13B. Clinical features of multiple sclerosis

Multiple sclerosis (MS) is a chronic, inflammatory demyelinating disease of the central nervous system. The demyelination occurs in the periventricular white matter, optic nerve, brainstem, cerebellum, and/or spinal cord.

MS affects caucasian ethnicities more often than others, and is more prevalent in northern countries. It more frequently affects women, and often begins around the age of 30.

Types

There are three types based on the clinical course:

  • Relapsing-remitting MS (RR-MS)
  • Primary progressive MS (PP-MS)
  • Secondary progressive MS (SP-MS)

Relapsing-remitting is the most common subtype, in which the patient has relapses with symptoms of MS followed by remission of the symptoms. The symptoms develop over hours or days and then remit over the next weeks. There is no progression of the symptoms in the periods between disease relapses.

Primary progressive type is the worst subtype, in which the patient has no remission of the symptoms but rather continuous progression and worsening.

Some cases of relapsing-remitting type may progress into secondary progressive type, where the patient stops having remissions and instead have continuous progression.

Etiology

The underlying cause is unknown, but several risk factors are known:

  • EBV infection
  • Smoking
  • Family history

A 2022 study[1] in the journal Science showed that EBV infection (but not other viruses) was associated with a 32-fold increased risk of subsequently developing MS, and that the development of MS occured after the infection. These findings suggest EBV infection as the leading cause of MS.

Clinical features

The patient may present with symptoms of a single lesion or with symptoms of lesions in multiple of the predilected sites in the CNS. The clinical features have a subacute onset and remit over the course of weeks/months (in the relapsing-remitting type)

The first symptoms are usually those of optic or retrobulbar neuritis, which appears as unilaterally impaired vision and retrobulbar pain.

Lesions in the spinal cord can manifest as weakness, spasticity, hyperreflexia, sensory loss, urinary incontinence. Lhermitte sign may be present, where the patient feels an electric shock down the spine when flexing the neck.

Lesions in the cerebellar involvement can manifest as cerebellar symptoms like dysarthria, ataxia, intention tremor and nystagmus. Lesions in the brainstem can manifest as diplopia, vertigo, facial numbness, etc.

Cognitive symptoms and fatigue are also common symptoms. Uhthoff’s phenomenon refers to how the symptoms of MS often worsen in heat, for example due to fever or a hot bath.

Precursor states

A clinically isolated syndrome (CIS) refers to the condition where the patient has had only one attack of MS-like symptoms, but don’t (yet) fulfill the criteria of MS.

A radiologically isolated syndrome (RIS) refers to the condition where the patient has coincidentally discovered radiological signs of MS, but no clinical features.

Both of these syndromes are precursor states to MS, with a high risk of progressing to MS. They should be followed up regularly.