USMLE® Step 1 style questions USMLE
USMLE® Step 2 style questions USMLE
A 53-year-old man presents to the urgent care clinic. He reports difficulty with standing and walking due to muscle weakness that started a week ago. The weakness is now beginning to affect his arms. He cannot recall any inciting factors such as drug use or toxin exposure. He has otherwise been in good health, apart from a minor respiratory illness several weeks ago. Analysis of the cerebrospinal fluid shows elevated protein level with normal white blood cell count. Which of the following neurological disorders shares the most similar pathologic mechanism as the disorder most likely responsible for this patient’s symptoms?
Guillain-Barré syndrome is named after two neurologists- Georges Guillain and Jean Barré, and it’s a demyelinating disease of the peripheral nervous system, which includes all of the neurons that extend beyond the brain and the spinal cord.
Guillain-Barré, or GBS for short, is also called acute inflammatory demyelinating polyneuropathy.
Neurons are made up of three main parts.
The dendrites, which are little branches that receive signals from other neurons, the soma or cell body, which has all of the neuron’s main organelles, and the axon, which transmits the signal to the next neuron in the series.
For peripheral nerves, the cell body can either be located in the spinal cord, where it’s called a spinal nerve, or the brain, where it’s called a cranial nerve.
Myelin is the protective sheath that surrounds the axons of the peripheral neurons, allowing them to quickly send electrical impulses.
This myelin is produced by Schwann cells, which are a group of cells that support neurons.
In Guillain-Barré syndrome, demyelination happens when the immune system inappropriately attacks and destroys the myelin, which makes communication between neurons break down, ultimately leading to all sorts of sensory, motor, and cognitive problems.
The cause of Guillain- Barré syndrome is unknown, but it’s known to develop after a bacterial infection, like Campylobacter jejuni and Mycoplasma pneumoniae, or a viral infection, like cytomegalovirus and Epstein-Barr virus.
Specifically, some strains of Campylobacter jejuni have a particular kind of oligosaccharides on their membrane, that are identical to gangliosides found on the surface of motor neurons.
So as a result, immune cells mistakenly attack and destroy the gangliosides, damaging the neurons.
This is called molecular mimicry, because from the perspective of the immune cells, a host substance is mimicking a foreign protein.
When a normal component of the cells triggers an immune response that component is called an autoantigen.
So in Guillain-Barré syndrome, neuronal autoantigens get picked up by antigen presenting cells, like dendritic cells, which present it to the helper T cells.
Once activated, the B-cells make antibodies that mark the autoantigens, and the macrophages use those antibody markers to bind to and strip the myelin sheath off of the peripheral neurons.
The demyelination occurs in patches along the length of the axon, so it’s called segmental demyelination.
Early on in Guillain-Barré syndrome, the Schwann cells make new myelin to cover the neurons, which is called remyelination.
But over time, the Schwann cells just can’t keep up, and there’s irreversible damage.
Absence of myelin sheath means that nerve impulses become slow and sluggish.
Symptoms of Guillain-Barré syndrome are based on the nerves that are affected.