Traumatic brain injury - similarities with and differences to ME/CFS, including PEM

Has anyone ever had all their pituitary and hypothalamus hormones tested (there are quite a lot of them) after severe illness or injury affecting the brain?

According to this link : https://en.wikipedia.org/wiki/List_of_human_hormones

(I'm dubious about the following numbers because I wasn't sure which column I should be counting!)

Anterior pituitary produces 8 hormones
Posterior pituitary produces 2 hormones
Hypothalamus produces 8 hormones

I don't think its true that if one hormone from the pituitary or hypothalamus is low that they will all be low. Nor that if one hormone is absent they will all be absent - but they might be.
 
I used to eat a lot of fruit but have a lot less now, after learning about the issues with fructose. Try to stick to the recommended 1-2 pieces a day, and shift the balance towards more vegetables.

Not always easy with lots of delicious tropical fruits available here, and often quite cheap. Mangosteens, of course, being the possibly the nicest food I have ever tasted, are exempt from that rule. :woot: But they are one of the expensive ones, even here where they are actually grown, so are self-limiting anyway.
 
Arnie Pye said:
Has anyone ever had all their pituitary and hypothalamus hormones tested (there are quite a lot of them) after severe illness or injury affecting the brain?

According to this link : https://en.wikipedia.org/wiki/List_of_human_hormones

(I'm dubious about the following numbers because I wasn't sure which column I should be counting!)

Anterior pituitary produces 8 hormones
Posterior pituitary produces 2 hormones
Hypothalamus produces 8 hormones

I don't think its true that if one hormone from the pituitary or hypothalamus is low that they will all be low. Nor that if one hormone is absent they will all be absent - but they might be.
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I want to look into this as I have a few abnormalities indicating I could have some hormonal issues.
 
Could PEM be, when neuron action potential fires, use of atp, atp require mitochondria and defective mitochondria generates more ROS, and then ROS causes DAMPS release from within the cell itself that the mitochondria is in, and that DAMPS released then activate glial cells which causes Inflammation cause pain and fatigue via activating pain nerves?
Do ROS damage the cells that they are released from?

Here i am just learning the very basics of biology and wondering
 
New Zealand scientists studying the brains of rugby players have made a significant breakthrough that could allow Chronic traumatic encephalopathy (CTE) to be diagnosed in living players.
article

Until now, the disease linked to repeated head knocks could only be confirmed after someone had died.

But new patterns of inflammation in affected people have been identified by Auckland University researchers, opening the door for diagnostic testing while someone is alive.

The discovery, a world first, could have far-reaching consequences for the treatment and management of people with head injuries, including rugby players.

“Our American colleagues are very confident that, within five to 10 years, we will have a more robust set of diagnostic tools for CTE,” said Dr Helen Murray, a research fellow at the Centre for Brain Research.

“Maybe it’s something we can actually treat and deal with during someone’s life. And that can be done through pharmaceuticals, thinking about resting and letting that inflammation go away.”
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The breakthrough was discovered by the Auckland University research team after examining the brain tissue of dozens of donors, including Guyton’s. The presence of tau proteins in someone with CTE was well known but Murray and her team discovered other proteins linked to inflammation.

"What we found is there’s a pattern of inflammation around blood vessels in CTE that is quite different to what we see in people who don’t have CTE,” Murray said.
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@SNT Gatchaman

Given the similarities in some of the symptoms and the hints we have had about issues with blood vessels in ME/CFS, it would be very interesting to have these researchers look at the brains of people with ME/CFS.

I have no doubt that some people with CTE are being diagnosed with FND, so, hopefully this discovery will at least stop some of that.

I don't know what the proteins they are suggesting are linked to inflammation are.
 
I was pleased to watch this too.

Hutan said:
I have no doubt that some people with CTE are being diagnosed with FND, so, hopefully this discovery will at least stop some of that.
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At least for rugby playing men an FND misdiagnosis would be less likely due to Neurologists’ bias.
Has the former player poster boy for LP/The Switch been active lately? EDIT - He’s doing fine Life Coaching & NLP& TV presenting etc - so obviously it was not CTE for him.
 
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Here is an old NYT article that empathized with ME/CFS patients after the columnist suffered concussion fatigue for a month. She didn't mention anything about her PEM though, so I asked AI for fun. The answer was: "While fatigue is a common symptom of post-concussion syndrome (PCS), post-exertional malaise (PEM), characterized by a worsening of symptoms after physical or mental exertion, is not a core defining feature of PCS like it is for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)"

It makes sense to me though, that PCS and ME/CFS should share features. The brain's immune system must get activated to make repairs after concussion and that obviously causes debilitating fatigue in PCS. But I can't think of a reason why PCS should involve PEM. In microglial model of ME/CFS, there are cells that are primed to get activated and they presumably cause PEM. PCS on the other hand involves normal activation. But maybe it's possible for some concussion to cause cells to get primed as well as activated.
 
poetinsf said:
Here is an old NYT article that empathized with ME/CFS patients after the columnist suffered concussion fatigue for a month. She didn't mention anything about her PEM though, so I asked AI for fun. The answer was: "While fatigue is a common symptom of post-concussion syndrome (PCS), post-exertional malaise (PEM), characterized by a worsening of symptoms after physical or mental exertion, is not a core defining feature of PCS like it is for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)"

It makes sense to me though, that PCS and ME/CFS should share features. The brain's immune system must get activated to make repairs after concussion and that obviously causes debilitating fatigue in PCS. But I can't think of a reason why PCS should involve PEM. In microglial model of ME/CFS, there are cells that are primed to get activated and they presumably cause PEM. PCS on the other hand involves normal activation. But maybe it's possible for some concussion to cause cells to get primed as well as activated.
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PCS does involve something that could be described as PEM though (at least a vague definition of worsening of symptoms after physical or mental exertion is very common, edit: an example where an athlete describes developing brain fog following physical activity). A majority of people with PCS describes something somewhat akin to this and from what I've heard treatment often also used to be "lie in a dark room until you feel better" whilst now it is, more often than not, seems to be something more akin to GET. I'm however not sure whether there is a delayed form of PEM though or whether it always tends to be instant in PCS. As far as I understand the cause of fatigue in PCS is unknown, what is obvious about "immune system activation causing fatigue" what exactly is it supposed to mean when nobody knows what PCS entails?
 
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EndME said:
PCS does involve something that could be described as PEM though (at least a vague definition of worsening of symptoms after physical or mental exertion is very common, edit: an example where an athlete describes developing brain fog following physical activity). A majority of people with PCS describes something somewhat akin to this and from what I've heard treatment often also used to be "lie in a dark room until you feel better" whilst now it is, more often than not, seems to be something more akin to GET. I'm however not sure whether there is a delayed form of PEM though or whether it always tends to be instant in PCS. As far as I understand the cause of fatigue in PCS is unknown, what is obvious about "immune system activation causing fatigue" what exactly is it supposed to mean when nobody knows what PCS entails?
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The old evidence based medicine tricking people into short term measures bolstered by false hope (and the natural frustration all humans have at not wanting to lie in a dark room) vs science and logic combined with long term outcomes
 
EndME said:
what is obvious about "immune system activation causing fatigue" what exactly is it supposed to mean when nobody knows what PCS entails?
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That was a poor choice of word on my part. I should've said "probably", not "obviously". "Probably" because immune system activation usually entails fatigue. Microglial activation in concussion has been observed, so the activation part is probably more than "probably".
 
@SNT Gatchaman sorry for this delayed and somewhat vague question:

As I understand Chronic traumatic encephalopathy is both a progressive disease neurological disease and also one where post-mortem autopsies deliver conclusive results. It is linked to both p-tau aggregates as well as atrophy of the brain that can be progressive and there is a loss of neurons and accumulation of plaques. Why are these changes occuring of a flavour that cannot be detected by current imagining techniques? Can longitudinal MRIs not be used to determine progressive atrophy, why is it so hard to design tags that are specific to these proteins and use those for PET-tagging, why is accumulation of plaque not seen (or is it seen but cannot be differentiated from other conditions where such an accumlation occurs)? Opening up the head of a living human might be no small feat, but what one hears from many CTE victims and their families, many would probably be willing to make such sacrifices if it is somehow useful.

What is the flavour of this problem where currently only post-mortem autopsies show anything useful?

I've tried some Googling but without anything I would consider meaningful success.

(I don't think CTE needs to be of direct revelance but it seems CTE might be a relative to post-concussion syndrome which might be in spirit more similar to what is seen in ME/CFS or what is seen after some viral infections.)
 
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The pathology is happening in a very localised fashion: adjacent to the depths of cortical sulci. Small vessel dysfunction (and vascular leakage) also looks implicated. I think the imaging is catching up, so by combination of MRI with anatomical (high resolution eg 7 Tesla), including diffusion, susceptibility and perfusion techniques; and PET molecular studies this may become much easier to see in vivo / pre-mortem. There may also be more obvious imaging markers whose significance hadn't been appreciated.

From the first reference below —

Gross neuropathological changes in CTE include prominent frontal lobe atrophy as well as temporal lobe, thalamic, and mammillary body atrophy in higher stage disease. CTE is defined neuropathologically by the perivascular accumulation of abnormally hyperphosphorylated tau in neurons and occasionally in astrocytes with a predilection for the depths of cortical sulci.
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Neurodegeneration in the cortical sulcus is a feature of chronic traumatic encephalopathy and associated with repetitive head impacts (2024)
Neurodegeneration is a seminal feature of many neurological disorders. Chronic traumatic encephalopathy (CTE) is caused by repetitive head impacts (RHI) and is characterized by sulcal tau pathology. However, quantitative assessments of regional neurodegeneration in CTE have not been described.

In this study, we quantified three key neurodegenerative measures, including cortical thickness, neuronal density, and synaptic proteins, in contact sport athletes (n = 185) and non-athlete controls (n = 52) within the sulcal depth, middle, and gyral crest of the dorsolateral frontal cortex. Cortical thickness and neuronal density were decreased within the sulcus in CTE compared to controls (p’s < 0.05).

Measurements of synaptic proteins within the gyral crest showed a reduction of α-synuclein with CTE stage (p = 0.002) and variable changes in PSD-95 density. After adjusting for age, multiple linear regression models demonstrated a strong association between the duration of contact sports play and cortical thinning (p = 0.001) and neuronal loss (p = 0.032) within the sulcus. Additional regression models, adjusted for tau pathology, suggest that within the sulcus, the duration of play was associated with neuronal loss predominantly through tau pathology. In contrast, the association of duration of play with cortical thinning was minimally impacted by tau pathology.

Overall, CTE is associated with cortical atrophy and a predominant sulcal neurodegeneration. Furthermore, the duration of contact sports play is associated with measures of neurodegeneration that are more severe in the cortical sulcus and may occur through tau-dependent and independent mechanisms.
Web | PDF | Acta Neuropathologica | Open Access

Enlarged cavum septum pellucidum as a neuroimaging signature of head impact exposure (2025)
Cavum septum pellucidum (CSP) is commonly observed upon neuroimaging examination in individuals exposed to repetitive head impacts (RHI) and post-mortem in cases with chronic traumatic encephalopathy. Consequently, CSP has been proposed as a potential biomarker for RHI-related neurodegeneration, yet prevalence estimates of CSP across other neurodegenerative diseases and its clinical implications are largely unknown. We assessed CSP prevalence and clinical correlates in individuals with RHI exposure, a history of traumatic brain injury (TBI), a neurodegenerative disease (i.e. Alzheimer’s disease or frontotemporal dementia) and normal cognition.

The primary group of interest, i.e. individuals exposed to RHI in contact sports or military service (n = 65; mean exposure 21.58 years), was compared against age-and sex-matched participants with TBI (n = 57; number of TBI range: 1–5) and non-exposed participants of the Amsterdam Dementia Cohort (Alzheimer’s disease, n = 30; frontotemporal dementia, n = 24; normal cognition, n = 27).

Structural 3D brain MRI scans were visually rated for CSP grade (ranging 0–4) by two raters blinded to the clinical information. A CSP of at least Grade 2 was considered enlarged/abnormal. Inter-rater reliability was assessed with Cohens’ weighted Kappa (κ). We investigated whether prevalence of enlarged CSP differed between groups and assessed associations with neuropsychological outcomes (verbal memory, processing speed, mental flexibility and semantic fluency), neuropsychiatric symptoms (neuropsychiatric inventory), ventricular enlargement as measured with Evan’s index and MRI volumes of composite regions (limbic, temporal-meta regions and the whole brain).

Inter-rater reliability was substantial [κ = 0.734 (95% confidence interval 0.67–0.80)]. An enlarged CSP was more often observed in the RHI group (44.6%) compared with individuals with Alzheimer’s disease [13.3%, odds ratio (OR) = 5.24 (1.79–19.26)], frontotemporal dementia [16.7%, OR = 4.03 (1.35–15.02)] and normal cognition [18.5%, OR = 3.54 (1.27–11.62)], all PFDR < 0.05, but not compared with the TBI group [29.8%, OR = 1.90 (0.90–4.06), PFDR = 0.094]. In those with RHI, enlarged CSP was associated with lower outcomes on verbal memory learning (η² = 0.09, PFDR = 0.023) and recall (η² = 0.08, PFDR = 0.030).

For TBI, enlarged CSP was associated with lower performance on verbal memory learning; however, this lost significance after multiple comparison correction (η² = 0.014, PFDR = 0.09). Enlarged CSP was not associated with the composite MRI volumes, ventricular enlargement or neuropsychiatric symptoms. In summary, enlarged CSP was more prevalent in RHI-exposed individuals compared with individuals with a neurodegenerative disease or normal cognition, but not compared with TBI, and was associated with lower verbal memory performance in the RHI group.

Our study highlights enlarged CSP as a potential consequence of long-term head impact exposure and, to a lesser extent, TBI, rather than a general consequence of neurodegeneration.
Web | PDF | Brain Communications | Open Access

Quantitative Susceptibility Mapping in Adults with Persistent Postconcussion Symptoms after Mild Traumatic Brain Injury: An Exploratory Study (2025)
BACKGROUND AND PURPOSE
It is estimated that 18%–30% of patients with concussion experience symptoms lasting more than 1 month, known as persistent post-concussion symptoms (PPCS). Symptoms can be debilitating, and include headache, dizziness, nausea, problems with memory and concentration, sleep and mood disruption, and exercise intolerance. Previous studies have used quantitative susceptibility mapping (QSM) to show altered tissue susceptibility levels in adults acutely following concussion, however this finding has yet to be investigated in participants with PPCS.

MATERIALS AND METHODS
In this exploratory case-controlled study, we measured tissue susceptibility using QSM in 24 participants with PPCS after mild traumatic brain injury (mTBI) and 23 healthy controls with no history of concussion. We compute tissue susceptibility for 7 white matter tracts and 3 deep gray matter regions and compare tissue susceptibility between groups using ANCOVA models controlling for age and sex. We also assess the relationship between regional tissue susceptibility and symptoms.

RESULTS
There were no significant differences between tissue susceptibility in participants with PPCS compared with control subjects in any of the evaluated regions. However, we show lower tissue susceptibility across 4 white matter tracts was generally associated with worse symptoms in the PPCS group. Specifically, we saw relationships between white matter susceptibility and headache (p = .006), time since injury (p = .03), depressive symptoms (p = .021), and daytime fatigue (p = .01) in participants with PPCS.

CONCLUSIONS
These results provide evidence in support of persistent changes in the brain months to years after injury and highlight the need to further understand the pathophysiology of PPCS, to determine effective prevention and treatment options.

Web | PDF | American Journal of Neuroradiology | Paywall


Neuroimaging and Clinical Findings in Healthy Middle-Aged Adults With Mild Traumatic Brain Injury in the PREVENT Dementia Study (2024)
IMPORTANCE
Traumatic brain injuries (TBI) represent an important, potentially modifiable risk factor for dementia. Despite frequently observed vascular imaging changes in individuals with TBI, the relationships between TBI-associated changes in brain imaging and clinical outcomes have largely been overlooked in community cases of TBI.

OBJECTIVES
To assess whether TBI are associated with and interact with midlife changes in neuroimaging and clinical features in otherwise healthy individuals.

DESIGN, SETTING AND PARTICIPANTS
This cross-sectional analysis used baseline data from the PREVENT Dementia program collected across 5 sites in the UK and Ireland between 2014 and 2020. Eligible participants were cognitively healthy midlife adults aged between 40 and 59 years. Data were analyzed between January 2023 and April 2024.

EXPOSURES
Lifetime TBI history was assessed using the Brain Injury Screening Questionnaire.

MAIN OUTCOMES AND MEASURES
Cerebral microbleeds and other markers of cerebral small vessel disease (white matter hyperintensities [WMH], lacunes, perivascular spaces) were assessed on 3T magnetic resonance imaging. Clinical measures were cognition, sleep, depression, gait, and cardiovascular disease (CVD) risk, assessed using Computerized Assessment of Information Processing (COGNITO), Pittsburgh Sleep Quality Index, Center for Epidemiologic Studies Depression Scale, clinical interviews, and the Framingham Risk Score, respectively.

RESULTS
Of 617 participants (median [IQR] age, 52 [47-56] years; 380 female [61.6%]), 223 (36.1%) had a history of TBI. TBI was associated with higher microbleed count (β = 0.10; 95% CI, 0.01-0.18;P = .03), with a dose-response association observed with increasing number of TBI events (β = 0.05; 95% CI, 0.01-0.09;P = .03). Conversely, TBI was not associated with other measures of small vessel disease, including WMH. Furthermore, TBI moderated microbleed associations with vascular risk factors and clinical outcomes, such that associations were present only in the absence of TBI. Importantly, observations held when analyses were restricted to individuals reporting only mild TBI.

CONCLUSIONS AND RELEVANCE
In this cross-sectional study of healthy middle-aged adults, detectable changes in brain imaging and clinical features were associated with remote, even mild, TBI in the general population. The potential contribution of vascular injury to TBI-related neurodegeneration presents promising avenues to identify potential targets, with findings highlighting the need to reduce TBI through early intervention and prevention in both clinical care and policymaking.

Web | PDF | JAMA Network Open | Open Access

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Older PET paper:

In vivo characterization of chronic traumatic encephalopathy using F-18FDDNP PET brain imaging (2015)
Chronic traumatic encephalopathy (CTE) is an acquired primary tauopathy with a variety of cognitive, behavioral, and motor symptoms linked to cumulative brain damage sustained from single, episodic, or repetitive traumatic brain injury (TBI). No definitive clinical diagnosis for this condition exists.

In this work, we used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution in retired professional American football players with suspected CTE (n = 14) and compared results with those of cognitively intact controls (n = 28) and patients with Alzheimer’s dementia (AD) (n = 24), a disease that has been cognitively associated with CTE. [F-18]FDDNP PET imaging results in the retired players suggested the presence of neuropathological patterns consistent with models of concussion wherein brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical brain circuitries supporting mood, emotions, and behavior.

This deposition pattern is distinctively different from the progressive pattern of neuropathology [paired helical filament (PHF)-tau and amyloid-β] in AD, which typically begins in the medial temporal lobe progressing along the cortical default mode network, with no or minimal involvement of subcortical structures. This particular [F-18]FDDNP PET imaging pattern in cases of suspected CTE also is primarily consistent with PHF-tau distribution observed at autopsy in subjects with a history of mild TBI and autopsy-confirmed diagnosis of CTE.

SIGNIFICANCE
Mild traumatic brain injuries are frequent events in the general population and are associated with a severe neurodegenerative disease, chronic traumatic encephalopathy (CTE). This disease is characterized by abnormal accumulation of protein aggregates, primarily tau proteins, which accumulate in brain areas responsible for mood, fear, stress, and cognition. There is no definitive clinical diagnosis of CTE at the present time, and this new work shows how a tau-sensitive brain imaging agent, [F-18]FDDNP, may be able to detect the disease in living people with varying degrees of symptoms. Early detection would facilitate the most effective management strategies and provide a baseline to measure the effectiveness of treatments.
Web | PDF | Proceedings of the National Academy of Sciences | Open Access

Recent review:

From imaging to intervention: emerging potential of PET biomarkers to shape therapeutic strategies for TBI-induced neurodegeneration (2025)
 
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SNT Gatchaman said:
The pathology is happening in a very localised fashion: adjacent to the depths of cortical sulci. Small vessel dysfunction (and vascular leakage) also looks implicated. I think the imaging is catching up, so by combination of MRI with anatomical (high resolution eg 7 Tesla), including diffusion, susceptibility and perfusion techniques; and PET molecular studies this may become much easier to see in vivo / pre-mortem. There may also be more obvious imaging markers whose significance hadn't been appreciated.
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Thanks.

From that I read: Designing tracers that specifically pick up the proteins associated with CTE is difficult (or at least takes a very long time) and using other tracers makes the sort of "patchy but globally spread" proteins hard to distinguish from noise whilst the resolution from PET isn't high enough to identify the location as precise as necessary (which would be sufficient since the process is very localised and could then easily be differentiated from noise).

So what I'm getting: If there were to be widespread, subtle and microscopic changes and these changes aren't related to the exact same thing seen elsewhere then these could be missed by current methods.
 
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