Relapse of neuromyelitis optica spectrum disorder occurred in 20% of patients who received satralizumab, a subcutaneous anti–interleukin-6 antibody, as compared with 43% of those in the placebo ...group. The drug may have been more effective in patients with anti–aquaporin-4 IgG antibody than in those without the antibody.
Introduction
Neurosarcoidosis is associated with a significant degree of morbidity and mortality and its treatments are varied and complex. There is a paucity of information in current literature on ...patterns of treatment and long term outcomes. This study aimed to evaluate the clinical outcomes and responses to immunosuppressive therapy in a large cohort of neurosarcoidosis patients .
Methods
We enrolled 80 patients with a diagnosis of neurosarcoidosis. Prescription patterns and clinical outcomes before and after treatment and differences between the treatment groups were compared using Kruskal–Wallis and Mann–Witney
U
tests.
Results
Patients with cranial mononeuropathy other than optic neuropathy were more likely to be treated with steroids alone whereas patients with other presentations were likely to require second and third level treatments. These included azathioprine, methotrexate, mycophenolate, infliximab, and cyclophosphamide often used in combination. Prednisolone alone at onset failed in 67% of patients but appeared most effective in those with isolated facial nerve palsy. Patients treated with prednisolone plus a standard immunosuppression first line generally did well except for those with brain parenchymal disease and /or hydrocephalus who responded better to the addition of infliximab, or cyclophosphamide. Triple therapy with prednisolone + azathioprine + infliximab was associated with significantly greater improvement on the Modified Rankin Scale than prednisolone alone whether used first line (
p
= 0.001 corrected) or subsequently (
p
= 0.021 corrected). Overall favourable outcomes in the form of improvement of MRS were reported in 87%,
Conclusions
Our results provides evidence that early immunosuppressive treatments, with azathioprine, methotrexate and infliximab could effectively improve clinical outcomes in many patients with neurosarcoidosis.
DOK7 congenital myasthenic syndrome Palace, Jacqueline
Annals of the New York Academy of Sciences,
December 2012, Letnik:
1275, Številka:
1
Journal Article
Recenzirano
Despite being a fairly recent discovery, DOK7 congenital myasthenic syndrome (CMS) is the third most common form of CMS in the United Kingdom. DOK7 is a postsynaptic protein associated with the AChR ...clustering pathway. In contrast to AChR deficiency due to epsilon subunit mutations, onset of DOK7 CMS tends to be later—ages two to three years—and in DOK7 CMS eye movements are usually spared and anticholinesterases can exacerbate the weakness. The typical phenotype of DOK7 CMS is of a limb girdle weakness with associated nonspecific myopathic features. The presence of stridor in early onset cases and the observation of tongue wasting may be specific clues. Worsening in adulthood is common, particularly affecting bulbar and respiratory function. Treatment with ephedrine or oral salbutamol can result in a slow, steady, and often dramatic improvement over months.
Summary In patients presenting with a clinically isolated syndrome, MRI can support and substitute clinical information in the diagnosis of multiple sclerosis by showing disease dissemination in ...space and time and by helping to exclude disorders that can mimic multiple sclerosis. MRI criteria were first included in the diagnostic work-up for multiple sclerosis in 2001, and since then several modifications to the criteria have been proposed in an attempt to simplify lesion-count models for showing disease dissemination in space, change the timing of MRI scanning to show dissemination in time, and increase the value of spinal cord imaging. Since the last update of these criteria, new data on the use of MRI to establish dissemination in space and time have become available, and MRI technology has improved. State-of-the-art MRI findings in these patients were discussed in a MAGNIMS workshop, the goal of which was to provide an evidence-based and expert-opinion consensus on proposed modifications to MRI criteria for the diagnosis of multiple sclerosis.
Myasthenia gravis (MG) is an autoimmune disease caused by antibodies against the acetylcholine receptor (AChR), muscle-specific kinase (MuSK) or other AChR-related proteins in the postsynaptic muscle ...membrane. Localized or general muscle weakness is the predominant symptom and is induced by the antibodies. Patients are grouped according to the presence of antibodies, symptoms, age at onset and thymus pathology. Diagnosis is straightforward in most patients with typical symptoms and a positive antibody test, although a detailed clinical and neurophysiological examination is important in antibody-negative patients. MG therapy should be ambitious and aim for clinical remission or only mild symptoms with near-normal function and quality of life. Treatment should be based on MG subgroup and includes symptomatic treatment using acetylcholinesterase inhibitors, thymectomy and immunotherapy. Intravenous immunoglobulin and plasma exchange are fast-acting treatments used for disease exacerbations, and intensive care is necessary during exacerbations with respiratory failure. Comorbidity is frequent, particularly in elderly patients. Active physical training should be encouraged.
Spinal cord involvement is a hallmark feature of multiple sclerosis, neuromyelitis optica with AQP4 antibodies and MOG-antibody disease. In this cross-sectional study we use quantitative spinal cord ...MRI to better understand these conditions, differentiate them and associate with relevant clinical outcomes. Eighty participants (20 in each disease group and 20 matched healthy volunteers) underwent spinal cord MRI (cervical cord: 3D T1, 3D T2, diffusion tensor imaging and magnetization transfer ratio; thoracic cord: 3D T2), together with disability, pain and fatigue scoring. All participants had documented spinal cord involvement and were at least 6 months post an acute event. MRI scans were analysed using publicly available software. Those with AQP4-antibody disease showed a significant reduction in cervical cord cross-sectional area (P = 0.038), thoracic cord cross-sectional area (P = 0.043), cervical cord grey matter (P = 0.011), magnetization transfer ratio (P ≤ 0.001), fractional anisotropy (P = 0.004) and increased mean diffusivity (P = 0.008). Those with multiple sclerosis showed significantly increased mean diffusivity (P = 0.001) and reduced fractional anisotropy (P = 0.013), grey matter volume (P = 0.002) and magnetization transfer ratio (P = 0.011). In AQP4-antibody disease the damage was localized to areas of the cord involved in the acute attack. In multiple sclerosis this relationship with lesions was absent. MOG-antibody disease did not show significant differences to healthy volunteers in any modality. However, when considering only areas involved at the time of the acute attack, a reduction in grey matter volume was found (P = 0.023). This suggests a predominant central grey matter component to MOG-antibody myelitis, which we hypothesize could be partially responsible for the significant residual sphincter dysfunction. Those with relapsing MOG-antibody disease showed a reduction in cord cross-sectional area compared to those with monophasic disease, even when relapses occurred elsewhere (P = 0.012). This suggests that relapsing MOG-antibody disease is a more severe phenotype. We then applied a principal component analysis, followed by an orthogonal partial least squares analysis. MOG-antibody disease was discriminated from both AQP4-antibody disease and multiple sclerosis with moderate predictive values. Finally, we assessed the clinical relevance of these metrics using a multiple regression model. Cervical cord cross-sectional area associated with disability scores (B = -0.07, P = 0.0440, R2 = 0.20) and cervical cord spinothalamic tract fractional anisotropy associated with pain scores (B = -19.57, P = 0.016, R2 = 0.55). No spinal cord metric captured fatigue. This work contributes to our understanding of myelitis in these conditions and highlights the clinical relevance of quantitative spinal cord MRI.
Neuromyelitis optica spectrum disorder is a relapsing inflammatory disorder of the central nervous system. Two thirds of patients have antibodies against aquaporin-4, and CNS damage is complement ...dependent. The inhibitor of terminal complement C5 cleavage, eculizumab, reduced relapses of NMOSD.
To date, more than 25 genes have been implicated in the etiology of the congenital myasthenic syndromes (CMS), and an ever‐growing phenotypic landscape is now encountered in the CMS clinic. Unlike ...the autoimmune form of myasthenia, there is no role for immunomodulatory agents in the treatment of CMS. The present‐day drug repertoire comprises acetylcholinesterase inhibitors (mainly pyridostigmine), 3,4‐diaminopyridine (3,4‐DAP), ephedrine, salbutamol/albuterol, open‐channel blockers (fluoxetine, quinidine), or a combination of these. These are prescribed by the specialist in an off‐label manner, as there is no drug currently licensed for the treatment of these rare diseases. The effective pharmacological agent varies according to the genetic form of CMS, and it is important to realize that an agent that provides benefit in one CMS subtype can be harmful in another. In addition, the time to treatment response is variable and tends to be commensurate with the drug used. Here, we summarize for the clinician the therapeutic strategies employed in this ever‐evolving disease spectrum. We also address the barriers to treatment and discuss the treatment of CMS in pregnancy.
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