Manifesto for the current understanding and management of traumatic brain injury-induced hypopituitarism.

Traumatic brain injury (TBI)-induced hypopituitarism remains a relevant medical problem, because it may affect a significant proportion of the population. In the last decade important studies have been published investigating pituitary dysfunction after TBI. Recently, a group of experts gathered and revisited the topic of TBI-induced hypopituitarism. During the 2-day meeting, the main issues of this topic were presented and discussed, and current understanding and management of TBI-induced hypopituitarism are summarized here.

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.

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.

Regional CBF in chronic stable TBI treated with hyperbaric oxygen.

To investigate whether Hyperbaric Oxygen Therapy (HBO2) could improve neurologic deficits and regional cerebral blood flow (rCBF) in chronic traumatic brain injuries (TBI), the authors employed a nonrandomized control pilot trial. Five subjects, at least three years post head injury, received HBO2. Five head injured controls (HIC) were matched for age, sex, and type of injury. Five healthy subjects served as normal controls. Sixty-eight normal volunteers comprised a reference data bank against which to compare SPECT brain scans. HBO2 subjects received 120 HBO2 in blocks of 80 and 40 treatments with an interval five-month break. Normal controls underwent a single SPECT brain scan, HBO2, and repeat SPECT battery. TBI subjects were evaluated by neurologic, neuropsychometric, exercise testing, and pre and post study MRIs, or CT scans if MRI was contraindicated. Statistical Parametric Mapping was applied to SPECT scans for rCBF analysis. There were no significant objective changes in neurologic, neuropsychometric, exercise testing, MRIs, or rCBF. In this small pilot study, HBO2 did not effect clinical or regional cerebral blood flow improvement in TBI subjects.

Ambulatory efficiency in persons with acquired brain injury after a rehabilitation intervention.

OBJECTIVE: the purpose was to assess changes in cardiorespiratory responses to treadmill ambulation in a sample of patients with acquired brain injury. RESEARCH DESIGN: a repeated measures, pre-test post-test design examined differences between submaximal and peak responses at admission and discharge. METHODS AND PROCEDURES: forty individuals (29 male, 11 female) were studied. Subjects performed an ambulatory treadmill test during which heart rate (EKG) and oxygen consumption (VO(2)) were monitored continuously. Total ambulation time (TAT) was also recorded. RESULTS: TAT increased from 10.3 (SD 3.1) minutes to 13.6 (SD 3.5) minutes (p < 0.01). Peak HR did not change (168 (SD 20) bpm vs. 167 (SD 21 bpm)) nor did peak VO(2) (23.5 (SD 6.6)ml/min/kg vs. 24.3 (SD 6.4)ml/min/kg; p = 0.09). However, both sub-maximal HR and VO(2) decreased (p < 0.05) between 2-12 minutes when most subjects were still capable of ambulating. CONCLUSIONS: the results suggest an improvement in both aerobic capacity and movement efficiency. Further controlled studies will be necessary to distinguish between cardiorespiratory and neuromuscular adaptations. The changes observed should allow for greater community participation and functional independence after discharge.

Excessive daytime sleepiness in adults with brain injuries.

OBJECTIVES: To determine the prevalence, demographics, and causes of excessive daytime sleepiness in adults with brain injuries after the acute phase of their injury and to investigate the relations between self-report and objective measures of hypersomnolence. DESIGN: A case series of patients enrolled consecutively into a residential rehabilitation program. SETTING: University sleep laboratory, live-in rehabilitation center. PATIENTS: Adults with brain injuries (n = 71); mean time +/- standard deviation from injury to study, 38 +/- 60 months. INTERVENTIONS: A polysomnogram and Multiple Sleep Latency Test (MSLT) were performed in each subject. Each subject also completed the Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI) questionnaires. MAIN OUTCOME MEASURES: Sleep patterns, by polysomnogram. Daytime hypersomnolence, diagnosed by mean sleep latency on the MSLT

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

OBJECTIVE: To assess selected cognitive functions of persons with traumatic brain injury using a computer-simulated virtual reality environment. STUDY DESIGN: A 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. RESULTS: Persons 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). CONCLUSION: A 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.

Prevalence of neuroendocrine dysfunction in patients recovering from traumatic brain injury.

Although hypopituitarism is a known complication of head injury, it may be underrecognized due to its subtle clinical manifestations. The nonspecific symptoms may be masked by and may contribute to the physical and psychological sequelae of brain trauma. This study examines the prevalence of neuroendocrine abnormalities in patients rehabilitating from traumatic brain injury. Seventy adults (mean age, 31.5 +/- 1.1 yr; range, 18--58; 46 men and 24 women) with traumatic brain injury an average of 49 +/- 8 months before the study (median, 13 months) underwent a series of standard endocrine tests, including serum levels of TSH, free T(4), insulin-like growth factor I, PRL, testosterone (males), and cosyntropin stimulation. Abnormal results of these tests were followed by dynamic tests of gonadotropin, TSH, and GH secretion. Glucagon stimulation testing in 48 subjects revealed GH deficiency (peak, <3 microg/L) in 14.6%. Free T(4) (n = 6; 8.6%), TSH (n = 7; 10%), or both (n = 2; 2.9%) were low in 21.7%, whereas 87% had both TSH and free T(4) below the midnormal level. Basal morning cortisol was below normal in 45.7% of subjects, whereas cosyntropin-stimulated levels were insufficient (peak, <500 nmol/L) in 7.1%. Hypogonadism and hyperprolactinemia were uncommon. In summary, pituitary hormone deficiencies were identified in a substantial proportion of patients with previous brain injury. GH deficiency, found in 15% by glucagon stimulation testing, may compound the physical and psychological complications of traumatic brain injury and interfere with rehabilitation.

The PPVT-R: validity as a quick screen of intelligence in a postacute rehabilitation setting for brain-injured adults.

The utility of the Peabody Picture Vocabulary Test-Revised (PPVT-R) as a surrogate for the Wechsler Adult Intelligence Test-Revised (WAIS-R) was investigated in 61 brain-injured adult participants in a postacute rehabilitation setting. Idiographic comparison revealed substantial disagreement in clinical classification between the two instruments, and it is concluded that the PPVT-R is not a good surrogate for the WAIS-R for this purpose. In contrast, the PPVT-R was judged an adequate surrogate for the WAIS-R for the purpose of group comparison, as is common in biomedical research. Finally, contrary to prior report, the PPVT-R was demonstrated to measure more than simply Vocabulary. As such, in the absence of independent validation research, perhaps the most parsimonious conclusion regarding what the PPVT-R is measuring is that like each of the various subtests of the WAIS-R, the PPVT-R shares some of the variance of the construct termed intelligence, as well as demonstrates some unique variance that is likely comprised of error and, perhaps, a unique or different facet of intelligence.

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.

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.

Symptomatic cerebral histoplasmoma. Case report.

A 53-year-old man, with a past history of a thoracotomy 7 years previously, developed seizures. A computerized tomography scan with contrast medium revealed a peripheral ring-like lesion in the anterolateral part of the right parietal lobe. Pathological evaluation of the resected lesion demonstrated it to be a histoplasmoma. Although rare, a histoplasmoma should be included in the differential diagnosis of a ring-shaped lesion in a patient with previous pulmonary disease.