Traumatic Brain Injury

[Michael Scally MD]

Barton DJ, Kumar RG, McCullough EH, Galang G, Arenth PM, et al. Persistent Hypogonadotropic Hypogonadism in Men After Severe Traumatic Brain Injury: Temporal Hormone Profiles and Outcome Prediction. J Head Trauma Rehabil. http://journals.lww.com/headtraumar...pogonadotropic_Hypogonadism_in_Men.99676.aspx

OBJECTIVE: To (1) examine relationships between persistent hypogonadotropic hypogonadism (PHH) and long-term outcomes after severe traumatic brain injury (TBI); and (2) determine whether subacute testosterone levels can predict PHH.

SETTING: Level 1 trauma center at a university hospital.

PARTICIPANTS: Consecutive sample of men with severe TBI between 2004 and 2009.

DESIGN: Prospective cohort study.

MAIN MEASURES: Post-TBI blood samples were collected during week 1, every 2 weeks until 26 weeks, and at 52 weeks. Serum hormone levels were measured, and individuals were designated as having PHH if 50% or more of samples met criteria for hypogonadotropic hypogonadism. At 6 and 12 months postinjury, we assessed global outcome, disability, functional cognition, depression, and quality of life.

RESULTS: We recruited 78 men; median (interquartile range) age was 28.5 (22-42) years. Thirty-four patients (44%) had PHH during the first year postinjury. Multivariable regression, controlling for age, demonstrated PHH status predicted worse global outcome scores, more disability, and reduced functional cognition at 6 and 12 months post-TBI. Two-step testosterone screening for PHH at 12 to 16 weeks postinjury yielded a sensitivity of 79% and specificity of 100%.

CONCLUSION: PHH status in men predicts poor outcome after severe TBI, and PHH can accurately be predicted at 12 to 16 weeks.

 

[Michael Scally MD]

Detection of Growth Hormone Deficiency in Adults with Chronic Traumatic Brain Injury

This study examined the prevalence of growth hormone deficiency (GHD) in patients with traumatic brain injury (TBI) during the post-acute phase of recovery and whether GHD was associated with increased disability, decreased independence and depression.

A secondary objective was to determine the accuracy of insulin-like growth factor-1 (IGF-1) levels in predicting GHD in patients with TBI.

Anterior pituitary function was assessed in 235 adult patients with TBI through evaluation of fasting morning hormone levels. Growth hormone levels were assessed through provocative testing, specifically the glucagon stimulation test.

GHD was diagnosed in a significant number of patients, with 45% falling into the severe GHD (<3 ug/L) category.

IGF-1 levels were not predictive of GHD.

Patients with GHD were more disabled and less independent compared to those patients who were not GHD. Those patients with more severe GHD also showed decreased levels of cortisol and testosterone. Symptoms of depression were also more prevalent in this group. In addition, patients with severe GHD had delayed admission to post-acute rehabilitation.

This study confirms the high prevalence of GHD in patients with TBI and the necessity to monitor clinical symptoms and perform provocative testing to definitively diagnose GHD.

Kreber L, Griesbach GS, Ashley M. Detection of Growth Hormone Deficiency in Adults with Chronic Traumatic Brain Injury. J Neurotrauma. http://online.liebertpub.com/doi/abs/10.1089/neu.2015.4127

 

[BBC3]

Well this one was fucked from the get-go... lol

"SETTING: Level 1 trauma center at a university hospital."

and somehow "trauma center" and "study" don't quite intersect... LOL At least dimensionally speaking...

Barton DJ, Kumar RG, McCullough EH, Galang G, Arenth PM, et al. Persistent Hypogonadotropic Hypogonadism in Men After Severe Traumatic Brain Injury: Temporal Hormone Profiles and Outcome Prediction. J Head Trauma Rehabil. http://journals.lww.com/headtraumar...pogonadotropic_Hypogonadism_in_Men.99676.aspx

OBJECTIVE: To (1) examine relationships between persistent hypogonadotropic hypogonadism (PHH) and long-term outcomes after severe traumatic brain injury (TBI); and (2) determine whether subacute testosterone levels can predict PHH.

SETTING: Level 1 trauma center at a university hospital.

PARTICIPANTS: Consecutive sample of men with severe TBI between 2004 and 2009.

DESIGN: Prospective cohort study.

MAIN MEASURES: Post-TBI blood samples were collected during week 1, every 2 weeks until 26 weeks, and at 52 weeks. Serum hormone levels were measured, and individuals were designated as having PHH if 50% or more of samples met criteria for hypogonadotropic hypogonadism. At 6 and 12 months postinjury, we assessed global outcome, disability, functional cognition, depression, and quality of life.

RESULTS: We recruited 78 men; median (interquartile range) age was 28.5 (22-42) years. Thirty-four patients (44%) had PHH during the first year postinjury. Multivariable regression, controlling for age, demonstrated PHH status predicted worse global outcome scores, more disability, and reduced functional cognition at 6 and 12 months post-TBI. Two-step testosterone screening for PHH at 12 to 16 weeks postinjury yielded a sensitivity of 79% and specificity of 100%.

CONCLUSION: PHH status in men predicts poor outcome after severe TBI, and PHH can accurately be predicted at 12 to 16 weeks.

 

[Dr JIM]

The results are not surprising to say the least.


In fact even Minor TBI may result to SD, in spite of GT/TT levels that are within reference range for age.

 

[Michael Scally MD]

[GMAFB] Chronic Exposure to Androgenic-Anabolic Steroids Exacerbates Axonal Injury and Microgliosis in the CHIMERA Mouse Model of Repetitive Concussion

Concussion is a serious health concern. Concussion in athletes is of particular interest with respect to the relationship of concussion exposure to risk of chronic traumatic encephalopathy (CTE), a neurodegenerative condition associated with altered cognitive and psychiatric functions and profound tauopathy. However, much remains to be learned about factors other than cumulative exposure that could influence concussion pathogenesis.

Approximately 20% of CTE cases report a history of substance use including androgenic-anabolic steroids (AAS). How acute, chronic, or historical AAS use may affect the vulnerability of the brain to concussion is unknown. We therefore tested whether antecedent AAS exposure in young, male C57Bl/6 mice affects acute behavioral and neuropathological responses to mild traumatic brain injury (TBI) induced with the CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration) platform.

Male C57Bl/6 mice received either vehicle or a cocktail of three AAS (testosterone, nandrolone and 17alpha-methyltestosterone) from 8-16 weeks of age. At the end of the 7th week of treatment, mice underwent two closed-head TBI or sham procedures spaced 24 h apart using CHIMERA. Post-repetitive TBI (rTBI) behavior was assessed for 7 d followed by tissue collection.

AAS treatment induced the expected physiological changes including increased body weight, testicular atrophy, aggression and downregulation of brain 5-HT1B receptor expression. rTBI induced behavioral deficits, widespread axonal injury and white matter microgliosis. While AAS treatment did not worsen post-rTBI behavioral changes, AAS-treated mice exhibited significantly exacerbated axonal injury and microgliosis, indicating that AAS exposure can alter neuronal and innate immune responses to concussive TBI.

Namjoshi DR, Cheng WH, Carr M, et al. Chronic Exposure to Androgenic-Anabolic Steroids Exacerbates Axonal Injury and Microgliosis in the CHIMERA Mouse Model of Repetitive Concussion. PLoS One 2016;11(1):e0146540. Chronic Exposure to Androgenic-Anabolic Steroids Exacerbates Axonal Injury and Microgliosis in the CHIMERA Mouse Model of Repetitive Concussion

 

[Michael Scally MD]

Chronic Traumatic Encephalopathy Is Found in an Ex-Giant Who Died at 27
http://www.nytimes.com/2016/01/27/s...safety-tyler-sash-found-to-have-cte.html?_r=0

When the former Giants safety Tyler Sash was found dead at age 27 of an accidental overdose of pain medications at his Iowa home on Sept. 8, his grieving family remained consumed by a host of unanswered questions about the final, perplexing years of Sash’s life.

Cut by the Giants in 2013 after what was at least his fifth concussion, Sash had returned to Iowa and increasingly displayed surprising and irregular behavior, family members said this week. He was arrested in his hometown, Oskaloosa, for public intoxication after leading the police on a four-block chase with a motorized scooter, a pursuit that ended with Sash fleeing toward a wooded area.

...

Last week, representatives from Boston University and the Concussion Legacy Foundation notified the Sash family that C.T.E. had been diagnosed in Tyler’s brain and that the disease, which can be confirmed only posthumously, had advanced to a stage rarely seen in someone his age.

...

Doctors grade C.T.E. on a severity scale from 0 to 4; Sash was at Stage 2. McKee, comparing the results to other athletes who died at a similar age, said she had seen only one case, that of a 25-year-old former college player, with a similar amount of the disease.

 

[Leancuisine]

I can personally vouch for this. In 2014 I got a two major TBI's. One was caused by an explosion, and the second was a rough landing on a static line parachute jump. After being half retarded and not sleeping for almost 2 weeks the doctors finally tested my hormones. Test was dangling around the 130ng/dl mark, compared to my late 2013 tests of 970. GH was never tested, but I was prescribed Fortesta Gel and Adex. Luckily after self medication I got myself bounced back up, but it was temporary.
Going in next week for my GH tests.

 

[integralbasic]

The results are not surprising to say the least.


In fact even Minor TBI may result to SD, in spite of GT/TT levels that are within reference range for age.

Dr. Jim, would you please elaborate on this further? What would it mean for mTBI to result to SD in spite of GT/TT levels within range? I ask because I've suffered multiple concussions in the past 1.5 years and have been searching for the relevant information for some time.

 

[integralbasic]

The results are not surprising to say the least.


In fact even Minor TBI may result to SD, in spite of GT/TT levels that are within reference range for age.

Dr Jim,
What does SD mean in reference to GT/TT level in range?

 

[Dr JIM]

It should read; even minor Traumaic Brain IInjury may result in Sexual Dysfunction in spite of NORMAL Testosterone levels.

 

[Dr JIM]

This suggests for many humans at least, the "emotional" component of "sex" defines the difference between having it and enjoying it.

 

[integralbasic]

This suggests for many humans at least, the "emotional" component of "sex" defines the difference between having it and enjoying it.

The idea here is brain injury affects psychological aspects, causing functional issues of "SD". The interesting part is that these psychological aspects have a physical catalyst, not an emotional one.

I'm interested in how the physical catalyst aligns with the mental, and to what extent these functional manifestations pertain to the nervous system vs psychological components.

 

[Michael Scally MD]

Jones GH, Kirkman-Brown J, Sharma DM, Bowley D. Traumatic andropause after combat injury. BMJ Case Reports. 2015. http://casereports.bmj.com/content/2015/bcr-2014-207924.abstract

In association with lower extremity amputation, complex genitourinary injuries have emerged as a specific challenge in modern military trauma surgery. Testicular injury or loss has profound implications for the recovering serviceman, in terms of hormone production and future fertility. The initial focus of treatment for patients with traumatic testicular loss is haemostasis, resuscitation and management of concurrent life-threatening injuries. Multiple reoperations are commonly required to control infection in combat wounds; in a review of 300 major lower extremity amputations, 53% of limbs required revisional surgery, with infection the commonest indication. Atypical infections, such as invasive fungal organisms, can also complicate military wounding. We report the case of a severely wounded serviceman with complete traumatic andropause, whose symptomatic temperature swings were initially mistaken for signs of occult sepsis.

 

[Dr JIM]

1) The idea here is brain injury affects psychological aspects, causing functional issues of "SD". The interesting part is that these psychological aspects have a physical catalyst, not an emotional one.

I'm interested in how the physical catalyst aligns with the mental, and to what extent these functional manifestations pertain to the nervous system vs psychological components.

And your point is? What rats are humans on an emotional level with respect to sexual activity.

Tell you what spend a little time in a research lab and observe RAT mating. To even the untrained eye the primary objective is NOT one of self gratification but that of PROCREATION.

Of course there are BIOCHEMICAL derangements that may occur bc of TBI but ascertaining which elementS are causative is another matter.

 

[integralbasic]

And your point is? What rats are humans on an emotional level with respect to sexual activity.

Tell you what spend a little time in a research lab and observe RAT mating. To even the untrained eye the primary objective is NOT one of self gratification but that of PROCREATION.

Of course there are BIOCHEMICAL derangements that may occur bc of TBI but ascertaining which elementS are causative is another matter.

Sure, rats mate for procreation. But smack a rat in the head hard enough and perhaps he would lose that ability due to biological derangements. I'm wondering what accounts for behavioral change when primary drivers like hormones are within range.

My thinking is that mIcrogliosis which results from axonal injury is a functional reaction that may cause behavioral change independent of the appeals to a pure emotional basis.

I don't think we're disagreeing - I'm rather trying to understand the physical and psychological basis for behavioral changes post TBI.

 

[Dr JIM]

I'm rather trying to understand the physical and psychological basis for behavioral changes post TBI.

And that's the focus of current research but choosing one study on RATS to further your understanding belies the complex nature of this ailment.

Good luck

 

[integralbasic]

And that's the focus of current research but choosing one study on RATS to further your understanding belies the complex nature of this ailment.

Good luck

Oh I didn't even look at the AAS repetitive concussion mouse model study; while taxonomically close, I've always been wary of studies which use mice.

Prima facie, mouse model's can't have anything to say about the intersection of psychology and physiology of behavioral changes post TBI. Psychology hasn't a coherent meaning wrt to mice.

But thank you for your well wishes! This intersection is indeed a focus of current research. Functional derangements are scary and I think it's important to emphasize both the physical and psychological components that lie therein.

 

[Michael Scally MD]

[OA] Association of Concussion Symptoms With Testosterone Levels and Erectile Dysfunction

Key Points

Question Are professional US-style football players with a history of multiple concussion symptoms more likely to report indicators of low testosterone levels or erectile dysfunction (ED)?

Findings In this cross-sectional study of 3409 former players, a monotonically increasing association was found between the number of concussion symptoms and the odds of reporting an indicator of low testosterone level and ED.

Meaning Concussion symptoms among former football players were associated with low testosterone levels and ED indicators, suggesting that men with a history of head injury may benefit from discussions with their health care clinicians regarding these treatable outcomes.

Grashow R, Weisskopf MG, Miller KK, et al. Association of Concussion Symptoms With Testosterone Levels and Erectile Dysfunction in Former Professional US-Style Football Players. JAMA Neurol. Published online August 26, 2019. Association of Concussion Symptoms With Testosterone Levels and Erectile Dysfunction

Importance - Small studies suggest that head trauma in men may be associated with low testosterone levels and sexual dysfunction through mechanisms that likely include hypopituitarism secondary to ischemic injury and pituitary axonal tract damage.

Athletes in contact sports may be at risk for pituitary insufficiencies or erectile dysfunction (ED) because of the high number of head traumas experienced during their careers.

Whether multiple symptomatic concussive events are associated with later indicators of low testosterone levels and ED is unknown.

Objective - To explore the associations between concussion symptom history and participant-reported indicators of low testosterone levels and ED.

Design, Setting, and Participants - This cross-sectional study of former professional US-style football players was conducted in Boston, Massachusetts, from January 2015 to March 2017.

Surveys on past football exposures, demographic factors, and current health conditions were sent via electronic and postal mail to participants within and outside of the United States.

Analyses were conducted in Boston, Massachusetts; the data analysis began in March 2018 and additional analyses were performed through June 2019. Of the 13 720 male former players eligible to enroll who were contacted, 3506 (25.6%) responded.

Exposures - Concussion symptom score was calculated by summing the frequency with which participants reported 10 symptoms, such as loss of consciousness, disorientation, nausea, memory problems, and dizziness, at the time of football-related head injury.

Main Outcomes and Measures - Self-reported recommendations or prescriptions for low testosterone or ED medication served as indicators for testosterone insufficiency and ED.

Results - In 3409 former players (mean [SD] age, 52.5 [14.1] years), the prevalence of indicators of low testosterone levels and ED was 18.3% and 22.7%, respectively. The odds of reporting low testosterone levels or ED indicators were elevated for previously established risk factors (eg, diabetes, sleep apnea, and mood disorders).

Models adjusted for demographic characteristics, football exposures, and current health factors showed a significant monotonically increasing association of concussion symptom score with the odds of reporting the low testosterone indicator (highest vs lowest quartile, odds ratio, 2.39; 95% CI, 1.79-3.19; P < .001). The ED indicator showed a similar association (highest quartile vs lowest, odds ratio, 1.72; 95% CI, 1.30-2.27; P < .001).

Conclusions and Relevance - Concussion symptoms at the time of injury among former football players were associated with current participant-reported low testosterone levels and ED indicators. These findings suggest that men with a history of head injury may benefit from discussions with their health care clinicians regarding testosterone deficiency and sexual dysfunction.

 

[Michael Scally MD]

Neurodegenerative Disease Mortality among Former Professional Soccer Players

BACKGROUND - Neurodegenerative disorders have been reported in elite athletes who participated in contact sports. The incidence of neurodegenerative disease among former professional soccer players has not been well characterized.

METHODS - We conducted a retrospective cohort study to compare mortality from neurodegenerative disease among 7676 former professional soccer players (identified from databases of Scottish players) with that among 23,028 controls from the general population who were matched to the players on the basis of sex, age, and degree of social deprivation.

Causes of death were determined from death certificates. Data on medications dispensed for the treatment of dementia in the two cohorts were also compared. Prescription information was obtained from the national Prescribing Information System.

RESULTS - Over a median of 18 years, 1180 former soccer players (15.4%) and 3807 controls (16.5%) died. All-cause mortality was lower among former players than among controls up to the age of 70 years and was higher thereafter.

Mortality from ischemic heart disease was lower among former players than among controls (hazard ratio, 0.80; 95% confidence interval [CI], 0.66 to 0.97; P=0.02), as was mortality from lung cancer (hazard ratio, 0.53; 95% CI, 0.40 to 0.70; P<0.001).

Mortality with neurodegenerative disease listed as the primary cause was 1.7% among former soccer players and 0.5% among controls (subhazard ratio [the hazard ratio adjusted for competing risks of death from ischemic heart disease and death from any cancer], 3.45; 95% CI, 2.11 to 5.62; P<0.001).

Among former players, mortality with neurodegenerative disease listed as the primary or a contributory cause on the death certificate varied according to disease subtype and was highest among those with Alzheimer’s disease (hazard ratio [former players vs. controls], 5.07; 95% CI, 2.92 to 8.82; P<0.001) and lowest among those with Parkinson’s disease (hazard ratio, 2.15; 95% CI, 1.17 to 3.96; P=0.01).

Dementia-related medications were prescribed more frequently to former players than to controls (odds ratio, 4.90; 95% CI, 3.81 to 6.31; P<0.001). Mortality with neurodegenerative disease listed as the primary or a contributory cause did not differ significantly between goalkeepers and outfield players (hazard ratio, 0.73; 95% CI, 0.43 to 1.24; P=0.24), but dementia-related medications were prescribed less frequently to goalkeepers (odds ratio, 0.41; 95% CI, 0.19 to 0.89; P=0.02).

CONCLUSIONS - In this retrospective epidemiologic analysis, mortality from neurodegenerative disease was higher and mortality from other common diseases lower among former Scottish professional soccer players than among matched controls. Dementia-related medications were prescribed more frequently to former players than to controls. These observations need to be confirmed in prospective matched-cohort studies.

Mackay DF, Russell ER, Stewart K, MacLean JA, Pell JP, Stewart W. Neurodegenerative Disease Mortality among Former Professional Soccer Players. New England Journal of Medicine 2019. https://doi.org/10.1056/NEJMoa1908483

 

[Michael Scally MD]

Neurodegenerative Disease Mortality among Former Professional Soccer Players

BACKGROUND - Neurodegenerative disorders have been reported in elite athletes who participated in contact sports. The incidence of neurodegenerative disease among former professional soccer players has not been well characterized.

METHODS - We conducted a retrospective cohort study to compare mortality from neurodegenerative disease among 7676 former professional soccer players (identified from databases of Scottish players) with that among 23,028 controls from the general population who were matched to the players on the basis of sex, age, and degree of social deprivation.

Causes of death were determined from death certificates. Data on medications dispensed for the treatment of dementia in the two cohorts were also compared. Prescription information was obtained from the national Prescribing Information System.

RESULTS - Over a median of 18 years, 1180 former soccer players (15.4%) and 3807 controls (16.5%) died. All-cause mortality was lower among former players than among controls up to the age of 70 years and was higher thereafter.

Mortality from ischemic heart disease was lower among former players than among controls (hazard ratio, 0.80; 95% confidence interval [CI], 0.66 to 0.97; P=0.02), as was mortality from lung cancer (hazard ratio, 0.53; 95% CI, 0.40 to 0.70; P<0.001).

Mortality with neurodegenerative disease listed as the primary cause was 1.7% among former soccer players and 0.5% among controls (subhazard ratio [the hazard ratio adjusted for competing risks of death from ischemic heart disease and death from any cancer], 3.45; 95% CI, 2.11 to 5.62; P<0.001).

Among former players, mortality with neurodegenerative disease listed as the primary or a contributory cause on the death certificate varied according to disease subtype and was highest among those with Alzheimer’s disease (hazard ratio [former players vs. controls], 5.07; 95% CI, 2.92 to 8.82; P<0.001) and lowest among those with Parkinson’s disease (hazard ratio, 2.15; 95% CI, 1.17 to 3.96; P=0.01).

Dementia-related medications were prescribed more frequently to former players than to controls (odds ratio, 4.90; 95% CI, 3.81 to 6.31; P<0.001). Mortality with neurodegenerative disease listed as the primary or a contributory cause did not differ significantly between goalkeepers and outfield players (hazard ratio, 0.73; 95% CI, 0.43 to 1.24; P=0.24), but dementia-related medications were prescribed less frequently to goalkeepers (odds ratio, 0.41; 95% CI, 0.19 to 0.89; P=0.02).

CONCLUSIONS - In this retrospective epidemiologic analysis, mortality from neurodegenerative disease was higher and mortality from other common diseases lower among former Scottish professional soccer players than among matched controls. Dementia-related medications were prescribed more frequently to former players than to controls. These observations need to be confirmed in prospective matched-cohort studies.

Mackay DF, Russell ER, Stewart K, MacLean JA, Pell JP, Stewart W. Neurodegenerative Disease Mortality among Former Professional Soccer Players. New England Journal of Medicine 2019. https://doi.org/10.1056/NEJMoa1908483

Soccer and Mortality — Good News and Bad News

In the general population, moderate exercise, physical activity, and participation in sports have important health benefits, including slowing cognitive decline and preventing dementia. Participation in elite-level sports, not surprisingly, is also associated with reductions in all-cause mortality and the risk of cardiovascular disease.

In recent years, however, there has been evidence that participation in some contact and collision sports may increase the risk of cognitive and neuropsychiatric impairment later in life, as well as the risk of neurodegenerative disease and chronic traumatic encephalopathy (CTE), because of repetitive brain trauma. It appears that it is not just the “big hits” resulting in symptomatic concussions that increase the risk of neurologic disorders later in life.

Rather, the total duration of exposure to repetitive head impacts, including “subconcussive” injuries without symptoms, has been associated with neuropathology, in vivo markers of neurodegeneration, and cognitive and neuropsychiatric symptoms later in life.

…

The article by Mackay and colleagues adds to the evidence that repetitive head impacts in some contact and collision sports may increase the risk of neurodegenerative disease and dementia.

Research on the neurologic consequences of heading in soccer is needed, including studies involving female former professional soccer players and male and female amateur soccer players, as well as prospective longitudinal investigations to examine possible relationships between heading and neurodegenerative disease in order to confirm or refute the findings of Mackay and colleagues.

Perhaps, however, there is already adequate evidence that repeated blows to the brain from heading in professional soccer is an occupational risk that needs to be addressed.

Stern RA. Soccer and Mortality — Good News and Bad News. New England Journal of Medicine 2019. https://doi.org/10.1056/NEJMe1912071