11th August 2024

Clinical features and diagnosis of multiple sclerosis

Symptoms of MS

The symptoms of MS vary and depend on the location of the demyelinating lesion. Common presentations of MS include optic neuritis, usually unilateral, and transverse myelitis. Individuals can also present with brainstem syndromes including internuclear ophthalmoplegia, cerebellar syndromes characterised by ataxia, and sensory syndromes. In addition, MS can present with symptoms of cognitive decline, depression or psychosis. As neural inflammation resolves and remyelination occurs there can be some recovery of function.

MS seems to be less active during pregnancy, especially in the last trimester, however many patients with MS have a relapse of symptoms within 3 months of delivery. MS does not affect fertility or increase the risk of miscarriage.

Uhthoff’s phenomenon is a transient worsening of symptoms when the body is overheated, such as in hot weather, during vigorous exercise or in a hot shower, and is often observed with MS.

Internuclear ophthalmoplegia (INO) is a gaze disorder where the affected eye shows impairment of adduction on conjugate lateral gaze. This is due to demyelination of the medial longitudinal fasciculus, a heavily myelinated tract connecting the oculomotor nucleus on the side of the lesion with the contralateral abducens nucleus. The commonest causes of INO are MS and brainstem infarcts.

Optic neuritis and MS

Optic neuritis is the first demyelinating event in 20% of patients who are diagnosed with MS. Approximately 40% of patients with MS experience optic neuritis at some point during their disease course.

Symptoms of optic neuritis include:

• Pain which is worsened by eye movement
• Temporary reduction in vision, the extent of which varies, and which can be permanent
• Visual field loss
• Loss of colour vision and colour perception
• Flashing lights, especially with eye movements
• Rapid afferent pupillary defect (RAPD), occurs due to asymmetrical disease of the optic nerve. The affected pupil will dilate to the light stimulus instead of constricting

A key differential for a RAPD is the Holmes-Adie pupil, which is often idiopathic but can be caused by a lesion in the efferent parasympathetic pathway. It is characterised by slow and incomplete constriction of the pupil to light, and, after the pupil has constricted, it remains so for a long time (tonic pupil). The full syndrome also includes an absence of deep tendon reflexes (although an abnormal pupil may be seen in isolation).

Diagnosis of MS

Diagnosis is based on clinical findings and further confirmatory tests, such as:

• MRI brain and spine: imaging modality of choice for both confirming and monitoring disease progression
• Evoked potentials: results not specific for MS but can be useful for the identification of subclinical lesions. Visual evoked potential testing can reveal slowing of conduction in the optic nerve due to demyelination
• Lumbar puncture: CSF evaluated for oligoclonal bands (OCB) and intrathecal IgG production. CSF protein levels can also be elevated. CSF OCB detection is not specific for MS and 5-10% patients diagnosed with MS do not show CSF abnormalities

Diagnosis of MS is made as per the McDonald diagnostic criteria, comprising clinical, radiographic, and laboratory factors. MS can be diagnosed when a patient has experienced at least two clinical attacks, or has evidence of MS plaques in at least two distinct brain areas on an MRI. This is described as having plaques separated in time and space.

Image Source: doi.org (2022), s00062-022-01144-3, Licensed under a creative commons licence. Available for free at: https://doi.org/10.1007/s00062-022-01144-3 (Accessed: 17 July 2024)

Classification of MS

• Relapsing remitting MS (RRMS): approximately 85% of cases. Characterised by unpredictable relapses followed by periods of remission, which can last for months to years. Deficits caused by relapses may resolve or be permanent. If they resolve completely between attacks it is classified as benign MS.
• Primary progressive MS (PPMS): approximately 10% of cases. Patients do not recover from their first relapse, and symptoms decline continuously without clear attacks or episodes of remission. This subtype is common in patients with older disease onset.
• Secondary progressive MS (SPMS): seen in approximately 80% of patients who initially present with RRMS. Characterised by  progressive neurological decline between acute attacks without definite periods of remission. SPMS causes the highest amount of disability.
• Progressive relapsing MS (PRMS): characterised by progressive worsening of neurological symptoms with superimposed flares from the onset of MS.
• Clinically isolated syndrome (CIS): a single episode of neurological symptoms lasting over 24 hours. Individuals who develop CIS may or may not go on to develop MS. Further investigation with an MRI is recommended. The detection of oligoclonal bands in CSF is the most sensitive predictor of conversion from CIS to MS.