Neuropsychological outcome and community re-integration following traumatic brain injury: the impact of frontal and non-frontal lesions.

PRIMARY OBJECTIVE: To examine the relationship between cortical lesion location and brain injury outcome. It was hypothesized that focal frontal lesions after traumatic brain injury (TBI) would result in decreased executive and memory functioning and poor community participation outcome. RESEARCH DESIGN: Three quasi-experimental, prospective studies employed a total of 643 patients with focal frontal, fronto-temporal, non-frontal or no lesions in CT scans. METHODS AND PROCEDURES: CT scan analysis, neuropsychological assessment, the Neurobehavioural Functioning Inventory (NFI), the Community Integration Questionnaire (CIQ). MAIN RESULTS: In study 1, frontal and fronto-temporal groups performed worse in executive functioning and better in constructional ability. Study 2 found no differences in neuropsychological and community re-integration measures at 1-year follow-up. Study 3 found comparable neuropsychological test score improvement across groups over 1 year. CONCLUSIONS: Results are consistent with previous findings and document the potential for test score improvement with rehabilitation and suggest that lesion location needs to be considered when individual rehabilitation plans are being implemented in the post-acute stage of TBI.

Charges and lengths of stay for acute and inpatient rehabilitation treatment of traumatic brain injury 1990-1996.

This investigation evaluated yearly trends in charges and lengths of stay for patients with brain injury in acute care and rehabilitation settings over a 7 year period. Data was collected from 800 consecutive patients enrolled in four NIDRR Model Systems Traumatic Brain Injury programmes. Acute care daily charges showed almost routine increases, averaging nearly $550 per year. Conversely, lengths of stay generally showed a downward trend, with annual reductions averaging 2.25 days. Admission lengths of stay averaged 22-29 days between 1990-1994. Admissions averaged less than 20 days beginning in 1995, with the 1996 average of 16 days, nearly half that of the 1993 average. Between 1990-1996, average daily rehabilitation charges increased each year, with the rise averaging $83 or 7%. The rise in daily rehabilitation charges was offset by corresponding decreases in lengths of stay averaging 3.65 days or 8% annually. Increases in daily charges for brain injury rehabilitation care were roughly comparable to those for general medical care prices. However, the rate of change in acute care charges was substantially greater, with annual increases averaging 10% more than national medical care prices. The steady downward trend in lengths of stay raises serious concerns about the future availability of health care services to persons with brain injury.

A multi-center analysis of rehospitalizations five years after brain injury.

OBJECTIVE: To investigate the incidence and cause of rehospitalizations 1 and 5 years after traumatic brain injury. DESIGN: Descriptive statistics were computed in a prospective study of the cause and incidence of rehospitalizations at years 1 and 5 after injury. Analysis of variance and chi-square tests were used to identify factors relating to rehospitalization; factors included length of stay, admission and discharge functional status, payer source, medical complications, injury severity, and demographics. SETTING: Seventeen medical centers in the federally sponsored Traumatic Brain Injury Model Systems. In each setting, the continuum of care includes emergency medical services, intensive and acute medical care, inpatient rehabilitation, and a spectrum of community rehabilitation services. PARTICIPANTS: Eight hundred ninety-five rehabilitation patients admitted to acute care within 24 hours of traumatic brain injury between 1989 and 1999 were examined at 1-year follow-up. MAIN OUTCOME MEASURES: Incidence and cause of rehospitalization at 1 and 5 years after injury. RESULTS: The incidence of rehospitalization ranged from 22.9% 1 year after injury to 17.0% at 5 years after injury. At 1 year after injury, a third of the rehospitalizations were for elective reasons. At 5 years after injury, the incidence of readmissions for seizures and psychiatric difficulties and general health maintenance increased substantially. T-tests and chi-square analyses were performed on the 5-year follow-up data to compare those rehospitalized for unplanned reasons with those not rehospitalized. CONCLUSIONS: There remains a relatively high rate of rehospitalization in the long term after traumatic brain injury. The costs of rehospitalization should be considered when evaluating the long-term consequences of injury.

Factors associated with balance deficits on admission to rehabilitation after traumatic brain injury: a multicenter analysis.

OBJECTIVE: To evaluate how demographics, measures of injury severity, and acute care complications relate to sitting and standing balance in patients with traumatic brain injury (TBI). DESIGN: Multicenter analysis of consecutive admissions to designated TBI Model Systems of Care (TBIMS). SETTING: Ten National Institute for Disability and Rehabilitation Research TBI Model System centers for coordinated acute and rehabilitation care. PARTICIPANTS: 908 adults with TBI were included in the study. MAIN OUTCOME MEASURES: Sitting and standing balance were assessed within 72 hours of admission to inpatient rehabilitation. RESULTS: Age less than 50 years had a significant association with normal sitting and standing balance (P =.001 and.05, respectively). Measures of severity of traumatic brain injury, including admission Glasgow Coma Score, length of posttraumatic amnesia (PTA), length of coma, and acute care length of stay were each significantly related to impaired sitting and standing balance ratings (P <.01). Initial abnormalities in pupillary response had a significant relationship with impairment of sitting (P =.009) but not standing balance. Incidence of respiratory failure, pneumonia, soft tissue infections, and urinary tract infections were all related to impaired sitting balance (P <.01). Presence of intracranial hemorrhages did not have a significant relationship with either sitting or standing balance. Intracranial compression had a significant relationship with standing (P =.05) but not sitting balance. A discriminant function analysis, which included neuroradiological findings, injury severity, and medical complications, could not accurately predict impaired balance ratings. CONCLUSIONS: This study demonstrated that rehabilitation admission balance ratings have a significant relationship with age, multiple measures of severity, and acute care medical complications after TBI. Prospective studies are indicated to evaluate the role balance at rehabilitation admission plays in the functional prognosis of patients with TBI.

AFM imaging in solution of protein-DNA complexes formed on DNA anchored to a gold surface.

A chemical procedure for anchoring DNA molecules to gold surfaces was used to facilitate the imaging of DNA and DNA-protein complexes in buffer solution by tapping mode atomic force microscopy (TMAFM). For preparing flat gold surfaces, a novel approach was employed by evaporating small amounts of gold onto freshly cleaved mica to give flat films that were stable under aqueous buffer conditions. The thickness of the investigated films ranged from 1 to 10 nm. For typical films of 4-6 nm, which were stable under aqueous buffer conditions, the root mean square (RMS) roughness ranged between 0.25 and 0.5 nm, as measured by atomic force microscopy (AFM). This roughness is comparable to that of obtained by the template stripped gold (TSG) technique, which is widely used in scanning probe microscopy but involves more preparation steps. In order to visualize DNA and DNA-protein complexes by TMAFM, the DNA was chemisorbed to the gold surface through a linker carrying a terminal thiol group at the 5'-end of each of the DNA strands. The modified DNA fragments were bound to the gold films and imaged in buffer solution, while unmodified DNA could not be visualized. Since the DNA was not dried during the process, it can be assumed that its native conformation was retained. This mode of anchoring did not prevent interaction with proteins, as confirmed by the observation that the topology of a complex formed by adding the protein to a surface-anchored DNA was the same as that obtained by anchoring a pre-formed complex to the gold surface. We attribute this observation to the fact that the DNA is anchored to the gold surfaces only through its ends, therefore the DNA-support interaction is minimized but imaging is still possible.

Etiology and incidence of rehospitalization after traumatic brain injury: a multicenter analysis.

OBJECTIVE: To investigate incidence and etiology of rehospitalizations at 1, 2, and 3 years after traumatic brain injury. DESIGN: Descriptive statistics were computed in a prospective study of etiology and incidence of rehospitalization at years 1, 2, and 3 postinjury. Analysis of variance (ANOVA) and chi2 were used to identify factors relating to rehospitalization; factors included length of stay, admission and discharge functional status, payer source, medical complications, injury severity, and demographics. SETTING: Four medical centers in the federally sponsored Traumatic Brain Injury Model Systems. In each setting, the continuum of care includes emergency medical services, intensive and acute medical care, inpatient rehabilitation, and a spectrum of community rehabilitation services. PARTICIPANTS: Six hundred sixty-five rehabilitation patients admitted to acute care within 24 hours of traumatic brain injury between 1989 and 1996. MAIN OUTCOME MEASURES: Annual incidence and etiology of rehospitalization. RESULTS: The annual incidence of rehospitalization ranged from 20% to 22.5%. Approximately half the rehospitalizations were for elective reasons. The most common reason for rehospitalization was for orthopedic or reconstructive surgery, followed by infectious disorders and general health maintenance. After the first year, the incidence of readmissions for seizures and psychiatric difficulties increased substantially. ANOVA and chi2 analyses were performed on data from the first year postinjury. No statistically significant associations were noted between incidence and etiology of rehospitalization and: demographics; injury severity; payer source for rehabilitation; concurrent injuries; acute care and rehabilitation length of stays; discharge Functional Assessment Measure; and discharge residence (p > .05). CONCLUSIONS: There is a relatively stable but high rate of rehospitalization for at least 3 years after injury. The costs of rehospitalization should be considered when evaluating the long-term consequences of injury.

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.

Brain injury as a result of violence: preliminary findings from the traumatic brain injury model systems.

OBJECTIVES: To identify possible risk factors that may predispose individuals to violent traumatic brain injury (TBI) and to determine the effect of etiology of injury on outcomes. STUDY DESIGN: Prospective, longitudinal multicenter study. SETTING: TBI Model Systems (TBIMS) located at Wayne State University/Rehabilitation Institute of Michigan, Detroit, MI; The Institute for Rehabilitation and Research, Houston, TX; Medical College of Virginia, Richmond, VA; and Santa Clara Valley Medical Center, San Jose, CA. SUBJECTS: Individuals treated in the four TBIMS programs between 3/89 and 9/96 who met the criteria for inclusion in the TBIMS National Database and for whom the etiology was known (n=812). MAIN OUTCOME MEASURES: Functional Independence Measure, Alcohol Quantity Frequency Variability Index, Community Integration Questionnaire. RESULTS: Individuals who incur violence-related TBI tend to be male, nonwhite, unmarried, living alone, less educated, and unemployed at time of injury. They tend to have less severe brain injuries and better motor function at the time of admission to inpatient rehabilitation. At 1 year postinjury, they score lower on community integration measures; however, no difference exists in functional status. Etiology of injury was found to only play a minor role in the prediction of social and productive integration at 1 year postinjury. CONCLUSIONS: Survivors of violent and nonviolent TBI have similar functional outcomes; however, they differ in preinjury and postinjury socio-economic characteristics, injury severity, and postinjury community integration. Socio-economic factors appear to play a large role in the risk for violent injury and in community integration following injury.

Energetic components of the allosteric machinery in hemoglobin measured by hydrogen exchange.

A hydrogen exchange (HX) functional labeling method was used to study allosterically active segments in human hemoglobin (Hb) at the alpha-chain N terminus and the beta-chain C terminus. Allosterically important interactions that contact these segments were removed one or more at a time by mutation (Hbs Cowtown, Bunbury, Barcelona, Kariya), proteolysis (desArg141alpha, desHis146beta), chemical modification (N-ethylsuccinimidyl-Cys93beta), and the withdrawal of extrinsic effectors (phosphate groups, chloride). The effects of each modification on HX rate at the local and the remote position were measured in the deoxy Hb T-state and translated into change in structural free energy at each position.The removal of individual salt links destabilizes local structure by 0.4 to 0.75 kcal/mol (pH 7.4, 0 degreesC, 0.35 M ionic strength) and often produces cross-subunit effects while hemoglobin remains in the T-state. In doubly modified hemoglobins, different changes that break the same links produce identical destabilization, changes that are structurally independent show energetic additivity, and changes that intersect show energetic overlap. For the overall T-state to R-state transition and for some but not all modifications within the T-state, the summed loss in stabilization free energy measured at the two chain termini matches the total loss in allosteric free energy measured by global methods. These observations illustrate the importance of evaluating the detailed energetics and the modes of energy transfer that define the allosteric machinery.

Signal transmission between subunits in the hemoglobin T-state.

To study allosteric mechanism in hemoglobin, a hydrogen-exchange method was used to measure ligand-dependent changes in structural free energy at defined allosterically sensitive positions. When the two alpha-subunits are CN-met liganded, effects can be measured locally, within the alpha-subunit, and also remotely, within the beta-subunit, even though the quaternary structure remains in the T conformation. When the two beta-subunits are liganded, effects occur at the same positions. The effects seen are the same, independently of whether ligands occupy the alpha-chain hemes or the beta-chain hemes. Control experiments rule out modes of energy transfer other than programmed cross-subunit interaction within the T-state. Cross-subunit transfer may depend on pulling the heme trigger (moving the heme iron into the heme plane) rather than on liganding alone.

Group psychotherapy for persons with traumatic brain injury: management of frustration and substance abuse.

Residual emotional and behavioral difficulties in individuals who have sustained a traumatic brain injury (TBI) have been well documented in the literature. The issues are complex, interdependent, and often include substance abuse, depression, anxiety, chronic suicidal or homicidal ideation, poor impulse control, and significant degrees of frustration and anger. Often, preexisting psychological conditions and poor coping strategies are exacerbated by the trauma. Emotional and behavioral difficulties can interfere with the neurorehabilitation process at all levels. In acute rehabilitation, these issues have traditionally been addressed on an individual basis. However, in postacute settings, an interpersonal group format can be effectively implemented. The majority of individuals with TBI have minimal funding for long-term cognitive and behavioral remediation; often the only avenue available is support groups. This article will describe group psychotherapy models used with individuals with acute or postacute TBI within a comprehensive rehabilitation center. Interdisciplinary treatment of frustration and substance abuse and a continuum of care will be emphasized. Education, social support, skills development, interpersonal process, and cognitive-behavioral approaches will also be discussed. The psychotherapy groups focus on treatment of substance abuse and frustration management through education, social support, and development of interpersonal skills. Practical considerations of running such groups are presented.

Premorbid history and traumatic brain injury.

The literature is replete with studies investigating predictors of outcomes in traumatic brain injury. Few, however, have addressed the pre morbid life events and behaviors that may significantly impact the physical, behavioral, cognitive, and/or psychosocial and vocational status of individuals after a traumatic brain injury (TBI). Findings of studies on premorbid history are reviewed and data are presented on a sample of 82 cases on which premorbid psychosocial information, severity of initial injury and outcome status were obtained. Cases were dichotomized into groups at high risk and at low risk for TBI, based on premorbid history. High risk and low risk groups were comparable in the severity of initial injury. Outcomes were defined by the Functional Independence Measure and the Disability Rating Scale scores at 1 year after injury. No differences were found in FIMTM or DRS scores between those with and without premorbid learning disability, psychiatric history, incarcerations, arrests, academic difficulties, or substance abuse. Explanations for the lack of significant differences are discussed. Based on experience in completing this study, a screening tool incorporating documentation of a number of pre morbid factors that might impact status at outcome is presented.

Acute predictors of successful return to work 1 year after traumatic brain injury: a multicenter analysis.

OBJECTIVE: To investigate the influence of acute injury characteristics on subsequent return to work in traumatic brain injury (TBI) patients. DESIGN: Descriptive statistics were performed in a comparative study of 49 TBI patients who were competitively employed at 1-year follow-up and 83 unemployed patients. Independent t tests were then performed to examine the differences between the two groups on specific measures including the Disability Rating Scale (DRS), Functional Assessment Measure (FIM), Rancho Los Amigos Scale (RLAS), Glasgow Coma Scale (GCS), Neurobehavioral Rating Scale (NRS), and neuropsychological test results. SETTING: Four medical centers in the federally sponsored Traumatic Brain Injury Model Systems Project that provide emergency medical services, intensive and acute medical care, inpatient rehabilitation, and a spectrum of community rehabilitation services. PARTICIPANTS: Patients were selected from a national database of 245 rehabilitation inpatients admitted to acute care within 8 hours of TBI and seen at 1-year follow-up. MAIN OUTCOME MEASURE: Return to work at 1-year follow-up. RESULTS: Persons employed at 1-year follow-up obtained significantly better scores on specific acute measures of physical functioning (Admission FIM, Admission DRS, Discharge DRS), cognitive functioning (Logical Memory Delay), behavioral functioning (Admission RLAS, Discharge RLAS, NRS Excitement factor), and injury severity (Admission GCS, Highest GCS, Length of Coma, Length of PTA) than their unemployed counterparts. CONCLUSIONS: Persons obtaining better scores on certain acute measures (e.g., Admission GCS) are more likely to return to the workforce. Future research should focus on developing a standardized tool to assess a patient's ability to return to work, as well as an operational definition for successful employment.

Functional outcomes of older adults with traumatic brain injury: a prospective, multicenter analysis.

OBJECTIVE: To investigate improvement rates and medical services costs in older brain injured adults relative to younger patients. DESIGN: Descriptive statistics were computed in a prospective comparative study of 50 patients 55 years and older and 50 patients 18 to 54 years old matched for gender and injury severity (number of days in coma, admission Glasgow Coma Score, intracranial pressure). Independent t tests were performed to examine differences between the two samples on specific variables. SETTING: Five medical centers in the federally sponsored Traumatic Brain Injury Model Systems Project that provide emergency medical services, intensive and acute medical care, inpatient rehabilitation, and a spectrum of community rehabilitation services. PARTICIPANTS: Patients were selected from a national database of 531 rehabilitation inpatients admitted to acute care within 8 hours of traumatic brain injury between 1989 and 1994. MAIN OUTCOME MEASURES: Disability Rating Scale, Functional Independence Measure, Rancho Los Amigos Levels of Cognitive Functioning Scale, length of stay, acute care and rehabilitation charges, and discharge disposition. RESULTS: Older persons averaged a significantly longer rehabilitation length of stay, higher total rehabilitation charges, and a lower rate of change on functional measures. No significant differences between groups were found for acute care length of stay, daily rehabilitation charges, acute care charges (daily or total), or discharge disposition. CONCLUSIONS: Although older persons demonstrated functional changes, the cost of change was substantially higher than for younger patients, coincident with longer lengths of stay. These higher overall charges and slower rates of change may effect changes in referral and management patterns.

Measurement of protein structure change in active muscle by hydrogen-tritium exchange.

A hydrogen-tritium exchange method was developed to study protein structure changes at the molecular level in active muscle. Skinned rabbit psoas fibers mounted on a specially designed holder were selectively tritium labeled at peptide group NH sites that change from a highly protected form in rigor to an easily exchangeable, essentially random coil condition when muscle is activated. The number of sites found to show this behavior varies linearly with thick filament-thin filament overlap, and would correspond to 83 amino acids per myosin molecule in the muscle, although the experiments do not yet place these sites in any given protein. Half of the sensitive sites respond to relaxing conditions as well to activation.

Mechanisms and uses of hydrogen exchange.

Recent work has largely completed our understanding of the hydrogen-exchange chemistry of unstructured proteins and nucleic acids. Some of the high-energy structural fluctuations that determine the hydrogen-exchange behavior of native macromolecules have been explained; others remain elusive. A growing number of applications are exploiting hydrogen-exchange behavior to study difficult molecular systems and elicit otherwise inaccessible information on protein structure, dynamics and energetics.

Thermodynamic parameters from hydrogen exchange measurements.

Just as exchangeable hydrogens that are controlled by global unfolding can be used to measure thermodynamic parameters at a global level, hydrogens that are exposed to exchange by local unfolding reactions may be used to obtain locally resolved energy parameters. Results with the hemoglobin system demonstrate the ability of HX methods to locate functionally important changes in a protein and to measure the energetic contribution of each. These results offer the promise that HX measurements may be used to delineate, in terms of definable bonds and their energies and interactions, the network of interactions that Hb and other proteins use to produce their various functions.

Late-onset post-concussion symptoms after mild brain injury: the role of premorbid, injury-related, environmental, and personality factors.

The present study investigated the possible role of a number of pre- peri-, and post-traumatic factors in the experience of post-concussion syndrome (PCS). These factors included: (1) history of premorbid risk factors, (2) severity of injury, and (3) post-morbid functioning and environmental factors. Subjects were 55 persons with mild brain injury. PCS was defined in terms of the severity and impact of 'late-onset' symptoms. Pre- and peri-traumatic factors were not associated with level of PCS symptom impact. Among post-traumatic factors, only level of psychological distress was strongly associated with impact level. The results suggest the importance of psychological factors in prolonged PCS.