy can be performed to exclude primary malignant lesions of thyroid gland and immunohistochemical studies can identify and characterize the amyloid deposits.
CONCLUSION
Amyloid goiter has to be suspected in all patients with a progressive, rapidly growing, bilateral thyroid enlargement and a concomitant history of chronic inflammatory processes. Moreover, this should be suspected in patients who are known to have disease predisposing to amyloid deposition.
Topics: Amyloidosis; Biopsy, Fine-Needle; Diagnosis, Differential; Goiter; Humans; Thyroid Gland; Tomography, X-Ray Computed; Ultrasonography
PubMed: 19168408
DOI: 10.1016/j.ijsu.2008.12.025 -
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