Predictors Of Long-term Disability Research Articles

Predictors of long-term disability in multiple sclerosis patients using routine magnetic resonance imaging data: A 15-year retrospective study.

Early identification of patients at high risk of progression could help with a personalised treatment strategy. Magnetic resonance imaging (MRI) measures have been proposed to predict long-term disability in multiple sclerosis (MS), but a reliable predictor that can be easily implemented clinically is still needed. Assess MRI measures during the first 5years of the MS disease course for the ability to predict progression at 10+ years. Eighty-two MS patients (53 females), with ≥10years of clinical follow-up and having two MRI scans, were included. Clinical data were obtained at baseline, follow-up and at ≥10years. White matter lesion (WML) counts and volumes, and four linear brain sizes were measured on T2/FLAIR 'Fluid-Attenuated-Inversion-Recovery' and T1-weighted images. Baseline and follow-up inter-caudate diameter (ICD) and third ventricular width (TVW) measures correlated positively with Expanded Disability Status Scale, ≥10 or more of WMLs showed a high sensitivity in predicting progression, at ≥10years. A steeper rate of lesion volume increase was observed in subjects converting to secondary progressive MS. The sensitivity and specificity of both ICD and TVW, to predict disability at ≥10years were 60% and 64%, respectively. Despite advances in brain imaging and computerised volumetric analysis, ICD and TVW remain relevant as they are simple, fast and have the potential in predicting long-term disability. However, in this study, despite the statistical significance of these measures, the clinical utility is still not reliable.

Longitudinal clinical study of patients with iron rim lesions in multiple sclerosis

Background: Iron rims (IRs) surrounding white matter lesions (WMLs) are suggested to predict a more severe disease course. Only small longitudinal cohorts of patients with and without iron rim lesions (IRLs) have been reported so far. Objective: To assess whether the presence and number of IRLs in patients with clinically isolated syndrome (CIS) and multiple sclerosis (MS) are associated with long-term disability or progressive disease. Methods: Ninety-one CIS/MS patients were recruited between 2008 and 2013 and scanned with 7 T magnetic resonance imaging (MRI). Expanded Disability Status Scale (EDSS) was used to calculate Age-related Multiple Sclerosis Severity Score (ARMSS) at the time of scan and at the latest clinical follow-up after 9 years. WMLs were assessed for the presence of IRL using Susceptibility weighted imaging (SWI)-filtered phase images. Results: In all, 132 IRLs were detected in 42 patients (46%); 9% of WMLs had IRs; 54% of the cohort had no rims, 30% had 1–3 rims and 16% had ⩾4. Patients with IRL had a higher EDSS and ARMSS. Presence of IRL was also a predictor of long-term disability, especially in patients with ⩾4 IRLs. IRLs have a greater impact on disability compared to the WML number and volume. Conclusion: The presence and number of perilesional IR on MRI hold prognostic value for long-term clinical disability in MS.

Imputed expression of schizophrenia-associated genes and cognitive measures in patients with schizophrenia.

BackgroundCognitive dysfunction is a core manifestation of schizophrenia and one of the best predictors of long‐term disability. Genes increasing risk for schizophrenia may partly act through the modulation of cognition.MethodsWe imputed the expression of 130 genes recently prioritized for association with schizophrenia, using PsychENCODE variant weights and genotypes of patients with schizophrenia in CATIE. Processing speed, reasoning, verbal memory, working memory, vigilance, and a composite cognitive score were used as phenotypes. We performed linear regression models for each cognitive measure and gene expression score, adjusting for age, years of education, antipsychotic treatment, years since the first antipsychotic treatment and population principal components.ResultsWe included 425 patients and expression scores of 91 genes (others had no heritable expression; Bonferroni corrected alpha = 5.49e‐4). No gene expression score was associated with cognitive measures, though ENOX1 expression was very close to the threshold for verbal memory (p = 6e‐4) and processing speed (p = 7e‐4). Other genes were nominally associated with multiple phenotypes (MAN2A1 and PCGF3).ConclusionA better understanding of the mechanisms mediating cognitive dysfunction in schizophrenia may help in the definition of disease prognosis and in the identification of new treatments, as the treatment of cognitive impairment remains an unmet therapeutic need.

Prediction of long-term disability in Chinese patients with multiple sclerosis: A prospective cohort study

BackgroundMuch information about outcomes of multiple sclerosis (MS) has been studied in Caucasian cohorts. However, little is known about the predictors of long-term disability in Chinese patients with MS. The aim of this prospective, observational study is to identify the prognostic factors associated with long-term disability progression (expanded disability status scale, EDSS=6.0) in Chinese patients with relapsing-onset MS. MethodsBased on data from the MSNMOBase registry within the neurology department of Peking Union Medical College Hospital (PUMCH) in China, this hospital-based cohort study was conducted to estimate the median time of attaining disability endpoint (EDSS = 6.0) by Kaplan-Meier curves, and identify factors that associated with disability progression by Cox proportional regression analysis. ResultsA total of 415 consecutive, eligible patients with MS were registered in the MSNMOBase of PUMCH and prospectively followed from 2011 to 2019. Of these patients, 365 patients with relapsing-onset MS were analyzed. The median time to reach an EDSS of 6.0 was 22.0 (95% CI 16.5-27.5) years. Age at disease onset greater than 50 years (HR 3.846, 95% CI 1.240–11.932, P=0.020), incomplete recovery from first attack (HR 2.107, 95% CI 1.168–3.800, P=0.013), and ≥2 relapses during the first 2 years after onset (HR 2.217, 95% CI 1.148–4.281, P=0.018) significantly associated with a higher hazard ratio to reach an EDSS of 6.0. ConclusionsOur results confirm the importance of age at onset, recovery from the first attack, and number of relapses during the first 2 years after disease onset as predictors of disability progression in Chinese patients with relapsing-onset MS.

Axonal damage in spinal cord is associated with gray matter atrophy in sensorimotor cortex in experimental autoimmune encephalomyelitis

Background: Gray matter (GM) atrophy in brain is one of the best predictors of long-term disability in multiple sclerosis (MS), and recent findings have revealed that localized GM atrophy is associated with clinical disabilities. GM atrophy associated with each disability mapped to a distinct brain region, revealing a disability-specific atlas (DSA) of GM loss. Objective: To uncover the mechanisms underlying the development of localized GM atrophy. Methods: We used voxel-based morphometry (VBM) to evaluate localized GM atrophy and Clear Lipid-exchanged Acrylamide-hybridized Rigid Imaging-compatible Tissue-hYdrogel (CLARITY) to evaluate specific pathologies in mice with experimental autoimmune encephalomyelitis (EAE). Results: We observed extensive GM atrophy throughout the cerebral cortex, with additional foci in the thalamus and caudoputamen, in mice with EAE compared to normal controls. Next, we generated pathology-specific atlases (PSAs), voxelwise mappings of the correlation between specific pathologies and localized GM atrophy. Interestingly, axonal damage (end-bulbs and ovoids) in the spinal cord strongly correlated with GM atrophy in the sensorimotor cortex of the brain. Conclusion: The combination of VBM with CLARITY in EAE can localize GM atrophy in brain that is associated with a specific pathology in spinal cord, revealing a PSA of GM loss.

Survival and health related quality of life after severe trauma − a 15 years follow up study

IntroductionAs the primary treatment of patients with severe trauma continues to improve, increasing interest has been directed towards long-term survival and Health Related Quality of Life (HRQoL). In trauma patients, there are few studies describing long-term outcome using tools specifically directed at HRQoL. HypothesisHRQoL measured with EQ-5D is significantly reduced compared to the Danish norm score 15 years after severe injury. Materials and methodsAll patients more than 18 years of age, admitted to a level 1 trauma center from March 1996 to September 1997 were prospectively included and scored with Injury Severity Score (ISS). Survival status was recorded in May 2012 and EQ-5D questionnaires were sent out. Results95 of the original 154 trauma patients were eligible for participation. The response rate was 66%. The average EQ-5D index score in the trauma population was significantly reduced compared to the index score in the Danish norm population (P=0.00, one-sample t-test). In addition, ISS is associated with HRQoL and ISS≥16 predicts poorer HRQoL. ConclusionEQ-5D is significantly reduced 15years after severe trauma High ISS was associated with low HRQoL. Knowledge of the distribution and predictors of long-term disability can be used to develop more efficient prevention policies and to improve trauma care in general.

Predictors of Long term disability in Pediatric patients with relapse-onset Multiple Sclerosis (MS) on immunomodulatory therapy (P1.344)

Predictors of Long term disability in Pediatric patients with relapse-onset Multiple Sclerosis (MS) on immunomodulatory therapy (P1.344)

Predictors of Long-Term Disability in Multiple Sclerosis

The MSBase registry is an international collaboration with data from more than 35,000 multiple sclerosis (MS) patients. Investigators evaluated 2466 of

Negative prognostic impact of MRI spinal lesions in the early stages of relapsing-remitting multiple sclerosis.

BackgroundThe presence of spinal cord (SC) magnetic resonance imaging (MRI) lesions can be expected to affect the mobility of people with relapsing–remitting MS (pwRRMS), but reports are ambiguous.ObjectiveThe objective of this paper is to determine whether the presence of SC MRI lesions in early diagnosed pwRRMS could be considered a predictor of long-term disability.MethodspwRRMS with an SC MRI performed within two years from the onset of symptoms and followed up for at least seven years were included. Patients were grouped into: (a) pwRRMs with at least one SC T2 MRI lesion, and (b) pwRRMs without SC T2 MRI lesions. The primary end point was to evaluate the effects of independent factors on reaching an Expanded Disability Status Score (EDSS) of 4.0.ResultsA total of 239 pwRRMS matched the required criteria: 116 in the group with SC lesions and 123 in the group without SC lesions. At baseline, there were no statistical differences between the two groups. The presence of SC lesions (Exp(b) 4.4, CI 2.1–9.0, p < 0.001) and higher basal EDSS (Exp(b) 3.3, CI 2.3–4.8, p < 0.001) proved to be the best predictors of reaching EDSS 4.0.ConclusionThe presence of T2 SC MRI lesions detected early from MS onset of RRMS predicts a worse prognosis.

Combined visual and motor evoked potentials predict multiple sclerosis disability after 20 years

Background: The development of predictors of multiple sclerosis (MS) disability is difficult due to the complex interplay of pathophysiological and adaptive processes. Objective: The purpose of this study was to investigate whether combined evoked potential (EP)-measures allow prediction of MS disability after 20 years. Methods: We examined 28 patients with clinically definite MS according to Poser’s criteria with Expanded Disability Status Scale (EDSS) scores, combined visual and motor EPs at entry (T0), 6 (T1), 12 (T2) and 24 (T3) months, and a cranial magnetic resonance imaging (MRI) scan at T0 and T2. EDSS testing was repeated at year 14 (T4) and year 20 (T5). Spearman rank correlation was used. We performed a multivariable regression analysis to examine predictive relationships of the sum of z-transformed EP latencies (s-EPT0) and other baseline variables with EDSST5. Results: We found that s-EPT0 correlated with EDSST5 (rho=0.72, p<0.0001) and ΔEDSST5-T0 (rho=0.50, p=0.006). Backward selection resulted in the prediction model: E (EDSST5)=3.91–2.22×therapy+0.079×age+0.057×s-EPT0 (Model 1, R2=0.58) with therapy as binary variable (1=any disease-modifying therapy between T3 and T5, 0=no therapy). Neither EDSST0 nor T2-lesion or gadolinium (Gd)-enhancing lesion quantities at T0 improved prediction of EDSST5. The area under the receiver operating characteristic (ROC) curve was 0.89 for model 1. Conclusions: These results further support a role for combined EP-measures as predictors of long-term disability in MS.

The short physical performance battery as a predictor for long term disability or institutionalization in the community dwelling population aged 65 years old or older

Background: The short physical performance battery (SPPB) is a physical performance measure that has been used to predict long term disability and/or future institutionalization in adults aged 65 years old or older. The test involves three dedicated physical performance activities, scored from 0 to 4, with a summated score of 12. Higher scores reflect higher levels of function.Objectives: The purpose of this systematic literature review was to investigate the ability of the SPPB to predict long term disability or future institutionalization in community dwellers aged 65 years old or older living in the United States.Methods: This review used the search engines PubMed, CINAHL, and the Cochrane Library, and investigated all articles that studied the SPPB as a predictor of either long term disability or future institutionalization. Studies were included if each incorporated the SPPB, involved a community dwelling population, was written in English, was a longitudinal trial, and reported on functional decline or disability, or institutionalization. Qualitative scoring was assessed using the Newcastle–Ottawa Scale (NOS); each study was scored in three categories: selection, comparability, and outcome.Results: Five articles met the inclusion criteria for this study, of the five, three evaluated the capability of the SPPB to predict long term disability and two used the SPPB to predict institutionalization. Studies found that a baseline score of 4–6 on the SPPB indicated that the individual had a 2·9–4·9 increase in risk of developing a future disability, and a score of 7–9 on the SPPB found a 1·6–2·1 relative risk of developing a future disability. A baseline score of 10–12 on the SPPB was predictive of no future disability. Lower SPPB scores were related to increased odds of institutionalization and increased functional decline/disability. The NOS scores of the included trials ranged from two to three stars for each category demonstrating moderate to good quality.Conclusion: Of the investigated studies on the subject, it can be concluded that the SPPB is a predictor of long term disability or institutionalization in US community dwellers aged 65 years old or older.

Prevalence and Prognostic Factors of Disability After Major Trauma

The primary aim of this study was to assess the health-related quality of life of survivors of severe trauma 1 year after injury, specified according to all the separate dimensions of the EuroQol-5D (EQ-5D) and the Health Utilities Index (HUI). A prospective cohort study was conducted in which all severely injured trauma patients presented at a Level I trauma center were included. After 12 months, the EQ-5D, HUI2 and HUI3 were used to analyze the health status. Follow-up assessments were obtained from 246 patients (response rate, 68%). The overall population EQ-5D (median) utility score was 0.73 (EQ-5D Dutch general population norm, 0.88). HUI2, HUI3, and EQ-5D Visual Analog Scale scores were 0.81, 0.65, and 70, respectively. Eighteen percent had at least one functional limitation 1 year after trauma, and 60% reported functional limitations on two or more domains using the EQ-5D. The female gender and comorbidity were significant independent predictors of disability. Functional outcome and quality of life of survivors of severe injury have not returned to normal 1 year after trauma. The prevalence of specific limitations in this population is very high (40-70%). Female gender and comorbidity are predictors of long-term disability.

Noninvasive brain stimulation and motor recovery after stroke

Upper limb function is the best predictor of long-term disability after stroke. Despite extensive rehabilitation, recovery of upper limb motor function is frequently incomplete after stroke. We review the pertinent literature on functional reorganization within the cerebral motor network after stroke and noninvasive techniques to modulate brain function towards beneficial plasticity. Direct current stimulation and repetitive transcranial magnetic stimulation are powerful tools to (i) modulate cortical excitability, (ii) induce remote changes within the cortical motor system and (iii) thereby improve upper limb motor function after stroke. Today no relevant side effects have been reported. Neuromodulation, by means of noninvasive brain stimulation techniques, has been shown to be a safe, feasible and effective method to promote recovery of motor function after stroke. However, several methodological and theoretical issues remain to be addressed in future work.

Relevancia clínica de la FDG-PET en los traumatismos craneoencefálicos graves

To evaluate the usefulness of positron emission tomography (PET) as a predictor of long-term disability after a severe traumatic brain injury (TBI).Fifty-six patients who had sustained a severe TBI were assessed with a broad battery of cognitive and functional scales at baseline and 6-months after inclusion in a multidisciplinary rehabilitation program. All patients underwent a FDG-PET at baseline. A physician blind to clinical data performed a semiquantitative analysis (normal vs altered) of functional neuroimaging (PET), including four cortical and three subcortical areas. The total number of lesions (cortical, subcortical and total) was correlated to the intensity of the TBI and to clinical data at admission and at follow-up.All patients showed changes in cerebral metabolism, being the thalamus the area most frequently affected. The degree of cerebral hypometabolism showed a significant correlation with TBI severity, functional disability, global outcome and cognitive impairment not only at baseline but also at follow-up.According to our results, FDG-PET may be a useful tool when studying brain dysfunction after severe TBI. FDG-PET findings correlate with the TBI severity, and with the level of patients' disability, as well as with the degree of memory and intelligence impairment. However, clinical variables related to the severity of the TBI, still are the best predictors of functional outcome after TBI.

Clinical and Demographic Predictors of Long-term Disability in Patients With Relapsing-Remitting Multiple Sclerosis: A Systematic Review

Clinical and Demographic Predictors of Long-term Disability in Patients With Relapsing-Remitting Multiple Sclerosis: A Systematic Review

Glutamatergic neurotransmission modulators as emerging new drugs for schizophrenia

Schizophrenia is a neurodevelopmental mental disorder whose aetiology includes genetic and environmental factors. Because of its early onset, chronicity and characteristic interference with education, employment and socialisation, this illness represents a tremendous human and economic burden to those who suffer from it, their families and society as a whole. Conventional and atypical antipsychotics, which mainly affect dopaminergic and serotonergic neurotransmission, are currently the cornerstone of schizophrenia treatment. Although the introduction of atypical antipsychotics represents a major development and, overall, antipsychotics are efficacious against psychotic symptoms, there remains a critical unmet need for innovative medications with improved efficacy and tolerability for the negative symptoms and cognitive deficits associated with schizophrenia. These dysfunction domains are reliable predictors of long-term disability and treatment outcome and are presently viewed as crucial targets for new pharmacological treatments of schizophrenia. Within this medication development framework, the modulation of glutamatergic neurotransmission has become the focus of intense research. Glutamate (GLU)-mediated neuronal processes are critical throughout the brain and glutamatergic neurotransmission dysfunctions have been hypothesised to play a crucial role in schizophrenia pathophysiology. Glutamatergic neurotransmission may be modulated at multiple levels, with GLU receptor families and their subtypes representing a modulatory site-rich environment for drug research. Numerous types of neurotransmission modulators, acting at the NMDA, AMPA and metabotropic GLU receptors, and/or affecting GLU synaptic release, are hypothesised to be beneficial for schizophrenia treatment, and are presently in various stages of development. For some of these compounds, preliminary studies have furnished encouraging clinical data. Ongoing and planned research is expected to provide, in the near future, critical information regarding the practical utility and tolerability of glutamatergic approaches for schizophrenia pharmacotherapy.

Use of attorneys and appeal filing in the Washington State workers' compensation program: does patient satisfaction matter?

Specify the frequency with which injured workers in Washington State's compensation system retained an attorney or filed an appeal, and the personal and job-related correlates of these actions. Analyze the relationship between workers' legal actions and their satisfaction in two domains: how well the claim was managed administratively, and how well the worker and claim manager communicated with one another. Characterize the relationship between retaining an attorney and long-term disability. Little is known about how often injured workers retain attorneys or file appeals in the workers' compensation system. We conducted a population-based study to examine the frequency of attorney retention and appeal filing in the Washington State workers' compensation program and the factors related to this event. Data for the study were provided by a survey conducted on 804 injured workers who were interviewed an average of 159 days after claim receipt. Attorney retention and appeal filing were examined up to 28 months later. Seven percent of the workers either retained an attorney or filed an appeal. Workers who were less satisfied with claims administration procedures were more likely to retain an attorney or file an appeal (P<0.05). The average length of time from claim receipt to attorney retention (368 days) suggests that retaining an attorney is a correlate rather than a predictor of long-term disability.