Diagnosis of MS and differential diagnosis

Neurologists pay particular attention to the criteria used to diagnose MS, and these are regularly reviewed in the light of the new technologies available to us. Schumacher's 1965 criteria were modified by Charles Poser in 1983 and then by Ian McDonald in 2001, with revisions in 2005, 2011, 2017 and 2024. The 2024 criteria were formally published in October 2025 and are intended to make the diagnosis of MS faster and more consistent while maintaining a high level of specificity. The principal change concerns dissemination in time, which no longer needs to be demonstrated in certain cases. As before, these criteria also emphasise the need to exclude any other neurological disease that might better explain the patient's symptoms, the MRI abnormalities and the CSF disturbances.

In the presence of a radiologically isolated syndrome, the diagnosis of MS may be made if there is at least one lesion in two distinct territories of the CNS : 1° in the periventricular region, or 2° in the cortical or juxta cortical area, or 3° in the posterior fossa (brainstem and cerebellum), or 4° in the spinal cord, or 5° in the optic nerve. In addition, one or more of the following criteria must be met: a ‘positive’ CSF (presence of specific IgG oligoclonal bands or an elevated kappa index); at least six lesions with a detectable central vein on MRI; temporal dissemination (a contrast-enhancing lesion on MRI together with other non-enhancing lesions, or the appearance of a new lesion on follow-up).

In the presence of a clinically isolated syndrome, the diagnosis of MS must be formally established if lesions are present in at least two typical MS locations and if one or more of the following criteria are met: positive CSF; at least six lesions with a central vein; temporal dissemination on MRI; lesions present in four or five of the typical MS locations. The diagnosis of MS may also be established when lesions are confined to a single typical MS site, provided there is positive CSF and six lesions with a central vein, or positive CSF and at least one paramagnetic rim, or temporal dissemination together with either lesions with a central vein or a paramagnetic rim.

To diagnose a primary progressive form of MS, the progression of disability must be determined retrospectively or prospectively over a period of at least one year. The other criteria are then the same as those described for the clinically isolated syndrome.

The rule is also to exclude other diseases that could "mimic" MS. We should be wary of relying excessively on brain imaging and avoid at all costs a falsediagnosis of MS. The differential diagnosis must therefore consider other pathologies:

• Migraines with aura or ophthalmic migraines: these are characterised by visual disturbances, sometimes in the absence of headaches, which may suggest optic neuritis, and may be accompanied by sensory disturbances (paraesthesia) which may last longer than the headache. In addition, migraine sufferers regularly present small hyperintense foci on MRI which could be interpreted as MS lesions. Given the high frequency of migraines in the general population, people can obviously suffer from both migraines and MS. Headache is NOT a symptom of an MS relapse.
• Neuromyelitis optica is an inflammatory disease of the CNS, preferentially affecting the spinal cord and optic nerves, and more rarely the brain itself. It can occur at any age in flare-ups. It is now well differentiated from MS and more easily diagnosed by the detection in the blood of specific antibodies, either anti-aquaporin 4 or anti-MOG (Myelin Oligodendrocyte Glycoprotein).
• Nervous Lyme disease or neuroborreliosis, in which the CSF is severely disturbed and specific anti-Borrelia antibodies are detectable in the blood and CSF.
• Systemic inflammatory diseases which sometimes manifest themselves mainly in the CNS: neurolupus, neurosarcoidosis, etc.
• Susac syndrome, which affects the retina, inner ear and periventricular white matter, is an inflammation of the arteriolar walls in these three areas which can be clearly seen in the retina using fluoangiography. IgG oligoclonal bands are never seen in this syndrome. The main after-effect is deafness, which is never seen in MS.
•  Abnormal signals are also seen on MRI in people over 55, especially if they have vascular risk factors (high blood pressure, diabetes, smoking, high cholesterol). In this case, brain imaging is less specific, but MS lesions have characteristics that are increasingly recognised by experienced radiologists and neurologists. 
• Amyotrophic Lateral Sclerosis (ALS) is, in principle, not a problem of differential diagnosis with MS. In France (and only in France...), it is known as Charcot's disease, but Charcot, a brilliant founder of neurology, described many neurological diseases, including ALS and MS. ALS is not an inflammatory disease, unlike MS, and never causes sensory disorders (optic nerves are intact). It is a neurodegenerative disease that selectively causes the death of motor nerve cells in both the brain and the spinal cord. The result is progressive paralysis of the 4 limbs, the respiratory muscles, swallowing and phonation. It is fatal within a few years and there is currently no cure.

This list, which is not exhaustive, explains why the initial diagnosis can sometimes remain in abeyance and can only be definitively retained or excluded on the basis of the clinical (new attack) and radiological (new lesions on MRI) evolution in the months and years that follow.