This document discusses electrodiagnostic criteria for Guillain-Barré syndrome (GBS) subtypes acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). It reviews the evolution of criteria sets over time, including those proposed by Asbury, Albers, Cornblath, Ho, Hadden, and others. Key findings include that early electrodiagnosis can be difficult, with reversible conduction failure in AMAN sometimes mimicking AIDP. Serial nerve conduction studies are important for distinguishing subtypes and determining prognosis, as features may change over time. The document also discusses pathological mechanisms and involvement of sensory fibers.

1. Electrodiagnosis of GBS

2. Introduction
• Most common cause of acute flaccid paralysis worldwide
• Collective term for several variants and subtypes
• Distinct clinical, pathological and electrophysiological features
• Difficult to distinguish on clinical grounds
• Electrophysiology plays a major role

3. • Two main GBS subtypes are AIDP and axonal GBS
• Nerve conduction studies (NCS) remain the mainstay in the
electrodiagnosis and classification into subtypes
• AIDP - conduction slowing, conduction block, and temporal dispersion
• Axonal - absence of demyelinating features and decrease in distal
CMAPs and SNAPs
• In the last three decades, different electrodiagnostic criteria sets have
been proposed
• Based on a single study

4. NCS changes in AIDP
• Initial changes - delayed, absent, or impersistent F and H responses,
reflecting proximal demyelination
• Later - prolonged distal latencies, along with other evidence of
segmental demyelination, especially conduction block and temporal
dispersion
• Present in 50% of patients by 2 weeks and in 85% by 3 weeks

9. Electrodiagnostic criteria for AIDP
• Asbury et al. (1978) summarised the electrophysiological features and
highlighted the parameters useful for GBS diagnosis:
• (1) approximately 80% of patients have evidence of nerve conduction
slowing or block at some point during the illness;
• (2) CV is usually less than 60% of normal, but the process is patchy
and not all nerves are affected;
• (3) DMLs may be increased to as much as three times normal;
• (4) F-waves often give good indication of slowing over proximal
portions of the nerve trunks and roots; and
• (5) up to 20% of patients will have normal conduction studies

10. Electrodiagnostic criteria

11. Albers et al. (1985)
• Must have one of the following in two nerves
• CV <95% LLN <85% if d-amp <50% LLN
• DL >110% ULN >120% if d-amp <LLN
• TD defined abnormal when ‘unequivocal’
• CB were both defined by a proximal to distal CMAP ratio <0.7
• F Lat >120% ULN

12. Cornblath (1990)
• Originally designed for detecting primary demyelination in CIDP
• Must have three of the following in two nerves - more stringent but
lacking of sensitivity
• CV <80% LLN <70% if d-amp <80% LLN
• DL >125% ULN >150% if d-amp <80% LNN
• TD >20% prox-dist NP area or amp decrease;>15% prox-dist dur
increase
• CB >20% prox-dist NP area or amp decrease;<15% prox-dist dur
increase
• F Lat >120% ULN >150% if d-amp <80% LNN

13. Ho et al. (1995)
• slightly modified version of the Albers’ criteria set, to differentiate
AIDP from AMAN in a Chinese population
• one of the following in two nerves
• CV <90% LLN <85% if d-amp <50%
• DL >110% ULN >120% if d-amp <LLN
• TD Unequivocal
• CB Not considered
• F Lat >120% ULN

14. Hadden et al. (1998)
• Further modified Albers’ criteria not considering TD but reintroducing
CB
• one of the following in two nerves
• CV <90% LLN <85% if d-amp <50% LNN
• DL >110% ULN >120% if d-amp <LLN
• TD Not considered
• CB <0.5 prox-dist amp ratio and d-amp >20% LLN
• F Lat >120% ULN

15. Electrodiagnostic criteria for AMAN
• Ho’s and Hadden’s criteria sets - based on the initial assumption -
AMAN was characterised by simple axonal degeneration
• Ho - No evidence of demyel
• d-amp <80% in two nerves
• Motor nerves with very low CMAP amplitudes due to axonal
degeneration may show prolonged DML and F-wave latency or
reduced CV

16. • Hadden’s criteria set for AMAN
• allows the existence of one demyelinating feature in one nerve if the
distal CMAP is <10% of lower limit of normal
• None of the criteria for demyelination, except in one nerve if d-amp
<10% of LLN
• d-amp <80% in two nerves

17. Reversible conduction failure in AMAN
• Kuwabara et al., 1998 - AMAN patients with antibody to gangliosides
may show in some nerves rapidly reversible CB/slowing - reversible
conduction failure (RCF)
• CB in intermediate nerve segments promptly resolves
• dCMAP amplitudes rapidly increase
• DMLs, when prolonged, return to normal values
• without the development of excessive TD and polyphasia of CMAPs

18. Acute motor axonal degeneration, IgG anti-
GM1 and anti-GD1a

19. Reversible conduction failure in intermediate
and distal nerve segments, antibodies to GM1

21. Reversible conduction failure in distal nerve
segment, antibodies to GD1b

23. Serial electrophysiological findings in patients
with axonal GBS and AIDP
dCMAP amplitudes expressed as percentages
of values at first recordings considered 100%
DML expressed as percentages of upper
limits of controls

24. AIDP, no antibodies to gangliosides

25. Acute Motor CB Neuropathy
• 2003, Capasso et al.
• two patients - acutely developed symmetric weakness without
sensory symptoms
• antecedent diarrhoea (C. jejuni was isolated from one)
• high titres of IgG antibodies to GM1, GD1a and GD1b

26. • Electrophysiological studies
• Reduction of dCMAP amplitudes and early partial motor CB in
intermediate nerve segments
• normal sensory conductions even at the sites of motor CB
• dCMAP amplitudes normalised and CB resolved in 2–5 weeks without
development of excessive TD
• Motor CV was slowed at the sites of CB, in the range considered
demyelinating
• At serial recordings, CVs increased with the decrease of CB and
reversed to normal when CB had disappeared

27. Serial electrophysiological findings of two patients
withc acute motor conduction block neuropathy
and antibodies to GM1, GD1a, GD1b

28. • conduction slowing at CB sites - not due to de-remyelinatin
• preferential block of large-diameter fastest conducting fibres
• altered resting membrane potential and sodium channel inactivation
with delay of the action potential rising time

29. • AMCBN - ‘arrested AMAN’
• anti-ganglioside antibodies bind to the nodal axolemma
• induce RCF not progressing to axonal degeneration in any nerve
• AMCBN, AMAN with RCF and AMAN with axonal degeneration are a
pathophysiological continuum
• AMCBN is a mild form of AMAN with RCF in most of nerves

30. Length-dependent conduction failure
• Abnormal amplitude reduction of proximal CMAP, which disappears
at serial recordings
• dCMAP amplitude decreases and equalises proximal CMAP
• without development of excessive TD or other features of
demyelination
• explained by progressive loss of excitability in fibres undergoing
Wallerian-like degeneration

31. Length-dependent conduction failure, IgG
anti-GM1 and anti-GD1a antibodies

32. • RCF occurring at first and progressing to axonal degeneration
• RCF in intermediate nerve segments followed by adjunctive axonal
degeneration in distal nerve terminals
• Distinction between these conditions is impossible
• Pattern has ben defined as length-dependent conduction failure
• Considered as an expression of axonal damage
• less favourable prognosis

33. Pathophysiology
• IgG deposit at the nodes of Ranvier
• Complement activation with the formation of the MAC at the nodal
axolemma
• disruption of nodal sodium channel clusters
• lengthening of nodal region
• detachment of paranodal myelin terminal loops
• eventually axonal degeneration
• All these changes lower the safety factor for impulse transmission

34. Immunopathological cascades in AMAN

35. • Pathophysiologic process in AMAN varies from
• mild functional axonal involvement manifesting electrophysiologically
as RCF
• axonal degeneration appearing as distal CMAP reduction or length-
dependent conduction failure
• these conditions are a continuum

36. • Explains why recovery in AMAN patients - either very rapid and
complete or very prolonged with poor outcome
• AMAN patients do not necessarily have a poor prognosis and
• may improve more rapidly or more slowly according to the relative
proportion of axonal degeneration and reversible conduction failure
• AMAN with reversible conduction failure or AMCBN - best prognosis
and complete recovery

37. Electrodiagnostic criteria of AMSAN
• Feasby et al, Rees et al electrodiagnostic criteria for AMSAN are
• (1) no evidence of demyelination
• (2) distal CMAP amplitude <80% of lower limit of normal (as in
AMAN)
• (3) reduction of sensory nerve action potential amplitude
(SNAP)<50% of lower limits of normal in at least two nerves

38. Sensory conductions in AIDP
• AIDP - abnormal sensory conductions were found in 85% in the
median and ulnar nerves and in 38% in the sural nerves
• sensory nerve conduction, especially in the distal nerve segments, is
impaired in almost all AIDP
• normal or relatively spared sural response
• sural-sparing pattern - combination of normal sural SNAPs and low-
amplitude or absent upper-extremity SNAPs

39. • Distinctive of AIDP
• highly specific (96% specific) for AIDP
• preferential, early involvement of the smaller myelinated fibers
• relative resistance of the larger diameter myelinated fibers in the
sural trunk compared to the smaller nerve fibers in the digital nerves
of the hands
• lack of length dependent axonal degeneration

40. Sural sparing pattern

41. Sensory conductions in AMAN and AMSAN
• Capasso et al., 2011
• Serial conductions in 13 AMAN and three AMSAN patients were
reviewed
• In 34% of initially normal sensory nerves of six AMAN patients SNAP
amplitude increased by 57–518%,
• whereas in three nerves of three patients SNAP decreased by 50 -69%
• Overall, serial recordings allowed detection of some sensory fibre
involvement in 49% of nerves and in 69% of AMAN patients

42. • In one AMSAN patient, SNAP increased in two nerves by 150–300%
• in another patient, SNAPs, unrecordable at baseline, reappeared
during follow-up and normalised
• In nerves of some patients, SNAP amplitudes increased rapidly,
suggesting RCF of sensory fibres.
• In other nerves, SNAP increased over months, as for axonal
regeneration.

43. • Sensory fibres - often involved subclinically in AMAN
• RCF may be present in sensory fibres of both AMAN and AMSAN
• RCF has been reported in sensory fibres in acute sensory ataxic
neuropathy, and in motor and sensory fibres in the pharingo-cervical
brachial variant of GBS and in GBS–Miller Fisher overlap

44. Pitfalls in electrodiagnosis
• Uncini et al., 2010
• Italian GBS population, investigated whether and how serial recordings
changed the initial classification
• Both the Ho’s and Hadden’s criteria sets were tested in 55 patients
• At first test, the electrodiagnosis was almost identical with both criteria
sets:
• 65–67% of patients were classifiable as AIDP
• 18% as axonal GBS (AMAN or AMSAN), 14–16% were equivocal.
• At follow-up, 24% of patients changed classification:
• AIDP decreased to 58%, axonal GBS increased to 38% and equivocal
patients decreased to 4%

46. • Majority of shifts - AIDP and equivocal groups to axonal GBS
• Main reasons - recognition of the RCF and of the length-dependent
conduction failure as expression of axonal pathology
• All patients who shifted to the axonal group had antibodies to
gangliosides

47. Utility of Serial NCS
• Early phase of GBS the distinction between AIDP and axonal GBS may
be impossible in some patients
• Lack of distinction among demyelinating CB, RCF and length-
dependent conduction failure
• may fallaciously classify patients with axonal GBS as having AIDP
• Serial NCS are advocated to establishing the electrodiagnosis of GBS

48. • AMAN and AIDP differ in their evolution of changes on serial NCS
• AMAN, 2 possible patterns of evolution
• Rapid improvement in CMAP amplitudes and CV from resolution of
nodal conduction failure
• decrease of distal CMAP amplitudes due to axonal degeneration
• AIDP with gradual remyelination, CV remains decreased, and
persistently increased TD is seen
• Such changes can best be demonstrated on serial NCS

49. Rajabally et al., 2015
AIDP Axonal
• At least one of the following in at least two
nerves:
MCV <70% LLN
DML >150% ULN
F lat >120% ULN, or >150% ULN (if distal CMAP
<50% of LLN)
OR
F-wave absence in two nerves with distal CMAP
≥20% LLN, with an additional parameter, in one
other nerve
OR
Proximal CMAP/distal CMAP ratio <0.7
(excluding the tibial nerve), in two nerves with
an additional parameter, in one other nerve
• None of the above features of demyelination
in any nerve and at least one of the following:
Distal CMAP <80% LLN in two nerves
F-wave absence in two nerves with distal CMAP
≥20% LLN, in absence of any demyelinating
feature in any nerve
Proximal CMAP/distal CMAP ratio <0.7, in two
nerves (excluding the tibial nerve)

50. Uncini 2017
• AIDP
• At first or second study at least one of the
following in at least two nerves:
• MCV <70% LLN
• DML>130 % ULN
• dCMAP duration >120% ULN
• pCMAP/dCMAP duration ratio >130%
• F Lat >120% ULN
• OR one of the above in one nerve
• PLUS:
• Absent F waves in two nerves with dCMAP >
20% LLN
• Abnormal ulnar SNAP amplitude and normal
sural SNAP amplitude
• AMAN
• At first and second study none of the above
AIDP features in any nerve (demyelinating
features allowed in one nerve if dCMAP <20%
LLN)
• At first study at least one of the following in
each of two nerves:
• dCMAP<80% LLN
• pCMAP/dCMAP amplitude ratio <0.7
• (excluding tibial nerve)
• isolated F wave absence (or <20%persistence)

51. • at least one of the followings in two nerves is
evidence of reversible conduction failure:
• >150% increase dCMAP amplitude without
increased dCMAP duration (<130% ULN)
• pCMAP/dCMAP amplitude ratio <0.7 at first test
which improves more than 0.2 because of
increased pCMAP without temporal dispersion
(pCMAP/d CMAP duration ratio <130%)
• isolated F wave absence (or <20% persistence) that
recovers without increased minimal latency
(<120% of ULN)
• AMSAN
• At first study the same criteria of AMAN in motor
nerves
• PLUS
• SNAP amplitudes < 50%LLN in at least two nerves
• At second study:
• evidence for axonal degeneration and reversible
conduction failure in motor nerves as in AMAN
• there is evidence of axonal degeneration in
sensory nerves if
• SNAP amplitude in two nerves it is stable or
decreased
• there is evidence of RCF in sensory nerves
• if SNAP amplitude in two nerves it is increased
(>50% in median and ulnarnerves and >60% in
sural)