peripheral neuropathy Flashcards
What peripheral neuropathy did the man in the video have and with what autoantibodies?
CANOMAD
With IgM ab against disialosyl
typical features of how peripheral neuropathy affects the somatic nervous system?
muscle weakness and loss of muscle tone. Loss of dexterity sensory loss tingling/pain or numbness temperature. imbalance suppression of reflexes
features of peripheral nueropathy affecting the autonomic nervous system?
postural hypotension
lack of sinus arrythmia (no HR changes with inspiratio/n/expiration)
impaired pupillary reflexes to light.
abnormal sweating (glands under autonomic control)
stomach and bowel contraction and emptying issues.
3 ways that Peripheral nerves are damaged.
axon injury if in centre can extend proximally and distally
Or axon damage distally will start to die away from muscle.
Or segmental demylination- unable to contract despite intact axon and muscle connection. because of loss of conduction.
Order of peripheral nerves head to bottom of spine/
cranial, thoracic, lumbar, sacral.
What sensory and motor inputs do the cranial nerves supply?
To face and neck as well as through vagus nerve: gut, innervates the lungs and heart
what are the differences in how the CNS and PNS nerves are myelinated?
PNS myelinated by schwann cells and CNS myelinaed by oligodendrocytes.
What are the subdivisoin of the PNS?
sensory (afferent: somatic sensory and visveral sensory.
motor efferent: somatic nervous system and autonomic nervous system
autonomic: sympathetic and parasympathetic.
Effect of parasympathetic on HR and glucose release , airway smooth muscles and stomach and pupils?
slows HR inhibits glucose release constricts ariway stimulates stomach activity. constricts pupils
Effect of sympathetic on HR and glucose release , airway smooth muscles and stomach and pupils?
Increases HR stimulates glucose releae relaxes airways inhibits stomach activity dilates pupils
Nerves from spinal cord come in pairs, drsal root and ventral root.
Where do sensory and motor nerves belong and their cell bodies?
dorsal route has sensory neurones with cell body in dorsal root ganglion.
Ventral root contains motor neurones, cell bodies in anterior horn of cord.
What categories of myelination are C IV and Aa?
Aa has the greatest myelination and diamter- the fastest conduction for skeletal muscles.
C IV has least myelination and diameter for pain an temperature receptors.
Skeletal muscle > mechanoreceptors > pain and temperature.
Which will demyelination affect more? C IV neurones or Aa neurones?
More heavily myelinated will be more affected.
What is a classical presentation of axonal sensory-motor peripheral polyneuropathy? What can cause this?
distal extremities to proximal spread - some numbness in the middle chest.
A whole host of things can cause this chronic axonal loss, drugs infections diseases, endocinre, etc.
How can you distinguish axonal from demyelinating pathology clinically?
axonal has a lenght dependent pattern with weakness proportional to wasting.
Demyelinating: proximal and distal weakness, without the wasting (can have rapid recovery)
use electrodiagnositic testing:
axonal: decrease in amplitude
demyelinating: decrease in conduction.
What are examples of acute and chronic demyelinating neuropathies?
acute: Guillian barre syndrome (caused by an infectious. vaccine/trauma trigger)
Chronic: CIDP (Chronic inflammatory demyelinating polyneuropathy)
Paraprotein related.
Differences in progression to worse symptoms in GBS vs CIDP?
GBS: 4 weeks till peak
CIDP: 8 weeks +
differences in the disease course in GBS and CIDP?
GBS: monophsic, will resolve.
CIDP: mostly chronically progressive- relapsing remitting or monophasic.
Is there often cranial, respiratory muscle, autonomic involvement in GBS vs CIDP?
often for GBS
rarer for CIDP
Pattern of progression GBS vs CIDP?
GBS: starts distally and progresses proximally.
CIDP: variable can start with upper limb onset.
Differences in pathological subtypes in GBS vs CIDP?
GBS: axonal, demyelinating, nodal/paranodal
CIDP: nodal/paranodal and demyelinating
Differences in the general treatment of GBS and CIDP?
GBS: IVg and plasma exchange. NO steroids
CIDP: steroid and plasma exchange, rituximab
5 different pathologies of immune-mediated neuropathies.
Ab targeting components of myelin sheath/ nodes of ranvier (complement activation and MAC damage)
peripheral deposition of immune complexes
amyloidosis
infiltrating immune cells (could be macrophages MMPs) and autoimmunity (cancer?)
cytokine production causing inflammation
Components of the myelin sheath that could be targeted?
MAG/SGPG
What kind of protein can cause molecular mimicry and GBS in infection?
C. jejuni, LPS coating mimics GM1 and GD1a antignes- AMAN GBS subtype.
Or mimicry of GD3 GQ1b and GT1 (MFS subtype).
What kind of neuropahy is AMAN?
axonal target GM1, GD1a antigens.
What kind of neuropathy is MFS and AIDP?
MFS is regional: GD3 and GT1 GQ1b
AIDP is demyelinating but ukown antigen targeted.
What antigens are targeted in chronic neuropathies CANOMAC? Antig-MAG/ DADS?
CANOMAC: GD1b, GD3 GQ1b GT1b.
Anti-MAG/DADS: myelin associated glycoproteins.
What neuropathy has antibodies against NF155, NF140 CNTN1 and CASPR1?
CIDP
By what mechanism can Ab mediated targeting of nodes of ranvier lead to axonal degradation?
gangliosides in nodes of Ranvier targeted,complement acivation and MAC formation.
Ca2+ will simulate axon degradation which means difficult to repair.
Where can protein targets also be found that aren’t in the nodes of ranvier?
paranode, juxtaparanode, internode.
CASPR1/2 in paranode can bind to myelin sheath,
Is NF140/186 in node or paranode?
Node
Are CASPR1, NF155 and CNTN1 in nodes or paranodes?
paranodes.
How might IgG4 be pathogenic in neuropathies?
they will block e.g. paranode proteins mediating myelin sheath adhesion
What does PDN stand for and different types?
painful diabetic neuropathy.
IgG/IgA indistinguishable from CIDP.
IgM PDN: particularly associated with tremor, slow progression and anti MAG ab.
Features of PEOMS
clonal expasion of plasma cell leading to elevated cytokine levels- mixed axonal/demyelinating neuropathy with poor outcome.
treatment for CIDP or IgA/IgG PDN?
steroids, or IVig
Plex, immunosuppressants
treamtent for GBS and MMN/pure motor CIDP?
no steroids, IVIg, PLEX
treatment for DADS/IgM PDN?
IVIg or rituximab
POEMS treatment?
chemotherapy and steroids, radiation and SCT.
