Single Test to ARrive at MS Diagnosis. Using a Single MRI Brain Scan to Help Diagnose Multiple Sclerosis

Study Overview
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Brief Summary
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This is a pilot study (a small scale study testing procedures so that the investigators can apply this to a larger scale study). This study will test the accuracy of a new brain scan (Magnetic Resonance Imaging) technique in predicting the diagnosis of multiple sclerosis (MS) in patients where there is uncertainty about the diagnosis. For patients where there is a suspicion (but not definite) diagnosis of MS, an additional MRI brain scan will be offered. There will be no other research tests and the patient is followed up to see what the eventual diagnosis is. The investigators will then review the original brain scan to see if this predicted the diagnosis of MS or not.

Detailed Description
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There is no single, simple test to differentiate MS from conditions that mimic it. Apart from the patient's symptoms, doctors use Magnetic Resonance Imaging (MRI) of the brain to see if there are abnormalities which are consistent with MS. In patients without typical symptoms or a typical MRI appearance, a firm diagnosis cannot be made as other neurological illnesses can mimic symptoms of MS and the MRI scans can look very similar. Further tests are often required such as lumbar punctures, resulting in delays, discomfort for the patient and additional healthcare costs. With time the diagnosis can become clearer as patients may develop other symptoms of MS but this may take months or years. The most common errors are from misinterpretation of the brain abnormalities or 'lesions' seen on the MRI scan. Subsequently if a patient is misdiagnosed with MS they may receive treatment they do not need. Furthermore a delay in a firm diagnosis delays treatment for another condition. With the rapid increase of new medications in the last few years, accurate and rapid diagnosis is paramount. Pathologically (when looking at lesions using a microscope) MS lesions usually have a vein running through the centre, whereas in lesions arising from other conditions, the investigators hypothesize that no central vein is seen. The investigators can therefore distinguish between patients with MS and patients without it. The researchers therefore want to test the value of a clinical 3-Tesla MRI brain scan in accurately distinguishing between MS and other conditions, with MRI sequences that have been refined over the last few years. Patients will only have one research MRI brain scan and then be followed up by their neurologist, who will confirm the final diagnosis. The investigators shall then look back at the original scans to see if those with MS had veins within their lesions and if those without MS had lesions without veins

Official Title
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Single Test to ARrive at MS Diagnosis. A Prospective, Longitudinal, Investigator Blinded, Pilot Study Assessing the Accuracy of a Single 3 Tesla MRI Scan in Predicting Multiple Sclerosis in Cases of Diagnostic Uncertainty

Conditions
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Multiple Sclerosis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to tolerate an MRI brain scan No contraindications to MRI Radiological suspicion of MS, but clinically atypical or Clinical suspicion of MS, but radiologically atypical Radiological or clinical suspicion of any of the following with a routine MRI brain scan showing white matter lesions; Autoimmune/Inflammatory; Antiphospholipid syndrome, Neurosarcoidosis, Neuro-Behcet's disease, Neuromyelitis Optica, Systemic lupus erythematosus, Primary CNS vasculitis, Secondary CNS vasculitis, Sjogren's syndrome, Susac syndrome. Ischaemic; Hypertensive ischaemic disease (small vessel disease), embolic disease. Infective ; Lyme disease, Cytomegalovirus CNS infection, Toxocariasis, Neurocysticercosis, Whipple's disease, Progressive Multifocal Leukoencephalopathy, Herpes virus (HHV) infection e.g VZV, HIV, Toxoplasmosis, Tuberculosis, Neurosyphilis. Neoplastic; Lymphoma, Glioma, Primary CNS Lymphoma, Cerebral metastases. Other; CADASIL, Histiocytosis, Migraine, Mitochondrial disease, Leukodystrophy. Exclusion Criteria: Unable to tolerate a further MRI scan Unsafe to perform an MRI scan Pregnancy Participants with normal routine clinical scans Unable to give written informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in the proportion of central veins:lesions in patients with MS and non-MS. | To detect this difference with an alpha of 0.05 and power of 0.8, (based on previous data that shows a mean proportion of approx. 60% in MS patients and 6% in ischaemic patients) we will need 12 patients with MS and 12 with non-MS at 1 year of follow up. However given the fact that approx. 40% of patients will have a diagnosis of MS at 1 year, we will need to scan 60 patients in total. | After 1 year of follow up with a confirmed diagnosis. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity of using a proportion of central veins:lesions in diagnosing MS. |  | After 1 year of follow up with a confirmed diagnosis | 
| Specificity of using a proportion of central veins:lesions in diagnosing MS. |  | After 1 year of follow up with a confirmed diagnosis | 
| Positive predictive value of the central vein:lesion MRI test. |  | After 1 year of follow up with a confirmed diagnosis | 
| Negative predictive value of the central vein:lesion MRI test. |  | After 1 year of follow up with a confirmed diagnosis | 
| Optimal proportion of central veins:lesions to make a diagnosis of MS. | Receiver Operating Characteristic (ROC) curves will be used. | After 1 year of follow up with a confirmed diagnosis. | 
| Rate of patient recruitment. |  | After 1 year | 
| Cohen's kappa inter-rater agreement for the diagnosis of MS using the MRI test. | Can different observers calculate the same proportion of central veins:lesions on each scan. | After 1 year of follow up. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MS, Multiple Sclerosis, Diagnostic test, Central veins, MRI