Prediagnostic presentations of multiple sclerosis in primary care: a case-control study

Date of ISAC Approval: 
27/10/2015
Lay Summary: 
Multiple sclerosis (MS) is the most common neurological disease affecting young adults. A diagnosis of MS is made after a historical review of events in a patient's life and findings from neurological tests. A number of symptoms such as fatigue and depression have been shown to be more common in patients with MS but whether these symptoms occur before a diagnosis of MS is unclear. The aim of this study is to understand what symptoms people with MS report to their general practitioners prior to them receiving a diagnosis of MS. This will provide a better understanding of the mechanisms that lead to the development of MS, the changes in normal body working that MS causes and hopefully aid in our abilities to predict who will develop MS. The results will be communicated in scientific forums and publications.
Technical Summary: 
Multiple sclerosis has an insidious onset and is diagnosed after a historical review of events in a patient's life, findings observed on neurological examination, data acquired from diagnostic tests, and after the exclusion of other diseases that could account for the clinical and paraclinical findings. Several motor and non-motor features can occur before diagnosis, early in the disease process. This study aims to assess the association between first presentation of several symptoms in primary care and a subsequent diagnosis of multiple sclerosis, and to chart the timeline of these first symptom presentations before multiple sclerosis diagnosis. Individuals with a first diagnosis of multiple sclerosis in CPRD until July 31, 2015 will be identified and a matched control cohort will be created of patients without multiple sclerosis. The frequency of a wide range of possible prediagnostic or early symptoms, comprising including motor features, autonomic features and neuropsychiatric disturbances in the years before multiple sclerosis diagnosis will be calculated. The incidence of symptoms recorded in more than 1% of cases per 1000 person-years and incidence risk ratios (RRs) for individuals with and without multiple sclerosis at 2, 5, and 10 years before diagnosis will be reported. Insight into the first clinical presentations of prediagnostic symptoms would help to delineate the pathophysiology of early multiple sclerosis progression and to identify people at increased risk of development of overt multiple sclerosis who would be eligible for inclusion in clinical trials of neuroprotective strategies.
Health Outcomes to be Measured: 
Diagnosis of multiple sclerosis
Collaborators: 

Dr Giulio Disanto - Chief Investigator - Neurocentre of Southern Switzerland
Dr Giulio Disanto - Corresponding Applicant - Neurocentre of Southern Switzerland
Sreeram Ramagopalan - Collaborator - Bristol-Myers Squibb Pharmaceuticals Limited - UK (BMS)