Last updated: September 5, 2017
Segmental demyelination (SD) - damage to myelin sheath: also see p. PN1 >>
primary SD - only myelin is affected; axon is spared.
secondary SD - changes in axon → damage to myelin.
negative effects - conduction abnormalities (slowing or block) → muscle weakness, large fiber sensory loss.
motor aspects: conduction slowing (vs. block) does not produce clinical weakness when it affects motor axons (fact that nerve impulses are reaching muscle fibers few milliseconds later than normal is of no significance!).
uniform (vs. differential) conduction slowing does not have clinical sensory correlate.
differential conduction slowing (different in different types of fibers) may be detected by certain examination techniques that require transmission of highly synchronized nerve volleys (e.g. deep tendon reflexes, vibratory sensation).
positive effects - ectopic impulse generation, abnormal "crosstalk" between demyelinated axons → fasciculations, myokymia, cramps, paresthesias.
Familial SD polyneuropathies - length-dependent polyneuropathies with predictable presentations (vary only in process severity):
lower extremity is affected earlier and more severely than upper extremity.
distal parts suffer first and ultimately most severely.
sensory component tends to be involved earlier and more severely than motor.
contralateral limbs are affected equally.
along any specific nerve, conduction rate abnormalities are uniform.
Acquired SD polyradiculoneuropathies (N.B. roots are always affected in acquired SD cases!):
presentation identical to familial SD polyneuropathies (e.g. CIDP, AIDP in recovery stages).
specific presentations (e.g. AIDP early in its course):
may be more severe in upper extremities (e.g. sural nerve may be normal, whereas median nerve may be grossly abnormal).
motor component may be more abnormal than sensory.
abnormalities may be (multi)focal (vs. generalized) - focal conduction slowing.
nerves of same type, in same limb, at same level, often show very dissimilar findings.
homologous nerves in contralateral limbs may be affected differently.
in acute SD polyradiculoneuropathies, conduction blocks dominate, whereas in chronic SD polyradiculoneuropathies, conduction slowing is prominent.
Acquired SD polyradiculoneuropathies
I. Acute - Guillain-Barré syndrome:
Acute inflammatory demyelinating polyradiculoneuropathy (AIDP)
Axonal form of GBS:
motor (i.e. acute motor axonal neuropathy)
motor-sensory (i.e. acute motor-sensory axonal neuropathy)
Chronic inflammatory demyelinating polyradiculopathy (CIDP)
CIDP with multiple myeloma
CIDP with osteosclerotic myeloma
CIDP with Waldenström macroglobulinemia
Monoclonal gammopathies of undetermined significance (MGUS):
MGUS IgM neuropathy with anti-MAC antibody
MGUS IgG, IgA, IgM neuropathy without anti-MAG antibody
Motor neuropathy with multifocal conduction block
Guillain-Barré Syndrome (GBS), Acute Inflammatory Demyelinating Polyradiculoneuropathy (AIDP)
- different autoimmune disorders with rapidly evolving sensorimotor polyradiculoneuropathy resulting from widespread:
inflammatory PNS demyelination (AIDP)
noninflammatory PNS axon loss (axonal form of GBS)
- autoimmune diseases against various components of peripheral nerve fibers.
Endoneural perivascular (mainly perivenous) lymphocytic infiltrates
segmental demyelination → wallerian degeneration
N.B. there is no dominant antigen–antibody reaction (any number of myelin and axonal elements may be involved in inciting immune reaction)
AIDP - myelin sheath is specific target structure.
both humoral << cell-mediated factors - macrophages penetrate basal lamina surrounding axon, displace Schwann cell from myelin sheath, and then phagocytose myelin lamellae.
circumscribed inflammatory perivenular and endoneurial infiltrates (lymphocytes, macrophages) and localized demyelination scattered throughout PNS (roots ÷ distal peripheral nerve fibers).
predilection (at least soon after onset) for roots and distal peripheral nerve fibers.
some axon loss also occurs.
during recovery, remyelination occurs, but lymphocytic infiltrates may persist.
Axonal form of GBS:
wallerian degeneration - axon loss.
roots affected far more extensively than peripheral nerves:
acute motor axon neuropathy - ventral roots alone;
acute motor-sensory axonal neuropathy - both ventral and dorsal roots.
in surviving axons, macrophages are present within periaxonal spaces, surrounding compressed but otherwise normal-appearing, axons.
some sparse demyelination also occurs.
most common acquired demyelinating neuropathy (incidence 1-2 per 100,000 population).
males > females.
any age (incidence is higher in elderly).
any time of year.
most cases are sporadic, but clusters have been reported (derive from obvious trigger factor, such as antirabies vaccination).
no clear relationship with HLA.
Axonal form of GBS
small proportion of GBS cases in North America and Europe.
occurs principally as summer epidemics in China (associated with Campylobacter jejuni).
typically children and young adults.
Antecedent events (triggers) - associated with GBS in ≈ 70% cases (occur 1-3 weeks before onset of symptoms):
Viral - CMV*, Epstein-Barr virus*, HIV*, herpes, influenza, hepatitis.
Bacterial - Campylobacter jejuni* (gastroenteritis), Mycoplasma pneumoniae*, Borrelia burgdorferi.
Vaccination - rabies (some strains), vaccinia, influenza.
Cause-and-effect relationship seems very likely with HIV infection (test all patients for HIV), Hodgkin's disease.
Ascending weakness, areflexia, paresthesias with little sensory loss
AIDP and axonal form of GBS are clinically indistinguishable and have similar CSF profiles!
most patients are essentially well and lack systemic symptoms (incl. fever, lymphadenopathy [may be sign of trigger event!]).
Initial neurological symptoms vary:
50% patients – distal symmetrical paresthesias (“pins and needles”) involving toes & fingers → spread proximally (but seldom beyond ankles and wrists); perioral paresthesias are less common.
N.B. do not mistake for hyperventilation symptoms!
symmetrical weakness can be presenting feature (but more often it is first noted few days after paresthesias begin) - begins in proximal lower extremities, soon spreads (ascends) to upper extremities; areflexia is one of earliest findings (esp. in axonal form)!
Normal ankle and knee reflexes in weak lower extremity virtually rules out diagnosis!
Progressive phase lasts few days ÷ 3-4 weeks (50% patients reach nadir by 2 weeks, 80-90% - by 3 weeks); prominent features are motor!
flaccid weakness varies considerably (often profound, ascending all four limbs, trunk, respiratory, bulbar, and facial muscles - Landry's ascending paralysis).
Facial diplegia is seen in 50% patients!!!
because spinal roots are prominently involved, GBS can involve short nerves (e.g. intercostal, cranial) as well as long ones.
sphincters are spared.
may even cause nonreactive pupils.
deep, poorly localized pain commonly occurs;
most severe in shoulder girdle, back, and posterior thighs.
more severe at night.
sometimes accompanied by muscle cramping.
sensory abnormalities (sensory loss) are found infrequently (vs. sensory symptoms) - vibration and proprioception are most severely affected (up to sensory ataxia and pseudoathetosis), esp. in distal extremities.
dysautonomia (occurs to some extent in majority of patients) - severe paroxysmal hypertension, orthostatic hypotension, cardiac arrhythmias (of all types) - may be life threatening!
Peaked symptoms persist unchanged for 2-4 weeks - plateau phase → begin to recede in extremely variable fashion (over 6-12 months).
improvement follows gradient inverse to direction of involvement (recovery of bulbar function →→→ lower extremity weakness resolving last).
tendon reflexes are usually last function to recover.
Acute axonal form of GBS - more rapid onset, more severe (early denervation atrphy), poor ultimate recovery.
Miller-Fisher syndrome (benign disorder - does not require specific immune therapy) - cranial nerve involvement predominates:
ophthalmoplegia - anti-GQ1b is found in almost all patients with ophthalmoplegia
No limb weakness!
Pathophysiologic, clinical, diagnostic stages: