Loren A. Rolak

Cerebrospinal fluid in acute optic neuritis Experience of the optic neuritis treatment trial

The Optic Neuritis Treatment Trial (ONTT) is a prospective study of corticosteroid treatment of acute optic neuritis (ON), with subsequent longitudinal follow-up to determine development of clinically definite multiple sclerosis (CDMS). We analyzed the CSF of 83 patients with clinically isolated ON who underwent lumbar puncture within 24 hours of enrollment into the ONTT to determine the value of CSF changes in ON, especially regarding diagnostic utility, immunologic changes, MRI correlations, and progression to CDMS All patients had baseline MRI scans graded for changes typical of MS CSF measurements included immunoglobulin G (IgG) synthesis, IgG ratio, myelin basic protein, IgG kappa light chains, and oligoclonal banding. No patients had their diagnosis or management altered as a result of CSF findings. Except for oligoclonal bands, few patients showed any abnormalities on CSF tests, and no tests correlated with the 2-year development of CDMS. Oligoclonal banding, present at baseline in 11 of 13 patients who developed CDMS, did predict progression to CDMS, but this was not independent of MRI abnormalities. Two patients with oligoclonal bands and a normal MRI did progress to CDMS. We conclude that CSF analysis may not be necessary in the routine evaluation of patients presenting with a typical clinical profile of acute ON, and that most CSF tests add little additional information to MRI results for predicting the 2-year development of CDMS. However, the precise role of oligoclonal banding in the analysis of such patients awaits longer follow-up of this cohort. NEUROLOGY 1996,46 368-372

The Differential Diagnosis of Multiple Sclerosis

Objective:This article will discuss the diagnosis of multiple sclerosis (MS), with particular attention to differentiating it from other diseases that can mimic it. Methods:We reviewed our own data, as well as the published experience on the differential diagnosis of MS and the most common errors leading to misdiagnosis. Results:Psychiatric diseases are mistaken for multiple sclerosis more often than any other conditions. Other multifocal illnesses or white-matter diseases are seldom confused with multiple sclerosis. Conclusion:Neurologists are most likely to misdiagnose multiple sclerosis in patients who have psychiatric problems or who have uncommon presentations of common diseases such as migraine, stroke, or neuropathies.

The diagnosis of multiple sclerosis.

The process of diagnosing multiple sclerosis (MS) is much like that of analyzing evidence in a courtroom; they both rely on reason, judgement, and experience, rather than on any formal set of diagnostic criteria. The history, physical examination, and laboratory tests all have limitations and pitfalls that make MS one of the most difficult diseases to diagnose.

Multiple sclerosis treatment 2001

Trials of new MS drugs now require MR imaging and clinical data and entail enormous expense. Therefore, science can ask and answer only a limited number of questions, so physicians must use their clinical acumen to judge (or conjecture) the best treatments for their patients. The drugs discussed earlier will dominate MS therapy in the next few years, but further advances may come from one of the more than forty new agents now under investigation for alleviating MS. It is an exciting time for patients and their doctors.

Phenome-wide association study maps new diseases to the human major histocompatibility complex region

Background Over 160 disease phenotypes have been mapped to the major histocompatibility complex (MHC) region on chromosome 6 by genome-wide association study (GWAS), suggesting that the MHC region as a whole may be involved in the aetiology of many phenotypes, including unstudied diseases. The phenome-wide association study (PheWAS), a powerful and complementary approach to GWAS, has demonstrated its ability to discover and rediscover genetic associations. The objective of this study is to comprehensively investigate the MHC region by PheWAS to identify new phenotypes mapped to this genetically important region. Methods In the current study, we systematically explored the MHC region using PheWAS to associate 2692 MHC-linked variants (minor allele frequency ≥0.01) with 6221 phenotypes in a cohort of 7481 subjects from the Marshfield Clinic Personalized Medicine Research Project. Results Findings showed that expected associations previously identified by GWAS could be identified by PheWAS (eg, psoriasis, ankylosing spondylitis, type I diabetes and coeliac disease) with some having strong cross-phenotype associations potentially driven by pleiotropic effects. Importantly, novel associations with eight diseases not previously assessed by GWAS (eg, lichen planus) were also identified and replicated in an independent population. Many of these associated diseases appear to be immune-related disorders. Further assessment of these diseases in 16 484 Marshfield Clinic twins suggests that some of these diseases, including lichen planus, may have genetic aetiologies. Conclusions These results demonstrate that the PheWAS approach is a powerful and novel method to discover SNP–disease associations, and is ideal when characterising cross-phenotype associations, and further emphasise the importance of the MHC region in human health and disease.

Safety and efficacy of helminth treatment in relapsing-remitting multiple sclerosis: Results of the HINT 2 clinical trial

Background: The hygiene hypothesis suggests that microbial replacement may be therapeutic in allergic and autoimmune diseases. Nevertheless, the results of helminth treatment, including in multiple sclerosis (MS), have been inconclusive. Objective: To assess safety and brain magnetic resonance imaging (MRI) activity in subjects with relapsing-remitting multiple sclerosis (RRMS) during oral administration of ova from the porcine whipworm, Trichuris suis (TSO). Methods: A total of 16 disease-modifying treatment (DMT) naive RRMS subjects were studied in a baseline versus treatment (BVT) controlled prospective study. MRI scans were performed during 5 months of screening-observation, 10 months of treatment, and 4 months of post-treatment surveillance. Results: No serious symptoms or adverse events occurred during treatment. For the cohort, there was a trend consistent with a 35% diminution in active lesions when observation MRIs were compared to treatment MRIs (p = 0.08), and at the level of individuals, 12 of 16 subjects improved during TSO treatment. T regulatory lymphocytes were increased during TSO treatment. Conclusion: TSO is safe in RRMS subjects. Potentially favorable MRI outcomes and immunoregulatory changes were observed during TSO treatment; however, the magnitude of these effects was modest, and there was considerable variation among the responses of individual subjects.