Approach
The diagnosis of MS is made by careful neurological history and examination and is confirmed by ancillary testing, such as magnetic resonance imaging (MRI) of the brain and spinal cord and evaluation of cerebrospinal fluid (CSF), in the absence of an alternative explanation for symptoms and signs.
Neurological history
A history of transient motor, cerebellar, sensory, gait, or visual dysfunction lasting over 48 hours and not accompanied by fever or other intercurrent illness is suggestive of a demyelinating episode of MS.
Symptoms are often asymmetric and involve only one side of the body or one limb, although bilateral involvement can occur. Patches of odd sensation such as wetness or tingling may occur, and band-like or hemiband-like sensations are pathognomonic for spinal cord lesions.
Neurological examination
Funduscopy should be performed to view the optic disc, and the 'swinging flashlight' test can be used to evaluate for an afferent pupillary defect. Colour vision should be assessed to look for red desaturation (a more subtle sign of optic neuritis). Eye movements may also be particularly revealing as patients may develop internuclear ophthalmoplegia (INO) or other abnormalities in the absence of symptoms. The presence of nystagmus or abnormal saccades may suggest a cerebellar lesion.
Testing of tone and reflexes in the upper and lower extremities to look for upper motor neuron signs, such as spasticity and hyperreflexia, is important.
The gait must be carefully assessed, preferably by walking the patient at least 7.6 metres (25 feet). Signs may include mild dragging of the foot as well as spasticity and balance problems.
Imaging
MRI is the definitive imaging test for MS. The images must be interpreted by specialists who are very familiar with typical MS findings on MRI, and in the context of the patient's history and examination. Recommendations on standardised MRI protocols were published in 2021.[3]
Brain imaging
Sagittal three-dimensional (3D) fluid-attenuated inversion recovery (FLAIR) with multiplanar reconstruction acquisition is recommended as the core sequence for diagnosis and monitoring of MS, due to its high sensitivity.[3] High quality two-dimensional (2D) pulse-sequences (i.e., ≤3 mm slice thickness and no gap between slices) are an acceptable alternative if it is not possible to acquire sufficiently high quality 3D FLAIR images. Pre-contrast T1-weighted sequences are not required. A 3 T scanner is preferred, but a 1.5 T system is acceptable; 7 T systems are not recommended except in a research setting. Intravenous gadolinium-based contrast agents are invaluable during initial investigations to show dissemination in time and to exclude alternative diagnoses, but only single doses should be used owing to the potential risk of gadolinium accumulation in the brain. Diffusion-weighted imaging may be useful for differential diagnosis or in patients for whom gadolinium is contraindicated, but should not be used as an alternative to gadolinium-enhanced T1-weighted imaging to show acute demyelinating lesions.[3]
Spinal cord imaging
MRI of the spinal cord is recommended for all patients. It is an extremely valuable, and often underused, non-invasive test that is helpful both for identifying MS lesions and for excluding alternative diagnoses. The cervical and thoracolumbar spinal cord, including conus, should be imaged. A 1.5 T or 3 T scanner is acceptable, but there is no evidence that 3 T results in greater detection of spinal cord lesions than scanning at lower field strengths. Axial sequences are helpful in characterising cord lesions, but these sequences are considered to be optional. The use of sagittal gadolinium-enhanced sequences for diagnostic purposes is recommended; these should be done immediately after the gadolinium-enhanced brain MRI if possible.[3]
Laboratory evaluation
Laboratory evaluations in MS are recommended to exclude MS mimics or diseases that may contribute to MS symptoms, such as thyroid disease, vitamin B12 deficiency, and diabetes mellitus.
People with large spinal cord lesions over several segments of spinal cord, poor recovery from optic neuritis, or atypical lesions on MRI brain should undergo antibody testing (anti-aquaporin 4 [AQP4] and anti-myelin oligodendrocyte glycoprotein [MOG] antibodies) to evaluate for neuromyelitis optica spectrum disorders.[5][7][8]
Lumbar puncture with CSF examination for oligoclonal bands, and CSF immunoglobulin G (IgG) index may be done. Due to the invasive nature of lumbar puncture, all other non-invasive tests should be pursued first. Note that the CSF is normal in 10% to 20% of MS cases.
Evoked potentials, particularly visual evoked potentials, should be performed to assist in establishing the diagnosis in patients for whom MRI is contraindicated (e.g., presence of a pacemaker or claustrophobia). These studies are not helpful in monitoring response to treatment.
How to perform a diagnostic lumbar puncture in adults. Includes a discussion of patient positioning, choice of needle, and measurement of opening and closing pressure.
How to take a venous blood sample from the antecubital fossa using a vacuum needle.
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