Cerebrospinal Fluid Drainage (CSFD) in Acute Spinal Cord Injury

Acute spinal cord injury (SCI) affects 10,000-14,000 persons per year in the United States
(Burke, Linden et al. 2001). There are 150,000-300,000 persons living with significant
disabilities from SCI at any given time (Bernhard, Gries et al. 2005). The average age of
incident cases of SCI is 47 years and about 78% of the cases are males (DeVivo and Chen
2011). Estimates of the lifetime costs to care for someone with a SCI range from $325,000 to
$1.35 million and the yearly cost to society reaches $8 billion (Sekhon and Fehlings 2001).
With better long term care technologies, these costs are expected to continue to rise.
Although there have been significant advances in accessibility for people with disabilities,
the goal of medical science is to overcome the physiological barriers imposed by the injury
itself and allow these individuals to regain their pre-injury level of neurological function
(Rowland, Hawryluk et al. 2008). The injury to the spinal cord occurs in two phases. The
first phase is the primary physical damage due to the impact energy of the compressive nature
of the injury. The damage can be very complex with shearing of the axons, destruction of the
cell bodies and disruption of the microvasculature at the site of injury. The secondary phase
of the injury begins soon after the primary injury has occurred and can be influenced by many
factors such as hypoxia, hypotension, and the extent of the primary injury. Spinal cord
ischemia post-injury causes a significant increase in cell death and more significant
neurological disability. Limiting tissue hypoperfusion post-injury can decrease the amount of
cell death and axonal damage. Lumbar cerebrospinal fluid drainage (CSFD) together with
increased mean arterial blood pressure (MAP) in the immediate post-injury period can reduce
spinal cord tissue hypoperfusion. By reducing spinal cord hypoperfusion through elevation of
MAP, less cell death and axonal damage will occur, leading to an improvement in neurological
function. The feasibility of CSFD as a means for reducing the intrathecal pressure (ITP) in
patients with acute SCI has been demonstrated in a small randomized controlled trial by Kwon
et al (Kwon, Curt et al. 2009). The limitations were a small sample size, broad inclusion
criteria, lack of statistical power calculation and restricted drainage regimen (maximum 10
mL per hour).

Inclusion Criteria:

- Aged 18-75 years inclusive;

- Diagnosis of acute SCI;

- Injury is less than 24 hours old;

- ISNCSCI Impairment Scale Grade "A," "B" or "C" based upon first ISNCSCI evaluation
after arrival to the hospital;

- Neurological level of injury between C4-C8 based upon first ISNCSCI evaluation after
arrival to the hospital;

- Women of childbearing potential must have a negative serum β-hCG pregnancy test or a
negative urine pregnancy test;

- Patient is willing to participate in the study;

- Informed consent document signed by patient or witnessed informed consent document;

- No contraindications for study treatment(s);

- Able to cooperate in the completion of a standardized neurological examination by
ISNCSCI standards (includes patients who are on a ventilator).

Exclusion Criteria:

- Injury arising from penetrating mechanism;

- Significant concomitant head injury defined by a Glasgow Coma Scale (GCS) score < 14
with a clinically significant abnormality on a head CT (head CT required only for
patients suspected to have a brain injury at the discretion of the investigator);

- Pre-existing neurologic or mental disorder which would preclude accurate evaluation
and follow-up (i.e. Alzheimer's disease, Parkinson's disease, unstable psychiatric
disorder with- hallucinations and/or delusions or schizophrenia);

- Prior history of SCI;

- Recent history (less than 1 year) of chemical substance dependency or significant
psychosocial disturbance that may impact the outcome or study participation, in the
opinion of the investigator;

- Is a prisoner;

- Participation in another clinical trial within the past 30 days;

- Acquired immune deficiency syndrome (AIDS) or AIDS-related complex;

- Active malignancy or history of invasive malignancy within the last five years, with
the exception of superficial basal cell carcinoma or squamous cell carcinoma of the
skin that has been definitely treated. Patients with carcinoma in situ of the uterine
cervix treated definitely more than 1 year prior to enrollment may enter the study.