Multiple Sclerosis Flashcards
What would a patient with MS describe in their history?
Varies depending on site of inflammation.
Optic neuritis (commonest):
Unilateral deterioration in visual acuity and colour perception.
Pain on eye movement.
Sensory system: Pins and needles, numbness, burning.
Motor: Limb weakness, spasms, stiffness, heaviness.
Autonomic: Urinary urgency, hesitancy, incontinence, impotence.
Psychological: Depression, psychosis.
Uhthoff’s phenomenon: Transient increase or recurrence of symptoms due to conduction block precipitated by a rise in body temperature.
Describe the pathogenesis of MS.
CNS inflammation in MS is mediated by activated T lymphocytes which cross the blood-brain barrier and initiate an inflammatory cascade resulting in areas (or plaques) of demyelination.
These places develop in any part of the CNS but certain areas, such as optic nerves, brain stem, spinal cord and peri ventricular white matter are particularly susceptible.
—Peripheral nerves are not affected.
Define multiple sclerosis •Relapsing-remitting MS •Clinically isolated syndrome •Primary progressive MS •Marburg variant
Inflammatory demyelinating disease of the central nervous system.
Relapsing-remitting MS:
•Commonest form.
•Characterised by clinical attacks of demyelination with complete recovery in between attacks.
Clinically isolated syndrome:
•Single clinical attack of demyelination; (does not qualify as MS);
•10–50% progress to developing MS.
Primary progressive MS:
•Steadily accumulation of disability with no clear relapsing-remitting
pattern.
Marburg variant:
•Severe fulminant variant of MS leading to advanced disability of death within a period of weeks.
•Distinct from acute disseminated encephalomyelitis (ADEM).
Describe the aetiology of MS.
Unknown.
Likely that genetic and environmental factors both play a role.
—1st degree relatives of an individual with MS have a 5% risk of developing the disease. (Compared with 0.1% in general population)
What would be found on examination of a patient with MS?
Optic neuritis:
Impaired visual acuity (most common), loss of coloured vision. On fundoscopy, in active disease, there is a swollen optic nerve head, in chronic disease, there may be optic atrophy.
Visual field testing:
Central scotoma (optic nerve affected) or field defects (optic radiations affected).
Relative afferent pupillary defect:
Tested with a swinging torch test. Both pupils contract when light is shone on the unaffected side, both pupils dilate when light is swung to the diseased (eye).
Internuclear opthalmoplegia:
Lateral horizontal gaze produces a failure of adduction of the contralateral eye. This indicates a lesion of the contralateral medial longitudinal fasciculus.
Sensory: Paraesthesia (vibration and joint position sense loss more common than pain and temperature).
Motor: UMN signs (e.g. spastic weakness, brisk reflexes).
Cerebellar: Limb ataxia (intention tremor, past-pointing and dysmetria on finger-nose test and heel-shin test), dysdiadochokinesis, ataxic wide-based gait, scanning speech.
Lhermitte’s phenomenon: Electric shock-like sensation in arms and legs precipitated by neck flexion.
Describe the three patterns that MS presents in.
Relapsing-remitting form (80-90%)
•Characterised by of early defined relapses caused by the appearance of new areas of demyelination.
•Symptoms develop gradually over days or weeks and resolve over several weeks.
•Resolution can be complete or incomplete, but there is no disease progression between specific relapses.
•Clinical features depend on location of demyelination plaques, Eg:
—Brain stem demyelination ➡️ double vision, nystagmus, vertigo, facial numbness, dysarthria and ataxia
—Spinal cord demyelination ➡️ weakness and paraesthesiae in limbs and impaired bladder function.
Primary progressive form (10-20%)
•Characterised by a slow and inexorable progression in neurological symptoms and disability.
•Tends to present at older age, most commonly with a paraparesis caused by thoracic spinal cord demyelination.
Secondary progressive form
•Approx 75% those presenting with relapsing-remitting MS will eventually develop secondary progressive disease.
•Characterised by slowly progressive disability unrelated to acute relapses.
•Patients may develop widespread neurological deficits.
—Spinal cord, cerebellum and brain stem dysfunction are common.
•Cognitive impairment may occur in advanced disease.
What investigations would you perform if you suspected your patient had MS?
Diagnosis based on two or more CNS lesions with corresponding symptoms, separated in time and space (McDonald criteria).
Lumbar puncture:
Microscopy to exclude other infective or inflammatory causes. CSF electrophoresis shows unmatched oligoclonal bands.
MRI-brain, cervical and thoracic spine (with gadolinium):
•Plaque detection is highlighted as high-signal lesions.
•Gadolinium enhancement indicates an active lesion.
•White matter lesions are found particularly in periventricular region, corpus callosum, brain stem and cervical cord.
Evoked potentials: Visual, auditory or somatosensory evoked potentials (VEP, BEP, SEP) may show delayed conduction velocity. VEPs are delayed in ~90% of patients with MS.
What are the McDonald’s criteria?
Diagnosis based on two or more CNS lesions with corresponding symptoms, separated in time and space.
How would you manage a patient with MS?
Multidisciplinary management:
Combined care involving neurologists, specialist nurses, physiotherapists, psychologists and pain team.
Acute attacks:
•Corticosteroids (IV methylprednisolone 1 g daily for 5 days) hastens recovery but not degree of recovery.
•Infection must first be ruled out.
•If poor response to high-dose corticosteroids: plasma exchange.
Relapsing–remitting MS:
•b-Inteferon or glatarimer SC injections may reduce relapse frequency by ~33% by modulating T-helper cell activity.
•Natalizumab (monoclonal against a4-integrin preventing T-cell movement into the CNS) monthly IV infusions reduces relapses by ~69% and disability progression.
•Mitoxantrone should be reserved for patients with rapidly advancing disease who have failed other therapies.
•Newer oral agents (cladiribine, fingolomid) have been shown to be superior to b-Inteferon, reducing relapse rate by ~50%.
Progressive MS: Clinical trials have shown no or limited effectiveness for the available treatments.
Symptomatic treatment:
•Bladder disturbances: Anticholinergics (e.g. oxybutynin), intermittent self-catheterization.
•Spasticity: Baclofen, gabapentin or tizanidine if generalised. Botox injections if localised.
—Consider intrathecal baclofen if immobile.
•Neuropathic pain: Consider carbamazepine or gabapentin.
•Depression: Psychological support, antidepressants.
•Fatigue: Modafinil has been shown to be beneficial.
What complications might you expect to arise in a patient with MS.
Progressive disability, cognitive impairment.
The expanded disability status scale (EDSS) is a standardised method of quantifying disability.
Complications of treatment: Treatment with natazulimab carries a 1 in 1000 risk of progressive multifocal leukoencophalopathy (PML).
What is the prognosis for a patient with MS?
Relapsing-remitting MS can eventually result in residual disability followed by a secondary progressive phase.
10% have a benign course (one or more initial episodes, then no symptoms for many years).
Relatively good prognostic features include; initial symptoms of optic neuritis or isolated sensor dysfunction, younger age at onset and little or no disability after 5yrs.
Relatively poor prognostic features include older age at onset, initial symptoms involving cerebellar, spinal or pyramidal systems, high initial disease activity and a large number of white matter lesions on MRI at time of first clinical attack.
