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stration that spike timing-dependent plasticity of residual corti-
cospinal-motoneuronal synapses provides a mechanism to improve
motor function after SCI. Modulation of residual corticospinal
connections may present therapeutic target for enhancing voluntary
motor output in motor disorders affecting the corticospinal tract.
Keywords: Motor control, Voluntary Movement, Transcranial
Magnetic Stimulation, Plasticity
PL02 Therapeutic Hypothermia and Targeted Tem-
perature Management after SCI and TBI - Is the
Verdict Still Out?
PL02-01
PERSPECTIVES ON HYPOTHERMIA AFTER TBI AND SCI -
REVIEW OF NEW BASIC RESEARCH IN TEMPERATURE
MANAGEMENT
W. Dalton Dietrich
University of Miami Miller School of Medicine, Neurological Surgery,
Miami, USA
Over the past several decades, basic, translational and clinical research
has evaluated the beneficial effects of therapeutic hypothermia (TH) in a
number of neurological conditions. These temperature studies have
provided a useful experimental tool by which to clarify temperature
sensitive injury mechanisms related to long term functional outcomes.
Today we know that relatively mild reductions, or increases in brain or
spinal cord temperature during or following neurotrauma or cerebral
ischemia can significantly alter multiple injury pathways associated
with neuronal dysfunction and death as well as functional deficits.
Recently new exciting data has emerged implicating novel cell sig-
naling pathways, innate immunity and genetic targets including several
temperature sensitive microRNAs related to this topic. The fact that
these same injury pathways are current drug targets for the development
of new therapeutic strategies emphasizes the importance of targeted
temperature management (TTM) strategies in the acute and subacute
injury settings. More recently the importance of posttraumatic brain
temperature on reparative strategies has also been discussed where
studies have reported the beneficial effects of TH in enhancing repar-
ative processes including neurogenesis. The ability of relatively minor
temperature modifications including mild hyperthermia to alter the
brain’s vulnerability to an insult such as concussion while also playing a
critical role in influencing secondary injury and reparative processes
emphasizes the need to take advantage of TTM practices to successfully
protect and treat our neurotrauma patients. Clinical investigations are
investigating new systemic cooling strategies using both surface and
endovascular approaches while local cooling approaches are also being
considered. The recent provocative findings emphasizing the possible
increased importance of TTM and fever control versus TH again points
to a need to continue basic and translational research in neurotrauma.
It’s clear that this is a fertile area for continued medical research that
should provide important new information that can hopefully be
translated to our patient populations to improve long term outcomes.
Keywords: hypothermia, hyperthermia, targeted temperature man-
agement
PL02-02
HYPOTHERMIA FOR TRAUMATIC BRAIN INJURY: IT
WORKS WITH CORRECT PATIENT SELECTION
David Okonkwo
University of Pittsburgh, Neurosurgery, Pittsburgh, PA
Hypothermia in the treatment of traumatic brain injury is under in-
tense investigation for a very specific subtype of TBI patient. Sub-
dural hematomas (SDH) occur in
*
45% of severe TBIs, with a
mortality above 60%, causing approximately 1 million deaths an-
nually worldwide. The high mortality associated with acute SDHs
can be lowered by rapid surgical intervention and aggressive medical
management; nonetheless, acute SDH remains one of the most
common causes of death due to TBI. Hypothermia has been shown to
improve histopathological and behavioral consequences of TBI us-
ing various experimental models. However, twenty-three hypother-
mia clinical trials involving 1614 patients with TBI have yielded
inconsistent results. Two randomized, multi-center trials of hypo-
thermia induction in patients with severe TBI performed in the
United States (NABIS:HI and NABIS:HII) were stopped due to fu-
tility, with no improvement in neurologic outcomes. The lack of
statistical effect was attributed in part to the heterogeneity of brain
injuries. Indeed, a retrospective subgroup analysis of these trials
revealed that hypothermia improved neurologic outcomes in the
subset of TBI patients undergoing surgical evacuation of acute
SDHs. These results have led us to the design and initiation of the
HOPES trial (HypOthermia for Patients requiring Evacuation of
Subdural Hematoma), a prospective, randomized clinical trial to
study the effects of
very early hypothermia
in patients undergoing
surgical evacuation of acute SDH. This trial will also assess whether
the beneficial effects of hypothermia are related to blunting ische-
mia/reperfusion injury and/or blunting the incidence of cortical
spreading depolarizations. The current role and future direction of
hypothermia and temperature management in TBI will be reviewed
and discussed.
Keywords: hypothermia, cortical spreading depression, reperfusion
injury, clinical trial, craniotomy,
PL02-03
THERAPEUTIC HYPOTHERMIA AND TARGETED TEM-
PERATURE MANAGEMENT AFTER SCI AND TBI - IS THE
VERDICT STILL OUT?
Allan Levi
University of Miami, Miller School of Medicine/Jackson Memorial
Hospital, Neurological Surgery, Miami, USA
Systemic hypo-thermia remains a pro-mising neuro-pro-tective
strategy for both spinal cord (SCI) and head injury (HI). We de-
scribe our ex-tended single center experience using in-tra-vascular
hypo-thermia for the treat-ment of cervical SCI. Forty-five acute
cervical SCI patients have now received modest (33 C) in-tra-vas-
cular hypo-thermia for 48 h. Neuro-logical outcome was assessed by
the Inter-national Standards for Neuro-logical Classification of
Spinal Cord Injury scale (ISNCSCI) de-velop-ed by the American
Spinal Injury Association. Local and systemic complications were
recorded. All patients were complete ISNCSCI A on admission, but
four con-verted to ISNCSCI B in 24 h post injury. The ISNCSCI
con-version rate of at least one grade was appro-ximately 43% at
latest fol-low up 10.07 (
–
1.03) months. The overall risk of any
thromboembolic complication was 14.2%. The results are pro-
mising in terms of safety and impro-vement in neuro-logical out-
come. To date, the study repre-sents the largest study cohort of
cervical SCI patients treated by modest hypo-thermia. A multi-
center, randomized study is needed to determine if systemic hypo-
thermia should be a part of SCI patients’ treat-ment for whom few
options exist. A review of the status of hypo-thermia for closed HI
will also be dis-cussed.
Keywords: head injury, ISNCSCI, spinal cord
A-131