Multiple Sclerosis – The Entity With Many Faces

Multiple sclerosis is the most widespread disabling neurological condition of young adults in the world, which got its name as it produces multiple lesions in the brain.

Moving on to what is multiple sclerosis (MS)? It's an autoimmune demyelinating disorder.

By autoimmune, we mean that the antibody from the body targets its own antigens.

Demyelination signifies that in this disease, the body’s immune system acts against its own myelin sheaths. Myelin sheath is nothing but a coat over the axon, which helps it in faster transmission of impulses. This process, destroying the myelin sheath, is called demyelination.

The damaged myelin sheath can no longer perform its functions effectively.  Thus, preventing the transmission of impulses, resulting in motor, sensory, and autonomic symptoms.

Who Can Develop Multiple Sclerosis?

Not everyone develops MS. There are certain predisposing factors for MS. 

• Patients with vitamin D deficiency are predisposed to MS. This explains the decreased prevalence of MS in the temperate zone.
• Previous exposure to Epstein Barr Virus poses a risk for MS.
• Genetic factors play a major role in the transmission of the disease. MS patients are found to have variations in HLA-DR2 genes.
• Females are found to have greater preponderance.

What Goes Wrong In MS?

You must be knowing that the blood-brain barrier (BBB) does not let the T cells gain entry into the brain. But in MS, there is a disruption of BBB, and T cells can now reach brain tissue.

The T cells inside the brain wrongly take myelin sheath to be a foreign body and destroy them. Myelin sheath responds to this by releasing cytokines and antibodies. These interact with macrophages and encourage them to engulf the oligodendrocytes.

Oligodendrocytes are the cells responsible for the production of myelin. On its injury, the production of myelin is also decreased. 

So during the early stage of the disease, there is remyelination, but over time remyelination stops, and there is an irreversible loss of myelin sheath.

Clinical Features

An important point to note is that not all patients present with all symptoms. Also, symptoms usually depend on the portion of the brain which is involved by the disease.

MS typically affects individuals in the 2nd and 4th decade of life.

Symptoms of MS can be explained by Charcot’s’ neurological triad:

1. Dysarthria (difficulty in speech) is due to a scar in the brainstem region that controls the muscles in the mouth and throat.
2. Nystagmus (involuntary rapid eye movements) is due to plaques around the nerves that control eye movements.
3. Intention Tremor is due to plaques along the motor pathways controlling skeletal muscles.

Other common symptoms:

Sensory symptoms: hyperesthesia (tingling or numbness), paraesthesia, and pain

Motor symptoms: weakness, loss of tendon reflexes, and spasticity.

Visual symptoms: optic neuritis causing diminished vision and color perception. Diplopia can develop due to damage to the 6^th nerve. 

Genitourinary symptoms: usually due to incoordination between the bladder muscles and sphincter

The bladder muscles contract, and the sphincter must relax to void urine. In MS patients, there are abnormalities in nerve conduction leading to a loss of this coordination. This leads to a urinary emergency and increased frequency.

Sexual dysfunction and constipation can also occur due to nerve conduction dysfunction.

Psychiatric symptoms: depression, memory loss, and problem-solving 

Special symptoms :

• Uhthoff's phenomenon: in which there is a worsening of neurological symptoms on exposure to heat. This occurs as heat increases nerve conduction.
• Lhermitte sign: it is an electrical sensation that is felt in the limb and back on the flexion of the neck.

Pattern of Disease

• Relapsing-remitting - discrete attack and complete recovery.
• Primary progressive - steady decline in function
• Secondary progression - begin as relapsing-remitting and steady deterioration.
• Malignant or aggressive - a rapid increase in symptoms.

Diagnosis

MS diagnosis is supported by MRI, which shows multiple CNS lesions called white matter plaques. They usually contain myelin.

Cerebrospinal fluid on examination shows high levels of antibodies and mononuclear cells.

Evoked potential is measured for both afferent and efferent pathways. Abnormality in one or more pathways is present in most of the patients.

Management

It is important to explain to the patient in detail about the disease. Advises are given to them for some lifestyle changes like exercise, ease stress, avoid exposure to heat, rest, and cease smoking as these will have some good effects on the patient.

If a patient presents with an acute episode, the first thing you need to do is to administer them glucocorticoids by oral or IV route. But recurrent doses must be avoided as they pose a serious risk.

For reducing the severity of the disease, interferon B is the drug of choice. It reduces the immune system activity of the body and also reduces chemotaxis. This will decrease cell infiltration.                                                                                                      

Glatiramer acetate can be given subcutaneously, and it works similar to interferon B.

Natalizumab is a monoclonal antibody that can prevent the adhesion of lymphocytes to the endothelium. By this, penetration of WBCs into the brain is decreased.

Symptomatic treatment is mainly given to improve the quality of life of the patients living with the disease. It includes:

• Sildenafil to treat sexual dysfunction.
• Bethanechol being a parasympathetic drug, is used to treat bladder hyperactivity.
• Baclofen, an antispasmodic drug, is used to relieve spasticity.
• Amantadine, an antiviral drug, has also been found to be effective in relieving fatigue.

References

1. Harrison's Principles of Internal medicine, 19^th edition, Page no: 2661-2673
2. Multiple Sclerosis: Pathogenesis, Symptoms, Diagnoses and Cell-Based Therapy, Nazem Ghasemi et al., Cell J. 2017 Apr-Jun; 19(1): 1–10. <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5241505/>

Authors footnote

The McDonald criteria for the diagnosis of MS is a crucial topic of discussion in many postgraduate entrance exams.

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