Journal of Neurology, Neurosurgery, and Psychiatry 1991;54:768-774

Patterns and severity of conduction abnormalitiesin Guillain-Barre syndrome

William F Brown, Robert Snow

AbstractWhether the conduction abnormalitiesand lesions underlying them are. ran-domly distributed throughout the peri-pheral nervous system (PNS) or certainregions are selectively more vulnerableto attack is an unresolved question inGuillain-Barre syndrome (GBS). Toexamine this question, 15 cases of GBSwere comprehensively examined usingelectrophysiological techniques whichallowed close examination, quantitationand comparison of conduction abnor-malities in motor and sensory fibres ofthe upper limb between the spinal cordand the distal extremities of the nervefibres. Comparison of these studies withresults expected in a model where thechances of conduction failure wereuniformly distributed led to the con-clusion that conduction slowing andblock were not uniformly distributed inmost cases. Conduction block was maxi-mal in the terminal segment distal to thewrist and to a lesser extent both conduc-tion block and conduction slowing weredisproportionately greater across theelbow and in the axillary to spinal rootsegments in over one half of the cases.These findings support the hypothesisthat certain regions, perhaps because ofrelative deficiences of the blood-nervebarrier, may be more vulnerable in GBSthan other regions.

Clinical NeurologicalSciences, UniversityHospital, London,Ontario, CanadaW F BrownR SnowCorrespondence to:Dr Brown, ClinicalNeurological Sciences,University Hospital, 339Windermere Road, London,Ontario, Canada N6A 5A5Received 12 March 1990and in final revised form22 November 1990.Accepted 6 December 1990

One question still unresolved in Guillain-Barre syndrome (GBS) is whether lesionsunderlying the conduction abnormalities inthis disease are uniformly distributedthroughout the peripheral nervous system(PNS) or certain regions consistently bear thebrunt of the attack. Previous studies havesuggested that the conduction abnormalitiesmight be uniformly distributed, a conclusionbased on close matches between actual chan-ges in maximum "M" potential amplitudes,between successively more proximally dis-placed stimulus sites and what might beexpected from a model where conductionblock was uniformly distributed throughoutthe PNS.'2 Other studies suggested conduc-tion block might not be uniformly distributedbut rather, greater in the distal terminal andproximal segments of the PNS and across

common sites of entrapment.' The latterhypothesis might suggest selective vul-nerability of the PNS in regions where theblood-nerve barrier is considered to be

relatively deficient,7'-0 and as a consequenceaffording less protection from circulatingcellular and humeral agents in the disease.Our study was designed to assess patterns

of conduction abnormalities throughout thecourse of motor fibres between the spinal rootsand their target muscles and sensory fibresbetween the spinal cord and digits.

MethodsSubjectsFifteen patients with clinically defined GBS"were studied, and their clinical states at peakdisability graded.'2 Two patients (8 and 15)briefly relapsed following a course of plasmaexchange.Approval from the Human Experimenta-

tion Committee of the University of WesternOntario was obtained for the study and infor-med consent obtained from all patients.

Electrophysiological studiesMotor conduction studiesSurface electrodes (DANTEC) in a belly-ten-don configuration were used to record themaximum hypothenar "M" potential. Theulnar nerve was stimulated using bipolar sur-face electrodes at the wrist, at least 2 cm distalto the cubital tunnel, 2-3 cm proximal to theelbow, and as high in the axilla as possible.A DEVICES D-180 high voltage stimulator

was employed to stimulate the spinal roots.The anode was positioned 1-2 cm lateral tothe tip of the C6 spine and the cathode di-rectly inferiorly. Manually triggered singlepulses were used to keep to a minimum thenumber of stimuli required to establish asupramaximal response (five or fewer usually).Most patients judge stimulation of the spinalroots in this manner as no more uncomfort-able than supramaximal stimulation of nervetrunks elsewhere, provided care is taken to usecarefully graded single pulses and the pro-cedure explained beforehand.

In controls and patients there was noappreciable volume conduction to the hypo-thenar recording sites from median suppliedintrinsic hand or forearm muscles. This wasimportant, as selective stimulation of ulnarnerve fibres is impossible at the spinal root oreven axillary sites.As the central objective of this study was to

assess the overall severity and distribution ofconduction slowing and block between thespinal cord and distal terminations of thenerve fibres, comparisons were made betweenthe fifteen GBS cases and controls for:

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1) "Overall" percentage reductions in maxi-mum "M" potential negative peak area("M"A) between the spinal roots and motorpoint.This was calculated by:

"M"'Amp - "M"ASR x 100"M"AMp

where "M"AMp and "M"ASR = maximumhypothenar "M" potential negative peak areaat the motor point and spinal roots respec-tively. As "M"A is more independent ofinterpotential phase cancellation thanamplitude, "M"A was chosen as better reflect-ing conduction block.

In eight controls, a needle electrode,insulated to within 2-3 mm of its tip wasinserted as close to the motor point as possibleand supramaximal stimuli used to evoke amaximum hypothenar "M" potential. Thistechnique, however, was sometimes uncom-fortable and precluded direct study of theterminal 5-15 mm of the nerve. A reasonablesubstitute for such a directly obtained valuefor the motor point hypothenar maximal "M"potential was therefore required if conductionin the terminal segment between the wrist andhypothenar motor point was to be assessed inour patients. As a practical alternative toneedle stimulation near the motor point weelected to substitute the control mean -2 SDvalue for the maximum hypothenar "M"A atthe wrist for the motor point value in thepatients. This was considered a reasonablecompromise as hypothenar "M"A values inresponse to near motor point stimulation werewithin 5% of one another in eight controls (fig1).While choice of the -2 SD value might

have underestimated reductions in "M"A in

Hypothenar recording

L

0 10Time (ims)

20

Figure I Maximum hypothenar "M" potentialsrecorded with surface electrodes in response tosupramaximal percutaneous stimulation at the wrist,below the elbow, above the elbow, axilla and spinal rootsin a control. Additionally, a monopolar needle electrodewas inserted as close to the hypothenar motor point aspossible and a supramaximal stimulus delivered throughthe needle (anode was a surface plate over the back of thehand). No significant differences between maximum "M"potentials elicited by stimulation at the motor point andwrist were seen in this or seven other controls.

the terminal segment in some cases, we con-sidered the choice a better alternative to poss-ibly over estimating terminal reductions in"M"A in other patients had we chosen thecontrol mean or mean -1 SD values.In GBS patients overall percentage reduc-

tions in "M"A between MP and SR werecalculated as follows:

Control "M"AMp - GBS "M"ASR X 100Control "M"AMp

where control "M"AMp = the mean -2 SDfor the control "M"A at the wrist, and GBS"M"ASR = "M"A evoked by stimulation ofthe spinal roots in the patient.

2) Percentage reductions in "M"A between thewrist and motor pointThis was calculated by:

Control "'M"Amp - GBS "M"Aw x 100Control "M"Amp

where GBS "M"Aw = the "M"A evoked bystimulation at the wrist in the patient.3) Percentage reductions in "M"A per 10millimetre (mm) length of nerve for eachsuccessively more proximal segment between themotor point and spinal rootsAs quantitative assessment of conductionblock in more proximal segments is con-ditioned by conduction in distal segments, themotor point value for the GBS patients servedas the denominator for calculating percentagereductions in "M"A for successively moreproximal segments. Moreover, as the distan-ces for the various segments were not equal,reductions in "M"A were adjusted to a stan-dard distance, here 10 mm, calculated by:

"M"Adistal- "M"Aproximal x 10Control "M"AMp d

where "M"Adista, and "M"Aproximal = M"Avalues elicited by supramaximal stimulation atthe distal and proximal stimulus sites for eachsegment.

4) The motor terminal latency in milliseconds(ms) in the terminal segment and maximummotor conduction velocities in metres per second(Mls) for each successively more proximalsegment.Conventional techniques were employed formeasuring the motor terminal latency (MTL)to the hypothenar muscles and maximummotor conduction velocities (MMCVs) acrossthe forearm, elbow, and proximal arm. Thedistance between the axillary and cervical(anode) stimulus sites was measured withcallipers and the MMCV between thesestimulus sites calculated in the conventionalmanner. All studies were carried out with theelbow extended.

5) Sensory conduction studiesTo examine sensory fibres of equivalentdiameter to the motor fibres, somatosensoryevoked potential studies were carried out onthe median nerve. While studies of ulnar sen-sory conduction would have been preferable,

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cervical potentials with the latter were simplytoo poorly defined to allow accurate identifica-tion of the onset in controls and patients.

Percutaneous stimuli at the wrist wereadjusted to evoke maximal antidromic sensorynerve action potential and sensory conductionvelocities (MSCVs) between the wrist anddigits, wrist to axilla, and axilla to spinal cordcalculated and the latency to the N20 potentialmeasured. Orthodromic nerve trunk poten-tials were recorded as high in the axilla aspossible with the reference electrodepositioned over the lateral deltoid. The latterpotentials no doubt include antidromic poten-tials in motor fibres as well as orthodromicallyconducted potentials in sensory fibres. Thecervical potential was recorded over the C6spine with FZ as reference. Additionally, thecortical evoked potential was recorded overthe primary sensory area for the hand, againwith FZ as reference. Surface electrodes wereused throughout to record these potentialsexcept for a bare needle electrode for the scalprecording. The latter provided a convenientlow resistance (less than 2k ohms) relativelypainless electrode with which to record fromthe hairy scalp. The ground was placed aboutthe proximal forearm. All patients wereexamined as close to peak disability aspossible.

ResultsMotor conductionControls: "M" potential size and motor conduc-tion velocitiesIn the controls the maximum hypothenar "M"potential negative peak areas (1 SD) inmillivolts milliseconds (mV ms) at the wristand spinal roots were 37-2 (7.3) and 32 4 (7.7)mV ms respectively, the maximum reduction inany control being 23-9% between the wrist andspinal roots. For comparison, the maximum

5 Days Wrist

J Below elbow/ Above elbow

Axilla

Spinal roots ]-5mV

I /+

] o5mV

__

0 20 40 60Time (ms)

Figure 2 Hypothenar maximum "M" potentialrecordingsfrom patient 4 studied atfive days illustratingthe pattern of reductions in "M" potential size. At thisstage the overall reduction in "M"A between the motorpoint (control wrist - 2 SD) and spinal roots was96-9%, while that between motor point and wrist was68%. This case represents a clear example whereconduction abnormalities were maximal across theterminal elbow and axillary to spinal root segments. Forexample, reductions in "M"A per 10 mm of nerve were9-7, 0-0, 0-6, 0-0, and 0-9 across the terminalforearm,elbow, proximal arm and axillary to spinal root segmentsrespectively. Furthermore, the MMCV between theaxilla and spinal roots was 37-2 M/s, a value clearlyslowed relative to the proximal arm (58-8 Mls) andrelatively normal MMCVsfor the elbow andforearm of44-3 and 49-8 M/s respectively.

5 Days Time (ms)0 20 40 60

II

]v-a

_C= ~~~~~~~~~+

IA

Time (ms)

Figure 3 Sensory conduction study in case 4 atfive days.At this time conduction between the wrist and axilla wasnormal (MSCV 62-2 M/s and the amplitude of theaxillary potential 12-S V), distal conduction, however,was characterised by a reduced antidromic sensory nerveaction potentialfrom digits II and III (5-6 pV) andproximal conduction was slowed between the axilla andspinal cord (42-4 Mls).

Top two traces: Contralateral cortical evoked potentialon two time scales. The configuration and latency to N20(20-4 ms) were within the normal range but withrecovery shortened to 19-S ms.Middle trace (cervical recording): gain 2-S p V/;

Second tracefrom bottom (axillary recording): gain 5js V/; Bottom trace (antidromic recorded sensory nerveaction potentialfrom digits II and III) : gain S p V/.

increase in negative peak duration of themaximum hypothenar "M" potential betweenthe wrist and spinal roots of any control was60 1% [mean (1 SD) 14-2 (9-2) fig 1]. MMCVs(1 SD) for hypothenar motor fibres across theforearm, elbow, proximal arm and axillary tospinal root segments respectively were 61-4(5-2), 52-8 (9-9), 60-5 (6-1) and 75-7 (7-1) M/s,and the hypothenar MTL 2-6 (0-4) ms. Themean MMCV across the elbow was 13-4% lessthan the mean of the forearm and proximal armcombined, the slowest conduction velocityacross the elbow in 20 controls being 37-5 M/s.

GBS patientsOverall and terminal reductions in "M"ATable 1 illustrates the overall percentagereductions in "M"A between the motor pointand spinal roots and between the motor pointand wrist at the time of maximal reductions in"M"A. The former exceeded 90% in six and50% in 12 of the 14 patients. The latterexceeded 50% in five and 20% in nine cases. Infive cases, "M"A at the wrist exceeded thecontrol mean -2 SD value. The changes in"M"A were unaccompanied by any significantincrease in negative peak duration at the spinalroot level, the increase-being less than 20% in10 cases and in all others less than the maxi-mum seen in any control.

Comparison of reductions in "M"A over success-ively more proximal segmentsDisproportionate reductions in "M"A per 10mm of nerve across the terminal, elbow and

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Patterns and severity of conduction abnormalities in Guillain-Barre syndrome

Table I Clinical characteristics and magnitude of reductions in "M"A in GBS patients

Patient Age Time Onset Clinical Percentage Reduction in "M"A Percent Increase(Years) to Peak Grade in Negative Peak

Weakness at Peak Overall Terminal Duration(Days) MP-SR MP-W

1 52 4 4 836 487 002 20 5 4 87-1 39-8 - 2-03 48 4 4 83-1 43 8 + 6-84 23 14 5 969 681 -1225 32 7 5 893 327 006 40 21 5 253 0.0 +5497 25 19 4 951 49 +25-3

*8 32 21 4 919 00 +4509 16 10 4 978 97-8 +15910 62 17 5 95-6 69-0 -14-41 1 20 20 4 22-9 0 0 + 9 512 33 9 3 578 00 +13-513 33 6 2 88 00 + 5814 63 3 5 100 0 100 0 ?

*15 57 7 3 84-0 340 + 74

Clinical and electrophysiological features of GBS patients.Percentage reductions are shown in "M"A relative to the motor point, both overall between the motor point and spinal roots andin the terminal segment between the motor point and wrist. Also shown are the percentage increases in negative peak duration foreach subject at the spinal root compared with wrist stimulus sites.Where MP = Motor point

SR = Spinal rootW =Wrist* = Relapse ofGBS briefly following course of plasma exchange.

axillary to spinal root segments in excess ofadjacent segments were present in five cases(cases 2, 3, 4, 5 and 15), the terminal and elbowsegments in one case (case 10 where spinal rootstimulation was not carried out), elbow andaxillary to spinal root segments in two cases

Table 2 Changes in Motor Terminal Latency and Maximum Motor ConductionVelocity in GBS Patients at the Time ofPeak Reduction in "M"A

Subject Terminal Forearm Elbow Proximal Axilla toArm Spinal Root

1 +++ + + + ++ + + Complete Block2 ++ + ++ - ++3 + +++ ++++ ++ ++++4 + + +++5 + + _ + +++6 - - - - ++7 - - - - +8 + ++ ++++ ++ +++9 - - - - +10 + - + + + + - Complete Block11 - - - - -

12 + - - - +13 - - - -

*14 ++++15 - - + + + N/A

MTL (ms)Normal3 5-5-05-0-10-0

10-0-15-0>15*Axonal case

+++ ++

MMCV (M/s)Normal<Mean -2 SD30-4020-30<20

+++ ++

(cases 7 and 12), and proximally in one case(case 6).

In most of the preceding cases there were

accompanying disproportionate reductions inMMCV or prolongations in MTL in excess ofadjacent segments (table 2). Also, reductions inMSCV between the axilla and spinal cord werepresent in cases 4, 5, 6, 7 and 12 in the face ofnormal MSCVs between the axilla and wrist.Furthermore, antidromic digital sensory nerveaction potentials were reduced in amplitude incases 3, 4, 6 and 9, or absent in cases 5, 7 and 12,while at the same time the axillary nerve trunkpotential exceeded the control lower limitingvalue (5 mV) in all but one of the same cases(table 3).

In cases 1, 8, 1 1 and 13 there was no apparentpattern to the reductions in "M"A. Indeed, incases 13 there was no significant overall reduc-tion in "M"A between the spinal roots andmotor point. In case 14 no responses from thehypothenar or thenar muscles could be elicitedby stimulation at the wrist although very small"M" potentials (less than 1 0 mVms) could beobtained by stimulation closer to their respec-tive motor points. This case fits all the criteriafor "axonal" GBS.'1'5Even in the cases where there was no

Table 3 Sensory conduction

Amplitude Axilla to Corticalantidromic Terminal Wrist-Axilla Amplitude spinal cord Amplitudedigits II and III MSCV MSCV axilla MSCV cervical Latency Amplitude

Normal values uV M/s M/s uV M/s uV ms mV

Mean (ISD) 22-9 (12 4) 58-7 (7-2) 63-9 (5-3) 11-1 (5-1) 60 9 (7 6) 2-2 (0 8) 20 2 (1 2) 4-8 (2-4)Least control value 7 1Patients (Days 1-7)3 3-0 46-0 70-0 8-9 53-8 1 1 N/A N/A4 49-9 69-2 12-5 42-4 1-0 20 4 2-35 0 - 70-8 14-0 40 3 30 N/A N/A6 3-0 51-1 72-0 10-2 37-0 14 N/A N/A9 1-3 579 53-3 12-6 46-7 2-3 N/A N/A14 44 560 648 1 0 499 1.9 21*1 1 9Patients (Days 8-14)

1 0 - <. 24-3 M/s.> 3-0 29-0 0-74 0 - 66-9 5.0 31-3 0-6 N/A N/A5 2-0 49-4 70-8 14-0 40 3 3-0 N/A N/A7 0 - 62-2 3-0 30 4 0 5 19-7 2-2

12 0 - 63-8 4-2 55-0 0-8 21-2 1-413 4 0 40 3 65 2 4-9 53-2 2-0 18-6 6-5

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Table 4 Percentage reductions in "M"A per 10 mm

Proximal Axilla toSubject Terminal Forearm Elbow arm spinal roots

1 6-8 0-4 0-7 0-8 0-42 6-1 0-6 1.1 0-0 1-03 6-7 0-6 1-5 0-1 0-54 97 0-0 0-6 0-0 0-95 55 0-1 2-3 0-9 1-3

* 6 0-0 0-0 0-1 0-4 1-27 0-9 1-5 1-9 1-0 1-8

* 8 0.0 2-8 1.1 0-2 0-49 12-8 0-0 0°0 0°0 0°010 10-6 0-0 3-7 0-0 N/A

*11 0-0 0-5 0-0 0-3 0-2*12 0-0 0-0 0-4 0-0 1-9*13 0-0 0-2 0-0 0-3 0-2±14 16-7 - - - -15 5-0 0-6 1.1 0-0 1-8

Where *denotes maximum "M" potential at wrist exceeding the control mean-2 SD at thewrist and tdenotes the axonal case of GBS where there were no thenar or hypothenar responsesto stimulation at the wrist.

apparent pattern to the reductions in "M"Aper 10 mm of nerve, motor and sensory con-duction studies sometimes revealed dispropor-tionate segmental conduction slowing. Forexample, in case 8 the MMCV was dispropor-tionately reduced across the elbow and axillaryto spinal root segments relative to nearbysegments (table 2). Only in cases 1 and 13 wassensory conduction assessed and in the latter itwas normal while in case 1 conduction wasabnormal throughout, between the digits andspinal cord (table 3).

DiscussionAt the outset it might be helpful to consider thetheoretical and practical problems presentedby assessing the magnitude and distribution ofconduction block using the methods employedin this study. In the simple model representedby fig 4 where conduction fails at only one siteper fibre, reductions in "M" size expressedeither as a percentage of the motor point valueor as an absolute value are constant oversuccessively more proximal and equidistantsegments.This is not the case where the frequency of

conduction failure is high enough for conduc-tion to fail at more than one site along thecourse of individual nerve fibres.'2 16 In thelatter case it is the most distal sites of conduc-tion failure in nerve fibres which determine thepattern of changes in "M" size, as the site ofstimulation is displaced proximally, not anyadditional more proximally situated sites ofconduction failure. Of course the latter con-tribute to the overall frequency of conductionfailure in the segment in which they reside buttheir contributions to the "M" potential aremasked by the most distal sites of conductionfailure in each fibre.Where the chance ofconduction failure is the

same for all nerve fibres and sites of failure arerandomly distributed between the roots andmotor point, the size of the "M" potential atsuccessively more proximally displacedstimulus sites is described by an exponentialfunction such that the size of the maximum"M" potential at any stimulus site distance "d"from the motor point equals: "M"MP x e-bxdwhere "M"Mp is the size ofthe "M" potential at

Si

100?-

S2 S3 S4 S5 S6I If y I I

80-

60 r-R

N

0

401-

201

0 20 40 60

Distance (%)80 100

Figure 4 Simple model comprised offive nerve fibressupplying a musclefrom which the maximum "M"potential is recorded on the left. The nerve is divided intofive equal segments and stimulated at six sites, beginningat the motor point (S,) and ending at the spinal roots(S6). The chance of conduction failure is the same foreach fibre and there is a one in five chance of conductionfailing in one of the five successively more proximalsegments. Sites where conduction failed are shown by theX. Shown below is a plot of the maximum "M" potentialsize as a percentage of the value at the motor point foreach of the successively more proximally displaced sites ofstimulation. In this model allfibres make an equalcontribution to the maximum "M" potential and haveidentical conduction velocities. No more than one site offailure per fibre between spinal roots and motor point ispresent.

the motor point, and "b" the probability ofconduction block per unit length of nerve.The resulting pattern of changes in "M" size

in models where conduction block is assumedto be uniformly distributed throughout thePNS' 216 is characterised by the steepest reduc-tion in "M" size in the terminal segment andever diminishing reductions in "M" size oversuccessively more proximal segments forequivalent distances between successivestimulus sites. This is true both for absolutereductions in "M" size and percentage reduc-tions in "M" size per unit length of nerverelative to the motor point value (fig 5).To bring this model in line with our studies

we substituted the control mean -2 SD valuefor the hypothenar "M"A at the wrist for the100% motor point value in the model. There-after, values for "M"A were calculated for sitesclosely corresponding to actual sites of stimula-tion used in our human studies. Such calcula-tions revealed that failure rates reducing "M"Aby more than 50% in the terminal segmentwere accompanied by "M"A values at theelbow and axillary stimulus sites smaller thanthe control hypothenar motor unit actionpotential. However, reductions in "M"A ofthis magnitude were not seen at the elbow andaxillary stimulus sites in any of our cases in theface of equivalent or greater than 50% reduc-tions in "M"A in the terminal segment. Thissuggested to us that conduction block was notuniformly distributed but greatest in the ter-minal segment in many of our patients. Factor-ing in known differences in conduction

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Total distance (%)

Figure 5 (A) Progressive reductions in "M" size as apercentage of the maximum "M" potential at the motorpoint as the distance between the motor point and site ofstimulation was increasedfrom 0 to 100% of the length ofthe nerve. All motor units were considered to generatemotor unit action potentials of equal size and their fibresto conduct with equal velocities. The chance of conductionfailure were equalfor allfibres and equally distributedforeach fibre between the motor point and most proximal siteof stimulation. Illustrated are cases where conductionfailed in 10, 30, 50, 70 and 90% offibres per 10% lengthof nerve. (B) Linear transformation ofplots in A. If100% corresponded to a 30 mV ms maximum "M"potential "M"A, 0 1% would correspond to an "M"Avalue of 30 pVms and 0 01 to 3 /lVms. As the smallestarea for any single hypothenar motor unit actionpotentials recorded with the same surface elctrodes is 25u Vms, "M"A values falling below 0 1% clearly fallbelow the size of any single motor unit action potential.

velocities between motor nerve fibres'7 ' as wellas the biphasic and even triphasic character ofhypothenar motor unit action potentials wouldonly serve to further reduce "M"A values atthe elbow and axilla in the model. This wouldfurther accentuate the differences between themodel where conduction failures were assumedto be randomly distributed and actual observa-tions in our GBS patients.What of the distribution of conduction

failures proximal to the wrist? To answer thisquestion the model of randomly distributed

Table 5 Percent reductions in "M"A per one percent length of nerve

Percentage nervefibres blocked Proximal Axillaper 10% length of nerve Terminal Forearm Elbow arm spinal roots

90 20 0 1 00 00 0080 1*8 0 1 00 00 0070 1-6 02 00 00 0060 1-4 03 00 0-0 0050 1 1 03 01 00 0040 09 04 0 1 0 1 0030 07 03 02 0.1 00

Percentage reductions in "M"A per one percentage length of nerve were calculated forcomparison with actual values in GBS patients (table 4). One per cent is approximatelyequivalent to the 10 mm segment in the patients where overall distances between the hypothenarmotor point and spinal root averaged 800 mm.Percentage reductions per one percentage length were calculated for lengths of nerve for theterminal, forearm, elbow, proximal arm, and axilla to spinal root segments, corresponding to 10,30, 10, 15 and 35 percentage of the nerve between motor point and spinal roots.

conduction failures described in fig 5 was adap-ted to allow direct comparison with valuesobserved in our patients. Percentage reduc-tions in "M"A relative to the motor pointwhere adjusted for a standard distance of 1% ofthe length ofthe modelled nerve. The 1% valueclosely approximates the percentage reductionin "M"A per 10 mm of nerve in our patientswhere the overall distance between the motorpoint and spinal roots averaged 800 mm. In themodel, for failure rates where 30% or more ofthe fibres were blocked in the terminal segment,percentage reductions in "M"A per 1% lengthof nerve fall off progressively as would beexpected where the risk of conduction failure issimilar for all fibres and randomly distributedbetween the motor point and spinal roots (table5).The foregoing pattern, however, was mani-

festly not the case in our subjects. In six of thelatter, disproportionately greater reductions in"M"A per 10 mm length of nerve wereobserved across the elbow relative to theforearm and proximal arm and between theaxilla and spinal roots relative to the proximalarm. This pattern received further supportfrom the motor and sensory conductionstudies. Reductions in MMCVs in excess ofthose in adjacent segments were commonacross the elbow and axilla to spinal rootsegments and the MTL often prolonged whilethe MMCV across the forearm was normal orrelatively normal. In several cases the earliestconduction slowing was seen in the axillary tospinal root, elbow and terminal segments.Disproportionate reductions in MMCV acrossthe axillary to spinal root segment relative tothe proximal arm and forearm received furthersupport from reductions in MSCV between theaxilla and spinal cord relative to the segmentbetween the wrist and axilla.Based on studies of the F-response, conduc-

tion slowing across proximal segments ofmotornerves in excess of more distal segments hasbeen shown,3 as well as proximal conductionblock early in the disease,'9 findings confirmedby Brown and Feasby45 and Berger et al.6

Overall, our studies suggest that the primaryconduction abnormalities in GBS, includingboth reductions in conduction velocity andconduction block, may not, in some cases, beuniformly distributed between the spinal cordand the peripheral terminations ofnerve fibres.In many cases conduction was slowest and"M"A most reduced across the terminal, elbowand axillary to spinal cord segments while somecases showed more variable patterns. In theformer cases, why should the distal andproximal regions be so preferentially affected?The blood-nerve barrier is known to be rela-tively deficient at the roots and nerve termi-nals,7'10 and perhaps as others have suggested,preferential access of circulatory toxins, anti-bodies, lymphocytes or monocytes at these sitescould determine the pattern of conductionabnormalities in the early course of the disease.

Reductions in "M"A and conductionvelocity across the elbow in excess of changesproximal and distal to the elbow could beexplained in two ways. First, these could

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Brown, Snow

simply reflect compression of the ulnar nervebehind the medial epicondyle or in the cubitaltunnel in patients unable to adjust the positionof their limbs because of paralysis. Alter-natively, the blood-nerve barrier may havebeen compromised at this common entrapmentsite before the onset of the disease. The lattercould render nerves vulnerable to attack atthese common entrapment sites, especiallyearly in the disease.One problem not resolved by this study was

determining the relative contributions of con-duction block in otherwise intact fibres, con-duction block in nerve fibres undergoing degen-eration, and axon losses, to the reduction in"M"A in the terminal segment. Nerve fibrescrushed severely enough to undergo degenera-tion retain the ability to transmit impulsesdistal to the crush for several days beforeconduction fails and the fibres break down.20The duration of the biological attack in GBS isunknown and different fibres or indeed differentsites on the same fibre could be attacked manydays apart. In case 4, however, despite thesevere reductions in "M"A with wrist stimula-tion at 5 (fig 2) and even 18 days, promptrecovery subsequently followed at 32 daysstrongly suggesting the previous terminalreduction in "M"A was largely explicable byconduction block in demyelinated nerve fibresrather than axonal degeneration. At the otherextreme, inexcitable nerve carries the gloomyprospect of substantial axonal degenerationhaving taken place""'5 and unfortunately wassubsequently borne out by our case 14.How well did our studies correspond with

the pathology of GBS? Haymaker and Kerno-han2' examined 50 fatal cases. The intervalbetween the onset of symptoms and the path-ological studies varied between two and 46days. Pathological changes were most evidentat the junction between motor and sensoryroots and the mixed spinal nerve roots. Lesionstended to be multifocal in distribution, oftenvarying widely in intensity from fascicle tofascicle. However, the PNS distal to the rootswas not assessed and intramuscular brancheswere not studied.

In the study by Asbury et al,22 19 fatal caseswere examined. The interval between the onsetof symptoms and necropsy was between oneday and six years. Nine cases were studiedwithin the first four weeks. Patterns varied frompredominant involvement of the roots, with theventral roots being the more affected, to wide-spread involvement of roots and peripheralnerve trunks, and still other cases where peri-pheral nerve trunks themselves were affectedwith little or no involvement ofthe roots. In thefew cases where intramuscular nerve twigswere examined, striking pathological changeswere not often seen. Overall the pattern wasquite variable and often multifocal. Unfortu-

nately, their study did not systematicallyexamine all regions between the roots andperipheral terminals of the PNS, nor werequantitative comparisons made of the extentof paranodal and internodal demyelination indifferent regions of the PNS. The latter isimportant as the frequency and distribution ofinflammatory infiltrates such as these authorsemphasised may bear little direct correspon-dence to sites of conduction failure. Theminimum requisite frequency of criticallydemyelinated fibres to produce striking reduc-tions in "M"A could be as low as 1-3% ofaffected internodes or paranodal regions,frequencies which could well pass unnoticedeven with quantitative studies of teased fibres.

1 Van Der Meche FGA, Meulstee J. Guillain-Barre syn-drome: a model of random conduction block. J NeurolNeurosurg Psychiatry 1988;51:1158-63.

2 Van Der Meche FGA, Meulstee J, Vermeulen M, Kievit A.Patterns of conduction failure in the Guillain-Barresyn-drome. Brain 1988;111:405-16.

3 Kimura J. Proximal versus distal slowing of motor nerveconduction velocity in the Guillain-Barresyndrome. AnnNeurol 1978;3:344-50.

4 Brown WF, Feasby TE. Conduction block and denervationin Guillain-Barre polyneuropathy. Brain 1984a;107:219-39.

5 Brown WF, Feasby TE. Sensory evoked potentials inGuillain-Barre polyneuropathy. J Neurol NeurosurgPsychiatry 1984;47:288-91.

6 Berger AR, Logigian EL, Shahani BT. Reversible proximalconduction block underlies rapid recovery in Guillain-Barre syndrome. Muscle Nerve 1988;11: 1039-42.

7 Burkel WE. The histological fine structure of perineurium.AnatRec 1967;158:177-90.

8 Olsson Y. Topographical differences in the vascular per-meability of the peripheral nervous system. ActaNeuropathol 1968;10:26-33.

9 Jacobs JM, MacFarlane RM, Cavanaugh JB. Vascularleakage in the dorsal root ganglia of the rat, studied withhorseradish peroxidase. J Neurol Sci 1976;29:95-107.

10 Seitz RJ, Heininger K, Schwendemann G, Toyka KV,Wechsler W. The mouse blood-brain barrier and blood-nerve barrier for IgG: A tracer study by use of the avidin-biotin system. Acta Neuropathol (Berl) 1985;68:15-21.

11 Asbury AK. Diagnostic considerations in Guillain-Barresyndrome. Ann Neurol 1981;9(suppl): 1-5.

12 Hughes RAC, Kadlubowski M, Hufschmidt A. Treatmentof acute inflammatory polyneuropathy. Ann Neurol1981;9(suppl): 125-33.

13 Feasby TE, Gilbert JJ, Brown WF, et al. Acute axonal formof Guillain-Barre polyneuropathy. Brain 1986;109:1115-26.

14 Cornblath DR, Mellts ED, Griffin JW, et aland the Guillain-Barre Study Group. Motor conduction studies inGuillain-Barre syndrome: description and prognosticvalue. Ann Neurol 1988;23:354-9.

15 Miller RG, Peterson GW, Daube JE, Albers JW. Prognosticvalue of electrodiagnosis in Guillain-Barresyndrome.Muscle Nerve 1988;1 1:769-74.

16 Yates SK, Hurst LN, Brown WF. The pathogenesis ofpneumatic tourniquet paralysis in man. J NeurolNeurosurg Psychiatry 1981;44:759-67.

17 Dengler R, Stein RB, Thomas CK. Axonal conductionvelocity and force of single human motor units. MuscleNerve 1988;11:136-45.

18 Brown WF. The physiological and technical basis of elec-tromyography. Boston: Bistterworths, 1984.

19 Mills KR, Murray NMF. Proximal conduction block inearly Guillain-Barresyndrome. Lancet 1985;ii:659.

20 Erlinger J, Schoepfle GM. A study ofnerve degeneration andregeneration. Am JPhysiol 1946;147:550-81.

21 Haymaker W, Kernohan JW. The Landry-Guillain-Barresyndrome. A clinicopathological report of fifty fatal casesand a critique of the literature. Medicine (Baltimore)1949;28:59-141.

22 Asbury AK, Arnason BG, Adams RD. The inflammatorylesion in idiopathic polyneuritis. Its role in pathogenesis.Medicine (Baltimore) 1969;48:173-215.

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