JOURNAL OF NEUROPSYCHIATRY 395

Received October 7, 1997; revised February 3, 1998; accepted March

20, 1998. From the Veterans Affairs Medical Center and Western Psy-
chiatric Institute and Clinic, Pittsburgh, Pennsylvania. Address cor-
respondence to Dr. Keshavan, Western Psychiatric Institute andClinic,
3811 OHara Street, Pittsburgh, PA15213; e-mail: keshavan@pitt.edu
Copyright 1998 American Psychiatric Press, Inc.
The Neurologic
Examination in Adult
Psychiatry: From Soft
Signs to Hard Science
Richard D. Sanders, M.D.
Matcheri S. Keshavan, M.D.
Of the proliferating approaches to neuropsychiat-
ric assessment, a relatively neglected technique is
the venerable, accessible, noninvasive, and inex-
pensive neurologic examination. This article or-
ganizes and synthesizes the literature on neuro-
logical ndings in adult psychiatric patients.
Problems in conducting and interpreting research
in this area are examined, clinically pertinent em-
pirical ndings are surveyed, and directions for
future investigation are outlined. Most of the
soft signs can be reliably evaluated, and many
have been validated against other techniques. Sev-
eral psychiatric diagnoses are associated with im-
paired neurologic performance. Prognosis and
treatment selection may also be informed by neu-
rologic ndings. The neurologic exam should be
regarded as a collection of neurobiologic probes
rather than as a single irreducible variable. Future
work must better establish interrater and test-
retest reliability of individual elements of the neu-
rologic exam in psychiatric populations and focus
on developing the clinical utility of individual and
combined elements of the neurologic exam.
(The Journal of Neuropsychiatry and Clinical
Neurosciences 1998; 10:395404)
T
he neurologic examination has two general func-
tions in psychiatry. The rst, screening for major
neurological disease, is accomplished with an exami-
nation emphasizing such hard or major signs as re-
ex and motor asymmetry and the Babinski reex. The
results of each component of the screening examination
can be described dichotomously as normal or abnormal.
These results reect the presence or absence of neuro-
pathology, particularly that which is focal and acquired
later in development. This article deals with the second
objective of the psychiatric neurologic exam: evaluating
performance decrements in psychiatric patients without
identiable neurologic disorders. This evaluation may
be accomplished with an extended exam, which in-
cludes assessment for soft signs such as inaccurate
motor sequencing and bilateral dysgraphesthesia. Such
assessments may be described in terms of degree of per-
formance decrement, rather than by the presence or ab-
sence of abnormality. These evaluations are often per-
formed by physicians but are also represented in some
neuropsychological batteries. Although these two func-
tionsscreening and evaluationare conceptually dis-
tinguishable, the examinations serving these ends over-
lap substantially, and ndings with signicance in either
context are hereafter referred to inclusively as neurologic
exam abnormalities (NEA).
Classic descriptions of the psychiatric disorders often
396 VOLUME 10 NUMBER 4 FALL 1998
NEUROLOGIC EXAMINATION IN PSYCHIATRY
included neurological exam ndings. Thus, insane
temperament,
1
hysteria,
2
schizophrenia,
3,4
mood dis-
orders,
5,6
and obsessive-compulsive disorder
7
were each
thought to have characteristic NEA. By mid-century the
American psychiatric literature rarely mentioned neu-
rologic ndings. NEA research in child psychiatry then
expanded as the concepts of soft neurological signs
8
and minimal brain dysfunction
9
became popular in
the 1960s. This trend led to large pediatric studies
10,11
and to much conceptual and methodologic clarica-
tion.
1215
Studies of NEA in adolescent
16,17
and then
adult
18,19
psychiatric patients followed. Studies of NEA
in adult psychiatric patients have increased in quantity
and quality in recent years; recent texts again include
NEA in descriptions of psychopathology.
20,21
Since its use by Bender in 1947 to describe ndings
suggesting possible neurologic disease, the term soft
signs has had other connotations, including a lack of di-
agnostic or anatomic specicity, a lack of reliability, and
evanescence. Also soft are the boundaries of the cate-
gory, considered by some to include such variedfeatures
as sinistrality, electroencephalographic dysrhythmias,
and learning disabilities, as well as the more widely in-
cluded NEA.
22
Not surprisingly, some view the topic
with derision: The use of the terms soft signs and
minimal brain damage is diagnostic of soft thinking.
23
However, summarily dismissing a heterogeneous col-
lection of simple, noninvasive, and inexpensive assess-
ment tools on the above bases could also be regarded as
diagnostic of soft thinking. First, although anatomic
specicity is uniquely valued in neurology, it may not
be as important in psychiatry, in which localization is
less central to diagnosis. Second, although the terms
hard and soft imply that the former are reproducible and
the latter not, the data suggest otherwise. Third, al-
though some of the soft NEA may be evanescent, the
extent of this has not been determined in adult psychi-
atric patients. Because state variation is common in psy-
chiatric syndromes, temporal variability in neurological
measures may offer some advantages; variability in per-
formance may itself be an important parameter in psy-
chiatry.
24
The term neurological soft signs thus has multiple mis-
leading meanings. Although it may be useful to char-
acterize a set of data as hard or soft evidence of
major neurologic disease, we suggest that the term not
be used to describe individual signs.
The potential for the neurologic examination to add
to diagnosis, prognosis, and treatment selection in an
era of increasing scal limitations warrants an exami-
nation of the signicance of NEA in adult psychiatry.
This article, written primarily for researchers, summa-
rizes the current knowledge base on the bedside neu-
rologic examination in adult psychiatry, focusing on
methodological issues and on enhancing the clinical
relevance of work in this eld. Although the boundaries
blur between this and such related areas as neurophys-
iology and neuropsychology, we address techniques
that can be readily applied in clinical settings and that
would not be considered part of the routine mental
status exam.
RELIABILITY AND VALIDITY
Components of the Examination
Psychiatric research on NEA has employed collections
of neurologic examination items culled fromclinical tra-
dition or previous research (Table 1). Some batteries are
partly or entirely drawn from general neurology
texts,
2527
and some are selected fromfamiliar neuropsy-
chological batteries.
28,29
Several scales were developed
for use with children in the heyday of research into neu-
rological aspects of pediatric psychiatry
1012,30,31
and
have found application in adult populations.
The Neurological Evaluation Scale (NES),
32
based on
a review of NEA in schizophrenia,
33
is the most fully
described and widely employed instrument in adult
psychiatry.
32,3439
Convit et al.
40
also developed a com-
posite examination, the Quantied Neurological Scale,
which has been used mostly within that group. Chen et
al.
41
recently published, for use in adult psychiatry, a
heterogeneous inventory of NEA and behavioral obser-
vations, with administration guidelines and reliability
data for some of the inventory. Some scales
31,40,41
addi-
tionally include items usually used to screen for frank
neurologic disease but not frequently seen in psychiatric
patients. The primitive (release, frontal release) reexes
are often dealt with separately.
42
Rudimentary sensory
function, extrapyramidal motor function, spontaneous
abnormal movements, and blink rate are not generally
included in these neurologic examination schedules.
Thus, the available scales tap into somewhat different
yet overlapping aspects of neurologic performance. It is
important to note this when comparing studies of NEA,
particularly when only summary scores are presented.
Each of the instruments referenced in Table 1 provides
directions for administration, as well as some reliability
and validity data. These instruments are best viewed as
collections of individual examinations that need not be
adopted in toto. It may often be more suitable to con-
sider the items individually for inclusion in a clinical or
research examination.
Reliability
Numerous threats to the reliability of NEA are worth
considering. Many examination items, such as motor
JOURNAL OF NEUROPSYCHIATRY 397
SANDERS AND KESHAVAN
TABLE 1. Elements of the neurological examination pertinent to
adult psychiatry
Element NES PANESS QNS CNI
Motor (station and gait)
Casual gait X X
Stressed gaits X
Tandem gait X X X X
Hopping X X
Romberg X X X
Complex movements
Fist-ring X X
Fist-edge-palm X X X
Alternating st-palm X X X
Diadochokinesis X X
Finger-thumb opposition X X X
Rhythm tapping X X X
Synchronous tapping X
Tap production X
Extraocular movements
Visual tracking X X
Convergence X
Gaze persistence X X
Other motor
Drift X
Motor persistence X X
Finger-nose X X X
Heel-shin X
Muscle tone X
Mirror movement X X X
Synkinesis of head X X
Tremor X X
Choreoathetotic movements X X
Sensory
Audiovisual integration X
Stereognosis X X X X
Graphesthesia X X X X
Face-hand/extinction X X X X
Face-noise test X
Two-point discrimination X
Right-left orientation X X X
Primitive reexes
Glabellar X X
Snout X X
Palmomental X
Grasp X X
Suck X
Note: NESNeurological Evaluation Scale;
32
PANESSPhysical
and Neurological Examination for Soft Signs;
30
QNSQuantied
Neurological Scale;
41
CNICambridge Neurological Inventory.
42
overow, require subjectivity in rating, defying quanti-
cation unless special instruments are employed. Inter-
rater agreement is more difcult to achieve when the
abnormal response is merely an exaggeration of a nor-
mal phenomenon (e.g., tremor and postural sway). Sub-
jectivity can also falsely elevate local agreement (attrib-
utable to the shared experience of examiners, as
opposed to communicable standards
13
) and predispose
to drift (weakening of interrater reliability over time
15
).
Because of the difculty of directly quantifying some
NEA, these studies tend to collapse all data into ordinal
or dichotomous formats for uniformity. This practice
complicates the statistical approach to reliability assess-
ment of individual exam items, reducing power and
producing data that fall in the gray zone between what
is suitable for intraclass correlation and what is suitable
for the kappa statistic.
43
Empirical data nevertheless suggest that interrater re-
liability is generally quite acceptable.
13
It is compro-
mised primarily in the more subjectively assessed
NEA
10,36,4446
and in those requiring discriminations be-
tween normal and slightly abnormal.
10,47
Establishing
reliability with some of the hard NEA, most strikingly
muscle stretch reexes, may be at least as problematic
as it is with psychiatrically signicant NEA.
10,44,46,4850
For example, reliability estimates in the Isle of Wight
study
10
were higher for measures of coordination and
developmental abnormalities than for muscle stretch
reexes. In studies of neurology inpatients, 25%
50
and
43%
49
of routinely assessed NEA fell belowthe common
reliability threshold of kappa0.4; in two populations
of psychiatric patients, the corresponding percentages
were 22% and 11%.
36
A clearer understanding of how
to conduct the examination improves reliability.
42,44,48
Clinicians might require additional training to assess
some of these signs as reliably as in research settings.
Such training could be facilitated by video technology.
Less attention has been paid to test-retest reliability.
Prospective studies of patients, involving repeated ex-
aminations,
28,29,5153
are required to clarify the state or
trait aspects of NEA in psychiatric patients. Interpreting
changes in performance over repeated neurologic exams
in patients as a function of state change, though, will
require data on the stability of NEA in the absence of
potentially relevant state changes. Summary indices of
NEAare stable in chronic schizophrenia.
32
However, the
test-retest reliability of individual NEA has rarely been
examined in adult psychiatric populations. Using kappa
greater than 0.4 as a threshold, and restricting analysis
to items with adequate interrater reliability, two small
studies have found that 33%
36
and 44%
54
of NEA could
be consistently reproduced. Thus, temporal stability of
NEA in adult psychiatric patients remains uncertain.
Determining which of the NEA are replicable over time
in stable patients is critical for interpreting longitudinal
studies of state-related inuences on neurologic func-
tioning in psychiatry.
Groupings of Neurologic Exam Elements
Some studies ignore the heterogeneity of NEA, deriving
a summary score to represent the overall severity of neu-
rologic dysfunction or the total number of abnormal
signs.
26
At the opposite extreme, analyzing NEA indi-
vidually has limitations due to limited statistical power
398 VOLUME 10 NUMBER 4 FALL 1998
NEUROLOGIC EXAMINATION IN PSYCHIATRY
with ordinal and categorical data, variable reliability
among individual items, and problems attendant on
multiple tests of signicance. Assigning NEA to sub-
scales might allow one to exploit the heterogeneity of
NEA while avoiding the limitations of item-by-item
analysis.
Some studies have grouped items on the basis of their
presumed neuroanatomic substrates.
25,41,55,56
This
grouping is debatable in psychiatric patients without fo-
cal lesions: NEA do not necessarily have localizing sig-
nicance in these populations. Rather than anatomical
regions, NEA batteries could be indexed in terms of dis-
tributed neuroanatomical or neurochemical systems.
Others
15,22
categorize individual NEA as signs repre-
senting developmental delay, signs consistent with ac-
quired focal brain injury, and subtle variants of focal
signs. Many other variables might dictate the associa-
tion of individual exam items, including their depen-
dence on general intelligence, sustained attention, or
motivation.
Five adult psychiatric studies, all involving schizo-
phrenic patients, have used factor analytic techniques to
derive item clusters for the neurologic exam,
34,37,51,57,58
with inconsistent results. Further study of the natural
organization of NEA in adult psychiatric patients, with
adequate numbers of subjects, using appropriate statis-
tics and limiting entered data to reliably assessed NEA,
should help to establish defensible subscales.
Relationships With Other Neurologic Tests
A variety of neurophysiologic techniques have been
used to characterize phenomena seen in the clinical neu-
rologic exam. Smooth pursuit eye movements (SPEM),
59
visual xation,
60
and extrapyramidal motor dysfunc-
tion
61
have been studied instrumentally, and the pal-
momental reex has been quantied following electrical
elicitation.
62
These relatively noninvasive and inexpen-
sive methods can obviously help validate the bedside
exam, but they have yet to be applied to most NEA.
Neurophysiologic methods may also be used to explore
biological correlates of NEA; two studies
63,64
found re-
lationships between EEG dysrhythmias and NEA, but
others
16,19,65
have not. SPEM dysfunction has been re-
lated to NEA among psychotic patients
39,66
and nonpa-
tients.
67
Startle habituation has been related to global
neurologic performance.
34
Functional neuroimaging parameters seem to be un-
related to NEA in resting patients.
56,68
However, less ac-
tivation of the appropriate cortical regions is seen dur-
ing motor tasks in schizophrenia and dementia patients
than in comparison subjects.
6971
Further application of
functional imaging and other neurophysiologic meth-
ods will be needed to clarify the mechanisms of NEA in
patients without acquired focal lesions.
CLINICAL UTILITY
Differential Diagnosis
Diagnostic comparisons of NEAhave mostly focusedon
dementia and the psychotic disorders. The neurologic
exam could signicantly clarify psychiatric differential
diagnosis, particularly when the available history is lim-
ited. We survey ndings to date in dementia and in psy-
chotic, mood, and anxiety disorders (Table 2, rst col-
umn).
Dementia has been studied with respect to differential
diagnosis and severity. In contrast with normal control
subjects, Alzheimers disease patients have excesses of
astereognosis, agraphesthesia, cerebellar ndings, olfac-
tory decits, primitive reexes, hyperreexia, abnormal
plantar responses, and extrapyramidal ndings.
72,73
Fo-
cal NEA, gait abnormalities, and dysarthria are associ-
ated with multi-infarct dementia, as opposed to other
dementias.
74,75
Early extrapyramidal ndings may sug-
gest dementia of the Lewy body type.
76
Dementia sec-
ondary to alcoholism was strongly associated with
ataxia and polyneuropathy in one study.
77
Several other
forms of dementia may be related to specic NEA.
78
Primitive reexes,
72,79
olfactory decits,
80
and pyrami-
dal,
72
extrapyramidal,
81,82
and other motor abnormali-
ties
79,81
are associated with the cross-sectional severity
of dementia; this factor thus needs to be controlled for
when comparing NEA across dementias. Potentially, in
addition to helping to identify focal and multifocal le-
sions in patients with dementia, NEA might be found
to distinguish between different types of primary de-
generative dementia and between dementia and de-
pressive pseudodementia.
The primary psychoses, particularly schizophrenia,
are much investigated with respect to NEA (see re-
views
33,82
). Many NEA, notably abnormalities of motor
sequencing, coordination, and higher order sensory
function,
33
are more common in schizophrenic than in
healthy subjects even when only neuroleptic-naive pa-
tients are included.
27,35,56
Parkinsonian ndings have
also been described in neuroleptic-naive patients.
60,83
Most data suggest that schizophrenic patients have
more neurologic dysfunction than nonpsychotic pa-
tients, but the evidence is more mixed when comparing
psychotic patients with different diagnoses.
33,8487
Some
longitudinal data suggest an improvement in neurolog-
ical performance with improvement in clinical state
and/or treatment with antipsychotic medication.
51,53
Variation in NEA due to clinical state or medications
JOURNAL OF NEUROPSYCHIATRY 399
SANDERS AND KESHAVAN
TABLE 2. Clinical utility of the neurologic examination in psychiatry: current status
Areas of Clinical Utility
Disorder Differential Diagnosis Treatment Selection Prognosis
Dementia Alzheimers vs. normal (S)
72,73
Ischemic vs. other (S)
74,75
Lewy body variant (W)
76
Alcohol-induced (W)
77
Treatment of cardiovascular risk
factors (S)
74,75
Select cases for more aggressive
treatment (N)
Predict onset (W)
113
Rapid decline (S)
114116,118,119
Psychotic
disorders
Psychotic vs. normal (S)
27,35,56
Psychotic vs. nonpsychotic but psychiatrically ill
(W)
88,9093
Primary psychotic disorder vs. psychiatric disorder
complicated by psychosis (W)
8587,90,92
Choice of antipsychotic agent (N)
EPSE prophylaxis (N)
Long-term poor prognosis
(W)
83,121,122
Persisting negative symptoms
(W)
40
EPSE (W)
83,129
TD (N)
Mood
disorders
Mood disorders vs. normal (W)
88,89
Psychotic mood disorder vs. primary psychosis
(W)
8587
Choice of medication (N)
Choice of psychotherapy (N)
Predict relapse in bipolar (W)
123
Anxiety
disorders
OCD vs. normal (S)
96100
PTSD vs. normal (W)
102
SP vs. normal (W)
103
OCD, PTSD, SP vs. other psychiatric groups (W)
97
Choice of medication (N)
Choice of psychotherapy N)
Short-term poor prognosis (W)
124,125
Note: Sstrong evidence (replicated at least once, minimal conicting data); Wweak evidence (no replications, or signicant conicting
evidence); Nno evidence to date; EPSEextrapyramidal side effects; TDtardive dyskinesia; OCDobsessive-compulsive disorder;
PTSDposttraumatic stress disorder; SPsocial phobia.
may thus obscure comparisons of diagnostic groups.
Signicant clinical benets might be realized if NEA
could distinguish between psychotic disorders, but fur-
ther studies comparing diagnoses while controlling for
treatment and clinical status will rst be necessary.
Mood disorders have been neglected in NEAresearch.
Abnormalities exceeding those of normal comparison
subjects have been found in manic
88
and mixed manic
and depressed patients.
89
Differences were found in mo-
tor control and sequencing, stereognosis, and graphes-
thesia. In studies comparing mood-disordered with
schizophrenic patients, global NEA were fewer and/or
milder in mood disorders,
18,9092
although two stud-
ies
88,93
found few differences. Consistent with early de-
scriptions of melancholia suggesting extrapyramidal
dysfunction,
5,6
depression and extrapyramidal dysfunc-
tion are related in Alzheimers disease.
81,94
There are few
differences in NEA between unipolar and bipolar pa-
tients.
25,29,89,92
The prevalence and diagnostic specicity
of NEA in mood disorders remain unclear. The strong
effects of psychiatric state on general functioning in the
mood disorders, along with the mood-relatedvariability
of neurologic functioning evidenced in psychiatric pa-
tients,
29,52
suggest that phase of illness will need to be
considered. Diurnal variation may also have a signi-
cant impact on neurologic function in the mood disor-
ders.
95
Anxiety disorders have scarcely been investigated,
with the exception of obsessive-compulsive disorder
(OCD). NEA are more frequent in OCD patients than in
normal comparison subjects,
9699
although this nding
was not replicated in female OCD patients.
100
Specic
ndings include poor motor coordination,
97,98
disinhi-
bited motor activity,
96,98,99
impaired balance,
97
an excess
of left-sided dysfunction,
96,98,99
and extrapyramidal mo-
tor ndings.
7,101
Difculties with motor control and with
presumably right-hemisphere tasks are fairly consistent
ndings in this body of work. The diagnostic specicity
of these ndings to OCD remains unclear.
97
More NEA
are seen in posttraumatic stress disorder patients
102
than
in control subjects, with signicantly greater abnormal-
ity in motor sequencing and the palmomental reex. So-
cial phobia patients had marginally more NEAthan nor-
mal control subjects in a small study.
103
Further work is
needed to address the specicity of these ndings to
anxiety disorders generally and to specic anxiety dis-
orders, while considering the possible effects of state
anxiety and medication.
Treatment Selection and Prognosis
To the extent that they are static or trait-like, NEAmight
be expected to predict such aspects of psychopathology
as illness onset, outcome, and complications of treat-
ment. These are areas in which the neurologic exam has
clear potential for complementing clinical assessment of
psychiatric patients. These areas of clinical utility are
represented in the last two columns of Table 2.
Onset Prediction: Follow-up of subsamples from the
National Collaborative Perinatal Project foundthat NEA
at age seven, particularly motor abnormalities, predict
depression,
14,104
anxiety,
14,104
and delinquency
105
in ad-
400 VOLUME 10 NUMBER 4 FALL 1998
NEUROLOGIC EXAMINATION IN PSYCHIATRY
olescence and also predict criminality
105
and perhaps
anxiety
106
in adulthood. Motor dysfunction and general
neurological impairment in preadolescence predicted
psychiatric morbidity in the New York schizophrenia
high-risk project.
107
Children with motor impairments
are more likely to develop schizophrenia by adult-
hood,
108110
and sensory decits may also enhance vul-
nerability to psychosis in youth
111
as well as in old
age.
112
In elderly persons, extrapyramidal ndings may
predict the onset of dementia.
113
Outcome Prediction: Neurologic ndings with possible
prognostic value in Alzheimers disease include extra-
pyramidal signs,
114116
myoclonus,
114,117
parietal
signs,
114,117119
and primitive reexes.
115
In schizophre-
nia and mood disorders, NEA at baseline may not pre-
dict short-term amelioration of psychiatric symp-
toms.
33,53,89,120
However, negative symptoms persisting
after treatment with conventional antipsychotic medi-
cation were predicted by baseline NEA.
40
Long-term
global outcome in schizophrenia was also anticipatedby
NEA, including motor sequencing and extrapyramidal
dysfunction.
83,121,122
Stable, medicated bipolar patients
with neurologic ndings were more likely to relapse
during follow-up.
123
NEA predicted a poor response to
medication in one of two studies of obsessive-
compulsive disorder.
124,125
Thus, neurologic signs may
have prognostic importance in a variety of psychiatric
contexts, with implications for treatment selection.
Predictions of Treatment Complications: Although NEA
might predict neurologic side effects from a variety of
psychiatric medications, the only data known to us per-
tain to typical antipsychotic agents. Tardive dyskinesia,
noted to coincide with motor and sensory ndings and
primitive reexes,
126128
may also be predicted by such
ndings: withdrawal-emergent dyskinesia was pre-
dicted by the number of NEA in one study.
26
Low blink
rate
129
and other parkinsonian signs
83
predict parkin-
sonism after treatment with conventional antipsychotic
drugs. Baseline neurological data may help to inform
choices regarding antipsychotics and prophylactic anti-
parkinsonian agents.
CONCLUSIONS
Psychiatry is progressively informed by the brain sci-
ences, but it is constrained in applying this knowledge
to the clinical assessment of the individual patient by
the high cost of the technologies applied in neuropsy-
chiatric research. The neurologic examination is inex-
pensive and available to all physicians, and thus it has
the potential to bridge the gulf between neurobiologic
research and clinical practice. It has shown promise as
an aid in differential diagnosis, prognosis, and treat-
ment selection in a variety of psychiatric conditions.
The neurologic examination also has important limi-
tations. It offers only indirect reections of the salient
properties of the brain, and it is presumably inferior to
such approaches as functional imaging and histopa-
thology in characterizing specic neural systems or in
elucidating the neurobiologic bases of psychiatric dis-
orders. Some may thus nd it less intellectually exciting
than many other techniques, and its utility may lie in
more immediately clinical questions. A second limita-
tion is that an extended neurologic exam requires time
to complete. Clinicians tend to avoid devoting time to
evaluative activities that shed only ambiguous light on
the case at hand and thus may be reluctant to perform
entire exam schedules routinely. Any extension beyond
the traditional cursory rule out examination will be
adopted only to the extent that it has clear implications
for patient care. The limitations on reliability, although
neither trivial nor entirely determined (especially in the
case of test-retest reliability), appear to be comparable
to those of the conventional neurologic exam.
Establishing efcient applications of the neurologic
exam for specic clinical questions will require consid-
erable renement of the knowledge base. As Table 2 il-
lustrates, many potential clinical applications have been
investigated insufciently, if at all.
First, it must be clearly established, for a given clinical
population, which examination items are frequently
enough abnormal to be of interest and can be readily
assessed with adequate interrater reliability. Batteries
must be developed that are limited to such items.
The reliability and validity of individual and aggre-
gate neurologic tests should be assessed as methodically
as are neuropsychological tests. These tests will require
further validation against other measures, particularly
those measuring regional brain function, so that we may
better understand the nature of the abnormalities and
explore the possibility that these tests offer more ef-
cient alternative routes to similar information yieldedby
these less accessible methods.
We need comprehensive developmental and norma-
tive assessments of such examinations, especially before
they are otherwise used in studies involving elderly sub-
jects. The exams should be applied to large samples of
diagnostically heterogeneous patients to clarify their
value in differential diagnosis; to longitudinal studies to
clarify their value in prognosis; and to therapeutic trials
to clarify their value in treatment selection. The current
tendency toward descriptive studies will have to give
way to the testing of more specic hypotheses.
JOURNAL OF NEUROPSYCHIATRY 401
SANDERS AND KESHAVAN
Much of the promise of the extended neurological ex-
amination lies in its heterogeneity. Its numerous ele-
ments individually have potential utility that may well
be lost when they are combined into summary indices
of soft signs or neuromotor dysfunction. Their po-
tential may be realized only through item-by-item anal-
yses. This approach is more feasible if these measures
are continuous, rather than categorical or ordinal. Com-
binations of items should be empirically rather than in-
tuitively determined; this might be done through a
quantitative distillation such as factor analysis.
Bringing neurobiological knowledge to bear on clini-
cal psychiatry is a task that can differ conceptually and
methodologically from the more vigorously pursued
task of uncovering the neurobiological bases of psychi-
atric disorders.
130
If pursued with comparable fervor to
that aroused by the more fundamental questions, such
work could have a substantial impact on the practice of
clinical psychiatry. The neurological examination offers
promising avenues for the reintegration of neurobiology
into psychiatric assessment.
The authors thank Joseph Pierri, M.D., for his comments on
this manuscript, Melissa Knox for library assistance, and
Tamera McLaughlin for secretarial support. This work was
supported in part by National Institute of Mental Health
Grants MH45203, MH01180, and MH45156 (M.S.K.) and
was previously presented at the Society of Biological Psychi-
atry annual meeting, San Diego, CA, May 1518, 1997.
References
1. Maudsley H: Body and Mind: An Inquiry Into Their Connec-
tion and Mutual Inuence, Especially in Reference to Mental
Disorders. New York, Appleton, 1874
2. Charcot JM: Clinical Lectures on Certain Diseases of the Ner-
vous System. Detroit, MI, GS Davis, 1888
3. Kraepelin E: Dementia Praecox and Paraphrenia. Huntington,
NY, Krieger, 1919
4. Bleuler E: Dementia Praecox or the Group of Schizophrenias.
New York, International Universities Press, 1911
5. Kraepelin E: Manic-Depressive Insanity and Paranoia. New
York, Arno, 1921
6. Stoddart WHB: Mind and Its Disorders: A Textbook for Stu-
dents and Practitioners of Medicine, 5th edition. London, Lewis
and Co, 1926
7. Schilder P: The organic background of obsessions and com-
pulsions. Am J Psychiatry 1938; 94:13971416
8. Bender L, Fink N, Green M: Childhood schizophrenia: clinical
study of 100 schizophrenic children. Am J Orthopsychiatry
1947; 17:4056
9. Clements SD, Peters J: Minimal brain dysfunction in the school-
age child. Arch Gen Psychiatry 1962; 6:185197
10. Rutter M, GrahamP, Yule W: Aneuropsychiatric study in child-
hood (monograph). Clin Dev Med 1970; 3536:1272
11. Nichols PL, Chen TC: Minimal Brain Dysfunction: A Prospec-
tive Study. Hillsdale, NJ, Erlbaum, 1981
12. Tupper DE: Soft Neurological Signs. New York, Grune and
Stratton, 1987
13. Shafer SQ, Shaffer D, OConnor PA, et al: Hard thoughts on
neurological soft signs, in Developmental Neuropsychiatry,
edited by Rutter M. New York, Guilford, 1983, pp 133143
14. Shaffer D, OConnor PA, Shafer S, et al: Neurological soft
signs: their origins and signicance for behavior, in Develop-
mental Neuropsychiatry, edited by Rutter M. New York, Guil-
ford, 1983, pp 144163
15. Neeper R, Greenwood RS: On the psychiatric importance of
neurological soft signs, in Advances in Clinical Child Psychol-
ogy, vol 10, edited by Lahey BB, Kazdin AE. NewYork, Plenum,
1987, pp 217258
16. Kennard M: The value of equivocal signs in neurological di-
agnosis. Neurology 1960; 10:753764
17. Hertzig ME, Birch HG: Neurologic organization in psychiatri-
cally disturbed adolescent girls. Arch Gen Psychiatry 1966;
15:590598
18. Rochford JM, Detre T, Tucker GJ, et al: Neuropsychological im-
pairments in functional psychiatric diseases. Arch Gen Psychi-
atry 1970; 22:114119
19. Mosher LR, Pollin W, Stabenau JR: Identical twins discordant
for schizophrenia: neurologic ndings. Arch Gen Psychiatry
1971; 24:422430
20. American Psychiatric Association: Diagnostic and Statistical
Manual of Mental Disorders, 4th edition. Washington, DC,
American Psychiatric Association, 1994
21. Lipton AA, Cancro R: Schizophrenia: clinical features, in Com-
prehensive Textbook of Psychiatry, 6th edition, edited by Kap-
lan HI, Sadock BJ. Baltimore, Williams and Wilkins, 1995,
pp 968987
22. Taylor HG: The meaning and value of soft signs in the behav-
ioral sciences, in Soft Neurological Signs, edited by Tupper DE.
New York, Grune and Stratton, 1987, pp 297335
23. Ingram TTS: Soft signs. Dev Med Child Neurol 1973; 15:527
529
24. King HE: Psychomotor Aspects of Mental Disease. Cambridge,
MA, Harvard University Press, 1954
25. Cox SM, Ludwig AM: Neurological soft signs and psychopa-
thology: incidence in diagnostic groups. Can J Psychiatry 1979;
24:668673
26. Schultz SK, Miller DD, Arndt S: Withdrawal-emergent dyski-
nesia in patients with schizophrenia during antipsychotic dis-
continuation. Biol Psychiatry 1995; 38:713719
27. Gupta S, Andreasen NC, Arndt S, et al: Neurological soft signs
in neuroleptic-naive and neuroleptic-treated schizophrenic pa-
tients and in normal comparison subjects. Am J Psychiatry
1995; 152:191196
28. Guenther W, Guenther R, Eich FX, et al: Psychomotor distur-
bances in psychiatric patients as a possible basis for new at-
tempts at differential diagnosis and therapy, II: cross validation
study on schizophrenic patients: persistence of a psychotic
motor syndrome as possible evidence of an independent bio-
logical marker syndrome for schizophrenia. Eur Arch Psychi-
atry Clin Neurosci 1986; 235:301308
29. Guenther W, Guenther R, Streck P, et al: Psychomotor distur-
bances in psychiatric patients as a possible basis for new at-
tempts at differential diagnosis and therapy, III: cross valida-
tion study on depressed patients: the psychotic motor
syndrome as a possible state marker for endogenous depres-
sion. Eur Arch Psychiatry Clin Neurosci 1988; 224:6573
402 VOLUME 10 NUMBER 4 FALL 1998
NEUROLOGIC EXAMINATION IN PSYCHIATRY
30. Denckla MB: Revised PANESS. Psychopharmacol Bull 1985;
21:773800
31. Hertzig ME: Neurologic Evaluation Schedule, in Soft Neuro-
logical Signs, edited by Tupper DE. NewYork, Grune andStrat-
ton, 1987, pp 355368
32. Buchanan RW, Heinrichs DW: The Neurological Evaluation
Scale (NES): a structured instrument for the assessment of neu-
rological signs in schizophrenia. Psychiatry Res 1989; 27:335
350
33. Heinrichs DW, Buchanan RW: Signicance and meaning of
neurological signs in schizophrenia. Am J Psychiatry 1988;
145:1118
34. Karper L, Grillon C, Lysaker P, et al: Soft signs, attention, and
startle in schizophrenia (abstract), in New Research Abstracts.
Washington, DC, American Psychiatric Association, 1994, p 358
35. Sanders RD, Keshavan MS, Schooler NR: Neurologic exam ab-
normalities in rst-break, neuroleptic-naive schizophrenia: pre-
liminary results. Am J Psychiatry 1994; 151:12311233
36. Sanders RD, Forman SD, Pierri JN, et al: Interrater reliability of
the Neurological Examination in Schizophrenia. Schizophr Res
1998; 29:287292
37. Sanders RD, Forman SD, Gupta B, et al: Factor structure of the
Neurological Evaluation Scale (abstract). Biol Psychiatry 1995;
37:680
38. Sanders RD, Forman SD, Keshavan MS, et al: Test-retest stabil-
ity of the neurologic examination in schizophrenia (abstract).
Biol Psychiatry 1996; 39:548
39. Schlenker R, Cohen R, Berg P, et al: Smooth-pursuit eye move-
ment dysfunction in schizophrenia: the role of attention and
general psychomotor dysfunction. Eur Arch Psychiatry Clin
Neurosci 1994; 244:153160
40. Convit A, Volavka J, Czobor P, et al: Effect of subtle neurolog-
ical dysfunction on response to haloperidol treatment inschizo-
phrenia. Am J Psychiatry 1994; 151:4956
41. Chen EYH, Shapleske J, Luque R, et al: The Cambridge Neu-
rological Inventory: a clinical instrument for assessment of soft
neurological signs in psychiatric patients. Psychiatry Res 1995;
56:183204
42. Vreeling FW, Jolles S, Verhey FRJ, et al: Primitive reexes in
healthy, adult volunteers and neurological patients: methodo-
logical issues. J Neurol 1993; 240:495504
43. Streiner DL: Learning how to differ: agreement and reliability
statistics in psychiatry. Can J Psychiatry 1995; 40:6066
44. Kuzma JW, Tourtelotte WW, Remington RD: Quantitative clini-
cal neurological testing, II: some statistical considerations of a
battery of tests. Journal of Chronic Diseases 1965; 18:303311
45. Stokman C, Shafer SQ, Shaffer D, et al: Assessment of neuro-
logical soft signs in adolescents: reliability studies. Dev Med
Child Neurol 1986; 28:428439
46. Mayo NE, Sullivan SJ, Swaine B: Observer variation in assess-
ing neurophysical signs among patients with head injuries. Am
J Phys Med Rehabil 1991; 3:118123
47. Richards M, Marder K, Bell K, et al: Interrater reliability of ex-
trapyramidal signs in a group assessed for dementia. Arch
Neurol 1991; 48:11471149
48. Sisk C, Ziegler DK, Zileli T: The discrepancies in recorded re-
sults from duplicate neurological history and examination in
patients studied for prognosis in cerebrovascular disease.
Stroke 1970; 1:1418
49. Shinar D, Gross CR, Mohr JP, et al: Interobserver variability in
the assessment of neurologic history and examination in the
Stroke Data Bank. Arch Neurol 1985; 42:557565
50. Hansen M, Sindrup SH, Christensen PB, et al: Interobserver
variation in the evaluation of neurological signs: observer de-
pendent factors. Acta Neurol Scand 1994; 90:145149
51. Schroder J, Niethammer R, Geider FJ, et al: Neurological soft
signs in schizophrenia. Schizophr Res 1992; 6:2530
52. Bulbena A, Berrios GE: Cognitive function in the affective dis-
orders: a prospective study. Psychopathology 1993; 26:612
53. Duncan E, Sanlipo N, Wieland S, et al: Neurological soft signs
in schizophrenia: relationship to thought disorder (abstract).
Biol Psychiatry 1994; 35:715
54. Quitkin F, Rifkin A, Klein DF: Neurologic soft signs in schizo-
phrenia and character disorders. Arch Gen Psychiatry 1976;
33:845853
55. Buchanan RW, Koeppl P, Breier A: Stability of neurological
signs with clozapine treatment. Biol Psychiatry 1994; 36:198
200
56. Rubin P, Vorstrup S, Hemmingsen R, et al: Neurological ab-
normalities in patients with schizophrenia or schizophreniform
disorder at rst admission to hospital: correlations with com-
puterized tomography and regional cerebral blood ow nd-
ings. Acta Psychiatr Scand 1994; 90:385390
57. Faber A, Costello R, Mitzel H, et al: Dimensionality of a neu-
ropsychiatric soft sign battery (abstract). Schizophr Res 1991;
5:382383
58. Malla AK, Norman RMG, Aguilar O, et al: Relationship be-
tween neurological soft signs and syndromes of schizophre-
nia. Acta Psychiatr Scand 1997; 96:274280.
59. Levy DL, Holzman PS, Matthysse S, et al: Eye-tracking dys-
function and schizophrenia: a critical perspective. Schizophr
Bull 1993; 19:461536
60. Amador XF, Malaspina D, Sackeim HA, et al: Visual xation
and smooth pursuit eye movement abnormalities in patients
with schizophrenia and their relatives. J Neuropsychiatry Clin
Neurosci 1995; 7:197206
61. Caligiuri MP, Lohr JB, Jeste DV: Parkinsonism in neuroleptic-
naive schizophrenic patients. Am J Psychiatry 1993; 150:1343
1348
62. Kleu G: The palmomental reex in psychiatry. Acta Psychiatr
Scand 1971; 47:230236
63. Davies RK, Neil JF, Himmelhoch JM: Cerebral dysrhythmias in
schizophrenics receiving phenothiazines: clinical correlates.
Clin Electroencephalogr 1975; 6:103115
64. Monroe R, Hulsh B: Neurologic abnormalities in prison sub-
jects, in Brain Dysfunction in Aggressive Criminals, edited by
Monroe RR. Lexington, MA, Lexington Books, 1978, pp 141
147
65. Woods BT, Short MP: Neurological dimensions of psychiatry.
Biol Psychiatry 1985; 20:192198
66. Siever LJ, Coursey RD, Alterman IS, et al: Psychological and
physiological correlates of variations in smooth pursuit eye
movements, in Biological Markers in Psychiatry and Neurol-
ogy, edited by Usdin E, Hanin I. New York, Pergamon, 1982,
pp 359370
67. Siever LJ, Coursey RD, Alterman IS, et al: Clinical, psycho-
physiological, and neurological characteristics of volunteers
with impaired smooth pursuit eye movements. Biol Psychiatry
1989; 26:3551
68. Baker RW, Schooler NR, Shah AN, et al: Association of clinical
variables with SPECT ndings in schizophrenia (abstract). Schi-
zophr Res 1993; 7:192
69. Guenther W, Giunta R, Klages U, et al: Findings of electroen-
cephalographic brain mapping in mild to moderate dementia
of the Alzheimer type during resting, motor, and music-
perception conditions. Psychiatry Res 1993; 50:163176
JOURNAL OF NEUROPSYCHIATRY 403
SANDERS AND KESHAVAN
70. Guenther W, Brodie JD, Bartlett EJ, et al: Diminished cerebral
metabolic response to motor stimulation in schizophrenics: a
PET study. Eur Arch Psychiatry Clin Neurosci 1994; 244:115
125
71. Schroder J, Wenz F, Schad LR, et al: Sensorimotor cortex and
supplementary motor area changes in schizophrenia: a study
with functional magnetic resonance imaging. Br J Psychiatry
1995; 167:197201
72. Franssen EH, Reisberg B, Kluger A, et al: Cognition-
independent neurologic symptoms in normal aging and prob-
able Alzheimers disease. Arch Neurol 1991; 48:148154
73. Funkenstein HH, Albert MS, Cook NR, et al: Extrapyramidal
signs and other neurologic ndings in clinically diagnosedAlz-
heimers disease: a community-based study. Arch Neurol 1993;
50:5156
74. Gilleard CJ, Kellett JM, Coles JA, et al: The St. Georges demen-
tia bed investigation study: cardiovascular, neurological and
neuropsychological correlates. Acta Psychiatr Scand 1993;
87:273278
75. Roman GC, Tatemichi TK, Erkinjuntti T, et al: Vascular demen-
tia: diagnostic criteria for research studies. Report of the
NINDS-AIREN International Workshop. Neurology 1993;
43:250260
76. Forstl H, Burns A, Luthert P, et al: The Lewy-body variant of
Alzheimers disease: clinical and pathological ndings. Br J
Psychiatry 1993; 162:385392
77. Osuntokun BO, Hendrie HC, Fisher K, et al: The diagnosis of
dementia associated with alcoholism: a preliminary report of
new approach. West Afr J Med 1994; 13:160163
78. Sanson TA, Price BH: Diagnostic testing and dementia. Neurol
Clin 1996; 14:4559
79. Benesch CG, McDaniel KD, Cox C, et al: End-stage Alzheimers
disease: Glasgow Coma Scale and the neurologic examination.
Arch Neurol 1993; 50:13091315
80. Bell IR, Amend D, Kaszniak AW, et al: Memory decits, sensory
impairment, and depression in the elderly (letter). Lancet 1993;
341:62
81. Bakchine S, Lacomblez L, Palisson E, et al: Relationship be-
tween primitive reexes, extrapyramidal signs, and reective
apraxia and severity of cognitive impairment in dementia of
the Alzheimer type. Acta Neurol Scand 1989; 79:3846
82. Cadet JL, Rickler KC, Weinberger DL: The clinical neurologic
examination in schizophrenia, in The Neurology of Schizo-
phrenia, edited by Nasrallah H, Weinberger D. New York, El-
sevier, 1986, pp 147
83. Chatterjee A, Chakos M, Koreen A, et al: Prevalence andclinical
correlates of extrapyramidal signs and spontaneous dyskinesia
in never-medicated schizophrenic patients. Am J Psychiatry
1995; 152:17241729
84. Tucker GJ, Silverfarb PM: Neurologic dysfunction in schizo-
phrenia: signicance for diagnostic practice, in Psychiatric Di-
agnosis: Exploration of Biological Predictors, edited by Akiskal
HS, Webb WL. New York, Spectrum, 1978, pp 453462
85. Woods BT, Kinney DIC, Yurgelun-Todd D: Neurologic abnor-
malities in schizophrenic patients and their families, I: com-
parison of schizophrenic, bipolar and substance abuse patients
and normal controls. Arch Gen Psychiatry 1986; 43:657663
86. Walker E, Shaye J: Familial schizophrenia: a predictor of neu-
romotor and attentional abnormalities in schizophrenia. Arch
Gen Psychiatry 1982; 39:11531156
87. Schwartz F, Carr A, Munich R, et al: Voluntary motor perfor-
mance in psychotic disorders: a replication study. Psychol Rep
1990; 66:12231234
88. Nasrallah HA, Tippin J, McCalley-Whitters M: Neurological
soft signs in manic patients: a comparison with schizophrenic
and control groups. J Affect Disord 1983; 5:4550
89. Cherian A, Kuruvilla K: Prevalance of neurological soft signs
in affective disorder and their correlation with response to
treatment. Indian Journal of Psychiatry 1989; 31:224229
90. Walker E: Attentional and neuromotor functions of schizo-
phrenics, schizoaffectives and patients with other affective dis-
orders. Arch Gen Psychiatry 1981; 38:13551358
91. Manschreck TC, Ames D: Neurologic features and psychopa-
thology in schizophrenic disorders. Biol Psychiatry 1984;
19:703719
92. Kinney DK, Yurgelun-Todd D, Woods BT: Neurological hard
signs in schizophrenia and major mood disorders. J Nerv Ment
Dis 1993; 181:202203
93. Gureje O: Neurological soft signs in Nigerian schizophrenics: a
controlled study. Acta Psychiatr Scand 1988; 78:505509
94. Merello M, Sabe L, Teson A, et al: Extrapyramidalism in Alz-
heimers disease: prevalence, psychiatric, andneuropsycholog-
ical correlates. J Neurol Neurosurg Psychiatry 1994; 57:1503
1509
95. Moffoot APR, OCarroll RE, Bennie J, et al: Diurnal variation
of mood and neuropsychological function in major depression
with melancholia. J Affect Disord 1994; 32:257269
96. Denckla MB: Neurological examination, in Obsessive Compul-
sive Disorder in Children and Adolescents, edited by Rapoport
JL. Washington, DC, American Psychiatric Press, 1989, pp 107
115
97. Conde Lo pez V, de la Gandara Mart n JJ, Blanco Lozano ML,
et al: Signos neurolo gicos menores en los trastornos obsesivo-
compulsivos [Neurologic soft signs in obsessive-compulsive
disorders]. Actas Luso Esp Neurol Psiquiatr Cienc Anes1990;
18:143164
98. Hollander E, Schiffman E, Cohen B, et al: Signs of central ner-
vous system dysfunction in obsessive-compulsive disorder.
Arch Gen Psychiatry 1990; 47:2732
99. Bihari K, Pato MT, Hill JL, et al: Neurologic soft signs in
obsessive-compulsive disorder (letter). Arch Gen Psychiatry
1991; 48:278279
100. Stein DJ, Hollander E, Simeon D, et al: Neurological soft signs
in female trichotillomania patients, obsessive-compulsive dis-
order patients, and healthy control subjects. J Neuropsychiatry
Clin Neurosci 1994; 6:184187
101. Hymas N, Lees A, Bolton D, et al: The neurology of obsessional
slowness. Brain 1991; 114:22032233
102. Gurvits TV, Lasko NB, Schachter SC, et al: Neurological status
of Vietnam veterans with chronic posttraumatic stress disorder.
J Neuropsychiatry Clin Neurosci 1993; 5:183188
103. Hollander E, Weiller F, Cohen L, et al: Neurological soft signs
in social phobia. Neuropsychiatry Neuropsychol Behav Neurol
1996; 9:182185
104. Pine D, Shaffer D, Schonfeld IS: Persistent emotional disorder
in children with neurological soft signs. J Am Acad Child Ado-
lesc Psychiatry 1993; 32:12291236
105. Denno DW: Biology and Violence: From Birth to Adulthood.
New York, Cambridge University Press, 1990
106. Hollander E, DeCaria CM, Aronowitz B, et al: A pilot follow-
up study of childhood soft signs and the development of adult
psychopathology. J Neuropsychiatry Clin Neurosci 1991; 3:186
189
107. Erlenmeyer-Kimling L, Kestenbaum C, Bird H, et al: Assess-
ment of the New York high-risk project subjects in sample A
who are now clinically deviant, in Children at Risk for Schizo-
404 VOLUME 10 NUMBER 4 FALL 1998
NEUROLOGIC EXAMINATION IN PSYCHIATRY
phrenia: A Longitudinal Perspective, edited by Watt F, Wynne
LC, Rolf JE. New York, Cambridge University Press, 1984, pp
227239
108. Fish B, Marcus J, Hans SL, et al: Infants at risk for schizophre-
nia: sequelae of a genetic neurointegrative defect. Arch Gen
Psychiatry 1992; 49:221235
109. Jones P, Rodgers B, Murray R, et al: Child developmental risk
factors for adult schizophrenia in the British 1946 birth cohort.
Lancet 1994; 344:13981402
110. Walker EF, Savoic T, Davis D: Neuromotor precursors of schizo-
phrenia. Schizophr Bull 1994; 20:441451
111. David AS, Maimberg A, Lewis G, et al: Are there neurological
and sensory risk factors for schizophrenia? Schizophr Res 1995;
14:247251
112. Kay DWK, Roth M: Environmental and hereditary factors in
the schizophrenias of old age (late paraphrenia) and their
bearing on the general problem of causation in schizophrenia.
J Ment Sci 1961; 107:649686
113. Richards M, Stern Y, Mayeux R: Subtle extrapyramidal signs
can predict the development of dementia in elderly individu-
als. Neurology 1993; 43:21842188
114. Mayeux R, Stern Y, Spanton S: Heterogeneity in dementia of
the Alzheimer type: evidence of subgroups. Neurology
1985;35:453461
115. Burns A, Jacoby R, Levy R: Neurological signs in Alzheimers
disease. Age Ageing 1991; 20:4551
116. Stern Y, Liu X, Albert M, et al: Modeling the inuence of extra-
pyramidal signs on the progression of Alzheimers disease.
Arch Neurol 1996; 53:11211126
117. Chui HC, Teng EL, Henderson VW, et al: Clinical subtypes of
dementia of the Alzheimer type. Neurology 1985; 35:15441550
118. Gilleard CJ, Spain E, OCarroll RE: Senile dementia andparietal
lobe dysfunction. Br J Psychiatry 1987; 150:114117
119. O Carroll RE, Whittick S, Baikie E: Parietal signs and sinister
prognosis in dementia: a four-year follow-up study. Br J Psy-
chiatry 1991; 158:358361
120. Bartko G, Frecska E, Zador G, et al: Neurological features, cog-
nitive impairment and neuroleptic response in schizophrenic
patients. Schizophr Res 1989; 2:311313
121. Johnstone EC, Macmillan JF, Frith CD, et al: Further investi-
gation of the predictors of outcome following rst schizo-
phrenic episodes. Br J Psychiatry 1990; 157:182189
122. Vaid G, Smith RC, Rosenberger S, et al: Neurological and neu-
ropsychological tests in schizophrenics (abstract). Biol Psychi-
atry 1993; 33:92A
123. Mukherjee S, Shukla S, Rosen A: Neurological abnormalities in
patients with bipolar disorder. Biol Psychiatry 1984; 19:337345
124. Hollander E, Decaria CM, Sanoud J, et al: Neurologic soft signs
in obsessive-compulsive disorder (reply). Arch Gen Psychiatry
1991; 48:278279
125. Thienemann N, Koran LM: Do soft signs predict treatment out-
come in obsessive-compulsive disorder? J Neuropsychiatry
Clin Neurosci 1995; 7:218222
126. Wegner JT, Catalano R, Gibralter S, et al: Schizophrenics with
tardive dyskinesia: neuropsychological decit and family psy-
chopathology. Arch Gen Psychiatry 1985; 42:860865
127. Manschreck TC: Motor and cognitive disturbances in schizo-
phrenic disorders, in Schizophrenia: Scientic Progress, edited
by Schulz SC, Tamminga CA. New York, Oxford University
Press, 1989, pp 372380
128. Waddington JL, Youssef HA, King DJ, et al: Association of cog-
nitive dysfunction, altered brain morphology, and release of
developmental reexes with tardive dyskinesia in schizophre-
nia and bipolar disorder, in Schizophrenia: Scientic Progress,
edited by Schulz SC, Tamminga CA. New York Oxford Uni-
versity Press, 1989, pp 396403
129. Keshavan MS, Narasimha RIVL, Narayanan HS: Rate of blink-
ing may predict neuroleptic-induced parkinsonism (letter). Br
J Psychiatry 1983; 142:423
130. Luchins DJ: How about something practical? Biol Psychiatry
1991; 30:11791181