Multiple Sclerosis

Remember: A single episode of demyelination should not lead to a diagnosis of MS as implied by the above definition.

Epidemiology

Affects approximately 1 in 1000 people in the United Kingdom. F:M = 1.5–2:1. Onset is typically between 20 and 40 years of age. Common in people of northern European ancestry.

Aetiology

The exact cause unknown and may occur due to a complex interaction between environmental and genetic factors.

Genetic factors: Relative risk for a first-degree relative is two–four times higher than background risk. HLA-DRB1 is a chromosomal locus consistently associated with susceptibility to MS.
Other aetiological factors: Viruses, molecular mimicry and auto-immunological mechanisms.

Associations/Risk Factors

Migration to high-risk areas in northern latitudes before 15 years of age increases the risk of developing MS. MS relapses can be associated with inter-current infection, while a reduction in relapse rate is noted during pregnancy.

Pathology/Pathogenesis

Remember: Demyelinated plaques are the pathological hallmark of MS and occur commonly in periventricular white matter and corpus callosum.

Perivascular infiltration of lymphocytes (T cells) and macrophages in brain parenchyma, brainstem, optic nerve and spinal cord; thought to be mediated by activated T cells.
Plaque (characterised by demyelination with preservation of axons): This pathological hallmark occurs more commonly in periventricular white matter and the corpus callosum.
CNS demyelination causes slowing or interruption of conduction through the brain and spinal cord as seen on neurophysiological testing.

History

Patients may report symptoms of visual, sensory, motor, coordination, bladder or sexual dysfunction with or without disturbance in cognition or mood. Principal subtypes are relapsing/remitting MS (RRMS), where symptoms of relapse are separated over time and anatomical location (optic neuritis, disequilibrium etc.) with recovery or partial recovery in between; secondary progressive MS (SPMS), where a period of relapse is followed by relentless progression producing ever-increasing disability; and primary progressive MS (PPMS), where patients relentlessly deteriorate from outset without a proceeding history of relapses or recovery. About 50–75% of RRMS patients will enter the SPMS phase 10–20 years post the onset of first symptom. PPMS is much rarer than the other subtypes; commoner in males with a greater effect on limb and bladder dysfunction.

Visual: Optic neuritis (a common initial complaint with pain on eye movement and mild to severe visual loss including colour vision typically involving only one eye at a time; full or partial recovery usually occurs over months), Uhthoff’s phenomenon (a temporary worsening of neurological symptoms such as visual loss in multiple sclerosis provoked by an increase in body temperature, for example during a fever or a hot bath).
Sensory: Paraesthesia and numbness affecting the limbs or trunk; Lhermitte’s phenomenon, an electric shock-like sensation down the back and limbs produced by neck flexion due to a demyelinating plaque in the cervical cord; trigeminal neuralgia (TN).
Motor: Limb weakness and stiffness.
Brainstem/cerebellum: Diplopia related to IIIrd, IVth or VIth nerve involvement or due to an internuclear ophthalmoplegia (INO); vertigo; dizziness; ataxia and tremor.
Sphincter and sexual function: These symptoms typically parallel limb symptoms due to cord involvement. Urinary urgency and frequency with retention (UMN-type unstable bladder); erectile dysfunction and impotence.
Others: Fatigue (a prominent symptom), cognitive deficits, pseudo-bulbar affect; euphoria and depression.

The Kurtzke Expanded Disability Status Scale is a rating scale of clinical disease severity. A score of (0–10) is assigned to the patient’s clinical status with mobility as the major determinant.

Examination

Eyes: Relative afferent pupillary defect (RAPD), central scotoma and colour disturbance (red desaturation) may be seen with optic neuritis; optic atrophy (pale discs) commonly seen post recurrent or unresolved optic neuritis; ataxic nystagmus is seen with unilateral or bilateral INO.
Motor: UMN signs (spasticity, hyperreflexia and up-going plantars).
Sensory: Impairment of light touch, pinprick, joint position or vibration sense. A truncal sensory level may be seen due to MS-related inflammation of the spinal cord—transverse myelitis.
Cerebellum: Nystagmus, dysarthria, intention tremor, dysdiadochokinesia, limb, truncal and gait ataxia.