Hypothermic treatment for acute spinal cord injury

Abstract

Spinal cord injury (SCI) is a devastating condition that affects approximately 11,000 patients each year in the United States. Although a significant amount of research has been conducted to clarify the pathophysiology of SCI, there are limited therapeutic interventions that are currently available in the clinic. Moderate hypothermia has been used in a variety of experimental and clinical situations to target several neurological disorders, including traumatic brain and SCI. Recent studies using clinically relevant animal models of SCI have reported the efficacy of therapeutic hypothermia (TH) in terms of promoting long-term behavioral improvement and reducing histopathological damage. In addition, several clinical studies have demonstrated encouraging evidence for the use of TH in patients with a severe cervical spinal cord injury. Moderate hypothermia (33°C) introduced systemically by intravascular cooling strategies appears to be safe and provides some improvement of long-term recovery of function. TH remains an experimental clinical approach and randomized multicenter trials are needed to critically evaluate this potentially exciting therapeutic intervention targeting this patient population.

FIG. 1

Graph showing time course of locomotor recovery as measured by Basso, Beattie and Bresnahan (BBB) scores following hypothermic and normothermic treatment. Mean BBB scores obtained in animals receiving modest hypothermia (32–33°C) 30 minutes after trauma for 4 h are represented by the filled circles, and normothermia (37°C) are represented by triangles. Data are presented as mean ± standard error of the mean. *p < 0.05; **p < 0.01. (Reprinted with permission from Yu et al. [25]).

FIG. 2

Hypothermia increased the numbers of preserved ventral motor neurons rostral and caudal to the injury site. Counts of cells labeled for NeuN (a neuron-specific marker) from transverse sections rostral (R) and caudal (C) to and within the injury epicenter of the cervical cord showed that acute application of mild systemic hypothermia could significantly increase the numbers of NeuN-immunoreactive neurons in the ventral horn (laminae VII–IX) at distances of 900 μm and greater from the injury epicenter compared with normothermic controls. Almost no preserved ventral motor neurons, however, were detected within the immediate injury site in both spinal cord injury (SCI) groups. Recordings from uninjured controls are provided for comparison, and the data are expressed as the average ± standard error of the mean. **p < 0.01 compared with normothermic controls; ***p < 0.001. (Reprinted with permission from Lo et al. [22]).

FIG. 3

Diagram demonstrating the location of the balloon catheter within the inferior vena cava after percutaneous insertion within the femoral vein. (Reprinted with permission from Levi et al. [43]).

FIG. 4

Temporal changes in temperature in a representative subject. In this patient (patient 9), three distinct phases can be observed: 1) cooling phase, in which the target temperature (33°C) was achieved at an approximate rate of 0.58°C/h; 2) hypothermia phase that lasted for 48 h; and 3) re-warming phase, which allowed for re-establishment of normal temperature (37°C) at 0.1°C = h rate. (Reprinted with permission from Levi et al. [43]).

FIG. 5

American Spinal Injury Association and International Medical Society of Paraplegia Impairment Scale (AIS) outcome of 14 patients treated with modest hypothermia. After 50.2 [9.7; standard error or the mean (SEM)] weeks, 57.1% of the patients were still AIS A, 21.4% were B, 14.3% were C, and 7.1% were D. In the control group, 11 patients remained AIS A, 1 converted to B, 1 converted to C, and 1 converted to D. A greater number of patients converted to AIS B and C in the hypothermia group (5 patients) when compared with the control (2 patients). There was no statistically significant difference between the final AIS grade in the control and hypothermia groups (2-way analysis of variance). (Reprinted with permission from Levi et al. [44]).

FIG. 6

Complications during hospital stay in 14 patients who underwent hypothermia and in 14 control subjects. Respiratory and infectious complications occurred in similar frequency in patients with or without hypothermia. ARDS = adult respiratory distress syndrome; DVT = deep venous thrombosis; MI = myocardial infarction; PE = pulmonary embolism; UGI = upper gastrointestinal bleeding; UTI = urinary tract infection. (Reprinted with permission from Levi et al. [44]).