Multiple sclerosis - causes, symptoms, diagnosis, treatment, pathology

Causes of Multiple sclerosis 

Multiple sclerosis is a demyelinating disease of the central nervous system. Which includes the brain and the spinal cord. Myelin is the protective sheath that surrounds the axon of neurons allowing them to quickly send electrical impulses. This myelin is produced by oligodendrocytes. 

Which is a group of cells that support neurons in multiple sclerosis? Demyelination happens when the immune system inappropriately attacks and destroys. The myelin which makes communications between neurons breakdown. 

Ultimately leading to all sorts of sensory-motor and cognitive problems brain. Including the neurons in the brain is protected from things in the blood by the blood-brain barrier. Which only lets certain molecules and cells through from the blood for immune cells like T and B cells. That means they have to have the right Lygon door surface. 

Molecule to get through the blood-brain barrier. This is kind of like having a VIP pass to get into an exclusive club. Once a T-cell makes its way in it can get activated by something it encounters. In the case of multiple sclerosis, it's activated by myelin. 

Once the T cell gets activated, it changes the blood-brain barrier. Cells to express more receptors and this allows Immune cells to more easily bind and get in.

It's kind of like bribing the bouncer to let in a lot of people. Now multiple sclerosis is a type 4 hypersensitivity reaction or a cell. Mediated hypersensitivity and this means that those myelin-specific. 

T cells release cytokines like interleukin 1 interleukin 6 tumor necrosis factor-alpha and interferon-gamma. Which together dilates the blood vessels. Which allows more immune cells to get in as well as directly caused damage to the oligodendrocytes. 

These cytokines also attract B cells and macrophages as part of the inflammatory reaction. Those B cells start to make antibodies. That marks the myelin sheath proteins and then the macrophages. Use those antibody markers to engulf and destroy the oligodendrocytes. 

Without oligodendrocytes, there's no myelin to cover the neurons and this leaves behind areas of the scar. The tissue also called plaques or sclera in multiple sclerosis of these immune attacks. Typically happen in bouts, in other words, an autoimmune attack on the oligodendrocytes might happen and then regulatory t-cells will come in to inhibit or calm down. 

The other immune cells leading to a reduction in the inflammation. Early on in multiple sclerosis the oligodendrocytes will heal and extend out new myelin to cover the neurons. Which is a process called demyelination.

Unfortunately though over time as the oligodendrocytes die off the demyelination stops and the damage becomes irreversible with the loss of axons. Just like other autoimmune diseases the exact cause of multiple sclerosis is unknown. 

But it's linked to both genetic and environmental factors genetic risk factors include. Being female and having genes that encode a specific type of immune molecule called HLA dr2. Which is used to identify and bind to foreign molecules? 

Environmental risk factors might include infections as well as vitamin D deficiency. Which is an interesting one because it might help explain. Why the rates of multiple sclerosis are higher at the northern and southern poles compared to the equator. 

Where there's a lot more sunlight together. These genetic and environmental influences might lead to the body not killing off immune cells. That target myelin so it turns out that. 

Multiple sclerosis based on the pattern of symptoms

There are four main types of multiple sclerosis based on the pattern of symptoms over time. To break this down we can use a graph with time. On the x-axis where time refers to the lifespan in the individual and disability and the y-axis the first in by far. 

The most common pattern of multiple sclerosis is called relapsing-remitting multiple sclerosis or RR MS. This condition is what we just described bouts of autoimmune attacks, happening months or even years apart and causing an increase in the level of disability.

For example, during the bout, a person might lose some vision. But then it might be followed by improvement. If there's demyelination unfortunately though more often than not.

The demyelination process isn't complete. So there's often some residual disability, that remains and that means that with each attack more and more the central nervous system gets irreversibly damaged in the relapsing-remitting. Multiple sclerosis type there's typically no increase in disability between bouts. So the line stays flat during that time.  

Now the second type is called secondary progressive multiple sclerosis or SPMS. Which initially is pretty similar to the relapsing-remitting type. But over time the immune attack becomes constant. Which causes a steady progression of disability.

The third type is primary progressive multiple sclerosis or PPMS. Which is basically one constant attack on myelin. Which causes a steady progression of disability over a person's lifetime.

The final type is progressive relapsing multiple sclerosis or PRMS. Which is also one constant attack but this time they're about superimposed. This means the disability happens even faster specific symptoms vary a lot from person to person and largely. It depends on the location of the plaques and multiple sclerosis. 

Typically affects individuals between the ages of 20 and 40. Symptoms related to bouts can typically worsen over weeks and can linger for months without treatment. 

One common trio of multiple sclerosis symptoms is called Shaco's neurologic triad and it includes dysarthria. Which is difficult or unclear speech nystagmus? Which are involuntary rapid eye movements and an intention tremor? 

Dysarthria is due to plaques in the brain stem. That affects nerve fibers that control muscles of a mouth and throat and this can interfere with conscious movements. 

·    Like eating and talking and could lead to things. 

·    Like a new stutter as well as unconscious movements. 

·    Like swallowing nystagmus is due to plaques around the nerves controlling eye movements. 

Plaques are on the optic nerve causes loss of vision in one or both of the eyes. Because of damage to the optic nerve, which is called optic neuritis. Sometimes there's blurring or greying of the vision or alternatively. 

There might be a dark point in the center of vision. Additionally, if there's damage to the nerves controlling eye movement then eye movements can be painful and there can even be double vision. If the eyes no longer move in a coordinated way.

Finally in tension tremors can be caused by plaques along the motor pathways in the spinal cord. Which can affect outbound signals like a skeletal muscle? Control motor symptoms can include muscle weakness, muscle spasms tremors and ataxia. Which is a loss of balance and coordination in serious cases?

Diagnosis of Multiple sclerosis

This can lead to paralysis. In addition plaques in the sensory pathways can affect inbound signals like sensations from the skin. Which causes symptoms like numbness pins and needles and paresthesias. Which are often a tingling feeling but might also be a painful itching or burning sensation occasionally.

There can be very specific sensory symptoms like Lera meet sign. Which is when an electric shock runs down the back and radiates through the limbs. When a person bends their neck forward. Black's can also involve the autonomic nervous system.

Which can lead to bowel and bladder symptoms like constipation and urinary incontinence as well as sexual symptoms like sexual dysfunction?

Finally, multiple sclerosis can also affect higher-order activities of the brain causing poor concentration and critical thinking as well as depression and anxiety. Multiple sclerosis is typically suspected when there are multiple neurologic symptoms separated in space.

This is attributable to damage in different locations in the nervous system as well as time meaning separate bouts or flare-ups, as well as remission. The diagnosis of multiple sclerosis is supported by an MRI that shows multiple central nervous system lesions called white matter plaques.

Since these regions tend to have a lot of myelin. Also in the cerebral spinal fluid, there might be high levels of antibodies. Which indicates an autoimmune process. Finally, a visual evoked potential can be helpful as well.

Which measures the nervous system's response to visual stimuli for treatment. There’s no cure for multiple sclerosis. But there are medications. Which are particularly effective for the relapsing-remitting type.

Because they lessen the severity of relapses and make them happen less frequently. Medications like corticosteroids cyclophosphamide. Which is a cell cycle inhibitor and intravenous? Immunoglobulin can all be used to help blunt the autoimmune process.

In addition, plasmapheresis can be effective as well. Which is when the plasma is filtered to remove disease-causing. Autoantibodies' chronic treatment for multiple sclerosis includes immunosuppressants like recombinant beta interferon.

This decreases the level of inflammatory cytokines in the brain as well as increases the function of T regulatory cells. Other immunosuppressants actually block T cells from getting into the brain by interfering with the cell surface molecules.

Treatment options for progressive multiple sclerosis

That used to gain passage through the blood-brain barrier. Unfortunately, though there are fewer treatment options available for progressive multiple sclerosis instead. Treatments are often targeted at managing specific symptoms. Everything ranging from depression to bladder dysfunction physical therapy and cognitive.

Rehabilitation therapy can be particularly helpful with sensory-motor and cognitive symptoms. Finally, there's also an increasing interest in the role of vitamin D as an effective treatment.

All right as a quick recap, multiple sclerosis is a chronic and progressive autoimmune disorder and the most common pattern is the relapsing-remitting type where individuals have flares. That comes and goes with each one's slightly worsening. Their overall condition during a flare t cell causes inflammation and damage to oligodendrocytes in the central nervous system.

Which leaves behind scarred areas of d myelinated neurons called plaques. Which causes a variety of symptoms depending on the location.