William F. Collins

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...

Evoked bulbar reticular unit activity following delta fiber stimulation of peripheral somatosensory nerve in cat

Abstract Evoked responses of neurons located in the nucleus reticularis gigantocellularis and lateral tegmental field of the medulla in 30 cats anesthetized with a mixture of 75% nitrous oxide and 25% oxygen were studied following electrical stimulation of peripheral somatosensory nerves. Single, and trains of multiple stimuli were applied above threshold levels for A-beta-delta fiber activity and the responses of 93 units in the nucleus reticularis gigantocellularis and 28 units in the lateral tegmental field were analyzed with respect to latency, duration, frequency, and afterdischarge. The adequate stimulus for altering unit activity was shown to be stimulation above A-beta-delta threshold. Multiple stimuli in the A-beta-delta range produced a more intense and longer response than single stimuli. A somatotopic organization suggesting predominantly contralateral input as well as predominantly upper extremity input was demonstrated but there was bilateral representation of all four extremities in the caudal nucleus gigantocellularis. Stimulation of the peripheral nerves of the four extremities had no effect on the activity of neurons in the adjacent lateral tegmental field.

Results of Trans-Sphenoidal Cryohypophysectomy for Carcinoma of the Breast

Abstract In 100 cases of widespread, disseminated carcinoma of the breast, with a follow-up between 14 and 40 months, overall remission rate after cryohypophysectomy was 40 per cent. Eighty-five of...

Norepinephrine levels in experimental spinal cord trauma

Alpha methyl tyrosine (AMT) or reserpine administered intravenously 24 hours before sacrificed in the nontraumatized cat resulted in significant reduction in tissue levels of norepinephrine (NE) tested at the T-5 spinal cord level. Phenoxybenzamine given 2 hours before sacrifice did not alter NE levels at T-5. Histological sections of spinal cord examined 1 hour after a 500-gm-cm trauma at the T-5 level in cats, pretreated 24 hours before trauma by a single dose of AMT or reserpine demonstrated no reduction of gray or white matter hemorrhages when compared tocontrols. In cats pretreated with phenoxybenzamine 2 hours before trauma there was a marked reduction of hemorrhages at 1 hour posttrauma when compared to controls. The animals treated with phenoxybenzamine had a 32% reduction of systemic blood pressure before trauma, demonstrated no pressor response to spinal cord trauma, and were severely hypotensive posttrauma. It is concluded that posttraumatic blood pressure has greater etiological significance in the pathogenesis of experimental spinal cord hemorrhages than tissue levels of NE.

Femoral nerve injury following inguinal hernia repair.

Insidious leg pain and weakness followed inguinal hernia repair. Despite the temporal relationship of the surgery and the symptoms, the diagnosis proved elusive, in part, because of the rarity of the complication.

Evoked cerebral cortical activity from small peripheral nerve fibers in cat.

Abstract In 19 cats anesthetized with 75% nitrous oxide/25% oxygen, two types of cortical activity have been demonstrated to respond to repetitive stimulation of small myelinated and unmyelinated peripheral nerve fibers. One is a rhythmic 3–4 c/sec high voltage activity seen most prominently in the cortical association areas. The other is a 20–40 c/sec small amplitude train of brief discharges appearing most prominently in the primary somatosensory area. This latter response is related to the activity of smaller peripheral nerve fibers. The two responses differ in that the 20–40 c/sec activity is not evoked by epinephrine, appears shortly after the stimulus, and has a shorter duration of activity than the higher voltage 3–4 c/sec theta activity. The slow rhythm is evoked by epinephrine, is delayed in onset and outlasts an evoking stimulus train. Neither response is evoked by optic stimulation or by stimulation of the larger peripheral afferent fibers. Both varieties of cortical activity are suppressed by intravenous phenobarbital.

Evaluation of Complicated Migraine in Childhood

We report on 3 patients with complicated migraine of childhood. Family history was positive for migraine in each case, and all experienced the acute onset pf neurologic deficits in associated with throbbing hemicranium. Abnormalities of cerebral blood flow determinations, electroencephalograms and cerebral arteriograms in addition to persistent neurologic sequelae were demonstrated. We propose that complicated migraine of childhood is not an entirely benign symptom complex.

Yale neurosurgery program.

Organized neurosurgery at Yale began in 1918 with Dr. Sam Harvey. In 1928, Dr. William German became the first surgeon at Yale who was dedicated to neurosurgery. Both of these surgeons were trained by Harvey Cushing, and upon the arrival of Drs. Cushing and Eisenhardt in 1934, Yale developed a strong tradition in surgery of the nervous system. In 1967, Dr. William Collins established a training program for residents that integrated laboratory research and clinical experience. This tradition has continued under the guidance of Dr. Dennis Spencer since 1987. This article provides a brief overview of the history of neurosurgery at Yale, its current practice, and plans for the future.

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

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 neurological examination on admission and six weeks and six months after injury. After six months the patients who were treated with methylprednisolone within eight hours of their injury had significant improvement as compared with those given placebo in motor function (neurologic change scores of 16.0 and 11.2, respectively; P = 0.03) and sensation to pinprick (change scores of 11.4 and 6.6; P = 0.02) and touch (change scores, 8.9 and 4.3; P = 0.03). Benefit from methylprednisolone was seen in patients whose injuries were initially evaluated as neurologically complete, as well as in those believed to have incomplete lesions. The patients treated with naloxone, or with methylprednisolone more than eight hours after their injury, did not differ in their neurologic outcomes from those given placebo. Mortality and major morbidity were similar in all three groups. We conclude that in patients with acute spinal-cord injury, treatment with methylprednisolone in the dose used in this study improves neurologic recovery when the medication is given in the first eight hours. We also conclude that treatment with naloxone in the dose used in this study does not improve neurologic recovery after acute spinal-cord injury.