Multiple Sclerosis

Multiple sclerosis (MS) is a chronic and progressive condition that involves demyelination of the myelinated neurones in the central nervous system. This is caused by an inflammatory process involving activation of immune cells against the myelin.

MS typically presents in young adults (under 50 years) and is more common women. Symptoms tend to improving in pregnancy and in the postpartum period.

 

Pathophysiology

Myelin covers the axons of neurones in the central nervous system. This myelin helps the electrical impulse move faster along the axon. Myelin is provided by cells that wrap themselves around the axons. These are Schwann cells in the peripheral nervous system and oligodendrocytes in the central nervous system.

Multiple sclerosis typically only affects the central nervous system (the oligodendrocytes). There is inflammation around myelin and infiltration of immune cells that cause damage to the myelin. This affects the way electrical signals travel along the nerve leading to the symptoms of multiple sclerosis.

When a patient presents with symptoms of a clinical “attack” of MS, for example an episode of optic neuritis, there are usually other lesions of demyelination at the same time throughout the central nervous system, most of which are not causing symptoms.

In early disease, re-myelination can occur and symptoms can resolve. In the later stages of the disease, re-myelination is incomplete and symptoms gradually become more permanent.

A characteristic features of MS is that lesions vary in their location over time, meaning that different nerves are affected and symptoms change over time. The key expression to remember to describe the way MS lesions change location over time is that they are “disseminated in time and space”.

 

Causes

The cause of the demyelination is unclear, but there is growing evidence that it is influenced by a combination of:

  • Multiple genes
  • Epstein–Barr virus (EBV)
  • Low vitamin D
  • Smoking
  • Obesity

 

Signs and Symptoms

Symptoms usually progress over more than 24 hours. At the first presentation symptoms tend to last days to weeks and then improve. There are a number of ways MS can present. These are described below.

 

Optic neuritis

Optic neuritis is the most common presentation of multiple sclerosis. It involves demyelination of the optic nerve and loss of vision in one eye. This is discussed in more detail below.

 

Eye movement abnormalities

Patients may present with double vision due to lesions with the sixth cranial nerve (abducens nerve). There are two key phrases to remember to describe a sixth cranial nerve palsy: internuclear ophthalmoplegia and conjugate lateral gaze disorder.

Unilateral lesions in the sixth nerve causes a condition called internuclear ophthalmoplegia. Internuclear refers to the nerve fibres that connect between the cranial nerve nuclei that control eye movements (3rd, 4th and 6th cranial nerve nuclei). The internuclear nerve fibres are responsible for coordinating the eye movements to ensure the eyes move together. Ophthalmoplegia means a problem with the muscles around the eye.

Lesions in the sixth cranial nerve cause a conjugate lateral gaze disorder. Conjugate means connected. Lateral gaze is where both eyes move together to look laterally to the left or right. It is disordered in a sixth cranial nerve palsy. When looking laterally in the direction of the affected eye, the affected eye will not be able to abduct. For example, in a lesion affecting the left eye, when looking to the left, the right eye will adduct (move towards the nose) and the left eye will remain in the middle as the muscle responsible for making it move laterally is not functioning.

 

Focal weakness

  • Bells palsy
  • Horners syndrome
  • Limb paralysis
  • Incontinence

 

Focal sensory symptoms

  • Trigeminal neuralgia
  • Numbness
  • Paraesthesia (pins and needles)
  • Lhermitte’s sign is an electric shock sensation travels down the spine and into the limbs when flexing the neck. It indicates disease in the cervical spinal cord in the dorsal column. It is caused by stretching the demyelinated dorsal column.

 

Ataxia

Ataxia is a problem with coordinated movement. It can be sensory or cerebellar:

  • Sensory ataxia is the result of loss of the proprioceptive sense, which is the ability to sense the position of the joint (e.g. is the joint flexed or extended). This results in a positive Romberg’s test and can cause pseudoathetosis.
  • Cerebellar ataxia is the result of problems with the cerebellum coordinating movement. This suggestions cerebellar lesions.

 

Disease Patterns

The disease course is highly variable between individuals. Some patients may have mild relapsing-remitting episodes for life whereas others have primary progressive MS that progresses without any improvement in symptoms. There are certain classifications used to describe the pattern of MS in an individual. These patterns are not separate conditions but part of a spectrum of disease activity.

 

Clinically Isolated Syndrome

This describes the first episode of demyelination and neurological signs and symptoms. MS cannot be diagnosed on one episode as the lesions have not been “disseminated in time and space”. Patients with clinically isolated syndrome may never have another episode or develop MS. If lesions are seen on MRI scan then they are more likely to progress to MS.

 

Relapsing-Remitting

Relapsing-remitting MS is the most common pattern at initial diagnosis. It is characterised by episodes of disease and neurological symptoms followed by recovery. In MS the symptoms occur in different areas with different episodes. This can be further classified based on whether the disease is active and/or worsening:

  • Active: new symptoms are developing or new lesions are appearing on MRI
  • Not active: no new symptoms or MRI lesions are developing
  • Worsening: there is an overall worsening of disability over time
  • Not worsening: there is no worsening of disability over time

 

Secondary Progressive

Secondary progressive MS is where there was relapsing-remitting disease at first, but now there is a progressive worsening of symptoms with incomplete remissions. Symptoms become more and more permanent. Secondary progressive MS can be further classified based on whether the disease is active and/or progressing.

  • Active: new symptoms are developing or new lesions are appearing on MRI
  • Not active: no new symptoms or MRI lesions are developing
  • Progressing: there is an overall worsening of disease over time (regardless of relapses)
  • Not progressing: there is no worsening of disease over time

 

Primary Progressive

Primary progressive MS is where there is a worsening of disease and neurological symptoms from the point of diagnosis without initial relapses and remissions. This can be further classified in a similar way to secondary progressive based on whether it is active and/or progressing.

 

Diagnosis

Diagnosis is made by a neurologist based on the clinical picture and symptoms suggesting lesions that change location over time. Symptoms have to be progressive over a period of 1 year to diagnose primary progressive MS. Other causes for the symptoms need to be excluded.

 

Investigations can support the diagnosis:

  • MRI scans can demonstrate typical lesions
  • Lumbar puncture can detect “oligoclonal bands” in the cerebrospinal fluid (CSF)

 

Optic Neuritis

Optic neuritis presents with unilateral reduced vision developing over hours to days. Key features are:

  • Central scotoma. This is an enlarged blind spot.
  • Pain on eye movement
  • Impaired colour vision
  • Relative afferent pupillary defect

 

Multiple sclerosis is the main cause of topic neuritis, however it can also be caused by:

  • Sarcoidosis
  • Systemic lupus erythematosus
  • Diabetes
  • Syphilis
  • Measles
  • Mumps
  • Lyme disease

 

Patients presenting with acute loss of vision should be seen urgently by an ophthalmologist for assessment. It is treated with steroids and recovery takes 2-6 weeks. Around 50% of patients with a single episode of optic neuritis will go on to develop MS over the next 15 years. Changes on an MRI scan help to predict which patients will go on to develop MS.

 

Management

Multiple sclerosis is managed by a specialist multidisciplinary team (MDT) including neurologists, specialist nurses, physiotherapy, occupational therapy and others. Patient should be fully educated about their condition and treatment.

 

Disease Modification

Treatment with disease-modifying drugs and biologic therapy has changed the management of multiple sclerosis so that the aim of treatment is now to induce long term remission with no evidence of disease activity. There are many options that target various mechanisms such as interleukins, inflammatory cytokines and various immune cells. Going into detail about these drugs is beyond what would be expected in your exams. Disease-modifying drug treatment will be coordinated by specialists in multiple sclerosis.

 

Treating Relapses

Relapses can be treated with steroids. NICE recommend methylprednisolone:

  • 500mg orally daily for 5 days
  • 1g intravenously daily for 3–5 days where oral treatment has failed previously or where relapses are severe

 

Symptomatic Treatments

It is important to treat the symptom that result from the disease process along with treating the disease process itself:

  • Exercise to maintain activity and strength
  • Neuropathic pain can be managed with medication such as amitriptyline or gabapentin
  • Depression can be managed with antidepressants such as SSRIs
  • Urge incontinence can be managed with anticholinergic medications such as tolterodine or oxybutynin (although be aware these can cause or worsen cognitive impairment)
  • Spasticity can be managed with baclofen, gabapentin and physiotherapy

 

Last updated April 2019
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