43 research outputs found
Chronic motor neuropathies: response to interferon-beta1a after failure of conventional therapies
OBJECTIVES: The effect of interferon-beta1a (INF-beta1a; Rebif) was
studied in patients with chronic motor neuropathies not improving after
conventional treatments such as immunoglobulins, steroids,
cyclophosphamide or plasma exchange. METHODS: A prospective open study was
performed with a duration of 6-12 months. Three patients with a multifocal
motor neuropathy and one patient with a pure motor form of chronic
inflammatory demyelinating polyneuropathy were enrolled. Three patients
had anti-GM1 antibodies. Treatment consisted of subcutaneous injections of
IBF-beta1a (6 MIU), three times a week. Primary outcome was assessed at
the level of disability using the nine hole peg test, the 10 metres
walking test, and the modified Rankin scale. Secondary outcome was
measured at the impairment level using a slightly modified MRC sumscore.
RESULTS: All patients showed a significant improvement on the modified MRC
sumscore. The time required to walk 10 metres and to fulfil the nine hole
peg test was also significantly reduced in the first 3 months in most
patients. However, the translation of these results to functional
improvement on the modified Rankin was only seen in two patients. There
were no severe adverse events. Motor conduction blocks were partially
restored in one patient only. Anti-GM1 antibody titres did not change.
CONCLUSION: These findings indicate that severely affected patients with
chronic motor neuropathies not responding to conventional therapies may
improve when treated with INF-beta1a. From this study it is suggested that
INF-beta1a should be administered in patients with chronic motor
neuropathies for a period of up to 3 months before deciding to cease
treatment. A controlled trial is necessary to confirm these findings
The Rasch-built Pompe-specific activity (R-PAct) scale.
We constructed a patient-based interval scale using Rasch analysis, specifically suited to quantify the effects of Pompe disease on patient's ability to carry out daily life activities and their social participation: Rasch-built Pompe-specific Activity scale. Between July 2005 and April 2011, 186 patients aged 16 or older, participated to develop this scale. External construct validity was determined through correlations with the MRC sumscore and Rotterdam Handicap Scale. Furthermore, test-retest reliability was determined in a subgroup of 44 patients. Finally, individual person-level responsiveness was used to determine the proportion of patients demonstrating significant improvement or deterioration during their natural disease course, or during treatment with enzyme replacement therapy. Of the original 49 items, 31 were removed after investigation of model fit, internal reliability, threshold examination, item bias, and local dependency. The remaining 18 items were ordered on a linearly weighted scale and demonstrated good discriminative ability (Person Separation Index 0.96), external construct validity (intraclass correlation coefficient (ICC) for MRC sumscore 0.82, and for the Rotterdam handicap scale 0.86), reliability of person's location (ability comparison: ICC 0.95), and responsiveness. We therefore conclude that the R-PAct scale enables us to accurately detect limitations in activities and social participation throughout the entire disease spectrum in patients with Pompe disease. Copyrigh
Discontinuation of enzyme replacement therapy in adults with Pompe disease: Evaluating the European POmpe Consortium stop criteria
Enzyme replacement therapy for Pompe disease received market authorization in 2006. To implement this costly treatment in the Netherlands in the most sensible way, a multidisciplinary expert committee was installed. We evaluated decision making in adult patients in relation to the European POmpe Consortium stop criteria. Of 125 adult Pompe patients, 111 started treatment; subsequently treatment stopped in 24 patients (21%). In 10 patients, treatment was discontinued for medical or personal reasons, as defined in the six stop criteria (median treatment duration: 2.1 years, range: 0.3–14.6 years). Three of these patients continued follow-up (follow-up: 1.3–8.0 years), these patients did not display a more rapid decline after discontinuation. In 14 of 24 patients, therapy ended at time of death. In 10 patients death was related to Pompe disease (median treatment duration: 7.2 years, range: 0.4–10.3 years). All 10 patients were severely affected at start of treatment, treatment had elicited positive effects in eight. The European POmpe Consortium guidelines worked well in decision making on stopping treatment. However, (re)evaluation of the rationale for continuation of treatment in advanced disease stage is not addressed. We suggest to add this to the treatment evaluation and to handle treatment decisions in a multidisciplinary expert team
Self reported stressful life events and exacerbations in multiple sclerosis: prospective study
OBJECTIVE: To study the relation between self reported stressful life
events not related to multiple sclerosis and the occurrence of
exacerbations in relapsing-remitting multiple sclerosis. DESIGN:
Longitudinal, prospective cohort study. SETTING: Outpatient clinic of
department of neurology in the Netherlands. PARTICIPANTS: Patients aged
18-55 with relapsing-remitting multiple sclerosis, who could walk with a
cane or better (score of 0-6.0 on the expanded disability status scale),
and had had at least two exacerbations in 24 months before inclusion in
the study. Patients with other serious conditions were excluded. MAIN
OUTCOME MEASURE: The risk of increased disease activity as measured by the
occurrence of exacerbations after weeks with stressful events. RESULTS:
Seventy out of 73 included patients (96%) reported at least one stressful
event. In total, 457 stressful life events were reported that were not
related to multiple sclerosis. Average follow up time was 1.4 years.
Throughout the study, 134 exacerbations occurred in 56 patients and 136
infections occurred in 57 patients. Cox regression analysis with time
dependent variables showed that stress was associated with a doubling of
the exacerbation rate (relative risk 2.2, 95% confidence interval 1.2 to
4.0, P = 0.014) during the subsequent four weeks. Infections were
associated with a threefold increase in the risk of exacerbation, but this
effect was found to be independent of experienced stress. CONCLUSION:
Stressful events were associated with increased exacerbations in
relapsing-remitting multiple sclerosis. This association was independent
of the triggering effect of infections on exacerbations of multiple
sclerosis
Hospital admissions, transfers and costs of guillain-Barré syndrome
Background Guillain-Barré syndrome (GBS) has a highly variable clinical course, leading to frequent transfers within and between hospitals and high associated costs. We defined the current admissions, transfers and costs in relation to disease severity of GBS. Methods Dutch neurologists were requested to report patients diagnosed with GBS between November 2009 and November 2010. Information regarding clinical course and transfers was obtained via neurologists and general practitioners. Results 87 GBS patients were included with maximal GBS disability score of 1 or 2 (28%), 3 or 4 (53%), 5 (18%) and 6 (1%). Four mildly affected GBS patients were not hospital admitted. Of the 83 hospitalized patients 68 (82%) were initially admitted at a neurology department, 4 (5%) at an ICU, 4 (5%) at pediatrics, 4 (5%) at pediatrics neurology and 3 (4%) at internal medicine. Median hospital stay was 17 days (IQR 11-26 days, absolute range 1-133 days). Transfers between departments or hospitals occurred in 33 (40%) patients and 25 (30%) were transferred 2 times or more. From a cost-effectiveness perspective 21 (25%) of the admissions was suboptimal. Median costs for hospital admission of GBS patients were 15,060 Euro (IQR 11,226-23,683). Maximal GBS disability score was significantly correlated with total length of stay, number of transfers, ICU admission and costs. Conclusions Hospital admissions for GBS patients are highly heterogeneous, with frequent transfers and higher costs for those with mo
Impact of enzyme replacement therapy on survival in adults with Pompe disease: Results from a prospective international observational study
Background: Pompe disease is a rare metabolic myopathy for which disease-specific enzyme replacement therapy (ERT) has been available since 2006. ERT has shown efficacy concerning muscle strength and pulmonary function in adult patients. However, no data on the effect of ERT on the survival of adult patients are currently available. The aim of this study was to assess the effect of ERT on survival in adult patients with Pompe disease. Methods. Data were collected as part of an international observational study conducted between 2002 and 2011, in which patients were followed on an annual basis. Time-dependent Cox's proportional hazards models were used for univariable and multivariable analyses. Results: Overall, 283 adult patients with a median age of 48 years (range, 19 to 81 years) were included in the study. Seventy-two percent of patients started ERT at some time during follow-up, and 28% never received ERT. During follow-up (median, 6 years; range, 0.04 to 9 years), 46 patients died, 28 (61%) of whom had never received ERT. After adjustment for age, sex, country of residence, and disease severity (based on wheelchair and ventilator use), ERT was positively associated with survival (hazard ratio, 0.41; 95% CI, 0.19 to 0.87). Conclusion: This prospective study was the first to demonstrate the positive effect of ERT on survival in adults with Pompe disease. Given the relatively recent registration of ERT for Pompe disease, these findings further support its beneficial impact in adult patients
Neonatal Fc receptor promoter gene polymorphism does not predict pharmacokinetics of IVIg or the clinical course of GBS
Treatment of Guillain-Barré syndrome with a standard course of high-dose intravenous immunoglobulin (IVIg) results in a variable clinical recovery which is associated with changes in serum IgG levels after treatment. The neonatal Fc-receptor protects IgG from degradation, and a genetic polymorphism in its promoter region that influences the expression of Fc-receptor, may in part explain the variation in IgG levels and outcome. This polymorphism was determined by polymerase chain reaction in a cohort of 257 patients with Guillain-Barré syndrome treated with IVIg. We could not demonstrate a relation between this polymorphism, the pharmacokinetics of IVIg, or the clinical course and outcome
Efficient design and analysis of randomized controlled trials in rare neurological diseases: An example in Guillain-Barre syndrome
Background
Randomized controlled trials (RCTs) pose specific challenges in rare and heterogeneous neurological diseases due to the small numbers of patients and heterogeneity in disease course. Two analytical approaches have been proposed to optimally handle these issues in RCTs: covariate adjustment and ord