Multiple Sclerosis Flashcards
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
Clinical Features
What are the ways multiple sclerosis can present?
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
- most common presentation of multiple sclerosis. It involves demyelination of the optic nerve and loss of vision in one eye
- Key features are:
Central scotoma. This is an enlarged blind spot.
Pain on eye movement
Impaired colour vision
Relative afferent pupillary defect
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: demylination of MEDIAL LONGDTUDINAL FASCICULUS (connection between 3rd, 4th and 6th cranial nerve nuclei): affected eye (ispsilateral to lesion side) is slow / unable to adduct and normal eye exhibits nystagmus on abduction
- 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.
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
(distinct gadolinium enhancing patches in the periventricular white matter)
- Lumbar puncture can detect “oligoclonal bands” in the cerebrospinal fluid (CSF)
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.
DMARDs
- Treatment with disease modifying drugs and biologic therapy has changed the management of multiple sclerosis
- First-line injectables such as BETA-INTERFERON and glatiramer
- New oral agents such as dimethyl fumarate, teriflunomide and fingolimod
- Biologics such as natalizumab and alemtuzumab.
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
