Alpha-fodrin autoantibodies in the differential diagnosis of MS and Sjögren syndrome.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
J de Seze
Publications and source records attributed to J de Seze.
Autonomic and respiratory dysfunction in Charcot-Marie-Tooth disease due to Thr124Met mutation in the myelin protein zero gene.
OBJECTIVE: To report the clinical and electrophysiological characteristics of a family presenting Charcot-Marie-Tooth disease (CMT) associated with autonomic nervous system disturbances. METHODS: We studied nerve conduction values, postural adaptation, sympathetic skin reflex, the variation in heart rate by the Valsalva ratio and pupillometry in 7 members of a French family in which CMT due to a Thr124Met mutation in the myelin protein zero (MPZ) gene was diagnosed. RESULTS: Clinical and laboratory evidence of autonomic nervous system disturbances were found in the affected individuals. The clinical phenotype was characterized by sensorimotor peripheral neuropathy, defined as axonal type by electrophysiological studies, and was associated with severe pain, bladder dysfunction, sudorimotor disturbances and abolished pupillary reflex to light. Moreover, two patients had severe restrictive respiratory insufficiency requiring noninvasive mechanical ventilation. CONCLUSIONS: Our study demonstrates that autonomic disturbances may be one of the major clinical signs associated with CMT secondary to MPZ gene mutation in codon 124. Testing of pupillary reflex allows the discrimination of affected and unaffected subjects in our family. However, involvement of the autonomic nervous system in this type of neuropathy is unclear and further studies are required to elucidate the role of the MPZ gene in the autonomic nervous system.
Adult↗
Multiple sclerosis, interferon beta and clinical thyroid dysfunction.
The objective of this study was to investigate frequency and presentation of clinical thyroid dysfunction in patients treated with interferon beta (IFN-beta). We have collected the cases of clinical thyroid dysfunction in 700 consecutive patients receiving IFN-beta for multiple sclerosis (MS). Five patients (four women, one man) treated with IFN-beta1b developed hyperthyroidism. Three of them have secondary progressive MS, and two have relapsing-remitting MS. It was necessary to stop IFN-beta in three cases; these patients still require carbimazole after several months. In the two other cases, hyperthyroidism disappeared spontaneously. Two patients (one man and one woman) treated with IFN-beta1a developed hypothyroidism. One of them required l-thyroxine. Lastly, an increased thyroid volume without modification of thyroid hormones plasma levels was discovered in a patient receiving IFN-beta1a. Among patients treated with IFN-beta, clinical thyroid dysfunction is much rarer than laboratory thyroid dysfunction. However, this side-effect is sometimes severe.
Adult↗
[Hypertrophy of the biceps surae after post-radiation lumbar radiculopathy].
A 44 year-old man who underwent radiotherapy for Hodgkin disease in 1987 developed in 1996 pain and calf hypertrophy. Nerve conduction studies were normal and needle electromyography revealed a neurogenic pattern in the L-5 and S-1 roots, predominantly on the left side. An abdominal tomodensitometry revealed a splenic and left renal atrophy. Cerebrospinal fluid analysis showed an elevated protein level (1.35 g/l) and no malignant cell. Spinal cord magnetic resonance imaging revealed no abnormality of the roots and the cauda equina. Muscular hypertrophy, as the consequence of post-irradiation lumbar radiculopathy is rarely reported. We discuss the possible mechanism of neurogenic muscular hypertrophy.
Adult↗
Devic's neuromyelitis optica: clinical, laboratory, MRI and outcome profile.
Devic's neuromyelitis optica (NMO) associates optic neuritis and myelitis without any other neurological signs. Many patients with NMO may be diagnosed as having multiple sclerosis (MS), optic neuritis and myelitis being the inaugural symptom in 20% and 5% of MS cases, respectively. The aim of our study was to compare a new NMO cohort with recent studies and to try to determine the place of NMO in the spectrum of MS. We retrospectively studied 13 patients with a complete diagnostic workup for NMO. We compared our data with the most recent studies on NMO and with the criteria proposed by Wingerchuck et al. [Neurology 53 (1999) 1107]. We also determined whether these patients fulfilled the diagnostic criteria for MS. Thirteen patients (10 women and three men, with a mean age of 37.4 years) were included in the study. We found similar results to previously published data, except for an association with vasculitis in 38% of our cases. All but three of the patients fulfilled the clinical criteria for MS and two patients fulfilled both clinical and MRI criteria for MS. However, if we applied more restrictive criteria concerning spinal cord and brain MRI and CSF, none of our NMO patients fulfilled the MS diagnostic criteria. NMO might therefore be differentiated from MS by the application of more stringent criteria. Furthermore, all NMO patients should be investigated for vasculitis, even those with no history of systemic disease.
Adrenal Cortex Hormones↗
Interferon beta1a (Avonex) treatment in multiple sclerosis: similarity of effect on progression of disability in patients with mild and moderate disability.
OBJECTIVE: To compare clinical responses to once-weekly intramuscular interferon-beta-1 a [IFNbeta-1 a, Avonex, Biogen] in multiple sclerosis (MS) patients with baseline Expanded Disability Status Scale (EDSS) < or = 3.5 or > 3.5. METHODS: Patients with relapsing-remitting MS (RRMS), 124 with baseline EDSS < or = 3.5 and 64 RRMS patients with EDSS > 3.5, were consecutively recruited to receive IFNbeta-1 a 30 microg as a once weekly injection for 18 months. The primary endpoint of the study was the number of patients in each group with sustained worsening in disability, defined as 1-point deterioration in EDSS that persisted for at least 6 months during the 18 month follow-up period. Subordinate endpoints included relapse rates and the number of treatment dropouts. RESULTS: Among patients with baseline EDSS < or = 3.5,16.9% experienced a deterioration in EDSS of at least 1 point; 22.5% experienced a deterioration of at least 0.5%. Corresponding rates in patients with baseline EDSS > 3.5 were 23.4% and 29% respectively (no significant differences between patients stratified according to baseline EDSS status). The proportion of patients discontinuing therapy was significantly higher in patients with baseline EDSS > 3.5 than in those with baseline EDSS < or = 3.5 (16/64 versus 12/124; p = 0.005). At the conclusion of follow-up, IFNbeta-1 a therapy was associated with a 31.7% reduction in relapse rate in patients with baseline EDSS < or = 3.5 and a 37% reduction in those with baseline EDSS > 3.5 (difference not significant). CONCLUSIONS: During 18 months of treatment and follow-up, no difference was observed in clinical responses to IFNbeta-1 a between RRMS patients with mild and moderate disability but discontinuation of therapy was more frequent in the more disabled group.
Adjuvants, Immunologic↗
Interferon beta in multiple sclerosis: relationship between sustained serum IgG levels and clinical outcome.
We investigated the effects of interferon beta-1a (IFN beta-1a) on specific response towards two immunodominant MBP peptides and on global production of IgG. We evaluated 54 sera from multiple sclerosis (MS) patients at baseline and 1 year after treatment. We did not observe any modification of immune response to the MBP peptides but we noted a significant decrease in mean IgG concentrations in patients with progression of the disease but not in stable patients. These results suggest that IFN beta1a restores or maintains a beneficial immune response.
Adult↗
[Interferons and neurologic diseases].
PURPOSES: Therapeutic strategies using interferons in neurology are limited to multiple sclerosis. In this disease, only beta interferons are used and now considered as a first line treatment in the relapsing-remitting forms of the disease. MAIN POINTS: Beta interferons have reduced the relapse rate by approximately 3% and also reduced the risk of disability progression. They have also favorably influenced the brain lesions on MRI. Numerous data have stressed the importance of starting treatment as early as possible. In the secondary form of the disease, the impact of beta interferons are still discussed. In some clinical endpoints, a dose-response has been demonstrated, probably related to the frequency of injections. Side effects are acceptable despite the high frequency of flu-like syndrome. PERSPECTIVES: Recent data argue for beta interferon treatment after the first demyelinating episode in subjects at risk for early new relapses. In some patients, in cases of treatment failure, combination strategies, including beta interferons, should be addressed in the near future. Interferons were also tested with disappointing results in other neuro-inflammatory disorders, such as chronic inflammatory demyelinating neuropathies.
Adjuvants, Immunologic↗
Quality of life in multiple sclerosis: influence of interferon-beta1 a (Avonex) treatment.
BACKGROUND: Numerous data argue for initiating treatment with interferon-beta (IFN-beta) at an early stage in multiple sderosis (MS). The consequences of its use may negatively influence the MS patient's quality of life (QoL). OBJECTIVE: To evaluate the QoL of MS patients before and after a one-year period of treatment with IFN-beta1a (Avonex). PATIENTS AND METHODS: QoL was assessed using the SF-36 in 121 relapsing-remitting MS patients. We compared QoL before and after treatment and with data from a normal population. We also studied the possible influence of disease progression on the SF-36 scores. RESULTS: One hundred six patients completed the study (87%). Compared to a normal population, patients were, at baseline, worse off for all QoL scales, varying from a minimum decrease of 0.73 SD in mental health, to a maximum decrease of 1.55 SD in general health. After treatment, we found no significant changes in any of the QoL scores, except for physical function, where we noted a slight but significant decrease (p = 0.03). Furthermore, there was no significant change either in the physical component summary (PCS) or mental component summary (MCS). The 'reported health transition' item was significantly improved compared to baseline (p = 0.001). At indusion, significant correlations were found between EDSS scores and scores of physical function (p < 0.001), role - physical (p < 0.01), general health and social function (both p < 0.01), and with the PCS (p < 0.01). Patients with dinical relapses and/or disability progression had a more significant decease in physical function (p < 0.05) and also in social function (p < 0.05). CONCLUSION: The QoL, assessed by the SF-36 scale, is correlated with disability in MS. IFN-beta1a treatment (Avonex) has no negative effect on MS patient's QoL.
Adjuvants, Immunologic↗
[Wernicke-Korsakoff syndrome: diagnostic contribution of magnetic resonance imaging].
Data regarding the magnetic resonance imaging (MRI) features in Wernicke-Korsakoff syndrome (WKS) are scarce. WKS usually combines a cerebellar syndrome, oculomotor disorder and confusion. The aim of this study was to determine more precisely the clinical presentation of WKS and the frequency and topography of MRI abnormalities. Furthermore, we try to assess the prognostic value of both clinical signs and MRI abnormalities. We retrospectively studied 25 patients with WKS in which an MRI was available. We assessed the initial clinical presentation and the outcome. We also analyzed the frequency and the location of MRI lesions. We then correlated clinical and MRI data with the clinical outcome. Eleven patients (44 p. 100) had the full WKS. Fourteen of the 25 patients (56 p. 100) had a poor evolution. The occurrence of full WKS was correlated with a poor outcome (p < 0.02). Signal abnormalities on T2-weighted images were found in the periacqueducal region, in the thalami or in the mamillar bodies in 16 cases (64 p. 100). There was a correlation between an hypersignal in at least one region and a poor clinical outcome (p < 0.02). Our study demonstrates the high frequency of brain MRI lesions in WKS and the correlation of both initial clinical signs and MRI abnormalities with a poor clinical outcome.
Adult↗
The prevalence of Sjögren syndrome in patients with primary progressive multiple sclerosis.
OBJECTIVE: To assess the prevalence of Sjögren syndrome (SS) in patients with primary progressive MS (PPMS). BACKGROUND: SS may be considered in the differential diagnosis of MS. Age at onset and clinical presentation are similar in SS and PPMS. However, occurrence of SS in definite cases of PPMS has been recently reported. METHODS: Proposed clinical and laboratory diagnostic criteria for SS were systematically assessed in 60 consecutive patients with PPMS. The authors questioned all patients about xerophthalmia and xerostomia, biopsied minor salivary glands, and performed a Schirmer test, a salivary gland scintigraphy, and anti-Ro (SSa) and anti-La (SSb) serologies. RESULTS: Ten patients (16.6%) met four or more criteria for SS. This prevalence is higher than in the general population (1 to 5%) and implies that SS can mimic PPMS. CONCLUSIONS: The authors propose that SS should be screened for systematically in patients with PPMS.
Adult↗
Long-term follow-up of neurosarcoidosis.
The authors evaluated the long-term clinical outcome of neurosarcoidosis and determined predictive factors of disease course. Twenty-seven patients with neurosarcoidosis were followed for at least 5 years from the onset of neurologic symptoms. Patients with CNS involvement during the course of the disease had a higher Modified Oxford Handicap Scale score than those with peripheral nervous system involvement (p < 0.02). CNS involvement may be a predictive factor for a less favorable disease course. Early and intensive treatment should be considered in such cases.
Adolescent↗
Pupillary disturbances in multiple sclerosis: correlation with MRI findings.
UNLABELLED: Autonomic nervous system disturbances such as pupillary abnormalities have rarely been evaluated in multiple sclerosis (MS). However, pupillary impairment is not uncommon in MS and its origin is still unclear. The aim of this study was to investigate pupillary disturbances in MS and to try to correlate pupillary defects with spinal cord and brainstem magnetic resonance imaging (MRI) findings. We prospectively studied 45 MS patients and 30 normal subjects. METHODS: The pupillary contraction latency and the amplitude of contraction were recorded by pupillometry. We also determined afferent and efferent pathway defects by comparing the direct and consensual pupillary reflexes. We evaluated brainstem and spinal cord demyelinating lesions and spinal cord cross-sectional area on MRI. At least one pupillometric parameters were significantly impaired in 60% of patients and in none of the controls. We did not find any correlation between pupillary defect and demyelinating lesions on MRI. The most frequent abnormality was efferent pathway shift and this was correlated with spinal cord atrophy (P<0.02). These results confirm that the autonomic nervous system, and especially pupillary function, is frequently impaired in MS. The parasympathetic system is most commonly affected and this is most likely linked to axonal loss (demonstrated by spinal cord atrophy) rather than to demyelinating lesions.
Adult↗
IgG reactivity against citrullinated myelin basic protein in multiple sclerosis.
An increased level of citrullinated myelin basic protein (MBP-C8) has been reported in the brains of multiple sclerosis (MS) patients. However, the involvement of the immune response to post-translational modified MBP in the pathophysiology of MS remains speculative. The aim of this study was to compare the levels of immunoglobulin G antibodies to several MBP epitopes, before and after citrullination, in the cerebrospinal fluid (CSF) and sera of MS patients using enzyme-linked immunosorbent assay (ELISA). We analyzed antibody reactivity against various MBP-peptides in the CSF and sera of 60 MS patients, and 30 patients with other neurological diseases (OND) as controls. The peptides tested were: MBP(75-98) (peptide 1), native (peptide 2) and citrullinated (peptide 3) MBP(108-126) (ARG(122)-->Cit(122)), and native (peptide 4) and citrullinated (peptide 5) MBP(151-170) (ARG(159, 170)-->Cit(159, 170)). All selected peptides could support an immune reactivity in CSF and sera of MS and OND patients. A higher reactivity against peptide 4 was found in the CSF of MS patients compared with OND patients (P<0.0001), but not against citrullinated peptides (peptides 3 and 5). However, we observed that the citrullination state of peptide 2 modified the patterns of immune reactivity more markedly in MS patients (P<0.0001) than in OND patients (P<0.02). Although some MBP epitopes could be a potential target in MS, our data did not demonstrate any difference of antibody response to MBP peptides in their citrullinated forms.
Adolescent↗
Silver stained isoelectrophoresis of tears and cerebrospinal fluid in multiple sclerosis.
Cerebrospinal fluid (CSF) analysis aids in the diagnosis of multiple sclerosis. However, this examination is invasive. The aim of this study was to assess the potentials of a new method of tears isoelectrophoresis (IEF). Silver staining of IEF was used to examined tears and CSF from 123 patients including 60 patients with multiple sclerosis (MS), 50 other neurological patients and 13 patients with inflammatory neurological diseases. Tears were collected on a Shirmer strip placed in one eye, avoiding reflex secretion. This method of IEF with silver staining allowed the detection of oligoclonal bands in tears that were truly immunoglobulin G on immunofixation. The concordance rate between tears and CSF was 83%, meaning that CSF provided no more information than tears analysis in 83% of cases. Sensitivity in tears (72%) and CSF (75%) was very close as was specificity (respectively 84 % and 86 %). High concordance between tears and CSF is the first step in developing a non invasive test which could replace lumbar puncture, particularly when this procedure is not fearalele or is refused by the patient.
Adolescent↗
Autonomic dysfunction in multiple sclerosis: cervical spinal cord atrophy correlates.
Autonomic dysfunction has rarely been studied in patients suffering from multiple sclerosis (MS). Some hypotheses have concerned the pathophysiology, especially with regard to a possible spinal cord origin. However, there have been no previous studies on autonomic dysfunction in MS and spinal cord lesions. This study assessed the frequency of autonomic dysfunction (AD) in MS and the correlation to spinal cord magnetic resonance imaging (MRI) findings. We prospectively studied 75 MS patients (25 with relapsing-remitting forms, 25 with secondary progressive forms and 25 with primary progressive forms). We performed sympathetic skin response, R-R interval variability and orthostatic hypotension testing. Spinal cord MRI was performed to detect demyelinating lesions (sagittal and axial plane) or spinal cord atrophy. Clinical and laboratory evidence of AD was found in 84% and 56% of MS patients, respectively. The correlation of the latter with disability was evaluated using the Extended Disability Status Scale. AD was more frequent in primary progressive MS than in the other two forms. AD was correlated with spinal cord cross-sectional area reduction but not with spinal cord hyperintensities. This study confirms that the frequency of AD in MS, especially in primary progressive forms, has until now been underestimated. Furthermore, AD appears to be more closely related to axonal loss, as demonstrated by spinal cord atrophy, than to demyelinating lesions.
Adult↗
Acute myelopathies: Clinical, laboratory and outcome profiles in 79 cases.
The main aetiologies of acute myelopathy (AM) are: multiple sclerosis, systemic disease (SD), spinal cord infarct (SCI), parainfectious myelopathy (PIM) and delayed radiation myelopathy (DRM). Although a large amount of data have been published for each individual aetiology, comparison studies are scarce. The aim of this study was to assess the various aetiological and outcome profiles of AM. We studied 79 cases: 34 (43%) in multiple sclerosis; 13 (16.5%) in SD; 11 (14%) in SCI; five (6%) in PIM; and three (4%) in DRM. Myelopathies were of unknown origin in 13 (16.5%) patients. We evaluated clinical, spinal cord and brain MRI, CSF and evoked potentials data at admission, MRI outcome at 6 months and clinical outcome at 12 months. A statistical comparison of clinical, laboratory and outcome data was only performed between multiple sclerosis, SD and SCI patients due to the small number of cases in the other groups. A motor deficit was more frequent in SD and SCI than in multiple sclerosis where initial symptoms were predominantly sensory (P < 0.001). Spinal cord MRI showed lateral or posterior lesions of less than two vertebral levels in multiple sclerosis, in contrast to SD and SCI, where lesions involved more vertebral levels and were centromedullar (P < 0.001). Brain MRI was most frequently abnormal in multiple sclerosis (68%), but was also abnormal in 31% of SD patients (P < 0.05). Oligoclonal bands in CSF were more frequent in multiple sclerosis than in SD (P < 0.001) and were never found in SCI. Clinical outcome at 12 months was good in 88% of multiple sclerosis cases, and poor or fair in 91% of SCI and 77% of SD. Aetiologies of AM may be differentiated on the basis of clinical, spinal cord and brain MRI, CSF and outcome data, and allow a probable diagnosis to be made in previously undetermined cases. These findings may have therapeutic implications for cases with a questionable diagnosis.
Acute Disease↗
[Myelopathy - Sjogren's syndrome association: analysis of clinical and radiological findings and clinical course].
Myelopathies associated with Sjögren's syndrome has been rarely described especially concerning magnetic resonance imaging (MRI) and treatment aspects. The aim of this study was to determine the clinical, laboratory and radiological features of myelopathies occurring in Sjögren's syndrome. Eleven patients were studied, 7 with an acute myelopathy and 4 with a chronic form. Acute myelopathy were clinically severe with a feature of transverse myelitis necessitating immunosuppressive drugs. On the other hand, chronic forms were closely similar to progressive multiple sclerosis (MS), for clinical and laboratory data. In 7 cases optic neuritis was found associated with myelopathy and fulfilled the diagnostic criteria of Devic's syndrome in 4 cases. The diagnosis of myelopathy associated with Sjögren's syndrome may be difficult especially compared with MS, HTLV1 or HIV myelopathy and sarcoidosis, in the chronic form but also with other vasculitis, MS or viral infection in the acute forms. However, in this last form, magnetic resonance imaging and cerebrospinal fluid data should bring to the diagnosis of Sjögren syndrome and confirmed by appropriate tests. This diagnosis will have direct consequences for an early treatment by immunosuppressive drugs.
Adult↗