Chapter 26: Multiple Sclerosis (MS)
January 26, 2021Elementary Immunology
- Multiple sclerosis (MS) is a common demyelinating disease of the central nervous system, related to the immune system.
- This is characterized by the relapsing, remitting course with CNS episodes separated in times, and the anatomic site involvement.
- Multiple sclerosis is a potentially disabling disease of the brain and spinal cord.
- This is a chronic relapsing progressive disease. There are episodic demyelination and the formation of “plaques” throughout the central nervous system, but peripheral nerves are unaffected.
- Several infectious disease pathogens have been blamed, but none confirmed.
- This is characterized by demyelination of varying sizes and ages scattered throughout the central nervous system’s white matter.
- Demylinization “plaque” is more common in the cerebrum, optic nerves, spinal cord, brain stem, and cerebellum.
- There is the presence of the immune system involvement as follows:
- Antimyelin antibodies.
- Oligoclonal proteins are increased in the cerebrospinal fluid.
- In vitro cell-mediated immunity by blood and cerebrospinal fluid cells to myelin components.
- Myelinotoxicity and glial toxicity of serum and cerebrospinal fluid in vitro.
- There is an increased incidence in some HLA group antigens, e.g., HLA-A3, HLA-B7, HLA-DW2, and HLA-DRw2.
- MS patients are positive for the anti myelin antibodies formed against the myelin sheath of the nerves and or myelin basic protein components.
- Myelin antibodies are not detected in the cerebrospinal fluid (CSF) of MS patients.
- Summary of MS pathogenesis:
- There is a focal disruption of the blood-brain barrier.
- There is myelin damage.
- There is an immune response.
- The oligoclonal band is due to oligoclonal immunoglobulin present in the CSF and serum.
- Oligoclonal Immunoglobulin faint band is seen in the γ- a fraction of electrophoresis done on the CSF.
- The oligoclonal band is due to IgG and is polyclonal in nature.
- A concentrated CSF is needed to see a good band, and it is run on the agarose or agarose gel.
- The serum is also run along with the CSF.
- If the oligoclonal band is present in the CSF and not in the serum, it results from increased IgG immunoglobulin production by the central nervous system. This is produced by the immune cells in the subarachnoid space of the brain.
- For confirmation of oligoclonal band, run serum diluted to 1:100 and unconcentrated CSF.
- Oligoclonal bands are present in the CSF and not in serum, indicates its production in the brain.
- Serum/CSF oligoclonal bands may be seen in:
- Hodgkin’s lymphoma.
- Burkitt’s lymphoma.
- Guillain- Barre syndrome.
- Paraneoplastic syndrome.
- Chronic tuberculous and fungal infections.
- Primary optic neuritis.
- Peripheral neuropathies.
- Cerebral infarction.
- This is a focal disseminated perivascular disease.
- There are a few monocytes and histiocytes around the blood vessels.
- There is myelin destruction/degeneration with less number of perivascular inflammatory cells than other condtions.
- There is astrocytic cell proliferation.
- This disease is more common in temperate climates with local variation.
- Immigrants to the USA take a risk with them.
Signs and symptoms
- S/S differs from person to person and over the time of the disease.
- Usually seen in young adults with single lesions like unilateral optic neuritis.
- There is rapid, painful monocular loss of vision.
- Or there may be transverse myelitis.
- Or isolated numbness or weakness.
- Other symptoms are:
- Incontinence of the urine.
- Numbness or weakness of one or more limbs, typically involving one side of the body at a time or may involve legs and trunk.
- The patient feels electric like a shock when bending the neck forward.
- There are tremors, an unsteady gait, and a lack of coordination.
- Vision problems are quite common, like:
- Pain during the eye movements and loss of vision in one eye at a time.
- There may blurred vision.
- The patient may have double vision.
- These patients may have:
- Slurred speech.
- Tingling and pain in parts of the body.
- These patients also have problems like sexual, bladder function, and bowel movement.
- MS is a relapsing and remitting disease.
- MS patients may get new S/S over a period of time.
- Summary of the S/S:
- The patient may feel fatigued.
- There is vertigo.
- There are weakness and spasticity.
- There are altered sensation, numbness, and paresthesia.
- There may be pain in attacks, trigeminal neuralgia, and dysesthetic.
- There may be urine incontinence, which is quite common. The patient may have urgency.
- These patients may have constipation.
- There is sexual dysfunction like impotence.
- There are swallowing disorders.
- There is optic neuritis, diplopia, and nystagmus.
- There are ataxia and intention tremors.
- There is memory impairment, europhile, and dementia.
- Rarely may see epilepsy, aphasia, and extrapyramidal disorder.
- Total proteins in the CSF are normal in MS or slightly raised.
- The oligoclonal band is characteristic of MS. This is present in >90% of the patients with MS.
- High-resolution gel electrophoresis for the oligoclonal band is 90% to 95% positive in MS.
- Total CSF proteins are mildly raised in 25% to 50% of the MS cases.
- If total CSF proteins are >100 mg/dL, then MS probably not the diagnosis.
- CSF IgG synthesis rate is <3 mg/dL while in 90% MS it is >3mg/dL.
- CSF IgG of the total CSF protein normally is <10.5%, while in MS, IgG is ≥10.5% in 70% of the cases.
- CSF IgG: albumin ratio normally is <25% to 28% while in MS ≥28% in ∼70% of the cases.
- MRI brain may diagnose it.
- There is no cure for this disease.
- Treatment is focused on symptoms to shorten the episode.
- For an acute attack, steroids are given.
- After 5 years, 70% are still working, and 20% may be dead from the complications.
- Relapse last a few months, and remission may last for many years.