Severe Cerebral Injury Research Articles

Assessment and prevention of shivering in patients with severe cerebral injury. A pilot study.

Low body temperature is induced by surface cooling to reduce metabolic demands in patients with severe cerebral injury. Shivering, which increases energy expenditure, is a common effect of surface cooling. The aim of this pilot study was to investigate whether increased gradient between the set point and peripheral temperature is related to shivering and whether modifying the loss of body heat during surface cooling decreases the frequency of shivering. Seven cerebrally injured patients at a neurosurgical ICU were studied. Shivering, surface cooling and the temperature gradient measured as the tympanic and the tip toe temperatures were registered every 30 min. Shivering was assessed at three levels: no shivering, mild shivering and severe shivering. In four patients the arms and legs were covered with a cotton cloth for part of the observation time to modify the rate of heat loss. The temperature measurements were repeated in each patient between 13 and 42 times. Four patients out of seven shivered. There was a significant association between increased temperature gradient and shivering (P < 0.01). Modifying the rate of heat loss decreased the temperature gradient (P < 0.001). By simultaneously measuring the tympanic and tip toe temperatures it may be possible to detect shivering earlier and decrease its frequency by modifying the loss of body heat during surface cooling.

Brain injury after cerebral arterial air embolism in the rabbit as determined by triphenyltetrazolium staining.

Microscopic cerebral arterial air embolism (CAAE) occurs commonly during cardiac surgery and causes acute and chronic nonfocal neurologic dysfunction. Nevertheless, most neuroimaging studies do not detect brain injury after cardiac surgery. Using a rabbit model, the authors hypothesized they could detect and quantitate severe brain injury and infarction 24 h after microscopic CAAE using the vital stain triphenyltetrazolium chloride. Experiments were conducted in methohexital anesthetized New Zealand white rabbits. Surgical shams (n = 5) underwent surgery but had no neurologic insult. Positive controls (n = 3) received 200 microl/kg of intracarotid air. Other animals were randomized to receive either 50 microl/kg intracarotid air, which produces microscopic CAAE (n = 18), or 300 microl intracarotid saline (control, n = 18). Outcomes included somatosensory evoked potential amplitude at 90 min, neurologic impairment score at 4 and 24 h (0 [normal] to 99 [coma]), and percentage of nonstaining brain at 24 h using color-discrimination image analysis. Severely injured or infarcted brain does not stain with triphenyltetrazolium chloride. Surgical shams had little neurologic impairment and a small amount of nonstaining brain at 24 h (5.2 +/- 2.4%; mean +/- SD). Positive controls had profound neurologic impairment and large amounts of nonstaining brain (40-97%). Ninety-minute somatosensory evoked potential amplitude was less in animals receiving 50 microl/kg air versus saline: 38 +/- 28% versus 102 +/- 32%, respectively, P < 1 x 10(-7). Neurologic impairment scores were greater in animals receiving 50 microl/kg air versus saline: at 4 h, 43 +/- 16 versus 23 +/- 9, P < 1 x 10(-7); at 24 h, 24 +/- 12 versus 15 +/- 8, P = 0.013. Nevertheless, there was no difference between 50 microl/kg air and saline in nonstaining brain: 5.5 +/- 2.9% versus 6.8 +/- 5.4%, P = 0.83. Neurologic injury after CAAE is dose-dependent. Although microscopic CAAE causes somatosensory evoked potential abnormalities and neurologic dysfunction, severe cerebral injury or infarction is not present at 24 h. The author's findings are consistent with clinical imaging studies that suggest microscopic CAAE causes neurologic dysfunction even though overt infarction is absent.

Percutaneous endoscopic gastrostomy for patients with severe cerebral injury

Early enteral nutrition improves the outcome of severely injured patients. To provide enteral nutrition, various methods are available. In a restrospective study we analysed the outcome of 24 severely traumatized patients (mean ISS = 44), in whom a perculaneous endoscopic gastrostomy (PEG) was used for enteral nutrition. All patients had been admitted to the intensive care unit with major cerebral injury. The mean duration of intensive care treatment and the in hospital stay were 28 and 71 days, respectively. PEG was introduced 14 days after hospital admittance. Enteral nutrition through the PEG was administered for 45 days. Four patients died, 8 patients were discharged from the hospital while being fed via the PEG and 12 patients resumed normal feeding and the PEG was removed. Three severe complications occurred; 1 patient aspirated massively and died; in 2 patients intra-abdominal leakage of the enteral nutrition occurred. Both patients recovered from this complication. We conclude that because of the advantages of early enteral nutrition on the one hand and the drawbacks of nasogastric feeding tubes on the other, in injured patients with severe cerebral damage, PEG placement is justified, despite the risk of complications.

Cerebral protection by intermittent reperfusion during temporary focal ischemia in the rat.

Temporary arterial occlusion has been routinely used as an adjunct in intracranial aneurysm surgery. This has commonly been performed using a protocol of multiple short periods of occlusion alternating with periods of restoration of normal circulation. Recently, the logical basis of this method has come under scrutiny. There is extensive experimental evidence to suggest that repetitive, brief periods of global ischemia may cause more severe cerebral injury than an equivalent single period of global ischemia. Only recently has this issue begun to be addressed with regard to focal ischemia. Hence, despite the common use of temporary clipping, little experimental data are available regarding the ischemic consequences of temporary arterial occlusion with periods of reperfusion versus uninterrupted temporary occlusion. To investigate this issue, a protocol of occlusion/reperfusion that simulates the temporal profile that occurs during surgery was performed in a rat model of focal ischemia. Sixteen anesthetized Sprague-Dawley rats were divided into two groups. The animals in Group I underwent 60 minutes of uninterrupted middle cerebral artery occlusion and the animals in Group II were subjected to six separate 10-minute occlusion periods with 5 minutes of reperfusion between occlusions. Histopathological analysis was performed 72 hours postischemia. Group I had significantly increased mean infarction volumes (50.0 +/- 12.1 mm3) compared to Group II (8.7 +/- 3.1 mm3) (p = 0.008). Injuries in Group I occurred in both the cortex and striatum, whereas Group II showed only striatal injuries. Furthermore, the extent of the injuries in Group II was less severe, characterized by ischemic neuronal injury rather than frank infarction. The results indicate that intermittent reperfusion is neuroprotective during temporary focal ischemia and support the hypothesis that intermittent reperfusion is beneficial if temporary clipping is required during aneurysm repair.

Cerebral damage caused by interrupted, repeated arterial occlusion versus uninterrupted occlusion in a focal ischemic model

Temporary intracranial arterial occlusion is often utilized during the surgical treatment of intracranial aneurysms. Although numerous experimental studies have suggested that repetitive, brief periods of global ischemia cause more severe cerebral injury than a similar single period of global ischemia, this issue has not been extensively studied in relation to focal ischemia. It remains controversial whether it is safer to use brief periods of interrupted, temporary occlusion separated by reperfusion periods, or a more prolonged, single temporary occlusion. This question is addressed in studies on a rabbit model of transient, focal cerebral ischemia. Sixteen anesthetized rabbits underwent transorbital occlusion of the left internal carotid, middle cerebral, and anterior cerebral arteries, with one of two paradigms:uninterrupted occlusion (1 hour of temporary occlusion followed by 5 hours of reperfusion in eight rabbits), or interrupted occlusion (three separate 20-minute periods of occlusion, with 10 minutes of reperfusion between occlusions, followed by 4 hours, 40 minutes of reperfusion in eight rabbits). Histopathological evaluation for ischemic neuronal damage and magnetic resonance imaging studies for ischemic edema were conducted 6 hours after the initial arterial occlusion. The animals in the interrupted, repeated occlusion group showed a 59% decrease in the area of cortical ischemic neuronal damage (mean +/- standard error of the mean 10.0% +/- 1.7%) compared with the uninterrupted occlusion group (24.4% +/- 5%, p = 0.016). There was no difference between the groups in the extent of striatal ischemic damage or area of ischemic edema. These results suggest that interrupted, repeated focal ischemia causes less cortical ischemic injury than uninterrupted transient ischemia of a similar total duration. Although caution should be exercised in extrapolating from these results to the clinical situation, they may have important implications for temporary arterial occlusion during intracranial surgery.

CBF and CBF/P co2 reactivity in childhood strangulation

Four children with self-inflicted strangulation injuries had cerebral blood flow determined by stable xenon computed tomography (XeCTCBF) within 24 hours of admission. All had suffered a severe hypoxic-ischemic cerebral injury; 3 initially had fixed pupils, all were apneic with varying bradyarrhythmias, and the initial mean arterial pH was 7.26 (± 0.18). The initial blood glucose values were > 300 mg/dl (334 and 351 mg/dl) in the 2 patients who died compared to the 2 who survived (104 and 295 mg/dl). The cardiac index was depressed during the first several days of hospitalization in the 2 patients who died (< 2.0 L/min/m 2) compared to the 2 who survived. Total CBF was normal (63 ± 8 ml/min/100 gm) and local variations in CBF were present. P co 2 reactivity was determined by hyperventilating the 4 patients for 20 min from an end tidal P co 2 of 39 ± 3 torr to 29 ± 1 torr and then repeating the XeCTCBF study. Marked regional variability in the CBF/P co 2 response was observed, ranging from 0.5–5.5 ml/min/100 gm/torr P co 2. In the 2 patients who died, the CBF/P co 2 was decreased (1.2 ml/min/100 gm/torr P co 2) compared to the 2 patients who survived (2.1 ml/min/100 gm/torr P co 2). Although CBF was normal in these 4 children, the hyperventilation response was depressed, variable, and even paradoxical which may be important in the evolution of further brain injury and is a critical factor in deciding whether hyperventilation may be of clinical benefit. Three factors correlated with poor outcome and ultimately death in 2 patients: initial blood glucose > 300 mg/dl; CBF/P co 2 response < 2.0 ml/min/100 gm/torr P co 2; and cardiac index < 2.0 L/min/m 2 for longer than 12–24 hours.

Cerebral blood flow, cross-brain oxygen extraction, and fontanelle pressure after hypoxic-ischemic injury in newborn infants

The relationship between mean arterial pressure, intracranial pressure, cerebral blood flow, cross-brain oxygen extraction, cerebral metabolic rate, and outcome was studied during therapy in nine neonates on 3 consecutive days after severe hypoxic-ischemic cerebral injury. Cross-brain oxygen extraction was significantly higher (5.06 +/- 0.5 vs 2.05 +/- 0.8 ml/dl; p = 0.012) in the five neonates who survived with normal neurologic outcome than in the four who died or sustained severe brain damage. In contrast, global cerebral blood flow in the five neonates with normal neurologic outcome was significantly lower (25.6 +/- 8.2 vs 83.2 +/- 44.9 ml/100 gm brain/min; p less than 0.05) during the study period. The differences in cross-brain oxygen extraction and global cerebral blood flow between infants who had neurologic recovery and those who died or sustained brain damage occurred in the presence of acceptable values for intracranial pressure, mean arterial pressure, and cerebral perfusion pressure. Our preliminary data suggest that cross-brain oxygen extraction and possibly global cerebral blood flow may be important variables associated with severe neuronal injury and death after hypoxic-ischemic cerebral injury.

Etiology and Pathophysiology of Postasphyxial Brain Damage

In spite of major developments in prenatal supervision, perinatal asphyxia remains an important reason for the development of brain damage (18). Epidemiological investigations suggest that perinatal asphyxia actually represents a factor of increasing frequency as a cause of severe cerebral injury (9).

Cervical Spine Injuries in Children

Cardiorespiratory arrest occurring immediately after multiple injuries is usually assumed to be due to severe cerebral injury, acute hemorrhage, or airway obstruction. We have identified a group of 19 children (mean age, 6.3 years) who presented with absent vital signs (VSA) or severe hypotension, unexplained by blood loss, where these findings were caused by injury to the high cervical spine and cord, demonstrated either by X-ray or postmortem examination. Fourteen had radiologic evidence of injury to the spine between C1 and C3. In two patients the bony injury was at the C6-7 level, while in two patients the cervical spine X-ray was normal. Eighteen of the 19 children were initially resuscitated but died from a combination of hypoxic/ischemic encephalopathy and cerebral injury. Sixteen patients underwent postmortem examination and in 13 there was evidence of cord laceration, up to and including cord transection. These findings demonstrate a distinct pattern of “juvenile” cervical spine injury involving the high spine and cord which results in either apnea and cardiorespiratory arrest, or severe hypotension. This previously unrecognized cause of cardiorespiratory arrest should be considered in all children presenting with VSA after multiple trauma, even when there is no apparent radiologic abnormality of the cervical spine.

Cervical Spine Injuries in Children

Cardiorespiratory arrest occurring immediately after multiple injuries is usually assumed to be due to severe cerebral injury, acute hemorrhage, or airway obstruction. We have identified a group of 19 children (mean age, 6.3 years) who presented with absent vital signs (VSA) or severe hypotension, unexplained by blood loss, where these findings were caused by injury to the high cervical spine and cord, demonstrated either by X-ray or postmortem examination. Fourteen had radiologic evidence of injury to the spine between C1 and C3. In two patients the bony injury was at the C6-7 level, while in two patients the cervical spine X-ray was normal. Eighteen of the 19 children were initially resuscitated but died from a combination of hypoxic/ischemic encephalopathy and cerebral injury. Sixteen patients underwent postmortem examination and in 13 there was evidence of cord laceration, up to and including cord transection. These findings demonstrate a distinct pattern of "juvenile" cervical spine injury involving the high spine and cord which results in either apnea and cardiorespiratory arrest, or severe hypotension. This previously unrecognized cause of cardiorespiratory arrest should be considered in all children presenting with VSA after multiple trauma, even when there is no apparent radiologic abnormality of the cervical spine.

Neonatal Seizures: Current Concepts and Revised Classification

In recent years, prolonged EEG monitoring with simultaneous observation by video recorder on by direct inspection has produced findings that suggest that (1) the number of certain neonatal seizures (when identified only clinically) has been overestimated in the past, and (2) the total number of neonatal seizures (identified electrographically but clinically silent) has been underestimated in the past. In this article, we propose a classification of seizures that includes the following as major seizure types: subtle, clonic, tonic, and myoclonic. Subtle seizure phenomena include those alterations in neonatal behavior, motor functions, and autonomic function that are easily overlooked and that are not characterized by clonic, tonic, or myoclonic activity. Such seizures include certain ocular phenomena, oral-buccal-lingual movements, peculiar limb movements, autonomic alterations, and apnea. Subtle seizures appear to be more common in premature than in full-term infants, and some subtle clinical phenomena in full-term infants are not associated with simultaneous EEG seizure activity. Clonic seizures include focal and multifocal varieties—both are accompanied by simultaneous EEG seizure activity. Tonic seizures include focal episodes (less common) and generalized episodes (more common). Generalized tonic seizures mimic decerebrate and decorticate posturing and are not consistently accompanied by EEG seizure activity. Focal tonic episodes are consistently accompanied by such electrographic activity. Myoclonic seizures may be focal, multifocal, or generalized. Only the last of these is commonly accompanied by EEG seizure activity. Thus, the clinical seizure types commonly associated with EEG seizure activity are certain subtle seizures, focal and multifocal clonic seizures, focal tonic seizures, and generalized myoclonic seizures. Neonatal clinical seizures not accompanied by EEG seizure activity may represent movements or posturing generated by diencephalon-brainstem, "released" from the inhibitory influence of cerebral cortex. This hypothesis is supported by the common occurrence of such clinical phenomena in infants with severe bilateral cerebral injury and certain experimental findings in animals subjected to decortication. The possibility that neonatal clinical phenomena not accompanied by EEG seizure activity are nevertheless epileptic in origin is raised by documentation of apparent epileptic phenomena in older patients in the absence of surface-recordable electrographic seizure, Certain observations in human newborns and in neonatal animals also suggest this possibility. Further study is needed to resolve this issue. Distinction of epileptic and nonepileptic phenomena can be made at the bedside in many cases. Thus, nonepileptic phenomena generally are provoked or exacerbated by sensory stimulation, are suppressed by passive restraint, and are not accompanied by autonomic phenomena; the opposite is true for epileptic phenomena. The issues raised have important implications for management—in particular, decisions concerning whom to treat, criteria for determining adequacy of therapy, and determination of duration of therapy. It has become increasingly clear that most infants with neonatal seizures require only relatively brief treatment with anticonvulsant medications.

Vascular aspects and hemodynamic consequences of central nervous system injury.

We document here microvascular alterations occurring in models of mild, moderate, and severe cerebral ischemic injury. The relationship of the vascular abnormalities to the generation of hemodynamic alterations was also evaluated. Following periods of severe incomplete ischemia, scanning electron microscopic analysis of cerebral microvessels revealed the widespread production of cerebral endothelial microvilli. These microvilli increased in frequency as the ischemic insult was prolonged and remained prominent during periods of recirculation. Although these luminal projections would not be expected to inhibit reperfusion completely, they might increase microvascular resistance, leading to moderate hemodynamic impediments extending into the post-ischemic period. Similar periods of complete ischemia resulted in more severe microvascular alterations. Light and electron microscopic studies revealed a high frequency of compressed capillary lumina with vascular stasis. These compressed vessels were consistently surrounded by swollen astrocytic foot processes. When recirculation was instituted for 1 hr following 1 hr of complete ischemia, regions of non-perfusion were detected autoradiographically within brain regions destined to undergo ischemic infarction. Finally, in an attempt to determine the consequences of a primary microvascular insult on brain structure and function, the endothelial layer of microvessels in the cerebral cortex was injured using a noninvasive photochemical method. Endothelial damage led to platelet aggregation in both pial and intraparenchymal vessels. Occlusive thrombi were frequently detected with perivascular edema associated with vascular compression and severe focal ischemia. Ultrastructural blood-brain barrier studies using the horseradish peroxidase tracer demonstrated that protein leakage at the site of primary vascular injury resulted in tracer material in brain regions remote from the pathological lesion. The widespread leakage of protein tracer was associated with decreased blood flow in remote brain regions at several postirradiation periods. These data emphasize the importance of injury-induced microvascular dysfunction in the generation of brain lesions and hemodynamic abnormalities.

Endogenous nickel release in injured patients: a possible cause of myocardial damage

Atom absorption spectrophotometry was used for the study of serum nickel levels in 58 injured patients. From 27 autopsies an electron cytochemical examination of the myocardium was performed in 19 patients. In patients with severe burns and cerebral injury, the serum nickel content showed a significant increase in the early period after injury. In these cases direct traumatic or toxic damage to the central nervous system and, in cases of early death, cerebral oedema, were present. The ECG tracings revealed disturbances in repolarization in a large majority. Nickel-dimethylglyoxim complex precipitates were found in the myocardium of all patients who died. In addition to disorientation, increased serum nickel levels and abnormal ECG records were observed in septicaemia. On the basis of these observations and the experimental data, we suggest that one of the causes of post-traumatic myocardial damage may be endogenous nickel release as part of the homeostatic disequilibrium arising as a direct or indirect effect of the injury.

Nonpenetrating subclavian artery injuries.

Nonpenetrating subclavian artery trauma, a potentially catastrophic injury, has been recognized more frequently with the liberal use of angiography in evaluating blunt cervicothoracic trauma. Six patients, five men and one woman, recently underwent surgical treatment at the University of Michigan Hospital for blunt injury of the subclavian artery. The diagnoses were established by arteriography. Physical findings, chest roentgenograms, and results of noninvasive vascular evaluation were found to be nonspecific or unreliable. Operative treatment with resection of the injured arterial segments and either primary anastomosis or bypass grafting resulted in restoration of distal, upper extremity blood flow in all of the cases. One patient died 20 days after trauma from a severe associated cerebral injury. Among the five survivors, residual soft tissue and neurologic injury compromised full recovery in three. Thus, only two of the six patients survived without sequelae, a fact that underscores the seriousness of this type of subclavian artery injury.

Cerebral microvascular injury in experimental drug abuse.

An experimental drug abuse research project is reported, in which monkeys and rats were placed on various I.V. amphetamine (Desoxyn) and I.V. barbiturate (Seconal) regimes. The monkeys were studied by serial cerebral angiography. At the end of the study all animals were sacrificed for histological examination. I.V. methamphetamine produced relatively severe cerebral vascular injury and brain damage in most animals. At least part of the damage seemed to be the result of direct vascular injury, arterial and venous. The misuse of Seconal and Ritalin also appeared to be hazardous, but these studies are incomplete, and the degree of hazard has not been fully evaluated.

Neonatal bilirubinemia in production of long-term neurological deficits.

ASSOCIATION of marked bilirubinemia in the early neonatal period with kernicterus is well established. The possibility has occurred to many that lesser degrees of bilirubinemia may be related to less severe cerebral injury, too mild to be detected during the newborn period, but recognizable in later years as mild to moderate impairment of intelligence, partial nerve deafness, and other neurological deficits. A closely analogous concept is that of a continuum of reproductive casualty developed by Pasamanick and Knobloch. 1 It was the purpose of the present study to investigate the application of such a hypothesis to children with mild to moderate neonatal bilirubinemia. In preparation for this study, the world literature was reviewed. The most significant reports are summarized in Table 1. This illustrates the conflicting results and complexities of relating moderate bilirubinemia to subsequent cerebral difficulties in surviving children. Examination of Table 1 reveals that a number of factors

The Role of Angiography in the Diagnosis of Extradural Haematomas

An extradural haematoma is the most dangerous and dramatic complication of a head injury. It is a distressing feature that although the surgical removal of an extradural haematoma presents little difficulty to a surgeon accustomed to cranial surgery, the mortality from this condition remains disastrously high, varying from 14 to 66 per cent (Table 1). Analysis of mortality figures from any series of extradural haematomas reveals that the majority of deaths are avoidable. Unavoidable mortality due to co-existent severe cerebral injury has been estimated at between 5 to 10 per cent (Hooper, 1959). In a series of 86 consecutive cases of extradural haematoma treated at this centre during a period of three years (1st January 1962 to 31st December 1964), the mortality rate was 14 per cent (12 cases). The unavoidable mortality was only 2·3 per cent (2 cases). The high avoidable mortality rate is usually due to failure to realise the variations in symptomatology and location of extradural haematomas. In this seri...

PRIMARY BEHAVIOR DISORDERS AND PSYCHOPATHIC PERSONALITY

IN PREVIOUS publications concerning the electroencephalographic evaluation of primary behavior disorders in children 1 and of psychopathic personality in adults, 2 we reported correlations with age, sex, family history and antecedent severe illness or cerebral injury of early childhood, which previously had not been considered of etiologic significance. Statistical analyses revealed that electroencephalographic abnormality was unrelated to age and sex but was related to either a positive family history or a personal history of cerebral trauma or severe illness. The inference was that the abnormal electroencephalogram was of either genogenic or histogenic origin and thus represented some aspect of the neural limits of the organism. The original number of patients under study has been increased, thus permitting more complete statistical analyses, from which further implications may be drawn. The present communication has this for its purpose. Because of the consistency of the findings in the two previous studies and the

On the Prophylactic Use of Morphine in Oases of Severe Cerebral Injury

On the Prophylactic Use of Morphine in Oases of Severe Cerebral Injury