Year Of Symptom Onset Research Articles

Atlanto-axial subluxation as the initial manifestation of spondyloarthritis

Patients with spondyloarthritis (SpA) typically present with inflammatory back pain, peripheral arthritis and enthesitis, often with distinctive clinical features such as psoriasis and inflammatory bowel diseases. Atlanto-axial subluxation (AAS) is a complication occurring rarely in these patients, and usually is seen in patients with longstanding, severe disease. We present three cases of AAS whose initial presentation of AAS was followed by subsequent development of signs and symptoms meeting the European Spondyloarthropathy Study Group (ESSG) classification criteria for SpA. All three patients were less than 30 years of age and had no other explanation for the AAS. Significantly, all three patients required C1/C2 surgical fusion within 1 year of symptom onset due to severe pain, though none of them developed neurologic complications related to AAS such as myelopathy. Peripheral arthritis/tendonitis, the presence of HLA-B27 gene and family history of SpA appeared to be associated with higher risk of evolution to SpA in these patients. No medical therapy has been systematically examined in this condition.

The long-term impact of early treatment of rheumatoid arthritis on radiographic progression: a population-based cohort study

To measure the long-term rate of radiographic progression in a cohort of patients treated early vs late with conventional DMARDs. The long-term rate of radiographic progression in patients included in the Swiss clinical quality management in rheumatoid arthritis (SCQM-RA) registry who initiated treatment with conventional DMARDs within the first year of symptom onset (early DMARD) vs patients who initiated treatment 1-5 years after symptom onset (late DMARD). Radiographic progression was assessed in 38 joints using a validated score (Ratingen Score). The rate of progression was calculated using a multivariate regression model for longitudinal data, adjusting for potential confounders. A total of 970 RA patients were included. The 368 patients in the early DMARD group started therapy after a median symptom duration of 6 months, whereas the 602 patients in the late DMARD group initiated therapy after median 2.5 years. RF, MTX use and other risk factors for erosive disease progression were similar between the two groups. However, the estimated rate of radiographic progression at baseline was higher in the early DMARD vs the late DMARD group (1.8 vs 0.6, P < 0.01). In spite of this, the long-term rate of radiographic progression was significantly lower in the early DMARD group after adjustment for confounding factors (-0.35 at 5 years, P = 0.012). This result supports the concept of a therapeutic window of opportunity early in the disease course and suggests that early initiation of DMARD therapy results in a long-lasting reduction of radiographic damage.

Vascular comorbidity is associated with more rapid disability progression in multiple sclerosis.

Vascular comorbidity adversely influences health outcomes in several chronic conditions. Vascular comorbidities are common in multiple sclerosis (MS), but their impact on disease severity is unknown. Vascular comorbidities may contribute to the poorly understood heterogeneity in MS disease severity. Treatment of vascular comorbidities may represent an avenue for treating MS. A total of 8,983 patients with MS enrolled in the North American Research Committee on Multiple Sclerosis Registry participated in this cohort study. Time from symptom onset or diagnosis until ambulatory disability was compared for patients with or without vascular comorbidities to determine their impact on MS severity. Multivariable proportional hazards models were adjusted for sex, race, age at symptom onset, year of symptom onset, socioeconomic status, and region of residence. Participants reporting one or more vascular comorbidities at diagnosis had an increased risk of ambulatory disability, and risk increased with the number of vascular conditions reported (hazard ratio [HR]/condition for early gait disability 1.51; 95% confidence interval [CI] 1.41-1.61). Vascular comorbidity at any time during the disease course also increased the risk of ambulatory disability (adjusted HR for unilateral walking assistance 1.54; 95% CI 1.44-1.65). The median time between diagnosis and need for ambulatory assistance was 18.8 years in patients without and 12.8 years in patients with vascular comorbidities. Vascular comorbidity, whether present at symptom onset, diagnosis, or later in the disease course, is associated with a substantially increased risk of disability progression in multiple sclerosis. The impact of treating vascular comorbidities on disease progression deserves investigation.

Time to diagnosis in the National Registry of Veterans with Amyotrophic Lateral Sclerosis

Our objective was to determine the interval from symptom onset to diagnosis, and to evaluate associated factors in a cohort of U.S. Veterans with motor neuron diseases. We retrospectively evaluated 1359 patients enrolled in the National Registry of Veterans with Amyotrophic Lateral Sclerosis (ALS). The main outcome measures were time from symptom onset to first diagnosis and to second opinion. Predictor variables included age at symptom onset, year of symptom onset, race, onset site, final diagnosis, number of diagnostic tests performed and clinical sites visited. Median time to first diagnosis was 11 months; median time to second opinion was two months. In a multivariable model, more recent calendar year of symptom onset, younger age, bulbar onset and a diagnosis of ALS versus non-ALS motor neuron disease were all significantly associated with a shorter time to first diagnosis. Later year of symptom onset and white race were significantly associated with a shorter time to second opinion. While the interval from symptom onset to diagnosis, and many of the associated factors are similar between our large cohort of U.S. Veterans with ALS and other smaller published cohorts, we found that the diagnostic interval among U.S. Veterans has significantly decreased over time.

Prognosis after West Nile Virus Infection

The long-term prognosis of patients infected with West Nile virus is not well understood. To describe the patterns of physical and mental function after infection with West Nile virus and to determine factors associated with recovery. Longitudinal cohort study. Data were collected during home visits and from ambulatory clinics in 4 Canadian provinces. 156 persons with West Nile virus infection. Scores on the Physical Component Summary and Mental Component Summary of the Short Form-36, Depression Anxiety Stress Scale, and Fatigue Severity Scale. Physical and mental function, as well as mood and fatigue, seemed to return to normal within 1 year of symptom onset. Participants with neuroinvasive disease took slightly longer to recover. Maximum predicted recovery or rate of recovery in any domain did not differ between participants with meningoencephalitis and those with encephalitis. Lack of preexisting comorbid conditions was associated with faster recovery of physical function, whereas lack of comorbid conditions and male sex were associated with faster recovery of mental function. The analysis excluded 7 patients who died shortly after diagnosis, so the study's estimates of prognosis may be overoptimistic. The authors did not formally assess neuropsychological difficulties. The estimates of recovery are relative to the U.S. population, not to participants' function levels before West Nile virus infection. Physical and mental outcome measures seem to normalize within approximately 1 year in patients with West Nile virus. The presence of preexisting comorbid conditions is associated with longer recovery.

Associations between HLA-DRB1, RANK, RANKL, OPG, and IL-17 genotypes and disease severity phenotypes in Japanese patients with early rheumatoid arthritis

We examined associations between human leukocyte antigen DRB1 (HLA-DRB1) shared epitope (SE), receptor activator of nuclear factor-kappaB (RANK), RANK ligand (RANKL), osteoprotegerin (OPG), and interleukin 17 (IL-17) genotypes with age of disease onset and radiographic progression in Japanese patients with early rheumatoid arthritis (RA). HLA-DRB1 genotypes were evaluated in 123 patients with early RA (98 female, 25 male) within 1 year of symptom onset. In 72 patients, radiographic progression over a 2-year period was evaluated using Larsen's methods, and genotypes of three polymorphic sites in RANK, five sites in RANKL, two sites in OPG, and three sites in IL-17 were determined by direct polymerase chain reaction sequencing. Possession of an SE allele was significantly associated with earlier disease onset in females (median 46.9 vs 51.9 years in SE- patients; P = 0.04). Single nucleotide polymorphisms (SNPs) in RANKL (rs2277438, P = 0.028) and IL-17 (rs3804513, P = 0.049) were significantly associated with radiographic progression at 2 years. RANKL-G-, SE- patients (n = 12) had significantly less joint damage than did RANKL-G+, SE- patients (n = 11; P = 0.0038), RANKL-G-, SE+ patients (n = 21; P = 0.0018) and RANKL-G+, SE+ patients (n = 28; P = 0.0024). In Japanese RA patients, HLA-DRB1 SE alleles are associated with disease onset at an earlier age, as has been observed in Caucasian RA patients. In addition, SNPs in RANKL and IL-17 may be associated with radiographic progression in Japanese patients with early RA.

Direct medical costs associated with Parkinson's disease: A population‐based study

The objective was to provide population-based estimates of incremental medical costs associated with Parkinson's disease (PD) from onset forward. All Olmsted County, Minnesota, residents with confirmed PD onset from 1987 through 1995 (n = 92) and one age- and sex-matched non-PD referent subject per case were identified with retrospective record review and followed in provider-linked billing data for direct medical costs (excluding outpatient pharmaceutical costs) from 1 year before index (i.e., year of symptom onset) through 10 years after index. Costs for each referent subject were subtracted from those for his/her matched case. Tests for statistical significance used Wilcoxon signed ranks. Preindex costs were similar [median difference in annual costs (MD) = -3 dollars; P = 0.59]. One year post index, PD subjects exhibited borderline significantly higher costs compared to referent subjects (MD = 581 dollars; P = 0.052); the difference diminished over 5 years (MD = 118 dollars; P = 0.82). By 5 to 10 years, however, PD subjects exhibited significantly higher costs (MD = 1,146 dollars; P = 0.01). Over the full 10 years, excess costs were concentrated among PD subjects without rest tremor (MD = 2,261 dollars, P < 0.01, for those without tremor and -229 dollars, P = 0.99, for those with tremor). These population-based estimates of PD-associated direct medical costs from onset forward can uniquely inform policy decisions and cost-effectiveness research.

Changes in the ascertainment of multiple sclerosis

With diagnostic criteria alterations, increased MRI availability, and awareness of therapies, temporal changes in incidence and prevalence rates may occur, with an increase in the proportion of mildly affected persons diagnosed with multiple sclerosis (MS). The authors assessed temporal trends in the delay from symptom onset to diagnosis (DONDX), and determined whether the degree of disability at diagnosis differs by year of symptom onset (YONSET), using the NARCOMS Registry. The authors selected US participants with an age at symptom onset of 10 to 60 years, and YONSET > or = 1980 (n = 16,581). The authors divided YONSET into 5-year groups and compared DONDX between groups using multivariate Cox regression. The authors classified participants enrolled within 2 years of diagnosis (n = 5,548) as having mild, moderate, or severe disability using Patient Determined Disease Steps, and assessed the association of disability with YONSET using polytomous logistic regression. DONDX decreased with later YONSET (r = -0.43, p < 0.0001). This association remained after adjustment for demographic factors in a multivariate Cox model. Later YONSET was associated with increased odds of having mild disability at diagnosis as compared to severe disability (OR = 1.10 per year; 1.09 to 1.11). The delay from symptom onset to diagnosis is steadily decreasing in MS. An increasing proportion of patients with MS have mild disability at diagnosis after accounting for confounders. As the effectiveness of therapies is influenced by disease duration, this has implications for comparison of treatment effects in modern clinical trials to earlier study results.

Is There Evidence for Surgery Triggering the Onset of Fibromyalgia Syndrome?

Objectives: This study explored evidence for surgery serving as a trigger for the onset of the fibromyalgia syndrome [FMS].Methods: Rheumatology patients with [N = 144] and without FMS [N = 45, controls] constructed a timeline of all surgeries and pain three and 14 days post-operatively. Dates of onset of FMS and other rheumatological conditions were indicated allowing for analysis of the relationship between the incidence of surgery and condition onset.Results: The mean number of lifetime surgeries was not significantly different between the groups [FMS: 5.7, non-FMS: 4.9], and there were no differences in types of surgery. To test our hypothesis that surgical trauma was a precipitant for onset of FMS, we examined incidence of surgery in the year preceding symptom onset and in the year of symptom onset. In both timeframes, only about 20 percent of patients in both groups reported having a surgery, and the rates were not different between groups. There were no differences in pain between the two groups fo...

Factors associated with a delay in the diagnosis of narcolepsy

Background: There can be a long interval from the onset of symptoms before a diagnosis of narcolepsy is made. There are no multivariate analyses reported in the literature of factors that may contribute to this delay. The aims of this study were to describe the delay in diagnosis of people with narcolepsy living in the UK and to identify associated factors.Methods: The study comprised a postal survey of 500 members of the Narcolepsy Association UK, which included questions regarding age of onset of symptoms, year of diagnosis and subject demographics. Cox's proportional hazards regression was performed.Results: A total of 313 questionnaires were returned of which 219 had been completed sufficiently for analysis. The interval between symptom onset and diagnosis ranged from within 1 to 61 years with a median of 10.5 years. Multivariate analysis showed that the presence of cataplexy as one of the initial symptoms and a more recent year of symptom onset were the only factors associated with time to diagnosis.Conclusions: We have confirmed that the diagnosis of narcolepsy can be delayed for many years particularly when cataplexy is absent initially. The delay in diagnosis in the UK appears to be decreasing, probably through greater doctor and patient awareness of the clinical manifestations of narcolepsy.

Surgical Treatment of Cubital Tunnel Syndrome with Subcutaneous Anterior Transposition of the Ulnar Nerve

Purpose : To evaluate the surgical outcomes and the clinical factors affecting the results of subcutaneous anterior transposition of the ulnar nerve in cubital tunnel syndrome. Materials and Methods : Eighteen patients diagnosed as having cubital tunnel syndrome and treated by subcutaneous anterior transposition of ulnar nerve were investigated retrospectively. According to preoperative Dellon's staging, 2 patients (11%) were in mild stage, 5 (28%) in moderate and 11 (61%) in severe. Results were evaluated using Dellon's staging and Mowlavi’s classification. Results : According to Mowlavi's outcome status, 2 patients (11%) showed total relief, 10 (56%) improvement, 5 (28%) no change and 1 (6%) was worse, therefore the results were satisfactory in 12 patients (67%). Patients with less severe symptoms received surgery within a year of symptom onset and showed better results. Conclusion : The result of subcutaneous anterior transposition of ulnar nerve in cubital tunnel syndrome is comparable to that of other surgical methods, but it is easier technically. Better results may be anticipated when surgery is performed within a year of symptom onset.

Diisocyanate-induced asthma: diagnosis, prognosis, and effects of medical surveillance measures.

Diisocyanates have been the most commonly identified cause for occupational asthma (OA) in industrialized areas. Asthma among diisocyanate workers may be true occupational asthma, caused by a high level of irritant exposure at work or by sensitization to diisocyanates. Alternatively, asthma may be coincidental to or may be aggravated by work exposures. A clear diagnosis usually requires a combination of investigations (serial peak expiratory flow recordings, methacholine challenges, and/or diisocyanate challenges), but it is important to provide the best management by identifying whether workplace changes are needed for the worker. Preventive measures to reduce the risk of occupational asthma from diisocyanates have not been prospectively evaluated. The introduction of a medical surveillance program (in Ontario, Canada) in 1983 was followed by retrospective assessments to determine benefits. Between 1980 and 1993, the proportion of all accepted compensation claims for OA that were attributed to diisocyanates, classified by year of symptom onset in the province with the program, rose to 64 percent by 1988, then fell significantly down to 29 percent in 1992 and 35 percent in 1993. Besides the medical surveillance program for diisocyanates, possible factors contributing to this reduction may include reduced diisocyanates exposures and better awareness of diisocyanate-induced asthma, both by workers and physicians. Compared with OA caused by other agents, those with OA due to diisocyanates had a significantly earlier onset of asthma after the start of the exposure (mean 5 yr vs. 7 yr), were younger and less likely to be atopic and to have smoked. The mean duration of asthma before the main medical assessment for compensation was significantly shorter among those with diisocyanate-induced asthma (mean 2 yr vs. 3 yr), and the severity was milder as assessed by medication use and pulmonary function. Those with diisocyanate-induced asthma were significantly less likely to be hospitalized for asthma. Among the subset whose outcome was determined at a mean of 2.1 years after the main medical assessment, the outcome severity was less for those with diisocyanate-induced OA. Among those with diisocyanate-induced OA, an earlier diagnosis and a trend to better outcome was found in workers from companies that were identified to be in compliance with surveillance measures.

A clinicopathological study of vascular progressive supranuclear palsy: a multi-infarct disorder presenting as progressive supranuclear palsy.

Clinical features suggesting a diagnosis of progressive supranuclear palsy (PSP) include early falls, axial rigidity, vertical supranuclear ophthalmoplegia, and levodopa unresponsiveness. When these clinical features are present, the diagnosis is almost always PSP, yet vascular disease sometimes has a similar presentation, referred to as vascular PSP. To evaluate clinical and pathologic features of cases of vascular PSP submitted to a PSP brain bank. Review of gross and microscopic neuropathological features, determination of tau haplotype, and medical record review of 4 patients with an antemortem diagnosis of PSP who did not meet the pathologic criteria for PSP and instead had vascular pathologic abnormalities. All patients had vertical supranuclear ophthalmoplegia, a history of falls, and a gradually progressive disease course. Falls began 1 year after symptom onset, and all patients had asymmetric findings on a neurological examination. A magnetic resonance imaging scan revealed lacunar basal ganglia infarcts in one patient and an increased T2-weighted signal in the corona radiata and centrum semiovale in another. Gross and microscopic neuropathological studies demonstrated infarcts in the cerebral cortex (n = 4), thalamus (n = 4), basal ganglia (n = 3), and cerebellum (n = 4). The brainstem was affected in one patient, but no infarcts were detected in the subthalamic nucleus or substantia nigra. Of the 4 patients, 3 carried an H2 tau haplotype, a rare occurrence in the general population. Asymmetric signs, falls after 1 year of symptom onset, vascular lesions on a magnetic resonance imaging scan, and an H2 tau haplotype may help differentiate vascular PSP from PSP. Thalamic and basal ganglia infarcts are common in patients with vascular PSP and, when present, may contribute to misdiagnosis.

Progression of falls in postmortem-confirmed parkinsonian disorders.

Although falls are known to occur in several parkinsonian disorders, such as Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP), differences in the evolution of this feature have not been studied systematically in pathologically confirmed cases. Seventy-seven cases with pathologically confirmed parkinsonian disorders (PD: n = 11, MSA: n = 15, DLB: n = 14, CBD: n = 13, PSP: n = 24), collected up to 1994, formed the basis for a multicenter clinicopathologic study organized by the National Institute of Neurological Disorders and Stroke to improve differential diagnosis of parkinsonian disorders. In the present study, we determined the time course, that is, the duration from first symptom to onset (latency) and duration from onset to death, of recurrent falls. Furthermore, we analyzed the diagnostic validity of a predefined latency to onset of recurrent falls within 1 year of symptom onset. Significant group differences for latency, but not duration, of recurrent falls were observed. Latencies to onset of falls were short in PSP patients, intermediate in MSA, DLB, and CBD, and long in PD. Recurrent falls occurring within the first year after disease onset predicted PSP in 68% of the patients. Our study demonstrates for the first time that latency to onset, but not duration, of recurrent falls differentiates PD from other parkinsonian disorders. Whereas early falls are important for the diagnosis of PSP, the addition of other features increases its diagnostic predictive value.

Incidence and prevalence of Huntington's disease in Olmsted County, Minnesota (1950 through 1989).

To calculate average annual incidence rates for Huntington's disease (HD) from 1950 through 1989 and to estimate prevalence rates of the disease for January 1, 1960, and January 1, 1990. Health care records from all sources, including hospitals, outpatient clinics, and long-term care institutions, are readily available for all inhabitants of Olmsted County, Minnesota. The diagnoses entered in these records have been coded and indexed. All health care records containing a diagnosis that might suggest HD were reviewed, and those patients for whom the symptoms of HD began between January 1, 1950, and December 31, 1989, were identified. We used specific criteria for diagnosing HD. Health care records were reviewed; residence in Olmsted County during the year of symptom onset was required. Average annual incidence rates and prevalence rates for January 1, 1960, and January 1, 1990. Overall incidence rates were 0.4 (95% confidence interval [CI], 0.1 to 0.8) for women and 0.2 (95% CI, 0.04 to 0.6) for men per 100,000 person-years. Estimated prevalence rates for January 1, 1960, per 100,000 person-years were 6 (95% CI, 0.7 to 21.5) for women and 6.6 (95% CI, 0.8 to 23.8) for men. For January 1, 1990, the prevalence rates were 1.8 (95% CI, 0.04 to 10.2) for women and 2 (95% CI, 0.05 to 10.9) for men. Incidence and prevalence rates of HD in this community are similar to those reported in other communities. The small numbers of affected persons do not allow an estimate of variation over time.