Multiple Sclerosis : Pathophysiology, Clinical Features, Diagnosis and Treatment

Multiple sclerosis is an autoimmune disease that disables the brain and spinal cord which is mainly the central nervous system. In this disease, the immune system attacks the protective sheath around the fibers and that sheet is called a myelin sheath. It leads to communication problems between the brain and the body organs. There is a demyelination of the spinal cord and it is caused by intrathecally synthesized immunoglobulins.

Pathophysiology of Multiple Sclerosis

• The autoimmune attack on the myelin sheath leads to:
  • Perivenous Demyelination- These are white lesions perpendicularly arranged to the ventricular surface also called Dawson's fingers. Gadolinium-based MRI can be used to view it.
  • Axonal Damage- The degeneration of the myelin sheath causes repetitive stimulation of the nerve fibers and that leads to hyperpolarization and conduction block.
  • This conduction block is variable and worsens with heat exposure, this is also called Uthoff’s phenomenon.
  • It can also lead to astrocytic gliosis.
  • The majority of the antibodies present in multiple sclerosis are locally synthesized in the brain and the spinal cord.
  • The auto-reactive T&B cells attack the myelin basic protein.
  • These auto-reactive T cells cause the damage. There is a cell adhesion molecule called integrin by which the T cells are able to bind and cause damage to the blood-brain barrier.
  • It is more common in whites and females.
  • The unique and special feature of multiple sclerosis is dissemination in time and dissemination in space.
  • Dissemination in time means the lesions can occur at different times and dissemination in space means the lesions can occur at different CNS locations.

Also Read: Spinal Cord Disorders

Clinical Features of Multiple Sclerosis

• Sensory Symptoms: The patient will present with tingling in extremities, pins and needle sensation, and reduced senses.
• Optic Neuritis: It is the most important clinical presentation of multiple sclerosis. There will be decreased visual activity, decreased color perception, and vision dimness, and the patient will have issues with central vision.
• Pain in eye movement.
• Marcus Gunn Pupil: It is an efferent pupillary defect in which the direct light reflex is absent but the consensual light reflex is present.
• The patient will present with weakness of the limb. There will be decreased strength and the patient will feel more weakness after exercise. The Babinski sign will be positive.
• Facial nerve weakness that may resemble Bell’s palsy. The taste sensation is spared.
• Optic neuritis can cause visual blurring.
• Truncal ataxia, limb ataxia, and dysdiadokokinesia due to cerebellar involvement.
• Lhermitte Sign: It is a common sign shown by many multiple sclerosis patients. It is a sudden shooting pain towards the lower spine on neck flexion.
• Trigeminal neuralgia
• There will be bladder involvement. The patient will be having detrusor hyperreflexia and that will cause urgency incontinence.
• Sexual complaints like inability to sustain erection for a long time in males and inability to sustain lubrication in females.
• Cognitive defects
• Epilepsy and falls
• Internuclear ophthalmoplegia.
• Mnemonic for key features in Multiple Sclerosis Patients (SCLEROS):
  • Sensory symptoms
  • Cerebellum involved
  • Lhermitte Sign
  • Eye manifestations
  • R- PPRF+MLF
  • Optic Neuritis
  • Spastic Weakness

Diagnosis of Multiple Sclerosis

• Revised MacDonald Criteria:
  • >= two attacks or episodes of symptoms. The duration of attacks is more than 24 hours and >= 2 signs.
  • If only one clinical sign is seen then the second involvement needs to be documented by MRI. The typical areas are the juxta cortical area, paraventricular area, infratentorial area, and spinal cord.
• Gadolinium-enhanced MRI is an imaging of choice.
• Dawson fingers on MRI.
• Documentation of intrathecal IgG synthesis by CSF electrophoresis.
• Evidence of oligoclonal bands.
• IgG index.
• Lumbar puncture will detect proteins. If the proteins are more than 1g then an alternate diagnosis is to be considered.
• ESR and treponemal antibody for alternative differential diagnosis.

Also Read: Alzheimer’s Disease: Symptoms, Causes and Treatment

Treatment of Multiple Sclerosis

There are many drugs available that can be used for recurrent multiple sclerosis.

• The highly effective drugs are:
  • Natalizumab- It acts on T cells and it works by binding the integrin protein.
  • Ocrelizumab- It acts against CD20 on mature cells.
  • Ofatumumab- It is anti-CD20. It is given subcutaneously and on a monthly basis.
  • Rituximab- It is an anti-CD 20.
• The moderately effective drugs are:
  • S1P modulators – it prevents the progress of lymphocytes from secondary lymphoid organs. The side effects are heart block and macular edema.
• Modestly effective- Beta interferon and Glatiramer.

Also Read: Meralgia Paresthetica: Causes, Symptoms, Risk Factors, Diagnosis and Treatment

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