What are the symptoms and diagnostic workup for Multiple Sclerosis (MS)?

From the Guidelines

Multiple sclerosis (MS) diagnosis should be based on the 2017 revision of the McDonald criteria, which emphasizes the importance of MRI in demonstrating dissemination in space and time, as well as the exclusion of other conditions that can mimic MS 1. The symptoms of MS can include fatigue, numbness or tingling in limbs, vision problems, muscle weakness, poor coordination, unsteady gait, and cognitive difficulties.

• The workup for MS involves several diagnostic tests, including:
  • MRI of the brain and spinal cord to look for characteristic demyelinating lesions in multiple areas of the central nervous system that are separated in both space and time
  • Lumbar puncture to analyze cerebrospinal fluid for oligoclonal bands and elevated IgG index, which are present in about 85-95% of MS patients
  • Evoked potential tests to measure electrical activity in response to stimulation, helping detect slowed nerve conduction due to demyelination
  • Blood tests to rule out other conditions that can mimic MS, such as vitamin B12 deficiency, lupus, or neuromyelitis optica
• A thorough neurological examination is essential to document objective neurological deficits. The diagnosis of MS requires evidence of damage in at least two separate areas of the central nervous system, occurring at different times, with all other possible diagnoses excluded, as outlined in the MAGNIMS consensus guidelines 1 and the International Panel on the Diagnosis of MS 1.
• Early diagnosis is crucial as starting disease-modifying therapies promptly can significantly slow disease progression and disability. It is also important to consider the imaging features included in the diagnostic criteria in detail, and guiding neurologists and neuroradiologists in correctly interpreting them, as described in the practical guidelines for assessing lesions on magnetic resonance imaging in multiple sclerosis 1.

From the Research

Symptoms of Multiple Sclerosis

• Typical symptoms of MS include discrete episodes of numbness, tingling, weakness, vision loss, gait impairment, incoordination, imbalance, and bladder dysfunction 2
• Patients may experience fatigue and heat sensitivity between attacks 2
• Some MS patients may experience an insidious worsening of neurologic function and accumulation of disability ("progression") that is not associated with discrete relapse activity 2

Diagnostic Workup for Multiple Sclerosis

• The diagnosis of MS is based on demonstrating evidence of inflammatory-demyelinating injury within the central nervous system that is disseminated in both time and space 2
• Diagnosis is made through a combination of the clinical history, neurologic examination, magnetic resonance imaging, and the exclusion of other diagnostic possibilities 2
• Other tests, including the examination of the cerebrospinal fluid, the recording of evoked potentials, urodynamic studies of bladder function, and ocular coherence tomography, may be helpful in establishing the diagnosis for individual patients 2
• Diagnostic criteria for MS have evolved over time, with each revision impacting the apparent prevalence and prognosis of the disorder 2, 3

Differential Diagnosis

• The exclusion of other diseases that can mimic MS is the cornerstone of current diagnostic criteria 4
• Alternative diagnoses were formulated in 24.4% of cases in a 3-year longitudinal study, with the most frequent being nonspecific neurologic symptoms, migraine, and neuromyelitis optica 4
• The absence of CSF oligoclonal immunoglobulin G bands, the presence of atypical MRI lesions, the absence of dissemination in space of the lesions, and normal visual evoked potentials were all independent predictors of an alternative diagnosis 4

Role of Imaging and Evoked Potentials

• MRI abnormalities were found in 50 cases, while at least one abnormal evoked potential was detected in each of 52 cases in a study of 60 MS patients 5
• Brain-stem auditory evoked potentials were more sensitive than MRI for the detection of brain-stem involvement 5
• The number and extent of MRI lesions were significantly correlated with the duration of disease and with the degree of disability 5

Patient Information and Diagnostic Decision-Making

• A patient information leaflet was developed and validated to engage patients in a diagnostic decision-making process for suspected MS 6
• Approximately 70% of patients wanted to be informed about a possible MS before testing, whereas 10% did not 6
• The leaflet did not seem to elicit anxieties, and the attitude to undergo diagnostic testing was not influenced by the leaflet 6