Pharmacotherapy for postacute traumatic brain injury: A literature review for guidance in psychological practice.

Objectives: The purpose of this review is to educate and guide the actions of rehabilitation psychologists by providing a summary of the current literature on pharmacotherapies and treatment effectiveness for the chronic sequelae associated with severe traumatic brain injury (TBI). A number of medications are reviewed for use in treating deficits in arousal, cognition, function, and other problems associated with TBI. Findings for their use in this population are summarized. Cautions, limitations, and directions for future research are discussed. Conclusions: Pharmacological management of chronic symptoms of TBI is commonplace in rehabilitation practice. Clear clinical guidelines for the use of pharmacotherapy in TBI are lacking, however, because of the few conclusive findings regarding the effectiveness of any particular agent. Rehabilitation psychologists frequently encounter patients treated with numerous medications and, therefore, need to be aware of potential effects on cognitive and functional abilities. Additionally, rehabilitation psychologists should be aware of available and empirically supported pharmacotherapies as they are in a position to comprehensively assess the patient and provide requested consultation to the treating physician concerning the patient's need for and likelihood of benefiting from various pharmacological agents. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differences in responses to norepinephrine and adenosine triphosphate in isolated, perfused mesenteric vascular beds between normotensive and spontaneously hypertensive rats

OBJECT: Although nitric oxide (NO) has been shown to play an important role in the pathophysiological process of cerebral ischemia, its contribution to the pathogenesis of traumatic brain injury (TBI) remains to be clarified. The authors investigated alterations in constitutive nitric oxide synthase (NOS) activity after TBI and the histopathological response to pharmacological manipulations of NO. METHODS: Male Sprague-Dawley rats underwent moderate (1.7-2.2 atm) parasagittal fluid-percussion brain injury. Constitutive NOS activity significantly increased within the ipsilateral parietal cerebral cortex, which is the site of histopathological vulnerability, 5 minutes after TBI occurred (234.5+/-60.2% of contralateral value [mean+/-standard error of the mean ?SEM?], p < 0.05), returned to control values by 30 minutes (114.1+/-17.4%), and was reduced at 1 day after TBI (50.5+/-13.1%, p < 0.01). The reduction in constitutive NOS activity remained for up to 7 days after TBI (31.8+/-6.0% at 3 days, p < 0.05; 20.1+/-12.7% at 7 days, p < 0.01). Pretreatment with 3-bromo-7-nitroindazole (7-NI) (25 mg/kg), a relatively specific inhibitor of neuronal NOS, significantly decreased contusion volume (1.27+/-0.17 mm3 [mean+/-SEM], p < 0.05) compared with that of control (2.52+/-0.35 mm3). However, posttreatment with 7-NI or pre- or posttreatment with nitro-L-arginine-methyl ester (L-NAME) (15 mg/kg), a nonspecific inhibitor of NOS, did not affect the contusion volume compared with that of control animals (1.87+/-0.46 mm3, 2.13+/-0.43 mm3, and 2.18+/-0.53 mm3, respectively). Posttreatment with L-arginine (1.1+/-0.3 mm3, p < 0.05), but not 3-morpholino-sydnonimine (SIN-1) (2.48+/-0.37 mm3), significantly reduced the contusion volume compared with that of control animals. CONCLUSIONS: These data indicate that constitutive NOS activity is affected after moderate parasagittal fluid percussion brain injury in a time-dependent manner. Inhibition of activated neuronal NOS and/or enhanced endothelial NOS activation may represent a potential therapeutic strategy for the treatment of TBI.     

Toward a neuropsychological model of functional disability after mild traumatic brain injury.

Discusses investigations into the nature, causes, predictors, and treatment of functional disability after minor traumatic brain injury (TBI). Distinctions among minor head injury, mild traumatic brain injury, postconcussion syndrome, and posttraumatic stress disorder (PTSD) are clarified, and methodological and information-processing issues in minor TBI are identified. Four stages of clinical research related to minor TBI are described: identification of functional scenarios (1983–1987), development of educational materials (1985–1986), ongoing research (1988–1992), and clinical applications (1992 and continuing). Finally, a neuropsychological model of functional disability after minor TBI is presented, with implications for assessment and treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A prospective study of short- and long-term outcomes after traumatic brain injury in children: Behavior and achievement.

Longitudinal behavior and achievement outcomes of traumatic brain injury (TBI) were investigated in 53 children with severe TBI, 56 children with moderate TBI, and 80 children with orthopedic injuries not involving brain insult. Measures of preinjury child and family status and of postinjury achievement skills were administered shortly after injury. Assessments were repeated 3 times across a mean follow-up interval of 4 years. Results from mixed model analysis revealed persisting sequelae of TBI. Recovery of math skills was observed in the severe TBI group but only for children from less stressed families. Social disadvantage in children with TBI predicted more adverse behavioral sequelae and less favorable changes in some outcome measures. The findings suggest that pediatric TBI has long-term effects on behavior and achievement but that postinjury progress is influenced by the family environment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Activating the posttraumatic cholinergic system for the treatment of cognitive impairment following traumatic brain injury

Cognitive impairment after traumatic brain injury (TBI) is correlated with decreased cholinergic markers of neuronal viability. The purpose of this experiment was to test the hypothesis that pharmacological activation of the muscarinic cholinergic system during the recovery period after TBI will improve cognitive performance. LU 25-109-T is a partial muscarinic M1 agonist that also acts as an antagonist at presynaptic M2 autoreceptors (thus increasing ACh release). Injured rats were injected subcutaneously daily for 15 days with either 0.0, 3.6, or 15 mumol/kg of LU 25-109-T beginning 24 h after a receiving a moderate (2.1 +/- 0.1 atm) level of central fluid percussion brain injury. Cognitive performance was assessed on days 11-15 postinjury in a Morris water maze (MWM). Injured rats treated with 15 mumol/kg, but not those treated with 3.6 mumol/kg, showed a significant improvement (p < 0.01) in MWM performance as compared with injured vehicle-treated rats. This result supports the hypotheses that a decrease in posttraumatic cholinergic neurotransmission contributes to TBI-induced cognitive deficits and that increasing cholinergic tone during the recovery period following TBI will improve cognitive performance.     

Combined therapy affects outcomes differentially after mild traumatic brain injury and secondary forebrain ischemia in rats

Muscarinic and NMDA receptors contribute to post-traumatic hypersensitivity to secondary ischemia. However, the effect of these receptor antagonists on behavior and CA1 neuronal death after traumatic brain injury (TBI) with acute (1 h after TBI) forebrain ischemia has not been systematically assessed. We examined cognitive and motor dysfunction and the relationship of behavior deficits to neuronal death in this model using muscarinic and NMDA antagonists. Three behavioral groups (n=10/group) of Wistar rats were subjected to mild TBI and 6 min of forebrain ischemia imposed 1 h after TBI with 45 days survival. Motor and spatial memory performance were assessed using the rotarod task and Morris water maze. Seven additional groups (n=6/group) were evaluated only for CA1 death after 7 days survival following sham, individual or combined injury with and without drug treatments. Rats were given 0.3 mg/kg MK-801 (M) and 1.0 mg/kg scopolamine (S) alone or combined (M-S) before or 45 min after TBI. Rotarod performance was tested at days 1-5 and maze performance on days 11-15 and 40-44 after M-S treatment. The 7-day studies showed M-S treatment (p<0.01) reduced CA1 neuronal death better than either S or M alone. Behavioral groups had inadvertent post-ischemic hypothermia that decreased CA1 death and likely influenced behavioral morbidity. M-S given before TBI (p<0.01) decreased memory deficits on day 15, while M-S treatment given after TBI was ineffective. Unexpectedly, M-S treatment before or after TBI produced transient motor deficits (p<0. 01). Memory improvement occurred independent of CA1 death.     

Symptomatic Helicobacter pylori infection in a neurorehabilitation population

Helicobacter pylori infection has been associated with acute and chronic gastritis, peptic ulcer disease, hypertension, and possibly gastric carcinoma and coronary artery disease. The prevalence of H pylori infection is more than 50% in people older than 60 years; however, the prevalence is not known in patients with traumatic brain injury (TBI) or cerebrovascular accidents who are treated in inpatient rehabilitation services. This report describes 10 symptomatic patients with TBI and strokes who were diagnosed with and treated for H pylori infection after transfer to a neurorehabilitation unit during a 12-month period. Physicians who treat patients with TBI and stroke need to be aware of the possible high prevalence of H pylori infection in their patients. The authors recommend H pylori screening for symptomatic patients in neurorehabilitation units and providing definitive treatment to prevent recurrent gastrointestinal bleeding, peptic ulcer disease, and gastritis.     

Use of family focused therapy in rehabilitation for veterans with traumatic brain injury.

Objective: Military personnel returning from Iraq and Afghanistan with traumatic brain injury (TBI) present with a complex array of stressors encountered during combat as well as upon re-entry, often with additional physical and mental health comorbidities. This requires an intensive approach to treatment that includes family intervention as a part of rehabilitation. There is a small but growing literature addressing the needs of families when a family member has sustained a TBI. An established treatment intervention for individuals with serious mental illness, such as family focused therapy (FFT), is uniquely suited to address the complexity of issues presented by returning military personnel, and may be adapted for moderate to severe TBI populations. In this article, we discuss the rationale for adapting this family intervention for this population and present a case vignette illustrating adaptations for TBI. Conclusions: The adaptation of an existing family intervention for a chronic condition that focuses on enhancing both individual and family functioning is a useful starting point. With further research to modify FFT for this unique population and establish feasibility, this approach may supplement existing models of family intervention. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Incidence of chronic pain following traumatic brain injury

OBJECTIVE: To index the frequency of reported chronic pain in patients with traumatic brain injury (TBI). DESIGN: A case series study was conducted on consecutive patients with TBI. SETTING: TBI patients were recruited from an adult tertiary care center brain injury clinic. PATIENTS: A consecutive sample of 132 patients who attended a brain injury rehabilitation center after TBI. The sample included 53 mild and 79 moderate/severe TBI patients. OUTCOME MEASURES: Patients were administered a protocol that indexed pain site, frequency, severity, and duration. RESULTS: Chronic pain was reported by 58% of mild TBI and 52% of moderate/severe TBI patients. Headaches were the most commonly reported pain problem. Chronic headaches were reported by 47% of mild TBI patients and 34% of moderate/ severe TBI patients. Neck/shoulder, back, upper limb, and lower limb pain were reported similarly by mild and moderate/severe TBI patients. CONCLUSIONS: Findings indicate that chronic pain is a significant problem in mild and moderate/severe TBI patients. More effective diagnosis of TBI patients with chronic pain may facilitate rehabilitation of these patients.     

Alcohol abuse and traumatic brain injury: effect on event-related potentials

OBJECTIVE: To examine the individual and combined impact that traumatic brain injury (TBI) and heavy social use of alcohol have on electrophysiologic correlates of working memory and evaluation of task-relevant information. DESIGN: Case-control study. SETTING: University hospital brain injury rehabilitation unit. PARTICIPANTS: Forty male volunteers divided into four groups on the basis of their history of TBI and alcohol intake. Subjects with TBI had experienced a severe closed head injury at least 1 year before testing. MAIN OUTCOME MEASURE: Event-related potentials (ERPs) and neuropsychometric tests. RESULTS: Groups showed no significant differences in average age or neuropsychological tests. TBI groups did not differ in time postinjury or on severity measures. Alcohol use measures were significantly greater in the two alcohol groups. N200 latency and P300 amplitude were impaired in heavy social drinkers and in nondrinking subjects with TBI relative to controls, but were significantly impaired in subjects with TBI who were also heavy social drinkers. CONCLUSION: The results indicate that although alcohol use and TBI independently produce mile alterations in some aspects of late ERP components, the ERP changes are significantly greater when alcohol use and TBI are combined. This study provides evidence that heavy social drinking after TBI has a measurable impact on electrophysiologic correlates of cognition.     

Care continuum in traumatic brain injury rehabilitation.

Discusses the range of services needed in traumatic brain injury (TBI) rehabilitation within the context of a services continuum owing to the nature of the recovery process. The TBI care continuum includes treatment during the following phases: injury onset, trauma center and emergency care, neurosurgery unit and acute hospitalization, coma stimulation, nursing home and long-term care programs, transitional living centers, day treatment and outpatient rehabilitation, supervised independent living center and support services, and vocational rehabilitation services. Obstacles to care continuity include funding concerns, lack of knowledge about TBI, the complex nature of TBI, and program accessibility issues. It is noted that major legislative, educational, and outreach efforts are under way to overcome these barriers to services provision. A comment by J. E. Sargent follows. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Extremity fractures in the patient with a traumatic brain injury

Extremity fractures are common in patients with traumatic brain injuries (TBIs). These injuries are often inadequately treated and occasionally are completely missed due to the unique problems inherent to the TBI patient. However, appropriate evaluation of the TBI patient allows prompt diagnosis and optimal treatment of extremity fractures. The increased survival rate of these patients has resulted in a greater emphasis on minimizing dysfunction and disability, especially that due to concomitant orthopaedic trauma. Advances in anesthestic technique permit earlier operative fixation of extremity fractures. Most injuries, particularly those in the lower extremity, require operative stabilization to allow early mobilization and rehabilitation. Upper extremity fractures are often associated with peripheral nerve injuries. Heterotopic ossification is common, especially about the elbow and hip. Contrary to prevalent belief, fracture healing is not necessarily accelerated in the TBI patient; hypertrophic callus, myositis ossificans, and heterotopic ossification occur frequently and are often misperceived as accelerated healing.     

The Latina Breast Cancer Control Study, year one: factors predicting screening mammography utilization by urban Latina women in Massachusetts

The mechanisms underlying secondary or delayed cell death following traumatic brain injury (TBI) are poorly understood. Recent evidence from experimental models of TBI suggest that diffuse and widespread neuronal damage and loss is progressive and prolonged for months to years after the initial insult in selectively vulnerable regions of the cortex, hippocampus, thalamus, striatum, and subcortical nuclei. The development of new neuropathological and molecular techniques has generated new insights into the cellular and molecular sequelae of brain trauma. This paper will review the literature suggesting that alterations in intracellular calcium with resulting changes in gene expression, activation of reactive oxygen species (ROS), activation of intracellular proteases (calpains), expression of neurotrophic factors, and activation of cell death genes (apoptosis) may play a role in mediating delayed cell death after trauma. Recent data suggesting that TBI should be considered as both an inflammatory and/or a neurodegenerative disease is also presented. Further research concerning the complex molecular and neuropathological cascades following brain trauma should be conducted, as novel therapeutic strategies continue to be developed.     

Beery-Buktenica Developmental Test of Visual-Motor Integration performance in children with traumatic brain injury and attention-deficit/hyperactivity disorder.

Evaluation of visuoconstructional abilities is a common part of clinical neuropsychological assessment, and the Beery-Buktenica Developmental Test of Visual-Motor Integration (VMI; K. E. Beery & N. A. Beery, 2004) is often used for this purpose. However, few studies have examined its psychometric properties when used to assess children and adolescents with traumatic brain injury (TBI) or attention-deficit/hyperactivity disorder (ADHD), even though these are among the most common acquired and neurodevelopmental forms of brain dysfunction in children. This study examined the validity of VMI scores in 123 children with TBI and 65 with ADHD. The TBI and ADHD groups performed significantly worse than the standardization sample, obtaining VMI mean scores of 87.2 (SD = 13.7) and 93.5 (SD = 11.27). Previous research has noted decrements in visuoconstructional abilities in TBI but relative sparing in ADHD. To examine the criterion validity of VMI scores, the authors therefore compared these 2 groups. As anticipated, the TBI group performed significantly worse than the ADHD group, but receiver operator characteristic analysis indicated that VMI scores were poor at discriminating between groups. Nonetheless, convergent validity evidence supported interpretation of VMI scores as measuring perceptual organization in both groups. In particular, principal components analysis indicated that VMI total scores loaded with perceptual organization tests from the Wechsler Intelligence Scale for Children, 3rd ed. (WISC-III; D. Wechsler, 1997), and its highest correlation was with the WISC-III Perceptual Organization Index. Also, the VMI correlated significantly with the Grooved Pegboard test for the group with TBI. These findings suggest that VMI scores are sensitive to visuoconstructional and motor deficits in children with developmental and acquired brain dysfunction. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Soluble adhesion molecules in CSF are increased in children with severe head injury

Leukocyte-endothelial adhesion molecules, critical to the development of acute inflammation, are expressed in brain as part of the acute inflammatory response to traumatic brain injury (TBI). We measured the concentrations of the adhesion molecules P-selectin, ICAM-1, E-selectin, L-selectin, and VCAM-1 in ventricular cerebrospinal fluid (CSF) from children with severe TBI (Glasgow coma score < 8) and compared these findings with those from children with bacterial meningitis. P-selectin, an adhesion molecule associated with ischemia/reperfusion, was increased in children with TBI versus meningitis and control. Univariate and multivariate regression analyses demonstrated associations between CSF P-selectin and child abuse and age of < 4 years, and a significant, independent association between CSF intercellular adhesion molecule-1 (ICAM-1) and child abuse. These results are consistent with a specific acute inflammatory component to TBI in children. Future studies of secondary injury mechanisms and therapy after TBI should assess on the roles of P-selectin and ICAM-1 in injury and repair processes in brain after TBI.     

Increased serum levels of macrophage colony-stimulating factor (M-CSF) in alpha- and beta-thalassaemia syndromes: correlation with anaemia and monocyte activation

The Glasgow Coma Scale (GCS) is routinely used in the acute care setting after traumatic brain injury (TBI) to guide decisions in triage, based on its ability to predict morbidity and mortality. Although the GCS has been previously demonstrated to predict mortality, efficacy in prediction of functional outcome has not been established. The purpose of this study was to assess the value of the acute GCS in predicting functional outcome in survivors of TBI. This study used the Multicenter National Institute on Disability and Rehabilitation Research TBI Model Systems database of 501 patients who had received acute medical care and inpatient rehabilitation within a coordinated neurotrauma program for treatment of TBI. Initial and lowest 24 hr GCS scores were correlated with the following outcome measures: the Disability Rating Scale (DRS), Rancho Los Amigos Levels of Cognitive Functioning Scale (LCFS), and cognitive and motor components of the Functional Independence Measure (FIM(SM)-COG and FIM(SM)-M). Outcome data were collected at admission to and discharge from the inpatient TBI rehabilitation unit. Correlation analysis revealed only modest, but statistically significant, relationships between initial and lowest GCS scores and outcome variables. Initial and lowest GCS score comparison with outcome demonstrated the following correlation coefficients: admission DRS, -0.25 and -0.28; discharge DRS, -0.24 and -0.24; admission LCFS, 0.31 and 0.33; discharge LCFS, 0.27 and 0.25; admission FIM-COG, 0.36 and 0.37; discharge FIM-COG, 0.23 and 0.23; admission FIM-M, 0.31 and 0.31; discharge FIM-M, 0.25 and 0.21. The GCS as a single variable may have limited value as a predictor of functional outcome.     

Response to "Programming for occupational outcomes following traumatic brain injury".

Responds to an article Programming for occupational outcomes following traumatic brain injury by William J. Haffey and Frank D. Lewis (see record 1990-02644-001). The dramatic upsurge in attention paid in the past 10 years to the rehabilitation of persons with traumatic brain injury (TBI) has resulted in an accelerating proliferation of treatment programs purporting to apply specialized techniques that will "remediate" the cognitive and behavioral deficits of this population, with implicit or explicit promises of functional gain. Specifically, given the epidemiologic realities of the TBI population, returning to work is a major goal of the rehabilitation process. With the movement of TBI rehabilitation programs out of academic medical centers and into the private sector, increasing numbers of zealous professionals are ready to apply a variety of treatment approaches, thousands of families are eager to find the "best" program, and more and more nervous insurers are both mandated and requested to pay for expensive treatments that hold out the promise of return to work. Unfortunately, the field of TBI rehabilitation has been more eager to provide services than critically evaluate the effectiveness of those services. The first major contribution of the Haffey and Lewis article is to call attention both to the paucity of posttreatment vocational outcome studies, and to emphasize the need to evaluate the success of various models of vocational rehabilitation. The second major contribution of the Haffey and Lewis article is their offering of a concrete example of one approach to systematic programming for vocational outcomes. Our experience is that vocational potential—and therefore reasonable goals—only emerge as the product of a process that involves testing the client's capacities not just cognitively and behaviorally, but also his or her capacity to conform to a series of messages and procedures that will determine the viability of any given vocational plan. Readers should take from the concrete programming suggestions in this article the laudable objective of making vocational goals, obstacles, and critical events specific and public, but beware of mechanically applying the approach without appreciating the complex subtleties in enabling a brain-injured person to become a productive worker. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The validity of the Katz Adjustment Scale among people with traumatic brain injury.

Deficits in self- and social awareness can impair adjustment following traumatic brain injury (TBI) and draw into question the accuracy of self-report measures of adjustment. This study evaluates the validity of Katz Adjustment Scale (KAS) factor components identified by R. J. Fabiano and D. A. Goran (1992). The KAS is an observer rating scale often used to assess the social adjustment of people with traumatic brain injury. The responses of 105 individuals with TBI to the Symptom Checklist 90—Revised (SCL-90–R; L. R. Derogatis, 1983), a self-report measure of distress, were correlated with observer ratings on the KAS. Results support the use of observer ratings and self-report to assess adjustment and social behavior following TBI. Each contributes valuable information that can guide treatment and enhance adaptive functioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Structured habituation training for movement provoked vertigo after severe traumatic brain injury: a single-case experiment

The purpose of this study was to evaluate the effect of structured habituation training (HT) for movement provoked vertigo (PV) secondary to unilateral peripheral hypofunction in a 16 year old patient who had sustained a severe TBI. Treatment of PV with severe TBI patients can be quite different from other patients with vestibular deficits because of the physiological, behavioural and cognitive sequelae of brain trauma. A single-subject experimental paradigm using an ABA protocol was used to assess efficacy of HT. The data were submitted to C statistic analysis. The transformed data were submitted to combined visual and statistical analysis by the celeration line with a directional one-tailed test and the two-standard deviation band method. Significant change in duration from sitting to supine without triggering vertigo was found between baseline phase (A) and structured HT phase (B) and was maintained for 1 month after the end of treatment. This single-case experiment demonstrates successful structured HT for PV for a 16 year old severe TBI patient. Important clinical decisions (time of introduction of treatment, type of activity, pacing, frequency, intensity, repetition, support and education) necessary to achieve optimal resolution of PV with HT in severe TBI patients are discussed.     

Attentional skills following traumatic brain injury in childhood: a componential analysis

Recent research has documented residual deficits in attention following traumatic brain injury in childhood. The present study aimed to investigate whether such deficits are global, or affect specific components of attention differentially. Four attentional domains were examined using a newly developed test of attention, the Test of Everyday Attention for Children: sustained attention, focussed attention, divided attention, and response inhibition. Eighteen children with a history of traumatic brain injury, aged between 8 and 14 years, and 18 non-injured matched controls participated in the study. Results indicated that attentional skills may be differentially impaired after TBI, with children who have sustained moderate-to-severe TBI exhibiting significant deficits for sustained and divided attention, and response inhibition, but relatively intact focussed attention.