Peripheral Nervous System Flashcards
What are non-myelinated neurons important for?
Regulating smooth muscles
How long can a peripheral nerve become?
Up to 1 meter
Differences between CNS and PNS
- Damage recovery (easier in PNS)
- CNS: Oligodendrocytes always myelinate more than one axon vs PVS: Schwann cell myelinate one axon
What is the function of the nodes on Ranvier?
Allow for ions to diffuse in and out of the neuron, propagating the electrical signal down the axon.
Describe the structural makeup of the nodes of Ranvier
These are the gaps formed between the myelin sheath where the axons are left uncovered. Accumulation of several ion channels also there.
How are peripheral nerves protected?
By the blood-nerve barrier, which consists of tight-junctions and supportive cells
What does this barrier prevent?
The transfer of substances from the plasma to the nerve fibers
Is this barrier absolute?
No, it is leaky at nerve roots, ganglion cells and nerve terminals
Characteristics of the blood-nerve barrier (3)
- Formed by tight-junctions endothelial cells
- Leaky at nerve roots, ganglion cells and nerve terminals
- Passage of activated T-cells, macrophages and immunoglobulin
Characteristics antigen-presentation in the PNS (2)
- Class II inducible on Schwann cells and endothelial cells
- Endoneurial macrophages – critical for Wallerian degeneration
What is wallerian degeneration?
Degeneration of the part of an axon that is severed from the neuron cell body after injury –> leading to its fragmentation into smaller pieces
Why are peripheral nerves highly vulnerable?
- Largest cells in human body
- Require intact cell surface for normal electrophysiology
Two categories of immune-mediated peripheral neuropathies
- Peripheral nerve specific
- Not peripheral nerve specific
Two categories of peripheral nerve specific immune-mediated neuropathies
- Acute
- Chronic
Which disease is an acute peripheral nerve specific immune-mediated neuropathy?
Guillain-Barré syndrome
Name diseases that are chronic peripheral nerve specific immune-mediated neuropathies (3)
- Chronic inflammatory demyelinating polyneurpathy (CIDP)
- Multifocal motor neuropathy (MMN)
- Paraprotein-related neuropathy (MAG)
Diseases ‘not peripheral nerve specific’ immune-mediated neuropathies (2)
- Critical illness neuropathy/myopathy
- Systemic autoimmune diseases/vasculitis
What are the neurological deficits in GBS? (4)
- Muscle paralysis
- Sensory deficits
- Autonomic dysfunction
- Areflexia
What are the symptoms of muscle paralysis in GBS?
- Arms and legs
- Eye movements, facial muscles, swallowing, speech
- Respiratory insufficiency
What are the symptoms of sensory deficits in GBS?
- Pain, tingling
- Numbness, absent pain and touch sense
- Absent position sense (ataxia)
What are the symptoms of autonomic deficits in GBS?
- Tension fluctuations and cardiac arrhythmia
Two categories of diagnostic criteria for GBS
- Clinical features
- Additional examinations
What are the clinical features to look out for when considering GBS?
- Rapidly progressive (<4 weeks)
- Symmetrical paresis of arms and legs
- Reduced or absent reflexes
What are the additional examinations you can perform when considering GBS?
- Blood
- Cerebrospinal fluid
- Electrophysiology
Sequence of events in GBS
- Progression
- Plateau phase
- Recovery phase
- Disability
What are the two histological classifications of GBS?
- Demyelination
- Axonal degeneration
How is demyelinating GBS called disease wise?
Acute inflammatory demyelinating polyneuropathy (AIDP)
How is axonal degenerating GBS called disease wise?
Acute motor axonal neuropathy (AMAN)
How can macrophages attack the myelin? (3)
- Phagocytosis of myelin debris and myelin sheaths
- Pro-inflammatory cytokines
- Antigen-presentation of myelin derived antigens to T cells
How does axonal degeneration work?
It disconnects myelin from the axon (NOT COMPLETE YET)
How does complement activation work in GBS?
Antibodies are directed against glycolipids/gangliosides, which are present in membranes of all of your cells BUT highly enriched in the nerve system. Antibody::antigen complex activate complement.
Where does compliment activation occur during GBS?
Along Schwann cell surfaces
Describe the concept of molecular mimicry in GBS
Generation of an immune response against the infectious agent generates anti-ganglioside antibodies that cross-react with glycolipids present in peripheral nerves and nerve roots.
Which antibodies are associated with GBS?
IgM, IgG1
Which ganglioside is often attacked?
GM1
Where is GM1 present?
- Myelin
- Axolemma
- Paranodes
- Nodes of Ranvier (peripheral motor nerves)
What are the three categories of treatments in GBS?
- Specific treatment
- Supportive treatment
- Rehabilitation
What are the options for specific GBS treatment?
- Plasma exchange or plasma pheresis
- Intravenous immunoglobulins
What are the options for supportive GBS treatment?
- Artificial respiration
- Prevention and treatment of complications (infections, pain)
- Physiotherapy
Why is GBS not a typical classic auto-immune disease? (5)
- No predominance in females
- No association with other auto-immune diseases
- No relapsing-remitting or chronic disease course
- No association with specific HLA haplotypes
- No improvement after corticosteroids
Why is GBS a typical post-infectious disease?
- 2/3 of patients have symptoms of a recent respiratory or GI-infection
- Antibodies to glycolipids in serum are detected in 50-60% of the cases
- Association type of infection and clinical features
- Association type of infection and prognosis
- > 95% has a monophasic disease course?
What is the most common clinical and electrophysiological phenotype of GBS related to a preceding C.jejuni infection?
Pure motor clinical variant and the acute motor axonal neuropathy
Which infections are associated with GBS?
- C.jejuni
- CMV
- EBV
- Mycoplasma pneumoniae
- HEV
Which infections commonly precede sensory motor GBS? What is their electrophysiological phenotype?
M. pneumoniae, CMV and EBV. Demyelinating (AIDP)
True or False: “Clinical outcome is better if you had a preceding C.jejuni infection than if you had a preceding M.pneumoniae infection.”
False. You actually have a worse outcome
What kind of data can you use to investigate an association between infections and GBS?
- Epidemiological data
- Case-control study
What do you look for in a case-control study to study an association between Zika infection and GBS?
- Zika virus positive cases vs Zika virus negative cases –> compare %GBS cases
- GBS cases vs control cases –> compare % Zika virus positives