Plaques can be found anywhere in the CNS, but particularly in the :

• Optic nerves
• Periventricular region
• Corpus callosum
• Brainstem and cerebellar connections
• Cervical spinal cord:
  • Posterior columns
  • Corticospinal tracts

 

Note that in all the below instances, the disease progressively gets worse. However! – some people may only have 1 (or a very small number of) attacks of the disease – which we could call benign MS. Essentially, this does not progressively deteriorate, although there is now some evidence that after several decades, there is actually a gradual decline in function, but not on the same scale as other varieties of the disease.

• Optic Nerve:
  • Optic Neuropathy – there is typically blurring of vision in one eye that develops over a period of days. It can vary from ‘frosted glass’ sensation, to severe visual loss, but there is rarely blindness. There might also be some slight eye pain. It is almost always unilateral, and full recovery occurs within 2 months.
  • Optic disc swelling can occur if this area of the nerve is affected, but if the lesion is higher up the nerve than this, there are unlikely to be any ophthalmoscopic abnormalities – ‘When the patient sees nothing the doctor sees nothing’ – this type of lesion is known as retrobulbar neuritis.
    • Disc swelling in optic neuritis causes early and gradual visual loss, which can help you differentiate it from disc swelling due to raised intracranial pressure – which causes sudden late, visual loss.  
  • Uthoff’s phenomenon – worsening of neurological symptoms (particularly vision), after a period of exercise and/or increase body heat (e.g. on a hot day, or after taking a hot bath). This is because conduction is slowed by an increased temperature. Another common finding with this is that the patient may be able to get into a hot bath, but cannot get out!
  • Relative afferent pupillary defect – this is often seen, and will usually persist even after recovery from the episode.
  • Late signs – often the vision fully resolves, and there are no lasting defects. But in some cases there may be:
    • Scotoma – a dark spot in the centre of the vision
    • Colour vision problems
    • Disc pallor
  • Diplopia
  • Nystagmus
  • Loss of colour vision – especially the colour red – which may appear grey
• Spinal cord:
  • Motor – UMN lesions – weakness, spacticity, brisk reflexes. Generally develops over a period of days or weeks, gradually getting worse. Usually the result of demyelination in the spinal cord. May have:
    • L’Hermitte sign – on voluntary flexing of the head, there is an electric shock sensation travelling down the spine and into the limbs. Sometimes called the barber chair phenomenon. Due to a lesion in the posterior columns.
  • Sensory – numbeness, parasthesia (pins + needles, neuropathic pain). Typically in an ascending pattern over a period of days
  • Autonomic – incontinence (urine)/constipation (bowel), sexual dysfunction (erection problems, reduced sensation)
• Brain stem – ophthalmaplegia (INO), neuralgia, hearing loss, vertigo, dysphagia, dysphonia
  • INO – Internucelar ophthalmoplegia – a condition affecting the movement of the eyes that is characteristic of MS. When covering one eye, unilateral movements will be normal. But when together, the adducting eye will not move past the midline. It may affect one or both of the eyes, and the patient may complain of horizontal diplopia. It is due to a lesion in the medial longitudinal fasciculus – which is a heavily myelinated tract, which connects optic brainstem nuclei on either side of the brainstem. Thus, conjugate movements, but not unilateral movement, is affected.

• • Facial numbness / weakness
  • Vertigo
  • Dysarthria
  • Dysphagia
• Cerebellum – ataxia
• Cerebral hemispheres – anything! Rarely there can be:
  • Epilepsy
  • Trigeminal neuralgia
  • Tonic spasms – a brief spasm of the limbs.
• Fatigue! – important to exclude other causes:
  • Anaemia
  • Lack of sleep
  • Hypothyroid
  • Medication
  • Depression
  • Sleep apnoea
  • Check sleep hygiene
    • Give modfinil

End-stage Multiple Sclerosis

• Spastic tetraparesis
• Ataxia
• Optic atrophy
• Brainstem signs
• Psuedobulbar palsy
• Urinary incontinence
• Dementia

• Optic neuritis
• Acute myelitis (especially in spinal cord)

Examination

A targeted neurological examination design to elicit features specific to MS may be useful in suspect patients:

• Eyes
  • Visual acuity
  • Eye movements (INO, pain, nystagmus)
  • Colour vision (may be reduced, especially red)
  • Fundoscopy – may show optic disc swelling
• Limbs
  • Tone, reflexes, power and co-ordination
  • Cerebellar sings – ataxia, hypotonia
  • Sensory impairment of face or limbs
• Cognitive function – may be reduced

Investigations

• MRI – this is THE definitive investigation.
  • Will show plaques in 85% of clinical presentations
  • Multiple plaques are usually present in MS – a typically flare up will have about 10 plaques.
  • The correlation of MRI plaques and clinical disease is poor.
  • CT scan is not helpful
• Bloods
  • May be useful to exclude differentials. Consider:
    • FBC
    • CRP
    • TSH
    • B12
    • LFTs
    • CMP
• Visual evoked potentials – can detect lesions in visual pathway. The patient has EEG probes placed on the skull to measure brain response to visual stimuli. They are then given a visual stimulus, and the time between the visual stimulus and the brain response (on EEG) is measured. If the response is delayed this is evidence of some sort of optic nerve lesion.
• Lumbar puncture – Oligoclonal bands in CSF
  • Similar to monoclonal bands seen in Lymphoma. However, where monoclonal bands represent massive proliferation of one type of plasma cell (and thus 1 antibody), oligoclonal bands represent massive proliferation of a small number of type of plasma cell.
  • Usually only necessary when MRI cannot confirm the diagnosis.
  • Actually not that useful! – in 80% of cases there will be oligoclonal bands, but these just show that there is a lot of antibody to something  in the CSF.

Differentials

• Migraine
• Cerebral neoplasms (primary and secondary)
• Nutritional deficiencies – particularly B12 or copper
• Infections – e.g. syphilis, HIV
• Motor neurone disease
• Psychiatric disease / functional
• Vascular Causes – tend to present suddenly
• Other progressive diseases – tend to follow a progressive, rather than relapsing/remitting pattern.
• MRI lesions – several other conditions can mimic the MRI lesions seen:
  • Sarcoidosis
  • SLE
  • Bechet’s syndrome

Diagnosis

• At least 1 ‘attack’ – typically several months apart
• Multiple plaques on MRI
• OR
• A single attack / progressive disease MS
• Multiple plaques on MRI
• Other evidence, e.g.
  • Oligoncloncal bands in CSF
  • Visual evoked potentials

Management

• Try to work out if true relapse vs pseudo-relapse (see Progression / Prognosis above)
• If pseudo-relapse  – treat the underlying cause
• If true relapse:
  • Short course of steroids – e.g. methylprednisolone, 1g/day for 3-5 days IV or PO
    • Can induce remission, and reduce the severity of the relapse – do not alter long-term outcome.
  • Urgent neurology referral – if acutely disabling symptoms consider same-day neurology review (either via Emergency Department or by liaising with patient’s previously known specialist)
  • Avoid using steroids in patients whose symptoms involve only fatigue or sensory loss, or induce only very minimal disability as the benefit is very limited

Rehabilitation

• VERY IMPORTANT – treat all infections promptly – particularly UTI’s – as these are known to exacerbate symptoms.
• Urinary incontinence – when residual volume is >100ml, manage with oxybutinin, or self-catheterisation.
• Physiotherapy – reduces pain in spasticity, particularly in flexor spasms of the lower limb. This can also be relieved with botox injections and other agents such as baclofen, diazepam, tizanidine. With these other agents, you should start at a low dose, and increase gradually as necessary.
• Cannabis – is used by many patients for symptom relief. There are trials currently ongoing of cannabis extracts (e.g. Sativea).
• Pressure sores – should be prevented at all costs!
• Depression and anxiety are common in MS patients. Management is typically similar to non-MS patients – including psychology and use of antidepressant medication.