scholarly journals Anti-NMDAR Encephalitis in the Netherlands, Focusing on Late-Onset Patients and Antibody Test Accuracy

2021 ◽  
Vol 9 (2) ◽  
pp. e1127
Author(s):  
Anna E.M. Bastiaansen ◽  
Marienke A.A.M. de Bruijn ◽  
Sabine L. Schuller ◽  
Eugenia Martinez-Hernandez ◽  
Juliëtte Brenner ◽  
...  
Keyword(s):  
Late Onset ◽  
Clinical Phenotype ◽  
Severe Disease ◽  
Age At Onset ◽  
Antibody Test ◽  
The Elderly ◽  
Test Accuracy ◽  
Disease Course ◽  
Test Characteristics ◽  
Nmdar Encephalitis

Background and ObjectivesTo describe the clinical features of anti-NMDAR encephalitis, emphasizing on late-onset patients and antibody test characteristics in serum and CSF.MethodsNationwide observational Dutch cohort study, in patients diagnosed with anti-NMDAR encephalitis between 2007 and 2019.ResultsOne hundred twenty-six patients with anti-NMDAR encephalitis were included with a median age of 24 years (range 1–86 years). The mean annual incidence was 1.00/million (95% CI 0.62–1.59). Patients ≥45 years of age at onset (19%) had fewer seizures (46% vs 71%, p = 0.021), fewer symptoms during disease course (3 vs 6 symptoms, p = 0.020), and more often undetectable serum antibodies compared with younger patients (p = 0.031). In the late-onset group, outcome was worse, and all tumors were carcinomas (both p < 0.0001). CSF was more accurate than serum to detect anti-NMDAR encephalitis (sensitivity 99% vs 68%, p < 0.0001). Using cell-based assay (CBA), CSF provided an unconfirmed positive test result in 11/2,600 patients (0.4%); 6/11 had a neuroinflammatory disease (other than anti-NMDAR encephalitis). Patients with anti-NMDAR encephalitis, who tested positive in CSF only, had lower CSF antibody titers (p = 0.003), but appeared to have an equally severe disease course.DiscussionAnti-NMDAR encephalitis occurs at all ages and is less rare in the elderly patients than initially anticipated. In older patients, the clinical phenotype is less outspoken, has different tumor association, and a less favorable recovery. Detection of antibodies in CSF is the gold standard, and although the CBA has very good validity, it is not perfect. The clinical phenotype should be leading, and confirmation in a research laboratory is recommended, when in doubt.

scholarly journals What do elderly problem drinkers aim for? Choice of goal for treatment among elderly treatment-seeking alcohol-dependent patients

2019 ◽  
Vol 36 (6) ◽  
pp. 511-521 ◽  
Author(s):  
Jakob Emiliussen ◽  
Kjeld Andersen ◽  
Anette Søgaard Nielsen ◽  
Barbara Braun ◽  
Randi Bilberg
Keyword(s):  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Late Onset ◽  
Age At Onset ◽  
The Elderly ◽  
Treatment Goal ◽  
Treatment Goals ◽  
Logistics Regression ◽  
Choice Of Treatment ◽  
General Individuals

Objective: The patient’s free choice of treatment goals for alcohol use disorder (AUD) is predictive for treatment outcome. Presently there is limited knowledge of whether the age at onset of AUD influences the choice of goal for treatment. The present study investigates whether there are differences in choice of treatment goal between patients with very late onset alcohol use disorder (VLO AUD ≥ 60 years) and those having early or mid-age onset of AUD (EMO AUD < 60 years). Method: Participants were 341 persons, voluntarily enrolled in the Elderly Study, who were seeking treatment for AUD in outpatient centres for alcohol treatment in Denmark. Data regarding thoughts about abstinence, alcohol use in the last 90 days, motivation for treatment and psychiatric diagnosis were collected via questionnaires. A logistics regression was used to analyse the data. Results: 32.1% of the participants with VLO AUD chose temporary abstinence goals, compared to 18.2% of the patients with earlier-onset AUD ( p = 0.024). Further, 10.7% of participants with VLO AUD chose total abstinence goals compared to 31.3% of participants with early or mid-age onset AUD ( p = 0.002). Conclusion: There are significant differences in choice of goal between participants with very late onset AUD and early or mid-age onset AUD. Individuals with very late onset alcohol use disorder tend to choose temporary abstinence over any other treatment goal whereas, in general, individuals with early onset alcohol use disorder choose permanent abstinence over other treatment goals.

Age at onset as a determinant of presenting phenotype and initial relapse recovery in multiple sclerosis

2011 ◽  
Vol 18 (1) ◽  
pp. 45-54 ◽  
Author(s):  
M Cossburn ◽  
G Ingram ◽  
C Hirst ◽  
Y Ben-Shlomo ◽  
TP Pickersgill ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Late Onset ◽  
Age At Onset ◽  
Disease Onset ◽  
Complete Recovery ◽  
Population Based ◽  
Disease Course ◽  
Index Event ◽  
Relapsing Remitting ◽  
Age Dependent

Background: Age at onset modifies prognosis in multiple sclerosis (MS) and may also exert an effect on the characteristics of disease ignition. Understanding how age influences presentation informs disease management and may allow differentiation of distinct clinical sub-groups. Objectives: To determine the nature of age-specific presentations of relapsing–remitting MS (RRMS) with respect to onset symptoms, gender ratios and index event outcomes. Methods: In a prospective, population-based sample of 1424 patients in South-East Wales we examined associations between age at onset, clinical features and outcome of the onset event, making specific comparisons between paediatric, adolescent and late-onset MS. Results: Age at onset varied significantly between sexes (Male 31.2, Female 29.3, p = 0.002), 0.7% had paediatric onset, 2.7% adolescent onset and 2.8% late-onset MS (>50 years). Optic neuritis was common in younger patients and declined after age 30. Lower limb motor, facial sensory, sexual and sphincteric symptoms rose with age independent of sex and disease course. F:M ratios were highest <16 years of age and declined with increasing age, with a male excess in those over 50. Probability of complete recovery from index event declined with age from 87.4% in the youngest group to 68% in the eldest ( p = 0.009). Conclusions: Age at disease onset in RRMS exerts a significant effect on gender ratios and presenting phenotype, and allows identification of specific clinical sub-groups. In addition, ability to recover from initial relapse declines with age, suggesting accumulation of disability in MS is an age-dependent response to relapse.

scholarly journals Towards genomic database of Alexander disease to identify variations modifying disease phenotype

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Rei Yasuda ◽  
Masakazu Nakano ◽  
Tomokatsu Yoshida ◽  
Ryuichi Sato ◽  
Hiroko Adachi ◽  
...  
Keyword(s):  
Neurodegenerative Disorder ◽  
Late Onset ◽  
Phenotypic Diversity ◽  
Association Studies ◽  
Age At Onset ◽  
The Elderly ◽  
Alexander Disease ◽  
Candidate Gene Approach ◽  
Intermediate Form ◽  
Independent Population

Abstract Alexander disease (AxD) is an extremely rare neurodegenerative disorder caused by glial fibrillary acidic protein (GFAP) gene mutations. Compared with the cerebral type, which is characterized by infantile onset, the bulbospinal type and intermediate form are associated with a late onset, spanning from juveniles to the elderly, and more diverse clinical spectrum, suggesting the existence of factors contributing to phenotypic diversity. To build a foundation for future genetic studies of this rare disease, we obtained genomic data by whole exome-sequencing (WES) and DNA microarray derived from thirty-one AxD patients with the bulbospinal type and intermediate form. Using this data, we aimed to identify genetic variations determining the age at onset (AAO) of AxD. As a result, WES- or microarray-based association studies between younger (<45 years; n = 13)- and older (≥45 years; n = 18)-onset patients considering the predicted GFAP-mutation pathogenicity identified no genome-wide significant variant. The candidate gene approach identified several variants likely correlated with AAO (p < 0.05): GAN, SLC1A2, CASP3, HDACs, and PI3K. Although we need to replicate the results using an independent population, this is the first step towards constructing a database, which may serve as an important tool to advance our understanding of AxD.

Hippocampal/amygdala volumes in geriatric depression

1999 ◽  
Vol 29 (3) ◽  
pp. 629-638 ◽  
Author(s):  
M. ASHTARI ◽  
B. S. GREENWALD ◽  
E. KRAMER-GINSBERG ◽  
J. HU ◽  
H. WU ◽  
...  
Keyword(s):  
Major Depression ◽  
Normal Control ◽  
Late Onset ◽  
Age At Onset ◽  
Imaging Study ◽  
The Elderly ◽  
Clinical Population ◽  
Control Subjects ◽  
Depressed Patients ◽  
Depressive Episodes

Background. The hippocampus, amygdala and related functional circuits have been implicated in the regulation of emotional expression and memory processes, which are affected in major depression. Several recent investigations have reported abnormalities in these structures in adult and elderly depressives.Methods. Elderly DSM-III-R unipolar depressives (N=40) and normal controls (N=46) participated in a magnetic resonance imaging study (1.0T). Brain images were obtained in the coronal plane. Using established anatomical guidelines for structure delineation, volumetric measurements of left and right hippocampus and anterior hippocampus/amygdala complex were completed under blinded conditions using a semi-automated computer mensuration system, with patients and controls in random order.Results. Medial temporal volumes did not significantly distinguish either elderly depressed and age-similar normal control subjects, or late onset and early onset depressed patients (ANCOVA). Major overlap of measured volumes existed between patient and control groups. In depressives, hippocampal volumes significantly correlated with age, and cognitive and depression ratings, but not with number of prior depressive episodes or age-at-onset of first depression.Conclusions. Hippocampal volumes do not discriminate a typical clinical population of elderly depressed patients from age-similar normal control subjects. If hippocampal dysfunction contributes to a diagnosis of syndromal depression in the elderly, such dysfunction does not appear to be regularly reflected in structural abnormalities captured by volumetric measurement as conducted. On the other hand, relationships between hippocampal volumes and clinical phenomena in depressives, but not controls, suggest potentially meaningful interactions between hippocampal structure and the expression of major depression in the elderly.

Late onset alcoholism

2003 ◽  
Vol 18 (3) ◽  
pp. 112-118 ◽  
Author(s):  
Tilman Wetterling ◽  
Clemens Veltrup ◽  
Ulrich John ◽  
Martin Driessen
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Dependence ◽  
Early Onset ◽  
Late Onset ◽  
Age At Onset ◽  
The Elderly ◽  
Alcohol Problems ◽  
Elderly Persons ◽  
Harmful Alcohol ◽  
Icd 10

AbstractRather high prevalence rates of alcohol abuse in the elderly have been reported in the literature. However, there is some evidence that many elderly persons with alcohol problems are not identified, probably due to the nonspecificity of alcohol-related presentations in old individuals. Thus, there is an ongoing discussion on appropriate diagnostic criteria for alcohol dependence in elder people who frequently begin to abuse alcohol in late life. This study was aimed to explore whether alcoholics with late onset (beginning after the age of 45) differ from those with an early onset (prior the age of 25). Two hundred and sixty eight subjects consecutively referred to a ward of a general hospital specialized for alcohol detoxification were divided into three groups by the age at onset of harmful alcohol consumption. The duration of harmful drinking was rather similar in all groups. However, alcohol dependence according to the ICD-10 criteria (three or more have to be fulfilled) was diagnosed in 94.1% of the alcoholics with an early onset (≤ 25 years), but only in 62.2% of those with late onset (P < 0.0001). Significant differences between these groups were found for the following criteria: preoccupation with drinking (P < 0.0001), impaired capacity to control drinking (P < 0.01), strong desire to drink alcohol (P < 0.01), and a trend towards a lower rate of lifetime psychiatric comorbidity. The alcoholics with late onset reported fewer previous detoxifications and a lower actual alcohol consumption. Moreover, they showed a higher rate of abstinence in the 12 month follow-up. Regarding the difficulties in comparing groups of different ages at onset of harmful alcohol use our results suggest that the alcoholics with late onset differ in many ways from those with early onset.

scholarly journals Waning of SARS-CoV-2 antibodies targeting the Spike protein in individuals post second dose of ChAdOx1 and BNT162b2 COVID-19 vaccines and risk of breakthrough infections: analysis of the Virus Watch community cohort.

2021 ◽  
Author(s):  
Robert William Aldridge ◽  
Alexei Yavlinsky ◽  
Vincent Grigori Nguyen ◽  
Max T Eyre ◽  
Madhumita Shrotri ◽  
...  
Keyword(s):  
Severe Disease ◽  
Vaccine Dose ◽  
Antibody Test ◽  
The Elderly ◽  
Spike Protein ◽  
Control Analysis ◽  
Correlate Of Protection ◽  
Increased Risk ◽  
Log Linear ◽  
Case Control Analysis

Background: SARS-CoV-2 vaccines stimulate production of antibodies targeting the spike protein (anti-S). The level of antibodies following vaccination and trajectories of waning may differ between vaccines influencing the level of protection, how soon protection is reduced and, consequently the optimum timing of booster doses. Methods: We measured SARS-CoV-2 anti-S titre in the context of seronegativity for SARS-CoV-2 anti-Nucleocapsid (anti-N), in samples collected between 1st July and 24th October 2021 in a subset of adults in the Virus Watch community cohort. We compared anti-S levels after BNT162b2 (BioNTech/Pfizer) or ChAdOx1 (AstraZeneca/Oxford) vaccination using time since second dose of vaccination, age, sex and clinical vulnerability to investigate antibody waning. To investigate the use of anti-S levels as a correlate of protection against SARS-CoV-2 infection, we undertook a survival analysis (Kaplan-Meier and Cox) with individuals entering 21 days after their second dose of vaccine, or first antibody test after 1st July (whichever was latest) and exiting with the outcome of SARS-Cov-2 infection or at the end of follow up 24th October 2021. We also undertook a negative test design case-control analysis of infections occurring after the second vaccine dose (breakthrough infections) to determine whether the type of vaccine affected the risk of becoming infected. Results: 24049 samples from 8858 individuals (5549 who received a second dose of ChAdOx1 and 3205 BNT162b2) who remained anti-N negative were included in the analysis of anti-S waning over time. Three weeks after the second dose of vaccine BNT162b2 mean anti-S levels were 9039 (95%CI: 7946-10905) U/ml and ChadOx1 were 1025 (95%CI: 917-1146) U/ml. For both vaccines, waning anti-S levels followed a log linear decline from three weeks after the second dose of vaccination. At 20 weeks after the second dose of vaccine, the mean anti-S levels were 1521 (95%CI: 1432-1616) U/ml for BNT162b2 and 342 (95%CI: 322-365) U/ml for ChadOx1. We identified 197 breakthrough infections and found a reduced risk of infection post second dose of vaccine for individuals with anti-S levels greater than or equal to 500 U/ml compared to those with levels under 500 U/ml (HR 0.62; 95%CIs:0.44-0.87; p=0.007). Time to reach an anti-S threshold of 500 U/ml was estimated at 96 days for ChAdOx1 and 257 days for BNT162b2. We found an increased risk of a breakthrough infection for those who received the ChAdOx1 compared to those who received BNT162b2 (OR: 1.43, 95% CIs:1.18-1.73, p<0.001). Discussion: Anti-S levels are substantially higher following the second dose of BNT162b2 compared to ChAdOx1. There is a log linear waning in levels for both vaccines following the second dose. Anti-S levels are an important correlate of protection as demonstrated by those with anti-S levels < 500U/ml following vaccination being at significantly greater risk of subsequent infection. Since anti-S levels are substantially lower in ChAdOx1 than in BNT162b2 and both decline at similar rates we would expect waning immunity to occur earlier in ChAdOx1 compared to BNT162b2. Our results showing an increased risk of breakthrough infections for those who were vaccinated with ChAdOx1 compared to BNT162b2 are in line with this hypothesis. Consistent with our data, national analyses of vaccine effectiveness also suggest that waning of immunity for infection and, to a lesser extent for severe disease, is seen earlier in ChAdOx1 than in BNT162b2. Our data demonstrate the importance of booster doses to maintain protection in the elderly and clinically vulnerable and suggest that these should be prioritised to those who received ChAdOx1 as their primary course.

scholarly journals Late onset multiple sclerosis: concerns in aging patients

2017 ◽  
Vol 75 (7) ◽  
pp. 451-456 ◽  
Author(s):  
Claudia Beatriz de Campos Lotti ◽  
Acary Souza Bulle Oliveira ◽  
Denis Bernardi Bichuetti ◽  
Isac de Castro ◽  
Enedina Maria Lobato Oliveira
Keyword(s):  
Multiple Sclerosis ◽  
Medical Records ◽  
Clinical Characteristics ◽  
Matched Control ◽  
Late Onset ◽  
Age At Onset ◽  
Control Group ◽  
Disease Course ◽  
Matched Control Group ◽  
Progressive Course

ABSTRACT Late onset multiple sclerosis (LOMS) is when the first symptom starts after 50 years of age, representing 4.5% of multiple sclerosis (MS) patients. This study describes the clinical characteristics of patients with LOMS followed at a specialized MS center in São Paulo. Data was obtained from medical records of 742 patients with MS. The LOMS frequency was 4.18%, median age at onset was 54 years and the predominant disease course was primary progressive (64.3%). The patients reached the disability landmarks of EDSS grades 3.0, 6.0 and 7.0 in the following proportion and time: EDSS 3.0: 77.42% of patients in 3.7 years; EDSS 6.0: 58.06% in 5.1 years and EDSS 7.0: 32.26% in 5.7 years. The comparative analysis with a matched control group of patients with early onset MS showed that late onset, associated with a progressive course, were predictors of reaching EDSS 3.0 and 6.0 in a shorter time.

Acquired haemophilia in the elderly is a severe disease: report of five new cases

Haemophilia ◽  
2001 ◽  
Vol 7 (4) ◽  
pp. 428-432 ◽  
Author(s):  
S. Godreuil ◽  
R. Navarro ◽  
P. Quittet ◽  
L. Landreau ◽  
J-F. Schved ◽  
...  
Keyword(s):  
Severe Disease ◽  
The Elderly ◽  
Acquired Haemophilia

Molecular Genetics of Early- and Late-Onset Alzheimer’s Disease

2020 ◽  
Vol 20 ◽  
Author(s):  
Md. Sahab Uddin ◽  
Sharifa Hasana ◽  
Md. Farhad Hossain ◽  
Md. Siddiqul Islam ◽  
Tapan Behl ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Massively Parallel Sequencing ◽  
Late Onset ◽  
Current Knowledge ◽  
The Elderly ◽  
Apoe Ε4 ◽  
Sequencing Technologies ◽  
Genetic Components ◽  
Ε4 Allele

: Alzheimer’s disease (AD) is the most common form of dementia in the elderly and this complex disorder is associated with environmental as well as genetic components. Early-onset AD (EOAD) and late-onset AD (LOAD, more common) are major identified types of AD. The genetics of EOAD is extensively understood with three genes variants such as APP, PSEN1, and PSEN2 leading to disease. On the other hand, some common alleles including APOE are effectively associated with LOAD identified but the genetics of LOAD is not clear to date. It has been accounted that about 5% to 10% of EOAD patients can be explained through mutations in the three familiar genes of EOAD. The APOE ε4 allele augmented the severity of EOAD risk in carriers, and APOE ε4 allele was considered as a hallmark of EOAD. A great number of EOAD patients, who are not genetically explained, indicate that it is not possible to identify disease- triggering genes yet. Although several genes have been identified through using the technology of next-generation sequencing in EOAD families including SORL1, TYROBP, and NOTCH3. A number of TYROBP variants were identified through exome sequencing in EOAD patients and these TYROBP variants may increase the pathogenesis of EOAD. The existence of ε4 allele is responsible for increasing the severity of EOAD. However, several ε4 allele carriers live into their 90s that propose the presence of other LOAD genetic as well as environmental risk factors that are not identified yet. It is urgent to find out missing genetics of EOAD and LOAD etiology to discover new potential genetics facets which will assist to understand the pathological mechanism of AD. These investigations should contribute to developing a new therapeutic candidate for alleviating, reversing and preventing AD. This article based on current knowledge represents the overview of the susceptible genes of EOAD, and LOAD. Next, we represent the probable molecular mechanism which might elucidate the genetic etiology of AD and highlight the role of massively parallel sequencing technologies for novel gene discoveries.

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