To develop a patient-based, linearly weighted scale that captures activity and social participation limitations in patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating ...polyradiculoneuropathy (CIDP), and gammopathy-related polyneuropathy (MGUSP).
A preliminary Rasch-built Overall Disability Scale (R-ODS) containing 146 activity and participation items was constructed, based on the WHO International Classification of Functioning, Disability and Health, literature search, and patient interviews. The preliminary R-ODS was assessed twice (interval: 2-4 weeks; test-retest reliability studies) in 294 patients who experienced GBS in the past (n = 174) or currently have stable CIDP (n = 80) or MGUSP (n = 40). Data were analyzed using the Rasch unidimensional measurement model (RUMM2020).
The preliminary R-ODS did not meet the Rasch model expectations. Based on disordered thresholds, misfit statistics, item bias, and local dependency, items were systematically removed to improve the model fit, regularly controlling the class intervals and model statistics. Finally, we succeeded in constructing a 24-item scale that fulfilled all Rasch requirements. "Reading a newspaper/book" and "eating" were the 2 easiest items; "standing for hours" and "running" were the most difficult ones. Good validity and reliability were obtained.
The R-ODS is a linearly weighted scale that specifically captures activity and social participation limitations in patients with GBS, CIDP, and MGUSP. Compared to the Overall Disability Sum Score, the R-ODS represents a wider range of item difficulties, thereby better targeting patients with different ability levels. If responsive, the R-ODS will be valuable for future clinical trials and follow-up studies in these conditions.
Background: Consensus guidelines on the definition, investigation, and treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) have been previously published in European ...Journal of Neurology and Journal of the Peripheral Nervous System.
Objectives: To revise these guidelines.
Methods: Disease experts, including a representative of patients, considered references retrieved from MEDLINE and Cochrane Systematic Reviews published between August 2004 and July 2009 and prepared statements that were agreed in an iterative fashion.
Recommendations: The Task Force agreed on Good Practice Points to define clinical and electrophysiological diagnostic criteria for CIDP with or without concomitant diseases and investigations to be considered. The principal treatment recommendations were: (i) intravenous immunoglobulin (IVIg) (Recommendation Level A) or corticosteroids (Recommendation Level C) should be considered in sensory and motor CIDP; (ii) IVIg should be considered as the initial treatment in pure motor CIDP (Good Practice Point); (iii) if IVIg and corticosteroids are ineffective, plasma exchange (PE) should be considered (Recommendation Level A); (iv) if the response is inadequate or the maintenance doses of the initial treatment are high, combination treatments or adding an immunosuppressant or immunomodulatory drug should be considered (Good Practice Point); (v) symptomatic treatment and multidisciplinary management should be considered (Good Practice Point).
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Background and purpose
Pompe disease is a rare inheritable muscle disorder for which enzyme replacement therapy (ERT) has been available since 2006. Uniform criteria for starting and stopping ERT in ...adult patients were developed and reported here.
Methods
Three consensus meetings were organized through the European Pompe Consortium, a network of experts from 11 European countries in the field of Pompe disease. A systematic review of the literature was undertaken to determine the effectiveness of ERT in adult patients on a range of clinical outcome measures and quality of life. A narrative synthesis is presented.
Results
Consensus was reached on how the diagnosis of Pompe disease should be confirmed, when treatment should be started, reasons for stopping treatment and the use of ERT during pregnancy. This was based on expert opinion and supported by the literature. One clinical trial and 43 observational studies, covering a total of 586 individual adult patients, provided evidence of a beneficial effect of ERT at group level. At individual patient level, the response to treatment varied, but factors associated with a patient's response to ERT were not described in many studies. Eleven observational studies focused on more severely affected patients, suggesting that ERT can also be beneficial in these patients. There are no studies on the effects of ERT in pre‐symptomatic patients.
Conclusions
This is the first European consensus recommendation for starting and stopping ERT in adult patients with Pompe disease, based on the extensive experience of experts from different countries.
The aim of the study was to provide criteria that can help to distinguish between GBS-TRF and A-CIDP in the early phase of disease.
The distinction between Guillain-Barré syndrome (GBS) with ...fluctuations shortly after start of treatment (treatment-related fluctuations, or GBS-TRF) and chronic inflammatory demyelinating polyneuropathy with acute onset (A-CIDP) is difficult but important because prognosis and treatment strategy largely differ.
Patients with GBS (n = 170) were included in a prospective longitudinal study. Patients with GBS-TRF (n = 16) and patients with A-CIDP (n = 8) were analyzed and compared. Extended clinical data, biologic material, and electrophysiologic data were collected during 1 year follow-up.
The first TRF in the GBS-TRF group always occurred within 8 weeks (median 18 days; range 10-54 days) from onset of weakness. In the GBS-TRF group, 5 (31%) patients had a second TRF and none had more TRFs. At all timepoints, patients in the A-CIDP group were less severely affected than patients with GBS-TRF, did not need artificial ventilation, rarely had cranial nerve dysfunction, and tended to have more CIDP-like electrophysiologic abnormalities. More GBS-TRF patients were severely affected and more patients had sensory disturbances when compared to the GBS group without fluctuations.
The diagnosis of acute-onset chronic inflammatory demyelinating polyneuropathy (CIDP) should be considered when a patient thought to have Guillain-Barré syndrome deteriorates again after 8 weeks from onset or when deterioration occurs 3 times or more. Especially when the patient remains able to walk independently and has no cranial nerve dysfunction or electrophysiologic features likely to be compatible with CIDP, maintenance treatment for CIDP should be considered.
Achieving long-term remission after a limited more intense treatment period would prevent prolonged use of corticosteroids or IV immunoglobulin (IVIg) in chronic inflammatory demyelinating ...polyradiculoneuropathy (CIDP). In this prospective cohort study we present long-term follow-up data on patients included in a multicenter randomized controlled trial comparing 6 monthly pulses of dexamethasone with 8 months of daily prednisolone.
Treatment effect was assessed with the Inflammatory Neuropathy Cause and Treatment disability scale and the Rivermead Mobility Index and was categorized using the CIDP Disease Activity Status (CDAS) scale.
By March 2011, 39 out of 40 patients were included with a median follow-up of 4.5 years. Cure (>5 years off treatment) or remission according to the CDAS criteria after 1 or 2 courses of pulsed dexamethasone or daily prednisolone was achieved in 10 out of 39 patients (26%). Half of the patients who were in remission after initial treatment experienced a relapse (median treatment-free interval: 17.5 months for dexamethasone, 11 months for prednisolone). Alternative diagnosis was made in 7 out of 12 (58%) who did not respond to any therapy and in none of the treatment-responsive patients.
Cure or long-term remission can be achieved in about one-quarter of patients with CIDP after 1 or 2 courses of pulsed dexamethasone or 8-month daily prednisolone. In treatment-nonresponsive patients, the diagnosis CIDP should be reconsidered.
This study provides Class IV evidence that pulsed dexamethasone or 8-month daily prednisolone can lead to long-term remission in CIDP.
Guillain-Barré syndrome is an acute polyradiculoneuropathy with a variable clinical presentation. Accurate diagnostic criteria are essential for patient care and research, including clinical trials ...and vaccine safety studies. Several diagnostic criteria for Guillain-Barré syndrome have been proposed, including the recent set by the Brighton Collaboration. In the present study we describe in detail the key diagnostic features required to meet these Brighton criteria in a study population of 494 adult patients with Guillain-Barré syndrome, previously included in therapeutic and observational studies. The patients had a median age of 53 years (interquartile range 36-66 years) and males slightly predominated (56%). All patients developed bilateral limb weakness which generally involved both upper and lower extremities. The weakness remained restricted to the legs in 6% and to the arms in 1% of the patients. Decreased reflexes in paretic arms or legs were found initially in 91% of patients and in all patients during follow-up. Ten (2%) patients however showed persistence of normal reflexes in paretic arms. Disease nadir was reached within 2 weeks in 80%, within 4 weeks in 97% and within 6 weeks in all patients. A monophasic disease course occurred in 95% of patients, of whom 10% had a treatment-related fluctuation. A clinical deterioration after 8 weeks of onset of weakness occurred in 23 (5%) patients. Cerebrospinal fluid was examined in 474 (96%) patients. A mild pleocytosis (5 to 50 cells/μl) was found in 15%, and none had more than 50 cells/μl. An increased cerebrospinal fluid protein concentration was found only in 64% of patients, highly dependent on the timing of the lumbar puncture after onset of weakness (49% at the first day to 88% after 2 weeks). Nerve electrophysiology was compatible with the presence of a neuropathy in 99% of patients, but only 59% fulfilled the current criteria for a distinct subtype of Guillain-Barré syndrome. Patients with a complete data set (335) were classified according to the Brighton criteria, ranging from a high to a low level of diagnostic certainty, as level 1 in 61%, level 2 in 33%, level 3 in none, and level 4 in 6% of patients. Patients categorized in these levels did not differ with respect to proportion of patients with preceding events, initial clinical manifestations or outcome. The observed variability in the key diagnostic features of Guillain-Barré syndrome in the current cohort study, can be used to improve the sensitivity of the diagnostic criteria.
Guillain-Barré syndrome (GBS) has a highly diverse clinical course and outcome, yet patients are treated with a standard therapy. Patients with poor prognosis may benefit from additional treatment, ...provided they can be identified early, when nerve degeneration is potentially reversible and treatment is most effective. We developed a clinical prognostic model for early prediction of outcome in GBS, applicable for clinical practice and future therapeutic trials.
Data collected prospectively from a derivation cohort of 397 patients with GBS were used to identify risk factors of being unable to walk at 4 weeks, 3 months, and 6 months. Potential predictors of poor outcome (unable to walk unaided) were considered in univariable and multivariable logistic regression models. The clinical model was based on the multivariable logistic regression coefficients of selected predictors and externally validated in an independent cohort of 158 patients with GBS.
High age, preceding diarrhea, and low Medical Research Council sumscore at hospital admission and at 1 week were independently associated with being unable to walk at 4 weeks, 3 months, and 6 months (all p 0.05-0.001). The model can be used at hospital admission and at day 7 of admission, the latter having a better predictive ability for the 3 endpoints; the area under the receiver operating characteristic curve (AUC) is 0.84-0.87 and at admission the AUC is 0.73-0.77. The model proved to be valid in the validation cohort.
A clinical prediction model applicable early in the course of disease accurately predicts the first 6 months outcome in GBS.
Identification and examination of all patients with multifocal motor neuropathy (MMN) in the Netherlands to document the clinical spectrum and response to IV immunoglobulin (IVIg) and to determine ...correlates of outcome.
A national cross-sectional descriptive study was performed. Ninety-seven patients were identified; 88 participated. Logistic regression analysis was used to study determinants of outcome.
Age at onset was younger in men than in women (38 vs 45 years, p = 0.05). Onset of weakness was in distal arm (61%) or distal leg (34%), and occasionally in the upper arm (5%). Initial diagnosis was motor neuron disease in one-third of patients. Brisk, but not pathologic, reflexes in weakened muscles were found in 8%. Conduction blocks were most frequently detected in the ulnar (80%) and median (77%) nerves, but occasionally only between Erb and axilla (6%), or in the musculocutaneous nerve (1%). Ninety-four percent responded to IVIg therapy: nonresponders had longer disease duration before the first treatment (p = 0.03). Seventy-six percent received IVIg maintenance treatment at the time of this study (median duration 6 years; range 0-17): the median dose increased over the years from 12 to 17 g per week (p < 0.01). Independent determinants of more severe weakness and disability were axon loss (p < 0.001; p < 0.0001) and longer disease duration without IVIg (p = 0.03; p = 0.07).
The results of this study may help aid recognition the clinical picture of MMN. Early IVIg treatment may help to postpone axonal degeneration and permanent deficits.
This study provides Class IV evidence that IVIg improves muscle strength of patients with MMN and disability (defined as an increase of >or=1 Medical Research Council grade in at least 2 muscle groups without decrease in other muscle groups) in 94% (95% confidence interval, 86.8%-97.4%) of patients.
Enzyme replacement therapy (ERT; alglucosidase alfa) has improved the prospects for patients with classic infantile Pompe disease considerably. However, over time we noticed that many of these ...children exhibit distal muscle weakness at an early age, which is in contrast to the primarily proximal and axial muscle weakness in patients with late-onset Pompe disease. This was reason to study the prevalence and severity of distal muscle weakness, and the sequence of muscle involvement over time in patients that had learned to walk under ERT.
In this prospective, single-center cohort study, we studied 16 classic infantile patients. We used video recordings that were made during regular standardized assessments to investigate distal muscle function (active dorsiflexion of the feet during walking; ability to use a pincer grasp/actively extend the fingers) and proximal muscle function (standing up from a supine position; raising the arms above the head).
Median age at start of ERT was 3.2 months (0.1-5.8 months), median age at study end was 5.6 years (2.9-18.2 years). Six patients (6/16, 38%) initially had no evident signs of distal muscle weakness and developed a gait with active dorsiflexion of the feet. The other 10 patients never exhibited active dorsiflexion of the feet during walking. At study-end two patients showed no loss of distal muscle function. A subset of five patients (5/16, 31%) developed also weakness of the hands, particularly of the extensors of the 3rd and 4th digit.
We found that the majority (14/16, 88%) of patients who had learned to walk exhibited distal muscle weakness of the lower extremities, while a subset (5/16, 31%) also developed weakness of the hands. The distal muscle weakness was often more serious than, and preceded the development of, the proximal muscle weakness.
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