Multiple Sclerosis

I went on my first GP home visit yesterday. The GP and us three medical students visited a housebound gentleman with MS in his home.

His full-time carer opened the door. There were lots of mobility aids at the entrance, one of those seats that take you up the stairs, and he was sat down when we arrived and remained in his seat for the duration of the visit. James (let’s call him James), currently in his late 60s, first started having problems when he was 17. His vision went blurry and he had tingling in his hands. James was admitted into hospital, treated with steroids, and then was fine until he started getting much older. He then started getting tingling sensations in his hands, stiffness in limbs, dizziness, difficulty clearing sputum, and his mobility is now very heavily affected.

I performed a lower limb neurological examination on James. He had wasted lower limb muscles, increased tone, a small degree of weakness upon hip flexion on the right, brisk reflexes, positive Babinski’s sign, areas of decreased light touch sensation, hypersensitivity in other areas, and reduced joint position sense of his right hallux.


Multiple Sclerosis (MS)

Definition: inflammatory demyelinating condition of the central nervous system (brain and spinal cord)

Types

-Relapsing-remitting MS- most common. 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- steady accumulation of disability with no clear relapsing- remitting pattern

Marburg variant- severe fulminant variant of MS leading to advanced disability or death within weeks.

Image result for multiple sclerosisAetiology/ risk factors:

-Discrete plaques of demyelination occur at multiple CNS sites, from T-cell mediated immune response, leading to impaired conduction along axons. Trigger unknown. There is also grey matter atrophy.

-Demyelination heals poorly, causing relapsing and remitting symptoms. Prolonged demyelination causes axonal loss and clinically progressive symptoms.

-Early exposure to sunlight/ Vitamin D seems important, and vitamin D status relates to prevention of MS, and fewer symptoms and fewer new lesions in established MS.

Epidemiology:

-Prevalence in England ≥42:100,000. Lifetime UK risk 1:1000.

-Mean age of onset 30 years (usually 20-40)

≥3 x more common in females

-Commoner in temperate areas and rare in Black Africa/Asia. Adult migrants take their risk with them, whilst children acquire the risk of where they settle

Symptoms & Signs: variable, depending on site of inflammation

Early on, relapses (can be stress induced) may be followed by remission and full recovery. As disease progresses, remissions are incomplete, so disability accumulates. There may be a steady progression of disability from the start in some patients or no progressive disablement at all in others.

Usually monosymptomatic, rarely polysymptomatic:

unilateral optic neuritis (pain on eye movement and rapid decline in central vision- visual acuity and colour vision: central scotoma) = commonest

Sensory

-Dysaesthesia (abnormal unpleasant sensation felt when touched)

-Pins and needles (paraesthesia), numbness, burning

-Decreased vibration sense (vibration and joint position sense loss more common than pain and temperature)

-Trigeminal neuralgia (paroxysmal facial pain in the distribution of 1 or more branches of the trigeminal nerve)

Motor

-Spastic weakness (increased tone) in limbs

-Spasms

-Stiffness, heaviness

-Myelitis = loss of motor, sensory, autonomic, reflex and sphincter function below the level of a lesion indicates transverse myelitis. Longitudinal myelitis also occurs. 

-Upper motor neurone sigs: brisk reflexes, spastic weakness

Sexual/GU

-Erectile dysfunction, impotence

-Anorgasmia

-Urine retention, incontinence, urgency, hesitancy

GI

-Swallowing disorders

-Constipation

Eye

-Diplopia

-Hemianopia and other visual field defects

-Optic neuritis (swollen optic nerve head on fundoscopy, optic atrophy possible in chronic disease)

Image result for optic neuritis fundoscopy

-Visual phenomena e.g. on exercise

-Bilateral internuclear opthalmogleia

Lesion in the medial longitudinal fasciculus causes means that when the patient’s gaze is directed away from the side of the lesion, the ipsilateral (adducting) eye will not adduct and the contralateral (abducting) eye demonstrates horizontal nystagmus.

Image result for internuclear ophthalmoplegia

-Pupil defects

e.g. Relative Afferent Pupillary Defect (RAPD) = swinging torch test- both pupils contract when light is shone on the unaffected side but both dilate when light is shone on the diseased eye.

e.g. Argyle Robertson-type pupil (rarer than RAPD) = pupil is constricted, non-reactive to light, but reactive to accommodation.

Cerebellum

-Trunk and limb ataxia

-Intention tremor

-Past-pointing and dysmetria on finger-nose test and heel-shin test

-Dysdiadochokinesia (difficulty performing rapidly alternating movement)

-Scanning (monotonous) speech

-Ataxic, wide-based gait

-Falls

Cognitive/ visuospatial decline/psychological

-Amnesia

-Elevated or decreased mood

-Decrease executive function

-Depression

-Psychosis

-Symptoms may worsen with heat e.g. hot bath, or overheating from exercise (Uhthoff’s phenomenon)

Lhermitte’s phenomenon- electric shock-like sensation in arms and legs precipitated by neck flexion

Investigations:

-Diagnosis is clinical and requires at least 2 lesions separated in time and space, unattributable to other causes.

-Early diagnosis and treatment reduce relapse rates and disability.

MRI brain/spine- sensitive but not specific for plaque detection

Gadolinium enhancement indicates an active lesion.

Image result for mri multiple sclerosis

         -may exclude other causes e.g cord compression

Lumbar puncture-CSF may show oligoclonal bands of IgG on electrophoresis that are not present in the serum, suggesting CNS inflammation.

Can also exclude other infective or inflammatory causes by microscopy.

Evoked potentials test- delayed visual, auditory, and somatosensory evoked potentials (VEP, BEP, SEP). VEP is delayed in approx. 90% of MS patients.

Evoked potential = electrical potential recorded following presentation of a stimulus, as distinct from spontaneous potentials as detected by electroencephalography (EEG).

McDonald criteria can be used to help diagnose MS. This takes into account clinical presentation and additional information such as MRI, CSF and evoked potentials.

Management:

-Encourage happy, stress-free life if possible (easier said than done)

-Minimise disability

-Optimise vitamin D levels

Acute attacks

Steroids- METHYLPREDNISOLONE = shortens acute relapses but does not alter overall prognosis (e.g. 0.5-1g/24 h IV/PO for ≲ 3d, no more than 2x/year). Consider plasma exchange if response is poor.

Relapsing-remitting MS

Interferons- IFN-1β, IFN-1α = reduce relapses by 30%

Monoclonal antibodies- ALEMTUZUMAB (against T cells), NATALIZUMAB (against VLA-4 receptors that allow immune cells to cross blood brain barrier, reduces relapses by 68%)

Non-immunosuppressives- GLATIRAMER, MITOXANTRONE (doxorubicin- a chemo drug- analogue, reserve for rapidly progressing disease if other therapies failed i.e. secondary progressive MS)

Other drugs: AZOTHIOPRINE

Palliation/ Symptomatic treatment

Spasticity: BACLOFEN, DIAZEPAM, DANTROLENE, TIZANIDINE, SAVITEX. Botox injection if spasticity is localised.

Tremor: BOTULINUM TOXIN TYPE A injections

Urgency/ frequency: TOLTERODINE or OXYBUTYNIN (anti-cholinergics), teach intermittent self-catheterisation if post-micturition residual volume > 100mL.

Neuropathic pain: CARBAMAZEPINE, GABAPENTIN

Depression: psychological support, anti-depressants

Complications:

-progressive disability

-cognitive impairment

Prognosis: relapsing-remitting MS can eventually result in residual disability followed by a secondary progressive phase. 10% have a benign course (1 or more initial episodes, then no symptoms for many years).

Poor prognostic signs: older male, motor signs at onset, many relapses early on, many MRI lesions, axonal loss.

References: Rapid Medicine, Cheese & Onion
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