Progression in acute stroke: value of the initial NIH stroke scale score on patient stratification in future trials.

BACKGROUND AND PURPOSE: The objective was to determine the occurrence of neurological changes during the first 48 hours after acute stroke as it relates to initial stroke severity. METHODS: The National Institutes of Health Stroke Scale (NIHSS) was performed serially for the first 48 hours on 127 consecutive ischemic stroke patients (129 strokes) admitted to the neuroscience intensive care unit. Incidence of stroke progression (a >/=3-point increase on the NIHSS) was recorded and analysis performed to determine its association with initial stroke severity and other demographic and physiological variables. Deficit resolution by 48 hours, defined as an NIHSS score of 0 or 1, measured the frequency of functional recovery predicted by the initial deficit. RESULTS: Overall progression was noted in 31% of events (40/129). Applying Bayes' solution to the observed frequency of worsening, the greatest likelihood of predicting future patient progression occurs with stratification at NIHSS scores of 7. Patients with an initial NIHSS of 7 with a 65.9% (27/41) worsening rate (P<0.000005). Forty-five percent (40/88) of those with an initial score of 7 returned to a normal examination within this period (chi2, P<0.000005). CONCLUSIONS: This study suggests that the early clinical course of the neurological deficit after acute stroke is dependent on the initial stroke severity and that a dichotomy in early outcome exists surrounding an initial NIHSS score of 7. These findings may have significant implications for the design and patient stratification in treatment protocols with respect to primary clinical outcome.

Acute carpal tunnel syndrome in a diver: evidence of peripheral nervous system involvement in decompression illness.

Conclusive evidence for involvement of the peripheral nervous system in decompression illness is lacking. We report a case of decompression illness associated with shoulder pain and the clinical features of median nerve injury at the wrist. Initial recompression and hyperbaric oxygen treatment produced prompt relief of all symptoms and signs, but carpal tunnel syndrome subsequently recurred. Nerve conduction studies confirmed median nerve conduction delay at the wrist. Repeat measurements after treatment with hyperbaric oxygen showed electrophysiologic improvement that was consistent with improvement in symptoms. We believe this is the first objectively substantiated case of injury to the peripheral nervous system caused by decompression illness.

Hyperbaric oxygen after global cerebral ischemia in rabbits reduces brain vascular permeability and blood flow.

BACKGROUND AND PURPOSE: Hyperbaric oxygen (HBO) has been advocated as a therapy to improve neurological recovery after ischemia, since HBO may improve tissue oxygen delivery. We examined the effect of HBO treatment after global cerebral ischemia on early brain injury. METHODS: Rabbits were subjected to 10 minutes of global cerebral ischemia by cerebrospinal fluid compression. After 30 minutes of reperfusion, rabbits either were subjected to HBO for 125 minutes and then breathed 100% O2 at ambient pressure for 90 minutes or breathed 100% O2 for 215 minutes. At the end of reperfusion and 90 minutes after exposure, brain vascular permeability and cerebral blood flow were measured. Somatosensory evoked potentials were monitored throughout the experiment. RESULTS: HBO treatment reduced (P < .05) brain vascular permeability by 16% in gray matter and by 20% in white matter. Cerebral blood flow was lower (P < .05) in the HBO group (40.9 +/- 1.9 mL/min per 100 g, mean +/- SEM) compared with controls (50.8 +/- 2.0 mL/min per 100 g). Somatosensory evoked potential recovery was similar in the two groups (P > .05). CONCLUSIONS: HBO administered after global cerebral ischemia promoted blood-brain barrier integrity. HBO treatment also reduced cerebral blood flow; this effect was not associated with a reduction in evoked potential recovery. Since neurological outcome after global cerebral ischemia is generally poor and treatment options are limited, HBO should be further investigated as a potential therapy.

Hyperbaric oxygen after global cerebral ischemia in rabbits does not promote brain lipid peroxidation.

OBJECTIVE: To determine whether hyperbaric oxygen administered immediately after global cerebral ischemia increases free radical generation and lipid peroxidation in the brain or alters neurophysiologic recovery. DESIGN: Prospective, randomized, controlled trial. SETTING: Animal research laboratory. SUBJECTS: Adult male New Zealand white rabbits. INTERVENTIONS: Anesthetized rabbits were subjected to 10 mins of global cerebral ischemia by infusing a mock cerebrospinal fluid into the subarachnoid space and increasing intracranial pressure equal to mean arterial pressure. Immediately upon reperfusion, one group of rabbits (n = 9) was treated with hyperbaric oxygen at 2.8 atmospheres absolute for 75 mins while the control group (n = 9) breathed room air for an equivalent period of time. At the end of the reperfusion period, oxyradical brain damage was determined by measuring brain levels of oxidized and total glutathione and free malondialdehyde. Neurophysiologic brain injury was assessed with cortical somatosensory evoked potentials. MEASUREMENTS AND MAIN RESULTS: Both oxidized glutathione and the ratio of oxidized glutathione to reduced glutathione (total minus oxidized) were higher (p < .05) in the hyperbaric oxygen group, indicating that hyperbaric oxygen increased free radical generation. Nonetheless, brain malondialdehyde content, an index of lipid peroxidation, was similar (p > .05) in the two groups. Cortical somatosensory evoked potential recovery at the end of reperfusion was 50% higher (p < .05) in the hyperbaric oxygen-treated animals compared with controls. CONCLUSIONS: Treatment with hyperbaric oxygen after ischemia increased the amount of oxygen free radicals in the brain. However, this increase in free radical generation was not associated with an increase in lipid peroxidation or a reduction in neurophysiologic recovery when measured after 75 mins of recirculation. These results suggest that hyperbaric oxygen administered immediately after global ischemia does not promote early brain injury.

Vestibulo-ocular reflex gain as a measure of vestibular function in guinea pigs while in a recompression chamber: apparatus design and effects of nitrogen narcosis.

There are several mechanisms whereby alteration of barometric pressure can produce vertigo in divers or aviators. Development of a reliable measure of vestibular function in an animal model is the first requirement for further study of these mechanisms. This report presents the development of a rotatory table device capable of evoking the vestibulo-ocular reflex (VOR) of a guinea pig while in a hyperbaric chamber. To assess the reproducibility of this response, eight animals were monitored by electronystagmography during rotations at three table velocities (62.4, 83.3, and 100 degrees/s). Two test sessions were performed on each animal with a 6-hour interval between sessions. The VOR gain was calculated by dividing the average peak velocity of the slow phase component of the nystagmus by the peak stimulus velocity. At least eight observations per test speed were averaged; calibration of eye movement was performed prior to each session by forced ocular abduction. Multifactorial analysis of variance revealed no significant differences (p > .05) between the differing rotation speeds nor between test sessions for individual animals. However, there was a significant difference in VOR gain between animals (p < .002). The VOR gain was then measured, using the same techniques, in another group of seven animals before, during, and after an air dive to the equivalent of 200 feet of seawater (7.06 atmospheres absolute) to assess the effects of nitrogen narcosis. Pre- and post-dive VOR gains were significantly greater than those measured at depth (p < .05). These results are consistent with the slow processing model of nitrogen narcosis and the controversial theory that central nervous system depressants decrease the VOR gain. The results also demonstrate the ability of this inexpensive apparatus to provide a sensitive measure of pressure-induced changes of vestibular function in guinea pigs.

Exercise conditioning reduces the risk of neurologic decompression illness in swine.

During development of a pig model of neurologic decompression illness (DCI) we noted that treadmill-trained pigs seemed less likely to develop DCI than sedentary pigs. The phenomenon was formally investigated. Twenty-four immature, male, castrated, pure-bred Yorkshire swine were conditioned by treadmill running, while 34 control pigs remained sedentary. All pigs (weight 18.75-21.90 kg) were dived on air to 200 feet of seawater (fsw) in a dry chamber. Bottom time was 24 min. Decompression rate was 60 fsw/min. Pigs that developed neurologic DCI were treated by recompression. Pigs without neurologic signs were considered neurologically normal if they ran on the treadmill without gait disturbance at 1 and 24 h postdive. Of the 24 exercise-conditioned pigs, only 10 (41.7%) developed neurologic DCI, compared to 25 of 34 (73.5%) sedentary pigs (X2 = 5.97; P = < 0.015). Neither mean carcass density (adiposity) nor mean age were significantly different between groups. No patent foramen ovale was detected at necropsy. An additional control group of 24 pigs was dived to clarify the influence of weight. The results suggest that the risk of neurologic DCI is reduced by physical conditioning, and the effect is independent of differences in age, adiposity, and weight.

Failure to prevent decompression illness in rats by pretreatment with a soluble complement receptor.

Controversy exists over the role of complement activation in the natural history of decompression illness (DCI), and whether an individual's predisposition to DCI might be influenced by susceptibility to activation of complement by intravascular gas bubbles. Treatment with a soluble complement receptor (sCR-1), which neutralizes activated complement components, is known to be beneficial in other complement-dependent disease processes. This study investigated the effect of treating rats with sCR-1 or saline before decompression from a dive profile known to produce a high incidence of DCI. No statistical difference in the incidence of DCI was observed between the 27 rats treated with sCR-1 and 26 control rats treated with saline. The study was unable to confirm the previously reported observation in rats of a positive correlation between DCI incidence and increasing weight.

Complement activation during saturation diving.

In this study, the levels of activated complement fragments C3a and C5a were measured on 11 U.S. Navy divers as they performed a 28-day saturation dive to a pressure equivalent of 1,000 feet of seawater (fsw, 31.3 atm abs). Two subjects developed symptoms consistent with the high pressure nervous syndrome (HPNS) and three were treated for type I DCS (joint pain only). These events allowed us to test two hypotheses: a) alterations in C3a or C5a levels during compression are related to the occurrence of HPNS and b) increases in complement fragments are an indicator of decompression stress associated with type I DCS. There was no correlation between changes in C3a and C5a levels during compression and the diagnosis of HPNS. Our results suggest that an increase in C3a and C5a levels during saturation diving correlates with decompression stress and the clinical diagnosis of type I DCS.

Effects of an increased PO2 during recompression therapy for the treatment of experimental cerebral arterial gas embolism.

In this study we investigated the efficacy of an initial compression to 6 atm abs on a 53% nitrogen:47% oxygen mixture (PO2 = 2.8 atm abs) before breathing oxygen at 2.8 and 1.9 atm abs for the treatment of feline cerebral arterial gas embolism. Neurophysiologic function was determined by measuring the cortical somatosensory evoked potential (SEP) amplitude in anesthetized ventilated cats. Air was infused into the carotid artery until the SEP amplitude was reduced to less than 10% of baseline values. The animals were randomly separated into 3 groups. The first group (CONTROL) (n = 7) served as control and remained at the surface, breathing air. The second group (NITROX) (n = 10) was compressed to 6 atm abs breathing a 53:47% nitrox mixture for 30 min followed by breathing 100% oxygen at 2.8 and 1.9 atm abs. The third group (HBO) (n = 10) was compressed to 2.8 and 1.9 atm abs breathing 100% oxygen. Air infusion suppressed the SEP amplitude to the same level in all groups. The CONTROL group recovered 27.6 +/- 31.2% (mean +/- standard deviation) of the baseline SEP amplitude, whereas the NITROX group recovered 63.2 +/- 28.2%, and the HBO group recovered 66.0 +/- 19.3%. An analysis of variance with repeated measures revealed that both treatment profiles promote significant (P = 0.03) recovery of the SEP amplitude compared to no treatment. We find no additional benefit, however, by initiating treatment at 6 atm abs, even when additional oxygen is provided.

Effect of lidocaine on somatosensory evoked response and cerebral blood flow after canine cerebral air embolism.

BACKGROUND AND PURPOSE: Victims of air embolism often recover rapidly on hyperbaric treatment then deteriorate again, even if hyperbaric treatment is continued. In previous animal experiments, lidocaine has been shown to improve recovery of somatosensory evoked response amplitude after air embolism. However, animals in these experiments rarely deteriorated. We have shown that the induction of air embolism and transient hypertension in canines produces deterioration despite hyperbaric treatment, and we decided to test the effect of lidocaine on somatosensory evoked potential recovery and cerebral blood flow in this model. METHODS: Dogs were treated with repeated doses of lidocaine or equivalent volumes of saline during hyperbaric therapy after internal carotid air embolism and transient hypertension. The investigators were unaware of treatment group assignment during the experiments. The amplitude of the median nerve somatosensory evoked potential and cerebral blood flow measured with carbon-14-labeled iodoantipyrine autoradiography were used to assess effect of therapy. RESULTS: Lidocaine-treated dogs recovered 60 +/- 10% (mean +/- 95% confidence limits) of the baseline somatosensory evoked potential amplitude 220 minutes after air embolism; saline-treated dogs recovered 32 +/- 10% (a significant difference at p less than 0.01). Lidocaine-treated dogs also had higher cerebral blood flow values than saline-treated dogs 220 minutes after air embolism. CONCLUSIONS: Lidocaine ameliorated the delayed deterioration of evoked potential associated with air embolism and hypertension in this canine model. The improved cerebral blood flow may be a mechanism of action of lidocaine or an associated effect of improved neuronal survival.

Management of herniated intervertebral disks during saturation dives: a case report.

During research saturation dives at 5.0 and 5.5 atm abs, 2 divers developed an acute herniation of the nucleus pulposus of the L5-S1 intervertebral disk. In both cases the pain was severe enough to require intravenous morphine or intramuscular meperidine. Although the symptoms presented by these divers are frequently considered to be an indication for immediate surgical consultation, we decided that emergency decompression posed an unacceptable risk that decompression sickness (DCS) would develop in the region of acute inflammation. In both cases strict bedrest and medical therapy were performed at depth. In the first case, 12 h was spent at depth before initiating a standard U.S. Navy saturation decompression schedule with the chamber partial pressure of oxygen elevated to 0.50 atm abs. In the second case, a conservative He-N2-O2 trimix decompression schedule was followed to the surface. In both cases, no initial upward excursion was performed. The required decompression time was 57 h 24 min from 5.5 atm abs and 55 h 38 min from 5.0 atm abs. During the course of decompression, the first diver's neurologic exam improved and he required decreasing amounts of intravenous narcotic; we considered both to be evidence against DCS. The second diver continued to have pain and muscle spasm throughout decompression, however he did not develop motor, reflex, or sphincter abnormalities. Both divers have responded well to nonsurgical therapy.

Comparison of two recompression profiles in treating experimental cerebral air embolism.

The standard treatment for cerebral arterial gas embolism (CAGE) is an initial recompression to 6 atm abs on air for 30 min followed by oxygen breathing at 2.8 and 1.9 atm abs. It has been suggested that initial recompression to 2.8 atm abs on O2 may be as beneficial, thus avoiding potential treatment complications associated with the deeper depth. To test this hypothesis, we measured the recovery of the somatosensory evoked potential (SEP) following air embolism in anesthetized, ventilated cats. Air was infused into the carotid artery in increments of 0.08 ml until the SEP amplitude was reduced to less than 10% of the baseline value for 15 min. Three groups were studied. A control group (n = 10) received no further treatment after SEP suppression. The second group (6 atm abs/HBO] (n = 8) was compressed to 6 atm abs on air for 30 min followed by O2 breathing at 2.8 atm abs for 100 min. The third group (HBO) (n = 8) was compressed to 2.8 atm abs on O2 for 130 min. The control group recovered 28.8 +/- 18.2% (mean +/- SD) of the baseline amplitude, whereas the 6 atm abs/HBO group recovered 48.6 +/- 22.6%, and the HBO group recovered 62.0 +/- 20.3%. An analysis of variance revealed that only the HBO group had significantly (P less than 0.01) better recovery than the control group. There was no significant difference in SEP recovery between the 2 treatment groups. These results suggest that treating CAGE at 2.8 atm abs with O2 is a viable alternative to the current therapy.

Blood flow and vascular permeability during motor dysfunction in a rabbit model of spinal cord ischemia.

BACKGROUND AND PURPOSE: Delayed deterioration of neurological function after central nervous system ischemia is a well-documented clinical problem. The purpose of our study was to elucidate the role of spinal cord blood flow and spinal cord-blood barrier integrity in the evolution of delayed neurological deterioration after transient spinal cord ischemia in rabbits. METHODS: Anesthetized rabbits were subjected to lumbar spinal cord ischemia (25 minutes) and variable periods of reperfusion (30 minutes to 48 hours after ischemia). Regional spinal cord blood flow was monitored by carbon-14-labeled iodoantipyrine autoradiography; vascular permeability was assessed by quantitative microhistofluorescence of Evans blue-albumin in frozen sections of spinal cord. Hindlimb motor function was assessed by standard scoring system and tissue edema by wet/dry weight method. RESULTS: Hindlimb motor function indicated complete paralysis during ischemia and partial gradual recovery upon reperfusion (up to 8 hours), followed by progressive deterioration to severe deficits over 48 hours. Severe vascular permeability disruption was noticed early (30 minutes) after reperfusion, but almost complete recovery reestablished at 8 hours was followed by a secondary progressive increase in vascular permeability. Blood flow was reduced by 20-30% (p less than 0.01) 4 hours after ischemia in the gray matter, but hyperemia (200-300%, p less than 0.01) was observed 12-24 hours after ischemia. Spinal cord water content increased by 5.7% (p less than 0.05) 24 hours after ischemia. CONCLUSIONS: This study demonstrates that delayed neurological and motor deterioration after spinal cord ischemia is associated with severe progressive breakdown of spinal cord-blood barrier integrity that develops late (hours) after the injury. Our data suggest that no ischemic insult in early or late reperfusion is associated with delayed motor deterioration.

Effects of treatment with dexamethasone on recovery from experimental cerebral arterial gas embolism.

Dexamethasone is often recommended as an adjunct to recompression in the treatment of serious central nervous system decompression accidents. We studied the effects of prophylactic and therapeutic administration of dexamethasone combined with hyperbaric treatment in anesthetized dogs that were subjected to carotid air embolism and a brief episode of arterial hypertension. To assess recovery we measured somatosensory evoked potential (SSEP) amplitude, intracranial pressure, brain water, and cerebral blood flow. Three groups were studied: pre-air treatment (dexamethasone 1 mg/kg 3-4 h before carotid air embolism, and 1 mg/kg immediately after air embolism); post-air treatment (2 mg/kg immediately after air embolism); and control (equivalent volumes of saline pre- and post-air). There was a slight improvement in SSEP early in the course of hyperbaric therapy in the pre-air treated group; the post-air group never differed from control. No differences in intracranial pressure or brain water were found among groups. No blood flows below those lethal to neurons occurred in treated animals but 4 of 7 control animals had low flows. Although prophylactic treatment with dexamethasone produces some improvement in recovery, we cannot confirm that dexamethasone is an effective adjunct to recompression when administered therapeutically.

Morphologic and electrophysiologic effects of cochlear implantation and electrical stimulation.

The nondeafened guinea pig model was utilized in this study to assess the functional and morphologic effects of cochlear implantation and electrical stimulation. Auditory brainstem responses (ABRs) were recorded prior to and following intrascalar implantation of a 3M-House cochlear electrode (n = 41 ears), as well as after electrical stimulation (n = 23 ears). The experimental population was divided into the following groups according to implantation and stimulation parameters: 200 microA for 3 hours (group I); 200 microA for 24 hours (group II); 400 microA for 3 hours (group III); implanted, but not stimulated (group IV); and nonimplanted, not stimulated ears (group V). Of those cochleae that sustained the trauma of implantation, 32 percent had no detectable ABR to 110 dB SPL clicks, while only 7 percent additionally failed to respond to 130 dB SPL clicks. No significant difference (one-way ANOVA with repeated measures at the 95 percent confidence limit) could be detected when comparing those ears that retained ABRs according to experimental grouping. Morphologic analysis was performed on 29 cochleae. Spiral ganglion "packing densities" were not found to be significantly different among the groups (ANOVA). The status of the organ of Corti was significantly better in groups II and V in comparison to the other groups (Kruskal-Wallis test with pairwise comparisons, p less than 0.05); there was no discernible dose-response relationship. Morphologic and electrophysiologic changes correlated with insertion trauma and infection rather than with electrical stimulation at the levels tested in this study.(ABSTRACT TRUNCATED AT 250 WORDS)

Allopurinol pretreatment improves evoked response recovery following global cerebral ischemia in dogs.

The reperfusion of previously ischemic tissue may lead to the formation of highly reactive free radicals that promote tissue injury. Xanthine oxidase has been implicated as one source of these free radicals. We examined the role of xanthine oxidase in brain injury using a cerebrospinal fluid compression model of global cerebral ischemia with 15 minutes of ischemia and 4 hours of reperfusion. Seven dogs were pretreated with the xanthine oxidase inhibitor allopurinol (50 mg/kg for 5 days). Neurophysiological recovery was monitored with cortical somatosensory evoked potentials. As an attempt to correlate brain recovery with the mechanism of protection, free brain malondialdehyde was measured at the end of reperfusion by high-performance liquid chromatography. Brain water content was measured by wet-dry weights. Compared with seven untreated control dogs, allopurinol pretreatment significantly improved recovery of somatosensory evoked potentials after 4 hours of reperfusion. However, the amount of free malondialdehyde in the allopurinol-treated dogs was 32% greater than that in the controls. Brain water content was similar in the two groups. These results suggest that xanthine oxidase contributes to brain injury after ischemia and reperfusion. However, tissue damage caused by xanthine oxidase may be mediated through mechanisms other than free radical production.

Cerebral air embolism treated by pressure and hyperbaric oxygen.

We used pressure and hyperbaric oxygen to treat 2 patients with cerebral air embolism, occurring as the result of invasive medical procedures, and neither suffered any permanent damage detectable by clinical examination and MRI. This outcome contrasts with reports of infarct and disability among untreated victims of air embolism.

Lipopolysaccharide-induced production of tumor necrosis factor activity in rats with and without risk factors for stroke.

Rats produced more TNF activity in cerebrospinal fluid (CSF) than in blood after intracerebroventricular (i.c.v.) injection of lipopolysaccharide (LPS). After intravenous (i.v.) LPS, blood TNF levels exceeded CSF levels. Thus, brain cells appear to produce TNF in response to LPS. Rats with the stroke-risk factors hypertension or combined hypertension and genetic stroke-proneness produce more TNF in response to a provocative dose of LPS i.v. than control animals free of these risk factors. The possible relevance to stroke vulnerability is discussed.

No conversion of xanthine dehydrogenase to oxidase in canine cerebral ischemia.

Xanthine oxidase (XO) has been implicated as a source of free radicals mediating ischemia-reperfusion injury. Conversion of the non-free radical generating xanthine dehydrogenase (XD) to the free radical producing XO during ischemia has been demonstrated in several tissues. We examined the irreversible conversion of XD to XO in the dog brain after ischemia and after ischemia and reperfusion. Under pentobarbital sodium anesthesia and by use of a cerebrospinal fluid compression model of global cerebral ischemia, dogs were subjected to 30 min of ischemia (n = 8) or 30 min of ischemia and 60 min of reperfusion (n = 8). A cerebral perfusion pressure of 60 mmHg was maintained during reperfusion. Eight control dogs were not subjected to ischemia. After the dogs were killed their brains were rapidly removed and frozen in liquid nitrogen. XO and XD + XO activities were measured with a radioassay utilizing 8-[14C]hypoxanthine and separating substrate and products by thin-layer chromatography. Total XD + XO activity was significantly (P less than 0.05) decreased after ischemia and reperfusion (35.6 +/- 8.0 vs. 60.8 +/- 20.8 nmol.min-1.g protein-1 in controls, means +/- SD) but not after ischemia alone (48.2 +/- 20.4). XO/(XD + XO) was approximately 20% in all three groups. Irreversible XD to XO conversion is not an important mechanism leading to early tissue injury in global cerebral ischemia.