What is multiple sclerosis?
MS is a chronic autoimmune T-cell mediated inflammatory disorder of the CNS. Multiple plaques of demyelination occur throughout the brain and spinal cord, occurring sporadically over years (dissemination in space and time which is crucial for diagnosis).
What gender does MS more commonly occur in?
What is the mean age of onset of the disease?
Approximatley 30 years (range 20-40)
What immune cell is impliated in the development of MS?
T-cell mediated autoimmune disease
What parts of the nervous system does MS affect?
- Optic nerve
- Spinal Cord
What neuronal structures are affected by MS?
- Myelin sheaths
What are the cardinal pathological features of of MS?
Plaques of demyelination (2-10mm)
Where do plaques most commonly occur in MS?
Can occur anywhere in CNS, but most commonly:
- Optic nerves
- Periventricular region
- Corpus callosum
- Brainstem and cerebellar connections
- Cervical cord (corticospinal and posterior columns)
What does the focal acute inflammation cause in terms of nerve conduction?
What are the pathologial outcomes that can occur from acute demyelinating episodes?
Recovery and remyelination, or permanent axonal destruction
What is the pathological basis for the progression of MS as a disesase?
Progressive axonal damage
What proportion of individuals with relapsing remitting MS develop secondary progressive MS?
What are the different types of progression of MS?
- Relapsing remitting MS
- Secondary Progressive MS
- Primary Progressive MS
What is relapsing remitting MS?
Symptoms occur in attacks (relapses) with a characteristic time course: onset over days and typically recovery, either partial or complete, over weeks. Patients may accumulate disability over time if relapses do not recover fully.
How often do relapses occur on average in relapsing remitting MS?
On average patients have one relapse per year but occasionally many years may separate relapses (benign MS – 10% of patients).
What is secondary progressive MS?
Late stage of MS consists of gradually worsening disability progressing slowly over years. 80% of those with RRMS progress to this stage by 35 years. Relapses may sometimes occur in this progressive phase (relapsing–progressive MS).
What is primary progressive MS?
Characterized by gradually worsening disability without relapses or remissions. Typically presents later and is associated with fewer inflammatory changes on MRI.
What proportion of those with MS have primary progressive MS?
How do those with MS most commonly present?
Wide variety of possible symptoms may occur depending on the anatomical site of lesions. Common ones include:
- Optic neuritis
- Brainstem demyelination
- Spinal cord lesions
What are features of MS affecting the brainstem?
- Vertigo with nystagmus
- Facial numbness/weakness
- Pyramidal signs
Bilateral internuclear opthalmoplegia - Pathognomonic of MS
What is internuclear opthalmoplegia?
- Impaired adduction of the eye on the abnormal side
- Horizontal jerk nystagmus in the opposite eye upon lateral gaze away from the side of the lesion
What is the mechanism behind internuclear opthalmoplegia?
INO is caused by a lesion in the medial longitudinal fasciculus (MLF). The MLF connects the abducens nerve (CNVI) nuclei to the oculomotor nerve (CNIII) nuclei and facilitates conjugate eye movements during lateral gaze by coordinating adduction with abduction.
What are features of spinal cord lesions in MS?
- Paraparesis - developing over days/weeks
- Limb numbness/weakness + tingling
- Lhermitte's sign positive
- Tight band sensation around chest - thoracic lesion
What is optic neuritis?
A demyelinating inflammation of the optic nerve. It is also known as optic papillitis (when the head of the optic nerve is involved) and retrobulbar neuritis (when the posterior part of the nerve is involved)
What are causes of optic neuritis?
- Sjogren's syndrome
- Behcets disease
- Vitamin deficiency
What are signs of optic neuritis?
- Altered visual acuity - may range from 6/6 to PL
- Lack of red reflex/retina obsured - large haemorrhage
- Red desaturation
- Central scotoma
- Swollen optic disc - if inflamamtion anterior
What are the symptoms of optic neuritis?
Usually a woman, aged 20-40
- Disturbance of vision of one eye - scotoma, floaters
- Pain that worsens on eye movement
What are common symptoms seen in MS?
- Visual changes
- Sensory symptoms
- Clumsy limbs
- Urinary incontince - urgency/frequency
- Sexual dysfunction
- Temperature sensitivity
What sensory features are often seen in individuals with MS?
- Pins and needles
- Trigeminal neuralgia
- Reduction/Loss in proprioception in feet
- Feeling of water trickling down skin
- Uthoff's Phenomenon
What eye signs might you see in MS?
- Blurred vision - optic neuropathy
- Optic neuritis - disc swelling
- Internuclear Opthalmoplegia
- Optic disc swelling
- Argyll-Robertson pupil
Why do individuals with MS become clumsy and ataxic?
Due to cerebellar lesions and loss of proprioception
Why do individuals with MS develop urinary urgency/frequency?
Hyper-reflexia of the bladder
What is Uthoff's Phenomenon?
Signs/symptoms worse on hot day or after exercise e.g. after a hot bath
What is the cause of Uthoff's Phenomenon?
Heat slows conduction in nerve fibres, causing worsening of symptoms
What are argyle robertson pupils?
- Miosis (small pupils)
- Absence of the pupillary light response
- Brisk accommodation reaction
- Bilateral involvement.
What is the mechanism behind Argyll-Robertson pupils?
Caused by a pretectal lesion in the dorsal midbrain affecting the fibres of light reflex, which spare the fibres of the accommodation pathway that innervate the Edinger–Westphal nuclei
What are motor features of MS?
- Features of Myelitis
What sexual/GU features can occur in MS?
- Erectile dysfunction
- Urine retention/incontinence
What are GI features of MS?
What features might suggest non-MS causes of some of the neurological features seen in MS?
- Positional vertigo
- Bilateral optic neuritis
- CSF leucocytosis
What are features of late stage MS?
- Spastic tetraparesis
- Optic atrophy
- Brainstem signs (e.g. bilateral INO)
- Pseudobulbar palsy
- Urinary incontinence
- Cognitive impairment, often with frontal lobe features
What criteria are used to diagnose MS?
The Mcdonald Criteria
What investigations would you perform if you suspected MS?
- Visual evoked potentials
What might you see on MRI in someone with
Demyelinating Plaques - in 85% of clinical presentations
- Multiple plaques are usually present in MS
If someone with MS was experiencing fatigue, what other causes of fatigue would you want to exclude?
- Lack of sleep/apnoea/poor sleep hygeine
What is Devic's Disease?
Considered a subtype of MS, presents with features of optic neuritis and Acute transverse myelitis
What do plaques signify in terms of disease activity in these areas?
There is active disease in areas where plaques are present
What would you be looking for on LP in someone with features of MS?
Oligoclonal bands of IgG on electrophoresis
What is rule of thumb with the presence of Oligoclonal bands in CSF and diagnosis of MS?
Present in CSF, but not in Serum
What is visual evoked potential testing?
Detect lesions in visual pathway - The patient has EEG probes on the skull the 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.
What other conditions can mimic MS lesions on MRI?
- Bechet's syndrome
What non-pharmacological apsects would you consider when managing someone with MS?
Discuss the following
- Living arrangements
- General future plans
- Lifestyle advice - exercise, smoking, avoid stress
- MDT input - physio, OT, psychiatry etc.
If someone had an acute relapse of MS, how would you manage them?
IV/PO Methyprenisolone - 3-5 days (shortens relapse)
What dose of methyprednisolone would you give someone having an acute relapse of MS?
What disease modifying medications would you use in an attempt to reduce relapse rate in RRMS?
- Dimethyl Fumarate
B-interferon and Glatiramer Acetate now no longer recommended by NICE in England and Wales
How would you manage symptoms of spasticity in someone with MS?
- 1st line - Baclofen, Gabapentin
- 2nd line - Tizanidine, dantrolene
- 3rd line - benzodiazepines
How would you manage tremor symptoms in someone with MS?
How would you manage symtpoms of urinary incontinence in someone with MS?
- Antimuscarinic medications - tolterodine, oxybutinin
- Teach self-Catheterisation
How would you manage symptoms of fatigue in someone with MS?
How would you manage symptoms of constipation in someone with MS?
How would you manage symptoms of dysaesthesia/pain in someone with MS?
How would you manage speech/swallowing difficulties in someone with MS?
When should you commence treatment for urinary symptoms seen in MS?
Once residual bladder volume > 100ml
Which individuals would be involved in an MDT managing someone with MS?
- MS nurse
- Occupational therapist
- Speech and language therapist
- Rehab sepcialist
- Continence advisor
- Care workers
How do individuals with MS most commonly die?
- Renal failure