Mary Jo Shepard

A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury: Results of the second national acute spinal cord injury study

In 1990, the Second National Acute Spinal Cord Injury Study reported that high-dosage methylprednisolone improves neurologic recovery in spinal-injured humans. The study showed that patients who received the drug within 8 hr after injury improved, whereas those who received the drug later did not. The drug significantly increased recovery even in severely injured patients who were admitted with no motor or sensory function below the lesion, contradicting a long-held dogma that such patients would not recover. Some researchers, however, have questioned the stratification of the patient population, the use of summed neurologic change scores, and the absence of functional assessments. The stratification by injury severity and treatment time was planned a priori and based on objective criteria. Detailed analyses revealed no differences between groups attributable to stratification or randomization. While multivariate analyses of the summed neurologic scores were used, the conclusions were corroborated by other analytical approaches that did not rely on summed scores. For example, treatment with methylprednisolone more than doubled the probability that patients would convert from quadriplegia or paraplegia to quadriparesis or paraparesis, analgesia to hypalgesia, and anesthesia to hypesthesia. The treatment also significantly improved neurologic scores in lumbosacral segments, indicating that beneficial effects were not limited to segments close to the lesion site. The treatment did not significantly affect mortality or morbidity. The study strongly suggests that methylprednisolone has significant beneficial effects in human spinal cord injury, that these effects occur only when the drug is given within 8 hr, and that it helps even in patients with severe spinal cord injuries. These conclusions have important implications for spinal cord injury care and research.

A Randomized, Controlled Trial of Methylprednisolone or Naloxone in the Treatment of Acute Spinal-Cord Injury

Abstract Studies in animals indicate that methylprednisolone and naloxone are both potentially beneficial in acute spinal-cord injury, but whether any treatment is clinically effective remains uncertain. We evaluated the efficacy and safety of methylprednisolone and naloxone in a multicenter randomized, double-blind, placebo-controlled trial in patients with acute spinal-cord injury, 95 percent of whom were treated within 14 hours of injury. Methylprednisolone was given to 162 patients as a bolus of 30 mg per kilogram of body weight, followed by infusion at 5.4 mg per kilogram per hour for 23 hours. Naloxone was given to 154 patients as a bolus of 5.4 mg per kilogram, followed by infusion at 4.0 mg per kilogram per hour for 23 hours. Placebos were given to 171 patients by bolus and infusion. Motor and sensory functions were assessed by systematic neurologic examination on admission and six weeks and six months after injury. After six months the patients who were treated with methylprednisolone within eigh...

An evaluation of two equations for predicting fetal weight by ultrasound.

In an earlier study we presented a method of determining fetal weight from ultrasound measurements of abdominal circumference (AC) and biparietal diameter (BPD). From an equation with these two measurements as independent variables we generated tables of estimated fetal weights (E1). Although these tables have been very useful, we had the impression we were underestimating fetal weight. Therefore, we reconsidered an earlier unpublished table generated from a different equation (E2). While most estimates from E1 and E2 were likely to be within 10% of actual weight, there was significant underestimation with E1. E2 provides a better balance between the distribution of overestimations and underestimations.

The Effectiveness of Surgery on the Treatment of Acute Spinal Cord Injury and Its Relation to Pharmacological Treatment

Using data from the Second National Acute Spinal Cord Injury Study (NASCIS II), the authors sought to characterize the role of surgery in the management of traumatic spinal cord injury and to examine the interaction between pharmacological treatment and surgery. Patients who did not undergo surgery had more severe spinal cord injuries initially than those who had surgery. However, no differences in neurological improvement at 1-year follow-up were found between those who underwent surgery and those who did not. The results suggest that either early surgery (< or = 25 hours after injury) or late surgery (> 200 hours) may be associated with increased neurological recovery, particularly motor function, but these results are equivocal. Surgery was not shown to interact with pharmacological treatments, indicating that the effect of drug treatment in NASCIS II, reported elsewhere, is not influenced by surgery. Other independent variables that best predicted improvement in motor score were age of 25 years or younger, incomplete injury, and lower baseline emergency department neurological scores. This study does not provide clinically relevant evidence concerning the efficacy of timing or the value of surgery in treating patients with spinal cord injuries. A randomized study on the timing and efficacy of spinal cord surgery is needed to obtain valid comparisons of the efficacy of surgical treatments.

Magnetic resonance imaging and neurological recovery in acute spinal cord injury : observations from the National Acute Spinal Cord Injury Study 3

Study design: Data are from a multicenter, randomized, double blind clinical trial of acute spinal cord injury. Objectives: To evaluate the prognostic value of magnetic resonance imaging (MRI) for randomized patients in the National Acute Spinal Cord Injury Study 3 (NASCIS). Setting: Sixteen spinal cord injury centers throughout the United States and Canada. Methods: Of 499 patients randomized in NASCIS 3 between December 1991 and September 1995, MRI was electively done on 191 patients within 72 h of injury. Indications of hemorrhage, edema, and contusion were recorded by standard protocol. Neurological impairment as determined by motor function, response to pin prick and light touch was assessed at admission to the participating center and 6 weeks after injury. Change in neurological function was obtained by subtracting the score of each neurological parameter at admission from that measured at 6 weeks. Spinal cord surgery performed within the 3 days after injury was noted. Data were analyzed by: chi square, analysis of variance, multiple logistic regression and linear regression models. Results: Patients with hemorrhage were much more likely to have a complete injury (OR=2.88, 95 Cl 1.32, 6.23); however this association was much reduced when the initial neurological examination was taken into account (AOR=1.43, 95% Cl 0.55, 3.73) and was no longer a significant predictor of injury. MRI evidence of cord edema was the strongest predictor of reduced improvement in motor function (−3.34 points, P=0.06) and light touch sensation (−3.41 points, P=0.05) at 6 weeks. Conclusions: Cord hemorrhage, contusion, and edema on MRI were not associated with diagnosis of a complete cord injury after neurological assessment from the initial clinical examination was taken into account. Prediction of a worse 6 week neurological status was weakly associated with the presence of edema diagnosed by MRI. As MRI technology improves, these diagnostic and predictive capabilities need to be re-assessed. Sponsorship: NASCIS 3 was funded by the National Institute of Neurological Disorders and Stroke at the National Institutes of Health, Washington, DC, USA. Pharmacia and Upjohn provided study drugs and placebos; they also monitored data quality, and funded additional tests, in accordance with Food and Drug Administration regulatory requirements. Dr Bracken has served as an occasional paid consultant to Pharmacia and Upjohn.

Proportional weight gain and complications of pregnancy, labor, and delivery in healthy women of normal prepregnant stature

Detailed reproductive information was obtained through interview at early prenatal visits to hospital clinics, private medical groups, or health maintenance organizations for 4186 women delivered at Yale-New Haven Hospital. From these women, 1,396 were selected who had no preexisting chronic disease, were within their normal prepregnant weight for height as determined by Quetelets Index (weight2/height2), and were delivered of single infants with no major congenital malformations between 37 and 42 weeks. These women were divided into four quartiles according to their proportional weight gain (weight gain/prepregnant weight): quartile 1 = gains less than or equal to 15%; quartile 2 = gains 16% to 25%; quartile 3 = gains 26% to 35%; quartile 4 = gains greater than 35%. Complications of pregnancy, labor, and delivery were recorded within 2 days of delivery. Compared with the women in quartile 2 those in quartile 4 were 3.8 times more likely to develop gestational hypertension and had a fourfold risk of becoming preeclamptic. They were also significantly more likely to require cesarean section. The size of the infant was a significant risk factor for prolonged second stage of labor in primigravid women (greater than 2 hours) but not in multigravid women (greater than 1 hour). Weight gains of more than 35% almost doubled the risk of a prolonged second stage of labor for multigravid women. High proportional gains were not associated with adverse neonatal outcomes. Clinicians should consider proportional weight gain when advising healthy women about weight gain during pregnancy.

Coping and adaptation following acute spinal cord injury: a theoretical analysis.

Coping and adaptation theory is used to synthesise existing data concerning psychological recovery from acute spinal cord injury. Psychological reactions to spinal cord trauma are similar to those of mourning and other situations of severe loss. Each reaction plays a specific role in fostering or hindering recovery depending upon when it occurs. Premorbid personality and the influence of significant others play a central role in coping with injury. These factors partly explain why some patients cope better than others to equally serious disability. A critique of research methodologies and suggestions for new studies are provided.

Psychological response to acute spinal cord injury: an epidemiological study

This study empirically examines psychological reactions to spinal cord injury from a coping and adaptation perspective. Ego defensive, affective and coping reactions, and long-term personality reactions are described at the time of discharge from the acute care hospital (n = 190). These psychological reactions are examined for their association with neurological function on admission, at discharge, and changes in neurological status during hospitalisation. Affective reactions to injury were still evident in this sample and related positively to severity of motor and, to a lesser degree, sensory disability. Affective reactions were also generally associated with negative coping responses which could interfere with successful rehabilitation therapy. The study indicates that intensive psychological counselling is required by many patients during acute hospitalisation and prior to transfer for rehabilitation.

Clinical measurement, statistical analysis, and risk-benefit: controversies from trials of spinal injury.

BACKGROUND The National Acute Spinal Cord Injury Studies have been a series of trials assessing the role of pharmacologic agents in the prevention of secondary neuronal damage after acute spinal cord injury. METHODS The trials were multicenter randomized, controlled studies. RESULTS Two trials have demonstrated the efficacy of high-dose methylprednisolone in improving neurologic and functional recovery and have shown a reassuring safety profile. CONCLUSION This study responds to a recent commentary on these trials and examines in particular the roles of clinical measurement, statistical analysis, and risk benefit in assembling evidence for or against innovative therapies.

The effect of methylprednisolone, naloxone, and spinal cord trauma on four liver enzymes: observations from NASCIS 2

In order to determine the impact of extremely large doses of methylpredniso-lone, naloxone, or of spinal cord injury itself, on liver enzymes, we examined the results of SGOT, SGPT, alkaline phosphatase and total bilirubin tests obtained 24 hours, 3 and 10 days after the end of the study drug infusions in spinal cord injured patients entered in the National Acute Spinal Cord Injury Study.1 The mean values of four liver enzymes, the amount of change between 24 hours and 3 and 10 days post infusion, and the proportion of liver enzyme levels considered to be abnormal did not appear to be affected by either drug protocol. Even when controlling for drug protocol and severity of injury (complete vs incomplete), variation in enzyme levels appeared to be the result of the spinal cord injury, not study drugs. Spinal cord injury is routinely treated with the NASCIS dose of methylprednisolone in many countries. It is reassuring to find no evidence of compromised liver function from this steroid protocol.