Cell-mediated immunity in severely head-injured patients: the role of suppressor lymphocytes and serum factors

1992 ◽  
Vol 77 (5) ◽  
pp. 694-699 ◽  
Author(s):  
Keith B. Quattrocchi ◽  
Claramae H. Miller ◽  
Franklin C. Wagner ◽  
Sally J. DeNardo ◽  
Gerald L. DeNardo ◽  
...  
Keyword(s):  
Head Injury ◽  
Cellular Immunity ◽  
Severe Head Injury ◽  
Normal Subjects ◽  
Lymphocyte Function ◽  
Serum Factors ◽  
Content Type ◽  
Head Injured ◽  
Injured Patients ◽  
Fine Print

✓ Severe head injury results in suppression of cellular immunity associated with defective in vitro functioning of effector lymphocytes, such as helper T cells and cytotoxic T cells. It is not known whether this suppression in effector lymphocyte function is due to intrinsic lymphocyte dysfunction, to suppressor peripheral blood mononuclear cells (PBMC's) such as suppressor lymphocytes or suppressor monocytes, or to serum factors capable of inhibiting effector lymphocyte function. The purpose of this study was to determine whether a subpopulation of PBMC's and/or serum factors) are responsible for this observed suppression in cell-mediated immunity. Cell-mediated immune activity was determined measuring in vitro lymphokine-activated killer (LAK) cytotoxicity following incubation of PBMC's from 15 head-injured patients with those from 15 heterologous normal subjects. The PBMC's were separated into lymphocyte-enriched and monocyte-enriched subpopulations by plastic adherence techniques, and the effect of each population on LAK cytotoxicity was determined. Additionally, the effect on cytotoxicity of serum from the head-injured patients was determined in a dose-response fashion. There was significant depression in LAK cytotoxicity when: 1) PBMC's from normal subjects were incubated with PBMC's from head-injured patients (p < 0.001); 2) lymphocytes (PBMC's depleted of monocytes) from head-injured patients were incubated with PBMC's from normal subjects (p < 0.001); and 3) PBMC's from normal subjects were incubated with serum from head-injured patients (p < 0.001). No suppression in cellular immunity was noted when lymphocytes from normal subjects were incubated with monocytes from head-injured patients. The results indicate that lymphocytes rather than monocytes actively inhibit cellular immunity following severe head injury. The detection of immmunosuppressive serum factors suggests a mechanism by which lymphocytes might be modulated by severe head injury.

Impairment of helper T-cell function and lymphokineactivated killer cytotoxicity following severe head injury

1991 ◽  
Vol 75 (5) ◽  
pp. 766-773 ◽  
Author(s):  
Keith B. Quattrocchi ◽  
Edmund H. Frank ◽  
Claramae H. Miller ◽  
Asim Amin ◽  
Bernardo W. Issel ◽  
...  
Keyword(s):  
T Cell ◽  
Head Injury ◽  
Severe Head Injury ◽  
Cell Cytotoxicity ◽  
Content Type ◽  
Lak Cell ◽  
Head Injured ◽  
Injured Patients ◽  
Fine Print

✓ Infection is a major complication of severe head injury, occurring in 50% to 75% of patients who survive to hospitalization. Previous investigations of immune activity following head injury have demonstrated suppression of helper T-cell activation. In this study, the in vitro production of interferon-gamma (INF-γ), interleukin-1 (IL-1), and interleukin-2 (IL-2) was determined in 25 head-injured patients following incubation of peripheral blood lymphocytes (PBL's) with the lymphocyte mitogen phytohemagglutinin (PHA). In order to elucidate the functional status of cellular cytotoxicity, lymphokine-activated killer (LAK) cell cytotoxicity assays were performed both prior to and following incubation of PBL's with IL-2 in five patients with severe head injury. The production of INF-γ and IL-2 by PHA-stimulated PBL's was maximally depressed within 24 hours of injury (p < 0.001 for INF-γ, p = 0.035 for IL-2) and partially normalized within 21 days of injury. There was no change in the production of IL-1. When comparing the in vitro LAK cell cytotoxicity of PBL's from head-injured patients and normal subjects, there was a significant depression in LAK cell cytotoxicity both prior to (p = 0.010) and following (p < 0.001) incubation of PBL's with IL-2. The results of this study indicate that IL-2 and INF-γ production, normally required for inducing cell-mediated immunity, is suppressed following severe head injury. The failure of IL-2 to enhance LAK cell cytotoxicity suggests that factors other than decreased IL-2 production, such as inhibitory soluble mediators or suppressor lymphocytes, may be responsible for the reduction in cellular immune activity following severe head injury. These findings may have significant implications in designing clinical studies aimed at reducing the incidence of infection following severe head injury.

Contribution of CSF and vascular factors to elevation of ICP in severely head-injured patients

1987 ◽  
Vol 66 (6) ◽  
pp. 883-890 ◽  
Author(s):  
Anthony Marmarou ◽  
Angelo L. Maset ◽  
John D. Ward ◽  
Sung Choi ◽  
Danny Brooks ◽  
...  
Keyword(s):  
Severe Head Injury ◽  
Ventricular Catheter ◽  
Outflow Resistance ◽  
Content Type ◽  
Relative Contribution ◽  
Temporal Course ◽  
Head Injured ◽  
Predominant Factor ◽  
Injured Patients ◽  
Fine Print

✓ The authors studied the relative contribution of cerebrospinal fluid (CSF) and vascular parameters to the level of intracranial pressure (ICP) in 34 severely head-injured patients with a Glasgow Coma Scale score of less than 8. This was accomplished by first characterizing the temporal course of CSF formation and outflow resistance during the 5-day period postinjury. The CSF formation and outflow resistance were obtained from pressure responses to bolus addition and removal of fluid from an indwelling ventricular catheter. The vascular contribution to the level of ICP was assessed by withdrawing fluid at its rate of formation and observing the resultant change in equilibrium ICP level. It was found that, with the exception of patients with subarachnoid hemorrhage, CSF parameters accounted for approximately one-third of the ICP rise after severe head injury, and that a vascular mechanism may be the predominant factor in elevation of ICP.

High-risk mild head injury

1997 ◽  
Vol 87 (2) ◽  
pp. 234-238 ◽  
Author(s):  
John N. K. Hsiang ◽  
Theresa Yeung ◽  
Ashley L. M. Yu ◽  
Wai S. Poon
Keyword(s):  
Head Injury ◽  
High Risk ◽  
Mild Head Injury ◽  
Radiographic Findings ◽  
Content Type ◽  
Head Injured ◽  
Definition Of ◽  
Gcs Score ◽  
Injured Patients ◽  
Fine Print

✓ The generally accepted definition of mild head injury includes Glasgow Coma Scale (GCS) scores of 13 to 15. However, many studies have shown that there is a heterogeneous pathophysiology among patients with GCS scores in this range. The current definition of mild head injury is misleading because patients classified in this category can have severe sequelae. Therefore, a prospective study of 1360 head-injured patients with GCS scores ranging from 13 to 15 who were admitted to the neurosurgery service during 1994 and 1995 was undertaken to modify the current definition of mild head injury. Data regarding patients' age, sex, GCS score, radiographic findings, neurosurgical intervention, and 6-month outcome were collected and analyzed. The results of this study showed that patients with lower GCS scores tended to have suffered more serious injury. There was a statistically significant trend across GCS scores for percentage of patients with positive acute radiographic findings, percentage receiving neurosurgical interventions, and percentage with poor outcome. The presence of postinjury vomiting did not correlate with findings of acute radiographic abnormalities. Based on the results of this study, the authors divided all head-injured patients with GCS scores ranging from 13 to 15 into mild head injury and high-risk mild head injury groups. Mild head injury is defined as a GCS score of 15 without acute radiographic abnormalities, whereas high-risk mild head injury is defined as GCS scores of 13 or 14, or a GCS score of 15 with acute radiographic abnormalities. This more precise definition of mild head injury is simple to use and may help avoid the confusion caused by the current classification.

Effect of apolipoprotein E genotype on hematoma volume after trauma

2002 ◽  
Vol 96 (1) ◽  
pp. 90-96 ◽  
Author(s):  
Imran Liaquat ◽  
Laurence T. Dunn ◽  
James A. R. Nicoll ◽  
Graham M. Teasdale ◽  
John D. Norrie
Keyword(s):  
Head Injury ◽  
Ct Scan ◽  
Injury Severity ◽  
Univariate Analysis ◽  
Hematoma Volume ◽  
Patient Age ◽  
Content Type ◽  
Head Injured ◽  
Injured Patients ◽  
Fine Print

Object. The apolipoprotein E-ϵ4 (APOE-ϵ4) allele is associated with poor outcome after head injury and spontaneous intracerebral hemorrhage (SICH). The aims of this study were to determine if patients in whom one or more APOE-ϵ4 alleles are present are more likely to sustain intracranial mass lesions after head injury and to determine whether there is an isoform-specific effect on the size of the intracranial hematoma. Methods. The authors performed a computerized volumetric analysis of 142 hematomas visible on computerized tomography (CT) scans obtained in 129 patients. The APOE genotype was determined by subjecting buccal smear samples to polymerase chain reaction and restriction enzyme digestion. Allele frequencies were similar in head-injured patients with and without intracranial hematomas (p = 0.36). Univariate analysis revealed that in those patients with one or more APOE-ϵ4 alleles hematoma volume was greater (cube root—transformed values) than that found in patients without the APOE-ϵ4 allele (3.1 cm compared with 2.5 cm, p = 0.0039). The results of univariate analysis also suggested significant effects of patient age, injury severity (mild, moderate, or severe according to admission Glasgow Coma Scale scores) and hematoma location (extraaxial, intraaxial, or both) on hematoma volume. The mechanism of injury (assault, fall, or other) was marginally associated with hematoma volume (p = 0.052). Time from injury to CT scan, hypoxia, and hypotension had no significant effect on hematoma volume. The results of multiple linear regression analysis showed that the presence of an APOE-ϵ4 allele and an extraaxial hematoma location were independent predictors of hematoma volume, after adjusting for patient age, hours between injury and CT scan, injury severity, and injury mechanism. Conclusions. Larger hematomas were found in head-injured patients with one or more APOE-ϵ4 alleles than in patients without the allele. This may contribute to the poorer outcomes observed in these patients.

Failure of prophylactic barbiturate coma in the treatment of severe head injury

1985 ◽  
Vol 62 (3) ◽  
pp. 383-388 ◽  
Author(s):  
John D. Ward ◽  
Donald P. Becker ◽  
J. Douglas Miller ◽  
Sung C. Choi ◽  
Anthony Marmarou ◽  
...  
Keyword(s):  
Head Injury ◽  
Severe Head Injury ◽  
Controlled Trial ◽  
Neurological Status ◽  
Treated Group ◽  
Control Group ◽  
Barbiturate Coma ◽  
Content Type ◽  
Head Injured ◽  
Injured Patients

✓ In certain subgroups of severely head-injured patients, the mortality rate remains unacceptably high. The authors describe a randomized, controlled trial of prophylactic pentobarbital therapy in a group of these patients. Pentobarbital was started as soon as possible after the head injury, regardless of the intracranial pressure (ICP), and was continued for a prescribed period of time. The study included 53 consecutive head-injured patients over the age of 12 years, who had either an acute intradural hematoma (subdural and/or intracerebral, large enough to warrant surgical decompression), or no mass lesion but whose best motor response was abnormal flexion or extension. All patients in the study were randomly assigned to a control group (26 cases) or a pentobarbital-treated group (27 cases) once the diagnosis had been made and informed consent obtained. All patients were treated with the same protocol of aggressive resuscitation, prompt diagnosis and treatment of mass lesions, and intensive care, with close follow-up monitoring. The randomization was effective in producing a close match between the control and treated groups with respect to age, sex distribution, cause of injury, neurological status, intracranial lesions, prevalence of early systemic insults, midline shift, and initial ICP. Outcome was essentially the same in each group. There was no difference between groups in the incidence of elevated ICP, the duration of ICP elevation, or the response of ICP elevations to treatment. Arterial hypotension occurred in 14 patients (54%) in the treated group and only two patients (7percnt;) in the untreated group. Based on these data the authors cannot recommend the prophylactic use of pentobarbital coma in the treatment of patients with severe head injury. They also believe that its use is accompanied by significant side effects which can potentially worsen the condition of a patient with severe head injury.

Cerebral autoregulation following head injury

2001 ◽  
Vol 95 (5) ◽  
pp. 756-763 ◽  
Author(s):  
Marek Czosnyka ◽  
Piotr Smielewski ◽  
Stefan Piechnik ◽  
Luzius A. Steiner ◽  
John D. Pickard
Keyword(s):  
Head Injury ◽  
Cerebral Autoregulation ◽  
Perfusion Pressure ◽  
Content Type ◽  
Arterial Blood ◽  
Head Injured ◽  
The Mean ◽  
Injured Patients ◽  
The Relationship ◽  
Fine Print

Object. The goal of this study was to examine the relationship between cerebral autoregulation, intracranial pressure (ICP), arterial blood pressure (ABP), and cerebral perfusion pressure (CPP) after head injury by using transcranial Doppler (TCD) ultrasonography. Methods. Using ICP monitoring and TCD ultrasonography, the authors previously investigated whether the response of flow velocity (FV) in the middle cerebral artery to spontaneous variations in ABP or CPP provides reliable information about cerebral autoregulatory reserve. In the present study, this method was validated in 187 head-injured patients who were sedated and receiving mechanical ventilation. Waveforms of ICP, ABP, and FV were recorded over intervals lasting 20 to 120 minutes. Time-averaged mean FV and CPP were determined. The correlation coefficient index between FV and CPP (the mean index of autoregulation [Mx]) was calculated over 4-minute epochs and averaged for each investigation. The distribution of averaged mean FV values converged with the shape of the autoregulatory curve, indicating lower (CPP < 55 mm Hg) and upper (CPP > 105 mm Hg) thresholds of autoregulation. The relationship between the Mx and either the CPP or ABP was depicted as a U-shaped curve. Autoregulation was disturbed in the presence of intracranial hypertension (ICP ≥ 25 mm Hg) and when mean ABP was too low (ABP < 75 mm Hg) or too high (ABP > 125 mm Hg). Disturbed autoregulation (p < 0.005) and higher ICP (p < 0.005) occurred more often in patients with unfavorable outcomes than in those with favorable outcomes. Conclusions. Autoregulation not only is impaired when associated with a high ICP or low ABP, but it can also be disturbed by too high a CPP. The Mx can be used to guide intensive care therapy when CPP-oriented protocols are used.

Cerebral autoregulation following minor head injury

1997 ◽  
Vol 86 (3) ◽  
pp. 425-432 ◽  
Author(s):  
Elisabeth C. Jünger ◽  
David W. Newell ◽  
Gerald A. Grant ◽  
Anthony M. Avellino ◽  
Saadi Ghatan ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Head Injury ◽  
Cerebral Autoregulation ◽  
Minor Head Injury ◽  
Lower Blood Pressure ◽  
Content Type ◽  
Lower Blood ◽  
Head Injured ◽  
Injured Patients ◽  
Fine Print

✓ The purpose of this study was to determine whether patients with minor head injury experience impairments in cerebral autoregulation. Twenty-nine patients with minor head injuries defined by Glasgow Coma Scale (GCS) scores of 13 to 15 underwent testing of dynamic cerebral autoregulation within 48 hours of their injury using continuous transcranial Doppler velocity recordings and blood pressure recordings. Twenty-nine age-matched normal volunteers underwent autoregulation testing in the same manner to establish comparison values. The function of the autoregulatory response was assessed by the cerebral blood flow velocity response to induced rapid brief changes in arterial blood pressure and measured as the autoregulation index (ARI). Eight (28%) of the 29 patients with minor head injury demonstrated poorly functioning or absent cerebral autoregulation versus none of the controls, and this difference was highly significant (p = 0.008). A significant correlation between lower blood pressure and worse autoregulation was found by regression analysis in head-injured patients (r = 0.6, p < 0.001); however, lower blood pressure did not account for the autoregulatory impairment in all patients. Within this group of head-injured patients there was no correlation between ARI and initial GCS or 1-month Glasgow Outcome Scale scores. This study indicates that a significant number of patients with minor head injury may have impaired cerebral autoregulation and may be at increased risk for secondary ischemic neuronal damage.

Carbon dioxide reactivity, pressure autoregulation, and metabolic suppression reactivity after head injury: a transcranial Doppler study

2001 ◽  
Vol 95 (2) ◽  
pp. 222-232 ◽  
Author(s):  
Jae Hong Lee ◽  
Daniel F. Kelly ◽  
Matthias Oertel ◽  
David L. McArthur ◽  
Thomas C. Glenn ◽  
...  
Keyword(s):  
Head Injury ◽  
Scale Score ◽  
Transcranial Doppler ◽  
Brain Lesions ◽  
Content Type ◽  
Head Injured ◽  
Metabolic Suppression ◽  
Injured Patients ◽  
Pressure Autoregulation ◽  
Fine Print

Object. Contemporary management of head-injured patients is based on assumptions about CO2 reactivity, pressure autoregulation (PA), and vascular reactivity to pharmacological metabolic suppression. In this study, serial assessments of vasoreactivity of the middle cerebral artery (MCA) were performed using bilateral transcranial Doppler (TCD) ultrasonography. Methods. Twenty-eight patients (mean age 33 ± 13 years, median Glasgow Coma Scale score of 7) underwent a total of 61 testing sessions during postinjury Days 0 to 13. The CO2 reactivity (58 studies in 28 patients), PA (51 studies in 23 patients), and metabolic suppression reactivity (35 studies in 16 patients) were quantified for each cerebral hemisphere by measuring changes in MCA velocity in response to transient hyperventilation, arterial blood pressure elevation, or propofol-induced burst suppression, respectively. One or both hemispheres registered below normal vasoreactivity scores in 40%, 69%, and 97% of study sessions for CO2 reactivity, PA, and metabolic suppression reactivity (p < 0.0001), respectively. Intracranial hypertension, classified as intracranial pressure (ICP) greater than 20 mm Hg at the time of testing, was associated with global impairment of CO2 reactivity, PA, and metabolic suppression reactivity (p < 0.05). A low baseline cerebral perfusion pressure (CPP) was also predictive of impaired CO2 reactivity and PA (p < 0.01). Early postinjury hypotension or hypoxia was also associated with impaired CO2 reactivity (p < 0.05), and hemorrhagic brain lesions in or overlying the MCA territory were predictive of impaired metabolic suppression reactivity (p < 0.01). The 6-month Glasgow Outcome Scale score correlated with the overall degree of impaired vasoreactivity (p < 0.05). Conclusions. During the first 2 weeks after moderate or severe head injury, CO2 reactivity remains relatively intact, PA is variably impaired, and metabolic suppression reactivity remains severely impaired. Elevated ICP appears to affect all three components of vasoreactivity that were tested, whereas other clinical factors such as CPP, hypotensive and hypoxic insults, and hemorrhagic brain lesions have distinctly different impacts on the state of vasoreactivity. Incorporation of TCD ultrasonography—derived vasoreactivity data may facilitate more injury- and time-specific therapies for head-injured patients.

Blood pressure and intracranial pressure-volume dynamics in severe head injury: relationship with cerebral blood flow

1992 ◽  
Vol 77 (1) ◽  
pp. 15-19 ◽  
Author(s):  
Gerrit J. Bouma ◽  
J. Paul Muizelaar ◽  
Kuniaki Bandoh ◽  
Anthony Marmarou
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Cerebral Perfusion ◽  
Severe Head Injury ◽  
Perfusion Pressure ◽  
Tissue Stiffness ◽  
Content Type ◽  
Head Injured ◽  
Injured Patients ◽  
Fine Print

✓ Increased brain tissue stiffness following severe traumatic brain injury is an important factor in the development of raised intracranial pressure (ICP). However, the mechanisms involved in brain tissue stiffness are not well understood, particularly the effect of changes in systemic blood pressure. Thus, controversy exists as to the optimum management of blood pressure in severe head injury, and diverging treatment strategies have been proposed. In the present study, the effect of induced alterations in blood pressure on ICP and brain stiffness as indicated by the pressure-volume index (PVI) was studied during 58 tests of autoregulation of cerebral blood flow in 47 comatose head-injured patients. In patients with intact autoregulation mechanisms, lowering the blood pressure caused a steep increase in ICP (from 20 ± 3 to 30 ± 2 mm Hg, mean ± standard error of the mean), while raising blood pressure did not change the ICP. When autoregulation was defective, ICP varied directly with blood pressure. Accordingly, with intact autoregulation, a weak positive correlation between PVI and cerebral perfusion pressure was found; however, with defective autoregulation, the PVI was inversely related to cerebral perfusion pressure. The various blood pressure manipulations did not significantly alter the cerebral metabolic rate of oxygen, irrespective of the status of autoregulation. It is concluded that the changes in ICP can be explained by changes in cerebral blood volume due to cerebral vasoconstriction or dilatation, while the changes in PVI can be largely attributed to alterations in transmural pressure, which may or may not be attenuated by cerebral arteriolar vasoconstriction, depending on the autoregulatory status. The data indicate that a decline in blood pressure should be avoided in head-injured patients, even when baseline blood pressure is high. On the other hand, induced hypertension did not consistently reduce ICP in patients with intact autoregulation and should only be attempted after thorough assessment of the cerebrovascular status and under careful monitoring of its effects.

The favorable effect of early parenteral feeding on survival in head-injured patients

1983 ◽  
Vol 58 (6) ◽  
pp. 906-912 ◽  
Author(s):  
Robert P. Rapp ◽  
D. Pharm ◽  
Byron Young ◽  
Diana Twyman ◽  
Brack A. Bivins ◽  
...  
Keyword(s):  
Head Injury ◽  
Enteral Nutrition ◽  
Parenteral Nutrition ◽  
Favorable Effect ◽  
Controlled Clinical Trial ◽  
Content Type ◽  
Significant Difference ◽  
Head Injured ◽  
Injured Patients ◽  
Fine Print

✓ This prospective randomized controlled clinical trial compares the effects of early parenteral nutrition and traditional delayed enteral nutrition upon the outcome of head-injured patients. Thirty-eight head-injured patients were randomly assigned to receive total parenteral nutrition (TPN) or standard enteral nutrition (SEN). Clinical and nutritional data were collected on all patients until death or for 18 days of hospitalization. Survival and functional recovery were monitored in survivors for 1 year. Of the 38 patients, 18 were randomized to the SEN group and 20 to the TPN group. Demographically, the two groups of patients were similar on admission. There was no significant difference in the severity of head injury between the two groups as measured by the Glasgow Coma Scale (p = 0.52). The outcome for the two groups was quite different, with eight of the 18 SEN patients dying within 18 days of injury, whereas no patient in the TPN group died within this period (p < 0.0001). The basis for the improved survival in the TPN patients appears to be improved nutrition. The TPN patients had a more positive nitrogen balance (p < 0.06), and a higher serum albumin level and total lymphocyte count. More adequate nutritional status may have improved the patients' immunocompetence, resulting in decreased susceptibility to sepsis. The data from this study strongly support the favorable effect of early TPN on survival from head injury.

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