Rudolf Magnus Bulletin 21 March 2006 - UMC Utrecht

Rudolf Magnus Bulletin 21
March 2006
interview
PINE assessed pain in herpes zoster
Chronic pain syndrome is a common complication of
herpes zoster. Bart Van Wijck, Wim Opstelten and
colleagues performed the first ever randomised, controlled
trial to establish the effect of a single injection
in the spine with both anti-inflammatory and painkilling
drugs. They demonstrated, in a Lancet article,
that these injections, although common practice, had
only limited effect and were ineffective for long-term
treatment of chronic pain after herpes zoster.
Postherpetic neuralgia is a neuropathic pain syndrome
associated with the reactivation of varicella zoster virus
(herpes zoster), which resides in latent form in sensory
trigeminal and dorsal root ganglia in the spine after primary
infection as varicella (chickenpox). This pain syndrome is
the most frequent complication of herpes zoster, which
occurs in 9–34% of varicella infections. Postherpetic
neuralgia often negatively affects quality of life, because
many patients develop severe physical, occupational, and
social disabilities as a consequence of their chronic pain.
Once the syndrome has developed, the effect of treatment
is disappointing. Although the effectiveness of a varicella
zoster vaccine on prevention of zoster-related morbidity is
promising, postherpetic neuralgia will remain a serious
problem for many years. Antiviral therapy can shorten the
duration of zoster-associated pain, but many patients with
herpes zoster develop postherpetic neuralgia despite such
treatment. Van Wijck: “As herpes zoster goes together with
local inflammation of the dorsal root ganglion, and this
inflammation is considered to be an important causative
factor for postherpetic neuralgia, interventions can be
aimed at reducing this inflammation. Although epidural
injections have been used for decades both to treat zosterassociated
pain and to prevent postherpetic neuralgia, the
effectiveness of this treatment was not previously assessed
in a randomised clinical trial.”
The PINE study (Prevention by epidural Injection of
postherpetic Neuralgia in the Elderly), an open randomised
multicentre trial, was designed to quantify the effectiveness
of a single epidural injection of 80 mg methylprednisolone
and 10 mg bupivacaine in addition to
standard treatment during the acute phase of herpes
zoster in preventing postherpetic neuralgia. A total of 598
patients was included older than 50 years with acute
herpes zoster (rash

PhD theses
2006-4
March 8, 2006
Frank R. Van Genderen
Functional limitations in severe haemophilia
P.J.M. Helders, H.M. Van den Berg,
N.L.U. Van Meeteren
supervisors
2006-5
Predicting complications in SAH
March 9, 2006
Wouter J. Schuiling
Extracerebral organ dysfunction and sleep disorders
in subarachnoid haemorrhage
G.J.E. Rinkel, A. Algra, A.W. De Weerd,
P.J.W. Dennesen
supervisors
Cardiac and pulmonary complications are common in
subarachnoid haemorrhage (SAH), but also other
extracerebral complications are frequently observed.
Wouter Schuiling found that these complications can
be predicted and probably treated better if attention is
given to cardiac troponin I. Incorporating signs of
extracerebral organ dysfunction in grading scales can
help in prognosticating outcome. Attention for sleep
disorders can further improve long-term outcome.
Schuiling performed an epidemiological study on a cohort
of 172 patients with aneurysmal SAH, who were treated
according to standard intensive care guidelines for at least
2 weeks. Schuiling about the results; “ECG abnormalities
have only limited value in predicting poor outcome. Cardiac
troponin I appeared to be a powerful predictor for the
occurrence of pulmonary and cardiac complications.
Pulmonary oedema and depressed cardiac contractile
function were frequently observed in the first 5 days after
SAH. A depressed cardiac contractile function in at least
one day in the first 5 days after SAH onset was more
prevalent in patients with an elevated cardiac troponin I.
Single transpulmonary thermodilution technique appeared
to be a promising tool for monitoring SAH patients
especially with elevated cardiac troponin I on admission.
The simplified acute physiology score (SAPS II) is a useful
and reliable prognosticator in SAH patients. This score
may in some circumstances provide more information than
specific SAH rating scales in predicting poor outcome or
the occurrence of delayed cerebral ischemia. In patients
with a good outcome according to the Rankin scale 50%
complained of tiredness. In these patients disorders of
sleep and wake occurred in one-third. Patients with severe
sleep disturbances often have a considerably reduced
quality of life.
Schuiling summarizes: “Extracerebral organ dysfunction is
frequently seen after SAH. Grading scales incorporating
signs of extracerebral organ dysfunction should be used
more frequently by neurologists and neurosurgeons
treating SAH patients. Cardiac troponin I can be used as
marker to identify patients who are at risk of developing
cardiopulmonary complications and could benefit from
early invasive hemodynamic monitoring. Additional studies
using single transpulmonary thermodilution are required to
study the effects of cardiac and pulmonary estimates on
delayed cerebral ischemia and outcome in SAH patients.
Also studies with extended follow-up are required to
evaluate whether a therapeutic strategy taking into account
cardiac index, cardiac contractile function and
extravascular lung water can improve supportive therapy
and outcome. The improvement of long-term outcome
should focus on attention for sleep disorders in patients
complaining of daytime fatigue, restless or non-restorative
sleep, snoring, and restless legs syndrome.”
Wouter Schuiling (April 4, 1968, Amsterdam). Secondary
education (Rijksscholengemeenschap, Amersfoort), 1986;
Medicine (Groningen University), MD 1995; registered as
neurologist, 2004 (Medisch Centrum Haaglanden, Den Haag).
During his residency in Neurology he started the research as
described in this thesis. He presently works as neurologist in the
Medisch Centrum Leeuwarden.
2006-6
Walking after stroke
March 14, 2006
Boudewijn J. Kollen
Recovery of gait after stroke
E. Lindeman, G. Kwakkel
supervisors
Boudewijn Kollen addressed the long-term recovery of
hemiplegic gait in severely affected stroke patients, by
clinimetric and prognostic, and by therapeutic intervenetion
studies. He was able to identify the determinants
of late outcome and he demonstrated that the
long-term effects of intensity of stroke rehabilitation,
implemented during the initial 20 post-stroke weeks,
are maintained for up to one year.
With the institutionalisation of stroke services across health
care facilities a reduction in mortality rates, length of
inpatient stay and improved independence in activities of
daily living have been reported. Recently developed
treatment strategies, that incorporate compensation
strategies with a strong emphasis on functional training,
may hold the key to optimal stroke rehabilitation. Kollen
describes the long-term recovery of hemiplegic gait in
web http://www.rudolfmagnus.nl coordination j.dekker@med.uu.nl, phone +31 30 253 8110

severely affected stroke patients. Based on the application
of a repeated measurement research design, data were
obtained within the first post-stroke year period. This
information subsequently enabled the identification of timerelated
changes and was used by Kollen to address the
following main questions: Are intensive stroke rehabilitation
programmes, implemented within the early and
subacute post-stroke phases, worthwhile in terms of longterm
functional gains and can this long-term recovery be
estimated early after stroke onset for better individualised
reliable therapeutic goal setting and discharge planning?
For this purpose, Kollen studied early and late recovery
patterns as functional recovery after stroke tends to be
non-linear and time-dependent. Subsequently, this
information was used in the interpretation of some of the
mechanisms involved in the long-term recovery of
hemiplegic gait and the impact of intensity of therapeutic
interventions on this recovery. The main findings of
Kollen’s clinimetric and prognostic studies indicate
predictive relationships between early determinants and
late outcome and the relevance of measuring frequently
and longitudinally in order to take into consideration the
non-linear time-dependent relationship of covariates with
recovery of gait after stroke. In the subsequent therapeutic
intervention studies Kollen demonstrated that the long-term
effects of intensity of stroke rehabilitation, implemented
during the initial 20 post-stroke weeks, are maintained for
up to one year.
Boudewijn Kollen (February 26, 1956). Physiotherapy
(Amsterdam), 1976; Epidemiology (Vrije Universiteit,
Amsterdam), 2004. Physiotherapist at the Valerius Clinic,
Amsterdam (1976-83), St. Michael’s Hospital, Toronto, Canada
(1983-86), Baycrest Centre for Geriatric Care, Toronto, Canada
(1986-89), and the Isala Clinics, Zwolle. Presently he works at
the Research Bureau, Isala Clinics, Zwolle.
2006-7
Do piglets suffer when the sow is stressed?
March 30, 2006
Godelieve Kranendonk
Prenatal stress in pigs
M.A.M. Taverne, V.M. Wiegant, E.D. Ekkel,
E.J.H. Mulder
supervisors
Stress in pregnant sows can affect both the wellbeing
and health of the sows and her piglets. Godelieve
Kranendonk applied hormonal and social stress to
pregnant sows and studied the behaviour and stress
physiology of the piglets. Stress during gestation
appeared to affect both performance and behaviour of
the piglets.
Prenatal stress may be a relevant issue for husbandry
pigs, since pregnant sows likely experience stressful
situations during gestation, for instance as a consequence
of housing and management practice. This may result in
prenatal stress for their piglets. Kranendonk studied
whether body weight, behaviour, or HPA-axis activity of
piglets were affected when their mothers are exposed to
stressors during gestation. In a first series of experiments
Kranendonk exposed pregnant sows to the stress
hormone cortisol and studied the performance of their
piglets. She demonstrated that piglets can indeed be
affected by elevated maternal cortisol concentrations
Courtesy of Godelieve Kranendonk
during gestation in their body weight, growth, survival,
behaviour, and adrenocortical response to ACTH. Further,
female piglets have an enhanced fever response when
challenged by lipopolysaccharide. Some of these effects
(e.g., response to challenges and behaviour) depended on
the period of gestation during which maternal cortisol
concentrations were elevated, or on the sex of the
offspring (e.g., with respect to behaviour).
In another series of experiments Kranendonk applied mild
stress to pregnant sows in the form of social challenge.
Social challenges did not elicit elevated cortisol concentrations
in the pregnant sows. Regular mixing of pregnant
sows, which produced a mild form of social stress during
the last month of gestation, did not affect piglet characteristics,
which can possibly be explained by this lack of
elevated maternal cortisol concentrations during gestation.
The social rank of sows (measured as winning of more
agonistic interactions than they lose) during gestation, did
affect piglet performance (in particular body weight at
weaning and lean meat percentage at slaughter) and
behaviour in a new environment. Furthermore, effects of
maternal treatment on piglet characteristics were studied
until eight weeks of age (behaviour and adrenocortical
aspects) or until slaughter. Kranendonk: “It would be
relevant to study whether piglets face long-term
consequences of maternal treatments as applied in the
experiments. This would be especially important for gilts
that are kept for breeding.”
Kranendonk explains the broader perspective of her
results: “Our studies provide data that indicate that
elevated maternal cortisol concentrations and social rank
of pregnant sows affect performance and behaviour of
their offspring. Whether these piglets are better off or
perform less optimal in daily stressful situations remains to
be elucidated. Nevertheless, stress during gestation does
impair welfare of the pregnant sow herself. Hence, pig
farmers should minimise stress exposure for pregnant
sows. The number of agonistic interactions of pregnant
sows around the feeding station in group housing should
be reduced, e.g., by use of a protected feeding area or
distraction materials.”
Godelieve Kranendonk (January 31, 1977, Rotterdam)
Secondary education (Christelijke Scholengemeenschap
Walcheren, Middelburg), 1995; Biology (Catholic University
Nijmegen and Utrecht University), 2001. From 2001-2005 she
worked on the project as described in her thesis. Presently she
works at the Department of Farm Animal Health, Veterinary
Faculty, University Utrecht.
secretariat Universiteitsweg 100, 3584 CG Utrecht, The Netherlands, m.vandenadort@med.uu.nl, phone +31 30 253 8847

news
Collaboration Institute of Psychiatry is funded
The UMC Utrecht stimulates the internationalisation of the
research within its perimeter. The major research institutes
of the UMC Utrecht were invited to apply for a competitive
grant of € 200,000. The Institute of Psychiatry, London,
U.K., was identified as partner of our Institute for a
strategic alliance. The Institute of Psychiatry is a large
neuroscience institute of undisputed reputation, which is
active on overlapping, and complementary, fields of
neuroscience research. In the past years meetings were
held at the Institute’s highest level to explore the possibilities
for such an alliance. It was agreed that both the
Rudolf Magnus Institute and the Institute of Psychiatry will
facilitate close contacts between their staff members in
order to actively encourage collaboration between both
institutes. On January 24, 2006, the UMC Utrecht
committee deciding on this issue announced that our
Institute was awarded with this grant to stimulate contact
and collaboration with the Institute of Psychiatry. With
some additional financial support of both institutes, the
programme (2006-2009) will support the collaboration by
travel grants for staff, organising workshops, and by
initiating a visiting professor programme. A list of planned
workshops and formal information how to apply for support
will be released soon.
Olaf Cremer wins Pfizer NVIC Award
Olaf Cremer, anaesthesiologist, has won the yearly award
of the Netherlands Society for Intensive Care (NVIC); this
year sponsored by Pfizer. The award is presented for the
best PhD thesis in the Netherlands in the field of intensive
care-related research. Cremer won the award with his
thesis entitled, ‘Goal-directed intensive care of traumatic
brain injury: pathophysiological and clinical studies’
(October 5, 2005, See Rudolf Magnus Bulletin 16). The
award consists of a sum of money, which is to be used in
part to re-print (150 copies) Cremer’s thesis for distribution
among all intensive care units in the Netherlands.
Saskia Van der Hel Lecturer of the Year
Saskia Van der Hel, assistant professor at the Department
of Pharmacology and Anatomy, was award with the title
‘Lecturer of the Year’ by the students of the UMC Utrecht.
Van der Hel received this much envied title for her
enthusiasm and her great ability to motivate students.
Marike Broekman wins Talma Eykman Award
The Talma Eyman Award is presented to excellent
undergraduate students at the UMC Utrecht who have
distinguished themselves during their research internship.
On February 9, 2006, this year’s award for medical
students was presented to Marike Broekman (supervisor
Peter Burbach, Dept Pharmacology and Anatomy) for her
work entitled, “Adeno-associated virus vectors serotyped
with AAV8 capsid are more efficient than AAV-1 or -2
serotypes for widespread gene delivery to the neonatal
mouse brain”. The work was performed at the Departments
of Neurology and Neuroscience, Mass. General
Hospital and Harvard Medical School, Charlestown, MA,
USA.
agenda
March 1, Rudolf Magnus Seminar
Ruud F.G.Toonen (CNCR, Vrije Universiteit, Amsterdam)
‘Molecular Mechanisms of secretory vesicle targeting
and docking’
Stratenum Building, UMC Utrecht, Room 4.208, 16:00-17:00
Contact j.pasterkamp@med.uu.nl
March 3, Helmholtz Lecture
David F. Clayton (University of Illinois, USA)
‘Neurogenomics of bird song memory’
‘Rode zaal’, Ruppert Building, Leuvenlaan 19, Utrecht, 16:00-17:00
Contact, v.maassen@fss.uu.nll
March 3, Rudolf Magnus Seminar
Rustam Al-Shahi (University of Edinburgh, UK)
‘'Epidemiology, prognosis and treatment of brain
arteriovenous malformations’
Lecture room, C3West, UMC Utrecht, 12:45-13:30
Contact, J.vanBeijnum@umcutrecht.nl
March 9, Winter Conference, Dutch Society of
Psychophysiology
‘Boothzaal’, University Library, Heidelberglaan 3, Utrecht, 10:00-
17:00. Programme, www.rudolfmagnus.nl
Contact, k.b.e.bocker@pharm.uu.nl
March 17, Inaugural address Carl Moons
Professor of Clinical Epidemiology.
Academy Building, Domplein 29, Utrecht, 16:15
March 31, Symp. on Pharmacotherapy for ADHD
See for programme our website, http://www.rudolfmagnus.nl
Contact, j.l.kenemans@fss.uu.nl
April 19-27, Course on Neuropsychopharmacology
Venue, partly in Amsterdam, Weesp, and Utrecht. Programme,
http://www.rudolfmagnus.nl. Registration, eam.borghols@vumc.nl
May 4-5, Meeting of the Association of European
Psychiatrists - Neuroimaging Section
‘Neuroimaging Change over Time in Psychiatry’
Academy Building, Domplein 29, Utrecht
Programme and registration, http://www.rudolfmagnus.nl
August 28-29, Rudolf Magnus-Helmholtz
Summerschool
Conference Centre Ottone, Kromme Nieuwegracht 62, Utrecht.
Programme to be announced, check our website for updates,
http://www.rudolfmagnus.nl
September 8-9, Brain Days
A two-days meeting with international experts on the
theme, ‘Brain plasticity in children’.
UMC Utrecht. Programme to be announced, check our website for
updates, http://www.rudolfmagnus.nl
November 8, Rudolf Magnus Symposium
Including the Rudolf Magnus Lecture 2006 by
Frans De Waal (Emory Univ. Atlanta, USA) and the
announcement of the winner of the Rudolf Magnus
Research Award 2006.
UMC Utrecht, 13:30-17:15. Programme to be announced, check
our website for updates, http://www.rudolfmagnus.nl
Contact, m.vandenadort@med.uu.nl
November 8, Rudolf Magnus Evening
A unique mixture of social and scientific events is
organised following the Rudolf Magnus Symposium.
UMC Utrecht, 18:00-21:30, programme will include diner, details to
be announced. The evening programme is only (and freely)
accessible for all members of the Rudolf Magnus Institute.
Registration is required, contact, m.vandenadort@med.uu.nl
© 2006 Rudolf Magnus Institute editor Jan Dekker photography Chris Timmers print Zuidam&Uithof ISSN 1574-3071