Non-specific symptoms occur years before multiple sclerosis diagnosis

A paper just published in the journal Neurology documents that diffuse, non-specific symptoms are experienced years before the diagnostic criteria for multiple sclerosis (MS) are satisfied. This illustrates the ‘prodrome’ that is typical of a wide variety of autoimmune disorders. It highlights the importance of investigating antibodies to self-tissue (autoantibodies) classified as ‘predictive’ when they occur before any symptoms and ‘reactive’ when there are symptoms present but the condition has not yet advanced to the pathological stage that qualifies for the canonical diagnosis of an autoimmune disease.

Though characterized by the authors as unrecognized ongoing disease rather than a preliminary phase, it is typical of the experience of many patients who experience diffuse symptoms as the prodrome of an autoimmune condition that may not be diagnosed until years later.

The authors state:

“Our analyses suggest that patients with MS are frequently not diagnosed at their first demyelinating event but often years later. Symptoms and physician encounters before MS diagnosis seem to be related to already ongoing disease rather than a prodrome.”

Need to recognize the prodrome as early as possible

Comments by the authors of an accompanying editorial note that there are a variety of non-specific symptoms that include fatigue, depression, anxiety, headache, sleep disturbances, pain, musculoskeletal, gastrointestinal, and genitourinary disorders that can precede the diagnosis:

“The term prodrome often refers to symptoms indicating disease onset before diagnostically specific signs or symptoms emerge. Data from several recent studies have pointed toward a possible prodromal phase of multiple sclerosis (MS).1 These studies have retrospectively identified increased prevalence of symptoms, diagnoses, and health care use in patients years before a new diagnosis of MS.1 An increased prevalence of fatigue, depression, anxiety, headache, sleep disturbances, pain, musculoskeletal disorders, gastrointestinal disorders, and genitourinary disorders, even when patients with diagnoses compatible with concurrent neurologic syndromes were excluded, appeared to precede diagnosis of MS.”

Recognizing as early as possible the diffuse inflammatory symptoms corresponding to loss of immune tolerance to self-tissue (autoimmunity) yields the best outcomes. This has become ever more important in the present era with autoimmunity expanding so greatly in the population.

The editorial states in regard to MS:

“These data suggest a potential window of opportunity to affect disease trajectory if prodromal symptoms attributable MS could be recognized at the time of onset, or through screening efforts, because earlier treatment is associated with better clinical outcomes…The unusually older median age at diagnosis in these investigations indicates that many MS cases escaped early recognition and were diagnosed years later and that reported prodromal symptoms may not have preceded neurologic symptoms diagnostically specific for MS.”

Clinicians should be alert to the possibility of an autoimmune component in case management and make appropriate use of tests that screen for autoantibodies (antibodies to self-tissue).