Multiple Sclerosis Primer

What is Nystagmus? How is it caused?

Involuntary rapid eye movements. Due to plaques in around the nerves controlling eye movements. Plaques on the optic nerve causes loss of vision on one or both of the eyes.

What kind of reaction is multiple sclerosis?

MS is a type IV hypersensitivity reaction (cell-mediated).

The diagnosis of MS is supported by what procedure? What does this procedure capture?

MS is supported by an MRI which detects multiple CNS lesions called white matter plaques since these regions tend to have a lot of myelin.

When is MS suspected?

MS is typically suspected when there are multiple neurologic symptoms separated in space (which is attributable to damage in different locations in the nervous system) and time (separate bouts /flare ups/ remission).

What does a visual evoked potential deduce?

Measures the response to visual stimuli.

What is Relapsing-Remitting MS?

Most common form of MS. This condition involves bouts of autoimmune attacks months or even years apart, causing an increase of disability. During a bout, a person might lose some vision, then it might be followed by improvement if there's remyelination. Unfortunately, more often than not, the remyelination process isn't complete so there's often some residual disability that remains. And that means, with each attack, more and more the CNS gets irreversibly damaged. In the RRMS, there's usually no increase in between bouts.

Why is Neurofilament sampling performed?

Neurofilament (NfL) is a component of the neuronal cytoskeleton and is released into the cerebrospinal fluid and subsequently into blood following neuro-axonal damage. It has been proposed as a biomarker to indicate treatment response and predict disability worsening in participants with MS

Describe the Auto-Immune Attack mechanism by which oligodendocytes are damaged by B-Cells & Macrophages.

Once B-Cells and Macrophages cross the blood brain barrier (due to cytokines), the b-cells start to make antibodies that mark the myelin sheath proteins. The macrophages uses those antibodies to engulf and destroy the oligodendrocytes. Without oligodendrocytes, there's no myelin to cover the neurons.

What is Primary Progressive MS?

PPMS is basically one constant attack on myelin which causes a steady progression of disability over a person's lifetime.

What is Progressive-Relapsing MS?

PRMS is also one constant attack but this time the bouts are superimposed which means that the disability happens even faster.

What causes intention tremors? Motor symptoms?

Plaques along the motor pathways on the spinal cord. Some motor symptoms: muscle weakness, muscle spasms, tremors, ataxia, paralysis.

What doe plaques in the sensory pathways affect?

Plaques in the sensory pathways can affect inbound signals like sensations in the skin causing numbness, pins & needles, paresthesias (tingling, itching, burning).

What is plasmaphresis?

Plasmapheresis is when plasma is filtered to remove disease causing autoantibodies.

How are plaques formed?

Post auto-immune attack, without oligodendrocytes, there's no myelin to cover neurons. This leaves behind areas of scar tissue also called plaques (sclera).

Since there's no cure for MS, what does RRMS treatment seek to achieve?

RRMS treatments aim to lessen the severity of relapses and make them happen less frequently.

What is Secondary Progressive MS?

Similar to the RRMS type until at one point the immune attack becomes constant which causes a steady progression in disability.

Once the t-cell crosses the blood brain barrier, how is it activated? What happens when it's activated?

T-Cell is activated by myelin. Once it's activated, it changes the blood brain barrier cells to express more receptors and this allows more immune cells to easily bind and get in.

MS can affect higher order activities of the brain. Name some examples

1. Poor concentration and critical thinking. 2. Depression and anxiety.

What are the four main types of MS?

1. Relapsing-Remitting (RRMS) 2. Secondary Progressive (SPMS) 3. Primary Progressive (PPMS) 4. Progressive-Relapsing (PRMS)

Plaques involving the autonomic nervous system leads to what two symptoms?

1. Bowel and bladder symptoms (constipation, urinary incontinence). 2. Sexual Dysfunction.

What does Dysarthria interfere with?

1. Conscious Movements (e.g. eating and talking) 2. Unconscious Movements (e.g. swallowing).

Name 3 RRMS medications.

1. Corticosteroids 2. Cyclophosphamide (cell cycle inhibitor) 3. Intravenous Immunoglobulin All block the autoimmune process.

What are two genetic risk factors of MS?

1. If you're Female 2. If you have genes encoding for HLA-DR2

What are two environmental factors for MS?

1. Infections 2. Vitamin D Deficiency

MS affects what age range?

20-40 years old

What is Charcots' Neurologic Triad?

A trio of common MS neurologic symptoms. 1. Dysarthria - Difficult or unclear speech (due to plaques in the brainstem and affect the nerve fibers that controls muscles in the mouth and throat)/ 2. Nystagmus - Involuntary Rapid Eye Movements 3. Intention Tremor

What is lhermitte's sign?

Another sensory symptom. When an electric shock runs down the back and radiates through the limbs when someone bends their neck forward.

Describe what happens in between MS attack bouts

Auto-immune attacks happen in bouts. After an attack on oligodendrocyte happens, regulatory t-cells cross the blood brain barrier to inhibit/calm down the other immune cells leading to a reduction in the inflammation.

Name and describe a chronic treatment for MS.

Immunosuppressants like recombinant B-IFN which decreases the level of inflammatory cytokines in the brain and increases the function of t-regulatory cells.

What protects the brain and how?

Blood Brain Barrier. Only allows certain molecules and cells through from the blood.

What is optic neuritis and symptoms?

Inflammation of the optic nerve. Blurring, greying of the vision; dark point in the center of vision. Painful eye movement. Double vision.

Multiple Sclerosis (MS)

Demyelinating Disease of the Central Nervous System

What is Dysarthria?

Difficult or unclear speech (due to plaques in the brainstem and affect the nerve fibers that controls muscles in the mouth and throat).

Describe what happens early on vs. over time in MS

Early on in MS, the oligodendrocytes will heal and extend out new myelin to cover the neurons in a process called remyelination. Overtime as the oligodendrocytes die off, the remyelination stops and the damage becomes irreversible with the loss of axons.

What is the EDSS?

Expanded Disability Status Scale (EDSS) is an ordinal scale used for assessing neurologic impairment in MS based on a neurological exam.

What are the treatment options for Progressive MS?

Fewer treatment options. Treatments targeted towards managing symptoms like depression or bladder dysfunction. Physical therapy and cognitive rehabilitation therapy. Potentially Vitamin D as a treatment.

Myelin

The protective sheath that surrounds the axon of neurons allowing neurons to quickly send electrical impulses.

When a patient has MS, what is typical of there cerebrospinal fluid?

Their cerebrospinal fluid has a high level of antibodies which indicates an autoimmune process.

How do t-cell & b cells cross the blood brain barrier?

They must have the right ligand (surface molecule) to get through the blood brain barrier.

What is the other mechanism by which other immunosuppressants work?

They work by blocking t-cells into the brain by interfering cell surface molecules that they use to gain passage into the blood brain barrier.

What is ataxia?

The loss of full control of bodily movements

How does this hypersensitivity (cell-mediated) reaction mechanism work? What happens when more immune cells cross the blood brain barrier?

This means that that myelin specific t-cells release cytokines (interleukin-1, interleukin-6, tumor necrosis factor-alpha, interferon-gamma) which together dilated the blood brain barrier vessels which allow for more immune cells to get in as well as directly cause damage to the oligodendrocytes. These cytokines also attract B-Cells and Macrophages.

Oligodendrocytes

Type of glial cell in the CNS that wrap axons in a myelin sheath. Group of Cells that Support Neurons.

What is the cause of MS?

Unknown

When does demyelination occur?

When the immune system inappropriately attacks and destroys the myelin which makes communications between neurons break down resulting in sensory, motor, and cognitive problems.