Education research: cognitive performance is preserved in sleep-deprived neurology residents.
ABSTRACT To test the hypotheses that sleep deprivation in neurology residents is associated with performance deficits and that vigilance and cognitive performance is more compromised after overnight on-call duty compared to night shift.
Thirty-eight neurology residents of a university teaching hospital participated in a prospective single-blind comparison study. Residents were recruited according to their working schedule and divided into 3 groups: 24 hours overnight on-call duty, night shift, and regular day shift (controls). All participants underwent serial measurements of sleepiness and cognitive performance in the morning directly after or before their shift. Pupillary sleepiness test and Paced Auditory Serial Addition Test were applied. Perceived sleepiness was assessed by a questionnaire.
Sleepiness was increased in residents after night shift and overnight call compared to controls while the type of night duty was not associated with the extent of sleepiness. Sleep-deprived residents did not show any performance deficits on the Paced Auditory Serial Addition Test. Cognitive performance was not associated with sleepiness measures.
Night shift and overnight call duty have a similar impact on alertness in neurology residents. Sleep-deprived neurology residents may be able to overcome sleep loss-related performance difficulties for short periods.
Article: Glutamate transporter EAAC-1-deficient mice develop dicarboxylic aminoaciduria and behavioral abnormalities but no neurodegeneration.[show abstract] [hide abstract]
ABSTRACT: Four L-glutamate neurotransmitter transporters, the three Na(+)-dependent GLAST-1, GLT-1 and EAAC-1, and the Cl(-)-dependent EAAT-4, form a new family of structurally related integral plasma membrane proteins with different distribution in the central nervous system. They may have pivotal functions in the regulation of synaptic L-glutamate concentration during neurotransmission and are believed to prevent glutamate neurotoxicity. To investigate the specific physiological and pathophysiological role of the neuronal EAAC-1, which is also expressed in kidney and small intestine, we have generated two independent mouse lines lacking EAAC-1. eaac-1(-/-) mice develop dicarboxylic aminoaciduria. No neurodegeneration has been observed during a period of >12 months, but homozygous mutants display a significantly reduced spontaneous locomotor activity.The EMBO Journal 07/1997; 16(13):3822-32. · 9.20 Impact Factor
[show abstract] [hide abstract]
ABSTRACT: 1. The interaction of L-cysteine with three excitatory amino acid transporter subtypes cloned from human brain (EAAT1-3) was examined by measuring transporter-mediated electrical currents and radiolabelled amino acid flux in voltage-clamped Xenopus oocytes expressing the transporters. 2. L-Cysteine was transported by the neuronal subtype EAAT3 (EAAC1) with an affinity constant of 190 microM and a maximal rate of flux similar to that of L-glutamate; the relative efficacies (Vmax/K(m)) of the EAAT1 and EAAT2 subtypes for transporting L-cysteine were 10- to 20-fold lower. 3. Changing the ionization state of L-cysteine by raising the external pH did not significantly change the apparent affinity, transport rate, or magnitude of currents induced by L-cysteine, suggesting that both the neutral zwitterionic and anionic forms of the amino acid are transported with the same net charge stoichiometry. 4. In addition to competing with L-glutamate for uptake by the neuronal carrier, L-cysteine caused transporter-mediated release of transmitter by heteroexchange; both actions would elevate extracellular glutamate concentrations and may thus contribute to the known excitotoxic actions of L-cysteine in the brain. 5. Because the EAAT3 transporter is also expressed in tissues including kidney and intestine, the results suggest the possibility of a heretofore unrecognized mechanism of L-cysteine uptake in peripheral tissues as well as in brain.The Journal of Physiology 07/1996; 493 ( Pt 2):419-23. · 4.72 Impact Factor
Article: Arginine 447 plays a pivotal role in substrate interactions in a neuronal glutamate transporter.[show abstract] [hide abstract]
ABSTRACT: Glutamate transporters from the central nervous system play a crucial role in the clearance of the transmitter from the synaptic cleft. Glutamate is cotransported with sodium ions, and the electrogenic translocation cycle is completed by countertransport of potassium. Mutants that cannot interact with potassium are only capable of catalyzing electroneutral exchange. Here we identify a residue involved in controlling substrate recognition in the neuronal transporter EAAC-1 that transports acidic amino acids as well as cysteine. When arginine 447, a residue conserved in all glutamate transporters, is replaced by cysteine, transport of glutamate or aspartate is abolished, but sodium-dependent cysteine transport is left intact. Analysis of other substitution mutants shows that the replacement of arginine rather than the introduced cysteine is responsible for the observed phenotype. In further contrast to wild type, acidic amino acids are unable to inhibit cysteine transport in R447C-EAAC-1, indicating that the selectivity change is manifested at the binding step. Electrophysiological analysis shows that in the mutant cysteine, transport has become electroneutral, and its interaction with the countertransported potassium is impaired. Thus arginine 447 plays a pivotal role in the sequential interaction of acidic amino acids and potassium with the transporter and, thereby, constitutes one of the molecular determinants of coupling their fluxes.Journal of Biological Chemistry 01/2001; 275(48):37436-42. · 4.77 Impact Factor
Cognitive performance is preserved in
sleep-deprived neurology residents
M. Reimann, PhD
R. Manz, MD
H. Reichmann, Prof
T. Ziemssen, MD
Objective: To test the hypotheses that sleep deprivation in neurology residents is associated with
performance deficits and that vigilance and cognitive performance is more compromised after
overnight on-call duty compared to night shift.
Methods: Thirty-eight neurology residents of a university teaching hospital participated in a prospec-
divided into 3 groups: 24 hours overnight on-call duty, night shift, and regular day shift (controls). All
participants underwent serial measurements of sleepiness and cognitive performance in the morning
directly after or before their shift. Pupillary sleepiness test and Paced Auditory Serial Addition Test
were applied. Perceived sleepiness was assessed by a questionnaire.
Results: Sleepiness was increased in residents after night shift and overnight call compared to
controls while the type of night duty was not associated with the extent of sleepiness. Sleep-
deprived residents did not show any performance deficits on the Paced Auditory Serial Addition
Test. Cognitive performance was not associated with sleepiness measures.
Conclusions: Night shift and overnight call duty have a similar impact on alertness in neurology
residents. Sleep-deprived neurology residents may be able to overcome sleep loss–related per-
formance difficulties for short periods. Neurology®2009;73:e99–e103
PASAT ? Paced Auditory Serial Addition Test; PST ? Pupillography Sleepiness Test; PUI ? pupillary unrest index; SSS ?
Despite recent changes in working schedule regulation for clinicians, long working hours remain a
concern for patient safety, but also places the health of health care professionals at risk. Serious
problems resulting from sleep loss range from performance deficits and erroneous decision making
to increased risk for motor vehicle accidents.2,4
The majority of sleepiness studies have been performed in certain medical specialties with a
reputation for demanding schedules, such as surgery or intensive care.2Neurologists are frequently
underrated in terms of intensity and heaviness of their working schedules due to their mistakenly
close relationship to psychiatry. Call rotation on the neurology ward and night shifts at the neurol-
ogy intensive care unit are as common as in internal medicine or surgery. Actually, neurologists are
frequently challenged by the high prevalence of life-threatening strokes in the Western society,
where any delay in action or poor performance may be fatal for the patient.
This prompted us to investigate sleepiness and cognitive performance in sleep-deprived and alert
neurologists working at a large university neurology clinic. We hypothesized that 1) sleep depriva-
tion in neurologists is associated with performance deficits as previously demonstrated for other
Address correspondence and
reprint requests to Dr. Manja
Reimann, ANF Laboratory,
Department of Neurology,
University Clinic Carl Gustav
Carus, Dresden University of
Technology, Fetscherstraße 74,
D-01307 Dresden, Germany
From the Autonomic and Neuroendocrinological Laboratory, Department of Neurology (M.R., R.M., S.P., H.R., T.Z.), and Research Group Neuro-
Metabolism, Department of Neurology and Internal Medicine III (M.R., T.Z.), University Hospital Carl Gustav Carus, Dresden University of
Supported by the University Hospital Carl Gustav Carus, Dresden, Germany.
Disclosure: Author disclosures are provided at the end of the article.
Mitchell S.V. Elkind,
Copyright © 2009 by AAN Enterprises, Inc.
medical specialties and that 2) vigilance as well
as cognitive performance is more compromised
after 24 hours overnight on-call duty compared
to night shift.
METHODS This pilot study included 38 neurology residents
Department of Neurology at the University Hospital Carl Gustav
Carus, Dresden, Germany. We screened residents for exclusion cri-
teria such as current use of medication known to affect the sleep/
disorder diagnosis. We then stratified eligible residents according to
their working schedule into 3 groups: group 1, 24 hours overnight
on-call duty; group 2, night shift; and group 0, regular day shift
Definitions of groups. Residents in group 1 (24 hours over-
night on-call duty) performed their regular shift from 8 AM–4
PM followed by overnight call until 8 AM the next day. During
their overnight duty, they were allowed to sleep but there was no
scheduled coverage. Residents have usually 3 to 4 overnight calls
per month. Residents in group 2 (night shift) worked at the
intensive care unit for 7 consecutive days daily from 8 PM to 8 AM
the following morning. Afterwards they had 1 week off. Sleeping
was not permitted during their shifts. From experience, residents
have on average 2 admissions and 30 internal and 3 outpatient
consultations per night. Night shift rotation was every 5 to 6
weeks over a period of 1 year. Residents in group 0 (day shift)
regularly worked from 7:30 AM to 3:30 PM. However, residents
on day shift frequently work overtime.
Standard protocol approvals, registrations, and patient con-
sents. The Ethics Committee on human experimentation of the
Dresden University of Technology approved the study and the in-
vestigation conformed with the principles outlined in the Declara-
tion of Helsinki. We informed all participating residents about the
objectives and procedures of the study and obtained written in-
formed consent prior to their inclusion. The serial data collection
ratory of the University Clinic. We measured all residents before 9
AM directly after their (night) shift rotation or just before day shift
commenced (controls). The assistant performing the measurements
was blinded. We measured objective sleepiness by Pupillography
Sleepiness Test (PST) and cognitive performance by Paced Audi-
tory Serial Addition Test (PASAT). We instructed the residents to
abstain from drinking alcoholic beverages, smoking, and drinking
coffee for at least 4 hours before the measurements. The residents
rated their sleepiness on a 5-point Likert scale based on the state-
in the previous 24 hours and assessed the perceived recovery effect
repeated up to a maximum of 13 times. Measurement frequency,
however, varied between individuals according to the rotation
schedules (4.8 ? 3.3).
Pupillary Sleepiness Test. We performed the PST (AMTech,
Dossenheim, Germany) in a quiet and darkened room after an ini-
goggles equipped with infrared light transmitting filter glasses im-
pervious to visible light. They were seated on a comfortable chair
and head position was adjusted by a chin rest fixed on a table. An
infrared video camera was fixed at a distance of 70 cm from the
examination subject. We instructed the clinicians to maintain fixa-
tion on a set of infrared light-emitting diodes. We then recorded
spontaneous pupillary oscillations over a period of 11 minutes by
infrared video pupillography and evaluated the recording by 25-Hz
real-time analysis as published elsewhere.5Pupillary unrest index
(PUI) is a measure of pupillomotor hippus in darkness and calcu-
lated as an integrated sum of slow movements of the pupillary mar-
gin during the measurement period.6This value is usually low in
alertness and increases with progressive sleepiness. We also calcu-
minutes. During sleepiness the initial diameter is reduced and the
Paced Auditory Serial Addition Test. The validated and
computer-aided PASAT allows for measuring the capacity and
velocity of information processing within the auditory-verbal do-
main (cognitive performance).7,8The test system entails the sub-
ject to continuously add the last 2 numbers of consecutive series
and to announce the sum aloud. Numbers from 1 to 9 are an-
nounced acoustically in random order by a PC with the screen
remaining dark. To avoid practice effects, clinicians were trained
on the PASAT at least 3 times before commencing the study. We
applied the 60-item short version of the test (maximal score of
60). Lower scores (small numbers of correct answers) indicate
worse cognitive performance.
Statistical analysis. We used the SPSS software package ver-
sion 16.0 for Windows (SPSS Inc., Chicago, IL) for all statistical
evaluation. Data are presented as median and 25th–75th percen-
tile unless otherwise stated. Owing to the small sample size we
assumed non-Gaussian distribution, and hence applied nonpara-
metric tests with Bonferroni correction for comparing groups.
Spearman correlation coefficients were calculated. A two-tailed
p ? 0.05 was regarded as the level of significance.
RESULTS Before we started the comparison among
the 3 groups, we assessed the strength of association
between the first measurement and the mean of serial
TableSleepiness and cognitive performance of neurology residents by type of night duty
ParametersOvernight call (n ? 17)Night shift (n ? 6)Control (n ? 15)
Pupil diameter (mm)
7.51 (6.25–7.75)7.23 (5.18–7.54)7.21 (6.61–8.00)0.59 (0.744)
Pupillary unrest index (mm/min)
56 (49–58)51 (42–58)54 (48–56)0.67 (0.715)
Data are median (interquartile range). Unequal superscript letters indicate significant differences (Mann-Whitney U test).
†Paced Auditory Serial Addition Test (number of correct answers/60).
Neurology 73November 24, 2009
measurements. We revealed significant correlations
with r values ranging from 0.763 to 0.904 (p ?
0.001). Based on these results, we continued our
analysis using the mean values.
PUI and self-stated sleepiness (SSS) were signifi-
appeared that PUI and SSS were significantly higher
after the night shift and the 24 hours overnight on-call
duty compared to a normal night at home. Residents
not differ with respect to sleepiness measures.
Neurology residents on 24 hours overnight on-
call duty had slept on average 4.3 (2.8–4.6) hours
(midshift nap) in the last 24 hours, which was signif-
icantly less compared to their colleagues on night
shift (5.9 [4.9–7.0] hours, p ? 0.006) or on day shift
(controls) (6.5 [6.0–7.0] hours, p ? 0.001). The
longest sleeping phase during 24 hours overnight on-
call duty was 3.0 (2.0–3.8) hours. Residents had on
average a mean (minimum–maximum) of 2 (1–3)
admissions, 2 (0–7) consultations, and 3 (1–5) tele-
phone inquiries during overnight on-call duty.
Figure 1 illustrates the proportion of respective
responses to the statement “Currently I feel . . .” Fig-
ure 2 depicts the self-stated recovery effect due to
sleep in the 24 hours preceding the examination.
Correlation analyses did not reveal any association
between the PUI and the PASAT score. However, the
PUI increased (r ? 0.507, p ? 0.001) and the PASAT
score decreased (r ? ?0.335, p ? 0.04) with increased
hours increased (r ? ?0.527, p ? 0.001). The above
associations could not be confirmed in subgroups (p ?
DISCUSSION Rotating shift work in clinics to pro-
vide 24-hour patient care has come increasingly under
scrutiny due to negative effects associated with sleep
loss, fatigue, and circadian disruption.9,10Although
night shift and 24 hours overnight on-call duty consid-
erably differ in terms of number of working hours, per-
mission for midshift naps, and rotation frequency, their
been distinguished. We hypothesized that residents on
24 hours call rotation would be more affected by sleep
loss due to a longer and more irregular working sched-
ule. We investigated this hypothesis in neurology resi-
dents of a large university clinic. This specialty group is
often underrated in terms of heaviness and intensity of
iness studies. Importantly, previous sleepiness studies in
selected medical specialties explicitly emphasized that
results must not be extrapolated to other medical spe-
cialty groups.3,4,11Although we could not verify the
above hypothesis, our results clearly demonstrate that
sleepiness is a common problem among neurology resi-
dents undergoing night shift and 24 hours overnight
We additionally demonstrated that vigilance mea-
sured by PST is in good agreement with SSS. This
finding corresponds with previous studies suggesting
the PST as a valid and objective tool to detect sleepi-
ness in healthy subjects.6
The lack of significant performance decrements in
sleep deprivation was found in previous studies.2,4,12
Differences in study design, medical specialty, and
methods for vigilance testing limit comparisons across
icant performance decrement on the complex PASAT
test in sleep-deprived normal subjects.13The investiga-
Figure 1 Self-stated sleepiness of neurology residents by type of night duty
Figure 2Self-stated recovery effect due to sleep in the past 24 hours
Neurology 73November 24, 2009
tion as a motivational incentive, which tends to offset
sleepiness effects on performance.13
Alternatively, the applied method for performance
testing may have been suboptimal for our population
logical syndromes. However, more recent studies also
results.7,14Originally assumed to measure rate of infor-
mation processing, the PASAT is now recognized as
tapping into different types of cognitive processes.15
This multifactorial nature may complicate the interpre-
tation of test result from sleep-deprived subjects espe-
cially under the assumption that sleep loss affects
different cognitive pathways differentially. The consis-
tently high PASAT score across all study groups sug-
gests that sleep-deprived neurology residents are able to
riod. This assumption seems plausible since stressful
working situations are routine in the clinic and thus
idence that sleep-deprived resident doctors are prone to
committing medical errors,4,9tasks of short duration
may be less likely to detect performance deficits in
chronically sleep deprived individuals.2
Importantly, we adequately controlled for prac-
tice effects8first by using a control group and sec-
ondly by training the clinicians on the PASAT prior
to the study. Consequently, we obtained a very good
agreement between the first measurement and the
mean of serial measurements. In addition, major
confounders of the PASAT such as age, gender, edu-
cation, and ethnicity14,16were accounted for by creat-
ing a homogenous study sample.
Nevertheless, it must be considered that our results
are compromised by a questionable rested control
our controls was equivalent to the accepted core sleep
requirement of 6.5 hours (many were also below).17In
addition, nearly two thirds of the controls felt fairly to
poorly rested, which indicates chronic partial sleep de-
privation (figure 3). This finding is relevant as chronic
partial sleep deprivation appears to be cumulative with
respect to performance decrements.18
Neurology residents on night shift and overnight
call are affected to a similar extent by sleepiness. In-
creased sleepiness, however, did not affect performance
on the complex PASAT test. It seems that sleep-
deprived neurology residents may be able to overcome
ods. This, however, may not necessarily apply for more
demanding procedures outside the laboratory.
Statistical analysis was conducted by Dr. Manja Reimann.
The authors thank all neurology residents for their participation in this study.
Dr. Reimann, Dr. Manz, and S. Prieur report no disclosures. Dr. Reich-
mann serves on scientific advisory boards, receives speaker honoraria,
and/or receives funding for travel from Cephalon, Inc., Novartis, Teva
Pharmaceutical Industries Ltd., Lundbeck Inc., GlaxoSmithKline, Boehr-
inger Ingelheim, Bayer Schering Pharma., UCB/Schwarz Pharma, Desitin
Pharmaceuticals, GmbH, Pfizer Inc., and Solvay Pharmaceuticals, Inc.
Dr. Ziemssen has received speaker honoraria from Biogen Idec, Sanofi-
Aventis, Merck Serono, Novartis, Teva Pharmaceutical Industries Ltd.,
and Bayer Schering Pharma; serves as a consultant for Teva Pharmaceuti-
cal Industries Ltd., Novartis, and Bayer Schering Pharma; and receives
research support from the Roland Ernst Foundation.
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