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SUPPLEMENTAL METHODS
Patient recruitment. The ISCoPE (Injured Spinal Cord Pressure Evaluation) study was set
up in 2009 (http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=8794) as follows:
Stage I aim: To develop a technique for monitoring ISP at the injury site after TSCI and
report the findings of the first 10 – 20 patients with TSCI (this manuscript). Estimated
completion is 2013.
Stage II aim: To investigate expansion duraplasty as a treatment option and report the
findings of the first 5 – 10 patients with TSCI (ongoing). Estimated completion is 2014.
Subsequent stages will aim to investigate whether prophylactically increasing SCPP is
safe and feasible, whether tissue oxygen and microdialysis monitoring at the site of injury is
possible, and whether ISP monitoring is feasible in patients with longitudinally extensive
transverse myelitis.
We recruited patients who were referred to the neurosurgery units of St George’s and
King’s College hospitals in London.
Inclusion/exclusion criteria for TSCI patients. We included patients who satisfied the
following criteria:
1) TSCI ASIA A, B or C.
2) Timing from injury to surgery < 72 hours.
3) Age between 18 and 70 years.
We excluded vulnerable groups, because they may be unable to understand the
consenting process. We also exclude patients with co-existing medical problems that could
confound our results. In particular, we excluded the following:
1) Vulnerable groups
a. Children (<18 years) and elderly (>70 years).
b. Patients who could not speak English.
c. Pre-existing mental impairment.
d. Glasgow Coma Score (GCS) <15.
2) Patients with medical problems:
a. Other organ damage that requires surgery to repair.
b. Penetrating spinal cord injury.
c. Pre-existing disease that affects the spinal cord.
Timing of surgery. We aimed to recruit patients as soon as possible after the TSC, but we
were limited by practical constraints within the British National Health Service. In the UK,
patients who sustain a spinal cord injury are collected by ambulance within minutes and
transferred to the nearest hospital where they are stabilized and have a CT scan +/- MR scan
of the spine. This process typically takes up to 24 hours. The patients are then referred to the
nearest neurosurgical unit, which are often off site. The urgency of transfer to the
neurosurgery center depends on bed availability, on other emergencies awaiting transfer and
on how busy the ambulance service is. TSCI patients, who arrive at the neurosurgery unit, are
booked on the next available operating list. We used 72 hours in our study, as a reasonable
time point given these constraints.
Surgical technique. The Codman probe was chosen because it is widely used to measure
ICP, the wire is 1 m long (therefore the patient does not lie on the connector), it has a small
diameter of 0.7 mm (thus reducing the risk of spinal cord injury), it has low 10-day drift
(<0.2 mmHg / day) and high response frequency (100 Hz). We elected to measure ISP
subdurally rather than intraparenchmally or extradurally. Placing the probe
intraparenchymally carries the risk of spinal cord damage, whereas extradural pressure is
unrelated to intradural pressure because of the non-distensible dura. Our ISP monitoring
technique is analogous to subdural ICP monitoring for TBI.
Laminectomy vs. laminotomy. After re-aligning and instrumenting the spine, the decision
to perform laminectomy vs. no laminectomy was at the discretion of the operating surgeon.
When laminectomy was not performed, the probe was inserted by perforating the dura
between two adjacent laminae under direct vision.
Cerebrovascular reactivity and compensatory reserve. In TBI, PRx (Pressure Reactivity
index) reflects the ability of the vascular smooth muscle to respond to changes in transmural
pressure and is used for evaluating whether autoregulation is intact or disturbed. Disturbed
cerebrovascular pressure reactivity (PRx) is an independent adverse prognostic factor in TBI
(11, 16, 19). For TBI, RAP (R: correlation coefficient, A: amplitude P: mean arterial blood
pressure) represents the dynamic pressure-volume relationship inside the intracranial space,
indicating whether the compensatory reserve is intact or exhausted. The equivalent indices
for TSCI are now termed sPRx and sRAP. To calculate sRAP, we used ISP (instead of ICP)
and for sPRx we correlated ABP with ISP (instead of ABP with ICP).
Indocyanine green (ICG). ICG is a water-soluble, near-infrared fluorescent dye which
penetrates tissue by several mm and is widely used to assess organ perfusion (13) including
brain (14). ICG binds albumin and is rapidly eliminated by the liver (t1/2 3 – 4 minutes) (15).
Statistics. We used the following statistical tests: Fig. 2, unpaired t-test; Fig. 4a, Pearson r;
Fig. 5, one-sample t-test; Fig. 6, unpaired t-test; Fig. 7, paired t-test; Fig. 8a, Spearman r and
unpaired t-test; Fig. 8c, one-sample t-test.