Indicates Higher Rate of Dementia in NFL Players by
ALAN SCHWARZ , September 2009: A study commissioned by the NFL reports
that Alzheimer’s disease or similar memory related diseases appear to have been diagnosed in the league’s former
players vastly more often than in the national population — including a rate of 19
times the normal rate for men ages 30 through 49. The N.F.L.
has long denied the existence of reliable data about cognitive decline among its players. These numbers would become the league’s
first public affirmation of any connection, though the league pointed to limitations of this study. NYTimes.com
Axis I and II psychiatric
disorders after traumatic brain injury: a 30-year follow-up study. Am J Psychiatry. 2002; 159(8):1315-21 . Koponen S; et al. Department of Psychiatry, Turku University Central Hospital, Finland. OBJECTIVE: Patients who had suffered traumatic brain injury were evaluated to determine
the occurrence of psychiatric disorders during a 30-year follow-up. METHOD: Sixty patients
were assessed on average 30 years after traumatic brain injury. DSM-IV axis I disorders were diagnosed on a clinical basis
with the aid of the Schedules for Clinical Assessment in Neuropsychiatry (version 2.1),
and axis II disorders were diagnosed with the Structured Clinical Interview for DSM-III-R
Personality Disorders. Cognitive impairment was measured with a neuropsychological test battery and the Mini-Mental State
Examination. RESULTS: Of the 60 patients, 29 (48.3%) had had an axis
I disorder that began after traumatic brain injury, and 37 (61.7%) had had an axis I disorder during their lifetimes. The most common novel disorders after traumatic brain injury were major depression (26.7%), alcohol
abuse or dependence (11.7%), panic disorder (8.3%), specific phobia (8.3%), and psychotic
disorders (6.7%). Fourteen patients (23.3%) had at least one personality disorder. The most prevalent individual disorders were avoidant (15.0%), paranoid (8.3%), and schizoid (6.7%) personality disorders. Nine patients
(15.0%) had DSM-III-R organic personality syndrome. CONCLUSIONS: The results
suggest that traumatic brain injury can cause decades-lasting vulnerability to psychiatric illness in some individuals. Traumatic brain injury seems to make patients particularly susceptible to depressive
episodes, delusional disorder, and personality disturbances. The high rate of psychiatric disorders found in this study emphasizes the importance of psychiatric
follow-up after traumatic brain injury.
Prevalence of hypopituitarism and growth
hormone deficiency in adults long-term after severe traumatic brain injury. Clin Endocrinol (Oxf)
2005 May;62(5):525-32/ Leal-Cerro A; et al. Division of Endocrinology, Vorgem del Rocio University Hospital, Sevilla,
Traumatic brain injury (TBI) has been associated with hypopituitarism and GH deficiency. However, TBI-mediated hypopituitarism
may be more frequent than previously thought. The present work, performed in patients with severe TBI at least 1 year before,
had three aims: (i) to evaluate the prevalence of hypopituitarism, (ii) in particular to evaluate the prevalence of GH deficiency,
and (iii) to compare three different tests of GH reserve in this cohort. DESIGN AND PATIENTS: From a nonselected group of
249 patients admitted to our Clinical Centre for severe TBI over the last 5 years, 200 of them answered a custom made questionnaire
of symptoms of hypopituitarism enclosed in the invitation letter to participate in the study. A total of 170 (99 men and 14
women), accepted to participate in the study (study cohort); 57 had normal questionnaires and were not further studied, 14
discontinued the study, and 99 attended the hospital for dynamic tests of pituitary hormone deficiencies. From these, 44 subjects
with IGF-I in the lower range were tested with GHRH+GHRP-6; ITT; and glucagon tests of GH reserve, on three different occasions.
MEASUREMENTS: Pituitary hormones plus IGF-I and target gland hormones were analysed. RESULTS: With regard to the initial cohort
of 170 subjects (100%), three (1.7%) showed diabetes insipidus; 10 (5.8%) TSH deficiency, 11 (6.4%) ACTH deficiency and 29
(17%) gonadotrophin deficiency. In 10 subjects (5.8%), GH deficiency was diagnosed by strict criteria. Finally, 15 (8.8%)
showed combined deficit of several hormones. CONCLUSION: After severe head trauma, gonadotrophin deficiency was the most common
pituitary deficit. GH deficiency showed a prevalence similar to ACTH and TSH deficits, i.e. near 6% of the cohort. Taken together,
24.7% of the subjects studied showed any type of pituitary hormone deficiency.
hypopituitarism following traumatic brain injury. Brain Injury. 2005; 19(5):349-58. Urban RJ; Harris P; Masel B.
Department of Internal Medicine, Division of Endocrinology, University of Texas Medical Branch, Galveston, TX, USA.
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. 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. ischemic 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.
Early predictors of
postconcussive syndrome in a population of trauma patients with mild traumatic brain injury(MTBI). J Trauma. 2009; 66(2):289-96; discussion 296-7. PC; Ryb;GE; Kufera JA; Auman KM.
National Study Center for Trauma and EMS, The University of Maryland School of Medicine, Baltimore, Maryland, USA. PURPOSE:
The purpose of this analysis was to determine which of the initial symptoms after mild traumatic brain injury (MTBI) can best
predict the development of persistent postconcussive syndrome (PCS). METHODS: One hundred eighty (180) MTBI patients admitted
to a level I trauma center were enrolled in a prospective study and 110 followed for 3 months. MTBI was defined as a Glasgow
Coma Score of 13 to 15 with a transient loss of consciousness or report of being dazed or confused. PCS was defined as the
persistence of four or more symptoms long term. Patients were screened at admission and at 3 days to 10 days and 3 months.
Symptom checklists were administered to ascertain the presence of symptoms (cognitive, emotional, and physical) after concussion.
For a subset of patients that were physically able, balance tests were also conducted. Stepwise logistic regression was used
to identify which symptoms best predicted PCS. RESULTS: The mean age of the subjects was 35 years, and 65% were men. Physical
symptoms were the most prevalent in the 3 days to 10 days postinjury with most declining thereafter to baseline levels. Emotional
and cognitive symptoms were less prevalent but more likely to remain elevated at 3 months; 41.8% of subjects reported
PCS at 3 months. In multivariate regressions including age, gender, and early symptoms, only anxiety, NS and gender remained
significant in the prediction of PCS. Interactions revealed that the effect of anxiety was seen primarily among women.
CONCLUSIONS: The strongest individual symptoms that predicted long-term PCS included anxiety, noise sensitivity (NS), and
trouble thinking; reported by 49%, 27%, and 31% of the subjects at 3 days to 10 days, respectively
on screening for hypopituitarism following traumatic brain injury. Brain Inj. ;2005; 19(9):711-24
Ghigo;E. et al. Department of Internal Medicine, University of Turin, Turin, Italy. 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 sequela 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
centers, (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.
dysfunction in the acute phase of traumatic brain injury. Clin Endocrinol (Oxf).
2004; 60(5):584-9. Agha A; Rogers B; Mylotte D; Taleb
F; Tormey W; Phillips J; Thompson CJ. Academic
Department of Endocrinology, Beaumount Hospital, Dublin, Ireland. BACKGROUND: Pituitary hormone abnormalities have been reported in up to 50% of survivors of traumatic
brain injury (TBI) who were investigated several months or longer following the event. The frequency of pituitary dysfunction
in the early post-TBI period is unknown. AIM: To evaluate the prevalence of anterior and posterior pituitary dysfunction in
the early phase following TBI. SUBJECTS: Fifty consecutive patients admitted to the neurosurgical unit with severe or moderate
TBI. RESULTS: 18% had GH response 16% had peak cortisol responses < 450 nmol/l. Compared to controls, basal
cortisol values were significantly lower in patients with subnormal cortisol responses to glucagon and significantly higher
in patients with normal cortisol responses. GH and cortisol deficiencies were unrelated to patient age, BMI, initial GCS or
IGF-1. 80% had gonadotrophin deficiency(testosterone). CONCLUSION: Our data show that post-traumatic
neuroendocrine abnormalities occur early and with high frequency, which may have significant implications for recovery and
rehabilitation of TBI patients.
as a consequence of traumatic brain injury (TBI) and its possible relation with cognitive disabilities and mental distress.
J Endocrinol Invest. 2004; 27(11):1048-54. Popovic V; et al. Institute of Endocrinology, University Clinical Center,
Belgrade, Union of Serbia and Montenegro. Recent studies have demonstrated that hypopituitarism, in particular GH deficiency,
is common among survivors of traumatic brain injury (TBI) tested several months or years following head trauma. We present
the results of endocrine, neurological, neuropsychological and psychiatric evaluation in a group of 67 patients who suffered
TBI at least one yr ago. Our study shows that decreased endocrine function is either restricted to one or more anterior
pituitary hormones and is present in 34% of patients with any pituitary hormone deficit, while multiple pituitary
hormone deficiencies are found in 10% of patients. Severe GHD is the most frequent deficiency present in
15% of TBI patients. Gonadotrophin deficiency was present in 9% of patients with TBI, while thyrotrophic
and corticotrophic function seemed more refractory to impairment. Patients with moderate-to-severe trauma are not necessarily
more likely to have hypopituitarism than those with mild injury. Neuropsychological testing revealed a significant positive
correlation of peak GH levels with verbal learning and verbal short term memory. Verbal and visual memory was significantly
lower, vasoconstriction abilities were significantly lower, Visual memory (free recall of complex figure after 30 min) significantly
correlated with lower IGF-I levels. Gonadotrophins and testosterone correlated significantly with vasoconstriction abilities.
Simple and complex conceptual tracking was significantly more impaired in older TBI patients and with longer time from trauma.
The psychiatric evaluation by using two different scales showed depression, phobic anxiety and psychoticism to be more prominent
in the TBI group. Paranoid ideation and somatization correlated with low GH responses to GHRH+GHRP-6 test. Depression
scale showed that nearly half of patients suffered from mild to moderate depression. The benefits of hormone replacement
therapy on cognitive functioning and mental distress in TBI patients can only be improved upon with the appropriate correction
of the underlying hormonal deficiencies.
The Clinical Significance of Major Depression Following Mild Traumatic Brain Injury
44:31-37, February 2003. Mark J. Rapoport, M.D., F.R.C.P.C., Scott McCullagh, M.D., F.R.C.P.C., David Streiner, Ph.D., C.Psych.,
and Anthony Feinstein, Ph.D., F.R.C.P.C. 13th annual meeting of the American Neuropsychiatric Association, La Jolla, Calif.,
March 10–12, 2002. Sunnybrook and Women's College Health Sciences Centre, 2075 Bayview Ave., Toronto, Ont. M4N 3M5,
OBJECTIVE: The authors assessed the association
of major depression with behavioral outcome following mild traumatic brain injury. RESULTS: Major depression was seen in 15.3%
of the subjects after traumatic brain injury, and these individuals showed subjective and objective evidence of poorer outcome.
CONCLUSIONS: Major depression is associated with poor outcome across multiple domains. This study highlights the need for
the early diagnosis and prompt treatment of major depression following mild traumatic brain injury. Comment: Confirming hormonal dysfunction after TBI and replacing it with physiological therapy has helped
to avoid the need for anti-depressant medication. Additionally, many of the Neuroactive and Neurosteroides have been shown
to participate in the repair of the damage. MLG.
in the brain: characteristics of specific brain targets for the hormone and their functional significance.
Neuroendocrinol 2000 Oct;21(4):330-48. Nyberg F Department of Pharmaceutical Biosciences,
Uppsala University, Uppsala, Sweden. During the past decade studies have shown that growth hormone (GH) exerts profound effects
on the central nervous system (CNS). For instance, GH replacement therapy was found to improve the psychological capabilities
in adult GH deficient (GHD) patients. Furthermore, beneficial effects of the hormone on certain functions, including memory,
mental alertness, motivation, and working capacity, have been reported. Likewise, GH treatment of GHD children has been observed
to produce significant improvement in many behavioral problems seen in these individuals. Studies also indicated that GH therapy
affects the cerebrospinal fluid levels of various hormones and neurotransmitters. Further support that the CNS is a target
for GH emerges from observations indicating that the hormone may cross the blood-brain barrier (BBB) and from studies confirming
the presence of GH receptors in the brain.
of Growth Hormone Replacement on Cerebral Metabolism in Adults with Growth Hormone Deficiency. Growth
Hormone and IGF Research, 1998, 8, 317, 318, 349. IC Cranston, et al., . Dept of Medicine; Clinical PET Centre, UMDS St Thomas
Hospital, London, UK. The beneficial effects of growth hormone (GH) replacement in GH-deficient adults on both quality of
life, mood and cognitive functioning have been previously described. It is however unclear if these effects represent a direct
central action of GH (perhaps via IGFI), or are secondary to the well-described peripheral effects of GH and the resulting
improvements in systemic well-being. In order to determine this, we have studied 15 GH-deficient adults before and 3 months
after growth hormone replacement or placebo (randomized, double-blind) using quantitative, dynamic cerebral positron
emission tomography (PET). Regional cerebral metabolic rate for glucose (RCMRglu) was determined by comparison of arterial
tracer disappearance with brain tracer uptake by the PET scanner over 1h after intravenous bolus of the positron
emitter 18-Fluoro-Deoxyglucose (18FDG)
as a glucose tracer. In both GHD groups, the baseline whole-brain CMRglu was lower than that for previous non-GHD
subjects after placebo this fell still further. In contrast, those receiving Growth Hormone sustained a significant rise
in whole-brain CMRglu up-take. This effect was similar across all brain regions, with the exception of brain-stem, where
the effect of GH on CMRglu was negligible. In summary, resting cerebral metabolic rate in GHD adults is low, replacement with
GH at physiological doses increases this towards normal, suggesting a direct effect of GH replacement on the central
nervous system. Comment: Improving the sugar metabolism in the brain leads
to improvement in all aspects of function. Without the adequate amount of GH/IGF-1 in the brain it cannot efficiently utilize
the sugar for optimal functioning.
cardiovascular risk of adult GH deficiency (GHD) improved after GH replacement and worsened in untreated GHD: a 12-month prospective
study. J Clin Endocrinol Metab. 2002 Mar;87(3):1088-93.Colao A, et al. Department of Molecular and Clinical
Endocrinology and Oncology, Federico II University of Naples, 80131 Naples, Italy. Increased cardiovascular morbidity and
mortality were reported in GH deficiency (GHD), and GH replacement can ameliorate cardiac abnormalities of adult GHD patients.
To test the potential progression of untreated GHD on the cardiovascular risk and cardiac function, cardiovascular risk factors,
cardiac size, and performance were prospectively evaluated in 15 GHD patients (age, 18-56 yr) who were treated with recombinant
GH at the dose of 0.15-1.0 mg/d, 15 GHD patients (age, 18-56 yr) who refused GH replacement, and 30 healthy subjects (age,
18-53 yr). Electrocardiogram, systolic and diastolic blood pressure, and heart rate measurement, serum IGF-I, total cholesterol,
low- and high-density lipoprotein (LDL, HDL) cholesterol, triglycerides, and fibrinogen level assay, echocardiography, and
equilibrium radionuclide angiography were performed basally and after 12 months. At study entry, low IGF-I levels, unfavorable
lipid profile, and inadequate cardiac and physical performance were found in GHD patients compared with controls. After 12
months of GH treatment, IGF-I levels normalized; HDL-cholesterol levels, left ventricular (LV) mass index (LVMi), left ventricular
ejection fraction (LVEF) at peak exercise, peak filling rate, exercise duration and capacity significantly increased; total-
and LDL-cholesterol levels significantly decreased. After 12 months in GH-untreated GHD patients, IGF-I levels remained stable,
and HDL-cholesterol levels, LVEF both at rest and at peak exercise, and exercise capacity were further reduced; total- and
LDL-cholesterol levels increased slightly. LVEF at rest and its response at peak exercise normalized in 60 and 53.3%, respectively,
of GH-treated patients and in none of the GH-untreated patients. In conclusion, 12 months
of GH replacement normalized IGF-I and improved lipid profile and cardiac performance in adult GHD patients. A similar period
of GH deprivation induced a further impairment of lipid profile and cardiac performance. This finding strongly supports
the need of GH replacement in adult GHD patients.
Medical Journal Articles that Support
TBI - Sequelae