Neuroscience Week 3: Diseases Associated with Peripheral Nerve Injury

Question 1

Guillain-Barre Syndrome Description

Answer 1

A rapidly progressive acute demyelinating disorder affecting motor axons resulting in ascending weakness that can lead to death from failure of respiratory muscles within days of onset of symptoms

Is one of the most common life-threatening diseases of the peripheral nervous system

Question 2

Guillain-Barre Syndrome Etiology

5 common agents

Answer 2

Appears to be triggered by an infection or vaccination that breaks down self-tolerance thereby leading to an autoimmune response

Associated infectious agents include

• Campylobacter jejuni
• Epstein Barr Virus
• Cytomegalovirus
• Human immunodeficiency virus
• Zika Virus

Question 3

Guillain-Barre Syndrome Pathophysiology

Answer 3

The injury is most extensive in the nerve roots and proximal nerve segments and is associated with mononuclear cell infiltrates rich in macrophages

both humoral and cellular immune responses are believed to play a role in the disease process

Question 4

Guillain-Barre Syndrome Treatments

Answer 4

Plasmapheresis (to remove offending antibodies)

Intravenous IVIg (suppress immune responses through unclear mechanisms)

supportive care (such as ventilary support

Question 5

Guillain-Barre Syndrome Prognosis

Answer 5

Patients who survive the initial acute phase of the disease usually recover with time

Question 6

Myasthenia Gravis Description

Answer 6

Myasthenia gravis is an autoimmune disease with fluctuating muscle weakness that is caused by autoantibodies that target the neuromuscular junction.

Question 7

Myasthenia Gravis Pathophysiology

Answer 7

• The most common antigenic target is the postsynaptic acetylcholine receptor (AChR).
• Other pathogenic antibodies recognize muscle-specific kinase (MuSK)
• and low-density lipoprotein receptor-related protein (LRP4) .

These antibodies lead to loss of receptors and damage to the structure of the junctions.

Question 8

Myasthenia Gravis​ Etiology & Age of onset

Answer 8

autoantibodies that target the neuromuscular junction

• Early onset before age 50 years is more common in females and is frequently associated with enlargement of the thymus due to the presence of B cell follicles and germinal centers (follicular thymic hyperplasia).
• Late-onset cases show a more equal gender distribution and are associated with thymoma, a neoplasm derived from thymic epithelium.
• Both of these thymic lesions are believed to perturb tolerance to self-antigens, setting the stage for the generation of autoreactive T and B cells.

Question 9

Myasthenia Gravis Clinical Presentation

Answer 9

• Clinically, myasthenia gravis frequently manifests with ptosis (drooping eyelids) ordiplopia (double vision) because of weakness in the extraocular muscles.
• This pattern of weakness is distinctly different from that of most primary myopathic diseases, in which there is relative sparing of facial and extraocular muscles.
• The severity of the weakness often fluctuates rapidly, sometimes over periods of a few minutes.
• Characteristically, repetitive firing of muscles makes the weakness more severe, whereas cholinesterase inhibitors improve strength markedly,

Question 10

Myasthenia Gravis diagnostically useful features

Answer 10

repetitive firing of muscles makes the weakness more severe, whereas cholinesterase inhibitors improve strength markedly

Question 11

Myasthenia Gravis Treatments

Answer 11

• cholinesterase inhibitors
• immunosuppression
• plasmapheresis
• and (in patients with thymic lesions) thymectomy.

These interventions have improved the 5-year survival rate to greater than 95%.