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Neurology Jul 2014To identify factors influencing age at symptom onset and disease course in autosomal dominant Alzheimer disease (ADAD), and develop evidence-based criteria for... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To identify factors influencing age at symptom onset and disease course in autosomal dominant Alzheimer disease (ADAD), and develop evidence-based criteria for predicting symptom onset in ADAD.
METHODS
We have collected individual-level data on ages at symptom onset and death from 387 ADAD pedigrees, compiled from 137 peer-reviewed publications, the Dominantly Inherited Alzheimer Network (DIAN) database, and 2 large kindreds of Colombian (PSEN1 E280A) and Volga German (PSEN2 N141I) ancestry. Our combined dataset includes 3,275 individuals, of whom 1,307 were affected by ADAD with known age at symptom onset. We assessed the relative contributions of several factors in influencing age at onset, including parental age at onset, age at onset by mutation type and family, and APOE genotype and sex. We additionally performed survival analysis using data on symptom onset collected from 183 ADAD mutation carriers followed longitudinally in the DIAN Study.
RESULTS
We report summary statistics on age at onset and disease course for 174 ADAD mutations, and discover strong and highly significant (p < 10(-16), r2 > 0.38) correlations between individual age at symptom onset and predicted values based on parental age at onset and mean ages at onset by mutation type and family, which persist after controlling for APOE genotype and sex.
CONCLUSIONS
Significant proportions of the observed variance in age at symptom onset in ADAD can be explained by family history and mutation type, providing empirical support for use of these data to estimate onset in clinical research.
Topics: Age of Onset; Alzheimer Disease; Chromosome Disorders; Genes, Dominant; Humans
PubMed: 24928124
DOI: 10.1212/WNL.0000000000000596 -
Movement Disorders Clinical Practice Nov 2022Cerebellar ataxias comprise a large group of heterogeneous disorders with both motor and non-motor symptoms (NMS). (Review)
Review
BACKGROUND
Cerebellar ataxias comprise a large group of heterogeneous disorders with both motor and non-motor symptoms (NMS).
OBJECTIVE
We wanted to ascertain the reported prevalence of NMS in different subtypes of hereditary cerebellar ataxias.
METHODS
Systematic review of studies of hereditary cerebellar ataxias (involving >5 patients) who were assessed for NMS, published in the English literature in PUBMED and EMBASE databases from 1947 to 2021.
RESULTS
A total of 35 papers, with data from 1311 autosomal dominant spinocerebellar ataxia (SCA), 893 autosomal recessive cerebellar ataxia (ARCA), and 53 X-linked ataxia cases were included with a total of 450 controls. Mean age for SCA cases at diagnosis was 47.6 (SD, 14.9) years, for ARCA cases was 34.6 (SD, 14.7) years and for X-linked ataxia cases was 68.6 (9.1) years. The prevalence of cognitive problems in SCAs was between 23% and 75% (ranging from mild to severe), being least prevalent in SCA6. The prevalence of depression in SCAs was between 13% and 69% and sleep disorders were between 7% and 80%. Pain was reported by 18% to 60% of patients, especially in SCA3, and fatigue by 53% to 70%. The prevalence of reported cognitive dysfunction in ARCA was 12.5% to 100% and depression between 14% and 51%. The prevalence of anxiety in X-linked ataxias (FXTAS) was 17 % and depression 55%.
CONCLUSIONS
The presence of NMS in hereditary cerebellar ataxias is common. The prevalence and spectrum of NMS in SCAs, ARCAs, and X-linked ataxias vary. In routine clinical practice, NMS in cerebellar ataxias are under-recognized and certainly under-reported. Therefore, they are unlikely to be addressed adequately. Improved ascertainment of NMS in cerebellar ataxias in clinical practice will enable holistic treatment of these patients.
PubMed: 36339305
DOI: 10.1002/mdc3.13532 -
PharmacoEconomics Apr 2022Spinal muscular atrophy (SMA) is a severe neuromuscular disease that is inherited in an autosomal recessive manner with an estimated incidence of 1 in 10,000 live...
BACKGROUND
Spinal muscular atrophy (SMA) is a severe neuromuscular disease that is inherited in an autosomal recessive manner with an estimated incidence of 1 in 10,000 live births. The traditional classification of SMA includes five types (Types 0-4 SMA) based on patient age at disease onset and the highest motor milestone achieved. Spinal muscular atrophy leads to progressive muscle denervation, skeletal muscle atrophy and loss of motor function and ambulation, though phenotypes vary along a disease continuum. Regardless of disease severity, or access to treatment, a multidisciplinary approach to care is required to ease the burden of disease. To date, limited global data exist regarding the cost and resource use associated with SMA management.
OBJECTIVE
We planned to perform a systematic literature review to identify studies on cost and healthcare resource use associated with SMA.
METHODS
A comprehensive search was conducted in 2019 using several electronic databases in addition to supplementary sources and updated in 2021 in order to capture recently published studies. Electronic searches performed in Embase, MEDLINE, Evidence-Based Medicine Reviews and EconLit via the Ovid platform were supplemented by searches of the grey literature (reference lists, conference proceedings, global Health Technology Assessment body websites and other relevant sources). Study eligibility criteria were based on the population, interventions, comparators and outcomes (PICO) framework. Quality assessment of full-text publications was evaluated with reference to a published checklist. To accommodate heterogeneity across studies including countries, currencies, populations, time units and methods of reporting used, costs were reported in Euros in 2019.
RESULTS
A total of 51 publications, comprising 49 unique studies of patients with SMA that met all eligibility criteria were included in the final selection. The publications comprised data from 14 countries and seven additional studies that reported multi-national data. Because of the heterogeneity between the different types of SMA, data were frequently reported separately for individuals with Type 1 or early-onset SMA and for Types 2, 3, and 4 SMA or later-onset SMA. Generally, direct medical costs and resource use were reported to be highest for patients with Type 1 SMA, decreasing incrementally for patients with Type 2 and Type 3 disease. Where cost categories were similar, direct costs were much lower in Europe than in the USA. Indirect costs were primarily associated with informal care, which was a substantial burden on patients and families in terms of both cost and time. Cost drivers were generally found to be dependent on SMA type.
CONCLUSIONS
Long-term robust studies are required to fully elucidate the economic burden of SMA. Considering that motor function can vary broadly, especially in Type 2 SMA, it would be beneficial to understand how costs and resource use are affected by different degrees of ambulation. Reporting data in terms of achieved motor function could also mitigate the challenges of comparing global data studies of small populations. Global, regional, and/or local data collection platforms and disease registry networks could play an important role in helping to address current data gaps.
Topics: Costs and Cost Analysis; Europe; Humans; Muscular Atrophy, Spinal; Spinal Muscular Atrophies of Childhood; Technology Assessment, Biomedical
PubMed: 34761360
DOI: 10.1007/s40273-021-01105-7 -
Frontiers in Genetics 2021Mutations in the STRC (MIM 606440) gene, inducing DFNB16, are considered a major cause of mild-moderate autosomal recessive non-syndromic hearing loss (ARNSHL). We...
Mutations in the STRC (MIM 606440) gene, inducing DFNB16, are considered a major cause of mild-moderate autosomal recessive non-syndromic hearing loss (ARNSHL). We conducted a systematic review and meta-analysis to determine the global prevalence and characteristics of STRC variations, important information required for genetic counseling. PubMed, Google Scholar, Medline, Embase, and Web of Science were searched for relevant articles published before January 2021. The pooled prevalence of DFNB16 in GJB2-negative patients with hearing loss was 4.08% (95% CI: 0.0289-0.0573), and the proportion of STRC variants in the mild-moderate hearing loss group was 14.36%. Monoallelic mutations of STRC were 4.84% (95% CI: 0.0343-0.0680) in patients with deafness (non-GJB2) and 1.36% (95% CI: 0.0025-0.0696) in people with normal hearing. The DFNB16 prevalence in genetically confirmed patients (non-GJB2) was 11.10% (95% CI: 0.0716-0.1682). Overall pooled prevalence of deafness-infertility syndrome (DIS) was 36.75% (95% CI: 0.2122-0.5563) in DFNB16. The prevalence of biallelic deletions in STRC gene mutations was 70.85% (95% CI: 0.5824-0.8213). Variants in the STRC gene significantly contribute to mild-moderate hearing impairment. Moreover, biallelic deletions are a main feature of STRC mutations. Copy number variations associated with infertility should be seriously considered when investigating DFNB16.
PubMed: 34621290
DOI: 10.3389/fgene.2021.707845 -
Health Technology Assessment... Sep 2014Lynch syndrome (LS) is an inherited autosomal dominant disorder characterised by an increased risk of colorectal cancer (CRC) and other cancers, and caused by mutations... (Review)
Review
BACKGROUND
Lynch syndrome (LS) is an inherited autosomal dominant disorder characterised by an increased risk of colorectal cancer (CRC) and other cancers, and caused by mutations in the deoxyribonucleic acid (DNA) mismatch repair genes.
OBJECTIVE
To evaluate the accuracy and cost-effectiveness of strategies to identify LS in newly diagnosed early-onset CRC patients (aged < 50 years). Cascade testing of relatives is employed in all strategies for individuals in whom LS is identified.
DATA SOURCES AND METHODS
Systematic reviews were conducted of the test accuracy of microsatellite instability (MSI) testing or immunohistochemistry (IHC) in individuals with CRC at risk of LS, and of economic evidence relating to diagnostic strategies for LS. Reviews were carried out in April 2012 (test accuracy); and in February 2012, repeated in February 2013 (economic evaluations). Databases searched included MEDLINE (1946 to April week 3, 2012), EMBASE (1980 to week 17, 2012) and Web of Science (inception to 30 April 2012), and risk of bias for test accuracy was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) quality appraisal tool. A de novo economic model of diagnostic strategies for LS was developed.
RESULTS
Inconsistencies in study designs precluded pooling of diagnostic test accuracy results from a previous systematic review and nine subsequent primary studies. These were of mixed quality, with significant methodological concerns identified for most. IHC and MSI can both play a part in diagnosing LS but neither is gold standard. No UK studies evaluated the cost-effectiveness of diagnosing and managing LS, although studies from other countries generally found some strategies to be cost-effective compared with no testing. The de novo model demonstrated that all strategies were cost-effective compared with no testing at a threshold of £20,000 per quality-adjusted life-year (QALY), with the most cost-effective strategy utilising MSI and BRAF testing [incremental cost-effectiveness ratio (ICER) = £5491 per QALY]. The maximum health benefit to the population of interest would be obtained using universal germline testing, but this would not be a cost-effective use of NHS resources compared with the next best strategy. When the age limit was raised from 50 to 60 and 70 years, the ICERs compared with no testing increased but remained below £20,000 per QALY (except for universal germline testing with an age limit of 70 years). The total net health benefit increased with the age limit as more individuals with LS were identified. Uncertainty was evaluated through univariate sensitivity analyses, which suggested that the parameters substantially affecting cost-effectiveness: were the risk of CRC for individuals with LS; the average number of relatives identified per index patient; the effectiveness of colonoscopy in preventing metachronous CRC; the cost of colonoscopy; the duration of the psychological impact of genetic testing on health-related quality of life (HRQoL); and the impact of prophylactic hysterectomy and bilateral salpingo-oophorectomy on HRQoL (this had the potential to make all testing strategies more expensive and less effective than no testing).
LIMITATIONS
The absence of high-quality data for the impact of prophylactic gynaecological surgery and the psychological impact of genetic testing on HRQoL is an acknowledged limitation.
CONCLUSIONS
Results suggest that reflex testing for LS in newly diagnosed CRC patients aged < 50 years is cost-effective. Such testing may also be cost-effective in newly diagnosed CRC patients aged < 60 or < 70 years. Results are subject to uncertainty due to a number of parameters, for some of which good estimates were not identified. We recommend future research to estimate the cost-effectiveness of testing for LS in individuals with newly diagnosed endometrial or ovarian cancer, and the inclusion of aspirin chemoprevention. Further research is required to accurately estimate the impact of interventions on HRQoL.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42012002436.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Aged; Colorectal Neoplasms, Hereditary Nonpolyposis; Cost-Benefit Analysis; Genetic Testing; Humans; Middle Aged
PubMed: 25244061
DOI: 10.3310/hta18580 -
International Journal of Molecular... Feb 2023Among the most common muscular dystrophies in adults is Myotonic Dystrophy type 1 (DM1), an autosomal dominant disorder characterized by myotonia, muscle wasting and... (Review)
Review
Among the most common muscular dystrophies in adults is Myotonic Dystrophy type 1 (DM1), an autosomal dominant disorder characterized by myotonia, muscle wasting and weakness, and multisystemic dysfunctions. This disorder is caused by an abnormal expansion of the CTG triplet at the gene that, when transcribed to expanded mRNA, can lead to RNA toxic gain of function, alternative splicing impairments, and dysfunction of different signaling pathways, many regulated by protein phosphorylation. In order to deeply characterize the protein phosphorylation alterations in DM1, a systematic review was conducted through PubMed and Web of Science databases. From a total of 962 articles screened, 41 were included for qualitative analysis, where we retrieved information about total and phosphorylated levels of protein kinases, protein phosphatases, and phosphoproteins in DM1 human samples and animal and cell models. Twenty-nine kinases, 3 phosphatases, and 17 phosphoproteins were reported altered in DM1. Signaling pathways that regulate cell functions such as glucose metabolism, cell cycle, myogenesis, and apoptosis were impaired, as seen by significant alterations to pathways such as AKT/mTOR, MEK/ERK, PKC/CUGBP1, AMPK, and others in DM1 samples. This explains the complexity of DM1 and its different manifestations and symptoms, such as increased insulin resistance and cancer risk. Further studies can be done to complement and explore in detail specific pathways and how their regulation is altered in DM1, to find what key phosphorylation alterations are responsible for these manifestations, and ultimately to find therapeutic targets for future treatments.
Topics: Animals; Adult; Humans; Myotonic Dystrophy; Phosphorylation; Alternative Splicing; RNA, Messenger; Muscular Atrophy; Muscle, Skeletal
PubMed: 36834509
DOI: 10.3390/ijms24043091 -
Health Technology Assessment... 2012Familial hypercholesterolemia (FH) is an autosomal dominant genetic condition causing a high risk of coronary heart disease. The prevalence of this disease is about 1 in... (Review)
Review
BACKGROUND
Familial hypercholesterolemia (FH) is an autosomal dominant genetic condition causing a high risk of coronary heart disease. The prevalence of this disease is about 1 in 500 in the UK, affecting about 120,000 people across the whole of the UK. Current guidelines recommend DNA testing, however, these guidelines are poorly implemented, therefore 102,000 or 85% of this group remain undiagnosed.
OBJECTIVES
To assess the diagnostic accuracy, effect on patient outcomes and cost-effectiveness of Elucigene FH20 and LIPOchip for the diagnosis of FH.
DATA SOURCES
Electronic databases including MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, BIOSIS, Science Citation Index, Conference Proceedings Citation Index - Science and Cochrane Controlled Trials Register were searched until January 2011.
REVIEW METHODS
A systematic review of the literature on diagnostic accuracy was carried out according to standard methods. An economic model was constructed to assess the cost-effectiveness of alternative diagnostic strategies for the confirmation of clinically diagnosed FH in index cases and for the identification and subsequent testing of first-, second- and possibly third-degree biological relatives of the index case. Twelve strategies were evaluated linking diagnostic accuracy to treatment outcomes and hence quality-adjusted life-years (QALYs). Deterministic and probabilistic sensitivity analyses were undertaken to investigate model and parameter uncertainty.
RESULTS
Fifteen studies were included for diagnostic accuracy; three reported Elucigene FH20, five reported LIPOchip, four reported low-density lipoprotein cholesterol (LDL-C) tests and three reported an age- and gender-specific LDL-C test against a reference standard of comprehensive genetic analysis (CGA). Sensitivity ranged from 44% to 52% for Elucigene FH20 and from 33.3% to 94.5% for various versions of LIPOchip in detecting FH-causing mutations in patients with a clinical diagnosis of FH. For LIPOchip version 10 (designed to detect 189 UK specific mutations), sensitivity would be 78.5% (based on single-centre data - Progenika, personal communication). For all other Elucigene FH20 or LIPOchip studies (apart from one LIPOchip study), specificity could not be calculated as no false-positive results could be derived from the given data. The LDL-C test was generally reported to be highly sensitive but with low specificity. For age- and gender-specific LDL-C cut-offs for cascade testing, sensitivity ranged from 68% to 96%. One UK-based study reported sensitivity of 91% and specificity of 93%. For the cost-effectiveness review, only one study reporting cost-effectiveness of any one of the comparators for this assessment was identified. Pre-screen strategies such as Elucigene FH20 followed by CGA were not cost-effective and were dominated by the single more comprehensive tests (e.g. CGA). Of the non-dominated strategies, Elucigene FH20, LIPOchip platform (Spain) and CGA were all cost-effective with associated incremental cost-effectiveness ratios (ICERs) relative to LDL-C of dominance (test is less costly and more effective), £871 and £1030 per QALY gained respectively. CGA generates the greatest QALY gain and, although other tests have lower ICERs relative to LDL-C, this is at the expense of QALY loss compared with the CGA test. Probabilistic sensitivity analysis shows that CGA is associated with an almost 100% probability of cost-effectiveness at the conventional value of willingness to pay of £20,000 per QALY gain.
LIMITATIONS
There was much uncertainty regarding the diagnostic accuracy of the included tests, with wide variation in sensitivity across reported studies. A lack of published information for the most recent version of LIPOchip created additional uncertainty, especially in relation to the chip's ability to detect copy number changes. For the economic modelling, we aimed to choose the best studies for the base-case sensitivity of the tests; however, a number of informed choices based on clinical expert opinion had to be made in the absence of published studies for a number of other parameters in the modelling. This adds some uncertainty to our results, although it is unlikely that these would be sufficient in magnitude to alter our main results and conclusions.
CONCLUSIONS
As targeted tests designed to detect a limited number of genetic mutations, Elucigene FH20 and LIPOchip cannot detect all cases of FH, in contrast with CGA. CGA is therefore the most effective test in terms of sensitivity and QALY gain, and is also highly cost-effective with an associated ICER of £1030 per QALY gain relative to current practice (LDL-C). Other tests such as Elucigene FH20 and LIPOchip are also cost-effective; however, because of inferior sensitivity compared with CGA, these tests offer cost savings but at the expense of large QALY losses compared with CGA. Further prospective multicentred studies are required to evaluate the diagnostic accuracy of new and emerging tests for FH with the LDL-C test in patients with a clinical diagnosis based on the Simon Broome criteria. Such studies should verify both test-positive and -negative results against a reference standard of CGA and should include a full economic evaluation.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Adolescent; Adult; Child; Child, Preschool; Cost-Benefit Analysis; Female; Genetic Testing; Humans; Hypercholesterolemia; Infant; Male; Middle Aged; Quality-Adjusted Life Years; Sensitivity and Specificity; Technology Assessment, Biomedical; United Kingdom; Young Adult
PubMed: 22469073
DOI: 10.3310/hta16170 -
Epilepsia Sep 2008Conflicting evidence about impairment of attention systems and the absence of a working model of attention has contributed to lack of clarity about comorbidity of... (Review)
Review
PURPOSE
Conflicting evidence about impairment of attention systems and the absence of a working model of attention has contributed to lack of clarity about comorbidity of attention problems in rolandic epilepsy (RE). Impairments in distributed attention systems may inform a disease model for RE, as well as direct interventions.
METHODS
We used a systematic review of the relevant literature published in English from 1990 to 2006 to evaluate impairment in attention in RE. The Mirsky and Posner models of attention were evaluated for applicability, and studies were reviewed for design, instrumentation, and congruence with the Posner model of attention.
RESULTS
Fourteen studies were identified: seven using a cross-sectional design (six active EEG abnormalities; one EEG remission) and seven longitudinal studies (abnormal EEGs and follow-up until normalized). According to the Posner model of attention, 12 studies employed measures that tapped the alerting network, 11 studies the orienting network, and eight the executive network. Nearly all controlled studies demonstrated impairments in all tested attention networks. In contrast, uncontrolled studies uniformly did not demonstrate impairments. Follow-up studies demonstrated complete or near complete resolution of attention impairments.
DISCUSSION
The weight of evidence, defined as the majority of studies evaluated, suggests that all three attention systems are impaired in children with active centrotemporal spikes (CTS), implying a more widespread functional cortical disturbance in RE than previously held. These impairments resolve upon EEG remission, suggesting a common pathological basis to the autosomal dominant CTS trait. Sources of methodological variation are discussed with recommendations for future investigations.
Topics: Attention; Cross-Sectional Studies; Electroencephalography; Epilepsy, Rolandic; Humans; Remission Induction
PubMed: 18410358
DOI: 10.1111/j.1528-1167.2008.01610.x -
The Cochrane Database of Systematic... Apr 2021Thalassaemia is an autosomal recessive blood disorder, caused by mutations in globin genes or their regulatory regions, resulting in a reduced rate of synthesis of one...
BACKGROUND
Thalassaemia is an autosomal recessive blood disorder, caused by mutations in globin genes or their regulatory regions, resulting in a reduced rate of synthesis of one of the globin chains that make up haemoglobin. In β-thalassaemia there is an underproduction of β-globin chains combined with excess of free α-globin chains. The excess free α-globin chains precipitate in red blood cells, leading to their increased destruction (haemolysis) and ineffective erythropoiesis. The conventional treatment is based on the correction of haemoglobin through regular red blood cell transfusions and treating the iron overload that develops subsequently with iron chelation therapy. Although, early detection and initiations of such supportive treatment has improved the quality of life for people with transfusion-dependent thalassaemia, allogeneic hematopoietic stem cell transplantation is the only widely available therapy with a curative potential. Gene therapy for β-thalassaemia has recently received conditional authorisation for marketing in Europe, and may soon become widely available as another alternative therapy with curative potential for people with transfusion-dependent thalassaemia. This is an update of a previously published Cochrane Review.
OBJECTIVES
To evaluate the effectiveness and safety of different types of hematopoietic stem cell transplantation, in people with transfusion-dependent β-thalassaemia.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched online trial registries. Date of the most recent search: 07 April 2021.
SELECTION CRITERIA
Randomised controlled trials and quasi-randomised controlled trials comparing hematopoietic stem cell transplantation with each other or with standard therapy (regular transfusion and chelation regimen).
DATA COLLECTION AND ANALYSIS
Two review authors independently screened trials and had planned to extract data and assess risk of bias using standard Cochrane methodologies and assess the quality using GRADE approach, but no trials were identified for inclusion in the current review.
MAIN RESULTS
No relevant trials were retrieved after a comprehensive search of the literature.
AUTHORS' CONCLUSIONS
We were unable to identify any randomised controlled trials or quasi-randomised controlled trials on the effectiveness and safety of different types of hematopoietic stem cell transplantation in people with transfusion-dependent β-thalassaemia. The absence of high-level evidence for the effectiveness of these interventions emphasises the need for well-designed, adequately-powered, randomised controlled clinical trials.
Topics: Hematopoietic Stem Cell Transplantation; Humans; beta-Thalassemia
PubMed: 33880750
DOI: 10.1002/14651858.CD008708.pub5 -
Journal of Neurology May 2024Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of stroke and is characterised by...
BACKGROUND
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of stroke and is characterised by early onset stroke and dementia. Most strokes are lacunar ischaemic strokes, but intracerebral haemorrhage (ICH) has also been reported, although there are limited published data on its frequency and characteristics.
METHODS
A retrospective review of a prospectively recruited CADASIL register from the British National Referral clinic was performed to identify acute ICH cases and their characteristics. In addition, a systematic review of ICH in CADASIL was performed. MEDLINE (Pubmed), Embase, and Web of Science were searched for articles published from inception until 31/05/2023.
RESULTS
Ten cases of ICH were identified from the National clinic register of 516 symptomatic patients, giving an estimated point prevalence of 1.9%. An additional 119 cases were identified from the systematic review, comprising 129 cases and 142 ICH events in total. Including all identified cases, the mean age at onset of ICH was 56.6 ± 15.7 (SD) years, and 74 (57.4%) were male. ICH was the first manifestation of the disease in 32 patients (38.1%), and ICH recurrence occurred in 16 (12.4%). Most ICHs were subcortical, with the thalamus, 58 (40.8%), and basal ganglia, 34 (23.9%), being the commonest sites. Anticoagulation, but not antiplatelet agents, was associated with an increased risk of ICH (20.0% vs. 1.9%, p = 0.006).
CONCLUSIONS
ICH is a relatively rare manifestation of CADASIL, occurring in about 2% of symptomatic cases. Most of the haemorrhages occurred in the subcortical regions.
Topics: Humans; CADASIL; Cerebral Hemorrhage; Middle Aged; Male; Prevalence; Risk Factors; Female; Aged; Adult; Retrospective Studies
PubMed: 38217707
DOI: 10.1007/s00415-023-12177-0