HINT - High Level Inferencing Tool:

An Expert System for the Interpretation

of Neurophysiological Studies

Ian S. Schofield

Consultant Clinical Neurophysiologist

Department of Neurophysiology, Regional Neurosciences Centre
Newcastle General Hospital, Newcastle-upon-Tyne, UK
e-mail: i.s.schofield@ncl.ac.uk

Abstract

This paper describes a knowledge based inferencing tool using an

anatomical network developed during the course of the ESTEEM project.
The results of a neurophysiological investigation are represented in the
network as modified pathophysiological states of nodes that correspond to
anatomical structures of the human peripheral nervous system. An
inferencing process is then applied to the network to define a minimal set of
lesions, either single or multiple. Subsequently an EMG diagnosis is
generated using the final state of the network.

Key Words: Expert system, Nerve conduction, Electromyography, Anatomy

1. Introduction

Neurophysiological studies are an important and integral part of the

investigation of neuromuscular disorders. There is a vast array of procedures
that may be used to investigate the function of both the central nervous
system (CNS) and the peripheral nervous system (PNS). The basis of inves-

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tigational neurophysiology is to evaluate the function of the nervous system

using one or more of these procedures or tests. A number of excellent texts
dedicated to the description of nerve condition techniques and their findings
in different disorders have been published [Goodgold et al., 1983; Kimura,
1983; Ludin, 1980], Accordingly, the emphasis of this paper reflects the
methodology of the interpretation of nerve conduction and related
techniques in the investigation of patients presenting with neuromuscular
disorders that have evolved during a multi-centre AIM (Advanced Informa-
tics in Medicine) programme titled ESTEEM (European Standardised
Telematic tool to Evaluate knowledge-based EMG systems and Methods).
The method of presentation of information in the texts referred to above
forms the fundamental rationale for the design of expert systems. In most
cases, the data is provided in the context of the expected findings in a
specific clinical diagnostic group. This is the opposite of the case while the
investigation is being performed in that the diagnosis may not be known at
the time. This gives rise to the following key issues during a
neurophysiological study:

1. Procedure selection.
2. The implication of the procedure findings in pathological terms.
3. A sufficiency of procedures to confirm or refute a diagnosis.

Procedure selection lies in the domain of strategy and is the essence of

investigational neurophysiology in contrast to descriptive neurophysiology
where a specific set of procedures are used on a pre-selected study
population. The goal is to define a series of procedures to evaluate
adequately the region where pathology might be expected to be found. To
attain this goal, a certain amount of clinical information is required. This
may be provided by the clinician requesting the investigation or from a
clinical examination of the patient by the clinician performing the
investigation. From this information, an initial set of procedures may be
selected. This particular area has been very poorly investigated and in
general is a very individual process as judged by an evaluation study
[Johnsen et al., 1995], despite the fact that there is a vast literature on the

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rationale of testing/fault finding in general. Guidelines for the neuro-

physiological investigations are now available [AAEE, 1992] but again,
these are presented as sets of procedures for the study of specific pathologies.
The implication of the findings in a given procedure has been a subject
of study dining the ESPRIT (European Science Program for Information
Technology) P599 project [P599, 1989], The concept of the pathophysio-
logical state (PS) was used with an explicit set of causal relationships
between test results and PS being defined in MUNIN [Andreassen et al.,
1989], Similarly, a PS description of the findings of an individual procedure
is used in KANDID [Fuglsang-Frederiksen et al., 1989]. This concept is
very useful in that the results of any procedure, using different techniques,
may be represented in a common form. The procedures for translating the
results of individual tests to pathophysiological states are as yet incomplete
and subject to significant observer variation [Johnsen et al., 1995],
The determination as to whether a sufficient number of procedures has
been performed to confirm or refute a diagnosis is also a matter of individual
opinion with due consideration of guidelines. This aspect is clearly linked
with the issue of procedure selection. This requires consideration of two
further issues. Firstly, what constitutes a 'diagnosis' and secondly, what
procedures are of relevance to a given diagnosis. There is a fairly well
defined group of diagnostic categories that have evolved along with medical
science. From this group a subset of diagnoses have been selected by
consensus that are detectable and separable using current neurophysiological
techniques [ESTEEM USER-2, 1992], An expert/knowledge based system
(KBS) is expected to have coverage of these. The second issue of relevance
is, as yet, undefined and is also subject to individual variation [Fuglsang-
Frederiksen et al., 1995].

2. Current Status

There are a number of systems functioning in the neurophysiological

domain. KANDID [Fuglsang-Frederiksen et al., 1989] uses heuristic rules to
associate pathophysiological states with diagnostic categories. MUNIN

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[Andreassen et al., 1989] is based upon a causal network including a

pathophysiological state representation and the more recent development,
DEMONSTRATOR [Barahona, 1992], has a number of similar features.
The Electrodiagnostic Assistant [Jamieson, 1990] is based on the use of
augmented transition networks. NEUROMYOSIS [Vila et al., 1985] is a
more complex system using a variety of knowledge representation schemes
and information processing procedures. LOCALIZE [First et al, 1982] uses
a symbolic representation of the anatomy of the peripheral nervous system.
All of these systems have certain strengths and weaknesses as judged from
evaluation studies [Andreassen et al., 1992; Vingtoft et al., 1993].
The major difficulties that have beset the application of systems of this
kind to routine use are to provide an acceptable range of alternative
diagnoses either single or multiple, the use of different study procedures and
philosophies and the degree of inclusion of clinical, i.e., non-electro-
physiological data.

3. Specification

The overriding design goal of HINT was to ensure complete coverage of

all possible peripheral nerve lesions including the difficult problem of
multiple lesions [Jamieson, 1991] and also to allow for any possible test
procedure to be used. Similarly, with reference to the variability of the
procedures that may be performed, a 'minimal' series of alternatives to
explain the findings must always be provided. The major issues are firstly,
an exhaustive diagnosis/hypothesis database and secondly, a scheme by
which means data from many different procedures might be easily included.
In view of the considerable complexity of an exhaustive diagnostic database,
it was apparent that the solution most likely to gain consensus was the use of
a system description via a map of the human nervous system anatomy. This
type of system has been used for fault finding in digital circuits, DART
[Genesereth, 1984] and in more general terms, GDE (General Diagnostic
Engine) p e Kleer et al., 1987], There are also a number of similarities to

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LOCALIZE [First et al., 1982] in that a neuro-anatomical map is used to

determine the site of a lesion. The use of an anatomical map allows the
inclusion of data from a procedure of any kind provided the implications of
the findings can be represented in a coherent fashion [ESTEEM, 1993], A
PS description of the findings from a conventional neurophysiological study
can be used in this way. Potentially, this allows non electrophysiological
(clinical) information to be used. In the first instance the inclusion of
clinical data has not been implemented due to the complexity of interpreting
the findings of a clinical examination in terms of the pathophysiological
states of anatomical structures.
Using this method eliminates the need for an explicit diagnosis database
but necessitates a reappraisal of what constitutes a diagnosis in view of the
lack of clinical information. The use of the term EMG diagnosis represents
the result where only the test data was interpreted with no clinical data being
considered. This was first used in the KANDID system [Fuglsang-
Frederiksen et al., 1989]. In this system, the EMG diagnosis is presented as
one or more statements from a pre-defined list of alternatives. To ensure
coverage of as many alternative outcomes as possible, a more general form
of presentation was developed. This is based on a classification scheme of
the range of pathologies which may be identified by a neurophysiological
study in isolation.
Three classes were identified, 'Functional', 'Anatomic' and
'Syndromic', Table 1. The functional class contains members where the
pathology involves a structure that can be unambiguously tested in such a
fashion that the result of the investigation constitutes a diagnosis. The
anatomic class contains all diagnoses that are due to single focal disorders.
The syndromic class is hierarchically above the anatomic class in that it
contains members for which there is a known association between a number
of lesions that belong to the anatomic class. This concept breaks down the
problem and explicitly separates the diagnostic groups so that they may be
analysed and presented in a different way.

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Table 1
The classes of the EMG diagnosis

Functional Anatomic Syndromic

End-plate disorders Focal and difluse mono- Polyneuropathies
Primary muscle disorders neuropathies / plexopathies Radiculopathies

4. The Anatomical Database

An evaluation version of HINT was implemented in ANSI C. There are

four major structural components: an anatomy database, an inferencing
engine, a diagnosis generator and a graphical network display.
The anatomy database representing the human peripheral nervous system
has been implemented at an intermediate level of detail such that there are
36 muscles and 16 nerves (per side), the primary limitation of detail being
the existence of normal anatomic variation. The basic structure of the system
has many parallels with electronic circuits and consists of many chains of
three type of objects. The objects are muscle, nerve and neurone. The system
also contains two other objects, receptors and neuromuscular junctions
(NMJ). Receptors are at present not included in the database but NMJs are
included as a separate single object. Receptors are not included at present
due to the substantial technical problems in evaluating their function.
Although procedures do exist for testing receptors, it is generally accepted
that these are not part of 'routine' neurophysiological studies.
Each chain is labelled as belonging to a particular peripheral nerve and
has a head which is either a muscle for the motor chains or a peripheral
anatomic site, e.g., Digit I, for a sensory chain. There are then a number of
intermediate nodes that relate to specific anatomical sites where there is
either access to the nerve for stimulation/recording, points at which nerves
branch, or well described anatomical landmarks. The chain tail corresponds
to the motor or sensory neurones lying within the spinal cord at a particular
anatomical level. The chain corresponding to the median nerve is outlined
in Table 2.

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Table 2
A chain of nodes

Nerve: N. medianus
Head: M. abductor pollicis brevis (Muscle node)
palm (Nerve nodes at anatomical
wrist sites)
elbow
axilla
erbs point
medial cord of plexus
lower trunk of plexus
Tail: T1 root (Neurones at the 1st thoracic
vertebra level)

In the current database there are 170 separate chains, each corresponding
to a population of nerve fibres running from the central neurones to a
peripheral site. These chains originate from one of eleven spinal levels to
innervate one of 49 peripheral sites. The remaining spinal levels are not
included at present. There are 70 intermediate nodes and a total of 130
separate sites included. Most peripheral muscles are 'innervated' by more
than one chain originating from the associated roots. Similarly, some of the
sensory chains originate from more than one root. The information to build
the database was drawn from many sources and compared with the primary
source [Gray, 1973], The collection of chains and the intermediate nodes
form a network representation of the PNS, Figure 1.
Each node in the network has one or two properties depending on the
type of node: Table 3. The selection of these properties is determined by the
data that can be obtained from neurophysiological tests but also by the
known functional anatomy of the objects. The values that the properties may
take are discrete such that for the motor unit size, the values may be
decreased, normal or increased. For the remainder, the values may be
normal, borderline abnormal or abnormal.

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^—^^ N.ulnaris Dxl

N.cutaneus antebrnchii medialis

Fig. 1: The graphical representation of the anatomy of the ulnar and

medial antebrachial cutaneous nerves of the right arm.

idl Interosseous Dorsalis 1 wr Wrist

adm Abductor Digiti Minimi ds Distal (to) Sulcus
d4 Digit 4 (sensory branch) ps Proximal (to) Sulcus
d5 Digit 5 (sensory branch) mc Medial Cord
feu Flexor Carpi Ulnaris It Lower Trunk
fo Forearm (a stimulation site) c8 Eighth Cervical Root
el elbow (a stimulation/recording tl First Thoracic Root
site) dpb Deep Palmar Branch
ax Axilla pa Palm
ca Canal (of Guyon)

Table 3
Object properties

Object Property 1 Property 2

Muscle No. of fibres Size of motor units
NMJ Endplate function index _
Spinal neurone No. of cells —

Nerve segment No. of fibres Myelination index

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5. Information in the Network

The inferencing process starts with the 'unknown' initial state of the
network in that no a priori assumptions of function are implied. The results
originating from a study are then impressed upon the network. The study
data are expected to be provided in a common data interchange format
ECCO [ESTEEM ECCO-4, 1993] which has been developed as a standard
as part of the ESTEEM project. This date format contains information on
the specific procedures that have been performed, the numerical results with
expected normal ranges and the interpretation of the findings in the form of
a PS description.
In general, all procedures can be reduced to one of three methods:

1. A test of a specific object in isolation

e.g. A Concentric Needle Electrode (CNE) study of M. Triceps.
Implied object: The muscle node M. Triceps.

2. Stimulation of a nerve at one site and record from another

site on the same nerve.
e.g. Median nerve, Digit I to wrist.
Implied objects: All nodes between Digit I and the wrist belonging to the
median nerve.

3. Stimulation at two sites and record from another site.

e.g. Median nerve, elbow to wrist recording from M. Abductor
Pollicis Brevis.
Implied objects: All nodes between the elbow and the wrist belonging to the
median nerve and terminating in the muscle.

The methodology of translating the numerical test data to object

properties is in itself complex and beyond the scope of this paper to outline
in its entirety. In essence, the numerical data is compared with the expected
normal ranges and mapped into a PS. An initial set of rules for this process

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has been suggested, similar to those used in KANDID. These were derived
from a multi-centre study [Johnsen et al, 1995] of the interpretations
provided by seven physicians of a number of studies covering a range of
pathologies. The properties of the objects that are implied by a procedure are
derived from this state data. This process is implemented in HINT for evalu-
ation purposes and is accomplished by means of a mapping table such that
there is an option to use either this data or the PS data provided with the
study by the user.
This procedure begins with the observation of, for example, a motor
nerve velocity of 27 m/sec over the forearm segment of the median nerve
with the M-response amplitude in M. Abductor Pollicis Brevis (APB) being
9 mV from both stimulation sites. After a comparison of the above para-
meters with the expected normal ranges, the velocity is seen to be reduced,
the M-response is normal and there is no conduction block. This is inter-
preted as the PS 'demyelination' in relation to the studied nerve segment.
The state of the objects in the median nerve chain that terminate in the APB
muscle are assigned a Myelination Index of 'Abnormal' and a number of
fibres value of 'Normal'.
Similarly, for muscles, the PSs defined are 'Normal', 'Myopathic' and
'Neurogenic', these being the conventional outcome measures of most
electromyographic (EMG) procedures.
The process of loading data into the network is complicated by the use of
multiple procedures which share a common chain of nodes. In this circum-
stance, a rule based method is used to assign the properties of the implied
objects to conform as closely as possible to the findings from each of the
procedures.
When all the individual tests have been loaded into the network a
graphical representation of the findings may be viewed, displayed in the
same form as Figure 1 with colour codes identifying the PS for each muscle
and nerve segment.

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6. Inferencing on the Network

At this point the network contains a representation of 'known'

information about the components that have been tested. The next process is
to infer from this data the possible anatomical sites where there may be a
lesion or lesions. This is performed in three stages using rules that are
derived from histo-pathological and functional studies of peripheral nerve.

1. If demyelination has been found in any chains between two anatomical

sites, the remaining chains are also demyelinated, if there is no evidence
to the contrary - similarly for normal findings.
2. If axonal loss or neurogenic changes have been found, this finding is
propagated proximally into the spinal neurone, if there is no evidence to
the contrary - similarly for normal findings.
3. If axonal loss has been found in any chains between two anatomical sites,
the other chains between the two sites also have axonal loss, if there is no
evidence to the contrary - similarly for normal findings.

This sequence is one of association, propagation and association and is

performed using a series of state transition rules that represent the above
statements. At this stage, a graphical display of the distribution of the
inferred lesions can be seen.

7. Generating a Diagnosis

The final stage of the process is the diagnoser. This is split into three
sections. Section 1 is a simple rule based procedure that examines the
network for evidence for functional disorders as specified above. Statements
are of the form:

<SeverityxType>end-plate disorder
or
<Severity><Stage>myopathic disorder

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where <Severity> Mild, moderate or severe

<Type> Pre-synaptic, post-synaptic or unknown
<Stage> Acute or chronic,

e.g., moderate pre-synaptic end-plate disorder.

Section 2 is the site identification procedure. This describes the current

state of the network by examining each nerve individually and generates one
or more statements that identify members of the anatomic class. These are of
the form:

1. <Severity> non-localised lesion of <Nerve>

or
2. <Severity> localised lesion of <Nerve> at <Anatomical site>

e.g., mild localised lesion of the median nerve at wrist.

The term localised is used in the sense that the current set of studies are
sufficient to identify the site of a lesion positively, the criterion being the
positive finding of a normal nerve segment proximal to the site of the lesion.
This is as opposed to a non-localised lesion where no evidence for a normal
segment in the given nerve has been presented to the system.
Section 3 examines the group of statements from section 2 (if any) and
looks for known associations of lesions that constitute the syndromic
diagnosis class, using production rules. For example, multiple non-localised
lesions of different nerves may be indicative of a polyneuropathy. Statements
are of the form:

<SeverityxLikelihoodxPathology><Involved fibres> neuropathy

or
<SeverityxLikelihood> root lesion of <Root>
or
where <Likelihood> is: Possible, probable or definite
<Pathology> is: Axonal, demyelinating, mixed or unknown
<Involved fibres> is: Sensory, motor, or sensori-motor
e.g., Mild possible axonal sensory neuropathy.

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The final output of the system is a series of statements from each of the
above sections.

8. Validation

This is a crucial factor for any expert system [O'Moore et al, 1990],
This is the fundamental area of study of the ESTEEM project. The intention
is to develop a series of evaluation tools, a case database of studies validated
by experts in the field and the information management technology required
to integrate the whole process. HINT will be validated using this system
during the course of this project in parallel with NEUROMYOSIS and
DEMONSTRATOR.
The concepts of validation have had a considerable influence on the
design of HINT. The initial factor considered was coverage. This has two
aspects, data source coverage, the ability to accept data from any test and
diagnostic coverage, the ability to generate a wide potential range of
different diagnoses. Data source coverage has been attained through the use
of a standard test representation format as outlined above and with the use of
PS representation of the results of an individual procedure. Diagnostic
coverage is an inherent characteristic of the basic methodology of HINT
with the caveat that the anatomic network is sufficiently precise in form and
verifiable against accepted knowledge.
The other key factor, conformance, remains to be adequately evaluated.
This process requires a dataset of cases where the true diagnostic class is
known either by means of explicit specification via simulated cases and/or a
consensus opinion on actual clinical studies. Data of this kind are now
available from the ESTEEM database.

9. Discussion

A number of aspects are of relevance. The first important feature of the

system is the ability to accept data from neurophysiological studies

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performed by different individuals. This is implied through the use of a

standard test representation scheme outlined in section 5 and a standard
interpretation scheme using pathophysiological states as description of the
implication of the findings of a given test.
The second feature of HINT is the ability of the system to resolve
multiple peripheral nerve lesions; this is in contrast to other implemented
systems (KANDID, MUNIN) which are able to resolve single nerve lesions
only. As a result, HINT is not implemented as part of a plan, test and
diagnose cycle as implemented in KANDID [Fuglsang-Frederiksen et al.,
1989], due to the complexity of a strategy generator that will cope with
multiple lesions. However, it is possible to use the network 'in reverse' to
simulate a particular lesion or lesions and indicate sites where abnormalities
could be expected. The basis of HINT is to determine the anatomical
distribution of lesions within individual nerves and, as such, this has failed
if the findings result in a 'non-localised lesion' of one or more nerves. To
solve this an experimental strategy generator using the specific goal of
localising all lesions, if possible, is currently under development.
Nonetheless, the system provides a description of the probable lesion or
lesions at any time during the study in terms of a 'minimal' explanation of
the positive findings. From this data, a decision may be made to perform
additional specific procedures with which the user is familiar.
Another issue is one of adequacy of the EMG diagnosis. This has a
number of facets. In particular there is the problem of the clinical relevance
of the findings. At this stage, it was elected to be an explicit task of a
clinician to determine this. For example - HINT EMG diagnosis: mild
lesion of the median nerve at the wrist; clinical opinion: given the patient's
symptoms in combination with the median nerve lesion, the findings are
compatible with the Carpal Tunnel Syndrome.
The issues of adequacy and relevance also apply to a number of other
pathological processes. The diagnosis of polyneuropathies is particularly
sensitive to minor abnormalities detected in the study with the rigorous use
of normal values. These minor abnormalities commonly manifest as
multiple mild 'non-localised' nerve lesions which will result in statements

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suggesting a polyneuropathy. Again, it is clearly an issue of clinical judge-

ment as to whether the findings are of relevance. Similarly, the issue of
causality requires further information than that obtainable from a
neurophysiological study. A typical and common circumstance is a patient
with diabetes presenting with an ulnar neuropathy, the question being
whether this is a pure compression neuropathy or a focal diabetic mono-
neuropathy.
Despite these significant limitations, the representation of the findings in
the form of an EMG diagnosis as statements outlined above provides for the
possibility of other diagnostic assistant systems, using data from other
sources, to use the important information that can be provided by a
neurophysiological study.
The primary application of HINT and other KB systems is for the pre-
sentation and interpretation of complex studies. In this circumstance a
graphical display of the pattern of findings can be of considerable assistance.
Similarly, systems of this kind are very useful for training purposes in that
the user can be reminded of alternative interpretations of the results of a
study. The current implementation of HINT will analyse data only in a non-
interactive mode as specified for packages to be used with the EMG platform
concept developed during the course of the ESTEEM project.

10. Conclusion

The use of an anatomical network to contain data from a

neurophysiological study can simplify the methodology of interpretation.
Similarly, the explicit representation of the test and inferred findings in
anatomical terms allows for a wide range of possible diagnoses limited only
by the precision of the representation of the anatomy of the peripheral
nervous system. Finally, the presentation of the EMG diagnosis as a series of
consistent statements allows for a coherent representation of the findings
from a neurophysiological study.

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11. References

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