Non-specificity of Laboratory Test for Diagnosis of Multiple Sclerosis

It has been claimed that the inhibiting effect of linoleic acid on the macrophage electrophoretic mobility test provides a specific laboratory method for the diagnosis of multiple sclerosis (M.S.) and may also enable susceptible relatives of M.S. patients to be identified. Three trials of the method under double-blind conditions have failed to confirm that the test is diagnostically useful.     

脑多发性硬化的MRI诊断

目的:探讨脑内多发性硬化(MS)的核磁共振(MRI)诊断价值.方法:回顾性分析48例经临床确诊为MS患者的MRI表现及相关资料.48例均行MRI常规平扫,46例加做增强扫描.结果:(1)病灶多发,主要分布于侧脑室周围及额、颞、顶、枕叶皮层下白质区,部分累及胼胝体、小脑、脑干、丘脑、基底节及大脑皮质;双侧侧脑室旁可见“垂直脱髓鞘征”;(2)病灶主要以长和较长T2、略长和等T1信号为主;(3)增强扫描显示强化与不强化病灶同时存在,强化病灶呈点状、斑片及环形;少数急性起病病例病灶呈较均匀一致的强化.结论:MRI是临床诊断MS的敏感、直观、最有价值的检查手段.     

Immunoglobulin M. Specific for Measles and Mumps in Multiple Sclerosis

Sera from 43 patients with multiple sclerosis were tested by immunofluorescence. Sera from patients with active multiple sclerosis included four with measles virus-specific immunoglobulin M (measles IgM) and two with mumps virus-specific IgM (mumps IgM). In one case each mumps IgM and measles IgM seem to have persisted for two and a half years and three years respectively. In a comparable group of 43 patients with other nervous diseases measles IgM was found in only one serum, and among 43 normal patients no measles or mumps IgM was found.Herpes simplex virus-specific IgM (herpes simplex IgM) was distributed among all three groups. Anticellular IgM was also found, predominantly in active multiple sclerosis, and persisted in two sera for two and a half years.     

Visual Evoked Response in Diagnosis of Multiple Sclerosis

The diagnostic value of the pattern-evoked response has been assessed in 73 patients referred because of suspected multiple sclerosis. Altogether 52 had delayed responses. Fifty-one patients in the group satisfied McAlpine''s criteria for diagnosing definite, probable, or possible multiple sclerosis. Of these, all but two had delayed responses in one or both eyes, while only three of the remaining 22 patients had delays. In those patients with multiple sclerosis but without any history of optic neuritis the incidence of delayed responses was only slightly less. Of 51 patients with delayed responses 23 had normal discs. Thus subclinical lesions of the visual pathways can be readily detected with this test. The high incidence of abnormal pattern responses, even in patients with no other ocular signs or symptoms, suggests that the test is of value in establishing the diagnosis.     

CSF Proteomics Identifies Specific and Shared Pathways for Multiple Sclerosis Clinical Subtypes

Multiple sclerosis (MS) is an immune-mediated, neuro-inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS) with a heterogeneous clinical presentation and course. There is a remarkable phenotypic heterogeneity in MS, and the molecular mechanisms underlying it remain unknown. We aimed to investigate further the etiopathogenesis related molecular pathways in subclinical types of MS using proteomic and bioinformatics approaches in cerebrospinal fluids of patients with clinically isolated syndrome, relapsing remitting MS and progressive MS (n=179). Comparison of disease groups with controls revealed a total of 151 proteins that are differentially expressed in clinically different MS subtypes. KEGG analysis using PANOGA tool revealed the disease related pathways including aldosterone-regulated sodium reabsorption (p=8.02x10^-5) which is important in the immune cell migration, renin-angiotensin (p=6.88x10^-5) system that induces Th17 dependent immunity, notch signaling (p=1.83x10^-10) pathway indicating the activated remyelination and vitamin digestion and absorption pathways (p=1.73x10^-5). An emerging theme from our studies is that whilst all MS clinical forms share common biological pathways, there are also clinical subtypes specific and pathophysiology related pathways which may have further therapeutic implications.     

Platelet Aggregation Test with Measles Antigen in Multiple Sclerosis

With the measles platelet aggregation test, a new technique recently developed for measuring virus antibody, 153 serum specimens from patients with multiple sclerosis and 164 controls were tested. With one of the three measles antigens used in the test a significantly higher positive rate (P<0·001) was obtained in the specimens from the patients with multiple sclerosis (40%) than in those from the controls (11%). The other two measles antigens also yielded slightly but not significantly higher positive rates in the patients with multiple sclerosis.     

Evaluation of the Corneal Test as a Laboratory Method for Rabies Diagnosis

The corneal test (CT) for rabies diagnosis was evaluated in samples from 313 subjects of different species. Some of the subjects were inoculated experimentally and others were naturally infected. When the CT was compared with immunofluorescence staining and mouse inoculation tests on brains of the same subjects, a sensitivity of 41.7% and a specificity of 100% were found. The authors conclude that a positive CT result would confirm the diagnosis of rabies, but a negative one would not exclude the possibility of disease.     

A Risk Score for Predicting Multiple Sclerosis

ObjectiveMultiple sclerosis (MS) develops as a result of environmental influences on the genetically susceptible. Siblings of people with MS have an increased risk of both MS and demonstrating asymptomatic changes in keeping with MS. We set out to develop an MS risk score integrating both genetic and environmental risk factors. We used this score to identify siblings at extremes of MS risk and attempted to validate the score using brain MRI.Methods78 probands with MS, 121 of their unaffected siblings and 103 healthy controls were studied. Personal history was taken, and serological and genetic analysis using the illumina immunochip was performed. Odds ratios for MS associated with each risk factor were derived from existing literature, and the log values of the odds ratios from each of the risk factors were combined in an additive model to provide an overall score. Scores were initially calculated using log odds ratio from the HLA-DRB1*1501 allele only, secondly using data from all MS-associated SNPs identified in the 2011 GWAS. Subjects with extreme risk scores underwent validation studies. MRI was performed on selected individuals.ResultsThere was a significant difference in the both risk scores between people with MS, their unaffected siblings and healthy controls (p<0.0005). Unaffected siblings had a risk score intermediate to people with MS and controls (p<0.0005). The best performing risk score generated an AUC of 0.82 (95%CI 0.75–0.88).InterpretationsThe risk score demonstrates an AUC on the threshold for clinical utility. Our score enables the identification of a high-risk sibling group to inform pre-symptomatic longitudinal studies.