To describe 16 patients with a coincidence of 2 rare diseases: aquaporin-4 antibody (AQP4-Ab)-mediated neuromyelitis optica spectrum disorder (AQP4-NMOSD) and acetylcholine receptor antibody ...(AChR-Ab)-mediated myasthenia gravis (AChR-MG).
The clinical details and antibody results of 16 patients with AChR-MG and AQP4-NMOSD were analyzed retrospectively.
All had early-onset AChR-MG, the majority with mild generalized disease, and a high proportion achieved remission. Fifteen were female; 11 were Caucasian. In 14/16, the MG preceded NMOSD (median interval: 16 years) and 11 of these had had a thymectomy although 1 only after NMOSD onset. In 4/5 patients tested, AQP4-Abs were detectable between 4 and 16 years prior to disease onset, including 2 patients with detectable AQP4-Abs prior to thymectomy. AChR-Abs decreased and the AQP4-Ab levels increased over time in concordance with the relevant disease. AChR-Abs were detectable at NMOSD onset in the one sample available from 1 of the 2 patients with NMOSD before MG.
Although both conditions are rare, the association of MG and NMOSD occurs much more frequently than by chance and the MG appears to follow a benign course. AChR-Abs or AQP4-Abs may be present years before onset of the relevant disease and the antibody titers against AQP4 and AChR tend to change in opposite directions. Although most cases had MG prior to NMOSD onset, and had undergone thymectomy, NMOSD can occur first and in patients who have not had their thymus removed.
Neuromyelitis optica (NMO) immunoglobulin G (IgG) (aquaporin-4 AQP4 IgG) is highly specific for NMO and related disorders, and autoantibody detection has become an essential investigation in patients ...with demyelinating disease. However, although different techniques are now used, no multicenter comparisons have been performed. This study compares the sensitivity and specificity of different assays, including an in-house flow cytometric assay and 2 commercial assays (ELISA and transfected cell-based assay CBA).
Six assay methods (in-house or commercial) were performed in 2 international centers using coded serum from patients with NMO (35 patients), NMO spectrum disorders (25 patients), relapsing-remitting multiple sclerosis (39 patients), miscellaneous autoimmune diseases (25 patients), and healthy subjects (22 subjects).
The highest sensitivities were yielded by assays detecting IgG binding to cells expressing recombinant AQP4 with quantitative flow cytometry (77; 46 of 60) or visual observation (CBA, 73%; 44 of 60). The fluorescence immunoprecipitation assay and tissue-based immunofluorescence assay were least sensitive (48%-53%). The CBA and ELISA commercial assays (100% specific) yielded sensitivities of 68% (41 of 60) and 60% (36 of 60), respectively, and sensitivity of 72% (43 of 60) when used in combination.
The greater sensitivity and excellent specificity of second-generation recombinant antigen-based assays for detection of NMO-IgG in a clinical setting should enable earlier diagnosis of NMO spectrum disorders and prompt initiation of disease-appropriate therapies.
The comparative clinical and demographic features of neuromyelitis optica (NMO) are not well known. In this review we analyzed peer-reviewed publications for incidence and prevalence, clinical ...phenotypes, and demographic features of NMO. Population-based studies from Europe, South East and Southern Asia, the Caribbean, and Cuba suggest that the incidence and prevalence of NMO ranges from 0.05–0.4 and 0.52–4.4 per 100,000, respectively. Mean age at onset (32.6–45.7) and median time to first relapse (8–12 months) was similar. Most studies reported an excess of disease in women and a relapsing course, particularly in anti-aquaporin 4 antibody (anti AQP4-IgG)-positive patients. Ethnicity may have a bearing on disease phenotype and clinical outcome. Despite limitations inherent to the review process, themes noted in clinical and demographic features of NMO among different populations promote a more global understanding of NMO and strategies to address it.
To investigate the influence of pregnancy on patients with neuromyelitis optica spectrum disorder (NMOSD).
A total of 190 women with NMOSD were enrolled from 7 referral hospitals in 4 countries. We ...reviewed medical records and used a structured questionnaire to investigate gravidity, parity, and the number of relapses during the 2 years before pregnancy, during each trimester of pregnancy, during the first and second trimesters after delivery, and for 6 months thereafter. The annualized relapse rate (ARR) was calculated for each period.
Of the 190 women with NMOSD, 40 patients experienced 54 informative pregnancies, and all of them were seropositive for aquaporin-4 antibody. Fourteen patients developed the first symptoms of NMOSD either during the pregnancy (3 patients) or within a year after delivery or abortion (8 and 3 patients, respectively). Twenty-six patients experienced 40 pregnancies after the onset of NMOSD (26 deliveries and 14 abortions 1 spontaneous and 13 elective). There was one preterm delivery with birth defects and no stillbirths. The ARR during pregnancy did not differ from that before pregnancy, but it increased significantly during the first and second trimesters after delivery (5.3 and 3.7 times, respectively). Moreover, 77% of the deliveries were associated with postpartum relapses.
The significantly increased relapse rate and numerous cases of NMOSD onset after pregnancy suggest that delivery adversely affects the course of NMOSD. Prospective studies are needed to confirm our findings.
Longitudinally extensive transverse myelitis refers to florid and widespread inflammation of the spinal cord causing T2 hyperintensity on spinal magnetic resonance imaging that is seen to extend over ...three or more vertebral segments. Whilst rare, longitudinally extensive transverse myelitis is clinically important as it can lead to catastrophic morbidity, and a group of these patients are at risk of further attacks. Early identification and establishment of the underlying aetiology is vital in order to initiate appropriate therapy and optimize outcomes. Whilst longitudinally extensive transverse myelitis is classically associated with neuromyelitis optica, there are many other causes. These include other inflammatory aetiologies, infection, malignancy and metabolic disturbance. Some of these are readily treatable. Laboratory and radiological investigations can help to differentiate these causes. Treatment of longitudinally extensive transverse myelitis hinges on distinguishing inflammatory and non-inflammatory aetiologies and identifying patients who are at high risk of a recurrent course.
Biodiversity loss from deforestation may be partly offset by the expansion of secondary forests and plantation forestry in the tropics. However, our current knowledge of the value of these habitats ...for biodiversity conservation is limited to very few taxa, and many studies are severely confounded by methodological shortcomings. We examined the conservation value of tropical primary, secondary, and plantation forests for 15 taxonomic groups using a robust and replicated sample design that minimized edge effects. Different taxa varied markedly in their response to patterns of land use in terms of species richness and the percentage of species restricted to primary forest (varying from 5% to 57%), yet almost all between-forest comparisons showed marked differences in community structure and composition. Cross-taxon congruence in response patterns was very weak when evaluated using abundance or species richness data, but much stronger when using metrics based upon community similarity. Our results show that, whereas the biodiversity indicator group concept may hold some validity for several taxa that are frequently sampled (such as birds and fruit-feeding butterflies), it fails for those exhibiting highly idiosyncratic responses to tropical land-use change (including highly vagile species groups such as bats and orchid bees), highlighting the problems associated with quantifying the biodiversity value of anthropogenic habitats. Finally, although we show that areas of native regeneration and exotic tree plantations can provide complementary conservation services, we also provide clear empirical evidence demonstrating the irreplaceable value of primary forests.
Abstract Temporomandibular joint (TMJ) disc displacement is a clinical sign often found in patients with temporomandibular disorders (TMDs) and associated with TMJ osteoarthrosis. Osteoarthrosis is a ...degenerative joint disease that may be associated with pain and functional disability. The aim of this study was to evaluate the odds ratio (OR) of joints with disc displacement presenting osteoarthrosis via magnetic resonance imaging (MRI) analysis. In total, 224 TMJ images from patients with signs and symptoms of a TMD were evaluated. The OR, a measure of association, was used to calculate the likelihood of TMJ disc displacement (with or without reduction) with osteoarthrosis. Joints with anterior disc displacement with reduction (ADDwR) and anterior disc displacement without reduction (ADDwoR) were 2.73- and 8.25-times, respectively, more likely to have osteoarthrosis. A nine-times greater likelihood of osteophyte occurrence was observed in cases of ADDwoR, whereas a lower OR for their occurrence (OR 2.96) was observed in cases of ADDwR. The significant OR of joints with disc displacement presenting osteoarthrosis, particularly in cases of ADDwoR, emphasizes the importance of accurate assessment of changes in disc position, which may be associated with other painful and functional disorders of the TMJ.
We describe a long-term observational study of a large cohort of patients with sporadic inclusion body myositis and propose a sporadic inclusion body myositis weakness composite index that is easy to ...perform during a clinic. Data collection from two groups of patients (Paris and Oxford) was completed either during a clinic visit (52%), or by extraction from previous medical records (48%). One hundred and thirty-six patients 57% males, 61 (interquartile range 55-69) years at onset were included. At the last visit all patients had muscle weakness (proximal British Medical Research Council scale <3/5 in 48%, distal British Medical Research Council scale <3/5 in 40%, swallowing problems in 46%). During their follow-up, 75% of patients had significant walking difficulties and 37% used a wheelchair (after a median duration from onset of 14 years). The sporadic inclusion body myositis weakness composite index, which correlated with grip strength (correlation coefficient: 0.47; P < 0.001) and Rivermead Mobility Index (correlation coefficient: 0.85; P < 0.001), decreased significantly with disease duration (correlation coefficient: −0.47; P < 0.001). The risk of death was only influenced by older age at onset of first symptoms. Seventy-one (52%) patients received immunosuppressive treatments prednisone in 91.5%, associated (in 64.8%) with other immunomodulatory drugs (intravenous immunoglobulins, methotrexate or azathioprine) for a median duration of 40.8 months. At the last assessment, patients who had been treated were more severely affected on disability scales (Walton P = 0.007, Rivermead Mobility Index P = 0.004) and on the sporadic inclusion body myositis weakness composite index (P = 0.04). The first stage of disease progression towards handicap for walking was more rapid among patients receiving immunosuppressive treatments (hazard ratio = 2.0, P = 0.002). This study confirms that sporadic inclusion body myositis is slowly progressive but not lethal and that immunosuppressive treatments do not ameliorate its natural course, thus confirming findings from smaller studies. Furthermore, our findings suggest that immunosuppressant drug therapy could have modestly exacerbated progression of disability. The sporadic inclusion body myositis weakness composite index might be a valuable outcome measure for future clinical trials, but requires further assessment and validation.
Severe, recurrent or bilateral optic neuritis (ON) often falls within the neuromyelitis optica spectrum disorders (NMOSD), but the diagnosis can be particularly challenging and has important ...treatment implications. We report the features, course and outcomes of patients presenting with atypical ON when isolated at onset. We retrospectively analyzed 69 sequential patients referred to a single UK NMO center with isolated ON at onset. Aquaporin-4 antibody (AQP4-Ab) assessment was performed in all patients and IgG1 myelin-oligodenrocyte glycoprotein (MOG-Ab) in AQP4-Ab
neg
patients. 37 AQP4-Ab positive (AQP4-Ab
pos
) and 32 AQP4-Ab negative (AQP4-Ab
neg
) patients (8 with MOG-Ab) were identified. The AQP4-Ab
neg
group included heterogeneous diagnoses: multiple sclerosis (MS), NMO, relapsing isolated ON (RION), monophasic isolated ON and relapsing acute disseminated encephalomyelitis (ADEM)-like syndromes. Compared to AQP4-Ab
neg
patients, AQP4-Ab
pos
patients had a worse residual visual outcome from first attack (median VFSS 4 vs. 0,
p
= 0.010) and at last assessment (median VFSS 5 versus 2,
p
= 0.005). However, AQP4-Ab
neg
patients with RION also had poor visual outcome. Up to 35 % of AQP4-Ab
neg
patients developed a LETM and two developed low positivity for AQP4-Ab over time. Eight AQP4-Ab
neg
patients (25 %) were MOG-Ab positive, covering a range of phenotypes excluding MS; the first ON attack was often bilateral and most had relapsing disease with a poor final visual outcome VFSS 4, range (0–6). In conlcusion, AQP4-Ab positivity is confirmed as a predictor of poor visual outcome but AQP4-Ab
neg
RION also had a poor visual outcome. Of those without AQP4-Ab, 25 % had MOG-Ab and another 25 % developed MS; thus, MOG-Ab is associated with AQP4-Ab
neg
non-MS ON.
Background:
Few data are available for patients with a late onset (≥ 50 years) of neuromyelitis optica (LONMO) or neuromyelitis optica spectrum disease (LONMOSD), defined by an optic ...neuritis/longitudinally extensive transverse myelitis with aquaporin-4 antibodies (AQP4-Ab).
Objective:
To characterize LONMO and LONMOSD, and to analyze their predictive factors of disability and death.
Methods:
We identified 430 patients from four cohorts of NMO/NMOSD in France, Germany, Turkey and UK. We extracted the late onset patients and analyzed them for predictive factors of disability and death, using the Cox proportional model.
Results:
We followed up on 63 patients with LONMO and 45 with LONMOSD during a mean of 4.6 years. This LONMO/LONMOSD cohort was mainly of Caucasian origin (93%), women (80%), seropositive for AQP4-Ab (85%) and from 50 to 82.5 years of age at onset. No progressive course was noted. At last follow-up, the median Expanded Disability Status Scale (EDSS) scores were 5.5 and 6 in the LONMO and LONMOSD groups, respectively. Outcome was mainly characterized by motor disability and relatively good visual function. At last follow-up, 14 patients had died, including seven (50%) due to acute myelitis and six (43%) because of opportunistic infections. The EDSS 4 score was independently predicted by an older age at onset, as a continuous variable after 50 years of age. Death was predicted by two independent factors: an older age at onset and a high annualized relapse rate.
Conclusion:
LONMO/LONMOSD is particularly severe, with a high rate of motor impairment and death.
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