Eugene S. Flamm

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...

Free radicals in cerebral ischemia.

The possibility that cerebral ischemia may initiate a series of pathological free radical reactions within the membrane components of the CNS was investigated in the cat. The normally occurring electron transport radicals require adequate molecular oxygen for orderly transport of electrons and protons. A decrease in tissue oxygen removes the controls over the electron transport radicals, and allows them to initiate pathologic radical reactions among cell membranes such as mitochondria. Pathologic radical reactions result in multiple products, each of which may be present in too small a concentration to permit their detection at early time periods. It is possible to follow the time course, however, by the decrease of a major antioxidant as it is consumed by the pathologic radical reactions. For this reason, ascorbic acid was measured in ischemic and control brain following middle cerebral artery occlusion. There was a progressive decrease in the amount of detectable ascorbic acid ranging from 25% at 1 hour to 65% at 24 hours after occlusion. The reduction of this normally occurring antioxidant and free radical scavenger may indicate consumption of ascorbic acid in an attempt to quench pathologic free radical reactions occurring within the components of cytomembranes.

Transvascular treatment of giant aneurysms of the cavernous carotid and vertebral arteries: Functional investigation and embolization

Functional angiographic investigation and percutaneous embolization using detachable balloons in nine carotid cavernous aneurysms, three petrous aneurysms, one vertebral artery aneurysm, and one posterior inferior cerebellar aneurysm are reported. A double-lumen balloon catheter is used to evaluate acute tolerance to occlusion of the carotid or vertebral arteries. Occlusion is tested under systemic heparinization. Local perfusion of heparinized saline, proximal as well as distal, to the balloon occlusion is used. The procedure was successful in all but one cavernous aneurysm. The arterial lumen was sacrificed in all cases. Clinical improvement occurred in all successful cases. Retro-orbital pain was relieved in all. Ocular cranial nerve palsies improved or resolved in most. One delayed ophthalmic episode that improved represents the only complication. No such embolic problems occurred in any case in which the cavernous carotid artery was occluded by balloon trapping. The delayed embolic complications after carotid artery occlusion are related to the collateral vessels to the C-4 and C-5 segments of the artery. Balloon trapping decreases the length of the thrombosed segment and prevents retrograde filing of the aneurysm.

Hypertension, small size, and deep venous drainage are associated with risk of hemorrhagic presentation of cerebral arteriovenous malformations

OBJECTIVE To identify clinical and angiographic factors of cerebral arteriovenous malformations (AVMs) associated with hemorrhage to improve the estimation of the risks and help guide management in clinical decision making. METHODS We conducted a retrospective analysis of 100 consecutive adults who have presented during the past 3 years to our institution with cerebral AVMs. Angiographic and clinical parameters were evaluated using multivariate logistic regression analysis to analyze factors associated with hemorrhagic presentation. RESULTS The group had a mean age of 37.8 years; 53% were men, 48% presented with intracranial hemorrhage, and 40% presented with seizures. All 10 patients with cerebellar AVMs presented with hemorrhage. The following factors were independently associated with AVM hemorrhage: history of hypertension (P = 0.019; odds ratio [OR] = 5.36), nidal diameter <3 cm (P = 0.023: OR = 4.60), and deep venous drainage (P = 0.009: OR = 5.77). Dural arterial supply (P = 0.008; OR = 0.15) was independently associated with decreased risk of bleed. Location, nidal aneurysms, patient age, and smoking were not associated with increased or decreased bleeding risk. CONCLUSION In this study, we found small AVM size and deep venous drainage to be positively associated with AVM hemorrhage. Dural supply was associated with a decreased likelihood of hemorrhagic presentation. Hypertension was found to be the only clinical factor positively associated with hemorrhage, a finding not previously reported. Smoking, although associated with increased risk of aneurysmal subarachnoid hemorrhage, was not associated with a higher risk of AVM hemorrhage.

Regional brain sodium, potassium, and water changes in the rat middle cerebral artery occlusion model of ischemia.

Middle cerebral artery occlusions (MCAo) in rats produce infarcts in the pyriform and frontoparietal cortex, extending into the lateral basal ganglia and parasagittal cortex. We estimated tissue H2O concentrations from wet and dry weight measurements and determined Na and K concentrations by atomic absorption spectroscopy in these areas of rat brains. Tissue samples were analyzed at 2, 4, and 24 hours after MCAo and sham MCAo, compared with normal values measured in unoperated rats. In the pyriform and frontoparietal areas, H2O concentrations increased to 34 and 7% greater than normal by 2 hours, and 89 and 94% by 24 hours after MCAo. Na concentrations rose in these areas to 73 and 37% greater than normal by 2 hours, and 281 and 330% by 24 hours. K concentrations did not change until 4 hours, but fell to 62 and 34% of normal in these areas by 24 hours. Such large ion shifts indicate severe tissue destruction. In the parasagittal cortex and basal ganglia areas, the ion and water changes were smaller and did not become significant until 24 hours after MCAo. Rates of Na entry into the infarct site were greatest at 0-2 hours, while the rates of K loss peaked later, between 2 and 4 hours. The difference in Na influx and K efflux resulted in net ion shifts that correlated highly with water entry, yielding a correlation coefficient of 0.992 (p less than 0.001) and a slope indicating that 1 ml of water entered the tissue with each 145 mumoles of ions. These findings strongly suggest that net ion shifts cause the early edema of regional brain ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Preliminary Experience with Ultrasonic Aspiration in Neurosurgery

A new instrument utilizing ultrasonic energy to fragment and aspirate normal and pathological tissue has been evaluated for neurosurgical use. The instrument has been tested in several animal models to assess its efficacy and safety. The instrument has been used clinically in 38 cases for removal of meningiomas, acoustic neurinomas, and other tumors. Future modifications and applications are discussed.

Experimental spinal cord injury: treatment with naloxone.

We studied the effect of the opiate antagonist naloxone on the recovery of cats injured with a 400-g-cm impact injury to T-9. The animals were evaluated by recording somatosensory evoked potentials and performing weekly neurological examinations. Several dose schedules were followed. Six of eight cats that received an intravenous or intraperitoneal bolus of naloxone (10 mg/kg) 45 minutes after injury regained the ability to walk. Recovery occurred in only one of five animals that were treated with an infusion of naloxone, 10 mg/kg/hour, and in none of five animals given 1 mg/kg as a bolus. Because these results are not related to any observed change in blood pressure, we believe that naloxone may be achieving its effect through the preservation of spinal cord blood flow, as well as other mechanisms that have yet to be defined.

Management of nontraumatic vascular shunts involving the cavernous sinus

The authors managed 38 consecutive cases of nontraumatic vascular shunts involving the cavernous sinus. Selective angiography demonstrated 12 carotid cavernous fistulas (CCFs) and 26 dural arteriovenous shunts (DAVSs). Visual disability occurred from glaucoma, venous retinopathy, optic neuropathy, or diplopia. Ten patients with slow-flow shunts and minimal dysfunction were treated medically to lower intraocular pressure (IOP) and/or instructed in manual compression of the internal carotid artery, ipsilateral to the lesion, using the contralateral hand. Percutaneous intraarterial embolization using detachable balloons, isobutylcyanoacrylate, or polyvinyl alcohol particles was successful in 16/18 DAVSs and 9/10 CCFs. The neuro-ophthalmic signs resolved in these 25 cases. Complications occurred in five patients. These included a transient hemiparesis, twelfth nerve palsy, unilateral nasal field loss, a pseudoaneurysm causing a third-nerve paresis, and temporary cavernous sinus thrombosis. Conservative therapy in mild cases and embolization in cases with visual disability or progressive signs are warranted.

Endovascular stent treatment of cervical internal carotid artery aneurysms with parent vessel preservation

BACKGROUND Aneurysms involving the cervical portion of the internal carotid artery (ICA) frequently result from prior trauma or dissection. CASE DESCRIPTIONS Two patients are reported with cervical internal carotid artery aneurysms. In both cases, disease involving the contralateral ICA precluded safe treatment of the aneurysms by ICA occlusion. Endovascular stents placed across the diseased portion of the artery resulted in thrombosis of the aneurysm with preservation of the parent artery. CONCLUSION Endovascular stent placement should be considered for treatment of aneurysms involving the cervical ICA when preservation of the parent vessel is necessary.