Brent E. Masel

Consensus guidelines on screening for hypopituitarism following traumatic brain injury

Primary objective: The goal of this consensus statement is to increase awareness among endocrinologists and physicians treating patients with traumatic brain injury (TBI) of the incidence and risks of hypopituitarism among patients with TBI. Rationale: TBI poses significant risk to the pituitary gland, leading to elevated risks of diabetes, hypopituitarism and other endocrinopathies. Signs and symptoms associated with hypopituitarism often mimic the sequellae of TBI, although the severity of symptoms is not necessarily related to the severity of the injury. Patients with TBI-induced hypopituitarism may benefit both physically and psychologically from appropriate hormone replacement therapy (HRT). Participants at this unique consensus meeting attempted to define and spearhead an approach to increase awareness of the risks of TBI-induced endocrinopathies, in particular growth hormone deficiency (GHD), and to outline necessary and practical objectives for managing this condition. Recommendations: Systematic screening of pituitary function is recommended for all patients with moderate-to-severe TBI at risk of developing pituitary deficits. Patients with hypopituitarism benefit from appropriate hormonal replacement and prospects for rehabilitation of patients with TBI-induced hypopituitarism may be enhanced by appropriate HRT. Further exploration of this possibility requires: (1) active collaboration between divisions of endocrinology and rehabilitation at the local level to perform a screening of pituitary function in patients after TBI, (2) creation of a consultancy service by endocrine societies for use by rehabilitation centres, (3) development of continuing medical education (CME) programmes that can be offered as crossover training to the physicians who manage the care of patients with TBIs, (4) targeting of patient organizations with educational information for dissemination to patients and their families, (5) continued efforts to more clearly define the population at greatest risk of TBI-induced hypopituitarism and (6) monitor results of efficacy studies as they become available to evaluate whether and how much replacement therapy can improve the symptoms of individuals with TBI-induced hypopituitarism.

Task performance in virtual environments used for cognitive rehabilitation after traumatic brain injury

OBJECTIVE This report describes a reliability study using a prototype computer-simulated virtual environment to assess basic daily living skills in a sample of persons with traumatic brain injury (TBI). The benefits of using virtual reality in training for situations where safety is a factor have been established in defense and industry, but have not been demonstrated in rehabilitation. SUBJECTS Thirty subjects with TBI receiving comprehensive rehabilitation services at a residential facility. METHODS An immersive virtual kitchen was developed in which a meal preparation task involving multiple steps could be performed. The prototype was tested using subjects who completed the task twice within 7 days. RESULTS The stability of performance was estimated using intraclass correlation coefficients (ICCs). The ICC value for total performance based on all steps involved in the meal preparation task was .73. When three items with low variance were removed the ICC improved to .81. Little evidence of vestibular optical side-effects was noted in the subjects tested. CONCLUSION Adequate initial reliability exists to continue development of the environment as an assessment and training prototype for persons with brain injury.

Effect of Growth Hormone Replacement Therapy on Cognition after Traumatic Brain Injury

Traumatic brain injury (TBI) is a major public health issue, and yet medical science has little to offer for the persistent symptoms that prevent many of these individuals from fully re-entering society. Post-traumatic hypopituitarism, and specifically growth hormone deficiency (GHD), has been found in a large percentage of individuals with chronic moderate to severe TBI. Presently, there are no published treatment studies of hormone replacement in this population. In this study, 83 subjects with chronic TBI were screened for hypopituitarism. Forty-two subjects were found to have either GHD or GH insufficiency (GHI), of which 23 agreed to be randomized to either a year of GH replacement or placebo. All subjects completed the study with no untoward side effects from treatment. A battery of neuropsychological tests and functional measures were administered before and after treatment. Improvement was seen on the following tests: Dominant Hand Finger Tapping Test, Wechsler Adult Intelligence Scale III-Information Processing Speed Index, California Verbal Learning Test II, and the Wisconsin Card Sorting Test (executive functioning). The findings of this pilot study provide preliminary evidence suggesting that some of the cognitive impairments observed in persons who are GHD/GHI after TBI may be partially reversible with appropriate GH replacement therapy.

Virtual reality in the assessment of selected cognitive function after brain injury

Zhang L, Abreu BC, Masel B, Scheibel RS, Christiansen CH, Huddleston N, Ottenbacher KJ: Virtual reality in the assessment of selected cognitive function after brain injury. Am J Phys Med Rehabil 2001;80:597–604. ObjectiveTo assess selected cognitive functions of persons with traumatic brain injury using a computer-simulated virtual reality environment. Study DesignA computer-simulated virtual kitchen was used to assess the ability of 30 patients with brain injury and 30 volunteers without brain injury to process and sequence information. The overall assessment score was based on the number of correct responses and the time needed to complete daily living tasks. Identical daily living tasks were tested and scored in participants with and without brain injury. Each subject was evaluated twice within 7 to 10 days. A total of 30 tasks were categorized as follows: information processing, problem solving, logical sequencing, and speed of responding. ResultsPersons with brain injuries consistently demonstrated a significant decrease in the ability to process information (P = 0.04–0.01), identify logical sequencing (P = 0.04–0.01), and complete the overall assessment (P < 0.01), compared with volunteers without brain injury. The time needed to process tasks, representing speed of cognitive responding, was also significantly different between the two groups (P < 0.01). ConclusionA computer-generated virtual reality environment represents a reproducible tool to assess selected cognitive functions and can be used as a supplement to traditional rehabilitation assessment in persons with acquired brain injury.

Comparison of 650 mg aspirin and 1,000 mg acetaminophen with each other, and with placebo in moderately severe headache

Two-hundred-sixty-nine otherwise healthy persons experiencing periodic, moderately severe headache of a type that had previously responded to nonprescription medications completed this randomized, parallel, double-blind study. The three demographically similar subgroups took either 1,000 mg acetaminophen, 650 mg aspirin, or an identical placebo, for headache. Headache intensity and relief scores over the following six hours were obtained and assessed by sums of pain intensity difference and values of pain relief scores analyses. Responses for the group, and for the subgroup with tension headaches (107 persons) showed no differences between the effects of the active medications. The effects of each medication were strongly superior to placebo. There were no differences in side effects among the three treatment modalities. In persons experiencing tension-vascular headaches (162), only aspirin, at two hours, was superior to placebo, but direct comparison with acetaminophen suggested no real difference. Acetaminophen (1,000 mg) and aspirin (650 mg) are clinically similar in treating the headaches for which they are commonly taken. Recommendations for their use in treating headache should be based on individual patient suitability and on cost factors.

Anterior hypopituitarism following traumatic brain injury

Primary objectives. To review evidence that there exists a substantial sub-population of patients with endocrine disorders as a result of traumatic brain injury (TBI) and to underscore the importance of screening patients with TBI considered most at risk for hypopituitarism with the goal of attaining beneficial effects in terms of morbidity and quality of life. Design and methods. Reviewed recent literature regarding the frequency of TBI-induced hypopituitarism. Main outcomes and results. Studies by Kelly DF, Gaw Gonzalo IT, Cohan P, et al. Hypopituitarism following traumatic brain injury and aneurysmal subarachnoid hemorrhage: A preliminary report. Journal of Neurosurgery 2000;93:743–751, Lieberman SA, Oberoi AL, Gilkison CR, et al. Prevalence of neuroendocrine dysfunction in patients recovering from traumatic brain injury. Journal of Clinical Endocrinology and Metabolism 2001;86:2752–2756 and Aimaretti G, Ambrosio MR, Di Somma C, et al. Traumatic brain injury and subarachnoid haemorrhage are conditions at high risk for hypopituitarism. Screening study at 3 months after the brain injury, In press., found that about one-half to one-third of patients with TBI had anterior pituitary hormone deficiencies, including growth hormone (GH) deficiency in 15–21%, and subtle deficiencies in thyroid, adrenal and gonadal axes. One or more hormonal deficiencies produce diverse physical and psychological symptoms that may mimic symptoms attributed to brain trauma and may impair rehabilitation. A more general concern is the fact that hypopituitarism increases the risk of significant morbidity (e.g. ischaemic heart disease) and mortality (shortened life span). Conclusions. To attain maximal improvement in mental and physical functioning as well as in quality of life for victims of TBI, it is crucial that anterior pituitary hormonal function be assessed. Appropriate hormone replacement therapy for those patients with both TBI and TBI-induced pituitary function impairment could, for the first time, allow treatment and correction of underlying causes of TBI sequelae rather than merely symptomatic treatment.

Comparison of the Community Integration Questionnaire, the Craig Handicap Assessment and Reporting Technique, and the Disability Rating Scale in traumatic brain injury.

Objective:To examine the concurrent validity of the Community Integration Questionnaire (CIQ) in assessing outcomes in traumatic brain injury (TBI) by comparing it with two widely used and well-validated measurements of rehabilitation outcome. Design:A retrospective relational study of the concurrent validity of the CIQ, Craig Handicap Assessment and Reporting Technique (CHART), and Disability Rating Scale (DRS). Setting:A postacute rehabilitation facility. Participants:Seventy patients with a medical diagnosis of TBI admitted between April 1996 and October 1998 participated in the study. Results:CIQ and CHART provide ratings that are similar in several areas to those provided by the DRS. Correlation (r) among total scores and subscales for all three instruments ranged from 0.021 to 0.671 (P < .01). Correlation between CIQ and CHART is stronger than that between CIQ and DRS or between CHART and DRS, and the correlation between CHART and DRS is stronger than that between CIQ and DRS. Conclusion:The CIQ appears to be the most appropriate instrument in quantifying rehabilitation outcome in patients with TBI at the participatory (handicap) level. The findings of this study can help clinicians gain a greater understanding of the nature, redundancy, and gaps among functional outcome measures. Monitoring outcomes can also help clinicians better understand the effectiveness of interventions.

Pituitary dysfunction after traumatic brain injury: a clinical and pathophysiological approach.

Traumatic brain injury (TBI) is a growing public health problem worldwide and is a leading cause of death and disability. The causes of TBI include motor vehicle accidents, which are the most common cause, falls, acts of violence, sports-related head traumas, and war accidents including blast-related brain injuries. Recently, pituitary dysfunction has also been described in boxers and kickboxers. Neuroendocrine dysfunction due to TBI was described for the first time in 1918. Only case reports and small case series were reported until 2000, but since then pituitary function in TBI victims has been investigated in more detail. The frequency of hypopituitarism after TBI varies widely among different studies (15-50% of the patients with TBI in most studies). The estimates of persistent hypopituitarism decrease to 12% if repeated testing is applied. GH is the most common hormone lost after TBI, followed by ACTH, gonadotropins (FSH and LH), and TSH. The underlying mechanisms responsible for pituitary dysfunction after TBI are not entirely clear; however, recent studies have shown that genetic predisposition and autoimmunity may have a role. Hypopituitarism after TBI may have a negative impact on the pace or degree of functional recovery and cognition. What is not clear is whether treatment of hypopituitarism has a beneficial effect on specific function. In this review, the current data related to anterior pituitary dysfunction after TBI in adult patients are updated, and guidelines for the diagnosis, follow-up strategies, and therapeutic approaches are reported.

Endurance training and cardiorespiratory conditioning after traumatic brain injury

ObjectiveTo examine the importance of cardiorespiratory conditioning after traumatic brain injury (TBI) and provide recommendations for patients recovering from TBI. MethodReview of literature assessing the effectiveness of endurance training programs. Main outcomes and resultsA sedentary lifestyle and lack of endurance are common characteristics of individuals with TBI who have a reduction in peak aerobic capacity of 25% to 30% compared with healthy sedentary persons. Increased physical activity and exercise training improves cardiorespiratory fitness in many populations with physical and cognitive impairments. Therefore, increasing the endurance and cardiorespiratory fitness of persons with TBI would seem to have important health implications. However, review of the TBI literature reveals that there have been few well-designed, well-controlled studies of physiologic and psychological adaptations of fitness training. Also lacking are long-term follow-up studies of persons with TBI. ConclusionsAssessing endurance capacity and cardiorespiratory fitness early in the TBI rehabilitation process merits consideration as a standard of care by professional rehabilitation societies. Also, providing effective, safe, and accessible training modalities would seem to be an important consideration for persons with TBI, given the mobility impairments many possess. Long-term follow-up studies are needed to assess the effectiveness of cardiorespiratory training programs on overall morbidity and mortality.

Aerobic capacity and growth hormone deficiency after traumatic brain injury

CONTEXT GH deficiency occurs in approximately 20% of all individuals who suffer from a moderate to severe traumatic brain injury. OBJECTIVE This study determined whether GH deficiency secondary to traumatic brain injury had an effect on aerobic capacity. DESIGN Subjects were screened for GH deficiency by the glucagon stimulation test and performed a maximal treadmill exercise test. SETTING Patients were studied in the postacute recovery phase after traumatic brain injury. PARTICIPANTS Thirty-five individuals were studied. Groups were formed as follows: normal GH axis, greater than 8 ng/ml response (n = 12); insufficient, GH 3-8 ng/ml response (n = 11); and deficient, less than 3 ng/ml response (n = 12). INTERVENTION There was no intervention. MAIN OUTCOME MEASURE Aerobic capacity was assessed by measuring expired gases during a graded treadmill exercise test. One-way and two-way ANOVAs were carried out on all peak and submaximal cardiorespiratory variables, respectively. Appropriate post hoc comparisons followed as necessary. RESULTS Significantly higher peak oxygen consumption was found in traumatic brain injury subjects with GH normal vs. GH insufficient and deficient [26.4 +/- 6.9, 20.8 +/- 4.6, and 19.7 +/- 5.0, respectively (P < 0.05)]. Submaximal oxygen consumption was significantly higher in the GH normal group. All other variables were statistically similar. CONCLUSIONS This study shows that individuals with traumatic brain injury with normal GH secretion have below normal aerobic capacity and those patients who have GH insufficiency/deficiency are further deconditioned. Studies of GH replacement in these subjects should be conducted to assess whether GH therapy can improve cardiorespiratory fitness and prevent secondary disability.