Clinical Neurophysiology 1E-mail address: affre@as.aaa.dk (A. Fuglsang-Frederiksen).Pathophysiology inferred from electrodiagnostic nerve tests and
classification of polyneuropathies. Suggested guidelines
Hatice Tankisi
a
, Kirsten Pugdahl
a
, Anders Fuglsang-Frederiksen
a,
*
, Birger Johnsen
a
,
Mamede de Carvalho
b
, Peter R.W. Fawcett
c
, Annick Labarre-Vila
d
,
Rocco Liguori
e
, Wilfred A. Nix
f
, Ian S. Schofield
c
a
Department of Neurophysiology, Aarhus University Hospital, Aarhus, Denmark
b
Laboratory of Electromyography, Department of Neurology, Institute of Molecular Medicine, Faculty of Medicine,
Hospital de Santa Maria, University of Lisbon, Lisbon, Portugal
c
Department of Clinical Neurophysiology, Newcastle General Hospital, Newcastle upon Tyne, UK
d
Laboratory of Electromyography, University of Grenoble, Centre Hospitalier Universitaire, Grenoble, France
e
Department of Neurological Sciences, University of Bologna, Bologna, Italy
f
Department of Neurology, University Clinics Mainz, Mainz, Germany
Accepted 6 April 2005
Abstract
Objective: To present criteria for pathophysiological interpretation of motor and sensory nerve conduction studies and for pathophysiological
classification of polyneuropathies suggested by a group of European neurophysiologists.
Methods: Since 1992 seven neurophysiologists from six European countries have collected random samples of their electrodiagnostic
examinations for peer review medical audit in the ESTEEM (European Standardized Telematic tool to Evaluate Electrodiagnostic Methods)
project. Based on existing criteria in the literature, the experience with a patient material of 572 peer reviewed electrodiagnostic
examinations, and productive discussions between the physicians at workshops, the collaboration has produced a set of criteria now routinely
used at the centres involved in the project.
Results: The first part of the paper considers pathophysiology of individual nerve segments. For interpretation of motor and sensory nerve
conduction studies, figures showing change in amplitude versus change in conduction velocity/distal latency and change in F-wave frequency
versus change in F-wave latency are presented. The suggested boundaries delimit areas corresponding to normal, axonal, demyelinated, or
neuropathic nerve segments. Criteria for motor conduction block in upper and lower extremities are schematically depicted using the
parameters CMAP amplitude and CMAP duration. The second part of the paper suggests criteria for classification of polyneuropathies into
axonal, demyelinating, or mixed using the above-mentioned criteria.
Conclusions: The suggested criteria are developed during many years of collaboration of different centres and may be useful for
standardization in clinical neurophysiology.
Significance: Consistent interpretation of nerve conduction studies is an important step in optimising diagnosis and treatment of nerve
disorders.
q 2005 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
Keywords: Nerve conduction studies; Pathophysiological states of nerves; Polyneuropathy classification; Criteria for demyelination; Criteria for axonal loss
1. Introduction16 (2005) 1571–1580
www.elsevier.com/locate/clinphpathy (PNP) due to its important implications for diagnosis,
treatment and prognosis. For instance, differentiation of
1388-2457/$30.00 q 2005 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.clinph.2005.04.003
Aarhus University Hospital, Nørrebrogade 44, 8000 Aarhus C, Denmark.
Tel.:C45 89 49 31 30; fax: C45 89 49 31 40.The distinction between axonal loss and demyelination is
one of the main goals of the examination of a polyneuro-
*
Corresponding author. Address: Department of Neurophysiology,

the
they
phy
2.1.
S
cou
thei
con
data
199
hete
tori
with
thre
(1)
(2)
reference materials vary considerably among the
pathophysiological test conclusion is given on the
basis of the measured data, the local reference material
rophysioloaxonal and demyelinating pathophysiologies is a major
determinant for the effective choice of therapy in the case of
acute inflammatory demyelinating polyradiculoneuropathy
(AIDP), chronic inflammatory demyelinating polyradiculo-
neuropathy (CIDP) or multifocal motor neuropathy (MMN).
Nerve biopsy findings may be the most accurate means of
classifying nerve abnormalities, however, in biopsies
changes may be overlooked whenever the abnormalities
are patchy or restricted to motor nerves. Besides, nerve
biopsy is an invasive and inconvenient procedure that
cannot be applied for follow-up studies. Nerve conduction
studies (NCS) are therefore essential for determining the
pathophysiology of peripheral nerves. In NCS primary
demyelination is indicated by marked reduction in motor or
sensory conduction velocity (CV), conduction block or
increased temporal dispersion, whereas primary axonal loss
may be indicated by a decrease in amplitude or area of the
sensory nerve action potential (SNAP) or the compound
muscle action potential (CMAP). However, electrophysio-
logical differentiation between demyelination and axonal
loss can be a challenging task as increased temporal
dispersion or distal conduction block due to demyelination
may result in amplitude reduction, and in axonal neuropathy
loss of large fast conducting fibres may cause conduction
slowing. Moreover, the pathophysiology is sometimes
difficult to interpret with secondary demyelination in
primary axonal neuropathy and vice versa (Johnsen and
Fuglsang-Frederiksen, 2000). Additionally, other pathophy-
siologies should be kept in mind, e.g. channelopathies may
lead to conduction slowing or failure via functional
disturbances of ion-channels at the nodal areas (Gutmann
and Gutmann, 1996; Kaji, 2003; Yokota et al., 1994).
For the past 12 years a European group of neurophysiol-
ogists have collected samples of their patient examinations
for peer review medical audit through the Internet and at
regular workshops in the multicentre project ESTEEM
(European Standardized Telematic tool to Evaluate Electro-
diagnostic Methods) (Fuglsang-Frederiksen et al., 1996;
Vingtoft et al., 1994, 1995). During the years, the group has
established its own sets of electrophysiological criteria for
pathophysiological interpretation of individual nerve tests
and for PNP classification, based on existing criteria in the
literature (Ad Hoc Subcommittee of the American Academy
of Neurology AIDS Task Force, 1991; Albers, 1993; Albers
and Kelly, 1989; Albers et al., 1985; Asbury and Cornblath,
1990; Barohn et al., 1989; Behse and Buchthal, 1977;
Bouche et al., 1983; Bromberg, 1991; Buchthal and Behse,
1977; Gherardi et al., 1983; Gilliatt, 1966; Hadden et al.,
1998; Harding and Thomas, 1980; Ho et al., 1997; Hughes
et al., 2001; Italian Guillain-Barre´ Study Group, 1996;
Meulstee et al.,1995; Nicolas et al., 2002; Saperstein et al.,
2001; Van den Bergh and Pieret, 2004; Van der Meche et
al., 2001), the experience with a patient material of 572 peer
reviewed electrodiagnostic examinations, and productive
discussions between the physicians at workshops.
H. Tankisi et al. / Clinical Neu1572The criteria have proved useful in daily practice atand the examiner’s symbolic value. Early in the
ESTEEM project, the participants agreed on categories
for test conclusions dependent on the type of anatomicaldifferent laboratories, probably due to differences in
examination practices (Fuglsang-Frederiksen et al.,
1995; Johnsen et al., 1999). Therefore, in order to
enable the physicians to interpret an examination in a
consistent fashion, the locally used reference values are
stored in the program and follow the case. The data
from the electrophysiological recordings are either
electronically or manually entered to the program, and
the percent deviation from mean of controls calculated
automatically. Finally, a corresponding symbolic value
(normal, decreased, increased, borderline decreased/
increased, inconclusive) is assigned to each measured
parameter by the examiner.
(3) Inferred data. For each nerve or muscle test aexamination techniques used in the clinical routine at
the participating laboratories are contained within the
program. Two laboratories use the reference material
from the Copenhagen University Hospital, Denmark
(Rosenfalck and Rosenfalck, 1975), but otherwise theData structure
ince 1992, seven physicians from six European
ntries have prospectively collected random samples of
r patient examinations into a database, which now
tains 1401 cases including 350 PNP cases. A common
structure implemented in a PC program (Johnsen et al.,
4b) is used to collect, exchange, and compare the
rogeneous data originating from the different labora-
es in electronic form. The data structure is, in accordance
the electrophysiological examination, composed of
e parts:
General data, i.e. patient demographics (age, sex,
height) and clinical information in free text fields for
referral diagnosis, patient history, neurological findings,
hereditary predispositions, clinical chemistry, pathol-
ogy, radiology, and medication.
Examination data from all tests, including values of the
measured parameters (distal latency, conduction vel-
ocity, CMAP or SNAP amplitude, etc.) and examin-
ation conditions (electrode type, temperature, segment
length). Parameter sets covering the 17 different2. Mparticipating laboratories and the group believe that
should now be presented to the international neuro-
siological community.
ethods
gy 116 (2005) 1571–1580structure (nerve, nerve segment, muscle, neuromuscular