Neurology - Multiple sclerosis Flashcards
What is multiple sclerosis
Chronic progressive demyelination of the neurones in the central nervous system
Caused by an inflammatory process involving the activation of immune cells against the myelin.
Pathophysiology of MS in more detail
Typically only the central nervous system (oligodendrocytes)
There is inflammation around the myelin and infiltration of immune cells that damage the myelin
This affects electrical signal transmission and results in symptoms
Lesions vary in their location over time - dissemination in time and space
What is the function of oligodendrocytes?
Produce myelin to wrap around the axons
Causes of MS
Cause of demyelination is unclear but it may be influenced by a combination of:
- Multiple genes
- EBV
- Low vitamin D
- Smoking
- Obesity
Is demyelination in MS permanent?
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.
Signs and symptoms of MS - broad
Optic neuritis - most common
Eye movement abnormalities
Focal weakness
Focal sensory symptoms
Ataxia
Depression/labile mood
Speech/swallowing difficulties
Bowel/bladder dysfunction
What is the presentation of optic neuritis?
Unilateral reduced vision over hours to days
Central scotoma (enlarged blind spot)
Pain on eye movement
Impaired colour vision
RAPD
What things other than MS can cause optic neuritis?
Sarcoidosis SLE Diabetes Syphilis Measles Mumps Lyme disease
How is optic neuritis treated?
Steroids
What eye movement abnormalities can occur in MS?
6th nerve lesions can occur - Can cause double vision
Unilateral lesions can cause intranuclear ophthalmoplegia
Lesions can also cause conjugate lateral gaze disorders
What is intranuclear 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). This is an interneuron called the medial longitudinal fasciculus (MLF).
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.
INO is a conjugate lateral gaze palsy
What is conjugate lateral gaze palsy?
Inability of both the eyes to look together to the side
In the affected eye the eye will not abduct, whereas the unaffected eye will adduct to the nose
Nystagmus is usually observed with the abduction of the contralateral eye, as it tries to normalise the two discordant images being sent to the brain simultaneously
What focal weakness problems can occur?
Bells Palsy
Horners syndrome
Limb paralysis
Incontinence
What focal sensory symptoms can occur?
Trigeminal neuralgia
Numbness
Paraesthesia (pins and needles)
Lhermitte’s sign
What is Lhermitte’s sign?
An electric shock sensation that 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.
What are the types of ataxia?
Sensory - loss of proprioceptive sense, resulting in positive Romberg’s test
Cerebellar - problems with the cerebellum coordinating movement
Most common symptoms on initial presentation
Limb numbness/tingling
Limb weakness (subacute onset)
Cerebellar symptoms
Optic neuritis
Central symptoms of MS
- Motor - loss of power/spacticity
- Sensory e.g. tingling, parasthesia
- Cerebellar - tremor, balance issues
- Fatigue
- Depression/labile mood
Ophthalmic symptoms of MS
Nystagmus
Optic neuritis
Diplopia - internuclear ophthalmoplegia
Otolaryngeal symptoms of MS
Dysphagia
Slurring/stuttering speech
Urinary and GI symptoms of MS
Urinary frequency, incontinence, retention
Constipation, diarrhoea
Important things to ask in the history of MS - other than HPC?
Past medical history (such as any history of focal neurologic deficit, or other autoimmune diseases)
Family history of MS/other autoimmune diseases
Smoking status Diet Impact on activities of daily living Driving status Falls risk assessment
Examination in suspected MS
Full neurological examination including CN exam and cerebellar examination
Lesions in these cranial nerves may cause
CN2 - optic neuritis, RAPD
CN3,4,6 - related eye movement abnormalities or INO
CN5 - facial paraesthesia
CN7 - weakness in facial muscles - can mimic stroke
CN8 - balance loss, sensorineural hearing loss
CN9,10,12 - loss of motor function to tongue/pharynx resulting in speech and swallowing problems
CN11 - Loss of motor function to sternocleidomastoid and trapezius resulting in neck weakness and hypertonia.
Cerebella signs of MS
Nystagmus - towards the side of the lesion
Intention tremor
Scanning dysarthria - sentences or even words are broken up into a number of separate syllables that can be expressed at varying volume. It may appear as though the patient is searching for (or scanning for) the correct next word/sound.
Risk factors for MS
Family history
Sex (F>M)
Age between 25-35
Other co-existing autoimmune diseases, such as type 1 diabetes mellitus
Smoking
Previous EBV infection; infectious mononucleosis
Vitamin D deficiency
What are some phenomena that can occur with MS?
Uhtoff’s - worsening of neurological symptoms on exercise/in warm environments (e.g. in a bath) e.g. worsening vision
Lhermitte’s phenomenon: lightning-shock pain down the spine on flexion of the neck secondary to cervical cord plaque formation.
Differential diagnosis
Broad due to the varied MS presentations
Spinal cord/brainstem compression e.g. cervical spondylosis, Chiari malformation, disc herniation
Peripheral neuropathy e.g. B12 deficiency, diabetic, MND
Guillain-Barre syndrome
Stroke
Space occupying lesion
Investigations in suspected MS
Bloods and lab investigations to rule out other pathology:
- FBC, CRP, LFTs, U&Es (to rule out infection, electrolyte imbalance)
- TFTs - to rule out hypothyroid
- Calcium/ACE - to rule out sarcoidosis
- Vitamin B12
- HIV serology?
MRI brain and spine with gadolinium contrast is the main investigation - will show high signal T2 white matter plaques
LP - high protein content and oligoclonal bands of immunoglobulin aggregates on CSF electrophoresis
Types of MS and description of each
Relapsing-remitting - episodes of disease followed by recovery
Secondary progressive -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
Primary progressive - worsening of disease and neurological symptoms from the point of diagnosis without initial relapses and remissions
Management of MS - relapse treatment
Acute relapse - high dose methylprednisolone can be given to shorten relapse for 5 days
- 500mg orally daily for 5 days
- 1g intravenously daily for 3–5 days where oral treatment has failed previously or where relapses are severe
Management of MS generally
MDT approach :
- Neurologists, specialist nurses
- SALT for speech/swallow problems
- OT - any home modifications/aids
- Physio - rehabilitation of balance, strength, mobility difficulties
Disease modifying drugs and biologic therapy to aim for long term remission with no evidence of disease activity
- Disease modifiers e.g. interferon-beta, glatiramer
- Biologics e.g. monoclonal antibodies e.g. alemtuzumab and natalizumab
For problems with spasticity:
- Baclofen or gabapentin are first line
- Dantrolene in severe renal failure
Treat:
- neuropathic pain e.g. amitriptyline/gabapentin,
- depression e.g. CBT, SSRIs
- Urge incontinence - ACh medications e.g. oxybutynin
Also exercise to maintain activity and strength
